On the number of trials needed to distinguish similar alternatives.

A/B testing is widely used to tune search and recommendation algorithms, to compare product variants as efficiently and effectively as possible, and even to study animal behavior. With ongoing investment, due to diminishing returns, the items produced by the new alternative B show smaller and smaller improvement in quality from the items produced by the current system A. By formalizing this observation, we develop closed-form analytical expressions for the sample efficiency of a number of widely used families of slate-based comparison tests. In empirical trials, these theoretical sample complexity results are shown to be predictive of real-world testing efficiency outcomes. These findings offer opportunities for both more cost-effective testing and a better analytical understanding of the problem.

Sequential Lonsdaleite to Diamond Formation in Ureilite Meteorites via In Situ Chemical Fluid/Vapor Deposition.

Ureilite meteorites are arguably our only large suite of samples from the mantle of a dwarf planet and typically contain greater abundances of diamond than any known rock. Some also contain lonsdaleite, which may be harder than diamond. Here, we use electron microscopy to map the relative distribution of coexisting lonsdaleite, diamond, and graphite in ureilites. These maps show that lonsdaleite tends to occur as polycrystalline grains, sometimes with distinctive fold morphologies, partially replaced by diamond + graphite in rims and cross-cutting veins. These observations provide strong evidence for how the carbon phases formed in ureilites, which, despite much conjecture and seemingly conflicting observations, has not been resolved. We suggest that lonsdaleite formed by pseudomorphic replacement of primary graphite shapes, facilitated by a supercritical C-H-O-S fluid during rapid decompression and cooling. Diamond + graphite formed after lonsdaleite via ongoing reaction with C-H-O-S gas. This graphite > lonsdaleite > diamond + graphite formation process is akin to industrial chemical vapor deposition but operates at higher pressure (∼1-100 bar) and provides a pathway toward manufacture of shaped lonsdaleite for industrial application. It also provides a unique model for ureilites that can reconcile all conflicting observations relating to diamond formation.

Ancient micrometeorites suggestive of an oxygen-rich Archaean upper atmosphere.

It is widely accepted that Earth's early atmosphere contained less than 0.001 per cent of the present-day atmospheric oxygen (O2) level, until the Great Oxidation Event resulted in a major rise in O2 concentration about 2.4 billion years ago. There are multiple lines of evidence for low O2 concentrations on early Earth, but all previous observations relate to the composition of the lower atmosphere in the Archaean era; to date no method has been developed to sample the Archaean upper atmosphere. We have extracted fossil micrometeorites from limestone sedimentary rock that had accumulated slowly 2.7 billion years ago before being preserved in Australia's Pilbara region. We propose that these micrometeorites formed when sand-sized particles entered Earth's atmosphere and melted at altitudes of about 75 to 90 kilometres (given an atmospheric density similar to that of today). Here we show that the FeNi metal in the resulting cosmic spherules was oxidized while molten, and quench-crystallized to form spheres of interlocking dendritic crystals primarily of magnetite (Fe3O4), with wüstite (FeO)+metal preserved in a few particles. Our model of atmospheric micrometeorite oxidation suggests that Archaean upper-atmosphere oxygen concentrations may have been close to those of the present-day Earth, and that the ratio of oxygen to carbon monoxide was sufficiently high to prevent noticeable inhibition of oxidation by carbon monoxide. The anomalous sulfur isotope (Δ(33)S) signature of pyrite (FeS2) in seafloor sediments from this period, which requires an anoxic surface environment, implies that there may have been minimal mixing between the upper and lower atmosphere during the Archaean.

Reviewer bias in single- versus double-blind peer review.

Peer review may be "single-blind," in which reviewers are aware of the names and affiliations of paper authors, or "double-blind," in which this information is hidden. Noting that computer science research often appears first or exclusively in peer-reviewed conferences rather than journals, we study these two reviewing models in the context of the 10th Association for Computing Machinery International Conference on Web Search and Data Mining, a highly selective venue (15.6% acceptance rate) in which expert committee members review full-length submissions for acceptance. We present a controlled experiment in which four committee members review each paper. Two of these four reviewers are drawn from a pool of committee members with access to author information; the other two are drawn from a disjoint pool without such access. This information asymmetry persists through the process of bidding for papers, reviewing papers, and entering scores. Reviewers in the single-blind condition typically bid for 22% fewer papers and preferentially bid for papers from top universities and companies. Once papers are allocated to reviewers, single-blind reviewers are significantly more likely than their double-blind counterparts to recommend for acceptance papers from famous authors, top universities, and top companies. The estimated odds multipliers are tangible, at 1.63, 1.58, and 2.10, respectively.

Screening for asymptomatic neurosyphilis in HIV patients after treatment of early syphilis: an observational study.

OBJECTIVE: To determine the prevalence of asymptomatic neurosyphilis (ANS) in HIV-positive individuals after treatment of early syphilis with single-dose benzathine penicillin G (BPG) or oral antibiotic alternatives. METHODS: Patients at high risk of neurosyphilis (defined by serum rapid plasma reagin (RPR) titre ≥1:32 and/or peripheral blood CD4 lymphocyte count ≤350/µL) underwent lumbar puncture (LP) at a median time of 8.2 months post treatment. ANS was diagnosed by a reactive cerebrospinal fluid (CSF) RPR test or CSF white blood cells (WBC) >20/µL plus a reactive CSF Treponema pallidum particle agglutination (TPPA) ≥1:640. RESULTS: Of 133 eligible patients, all were men who have sex with men. Of these, 64 consented to LP. Full CSF results were available for 59 patients. Inclusion criteria were serum RPR (21/59), CD4 count (22/59) and combined RPR and CD4 (16/59). The LP patients were white British (82%), median age 40. Syphilis stages were primary (17%) secondary (43%) and early latent (41%). Syphilis was treated with BPG (47/59), doxycycline 100 mg two times per day for 14 days (10/59) and for 21 days (1/59). Azithromycin 500 mg one time per day for 10 days was given to 1/59. At the time of LP, 100% of patients had achieved serological cure, and 66% were taking antiretroviral treatment. Only 1/59 was diagnosed with ANS. The CSF showed: RPR non-reactive (59/59); TPPA non-reactive in 54/59; WBC ≤5/µL in 51/59. CONCLUSIONS: Although the number of patients in our study is modest, single-dose BPG appears to be highly effective even in patients at high risk of neurosyphilis.

Controversies in faith and health care.

Differences in religious faith-based viewpoints (controversies) on the sanctity of human life, acceptable behaviour, health-care technologies and health-care services contribute to the widespread variations in health care worldwide. Faith-linked controversies include family planning, child protection (especially child marriage, female genital mutilation, and immunisation), stigma and harm reduction, violence against women, sexual and reproductive health and HIV, gender, end-of-life issues, and faith activities including prayer. Buddhism, Christianity, Hinduism, Islam, Judaism, and traditional beliefs have similarities and differences in their viewpoints. Improved understanding by health-care providers of the heterogeneity of viewpoints, both within and between faiths, and their effect on health care is important for clinical medicine, public-health programmes, and health-care policy. Increased appreciation in faith leaders of the effect of their teachings on health care is also crucial. This Series paper outlines some faith-related controversies, describes how they influence health-care provision and uptake, and identifies opportunities for research and increased interaction between faith leaders and health-care providers to improve health care.

Giant inflamed fibroepithelial scrotal polyp mimicking an anogenital wart.

We report the case of a young man who has never had any sexual contact presenting with a large scrotal lump with secondary bacterial infection. He reported no prior warts - genital or cutaneous. On examination, he had a large pink cauliform mass on the scrotum with four smaller but similar satellite lesions. Appearances were thought to be consistent with giant condyloma of Buschke and Lowenstein. Once superinfection was treated with oral antibiotics, he had a trial of imiquimod without success and was then referred to urology. After surgical excision, pathology concluded it was an inflamed fibroepithelial polyp with no malignant changes. To our knowledge, this is the first case report of a giant scrotal fibroepithelial polyp with characteristic gross warty features in an adult.

