Spatiotemporal dynamics of vector-borne disease risk across human land-use gradients: examining the role of agriculture, indigenous territories, and protected areas in Costa Rica

Background Costa Rica has undergone significant changes to its forest ecosystems due, in part, to the proliferation of palm oil and other industrial agriculture operations. However, the country also boasts conservation programmes that are among the most robust in the neotropics. Consequently, gradients of anthropogenic to intact ecosystems are found throughout the country. Forest ecosystems may decrease vector-borne disease (VBD) risk by maintaining insect populations in a state of relative equilibrium; however, evidence suggests that intact forests foster biodiversity and may also amplify VBD risk in some circumstances. As a result, focal points of human-vector contact are likely idiosyncratic. This may be particularly true in indigenous territories, which have been shown to play a vital role in maintaining the ecological integrity of conservation areas. Here, we investigate the relationships between anthropogenic landscapes, indigenous territories, protected areas, and risk of VBD. Methods We quantified spatial dynamics of risk across three distinct categories of VBD in Costa Rica: emerging flaviviruses (Zika virus disease and dengue); neglected tropical diseases (cutaneous leishmaniasis and Chagas disease); and a disease nearing eradication (malaria). We collected district-level incidence data from between 2006 and 2017 and used spatial statistics to identify hotspots of elevated risk. We then quantified the associations between anthropogenic landscapes, intact forest ecosystems, and indigenous territories with both the presence and persistence of elevated transmission risk over time using multivariate hurdle models. Findings We detected clear patterns of non-random disease risk across each of the three categories of VBD. Compared with protected areas, districts with higher proportions of human-altered landscapes, particularly agricultural intensification, were at higher risk for VBD across all categories. Districts with the highest proportion of crop cover, compared with the lowest proportion, were significantly associated with the presence of hotspots for Zika virus disease (OR 15·19 [95% CI 6·19–37·26]), dengue (13·00 [7·24–23·35]), leishmaniasis (4·46 [1·18–16·84]), Chagas disease (3·09 [1·47–6·49]), and malaria (8·40 [3·56–19·83]). Interpretation A set of spatial epidemiology tools within a planetary health framework allowed for a refined understanding of the risk of VBD of global public health significance in a biodiversity hotspot. Our findings may be used to better guide targeted public health disease surveillance, control, and prevention programmes. Additional research to understand the role that socioeconomic factors play in the variating VBD risk would contribute additional context to these findings, as these factors are often also spatially associated

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

New Technique for Probing the Protecting Character of the Solid Electrolyte Interphase as a Critical but Elusive Property for Pursuing Long Cycle Life Lithium-Ion Batteries

The formation of a protecting nanolayer, so-called solid electrolyte interphase (SEI), on the negative electrode of Li-ion batteries (LIBs) from product precipitation of the cathodic decomposition of the electrolyte is a blessing since the electrically insulating nature of this nanolayer protects the electrode surface, preventing continuous electrolyte decomposition and enabling the large nominal cell voltage of LIBs, e.g., 3.3–3.8 V. Thus, the protection performance of the nanolayer SEI is essential for LIBs to achieve a long cycle life. Unfortunately, the evaluation of this critical property of the SEI is not trivial. Herein, a new, cheap, and easily implementable methodology, the redox-mediated enhanced coulometry, is presented to estimate the protecting quality of the SEI. The key element of the methodology is the addition of a redox mediator in the electrolyte during the degassing step (after the SEI formation cycle). The redox mediator leads to an internal self-discharge process that is inversely proportional to the protecting character of the SEI. Also, the self-discharge process results in an easily measurable decrease in Coulombic efficiency. The influence of vinylene carbonate as an electrolyte additive in the resulting SEI is used as a case study to showcase the potential of the proposed methodology

Surface-Enhanced Raman Scattering-Based Detection of the Interactions between the Essential Cell Division FtsZ Protein and Bacterial Membrane Elements

Surface-enhanced Raman scattering (SERS) spectroscopy has been applied to detect the interaction of the FtsZ protein from <i>Escherichia coli</i>, an essential component of the bacterial division machinery, with either a soluble variant of the ZipA protein (that provides membrane tethering to FtsZ) or the bacterial membrane (containing the full-length ZipA naturally incorporated), on silver-coated polystyrene micrometer-sized beads. The engineered microbeads were used not only to support the bilayers but also to offer a stable support with a high density of SERS hot spots, allowing the detection of ZipA structural changes linked to the binding of FtsZ. These changes were different upon incubating the coated beads with FtsZ polymers (GTP form) as compared to oligomers (GDP form) and more pronounced when the plasmonic sensors were coated with natural bacterial membranes

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system. Results A total of 3288 patients were included in the analysis, of whom 301 (9 center dot 2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P &lt; 0 center dot 001). There were no significant differences in rates of readmission between these groups (6 center dot 6 versus 8 center dot 0 per cent; P = 0 center dot 499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0 center dot 90, 95 per cent c.i. 0 center dot 55 to 1 center dot 46; P = 0 center dot 659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34 center dot 7 versus 39 center dot 5 per cent; major 3 center dot 3 versus 3 center dot 4 per cent; P = 0 center dot 110). Conclusion Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients