Venom insulins of cone snails diversify rapidly and track prey taxa

A specialized insulin was recently found in the venom of a fish-hunting cone snail, Conus geographus. Here we show that many worm-hunting and snail-hunting cones also express venom insulins, and that this novel gene family has diversified explosively. Cone snails express a highly conserved insulin in their nerve ring; presumably this conventional signaling insulin is finely tuned to the Conus insulin receptor, which also evolves very slowly. By contrast, the venom insulins diverge rapidly, apparently in response to biotic interactions with prey and also possibly the cones’ own predators and competitors. Thus, the inwardly directed signaling insulins appear to experience predominantly purifying sele\ction to target an internal receptor that seldom changes, while the outwardly directed venom insulins frequently experience directional selection to target heterospecific insulin receptors in a changing mix of prey, predators and competitors. Prey insulin receptors may often be constrained in ways that prevent their evolutionary escape from targeted venom insulins, if amino-acid substitutions that result in escape also degrade the receptor’s signaling functions

Applying Research Ethics Guidelines: The View from a Sub-Saharan Research Ethics Committee

Considerable variation has been demonstrated in applying regulations across research ethics committees (RECs) in the U.S., U.K., and European nations. With the rise of international research collaborations, RECs in developing countries apply a variety of international regulations. We conducted a qualitative descriptive pilot study with members of the national REC in Malawi to determine criteria they use to review research, and their views on international collaborations. Qualitative content analysis demonstrated that international guidelines are interpreted in light of local African conditions such that emphasis is placed on examining benefit to the community and ensuring the informed consent process translates concepts in locally-meaningful ways. Members suggest that RECs often must comply with regulations that do not fit local conditions. Recommendations are provided for improving such international collaborations

Differences between international recommendations on breastfeeding in the presence of HIV and the attitudes and counselling messages of health workers in Lilongwe, Malawi

BACKGROUND: To prevent postnatal transmission of HIV in settings where safe alternatives to breastfeeding are unavailable, the World Health Organization (WHO) recommends exclusive breastfeeding followed by early, rapid cessation of breastfeeding. Only limited data are available on the attitudes of health workers toward this recommendation and the impact of these attitudes on infant feeding counselling messages given to mothers. METHODS: As part of the Breastfeeding, Antiretroviral, and Nutrition (BAN) clinical trial, we carried out an in-depth qualitative study of the attitudes, beliefs, and counselling messages of 19 health workers in Lilongwe, Malawi. RESULTS: Although none of the workers had received formal training, several reported having counseled HIV-positive mothers about infant feeding. Health workers with counselling experience believed that HIV-infected mothers should breastfeed exclusively, rather than infant formula feed, citing poverty as the primary reason. Because of high levels of malnutrition, all the workers had concerns about early cessation of breastfeeding. CONCLUSION: Important differences were observed between the WHO recommendations and the attitudes and practices of the health workers. Understanding these differences is important for designing effective interventions

Comparative genomic and phylogenetic approaches to characterize the role of genetic recombination in mycobacterial evolution

The genus Mycobacterium encompasses over one hundred named species of environmental and pathogenic organisms, including the causative agents of devastating human diseases such as tuberculosis and leprosy. The success of these human pathogens is due in part to their ability to rapidly adapt to their changing environment and host. Recombination is the fastest way for bacterial genomes to acquire genetic material, but conflicting results about the extent of recombination in the genus Mycobacterium have been reported. We examined a data set comprising 18 distinct strains from 13 named species for evidence of recombination. Genomic regions common to all strains (accounting for 10% to 22% of the full genomes of all examined species) were aligned and concatenated in the chromosomal order of one mycobacterial reference species. The concatenated sequence was screened for evidence of recombination using a variety of statistical methods, with each proposed event evaluated by comparing maximum-likelihood phylogenies of the recombinant section with the non-recombinant portion of the dataset. Incongruent phylogenies were identified by comparing the site-wise log-likelihoods of each tree using multiple tests. We also used a phylogenomic approach to identify genes that may have been acquired through horizontal transfer from non-mycobacterial sources. The most frequent associated lineages (and potential gene transfer partners) in the Mycobacterium lineage-restricted gene trees are other members of suborder Corynebacterinae, but more-distant partners were identified as well. In two examined cases of potentially frequent and habitat-directed transfer ( M. abscessus to Segniliparus and M. smegmatis to Streptomyces ), observed sequence distances were small and consistent with a hypothesis of transfer, while in a third case ( M. vanbaalenii to Streptomyces ) distances were larger. The analyses described here indicate that whereas evidence of recombination in core regions within the genus is relatively sparse, the acquisition of genes from non-mycobacterial lineages is a significant feature of mycobacterial evolution