What works and why? Evaluation of a community nutrition programme in Kenya.

OBJECTIVE: To investigate the nutritional impact of a community-based programme that focused on social cohesion and action. DESIGN: The change in nutritional status of children aged 12­60 months was examined over a period of 3 years in Makueni District in Eastern Province of Kenya in six communities in which an intervention programme of Participatory Learning and Action was introduced and in ten communities in which only basic preparations were made but no intervention was started. SETTING: The intervention was part of the Government of Kenya Community Based Nutrition Programme and was supported by the Government of Denmark. SUBJECTS: Children aged 12­60 months. RESULTS: Among communities without intervention there were similar levels of underweight (mean Z-score: −1·63 v. −1·50 (NS); % with Z-score<­2: 36·6% v. 34·5% (NS)) and stunting (mean Z-score: −2·0 v. −1·99 (NS); % with Z-score<­2: 44·3% and 47·4% (NS)) at baseline and after 3 years. By contrast, among communities who had received interventions, there were significant improvements after 3 years in the levels of underweight (mean Z-score: −1·66 v. −1·37 (P<0·02); % with Z-score <­2: 42·9% v. 31·4% (P<0·035)) and stunting (mean Z-score: −2·05 v. −1·59 (P<0·05); % with Z-score<­2: 52·7% v. 39·7% (P<0·02)). CONCLUSIONS: The results indicate considerable potential for using Participatory Learning and Action as a community-based approach to effectively address child undernutrition. It is suggested that these interventions are developed, implemented and evaluated more widely as a mean of tackling childhood undernutrition and improving child survival and development.

A re-audit of individuals with a late diagnosis of HIV in 2016 and 2019 in Greater Manchester.

BACKGROUND: New late HIV diagnosis (CD4 count <350cells/mm3) are higher in North West England compared to the UK average. A Greater Manchester-wide audit into individuals diagnosed with late or very late HIV was conducted in 2016 and re-audited in 2019. Our aim was to gain intelligence into key demographics of late diagnosed individuals across Greater Manchester, review opportunities for earlier diagnosis and determine if key recommendations from the 2016 audit were followed. METHODS: Individuals were identified from locally kept data or HIV and AIDS Reporting System (HARS) data. A retrospective case note review was performed for each patient using data from local notes, General Practice summary of care records and relevant clinical letters. Data was collected for 2019 and compared to 2016 results. RESULTS: In 2016, nine departments contributed data and 104 individuals were identified as having been diagnosed late. In 2019, seven departments contributed data and 65 individuals were identified as having been diagnosed late. In both years, a greater proportion of males diagnosed late were White British and for females Black African. A greater proportion of late diagnosis occurred in men who have sex with men (MSM) and in heterosexual females. In 2019, a greater proportion of patients had an AIDS-defining illness at time of diagnosis. Whilst in 2016, most patients were asymptomatic. Over one third of patients had a clinical indicator disease in their past medical history, which is an increase in proportion from 2016. The proportion of cases where clinicians felt that there had been probable missed opportunities for earlier diagnosis also increased in 2019. CONCLUSIONS: There are continued missed opportunities for earlier diagnosis. We recommend targeted interventions for groups at higher risk of late presentation, education in primary/secondary care regarding clinical indicator conditions, a formal review process for all late diagnosed cases, communication with primary/secondary care if missed opportunities are identified and broader HIV testing especially in high prevalence areas.

Preservation of Terrestrial Microorganisms and Organics Within Alteration Products of Chondritic Meteorites from the Nullarbor Plain, Australia.

