Candidates registered for reasonable adjustments underperform compared to other candidates in the national undergraduate Prescribing Safety Assessment: Retrospective cohort analysis (2014-2018).

AIMS: Candidates with disabilities are eligible for reasonable adjustments (RA) while undertaking the national Prescribing Safety Assessment (PSA). The PSA is a novel open-book, time-constrained, multiformat assessment that may pose challenges to candidates with dyslexia and other disabilities. METHODS: Retrospective cohort analysis of 36 140 UK candidates undertaking first-sitting of the PSA (2014-2018). RESULTS: Of the 36 140 candidates, 9.1% (3284) were registered for RA. The RA group had lower pass rates (absolute difference 1.94%, 95% confidence interval 1.01-2.87%; P < .001) and assessment scores (1.16 percentage marks, 95% confidence interval 0.83-1.48; P < .001) compared with the non-RA group. This absolute difference is small relative to overall variability. This difference persists after adjusting for confounding factors (medical school and paper), and was present for all 8 different question types. The attainment gap within each medical school is negatively correlated with the school's overall performance, both in terms of pass rate (P < .001) and scores (P = .01). The RA group were also less likely to perceive the PSA as an appropriate test, having easy to follow layout/presentation or clear/unambiguous questions, even after adjusting for candidate performance. CONCLUSION: This analysis identifies slight differences in academic performance of candidates requiring RA in a national undergraduate assessment. The study is limited by the unavailability of data on ethnicity, sex, age, diagnosis and time of diagnosis. While further research is required to determine the cause of the attainment gap, this study emphasises the need to maintain a careful review on the fairness and validity of all aspects of the assessment

Chronic Toxoplasma Infection Modifies the Structure and the Risk of Host Behavior

The intracellular parasite Toxoplasma has an indirect life cycle, in which felids are the definitive host. It has been suggested that this parasite developed mechanisms for enhancing its transmission rate to felids by inducing behavioral modifications in the intermediate rodent host. For example, Toxoplasma-infected rodents display a reduction in the innate fear of predator odor. However, animals with Toxoplasma infection acquired in the wild are more often caught in traps, suggesting that there are manipulations of intermediate host behavior beyond those that increase predation by felids. We investigated the behavioral modifications of Toxoplasma-infected mice in environments with exposed versus non-exposed areas, and found that chronically infected mice with brain cysts display a plethora of behavioral alterations. Using principal component analysis, we discovered that most of the behavioral differences observed in cyst-containing animals reflected changes in the microstructure of exploratory behavior and risk/unconditioned fear. We next examined whether these behavioral changes were related to the presence and distribution of parasitic cysts in the brain of chronically infected mice. We found no strong cyst tropism for any particular brain area but found that the distribution of Toxoplasma cysts in the brain of infected animals was not random, and that particular combinations of cyst localizations changed risk/unconditioned fear in the host. These results suggest that brain cysts in animals chronically infected with Toxoplasma alter the fine structure of exploratory behavior and risk/unconditioned fear, which may result in greater capture probability of infected rodents. These data also raise the possibility that selective pressures acted on Toxoplasma to broaden its transmission between intermediate predator hosts, in addition to felid definitive hosts

Emerging Infectious Disease leads to Rapid Population Decline of Common British Birds

Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period

Nucleotide Binding Switches the Information Flow in Ras GTPases

The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins) that are essential to intracellular signal transduction. The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (SGDP and SGTP, respectively). For all the considered systems, the intrinsic flexibility of SGDP was higher than that of SGTP, suggesting that Guanine Exchange Factor (GEF) recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. Indeed, SGDP of Gαt, is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. Moreover, mechanically distinct domains implicated in nucleotide switch could be detected in the presence of GDP but not in the presence of GTP. Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. The average solvent exposure of these amino acids correlates in turn with the rate of GDP release, suggesting for them either direct or indirect roles in the process of nucleotide switch. Collectively, nucleotide binding changes the information flow through the conserved Ras-like domain, where GDP enhances the flexibility of mechanically distinct portions involved in nucleotide switch, and favors long distance allosteric communication (in Gα proteins), compared to GTP

Submarine groundwater discharge to Tampa Bay : nutrient fluxes and biogeochemistry of the coastal aquifer

