The pathogenesis of transient global amnesia (TGA), a dramatic but self-limiting episode of anterograde amnesia with a variable duration of retrograde amnesia, remains unknown. Although most episodes are single, TGA has a finite recurrence rate. Studies of case series and large patient cohorts have typically been used to investigate possible precipitating and predisposing factors for TGA. Study of recurrent TGA episodes in single cases might provide another way to address pathogenetic factors. A patient with recurrent TGA is presented to illustrate such considerations with respect to possible chronobiological factors in TGA pathogenesis.

Ageing is the strongest known risk factor for many of the neurodegenerative diseases causing cognitive decline and dementia. Identification of cognitive impairment may be a prelude to appropriate treatment, hopefully disease-modifying. Use of cognitive screening instruments may be an equitable way to identify cognitive impairment. This study examined the use of two such instruments, Free-Cog and Mini-Addenbrooke’s Cognitive Examination (MACE), in patient cohorts referred to a dedicated cognitive disorders clinic based at a tertiary neurosciences centre. Results showed that: (1) specificity and positive predictive value increased with patient age for both tests with some loss of sensitivity and negative predictive value. (2) In the oldest age groups (≥75 and ≥70 years respectively) where specificity was at maximum, a positive test result (i.e. below the specified test cut-off) rules in the diagnosis of cognitive impairment. (3) Values of an “Efficiency Index” for each test indicated qualitatively a moderate change in the probability of correct diagnosis and quantitatively an approximately 15-25% increase in the probability of correct diagnosis. These findings show that both Free-Cog and MACE may be used with confidence for the identification of cognitive impairment and dementia in older patient cohorts. These findings may have implications for public health policies directed to case-finding in clinical practice as opposed to population-based screening.

Many metrics exist for the evaluation of binary classifiers, all with their particular advantages and shortcomings. Recently an “Efficiency Index” for the evaluation of classifiers has been proposed, based on the consistency, or matching, and contradiction, or mismatching, of outcomes. This metric and its confidence intervals are easy to calculate from base data in a 2x2 contingency table, and values can be qualitatively and semi-quantitatively categorised. For medical tests, in which context the Efficiency Index was originally proposed, it facilitates communication of risk (of correct diagnosis versus misdiagnosis) to both clinicians and patients. Variants of the efficiency index (balanced, unbiased) which take into account disease prevalence and test cut-offs have also been described. The objectives of the current paper were firstly to extend the EI construct to other formulations (balanced level, quality) and secondly to explore the utility of EI and all four of its variants when applied to the dataset of a large prospective test accuracy study of a cognitive screening instrument. This showed that the balanced level, quality, and unbiased formulations of EI are more stringent measures.

Complaint of transient impairment or loss of memory as an attendant feature in some migraine attacks has long been recognised. In some cases, migraine may be a trigger or precipitating factor for the syndrome of transient global amnesia (TGA). However, the exact frequency of this concurrence is unknown, perhaps related to the absence from the International Classification of Headache Disorders (ICHD3) of amnesia or memory loss symptoms in association with migraine, unlike the situation with epileptic seizure (migralepsy) or stroke (migrainous infarction). Similarly, headache has generally been regarded as an incidental feature of TGA, reported in about 10% of cases. We present further examples of TGA in the context of migraine headache; consider possible reasons why this concurrence might be under-recognised, such as the retrograde amnesia characteristic of TGA; review possible shared pathogenetic mechanisms; and suggest a new terminology, “migramnesia”, which may encourage clinicians to address the possible significance of migraine in the context of an episode of TGA.

Bodybuilders utilize peaking strategies in a bid to fine-tune their aesthetics for competition day. The most prevalent peaking strategies utilized by natural bodybuilders are unreported in the current literature. Eighty-one (M - 59, F - 22) natural bodybuilders were recruited from competitions during the 2016 and 2017 British Natural Bodybuilder Federation seasons. Competitors completed a 34-item questionnaire designed to investigate peaking and contest day strategies. The questionnaire listed commonly utilized peaking strategies and provided additional space for qualitative information. Analysis of the data indicated that carbohydrate (CHO), water and sodium manipulation were the most commonly utilized peak week strategies. The consumption of high glycemic index CHO was the most common competition day strategy. Only 6.2 % of competitors reported following their regular diet the week prior to competition. The CHO manipulation strategies were similar to classical CHO loading, whereby bodybuilders attempt to maximize muscle glycogen concentrations. Furthermore, bodybuilders attempted to remove superfluous water by exploiting the diuretic/polyuria effect associated with water loading/restriction. The potentially deleterious effects of peaking on bodybuilders' health is considered and the efficacy of these strategies to enhance appearance is discussed. The findings of the present investigation are likely to be of interest to bodybuilders and their coaches.

Recently a measure termed F* was described, as an interpretable transformation of the F measure, also known as the Dice coefficient. Using elementary mathematical methods, it is shown that F* is in fact identical to a previously described measure, monotonically related to the F measure, and variously termed in previous publications, dating from the late 19^th to the late 20^th century, as the ratio of verification, the Jaccard similarity measure or index, the threat score, the Tanimoto index, and the critical success index. The origins of these different terms in different disciplines (weather forecasting, ecology, machine learning) may explain the repeated independent redescription of this measure.

Eyes are quintessential complex traits and our understanding of their evolution guides models of trait evolution in general. A long-standing account of eye evolution argues natural selection favors morphological variations that allow increased functionality for sensing light (Darwin 1859; v. Salvini-Plawen and Mayr 1977; Nilsson and Pelger 1994; Nilsson 2013). While certainly true in part, this focus on visual performance does not entirely explain why diffuse photosensitivity persists even after eyes evolve, or why eyes evolved many times, each time using similar building blocks. Here we briefly review a vast literature indicating most genetic components of eyes historically responded to stress caused directly by light, including UV damage of DNA, oxidative stress, and production of aldehydes. We propose light-induced stress had a direct and prominent role in the evolution of eyes by bringing together genes to repair and prevent damage from light-stress, both before and during the evolution of eyes themselves. Stress-repair and stress-prevention genes were perhaps originally deployed as plastic responses to light and/or as beneficial mutations genetically driving expression where light was prominent. These stress-response genes sense, shield, and refract light but only as reactions to ongoing light stress. Once under regulatory-genetic control, they could be expressed before light stress appeared, evolve as a module, and be influenced by natural selection to increase functionality for sensing light, ultimately leading to complex eyes and behaviors. Recognizing the potentially prominent role of stress in eye evolution invites discussions of plasticity and assimilation and provides a hypothesis for why similar genes are repeatedly used in convergent eyes. Broadening the drivers of eye evolution encourages consideration of multi-faceted mechanisms of plasticity/assimilation and mutation/selection for complex novelties and innovations in general.

Basaltic activity is the most common class of volcanism on Earth, characterized by magmas of sufficiently low viscosities such that bubbles can move independently of the melt. Following exsolution, spherical bubbles can then expand and/or coalesce to generate larger bubbles of spherical-cap or Taylor bubble (slug) morphologies. Puffing and strombolian explosive activity are driven by bursting of these larger bubbles at the surface. Here, we present the first combined model classification of spherical-cap and Taylor bubble driven puffing and strombolian activity modes on volcanoes. We furthermore incorporate the possibility that neighboring bubbles might coalesce, leading to elevated strombolian explosivity. The model categorizes behavior in terms of the temporal separation between the arrival of successive bubbles at the surface and bubble gas volume or length, with the output presented on visually intuitive two-dimensional plots. The categorized behavior is grouped into the following regimes: puffing from a) cap bubbles; and b) non-overpressurised Taylor bubbles; and c) Taylor bubble driven strombolian explosions; each of these regimes is further subdivided into scenarios whereby inter-bubble interaction does/doesn't occur. The model performance is corroborated using field data from Stromboli (Aeolian Islands, Italy), Etna (Sicily, Italy) and Yasur (Vanuatu), representing one of the very first studies, focused on combining high temporal resolution degassing data with fluid dynamics, as a means of deepening our understanding of the processes which drive basaltic volcanism.

A primary challenge facing conservationists is reconciling the human needs of forest adjacent communities with the needs of conserving forest biodiversity, especially in tropical regions with growing populations of rural poor. Agroforestry has the potential to simultaneously provide for human needs and enhance forest biodiversity, but the complex interactions and feedbacks between the social and natural dimensions are relatively undescribed and thus systematic implementation is rare. The attributes of trees on farms required for human needs and conservation value may conflict. For example, exotic species in monoculture may provide the most economic value for farmers, while relic or planted indigenous tree mixtures may be more valuable for biological conservation. The objective of this study was to explore whether agroforestry practices in a moist tropical forest ecosystem in Kenya can simultaneously provide timber and fuelwood value to small-holder farmers while extending forest tree biodiversity. We described the agroforestry attributes on farms around a tropical forest, assessed the relationship between number and biomass of timber/fuelwood trees and tree biodiversity, and explored the relationships between forest tree diversity attributes and farm tree diversity attributes on a landscape scale using spatial analysis. We found that the diversity and number of trees on farms in this area are extensive yet variable, but that no significant relationship exists between the number of timber/fuelwood trees and tree diversity. This suggests that the two values of agroforestry may not be in conflict, due mainly to the high diversity of trees used for fuelwood. We also found that trees on farms in the larger landscape add to the conservation value of forest tree biodiversity and could be important components in conservation management. If agroforestry is to play an increasingly active role in conserving biodiversity in human-dominated landscapes, particularly in areas of dense subsistence farmer populations, increase recognition needs to be given to farmer’s perception of the value of trees and their selection of what trees to plant or maintain.

Acquisition of real-time hydraulic data is an essential component for flood forecasting. However, we frequently face difficulties in obtaining discharge data using classical contact methods during high magnitude floods and for systems experiencing rapid hydro-geomorphological adjustment. Therefore, we developed low-cost, non-contact sensors and platforms that are designed to overcome these difficulties. These advances enable flood flow properties to be monitored at multiple locations across a river catchment, at low-cost, and communicated in near real-time by using an image velocimetry method. This is an optics-based approach for stream flow measurement using commercially available near-infrared digital cameras to acquire video footage in full HD (30fps). Video footage is then subjected to optical flow tracking techniques based on cross-correlation, and feature-based tracking, enabling the displacement rates of detected features (for example natural foam, seeds, woody debris, and turbulent structures) to be computed. This manual provides step by step guidance to install an image-based gauging station. It contains the list of necessary components, the calibration process of a new camera and the assembly procedure of the system.

Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways leads to the accumulation of lipofuscin and N-retinylidene-N-retinylethanolamine aggregates and chemically-modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as Age-related Macular Degeneration, Stargardt disease and Choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, a-synuclein pathologies and Alzheimer’s disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived.

The selection of biomaterials for biomedical application is a significant challenge. In the last few decades, various bioabsorbable and stable biopolymers have been applied for use as biomedical devices in orthopedic applications. Ultra-high molecular weight polyethylene (UHMWPE) has been extensively used in medical implants, notably in the bearings of hip, knee, and other joint prostheses, owing to its biocompatibility and high wear resistance. For the ACL graft, synthetic UHMWPE is an ideal candidate due to its biocompatibility and its extremely high tensile strength. Despite the appeal of new advanced materials such as carbon fiber, poly-ether-ether ketone, and other load-bearing materials, UHMWPE remains a primary load-bearing candidate material for ACL reconstructions because of its extremely high strength, the simplicity of the fabrication process, its biocompatibility, and low friction. However, some significant problems are observed in UHMWPE based implants, such as wear debris, and oxidative degradation due to the generation of free radicals when exposed to irradiation with gamma rays for grafting or sterilization. Various innovative methodologies have been developed to resolve those problems and enhance the properties of UHMWPE. In this review, we will explore in detail the methods for surface functionalization of UHMWPE and will apply these findings to the case study of UHMWPE for Anterior Cruciate Ligament repair.

Objective: In low- and middle-income countries (LMICs), household survey data are a main source of information for planning, evaluation, and decision-making. Standard surveys are based on censuses, however, for many LMICs it has been more than ten years since their last census and they face high urban growth rates. Over the last decade, survey designers have begun to use modelled gridded population estimates as sample frames. We summarize the state of the emerging field of gridded population survey sampling, focussing on LMICs. Methods: We performed a systematic review and identified 43 national and sub-national gridded population-based household surveys implemented across 29 LMICs. Findings: Gridded population surveys used automated and manual approaches to derive clusters from WorldPop and LandScan gridded population estimates. After sampling, many surveys interviewed all households in each cluster or segment, though some sampled households from larger clusters. Tools to select gridded population survey clusters include the GridSample R package, Geo-sampling tool, and GridSample.org. In the field, gridded population surveys generally relied on geographically accurate maps based on satellite imagery or OpenStreetMap, and a tablet or GPS technology for navigation. Conclusions: For gridded population survey sampling to be adopted more widely, several strategic questions need answering regarding cell-level accuracy and uncertainty of gridded population estimates, the methods used to group/split cells into sample frame units, design effects of new sample designs, and feasibility of tools and methods to implement surveys across diverse settings.

Chlorotoxin (CTX) is a 36–amino acid peptide with 8 Cys residues that forms four Cys-Cys bonds. It has high affinity for the glioma-specific chloride channel and matrix metalloprotease-2. Structural and binding properties of CTX analogs with various Cys residue substitutions with L-a-aminobutyric acid (Abu) have been previously reported. Using 4.2 ìs molecular dynamics, we compared the conformational and essential space sampling of CTX and analogs [Abu/Ser^2,19]CTX, [Abu/Ser^5,28]CTX, [Abu/Ser^16,33]CTX, [Abu/Ser^20,35]CTX, and [Abu/Ser^{2,5,16,19,20,28,33,35}]CTX. The native and substituted peptides maintained a high degree of a-helix propensity from residues 8 through 21, with the exception of [Ser^5,28]CTX and [Abu^16,33]CTX. In agreement with previous circular dichroism spectropolarimetry results, the C-terminal b-sheet content varied less from residues 25 through 29 and 32 through 36 and was well conserved in all analogs, except: [Abu^16,33]CTX, [Ser^20,35]CTX, [Abu^{2,5,16,19,20,28,33,35}]CTX, and [Ser^{2,5,16,19,20,28,33,35}]CTX. The Cys¹⁶-Cys³³ and Cys²⁰-Cys³⁵ Cys-Cys bonds appear to be required to maintain the ab-motif of CTX. Their selective substitution with Ser^16,33 however, may mitigate the destabilizing effect of Cys¹⁶-Cys³³ substitution by the formation of an inter residue H-bond from OgH of Ser¹⁶ to OgH of Ser³³ bridged by a water molecule. All peptides shared considerable sampled conformational space, which explains the retained receptor binding of the nonnative analogs.

Pigment nephropathy is an acute decline in renal function following the deposition of endogenous haem-containing proteins in the kidneys. Haem pigments such as myoglobin and haemoglobin are filtered by glomeruli and absorbed by the proximal tubules. They cause renal vasoconstriction, tubular obstruction, increased oxidative stress and inflammation. Haem is associated with inflammation in sterile and infectious conditions, contributing to the pathogenesis of many disorders such as rhabdomyolysis and haemolytic diseases. In fact, haem appears to be a signaling molecule that is able to activate the inflammasome pathway. Recent studies highlight a pathogenic function for haem in triggering inflammatory responses through the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Among the inflammasome multiprotein complexes, the NLRP3 inflammasome has been the most widely characterized as a trigger of inflammatory caspases and the maturation of interleukin-18 and -1β. In the present review, we discuss the latest evidence on the importance of inflammasome-mediated inflammation in pigment nephropathy. Finally, we highlight the potential role of inflammasome inhibitors in the prophylaxis and treatment of pigment nephropathy.

Imperceptible vibratory noise stimulation has shown to be an effective means of improving stability for both whole body postural control and simple motor control tasks. While the physiological mechanism affording this improvement is uncertain, it is suspected that sensory noise stimulation may elicit a stochastic resonance-like effect within the somatosensory system. A stochastic resonance effect describes the phenomenon in which noise added to a non-linear system improves signal detection rather than degrading it. One hallmark of stochastic resonance is the existence of an optimal noise level which elicits the best system performance. There is disagreement in the literature regarding the presence of an optimal stimulation level for motor stability in humans. The goals of this study were to: 1) determine optimal stimulation level as a function of an individual’s sub-sensory threshold level, and 2) to determine whether performance of a force stability task was significantly better when subjects received stimulation at this identified optimal level compared to other sub-sensory threshold stimulation levels. Eighteen (18) participants completed an isometric finger flexion task with visual feedback while receiving noise stimulation scaled to varying percentages of their individual sub-sensory threshold level. Performance for this force stabilization task was quantified as the root-mean-square (RMS) error between the target force and the actual generated force values. Despite controlling all other signal properties and varying only amplitude, optimal noise stimulation values still varied widely across participants (10-100% sub-sensory threshold level). Statistical modeling revealed a significant improvement in task performance with optimal noise stimulation compared to other sub-sensory stimulation levels (p ≤ 0.019) with estimated marginal mean differences in force errors ranging from 0.13 to 0.23 N. Moderate significant Spearman correlations (r_s = 0.49 and r_s = 0.56, respectively) were found between finger flexion maximal voluntary contraction (MVC) and sub-sensory threshold level and MVC and optimal stimulation level. A strong, significant Spearman correlation (r_s = 0.65) was observed between sub-sensory threshold level and optimal stimulation level. Although these correlations do not provide a means to predict optimal stimulation level as a function of these other measures, optimal stimulation level appears to increase with sub-sensory threshold and MVC.

Disaggregated population counts are needed to calculate health, economic, and development indicators in Low- and Middle-Income Countries (LMICs), especially in settings of rapid urbanisation. Censuses are often outdated and inaccurate in LMIC settings, and rarely disaggregated at fine geographic scale. Modelled gridded population datasets derived from census data have become widely used by development researchers and practitioners. These datasets are evaluated for accuracy at the spatial scale of the input data which is often much courser (e.g. administrative units) than the neighbourhood or cell-level scale of many applications. We simulate a realistic "true" 2016 population in Khomas, Namibia, a majority urban region, and introduce realistic levels of outdatedness (over 15 years) and inaccuracy in slum, non-slum, and rural areas. We aggregate these simulated realistic populations by census and administrative boundaries (to mimic census data), and generate 32 gridded population datasets that are typical of a LMIC setting using WorldPop-Global-Unconstrained gridded population approach. We evaluate the cell-level accuracy of these simulated datasets using the original "true" population as a reference. In our simulation, we found large cell-level errors, particularly in slum cells, driven by the use of average population densities in large areal units to determine cell-level population densities. Age, accuracy, and aggregation of the input data also played a role in these errors. We suggest incorporating finer-scale training data into gridded population models generally, and WorldPop-Global-Unconstrained in particular (e.g., from routine household surveys or slum community population counts), and use of new building footprint datasets as a covariate to improve cell-level accuracy. It is important to measure accuracy of gridded population datasets at spatial scales more consistent with how the data are being applied, especially if they are to be used for monitoring key development indicators at neighbourhood scales with relevance to small dense deprived areas within larger administrative units.

Objective: Food security during public health emergencies relies on situational awareness of needs and resources. Artificial intelligence (AI) has revolutionized situational awareness during crises, allowing the allocation of resources to needs through machine learning algorithms. Limited research exists monitoring Twitter for changes in the food security-related public discourse during the COVID-19 pandemic. We aim to address that gap with AI by classifying food security topics on Twitter and showing topic frequency per day. Methods: Tweets were scraped from Twitter from January 2020 through December 2021 using food security keywords. Latent Dirichlet Allocation (LDA) topic modeling was performed, followed by time-series analyses on topic frequency per day.Results: 237,107 tweets were scraped and classified into topics, including food needs and resources, emergency preparedness and response, and mental/physical health. After the WHO’s pandemic declaration, there were relative increases in topic density per day regarding food pantries, food banks, economic and food security crises, essential services, and emergency preparedness advice. Threats to food security in Tigray emerged in 2021.Conclusions: AI is a powerful yet underused tool to monitor food insecurity on social media. Machine learning tools to improve emergency response should be prioritized, along with measurement of impact. Further food insecurity word patterns testing, as generated by this research, with supervised machine learning models can accelerate the uptake of these tools by policymakers and aid organizations.

Background: Machine learning has revolutionized situational awareness during disaster management by classifying, clustering, and predicting impacted locations and people. Despite its importance, no review has been conducted on machine learning tools for food assistance efforts during emergency or non-emergency situations. The purpose of this scoping review is to address that gap. Methods: Keywords were defined within the concepts of food assistance and machine learning. After the database searches, PRISMA guidelines were followed to perform a partnered, two-round scoping literature review. Text mining and Latent Dirichlet Allocation topic modeling algorithms were used to determine trends. Results: 28 articles met criteria and were included in the analysis. The types of study designs included: model development (42.9%), non-study (i.e., text and opinion) (28.6%), qualitative research (14.3%), case study (10.7%), and meta-analysis (3.6%). There were no quantitative studies. The machine learning tools’ main functions were improving SNAP programs (32.1%), detecting needs and resources (25%), predicting food insecurity (21.4%), and situational awareness of current food insecurity issues (21.4%). None of these studies took place during a disaster or explicitly addressed emergency mitigation, preparedness, or recovery. All of the studies were in early phases of development and implementation. Conclusion: Machine learning tools for improving situational awareness, resource allocation, policymaking, and prediction have the potential to improve food assistance, but there is a lack of implementation and evaluation during all disaster phases. Also needed is more formative work on generating food-related queries and defining variables and features of food security.

Understanding surfactant self-assembly in deep eutectic solvents (DES) is important to their potential use in industrial formulations. We have recently reported the formation of a fracto-eutectogel comprising SDS fractal aggregates at a concentration as low as 1.6 wt% in glyceline (a DES comprising glycerol and choline chloride) at room temperature. The building units of the fractals consisted of multilayers of self-assembled SDS lamellae arranged in a dendritic pattern. Here we report that this fractal phase transitions into a fluid phase above a critical gelation temperature, TCG ~ 45 oC, evident from polarized light microscopy (PLM) observations. Small-angle neutron scattering (SANS) reveals that this phase transition is underpinned by the nanoscopic morphological transformation of the SDS lamellae into cylindrical micelles at T > TGC. Fitting SANS profiles confirms that the morphology of the micelles is SDS-concentration (cSDS) dependent at T > TGC: cylindrical at cSDS > 0.6 wt% and spherical at cSDS = 0.6 wt%. At cSDS < 0.6 wt%, only isotropic scattering was observed in the SANS profiles. Such SDS self-assembly behaviors contrast with those we have previously observed in glycerol, which we attribute to the presence of ions (i.e. choline chloride) in glyceline. Our findings have general implications to surfactant self-assembly in DES, solvents that are rich in hydrogen bonding and ions.

The COVID-19 pandemic continues to affect individuals across the globe, with some individuals experiencing more severe disease than others. The relatively high frequency of re-infections and breakthrough infections observed with SARS-CoV-2 highlights the importance of extending our understanding of immunity to COVID-19. Here we aim to shed light on the importance of antibody titers and epitope utilization in protection from re-infection. Health care workers are highly exposed to COVID-19 and are therefore also more likely to become re-infected. We utilized quantitative, multi-antigen, multi-epitope SARS-CoV-2 protein microarrays to measure IgG and IgA titers against various domains of the nucleocapsid and spike proteins. Potential re-infections in a large, diverse health care worker cohort (N=300) during the second wave of the pandemic were identified by assessing the IgG anti-N titers before and after the second wave. We assessed epitope coverage and antibody titers between the 'single infection’ and ‘re-infection’ groups. Clear differences were observed in the breadth of the anti-N response before the second wave, with the epitope coverage for both IgG (p=0.019) and IgA (p=0.015) being significantly increased in those who did not become re-infected compared to those who did. Additionally, the IgG anti-N (p=0.004) and anti-S titers (p=0.018) were significantly higher in those not re-infected. These results highlight the importance of the breadth of elicited antibody epitope coverage following natural infection in protection from re-infection and disease in the COVID-19 pandemic.

There is a need for developmental screening that is easily administered in resource-poor settings. 1) We hypothesized that known risk factors would predict failed developmental screening on an adapted screening tool in East African children living in poverty. 2) The sample included 100 healthy Ugandan children aged 6-59 months. We adapted a parent-reported developmental screener based on the Child Development Review chart. The primary outcome was failure to meet age-appropriate milestones for any developmental domain. Venous blood was analyzed for lead, and caregivers completed a demographics questionnaire. We used multivariate logistic regression models to determine if elevated blood lead and stunting predicted failure on the screener, controlling for maternal education level, age in months past the lower bound of the child’s developmental age group, and absence of home electricity. 3) In the sample, 14% (n=14) of children failed one or more milestones on the screener. Lead levels or stunting did not predict failing the screener after controlling for covariates. 4) Though this tool was feasibly administered, it did not demonstrate preliminary construct validity and is not yet recommended for screening in high-risk populations. Future research should include a larger sample size and cognitive interviews to ensure it is contextually relevant.

Cross-institutional secondary use of medical data benefits from structured semantic annotation, which, ideally, enables matching and merging semantically related data items from different sources and sites. While numerous medical terminologies and ontologies, as well as some tooling, exist to support such annotation, cross-institutional data usage based on independently annotated datasets is challenging for multiple reasons: the annotation process is resource intensive and requires a combination of medical and technical expertise since it often requires judgment calls to resolve ambiguities resulting from non-uniqueness of potential mappings to various levels of ontological hierarchies and relational and representational systems. Divergent resolution of such ambiguities can inhibit joint cross-institutional data usage based on semantic annotation since data items with related content from different sites will not be identifiable based on their respective annotations if different choices were made without further steps such as ontological inference, which is still an active area of research. We hypothesize that a collaborative approach to semantic annotation of medical data can contribute to more resource efficient and high-quality annotation by utilizing prior annotational choices of others to inform the annotation process, thus both speeding up the annotation itself and fostering a consensus approach to resolving annotational ambiguities by enabling annotators to discover and follow pre-existing annotational choices. Therefore, we have implemented a prototypical Collaborative Annotation Tool (CoAT), evaluated its usability, and present first inter-institutional experiences with this novel approach to promoting practically relevant interoperability driven by use of standardized ontologies.

This randomized trial compared pea protein, whey protein, and water-only supplementation on muscle damage, inflammation, delayed onset of muscle soreness (DOMS), and physical fitness test performance during a 5-day period after a 90-minute eccentric exercise bout in non-athletic, non-obese males (n=92, ages 18-55 years). The two protein sources (0.9 g protein/kg divided into three doses/day) were administered under double blind procedures. The eccentric exercise protocol induced significant muscle damage and soreness, and reduced bench press and 30-second Wingate performance. Whey protein supplementation significantly attenuated post-exercise blood levels for biomarkers of muscle damage compared to water-only, with large effect sizes for creatine kinase and myoglobin during the 4th and 5th days of recovery (Cohen's d >0.80); pea protein versus water supplementation had an intermediate, non-significant effect (Cohen's d <0.50); and no significant differences between whey and pea protein were found. Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests. In conclusion, high intake of whey protein for 5 days after intensive eccentric exercise mitigated efflux of muscle damage biomarkers, with intake of pea protein having an intermediate effect in part due to the 24% lower leucine amino acid content.

Advances in the availability of multitemporal and global built-/human-settlements datasets as derived from Remote Sensing (RS) can now provide globally consistent definitions of “human-settlement” at unprecedented spatial fineness. Yet, these data only provide a time-series of past extents and urban growth/expansion models have not had parallel advances at high-spatial resolution. We present a flexible modelling framework for producing annual built-settlement extents in the near future past last observed extents as provided by RS-based data. Using a random forest and autoregressive temporal models with short time-series of built-settlement extents and subnational level data, we predict annual 100m resolution binary settlement extents five years beyond the last observations. We applied this framework within varying contexts and predicted annual extents from 2010 to 2015. We found that our model framework preformed consistently across all sample countries and, when compared to time-specific imagery, demonstrated the capacity to capture human-settlement missed by the input time-series and validation extents. When comparing building footprints of small settlements to forecast extents, we saw that the modelling framework had a 12 percent increase in ground-truth accuracy. This framework shows promise for predicting near-future settlement extents, and provides a foundation for forecasts further into the future.

Anion exchange of the halides, Br and I, is demonstrated through the direct mixing of two pure perovskite quantum dot solutions, CsPbBr3 and CsPbI3, and is shown to be both facile and result in a completely alloyed single phase mixed halide perovskite. Anion exchange is also observed in an interlayer printing method utilizing the pure, unalloyed perovskite solutions and a commercial inkjet printer. The halide exchange was confirmed by optical absorption spectroscopy, photoluminescent spectroscopy, X-ray diffraction, and X-ray photoemission spectroscopy characterization, and indicates that alloying is thermodynamically favorable, while the formation of a clustered alloy is not favored. Additionally, a surface-to-bulk photoemission core level transition is observed for the Cs 4d photoemission feature which indicates the electronic structure of the surface is different from the bulk. Time resolved photoluminescence spectroscopy indicates the presence of multiple excitonic decay features which is argued to originate from states residing at surface and bulk environments.

Mapping settlement extents at the annual time step has a wide variety of applications in demography, public health, sustainable development, and many other fields. Recently, while more multitemporal urban feature or human settlement datasets have become available, issues still exist in remotely-sensed imagery due to coverage, adverse atmospheric conditions, and expenses involved in producing such feature sets. These challenges make it difficult to increase temporal coverage while maintaining high fidelity in the spatial resolution. Here we demonstrate an interpolative and flexible modeling framework for producing annual built-settlement extents. We use a combined technique of random forest and spatio-temporal dasymetric modeling with open source subnational data to produce annual 100m x 100m resolution binary settlement maps in four test countries of varying environmental and developmental contexts for test periods of five-year gaps. We find that in the majority of years, across all study areas, the model correctly identified between 85-99% of pixels that transition to built-settlement. Additionally, with few exceptions, the model substantially out performed a model that gave every pixel equal chance of transitioning to the category “built” in each year. This modelling framework shows strong promise for filling gaps in cross-sectional urban feature datasets derived from remotely-sensed imagery, provide a base upon which to create future built/settlement extent projections, and further explore the relationships between built area and population dynamics.

The persistence of geographic inequities in vaccination coverage often evidences the presence of zero-dose and missed communities and vulnerabilities to vaccine-preventable diseases. These inequities were exacerbated in many places during the COVID-19 pandemic, due to severe disruptions to vaccination services. Understanding changes in zero-dose prevalence and associated risk factors in the context of the COVID-19 pandemic is, therefore, critical to designing effective strategies to reach vulnerable populations. Using data from nationally representative household surveys conducted before the COVID-19 pandemic in 2018 and during the pandemic in 2021 in Nigeria, we fitted Bayesian geostatistical models to map the distribution of three vaccination coverage indicators: receipt of DTP1, MCV1 and any of the four basic vaccines (BCG, OPV0, DTP1 and MCV1), and corresponding zero-dose estimates independently at 1x1 km resolution and the district level during both time periods. We also explored changes in the factors associated with non-vaccination at the national and regional levels using multilevel logistic regression models. Our results revealed no increases in zero-dose prevalence due to the pandemic at the national level, although considerable increases were observed in a few districts. We found substantial subnational heterogeneities in vaccination coverage and zero-dose prevalence both before and during the pandemic, showing broadly similar patterns in both time periods. Areas with relatively higher zero-dose prevalence occurred mostly in the north and a few places in the south in both time periods. We also found consistent areas of low coverage and high zero-dose prevalence using all three zero-dose indicators, revealing areas in greatest need. At the national level, risk factors related to socioeconomic/ demographic status (e.g., maternal education), maternal access to and utilization of health services and remoteness were strongly associated with the odds of zero dose in both time periods, while those related to communication were mostly relevant before the pandemic. These associations were also supported at the regional level, but we additionally identified risk factors specific to zero dose in each region; for example, communication and cross-border migration in the northwest. Our findings can help guide tailored strategies to reduce zero-dose prevalence and boost coverage levels in Nigeria.

Background: Since cytokine receptor like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. Methods: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno associated virus (AAV) or AAV containing CRLF1 was determined by morpholog-ical, histological and microCT analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were deter-mined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes us-ing real time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. Results: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondro-genic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and Cardiotrophin like Cytokine (CLC) stimulated catabolic events via STAT3 activation. Conclusion: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Kaposi’s sarcoma associated-herpesvirus (KSHV, also known as human herpesvirus-8) is a gammaherpesvirus that establishes life-long infection in human B lymphocytes. KSHV infection is typically asymptomatic but immunosuppression can predispose KSHV-infected individuals to primary effusion lymphoma (PEL); a malignancy driven by aberrant proliferation of latently infected B lymphocytes, and supported by pro-inflammatory cytokines and angiogenic factors produced by cells that succumb to lytic viral replication. Here, we report the development of the first in vivo model for a virally-induced lymphoma in zebrafish, whereby KSHV-infected PEL tumour cells engraft and proliferate in the yolk sac of zebrafish larvae. Using a PEL cell line engineered to produce the viral lytic switch protein RTA in the presence of doxycycline, we demonstrate drug-inducible reactivation from KSHV latency in vivo, which enabled real-time observation and evaluation of latent and lytic phases of KSHV infection. In addition, we developed a sensitive droplet digital PCR method to monitor latent and lytic viral gene expression and host cell gene expression in xenografts. The zebrafish yolk sac is not well-vascularized and using fluorogenic assays we confirmed that this site provides a hypoxic environment that may mimic the microenvironment of some human tumors. We found that PEL cell proliferation in xenografts was dependent on the host hypoxia-dependent translation initiation factor, eukaryotic initiation factor 4E2 (eIF4E2). This demonstrates that the zebrafish yolk sac is a functionally hypoxic environment and xenografted cells must switch to dedicated hypoxic gene expression machinery to survive and proliferate. The establishment of the PEL xenograft model enables future studies that exploit the innate advantages of the zebrafish as a model for genetic and pharmacologic screens.

The choice of effective biocides used for routine hospital practice should consider the role of disinfectants in the maintenance and development of local resistome and how they might affect antibiotic resistance gene transfer within the hospital microbial population. Currently, there is little understanding of how different biocides contribute to eDNA release that may contribute to gene transfer and subsequent environmental retention. Here we investigated how different biocides affected the release of eDNA from mature biofilms of two opportunistic model strains Pseudomonas aeruginosa ATCC 27853 (PA) and Staphylococcus aureus ATCC 25923 (SA) and contribute to the hospital resistome in the form of surface and water contaminants and dust particles. The effect of four groups of biocides including alcohols, hydrogen peroxide, quaternary ammonium compounds, and polymeric guanidines were evaluated using PA and SA biofilms. Most biocides, except for PHMG-Cl and 70% ethanol, caused substantial eDNA release and PHMG-Cl was found to block biofilm development when used at concentrations of 0.5% and 0.1%. This might be associated with the formation of DNA-PHMG-Cl complexes as PHMG-Cl is predicted to bind to AT base pairs by molecular docking assays. PHMG-Cl was found to bind high molecular DNA and plasmid DNA and continued to inactivate DNA on surfaces even after four weeks. PHMG-Cl also effectively inactivated biofilm-associated antibiotic resistance gene eDNA released by a pan-drug-resistant Klebsiella strain which demonstrates the potential of PHMG-Cl as a new surface-active agent to combat the spread of antibiotic resistance in hospital settings.

Groundwater is a strategic resource for economic development, social justice, environmental sustainability, and water governance. The Lower Casas Grandes Basin located in the state of Chihuahua, Mexico is in a semi-arid region that has increasing groundwater demands while confronting regional challenges such as adverse climate change scenarios and depleting aquifers. Even though there is official information about the availability of groundwater, comprehensive aquifer characterization is still uncertain and needs interdisciplinary investigation using a diverse suite of tools and multiple data sources. This study presents a multi-technique framework to evaluate potential sites to drill for groundwater resources. The main components of the methodology included: wellhead leveling correction with a differential global positioning survey to define piezometric levels, principal component analysis using Landsat-8 images, application of geospatial tools, geophysics using Time Domain Electromagnetic Surveys and Vertical Electric Soundings and structural geohydrology to define aquifer characteristics. Results show that the application of the framework enhances the possibility of successful drilling for groundwater while saving time and money using “pin-point” positioning for drilling sites as compared to a traditional extensive groundwater exploration approach. Low resistivity values (35 Ohm-m) were found at depths from 50m to 85m at sites where the regional static water level reached 245 m deep adding a shallow groundwater potential at sites where the intersection of fracture trace was identified. This procedure can be used at other sites where limited or minimum information is available for groundwater exploration to reduce the risk of drilling dry wells in complex hydrogeological environments.

Schistosomiasis is a debilitating parasitic disease of poverty that affects more than 200 million people worldwide, mostly in sub-Saharan Africa, and is clearly associated with the construction of dams and water resource management infrastructure in tropical and subtropical areas. Changes to hydrology and salinity linked to water infrastructure development may create conditions favorable to the aquatic vegetation that is suitable habitat for the intermediate snail hosts of schistosome parasites. With thousands of small and large water reservoirs, irrigation canals, and dams developed or under construction in Africa, it is crucial to accurately assess the spatial distribution of high-risk environments that are habitat for freshwater snail intermediate hosts of schistosomiasis in rapidly changing ecosystems. Yet, standard techniques for monitoring snails are labor-intensive, time-consuming, and provide information limited to the small areas that can be manually sampled. Consequently, in low-income countries where schistosomiasis control is most needed, there are formidable challenges to identify potential transmission hotspots for targeted medical and environmental interventions. In this study, we developed a new framework to map the spatial distribution of suitable snail habitat across large spatial scales in the Senegal River Basin by integrating satellite data, high-definition, low-cost drone imagery, and an artificial intelligence (AI)-powered computer vision technique called semantic segmentation. A deep learning model (U-Net) was built to automatically analyze high-resolution satellite imagery to produce segmentation maps of aquatic vegetation, with a fast and robust generalized prediction that proved more accurate than a more commonly used random forest approach. Accurate and up-to-date knowledge of areas at highest risk for disease transmission can increase the effectiveness of control interventions by targeting habitat of disease-carrying snails. With the deployment of this new framework, local governments or health actors might better target environmental interventions to where and when they are most needed in an integrated effort to reach the goal of schistosomiasis elimination.

The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatic tools and resources, and advocate for greater openness, interoperability, accessibility and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a clear and present need for a fit-for-purpose, open source SARS-CoV-2 contextual data standard. As such, we have developed an extension to the INSDC pathogen package, providing a SARS-CoV-2 contextual data specification based on harmonisable, publicly available, community standards. The specification is implementable via a collection template, as well as an array of protocols and tools to support the harmonisation and submission of sequence data and contextual information to public repositories. Well-structured, rich contextual data adds value, promotes reuse, and enables aggregation and integration of disparate data sets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19.