CRISPR‐Cas technology accelerates development of fast, accurate, and portable diagnostic tools, typified by recent applications in COVID‐19 diagnosis. Parasitic helminths cause devastating diseases afflicting 1.5 billion people globally, representing a significant public health and economic burden, especially in developing countries. Currently available diagnostic tests for worm infection are neither sufficiently sensitive nor field‐friendly for use in low‐endemic or resource‐poor settings, leading to underestimation of true prevalence rates. Mass drug administration programs are unsustainable long‐term, and diagnostic tools – required (...) to be rapid, specific, sensitive, cost‐effective, and user‐friendly without specialized equipment and expertise – are urgently needed for rapid mapping of helminthic diseases and monitoring control programs. We describe the key features of the CRISPR‐Cas12/13 system and emphasise its potential for the development of effective tools for the diagnosis of parasitic and other neglected tropical diseases (NTDs), a key recommendation of the NTDs 2021–2030 roadmap released by the World Health Organization. (shrink)

Nucleic acid hybridization is being increasingly used in viral diagnosis. Most of the assays described so far for this purpose require the use of radioactive probes. Their replacement by Non‐radioactive assays has many advantages and makes the technique feasible in routine diagnostic work. Non‐radioactive assays have had limited use but their diagnostic value has been demonstrated for a number of virus infections. They have the main advantages of employing stable probes, of avoiding safety hazards and of being easy (...) and rapid to perform with limited laboratory facilities. Their main disadvantage compared to radioactive assays is in having relatively low sensitivity. Improvements in probe construction, in labelling and detecting methods, in sample treatment and in hybridization conditions may well increase their usefulness. (shrink)

Fast and effective detection of the causative agent of malaria in humans, protozoan Plasmodium parasites, is of crucial importance for increasing the effectiveness of treatment and to control a devastating disease that affects millions of people living in endemic areas. The microscopic examination of Giemsa‐stained blood films still remains the gold‐standard in Plasmodium detection today. However, there is a high demand for alternative diagnostic methods that are simple, fast, highly sensitive, ideally do not rely on blood‐drawing and can potentially be (...) conducted by the patients themselves. Here, the history of Plasmodium detection is discussed, and advantages and disadvantages of diagnostic methods that are currently being applied are assessed. (shrink)

What is the origin of individual differences in ideology and personality? According to the parasite stress hypothesis, the structure of a society and the values of individuals within it are both influenced by the prevalence of infectious disease within the society's geographical region. High levels of infection threat are associated with more ethnocentric and collectivist social structures and greater adherence to social norms, as well as with socially conservative political ideology and less open but more conscientious personalities. Here we use (...) an agent-based model to explore a specific opportunities-parasites trade-off hypothesis, according to which utility-maximizing agents place themselves at an optimal point on a trade-off between the gains that may be achieved through accessing the resources of geographically or socially distant out-group members through openness to out-group interaction, and the losses arising due to consequently increased risks of exotic infection to which immunity has not been developed. We examine the evolution of cooperation and the formation of social groups within social networks, and we show that the groups that spontaneously form exhibit greater local rather than global cooperative networks when levels of infection are high. It is suggested that the OPTO model offers a first step toward understanding the specific mechanisms through which environmental conditions may influence cognition, ideology, personality, and social organization. (shrink)

Study of the multiplicity of interactions between invertebrate hosts and their parasites helps to define the aspects of the host immune systems that have ecological and evolutionary significance. Such study, however, reveals how much is yet unknown. For instance, the costs of mounting an immune response, the nature of the long-lasting protection sometimes attained, and the high degree of specificity observed in certain hosts are phenomena that still await full explanation. An additional puzzle is the high degree of specificity achieved (...) in light of the apparent low degree of specificity in the recognition and effector mechanisms of insect immune systems. Furthermore, while protective immunity is typically associated with vertebrate adaptive immune systems, invertebrates may have analogous capacities, whose nature is still largely unknown. This review will illustrate how the traditional host-centred view of immune defence can be usefully extended by taking account of parasite immune evasion strategies and the variation that such strategies create in the observed outcomes of infection. BioEssays 27:1026–1034, 2005. © 2005 Wiley Peiodicals, Inc. (shrink)

The versatile clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system has emerged as a promising technology for therapy and molecular diagnosis. It is especially suited for overcoming viral infections outbreaks, since their effective control relies on an efficient treatment, but also on a fast diagnosis to prevent disease dissemination. The CRISPR toolbox offers DNA‐ and RNA‐targeting nucleases that constitute dual weapons against viruses. They allow both the manipulation of viral and host genomes for therapeutic purposes and the (...) detection of viral nucleic acids in “Point of Care” sensor devices. Here, we thoroughly review recent advances in the use of the CRISPR/Cas system for the treatment and diagnosis of viral deleterious infections such as HIV or SARS‐CoV‐2, examining their strengths and limitations. We describe the main points to consider when designing CRISPR antiviral strategies and the scientific efforts to develop more sensitive CRISPR‐based viral detectors. Finally, we discuss future prospects to improve both applications. Also see the video abstract here: https://www.youtube.com/watch?v=C0z1dLpJWl4. (shrink)

Controlled human malaria infection (CHMI) studies involve the deliberate infection of healthy volunteers with malaria parasites under controlled conditions to study immune responses and/or test drug or vaccine efficacy. An empirical ethics study was embedded in a CHMI study at a Kenyan research programme to explore stakeholders’ perceptions and experiences of deliberate infection and moral implications of these. Data for this qualitative study were collected through focus group discussions, in‐depth interviews and non‐participant observation. Sixty‐nine participants were involved, including CHMI study (...) volunteers, community representatives and research staff. Data were managed using QSR Nvivo 10 and analysed using an inductive‐deductive approach, guided by ethics literature. CHMI volunteers had reasonable understanding of the study procedures. Decisions to join were influenced by study incentives, trust in the research institution, their assessment of associated burdens and motivation to support malaria vaccine development. However, deliberate malaria infection was a highly unusual research strategy for volunteers, community representatives and some study staff. Volunteers’ experiences of physical, emotional and social burdens or harms were often greater than anticipated initially, and fluctuated over time, related to specific procedures and events. Although unlikely to deter volunteers' participation in similar studies in furture, we argue that the dissonance between level of understanding of the burdens involved and actual experiences are morally relevant in relation to community engagement, informed consent processes, and ongoing support for volunteers and research staff. We further argue that ethics oversight of CHMI studies should take account of these issues in deciding whether consent, engagement and the balance of benefits and harms are reasonable in a given context. (shrink)

Definitive diagnosis of malaria requires the demonstration through laboratory tests of the presence within the patient of malaria parasites or their components. Since malaria parasites can be present even in the absence of malaria manifestations, and since symptoms of malaria can be manifested even in the absence of malaria parasites, malaria diagnosis raises important issues for the adequate understanding of disease, etiology and diagnosis. One approach to the resolution of these issues adopts a realist view, according to (...) which the needed clarifications will be derived from a careful representation of the entities on the side of the patient which form the ultimate truthmakers for clinical statements. We here address a challenge to this realist approach relating to the diagnosis of malaria, and show how this challenge can be resolved by appeal to Basic Formal Ontology (BFO) and to the Ontology for General Medical Science (OGMS) constructed in its terms. (shrink)

When parasites have different interests in regard to how their host should behave this can result in a conflict over host manipulation, i.e. parasite induced changes in host behaviour that enhance parasite fitness. Such a conflict can result in the alteration, or even complete suppression, of one parasite's host manipulation. Many parasites, and probably also symbionts and commensals, have the ability to manipulate the behaviour of their host. Non‐manipulating parasites should also have an interest in host behaviour. Given the frequency (...) of multiple parasite infections in nature, potential conflicts of interest over host behaviour and manipulation may be common. This review summarizes the evidence on how parasites can alter other parasite's host manipulation. Host manipulation can have important ecological and medical consequences. I speculate on how a conflict over host manipulation could alter these consequences and potentially offer a new avenue of research to ameliorate harmful consequences of host manipulation. (shrink)

The Diagnosis Confirmation Model includes a dual-pricing mechanism designed to support value-based pricing of novel antibiotics while improving the alignment of financial incentives with their optimal use in patients at high risk of drug-resistant infections. DCM is a market-based model and complementary to delinked models. Policymakers interested in stimulating antibiotic innovation could consider tailoring the DCM to their reimbursement systems and incorporating it into the suite of incentives to improve the economics of antibiotics.

In 1960, American parasitologist Don Eyles was unexpectedly infected with a malariaparasite isolated from a macaque. He and his supervisor, G. Robert Coatney of the National Institutes of Health, had started this series of experiments with the assumption that humans were not susceptible to “monkey malaria.” The revelation that a mosquito carrying a macaque parasite could infect a human raised a whole range of public health and biological questions. This paper follows Coatney’s team of parasitologists and their subjects: from the (...) human to the nonhuman; from the American laboratory to the forests of Malaysia; and between the domains of medical research and natural history. In the course of this research, Coatney and his colleagues inverted Koch’s postulate, by which animal subjects are used to identify and understand human parasites. In contrast, Coatney’s experimental protocol used human subjects to identify and understand monkey parasites. In so doing, the team repeatedly followed malaria parasites across the purported boundary separating monkeys and humans, a practical experience that created a sense of biological symmetry between these separate species. Ultimately, this led Coatney and his colleagues make evolutionary inferences, concluding “that monkeys and man are more closely related than some of us wish to admit.” In following monkeys, men, and malaria across biological, geographical, and disciplinary boundaries, this paper offers a new historical narrative, demonstrating that the pursuit of public health agendas can fuel the expansion of evolutionary knowledge. (shrink)

Don't tell terrible stories—everyone here has enough of their own. Everyone here has a whole bloody sack of terrible stories, and at the bottom of the sack is a hammer the narrator uses to pound you on the skull the instant you dare not believe your ears. Or to pound you when you do believe. Not long ago I saw a tomboyish girl on Khreshchatyk Street demand money of an elderly woman, threatening to bite her and infect her with syphilis. (...) Don't stroll through Volodymyr Hill Park, don't stroll around the botanical garden, and especially don't stroll on Kontraktova Square. Don't stroll anywhere. Don't go to the pavilion with the Golgotha panorama near St. Alexander's Church. Not even the twelve-meter-tall crucified Christ will save you. Don't go outside when it's dark and people turn into shadows a shade darker than dark. Also don't go where you can be seen from far away. Not to imply that people used to be like a bunch of lilies, but now they stink like a cellar of cabbage.The city, which earlier might have had some fun, is now going crazy. It's like a fish in warm water: it doesn't react to anything, swims slowly like it doesn't care if it swallows a hook or not. The excitement and exaltation pass into oppression, just as our necks have sunk into our shoulders, our shoulders into our lumbars, our lumbars into our nether regions. The holiday turns into a funeral, the parades into explosions, depression into mania. Winter passes into summer, people turn into beasts, the hours into ages, and the ages into hours. It's worth simply walking around the city to see a soldier from an unknown army taking a piss near the opera. Farther on is a row of identical old widows selling ball gowns and candelabra. Then there are the aristocrats and manufacturers who throw so much at the prostitutes that they'll soon be richer than their wives.I returned late through the Kyryliv Wood, not heeding all the warnings that I myself have given here. It really is dangerous—the place is famous for it. There's a madhouse nearby, caves where criminals and the sick can hide out. Also, once upon a time, as they say in fairy tales, the great dragon Zmei Gorynich lived here beside the Puchai River. The stench in these places drives away the most committed misanthropes and even one type of philanthrope—that is, perverts. It sounds dumb, but the stench is cleansing. I don't know where it comes from. After the operating theaters and the rooms with amputees, the stench no longer repelled or attracted me; it just was. And this was a great place to think. As I walked, I considered an incident with our patient.The patient, a respectable individual whose name carries too much weight for me to state it directly, one day began to assault people. He nearly strangled a merchant who he believed asked too much for a beaver coat. He likewise wanted to kill his business partner when he didn't say hello loudly enough. But the worst was, he lost all shame of his own nakedness. At first it was the police who took care of it. When our future patient slipped off his pants and undergarments, he was taken to Kyrylivska, which has had means for dealing with such cases dating back to the day when unhinged Cossacks and composers from Kyiv Mohyla Academy were taken there.During the examination we determined that the patient was experiencing a severe breakdown. His wife added that lately, more than once, he had allowed himself strong words in front of the children and often suffered from ennui. Furthermore, she said, the patient had been undergoing treatment for “the French disease” for some years—which was, obviously, where we needed to start.“Syphilis!” Skorsky spat out the matchstick he was chewing on. He was a specialist on the psychological aspects of diseases related to the venereal. “Tertiary syphilis! When poorly treated, over time ‘the French disease’ can destroy the central nervous system. Hence the patient's chicanery. Such theater!”Skorsky and I had not spoken since the incident at Bilinsky's. Meanwhile, something significant had happened to him. The most boring person on earth, Skorsky had simply caught fire. He said hello and kibitzed. I even heard the doctor got drunk alone in his office, then wandered through the forest. Could he be using narcotic substances?“Cocaine!” was the doctor's second proclamation. It was his favorite treatment for the psychological complications of syphilis. Skorsky himself never took what he called “the universal drug”—good for alcoholism and toothaches, neuroses and morphine dependency—though he had read in an article by a respectable Viennese physician, who used cocaine as a panacea, that it was not addictive. That doctor subsequently recanted, but Skorsky paid no attention. He believed the retraction was made under pressure from pharmacologists who had no incentive to cease production of the medications that cocaine might supplant. Their representatives either paid or threatened the Viennese to repent.As the patient was escorted to his room, he assaulted the orderly, Alevtyna. They tried pulling him off her, but, though he released his fingers from her neck, he buried his teeth in her leg. The poor orderly, who had not until then been attacked by a psychotic, nearly died of fear. Later, panic set in over Skorsky's diagnosis. He told her about the consequences of syphilis: grotesque patterns on one's face due to infection of the skin, mucous membranes, cartilage, and bones. He went on about the devastation to the central nervous system, which they had just observed in real life: “The face starts to look like lace some mangy dogs fought over before rolling in the mud.”Alevtyna, who had not yet regained her faculty of speech, straightened up. Ignoring the slavering male orderlies, she bared her leg to get a better look at the wound. She then ran down the hall and out into the garden, where she fell on the ground to rip up grass and small bunches of daisies. Alevtyna ate them along with the soil in their roots.“Minor hysteria. She needs fifteen milligrams of cocaine.”Skorsky took a snuff box out of his pocket and scooped up some white powder with a toothpick made from a goose feather. He gave the order to close Alevtyna's mouth and one of her nostrils, forcing her to snort the medication.We fretted over her so long that evening fell. I decided to walk down, along the ravine, behind the church.It was unlikely there were any large beasts there, but something was rustling. The pits and mounds, ravines, paths, graves of witches whose living sisters flew in the treetops from time to time, the whispers of the forest spirits, the spirits of the nutcases who died in the hospital, the spirits of the monks from the St. Cyril Monastery, Zmei Gorynich and the bogatyrs who wanted to defeat him. The city would be calmer without this forest. I saw the gaps between the trees and went off in the direction of the tram tracks.As I was coming out of the forest, there was a patch of Amanita muscaria that had been trampled into porridge. A bit farther on, the body of Professor Bilinsky lay killed in the blackberry bushes. The way he was lying it looked as though he had not struggled before death. I quickly examined his body but saw nothing out of the ordinary. There were no wounds, no dirt under the fingernails. Animals had not yet smelled the carrion, but swarms of various insects covered him. Oh, why did I have to find the putrid body?The best thing would be to take the tram to his house to inform his relatives. The doors closed, and I noticed my own calm. This death had not evoked any emotions in me other than a feeling of responsibility, the need to tell the family. But also—some alarm at the thought of who the murderer could be. I knew that it was murder.“Your nose is bleeding.” A woman as round as an onion, carrying two baskets full of strawberries, offered me an ironed and starched handkerchief.“Have I dirtied my shirt?”“No, it's as neat as a pin. It's just your nose that's dirty. Wipe it now before you spray blood on my strawberries.”“No one will see the red on red.”“Ah, but it's salty!”“You know why it's not sweet? We'd drink it like syrup.”“Those with Christ in their heart do not talk that way.”“Are your strawberries expensive?”“Why? What?”“I'm checking to see if you have God in your heart.”“Child, if you knew how I have to work for this berry! I have to weed it a hundred times. In a week, the quitch grass grows as high as a horse. And I water it with water I carry from the stream, it kills my arms... ”“How much are the berries?”“They're not for sale. Anyway, soon money won't mean a thing. Soon all money, all these papers made from the skins of sinners on their satanic presses will be annulled. What matters is how we treat each other.”“So if I try your strawberries for free, my ‘thank you’ will be enough?”“Hands off!” she said and thwacked my fingers.I heard loud laughter behind me—same laughter as from the café near the Continental. There was no one sitting near Alina. (This is what fate looks like, remember.) Without asking, I sat next to her, away from the old lady.“Excuse me, but the night before last didn't you, yes, didn't you intrude on my privacy?” She started right away.“I saw it a little differently. Who was that young man with the mustache who paid me for you?”“Are you checking to see if you can flirt?”The tram stopped. People got on and off.“Are you coming back from the hospital?” she asked. “Don't be shocked. My uncle works there. He's told me all about you.”“An uncle by the name of Skorsky?”(Remember: this is what fate looks like.)“Yes. Skorsky's been strange recently—says things that make me wonder if he hasn't lost his mind. Have you noticed anything?”“I don't know.”“You know perfectly well.”“Where are you going?” I tried to change the subject.“I have to send something to my theater friends in Odesa. By the way, they'll be putting on Oedipus Rex soon in Kyiv—in Ukrainian.”“Greek tragedy in Ukrainian! That's a first.”“Exactly. The troupe is rehearsing now in Odesa. The theater where they will perform this fall is being remodeled.”“Wait. Now I remember where I've seen you before—it was at a performance! Vynnychenko's Black Panther and White Bear, at the Bergonier on Fundukleivska.“The same director is doing the Oedipus. He's my friend.”“He's your friend in what sense?”“Again with that tired subject. By the way, I've been thinking about you.”“And I about you.”“That's good. I was thinking not about you, to be precise, but about that elevator you invited me on.”“Who was that man with you?”“Like a broken record! Even if he had been my fiancé, I'm not bought or inherited. I'm not a brooch or a hundred acres of land, and I'm not a house in Kaniv!... Who was with you when you saw Black Panther?“Ah, so.”“Answer!”“That was my mother. She looks very young. She is coming to Kyiv the day after tomorrow. I can introduce you.”“Oh, this is my stop.”I looked out the window and realized that I had long since passed the stop for Bilinsky's.“Can we see each other again?”“We can. But you have only one chance.”Alina the anarchist wrote something on a scrap of paper and handed it to me.Morning, not morning but a thick porridge (I hate porridge). Dew, thick spit, crushed fruits, urine, all on the sparkling cobblestones. The sun, just barely having made its appearance, is already scorching. The human masses scurry and grumble like poorly digested food inside a stomach.I walked diagonally across St. Sofia's Square, then along the perimeter, then one edge, then again diagonally across. I went underground. The basement café of the Continental Hotel was practically empty. I again asked the server to bring the cloth with the embroidered portrait, but I couldn't remember the musician's last name, only that it ended with -sky. The server said that -sky was currently in the southern cities of Yalta and Odesa. I added that Kurbas, the director, Alina's friend, was also in Odesa, rehearsing Oedipus Rex, and that he'd previously put on Black Panther.I was bored, so I walked along Khreshchatyk and then headed down, calling to mind all the Kyiv churches of Podil: there's Birth of Christ, St. Nicholas on the Shore, Intercession, Pyrohoshcha, Holy Presentation, St. Dymytrii Rostovsky, St. Illia's. And also the Epiphany Brotherhood Monastery, Ascension Convent, and St. Katherine's, all these whipped-cream churches on the waffles of our streets. A few of them reminded me of themselves by appearing suddenly out of nowhere.The smells on Kontraktova Plaza where commerce buzzed were like multicolored light bulbs turning on one after another. Here you could catch the aroma of Balabukha jam, which blended with the next smell, English shoe polish at the Raiskys’ shop. Then the crunchy-smelling cabbage from old women standing in a row like herons and spitting out the shells of sunflower seeds. Farther on, the stench of a good-sized rat that crawled under Mrs. Shevchuk's shop where she sells broadcloth. Oh, she can't scream: no, she'll quietly dig that rat out herself so as to not scare off her clients.I bought a paper and two pairs of underwear. I asked two laughing young chambermaids who were secretly puffing in a grape-filled yard for a smoke. I wandered around Podil until evening when I came across a sawmill near the Dnipro that surprisingly smelled pleasantly of mazut fuel oil. The weather was dry, yet in the middle of the road was an enormous puddle, a deep dark black. A forty-year-old woman in a pale pink dress stood near it. The theatricality of it all provoked me to pose her a question,“Ma'am, what should I do?”But she paid me no attention. I shouted,“What should I do?”“What to do, what to do?” she said in Polish. “Jump in the water and swim so far away that you cannot return.”I quickly crossed a section of the forest. The wind brought a mixture of unpleasant air, like a stinky handkerchief held under one's nose. Passing the trees, I saw light in the spaces between them and exited at the hospital.Outside the windows, two orderlies lay in chairs with their heads thrown back. Two others—fools—ran around the yard in different directions, peering out at... something. The lights on the first floor of the hospital were on, and the staff milled about.“You're just in time!” said Ivan, a tall, young orderly.“For what?”“Your patient ran away! We went into his room and he wasn't there.”“What patient?”“The one who bit Alevtyna,” said Danylo, the other orderly, short and middle-aged.“That's Skorsky's patient, not mine.”I had no intention of helping them. This was all history—like my family, Kyiv, and my previous life. I had no intention of thinking about it. I wanted to go to my office, pack up my field surgery kit, and get out. So what? Their psychotic syphilitic ran away—it happened.Of course, that patient could have something to do with Bilinsky's murder. But that was no longer my problem.“What a strange coincidence!” the doctor on duty said. “Comrade doctor, the other one responsible for this patient was just here.”“And where is he now?”“He took off toward the church to look for the patient.”“Didn't the patient escape earlier?”“Don't know.”“How do you not know? You had better call the police, moron, before he kills someone. And get those sleeping orderlies to look for him.”“They can't... ”“Why not? Should I go wake them?”“They're on morphine.”“And you, I can see, have lost your mind. Go, catch your psycho! If it turns out that he killed Bilinsky—and on your watch—you can't imagine what's in store for you.”I adjusted my homburg and set off in the direction of St. Cyril's, that unwelcoming monolithic cube. I glanced around—what if our escaped syphilitic were to jump out of the bushes and bite or strangle me. I looked around because I wasn't sure of my actions, wasn't sure of my choices. Tripping over a clump of clover, I reached the open doors of the church. I couldn't stop myself from going in.The walls and ceiling were covered with frescoes. There was what used to be an angel rolling up the sky on the southern column of the narthex. But also graffiti: people scratched their names on it so as not to be forgotten—their idea of eternity. Prince Volodymyr the Great compared this activity to the desecration of graves. The vandals paid a fine and were beaten with canes. During the raids of Batu Khan, the church was deserted and cracks appeared all over it. Wild martens and feral dogs sought shelter here; insects swarmed under the ceiling with its red mosaics. Birches grew in its midst. Water seeped in the cracks, the water became ice, the ice widened the cracks, more water seeped in the cracks, becoming more ice that further widened the cracks, the wall split and nearly fell over, and then the wall fell over. Yet the angel is still rolling up the sky... When I reached the exit, I heard a rustling behind me. I turned after I stepped outside: in the depths of the church, like a stick in a pot of tar, stood a man with a large bag thrown over his shoulder and a revolver pointed right at me.“Is that you, Doctor?“Don't move!”“What's... Skorsky, what's with you?”“Don't move, I say!”“What are you doing here?”And finally I understood... Skorsky was himself the psycho! (Really, I had known for a while.)“You are the murderer! I knew it! But—why?”“Shut up.”“It was you. You! The stolen cigarettes, the strange behavior, Bilinsky. If I shout, everybody will come running. They've already called the police!”There was heavy breathing behind me. And then a gun rang out.The city is overgrown with new buildings. They encircle everything that was once on the periphery. Kyiv has become an old lady that can no longer restrain herself in the face of pastries. The city climbs farther. It steps over the swamps, turns the old rivers into a series of lakes; the other bodies of water it drives into canals. The grain that falls from the wild wheat is black. When the sun heats it, the grain melts and trickles into the earth. St. Cyril's stands indestructible. No one spackles the small cracks in its walls with either expensive putty or glues, nor with cheap cement and whitewash. One day a small fox appears in the doorway. It runs inside and along the floor of simple gray tiles. The gods watch from the walls, watch and fall into ruin. The fox runs to the iconostasis. Before it is a time-darkened Virgin Mother and Child in oil on sheets of zinc. The fox runs the metal steps that wind up to the second floor. The fox runs past all the vaults, naves, all the frescoes. A buckthorn seed flies in through a broken window. It will be the first. Soon the buckthorn will grow everywhere. A dumb hare will make its nest in the buckthorn bushes and nightingales will settle in the upper branches to sing until the end of the world. The fox runs between the thick rays that penetrate the windows. It catches one of the rays, squints its eyes, and warms itself in the sun.The shot rang out, but I did not fall. I looked around—and on the church threshold was our syphilis patient bearing a rod. His head lay on the rocks by the doorway.“If only he'd been at the stage of nose deformity! Just imagine: a hole instead of a nose plus a hole from the bullet—like an extra pair of eyes!” Skorsky laughed at the corpse.“We need to call the orderlies.”“They heard the shot. They'll run here on their own. You see, Professor Bilinsky believed it would take two or three years to wrap up this patient's case,” Skorsky told me. “But I took care of it much faster!”“Excuse me, but I'm going crazy in this city. I thought that you were Bilinsky's murderer.”“Just so. Why not? I am Bilinsky's murderer.”“Don't tease. You've changed a lot recently, so... ”“Yes, I've started killing people. You might term such a change significant.”“You have the right to irony.”“I am not being ironic.”“Let's call it sarcasm.”“It's the honest-to-God truth.”“And yes, you have the right to mock me.”“Well then, let's be done. To the horses!”“What horses?”“Alina's waiting!”Alina, her uncle Skorsky, a few others I didn't know, and I rode like the wind that ripped off my homburg and carried it back to Kyiv.“There's a fresco in the choir loft at St. Cyril's where Vrubel painted himself and patients from the hospital as the apostles. When I came across it by accident, I really believed they were saints,” Alina said.“I've never been up there. I've only seen the church from below.”“Remember the way back so you can see it sometime.”“The Puchai River used to flow here. You shouldn't trust the landscape,” Skorsky said, reaching for something, perhaps his bag, just when we left the darkness of the trees and saw the endless steppe ahead of us.We rode all night without stopping. Though no one was chasing us. Though we had nowhere to be. We rode like beasts released from a cage. The promises of the horizon turned what we'd left behind into a cage fit for those from whom freedom had been severed, like an anomaly, at birth.The pre-morning sky looked at first like a sack of turnips—filled with something heavy. But with each verst, the sky became lighter. When it was finally light enough to see clearly, we arrived at a knoll at the foot of a stone wall that from a distance had appeared to be a gigantic piece of halva. The exterior ruins of the castle gave no hint of how it was when all was fine here, when people defended themselves successfully from the nomads’ raids. From far off, the wreckage looked like a natural agglomeration of stones—a rocky elevation, no more: a cluster of cliffs. It would rain a few hundred more times, a few hundred more winds from a few hundred directions would blow on this heap, and it would collapse as though nothing had ever been here.A few stalks of wheat grew from one of the rocks. Someone had probably cast a handful of grain here for some birds that forgot to eat it.“Who could this castle belong to?” I asked Skorsky.“I reckon the Swan Princess,” the doctor rejoined, hoping to sound knowledgeable.From behind one of the piles of gray sandstone emerged a young man in a black reptilian coat and a white papakha as lush, bright, and out of place as a dahlia. His name was Artem. The heat was melting our brains, but he was dressed like that, in rooster fashion, which was popular among the otamans. Artem helped Alina dismount her horse and tried to kiss her on the lips, but she offered him a cheek instead.Had she been racing to see this clown?We entered the yard—the ruins had fashioned an internal space that was more or less protected, at least from strangers’ eyes. It turned out that there were even places where it was possible to hide from the rain, and from there the ruins didn't look half bad.In the center of the court was a table, and on it a wooden bucket with pink gladiolas. How romantic! It all looked like it came from outer space. Where on earth, in the middle of the steppe, far from any village or town, did this table, this simple table, come from? And the gladiolas? The steppe hadn't been plowed in so long that any cultivars would have gone wild, degenerated, dried up completely.A campfire crackled nearby—a little preview of what we would soon do to the houses, villages, and cities. Artem the otaman brought over a cezve from the fire and poured the first portion into a small, copper cup for Alina. He also got out a porcelain cup with images of rosy cherubim—but how...?“Who else would like coffee?”Only Skorsky and I responded. The question excited me, even distracted me from the thought of the kiss I had recently witnessed and the Kyiv I had recently left.“It's obvious who the professors here are; cultured people drink coffee. Are you both doctors?”“Uh-huh.”“For wolves of the steppe, like us, doctors are gold, even more precious than gold. Actually, a Hippocrates like you should eat more, because those in your profession will soon be worth your weight in gold. Work on your figures, both of you.”“Who will take pity on the horses that have to carry us?”“We'll find the horses. And very large doctors can be transported on machine-gun carts. We'll need to seat the otamans near you. Only a fool would shoot at a doctor.”“I think we'll find quite enough fools here.”“With your beard, Doctor, you look like Tsar Nicholas II. But even so you won't be shot. You might even be canonized!”“We've only just arrived and you're going on about executions,” Skorsky grumbled and checked to make sure that he still had his bag.“Apologies, apologies, pardonnez-moi. But you are not merely a doctor. A venereologist! Skorsky, you're a specialist! A venereologist is the most important person in wartime. The most valuable! You are the botanists of war. You can't imagine what varieties of flowers grow here, and these beds have long awaited a proper gardener. Or even just a man with a scythe!”“Bite your tongue,” Alina said. “I don't need to listen to this.”“Yes, yes, of course. Excuse me, my r—. ” He almost said “rose.”We rested all day. We went down to a surprisingly close river overgrown with lilies. We rowed the boats left by fishermen. I talked to Skorsky. He took his bag everywhere, refusing even to swim so he wouldn't have to part with it. I asked him what he had in it, but he said it wasn't my damned business.Alina rowed with the otaman to the middle of the river. They were having a loud discussion. She was waving her hands. The current carried their boat downstream slowly and smoothly. What a nuisance, that current!I tried to meet with Alina one-on-one, but she was avoiding me. In the morning I was confused, by lunch I was sad, and after lunch I got angry.In the evening, I lay on the hot grass and drank another cup (I have no idea where they got such good coffee), which had no effect at all on my sleep. I watched the Perseids. Every year, the Earth passes through the tail of Comet Swift-Tuttle. People can see the meteor shower and make a wish. I wished. I counted forty-seven falling stars. All forty-seven of my wishes were for the same thing.Around the campfire, they were sitting, talking. I saw how he tickled her face with a piece of grass and she brushed him off in annoyance. Then they were screaming at each other. Later they again spoke kindly, after which they again quarreled. My joy grew after each tiny mistake that Artem made. I wanted him to show the worst he was capable of.They were screaming at each other, but all I could hear was beautiful opera singing. The stars fell to the sound of their screaming. The stars blessed my joy.Then this happened: Alina kicked the fire, scattered burnt kindling, and burned some of the grass. Artem grabbed her by the arm, but she broke away from him and ran off to the horses.“Go then! I guarantee you'll get to Katerynoslav and return with your tail between your legs.”“I'm going to Huliai-Pole! To Father Makhno!”I jumped up and ran after her.“Where do you think you're going?” Artem shouted.Really—where was I going? I was going after her: to Huliai-Pole, to Katerynoslav, to Rome, to Washington, to Istanbul, to Montevideo... “Go to sleep,” he said. “Come morning, this coquette will be here, right as rain. We've already been through this show. Tomorrow she'll be right here next to my boot!”... No, she won't.In some sort of shape we entered some town. There were some buildings that were some colors, some trees, some streets, some roads, and some signs. Posts, flustered birds’ nests, echoes, colors, shapes—each of some kind. A wedding procession was coming toward us. If you want to make orange, you need to add yellow to red, and then bam—it's black. If you want to salt the soup, shake in a little, and then bam—two handfuls. You want to say a kind word, and then bam—a punch in the face. I was rocked around like a watermelon on a boat and threw up my breakfast straight into the horse's fluffy mane. Sanko found this hilarious, but I said I'd pulverize him. So Sanko sped ahead.No one knew anything about Alina. The daytime sky was like a poorly washed bowl. The sun was a squashed, rotten apricot. The night sky looked like the sole of a boot to me. The moon was a dirty cheap copper coin that had gotten stuck to the sole. Everything seemed spoiled to me, irrelevant, unnecessary. Without her, this journey was a waste of time.“You'd better stay away from everyone,” Artem said. “You'll infect us with your pining, and pining is worse than the clap.”The wedding procession was before us. The young couple, still utter children, walked so calmly it was as if they didn't see us. As if we were made of a light breeze—our bodies, clothes, our horses and their iron shoes—of the lightest gasses. As if we were visible only to ourselves and the coal-black dog that barked, panting and gasping.The wedding was headed straight for us. We were in the middle of the road, and so were they. We approached each other slowly, a wave going toward a wave. Some ten meters before their indifferent faces, I noticed the color of the bride's eyes. And the coral-colored tulips that fell on the road before her. Round goose eggs on meaty stems, the flowers were falling and falling before her. The bride's eyes were almond shaped.“Hey there,” Artem shouted at me. “Wake up!”I came to and saw the whole village, everyone there, not realizing my group had turned left onto a side street away from the procession. The tulips disappeared—where'd they get tulips in the fall? I was sitting alone on my horse in the middle of the road, and the entire wedding procession came to a stop. I moved to the side, and the throng marched on, cutting off our escape route. We rode a few more meters and came across the synagogue.“You know what, you're right,” said the otaman.“Who is?”“Oleksii is the only one here who's right.”“About what?”Artem turned his horse and raced back. Everyone stood still while he ran his horse into the crowd and began firing his revolver. People scattered in all directions. Artem trotted, cackling like an imbecile. The horse kicked an old guy in the mouth. The man fell, spitting out his gold teeth. We rode up to the commotion and formed ranks, but none of us wanted to join the otaman.The bride stopped in the middle of the street. On both sides were buildings and trees, as well as dust, sky, and sun. She stood still, beautiful, as if nothing had happened. Then she adjusted her garland and walked calmly on.“Well, should we get some sugar now?” Artem laughed, looking at the bride, and off he went toward the sugar factory.It was then I noticed that all of the houses had shutters—fuchsia, blue, ocher—and that all the shutters were closed.We flew toward the dirty building, whistling and shouting. If there had been aesthetes among the otamans, they would certainly have razed the abomination in this field after seizing it. They would have spread soil on top and sown buckwheat. Long live buckwheat!, that wonderful crop. Like hunting dogs hot on the trail, we raced to our defenseless victim, with the baying of hundreds of hounds behind us. The field shook beneath us. We became an artist's canvas, evolving from Realism to Romanticism, Romanticism to Expressionism, Expressionism to Suprematism. If we had been painted in black and white, we would have been splotches (until the ink ran, annihilating all remaining patches of white).Two men stood near the gate—unarmed and undressed, in nothing but their undershirts and boots. Our fervor, our kinship with the elements, our entirety, were all for naught.“Jesus Christ! What bores!” Artem exclaimed. “How boring you are!”“Maybe boring for us, but fireworks for them,” Sanko said, dismounting his horse.“The fear of death engenders creativity,” our otaman—a distinguished philosopher of the early twentieth century, that demonic breed—prophesied.He went on, “Excuse me, but with all due respect, we are not going to search you. Just show us right away where the money is. Why are there so few of you? Don't say there's not much money. I want piles and piles of money! If you don't show it to us, we'll print our own on your skin. Believe me, we will.”We entered the factory grounds. There were no workers, only an enormous mountain of sugar beets that looked like a pile of coal from a distance and a pile of dead rats from up close.“So, did you have a good year?” Artem asked a man in an undershirt.“Not really—too dry.”“Nah, that's fine. You wouldn't have been able to gather most of the harvest this year anyway. There's a fire burning across all of Ukraine, all of Russia. The whole world!”While Artem tossed thoughts like well-chewed sunflower seeds into the crowd, the two men quietly stepped aside and then ran fast ahead to the factory's main hall. The gigantic door slammed shut. The gate was locked behind us! The windows were smashed! The factory roared from inside like a cumbersome machine starting up. Bullets whirred through every window.“Bastards! It's a trap! Quick, after me!”Still on horseback, Artem bounded over to a vast window, low to the ground, and smashed it mercilessly. He broke the frame and jumped inside on his horse. I and a few others followed. We broke into their lair, threw open the doors, and let the other warriors inside.Iron vats of hot sugar were steaming, pipes were clattering; machinery groaned.“Parasites!” Artem gritted his teeth. “I'll get you. I'll get you red sons of bitches. Painted whores!”At the word “painted,” his horse fell to the ground. Lying prone, Artem continued fighting, but the red soldiers wouldn't let him stand. Fighting nearby, I rode over to assist but did not know where to aim. Artem got up, ran forward, and brought his sword down on the head of the closest soldier, all the way to the middle of his skull, to the bridge of his nose. It was like butchering a pig. Artem thrust the sword into the buttock of another who was fleeing and cut off his leg at the bend in the knee.“I'll cut off every last one of your asses! Cut off your asses!” Artem bellowed.A half hour later, the dead were lying, the captured sitting, and the victors doing anything they pleased.“Skorsky, are there a lot of casualties?” I asked the doctor, whose hour it was. I hoped not, because I was too tired to help him.“Just a few. The dead are already dead, and the wounded are not ours.”Though Skorsky rarely asked my help, and though I'd become an ordinary soldier, the doctor in me was still present in the most unpleasant attribute—knowledge. Others saw an eviscerated man, pieces of dusty flesh smeared with clay, soil, sand, and straw. I saw a perfectly formed kidney hanging perfectly from the rest of its body like a child's mitten from its coat. You could try this death on for size. Wear it like a sanbenito of the Inquisition.Artem counted the money and then lay on the floor alongside the gigantic sugar mountain in the middle of the room. From time to time, the crystals rustled as they fell.“I didn't think you'd be such a fighter!” the otaman said without turning toward me. “I thought you'd be healing us. You'd keep to the rear and we'd hide you like a girl. But here you are, in the vanguard, like a lion!”“I got excited,” I told him, choosing not to react to the “girl” part.“’Cause Alina said there was no sense counting on you to fight.”“Really?”“Does that sting?”“Why would it? I'm a doctor—not everyone is. It requires a brain. Unlike waving a sword.”“Yeah, yeah. I gave her gladiolas. We were lying in the boat near that castle, doing all manner of things, and she told me all about you. How you met.”“You were lying in that boat talking about me?”“It was the day before you left Kyiv. You agreed to go with the anarchists so quickly!”“Were you surprised? Doctors make fast decisions.”“But you probably had great prospects. Your parents are rich, right?”“And who are your parents?”“Probably all your relatives fled abroad—bourgeois. Why did you stay?”“What the hell's your point?”“Alina, by the way, died a while ago. Probably.”“Don't jinx her.”“Listen here,” he said, staring at the ceiling. “And listen good. If you have designs on her—dead or alive—it's best you castrate yourself now.”“After you.”“If I want to kill somebody, you know, I just do it.”At last he looked at me. I was lying on the floor nearby and looking in his direction, sweaty and relaxed, my appearance complemented by my disdain for his opinion, his authority, his stupid hat. His everything.Artem raised his arm above his head, stuck a finger in the sugar mountain, and licked it. We both got up. Had I anticipated this turn of events, I would have readied a gift for him. Artem held his revolver. Under my hand I found a knife the workers used for gathering beets: it was a deliberately sharpened arc they sank into the swollen brassicas. I jumped up and quickly stepped around the sugar mountain.Artem's bullet hit a pane and broke the glass.