Rates of dinosaur limb evolution provide evidence for exceptional radiation in Mesozoic birds

Birds are the most diverse living tetrapod group and are a model of large-scale adaptive radiation. Neontological studies suggest a radiation within the avian crown group, long after the origin of flight. However, deep time patterns of bird evolution remain obscure because only limited fossil data have been considered. We analyse cladogenesis and limb evolution on the entire tree of Mesozoic theropods, documenting the dinosaur–bird transition and immediate origins of powered flight. Mesozoic birds inherited constraints on forelimb evolution from non-flying ancestors, and species diversification rates did not accelerate in the earliest flying taxa. However, Early Cretaceous short-tailed birds exhibit both phenotypic release of the hindlimb and increased diversification rates, unparalleled in magnitude at any other time in the first 155 Myr of theropod evolution. Thus, a Cretaceous adaptive radiation of stem-group birds was enabled by restructuring of the terrestrial locomotor module, which represents a key innovation. Our results suggest two phases of radiation in Avialae: with the Cretaceous diversification overwritten by extinctions of stem-group birds at the Cretaceous–Palaeogene boundary, and subsequent diversification of the crown group. Our findings illustrate the importance of fossil data for understanding the macroevolutionary processes generating modern biodiversity.     

Rapid removal of glycerol from frozen‐thawed red blood cells

The storage of red blood cells (RBCs) in a refrigerated state allows a shelf life of a few weeks, whereas RBCs frozen in 40% glycerol have a shelf life of 10 years. Despite the clear logistical advantages of frozen blood, it is not widely used in transfusion medicine. One of the main reasons is that existing post‐thaw washing methods to remove glycerol are prohibitively time consuming, requiring about an hour to remove glycerol from a single unit of blood. In this study, we have investigated the potential for more rapid removal of glycerol. Using published biophysical data for human RBCs, we mathematically optimized a three‐step deglycerolization process, yielding a procedure that was less than 32 s long. This procedure was found to yield 70% hemolysis, a value that was much higher than expected. Consequently, we systematically evaluated three‐step deglycerolization procedures, varying the solution composition and equilibration time in each step. Our best results consisted of less than 20% hemolysis for a deglycerolization time of 3 min, and it is expected that even further improvements could be made with a more thorough optimization and more reliable biophysical data. Our results demonstrate the potential for significantly reducing the deglycerolization time compared with existing methods. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:609–620, 2013     

Increased Brain White Matter Axial Diffusivity Associated with Fatigue,Pain and Hyperalgesia in Gulf War Illness

Background

Gulf War exposures in 1990 and 1991 have caused 25% to 30% of deployed personnel to develop a syndrome of chronic fatigue, pain, hyperalgesia, cognitive and affective dysfunction.

Methods

Gulf War veterans (n = 31) and sedentary veteran and civilian controls (n = 20) completed fMRI scans for diffusion tensor imaging. A combination of dolorimetry, subjective reports of pain and fatigue were correlated to white matter diffusivity properties to identify tracts associated with symptom constructs.

Results

Gulf War Illness subjects had significantly correlated fatigue, pain, hyperalgesia, and increased axial diffusivity in the right inferior fronto-occipital fasciculus. ROC generated thresholds and subsequent binary regression analysis predicted CMI classification based upon axial diffusivity in the right inferior fronto-occipital fasciculus. These correlates were absent for controls in dichotomous regression analysis.

Conclusion

The right inferior fronto-occipital fasciculus may be a potential biomarker for Gulf War Illness. This tract links cortical regions involved in fatigue, pain, emotional and reward processing, and the right ventral attention network in cognition. The axonal neuropathological mechanism(s) explaining increased axial diffusivity may account for the most prominent symptoms of Gulf War Illness.     

Herpes Zoster Risk Reduction through Exposure to Chickenpox Patients: A Systematic Multidisciplinary Review

Varicella-zoster virus (VZV) causes chickenpox and may subsequently reactivate to cause herpes zoster later in life. The exogenous boosting hypothesis states that re-exposure to circulating VZV can inhibit VZV reactivation and consequently also herpes zoster in VZV-immune individuals. Using this hypothesis, mathematical models predicted widespread chickenpox vaccination to increase herpes zoster incidence over more than 30 years. Some countries have postponed universal chickenpox vaccination, at least partially based on this prediction. After a systematic search and selection procedure, we analyzed different types of exogenous boosting studies. We graded 13 observational studies on herpes zoster incidence after widespread chickenpox vaccination, 4 longitudinal studies on VZV immunity after re-exposure, 9 epidemiological risk factor studies, 7 mathematical modeling studies as well as 7 other studies. We conclude that exogenous boosting exists, although not for all persons, nor in all situations. Its magnitude is yet to be determined adequately in any study field.     

Molecular Characterization of Staphylococcus aureus from Patients with Surgical Site Infections at Mulago Hospital in Kampala,Uganda

Background

The prevalence of Methicillin resistant Staphylococcus aureus (MRSA) is progressively increasing globally with significant regional variation. Understanding the Staphylococcus aureus lineages is crucial in controlling nosocomial infections. Recent studies on S. aureus in Uganda have revealed an escalating burden of MRSA. However, the S. aureus genotypes circulating among patients are not known. Here, we report S. aureus lineages circulating in patients with surgical site infections (SSI) at Mulago National hospital, Kampala, Uganda.

Methods

A cross-sectional study involving 314 patients with SSI at Mulago National Hospital was conducted from September 2011 to April 2012. Pus swabs from the patients’ SSI were processed using standard microbiological procedures. Methicillin sensitive Staphylococcus aureus (MSSA) and MRSA were identified using phenotypic tests and confirmed by PCR-detection of the nuc and mecA genes, respectively. SCCmec genotypes were determined among MRSA isolates using multiplex PCR. Furthermore, to determine lineages, spa sequence based-genotyping was performed on all S. aureus isolates.

Results

Of the 314 patients with SSI, S. aureus accounted for 20.4% (64/314), of which 37.5% (24/64) were MRSA. The predominant SCCmec types were type V (33.3%, 8/24) and type I (16.7%, 4/24). The predominant spa lineages were t645 (17.2%, 11/64) and t4353 (15.6%, 10/64), and these were found to be clonally circulating in all the surgical wards. On the other hand, lineages t064, t355, and t4609 were confined to the obstetrics and gynecology wards. A new spa type (t10277) was identified from MSSA isolate. On multivariate logistic regression analysis, cancer and inducible clindamycin resistance remained as independent predictors of MRSA-SSI.

Conclusion

SCCmec types I and V are the most prevalent MRSA mecA types from the patients’ SSI. The predominant spa lineages (t645 and t4353) are clonally circulating in all the surgical wards, calling for strengthening of infection control practices at Mulago National Hospital.     

Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial

Background

Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organization (WHO) for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART). The threshold for CTX discontinuation following ART is undefined in resource-limited settings.

Methods and Findings

Between 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥18 mo with CD4 count > 350 cells/mm³ in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea) and mortality. Incidence rate ratios (IRRs) were estimated using Poisson regression.Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72%) were women, and 442 (88%) reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52–3.38; p < 0.001), driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52–241.02; p = 0.001). Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82–2.27, and IRR = 1.43, 95% CI 0.54–3.75, respectively). Study limitations include a lack of placebo and a lower incidence of morbidity events than expected.

Conclusions

CTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence. These data support the 2014 WHO CTX guidelines.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01425073","term_id":"NCT01425073"}}NCT01425073     

An Evaluation of Rebuilding Policies for U.S. Fisheries

Rebuilding depleted fish populations is a priority of modern fisheries management. In the U.S., strong statutory mandates extend to both the goals and process by which stocks are to be rebuilt. However, the National Standard Guidelines that govern the implementation of the Magnuson-Stevens Fishery Conservation and Management Act may change to increase flexibility in rebuilding requirements. In this study we evaluate performance of the status quo approach to fish stock rebuilding in the United States against 3 alternatives that have been proposed to improve rebuilding outcomes. These alternatives either simplify the analytical requirements of rebuilding analyses or apply ‘best practices’ in fisheries management, thereby avoiding the need for rebuilding analyses altogether. We use a Management Strategy Evaluation framework to evaluate rebuilding options across 6 fish life history types and 5 possible real-world fishery scenarios that include options for stock assessment quality, multiple fleets, and the degree to which the stocks are overfished at the start of the analysis. We show that the status quo rebuilding plan and a harvest control rule that reduces harvest rates at low stock size generally achieve the best rebuilding outcomes across all life-history types and fishery scenarios. Both approaches constrain fishing in the short term, but achieve high catches in the medium and long term as stocks rebuild to productive levels. These results support a growing body of literature that indicates that efforts to end overfishing early pay off in the medium- to long-term with higher cumulative catches than the alternative.     

Thermal stability of single‐domain antibodies estimated by molecular dynamics simulations

Single‐domain antibodies (sdAbs) function like regular antibodies, however, consist of only one domain. Because of their low molecular weight, sdAbs have advantages with respect to production and delivery to their targets and for applications such as antibody drugs and biosensors. Thus, sdAbs with high thermal stability are required. In this work, we chose seven sdAbs, which have a wide range of melting temperature (T_m) values and known structures. We applied molecular dynamics (MD) simulations to estimate their relative stability and compared them with the experimental data. High‐temperature MD simulations at 400 K and 500 K were executed with simulations at 300 K as a control. The fraction of native atomic contacts, Q, measured for the 400 K simulations showed a fairly good correlation with the T_m values. Interestingly, when the residues were classified by their hydrophobicity and size, the Q values of hydrophilic residues exhibited an even better correlation, suggesting that stabilization is correlated with favorable interactions of hydrophilic residues. Measuring the Q value on a per‐residue level enabled us to identify residues that contribute significantly to the instability and thus demonstrating how our analysis can be used in a mutant case study.     

Extracurricular involvement and psychological adjustment in the transition from adolescence to emerging adulthood: The role of mastery and creative self-efficacy

A minimal amount is known regarding the mechanisms underlying the potential benefits of extracurricular activities (ECAs) for adolescents’ psychological adjustment. This preliminary cross-sectional study, during which 512 undergraduates retrospectively reported information about high school ECAs, used structural equation modeling to show that feelings of mastery and creative self-efficacy partially explained relationships between past ECA involvement and current psychological adjustment (depression, anxiety, and well-being) as well as creative achievement, though results varied according to the type of ECAs examined. These findings support the importance of studying the specific processes that may account for the benefits of extracurricular involvement within and across activity domains. Future studies using longitudinal designs are needed to assess the causal nature of these findings.