This paper is not subject to U.S. copyright. The definitive version was published in Marine Chemistry 104 (2007): 85-97, doi:10.1016/j.marchem.2006.10.012.To separately quantify the roles of fresh and saline submarine groundwater discharge (SGD), relative to that of rivers, in transporting nutrients to Tampa Bay, Florida, we used three approaches (Darcy's Law calculations, a watershed water budget, and a 222Rn mass-balance) to estimate rate of SGD from the Pinellas peninsula. Groundwater samples were collected in 69 locations in the coastal aquifer to examine biogeochemical conditions, nutrient concentrations and stoichiometry, and salinity structure. Salinity structure was also examined using stationary electrical resistivity measurements. The coastal aquifer along the Pinellas peninsula was chemically reducing in all locations sampled, and that condition influences nitrogen (N) form and mobility of N and PO43−. Concentrations of NH4+, PO43− and ratio of dissolved inorganic N (DIN) to PO43− were all related to measured oxidation/reduction potential (pε) of the groundwater. Ratio of DIN: PO43− was below Redfield ratio in both fresh and saline groundwater. Nitrogen occurred almost exclusively in reduced forms, NH4+ and dissolved organic nitrogen (DON), suggesting that anthropogenic N is exported from the watershed in those forms. In comparison to other SGD studies, rate of PO43− flux in the seepage zone (μM m− 2 d− 1) in Tampa Bay was higher than previous estimates, likely due to 1) high watershed population density, 2) chemically reducing conditions, and 3) high ion concentrations in fresh groundwater. Estimates of freshwater groundwater flux indicate that the ratio of groundwater discharge to stream flow is not, vert, similar 20 to 50%, and that the magnitudes of both the total dissolved nitrogen and PO43− loads due to fresh SGD are not, vert, similar 40 to 100% of loads carried by streams. Estimates of SGD based on radon inventories in near-shore waters were 2 to 5 times greater than the estimates of freshwater groundwater discharge, suggesting that brackish and saline SGD is also an important process in Tampa Bay and results in flux of regenerated N and P from sediment to surface water.This work was supported by a USGS Mendenhall Postdoctoral Fellowship to K.D.K. and by the USGS Coastal and Marine Geology Program's (CMGP) Tampa Bay Project

Operative versus non-operative management of pediatric medial epicondyle fractures: a systematic review

There is ongoing debate about the management of medial epicondyle fractures in the pediatric population. This systematic review evaluated non-operative versus operative treatment of medial epicondyle fractures in pediatric and adolescent patients over the last six decades. A systematic review of the available literature was performed. Frequency-weighted mean union times were used to compare union rates for closed versus open treatments. Moreover, functional outcomes and range-of-motion variables were correlated with varying treatment modalities. Any complications, including ulnar nerve symptoms, pain, instability, infection, and residual deformity, were cataloged. Fourteen studies, encompassing 498 patients, met the inclusion/exclusion criteria. There were 261 males and 132 female patients; the frequency-weighted average age was 11.93 years. The follow-up range was 6–216 months. Under the cumulative random effects model, the odds of union with operative fixation was 9.33 times the odds of union with non-operative treatment (P &lt; 0.0001). There was no significant difference between operative and non-operative treatments in terms of pain at final follow-up (P = 0.73) or ulnar nerve symptoms (P = 0.412). Operative treatment affords a significantly higher union rate over the non-operative management of medial epicondyle fractures. There was no difference in pain at final follow-up between operative and non-operative treatments. As surgical indications evolve, and the functional demands of pediatric patients increase, surgical fixation should be strongly considered to achieve stable fixation and bony union

Factors Associated with Refusal of Rapid HIV Testing in an Emergency Department

HIV screening studies in the emergency department (ED) have demonstrated rates of HIV test refusal ranging from 40–67%. This study aimed to determine the factors associated with refusal to undergo routine rapid HIV testing in an academic ED in Boston. HIV counselors offered routine testing to 1,959 patients; almost one-third of patients (29%) refused. Data from a self-administered survey were used to determine independent correlates of HIV testing refusal. In multivariate analysis, women and patients with annual household incomes of $50,000 or more were more likely to refuse testing, as were those who reported not engaging in HIV risk behaviors, those previously HIV tested and those who did not perceive a need for testing. Enrollment during morning hours was also associated with an increased risk of refusal. Increased educational efforts to convey the rationale and benefits of universal screening may improve testing uptake among these groups

Management of congestive heart failure: a gender gap may still exist. Observations from a contemporary cohort

BACKGROUND: Unlike other cardiovascular diseases the incidence and prevalence of congestive heart failure (CHF) continues to increase. While gender differences in coronary artery disease have been well described, to date, there has been a relative paucity of similar data in patients with CHF. We conducted a pilot study to evaluate the profile and management of patients with CHF at a tertiary care centre to determine if a gender difference exists. METHODS: A chart review was performed at a tertiary care centre on consecutive patients admitted with a primary diagnosis of CHF between June 1997 and 1998. Co-morbidity, diagnostic investigations, and management of CHF were recorded. Comparisons between male and female patients were conducted. RESULTS: One hundred and forty five patients were reviewed. There were 80 male (M) and 65 female (F) patients of similar age [71.6 vs. 71.3 (M vs. F), p = NS]. Male patients were more likely to have had a previous myocardial infarction (66% vs. 35%, p < 0.01) and revascularization (41% vs. 20%, p < 0.05), and had worse left ventricular ejection fraction (LVEF) than women, [median LVEF 3 vs. 2 (M vs. F), p < 0.01]. Male patients were more likely to have a non-invasive assessment of left ventricular (LV) function [85% vs. 69%, (M vs. F), p < 0.05]. A logistic regression analysis suggests that amongst those without coronary disease, males were more likely to receive non-invasive testing. There were no differences in the use of prescribed medications, in this cohort. CONCLUSIONS: This pilot study demonstrated that there seem to be important gender differences in the profile and management of patients with CHF. Importantly women were less likely to have an evaluation of LV function. As assessment of LV function has significant implications on patient management, this data justifies the need for larger studies to assess gender differences in CHF profile and treatment