Meteorites that fall to Earth quickly become contaminated with terrestrial microorganisms. These meteorites are out of chemical equilibrium in the environments where they fall, and equilibration promotes formation of low-temperature alteration minerals that can entomb contaminant microorganisms and thus preserve them as microfossils. Given the well-understood chemistry of meteorites and their recent discovery on Mars by rovers, a similarly weathered meteorite on Mars could preserve organic and fossil evidence of a putative past biosphere at the martian surface. Here, we used several techniques to assess the potential of alteration minerals to preserve microfossils and biogenic organics in terrestrially weathered ordinary chondrites from the Nullarbor Plain, Australia. We used acid etching of ordinary chondrites to reveal entombed fungal hyphae, modern biofilms, and diatoms within alteration minerals. We employed synchrotron X-ray fluorescence microscopy of alteration mineral veins to map the distribution of redox-sensitive elements of relevance to chemolithotrophic organisms, such as Mn-cycling bacteria. We assessed the biogenicity of fungal hyphae within alteration veins using a combination of Fourier-transform infrared spectroscopy and pyrolysis gas chromatography-mass spectrometry, which showed that alteration minerals sequester and preserve organic molecules at various levels of decomposition. Our combined analyses results show that fossil microorganisms and the organic molecules they produce are preserved within calcite-gypsum admixtures in meteorites. Furthermore, the distributions of redox-sensitive elements (e.g., Mn) within alteration minerals are localized, which qualitatively suggests that climatically or microbially facilitated element mobilization occurred during the meteorite's residency on Earth. If returned as part of a sample suite from the martian surface, ordinary chondrites could preserve similar, recognizable evidence of putative past life and/or environmental change.

Dendritic cell anergy results from endotoxemia in severe malnutrition.

Malnutrition predicts an increased risk of morbidity and mortality from infection. Defects in cell-mediated immunity, such as thymic atrophy, impaired cutaneous tuberculin responses, and reduced T cell mitogenesis in vitro, are well characterized. There has been no convincing mechanism proposed for these T cell defects. However, as T cell responses rely on signals received from APCs, this study evaluates dendritic cell (DC) function in children with severe malnutrition. Repeated sampling of peripheral blood from 81 severely malnourished children at the University Teaching Hospital, Lusaka, Zambia, demonstrated for the first time a defect in DC numbers in children with malnutrition (28 per microliter) and a recovery in cell number (48 per microliter; p < 0.01) with standard treatment. We describe normal DC maturation in the majority of malnourished children. However, in 17% of our study patients, in association with endotoxemia we describe the novel finding of DC maturation failure (down-regulation rather than up-regulation of HLA-DR). There was a strong correlation between the strength of HLA-DR up or down-regulation and the generation of IL-10 (r = -0.481; p = 0.003). These "anergic" DCs failed to support T cell proliferation. Defects in DC number and the immunosuppressive phenotype of DCs from severely malnourished children with endotoxemia provide a rational basis for the anergy found in severe malnutrition.

Trace element catalyses mineral replacement reactions and facilitates ore formation.

Reaction-induced porosity is a key factor enabling protracted fluid-rock interactions in the Earth's crust, promoting large-scale mineralogical changes during diagenesis, metamorphism, and ore formation. Here, we show experimentally that the presence of trace amounts of dissolved cerium increases the porosity of hematite (Fe2O3) formed via fluid-induced, redox-independent replacement of magnetite (Fe3O4), thereby increasing the efficiency of coupled magnetite replacement, fluid flow, and element mass transfer. Cerium acts as a catalyst affecting the nucleation and growth of hematite by modifying the Fe2+(aq)/Fe3+(aq) ratio at the reaction interface. Our results demonstrate that trace elements can enhance fluid-mediated mineral replacement reactions, ultimately controlling the kinetics, texture, and composition of fluid-mineral systems. Applied to some of the world's most valuable orebodies, these results provide new insights into how early formation of extensive magnetite alteration may have preconditioned these ore systems for later enhanced metal accumulation, contributing to their sizes and metal endowment.

Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi.

