Provisional Logistics 2

Hi

Traits controlled by a single gene

The ABO blood group is determined by the ABO gene, which carries information about a protein called glycosyltransferase. The ABO gene carries information about a protein called glycosyltransferase, which is mainly responsible for adding another sugar to the end of the sugar chain exposed on the surface of the cell. However, the DNA sequence of the ABO gene can be divided into three main types depending on the function of this protein. In genetics, different types of the same gene are called alleles. In the case of the ABO gene, there are three alleles, A, B and O. These alleles contain information about the same type of protein, but the proteins produced from these alleles have slightly different functions. This is because the sequence of bases is slightly different between the alleles, resulting in a slight difference in the amino acid sequence. All genes have such different types and alleles.

In the ABO gene, the enzyme synthesized from the allele classified as O is an enzyme that cannot link sugars. A adds the sugar N-acetylglucosamine. B adds the sugar galactose. There are also three types of alleles that produce type O. In one case, the 261st base is missing. So that the correct enzyme cannot be synthesized. There are several differences between the sequences of the A and B alleles compared. Four of these differences, at bases 526, 703, 796 and 803, all result in amino acid differences when translated into protein. This difference in amino acids causes the enzymes synthesized from each allele to function differently.

In each individual, one allele of the ABO gene is transmitted from each parent. The cell then synthesizes an enzyme from both alleles. Thus, the two alleles of the ABO gene in each individual can be one of six possible combinations. If both alleles are O, the ABO blood group will be type O. If A and A or A and O, type A. If B and B or B and O, type B. If A and B, type AB. Therefore, it is possible to distinguish any of these six types by examining the above sequence of the ABO gene. Then, we can predict the blood group from only a little genetic information without studying the blood group of parents, the actual blood group, or the whole ABO gene sequence. However, there are basic exceptions in living organisms, and even in this case there are special alleles which cannot be estimated by the above combinations. For example, some of the alleles classified as O consist of different sequences and are present in low frequency in the population.

The natural avoidance of spontaneity may be a remote cause of autonomic dysreflexia.

Howdy?

>>128 I think it will function properly as a nightgown only under unheated conditions below 10 degrees Celsius.

In the first place, without basic bodily mechanisms and skills based on biological evolution, culture itself would not exist. In this sense, we can say that culture is a mechanism to extend biological body mechanisms and skills. Culture extends humanity's biological skills: many tools are extensions of the hand, microscopes and radio telescopes are extensions of the eye, loudspeakers and printing technology are extensions of the voice, trains, automobiles and other means of transportation are extensions of the foot, computers are extensions of the brain, and fire is an extension of the digestive system. Moreover, only human beings are capable of not only making tools, but also of extending such body extensions to any extent by flexibly combining them in many kinds and many layers: we make the tools needed to make tools, we make the means of transportation needed to carry tools, we make the tools needed to convey information... and so on. Culture is a device for the multiple and flexible extension of humanity's biological mechanisms and skills to any extent.

Voulez-vous arrêter de penser?

Velim ut pubes meas etiam exhauriat.

Il y a du sang frais qui sort de l'anus.

Lorsque j'ai porté le "Men's Organic Cotton Mix Heat Generating V Neck Long Sleeves T-Shirt" de MUJI comme chemise de nuit la nuit dernière, j'ai ressenti des démangeaisons soudaines et sévères. Cela était vraisemblablement dû à la fonction de stockage thermique du produit, qui a contribué à l'augmentation de la température corporelle. Par conséquent, j'interdis le port de tout sous-vêtement à stockage thermique, y compris le produit en question, au moment du coucher et je gèle indéfiniment tout projet d'achat du produit en question.

Une personne était très intéressée par mon histoire "J'ai récemment réalisé que si j'utilise des images de personnages comme objet de mon étude, je ne serai jamais capable d'écrire une théorie des images de personnages", alors j'ai mentionné la fappabilité et la zéro-fappabilité et j'ai dit "En bref, 'Moe' est un concept dans le domaine de la littérature et de l'art, et qu'il est impossible de faire une analyse rationnelle dans le domaine de la recherche en art visuel sans introduire la "fappabilité", il m'a écouté avec grand intérêt, ce qui a peut-être augmenté ma motivation pour écrire un livre sur la "fappabilité".

La croyance qu'une préparation méticuleuse fera naître nos désirs n'est ni bonne ni mauvaise en soi.
Les organes génitaux féminins bipolaires et décentrés : le sein et la vulve sont littéralement des symboles du corps féminin et sont essentiels à l'histoire de l'industrie du sexe.
Pourquoi le récit négatif est-il si répandu dans la société moderne ?
Nous devons vivre en tant que personnes nées dans un pays de perdants et il est important et bénéfique pour nous individuellement et pour ce pays d'en prendre conscience.
Underachiever ou Procrastinator - quel est mon véritable alias ?
Je veux être une sorte d'agent de circulation pour notre société en tant que collectif intellectuel.
Il n'y a rien de naturel ou de fondé sur des principes à ressentir un sentiment d'appartenance à un système politique tel que l'État.

Une perspective fantomatique, une vision fantomatique, une vue fantomatique (17:52, 2021/06/10)
Voir la vraie nature des fantômes et des fleurs à queue flétrie (17:52, 10 juin 2021)
L'univers agité (17:54, 2021/06/10)
A Senior Conflits entre raison et instinct (2021/06/13/0:30)
D'aussi loin que je me souvienne, une motion de défiance à l'égard du parti au pouvoir, l'ego, a été proposée au parlement de mon cerveau, ma plus haute instance de décision (11:01, 16/06/2021).
La compréhension de Mario-like comme sous-catégorie de la gamification (22/07/2021, 7:25 pm)
Heattech peut remplacer le chauffage, mais Airism ne peut pas remplacer le refroidissement (16:01, 27/07/2021)
S'il y a quelque chose à rechercher, c'est bien l'accomplissement de la justice (07/08/2021, 0:01)
La peur de l'effondrement des constructions intellectuelles décourage la pensée et l'action constructives, quelles qu'elles soient. (2021/08/09/5:04)
Seuls ceux qui peuvent utiliser la boussole du devoir lorsqu'ils nagent dans une mer de droits illimités sont libres (21:45, 2021/09/02)
À la recherche d'une intelligence externe (ht 22:12, 2021/09/02)
C'est pratique de mettre toute sa monnaie dans une caisse automatique et elle ressort avec la plus petite combinaison (23:31, 10 septembre 2021).
Penser horizontalement quand on manque de sommeil (8:02, 12/09/2021)
Les informations véritablement utiles devraient être les plus personnalisées, n'est-ce pas ? (2021/09/14/0:29)
Je veux être un guide de circulation pour la société en tant que collectif intellectuel (23:07, 10/04/2021)
Déconstruire la problématique (19:55, 29/10/2021)
L'objectif suprême d'Apple pourrait être l'égalité des chances grâce aux machines (3:56, 11/09/2021)
Des philosophes qui possèdent et luttent avec un Hiroyuki altéré (0:41, 21 novembre 2021)
Sur ses propres caractéristiques physiques.

Comment allez-vous tous?

Je pense personnellement que la raison pour laquelle les personnes intelligentes ont une vision positive de la mort, ou pourquoi les personnes âgées s'accrochent à leur emploi mal payé, est un problème qui peut être résolu en formant une sorte de communauté appropriée pour chaque personne, en leur donnant une nouvelle réalisation sociale, et en développant des divertissements inconnus au-delà de notre imagination. Pensez-vous qu'il est possible de créer un avenir où les gens ont une vision plus positive de la vie en stimulant leurs loisirs d'une manière plus rationnelle pour leur cerveau?

Le rêve changeant, le souvenir d'un monde de brume matinale illusoire. Ce monde actuel, assis sur une fondation de sable qui s'effrite. L'histoire d'un rêve fabriqué, racontant un monde ancien et profond. En plein jour, une ville coule.

Est-ce une illusion, ou une tour construite sur du sable ? Ce rêve, jusqu'au lever du jour, est un rêve de papillon.

Le rêve change, la couleur voyante d'un manoir écarlate illusoire. Ce monde actuel, assis au sommet d'une froide fondation de pierre. Le conte de fées d'un rêve fabriqué, racontant une ancienne et belle capitale. En plein jour, une ville est corrompue.

D'un point de vue fantomatique, d'une vision fantomatique, d'une perspective fantomatique, mes aînés, qui luttent entre la raison et l'instinct de l'univers, qui voient la vraie nature des fantômes et l'agitation au sein des fleurs à queue fanée, ont été dans le plus haut organe de décision de mon cerveau, la Diète, depuis aussi longtemps que je me souvienne, il y a eu un vote de défiance dans le parti au pouvoir, l'ego. Avec la compréhension de Mario de la gamification comme sous-catégorie, le heattech est un substitut du chauffage, mais l'airism n'est pas un substitut du refroidissement, donc s'il y a quelque chose à rechercher, c'est seulement la réalisation de la justice. Je vous ai appris à maintes reprises que la peur de l'effondrement des constructions intellectuelles nous fait nous abstenir de pensées et d'actions constructives, quelles qu'elles soient, mais seuls ceux qui savent utiliser la boussole du devoir sont libres lorsqu'ils nagent dans une mer de droits infinis, et il est commode de mettre toutes ses pièces dans la caisse automatique de l'intelligence extérieure, car elles en ressortent dans la plus petite combinaison possible. La pensée horizontale pendant la privation de sommeil est également vraie, et j'ai dit que l'information véritablement utile devrait être la plus personnalisée, et je veux être un guide de circulation pour la société en tant que collectif intellectuel, et le démantèlement de la conscience des problèmes et la suprématie d'Apple peut être l'égalité des chances par la machine, et possédée par l'altéré Hiroyuki. Les philosophes qui se débattent avec leurs propres caractéristiques physiques sont éliminés ou torturés.

OC2(h)

By Hanako and Shinichi's first intercourse, estimated about 2 hours ago.

Contemporary Individualism was born at 23:19 on June 9, 2020. Today, January 18, 2021, at 8:56 pm, it has lived a little over seven months and has been completely deleted from the trash. There is no need for pessimism, as I will be irresponsibly raising its descendants. Please keep in mind that the descendants will be purely cultivated and gradually propagated at https://ha10.net/ and https://jeison.biz/casphy/.

>>147 It's 8:56 am, not pm.

Me: I'm cold.
Siri: I'm relieved to hear that.

The intelligible truths underlying all of our thoughts are clear but subtle, and depend on nothing more than the differences that are actually possible, since none of them are good. In order to achieve complete clarity in our thinking about an object, we need only consider the practical kinds of perceptible effects that the object has. In other words, what sensations we should expect from it and what reactions we should prepare for.

(Ramanujan's work) did not have the simplicity and inevitability of truly great work. It would have been greater if it had been less strange. But there was a natural talent there that no one could deny. It was a deep and invincible originality. If he had been discovered and acclimatized at a younger age, he probably would have become an even greater mathematician, making new and more important discoveries. On the other hand, he might have become less "Ramanujan-like" and more European professorial, losing more than he gained.

Airi(h), estimated 8 hours ago.

Uncensored Girl from the North Country, estimated 20 minutes ago.

>>153 This is the quintessential serendipitous/algorithmic discovery. I sacrificed the synchronicity to identify her genuineness. Consequently, I'm kind of grateful to her and her appendage.

In French and German, they say I'm rather grateful for her appendage. Don't distort the facts.

The question is whether there is anything I (we) can do in the first place.

Laggards know no innovators, shun the early adapters, despise the majority.

During the COVID lockdown, this headline went viral: "Nearly half of men say they do most of the homeschooling... ...three percent of women agree." I bring this up not to debate who's right, but because it's a great example of something called egocentric bias: Most people think they do most of the work. For example, researchers have asked authors of multi-author papers what percentage of the work they personally did, and when they add up those percentages, the sum is on average 140 percent. When couples are asked to estimate how much of the housework they do, the combined total is almost always over 100%. Now you might think this is because people want to appear more helpful than they actually are, but that's not it. When couples are asked what fraction of the fights they start or how much of the mess is theirs, the total is again over a hundred. People think they do more of the work, but they also think they cause more of the problems. So why is this? I think it's simply because you experience and remember vividly all of what you do, but not all of what everyone else does, so naturally you overestimate your own contributions and underestimate others. And I think this bias leads us to underestimate the influence of other things on our lives like the role luck plays in our success. Take hockey players, for example. If you ask a professional hockey player how they managed to reach the NHL, they might mention their hard work, determination, great coaches, their parents willingness to get up at 5 AM, and so on, but they probably won't acknowledge how lucky they were to be born in January. And yet, in many years 40% of hockey players selected into top tier leagues are born in the first quarter of the year, compared to just 10% in the fourth quarter; an early birthday can make you up to four times as likely to be a pro hockey player. And the reason for this disparity is presumably because the cutoff date for kids hockey leagues is January 1st. Those born in the first part of the year are a little older and so on average bigger and faster than kids in their league born late in the year. Now as they grow up, this difference should eventually shrink to nothing, but it doesn't. Because the young kids who share the most promise are given more time on the ice and enter more tournaments, where they receive better coaching and improve their skills. And these advantages compound year after year, so by the time you get to the pros, birthdays are heavily skewed towards the start of the year. But does any professional hockey player feel thankful for their birthday? Probably not. And we are all like that, largely oblivious to the fortunate events that support our success. Probably the most significant bit of luck many of us enjoy is being born into a prosperous country; around half the variance in income received by people around the world is explained by their country of residence and that country's income distribution. If you were born in Burundi, for example, which has the world's lowest gross national income per capita of just 730 dollars a year, it doesn't matter how smart or hard-working you are; you're unlikely to earn much as an adult. Now many people get offended if you point out how big a role chance plays in their success and I get it. If we are just a product of our circumstances, then our hard work and our talent seem to count for nothing. People think it has to be either skill or luck that explains success, but the truth is you need both. Take these eight track and field world records: all the athletes who achieve these records are obviously world class, extremely dedicated, and talented and yet, when they achieved their world records, seven out of eight had a tailwind. Now these athletes all had the ability to win a gold medal, but to set the world record required a bit of luck as well. The importance of luck increases the greater the number of applicants applying for just a few spaces.

Consider the most recent class of NASA astronauts. From over 18,300 applicants in 2017, only 11 were selected and went on to graduate from the astronaut training program. Now we can make a toy model of the selection process. Let's assume that astronauts are selected mostly based on skill, experience, and hard work, but also say five percent as a result of luck — fortunate circumstances. For each applicant, I randomly generated a skill score out of a hundred, and I also randomly generated a luck score out of a hundred. Then I added those numbers together, weighted in the 95-to-5 ratio to get an overall score. This score represents the selector's judgments, meaning the top 11 by this metric would become astronauts. And I repeated this simulation a thousand times representing a thousand different astronaut selections. And what I found was the astronauts who were picked were very lucky; they had an average luck score of 94.7. So how many of the selected astronauts would have been in the top 11 based on skill alone? The answer was, on average, only 1.6. That means, even with luck accounting for just 5% of the outcome, 9 or maybe 10 of the 11 applicants selected would have been different if luck played no role at all. When competition is fierce, being talented and hard-working is important, but it's not enough to guarantee success. You also need to catch a break. Largely, I think we're unaware of our good luck because, by definition, it's not something we did. Like the housework done by your significant other, it goes unappreciated. And here's the crazy thing: Downplaying the importance of chance events may actually improve your probability of success because if you perceive an outcome to be uncertain, you're less likely to invest effort in it, which further decreases your chances of success. So, it's a useful delusion to believe you are in full control of your destiny. I mean, if I had known how bad I was when I started YouTube or how much work it would take, I might have given up right then. "Welcome to Veritasium: an online science video blog." Now there may be another benefit to overlooking your lucky breaks, which is it makes it easier to justify your place in society: if you have a lot of wealth or power, you can just chalk it up to your own intelligence, effort, and perseverance. It makes it easier to accept inequality. In one experiment, participants were put in groups of three in small rooms to discuss a complex moral problem, and one person in each group was randomly designated the team leader. Half an hour later, the experimenter came by with four cookies for each team. So who got the extra cookie? In each case, it went to the team leader. Even though they had no special aptitude, they didn't have extra responsibilities and they'd gotten their position through chance alone. Once you have achieved a certain status, it seems natural to feel like you deserve it and all the other good things that come your way. Now this is just an anecdote, but whenever I've been upgraded to fly a business class, I've always observed the worst behavior in my fellow privileged passengers; they just act so entitled and uncourteous. And research has found evidence for this as well. In another experiment, participants were asked to think of a good thing that happened to them recently, and then one group was asked to list their own personal qualities or actions that made that good thing happen, another group was asked to list external factors beyond their control that led to the event, and a control group was simply asked to list reasons why the good thing happened. Now for completing this task, participants were told they would be paid a dollar, but at the end they were offered the option to donate some or all of the money to a charity. Results showed those who listed their own personal attributes contributed 25% less than those who listed external factors beyond their control. Now think of what all this means for people in our society, specifically for people in positions of power like business leaders and politicians.

Now undoubtedly most of them are talented and hard-working, but they have also been luckier than most, and like most of us, they don't realize just how lucky they are. And this gives them a distorted view of reality. They're kind of living in a form of survivor bias: all these leaders have worked hard and ultimately succeeded, so to them the world appears fair. In their experience, it rewards hard work, but what they don't have is the experience of all the people who have worked hard and failed. So what are they to make of people less successful than themselves? Well, the natural conclusion is that they must just be less talented or less hard-working, and this perspective makes them less inclined to be generous — to give back. And they are the ones who set the rules for how society operates. And this is particularly unfortunate since one of the main ways many of us are lucky is in our country of residence. But what is a country except for the things put there by people who came before? The roads and the schools, public transport, emergency services, clean air and water, everything like that. It seems a cruel trick of our psychology that successful people without any malice will credit their success largely to their own hard work and ingenuity, and therefore contribute less to maintaining the very circumstances that made that success possible in the first place. The good news is that acknowledging our fortunate circumstances not only brings us more in line with reality, it also makes us more likeable. In a study where people had to read the transcript of a fictional 60-minutes interview with a biotech entrepreneur, experimenters tried changing just the last paragraph where the interviewee is talking about the reasons for their company's success. In one version, the entrepreneur personally takes credit for the success they've had, but in the other, he says luck played a significant role. Now people who read the luck version of the transcript judged the entrepreneur as kinder, and thought they'd be more likely to be close friends with him than those who read the other version of the transcript. And raising our awareness of fortunate events can also make us happier because it allows us to feel gratitude. Personally, I am grateful to Michael Stevens of Vsauce, who on October 7th, 2012, posted the video: "How Much Does a Shadow Weigh?", which shouts out my slow-motion slinky drop video, and within three days my subscribers had increased by a third, and within a month, they had doubled, leading me to quit my part-time job and work exclusively on YouTube videos. And I'm grateful to the writer of the free newspaper they give out on the trains in Sydney who didn't quite understand electricity, leading me to post this picture of their article to my Instagram with the caption: "What's wrong with this picture?" And I'm lucky that the first person to answer correctly was a beautiful woman who became my future wife. Yep! That is how I met your mother. Now initially, I wanted to make this video just to say our circumstances and psychology conspire to make us oblivious to our own luck. This leads successful people to view the world as fair, and those less successful than them as less talented or less hard-working. And this is before you factor in any discrimination or prejudice. But, it also became apparent to me that I should talk about what to do if you want to be successful in such a world, and I think the best advice is paradoxical. First, you must believe that you are in complete control of your destiny, and that your success comes down only to your own talent and hard work. But second, you've got to know that's not true for you or anyone else. So you have to remember: if you do achieve success that luck played a significant role and given your good fortune, you should do what you can to increase the luck of others. Hey, so I had an idea for what I could do to increase the luck of others and that is to give away a hundred snatoms kits to people who couldn't otherwise afford them.

OC2(h)

OC2(b), estimated to be about 12 hours ago.

Module strength is one of the terms used to describe the nature of the modules (parts) of a program that make up software, and refers to the strength of the relationship between multiple functions contained in a module.

The state with the highest module strength is called "functional strength," which refers to the case where a module provides only one function. The next highest is "informational strength," which refers to the state in which functions for handling specific and identical data are combined into one. The next highest is "communicative strength," which refers to the state in which data is passed between functions within a module. The next highest is "procedural strength," which refers to the state in which multiple functions that are always executed in sequence are grouped together.

The next highest is "temporal intensity," which refers to the state in which multiple functions that are used at a certain point in time during execution, such as initialization of various elements at the start of execution, are combined into one (even if there is no relationship between the functions). The next highest is "logical strength," which refers to a state in which multiple functions are logically related and grouped together in a structure that allows the user to select which process to perform by means of arguments. The lowest is "implicit strength," which refers to the state in which multiple functions are combined into one by simply dividing the program without considering the relationship between the functions.

What is rationality?

I wrote about it in an exam the other day and my teacher seemed to like it, so I'd like to write about it more properly.

In recent years, in the field of political science, especially in political science, this "rationality" is very popular. However, it does not mean that anything is good because it is rational.
　That's true. If you say it is rational, you can manage most things. For example, if we assume that irrational claims are basically false, we can develop a very clear argument. That is to say, the truth or falsehood of any proposition can be established only by examining its rationality. Well, in the natural sciences, this is enough.
　However, when it comes to social sciences, it is not so. In political science, what is called "rationality" is at best only "economic rationality". The point is how much benefit is returned to the individual by a particular choice. And the benefits are only fundamentally economic. In other words, you can't count the satisfaction of properly internalising an ethical code.

　So let's assume for the moment that "rationality" is a logical path that connects the shortest distance from a particular starting point (premise) to a particular ending point (goal). At this point, I feel that I have done something quite absurd.
　Now let's consider this rationality. In this case, rationality can be understood in a very pluralistic way by transforming the purpose. In other words, if we set an economic purpose, we can make a common argument for rationality. And if we set 'emotions' as ends, we can bring a sense of fulfilment based on ethical norms into the analysis of rationality. There's really no end to the discussion of emotions, so I'll leave that for another time. I'll get back to it when I'm able.
　Well, to add, if we understand rationality on the basis of this concept of rationality, I think Habermas's criticism of rationality is not so effective. When I say "purposive rationality", it means that the "purposive" part praises economic rationality, or the rationality is judged in a way that excludes individual human rights. I feel that it is enough to consider the rationality that brings communication or criticism possibility (I think this is easier to understand) to the "purpose" part.

　However, this concept of rationality is not universal at all, and now the question arises as to how to use it in analysis. In short, "Sure, we can discuss comprehensively now. Then, what is the use of that? As long as it is conceptualized, it is meaningless unless it is useful in some way for analysis or discussion. In fact, the fact that we have made it too comprehensive makes it difficult to use for analysis.
　The point is, "this is rational, that is rational, it's also..." In other words, there are so many things to consider that it becomes impossible to follow up, or even if you do, it becomes impossible to estimate a valid causal relationship. At least in the case of political science, such a problem arises. On the contrary, this is why there are so many analyses that focus on economic rationality.
　However, since political science is good at the analysis of the current situation, I would like to offer the analysis which can guarantee the predictability a little more. It would be nice if we could somehow construct a theory that can bring us to an analysis with high predictability, while sufficiently considering the value norms in a comprehensive judgment. If we could do that, it would be a real classic. Whew!

New: Meisa Hanai (https://jjgirls.com/japanese/meisa-hanai/3/meisa-hanai-4.jpg), about 1 hour ago. Current information suggests that the highest point of her fappability is observability in static images without makeup.

Her pie, about 10 minutes ago.

In the practical world of small and medium-sized companies, many of which are unlisted, financial documents are often deliberately falsified or concealed from the public as they should be. This book provides a concise explanation of professional perspectives for effective analysis in light of such situations, based on the author's extensive experience.

I couldn't figure out the difference between fapability and fappability and which one is correct even after googling. If there are any native English speakers, please let me know.

Despite being just after the observation of the rare phenomenon of ejaculating twice in 24 hours, my penis seems to be getting erect often remembering Meisa Hanai. Or maybe the whimsical post "Four Wives" by Gorgonzola is contributing to this. Either way, take care of your prostate.

New: "The story of my sister's friend seducing me and doing naughty things in secret (tentative)" by Anon200million - first genuine creampie, about 2 hours and 45 minutes ago. I discovered it algorithmically/serendipitously on Pixiv as usual.

First prevented creampie, about 7 minutes ago.

For me, eating a lot in a short time is usually bad. Especially in an environment with temperatures of 5 degrees Celsius, which can easily induce cold irritant diarrhoea.

>>172
Correction: "temperatures of 5 degrees Celsius" to "temperatures below 5 degrees Celsius".

I can't get out of the futon and stop farting.

Well, farting seems to be gradually declining spontaneously.

It's a short life that will be over in the blink of an eye. Let's cherish this life and live it to the fullest together! You are not alone. We are all connected in this world. You are a miracle born in this world, with a kind heart, you are a perfect being with great value from the beginning, no matter what happens. It's a shame to die by yourself. Even if you are suffering at the moment, you have to be aware of yourself, of the people around you who are as valuable and kind as you are, of the state of your body and the things you have thanks to the miracle, and understand from the bottom of your heart that your life will surely come to an end very soon, and that no one knows when that end will come. If you live your life with gratitude, you will always feel happy, you will know that every moment is a miracle and that you are alive, you will find hope and you will have the best end of your life! Let's not give up!

Source: https://www.amazon.co.jp/gp/profile/amzn1.account.AFCKXGMPRXS2OCYK4DYR4I6QVQ4Q/ref=cm_cr_dp_d_gw_tr?ie=UTF8

DON'T DRINK COLD MILK IN THE MORNING

Oral cavity after 1 week, estimated to be 20 minutes ago.

Coincidentally, it had been a week.

By showing off her gymnastic skills, 17 minutes ago.

>>177
You can offset this with a hot drink.

Spinoza Picture: the denial of free will and the fictional nature of the "ought" argument (ought proposition)

Here is the relevant content of the PDF that I have linked to on the Metaphysics home page, mainly on the negation of free will. This is also a stopgap measure to separate jokes and bad writing that could be seen as insincere. The whole thing is chaotic, and there are many parts that should be rewritten, but I will leave it for a while. As soon as I think of something, I'll add it.

For those who don't understand the free will issue
Some of you may be confused about what the free will debate is all about.
In the following, I will try to explain briefly what the concept of free will is.
Of course, this may not be the best way to introduce the problem of free will.
It is better to think of what I am going to say below as an interpretation of free will.

First of all, the dictionary definition of free will can be restated as follows.
Free will is defined as the pure and absolute beginning of an action or action of the mind which breaks free from the influence of the past or of the laws of physics and causes a voluntary action.
Free will is assumed to be that which can be freely invoked in the midst of apathy, and which can compel a disobedient body to action.

However, such a dictionary definition may not be enough to make sense.
Let's look at apathy as a metaphor.
What is lethargy?
If we think of a human being as an automobile, lethargy may be compared to running out of petrol.
When you run out of petrol, you can't move any more, unless you refuel from outside.
But you may think that this is an inappropriate analogy.
You might think that man is capable of taking action under his own power, unlike the car.
Well, that's certainly a sensible way of looking at it.
But, of course, just because something is a common sense decision doesn't mean that it is always the right one.
In fact, it is a self-contradiction to say that it is up to us to steer ourselves, and in this case, we need to assume a supernatural power that can start the engine in the face of any lethargy.
And that very supernatural power, which can start the engine in any lethargy, is what we call free will, and which is philosophically unsupportable.

A Mathematical Model of "How Many People Believe in Free Will"
With regard to free will, we can ask not only whether it exists, but also how many people in the world believe in its existence.
Mathematical models, such as infectious disease models, may provide insights in this regard.
In the following, we use a simple mathematical model to describe the dynamics of the proportion of people who believe in or deny free will, and briefly investigate the properties of the model.
However, to be honest, this is not a realistic model, but rather a "toy" mathematical model that we play with, giving meaning to variables with interpretations such as "the number of people who believe in free will".
So let's play with it.

Model 1
For simplicity, we assume that all people are either free will affirmers or deniers, and denote the number of free will affirmers by x and the number of deniers by y.
Our goal is to build a model that governs the change in the number of people x and y over time, under appropriate assumptions, and to understand its behavior.
We then assume that people are born free will positive.
We also assume that each free-will positivist has a probability of becoming a free-will negativist of \alpha per unit time.
Let us assume that this probability does not depend on the number of free will deniers, y.
This corresponds, for example, to the situation where a denialist can argue to a positive denialist that free will does not exist, but will not be understood.
Furthermore, we assume that once you become a free will denialist, you will never return to being a free will affirmative.
This may be a rather unfair argument, but we can think of a situation in which one comes to the conclusion that free will does not exist, and is convinced that it is true.
Of course, if we wanted to, we could create a model in which, on the contrary, a person who has been misled by the whispers of the devil into denying free will is converted back into a pro-free will person.
Now, assuming the above, we can write down the following differential equation
\dot{x}=-\alpha x,\qquad \dot{y}=\alpha x.
where the dot represents the derivative with time t.
Note that the number of free-will deniers decreases as the number of free-will supporters increases, so that the combined number of people, N, is kept constant: \frac
\displaystyle \frac{\mathrm{d}}{\mathrm{d}t}(x+y)=0,\qquad x+y=\mathrm{const}=N.
At this point, the number of free-will proponents decreases exponentially, and after about 1/\alpha time, free-will deniers make up the majority of the population: x
x=x_0e^{-\alpha t},\qquad y=N-x_0e^{-\alpha t}.
This result means that eventually (or after infinite time) everyone will be a free will denialist.
This is what we would expect from the way the model is set up.

Model 2 (Introduction)
Now, for a more non-trivial result, consider the births and deaths of people.
How does the number of affirmers and deniers change if the generational change takes place before everyone becomes a free will deniers?
In the following, we introduce the number of people born per unit of time β.
This has the same dimension as the parameter α, which is the reciprocal of time.
Given that we have already assumed that people are born free will affirmers, we consider this number β to be the increase in the number of free will affirmers.
If we consider a model in which the total number of people in the system is constant, then this same number of people must die in a unit of time.
In this case, it is natural to assign the number of people β to each death, according to the ratio of the number of free will affirmers to the number of deniers x,y at each time.
The equation of the model can thus be extended as follows
\displaystyle \dot{x}=-\alpha x+\beta-\beta \frac{x}{x+y},\qquad \dot{y}=\alpha x-\beta \frac{y}{x+y}.

A way of looking at differential equations
In order to understand qualitatively the evolution of the number of people x,y according to this equation, we introduce a way of looking at the differential equation.
If we consider a point (x,y) in the xy-plane whose coordinates are the values of x,y at each time, this point moves in the xy-plane with time.
Identifying the motion of this moving point corresponds to understanding the behaviour of the solution of the differential equation.
The above equation gives the velocity (\dot{x},\dot{y}) that the point under consideration has at position (x,y).
Since this is defined at any position (x,y), it forms a velocity field (in this case it is a stationary, i.e. time-invariant field).
If we can draw the velocity field in the xy-plane, we can qualitatively understand the motion of the moving point as follows.
That is, if the moving point is at position \bm{r}_0 at the initial time, then given the velocity \bm{v}(\bm{r}_0) at that position, the position after a small time \varDelta t is
\bm{r}(\varDelta t)=\bm{r}_0+ \bm{v}(\bm{r}_0) \varDelta t
which is determined as follows.
In this way, the position of the kinematic point at a later time is also determined sequentially.

Model 2 (Results)
Now, let's apply the above to our current model.
The velocity vector field in the xy-plane will look like the one below.
Note that the total number of people, N, is determined by the initial conditions and that the moving point moves on the line x+y=N.
The vector field follows this group of lines and is directed towards the intersection of the red line in the diagram and the line where the number of people is constant.
The coordinates of the intersection point are
\displaystyle x=\frac{\beta N}{\alpha N+\beta},\qquad y=\frac{\alpha N^2}{\alpha N+\beta}
and we can see that the number of people x and y will settle down to this value after a long enough time.
The ratio of free will affirmers to deniers is then
x:y=β:α N
So we can see that the ratio of free will deniers to the total population increases as \alpha and total population N increase, and as the generational "metabolism" β decreases.
As one would expect, setting β=0 gives a ratio of 0:1, which is consistent with the results of the original model.

Phase diagram of the number of positive arguments for free will (x) and the number of negative arguments (y). Here we set α=1 and β=3, and we draw the line x+y=N=4 (blue) and the set of fixed points (red).

Palindrome
Fallen Spinoza's Pistachio (Japanese: Ochita Supinoza no Pisutachio)

Ghosts and free will
A "I wonder if ghosts really exist".
B "Of course not".
A "Then don't we have free will?"
B "Of course we do".

Magic and Free Will
Magic is a kind of freedom, in the sense that it enables us to do things that are normally considered impossible.
However, the exercise of freedom is often subject to a number of constraints.
In fact, to take an oft-mentioned example, the freedom to use language comes at the price of the inconvenience of being bound by a number of complex rules, such as grammar.
On the other hand, if you watch Harry Potter, you will see that magic also has rules and mechanisms.
If you don't cast a spell correctly, the spell can misfire, leading to accidents.
Given these circumstances, magic is similar to free will in that it is supernatural, but being able to use magic is not a matter of doing what you want, as in the exercise of free will, but rather closer to the Spinoza philosophy of activeness and 'freedom as necessity'.

OC2(h), about 30 minutes ago.

えっ！

Spinoza Picture: the denial of free will and the fictional nature of the "ought" argument (ought proposition)

Here is the relevant content of the PDF that I have linked to on the Metaphysics home page, mainly on the negation of free will. This is also a stopgap measure to separate jokes and bad writing that could be seen as insincere. The whole thing is chaotic, and there are many parts that should be rewritten, but I will leave it for a while. As soon as I think of something, I'll add it.

For those who don't understand the free will issue
Some of you may be confused about what the free will debate is all about. In the following, I will try to explain briefly what the concept of free will is. Of course, this may not be the best way to introduce the problem of free will. It is better to think of what I am going to say below as an interpretation of free will.

First of all, the dictionary definition of free will can be restated as follows. Free will is defined as the pure and absolute beginning of an action or action of the mind which breaks free from the influence of the past or of the laws of physics and causes a voluntary action. Free will is assumed to be that which can be freely invoked in the midst of apathy, and which can compel a disobedient body to action.

However, such a dictionary definition may not be enough to make sense. Let's look at apathy as a metaphor. What is lethargy? If we think of a human being as an automobile, lethargy may be compared to running out of petrol. When you run out of petrol, you can't move any more, unless you refuel from outside. But you may think that this is an inappropriate analogy. You might think that man is capable of taking action under his own power, unlike the car. Well, that's certainly a sensible way of looking at it. But, of course, just because something is a common sense decision doesn't mean that it is always the right one. In fact, it is a self-contradiction to say that it is up to us to steer ourselves, and in this case, we need to assume a supernatural power that can start the engine in the face of any lethargy. And that very supernatural power, which can start the engine in any lethargy, is what we call free will, and which is philosophically unsupportable.

