Long-term patterns of body mass and stature evolution within the hominin lineage.

Body size is a central determinant of a species' biology and adaptive strategy, but the number of reliable estimates of hominin body mass and stature have been insufficient to determine long-term patterns and subtle interactions in these size components within our lineage. Here, we analyse 254 body mass and 204 stature estimates from a total of 311 hominin specimens dating from 4.4 Ma to the Holocene using multi-level chronological and taxonomic analytical categories. The results demonstrate complex temporal patterns of body size variation with phases of relative stasis intermitted by periods of rapid increases. The observed trajectories could result from punctuated increases at speciation events, but also differential proliferation of large-bodied taxa or the extinction of small-bodied populations. Combined taxonomic and temporal analyses show that in relation to australopithecines, early Homo is characterized by significantly larger average body mass and stature but retains considerable diversity, including small body sizes. Within later Homo, stature and body mass evolution follow different trajectories: average modern stature is maintained from ca 1.6 Ma, while consistently higher body masses are not established until the Middle Pleistocene at ca 0.5-0.4 Ma, likely caused by directional selection related to colonizing higher latitudes. Selection against small-bodied individuals (less than 40 kg; less than 140 cm) after 1.4 Ma is associated with a decrease in relative size variability in later Homo species compared with earlier Homo and australopithecines. The isolated small-bodied individuals of Homo naledi (ca 0.3 Ma) and Homo floresiensis (ca 100-60 ka) constitute important exceptions to these general patterns, adding further layers of complexity to the evolution of body size within the genus Homo. At the end of the Late Pleistocene and Holocene, body size in Homo sapiens declines on average, but also extends to lower limits not seen in comparable frequency since early Homo

Differences in wild-type– and R338L-tenase complex formation are at the root of R338L-factor IX assay discrepancies

Adeno-associated virus (AAV) gene therapy has the potential to functionally cure hemophilia B by restoring factor (F)IX concentrations into the normal range. Next-generation AAV therapies express a naturally occurring gain-of-function FIX variant, FIX-Padua (R338L-FIX), that increases FIX activity (FIX:C) by approximately eightfold compared with wild-type FIX (FIX-WT). Previous studies have shown that R338L-FIX activity varies dramatically across different clinical FIX:C assays, which complicates the monitoring and management of patients. To better understand mechanisms that contribute to R338L-FIX assay discrepancies, we characterized the performance of R338L-FIX in 13 1-stage clotting assays (OSAs) and 2 chromogenic substrate assays (CSAs) in a global field study. This study produced the largest R338L-FIX assay dataset to date and confirmed that clinical FIX:C assay results vary over threefold. Both phospholipid and activating reagents play a role in OSA discrepancies. CSA generated the most divergent FIX:C results. Manipulation of FIX:C CSA kits demonstrated that specific activity gains for R338L-FIX were most profound at lower FIX:C concentrations and that these effects were enhanced during the early phases of FXa generation. Supplementing FX into CSA had the effect of dampening FIX-WT activity relative to R338L-FIX activity, suggesting that FX impairs WT tenase formation to a greater extent than R338L-FIX tenase. Our data describe the scale of R338L-FIX assay discrepancies and provide insights into the causative mechanisms that will help establish best practices for the measurement of R338LFIX activity in patients after gene therapy

Validation of a chloroquine-induced cell death mechanism for clinical use against malaria

An alternative antimalarial pathway of an ‘outdated’ drug, chloroquine (CQ), may facilitate its return to the shrinking list of effective antimalarials. Conventionally, CQ is believed to interfere with hemozoin formation at nanomolar concentrations, but resistant parasites are able to efflux this drug from the digestive vacuole (DV). However, we show that the DV membrane of both resistant and sensitive laboratory and field parasites is compromised after exposure to micromolar concentrations of CQ, leading to an extrusion of DV proteases. Furthermore, only a short period of exposure is required to compromise the viability of late-stage parasites. To study the feasibility of this strategy, mice malaria models were used to demonstrate that high doses of CQ also triggered DV permeabilization in vivo and reduced reinvasion efficiency. We suggest that a time-release oral formulation of CQ may sustain elevated blood CQ levels sufficiently to clear even CQ-resistant parasites

Age-related change in sedentary behavior during childhood and adolescence: A systematic review and meta-analysis.

Funder: University of East Anglia, Faculty of Medicine and Health SciencesSedentary behaviors are highly prevalent in youth and may be associated with markers of physical and mental health. This systematic review and meta-analysis aimed to quantify the age-related change in sedentary behavior during childhood and adolescence. Ten electronic databases were searched. Inclusion criteria specified longitudinal observational studies or control group from an intervention; participants aged ≥5 and ≤18 years; a quantitative estimate of the duration of SB; and English language, peer-reviewed publication. Meta-analyses summarized weighted mean differences (WMD) in device-assessed sedentary time and questionnaire-assessed screen-behaviors over 1-, 2-, 3-, or more than 4-year follow-up. Effect modification was explored using meta-regression. Eighty-five studies met inclusion criteria. Device-assessed sedentary time increased by (WMD 95% confidence interval [CI]) 27.9 (23.2, 32.7), 61.0 (50.7, 71.4), 63.7 (53.3, 74.0), and 140.7 (105.1, 176.4) min/day over 1-, 2-, 3-, and more than 4-year follow-up. We observed no effect modification by gender, baseline age, study location, attrition, or quality. Questionnaire-assessed time spent playing video games, computer use, and a composite measure of sedentary behavior increased over follow-up duration. Evidence is consistent in showing an age-related increase in various forms of sedentary behavior; evidence pertaining to variability across socio-demographic subgroups and contemporary sedentary behaviors are avenues for future research

Age-related change in sedentary behavior during childhood and adolescence: A systematic review and meta-analysis.

Funder: University of East Anglia, Faculty of Medicine and Health SciencesSedentary behaviors are highly prevalent in youth and may be associated with markers of physical and mental health. This systematic review and meta-analysis aimed to quantify the age-related change in sedentary behavior during childhood and adolescence. Ten electronic databases were searched. Inclusion criteria specified longitudinal observational studies or control group from an intervention; participants aged ≥5 and ≤18 years; a quantitative estimate of the duration of SB; and English language, peer-reviewed publication. Meta-analyses summarized weighted mean differences (WMD) in device-assessed sedentary time and questionnaire-assessed screen-behaviors over 1-, 2-, 3-, or more than 4-year follow-up. Effect modification was explored using meta-regression. Eighty-five studies met inclusion criteria. Device-assessed sedentary time increased by (WMD 95% confidence interval [CI]) 27.9 (23.2, 32.7), 61.0 (50.7, 71.4), 63.7 (53.3, 74.0), and 140.7 (105.1, 176.4) min/day over 1-, 2-, 3-, and more than 4-year follow-up. We observed no effect modification by gender, baseline age, study location, attrition, or quality. Questionnaire-assessed time spent playing video games, computer use, and a composite measure of sedentary behavior increased over follow-up duration. Evidence is consistent in showing an age-related increase in various forms of sedentary behavior; evidence pertaining to variability across socio-demographic subgroups and contemporary sedentary behaviors are avenues for future research

Evaluating the quality of interaction between medical students and nurses in a large teaching hospital

BACKGROUND: Effective health care depends on multidisciplinary collaboration and teamwork, yet little is known about how well medical students and nurses interact in the hospital environment, where physicians-in-training acquire their first experiences as members of the health care team. The objective of this study was to evaluate the quality of interaction between third-year medical students and nurses during clinical rotations. METHODS: We surveyed 268 Indiana University medical students and 175 nurses who worked at Indiana University Hospital, the School's chief clinical training site. The students had just completed their third year of training. The survey instrument consisted of 7 items that measured "relational coordination" among members of the health care team, and 9 items that measured psychological distress. RESULTS: Sixty-eight medical students (25.4%) and 99 nurses (56.6%) completed the survey. The relational coordination score (ranked 1 to 5, low to high), which provides an overall measure of interaction quality, showed that medical students interacted with residents the best (4.16) and with nurses the worst (2.98; p < 0.01). Conversely, nurses interacted with other nurses the best (4.36) and with medical students the worst (2.68; p < 0.01). Regarding measures of psychological distress (ranked 0 to 4, low to high), the interpersonal sensitivity score of medical students (1.56) was significantly greater than that of nurses (1.03; p < 0.01), whereas the hostility score of nurses (0.59) was significantly greater than that of medical students (0.39; p < 0.01). CONCLUSION: The quality of interaction between medical students and nurses during third-year clinical rotations is poor, which suggests that medical students are not receiving the sorts of educational experiences that promote optimal physician-nurse collaboration. Medical students and nurses experience different levels of psychological distress, which may adversely impact the quality of their interaction

Mapping Exoplanets

The varied surfaces and atmospheres of planets make them interesting places to live, explore, and study from afar. Unfortunately, the great distance to exoplanets makes it impossible to resolve their disk with current or near-term technology. It is still possible, however, to deduce spatial inhomogeneities in exoplanets provided that different regions are visible at different times---this can be due to rotation, orbital motion, and occultations by a star, planet, or moon. Astronomers have so far constructed maps of thermal emission and albedo for short period giant planets. These maps constrain atmospheric dynamics and cloud patterns in exotic atmospheres. In the future, exo-cartography could yield surface maps of terrestrial planets, hinting at the geophysical and geochemical processes that shape them.Comment: Updated chapter for Handbook of Exoplanets, eds. Deeg & Belmonte. 17 pages, including 6 figures and 4 pages of reference

Eta Carinae and the Luminous Blue Variables

We evaluate the place of Eta Carinae amongst the class of luminous blue variables (LBVs) and show that the LBV phenomenon is not restricted to extremely luminous objects like Eta Car, but extends luminosities as low as log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses as low as ~10-15 Msun. We present a census of S Doradus variability, and discuss basic LBV properties, their mass-loss behaviour, and whether at maximum light they form pseudo-photospheres. We argue that those objects that exhibit giant Eta Car-type eruptions are most likely related to the more common type of S Doradus variability. Alternative atmospheric models as well as sub-photospheric models for the instability are presented, but the true nature of the LBV phenomenon remains as yet elusive. We end with a discussion on the evolutionary status of LBVs - highlighting recent indications that some LBVs may be in a direct pre-supernova state, in contradiction to the standard paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova imposters" (eds R. Humphreys and K. Davidson) new version submitted to Springe

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

&lt;b&gt;Background&lt;/b&gt; Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation