Summary 1: Microbes are constantly evolving. Laboratory studies of bacterial evolution increase our understanding of evolutionary dynamics, identify adaptive changes, and answer important questions that impact human health. During bacterial infections in humans, however, the evolutionary parameters acting on infecting populations are likely to be much more complex than those that can be tested in the laboratory. Nonetheless, human infections can be thought of as naturally occurring in vivo bacterial evolution experiments, which can teach us about antibiotic resistance, pathogenesis, and transmission. Here, we review recent advances in the study of within-host bacterial evolution during human infection and discuss practical considerations for conducting such studies. We focus on 2 possible outcomes for de novo adaptive mutations, which we have termed “adapt-and-live” and “adapt-and-die.” In the adapt-and-live scenario, a mutation is long lived, enabling its transmission on to other individuals, or the establishment of chronic infection. In the adapt-and-die scenario, a mutation is rapidly extinguished, either because it carries a substantial fitness cost, it arises within tissues that block transmission to new hosts, it is outcompeted by more fit clones, or the infection resolves. Adapt-and-die mutations can provide rich information about selection pressures in vivo, yet they can easily elude detection because they are short lived, may be more difficult to sample, or could be maladaptive in the long term. Understanding how bacteria adapt under each of these scenarios can reveal new insights about the basic biology of pathogenic microbes and could aid in the design of new translational approaches to combat bacterial infections. Summary 2: Long‐lived hydrothermal circulation is now well documented along slow and ultraslow spreading mid‐ocean ridges, even though these settings only receive a moderate and intermittent supply of magma. This challenges the notion that hydrothermal convection must be sustained by a continuously replenished magma body. Here we investigate the possibility of sustaining hydrothermal circulation by infrequent magmatic intrusions separated by episodes of downward propagation of small cracks enabling fluids to tap heat from deep hot rocks. We focus on cracks nucleating from grain boundary flaws in response to the buildup of cooling stresses at the base of the convection system. We develop an analytical model describing the stable propagation of a percolation front and the associated heat transfer through hydrothermal circulation. Convection ceases when thermoelastic stresses can no longer overcome lithostatic pressure and hydrothermal circulation can no longer mine heat from underlying units. For lithospheric permeabilities greater than ∼10−15 m2 and over a wide range of grain and flaw sizes, this occurs within ∼100 kyr to ∼1 Myr from the onset of cracking, after the cracking front has moved by a few kilometers. We validate this analytical prediction by developing two‐dimensional numerical models of porous convection subjected to a lower boundary condition representing the dynamics of the cracking front. These models suggest that moderate‐ to low‐temperature hydrothermal venting in off‐axis, ultramafic‐hosted sites does not require an underlying magma sill at all times, but instead repeated sill intrusions every ∼10–100 kyr, which periodically reinvigorate hydrothermal convection without building a continuous crustal section. Summary 3: As the term “computer” and the processes and effects of technologies in human communication broaden, there is a need to have an accounting of the computer-mediated communication (CMC) subdiscipline. After identifying some of the changes that have occurred in both devices and our theories of CMC, suggestions are offered for how to uniquely situate CMC in the future. Ultimately, this article calls for a realignment of CMC scholarship away from focusing on the technological devices and toward an increased focus on the process, role, and effects of mediation. A litmus test whereby future researchers, authors, reviewers, and editors can help assess whether a study is of CMC or simply uses CMC is offered, and in doing so this work provides a foundation to develop theory and scholarship germane to the context of mediated interaction for the future. Summary 4: In March 2015, Sri Lanka’s then-President Maithripala Sirisena launched the Toxic Free Nation Movement as a long-term solution to a mysterious form of kidney disease (CKDu) now endemic in the island’s dry zone. As part of this strategy, in 2016 the movement worked with farmers in north-central Sri Lanka to cultivate indigenous rice varieties without agrochemicals. Yet, within a year, 80 percent of farmers who experimented with indigenous and organic rice farming had switched back to some form of agrochemically intensive cultivation. In this article, I examine farmers’ narratives of why this happened, demonstrating how the movement’s conceptualization of agricultural