A Mathematical Model of "How Many People Believe in Free Will"
With regard to free will, we can ask not only whether it exists, but also how many people in the world believe in its existence. Mathematical models, such as infectious disease models, may provide insights in this regard. In the following, we use a simple mathematical model to describe the dynamics of the proportion of people who believe in or deny free will, and briefly investigate the properties of the model. However, to be honest, this is not a realistic model, but rather a "toy" mathematical model that we play with, giving meaning to variables with interpretations such as "the number of people who believe in free will". So let's play with it.

Model 1
For simplicity, we assume that all people are either free will affirmers or deniers, and denote the number of free will affirmers by x and the number of deniers by y. Our goal is to build a model that governs the change in the number of people x and y over time, under appropriate assumptions, and to understand its behavior. We then assume that people are born free will positive. We also assume that each free-will positivist has a probability of becoming a free-will negativist of \alpha per unit time. Let us assume that this probability does not depend on the number of free will deniers, y. This corresponds, for example, to the situation where a denialist can argue to a positive denialist that free will does not exist, but will not be understood. Furthermore, we assume that once you become a free will denialist, you will never return to being a free will affirmative. This may be a rather unfair argument, but we can think of a situation in which one comes to the conclusion that free will does not exist, and is convinced that it is true. Of course, if we wanted to, we could create a model in which, on the contrary, a person who has been misled by the whispers of the devil into denying free will is converted back into a pro-free will person. Now, assuming the above, we can write down the following differential equation \dot{x}=-\alpha x,\qquad \dot{y}=\alpha x. where the dot represents the derivative with time t. Note that the number of free-will deniers decreases as the number of free-will supporters increases, so that the combined number of people, N, is kept constant: \frac \displaystyle \frac{\mathrm{d}}{\mathrm{d}t}(x+y)=0,\qquad x+y=\mathrm{const}=N. At this point, the number of free-will proponents decreases exponentially, and after about 1/\alpha time, free-will deniers make up the majority of the population: x x=x_0e^{-\alpha t},\qquad y=N-x_0e^{-\alpha t}. This result means that eventually (or after infinite time) everyone will be a free will denialist. This is what we would expect from the way the model is set up.

Model 2 (Introduction)
Now, for a more non-trivial result, consider the births and deaths of people. How does the number of affirmers and deniers change if the generational change takes place before everyone becomes a free will deniers? In the following, we introduce the number of people born per unit of time β. This has the same dimension as the parameter α, which is the reciprocal of time. Given that we have already assumed that people are born free will affirmers, we consider this number β to be the increase in the number of free will affirmers. If we consider a model in which the total number of people in the system is constant, then this same number of people must die in a unit of time. In this case, it is natural to assign the number of people β to each death, according to the ratio of the number of free will affirmers to the number of deniers x,y at each time. The equation of the model can thus be extended as follows \displaystyle \dot{x}=-\alpha x+\beta-\beta \frac{x}{x+y},\qquad \dot{y}=\alpha x-\beta \frac{y}{x+y}.

A way of looking at differential equations
In order to understand qualitatively the evolution of the number of people x,y according to this equation, we introduce a way of looking at the differential equation. If we consider a point (x,y) in the xy-plane whose coordinates are the values of x,y at each time, this point moves in the xy-plane with time. Identifying the motion of this moving point corresponds to understanding the behaviour of the solution of the differential equation. The above equation gives the velocity (\dot{x},\dot{y}) that the point under consideration has at position (x,y). Since this is defined at any position (x,y), it forms a velocity field (in this case it is a stationary, i.e. time-invariant field). If we can draw the velocity field in the xy-plane, we can qualitatively understand the motion of the moving point as follows. That is, if the moving point is at position \bm{r}_0 at the initial time, then given the velocity \bm{v}(\bm{r}_0) at that position, the position after a small time \varDelta t is \bm{r}(\varDelta t)=\bm{r}_0+ \bm{v}(\bm{r}_0) \varDelta t which is determined as follows. In this way, the position of the kinematic point at a later time is also determined sequentially.

Model 2 (Results)
Now, let's apply the above to our current model. The velocity vector field in the xy-plane will look like the one below. Note that the total number of people, N, is determined by the initial conditions and that the moving point moves on the line x+y=N. The vector field follows this group of lines and is directed towards the intersection of the red line in the diagram and the line where the number of people is constant. The coordinates of the intersection point are \displaystyle x=\frac{\beta N}{\alpha N+\beta},\qquad y=\frac{\alpha N^2}{\alpha N+\beta} and we can see that the number of people x and y will settle down to this value after a long enough time. The ratio of free will affirmers to deniers is then x:y=β:α N So we can see that the ratio of free will deniers to the total population increases as \alpha and total population N increase, and as the generational "metabolism" β decreases. As one would expect, setting β=0 gives a ratio of 0:1, which is consistent with the results of the original model.

Phase diagram of the number of positive arguments for free will (x) and the number of negative arguments (y). Here we set α=1 and β=3, and we draw the line x+y=N=4 (blue) and the set of fixed points (red).

Palindrome
Fallen Spinoza's Pistachio (Japanese: Ochita Supinoza no Pisutachio)

Ghosts and free will
A "I wonder if ghosts really exist".
B "Of course not".
A "Then don't we have free will?"
B "Of course we do".

Magic and Free Will
Magic is a kind of freedom, in the sense that it enables us to do things that are normally considered impossible. However, the exercise of freedom is often subject to a number of constraints. In fact, to take an oft-mentioned example, the freedom to use language comes at the price of the inconvenience of being bound by a number of complex rules, such as grammar. On the other hand, if you watch Harry Potter, you will see that magic also has rules and mechanisms. If you don't cast a spell correctly, the spell can misfire, leading to accidents. Given these circumstances, magic is similar to free will in that it is supernatural, but being able to use magic is not a matter of doing what you want, as in the exercise of free will, but rather closer to the Spinoza philosophy of activeness and 'freedom as necessity'.

About "nothing more, nothing less"
Precisely, everything is both greater than and less than. Note that this is true for any real number a, since a≥a implies a>a or a=a. In English, it is nothing more, nothing less, which is correct because it does not contain an equal sign.

Ability is part of your luck
It is said that "luck is part of your ability", but it is true that "ability is part of your luck". Even if we could define what we could call "ability", there is no free will to acquire as much ability as we want. There is a book, which I learned later, called “Ability is part of your luck (original title: The Tyranny of Merit: What's Become of the Common Good?)" (Sandel).

The antonym of phenomenon is...
The antonym for phenomenon is essence, which may be thought of as the essence of physics. Or as I see it, the antonym of phenomenon is physics. Essence and phenomenon may be thought of as corresponding to substance and form respectively in Spinoza's philosophy.

Science without faith?
At the heart of the scientific worldview, and physics in particular, is the metaphysical idea that "everything is inevitable". However, its correctness is not proved by science, and science can be discussed separately from philosophy and religion. Nevertheless, can we any longer find meaning in a "pure" science that is separated from philosophy and religion? Even if we are familiar with such a faithless science and physics, it would be like saying "I have studied physics, but in the end I don't believe in the laws of physics, and I believe that they can be easily broken by human free will" (though I don't think that is a bad thing). Such a non-religious view of science can only degenerate into the nonsense that, on the one hand, recognises the search for universal natural laws as an intellectual attitude, but, on the other hand, says that natural laws do not always have to be true. Such a question is probably shared by Einstein's thinking.

A religious worldview is more coherent (Freud)
Freud criticises those who try to dismiss misbehaviour, such as misspoken words, as mere coincidence. The following remarks are equally applicable to those who do not doubt the existence of free will.

What does he mean by this? Is he going to argue that there are trivial events that may or may not be out of the continuum of events in the world? If you break the determinism of the natural world in this way, even at any one point, you are abandoning the academic worldview. You can point out to him how much more coherent is the religious worldview which declares that not a single sparrow will fall from a roof unless God's will is at work. (Freud, 2019, Introduction to Psychoanalysis (translated by Katsumi Kaketa), Chuokoron Shinsha, Tokyo, 33.)

Of course, as I have already said many times, the introduction of chance and non-determinism does not help to save free will in any way.

"Strength of will" as an example of self-promotion
A job-hunting support site introduces example sentences for an entry sheet. The first sentence of the self-promotion is "My strength is that I have a strong will to carry through with the decisions I make" (https://job.mynavi.jp/conts/2022/es_perfect/study/#anc02). Needless to say, the ability to get things done cannot be simply attributed to personal characteristics such as "strength of will". Nor can the will be a purely subjective, voluntary, and active capacity to initiate action for which one can be held accountable. Nevertheless, modern society considers the will as absolute and elevates it to the status of free will. Of course, it may be short-sighted to say that this example is proof of modern society's blind faith in the will, but isn't it suggestive and symbolic of the importance modern society places on things like "will", "decision" and "choice"?

If we dare to write an example sentence that clearly denies free will without being caught up in this trend, it would be something like the following

Self-promotion (fictional)
I have studied physics. I have always had doubts and opposition to the ideology that humans have free will and to the claim that "this is how people and the world should be", and I think that physics, which simply tries to understand how the world is, is a good match for me.

Motivation (fictional)
The idea that humans have free will is the dominant ideology that pervades modern society, and education is a typical place where free will is sought as a supernatural ability to motivate. However, I believe that learning is achieved through necessity, as in "I study because I like it". I hope to contribute to such a paradigm shift through my work in education.

Empty the mind and one pitch of consecration?
Sophisticated movements are achieved by the unconscious mind, which in turn is seen to be in free control of one's body. In sports, therefore, the mind must be absent and the movements must be put into the unconscious. However, slogans such as "One pitch of consecration" ("One shot of consecration" in Kyudo) seem to point in the opposite direction.

OC2(h), about 2 hours ago.

I woke up surprisingly early.

I woke up 45 minutes ago.

What is Colombin?

Wikipedia: It’s a confectionery company of French pastries, mainly shortcakes, cookies and Harajuku baked chocolates, with its head office in Jingumae, Shibuya-ku, Tokyo and its main shop in Ginza, Chuo-ku, Tokyo.

DeepL: It’s turd.

Swimming in a sea of arbitrariness...

In the aftermath of heartbreak after Karuta, estimated to be 21.5 hours ago.

UGftNC, about 15 minutes ago.

Unless otherwise noted, Uncensored Girl from the North Country (abbreviated UGftNC or UGNC) refers to creampie.

OC2(h)

I may release a set of records for the first three months of this year with corrected estimated time errors at the end of March.

>>200
A newly arrived prequel concerning the young Kimika, its educators and their victims served as a catalyst.

Although there is some confusion in the practice of atopic dermatitis, particularly in terms of treatment, many dermatologists are not questioning the treatment methods that are appropriate to the pathogenesis of atopic dermatitis. In other words, atopic dermatitis is regarded as eczema with a chronic course due to inflammation caused by multiple nonspecific irritants or specific allergens, accompanied by physiological dysfunctions of the skin, and topical steroid therapy is mainly used to treat the inflammation, while topical moisturisers and other treatments are used to treat the physiological dysfunctions. There is an established consensus that the basis of treatment is to eliminate aggravating factors as far as possible, with skincare and the use of antihistamines and anti-allergic agents as adjunctive therapies for pruritus.
　
However, what is currently confusing dermatologists involved in the treatment of atopic dermatitis based on this understanding is that patients and society in general have developed a distrust of topical steroids, which are the mainstay of treatment, with little evidence, and a tendency to avoid topical steroids has grown stronger, leading to severe cases without the necessary and appropriate treatment. The number of patients is increasing, resulting in significant disadvantages for patients.
　
The "Committee for Future Dermatology", an advisory body to the President of the Japanese Dermatological Association, agreed that it is an urgent task for the Japanese Dermatological Association to improve this situation, and as part of this process, it was agreed that "Atopic Dermatitis Treatment Guidelines" should be prepared and the basic treatment methods made publicly known to society. The proposal was submitted to the Board of Directors of the Dermatological Society, which gave its approval, and at the request of the Scientific Committee, a preparatory committee was organised with the following members.
　
The guidelines are intended only to reaffirm the principles of treatment for dermatologists who have acquired sufficient dermatological skills, understand the pathogenesis of atopic dermatitis and have sufficient experience in the treatment of atopic dermatitis, but are not intended to be a guide to the treatment of atopic dermatitis for those who are otherwise involved in the treatment of atopic dermatitis. For physicians, it explains the need for dermatological training as a prerequisite for medical treatment, and for patients and society, it presents a basic policy that the Japanese Dermatological Association considers appropriate at the present time.
　
In 1999, the Health and Welfare Science Research Group published guidelines for the treatment of atopic dermatitis, which were "designed for a wide range of clinicians involved in the treatment of atopic dermatitis" and also stated that "if no improvement is seen after about one month of treatment, the patient should be referred to a specialist doctor or facility". It states that 'referral should be considered' and is designed for primary care physicians. On the other hand, these guidelines are intended for doctors specialising in dermatological care, who treat atopic dermatitis from the primary care stage to the stage where a high degree of specialisation is required, and therefore have a different raison d'être.

2. Pathogenesis
　
Eczema and dermatitis is a group of eczema and dermatitis diseases characterized by chronic inflammation of the skin with pruritus, which is caused by a variety of non-specific irritant reactions and specific allergic reactions in association with physiological abnormalities of the skin, such as dryness and abnormal barrier function of the skin, particularly due to abnormalities in the stratum corneum.
　
Although the disease is generally chronic, spontaneous remission can be expected if symptoms are kept under control by appropriate treatment.
　
3. Diagnosis
　
The diagnosis of atopic dermatitis is easy for dermatologists because of the presence of so-called atopic skin which is dry and goosebump-like and characteristic eczematous lesions, but there is no problem in referring to the diagnostic criteria of the Japanese Dermatological Association. However, it is necessary to be familiar with the diseases listed as diagnoses to be ruled out, with extensive dermatological knowledge and diagnostic skills.
　
4. Severity of the disease
　
The choice of topical therapy, which is the mainstay of treatment, is made according to the 'severity of the individual skin rash' and is not determined by the 'severity of the disease as a disease' as assessed by the severity of the skin rash and its spread. In other words, a sufficiently potent topical treatment is selected for a narrow but severe skin rash, while a broad but mild skin rash does not require a potent topical treatment. Therefore, from the point of view of selecting topical therapy, the most important factor is the 'severity of individual skin rashes', which is judged comprehensively from the following skin rash characteristics, and the severity of skin rashes must be judged by a doctor with dermatological skills sufficient to make this judgement and to predict the effectiveness of treatment. The biggest difference between the guidelines of the Health Science Research Group and these guidelines is the method of determining the severity of the condition. This is because a high degree of expertise is required to determine the 'severity of the rash'.
　
Characteristics of the rash
　
Dryness, erythema (degree of swelling/edema/infiltration, degree of lichenification), papules (full, serous), prurigo nodules, scales (pityriasis, lobular, membranous, etc.), crusts (blood crusts), blisters, pustules, erosions, ulcers, scars, pigmentation, depigmentation, etc.
　
Severity of skin rash
　
Severe: Mainly erythema with severe swelling/edema/infiltration or lichenification, multiple papules, severe scaling, crusting, vesicles, erosions, numerous scrape marks and pruritic nodules.
　
Moderate: Mainly erythema and scaling up to moderate severity.
　
Mild: Mainly dry and mild erythema, scaling, etc.
　
Minor: Mainly dry symptoms with poor inflammatory symptoms.
　
5. Treatment goals
　
The goal of treatment is to bring the patient to a state of
　
1) No symptoms, or if present, they are minor, do not interfere with daily life and do not require much drug treatment.
　
2) Minor or mild inflammation persists, but rarely worsens acutely or, if it does, it is not prolonged.

6. Drug therapy
　
Atopic dermatitis is a multi-pathogenic disease with a genetic predisposition and there is no drug therapy that can cure the disease itself. Symptomatic treatment is therefore the rule.
　
(1) At present, topical steroids are the only drugs that can sufficiently calm the inflammation of atopic dermatitis and whose efficacy and safety have been scientifically proven. Other topical agents include topical non-steroidal anti-inflammatory drugs (topical NSAIDs), but their anti-inflammatory action is very weak, contact dermatitis is not uncommon and their indications are narrow. A further topical agent that has recently come into use is topical tacrolimus, a transplantation immunosuppressant. Although this drug is intended only for the treatment of atopic dermatitis in adults, it is highly indicated for the treatment of skin rashes, particularly on the face, where it is more useful than the medium class of topical steroids, although transient irritation is a frequent occurrence. However, the drug's efficacy is comparable to that of the strong class of topical steroids and is not sufficient for severe skin rashes. In addition, the drug is not currently indicated for the treatment of atopic dermatitis in children and is not a drug that can be used for the treatment of all atopic dermatitis. Therefore, at present, its use must be in accordance with the Guidance on the Use of Tacrolimus Ointment in Atopic Dermatitis (Rin-Ki 53:1057-1068, 1999) and must be used by physicians with a high degree of expertise who fully understand its content.
　
Therefore, there is currently no other topical steroid that can rapidly and reliably soothe the inflammation of atopic dermatitis and relieve the patient's pain, is widely available and has been fully evaluated for its efficacy and safety, and how it is selected and used is fundamental to its treatment. Because they are drugs, topical steroids naturally have side effects, especially topical side effects, but it is important to select the appropriate drug for the severity of the skin rash, rather than selecting a topical steroid that is stronger than necessary, as there is generally a parallel between high efficacy and the likelihood of topical side effects. Therefore, the following choices should be made according to the 'severity of the individual skin rash'.
　
Severe: The first choice should be a necessary and sufficiently effective topical steroid from the Very Strong or Strong class. Medium and lower classes are usually not sufficiently effective. If pruritic nodules do not respond adequately to the Very Strong class, the Strongest class may be selected for use in that area only.
　
Moderate: Topical steroids of the Strong or Medium class are the first choice. Weak classes are usually not sufficiently effective.
　
Mild: Topical steroids of medium class or lower should be the first choice.
　
Minor: Topical preparations without steroids (e.g. Vaseline, urea ointments, ointments containing heparin-like substances, zinc oxide ointments, hydrophilic ointments) should be selected.
　
Formulation of topical steroids: The choice of formulation, such as ointment, cream, lotion or tape, should be based on the nature and site of the lesion.
　
Frequency of topical application: In principle, twice daily (morning and evening: after bathing). However, when reducing the rank of topical steroids or switching to topical preparations that do not contain steroids, it is necessary to ensure that there are no flare-ups while administering intermittent doses, such as once daily or every other day.

Topical dosage: Results of long-term use studies of the Very Strong class of topical steroids have shown that, in normal adult patients, starting with an initial topical dose of 5-10 g/day, which is a sufficient dose, and tapering off according to symptoms, can result in transient and reversible suppression of adrenal function over a period of 3 months, but not irreversible systemic suppression. Continuous daily use of 5-10 g of topical steroids for more than three months is highly unusual, but in such cases, adequate testing for systemic effects should be performed regularly, and appropriate measures should be taken to allow dose reduction of topical steroids in individual patients. In infants and children, a smaller initial topical dose is usually initiated, but a daily dose based on body weight should be converted from the adult dose and used as a guide.
　
Discontinuation of topical application: Topical steroids should not be discontinued abruptly after resolution of inflammatory symptoms, but should be discontinued gradually with gradual reduction or intermittent administration while monitoring symptoms. However, this does not apply if adverse effects of topical steroids are evident.
　
Infants and children: As a rule, topical steroids of one rank lower than the above should be used in severe and moderate cases. However, if ineffective, topical steroids of the above ranks should be used under adequate supervision.
　
Facial: As a rule, topical steroids of medium class or lower should be used, taking into account the high drug absorption rate. Even in such cases, twice-daily topical application should be limited to about one week, with a shift to intermittent administration and a rest period. Although many of the erythematous lesions on the face in adult patients seen more frequently in recent years are due to factors other than topical steroids, including scratching, the area should be carefully monitored for local side effects and a thorough medical examination should be carried out before prescribing.
　
The face is a highly indicated area for tacrolimus ointment and its use according to these guidelines should be actively considered.
　
Compliance: Misconceptions about topical steroids (confusion with the side effects of oral steroids and with worsening atopic dermatitis itself) often lead to fear and avoidance of topical steroids, resulting in poor compliance. It is necessary to spend sufficient consultation time explaining and guiding the patient to overcome this misunderstanding, which in turn influences the effectiveness of treatment.
　
Side effects of topical steroids: With appropriate use of topical steroids, the systemic side effects seen with oral agents, such as adrenal insufficiency, diabetes mellitus and moon face, are unlikely to occur. Topical side effects such as steroid suppuration, steroid flushing, skin atrophy, hypertrichosis, bacterial, fungal and viral skin infections may occasionally occur but are reversible with discontinuation or appropriate treatment. Events of steroid resistance (reduced efficacy with repeated use) are also not experienced with normal use. Pigmentation may occur after the use of topical steroids, but this is after the dermatitis has subsided and is not caused by topical steroids. Rarely, allergic contact dermatitis due to topical steroids can occur.

(2) Topical therapy for abnormal skin physiology
　
After sufficient quenching of inflammation with topical steroids has been achieved, skincare with topical, steroid-free products should be applied with the aim of complementing dryness and impaired barrier function and preventing inflammation flare-ups. In principle, topical treatment should be continued even for minor skin symptoms, as failure to do so can easily lead to flare-ups of inflammation and reduce the value of topical steroids, which should be applied twice daily, with gradual reduction or intermittent dosing once flare-ups are confirmed to be non-existent. Caution should be exercised in the development of contact dermatitis as a side effect, and it is important to distinguish it from flare-ups of atopic dermatitis. If a flare-up of atopic dermatitis occurs during maintenance treatment with topical steroid-free agents, do not hesitate to return to topical steroid treatment, aiming for early resolution of inflammation and return to maintenance treatment.
　
(3) Systemic therapy
　
Atopic dermatitis is characterised by subjective symptoms of pruritus, and drugs with antihistaminic properties are used to reduce the distress with the aim of preventing aggravation due to scratching caused by itching. The so-called anti-allergic effects of anti-allergic agents, such as inhibition of chemical mediator release, are expected to be effective as an adjunctive therapy to topical therapy and do not independently suppress inflammation in atopic dermatitis.

7. Search for aggravating factors
　
If a trusting relationship between patient and doctor is established and the above-mentioned pharmacotherapy is sufficiently effective, the goals of treatment can be achieved in most cases. In cases where this is not achieved, a search for aggravating factors is necessary, with some differences in the factors suspected to be involved depending on the age group.
　
In infants, dietary allergens are involved to some extent. In later age groups, environmental allergens (dust mites, house dust, etc.) are suspected to be involved, while contact factors, including topical products, and stress may be aggravating factors in all age groups.
　
The relevance of allergens should be determined after removal or challenge testing, if possible, with reference to medical history, blood tests and skin tests, and should not be determined solely on the basis of clinical symptoms or blood tests alone, for example. Even if the allergen can be identified, the disease is multifactorial and allergen elimination is an adjunctive therapy to drug therapy, and is not expected to be sufficient to cure the disease.
　
8. Psychosomatic aspects
　
In severe cases of atopic dermatitis, especially in adults, psychosocial stresses other than atopic dermatitis, such as relationships, busyness, career conflicts and autonomic anxiety, are involved, and not infrequently cause a scratching behaviour that can be called addictive or dependent, resulting in a worsening of the skin rash by the patient. Similar scratching behaviour may also be observed in paediatric patients due to frustration at not being able to satisfy their need for affection. In such cases, treatment from both a physical and mental perspective is necessary and may require a team approach, including psychiatrists.

9. Lifestyle guidance
　
Keep skin clean by bathing and showering.
　
Keep the room clean and create an environment with the right temperature and humidity.
　
Maintain a regular lifestyle and avoid excessive drinking and eating.
　
Wear non-irritating clothing.
　
Cut nails short to avoid skin damage due to scratching.
　
Note that ocular lesions (cataract, retinal rupture, retinal detachment) can occur not only due to the use of topical steroids but also due to the scratching and beating of the skin rash around the eye, and in cases of severe facial symptoms, the patient should be examined by an ophthalmologist on a regular basis.
　
Bacterial, fungal and viral skin infections may occur. Care should be taken to keep the skin in good condition.
　
10. Other treatments
　
Other specialised treatments, the effectiveness of which has only been highlighted in some centres and many of which have not been scientifically proven effective, are not covered in these guidelines for basic treatment. Among special therapies, PUVA therapy has received some recognition, but a separate guideline needs to be established for it to be commonly used.

1. Introduction
Atopic dermatitis is a condition frequently encountered in daily practice. In Japan, there have been two guidelines for the treatment of atopic dermatitis: the Japanese Dermatological Association Guidelines for the Treatment of Atopic Dermatitis, which were developed for doctors specialising in dermatology who treat patients with atopic dermatitis from the primary care stage to the stage where a high level of specialisation is required; and the Japanese Society of Allergology Guidelines for the Treatment of Allergic Diseases, which are intended for doctors who treat patients with allergic diseases other than dermatological diseases. In 2018, these two guidelines were integrated into a single guideline for all doctors and healthcare professionals involved in the treatment of patients with atopic dermatitis. Guidelines have been developed. This revised edition of the Atopic Dermatitis Clinical Practice Guideline has been developed by adding new findings on atopic dermatitis* published in Japan and abroad. The descriptions of medical practices in this guideline provide a guide to medical treatment of atopic dermatitis in Japan at the present time* from the perspective of evidence-based medicine (EBM), including guidelines and goals of treatment, and can be used for decision-making in the field of medical practice. The following table shows the most common types of information on the use of the system. The final decision in clinical practice must be made by the attending physician in collaboration with the patient, fully reflecting the patient's values and wishes for treatment. *In principle, until the end of December 2020.

1) Department of Cutaneous and Mucosal Pathology, Graduate School of Medicine, Nippon Medical School (Chairperson).
2) National Centre for Allergy, National Centre for Child Health and Development (Vice-Chair)
3) University of Tsukuba, Faculty of Medicine and Medical Sciences, Medical Information Management (Vice-Chair).
4) North Kanto Allergy Research Institute affiliated with the House of Hope
5) Department of Cutaneous and Mucosal Pathology, Graduate School of Medicine, Nippon Medical School
6) Department of Paediatrics, The Third Hospital of The Jikei University Hospital
7) Dermatology, Graduate School of Medicine, Kyoto Prefectural University of Medicine
8) Hiroshima University Graduate School of Medical Sciences, Dermatology
9) Department of Dermatology, Saitama Medical University
10) Department of Dermatology, Graduate School of Medicine, Kyushu University
11) National Hospital Organisation Mie Hospital, Clinical Research Department, Allergic Disease Therapy Development
Laboratory.
12) Department of Paediatrics, Kyorin University School of Medicine
13) Dermatology, Graduate School of Medical Sciences, Hiroshima University
14) Allergy Centre, National Hospital Organisation Mie Hospital
15) Department of Paediatrics, National Hospital Organisation Nagoya Medical Centre
16) Dermatology, Graduate School of Medicine, Kyoto Prefectural University of Medicine
17) Department of Paediatrics, Saitama Medical Centre, Dokkyo Medical University
18) Department of Dermatopathology, Nagasaki University Graduate School of Medical and Dental Sciences
19) National Centre for Allergy, National Centre for Child Health and Development

1.1 Disclaimer
These practice guidelines are not intended to prevent the medical treatment performed based on the circumstances of each case from being different from that described here, nor are they intended to negate the experience of the medical practitioner. Conversely, the failure to implement what is described in these Guidelines does not provide grounds for holding the doctors responsible for the actual practice. The use of these Guidelines as a source for medical disputes or medical litigation is a deviation from their original purpose. Even if a treatment is not covered by insurance (unapproved drug), if it has evidence in Japan or abroad, it may be listed in the guideline and a recommendation may be added. It is not correct to assume that drugs and treatments listed in guidelines can be used freely in practice. The same applies to the use and intended use of drugs that are listed as contraindicated or prudently administered in the accompanying text, and their inclusion in the guidelines does not exempt them from such restrictions. It is important to take action on individual drugs based on the latest information on safety and other relevant information in the package inserts.

1.2 Conflicts of interest
Based on the standards for conflicts of interest of the institution to which each committee member belongs or the COI Management Guidelines* of the Japan Medical Association and the Guidance on Eligibility Criteria for Participation in the Formulation of Clinical Practice Guidelines**, the committee members were asked to prepare a list of conflicts of interest (COI) for the past three years back to the previous year and every year until the publication of the guidelines when they assumed their posts. Self-reporting of COI status was carried out. Costs for the preparation of these guidelines were funded by the research funds of the Japanese Dermatological Association and the Japanese Society of Allergology Guideline Development Committee. The members of the preparation committee did not receive any remuneration for preparing the manuscript of this guideline or for participating in meetings. There were no interventions by the Ministry of Health, Labour and Welfare, the Japanese Dermatological Association or the Japanese Society of Allergology to influence the content of the guidelines. To ensure that the existence of conflicts of interest did not influence the content of the guidelines, all recommended decisions were made by consensus with all members voting, rather than by individual assignments. Committee members with a financial or academic COI or other COI in relation to the Clinical Question (CQ) being voted on could participate in the discussion but abstain from voting, or they could choose to abstain from voting on a CQ that they judged to be completely outside their expertise. The proposal was also refined with reference to the opinions (public comments) from the delegates of the conference.

Guideline members and their relatives within the first degree of consanguinity were asked to report whether they received any remuneration from companies or other organisations involved in the diagnosis and treatment of atopic dermatitis for the following items. The period covered was from 1 January 2017 to 31 December 2020: 1. directors' and advisers' remuneration, 2. shareholding interests, 3. royalties, 4. speaking fees, 5. manuscript fees, 6. clinical research funding (e.g. contract research funding, collaborative research funding, investigational research funding), 7. scholarship donations, 8. endowed courses from companies and others, 9. travel expenses, 10. Receipt of gifts etc. . Companies and organisations concerned: Hidehisa Saeki [Mitsubishi Tanabe Pharma Corporation (lecture fees, scholarship donation), Taiho Pharmaceutical Co. (lecture fees, clinical research expenses), Sanofi K.K. (lecture fees, clinical research expenses), AbbVie G.K. (lecture fees, clinical research expenses), Novartis Pharma K.K. (lecture fees), Eli Lilly Japan K.K. (lecture fees), Kyorin Pharmaceutical K.K. (lecture fees), Eisai K.K. (scholarship donation), Tokiwa Pharmaceutical Co. (scholarship donation), Japan Tobacco Inc. (lecture fees), LeoPharma K.K. (clinical research funding)], Yukihiro Oya [Kyorin Pharmaceutical Co. (lecture fees), Dainippon Sumitomo Pharma (lecture fees), Mitsubishi Tanabe Pharma (lecture fees), Maruho (lecture fees, scholarship donation), AbbVie GK (lecture fees), Sanofi (lecture fees), Shiseido Japan (lecture fees), Teijin (e.g. lecture fees), Chugai Pharmaceutical (e.g. lecture fees), Torii Pharmaceutical (e.g. lecture fees), Eli Lilly Japan (e.g. lecture fees), Bayer (e.g. lecture fees), Pola Pharma (e.g. lecture fees), Mylan EPD (e.g. lecture fees), Sinotest (e.g. lecture fees) (scholarship donation)], Koichi Arakawa [Novartis Pharma (scholarship donation), Maruho K.K. (scholarship donation)], Toshio Katsunuma [Torii Pharmaceuticals (lecture fee), Maruho K.K. (lecture fee), Kyorin Pharmaceutical (lecture fee)], Norito Kato [Mitsubishi Tanabe Pharma Corporation (lecture fee, scholarship donation) (lecture fees, scholarship donation), Torii Pharmaceuticals (lecture fees, scholarship donation), Maruho (lecture fees, scholarship donation), Kyowa Kirin (lecture fees, scholarship donation), Sanofi (lecture fees, scholarship donation, clinical research expenses), AbbVie LLC (lecture fees) (lecture fees, scholarship donation), Janssen Pharma K.K. (lecture fees, clinical research funding), Eli Lilly Japan K.K. (lecture fees, clinical research funding), Celgene Corporation (lecture fees), Eisai Corporation (scholarship donation), Nippon Boehringer Ingelheim (clinical research funding), Japan Tobacco Inc. (clinical research expenses), UCB Japan K.K. (clinical research expenses), A2 Healthcare K.K. (clinical research expenses), Leo Pharma K.K. (lecture fees, clinical research expenses)],

Akio Tanaka [Torii Pharmaceuticals K.K. (lecture fees), Maruho K.K. (lecture fees, scholarship donation), Kyowa Kirin Co. (scholarship donation), Sanofi K.K. (lecture fees, scholarship donation)], Yuichiro Tsunemuka [Eisai K.K. (lecture fees), Sanofi K.K. (lecture fees), Taiho Pharmaceutical Co. (lecture fees), Kyowa Hakko Kirin (lecture fees)], Mizuho Nagao [Novartis Pharma (lecture fees)], Takeshi Nakahara [Maruho K.K. (lecture fees, endowed lecture), Taiho Pharmaceutical K.K. (scholarship donation), Sanofi K.K. 2692● Journal of the Japan Skin Society: 131 (13), 2691-. 2777, 2021 (2021/3) Atopic Dermatitis Clinical Practice Guidelines Development Committee (lecture fees, etc.)], Shudohiro [GlaxoSmithKline (lecture fees, scholarship donation), Sanofi (lecture fees, clinical research funding), Taiho Pharmaceutical Industry (lecture fees, scholarship donation), Takeda Pharmaceutical Industry (lecture fees), Mitsubishi Tanabe (lecture fees) (lecture fees, etc.), Novartis Pharma (lecture fees, clinical research fees), Maruho (lecture fees, etc.), Vasclin (clinical research fees)], Takao Fujisawa [Maruho K.K. (lecture fees, clinical research fees), Torii Pharmaceutical (lecture fees)], Masaki Futamura [Maruho K.K. (lecture fees)], Koji Masuda [Sanofi K.K. ( (lecture fees), Mitsubishi Tanabe Pharma Corporation (lecture fees), Eli Lilly Japan K.K. (clinical research expenses)], Hiroyuki Murota [Mitsubishi Tanabe Pharma Corporation (lecture fees), Shiseido Company, Limited (lecture fees), Sanofi Corporation (lecture fees), Maruho Corporation (lecture fees), Japan Tobacco Inc. (e.g. fees), Novartis Pharma (e.g. fees)]

2. definition, pathogenesis, epidemiology, diagnosis, severity, etc.

2.1 Definition and disease concept of atopic dermatitis
Atopic dermatitis is a disease characterised by itchy eczema with recurrent exacerbations and flares, with many patients having a 'predisposition to atopy'*.
It is an eczematous disease with a characteristic symmetrical distribution, and the site of predilection differs according to age. The disease begins in infancy or early childhood and either goes into remission in childhood or recurs without remission, with symptoms persisting into adulthood, with characteristic eczematous lesions chronically present. Adolescent/adult-onset atopic dermatitis also exists, although less frequently.
*"Predisposition to atopy".
(1) Family history or history of (bronchial asthma, allergic rhinitis, conjunctivitis, atopic dermatitis, one or more of these diseases), or (2) predisposition to IgE antibody production. The presence of allergy is not essential for the definition of atopic dermatitis. This differs from, for example, allergic rhinitis, where proof of allergy is mandatory for diagnosis. Family and medical history does not consider urticaria; predisposition to produce IgE antibodies is considered in terms of blood total IgE levels and allergen-specific IgE antibody titres. Total IgE levels increase with the activity of the dermatitis and are often low in mild cases. Allergen-specific IgE antibody titres are helpful in mild cases.

