Aims
To validate host‐specific Bacteroidales assays to identify faecal‐source contamination of drinking water sources in the Kathmandu Valley, Nepal.
Methods and Results
A total of 54 composite ...faecal‐source samples were collected from human sewage, ruminants, pigs, dogs, chickens and ducks, which were analysed by quantitative polymerase chain reaction using human‐specific (BacHum, HF183 SYBR, gyrB and HF183 TaqMan), ruminant‐specific (BacCow and BacR), pig‐specific (Pig2Bac and PF163) and dog‐specific assays (BacCan SYBR). The BacHum, BacR and Pig2Bac assays were judged the best performing human‐specific, ruminant‐specific and pig‐specific assays respectively. The BacCan SYBR assay highly cross‐reacted with other species, resulting in poor performance. Furthermore, these validated assays were applied to microbial source tracking (MST) of 74 drinking water samples. Out of these, 20, 12 and 4% samples were judged contaminated by human, ruminant and pig faeces respectively. Detection ratios of human and ruminant faecal markers were relatively higher in built‐up and agricultural areas respectively.
Conclusion
BacHum, BacR and Pig2Bac assays were found suitable for MST and both, human and animal faecal contaminations of drinking water sources were common in the valley.
Significance and Impact of the study
MST could be an effective tool for preparing the faecal pollution strategies as these are site specific.
Intrinsically disordered proteins (IDPs) are abundant in eukaryotic proteomes, play a major role in cell signaling, and are associated with human diseases. To understand IDP function it is critical ...to determine their configurational ensemble, i.e., the collection of 3-dimensional structures they adopt, and this remains an immense challenge in structural biology. Attempts to determine this ensemble computationally have been hitherto hampered by the necessity of reweighting molecular dynamics (MD) results or biasing simulation in order to match ensemble-averaged experimental observables, operations that reduce the precision of the generated model because different structural ensembles may yield the same experimental observable. Here, by employing enhanced sampling MD we reproduce the experimental small-angle neutron and X-ray scattering profiles and the NMR chemical shifts of the disordered N terminal (SH4UD) of c-Src kinase without reweighting or constraining the simulations. The unbiased simulation results reveal a weakly funneled and rugged free energy landscape of SH4UD, which gives rise to a heterogeneous ensemble of structures that cannot be described by simple polymer theory. SH4UD adopts transient helices, which are found away from known phosphorylation sites and could play a key role in the stabilization of structural regions necessary for phosphorylation. Our findings indicate that adequately sampled molecular simulations can be performed to provide accurate physical models of flexible biosystems, thus rationalizing their biological function.
Uptake of next‐generation sequencing (NGS) has increased dramatically due to significant cost reductions and broader community acceptance of NGS. To systematically review the evidence on both the ...clinical effectiveness and the cost‐effectiveness of applying NGS to cancer care. A systematic search for full‐length original research articles on the clinical effectiveness and cost‐effectiveness of NGS in MEDLINE and EMBASE. Articles that focussed on cancer care and involved the application of NGS were included for the review of clinical effectiveness. For the cost‐effectiveness review, we only included the articles with economic evaluations of NGS in cancer care. We report the rate of successfully detecting mutations from the clinical studies. The incremental cost‐effectiveness ratio and sensitivity analysis outcomes are reported for the cost‐effectiveness articles. Fifty‐six articles reported that sequencing patient samples using targeted gene panels, and 83% of the successfully sequenced patients harboured at least 1 mutation. Only 6 studies reported on the cost‐effectiveness of the application of NGS in cancer care. NGS is an effective tool for identifying mutation in cancer patients. However, more rigorous cost‐effectiveness studies of NGS applied to cancer management are needed to determine whether NGS can improve patient outcomes cost‐effectively.
Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow diagram describing article selection process for the effectiveness of next‐generation sequencing (NGS) in cancer management.
Introduction Although great strides have been made in maternal and newborn health in Nepal, the maternal mortality ratio (MMR) is still high at 186 per 100,000 births. Many maternal deaths are ...preventable if there is access to a skilled birth attendant (SBA). The Ministry of Health and Population of Nepal launched the in-service SBA training program in 2007 and has trained over 10,000 SBAs to date. Evidence shows that one episode of training is not enough to retain skills. Therefore, the Nick Simons Institute (NSI) in collaboration with National Health Training Center (NHTC) devised a Follow-Up and Enhancement Program (FEP) in 2011 where the knowledge, clinical skills, and working environment of SBA graduates were assessed directly at their worksites. FEP allows on-site coaching and feedback so that graduates may continue to improve upon any gaps in their knowledge, skills, and working environment. This study aims to assess the effectiveness of FEP. Methods We used a mixed-methods research design. A total of 73 SBAs who had a pre-FEP assessment in 2016 were followed up for a post-FEP assessment in 2017. We also collected data from 3 additional districts (115 SBAs) that had not previously had FEP, to compare SBAs in FEP versus non-FEP districts. Qualitative data was collected from 16 health facilities on the perceptions, motivation, and satisfaction of stakeholders. Results Of the total 188 SBAs that were sampled, a one-time FEP increased knowledge scores by 9%, clinical skills scores by 29%, and enabling environment scores by 7%. The number of deliveries conducted improved with a one-time FEP, although this increase was not statistically significant. We found a trickle-down effect of working in a facility that has had prior FEP, with SBAs that have never had FEP improving their clinical skills. FEP was found to be a highly accepted program and is beneficial to SBAs, trainers, and the Hospital Management Committee (HFOMC). However, a one-time FEP is not sufficient in retaining clinical skills and knowledge. Conclusion FEP is a highly effective program by both quantitative and qualitative evaluation. Our study suggests that FEP should be frequent and continuous to retain the knowledge and clinical skills of SBAs, motivate them through on-site coaching, and improve their working environment through direct feedback to the Ministry of Health and Population.
The past decade has seen an explosive increase in the number of peer reviewed papers reporting new scientific findings in geomorphology (including fans, channels, floodplains and landscape ...evolution), geologic mapping, tectonics and faulting, coastal processes, lava flows, hydrology (especially snow and runoff routing), glaciers and geo-archaeology. A common genesis of such findings is often newly available decimeter resolution 'bare Earth' geodetic images, derived from airborne laser swath mapping, a.k.a. airborne LiDAR, observations. In this paper we trace nearly a half century of advances in geodetic science made possible by space age technology, such as the invention of short-pulse-length high-pulse-rate lasers, solid state inertial measurement units, chip-based high speed electronics and the GPS satellite navigation system, that today make it possible to map hundreds of square kilometers of terrain in hours, even in areas covered with dense vegetation or shallow water. To illustrate the impact of the LiDAR observations we present examples of geodetic images that are not only stunning to the eye, but help researchers to develop quantitative models explaining how terrain evolved to its present form, and how it will likely change with time. Airborne LiDAR technology continues to develop quickly, promising ever more scientific discoveries in the years ahead.
Molecular dynamics (MD) simulation is widely used to complement ensemble-averaged experiments of intrinsically disordered proteins (IDPs). However, MD often suffers from limitations of inaccuracy. ...Here, we show that enhancing the sampling using Hamiltonian replica-exchange MD (HREMD) led to unbiased and accurate ensembles, reproducing small-angle scattering and NMR chemical shift experiments, for three IDPs of varying sequence properties using two recently optimized force fields, indicating the general applicability of HREMD for IDPs. We further demonstrate that, unlike HREMD, standard MD can reproduce experimental NMR chemical shifts, but not small-angle scattering data, suggesting chemical shifts are insufficient for testing the validity of IDP ensembles. Surprisingly, we reveal that despite differences in their sequence, the inter-chain statistics of all three IDPs are similar for short contour lengths (< 10 residues). The results suggest that the major hurdle of generating an accurate unbiased ensemble for IDPs has now been largely overcome.
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