Search

BackgroundThe International Society of Nephrology proposes an acute kidney disease (AKD) management strategy that includes a risk score to aid AKD identification in low- and low-middle-income countries (LLMICs). We investigated the performance of the risk score and determined kidney and patient outcomes from AKD at multiple LLMIC sites.Methods and findingsAdult patients presenting to healthcare facilities in Bolivia, Brazil, South Africa, and Nepal were screened using a symptom-based risk score and clinical judgment. Those at AKD risk underwent serum creatinine testing, predominantly with a point-of-care (POC) device. Clinical data were collected prospectively between September 2018 and November 2020. We analyzed risk score performance and determined AKD outcomes at discharge and over follow-up of 90 days. A total of 4,311 patients were at increased risk of AKD, and 2,922 (67.8%) had AKD confirmed. AKD prevalence was 80.2% in patients enrolled based on the risk score and 32.5% when enrolled on clinical judgment alone (p < 0.0001). The area under the receiver operating characteristic curve was 0.73 for the risk score to detect AKD. Death during admission occurred in 84 (2.9%) patients with AKD and 3 (0.2%) patients without kidney disease (p < 0.0001). Death after discharge occurred in 206 (9.7%) AKD patients, and 1865 AKD patients underwent reassessment of kidney function after discharge; 902 (48.4%) patients had persistent kidney disease including 740 (39.7%) patients reclassified with de novo or previously undiagnosed chronic kidney disease (CKD). The study was pragmatically designed to assess outcomes as part of routine healthcare, and there was heterogeneity in clinical practice and outcomes between sites, in addition to selection bias during cohort identification.ConclusionsThe use of a risk score can aid AKD identification in LLMICs. High rates of persistent kidney disease and mortality after discharge highlight the importance of AKD follow-up in low-resource settings.

Abstract Cancer risk is associated with the widely debated measure body mass index (BMI). Fat mass and fat-free mass measurements from bioelectrical impedance may further clarify this association. The UK Biobank is a rare resource in which bioelectrical impedance and BMI data was collected on ~ 500,000 individuals. Using this dataset, a comprehensive analysis using regression, principal component and genome-wide genetic association, provided multiple levels of evidence that increasing whole body fat (WBFM) and fat-free mass (WBFFM) are both associated with increased post-menopausal breast cancer risk, and colorectal cancer risk in men. WBFM was inversely associated with prostate cancer. We also identified rs615029[T] and rs1485995[G] as associated in independent analyses with both PMBC (p = 1.56E–17 and 1.78E–11) and WBFFM (p = 2.88E–08 and 8.24E–12), highlighting splice variants of the intriguing long non-coding RNA CUPID1 (LINC01488) as a potential link between PMBC risk and fat-free mass.

Background and aims – The forests of the Congo Basin contain high levels of biodiversity, and are globally important for carbon storage. In order to design effective conservation strategies, and to accurately model carbon stocks, a fine-scale understanding of the different forest types that make up this forest block is needed. Monodominant Gilbertiodendron dewevrei forest covers large areas of the Congo Basin, but it is currently unclear whether it is sufficiently distinct from adjacent mixed terre firme forest to warrant separate treatment for conservation planning and carbon calculations. This study aimed to compare the structure and diversity of monodominant and mixed forest, and ask whether there is a unique vascular plant community associated with G. dewevrei forest. Material and methods – We utilised a combination of plot data and herbarium specimens collected in the Sangha Trinational (a network of protect areas in Cameroon, Central African Republic, and the Republic of Congo). Plot inventories were used to compare G. dewevrei forest and mixed forest for stem density, basal area, above ground biomass, stem size distribution, species diversity, and species composition. In addition, a database of 3,557 herbarium specimens was used to identify species of vascular plant that are associated with G. dewevrei forest. Key results – Gilbertiodendron dewevrei forest is distinct in both structure and species composition from mixed forest. Gilbertiodendron dewevrei forest has a lower stem number (of trees ≥ 10 cm), but a greater proportion of larger trees (> 70 cm), suggesting higher carbon stocks. The species composition is distinct from mixed forest, with 56 species of vascular plant significantly associated with G. dewevrei forest. Conclusion – Monodominant G. dewevrei forest in the Sangha Trinational is both compositionally and structurally distinct from mixed forest. We therefore recommend this forest type be considered separately from mixed forest for conservation planning and carbon stock calculations.

The vast regenerative potential of stem cells has laid the foundation for stem cell-based therapies. However, certain challenges limit the application of cell-based therapies. The therapeutic use of cell-free therapy can avoid limitations associated with cell-based therapies. Acellular stem cell-based therapies rely on the use of biological factors released by stem cells, including growth factors and extracellular vesicles such as exosomes. Due to their comparable regenerative potential, acellular therapies may provide a feasible and scalable alternative to stem cell-based therapies. Exosomes are small vesicles secreted by various types of cells, including stem cells. Exosomes contain parent cell-derived nucleic acids, proteins, lipids, and other bioactive molecules. They play an important role in intra-cellular communication and influence the biological characteristics of cells. Exosomes inherit the properties of their parent cells; therefore, stem cell-derived exosomes are of particular interest for applications of regenerative medicine. In comparison to stem cell-based therapy, exosome therapy offers several benefits, such as easy transport and storage, no risk of immunological rejection, and few ethical dilemmas. Unlike stem cells, exosomes can be lyophilized and stored off-the-shelf, making acellular therapies standardized and more accessible while reducing overall treatment costs. Exosome-based acellular treatments are therefore readily available for applications in patients at the time of care. The current review discusses the use of exosomes as an acellular therapy. The review explores the molecular mechanism of exosome biogenesis, various methods for exosome isolation, and characterization. In addition, the latest advancements in bioengineering techniques to enhance exosome potential for acellular therapies have been discussed. The challenges in the use of exosomes as well as their diverse applications for the diagnosis and treatment of diseases have been reviewed in detail.

Abstract Background In autosomal dominant polycystic kidney disease (ADPKD) impaired nitric oxide (NO) synthesis, in part, contributes to early-onset hypertension. Beetroot juice (BRJ) reduces blood pressure (BP) by increasing NO-mediated vasodilation. The aim of this double-blind, randomised, placebo-controlled study is to test the hypothesis that BRJ reduces systolic and diastolic clinic BP in hypertensive adults with ADPKD. Methods Participants with ADPKD and treated hypertension (n = 60) will be randomly allocated (1:1) to receive a daily dose of either nitrate-replete (400 mg nitrate/day) or nitrate-deplete BRJ for 4 weeks. The co-primary outcomes are change in mean systolic and diastolic clinic BP before and after 4 weeks of treatment with daily BRJ. Secondary outcomes are changes in daily home BP, urinary albumin to creatinine ratio, serum and salivary nitrate/nitrite levels and serum asymmetric dimethylarginine levels before and after 4 weeks of BRJ. Discussion The effect of BRJ in ADPKD has not been previously tested. BRJ is an accessible, natural dietary supplement that, if effective, will provide a novel adjunctive approach for treating hypertension in ADPKD. Trial registration ClinicalTrials.gov NCT05401409. Retrospectively registered on 27th May 2022.