2.2 Pathophysiology
Atopic dermatitis is a multi-pathogenic disease. The pathogenesis of atopic dermatitis is mediated by a complex combination of various aetiological factors against a background of hypersensitivity of the skin and other organs due to a predisposition to atopy (constitution) and a weak barrier function. The lack of hierarchy among these aetiologies contributes to the diversity of symptoms and phenotypes of atopic dermatitis.

(1) Skin sensitivity

1) Abnormalities of the stratum corneum
The stratum corneum is a thin film-like structure 10-20 µm thick that exists on the outermost surface of the skin and is composed of more than ten layers of stratum corneum cells and intercellular lipids that fill the spaces between them, forming a barrier that prevents leakage of body fluids, retains water in the stratum corneum and contributes to biological defence. Barrier dysfunction in the stratum corneum increases the skin's susceptibility to non-specific stimuli, and also predisposes to antigen sensitisation and inflammation. The main components of intercellular lipids are ceramide, cholesterol and free fatty acids, but in atopic dermatitis the function of intercellular lipids is impaired due to an abnormally low ceramide content, mainly impairing their ability to retain water. Keratinocytes with keratin and filaggrin parenchyma are structurally robust because the cell membrane is lined by insoluble structures called pericellular zones, which contribute to the formation of a strong barrier. Loss-of-function genetic mutations and inflammation-associated down-regulation of filaggrin have been identified in atopic dermatitis.

2) Epidermal abnormalities
The epidermis also performs an important skin barrier function. There are intercellular adhesive structures called tight junctions between epidermal cells to ensure that there are no gaps between them. In particular, tight junctions in the granular layer regulate the movement of substances in and out of the body, and reduced expression of claudin-1, which plays an important role in their formation, and the presence of single nucleotide polymorphisms have been identified in patients with atopic dermatitis.

(2) Mechanisms of inflammation
Impairment of the skin barrier function leads to increased penetration of antigens (allergens) into the skin. Antigens that are non-self are eliminated by the immune response, and an excessive immune response leads to an allergic reaction. Allergens induce type 2 immune responses not only as protein antigens but also by protease action, as in the case of mite antigens. In addition, IL-33, IL-25 and TSLP produced by epidermal keratinocytes induce type 2 immune responses by activating type 2 innate lymphocytes and Th2 cells in the lesions, and type 2 immune responses lead to the induction of allergen-specific IgE. Langerhans cells and mast cells express IgE high-affinity receptors (FcεRI) and release cytokines and chemical transmitters (e.g. histamine) via allergen-specific IgE, which induce inflammation. Furthermore, under such inflammation, TARCs are produced in the lesional skin, promoting infiltration of Th2 cells into the lesion; Th22 cells migrate into the skin by activated dendritic cells and produce IL-22, which induces epidermal thickening. The S100 protein produced by epidermal injury further activates lymphocytes. Infiltration of other T-cell subsets (Th1, Th17 cells) into the lesional skin has also been reported, but their detailed role in the pathogenesis of the disease remains unclear.

(3) Itching
Itching is defined as 'an unpleasant sensation in the skin that causes an urge to scratch'. Itching is diverse and can be described as 'itchy', 'prickly' or 'jittery'. Visual or auditory stimuli that evoke itching may cause itching, a phenomenon that is particularly strong in atopic dermatitis. There is a condition in which tactile stimuli, such as thermal pain or friction from clothing, are perceived as itchy (itch hypersensitivity).
Epidermal damage due to trauma and scratch, and exposure to antigens and irritants activate innate and acquired immunity, respectively, and establish a cytokine network that maintains a Th2-type immune response. Epidermis exposed to scratch and pathogens produces Th2 cytokines/chemokines called alarmins, such as IL-25, IL-33 and TSLP (thymic stromal lymphoprotein). Dendritic cells and Langerhans cells activated by antigen exposure also produce TARC (thymus and activation-regulated chemokine) and MDC (macrophage-derived chemokine), which activate migration of Th2 cells. As a result, Th2 cells infiltrating the skin produce IL-31 and IL-4, cytokines that directly induce itch by acting on functional IL-31 receptors expressed on peripheral nerves; IL-4 lowers the response threshold to pruritogenic factors via IL-4 receptors on peripheral nerves, resulting in chronic itch. IL-4 is also involved in pruritus, which is caused by exposure to histamine through eosinophil migration and mast cell degranulation due to increased IgE production.
Activation of spinal dorsal horn astrocytes and expression of lipocalin 2 by chronic dermatitis reduce the activity threshold of neurons, resulting in itch hypersensitivity. The extension of cutaneous sensory nerves to just below the stratum corneum on the skin surface in association with dry skin and inflammation is considered to contribute to itch hypersensitivity.
Substance P, which is mainly derived from peripheral nerves, produces itch by degranulation via neurokinin1 receptors on peripheral nerves or via MrgprX2 (sensory neuron-specific G protein-coupled receptor) on mast cells.

2.3 Genetic factors
Candidate genes for aetiology associated with atopic dermatitis include CTLA4, IL18, TLR9, CD14, CARD4, PHF11, TLR2, SCCE, MCC, IL4R, GM-CSF, TIM1, CARD15, GSTT1, SPINK5, SCYA11, TGFβ1, IL-13,. RANTES, IL4 and FCER1B have been reported14) . Furthermore, whole-genome linkage analysis of Japanese samples revealed 2q12 (IL1RL1/IL18R1/IL18RAP), 3q21.33 (GLB1), 3q13.2 (CCDC80), 6p21.3 (MHC region), 7p22 (CARD11), 10q21.2 (ZNF365) and 11q15.4 (ZNF365). OR10A3/NLRP10) and 20q13 (CYP24A1/PFDN4) were reported as candidate genes associated with atopic dermatitis.

2.4 Onset and exacerbating factors
Factors involved in the onset and exacerbation of the disease must be taken into account when considering the pathogenesis of the disease. Adherence to treatment, as well as exposure to antigens and irritants in the workplace and daily living environment, lifestyle and environmental factors such as temperature and humidity, and alterations in skin physiology are involved in the maintenance and exacerbation of dermatitis. Heat, perspiration, wool fibres, mental stress, food, alcohol consumption and the common cold are particularly important factors that induce or aggravate itching in atopic dermatitis. The nature of these onset and aggravating factors and specific countermeasures are discussed below.

2.5 Epidemiology

(1) Worldwide prevalence and trends in atopic dermatitis
A worldwide study of the prevalence of atopic dermatitis was conducted by the International Study of Asthma and Allergies in Childhood (ISAAC) in 1994-1996 in an epidemiological survey (phase I). This was a questionnaire survey, but a large one, covering 56 countries: at 6-7 years of age, prevalence ranged from 1.1% in Iran to 18.4% in Sweden, with an overall prevalence of 7.3%; at 13-14 years of age, prevalence ranged from 0.8% in Albania to 17.7% in Nigeria, with an overall prevalence of 7.3%; at 13-14 years of age, prevalence ranged from 0.8% in Albania to 17.7% in Nigeria, with an overall prevalence of 7.3%. The overall rate was 7.4%. Generally, prevalence was higher in Oceania and Northern Europe, and lower in Asia and Eastern Europe. The countries with the highest prevalence rates were Sweden (18.4% at 6-7 years and 14.5% at 13-14 years), Finland (14.5% at 13-14 years), the UK (13.0% at 6-7 years and 15.8% at 13-14 years), Japan (16.9% at 6-7 years and 10.5% at 13-14 years) and Australia (6-7 years and 10.5% at 13-14 years). (10.9%, 13-14 years: 9.7%) and New Zealand (6-7 years: 14.7%, 13-14 years: 12.7%).
An ISAAC epidemiological survey (phase III) was also conducted between 2001 and 2003 (Japan did not participate), and among countries with high prevalence in phase I at age 13-14 years, some countries showed a decrease in prevalence in phase III (e.g. UK: 15.8% to 10.6%, New Zealand: 12.7% to 8.8%).

(2) Epidemiological surveys in Japan

1) Prevalence in childhood to adolescence
Atopic dermatitis generally develops in infancy and childhood, and the number of patients declines with age, with some patients transitioning to adult-onset atopic dermatitis. 14 papers in the literature on prevalence studies of atopic dermatitis based on dermatologists' physical examinations in Japan over a 10-year period from 1992 to 2002. Analysis of age-specific prevalence rates showed that they varied from 6-32% for infants, 5-27% for toddlers, 5-15% for schoolchildren and 5-9% for university students, but overall there was a tendency for prevalence rates to decrease with age. A nationwide survey on the prevalence of atopic dermatitis was conducted based on physician diagnoses at primary schools health check-ups. Health examinations were conducted by specialist physicians at base facilities in the Hokkaido, Tohoku, Kanto, Chubu, Kinki, Chugoku, Shikoku and Kyushu regions. Age-specific prevalence rates are shown in Figure 3A. The national average prevalence rates of symptomatology by health check-up were 12.8% (351/2,744) in 4-month-old children, 9.8% (631/6,424) in 1-year and 6-month-old children, 13.2% (906/6,868) in 3-year-old children, 11.8% (1,479/12,489) in first-grade children, 10.6% (1,185/11,230) in sixth-grade children and 10.6% (1,185/11,230) in university students. 8.2% (684/8,317). Although prevalence rates by district have traditionally been higher in urban areas and lower in suburban areas, this study found no significant differences in prevalence rates among schoolchildren between urban and suburban areas, and no differences between boys and girls.

First BJ at Poison in a Pot 3, 40 minutes ago.

1. Introduction
Atopic dermatitis is a condition frequently encountered in daily practice. In Japan, there have been two guidelines for the treatment of atopic dermatitis: the Japanese Dermatological Association Guidelines for the Treatment of Atopic Dermatitis, which were developed for doctors specialising in dermatology who treat patients with atopic dermatitis from the primary care stage to the stage where a high level of specialisation is required; and the Japanese Society of Allergology Guidelines for the Treatment of Allergic Diseases, which are intended for doctors who treat patients with allergic diseases other than dermatological diseases. In 2018, these two guidelines were integrated into a single guideline for all doctors and healthcare professionals involved in the treatment of patients with atopic dermatitis. Guidelines have been developed. This revised edition of the Atopic Dermatitis Clinical Practice Guideline has been developed by adding new findings on atopic dermatitis* published in Japan and abroad. The descriptions of medical practices in this guideline provide a guide to medical treatment of atopic dermatitis in Japan at the present time* from the perspective of evidence-based medicine (EBM), including guidelines and goals of treatment, and can be used for decision-making in the field of medical practice. The following table shows the most common types of information on the use of the system. The final decision in clinical practice must be made by the attending physician in collaboration with the patient, fully reflecting the patient's values and wishes for treatment. *In principle, until the end of December 2020.

