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Today, Connecticut begins the long, winding process of reopening. Were kicking off a new series on Steady Habits to explore some of the most challenging questions as it plays out.

Date: Wednesday, May 20, 2020

Its May 20, which means the reopening process in Connecticut is underway. Thousands of workers across the state will return to their workplaces as some businesses resume their operations. It comes as the state has seen a steady decline in coronavirus-related hospitalizations in recent weeks, and dramatically increased its testing capacity.

Still, some say more time may have been needed, including one of our guests this week.

Dean Sten Vermund of the Yale School of Public Health and Dr. Tom Tsai of the Harvard Global Health Institute talk with John Dankosky on the inaugural episode of our new reopening series on Steady Habits.

Listen to the episode using the player above or read an edited transcript of the conversation below.

DANKOSKY: If youre listening on the day we drop this episode, May 20th, you will note its the day the states been targeting for a partial reopening of state businesses. Now, to this point, only businesses considered essential have been operating in Connecticut. And thats meant a lot of people are out of work and a big part of our economy is suffering. The phased reopening is being done based on meeting goals for testing and a reduction in the transmission of coronavirus. And as youll hear, the state is making some progress. So that means pretty soon youll be able to eat in restaurants again. But only if you eat outside, and only if not that many of you are in the restaurant. And frankly, your waitress will be wearing a mask. And it probably doesnt sound like a whole lot of fun. You might, though, have been looking forward to getting a haircut. I mean, I dont know about you, but Ive been getting these kind of homemade haircuts for the last couple months.

My wifes been doing as well as she possibly can, but I could use to go back to the barber. But thats going to have to wait because this week, Governor Lamont pushed when salons could open up until June to coincide with the neighboring state of Rhode Island. Other businesses are being told now that theyll have to wait until later in June. Some businesses feel like, well, this pace is too slow. We want to open up more quickly. Others say give us more time and public health experts to kind of split on when to reopen different parts of the economy. So on this episode, two views from the public health sphere, from Dr. Tom Tsai from the Harvard Global Health Institute. And first from Sten Vermund. Hes dean of the Yale School of Public Health. Now, his colleague, Dr. Albert Ko, who has been helping to lead Connecticuts effort to reopen the economy. Vermund told me hes been pleased with the states response so far.

VERMUND: Im happy that the governor and legislature havent tried to move too quickly. Just two weeks ago, we had 440 patients in Yale New Haven Hospital with coronavirus. And now we have 240. Thats clear progress and were clearly on the downswing. But thats still a lot of patients and a lot of people got infected last week. So we are prudent and I think thats good. I also feel like, you know, opening up some industries, some businesses can be done expeditiously. Others may have to wait a little bit.

DANKOSKY: When we talk about this phased in nature of the reopening of our economy, some businesses going back, others taking a little bit longer. From a public health standpoint, are there certain benchmarks that you feel the state needs to meet before we start to open up restaurants? And what are what are some of those guide points that we have to hit?

VERMUND: Well, over a month ago, we had federal guidance that I thought was very thoughtful, 14 days of steady, declining case numbers. And that is a rule of thumb that was evaluated by the folks who do the mathematical modeling and forecasting. And they had reason to recommend that a two week span, because that would suggest that the wave of transmission was moving on, shall we say. And its a shame that states have ignored that guidance, because I think that would have been much more prudent. Georgias whats highlighted the news. I dont have any special knowledge about Georgia, but certainly judging from the news, they were especially aggressive at reopening. And Im not so sure that was such a good idea. Texas seems to have had a surge now. Maybe thats just a pocket or maybe its going to be more generalizable. But I dont think that you can be penny wise and pound foolish. Opening up too early and substantially risking another wave will simply disrupt the entire point of this shutdown to begin with. So I do feel like were in a good position now to thoughtfully reopen the state in stages. Other parts of the state that are considerably lower risk than other parts. And we can be more liberal in opening them. And we can also take a look at the big three. This is physical distancing, hand and face hygiene and mask use. And theres a lot we can do when we adhere to those big three.

DANKOSKY: I think my big question, though, comes with some of the the social aspects of of this crisis and how weve seen human behavior around these various milestones that were hitting. When the states start to open up, and a state like Connecticut which is I think we can all agree more thoughtfully doing it then Georgia starts to open up a bit more, youll start to see what I think you and I both might have witnessed over this past weekend. You had a couple sunny days. You get more people out and about. Maybe we get more people going to the stores that are open, not wearing masks. Theres almost a social effect of saying, well, were past this certain point and now were going to start to open up. Do you fear from a public health standpoint that people are going to take the message that things are fine and we dont have to be as vigilant as we have been for the past two or three months?

VERMUND: That is a challenge for the policymakers, political leaders, journalists, public health officials, academics. We need to impress upon people that a declining rate is not a zero rate. And if we continue to have transmission of the virus in the state of Connecticut, which we expect to well into the summer, it is highly prudent to physically distance, use masks and be aggressive with hand hygiene. Its not asking very much. Thats not a huge burden. If I can go to the movies and be a few seats away, lets be honest, most the movies I go to are not jam packed anyway. So its a matter of the movie theater owner being thoughtful in sort of the hot cross bun seating arrangement and making a bit of an educational effort to please sit in the seat where you see a mark and youll distribute people in the theater and people will be safer. Its not so difficult to sit in a theater and wear a mask, and its not so difficult to use the hand sanitizer that the clever theater owner will place conveniently at the entrance and exit and the bathroom.

DANKOSKY: But let me just stop you, because I think what were all though, noticing that there will probably be some theater owners, there will probably some bar owners, when bars are able to open up, that arent going to be so thoughtful. And there will be some places where people will crowd in as though its Mardi Gras and we just have had been locked up and cant wait to go party. Im wondering how much of a problem you see from a potential transmission standpoint, increased contact over the summertime as people begin to get into situations where, frankly, the businesses or the individuals themselves are not being that thoughtful?

VERMUND: Well, I think that the Department of Public Health and some of us in public health academia can be helpful. If our data in the state suggests that our problem is exceedingly low at the time, then liberalization is not unreasonable. If there is little to no transmission, then one might resume normal behavior, much as we do outside of flu season. Were much more cautious about hygiene in flu season than we are at the rest of the year. And maybe we should always be that cautious, but we arent. And so if the circumstances are highly favorable, liberalization is fine. But if we continue to have transmission, then were just inviting another wave. If were too relaxed and and we dont take those precautions and were going to open up the state. The governors aside of this, theres a broad consensus across the state that when we hit that sort of two week declining span, there is good reason to believe that the wave of transmission that washed over us from New York City will have largely dissipated. And until we know for sure, it is a fools errand to ignore physical distancing, handwashing and mask use. I honestly think we owe it to each other as denizens of our state to try to keep each other safe.

DANKOSKY: Even though its a small state, do you do you feel, though, because New York City has been the hot spot in the United States, maybe in the world, that Fairfield County and surrounding areas are in a little bit of a different situation than than Hartford County or the or the eastern part of the state?

VERMUND: I do believe they are, yes. They have business and social intimacy with New York City, far greater than any other part of the state. Their home of Stamford and Greenwich, which were hit right away very hard. And theres just no question that it was due to the tied by the hip kind of relationship theyve got with New York City. So I was disturbed seeing the evening news yesterday by folks in New York City, not bothering with masks, not bothering with any kind of distancing in some of the bars. And itll be interesting to see what Mayor de Blasio does about that, because we do have a tradition in public health of getting tough with people if theyre unsafe and theyre threatening the health of the community. It is it is true in all 50 states that an active tuberculosis patient who refuses therapy can be incarcerated and treated for two weeks until theyre no longer infectious to others.

And nobody sees that as a violation of individual liberty because theres a point at which that individuals irresponsible behavior threatens me. Its similar to running a red light or are driving recklessly or driving under the influence. We dont hesitate to enforce these things. And all of a sudden, public health people are saying, well, Im not so sure that that persons behavior is a risk to me. So I just all let it pass. But I think we should remind people courteously and in a cordial and reasonable way. Would you mind wearing a mask? Could you use that hand sanitizer? Could you stay a couple feet away, a couple more feet away? Thats not unreasonable. And I do it with people. I try to do it in a way thats friendly and supportive. And Im getting away with it without having my face smashed in so far. And I think if we do that with each other and set up a different kind of social contract that we agree to try to protect each other, then perhaps well be better off.

DANKOSKY: I want to ask you about this. The social contract or social compact? I think its such an important point and theres two questions I want to ask about it. One is that that is a slightly different thing than an enforcement mechanism, right? If theres a mechanism that says we cannot tolerate people without masks going into a certain establishment or we cannot tolerate someone who we know is actually a carrier of this virus being out in public, were going to incarcerate them. Thats a very different thing than us all getting together in deciding that were gonna take care of each other. Can you just parse those two things out for us? Because I believe that the social compact is a wonderful idea, but it may be a utopian idea in the America that we live in currently.

VERMUND: Good point. Now that weve been in a bit of a plateau of a peak of infection, there have been more rigorous regulations. The governor has required mask use to go into a store. A friend of mine was at a store the other day that was doing, you know, you were ordering in advance and then they would bring it to you and you could even pay in advance. And they had the six foot distancing of people. There was one gentleman in the whole line who wasnt wearing a mask and the store owner refused to serve him. And he got all upset, but the store owner said the governor has said that you have to wear a mask. Im not serving people who dont wear a mask. And everybody in the line cheered the store owner. Nobody took the side of the one person out of six or seven who refused to wear a mask because it was sociopathic. It was anti-social behavior. It was not a reasonable point of view. And as the gentleman left, my friend told me that he he mumbled, Oh masks dont help anyway. Which is simply untrue. So, you know, we do have a problem with people who dont want to do what they feel is inconvenient it for them. And these are not the people who are helpful in a pandemic.

DANKOSKY: The last thing for you, sir. Where do you think we need to get to in terms of testing in the state for us to more fully open back up? Because we hear from so many health experts that without an expanded and increased testing, were not going to be able to take those next steps toward more liberalization.

VERMUND: So if Im a store owner and I want to protect all my employees and my clients, I would like to get my employees tested for the antigen, meaning for the virus, before they return to work. So I might ask them to go to the CVS or other drivethrough or whatever is available my community and get a test. I think I would reimburse them for the costs of the test, because I would want to incentivize them to get that test. And then I would know that I have a returning workforce, none of whom is infectious to others. And they will stay uninfected the same way the health workers stay uninfected, which is use of personal protective equipment. In this case, were only asking for handwashing and masks and distancing, and that would protect my business. I will not then end up in the newspaper as a place that had a coronavirus case because Im going to lose a lot of business as soon as people see that my employees have gotten ill. And so I think its mutually self-interested. Its good for the business. Its good for the client. And having that ability to test people as they come back into group settings would be a powerful tool.

DANKOSKY: And do you think that theres some magic in the state number of wanting to get 40000 tests a week?

VERMUND: Others have done that calculation. I havent double checked it, but my colleague Albert Ko was happy with that number and I think hes done the research. One of my other colleagues, Forest Crawford, is working with the state. I dont think hes actually on the advisory group, but hes consulting the advisory group and I think theyre coming up with those numbers with his assistance. I believe that tens of thousands of tests that we could definitely quite to be needed because we may not think of ourselves as a large state, but there are three and a half million of us. If you take a million children out of the equation for the need for testing, you still have a couple of million people. And thats a lot of people.

DANKOSKY: So were starting a series this week called Reopening Connecticut. And we wanted to go outside the state for some perspective. Dr. Tom Tsai is from the Harvard Global Health Institute. Theyve been taking a close look at testing for coronavirus and how that can be used as a gauge for loosening restrictions on businesses. I asked him what hes looking for states to do as they consider how to reopen.

TSAI: The most important things to focus on as we look forward to next few weeks in terms of reopening is making sure that we continue to test broadly and counterintuitively the need for testing may actually increase as you reopen despite lower cases, because the reason for testing is going to change. Over the last several months, weve been really focused on just diagnosing COVID-19, basically testing patients with symptoms and confirming that they had coronavirus infection. But as we move towards reopening, were moving from a paradigm of diagnosis to one of screening and surveillance. So we need to get the tests out of the hospital and really into the communities and be able to adequately perform testing, contact tracing and supported isolation.

So I think there are two key metrics we need it will be looking at and state governors should be looking at as you move from looking at just the structural indicators of whether or not we have enough tests to now actually measuring our processes for testing and for reopening. That means we need to be measuring the number of people who are actually being traced through contact tracing. Among those, the number of people who are actually being tested because we have to make sure were testing those contacts in order to cast a wide enough net to get our arms around infection. The second part is to make sure that our tests are coming back at a fast enough rate so we can actually inform behavior. If testing is supposed to increase peoples confidence in the health care system, in society and in the economy, they cant wait four to five days for a result to come back. Thats four to five days of being self-isolated at home, unsure if you have the coronavirus and unsure if you may have inadvertently affected your friends, families or loved ones. So we really also need to be measuring the turnaround time. And ideally, that needs to be, you know, below 48 hours, below 24 hours if we have to make sure that the tests are immediately actionable.

DANKOSKY: How close do you think we are toward getting the right number of tests done, toward getting that turnaround time so that we can have the sorts of impact that youre looking for?

TSAI: I think were heading in the right direction. In Massachusetts, the governor recently announced a testing threshold, a target of 45000 by July and 75000 by December. I think similarly, Connecticut and other states have also increased their testing goals for the next few weeks to months. But, you know, Connecticut still has a test positive rate thats close to about 10 percent. And we need to be making sure that states like Connecticut are continuing to drive down the test positive rate.

The way to think about this is its not enough to make sure your car is going slower, going 10 miles per hour versus 60 miles per hour. The goal is to bring that car to a stop. So we have to actively be applying the brakes, actively decelerating and slowing down. And the quality of that is the test positive rate, continue to decrease and decrease in a fast enough rate. Thats what we know that the infection rate is going down, that fewer and fewer people are being infected. So a lot of progress has been made. I think were heading in the right direction, especially as states begin to move into phase reopening. There is an even more important need for continued vigilance around all the things that work. You know, that includes universal masking, physical distancing and really minimizing unnecessary social contact and exposure again. Because even though the infection has slowed down, its not over yet. And theres always a chance that if we take the lid off that things could bubble over again.

DANKOSKY: What conditions might make it easier for the virus to come back in another wave, to bubble back over again? I mean, if you if you look at a phased reopening like this, what could go wrong in a state like Massachusetts or Connecticut that would they would have the numbers start to head in the wrong direction again?

TSAI: We know that the virus tends to be spread easiest in close settings, indoor settings where theres not a lot of air circulation, but theres a lot of high frequency and high duration of contacts. So, you know, these are things like factories and plants. You know, weve seen how rapidly clusters can emerge and some of these meat packing or food processing plants. So thats why we have to be even more vigilant going forward to make sure that were testing, but also redoing repeated surveillance testing of nursing home residents and nursing home workers, testing any visitors. Now, the same goes for prisons. The same goes for new workplaces. You know, as they open, that may be sort of that higher risk.

So I think its really a focusing of the vulnerable populations or underserved communities. And the way this works is its a snowball effect if youre testing widely in these vulnerable populations, not only protecting the high-risk individuals, but if you actually following through with not just testing, but contact tracing for each new case, youre testing at least five to 10 additional individuals. And some of those may be new cases. And then you go contact tracing those individuals so that this becomes a snowball where, you know, one test becomes 10 tests, becomes 100 tests. And thats how you do sort of a targeted surveillance thats both screening the population, but also, you know, following the epidemiologist for the disease through contact tracing. And thats the way to move forward is by making sure that we can identify some of these cases early enough before they become, you know, emerging as huge clusters of cases.

DANKOSKY: The states are really only starting to ramp up their contact tracing efforts. Do you think that enough has been done at the state level in order for us to feel confident that we can start to go back to work? Because were testing more people, obviously, but still, those numbers are relatively low compared to what public health experts would have wanted. And now we seem to be just slowly ramping up contact tracing. I guess Im just wondering, Doctor, if weve if weve done enough so far to give you confidence.

TSAI: I think weve made a good start in lots of states, but I think we could be doing better. We always can be doing better. The goal of testing and the contact tracing is to make sure that we are creating confidence in the society and the public and the economy to safely reopen. And the best way to create that confidence is to make sure were testing broadly. I mean, think about, you know, your confidence in going back to work or bringing children back to school would be many fold higher if you know that you didnt have coronavirus, your child didnt have coronavirus, their teachers didnt have coronavirus, your colleagues have coronavirus. So, you know, I dont think were there yet. But thats the degree of confidence we need to be building in society. And the only way to do that is to be making sure that were testing broadly. And the only way to make sure we are testing broadly is to make sure that were actually doing adequate contact tracing. So I think weve made an important start.