harm often missed the forms of accounting most salient for residents themselves. Instead, through their testimonies, residents track how polyvalent relationships with agrarian toxicity mediate (1) vulnerabilities to simple reproduction squeezes, (2) reliance on grain fungibility, and (3) strong but bittersweet attachments to dry zone agrarian landscapes. As a consequence, I document how residents respatialize their knotted relationships to agrarian toxicity to include moments of what I call “agrichemical kinship.” I argue that this optic helps us grasp the ways in which agrochemicals simultaneously erode and enable modes of social reproduction against a backdrop of rural stagnation. Following feminist scholars of toxicity, this article not only reveals intimate, yet undertheorized, connections between the field of toxic geographies and the concept of social reproduction but also dashes hopes of any simple equation between banning agrichemical inputs and enacting health in the wake of CKDu. Summary 5: STUDY QUESTION What are the long-term chances of having a child for couples starting fertility treatments and how many conceive with ART, IUI and without treatment? SUMMARY ANSWER Total 5-year live birthrates were strongly influenced by female age and ranged from 80% in women under 35-26% in women ≥40 years, overall, 14% of couples conceived naturally and one-third of couples starting treatments with intrauterine insemination delivered from that treatment. WHAT IS KNOWN ALREADY Few studies report success rates in fertility treatments across a couple's complete fertility treatment history, across clinics, evaluating live births after insemination, ART and natural conceptions. STUDY DESIGN, SIZE, DURATION This register-based national cohort study from Denmark includes all women initiating fertility treatments in public and private clinics with homologous gametes in 2007-2010. PARTICIPANTS/MATERIALS, SETTING, METHODS Women were identified in the Danish ART Registry and were cross-linked with the Medical Birth Registry to identify live births. Subfertile couples were followed 2 years (N = 19 884), 3 years (N = 14 445) and 5 years (N = 5165), or until their first live birth. Cumulative live birthrates were estimated 2, 3 and 5 years from the first treatment cycle, in all women, including drop-outs. Birthrates were stratified by type of first treatment (ART/IUI), mode of conception (ART/IUI/natural conception) and female age. MAIN RESULTS AND THE ROLE OF CHANCE Within 5 years, in women aged <35 years (N = 3553), 35-39 years (N = 1156) and ≥40 years (N = 451), a total of 64%, 49% and 16% had a live birth due to treatment, respectively. Additionally, in women aged < 35 years, 35-39 years and ≥40 years, 16%, 11% and 10% delivered after natural conception, yielding total 5-year birthrates of 80%, 60% and 26%. In women starting treatments with IUI (N = 3028), 35% delivered after IUI within 5 years, 24% delivered after shift to ART treatments and 17% delivered after natural conception. Within 5 years from starting treatments with ART (N = 2137), 53% delivered after ART, 11% delivered after natural conception and 0.6% delivered after IUI. LIMITATIONS, REASONS FOR CAUTION Birthrates are most likely higher compared to countries without national coverage of treatments and results are influenced by laws and regulations. Information on duration of infertility prior to treatment was not available. Future prospective intervention studies should focus on the role of expectant management. WIDER IMPLICATIONS OF THE FINDINGS Our results can provide couples with a comprehensible age-stratified prognosis at start of treatment. STUDY FUNDING/COMPETING INTEREST(S) This study was unconditionally funded by Ferring Pharmaceuticals and the Augustinus foundation. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: S.S.M. received an unconditional grant from Ferring Pharmaceuticals; A.A.H. has received personal fees from Ferring Pharmaceuticals not related to this work; A.N.A. reports grants and personal fees from Ferring Pharmaceuticals, personal fees from Merck Serono, grants and personal fees from MSD, outside the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER The study was approved by the Danish Data Protection Agency (J.nr. 2012-41-1330). Summary 6: INTRODUCTION: Despite all our dreams and enthusiasm, the essential question of whether our species can ever live permanently in space remains unanswered. The 1975 NASA Ames Design Study on Space Settlements demonstrated how human physiology constrains and determines human habitat design in space. Our scientific understanding about the risks of and standards for microgravity (and rotation rate if centrifugally generated), ionizing radiation, and atmosphere pressure and composition, remains inadequate a half century later. In addition, there are newly recognized physiological challenges to living safely in space, including spaceflight-associated neuro-ocular syndrome (SANS), extravascular hemolytic anemia, and other factors that affect every human cell and organ system. A comprehensive review was conducted to establish what we have learned and what is still required to know about the pathophysiology of long-term space travel and living in space since my first report in 1978. The results determine not only how, but if we can realistically plan to inhabit the cosmos that surrounds us.Winkler LH. Human physiological limitations to long-term spaceflight and living in space. Aerosp Med Hum Perform. 2023; 94(6):444-456. Summary 7: How do human embryos implant in physiological conditions and develop beyond blastocyst stage? Human embryos apply forces during invasion of the matrix, the mural trophectoderm undergoes a quick compaction leading to a fast radial expansion of polar side Human embryos can be cultured beyond blastocyst stage using supplements of animal origin, such as fetal bovine serum. However, two main issues limit our understanding of the implantation of the human embryo. First, human embryos do not express fluorescent proteins, severely limiting the access to advanced live-imaging tools. Second, the animal serums may not represent the physiological peri-implantation conditions of the human embryo, thus limiting the reproducibility of the in vitro experiments. Here we combine label-free multiphoton imaging with media formulations including clinical-grade protein supplements from human plasma unlocking the observation of the human embryo in 3D and physiological conditions We have cultured 150 human embryos from D3 until blastocyst stage and also more than 600 mouse embryos from zygote until blastocyst stage and then transferred them into a 3D implantation platform. All embryos were supplemented with clinical-grade human-derived serum, which is rich in globulins and growth factors, and commercial basal media. The implantation was monitored for 3-to-5 days up until day 11. Traction-force microscopy and molecular imaging was employed to quantify implantation markers. Implantation was measured using our novel version of traction-force microscopy, which reveals the force applied by entire embryos during live-imaging experiments. Multiphoton illumination of autofluorescent molecules allows to reconstruct images of live human embryos on 3D at unprecedented resolution. Key molecular markers for the formation of the epiblast rosette (OCT4), extra-embryonic visceral endoderm (GATA4), extra-embryonic ectoderm and trophoblast (CDX2) and primary yolk sac and pre-amniotic cavity were reconstructed in 3D using high resolution confocal imaging. The implantation of human embryos was visualized in 3D movies at high resolution, during time-resolved experiments and compared to implantation in mouse embryos. Human embryos undergo a remarkable compaction upon attachment of the polar trophectoderm and thereafter they implant by engaging the matrix through many different points (>8). The post-implantation compaction leads to a strong invasion of the polar trophectoderm, digging large holes in the matrix and expanding radially. Some trophoblast cells escape the embryo colonizing the matrix. Human embryos expressed the correct pattern of molecular markers by day 11 of culture. Actin staining and OCT4 expression revealed the formation of a central rosette defining the pre-amniotic cavity. GATA6 expression defined the visceral endoderm and the formation of a primordial yolk sac. Mouse embryos conversely, compact upon implantation of the mural trophectoderm and are less invasive, typically anchoring to the matrix through 2-to-3 points. Post-implantation culture of mouse embryos starting at zygote was possible until the formation and large expansion of the amniotic cavity, which constituted 2/3 of the whole embryo size, corresponding with the initial steps of gastrulation, longer than any previous protocol Transfer of mouse blastocysts back to receptive mothers resulted in birth of viable litter. This study has been performed with human embryos ex vivo using bioengineering technology to implant embryos outside the mother uterus. The bio-compatibility of our serum supplements was validated by live birth of transferred embryos in animal models, but would require further evaluation in clinical trials. Our work stresses the safety and efficiency of supplementing embryo culture and particularly embryo transfer, with human plasma-derived serums of clinical-grade. The correct expression of main molecular markers indicates that this type of supplementation promotes implantation physiologically, which opens the possibility to employ these serums in the IVF laboratory. Not applicable Summary 8: Objective: When own mother's milk falls short, pasteurized human donor milk is recommended as alternative feeding for preterm infants. Donor milk has to meet the highest safety standards, but its processing and storage is expensive. The recommended storage time of pasteurized donor milk is 3 months. The objective of the present study was to determine whether the frozen storage time of pasteurized donor milk can be extended beyond 3 months without