“Not man enough for hand-to-hand?”The otaman shot again.“You should've challenged me to a duel, you romantic!”Encrusted with white crystals, I charged Artem from the sugar mountain. We fell in, and the sugar stuck in our hair, mustaches, nostrils, armpits.The gang ran in to get us apart, then backed off because it had nothing to do with them. By now the sugar mountain had burst its banks. Of the once perfect pyramid, a deformed mound remained.Wounded, Artem fell on the sugar mound, turning the white red.I stood before the gang sugar-coated and holding a bloody hook. The old otaman was drawing his last breath. Blood trickled from the corner of Artem's mouth and streamed from the left side of his breast.“What's the commotion?” Old Roman had just come in.“Be quiet,” the boys told him. And a good thing they did.“You killed him? You killed the otaman!”“Shut your mouth,” the boys told him.“You... ”I slugged Roman's stinky herring mouth. How did that son of a bitch find pickled herring in a sugar factory? My fist was now bigger and stronger than ever before, a steel anvil that could split nails and shatter memorial plaques. The unfortunate man's jaw twisted like an upper millstone that had gone off track from the lower.“Let's get out of here and go to Makhno's camp,” I gave my first order.We galloped so fast the grass burned beneath us. The birds and bugs had no time to fly out of the way; hooves trampled the burrows of rodents who didn't dare crawl out of their holes for a long time after. We raced like no one had ever raced before.The steppe, that sly fox, pretended to be an innocent fool. The steppe said, “I'm like Adam: I don't even know my own name.” But its grass harbored the tracks of thousands of armies and the heels of Herodotus, the crunch of Trypillia vessels, and the smell of Scythian hemp, Roman coins, clay figures of wolf people, the chevrons of Denikin's army, glass from the Chekists’ ruby stars, traces of uranium from flying saucers. I threatened it: “Steppe, show me your layers, or I will burn you, plow you under, flood you.” But it just replied: “I'm like Adam: I don't yet know my name.”I lost geography as if it were a silver coin. It fell out of my pocket and rolled through the feather grass that blanketed the steppe in white foam. The open space ahead was so endless that the whole world might as well have been steppe. If people ended up here from somewhere else, they would conclude they were on another planet. The coin fell and became an argentum, became one with the ring on the hand of the princess who had one green eye and one blue, with the twisted candlestick at the monastery on the other side of the steppe, with melted ingots. It broke down into simpler elements, simpler and simpler yet. The horse carried me spreading the seeds of northern plants to the south, just as southern riders had once brought flowers and weeds to the north. And then I turned back. Just as I had no geography, I had no time. Every night I fell asleep with the thought that the next day I would again race. Through all spacelessness, all timelessness. I exchanged one horse for another, got on a train, on a boat, traversed forty versts on foot—in rain that brought the river up to the road, in heat that overturned cattle. The earth I walked on became mine. Mine was the water in the lakes and springs, clean water, dirty water, enlightened water, contaminated with oil, stinking of algae, of fish that died in wells, stinking of the memory of atrocities, water as clean as broken bread. The water did not become Alina.I was doing this for her: I got the basturma out from under my saddle, sodden with the horse's sweat, sliced the throat of a rich man whose daughter I had danced with at a ball, climbed into a vat of beet juice and took a sugar bath, carried out the expropriation of the savings banks, wiped the sweat from my face with my shirt—and the cloth turned red; I didn't know from what. If it was someone else's blood, I didn't care; if it was my own, even less.We mostly came across Reds. We scraped them up like old red paint on a door in order to repaint the boards black. Black looked better. Red is tasteless, but black has style. Healthy men died before us of myocardial rupture like bunnies found in the nest. The ones whose hearts were sewn of steel wire envied the deceased. Seizing estates, banks, distilleries, and prisons reminded us of gathering in the harvest. If you're too lazy to pick an apple, you can shake the tree; some of the fruit gets bruised when it falls. We seized buildings like we were shaking apple trees. No one picked the fruits, we just shook: shook under the beds, under the tables, behind the curtains. No, there was no picking. We just shook until the red juice spurted from the apples.Near the Khorol River with Father Makhno and me in charge, we captured sixteen machine guns and four cannons, as well as five hundred prisoners who immediately came over to our side. The villagers voluntarily gave us bread and cheese, chickens and kvas. People joined us. The front of the machine-gun cart said “You can't run,” and “You won't catch us” at the back. We took factory after factory. Millions of karbovantsi, thousands of poods of sugar, weapons. We smashed the telephone exchanges and captured the telegraphs. We made alliances with some and then with others. Lenin, Wrangel, Frunze, the Germans, Chinese, Australians, Kaiser Wilhelm II, Cleopatra, Maria Theresa Walburga Amalia Christina. We ran the steppe. There were a hundred thousand of us. There were three hundred thousand of them. There were three hundred thousand of us. There were a million of them. There were two million of them. We were all of humanity. We were so many that we were none.The nobles’ estates were long ago forsaken. In the people's deepest trunks lay silks and guipure laces that were once perhaps used only to cover a table. Five steps from the barn in the direction of the pear tree, some silver candlesticks are buried; there's a plaster figure of an angel in the chicken coop, covered with shit and feathers.I was reluctant to be going to my home, but I didn't see any way out. Fate intended me to be a different being from the one I was before.Here my grandfathers and great-grandfathers were born. Here the ones who caused my grandfathers and great-grandfathers to flee had stopped. When we were still far off I noticed that someone was in the house. It was our men—Skorsky had brought them here, about twenty in all. I asked Sanko, whom I had walked with side by side more than once, where the doctor was now. All the men answered that he was around somewhere, but I didn't see him that evening.In 1918, the spirit of my great-grandfather Stepan, along with my mother and uncle, had gotten into a britzka and scrambled off to Paris, to Napoleon, against whom my great-grandfather had fought with the Cossacks, to whom the Russians promised to return self-rule. Following him in the cart went the soul of Grandpa Oleh, who lost a finger when he cut down the old linden near the house; his second finger was blown off by a cannonball near Balaklava, and later his entire hand was cut off by some Turk. Next went the spirit of my father, also Stepan, who did not take part in any war but died of measles at the age of forty. They all got the hell out of here. First, they went to Kyiv, led by my mother, Tamara Makarivna, in order to collect Uncle's family and me, their son. And their son, it turns out, has now come back to rob his own home (I didn't drive my war buddies away, did I?). It's a shame that I didn't know where the bathtub was, or whatever they bathed me in when I was small. It would have been good to walk through the ranks of anarchists with that basin and tell them all to spit into it.Remembering every room, I carried Alina upstairs to my mother's bedchamber. There was no longer furniture or pictures, only bare walls. The bed and mattress remained, but that was enough. Mother hated noise, so she set up her room far away from the running in the halls and the creaks on the stairs. I adjusted the mattress; in a gap, looking like a stalk of wheat, there lay a gold bracelet that she lost in the haste and that the thieves could not find in the mayhem. I tucked it into my pocket.The place could still be saved. It was strong, built under the leadership of my grandfather, who knew how to do it right. He built a sawmill, a gristmill, a dress factory (today it's probably been ransacked, maybe even by our own men).Alina had a complete, displaced break in her right fibula. We needed water first. I went downstairs—the guys were dragging out the piano like an old cow to the slaughter.“What are you doing with that?”“Taking it out.”“Why?”“What's it to you? We want to have fun.”“Can you play?”“We're not your bourgeois lily-handed bitches.”They couldn't play, but they were famous at destruction. “Noise is the music of the new time,” one of the smarter among them might have said. “But noise is the opposite of music. Just as a rose is the opposite of your ugly mugs,” I'd have responded if there was anyone to say it to. I could also have said that this was a Bosendorfer grand piano, that it was very valuable—but do the guys not deserve such a luxury?“Why are you so boring? We're relaxing.”“Then let me play a little first.”“Go ahead, but fast. One-two.”So I played. As before. My fingers ran up and down the black and white keys, which weren't simply keys of these, the simplest, colors. These were the keys that remembered my fingers specifically—achieved by that slovenly German Katerina, our governess. She knew a bundle of languages, could play the piano, and was interested in the latest scientific discoveries. But she had not an ounce of sympathy for anyone who couldn't master anything on the first try. More than once she hit my pinkie against the black key that remembered every one of its four thousand touches. She would pound it on the key and shout, “Si bémol! Si bémol,” and later bang my fingers and translate, “B flach! B flach!”I played. I could not expose myself, so the only thing I could do was believe in miracles. What if these coarse men saw value in this bit of furniture so unintelligible to them? And what if they didn't destroy it, this emblem of my childhood, my land, my air, which I could protect in no other way? My air. My water.“Shchedryk, shchedryk, shchedrivochka,” one of them who recognized the tune began to sing along.“Look at you.” They did not expect music from me, who had until recently been drinking blood like water.They said, “Again, again!”A group of curious men gathered around me. They were ordinary farmers, thieves, and recidivists, peasants and workers, everyone except for Skorsky. They needed this music as they needed baths. The music cleansed them from the inside, perhaps. They had not heard anything besides the whistle of a bullet, the neighing of a horse, or the knocking of a chisel and the whirring of a saw, amputating limbs, for a long time.But it could not go on long. I did not close the piano lid, just stood and went to fetch water for Alina, leaving the unfinished song for later. The well was to the north—that is, at the “Head.” My father once promised to give me a compass if I could learn to identify the ends of the earth by means of the sun. And to make it easier to remember, I gave each one of them a name: the east where the day begins was “Right” (my right hand), the west “Left,” the north “Head,” and the south “Feet.” Back when I could still do whatever I wanted all day long, I would wake in the morning and say: I'm going to the Feet. The mound was at the Feet, Left had the river, Right had the forest. It was only to the Head that I rarely went, because a village was located there. When the villagers saw me, they would speak in whispers and avoid the master's son.... I wiped her brow and her burning, sunken cheeks. I lay down next to her to feel the heat of her skin.When the fire in Alina calmed slightly, I went out into our orchard. My father had once been given a gift from Japan—a tulip tree that blossomed with yellow-green flowers. It had to have grown in the time that I was away. It would have been fatal had it been cut down. I again took the stairs down into the drawing room and came across nobody—they had all disappeared in search of food or were hidden away in their burrows. In the middle of the hall, like an opened rib cage, was the piano, irreparably shattered.B Flach! B Flach!Translation © Ali Kinsella 2022. (shrink)

The epidemic of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) has led to many ethical problems. Most studies have focused on the ethical issues faced by nurses who provide care to persons with AIDS (PWA), rather than the ethical issues faced by PWAs themselves. The purpose of this study, therefore, was to explore the ethical issues faced by five HIV/AIDS-infected African-American women. An analysis of interview data revealed that these women deal with four broad categories of ethical issues: (...) diagnosis; disclosure; treatment by, and of, others; and future pregnancies. The results of this study provide an initial description of the ethical issues faced by HIV/AIDS-infected African-American women, and begin to lay the foundation necessary for nurses appropriately to facilitate and support their decisions. (shrink)

Zonulin is a physiological modulator of intercellular tight junctions, which upregulation is involved in several diseases like celiac disease (CeD). The polyQ gliadin fragment binds to the CXCR3 chemokine receptor that activates zonulin upregulation, leading to increased intestinal permeability in humans. Here, we report a general hypothesis based on the structural connection between the polyQ sequence of the immunogenic CeD protein, gliadin, and enteric coccidian parasites proteins. Firstly, a novel interaction pathway between the parasites and the host is described based (...) on the structural similarities between polyQ gliadin fragments and the parasite proteins. Secondly, a potential connection between coccidial infections as a novel environmental trigger of CeD is hypothesized. Therefore, this report represents a promising breakthrough for coccidian research and points out the potential role of coccidian parasites as a novel trigger of CeD that might define a preventive strategy for gluten‐related disorders in general. Also see the video abstract here: https://youtu.be/oMaQasStcFI. (shrink)