Massively distributed authorship of academic papers

Wiki-like or crowdsourcing models of collaboration can provide a number of benefits to academic work. These techniques may engage expertise from different disciplines, and potentially increase productivity. This paper presents a model of massively distributed collaborative authorship of academic papers. This model, developed by a collective of thirty authors, identifies key tools and techniques that would be necessary or useful to the writing process. The process of collaboratively writing this paper was used to discover, negotiate, and document issues in massively authored scholarship. Our work provides the first extensive discussion of the experiential aspects of large-scale collaborative researc

Improving Participant Understanding of Informed Consent in an HIV-Prevention Clinical Trial: A Comparison of Methods

Empirical research on informed consent has shown that study participants often do not fully understand consent information. This study assessed participant understanding of three mock consent approaches describing an HIV-prevention clinical trial in Lilongwe, Malawi prior to trial implementation. Pregnant women (n = 297) were systematically selected from antenatal-care waiting lines and sequentially allocated to receive an enhanced standard consent form (group 1), a context-specific consent form (group 2), or context-specific counseling cards (group 3). Understanding of research concepts and study procedures was assessed immediately postintervention and at 1-week follow-up. At postintervention, participants in groups 2 and 3 understood more about research concepts and study procedures compared with group 1. Group 3 participants also understood more about study procedures compared with group 2. At follow-up, participants in groups 2 and 3 continued to understand more about research concepts and study procedures. Context-specific approaches improved understanding of consent information in this study

Involving communities in the design of clinical trial protocols: The BAN Study in Lilongwe, Malawi

To learn the attitudes and concerns of the local community on participating in research, infant feeding practices, and maternal nutrition in order to inform the design of a clinical trial in Lilongwe, Malawi on the safety and efficacy of antiretroviral and nutrition interventions to reduce postnatal transmission of HIV

Masking Adherence in K–12 Schools and SARS-CoV-2 Secondary Transmission

OBJECTIVES: Masking is an essential coronavirus 2019 mitigation tool assisting in the safe return of kindergarten through 12th grade children and staff to in-person instruction; however, masking adherence, compliance evaluation methods, and potential consequences of surveillance are currently unknown. We describe two school districts' approaches to promote in-school masking and the consequent impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) secondary transmission.METHODS: Two North Carolina school districts developed surveillance programs with daily vs. weekly interventions to monitor in-school masking adherence. Safety teams recorded the proportion of students and staff appropriately wearing masks and provided real-time education after observation of improper masking. Primary infections, within-school transmission, and county-level SARS-CoV-2 infection rates were assessed.RESULTS: Proper mask use was high in both intervention groups and districts. There were variations by grade level, with lower rates in elementary schools, and proper adherence being higher in the weekly surveillance group. Rates of secondary transmission were low in both districts with surveillance programs, regardless of intervention frequency.CONCLUSIONS: Masking surveillance interventions are effective at ensuring appropriate masking at all school levels. Creating a culture of safety within schools led by local leadership is important and a feasible opportunity for school districts with return to in-person school. In our study of schools with high masking adherence, secondary transmission was low

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys