Molecular Docking with Open Access Software: Development of an Online Laboratory Handbook and Remote Workflow for Chemistry and Pharmacy Master's Students to Undertake Computer-Aided Drug Design

In response to the closure of many university laboratories due to the Covid-19 pandemic in 2020, a handbook and remote webinar approach designed to support students in the use of software tools for computer-aided drug design has been developed. Specifically, the course has been designed for chemistry and pharmacy students who have little or no experience of computational techniques and can use open-source software on their own machines. In this way a flexible and relevant course, giving a rigorous academic experience, could be delivered even in the most challenging of circumstances. We believe that this laboratory protocol will help to "democratize"the scientific process in this field

Investigation of polycystic ovarian syndrome

Objective Accurate diagnosis of polycystic ovarian syndrome (PCOS) enables clinical interventions/cardiometabolic risk factor management. Diagnosis can take over 2 years and multiple clinician contacts. We examined patterns of PCOS-associated biochemical investigations following initial consultation prior to pelvic ultrasound scan (USS). Methods We determined in 206 women (i) the range of different biochemical test panels used in the diagnosis of PCOS in primary/secondary care prior to USS relative to national guidance in the UK and (ii) the relation between testing patterns and time to USS to highlight potential delays introduced by inappropriate testing. Results In these 206 women, 47 different test combinations were requested at initial venepuncture; only 7 (3%) had the test panel suggested in UK guidance (follicle-stimulating hormone/luteinizing hormone/testosterone/sex hormone-binding globulin/prolactin). The number of tests performed prior to USS varied from one test to all seven tests. There was an inverse relation between the number of biochemistry tests requested at initial venepuncture episode and ‘time to scan’. Those who had <3 tests had a significantly longer time from first request to USS (median 70 days) than those with 3–7 tests (median 40 days; P = 0.002). One venepuncture episode prior to USS was associated with shorter ‘time to scan’ (median 29 days) than those with 2–4 episodes (median 255 days; P < 0.001). Conclusion There was no identifiable pattern to biochemical investigations requested as part of the initial diagnostic evaluation in women with suspected PCOS. We recommend standardization of the initial biochemical panel of analytes for PCOS workup, with incorporation into hospital/general practice ordering software systems

The effects of land use disturbance varies with trophic position in littoral cichlid fish communities from Lake Tanganyika

Impacts of anthropogenic disturbance are especially severe in freshwater ecosystems. In particular, land use disturbance can lead to increased levels of pollution, including elevated nutrient and sediment loads whose negative impacts range from the community to the individual level. However, few studies have investigated if these impacts are uniform across species represented by multiple trophic levels. To address this knowledge gap, we focused on Lake Tanganyika cichlid fishes, which comprise hundreds of species representing a wide range of feeding strategies. Cichlids are at their most diverse within the near‐shore environment; however, land use disturbance of this environment has led to decreasing diversity, particularly in herbivores. We therefore tested if there is a uniform effect of pollution across species and trophic groups within the hyper‐diverse rocky shore cichlid fish community. We selected three sites with differing levels of human impact along the Tanzanian coastline and 10 cichlid species, comprising varying taxonomic and trophic groups, common to these sites. Nitrogen and carbon stable isotope values for 528 samples were generated and analysed using generalised linear mixed models. We also estimated stomach contents including sediment proportions. Our study highlights that multiple sources of pollution are having differing effects across species within a diverse fish community. We found that nitrogen stable isotope values were significantly higher at the most disturbed (urbanised) site for benthic feeding species, whereas there was no difference in these isotopes between sites for the water column feeding trophic group. Stomach contents revealed that the elevated δ15N values were unlikely to have been caused by differences in diet between sites. However, at the most disturbed site, higher proportions of sediment were present in most herbivores, irrespective of foraging behaviour. It is likely that anthropogenic nitrogen loading is the cause of higher nitrogen stable isotope values since there was no evidence of species shifting trophic levels between sites. Results support our previous study showing herbivore species to be most affected by human disturbance and make the link to pollution much more explicit. As lower diversity of consumers can negatively affect ecosystem processes such as stability, alleviating environmental impact through sewage treatment and afforestation programmes should continue to be a global priority for the conservation of aquatic ecosystems, as well as human health

Understanding the threats posed by non-native species: public vs. conservation managers.

Public perception is a key factor influencing current conservation policy. Therefore, it is important to determine the influence of the public, end-users and scientists on the prioritisation of conservation issues and the direct implications for policy makers. Here, we assessed public attitudes and the perception of conservation managers to five non-native species in the UK, with these supplemented by those of an ecosystem user, freshwater anglers. We found that threat perception was not influenced by the volume of scientific research or by the actual threats posed by the specific non-native species. Media interest also reflected public perception and vice versa. Anglers were most concerned with perceived threats to their recreational activities but their concerns did not correspond to the greatest demonstrated ecological threat. The perception of conservation managers was an amalgamation of public and angler opinions but was mismatched to quantified ecological risks of the species. As this suggests that invasive species management in the UK is vulnerable to a knowledge gap, researchers must consider the intrinsic characteristics of their study species to determine whether raising public perception will be effective. The case study of the topmouth gudgeon Pseudorasbora parva reveals that media pressure and political debate has greater capacity to ignite policy changes and impact studies on non-native species than scientific evidence alone

One-stop diagnostic breast clinics: how often are breast cancers missed?

The aim of this study was to estimate the number of patients discharged from a symptomatic breast clinic who subsequently develop breast cancer and to determine how many of these cancers had been ‘missed' at initial assessment. Over a 3-year period, 7004 patients were discharged with a nonmalignant diagnosis. Twenty-nine patients were subsequently diagnosed with breast cancer over the next 36 months. This equates to a symptomatic ‘interval' cancer rate of 4.1 per 1000 women in the 36 months after initial assessment (0.9 per 1000 women within 12 months, 2.6 per 1000 women within 24 months). The lowest sensitivity of initial assessment was seen in patients of 40–49 years of age, and these patients present the greatest imaging and diagnostic challenge. Following multidisciplinary review, a consensus was reached on whether a cancer had been missed or not. No delay occurred in 10 patients (35%) and probably no delay in 7 patients (24%). Possible delay occurred in three patients (10%) and definite delay in diagnosis (i.e., a ‘missed' cancer) occurred in only nine patients (31%). The overall diagnostic accuracy of ‘triple' assessment is 99.6% and the ‘missed' cancer rate is 1.7 per 1000 women discharged

Terrestrial-focused protected areas are effective for conservation of freshwater fish diversity in Lake Tanganyika

Freshwater protected areas are rarely designed specifically for this purpose and consequently their conservation benefit cannot be guaranteed. Using Lake Tanganyika as a test case we investigated the benefits of terrestrial-focussed protected areas on the alpha and beta taxonomic and functional diversity of the diverse endemic rocky-shore cichlid fishes. Lake Tanganyika has limited protected shorelines and continued human population growth in its catchment, which has potential for negative impacts on habitat quality and key biological processes. We conducted 554 underwater surveys across a gradient of human disturbance including two protected areas, along 180 km of Tanzanian coastline, sampling 70 cichlid species representing a diverse range of life-histories and trophic groups. Alpha diversity was up to 50% lower outside of protected areas, and herbivores appeared most affected. Turnover dominated within-locality variation in beta diversity, but the nestedness component was positively related to human disturbance indicating an increase in generalist species outside of protected areas. Within protected areas the decline in zeta diversity (the expected number of shared species across multiple surveys) was best described by power law functions, which occur when local abundance is predicted by regional abundance; but declined exponentially in unprotected waters indicating a dominance of stochastic assembly. Despite not being designed for the purpose, the protected areas are clearly benefitting cichlid taxonomic and functional diversity within Lake Tanganyika, probably through local reduction in sediment deposition and/or pollution, but as cichlids can be poor dispersers protected area coverage should be expanded to benefit isolated communities

A novel method for identifying coded tags recorded on aquatic acoustic monitoring systems.

Aquatic biotelemetry increasingly relies on using acoustic transmitters ('tags') that enable passive detection of tagged animals using fixed or mobile receivers. Both tracking methods are resource-limited, restricting the spatial area in which movements of highly mobile animals can be measured using proprietary detection systems. Transmissions from tags are recorded by underwater noise monitoring systems designed for other purposes, such as cetacean monitoring devices, which have been widely deployed in the marine environment; however, no tools currently exist to decode these detections, and thus valuable additional information on animal movements may be missed. Here, we describe simple hybrid methods, with potentially wide application, for obtaining information from otherwise unused data sources. The methods were developed using data from moored, acoustic cetacean detectors (C-PODs) and towed passive receiver arrays, often deployed to monitor the vocalisations of cetaceans, but any similarly formatted data source could be used. The method was applied to decode tag detections that were found to have come from two highly mobile fish species, bass (Dicentrarchus labrax) and Twaite shad (Alosa fallax), that had been tagged in other studies. Decoding results were validated using test tags; range testing data were used to demonstrate the relative efficiency of these receiver methods in detecting tags. This approach broadens the range of equipment from which acoustic tag detections can be decoded. Novel detections derived from the method could add significant value to past and present tracking studies at little additional cost, by providing new insights into the movement of mobile animals at sea

Predicting global invasion risks: a management tool to prevent future introductions

Predicting regions at risk from introductions of non-native species and the subsequent invasions is a fundamental aspect of horizon scanning activities that enable the development of more effective preventative actions and planning of management measures. The Asian cyprinid fish topmouth gudgeon Pseudorasbora parva has proved highly invasive across Europe since its introduction in the 1960s. In addition to direct negative impacts on native fish populations, P. parva has potential for further damage through transmission of an emergent infectious disease, known to cause mortality in other species. To quantify its invasion risk, in regions where it has yet to be introduced, we trained 900 ecological niche models and constructed an Ensemble Model predicting suitability, then integrated a proxy for introduction likelihood. This revealed high potential for P. parva to invade regions well beyond its current invasive range. These included areas in all modelled continents, with several hotspots of climatic suitability and risk of introduction. We believe that these methods are easily adapted for a variety of other invasive species and that such risk maps could be used by policy-makers and managers in hotspots to formulate increased surveillance and early-warning systems that aim to prevent introductions and subsequent invasions

Using liminality to understand mothers’ experiences of long-term breastfeeding: ‘Betwixt and between’, and ‘matter out of place’

© 2015, © The Author(s) 2015. Breastmilk is widely considered as the optimum nutrition source for babies and an important factor in both improving public health and reducing health inequalities. Current international/national policy supports long-term breastfeeding. UK breastfeeding initiation rates are high but rapidly decline, and the numbers breastfeeding in the second year and beyond are unknown. This study used the concept of liminality to explore the experiences of a group of women breastfeeding long-term in the United Kingdom, building on Mahon-Daly and Andrews. Over 80 breastfeeding women were included within the study, which used micro-ethnographic methods (participant observation in breastfeeding support groups, face-to-face interviews and online asynchronous interviews via email). Findings about women’s experiences are congruent with the existing literature, although it is mostly dated and from outside the United Kingdom. Liminality was found to be useful in providing insight into women’s experiences of long-term breastfeeding in relation to both time and place. Understanding women’s experience of breastfeeding beyond current usual norms can be used to inform work with breastfeeding mothers and to encourage more women to breastfeed for longer