We want the states hiring contact tracers. In Massachusetts, over 10,000 phone calls have been made to potentially exposed contacts. But I think thats just stage one. You know, step one. Where we really need to be moving is making sure those 10,000 individuals all get tested. I think thats where we need to be looking beyond just the number of tests as our metric for success and start measuring how effective our policies are, how effective our processes are. Thats where we need to be looking at the number of tests per contact, the turnaround time per test. These are second order metrics that will shine some light on how well the phase reopening plans are actually being implemented, because that will tell us whether or not ultimately were improving the outcomes for the public, which is decreasing the number of COVID-19 cases.

DANKOSKY: If you were on the line with Ned Lamont, the governor of Connecticut, and he asked you, Is it time to start a phased reopening, to start some businesses going back as early as the 20th of May, some others starting as early as June 1st? what would you tell him? I mean, do you think that we are going about this too quickly or not quickly enough? Do you think that were doing it just about right?

TSAI: So Im just looking at the numbers and in Connecticut so I have no skin in the game, being a resident in Massachusetts. By looking at the numbers in Connecticut, the positive rate seems to be stabilizing around 10 percent. Thats good, but not good enough. I want to see that drop below 10 percent and keep dropping. The number of positive tests has also stabilized, but I want to see it continue to go down. So, you know, the good news that the number of tests has increased over the last several weeks in Connecticut. So, again, I think there are some there are some early signals. Want to make sure that what were seeing are truly signals and not noise. So I think it may still be too early for Connecticut. But whats more important than dates is that our deadline should be driven by the data. So we shouldnt hold ourselves to specific dates.

But what we should really be holding ourselves accountable to is what the data show us. The data shows that the number of cases continues to go down at the positive rate is not just stable, but continues to go down below 10 percent. Number of deaths continue to go down and our number of tests continue to go up. All these, you know, signs have been are pointing the right direction that the pandemic is truly slowing down. I think thats a point where the phased reopening approach is important. The second part I would tell Governor Lamont is that just as important as to the goals, the gating criteria for moving to phase one, is how do we measure how was success in phase one looks like? Because if we see that rise in cases during phase one, how do we hold ourselves accountable for having made the right policy decisions? We wont even be making sure that the state of Connecticut, and that goes for every state in the Union, needs to have very transparent metrics on what success or failure looks like in terms of phase reopening because our lives that are at stake.

So we need to be making sure that we are very clear about what the goalposts are and we hold ourselves accountable to those moving forward. We cant have, you know, sort of moving targets. You know, there needs to be something that we work towards to during phase one for reopening. And if we meet those, great, move on to the next phase. But we all seem to know what happens if we dont meet those and we may have to reinstitute some forms of social distancing or even though double down on even more testing in order to be able to contain the pandemic. So its the the response is what Ive been seeing in a lot of the state plans. And I think thats incredibly important because that transparency is whats going to breed accountability, which is whats going to breed confidence in our public health system and our economy as well.

DANKOSKY: For the last couple months, we went from thinking that maybe if we elbow bumped instead of shook hands, that would be OK. And then we started to distance ourselves a little bit more. And then there was a lockdown and then more and more things shut down. And weve been only really essentially increasing the amount that we have distanced from each other and protected ourselves and each other. And now with this phased reopening, there seems to be a sense in society that weve turned a corner and that the behavior is going to start heading in the other direction. And I guess from a public health standpoint, Im wondering if it worries you that even if the testing gets up to a certain point, even if our metrics look good, we are sending a signal that things are back to normal and so that people who have heretofore been acting a lot differently than they ever have are going to go back to acting exactly the way they were in January of this year.

TSAI: There is no normal. The new normal is this brave new world that were in now. It is no longer ever going to look like December 2019. Now, this is a once in a generation, once in a lifetime pandemic. And what the public needs to realize is that, you know, it was actually easy to do one really big thing. Well, the big thing was staying at home. Now we have do lots of small things well. You know, masking, physical distancing, making sure we get tested, you know, making sure we answer the phone if we get contact traced, you know, following the guidelines at work. You know, were at school. You know, all these things are really hard to do well and to have this complete cultural change than just doing the one big thing while staying at home. So I think the next few months are actually going to be very challenging and difficult.

But, you know, Im confident that, you know, residents of Connecticut, as in every other state, you know, get it. People understand, you know, their friends, family members whose lives have been lost in this. People understand the tragedy and the depths of this pandemic. So my hope is that people will continue to translate, you know, that level of concern into their everyday practice, because its not just, you know, going back to the way things were. You know, this is a new world that were sort of reopening to and thats a world that requires vigilance. But the important thing to understand is that everybody has a role to play, that in this new world means that everybody has a sense of control because you are responsible for breaking your link in the chain. And when you do that, youre not just helping some hypothetical person across the country. Youre helping your friends, your family, your loved ones for potentially being infected.

So I think theres a credible role for individual responsibility on that. I think thats the message we have to focus on going forward.

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Reopening Connecticut: Is It Too Soon To Reopen Our State? - The CT Mirror

Human Behavior

Horace’s How-To | by Gregory Hays – The New York Review of Books

May 21, 2020 medical

Horaces Ars Poetica: Family, Friendship, and the Art of Living

by Jennifer Ferriss-Hill

Princeton University Press, 301 pp., $45.00

Among the previously uncollected pieces in Donald Barthelmes Sixty Stories is a six-pager called How I Write My Songs. The I, like many of Barthelmes narrators, is initially anonymous; we learn his nameit turns out to be Bill B. Whiteonly in the second-to-last sentence. The songs he writes, or that Barthelme has written for him, are country- and blues-inflected numbers, vacuous yet weirdly plausible:

Goin to get to-geth-erGoin to get to-geth-erIf the good Lords willin and the creek dont rise.

White is evidently a master of his craft: When Last Night was first recorded, the engineer said Thats a keeper on the first take and it was subsequently covered by sixteen artists including Walls. Such reminiscences alternate with helpful hints, all of them comically banal: Various artists have their own unique ways of doing a song. It is also possible to give a song a funny or humorous twist. In the final paragraph the lecture modulates into a pep talk (The main thing is to persevere and to believe in yourself) before ending on an oddly defiant note: I will continue to write my songs, for the nation as a whole and for the world.

The story reads like a parody of something we half-recognize but cannot quite put our finger on. Is it the emptiness of popular song lyrics? The vapid idiom of Parade magazine? Or is it, we might wonder uneasily, Barthelmes own readers who are being gently mocked? For the story purports to answer that question asked innumerable times of every famous artistWhere do you get your ideas?with its implicit corollary: How can I do it?

Whatever else Barthelmes story may be, it is a sly rewriting of one of the classics of American literary criticism, Edgar Allan Poes The Philosophy of Composition. In that essay Poe, in his best professorial voice, explains how he went about writing his most successful poem, The Raven. He began, he tells us, by settling on the ideal length (a hundred lines or so), the effect to be aimed at (beauty), the tone (sadness), the central device (a refrain), the nature of the refrain (a single word), and the kind of word needed (one with prominent o and r sounds, these being sonorous and susceptible of protracted emphasis). In such a search, he adds complacently, it would have been absolutely impossible to overlook the word Nevermore. In fact, it was the very first which presented itself.

But how should the refrain be introduced? At this point things take a perilous turn: Hereimmediately arose the idea of a non-reasoning creature capable of speech; and, very naturally, a parrot, in the first instance, suggested itself. A brief vision flashes before our eyes: a nervous schoolchild standing before a prize-day audience to recite Edgar Allan Poes The Parrot. But no, disaster is averted: the parrot is weighed and considered, but ultimately discarded in favor of a raven (equally capable of speech, and infinitely more in keeping with the intended tone). Like his great detective, C. Auguste Dupin, Poe reconstructs logically for us the process that led ineluctably to the poem we know and love. This most emotional and romantic of poems was, it turns out, the product of cold calculation at every turn.

Or was it? Is this how anyone writes a poem? And if Poe could really reason himself into writing this smash hit, how is it that he never wrote another poem as successful? The more one reads the essay, the more one suspects that Poes account is a typical Poe hoax, swallowed whole by gullible readers as his circumstantial account of crossing the Atlantic in a balloon was by the New York Sun. Surely it was the poem that came first. The Philosophy of Composition is an elaborate piece of reverse engineering, designed to conceal from the public (and perhaps, at some level, from the author himself) the unsettling truth: that Poe had no idea how he had managed to write The Raven, and no idea how to write another one.

The ultimate ancestor of all such literary howdunits is Horaces Ars Poetica. In 476 lines of dactylic hexameter, one of the great Roman poets tells us, if not how he wrote his songs, at any rate how we should go about writing ours. The advice is not all his own; an ancient commentator notes that the poet drew some of it from a third-century BC Greek critic called Neoptolemus of Parium. But it is Horaces version that has lasted. The Ars lays down literary laws observed by writers for centuries: modern editions divide Shakespeares plays into five acts, for instance, because thats how many Horace said a play should have. It canonized critical ideas, like the concept of artistic unity, that we now take as self-evident. Phrases from it have become conventional tags, some typically encountered in translation (purple patch from purpureuspannus), but others familiar in the original Latin: ut pictura poesis; norma loquendi; in medias res; laudator temporis acti; sub iudice; ab ovo.