BACKGROUND: Severe acute malnutrition affects 13 million children worldwide and causes 1-2 million deaths every year. Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting. METHODS: We recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised, placebo-controlled efficacy trial. For generalisability, all admissions for severe acute malnutrition treatment were eligible for recruitment. After stabilisation with milk feeds, children were randomly assigned to ready-to-use therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte. Average prescribed Synbiotic dose was 10(10) colony-forming units or more of lactic acid bacteria per day for the duration of treatment (median 33 days). Primary outcome was nutritional cure (weight-for-height >80% of National Center for Health Statistics median on two consecutive outpatient visits). Secondary outcomes included death, weight gain, time to cure, and prevalence of clinical symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an intention-to-treat basis. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN19364765. FINDINGS: Nutritional cure was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3% [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV seropositivity was associated with worse outcomes overall, but did not modify or confound the negative results. Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group (p=0.06). INTERPRETATION: In Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes. The observation of reduced outpatient mortality might be caused by bias, confounding, or chance, but is biologically plausible, has potential for public health impact, and should be explored in future studies. FUNDING: Department for International Development (DfID).

Effect on longitudinal growth and anemia of zinc or multiple micronutrients added to vitamin A: a randomized controlled trial in children aged 6-24 months.

BACKGROUND: The benefits of zinc or multiple micronutrient supplementations in African children are uncertain. African children may differ from other populations of children in developing countries because of differences in the prevalence of zinc deficiency, low birth weight and preterm delivery, recurrent or chronic infections such as HIV, or the quality of complementary diets and genetic polymorphisms affecting iron metabolism.The aim of this study was to ascertain whether adding zinc or multiple micronutrients to vitamin A supplementation improves longitudinal growth or reduces prevalence of anemia in children aged 6-24 months. METHODS: Randomized, controlled double-blinded trial of prophylactic micronutrient supplementation to children aged 6-24 months. Children in three cohorts - 32 HIV-infected children, 154 HIV-uninfected children born to HIV-infected mothers, and 187 uninfected children born to HIV-uninfected mothers - were separately randomly assigned to receive daily vitamin A (VA) [n = 124], vitamin A plus zinc (VAZ) [n = 123], or multiple micronutrients that included vitamin A and zinc (MM) [n = 126]. RESULTS: Among all children there were no significant differences between intervention arms in length-for-age Z scores (LAZ) changes over 18 months. Among stunted children (LAZ below -2) [n = 62], those receiving MM had a 0.7 Z-score improvement in LAZ versus declines of 0.3 in VAZ and 0.2 in VA (P = 0.029 when comparing effects of treatment over time). In the 154 HIV-uninfected children, MM ameliorated the effect of repeated diarrhea on growth. Among those experiencing more than six episodes, those receiving MM had no decline in LAZ compared to 0.5 and 0.6 Z-score declines in children receiving VAZ and VA respectively (P = 0.06 for treatment by time interaction). After 12 months, there was 24% reduction in proportion of children with anemia (hemoglobin below 11 g/dL) in MM arm (P = 0.001), 11% in VAZ (P = 0.131) and 18% in VA (P = 0.019). Although the within arm changes were significant; the between-group differences were not significant. CONCLUSIONS: Daily multiple micronutrient supplementation combined with vitamin A was beneficial in improving growth among children with stunting, compared to vitamin A alone or to vitamin A plus zinc. Effects on anemia require further study. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number. NCT00156832.

Eukaryotic Colonization of Micrometer-Scale Cracks in Rocks: A "Microfluidics" Experiment Using Naturally Weathered Meteorites from the Nullarbor Plain, Australia.

