Can AlphaFold's breakthrough in protein structure help decode the fundamental principles of adaptive cellular immunity?

T cells are essential immune cells responsible for identifying and eliminating pathogens. Through interactions between their T-cell antigen receptors (TCRs) and antigens presented by major histocompatibility complex molecules (MHCs) or MHC-like molecules, T cells discriminate foreign and self peptides. Determining the fundamental principles that govern these interactions has important implications in numerous medical contexts. However, reconstructing a map between T cells and their antagonist antigens remains an open challenge for the field of immunology, and success of in silico reconstructions of this relationship has remained incremental. In this Perspective, we discuss the role that new state-of-the-art deep-learning models for predicting protein structure may play in resolving some of the unanswered questions the field faces linking TCR and peptide-MHC properties to T-cell specificity. We provide a comprehensive overview of structural databases and the evolution of predictive models, and highlight the breakthrough AlphaFold provided the field.

Beyond the "inimitable" Goffman: from "social theory" to social theorizing in a Goffmanesque manner.

Erving Goffman's status as a great social scientist today seems relatively secure. Many commentators highlight his extraordinary capacities to pinpoint the fine-grained details of human behavior in the "interaction order". But if Goffman's brilliance in this respect was deeply rooted in his various and interlocking personal, existential, social, and intellectual idiosyncrasies, and his intellectual practice is inimitable, the degree to which anyone else could, or should try to, imitate Goffman's intellectual practice today, remains an open question. This is especially so when we consider that such practice was grounded in notably wide reading across disciplines and in world literature, a highly developed analytical manner that was inseparable from a notable literary talent in composing published texts, and an open-mindedness about the gathering of data sources in ways that some today find methodologically much too promiscuous. The paper initially considers these issues: the multiple "Goffmans" that exegetes and commentators have identified; how such persons have claimed Goffman to be essentially of one or more theoretical persuasions; and how various social theorists have drawn upon Goffman's work. It then moves on to argue that a Goffmanesque kind of social theorizing, is not only possible (if difficult) today, but also vital too. Such theorizing insists on the ongoing role of literary-intellectual and metaphorical ways of thinking and writing, at a time when these are becoming apparently less crucial in studies of human interaction. No matter how technologically advanced such studies may become, they still require some of the intellectual and literary flair that Goffman brought to his scholarly doings. Goffmanesque theorizing can inform new insights into various domains, including the very nature of social change.

John Goodsir (1814-1867) and his neurological illness.

John Goodsir, conservator and professor of anatomy at the University of Edinburgh, suffered an unidentified illness described by experts after his death as tabes. The features that led to this diagnosis, the understanding of tabes at that time and its relationship in some cases to syphilis, are discussed. It is concluded that the most likely diagnoses are subacute combined degeneration of the cord as a result of malnutrition or tabes dorsalis resulting from earlier syphilis. The presence of 'lightning pains' leans towards the latter diagnosis but evidence for a means of acquisition of syphilis is lacking. The disadvantages of retrospective diagnosis are discussed.

Charles Bell's (1774-1842) contribution to our understanding of facial expression.

The human face reflects a person's character and emotions, both in health and disease. Charles Bell, published in 1806 Essays on the Anatomy of Expression in Painting in which he stressed the importance of understanding anatomy when studying art. He concluded that emotions were revealed in facial expression and that these expressions were only to be found in humans, not in lower animals. Charles Darwin in 1872 published The Expression of the Emotions in Man and Animals, where he acknowledged Bell's contribution to facial expression especially the role of the nervous system, but questioned Bell's conclusion, that animals were incapable of showing emotions through facial expression. Darwin reasoned that human facial expressions reflected emotions, some from our primeval state, some from habit but most were universal and controlled by an involuntary nervous system, described by Bell, and now known as the parasympathetic system. This paper explores Bell's contribution to the understanding of facial expression. We conclude that his understanding of neuroanatomy along with his artistic ability enhanced our comprehension of human facial expressions, although his theological interpretation of the reason for facial expressions and emotions needs to be seen more in the context of nineteenth century Natural Theology.

Intensive care medicine in smaller hospitals: here to stay.

Intensive care medicine is a relatively new specialty. In developing standards of care, it became apparent that some aspects were not achievable by smaller units. Within the intensive care community, there has been a gradual acceptance that smaller hospitals cannot necessarily implement structures that are used in large hospitals, and that outcomes can be comparable with larger units despite this. The Faculty of Intensive Care Medicine set up a Smaller and Specialist Units Advisory Group to explore this area, and this article initially explains the background and work of the faculty to support and sustain these units. We then move on to look at critical care in the context of the recent emergence of wider work on remote and rural healthcare. Finally, we explore our future horizons and look in detail at the areas where further developments will transform the care of critically ill patients within the smaller hospitals of the next 20 years.

Charles Bell (1774-1842) and Natural Theology.

Sir Charles Bell, a 19th century surgeon, anatomist and artist, was heavily influenced by the religious practice of Natural Theology, a belief which implied that the world is created by an Intelligent Designer. In the 18th century, William Paley, later Rector of Bishop Wearmouth, wrote the seminal book about Natural Theology. Charles Bell who practised in London and Edinburgh used his artistic skills to underline his teaching of anatomy and surgery. Later, Bell wrote one of the eight Bridgewater Treatises on the Hand. Bell went on to illustrate the final edition of Paley's Natural Theology in which he demonstrated that proof of Design were to be found in the animal frame, reflecting his earlier work on art and human structure. It is concluded that Charles Bell and William Paley's ideals were in harmony with each other, holding the same belief about Creation. This paper argues that Bell's understanding and devotion to Natural Theology allowed him to accurately explain function, realism and expression in the human body, all revealing the direct influence of the Divine Creator.

Climate structuring of Batrachochytrium dendrobatidis infection in the threatened amphibians of the northern Western Ghats, India.

Batrachochytrium dendrobatidis (Bd) is a pathogen killing amphibians worldwide. Its impact across much of Asia is poorly characterized. This study systematically surveyed amphibians for Bd across rocky plateaus in the northern section of the Western Ghats biodiversity hotspot, India, including the first surveys of the plateaus in the coastal region. These ecosystems offer an epidemiological model system since they are characterized by differing levels of connectivity, edaphic and climatic conditions, and anthropogenic stressors. One hundred and eighteen individuals of 21 species of Anura and Apoda on 13 plateaus ranging from 67 to 1179 m above sea level and 15.89 to 17.92° North latitude were sampled. Using qPCR protocols, 79% of species and 27% of individuals tested were positive for Bd. This is the first record of Bd in caecilians in India, the Critically Endangered Xanthophryne tigerina and Endangered Fejervarya cf. sahyadris. Mean site prevalence was 28.15%. Prevalence below the escarpment was 31.2% and 25.4% above. The intensity of infection (GE) showed the reverse pattern. Infection may be related to elevational temperature changes, thermal exclusion, inter-site connectivity and anthropogenic disturbance. Coastal plateaus may be thermal refuges from Bd. Infected amphibians represented a wide range of ecological traits posing interesting questions about transmission routes.

Micro-habitat distribution drives patch quality for sub-tropical rocky plateau amphibians in the northern Western Ghats, India.

The importance of patch quality for amphibians is frequently overlooked in distribution models. Here we demonstrate that it is highly important for the persistence of endemic and endangered amphibians found in the threatened and fragile ecosystems that are the rocky plateaus in Western Maharashtra, India. These plateaus are ferricretes of laterite and characterise the northern section of the Western Ghats/Sri Lanka Biodiversity Hotspot, the eighth most important global hotspot and one of the three most threatened by population growth. We present statistically supported habitat associations for endangered and data-deficient Indian amphibians, demonstrating significant relationships between individual species and their microhabitats. Data were collected during early monsoon across two seasons. Twenty-one amphibian taxa were identified from 14 lateritic plateaus between 67 and 1179m above sea level. Twelve of the study taxa had significant associations with microhabitats using a stepwise analysis of the AICc subroutine (distLM, Primer-e, v7). Generalist taxa were associated with increased numbers of microhabitat types. Non-significant associations are reported for the remaining 9 taxa. Microhabitat distribution was spatially structured and driven by climate and human activity. Woody plants were associated with 44% of high-elevation taxa. Of the 8 low-elevation taxa 63% related to water bodies and 60% of those were associated with pools. Rock size and abundance were important for 33% of high elevation specialists. Three of the 4 caecilians were associated with rocks in addition to soil and stream presence. We conclude the plateaus are individualistic patches whose habitat quality is defined by their microhabitats within climatic zones.

