Comparison of baseline drinking practices, knowledge, and attitudes of adult s residing in communities taking part in the FAS prevention study in South Africa

Foetal Alcohol Syndrome (FAS) has been identified as among the most serious consequences associated with hazardous and harmful drinking in the Western Cape province, South Africa. Community surveys were conducted in two wine growing regions in this province to assess drinking behaviour, guide interventions and serve as a baseline for assessing the impact of population-level interventions. As part of a cross-sectional comparative study interviews were conducted with 384 and 209 randomly selected adults in the prevention (PC) and comparison communities (CC) respectively. Over 80% of respondents resided in urban areas, except inthe CC, where 61% of males resided on farms. Symptoms of hazardous or harmful drinking were reported by 16.0% of females and 32.5% of males in the PC, while 19.3% of females and 56.2% of males in the CC reported such drinking. Over two-thirds of respondents indicated that it was equally harmful for a woman to drink during any of the trimesters of pregnancy, but more than 30% of the women interviewed had never had a health worker speak to them about the effects of drinking during pregnancy. Over 10% had never heard of fetal alcohol syndrome. The findings reinforce the need for interventions to address hazardous/harmful use of alcohol inboth communities and also to address gaps in knowledge regarding the effects of drinking during pregnancy.Key Words: Alcohol, epidemiology, pregnancy, South Afric

Multi‐decadal coastline dynamics in Suriname controlled by migrating subtidal mudbanks

This is the final version. Available from Wiley via the DOI in this record. DATA AVAILABILITY STATEMENT The pre-processing scripts that are used to define outliers for coastline position estimates and annual change metrics are available through Github: https://github.com/jobbo90/offshore_boundary/ releases/tag/v0.2 The reported coastline position estimates and indications of mudbank presence can be found in the online GEE repository (v02), which also includes the scripts used to derive these indicators: https://code.earthengine.google.com/?accept_repo=users/jobdevries90/ MangroMud The UAV drone datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.For the development of climate-resilient coastal management strategies, which focus on challenges in the decades to come, it is critical to incorporate spatial and temporal variability of coastline changes. This is particularly true for the mud-dominated coastline of Suriname, part of the Guianas, where migrating subtidal mudbanks cause a cyclic instability of erosion and accretion of the coast that can be directly related to interbank and bank phases. The coastline hosts extensive mangrove forests, providing valuable ecosystem services to local communities. Recent studies on mudbank dynamics in Suriname predominantly focused on large-scale trends without accounting for local variability, or on local changes considering the dynamics of a single mudbank over relatively short time scales. Here we use a remote sensing approach, with sufficient spatial and temporal resolution and full spatial and temporal coverage, to quantify the influence of mudbank migration on spatiotemporal coastline dynamics along the entire coast of Suriname. We show that migration of six to eight subtidal mudbanks in front of the Suriname coast has a strong imprint on local coastline dynamics between 1986 and 2020, with an average 32 m/yr accretion during mudbank presence and 4 m/yr retreat of the coastline during mudbank absence. Yet, coastal erosion can still occur when mudbanks are present and coastal aggregation may happen in the absence of mudbanks, exemplifying local variability and thus suggesting the importance of other drivers of coastline changes. The novel remote sensing workflow allowed us to analyse local spatial and temporal variations in the magnitude and timing of expanding and retreating trajectories. Our results demonstrate that it is essential that all coastal behaviours, including changes that cannot be explained by the migration of mudbanks, are included in multi-decadal management frameworks that try to explain current variability, and predict future coastline changes in Suriname.NWO WOTRO Joint Sustainability Development Goal Research Progra

Unmixing water and mud: Characterizing diffuse boundaries of subtidal mud banks from individual satellite observations

This is the final version. Available from Elsevier via the DOI in this record. Mapping of subtidal banks in mud-dominated coastal systems is crucial as they influence not only shoreline and ecosystem dynamics but also economic activities and livelihoods of local communities. Due to associated spatiotemporal variations in suspended particulate matter concentrations, subtidal mudbanks are often confined by diffuse and rapidly changing boundaries. To avoid inaccurate representations of these mudbanks in remote sensing images, it is necessary to unmix distinctive reflectance signals into representative landcover fractions. Yet, extracting mud fractions, in order to characterize such diffuse boundaries, is challenging because of the spectral similarity between subtidal- and intertidal features. Here we show that an unsupervised decision tree, used to derive spatially explicit and spectrally coherent image endmembers, facilitates robust linear spectral unmixing on an image-to-image basis, enabling the separation of these coastal features. We found that resulting abundance maps represent cross-shore gradients of vegetation, water and mud fractions present at the coast of Suriname. Furthermore, we confirmed that it is possible to separate land, water and an initial estimate of intertidal zones on individual images. Thus, spectral signatures of end-member candidates, determined from relevant index histograms within these initial estimates, are consistent. These results demonstrate that spectral information from well-defined spatial neighbourhoods facilitates the detection of diffuse boundaries of mudbanks with a spectral unmixing approach.NWO WOTR

Using Three-Dimensional Gait Data for Foot/Ankle Orthopaedic Surgery

We present the case of a forty year old male who sustained a torn carotid during strenuous physical activity. This was followed by a right hemispheric stroke due to a clot associated with the carotid. Upon recovery, the patient’s gait was characterized as hemiparetic with a stiff-knee pattern, a fixed flexion deformity of the toe flexors, and a hindfoot varus. Based on clinical exams and radiographs, the surgical treatment plan was established and consisted of correction of the forefoot deformities, possible hamstrings lengthening, and tendon transfer of the posterior tibial tendon to the dorsolateral foot. To aid in surgical planning, a three-dimensional gait analysis was conducted using a state-of-the-art motion capture system. Data from this analysis provided insight into the pathomechanics of the patient’s gait pattern. A forefoot driven hindfoot varus was evident from the presurgical data and the tendon transfer procedure was deemed unnecessary. A computer was used in the OR to provide surgeons with animations of the patient’s gait and graphical results as needed. A second gait analysis was conducted 6 weeks post surgery, shortly after cast removal. Post-surgical gait data showed improved foot segment orientation and position. Motion capture data provides clinicians with detailed information on the multisegment kinematics of foot motion during gait, before and during surgery. Further, treatment effectiveness can be evaluated by repeating gait analyses after recovery

The role of causal knowledge in stigma considerations in African genomics research

Introduction: Advances in genomics research have raised several ethical concerns. One concern is the potential impact of genomics research on stigma experienced by people affected by a disease. Studies have found that the type of illness as well as disease causal beliefs impact on the relation between genetic attribution and stigma. This study explored the potential impact of genetic attribution of disease on stigma among Xhosa people with Rheumatic Heart Disease (RHD). Methods: Study participants were 46 Xhosa people with RHD living in the Western Cape Province of South Africa. Using video vignettes in 7 focus group discussions we explored whether and how genetic attribution may impact on disease-stigma. Vignettes introduced participants to non-genetic and genetic causal explanations and were followed-up with a series of open-ended questions eliciting their perceptions of non-genetic disease causes as well as genetic causation and its impact on internalised stigma. Results: This study found that Xhosa people with RHD have a general understanding of genetics and genetic attribution for disease. Additionally, and not withstanding their genetic knowledge, these participants hold multiple disease causal beliefs including genetic, infectious disease, psychosocial, behavioural and cultural explanations. While there was evidence of internalised stigma experiences among participants, these appeared not to be related to a genetic attribution to the disease. Discussion: The findings of this study provide clues as to why it is unlikely that a genetic conceptualisation of disease impacts internalised stigma experiences of Xhosa people. The causal explanations provided by participants reflect their cultural understandings and their context, namely, living in low-income and poverty-stricken environments. Divergence in these findings from much of the evidence from high-income countries emphasises that context matters when considering the impact of genetic attribution on stigma and caution against generalising findings from one part of the globe to another

A broader role for AmyR in Aspergillus niger: regulation of the utilisation of d-glucose or d-galactose containing oligo- and polysaccharides

AmyR is commonly considered a regulator of starch degradation whose activity is induced by the presence of maltose, the disaccharide building block of starch. In this study, we demonstrate that the role of AmyR extends beyond starch degradation. Enzyme activity assays, genes expression analysis and growth profiling on d-glucose- and d-galactose-containing oligo- and polysaccharides showed that AmyR regulates the expression of some of the Aspergillus niger genes encoding α- and β-glucosidases, α- and β- galactosidases, as well as genes encoding α-amlyases and glucoamylases. In addition, we provide evidence that d-glucose or a metabolic product thereof may be the inducer of the AmyR system in A. niger and not maltose, as is commonly assumed

CX-072 (pacmilimab), a Probody® PD-L1 inhibitor, in advanced or recurrent solid tumors (PROCLAIM-CX-072): an open-label dose-finding and first-in-human study

Background: Probody® therapeutics are antibody prodrugs that are activated in the tumor microenvironment by tumor-associated proteases, thereby restricting the activity to the tumor microenvironment and minimizing ‘off-tumor’ toxicity. We report dose-escalation and single-agent expansion phase data from the first-in-human study of CX-072 (pacmilimab), a Probody checkpoint inhibitor directed against programmed death-ligand 1 (PD-L1). / Methods: In the dose-escalation phase of this multicenter, open-label study (NCT03013491), adults with advanced solid tumors (naive to programmed-death-1/PD-L1 or cytotoxic T-lymphocyte-associated antigen 4 inhibitors) were enrolled into one of seven dose-escalation cohorts, with pacmilimab administered intravenously every 14 days. The primary endpoints were safety and determination of the maximum tolerated dose (MTD). In the expansion phase, patients with one of six prespecified malignancies (triple-negative breast cancer [TNBC]; anal squamous cell carcinoma [aSCC]; cutaneous SCC [cSCC]; undifferentiated pleomorphic sarcoma [UPS]; small bowel adenocarcinoma [SBA]; and thymic epithelial tumor [TET]); or high tumor mutational burden (hTMB) tumors were enrolled. The primary endpoint was objective response (Response Evaluation Criteria In Solid Tumors v.1.1). / Results: An MTD was not reached with doses up to 30 mg/kg. A recommended phase 2 dose (RP2D) of 10 mg/kg was chosen based on pharmacokinetic and pharmacodynamic findings in the expansion phase. Ninety-eight patients enrolled in the expansion phase: TNBC (n=14), aSCC (n=14), cSCC (n=14), UPS (n=20), SBA (n=14), TET (n=8), and hTMB tumors (n=14). Of 114 patients receiving pacmilimab at the RP2D, grade ≥3 treatment-related adverse events (TRAEs) were reported in 10 patients (9%), serious TRAEs in six patients (5%), and treatment discontinuation due to TRAEs in two patients (2%). Grade ≥3 immune-related AEs occurred in two patients (rash, myocarditis). High PD-L1 expression (ie, >50% Tumor Proportion Score) was observed in 22/144 (19%) patients. Confirmed objective responses were observed in patients with cSCC (n=5, including one complete response), hTMB (n=4, including one complete response), aSCC (n=2), TNBC (n=1), UPS (n=1), and anaplastic thyroid cancer (n=1). / Conclusions: Pacmilimab can be administered safely at the RP2D of 10 mg/kg every 14 days. At this dose, pacmilimab had a low rate of immune-mediated toxicity and showed signs of antitumor activity in patients not selected for high PD-L1 expression. / Trial registration number: NCT03013491

Contrasting responses of mean and extreme snowfall to climate change

Snowfall is an important element of the climate system, and one that is expected to change in a warming climate. Both mean snowfall and the intensity distribution of snowfall are important, with heavy snowfall events having particularly large economic and human impacts. Simulations with climate models indicate that annual mean snowfall declines with warming in most regions but increases in regions with very low surface temperatures. The response of heavy snowfall events to a changing climate, however, is unclear. Here I show that in simulations with climate models under a scenario of high emissions of greenhouse gases, by the late twenty-first century there are smaller fractional changes in the intensities of daily snowfall extremes than in mean snowfall over many Northern Hemisphere land regions. For example, for monthly climatological temperatures just below freezing and surface elevations below 1,000 metres, the 99.99th percentile of daily snowfall decreases by 8% in the multimodel median, compared to a 65% reduction in mean snowfall. Both mean and extreme snowfall must decrease for a sufficiently large warming, but the climatological temperature above which snowfall extremes decrease with warming in the simulations is as high as −9 °C, compared to −14 °C for mean snowfall. These results are supported by a physically based theory that is consistent with the observed rain–snow transition. According to the theory, snowfall extremes occur near an optimal temperature that is insensitive to climate warming, and this results in smaller fractional changes for higher percentiles of daily snowfall. The simulated changes in snowfall that I find would influence surface snow and its hazards; these changes also suggest that it may be difficult to detect a regional climate-change signal in snowfall extremes.National Science Foundation (U.S.) (Grant AGS-1148594)United States. National Aeronautics and Space Administration (ROSES Grant 09-IDS09-0049