The advent of microfluidics has revolutionized the way we understand how microorganisms propagate through microporous spaces. Here, we apply this understanding to the study of how endolithic environmental microorganisms colonize the interiors of sterile rock. The substrates used for our study are stony meteorites from the Nullarbor Plain, Australia; a semiarid limestone karst that provides an ideal setting for preserving meteorites. Periodic flooding of the Nullarbor provides a mechanism by which microorganisms and exogenous nutrients may infiltrate meteorites. Our laboratory experiments show that environmental microorganisms reach depths greater than 400 µm by propagating through existing brecciation, passing through cracks no wider than the diameter of a resident cell (i.e., ∼5 µm). Our observations are consistent with the propagation of these eukaryotic cells via growth and cell division rather than motility. The morphology of the microorganisms changed as a result of propagation through micrometer-scale cracks, as has been observed previously for bacteria on microfluidic chips. It has been suggested that meteorites could have served as preferred habitats for microorganisms on ancient Mars. Based on our results, the depths reached by terrestrial microorganisms within meteorites would be sufficient to mitigate against the harmful effects of ionizing radiation, such as UV light, in Earth's deserts and potentially on Mars, if similar processes of microbial colonization had once been active there. Thus, meteorites landing in ancient lakes on Mars, that later dried out, could have been some of the last inhabited locations on the surface, serving as refugia before the planet's surface became inhospitable. Finally, our observations suggest that terrestrial microorganisms can colonize very fine cracks within meteorites (and potentially spaceships and rovers) on unexpectedly short timescales, with important implications for both recognition of extraterrestrial life in returned geological samples and planetary protection.

Trends in low birthweight among the Bhutanese refugee population in Nepal.

BACKGROUND: Although much is known about risk factors for low birthweight, an important cause of neonatal death, little is known about how to reduce or prevent low birthweight. OBJECTIVE: This study aimed to verify a low rate in the incidence of low birthweight reported in the Bhutanese refugee camps in Nepal and, if true, to try to understand how this came about. METHODS: Medical records from 1994 to 2001 were recovered for half of the refugee population, and birthweight and other maternal factors were analyzed. The adequacy of the food ration provided to the general population was assessed by comparing it with the nutrient requirements of pregnant women. RESULTS: The rates of low birthweight were indeed low in the refugee camps, averaging 11% in the years reviewed. Between 1996 and 1998, the mean rate of low birthweight fell from 16% to 8% and mean birthweight increased from 2.84 kg (SE, 2.80-2.87) to 3.0 kg (SE, 2.97-3.03). The increase in birthweight occurred following improvements in the micronutrient-to-energy ratios of the general ration. CONCLUSIONS: Rates of low birthweight comparable to those in developed countries were achieved in an ethnic Nepali population within 5 years of settlement in refugee camps. These low rates were probably achieved because basic needs of mothers were met, including both the quantity and the micronutrient content of food, water and sanitation, antenatal care, and education. The improvement from 1996 to 1998 coincided with increased availability of micronutrients in the food ration. We hypothesize that increased periconceptional micronutrient intake may be responsible for the increase in birthweight.

Sexualised drug taking among men who have sex with men: a systematic review.

AIMS:: Sexualised drug taking is increasingly reported on national and international levels. We aim to review existing evidence of the relationship between recreational drug use (RDU) and sexual intercourse among men who have sex with men (MSM). METHODS:: We reviewed published abstracts and full articles identified from Cochrane, MEDLINE and Embase databases from November 2010 to 2017. We included any existing studies investigating RDU in MSM and at least one of the following: high-risk sexual practices, sexually transmitted infections (STIs) or barriers to accessing specialist support. RESULTS:: In total, 112 studies were included. Of them, 38 studies specifically reported the prevalence of chemsex-related drug use. Links with sexualised drug taking and high-risk sexual practices including condomless sex and group sex were reported by several studies. Recreational drug use in the sexual setting appears linked to the acquisition of STIs, including hepatitis C, syphilis and gonorrhoea. Reports of adverse mental health outcomes are increasingly described, with several studies documenting chemsex-related inpatient admission. A paucity of research addressing barriers to those accessing specialist drug support services was identified. CONCLUSION:: This review demonstrates the complex interplay between recreational drug use, high-risk sexual practices and STIs. It identifies the description of adverse mental health outcomes in the chemsex setting, thus highlighting the need for a multidisciplinary approach across specialties in the management of those adversely affected. Finally, it illuminates the need for future research into perceived barriers of those who require access to support services to ensure timely and comprehensive support provision.