Neurology, poetry and the first world war of 1914-1918.

The First World War of 1914-1918 produced a wealth of disability and death and much has been written of this catastrophe for mankind. Prose is prolific and much poetry has been written too, some of it discussed here; it consists of works by healthcare workers and also about the effects of the war upon those who fought and those who were left behind. Some of the work is by neurologists and some deals with the neurological disorders of those who fought.

A coprime blur scheme for data security in video surveillance.

This paper presents a novel coprime blurred pair (CBP) model to improve data security in camera surveillance. While most previous approaches have focused on completely encrypting the video stream, we introduce a spatial encryption scheme by strategically blurring the image/video contents. Specifically, we form a public stream and a private stream by blurring the original video data using two different kernels. Each blurred stream will provide the user who has lower clearance less access to personally identifiable details while still allowing behavior to be monitored. If the behavior is recognized as suspicious, a supervisor can use both streams to deblur the contents. Our approach is based on a new CBP theory where the two kernels are coprime when mapped to bivariate polynomials in the $(z)$ domain. We show that coprimality can be derived in terms of the rank of Bézout matrix formed by sampled polynomials, and we present an efficient algorithm to factor the Bézout matrix for recovering the latent image. To make our solution practical, we implement our decryption scheme on a graphics processing unit (GPU) to achieve real-time performance. Extensive experiments demonstrate that our new scheme can effectively protect sensitive identity information in surveillance videos and faithfully reconstruct the unblurred video stream when both CBP sequences are available.

Electronic bed weighing vs daily fluid balance changes after cardiac surgery.

PURPOSE: The purpose of this study is to establish the validity and reliability of measuring weight in critically ill patients with electronic weighing beds. METHODS: All patients admitted to a private intensive care unit (ICU) after cardiac surgery over a 7-month period were weighed on admission and then twice daily (1200 and 2400 hours) using electronic weighing beds (Hill-Rom, Batesville, AR). For each measurement, nonremovable items were recorded, and an average value was deducted from measured weight. We compared differences in body weights (BWs) between 2 consecutive 12-hour periods with the corresponding fluid balance (FB). In addition, we compared weights obtained with electronic weighing beds with those obtained with a regular calibrated scale on ICU discharge. RESULTS: We obtained data in 103 patients for 414 (75.5%) of 548 of all possible BW measurements. On average, we identified a total of 3.5 kg (SD, 1.4) of nonremovable items on patients' beds. The correlation between 12-hourly changes in BW and FB was weak (r = 0.28; 95% confidence interval [CI], 0.17-0.39), even after correction for insensible fluid losses (r = 0.27; 95% CI, 0.15-0.38) and when only values obtained in intubated patients were taken into account (r = 0.34; 95% CI, 0.16-0.49). Similarly, limits of agreements were wide (95% CI, -3.3 to 3.5 kg). There was also poor agreement between weights obtained on electronic beds and those obtained on the regular scale on ICU discharge (95% CI, -7.6 to 7.6 kg). CONCLUSION: Body weight measured by electronic weighing beds does not seem sufficiently robust or accurate to replace daily FB in ICU. The clinical value of purchasing such beds remains uncertain.

John Bell (1763-1820): brother artist and anatomist.

John Bell, brother-surgeon of Charles Bell, was, like Charles, an outstanding surgeon and a good artist. John was one of the few who illustrated his work with their own drawings in the days before audiovisual aids were available and without the benefit of reliable drawing aids, photography and computer-aided design. Charles, on the other hand, was the better artist and illustrated much of the normal anatomy of the nervous system. Each brother undertook extensive surgery of men who had been wounded in war; John Bell left us his engravings from the textbooks, more numerous perhaps than Charles, but Charles left us a series of oil paintings and watercolours in addition to the illustrations in his textbooks.