compromising its safety and quality. Methods: For this prospective observational study breast milk samples of 34 unique women, collected between November 2014 and June 2015, were provided by the Dutch Human Milk Bank. Samples were Holder pasteurized within 3 months after expression and stored at −20°C. Analysis of both bacterial growth (by inoculation of milk on a blood and a cysteine-, lactose-, and electrolyte-deficient agar) and fat, crude protein, carbohydrate and energy content of milk (analyzed by infrared spectroscopy) was done monthly during the first 6 months and every 2 months thereafter, up to 1 year postpasteurization. Results: Thirty of 306 (9.8%) follow-up samples showed bacterial growth when cultured. None of the samples showed sequential contamination with the same strain up to 8 months of frozen storage. No significant decreases in macronutrients and energy content were observed over 8 months. Conclusion: Pasteurized human donor milk can be stored safely for 8 months at −20°C, without compromising its macronutrient and energy content. This longer storage time will reduce disposal of expired donor milk and subsequently reduce costs. Summary 9: Formation of transplantable reproducible hiPSC organoids can be aided with real-time label-free intracellular spectroscopy. Organoids formed from human induced pluripotent stem cells (hiPSCs) could be a limitless source of functional tissue for transplantations in many organs. Unfortunately, fine-tuning differentiation protocols to form large quantities of hiPSC organoids in a controlled, scalable, and reproducible manner is quite difficult and often takes a very long time. Recently, we introduced a new approach of rapid organoid formation from dissociated hiPSCs and endothelial cells using microfabricated cell-repellent microwell arrays. This approach, when combined with real-time label-free Raman spectroscopy of biochemical composition changes and confocal light scattering spectroscopic microscopy of chromatin transition, allows for monitoring live differentiating organoids without the need to sacrifice a sample, substantially shortening the time of protocol fine-tuning. We used this approach to both culture and monitor homogeneous liver organoids that have the main functional features of the human liver and which could be used for cell transplantation liver therapy in humans. Summary 10: In the future, human-like robots will live among people to provide company and help carrying out tasks in cooperation with humans. These interactions require that robots understand not only human actions, but also the way in which we perceive the world. Human perception heavily relies on the time dimension, especially when it comes to processing visual motion. Critically, human time perception for dynamic events is often inaccurate. Robots interacting with humans may want to see the world and tell time the way humans do: if so, they must incorporate human-like fallacy. Observers asked to judge the duration of brief scenes are prone to errors: perceived duration often does not match the physical duration of the event. Several kinds of temporal distortions have been described in the specialized literature. Here we review the topic with a special emphasis on our work dealing with time perception of animate actors versus inanimate actors. This work shows the existence of specialized time bases for different categories of targets. The time base used by the human brain to process visual motion appears to be calibrated against the specific predictions regarding the motion of human figures in case of animate motion, while it can be calibrated against the predictions of motion of passive objects in case of inanimate motion. Human perception of time appears to be strictly linked with the mechanisms used to control movements. Thus, neural time can be entrained by external cues in a similar manner for both perceptual judgments of elapsed time and in motor control tasks. One possible strategy could be to implement in humanoids a unique architecture for dealing with time, which would apply the same specialized mechanisms to both perception and action, similarly to humans. This shared implementation might render the humanoids more acceptable to humans, thus facilitating reciprocal interactions. Summary 11: Abstract Study question Male recovered from covid19 showed negative impact on sperm quality- are these changes reversible and are antioxidant therapy beneficial to overcome sperm quality changes? Summary answer Oxidative stress created by the proinflammatory cytokine storm by covid19 virion might interect with spermatozoa to cause changes in spermiogram and antioxidant is the treatment What is known already Covid19 virion might interect with human spermatozoa and disrupt male fertility. Suppression of semen volume, progressive motility, morphology, sperm number and DNA integrity as a result of covid19 infection were correlated with markers of oxidative stress and inflammation. Sperm DNA damage is the key feature of the disease but the effect on semen quality seem to subside with the passage of time although further studies are needed to substantiate this point. My study is to determine whether the proposed antioxidant treatment to restore the negative impact of covid19 on sperm vitality is beneficial or not. Study design, size, duration The study included 20 male aged 20-45yrs among those couples who were undergoing infertility treatment at Shristi Healthcare between April/2020 to October/2020 with a positive covid19 test and has recovered from the disease atleast 3-5months earlier and who had undergone spermiogram test before the onset of the disease. Semen samples were taken3-5months after recovery from covid19 and after 3 months treatment with antioxidant(CoenzQ10/300mg). Participants/materials, setting, methods Inclusion criteria: precovid normal spermiogram, with mild to moderate covid symptoms without hospitalisation. Exclusion criteria: those with precovid oligospermia or azooospermia, h/o steroid therapy for covid, h/o hormonal drug use that could affect spermiogenesis, with severe covid symptoms requiring ICU treatment. Time between last negative nasal swab test to semen analysis was 120-150days. Antioxidant(CoenzQ10/300mg)given as once daily dose for 3months after recovery from covid and semen test reviewed after treatment and compared with precovid data. Main results and the role of chance The mean age of participants were 30.4±4.8yrs and smoking status, BMI, medical history, presence of varicocele were recorded. Semen samples were processed according to WHO guidelines(2010, 5th edition). Statistical analysis was done by paired t test for paired samples and p value <0.05 was considered statistically significant. When semen samples before and after covid19 were evaluated, it showed marked decline in sperm volume/ml(precovid 3(2.5-3.5) to postcovid 1.5(1-2), p < 0.005); total sperm count x10^6per ejaculate(precovid 42(25-65) to postcovid 5(1-10), p < 0.005); progressive motility% (precovid 55.1±21.7 to postcovid 15.1±5.7, p < 0.001); sperm morphology%(precovid 45(30-60)to postcovid10(5-25), p < 0.001).After 3months CoenzQ10/300mg treatment semen showed significant improvement in all 3 parameters eg sperm count (3.15±3.38-20.9±2.11, p < 0.001), sperm motility(5.25±3.25- 42.85±3.30, p < 0.001) sperm morphology(7.81±2.26- 25.89±7.05, p < 0.001). All previous studies about postcovid semen changes used normal male as reference but strength of my study was precovid semen profile of same participant was available as a reference point. It was seen that fertility of male restores between3-6months postcovid with antioxidant treatment and can resume planning pregnancy. Limitations, reasons for caution Small sample size, interpatient variation in the severity of covid19, inadequate study design and retrospective nature. All patient examined had mild to moderate symptoms and none suffered from severe covid19 symptoms or needed ICU treatment so no data available to comment on severe postcovid19 case semen changes. Wider implications of the findings Many couples initially deferred fertility care due to concern about covid19 disease. Globally many fertility centre has resumed delivering care. Men and their partners must be appropriately counselled regarding what is known and remains unknown about covid19 and male reproductive health. Trial registration number not applicable Summary 12: Species are defined by biological criteria. This characterization, however, misses the most unique aspect of our species; namely, an ability to invent technologies that reduce mortality risks. Old animals are rare in nature, but survival to old age has become commonplace in humans. Science now asks how long can humans live, but we suggest a more appropriate question is: How long must humans live? Three lines of evidence are used to identify the biological equivalent of a warranty period for humans and why it exists. The effective end of reproduction, the age when the sex ratio is unity, and the acceleration of mortality reveal that approximately 50-55 years is sufficient time for our species to achieve its biological mandate-Darwinian fitness. Identifying this boundary is biomedically important because it represents a transition from expected health and vigor to a period when health and vigor become progressively harder to maintain. Summary 13: The emergence of the new highly pathogenic human coronavirus SARS-CoV-2 that has already infected more than 80 million persons, killing nearly two million of them, clearly indicates the need to design efficient and safe vaccines protecting from these coronaviruses. Modern vaccines can be derived from virus-host interaction research directed to the identification of signaling pathways essential for virus replication and for virus-induced pathogenesis, in order to learn how to attenuate these viruses and design vaccines. ABSTRACT There are no approved vaccines against the life-threatening Middle East respiratory syndrome coronavirus (MERS-CoV). Attenuated vaccines have proven their