BackgroundWith an aging population, the prevalence of hearing loss and dementia are increasing rapidly. Hearing loss is currently considered the largest potentially modifiable risk factor for dementia. The effect of hearing interventions on cognitive function should therefore be investigated, as if effective, these may be successfully implemented to modify cognitive outcomes for older adults with hearing loss.MethodsThis prospective longitudinal observational cohort study compared outcomes of a convenience sample of prospectively recruited first-time hearing aid users without dementia from an audiology center with those of community-living older adults participating in a large prospective longitudinal cohort study with/without hearing loss and/or hearing aids. All participants were assessed at baseline, 18 months, and 36 months using the same measures.ResultsParticipants were 160 audiology clinic patients (48.8% female patient; mean age 73.5 years) with mild–severe hearing loss, fitted with hearing aids at baseline, and 102 participants of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Aging (AIBL) (55.9% female patient; mean age 74.5 years). 18- and 36-month outcomes of subsets of the first participants to reach these points and complete the cognition assessment to date are compared. Primary comparative analysis showed cognitive stability for the hearing aid group while the AIBL group declined on working memory, visual attention, and psychomotor function. There was a non-significant trend for decline in visual learning for the AIBL group versus no decline for the hearing aid group. The hearing aid group showed significant decline on only 1 subtest and at a significantly slower rate than for the AIBL participants (p

Background and aims – Specimens of a new tree species in the genus Drypetes (Putranjivaceae) distributed in Cameroon and eastern Nigeria, D. stevartii, were associated with D. verrucosa, another tree species endemic to Gabon, due to its warty fruits and to the overall morphological resemblances of both species. Material and methods – The present study is based on the study of 20 gatherings of D. verrucosa and 26 gatherings of D. stevartii. Morphological observations on herbarium specimens belonging to the new species and D. verrucosa were carried out in order to describe them. Key results – This treatment includes the detailed descriptions of these two species, the typification of their names, a comparative table summarizing their main morphological differences, an identification key, photographs of both, as well as information about their distribution, habitat, and phenology. Preliminary IUCN Red List assessments show that both D. verrucosa and D. stevartii are ‘Near Threatened’ species.

Background and Aims: Although type 2 innate lymphoid cells (ILC2s) were originally found to be liver-resident lymphocytes, the role and importance of ILC2 in liver injury remains poorly understood. In the current study, we sought to determine whether ILC2 is an important regulator of hepatic ischaemia/reperfusion injury (IRI). Methods: ILC2-deficient mice (ICOS-T or NSG) and genetically modified ILC2s were used to investigate the role of ILC2s in murine hepatic IRI. Interactions between ILC2s and eosinophils or macrophages were studied in coculture. The role of human ILC2s was assessed in an immunocompromised mouse model of hepatic IRI. Results: Administration of IL-33 prevented hepatic IRI in association with reduction of neutrophil infiltration and inflammatory mediators in the liver. IL-33-treated mice had elevated numbers of ILC2s, eosinophils, and regulatory T cells. Eosinophils, but not regulatory T cells, were required for IL-33-mediated hepatoprotection in IRI mice. Depletion of ILC2s substantially abolished the protective effect of IL-33 in hepatic IRI, indicating that ILC2s play critical roles in IL-33-mediated liver protection. Adoptive transfer of ex vivo-expanded ILC2s improved liver function and attenuated histologic damage in mice subjected to IRI. Mechanistic studies combining genetic and adoptive transfer approaches identified a protective role of ILC2s through promoting IL-13-dependent induction of anti-inflammatory macrophages and IL-5-dependent elevation of eosinophils in IRI. Furthermore, in vivo expansion of human ILC2s by IL-33 or transfer of ex vivo-expanded human ILC2s ameliorated hepatic IRI in an immunocompromised mouse model of hepatic IRI. Conclusions: This study provides insight into the mechanisms of ILC2-mediated liver protection that could serve as therapeutic targets to treat acute liver injury. Impact and Implications: We report that type 2 innate lymphoid cells (ILC2s) are important regulators in a mouse model of liver ischaemia/reperfusion injury (IRI). Through manipulation of macrophage and eosinophil phenotypes, ILC2s mitigate liver inflammation and injury during liver IRI. We propose that ILC2s have the potential to serve as a therapeutic tool for protecting against acute liver injury and lay the foundation for translation of ILC2 therapy to human liver disease.

The access to molecular collections worldwide greatly improves the quality of scientific research by making a growing number of data available for investigation. The efforts on digitisation also aim at facilitating the exchange of material between institutions and researchers that must follow regulations in place and respect best practice. The handbook presented here proposes a workflow to follow to safely exchange materials, in accordance with international laws and legislation. We make numerous recommendations here to help the institutions and researchers to navigate the legal and administrative procedures, in order to manage molecular collections in the best way possible.

Parasitic nematodes and hymenopteran parasitoids have been introduced and used extensively to control invasive Eurasian Sirex noctilio woodwasps in pine plantations in the Southern Hemisphere where no members of this community are native. Sirex noctilio has more recently invaded North America where Sirex-associated communities are native. Sirex noctilio and its parasitic nematode, Deladenus siricidicola, plus six native hymenopteran woodwasp parasitoids in New York and Pennsylvania, were sampled from 204 pines in 2011–2019. Sirex noctilio had become the most common woodwasp in this region and the native parasitoids associated with the native woodwasps had expanded their host ranges to use this invader. We investigated the distributions of these species among occupied trees and the interactions between S. noctilio and natural enemies as well as among the natural enemies. Sirex noctilio were strongly aggregated, with a few of the occupied trees hosting hundreds of woodwasps. Nematode parasitism was positively associated with S. noctilio density, and negatively associated with the density of rhyssine parasitoids. Parasitism by the parasitoid Ibalia leucospoides was positively associated with host (S. noctilio) density, while parasitism by the rhyssine parasitoids was negatively associated with density of S. noctilio. Thus, most S. noctilio come from a few attacked trees in a forest, and S. noctilio from those high-density trees experienced high parasitism by both the invasive nematode and the most abundant native parasitoid, I. l. ensiger. There is little evidence for direct competition between the nematodes and parasitoids. The negative association occurring between rhyssine parasitoids and I. l. ensiger suggests rhyssines may suffer from competition with I. l. ensiger which parasitize the host at an earlier life stage. In addition to direct competition with the native woodwasp Sirex nigricornis for suitable larval habitat within weakened trees, the large S. noctilio population increases the parasitoid and nematode populations, which may increase parasitism of S. nigricornis.

An expanded role for cardiac implantable electronic devices (CIEDs) in recent decades reflects an aging population and broader indications for devices, including both primary prevention and management of dysrhythmias. CIED infection is one of the most important device-related complications and has a major impact on mortality, quality of life, healthcare utilization, and cost. Unfortunately, the investigation and management of CIED infection remain complex, often necessitating complete and timely removal of the device and leads in order to eradicate the infection. In addition, the translation of knowledge from an extensive literature to a disparate group of medical practitioners has often been inadequate. This review of CIED infection management highlights the significant advances made during the past decade, including diagnostic criteria, advanced imaging, and next-generation sequencing for culture-negative cases or those in which uncertainty remains. We also outline the role and indication for powered lead extraction, the process of antibiotic choice and treatment duration, considerations related to the timing and location for reimplantation, and preimplantation risk stratification and associated interventions to reduce the risk of CIED infection. Résumé: L’élargissement du rôle des dispositifs électroniques cardiaques implantables (DECI) au cours des dernières décennies reflète le vieillissement de la population et les indications plus vastes des dispositifs, notamment dans la prévention primaire et la prise en charge des dysrythmies. Les infections liées aux DECI sont l’une des plus importantes complications liées aux dispositifs et ont des conséquences majeures sur la mortalité, la qualité de vie, l’utilisation et les coûts des soins de santé. Malheureusement, le dépistage et la prise en charge des infections liées aux DECI demeurent complexes et nécessitent souvent le retrait complet et rapide du dispositif et des sondes en vue d’éradiquer l’infection. De plus, l’application des connaissances issues d’une vaste littérature à un groupe disparate de médecins praticiens a souvent été inadéquate. La présente revue sur la prise en charge des infections liées aux DECI illustre les avancées importantes réalisées au cours de la dernière décennie, notamment les critères diagnostiques, l’imagerie avancée et le séquençage de prochaine génération des cas à culture négative ou de ceux pour lesquels des incertitudes demeurent. Nous avons aussi décrit le rôle et les indications d’extraction des sondes fonctionnelles, le processus du choix des antibiotiques et de la durée du traitement, les considérations relatives au moment et au lieu de la réimplantation, et la stratification du risque en préimplantation et les interventions associées afin de réduire le risque d’infections liées aux DECI.

Rationale & Objective: The development of new therapies for autosomal dominant polycystic kidney disease requires clinical trials to be conducted efficiently. In this study, the factors affecting the recruitment and retention of participants enrolled in a 3-year randomized controlled trial in autosomal dominant polycystic kidney disease were investigated. Study Design: Qualitative study. Setting & Participants: All participants (N=187) were invited to complete a 16-item questionnaire at the final study visit of the primary trial. Participants were recruited to complete a semistructured interview using purposeful sampling according to age, self-reported gender, and randomization group. Analytical Approach: Descriptive statistics were used for demographic data and questionnaires. The interview transcripts underwent inductive thematic coding. Results: One hundred and forty-six of the 187 randomized participants (79%) completed the post-trial questionnaire, and 31 of the 187 participants (21%) completed the interview. Most participants (94%) rated their global satisfaction with the trial as high (a score of 8 or more out of 10). Altruism, knowledge gain, and access to new treatments were the main motivators for recruitment. The main reasons for considering leaving the study were concerns about the risk of intervention and family or work issues. Strategies that favored retention included flexibility in attending different study sites, schedule flexibility, staff interactions, and practical support with parking and reminders. The main burden was time away from work with lost wages, and burden associated with magnetic resonance imaging scans and 24-hour urine output collections. Limitations: The study population was restricted to participants in a single nondrug clinical trial, and the results could be influenced by selection and possible social desirability bias. Conclusions: Participants reported high levels of satisfaction that occurred as a function of the trial meeting participants’ expectations. Furthermore, retention was a balance between the perceived benefits and burden of participation. Consideration of these perspectives in the design of future clinical trials will improve their efficiency and conduct. Plain-Language Summary: Advances in the clinical practice of autosomal dominant polycystic kidney disease (ADPKD) require affected individuals to voluntarily participate in long-term multicenter randomized controlled trials (RCTs). In this qualitative post hoc study of a 3-year RCT of increased water intake in ADPKD, altruism, knowledge gain, and access to a nondrug treatment positively influenced the decision to volunteer. Ongoing participation was enabled by building flexibility into the study protocol and staff prioritizing a participant’s needs during study visits. Although participants completed the required tests, most were considered burdensome. This study highlights the importance of incorporating protocol flexibility into trial design; the preference for interventions with a low risk of adverse effects; and the urgent requirement for robust surrogate noninvasive biomarkers to enable shorter RCTs in ADPKD.

We present a preliminary discussion about cauliflory, sexual dimorphism and biogeographic patterns in Drypetes Vahl (Putranjivaceae Endl.), focused on Africa. We also present a taxonomic treatment for two new species of cauliflorous trees of this genus from the rainforests of western Central Africa, one endemic to Gabon and known from six gatherings, D. aphanes Quintanar, D.J.Harris & Barberá sp. nov., and the other distributed in Gabon and the Republic of the Congo, D. cauta D.J.Harris, Barberá & Quintanar sp. nov., also known from another six gatherings. They are presented along with D. gabonensis Pierre ex Hutch., known from 25 gatherings made throughout western Central Africa, a species with markedly dimorphic flowers between sexes compared to the rest of the species in the genus. Specimens of these two new species have been confused with D. gabonensis due to some morphological resemblances. This treatment includes the detailed descriptions of these three species, the typification of their names, a comparative table summarizing their main morphological differences, an identification key, an illustration and information about their habitat and distribution. A provisional IUCN Red List assessment shows that D. gabonensis and D. cauta sp. nov. are ‘Vulnerable’ species, and D. aphanes sp. nov. is ‘Endangered’. After the publication of these new species, Drypetes consists of 86 species in continental Africa and the Malagasy Region and 219 species for the whole world.

IntroductionWhilst the disruptive effects of anxiety on attention and performance have been well documented, the antecedents to anxiety in motivated performance scenarios are less well understood. We therefore sought to understand the cognitive appraisals that mediate the relationship between pressurised performance situations and the onset of anxiety. MethodsWe tested the effects of performance pressure and error feedback on appraisals of the probability and cost of failure, the experience of anxiety, and subsequent impacts on visual attention, movement kinematics, and task performance during a virtual reality interception task.ResultsA series of linear mixed effects models indicated that failure feedback and situational pressure influenced appraisals of the probability and cost of failure, which subsequently predicted the onset of anxious states. We did not, however, observe downstream effects on performance and attention.Discussion The findings support the predictions of Attentional Control Theory Sport, that (i) momentary errors lead to negative appraisals of the probability of future failure; and (ii) that appraisals of both the cost and probability of future failure are important predictors of anxiety. The results contribute to a better understanding of the precursors to anxiety and the feedback loops that may maintain anxious states.

Leishmaniasis, one of the most neglected tropical diseases (NTDs), is the third most important vector-borne disease worldwide. This disease has a global impact and severity of the infection and is greatest in the Middle East. The agent of infection is a protozoan parasite of the genus, Leishmania, and is generally transmitted by blood-sucking female sandflies. In humans, there are three clinical forms of infection: (1) cutaneous (CL), (2) mucocutaneous (ML), and (3) visceral leishmaniasis (VL). This review aims to discuss the current epidemiological status of leishmaniasis in Saudi Arabia, Iraq, Syria, and Yemen with a consideration of treatment options. The elevated risk of leishmaniasis is influenced by the transmission of the disease across endemic countries into neighboring non-infected regions.

Despite early promise, cognitive training research has failed to deliver consistent real-world benefits and questions have been raised about the experimental rigour of many studies. Several meta-analyses have suggested that there is little to no evidence for transfer of training from computerised tasks to real-world skills. More targeted training approaches that aim to optimise performance on specific tasks have, however, shown more promising effects. In particular, the use of inhibition training for improving shoot/don't-shoot decision-making has returned positive far transfer effects. In the present work, we tested whether an online inhibition training task could generate near and mid-transfer effects in the context of response inhibition tasks. As there has been relatively little testing of retention effects in the literature to date, we also examined whether any benefits would persist over a 1-month interval. In a pre-registered, randomised-controlled trial, participants (n = 73) were allocated to either an inhibition training programme (six training sessions of a visual search task with singleton distractor) or a closely matched active control task (that omitted the distractor element). We assessed near transfer to a Flanker task, and mid-transfer to a computerised shoot/don't-shoot task. There was evidence for a near transfer effect, but no evidence for mid-transfer. There was also no evidence that the magnitude of training improvement was related to transfer task performance. This finding adds to the growing body of literature questioning the effectiveness of cognitive training. Given previous positive findings, however, there may still be value in continuing to explore the extent to which cognitive training can capitalise on near or mid-transfer effects for performance optimisation.

The final fixation to a target in far-aiming tasks, known as the quiet eye, has been consistently identified as an important perceptual-cognitive variable for task execution. Yet, despite a number of proposed mechanisms it remains unclear whether the fixation itself is driving performance effects or is simply an emergent property of underpinning cognitions. Across two pre-registered studies, novice golfers (n = 127) completed a series of golf putts in a virtual reality simulation to examine the function of the quiet eye in the absence of visual information. In experiment 1 participants maintained a quiet eye fixation even when all visual information was occluded. Visual occlusion did significantly disrupt motor skill accuracy, but the effect was relatively small (89cm vs 105cm radial error, std. beta = 0.25). In experiment 2, a 'noisy eye' was induced using covertly moving fixation points, which disrupted skill execution (p = .04, BF = 318.07, std. beta = -0.25) even though visual input was equivalent across conditions. Overall, the results showed that performers persist with a long pre-shot fixation even in the absence of visual information, and that the stillness of this fixation confers a functional benefit that is not merely related to improved information extraction.

National strategies for addressing chronic kidney disease (CKD) are crucial to improving kidney health. We sought to describe country-level variations in non-communicable disease (NCD) strategies and CKD-specific policies across different regions and income levels worldwide. The International Society of Nephrology Global Kidney Health Atlas (GKHA) was a multinational cross-sectional survey conducted between July and October 2018. Responses from key opinion leaders in each country regarding national NCD strategies, the presence and scope of CKD-specific policies, and government recognition of CKD as a health priority were described overall and according to region and income level. 160 countries participated in the GKHA survey, comprising 97.8% of the world's population. Seventy-four (47%) countries had an established national NCD strategy, and 53 (34%) countries reported the existence of CKD-specific policies, with substantial variation across regions and income levels. Where CKD-specific policies existed, non-dialysis CKD care was variably addressed. 79 (51%) countries identified government recognition of CKD as a health priority. Low- and low-middle income countries were less likely to have strategies and policies for addressing CKD and have governments which recognise it as a health priority. The existence of CKD-specific policies, and a national NCD strategy more broadly, varied substantially across different regions around the world but was overall suboptimal, with major discrepancies between the burden of CKD in many countries and governmental recognition of CKD as a health priority. Greater recognition of CKD within national health policy is critical to improving kidney healthcare globally.

The Kentucky Geological Survey (KGS) 1 Hanson Aggregates stratigraphic research well, Carter County, Kentucky, USA, was drilled to a total depth of 1474 m as a field-scale test of potential CO2 storage reservoir properties in the Central Appalachian Basin. Geomechanical properties of the Rose Run sandstone (upper Ordovician Knox group) were tested for its suitability as a storage reservoir. A 9.8-m thick section of the Rose Run was penetrated at 1000 m drilled depth and a whole-diameter core and rotary sidewall cores were taken. Average porosity and permeability measured in core plugs were 9.1% and 44.6 mD, respectively. Maximum vertical stress gradient calculated in the wellbore was 26 MPa/km. Wellbore fractures in dolomites underlying and overlying the Rose Run follow the contemporary N53°E Appalachian Basin stress field. The Rose Run elastic geomechanical properties were calibrated to values measured in core plugs to evaluate its fracturing risk as a CO2 storage reservoir. Mean Young's modulus and Poisson's ratio values of the Rose Run were 45 GPa and 0.23, respectively, whereas Young's modulus and Poisson's ratio values were 77.1 GPa and 0.28, respectively, in the overlying Beekmantown dolomite, suggesting the Rose Run may fracture if overpressured during CO2 injection but be confined by the Beekmantown. Triaxial compressive strength measured in core plugs found the Rose Run and Beekmantown fractured at mean axial stresses of 156.5 MPa and 282.2 MPa, respectively, confirming the Beekmantown as suitable for confining CO2 injected into the Rose Run. A step-rate test was conducted in a mechanically-isolated 18.6-m interval bracketing the Rose Run. Static Rose Run reservoir pressure was 9.3 MPa, and fracture gradient under injection was 13.6 MPa/km, suggesting step-rate testing before CO2 injection, and subsequent pressure monitoring to ensure confinement. As the region around the KGS 1 Hanson Aggregates well is underpressured and adjacent to faulted Precambrian basement, further research is needed to evaluate its induced seismicity risk during CO2 injection.

Several types of phototherapy target human pathogens and Porphyromonas gingivitis (Pg) in particular. The various approaches can be organized into five different treatment modes sorted by different power densities, interaction times, effective wavelengths and mechanisms of action. Mode 1: antimicrobial ultraviolet (aUV); mode 2: antimicrobial blue light (aBL); mode 3: antimicrobial selective photothermolysis (aSP); mode 4: antimicrobial vaporization; mode 5: antimicrobial photodynamic therapy (aPDT). This report reviews the literature to identify for each mode (a) the putative molecular mechanism of action; (b) the effective wavelength range and penetration depth; (c) selectivity; (d) in vitro outcomes; and (e) clinical trial/study outcomes as these elements apply to Porphyromonas gingivalis (Pg). The characteristics of each mode influence how each is translated into the clinic.

In tropical Africa, forests and savannas are the two most widespread biomes and potentially represent alternative stable states with a divergent species composition. A classic, but untested, hypothesis posited by White (1983) suggests that the transition zones between forests and savannas contain a floristically impoverished assemblage, with few representatives from each biome. Further, the evolutionary dimension of diversity has received limited attention, despite its importance for understanding the biogeographic history of biomes. Here, we quantified species richness and several measures of evolutionary diversity in 1° grid cells, using c. 300,000 occurrence records of trees and shrubs combined with biome affiliation data for 3203 species. We found that assemblages in transition zones hold fewer woody species than assemblages in forest and savanna zones, as posited by White. However, transition zones hold more phylogenetic diversity than expected given their species richness, whether one considers forest and savanna assemblages separately or together. We also show that the Congo Basin forest has low levels of phylogenetic diversity, given the number of species, and highlight south-eastern African savannas as a centre of savanna woody species richness and phylogenetic diversity. Regions with high phylogenetic diversity, given the number of both forest and savanna species, were centred around the Dahomey Gap and Cameroon, mainly in transition zones. Overall, our study shows that even if floristically impoverished, transition zones hold unexpectedly high evolutionary diversity. This suggests that they are important centres of evolutionary innovation and diversification and/or serve as evolutionary crossroads, where lineages that diversified in contrasting environments coexist within a single area.

The Lower Ordovician Rose Run Sandstone is a potential CO2 storage reservoir in the Central Appalachian Basin in northeast Kentucky where the Kentucky Geological Survey’s 1 Hanson Aggregates research well penetrated it at drill depths of 1,000–1,009.5 m. Average Rose Run porosity and permeability from core plugs are 9.1% and 44.6 mD, respectively. In situ reservoir properties were determined by step-rate testing an 18.6-m interval bracketing the Rose Run. Pressure derivative analysis of wellbore falloff pressure suggests that the Rose Run shares properties of both dual-porosity and dual-permeability reservoirs, consistent with its mixed lithologies. The Rose Run pore pressure was 9.3 MPa/km, 1.1 MPa/km underpressured compared to the expected hydrostatic gradient of 10.4 MPa/km. Average porosity of the Rose Run, at the industry-standard 7% porosity cutoff for assessing CO2 storage capacity, calculated from 27 wells in the surrounding region, was 11.6% and the average net reservoir thickness was 6.2 m. Geomechanical properties of the overlying Beekmantown Dolomite show that it would act as a reservoir confining interval during CO2 injection. The estimated P50 supercritical CO2 storage volume is 77.2 kt/km2, yielding P50 storage capacity of 165.7 Mt in the region. By itself, an average surface area of 12.9 km2 would be required to store 1 Mt of supercritical CO2 in the Rose Run, thus lacking the volume to act as a stand-alone CO2 storage reservoir in this area. It could contribute to a stacked-reservoir storage project developed in the larger Knox section, however. CO2–brine relative permeability tests suggest that nearly half of any supercritical CO2 injected into the Rose Run would be residually trapped, and another portion would be trapped by mineral precipitation. The Rose Run in the KGS 1 Hanson Aggregates well is very close to the subsurface CO2 critical depth in the northeast Kentucky region and lacks an updip reservoir trap. How far and fast the mobile CO2 migration might occur at this site remains for future research and reservoir modeling.

We publish in this article a new species of tree of Drypetes (Putranjivaceae) from the Democratic Republic of the Congo and Republic of the Congo, D. palustris, which occurs in the Western Congolian Swamp Forests ecoregion. It is known from eight gatherings and we compare it with the species with the most similar morphology, D. calvescens, of which we have studied 51 gatherings collected in Central Africa. A taxonomic treatment of both species, including their detailed descriptions, typification of their names, a comparative table summarizing their main morphological differences, an illustration and information about their habitat and distribution are provided. A provisional IUCN Red List assessment shows that D. palustris is Endangered and D. calvescens is of Least Concern.

PrPC, a receptor for Aβ oligomers, blocks polarized elongation of Aβ fibrils by binding to the rapidly growing end of each fibril. PrPC and other receptors may trap Aβ oligomers and protofibrils on the neuronal surface by binding to a common molecular determinant, initiating a neurotoxic signal.

Societal Impact Statement Large areas of tropical forest are degraded. While global tree cover is being mapped with increasing accuracy from space, much less is known about the quality of that tree cover. Here we present a field protocol for rapid assessments of forest condition. Using extensive field data from Tanzania, we show that a focus on remotely‐sensed deforestation would not detect significant reductions in forest quality. Radar‐based remote sensing of degradation had good agreement with the ground data, but the ground surveys provided more insights into the nature and drivers of degradation. We recommend the combined use of rapid field assessments and remote sensing to provide an early warning, and to allow timely and appropriately targeted conservation and policy responses. Summary Tropical forest degradation is widely recognised as a driver of biodiversity loss and a major source of carbon emissions. However, in contrast to deforestation, more gradual changes from degradation are challenging to detect, quantify and monitor. Here, we present a field protocol for rapid, area‐standardised quantifications of forest condition, which can also be implemented by non‐specialists. Using the example of threatened high‐biodiversity forests in Tanzania, we analyse and predict degradation based on this method. We also compare the field data to optical and radar remote‐sensing datasets, thereby conducting a large‐scale, independent test of the ability of these products to map degradation in East Africa from space. Our field data consist of 551 ‘degradation’ transects collected between 1996 and 2010, covering >600 ha across 86 forests in the Eastern Arc Mountains and coastal forests. Degradation was widespread, with over one‐third of the study forests—mostly protected areas—having more than 10% of their trees cut. Commonly used optical remote‐sensing maps of complete tree cover loss only detected severe impacts (≥25% of trees cut), that is, a focus on remotely‐sensed deforestation would have significantly underestimated carbon emissions and declines in forest quality. Radar‐based maps detected even low impacts (

Societal Impact Statement Globally, the conservation value of big trees is linked to biodiversity and carbon sequestration. We studied trees, greater than 80 cm in diameter, in a forest in the Republic of Congo. We found that more than 100 species reach this size and the most abundant species is Sapele (Entandrophragma cylindricum), which is exploited for global timber markets. More than 40% of the large tree species are used by local people for food. Our results show that big trees are important to local people in the Congo Basin in addition to being the focus of industrial logging and in many areas the basis for the formal economy. Summary The main aim of this paper is to establish standard techniques for surveying the biggest trees in tropical rain forests. One hundred and thirty hectares (13 plots of 10 ha) of unlogged mixed species terra firma forest in the Republic of Congo were surveyed for trees greater than 80 cm in diameter. More than 100 species of tree exceed 80 cm in diameter and one species, Entandrophragma cylindricum (Sapele or Sapelli), dominates this size class. Obtaining comparable data of big trees from different sites across the tropics is a priority. We propose a standardised plot size of 10 ha, replicated 10 times for each forest type at different study sites and a minimum trunk diameter of 70 cm at breast height or above buttresses.

Abstract Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL‐33 significantly prolonged islet allograft survival. IL‐33‐treated mice had elevated numbers of ILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect of IL‐33 on allograft survival, and additional ILC2 depletion in Treg‐depleted DEREG mice completely abolished the protective effects of IL‐33, indicating that ILC2s play critical roles in IL‐33‐mediated islet graft protection. Two subsets of ILC2s were identified in islet allografts of IL‐33‐treated mice: IL‐10 producing ILC2s (ILC210) and non‐IL‐10 producing ILC2s (non‐ILC10). Intravenous transfer of ILC210 cells, but not non‐ILC10, prolonged islet allograft survival in an IL‐10‐dependent manner. Locally transferred ILC210 cells led to long‐term islet graft survival, suggesting that ILC210 cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role of ILC210 in islet transplantation which could be potentiated as a therapeutic strategy.

Abstract Cardiomyopathy is a frequent complication of propionic acidemia (PA). It is often fatal, and its occurrence is largely independent of classic metabolic treatment modalities. Liver transplantation (LT) is a treatment option for severe PA as the liver plays a vital role in metabolism of the precursors that accumulate in patients with PA. LT in PA is now considered to be a long‐lasting and valid treatment to prevent cardiac disease. The subject of this report had severe cardiomyopathy that largely disappeared prior to undergoing a LT. Three years following the transplant, there was recurrence of cardiomyopathy following a surgery that was complicated with a postoperative aspiration pneumonia. On his last hospital admission, he was presented with pulmonary edema and heart failure. He continued with episodes of intractable hypotension, despite maximum inotropic and diuretic support. He died following redirection of care. We conclude that lethal cardiomyopathy may develop several years after successful LT in patients with PA.

Background – During his stay in Yangambi in the 1940s, the Belgian botanist J. Léonard collected a species of the genus Drypetes endemic to the Democratic Republic of the Congo. He named it D. morocarpa on herbarium labels, but never published it.Methods – The present study is based on the revision of 26 collections of D. morocarpa. Morphometric measurements on herbarium specimens belonging to the new species and its closest relatives in Drypetes were carried out in order to describe this new species.Results – We describe here D. morocarpa J.Léonard ex D.J.Harris & Quintanar. It is easily recognisable by its blackish twigs and young branchlets, orbicular stipules, leaf blades usually entire, and hard fruits, covered with irregular protuberances. It has been collected in two areas along the course of the Congo river or its tributaries. A differential diagnosis, a detailed morphological description, a key to distinguish it from the most similar species, an illustration and all the available information about its habitat, distribution and conservation status are provided.

Chromatin-mediated silencing, including the formation of heterochromatin, silent chromosome territories, and repressed gene promoters, acts to stabilize patterns of gene regulation and the physical structure of the genome. Reduction of chromatin-mediated silencing can result in genome rearrangements, particularly at intrinsically unstable regions of the genome such as transposons, satellite repeats, and repetitive gene clusters including the rRNA gene clusters (rDNA). It is thus expected that mutational or environmental conditions that compromise heterochromatin function might cause genome instability, and diseases associated with decreased epigenetic stability might exhibit genome changes as part of their aetiology. We find the support of this hypothesis in invasive ductal breast carcinoma, in which reduced epigenetic silencing has been previously described, by using a facile method to quantify rDNA copy number in biopsied breast tumours and pair-matched healthy tissue. We found that rDNA and satellite DNA sequences had significant copy number variation – both losses and gains of copies – compared to healthy tissue, arguing that these genome rearrangements are common in developing breast cancer. Thus, any proposed aetiology onset or progression of breast cancer should consider alterations to the epigenome, but must also accommodate concomitant changes to genome sequence at heterochromatic loci.

Summary: We report seven affected individuals from six families with a recurrent, de novo variant in the ARPC4 gene (c.472C>T [p.Arg158Cys (GenBank: NM_005718.4)]). Core features in affected individuals include microcephaly, mild motor delays, and significant speech impairment. ARPC4 is a core subunit of the actin-related protein (ARP2/3) complex, which catalyzes the formation of F-actin networks. We show that the recurrent ARPC4 missense change is associated with a decreased amount of F-actin in cells from two affected individuals. Taken together, our results implicate heterozygous ARPC4 missense variants as a cause of neurodevelopmental disorders and microcephaly.

Ventricular tachycardia (VT) or ventricular fibrillation (VF) storm associated with severe acute respiratory syndrome coronavirus 2 infection is a potentially fatal complication; the correlation of these 2 disorders, however, has not been well studied. This retrospective case series examined outcomes of 2 patients who were admitted for repeated implantable cardioverter-defibrillator shocks with or without syncope and observed to have VT/VF storms with COVID-19. Mechanisms of VT/VF storms in COVID-19 are multifactorial including myocarditis, systemic inflammation, hyperadrenergic state, hemodynamic instability, hypoxia, acidosis, and proarrhythmic drugs. A higher incidence of VT/VF storm is observed in patients with comorbidities and those requiring critical care, with some studies reporting increased mortality. In our cohort, 1 of the 2 patients succumbed to the complications from COVID-19, and the other patient was discharged to home in stable condition. Monitoring of life-threatening arrhythmias in the setting of COVID-19 may need to be adopted to prevent morbidity and mortality.

Background: A 25-base pair (25bp) intronic deletion in the MYBPC3 gene enriched in South Asians (SAs) is a risk allele for late-onset left ventricular (LV) dysfunction, hypertrophy, and heart failure (HF) with several forms of cardiomyopathy. However, the effect of this variant on exercise parameters has not been evaluated.Methods: As a pilot study, 10 asymptomatic SA carriers of the MYBPC3Δ25bp variant (52.9 ± 2.14 years) and 10 age- and gender-matched non-carriers (NCs) (50.1 ± 2.7 years) were evaluated at baseline and under exercise stress conditions using bicycle exercise echocardiography and continuous cardiac monitoring.Results: Baseline echocardiography parameters were not different between the two groups. However, in response to exercise stress, the carriers of Δ25bp had significantly higher LV ejection fraction (%) (CI: 4.57 ± 1.93; p < 0.0001), LV outflow tract peak velocity (m/s) (CI: 0.19 ± 0.07; p < 0.0001), and higher aortic valve (AV) peak velocity (m/s) (CI: 0.103 ± 0.08; p = 0.01) in comparison to NCs, and E/A ratio, a marker of diastolic compliance, was significantly lower in Δ25bp carriers (CI: 0.107 ± 0.102; p = 0.038). Interestingly, LV end-diastolic diameter (LVIDdia) was augmented in NCs in response to stress, while it did not increase in Δ25bp carriers (CI: 0.239 ± 0.125; p = 0.0002). Further, stress-induced right ventricular systolic excursion velocity s' (m/s), as a marker of right ventricle function, increased similarly in both groups, but tricuspid annular plane systolic excursion increased more in carriers (slope: 0.008; p = 0.0001), suggesting right ventricle functional differences between the two groups.Conclusions: These data support that MYBPC3Δ25bp is associated with LV hypercontraction under stress conditions with evidence of diastolic impairment.

Emerging antimicrobial drug resistance is increasing the complexity involved in treating critical conditions such as bacterial induced sepsis. Methods for diagnosing specific drug resistance tend to be rapid or sensitive, but not both. Detection methods like sequence-specific single-molecule analysis could address this concern if they could be adapted to work on smaller targets similar to those produced in traditional clinical situations. In this work we demonstrate that a 120 bp double stranded polynucleotide with an overhanging single stranded 25 bp probe sequence can be created by immobilizing DNA with a biotin/streptavidin magnetic bead system, labeling with SYBR Gold, and rinsing the excess away while the probe retains multiple fluorophores. These probes with multiple fluorophores can then be used to label a bacterial plasmid target in a sequence-specific manner. These probes enabled the detection of 1 pM plasmid samples containing a portion of an antibiotic resistance gene sequence. This system shows the possibility of improving capture and fluorescence labeling of small nucleic acid fragments, generating lower limits of detection for clinically relevant samples while maintaining rapid processing times.

Objectives The Global Kidney Health Atlas (GKHA) is a multinational, cross-sectional survey designed to assess the current capacity for kidney care across all world regions. The 2017 GKHA involved 125 countries and identified significant gaps in oversight, funding and infrastructure to support care for patients with kidney disease, especially in lower-middle-income countries. Here, we report results from the survey for the second iteration of the GKHA conducted in 2018, which included specific questions about health financing and oversight of end-stage kidney disease (ESKD) care worldwide.Setting A cross-sectional global survey.Participants Key stakeholders from 182 countries were invited to participate. Of those, stakeholders from 160 countries participated and were included.Primary outcomes Primary outcomes included cost of kidney replacement therapy (KRT), funding for dialysis and transplantation, funding for conservative kidney management, extent of universal health coverage, out-of-pocket costs for KRT, within-country variability in ESKD care delivery and oversight systems for ESKD care. Outcomes were determined from a combination of desk research and input from key stakeholders in participating countries.Results 160 countries (covering 98% of the world’s population) responded to the survey. Economic factors were identified as the top barrier to optimal ESKD care in 99 countries (64%). Full public funding for KRT was more common than for conservative kidney management (43% vs 28%). Among countries that provided at least some public coverage for KRT, 75% covered all citizens. Within-country variation in ESKD care delivery was reported in 40% of countries. Oversight of ESKD care was present in all high-income countries but was absent in 13% of low-income, 3% of lower-middle-income, and 10% of upper-middle-income countries.Conclusion Significant gaps and variability exist in the public funding and oversight of ESKD care in many countries, particularly for those in low-income and lower-middle-income countries.

Self-propagating form of the prion protein (PrPSc) causes many neurodegenerative diseases, such as Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker syndrome (GSS). Heparin is a highly sulfated linear glycosaminoglycan (GAG) and is composed of alternating D-glucosamine and L-iduronic acid or D-glucuronic acid sugar residues. The interactions of heparin with various proteins in a domain-specific or charged-dependent manner provide key roles on many physiological and pathological processes. While GAG-PrP interactions had been previously reported, the specific glycan structures that facilitate interactions with different regions of PrP and their binding kinetics have not been systematically investigated. In this study, we performed direct binding surface plasmon resonance (SPR) assay to characterize the kinetics of heparin binding to four recombinant murine PrP constructs including full length (M23–230), a deletion mutant lacking the four histidine-containing octapeptide repeats (M23–230 Δ59–90), the isolated N-terminal domain (M23–109), and the isolated C-terminal domain (M90–230). Additionally, we found the specific structural determinants required for GAG binding to the four PrP constructs with chemically defined derivatives of heparin and other GAGs by an SPR competition assay. Our findings may be instrumental in developing designer GAGs for specific targets within the PrP to fine-tune biological and pathophysiological activities of PrP.

Parenteral prostanoids are effective for improving outcomes in patients with pulmonary arterial hypertension. However, subcutaneous or intravenous delivery via an external pump places a significant burden on patients. Consequently, the Implantable System for Remodulin© (treprostinil) was developed and is associated with a low rate of complications (United Therapeutics (Research Triangle Park, NC) in collaboration with Medtronic, Inc. (Mounds View, MN)). The current real-world experience study evaluated pulmonary arterial hypertension patients' perceptions of their quality of life, ability to perform activities of daily living, perceptions on the benefits and risks of the implantable system, and their social interactions before and after receiving the implantable system. Pulmonary arterial hypertension patients who had been transitioned from an external infusion pump to the implantable system completed a mix of quantitative and qualitative questions administered online over the course of a six-day period. A total of 20 patients completed the study. All patients reported that their quality of life, confidence out in public, and ability to travel long distances had improved. Over 90% of patients reported that their overall level of independence was better since receiving the implantable system, and most patients indicated that their ability to independently perform specific activities of daily living had improved. Responses to the qualitative questions suggested that the implantable system saved time, improved interpersonal relationships, and increased freedom. Results from this real-world patient experience study suggest this novel delivery system provides improvements in factors that are of substantial importance to patients.

New computer technologies, like virtual reality (VR), have created opportunities to study human behavior and train skills in novel ways. VR holds significant promise for maximizing the efficiency and effectiveness of skill learning in a variety of settings (e.g., sport, medicine, safety-critical industries) through immersive learning and augmentation of existing training methods. In many cases the adoption of VR for training has, however, preceded rigorous testing and validation of the simulation tool. In order for VR to be implemented successfully for both training and psychological experimentation it is necessary to first establish whether the simulation captures fundamental features of the real task and environment, and elicits realistic behaviors. Unfortunately evaluation of VR environments too often confuses presentation and function, and relies on superficial visual features that are not the key determinants of successful training outcomes. Therefore evidence-based methods of establishing the fidelity and validity of VR environments are required. To this end, we outline a taxonomy of the subtypes of fidelity and validity, and propose a variety of practical methods for testing and validating VR training simulations. Ultimately, a successful VR environment is one that enables transfer of learning to the real-world. We propose that key elements of psychological, affective and ergonomic fidelity, are the real determinants of successful transfer. By adopting an evidence-based approach to VR simulation design and testing it is possible to develop valid environments that allow the potential of VR training to be maximized.

Cognitive training (CT) aims to develop domain general mental abilities to support functions like decision making, multitasking, and performance under pressure. Research to date has indicated that CT likely aids performance on lab-based cognitive tests, but there has been little demonstration of transfer to tasks representative of real-world high performance environments. This study aimed to assess transfer from a CT intervention to near and mid-level transfer tasks, plus a far transfer test representative of real-world multitasking in a military environment. 84 participants were randomized to four independent training groups, using NeuroTracker, a CT task based on 3D object tracking. There was no evidence for near transfer (to another object tracking task) or for far transfer to a route monitoring task designed to replicate real-world multitasking. There may, however, have been some improvement in working memory performance as a result of training. These findings raise further questions about whether domain general CT will transfer to real-world performance. Effective uses of CT may require more task specific training targeting mid-level transfer effects.

The cell cycle regulator p27Kip1 is a critical factor controlling cell number in many lineages. While its anti-proliferative effects are well-established, the extent to which this is a result of its function as a cyclin-dependent kinase (CDK) inhibitor or through other known molecular interactions is not clear. To genetically dissect its role in the developing corneal endothelium, we examined mice harboring two loss-of-function alleles, a null allele (p27-) that abrogates all protein function and a knockin allele (p27CK-) that targets only its interaction with cyclins and CDKs. Whole-animal mutants, in which all cells are either homozygous knockout or knockin, exhibit identical proliferative increases (~0.6-fold) compared with wild-type tissues. On the other hand, use of mosaic analysis with double markers (MADM) to produce infrequently-occurring clones of wild-type and mutant cells within the same tissue environment uncovers a roughly three- and six-fold expansion of individual p27CK-/CK- and p27-/- cells, respectively. Mosaicism also reveals distinct migration phenotypes, with p27-/- cells being highly restricted to their site of production and p27CK-/CK- cells more widely scattered within the endothelium. Using a density-based clustering algorithm to quantify dispersal of MADM-generated clones, a four-fold difference in aggregation is seen between the two types of mutant cells. Overall, our analysis reveals that, in developing mouse corneal endothelium, p27 regulates cell number by acting cell autonomously, both through its interactions with cyclins and CDKs and through a cyclin-CDK-independent mechanism(s). Combined with its parallel influence on cell motility, it constitutes a potent multi-functional effector mechanism with major impact on tissue organization.