Yet the work is full of mysteries, starting with its very title. The rhetorician Quintilian, several generations later than Horace, evidently knew it as the Ars Poetica, but we cant be sure that Horace called it that. The poem, now normally printed after the second book of Horaces Epistles, is addressed to three members of the Piso family: a father and two sons. Some critics therefore prefer to call it the Epistle to the Pisos. But which Pisos? Piso pre might be Lucius Calpurnius Piso Caesoninus, Julius Caesars father-in-law and the target of one of Ciceros nastier invectives. Or it might be his son, consul in 15 BC. Both had literary interests, although the younger Piso is not known to have had a brother, nor can we be sure that he had two sons himself. Another candidate, Gnaeus Calpurnius Piso, did have two sonsbut no known interest in literature. And why is the poem addressed to any Piso? Why not to Horaces longtime friend and patron Gaius Maecenas, or to someone mentioned elsewhere in his oeuvre?

We also cant be certain where the poem falls in Horaces career. Many readers have wanted to make it a late work, or even Horaces lasta poetic testament comparable to Yeatss Under Ben Bulben or Stevenss The Planet on the Table. A late date would fit the younger Lucius and his putative sons, and some metrical features might also support it. But there is no external evidence; if we opt for Gnaeus Piso or the senior Lucius as addressee, then the poem could be considerably earlier, a product of Horaces prime.

That Horace should write a poem about writing poetry is not in itself surprising. But here too there are puzzles. The rest of his oeuvre falls into two parts. On the one hand, we have the Odes and Epodes, short lyric poems of great metrical virtuosity. On the other, the Satires and Epistles, loose, talky poems written, like the Ars, in dactylic hexameter. Yet the Ars itself is primarily about how to write drama, a form that Horace never practiced and which employs a meter (iambic trimeter) that he barely used. It includes side notes on epic, another non-Horatian genre.

Equally mysterious is the poems organization. Generations of critics have struggled to discernand some have tried by main force to restorea coherent structure in a text in which everything seems like a digression. Horace goes off on tangents, extends similes beyond their relevance, circles back to topics already covered. He includes a potted history of theater, not obviously useful to the aspiring dramatist, and answers elementary questions (like what an iamb is) that no likely reader could have had. As an actual manual, indeed, the Ars seems notably unhelpful. Much of its advice is negative (Dont put scenes that belong offstage onstage), or uselessly vague (Choose a subject appropriate to your strengths), or comes down on both sides of a question (Either take a traditional plot or invent a plausible one of your own). A much later Ars Poetica, the brief poem by Archibald MacLeish, catches this quality well when it instructs us that a poem should be palpable and mute/as a globed fruit. Its a lovely image, but perhaps not all that helpful to the aspiring author.

Some of the difficulty may stem from the works genre. The Ars is a didactic poem, a form that goes back to the beginnings of ancient literature and remained vibrant into late antiquity. The oldest surviving example is Hesiods Works and Days, a kind of versified farmers almanac. The early thinkers Parmenides and Empedocles wrote philosophical treatises in verse, and the Roman Lucretius used Latin hexameters to expound the philosophy of Epicurus. The Hellenistic Greek Nicander wrote poems about venomous snakes and cures for poisons. Aratus of Soli composed a manual of astronomy in verse, which was translated several times into Latin (once by Cicero). Later Greek poets wrote about hunting dogs and ichthyology. Ovid, predictably, wrote an Art of Love, a send-up of the whole genre, and at least started a didactic poem on cosmetology.

The didactic poet aimed both to instruct and delightat least in theory. As Horace says in the Ars, he hits the bulls eye who has mingled utility with pleasure. Of the extant poets it is perhaps Lucretius (and, ironically, Ovid) who did this most successfully. But usually utility was the junior partner. A doctor faced with a case of poisoning would have needed a scholarly commentary to understand Nicanders Alexipharmaca, and one does not envy the aspiring farmer who tried to use the Works and Days as a real guide. This is even more true of Vergils Georgics, by common consent the greatest example of the form. It offers some practical information on agriculture, but in small dosesenough to give it that textbook feel, and to make digressions a welcome respite. But then, the Georgics is only ostensibly a poem about farming. Its real subject matter is what it means to be Roman, and, at a deeper level, what it means to live as a human being in a world governed by nonhuman forces.

Human, as it happens, is the opening word of the Ars Poetica. This is unlikely to be an accident. Ancient writers gave thought to beginnings; after Platos death, his heirs supposedly found a tablet with various versions of the opening of the Republic: I went down yesterday to the Piraeus. The story is probably apocryphal, yet it reveals something about the Republic, a work in which we descend from intangible verities to their pale shadows in earthly societies. The Aeneids first two wordsarms and manlay out its subject: warfare and a man at war, as Robert Fitzgerald expanded them. Simultaneously, they establish the poems relationship to the Iliad (a poem of arms) and the Odyssey (whose own first word is man).

It might seem odd, then, that the opening word of the Ars does not point more clearly to poetrysongs, say, or lyre. But it does not seem strange to Jennifer Ferriss-Hill, a classics professor at the University of Miami; her new book argues that the Ars Poetica is not really about poetry at all. It may masquerade as a guide for would-be writers, but its real concerns are larger: human behavior, family relationships, friendship, and laughter. Rather than a new departure, the poem is in her view a continuation ofor, if it is a late work, a return tothe poetry of the Satires. In those early poems, Horace explores human weaknesses and self-deception, not least his own, as they play out in social interactions. Here he does the same.

We do not typically think of literature as a branch of ethics. When W. Som- erset Maugham said that to write simply is as difficult as to be good, he was not equating the two. But earlier readers saw closer connections: medieval commentators categorized Ovids Art of Love as a work of moral philosophy. A letter of Senecas famously makes the case, summed up in Buffons aphorism, that le style cest lhomme mme. An important predecessor of Horace in this respect is the Greek Epicurean philosopher Philodemus, parts of whose treatises have been restored to us in recent years as scholars unroll and decipher charred papyrus scrolls from Herculaneum. A poet himself (he wrote epigrams), Philodemus was known personally to Vergil and perhaps to Horace too; it may not be coincidental that his principal patron was the older Lucius Calpurnius Piso. Horace mentions him by name in the Satires, and for Ferriss-Hill his fingerprints can be discerned all over the Ars Poetica, from the passing interest evinced in anger, death, and property management to the abiding importance of friendship, teaching, and criticism.

It is striking that the things Horace values in poetry are virtues he endorses in life as well: the importance of decorum, for example, and of knowing your place. A concept that crops up at various points in the poem is pudor, a sense of modesty or propriety, a quality as relevant to writing (for Horace) as to manners. Indeed, many terms that apply to writing can also apply to ones character or actions. A poem, we are told, should be uncomplicated (simplex), but simplicity or the absence of duplicitousness is also a virtue in people.

Another example of this is rectum, a word that can mean anything between correct, by the book and morally right. Horace tells us that most of us poetsare led astray by the illusion of correctness (specie recti). Our writerly errors, that is, spring from a mistaken belief that we are following the rules, doing what we should. But is that not also true of many of our nonwriterly errors? Again, we are told that the basis and wellspring of writing properly (recte) is good taste. But good taste here is sapere, which can also mean wisdom, the quality that allows us not only to write well but to act rightly. The two words will be juxtaposed again when Horace compliments the older Piso son, who is being brought up by his father to behave properly (ad rectum) but also has good sense himself (sapis). Ferriss-Hill is attentive to such repetitions. As she notes:

Horace creates meaning by repeating specific terms, clustering them close together or layering them at intervalsoften in such a way that on the second or third recurrence of a term we feel we have met it before but cannot say so for certain or recall where exactly that might have been.

If poetry in the Ars is really a stalking-horse for ethics, that might help explain something about the structure of the poem. A little over halfway through, the Ars shifts its focus noticeably, from poetry and poetic creation to the poet himself. Horace lures us in by promising to help us with our writing, but his real goal is our character and our relations with those around us. The focus on human affairs might also explain why the Ars privileges drama among other poetic forms: drama is built on human interaction and thus provides for Horace the ideal vehicle for connecting writing with living.

Living, and also dying. For the Ars is notably concerned with transience and mortality. Its reflections on the coining of new words and their obsolescence plainly echo Homers famous comparison of the generations of men to leaves. The principle that characters in drama should be portrayed in a way appropriate to their age prompts a character sketch of an irascible old man, far longer than the context seems to require, leading to a poignant meditation: The arriving years bring many enjoyments with them/and many in their departure they take away. The presence as addressees of two generations of Pisos allows Horace to touch on related topics: youth and age, birth and death, parents and children.

The Pisos are important to Ferriss-Hills reading in other respects as well. Not their exact identity, on which she is agnostic. Indeed, she suggests that it does not really matter much which Pisos are meant. Rather the aristocratic Piso functions in the poem primarily as a symbolic name, like Rockefeller. What matters is the relationship the poem itself constructs between the author and his addressees. Yet that relationship is curiously elusive. Horace shifts unpredictably from the second person plural to a singular you (one of the Pisos? the reader?) to an all-embracing we. The Pisos undergo a similar slippage. Nominally the addressees of the poem, they gradually prove to be in some ways its subject: a wealthy amateur and his two failsons in search of a writing coachor perhaps just a cheerleader. Didactic addressees are sometimes portrayed as slow or troublesome students in need of a stern lecture. Hesiod characterizes his brother, Perses, as an idiot; Lucretius sometimes seems to show impatience with his addressee, Memmius. Ferriss-Hill reads the relationship between Horace and the Pisos as similarly fraught, his attitude to them as implicitly critical.

For she sees the Ars Poetica as also an essay on criticism (the title of Popes imitation catches something important about Horaces original)and not just literary criticism, either. Indeed, the famous vignette that opens the poem is a scene of assessment and critique. Suppose, says Horace, that a painter depicted a human head on a horses neck with feathers and a tail: If you were admitted to view it, friends, would you be able to restrain your laughter? On the surface the scene is there to illustrate an aesthetic principle: a work should possess organic unity (Be a Rothko, not a Rauschenberg!). But for Ferriss-Hill it is the final line that we should be looking at. Horace here depicts criticism as something that takes place in a social context, among friends. The image will return toward the end of the poem as the poet questions how to tell a true friend from an insincere yes-man. (Philodemus, author of the treatises On Flattery and On Frank Criticism, may be lurking here too.) The real friend, it turns out, is the one who is willing to laugh at youand not only at your bad poetrywith a view to your improvement. And this, we might suppose, is what Horace does for the Pisos. In fact, it is what the poem itself does for them.

Didactic poets sometimes close on a darker note. Lucretiuss poem, On the Nature of Things, meant to teach us inner tranquility, concludes with a description of a devastating plague. The first book of Vergils Georgics closes with the image of a chariotthe Roman staterunning out of control, its driver powerless to stop it. The late Greek writer Oppians five-book poem on fishing ends with a sponge-diver mauled to death by creatures of the deep, his colleagues grieving over his remains. And the Ars? It ends with a comic yet disturbing portrait of a mad poet, lashing out at others like a savage bear or bleeding them dry like a parasite. (Leech is the final word of the poem, as human is the first.) For the poems message is in the end a negative one: Horace does not concretely help his addresseesbecome better poets or become poets at all because he cannot; in fact, no one can. Poets need talent as well as training, and for those who want to write without the former, Horaces implicit advice is, Dont.

Ferriss-Hill has written a dense book, frustrating to the reader in the same way, and for much the same reasons, as the Ars itself. Her method is close reading in its most austere form: she worries at Horaces phrasing, teases out implications, toys with alternative interpretations, follows him down blind alleys. The book loosely follows the trajectory of the poem, but it assumes knowledge of the whole: the discussion can jump forward unexpectedly, and passages we had thought we were done with will crop up again later, now viewed from a new angle or in light of new information. Readers without Latin are likely to find it hard going. Ferriss-Hill does provide an English translation facing the Latin text at the beginning of the book, though one that egregiously disobeys the poems own injunction not to translate word for word. When Horace discusses the coining of new words, for instance, we get:

If it is perhaps necessaryto show with recent symbols the hidden ones of things,it will fall to you to craft ones not heard by the girdedCethegi and a license taken up prudently will be granted.

This painful woodenness is plainly deliberate; the rendering is meant solely as an aid in construing the facing Latin. Yet no reader new to Horace will emerge from the book with much sense of why he is a great poet.

What the book does do well is to document an intelligent readers journey through this most elusive of poems. In the process it offers us a new way of thinking about it, one in which its apparent center moves to the margins and its apparent defects become strengths. It offers a richer and more interesting Ars than most of us are used to, but one recognizably by the Horace we know from other works. Of this Horace it could be said, as Robert B. Parker wrote of Ross Macdonald, It was not just that [he] taught us how to write; he did something more, he taught us how to read, and how to think about life, and maybe, in some small, but mattering way, how to live.

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Horace's How-To | by Gregory Hays - The New York Review of Books

Immunology

The immunology of COVID-19: is immune modulation an option for treatment? – The Lancet

May 21, 2020 medical

The immunology of COVID-19: is immune modulation an option for treatment? The Lancet

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The immunology of COVID-19: is immune modulation an option for treatment? - The Lancet

Immunology

Stony Brook Team to Test Effectiveness of Inhibitor Drugs on COVID-19 – Stony Brook News

May 21, 2020 medical

The effectiveness of two inhibitor drugs in the treatment of COVID-19 will be tested by a team of researchers in the Department of Microbiology and Immunology at the Renaissance School of Medicine.

Led byNancy Reich, PhD, a Professor in the Department of Microbiology and Immunology and recent President of the International Cytokine and Interferon Society, the research will test the efficacy ofinterferon-lambda and bradykinin inhibitors both FDA-approved drugs for other uses in the treatment and prevention of COVID-19 in laboratory models. The collaborative work will be supported by a $450,000 grant, effective June 1, from the G. Harold and Leila Y. Mathers Foundation.

Safe and effective vaccines take months to years to develop, if even attainable. For this reason, there is an urgent need to identify first-line, broad-spectrum, therapeutic agents that will block viral replication and will alleviate the effects of severe inflammatory responses caused by COVID-19, said Dr. Reich, Principal Investigator.

She and colleagues believe these two drugs have promise in the treatment against COVID-19 because interferon is a natural antiviral hormone known to be the only cytokine that inhibits virus replication, and bradykinin inhibitors are effective in reducing the lung inflammatory responses to viral infection.

The research will take two approaches. One is to test the effectiveness of interferon-lambda to block viral replication. Interferon-lambda protects the epithelial cells that line the lung and digestive system and reduce viral load. The second approach is to block the severe pulmonary edema that occurs with COVID-19. To reduce the leakiness of blood vessels that causes inflammation, they will test inhibitors of bradykinin, a natural and potent mediator of vascular permeability.

In addition to the laboratory investigation, Dr. Reich said that the team will evaluate primary human lung cells and cells from other affected human tissues to define the molecular mechanisms by which COVID-19 takes over the infected cells and suppresses natural defense mechanisms.

The departmental effortinvolves collaborators with expertise in infections and immune defense. These include: Dr. Nancy Reich, Dr. Patrick Hearing and Dr. Erich Mackow, who will investigate molecular aspects of COVID-19; and Dr. Janet Hearing and Dr. Hwan Kim who are certified to work in high containment biosafety laboratories.

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Stony Brook Team to Test Effectiveness of Inhibitor Drugs on COVID-19 - Stony Brook News

Immunology

Preliminary study on the effects of treatment for breast cancer: immunological markers as they relate to quality of life and neuropsychological…

May 21, 2020 medical

Participants

IRB approval for this study was obtained from both Indiana Wesleyan University and Lutheran Hospital (Fort Wayne, IN) and informed written consent was obtained from all women prior to study participation. All patients were recently diagnosed with Stage 1 to 3a breast cancer (using the Tumor, Node, Metastasis (TNM) Stage Grouping System) at the Lutheran Hospital Breast Center and Womens Health clinic in Fort Wayne, Indiana (see Table1). They were contacted over a two-month period, and 20 of them (66%) agreed to participate. Following initial surgery (lumpectomy and/or mastectomy) all participating women (active treatment group) in the present study underwent radiation therapy (N=20). Depending on the staging and recommended treatment guidelines, most active treatment women then had chemotherapy (Cyclophosphamide, Methotrexate, Fluorouracil or CMF) or Taxotere (Docetaxel) (Table 1). These were all women in the active treatment group with a positive lymph node biopsy during surgery (N=9) as per the hospital oncology department standard of care for breast cancer at that time. Unfortunately, the molecular subtype of breast cancer (e.g., triple negative, HER2+, HR+) was not available for the active patient or breast cancer survivor (remission) groups in the present study. Though data on molecular subtype of breast cancer is not available, some patients in both groups received tamoxifen (Table 1), suggesting a hormone-dependent (luminal) disease. Those not receiving the drug most likely belonged to HER2-positive or triple-negative subtype.

Women were excluded if their medical chart review revealed significant neuropsychological risk from a history of central nervous system disease or infection (e.g., meningitis, HIV, stroke), seizures, prior cancer diagnoses, or traumatic brain injury or accident.

Through a breast cancer survivors support group meeting monthly at the Lutheran Hospital Breast Center, a comparison group was enrolled. These were all women who had completed treatment for breast cancer at least a year previously (N=26), including chemotherapy (N=18). All present women in the active treatment group given chemotherapy completed the full course of treatment in accordance with the American Cancer Association guidelines for early stage breast cancer, either CMF or Taxotere. The cancer survivor comparison group members were also excluded if a medical history revealed any of the exclusion neuropsychological risk factors as noted above for the active treatment group. Although the breast cancer survivor comparison group could report their treatment history, we did not have access to their original disease stage at diagnosis. The two groups were equivalent on age and education, all were Caucasian and the majority were married, employed, and with at least some college education (Table 1).

Zung Self-Rating Depression Scale [19, 20]. The Zung Self-Rating Depression Scale (Zung SDS) is a self-administered 20-item questionnaire that includes a variety of statements associated with depressed moods and is a helpful tool used to assess depression in individuals. The inventory looks at various symptoms of depression such as insomnia, fatigue, suicidal thoughts, and anxiety. The 20 items are based on a Likert scale and the four possible responses range from None or little of the time to Most or all of the time. The higher the score, the more depressed the respondent.

The State-Trait Anxiety Inventory [21,22,23]. The State-Trait Anxiety Inventory (STAI) is a measure that looks specifically at anxiety. It measures a persons current anxiety (state) and characteristic anxiety (trait). The full STAI is a 40-item self-report anxiety inventory, but a shortened version of the STAI consisting of five items was used in this study [21, 22]. The higher the score, the more anxious the respondent.

Hope Quality of Life Scale Breast Cancer Patient Version [24,25,26,27]. This version of the Quality of Life Scale (Ferrell, Dow, & Grant, 1995) is based on previous versions created by the City of Hope National Medical Center. The assessment is a 46-item questionnaire that looks at the four domains of quality of life: physical well-being, psychological well-being, social well-being, and spiritual well-being. This instrument has been validated and reliability has been insured over multiple uses in hospital studies [26,27,28]. The higher the score, the better the quality of life.

Pittsburgh Sleep Quality Index [29, 30]. A modified version of the Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality in the patients. The PSQI is broken down into seven parts for scoring. They are subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of medication, and daytime dysfunction. The higher the score on these seven components the more likely the person is to have sleep disturbances. We also included the Sleep Hygiene Likert Scale optional items with this questionnaire.

Functional Assessment of Cancer Therapy - General (FACT-G) [31]. This assessment is a comprehensive compilation of questions which measures health-related quality of life (QOL) in patients with cancer and other chronic illnesses. This study used the FACT-G in conjunction with the subscale for assessing specific problems related to anemia in cancer patients (FACT-An), a subscale which is represented by questions addressing the cardinal symptom of anemia, which is fatigue. This measure also helped gauge the impact of cancer treatment, such as chemotherapy, on other measures of emotional, psychological, and spiritual well-being. For two of the scales (Physical, Functional) higher scores indicate poorer functionality. For the other two scales (Social/Family Well-being, Emotional Well-being), higher scores indicate higher well-being.

Fatigue Symptom Inventory (FSI) and the Multidimensional Fatigue Symptom Inventory (MFSI) [32,33,34]. The MFSI (Hann, et al., 1998) is a 14-item self-report measure designed to measure the daily patterns of fatigue including intensity, frequency, and impact on overall quality of life. The MFSI (Stein, Martin, Hann, & Jacobsen, 1998) is an 83-item self-report measure that evaluates the principal manifestations of fatigue; and includes the subscales of global, somatic, affective, cognitive, and behavioral manifestations of fatigue. These instruments have been validated in a variety of clinical contexts with cancer patients, and provide for a sensitive overview of the impact of the disease on patients overall quality of life as well as activities of daily living (ADL) [32, 34]. Lower scores indicate less intense symptoms of fatigue, so the lower the score the better.

Spiritual Beliefs Inventories (SBI) [35, 36]. In a landmark publication which gained credibility for the inclusion of spiritual well-being assessment within the broader evaluation of quality of life (QOL) issues in psycho-oncology research, Holland and her co-workers (Holland et al., 1998) developed and published the Spiritual Beliefs Inventory. Unlike previous spiritual well-being inventories (e.g., the Spiritual Well-Being Scale in Paloutzian and Ellison, 1991) used in health-related research (e.g., Carson & Green, 1992; Kaczorowski, 1989), the SBI does not rely exclusively on spiritual and religious beliefs, but also includes a social support measure derived from involvement with church or religious groups. The result of their efforts is a well-validated 15-item questionnaire that is a brief, yet robust, measure of the more universal aspects of religious, spiritual, and religious community social support coping with a life-threatening illness as well as the subsequent QOL impact. Also included was the Paloutzian and Ellison 20-item Spiritual Well-Being scale (SWB) that was developed to look at just spiritual and religious beliefs [37]. For both instruments, a higher score indicates a stronger sense of spiritual wellbeing.

Bottomley Social Support Breast Cancer Scale [38,39,40]. This is a cancer-specific questionnaire that is well validated in the clinical cancer-care context and also quick and easy to use in a busy clinical environment. The Bottomley Social Support Scale has good construct validity with the Hospital Anxiety and Depression Scale. It is reliable, allowing medical and support staff to assess the levels of social support and implement any appropriate social support interventions and sensitive to the duress of breast cancer treatment and care [41]. The higher the score, the less the perceived social support on the part of the respondent.

Automated Neuropsychological Assessment Metric (ANAM) [42]. This is a computerized neuropsychological assessment battery developed by researchers at the Walter Reed Medical Center for use in human performance factor studies (e.g., neuropsychological effects of fatigue, chronic stress, sleeplessness, toxic exposure). It takes about 45 to 60min to complete for the average adult. The components of the assessment are derived from well-validated brain/behavior tests such as those encompassed in the Halstead-Reitan Neuropsychological Assessment Battery and the Wechsler Adult scales for both intelligence and memory. The principal measures that we were taken from this assessment pertain to executive functioning and problem solving (Tower of Hanoi Task, Symbolic Logical Reasoning Test), encoding and memory, and a continuous performance task measure of attentional capacity and response time. Furthermore, the ANAM battery has been validated in the hospital or clinic setting [42,43,44]. For all of the ANAM tests, the higher the score the better the performance with the exception of simple reaction time.

Twenty-five ml blood samples were drawn (210ml Na-heparin, 15ml clot) immediately before the computerized questionnaire and ANAM assessment at each of our four study assessment points. Blood was placed in heparinized tubes and was evaluated for hematocrit (percent of red blood cells) and total plasma protein (g/dl). Standard Wrights staining procedure was used to obtain complete blood counts (CBC). The heparinized samples were then separated into the leukocyte and erythrocyte fractions by Histopaque-1077 gradient centrifugation. FITC-conjugated murine monoclonal antibodies were used to label and measure total T cell count (CD3), helper T cell (CD4+), cytotoxic T cell (CD8+), B cell (CD19+), and NK cell (CD16+) using flow cytometry. Each of these assays was conducted at the Indiana Wesleyan University (IWU) research laboratory facility under the direction of Burton Webb. To accomplish this, blood specimens at room temperature were transported from the Lutheran Hospital Fort Wayne study site (about a 1-h drive) within 24h of the blood draw by an IWU student lab assistant trained in the safe handling of biohazard material, employed by Dr. Webb in his lab on a work-study program. Upon receipt at IWU, the blood specimens were immediately processed and placed in deep freeze frozen storage (70C) for later analysis. Dr. Webb, who at the time taught immunology to first-year medical students at Indiana University-Purdue University Indianapolis (IUPUI) Medical School-Muncie, supervised all immunology specimen processing and assay procedures directly in his laboratory at Indiana Wesleyan University, Marion.