potential to induce strong and long-lasting immune responses. We have previously described that severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a virulence factor. Based on this knowledge, a collection of mutants carrying partial deletions spanning the C-terminal domain of the E protein (rMERS-CoV-E*) has been generated using a reverse genetics system. One of these mutants, MERS-CoV-E*Δ2in, was attenuated and provided full protection in a challenge with virulent MERS-CoV after a single immunization dose. The MERS-CoV-E*Δ2in mutant was stable as it maintained its attenuation after 16 passages in cell cultures and has been selected as a promising vaccine candidate. IMPORTANCE The emergence of the new highly pathogenic human coronavirus SARS-CoV-2 that has already infected more than 80 million persons, killing nearly two million of them, clearly indicates the need to design efficient and safe vaccines protecting from these coronaviruses. Modern vaccines can be derived from virus-host interaction research directed to the identification of signaling pathways essential for virus replication and for virus-induced pathogenesis, in order to learn how to attenuate these viruses and design vaccines. Using a reverse genetics system developed in our laboratory, an infectious cDNA clone of MERS-CoV was engineered. Using this cDNA, we sequentially deleted several predicted and conserved motifs within the envelope (E) protein of MERS-CoV, previously associated with the presence of virulence factors. The in vitro and in vivo evaluation of these deletion mutants highlighted the relevance of predicted linear motifs in viral pathogenesis. Two of them, an Atg8 protein binding motif (Atg8-BM), and a forkhead-associated binding motif (FHA-BM), when deleted, rendered an attenuated virus that was evaluated as a vaccine candidate, leading to full protection against challenge with a lethal dose of MERS-CoV. This approach can be extended to the engineering of vaccines protecting against the new pandemic SARS-CoV-2. Summary 14: Abstract Abstract Emotions are critical for humans, not only feeling and expressing them, but also reading the emotional expressions of others. For a long time, this ability was thought to be exclusive to people; however, there is now evidence that other animals also rely on emotion perception to guide their behaviour and to adjust their actions in such way as to guarantee success in their social groups. This is the case for domestic dogs, who have tremendously complex abilities to perceive the emotional expressions not only of their conspecifics but also of human beings. In this paper we discuss dogs’ capacities to read human emotions. More than perception, though, are dogs able to use this emotional information in a functional way? Does reading emotional expressions allow them to live functional social lives? Dogs can respond functionally to emotional expressions and can use the emotional information they obtain from others during problem-solving, that is, acquiring information from faces and body postures allows them to make decisions. Here, we tackle questions related to the abilities of responding to and using emotional information from human expressions in a functional way and discuss how far dogs can go when reading our emotions. Summary 15: The claim that human persons are physical things does not, of necessity and all by itself, render personal immortality problematic. After all, there doesn’t seem to be a problem with the mere idea of a physical thing, even a living physical thing, that lasts forever. Nevertheless, the physicalist who believes in immortality has a worry that her dualist counterpart does not. This worry is grounded in a bit of empirical, contingent fact: If human persons are physical objects, then they die and, as a result, cease to exist. Exactly how death results in a physical person’s ceasing to exist does not matter for our purposes. It could be that everyone ceases to exist immediately upon dying, because the atoms they comprise cease to be caught up in a life and so cease to compose anything at all. Or perhaps the mummified linger longer than the cremated. Or perhaps there is some other story to be told here. The details about how and when death results in ceasing to exist are not important for our purposes. All that matters here is that human persons, if physical, cease to exist as a result of dying. (If, on the other hand, human Summary 16: How would you feel if the Royal Society of Medicine promoted the sale of cigarettes? What about if the president and trustees decided to hold a seminar sponsored by poppy farmers? Or the chief executive decided to close the academic department and replace it with a department of human trafficking? What would you do with your membership? Would you be proud of your involvement with a scientific society? Would you be happy to contribute to meetings and conferences in the knowledge that you were furthering your career in a respected organization, even though it was making a healthy profit by