The ways in which ethical issues arise in making clinical judgments are briefly discussed. By showing the topography of the role of value judgments in medical diagnostics it is suggested why clinical medicine remains inextricably a value-infected science.

The examination of the complex cell biology of the human malaria parasite Plasmodium falciparum usually relies on the time‐consuming generation of transgenic parasites. Here, metabolic labeling and click chemistry are employed as a fast transfection‐independent method for the microscopic examination of protein S‐palmitoylation, an important post‐translational modification during the asexual intraerythrocytic replication of P. falciparum. Applying various microscopy approaches such as confocal, single‐molecule switching, and electron microscopy, differences in the extent of labeling within the different asexual developmental stages of P. (...) falciparum and the host erythrocytes over time are observed. (shrink)

This study aimed to examine the relationship between anxiety, depression, subjective well-being, and academic performance in Peruvian university health science students with COVID-19-infected relatives. Eight hundred two university students aged 17–54 years ; 658 females and 144 males ; who completed the Patient Health Questionnaire-2, Coronavirus Anxiety Scale, Subjective Well-being Scale, and Self-reporting of Academic Performance participated. A partial unregularized network was estimated using the ggmModSelect function. Expected influence values were calculated to identify the central nodes and a two-tailed permutation (...) test for the difference between the two groups. The results reveal that a depression and well-being node presents the highest relationship. The most central nodes belonged to COVID-19 anxiety, and there are no global differences between the comparison networks; but at the local level, there are connections in the network of COVID-19-infected students that are not in the group that did not present this diagnosis. It is concluded that anxious–depressive symptomatology and its relationship with well-being and evaluation of academic performance should be considered in order to understand the impact that COVID-19 had on health sciences students. (shrink)

HIV remission clinical researchers are increasingly seeking study participants who are diagnosed and treated during acute HIV infection—the brief period between infection and the point when the body creates detectable HIV antibodies. This earliest stage of infection is often marked by flu-like illness and may be an especially tumultuous period of confusion, guilt, anger, and uncertainty. Such experiences may present added ethical challenges for HIV research recruitment, participation, and retention. The purpose of this paper is to identify potential ethical challenges (...) associated with involving acutely diagnosed people living with HIV in remission research and considerations for how to mitigate them. We identify three domains of potential ethical concern for clinicians, researchers, and ethics committee members to consider: 1) Recruitment and informed consent; (2) Transmission risks and partner protection; and (3) Ancillary and continuing care. We discuss each of these domains with the aim of inspiring further work to advance the ethical conduct of HIV remission research. For example, experiences of confusion and uncertainty regarding illness and diagnosis during acute HIV infection may complicate informed consent procedures in studies that seek to recruit directly after diagnosis. To address this, it may be appropriate to use staged re-consent procedures or comprehension assessment. Responsible conduct of research requires a broad understanding of acute HIV infection that encompasses its biomedical, psychological, social, and behavioral dimensions. We argue that the lived experience of acute HIV infection may introduce ethical concerns that researchers and reviewers should address during study design and ethical approval. (shrink)

This essay argues that stable, heritable, habituated semiotics on one scale of life allows for opportunism, origination, and the solving of novel problems on others. This is grounded in how interpretation is neither caused nor determined by its object, such that success at interpretation simply cannot be defined by any comparison between an interpretation and its object. Rather, an interpretation is a reciprocated incorporation of a living thing and its environment, and successful if it furthers the living, interpreting thing. By (...) applying biosemiotic theory to seemingly disparate studies of parasitic infections, autonomic nervous systems, and social change as well as the classical pragmatic notion that biology, psychology and sociology are disparate approaches to the singular, radically continuous, and perennial question of who am I. I argue that the distinction between voluntary and autonomic behavior is but a ghost of older dualisms, the pseudo-contradictions of matter v. mind, body v. soul, but also self v. not self. Moreover, all such pseudo-contradictions are resolved as scale thick, self-similar examples of semiotic transaction wherein degeneration or habituation on one scale of life allows for generative or novel interaction on another. (shrink)

Schistosomes are intravascular parasitic helminths (blood flukes) that infect more than 200 million people globally. Proteomic analysis of the tegument (skin) of these worms has revealed the surprising presence of glycolytic enzymes on the parasite's external surface. Immunolocalization data as well as enzyme activity displayed by live worms confirm that functional glycolytic enzymes are indeed expressed at the host–parasite interface. Since these enzymes are traditionally considered to function intracellularly to drive glycolysis, in an extracellular location they are hypothesized to (...) engage in novel “moonlighting” functions such as immune modulation and blood clot dissolution that promote parasite survival. For instance, several glycolytic enzymes can interact with plasminogen and promote its activation to the thrombolytic plasmin; some can inhibit complement function; some induce B cell proliferation or macrophage apoptosis. Several pathogenic bacteria and protists also express glycolytic enzymes externally, suggesting that moonlighting functions of extracellular glycolytic enzymes can contribute broadly to pathogen virulence. Also see the video abstract here https://youtu.be/njtWZ2y3k_I. (shrink)

This paper is about the uses of language which the Oxford philosopher of language, J.L. Austin excluded from theoretical consideration in his William James Lectures delivered in 1955 and posthumously published as How to Do Things with Words. Uses of language, such as dramatic, poetic or comedic, are said by Austin to be non-serious, deviant and parasitic upon the everyday normal ordinary language. This leaves literature out of consideration as an etiolation. Derrida, who is not merely a trained philosopher (...) but also one of the finest literary critics of our day, fails to agree with Austin. In his “Signature, Event, Context”, and Limited Inc, he criticizes Austin of “totalization” and “idealization” of the norm or the standard; his inability to see that the parasitic is necessarily inbuilt in the standard. This paper is an attempt at seeing how far Derrida is justified in his critique as there is much that is common between his and Austin’s approaches towards language. (shrink)

I propose the first strictly compositional semantic account of same. New data, including especially NP-internal uses such as two men with the same name, suggests that same in its basic use is a quantificational element taking scope over nominals. Given type-lifting as a generally available mechanism, I show that this follows naturally from the fact that same is an adjective. Independently-motivated assumptions extend the analysis to standard examples such as Anna and Bill read the same book via a mechanism I (...) call PARASITIC SCOPE, in which the scope of same depends on the scope of some other scopetaking element in the sentence. Although I will initially discuss the analysis in terms of a familiar Quantifier Raising framework, I go on to implement the analysis within an innovative continuation-based Type-Logical Grammar. The empirical payoff for dealing in continuations is that a simple generalization of the basic analysis gives the first ever formal account of cases in which same distributes over objects other than NP denotations, as in the relevant interpretation of John hit and killed the same man. (shrink)

© 2014 Taylor Francis. The Centers for Disease Control and Prevention recommends routine human immunodeficiency virus testing of every client presenting for services in venues where HIV prevalence is high. Because older adults have particularly poor prognosis if they receive their diagnosis late in the course of HIV disease, any screening provided to younger adults in these venues should also be provided to older adults. We examined aging-related disparities in recent and ever HIV testing in a probability sample of (...) at-risk adults seeking services in needle exchange sites, sexually transmitted disease clinics, and Latino community clinics that provide HIV testing. Using multiple logistic regression with generalized estimating equations, we estimated associations between age category and each HIV testing outcome. Even after controlling for covariates such as recent injection drug use, older adults had 40% lower odds than younger adults did of having tested in the past 12 months or ever. Aging-related disparities in HIV testing exist among clients of these high HIV prevalence venues and may contribute to known aging-related disparities in late diagnosis of HIV infection and poor long-term prognosis. (shrink)

Influential philosopher Michel Serres’s foundational work uses fable to explore how human relations are identical to that of the parasite to the host body. Among Serres’s arguments is that by being pests, minor groups can become major players in public dialogue—creating diversity and complexity vital to human life and thought. Michel Serres is professor in history of science at the Sorbonne, professor of Romance languages at Stanford University, and author of several books, including _Genesis._ Lawrence R. Schehr is professor of (...) French at the University of Illinois, Urbana-Champaign. Cary Wolfe is Bruce and Elizabeth Dunlevie Professor of English at Rice University. His books include _Zoontologies: The Question of the Animal _. (shrink)

Karttunen observes that a presupposition triggered inside an attitude ascription, can be filtered out by a seemingly inaccessible antecedent under the scope of a preceding belief ascription. This poses a major challenge for presupposition theory and the semantics of attitude ascriptions. I solve the problem by enriching the semantics of attitude ascriptions with some independently argued assumptions on the structure and interpretation of mental states. In particular, I propose a DRT-based representation of mental states with a global belief-layer and a (...) variety of labeled attitude compartments embedded within it. Hence, desires and other non-doxastic attitudes are asymmetrically dependent on beliefs. I integrate these mental state representations into a general semantic account of attitude ascriptions which relies on the parasitic nature of non-doxastic attitudes to solve Karttunen’s puzzle. (shrink)

Epidemiological data suggest that previous infections can alter an individual's susceptibility to unrelated diseases. Nevertheless, the underlying mechanisms are not completely understood. Substantial research efforts have expanded the classical concept of immune memory to also include long‐lasting changes in innate immunity and antigen‐independent reactivation of adaptive immunity. Collectively, these processes provide possible explanations on how acute infections might induce long‐term changes that also affect immunity to unrelated diseases. Here, we review lasting changes the immune compartment undergoes upon infection (...) and how infection experience alters the responsiveness of immune cells towards universal signals. This heightened state of alert enhances the ability of the immune system to combat even unrelated infections but may also increase susceptibility to autoimmunity. At the same time, infection‐induced changes in the regulatory compartment may dampen subsequent immune responses and promote pathogen persistence. The concepts presented here outline how infection‐induced changes in the immune system may affect human health. (shrink)

In the last few years, annexins have been discovered in several nematodes and other parasites, and distinct differences between the parasite annexins and those of the hosts make them potentially attractive targets for anti‐parasite therapeutics. Annexins are ubiquitous proteins found in almost all organisms across all kingdoms. Here, we present an overview of novel annexins from parasitic organisms, and summarize their phylogenetic and biochemical properties, with a view to using them as drug or vaccine targets. Building on structural and (...) biological information that has been accumulated for mammalian and plant annexins, we describe a predicted additional secondary structure element found in many parasite annexins that may confer unique functional properties, and present a specific antigenic epitope for use as a vaccine. (shrink)

This article considers what can be learned regarding the ethical acceptability of intrusive interventions intended to halt the spread of infectious disease (‘Infection Control’ measures) from existing ethical discussion of intrusive interventions used to prevent criminal conduct (‘Crime Control’ measures). The main body of the article identifies and briefly describes six objections that have been advanced against Crime Control, and considers how these might apply to Infection Control. The final section then draws out some more general lessons from the foregoing (...) analysis for the ethical acceptability of different kinds of Infection Control. (shrink)

An additional compartment of vaccinated individuals is considered in a SIS stochastic epidemic model with infection reintroduction. The quantification of the spread of the disease is modeled by a continuous time Markov chain. A well-known measure of the initial transmission potential is the basic reproduction number $$R_0$$, which determines the herd immunity threshold or the critical proportion of immune individuals required to stop the spread of a disease when a vaccine offers a complete protection. Due to repeated contacts between the (...) typical infective and previously infected individuals, $$R_0$$ overestimates the average number of secondary infections and leads to, perhaps unnecessary, high immunization coverage. Assuming that the vaccine is imperfect, alternative measures to $$R_0$$ are defined in order to study the influence of the initial coverage and vaccine efficacy on the transmission of the epidemic. (shrink)

Abstract:Austin’s (in)famous characterization of poetry as parasitical has been subject to many interpretations, from Derrida’s considering it a limit of and a central problem in Austin’s theory to Cavell’s attempt to reintegrate poetic uses of language within the framework of Ordinary Language Philosophy. In this essay, I argue that poetry, rather than being excluded from the realm of the performative, can be considered as a performative dispositif that acts upon ordinary language and, through it, upon our forms of life. To (...) reevaluate poetry, I suggest moving from the ‘parasite’ metaphor (poetry is passively feeding on ordinary uses of language) to a ‘virus’ metaphor (poetry is actively disrupting ordinary uses of language). By building on works of French theorists and poets Christophe Hanna, Franck Leibovici, and Manuel Joseph among others, I explore how poetry reveals the virality of language. (shrink)

Many of the most virulent and problematic eukaryotic pathogens have evolved from photosynthetic ancestors, such as apicomplexans, which are responsible for a wide range of diseases including malaria and toxoplasmosis. The primary barrier to understanding the early stages of evolution of these parasites has been the difficulty in finding parasites with closely related free‐living lineages with which to make comparisons. Parasites found throughout the florideophyte red algal lineage, however, provide a unique and powerful model to investigate the genetic origins of (...) a parasitic lifestyle. This is because they share a recent common ancestor with an extant free‐living red algal species and parasitism has independently arisen over 100 times within this group. Here, we synthesize the relevant hypotheses with respect to how these parasites have proliferated. We also place red algal research in the context of recent developments in understanding the genome evolution of other eukaryotic photosynthesizers turned parasites. (shrink)

This paper investigates gaps in degree phrases with too, as in John is too rich [for the monastery to hire ___ ]. We present two curious restrictions on such gapped degree phrases. First, the gaps must ordinarily be anteceded by the subject of the associated gradable adjective. Second, when embedded under intensional verbs, gapped degree phrases are ordinarily restricted to surface scope, unlike their counterparts without gaps. Just as puzzlingly, we show that these restrictions are lifted when there is overt (...) wh-movement in the main clause, revealing a striking similarity between the distribution of gapped degree phrases and so-called parasitic gap constructions. These findings, we argue, suggest that the theory of parasitic gaps needs to accommodate gapped degree phrases. Specifically, they argue that parasitic constituents are null operator structures—and under the right conditions need not be accompanied by matrix wh-movement. (shrink)

The goal of this article is to present the possibility of using Diagnosis- Related Groups (DRG) in the hospital management process and to analyse the need for business performance management on the part of hospital management staff. The following research methods were used: literature analysis, case studies, and poll analysis. It is not possible to increase the effectiveness of operation of healthcare entities without increasing the importance of IT systems and using DRG more effectively in the management process. Training (...) users in IT and the use of DRGs is important to achieving hospital effectiveness. The increased importance of analyses and planning in a hospital should be reflected in the organisational structure of service providers. Hospital controllers should have a similar role to those present in most companies in other industries. (shrink)

This paper presents a novel argument against intentionalism about demonstrative reference. The term ‘intentionalism’ is used to denote the view saying that the referent of a demonstrative expression is determined by the speaker’s intention. My argument focuses on ‘mismatch cases’, roughly, the cases in which the speaker’s intention determines a different object from the one which appears to be the referent in the light of contextual factors. The opponents of intentionalism claim that intentionalism yields simply incorrect reference predictions in these (...) cases. Many intentionalism defenders claim to the contrary, i.e. that the relevant kind of intention fixes the referent in line with the contextual factors and thus the theory provides correct predictions. I will argue that this strategy is objectionable as the concept of the relevant referential intention is genuinely parasitic on non-intentional accounts of demonstrative reference. (shrink)

Clinical decisionmaking includes reasoning from prescientific or scientific theories, reasoning from uncontrolled or controlled experience, and reasoning based on empathic understanding and moral beliefe. The development of contemporary clinical thinking is discussed, and it is found that successive generations of medical practitioners have had different views of the rationality and relative importance of these modes of reasoning: that which is considered rational by one generation of doctors is sometimes denounced by the next. The author's book, Rational Diagnosis and Treatment (...) , which is an example of clinical thinking in the 1960s and early 70s, is used to illustrate one particular view of clinical decisionmaking. Keywords: rational, clinical decisionmaking, biological theory, controlled clinical studies, empathic understanding, ethical reasoning CiteULike Connotea Del.icio.us What's this? (shrink)

The AIDS epidemic calls for an ethical analysis of conflicting obligations surrounding HIV-infected psychiatric patients and confidentiality, as well as issues that go beyond confidentiality. Although laws pertaining to HIV infection have been enacted in a number of states, these statutes leave much discretion to health professionals. The ethical principle known as "the harm principle" can permit disclosure of confidential information and detention or isolation of psychiatric patients who pose a threat of infecting other patients. From an ethical point of (...) view, however, the circumstances under which traditional protections may be weakened or abandoned remain limited. (shrink)

Global fatalities related to COVID-19 are expected to be high in 2020–2021. Developing and delivering a vaccine may be the most likely way to end the pandemic. If it were possible to shorten this development time by weeks or months, this may have a significant effect on reducing deaths. Phase II and phase III trials could take less long to conduct if they used human challenge methods—that is, deliberately infecting participants with COVID-19 following inoculation. This article analyses arguments for and (...) against such methods and provides suggested broad guidelines for regulators, researchers and ethics committees when considering these matters. It concludes that it may be possible to maintain current ethical standards yet still permit human challenge trials in a context where delay is critical. The implications are that regulators and researchers need to work together now to design robust but short trials and streamline ethics approval processes so that they are in place when applications for trials are made. (shrink)

Whether any property is internal to a particular object may be taken to depend upon the way in which the object is described. Thus it is not an internal property of Scott to have been the author of Waverley , neither is it an internal property of the author of Ivanhoe . But what of the author of Waverley? Is the proposition that the author of Waverley composed Waverley necessarily true? On one interpretation of it it surely is. Even so, (...) one can attach a sense to saying that the person who was in fact the author of Waverley might not have been so. All that is needed for this is that he be capable of being otherwise identified. (shrink)

In this commentary we suggest that Fincher & Thornhill's (F&T's) parasite-stress theory of social behaviors and attitudes can be extended to mating behaviors and preferences. We discuss evidence from prior correlational and experimental studies that support this claim. We also reanalyze data from two of those studies using F&T's new parasite stress measures.

Fincher & Thornhill (F&T) present a compelling argument that parasite stress underlies certain cultural practices promoting assortative sociality. However, we suggest that the theoretical framework proposed is limited in several ways, and that life history theory provides a more explanatory and inclusive framework, making more specific predictions about the trade-offs faced by organisms in the allocation of bioenergetic and material resources.

My purpose in this paper is, firstly, to investigate the relationship of the three passages printed below, and, secondly, to illustrate in passing the curious chain of historical accidents which have prevented the truth about that relationship from becoming common lore long ago.