1) Department of Cutaneous and Mucosal Pathology, Graduate School of Medicine, Nippon Medical School (Chairperson).
2) National Centre for Allergy, National Centre for Child Health and Development (Vice-Chair)
3) University of Tsukuba, Faculty of Medicine and Medical Sciences, Medical Information Management (Vice-Chair).
4) North Kanto Allergy Research Institute affiliated with the House of Hope
5) Department of Cutaneous and Mucosal Pathology, Graduate School of Medicine, Nippon Medical School
6) Department of Paediatrics, The Third Hospital of The Jikei University Hospital
7) Dermatology, Graduate School of Medicine, Kyoto Prefectural University of Medicine
8) Hiroshima University Graduate School of Medical Sciences, Dermatology
9) Department of Dermatology, Saitama Medical University
10) Department of Dermatology, Graduate School of Medicine, Kyushu University
11) National Hospital Organisation Mie Hospital, Clinical Research Department, Allergic Disease Therapy Development
Laboratory.
12) Department of Paediatrics, Kyorin University School of Medicine
13) Dermatology, Graduate School of Medical Sciences, Hiroshima University
14) Allergy Centre, National Hospital Organisation Mie Hospital
15) Department of Paediatrics, National Hospital Organisation Nagoya Medical Centre
16) Dermatology, Graduate School of Medicine, Kyoto Prefectural University of Medicine
17) Department of Paediatrics, Saitama Medical Centre, Dokkyo Medical University
18) Department of Dermatopathology, Nagasaki University Graduate School of Medical and Dental Sciences
19) National Centre for Allergy, National Centre for Child Health and Development

I'm aware that it is my vice to immediately try to trace back to nostalgia.

I think this is the first time two in a row as far as I can remember. Does it hasten the dying process as the group name suggests?

Plus Ultra

The grid system is a widely used system in design activities. Josef Müller-Brockmann, a designer and educator at the Zurich University of the Arts and the Ulm School of Design, states that designing with a grid system means following universally valid laws and that below.

What is meant by the use of the grid system is the will to systematise and clarify, the will to find and consolidate the essence, the will to foster objectivity instead of subjectivity, the will to rationalise the creative and technical production process, the will to integrate the colour, form and material, the will to integrate the various elements, the will to architectural control of surfaces and spaces, the will to adopt a positive and forward-looking attitude, the recognition of the importance of education and the impact of work conceived in a constructive and creative spirit.

I can't help but think that handjob is underutilized. Even though its drawing difficulty makes it a means by which sexual content via video and text media can have an advantage over the two-dimensional media represented by manga, doujinshi, and illustrations.

Conscience is itself an ambiguous sum of information, such as a normative consciousness, and a mind that does good deeds and avoids evil deeds. There are two theories concerning human beings: one is the theory of sexual goodness, in which people are born with a conscience that favors good and dislikes evil, and the other is the theory of sexual evil, in which people are born without a conscience and must be educated to develop and nurture it. In any case, we are expected to act in accordance with our conscience.

In particular, the function of conscience is a personal one, and following it increases one's sense of self-affirmation, while violating it leads to self-negativity. In many cases, people also rely on their self-esteem and do not like to violate their conscience. Conscience is usually unconscious.

The function of the mind is to benefit the society to which one belongs, but the degree to which it works varies from person to person. Just as justice and morality vary according to the values of the society, the destination of conscience also varies somewhat according to other factors such as culture.

Sometimes conscience is aroused by the inspiration of others, and sometimes it is aroused by the mental shock of the situation at hand. On the other hand, there are cases in which people dare to act against their conscience (emergency evacuation) due to unavoidable circumstances.

Conscience itself is not a clear-cut value concept, and it is difficult to codify it into an article like a creed. Sigmund Freud considered conscience to be a cultural effect of unconscious repressive structures. Bert Hellinger describes the conscience as a sensory organ that perceives the right or wrong of belonging to a group.

Some stories deal with the conscience as a subject matter. For example, there are "Les Miserables" and "A Christmas Carol" in which a selfish person (putting his own interests first and not caring about others) awakens to his conscience through some experience, while there are stories like "Rashomon" in which a person abandons his conscience and turns to crime in order to survive.

Conscience, as stipulated in Article 76, Paragraph 3 of the Constitution of Japan, is defined by the Japanese Supreme Court in its decision of November 17, 1948 as "the meaning of following one's own inner sense of decency and morality without yielding to external pressures or temptations, tangible or intangible.

The derivation of concrete forms from abstract formulae and principles is called deduction, and the idea of generation we have just seen is a typical deductive explanation, and is also very deductive in the second point I will discuss below. The second point is the idea of the relationship between "universal grammar" and real languages. If we know the kinds of rules that make up the grammar of many languages of the world and how they are applied, then by comparing and contrasting them we can find universal principles common to the languages of the world. The aggregation of the elements and principles common to the grammars of the languages should be called a "universal grammar". One of the major assumptions of generative grammar is that humans have an "innate capacity for language". Infants with linguistic competence have a universal grammar. The universal grammar is not yet in the form of any language, but is acquired as a specific language when exposed to a particular language at a certain point in the developmental process.

In linguistics, a school of thought emerged in the late 1950s, a little later than structuralism, which held a deductive principle with an extremely high degree of abstraction, as if "structure" were even more fundamental and dynamic. This is the 'Generative Grammar' proposed by Noam Chomsky (1928-). In addition to its strong formalism and unique concepts and terminology, it undergoes major changes every ten years or so, so that it is not easy to grasp the whole picture or to give a simple explanation. Therefore, here I will only highlight two points in particular that contrast with the new linguistics as a way of thinking and try to explain them in ordinary language.

The first is about generation, which is also the name of the school. We can produce any number of grammatically correct sentences, even if none of them have ever been uttered before. This means that our brains must contain a (probably not very large) set of rules that can 'generate' an infinite number of correct sentences. Generative grammar considers such a set of rules to be a 'grammar' and attempts to elucidate its types and how sentences are generated.

The basic idea of sentence construction was that there is an abstract sentence structure and that the rules for transforming and concretising it lead to the final sentence. This way of thinking can explain, for example, the existence of sentence pairs such as active and passive sentences, which are clearly closely related but have distinctly different apparent sentence structures. Let me illustrate this with an example. The following three expressions could be explained individually in previous grammars, but it was difficult to explain the continuity between the three.

(1)
a. Active sentence
The troop attacked the town.

b. Passive sentence
The town was attacked by the troop.

c. Noun phrase
The attack of the town by the troop.

The resulting sentence is: a is an active sentence in which the verb attack is used in the past tense with the attacking troop as the subject, b is a passive sentence in which the town is the subject of the attack and the verb is in the passive form be attacked, c is a sentence equivalent by nominalising the predicate in a or b, and The explanation for each of these three types of sentences is also different.

However, it is clear that the three have a great deal in common, both as a whole and in terms of the semantic relationship between their parts, as can be seen from their meanings. For example, even when taught in Japanese schools, the passive voice of b is explained as follows: replace the two nouns in a and change the verb form to be + past participle... The passive voice of b is often explained in this way. In fact, this is the process of transformation that early generative grammars largely adopted. Abc above was seen as three different forms derived from an abstract sentence structure (deep structure) with the same underlying meaning. In this case, the active sentence in a is almost the same as the deep structure, and the passive sentence in b is obtained by applying the 'passivisation' transformation rule to the deep structure and the verb phrase attack... The active sentence in a is almost the same as the deep structure, while the passive sentence in b is obtained by applying the 'passivisation' rule to the deep structure. The application of the passivisation rule is shown diagrammatically below.

(1)b Process of generating passive sentences
Deep structure:　 　　　　the troop　　　 attacked　　　　　　　 the town
　　　　　　　 　　　　1 2 　　 3
Passivising transformation: 　3 　　be [past] +2 [past participle] 　 by +1
　　　　the town 　　　was attacked 　　　　　by the troop

The idea that sentences are generated rather than initially existing, and the idea of transformation in this process, can provide a reasonable explanation for the way in which they are closely related to each other despite the differences in their finished forms.

In geometry, the rhombicosidodecahedron is an Archimedean solid, one of thirteen convex isogonal nonprismatic solids constructed of two or more types of regular polygon faces.
It has 20 regular triangular faces, 30 square faces, 12 regular pentagonal faces, 60 vertices, and 120 edges.

Names
Johannes Kepler in Harmonices Mundi (1618) named this polyhedron a rhombicosidodecahedron, being short for truncated icosidodecahedral rhombus, with icosidodecahedral rhombus being his name for a rhombic triacontahedron. There are different truncations of a rhombic triacontahedron into a topological rhombicosidodecahedron: Prominently its rectification (left), the one that creates the uniform solid (center), and the rectification of the dual icosidodecahedron (right), which is the core of the dual compound.
It can also be called an expanded or cantellated dodecahedron or icosahedron, from truncation operations on either uniform polyhedron.

Geometric relations
If you expand an icosahedron by moving the faces away from the origin the right amount, without changing the orientation or size of the faces, and do the same to its dual dodecahedron, and patch the square holes in the result, you get a rhombicosidodecahedron. Therefore, it has the same number of triangles as an icosahedron and the same number of pentagons as a dodecahedron, with a square for each edge of either.
Alternatively, if you expand each of five cubes by moving the faces away from the origin the right amount and rotating each of the five 72° around so they are equidistant from each other, without changing the orientation or size of the faces, and patch the pentagonal and triangular holes in the result, you get a rhombicosidodecahedron. Therefore, it has the same number of squares as five cubes.
Two clusters of faces of the bilunabirotunda, the lunes (each lune featuring two triangles adjacent to opposite sides of one square), can be aligned with a congruent patch of faces on the rhombicosidodecahedron. If two bilunabirotundae are aligned this way on opposite sides of the rhombicosidodecahedron, then a cube can be put between the bilunabirotundae at the very center of the rhombicosidodecahedron.
The rhombicosidodecahedron shares the vertex arrangement with the small stellated truncated dodecahedron, and with the uniform compounds of six or twelve pentagrammic prisms.
The Zometool kits for making geodesic domes and other polyhedra use slotted balls as connectors. The balls are "expanded" rhombicosidodecahedra, with the squares replaced by rectangles. The expansion is chosen so that the resulting rectangles are golden rectangles.
Twelve of the 92 Johnson solids are derived from the rhombicosidodecahedron, four of them by rotation of one or more pentagonal cupolae: the gyrate, parabigyrate, metabigyrate, and trigyrate rhombicosidodecahedron. Eight more can be constructed by removing up to three cupolae, sometimes also rotating one or more of the other cupolae.

Orthogonal projections
The rhombicosidodecahedron has six special orthogonal projections, centered, on a vertex, on two types of edges, and three types of faces: triangles, squares, and pentagons. The last two correspond to the A2 and H2 Coxeter planes.

Spherical tiling
The rhombicosidodecahedron can also be represented as a spherical tiling, and projected onto the plane via a stereographic projection. This projection is conformal, preserving angles but not areas or lengths. Straight lines on the sphere are projected as circular arcs on the plane.

Symmetry mutations
This polyhedron is topologically related as a part of a sequence of cantellated polyhedra with vertex figure (3.4.n.4), which continues as tilings of the hyperbolic plane. These vertex-transitive figures have (*n32) reflectional symmetry.

Mon père disait que le plus délicieux de tous les aliments était la pêche. Le steak semble aussi être son préféré. La croyance qu'une préparation méticuleuse fera naître nos désirs n'est ni bonne ni mauvaise en soi. Les organes génitaux féminins bipolaires et décentralisés : le sein et la vulve sont littéralement des symboles du corps féminin et sont essentiels à l'histoire de l'industrie du sexe. Pourquoi le récit négatif est-il si répandu dans la société moderne ? Nous devons vivre en tant que personnes nées dans un pays de perdants et il est important et bénéfique pour nous individuellement et pour ce pays d'en prendre conscience. Underachiever ou Procrastinator - quel est mon véritable alias ? Je veux être une sorte d'agent de circulation pour notre société en tant que collectif intellectuel. Il n'y a rien de naturel ou de fondé sur des principes à ressentir un sentiment d'appartenance à un système politique tel que l'État. Neutralité. Justificateur. Mon frère vient de me dire "Tu as l'air d'un être humain même si ça ne m'est jamais arrivé quand on était chez nos parents". C'est bizarre, n'est-ce pas ? Si je me souviens bien, je me suis longtemps sentie coupable d'être financièrement et émotionnellement dépendante de mes parents. Même si je somnolais dans un sentiment de sécurité superficiel sans y faire face. Je me suis donc récemment dit qu'il était logique de voir cette tournure des événements sous un angle positif.