unhealthy means? Just in case you were beginning to wonder if I was building up to a climactic announcement, you can relax. As far as I understand it, the RSM is flourishing by entirely reputable means. But can we say that about all publishers? Some of the larger ones have been criticized for years for behaving like parasites, sucking every last drop of effort from authors, reviewers and editors, simply to boost their operating income and please their shareholders. Now Reed Elsevier—considered by many in the world of publishing to be the biggest, baddest wolf of them all—finds itself under attack for promoting arms sales. Richard Smith identifies the cynical contradiction at the heart of this approach: ‘Surely the company's business mission would be impossibly confused: would the company be in the business of killing people or keeping them alive?’ (pp. 114-115) Scientific publishing is a major part of Reed Elsevier's armoury, responsible for just under half a billion pounds of its profits. It publishes some of the world's best journals, including The Lancet, which has established itself as the world's premier journal for global health as well as being the weekly medical journal most feared for its piercing critique. Indeed, The Lancet's editors famously rebuked Reed Elsevier for its support of an exhibition for the arms trade. Last month, the Joseph Rowntree Charitable Trust—a displeased shareholder—sold its shares in the publishing giant over the same malign entanglement. Now Smith calls for authors, reviewers and readers of The Lancet and other Reed Elsevier journals to orchestrate a campaign. ‘This is where Reed Elsevier is vulnerable,’ he urges. ‘Were those researchers to go elsewhere, the company would promptly pull out of arms exhibitions.’ One strong motivation to publish in The Lancet is its high impact factor (24 and rising)—that is, if you care for impact factor. Mabel Chew and colleagues studied impact factors in seven general medical journals over an 11-year period, and interviewed ten journal editors (pp. 142-150). They confirmed what we know: that impact factors have been rising over the last decade. They also confirmed what we suspected: that deliberate editorial practices and manipulation were a factor in this rise. Despite their successful manipulation of impact factor, journal editors were dissatisfied with it as a measure, leading the authors to conclude that their study adds weight to the need for complementary measures. The problem is that the hypocrisy of publishers is mirrored by the hypocrisy of editors. They might be dissatisfied, but too many of my illustrious colleagues are hell-bent on doing whatever their conscience allows in pursuit of a higher impact factor and a stronger marketing message. I have an alternative: forget this impact factor obsession and try one of Nick Black's walks through London's medical history. This month, he takes you to the lost hospitals of St Luke's, home to seven of the leading hospitals of the 19th century (pp. 125-129). Or you could walk to the Strand offices of Reed Elsevier and throw some rotten eggs and ethical indignation in support of The Lancet. It is a journal whose history, standing, and integrity matter far more than its impact factor ever could. Summary 17: Balancing selection maintains advantageous diversity in populations through various mechanisms. While extensively explored from a theoretical perspective, an empirical understanding of its prevalence and targets lags behind our knowledge of positive selection. Here we describe the Non-Central Deviation (NCD), a simple yet powerful statistic to detect long-term balancing selection (LTBS) which quantifies how close frequencies are to expectations under LTBS, and provides the basis for a neutrality test. NCD can be applied to single loci or genomic data, to populations with or without known demographic history, and can be implemented considering only polymorphisms (NCD1) or also considering fixed differences (NCD2). Both statistics have very high power to detect LTBS in humans under different frequencies of the balanced allele(s), with NCD2 having the highest power. Applied to genome-wide data from African and European human populations NCD2 shows that, albeit not prevalent, LTBS affects a sizable portion of the genome: about 0.6% of analyzed genomic windows and 0.8% of analyzed positions. These windows overlap about 8% of the protein-coding genes, which interestingly have larger number of transcripts than expected by chance. Significant windows contain 1.6% of the SNPs in the genome, which disproportionally overlap sites within exons and that alter protein sequence, but not putatively regulatory sites. Our catalog of candidates includes known targets of LTBS, but a majority of them are novel. As expected, immune-related genes are among those with the strongest signatures, although most candidates are involved in other biological functions, suggesting that LTBS potentially influences diverse human phenotypes.

How long human can live without oxigen