Neuman and colleagues documented a relationship between immunological response and mental health [45]. A protocol similar to theirs for assessing the integrity of immunological response as it relates to psychological, emotional, neuropsychological, and spiritual well-being in the breast cancer patients was used. Blood samples were drawn immediately before the ANAM (computerized neuropsychological assessment) battery. Blood placed in heparinized tubes were evaluated for microhematocrit % (percent of red blood cells) using a centrifuge; and plasma protein values (g/dl) using a standard refractometer were determined from these samples. A radioimmunoassay kit was used to measure plasma cortisol (a stress hormone emitted by the adrenal cortex) and Toxicity-preventing activity (TxPA) (a serum albumin factor correlated with cardiovascular risk), along with lipid density measures. Standard staining procedures were used to obtain total white blood cells (WBC) as well as specific types of WBC important in combating disease and infections (mononuclear cells or lymphocytes, neutrophils, and monocytes). Fluorescein-labeled murine monoclonal antibodies were used to label and measure CD3, CD4, CD8, CD19, and CD16/CD56 lymphocytes using fluorescence-activated cell sorting (FACS) scan. NK (natural killer) white blood cells were also measured, since these provide protection against cancer cells and are related to blood vessel constriction following a stressor condition (Neumann & Chi, 1999). These assays were completed at the Indiana University Medical School Muncie Center for Medical Education immunology laboratory.

For the newly diagnosed breast cancer group, the first assessment point was at enrollment, within the first few weeks of diagnosis, usually following lumpectomy surgery and just before radiation treatment. The second assessment point was generally after surgery and during or just after radiation therapy, usually about one to 2 months after initial diagnosis for the active treatment group and enrollment for the remission breast cancer survivor group (Fig.1). The third assessment point was at 2 months after treatment had started (after the conclusion of radiation therapy and in the initial stages of chemotherapy if recommended). The fourth assessment point occurred a month following completion of all chemotherapy if recommended. This was usually at the six- to eight-month point for the active treatment group and about 6 months following enrollment for the remission group. The second, third, and fourth assessments occurred 23days after treatment (radiation and/or chemotherapy).

legend. The approximate timing of the 4 principal assessment domains (Spiritual Well-being, Quality of Life, Computerized Neurocognitive Performance, Immunological Biomarkers) is depicted for both the active treatment and remission (breast cancer survivor) groups in the present study. Timing of the assessments coincided with the approximate course of treatment from diagnosis/enrollment (Assessment 1), initial surgery and radiation treatment (Assessment 2), continuation/completion of radiation and initiation of chemotherapy (if needed) (Assessment 3), and completion of radiation and/or chemotherapy if needed (Assessment 4)

For the breast cancer survivor comparison group, the assessments occurred at enrollment, 1 month, 2 months, and at 6 months. The completed surveys and computerized ANAM neuropsychological assessment were completed in a quiet counseling room at the Womens Cancer Center at Lutheran Hospital. Each blood drawn was completed by a registered nurse immediately following the assessments. Specimens then were processed at Muncie Center for Biomedical Education, where immunological biomarkers were assayed using flow cytometry.

Descriptive statistics at enrollment for active treatment breast cancer group and the breast cancer post-treatment (remission) comparison group not on active treatment, were compared using item averages for all questions (reverse coded where necessary) for each of the questionnaire measures (psychosocial, emotional wellbeing, quality of life, spiritual wellbeing, physical symptoms of cancer treatment). Statistically significant differences between the two groups were compared for these measures at p<0.05 using an independent samples Tukey t test (nonparametric). The ANAM neuropsychological performance measures were computed automatically as age- and gender-based standardized scores using the ANAM norms built into the software package for American adults. Adjusting for age and years of formal education at enrollment (diagnosis), partial correlation coefficients were computed for the emotional wellbeing, quality of life, physical and health symptoms, and spiritual wellbeing measures when correlated with the immunology T cell biomarkers (CD4, CD8, CD16) for the active treatment and for the cancer survivor comparison groups separately. The most significant correlations were visually depicted in a scatterplot in the study figures.

Active treatment women were also compared across principal outcomes based on type of treatment prescribed (chemotherapy and radiation versus radiation only). For the active treatment subgroup comparisons (chemotherapy and radiation versus radiation only), an ANOVA repeated-measures analysis was used to evaluate whether a significant group by time interaction effect was apparent, indicating a greater degree of change over time for one treatment subgroup compared to the other. The most significant questionnaire-based (psychosocial support, quality of life, emotional wellbeing, spirituality, physical symptoms) time by treatment subgroup interaction effects was then depicted in the form of visual plot. The same was done with the most significant time by treatment subgroup interaction effect for the immunology biomarkers (CD4, CD8, CD16). IBM SPSS statistical software version 21 was used for all analyses, graphs, and plots [46].

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Preliminary study on the effects of treatment for breast cancer: immunological markers as they relate to quality of life and neuropsychological...

Immunology

Deal Watch: Roche And Vividion Will Investigate E3 Ligases In Cancer, Immunology – Scrip

May 21, 2020 medical

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Deal Watch: Roche And Vividion Will Investigate E3 Ligases In Cancer, Immunology - Scrip

Immunology

Your chances of COVID-19 recovery could be compromised by ‘scars’ left behind by past lung infections | Daily Sabah – Daily Sabah

May 21, 2020 medical

Patients recovering from severe lung infections develop "immunological scars" that stifle their body's immune response and heighten their risk of contracting pneumonia, a common killer of COVID-19 sufferers, researchers said Monday.

Studies in both humans and mice showed that the body's immune response is temporarily switched off after some severe infections, rendering patients more vulnerable to new bacterial or viral diseases.

A team of researchers from the University of Melbourne's Peter Doherty Institute for Infection and Immunity and the University Hospital of Nantes found that the cells that form the immune system's first line of defense macrophages were "paralyzed" after severe infections.

Macrophages neutralize bacteria and raise an internal alarm that sends immune cells rushing to the site of infection. Once the threat is taken care of, the macrophages down tools and the body goes back to running as normal. But by analyzing blood samples from patients who had suffered severe infections, researchers found that their macrophages had been deactivated. This left patients at greater risk of contracting potentially fatal secondary infections such as pneumonia while in the hospital.

Turkey sees around 90,000 people infected with pneumonia annually around 22% of those die. This high rate is attributed to the misuse of antibiotics, which creates the perfect ground for pneumococcal bacteria to resist standard drugs. According to the World Health Organization's (WHO) 2019 report, pneumonia is also fourth on the list of biggest killers worldwide.

Researchers also identified the trigger or "switch" for reanimating the macrophages, a receptor known as SIRP-alpha. This was found to restore the macrophages to their "full capacity."

The team said their findings could influence how hospital infections are treated including rethinking the systematic use of antibiotics, to which superbugs are increasingly resistant.

"We believe an alternative approach is to recharge the immune system to take it out of its paralyzed state or to prevent paralysis in the first place so that patients will be able to protect themselves against secondary infections without resorting to antibiotics," said Jose Villadangos from the Peter Doherty Institute.

"Turning off the newly described switch may be such an approach," said Villadangos, lead author of the study published in Nature Immunology.

The research may have significant implications on how COVID-19 cases are treated in the future.

Most COVID-19 deaths occur due to a cytokine storm, a process whereby the body's own immune response runs wild causing acute and often fatal inflammation.

Antoine Roquilly, from the University Hospital of Nantes, said better understanding the SIRP-alpha and other immune switches that temporarily shut down the body's immune response "may prevent the storm from occurring and improve the survival of these patients."

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Your chances of COVID-19 recovery could be compromised by 'scars' left behind by past lung infections | Daily Sabah - Daily Sabah

Immunology

Interferon therapy may speed recovery from COVID-19 – Reuters

May 21, 2020 medical

NEW YORK (Reuters Health) - Treatment with the antiviral interferon alfa-2b (IFN-a2b) appears to speed up virus clearance and lower levels of key inflammatory markers in patients with COVID-19, according to an exploratory study conducted in Wuhan, China.

This study provides the first compelling evidence of a potential treatment that is approved and we have decades of experience with, Dr. Eleanor Fish of the Toronto General Hospital Research Institute and the University of Toronto Department of Immunology, in Canada, told Reuters Health by phone.

In a paper in Frontiers of Immunology, Dr. Fish and colleagues report the clinical course of 77 adults with confirmed COVID-19 who were treated with inhaled IFN-a2b (5 mU b.i.d), arbidol (200 mg t.i.d) or the combination of both broad-spectrum antivirals. All patients had only moderate illness; none required intensive care or oxygen supplementation or intubation.

Compared with arbidol alone (27.9 days), IFN-a2b treatment, with (20.3 days) or without arbidol (21.1 days), was associated with significantly accelerated viral clearance from the respiratory tract and reduced duration of elevated blood levels of the inflammatory markers interleukin-6 and C-reactive protein, the researchers report.

With IFN-a2b, we achieved accelerated viral clearance by about seven days, which is faster than with remdesivir, and we showed a reduction in circulating levels of inflammatory markers, which really exacerbate disease, Dr. Fish told Reuters Health.

Age, co-morbidities and sex did not negate the effects of IFN treatment on viral clearance times or on the reduction in the inflammatory markers.

This was an exploratory study, but I see absolutely no reason why these exploratory studies should not have relevancy. Very often they are dismissed because they are not the gold-standard randomized controlled trial, which are very difficult to do during an outbreak, Dr. Fish commented.

She and her colleagues previously demonstrated the therapeutic benefit of interferon during the Toronto SARS outbreak of 2002 and 2003. In that study, IFN treatment seemed to speed up the resolution of lung abnormalities in SARS-infected patients.

Interferons are broad-spectrum antivirals that should be considered as first responders for all acute virus infections that are severe, Dr. Fish said. The beauty is you dont have to know the virus. Because they are polytrophic, they target many different facets and stages of a virus lifecycle and in addition they muster and activate immune cells to help clear the virus.

In response to any and all viruses, the very first we do is make interferons. That, if nothing else, should tell you they are important. In addition, viruses have evolved to very specifically block interferon production. So coming in with interferon has the potential to override or swing the balance in favor of the host, she explained.

Dr. Fish noted that the biggest fear with interferon is the potential to generate a cytokine storm, but there is absolutely no evidence of that from the SARS outbreak in Toronto or in COVID-19 patients. If anything, the evidence was in the other direction, that we reduce the inflammatory response. Fear of cytokine storm I really think needs to be put to bed once and for all, Dr. Fish said.

Why inhaled interferon in this study? We went with what we could mobilize quickly and in Wuhan that was nebulized interferon, Dr. Fish said. Its unclear now which route of administration is going to be most efficient. We are doing trials now to answer that.

Dr. Fish also sees a potential prophylactic role for interferon for healthcare workers, others severely at risk, the elderly, the immunocompromised, and post-exposure individuals.

She and her coauthors report no conflicts of interest.

SOURCE: bit.ly/3dZyTzt Frontiers in Immunology, published online May 15, 2020.

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Interferon therapy may speed recovery from COVID-19 - Reuters

Immunology

Study may help to improve diagnosis and treatment of allergies – News-Medical.net

May 21, 2020 medical

Reviewed by Emily Henderson, B.Sc.May 20 2020

Results from a study led by investigators at Massachusetts General Hospital may help to improve the diagnosis and treatment of allergies, pointing to a potential marker of these conditions and a new therapeutic strategy. The research is published in Nature.

Nearly one third of the world's population suffers from allergies. These conditions are caused by certain antibodies--called IgE antibodies--that bind to allergens such as peanuts and trigger a reaction that releases an array of molecules that cause allergic symptoms, and in extreme cases, potentially life-threatening anaphylaxis.

Scientists have been perplexed by the fact that many individuals have circulating allergen-specific IgE antibodies without ever developing allergy symptoms. For example, about half of the people who have peanut-specific IgE antibodies (or test positive to a peanut skin prick test) do not have peanut allergies. In addition, some allergic individuals outgrow their symptoms yet still retain detectable levels of circulating allergen-specific IgE.

To look into these mysteries, Robert Anthony, PhD, of the Center for Immunology and Inflammatory Diseases, and his colleagues compared IgE from individuals with peanut allergies with IgE from individuals without any allergies. The analyses revealed an increase in a particular sugar residue called sialic acid on IgE from peanut allergic individuals.

The researchers also found that adding sialic acid to IgE enhanced allergic reactions triggered by IgE in animal models, while removing sialic acid from IgE dampened these reactions and reduced anaphylaxis.

Our results indicate that quantifying sialic acid on IgE may serve as a marker for more accurate diagnoses of allergic disease, and that removal of sialic acid from IgE is a novel strategy for treating affected patients."

Dr. Robert Anthony, Center for Immunology and Inflammatory Diseases

Additional research on the mechanisms behind sialic acid's effects on IgE activity could provide additional insights into allergies and their causes. The team is currently planning studies to determine how removing sialic acid from IgE attenuates allergy, and develop strategies to exploit this therapeutically.

Source:

Journal reference:

Shade, K.C., et al. (2020) Sialylation of immunoglobulin E is a determinant of allergic pathogenicity. Nature. doi.org/10.1038/s41586-020-2311-z.

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Study may help to improve diagnosis and treatment of allergies - News-Medical.net

Immunology

Focusing on the Genes that Matter Most: 10x Genomics Launches Targeted Gene Expression Solution – GlobeNewswire

May 21, 2020 medical

PLEASANTON, Calif., May 20, 2020 (GLOBE NEWSWIRE) -- Building on its earlier reveal at the Advances in Genome Biology and Technology (AGBT) General Meeting, 10x Genomics, Inc. (Nasdaq: TXG) today launched its Targeted Gene Expression Solution for single cell and shortly following for spatial genomic research. Targeted Gene Expression gives scientists the ability to focus their research on the cell types and biomarkers that matter most to their research, enabling them to answer biological questions quickly and efficiently.

Our Targeted Gene Expression Solution provides customers the option to progress from unbiased discoveries to more focused research questions by looking at a subset of genes of interest, which can increase sample throughput, streamline data analysis, and reduce sequencing and computational burdens, said Ben Hindson, Co-founder, President and Chief Scientific Officer of 10x Genomics. By focusing on the genes that matter most, researchers can ultimately bring better treatments and therapeutics through clinical trials more efficiently.

This approach also captures unique gene expression signatures, probes disease and drug targets and allows for the discovery of mechanisms through which small molecules act. Using this technology, researchers can measure the effects of activation or inhibition of signalling pathways. In addition, it also allows the scientific community to dissect signalling pathways using targeted CRISPR screens.

10x-targeted single-cell RNA sequencing will allow us to focus on the expression of relevant immuno-oncology genes, streamline our data analysis and reduce our sequencing costs, said Aude Chapuis, M.D., Assistant Member, Program in Immunology Clinical Research Division, Fred Hutchinson Cancer Research Center.

10xs Targeted Gene Expression Solution benefits from a list of comprehensive pre-designed gene panels that are relevant for different research areas, including cancer, immunology, neuroscience and various disease and drug targeting applications. This technology is also customizable for individualized research goals, improving experimental efficiency while maintaining high gene sensitivities. A 10x Custom Panel Designer, which will be released later this year, will enable customers to either add on genes to existing panels or create fully custom panels.

Target enrichment of informative transcripts balances costs with biological insight, added Joseph Replogle, Weissman Lab, UCSF, and enables users to easily adapt the 10x Genomics platform to their question of interest."

The Targeted Gene Expression Solution is available for pre-orders beginning today. In conjunction with the announcement, 10x Genomics is offering a webinar to help researchers better understand how their research could benefit from Targeted Gene Expression. To learn more, visit 10xgenomics.com/products/targeted-gene-expression.

About 10x Genomics10x Genomics is a life science technology company building products to interrogate, understand and master biology to advance human health. The companys integrated solutions include instruments, consumables and software for analyzing biological systems at a resolution and scale that matches the complexity of biology. 10x Genomics products have been adopted by researchers around the world including 97 of the top 100 global research institutions and 19 of the top 20 global pharmaceutical companies, and have been cited in over 860 research papers on discoveries ranging from oncology to immunology and neuroscience. The company's patent portfolio comprises more than 740 issued patents and patent applications.

Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements generally can be identified by the use of forward-looking terminology such as may, will, should, expect, plan, anticipate, could, intend, target, project, contemplate, believe, estimate, predict, potential or continue or the negatives of these terms or variations of them or similar terminology. These forward-looking statements include statements regarding 10x Genomics, Inc.s current and upcoming products and solutions, which involve risks and uncertainties that could cause actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on managements current expectations, forecasts, beliefs, assumptions and information currently available to management, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect 10x Genomics, Inc.s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere in the documents 10x Genomics, Inc. files with the Securities and Exchange Commission from time to time. The forward-looking statements in this press release are based on information available to 10x Genomics, Inc. as of the date hereof, and 10x Genomics, Inc. disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing 10x Genomics, Inc.s views as of any date subsequent to the date of this press release.

Disclosure Information10x Genomics uses filings with the Securities and Exchange Commission, its website (www.10xgenomics.com), press releases, public conference calls, public webcasts and its social media accounts as means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.

ContactsInvestors:investors@10xgenomics.comMedia:media@10xgenomics.com

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Focusing on the Genes that Matter Most: 10x Genomics Launches Targeted Gene Expression Solution - GlobeNewswire