BackgroundResidual kidney function (RKF) is associated with improved survival and quality of life in dialysis patients. Previous studies have suggested that initiation of peritoneal dialysis (PD) may slow RKF decline compared to the pre-dialysis period. We sought to evaluate the association between PD initiation and RKF decline in the Initiating Dialysis Early And Late (IDEAL) trial.MethodsIn this post hoc analysis of the IDEAL randomized controlled trial, PD participants were included if results from 24-hour urine collections had been recorded within 30 days of dialysis initiation, and at least one value pre- and one value post-dialysis commencement were available. The primary outcome was slope of RKF decline, calculated as mean of urinary creatinine and urea clearances. Secondary outcomes included slope of urine volume decline and time from PD initiation to anuria.ResultsThe study included 151 participants (79 early start, 72 late start). The slope of RKF decline was slower after PD initiation (-2.69±0.18mL/min/1.73m2/yr) compared to before PD (-4.09±0.33mL/min/1.73m2/yr; change in slope +1.19 mL/min/1.73m2/yr, 95%CI 0.48-1.90, pConclusionsInitiation of PD was associated with a slower decline of RKF compared to the pre-dialysis period.

A taxonomic revision of Desplatsia Bocq. (Malvaceae s. lat. Juss., subfamily Grewioideae Hochr., tribe Grewieae Endl.) based on about 800 herbarium specimens is presented. Desplatsia is a genus of trees and shrubs found in tropical West and Central Africa and is characterized by subulately divided stipules, the absence of an androgynophore, stamens that are fused to a tube at the base, and large and distinctive fruits that are dispersed by elephants. Four species are recognized (D. subericarpa Bocq., D. chrysochlamys (Mildbr. & Burret) Mildbr. & Burret, D. dewevrei (De Wild. & T.Durand) Burret and D. mildbraedii Burret) and 12 species names are placed into synonymy, two of which have been put into synonymy for the first time: D. floribunda Burret syn. nov. and D. trillesiana (Pierre ex De Wild.) Pierre ex A.Chev. syn. nov. All four species are widely distributed and their conservation status is assessed as Least Concern (LC). A key to the species, full species descriptions, illustrations, a specimen citation list and distribution maps are provided.

Purpose There are no uniform standards to inform patients to what extent trainees are involved in their care. This may lead to inequities in sharing the potential risks associated with receiving care in an academic setting. This study was designed to determine patients' level of knowledge of the medical education system, their preferences regarding who provides treatment, and how strongly they would react if they found certain members of the care team were involved without their consent. Design This study is a prospective, nonrandomized, and observational survey of a convenience sample. Methods Consecutive patients referred for a cataract surgery evaluation to the Veteran's Affairs Ophthalmology Department in Lexington, KY between 2015 and 2017 were recruited. Results Ninety-six of 113 eligible patients (response rate 85%) completed the survey. About 33, 69, 33, and 49% of respondents recognized an intern, resident, fellow, and attending as a doctor, respectively. Three quarters (76.1%) felt it was important to be asked permission in advance of a resident assisting or performing surgery, and 21% indicated they would go elsewhere if they found that a resident would assist in, or perform their surgery. About 21, 21, and 58% of respondents would be upset or very upset if a resident was in the operating room, assisted in, or performed surgery without their permission, respectively. Conclusion This survey demonstrates an overall willingness of this specific, largely confined patient population to receive supervised care from training physicians provided they are fully informed and educated on the role of those involved in their care.

To confirm that neoplastic monocyte-derived collagen- and fibronectin-producing fibrocytes induce bone marrow (BM) fibrosis in primary myelofibrosis (PMF), we injected PMF BM-derived fibrocyte-precursor CD14+/CD34- monocytes into the tail vein of NOD-SCID-γ (NSG) mice. PMF BM-derived CD14+/CD34- monocytes engrafted and induced a PMF-like phenotype with splenomegaly, myeloid hyperplasia with clusters of atypical megakaryocytes, persistence of the JAK2V617F mutation, and BM and spleen fibrosis. As control we used normal human BM-derived CD14+/CD34- monocytes. These monocytes also engrafted and gave rise to normal megakaryocytes that, like PMF CD14+/CD34--derived megakaryocytes, expressed HLA-ABC and human CD42b antigens. Using 2 clonogenic assays we confirmed that PMF and normal BM-derived CD14+/CD34- monocytes give rise to megakaryocyte colony-forming cells, suggesting that a subpopulation BM monocytes harbors megakaryocyte progenitor capacity. Taken together, our data suggest that PMF monocytes induce myelofibrosis-like phenotype in immunodeficient mice and that PMF and normal BM-derived CD14+/CD34- monocytes give rise to megakaryocyte progenitor cells.

SARS-CoV-2, the cause of COVID19, has caused a pandemic that has infected more than 80 M and killed more than 1.6 M persons worldwide. In the US as of December 2020, it has infected more than 32 M people while causing more than 570,000 deaths. As the pandemic persists, there has been a public demand to reopen schools and university campuses. To consider these demands, it is necessary to rapidly identify those individuals infected with the virus and isolate them so that disease transmission can be stopped. In the present study, we examined the sensitivity of the Quidel Rapid Antigen test for use in screening both symptomatic and asymptomatic individuals at the University of Arizona from June to August 2020. A total of 885 symptomatic and 1551 asymptomatic subjects were assessed by antigen testing and real-time PCR testing. The sensitivity of the test for both symptomatic and asymptomatic persons was between 82 and 90%, with some caveats.

The tropical vegetation of Africa is characterized by high levels of species diversity but is undergoing important shifts in response to ongoing climate change and increasing anthropogenic pressures. Although our knowledge of plant species distribution patterns in the African tropics has been improving over the years, it remains limited. Here we present RAINBIO, a unique comprehensive mega-database of georeferenced records for vascular plants in continental tropical Africa. The geographic focus of the database is the region south of the Sahel and north of Southern Africa, and the majority of data originate from tropical forest regions. RAINBIO is a compilation of 13 datasets either publicly available or personal ones. Numerous in depth data quality checks, automatic and manual via several African flora experts, were undertaken for georeferencing, standardization of taxonomic names and identification and merging of duplicated records. The resulting RAINBIO data allows exploration and extraction of distribution data for 25,356 native tropical African vascular plant species, which represents ca. 89% of all known plant species in the area of interest. Habit information is also provided for 91% of these species.

Synaptic degeneration is one of the earliest pathological correlates of prion disease, and it is a major determinant of the progression of clinical symptoms. However, the cellular and molecular mechanisms underlying prion synaptotoxicity are poorly understood. Previously, we described an experimental system in which treatment of cultured hippocampal neurons with purified PrPSc, the infectious form of the prion protein, induces rapid retraction of dendritic spines, an effect that is entirely dependent on expression of endogenous PrPC by the target neurons. Here, we use this system to dissect pharmacologically the underlying cellular and molecular mechanisms. We show that PrPSc initiates a stepwise synaptotoxic signaling cascade that includes activation of NMDA receptors, calcium influx, stimulation of p38 MAPK and several downstream kinases, and collapse of the actin cytoskeleton within dendritic spines. Synaptic degeneration is restricted to excitatory synapses, spares presynaptic structures, and results in decrements in functional synaptic transmission. Pharmacological inhibition of any one of the steps in the signaling cascade, as well as expression of a dominant-negative form of p38 MAPK, block PrPSc-induced spine degeneration. Moreover, p38 MAPK inhibitors actually reverse the degenerative process after it has already begun. We also show that, while PrPC mediates the synaptotoxic effects of both PrPSc and the Alzheimer's Aβ peptide in this system, the two species activate distinct signaling pathways. Taken together, our results provide powerful insights into the biology of prion neurotoxicity, they identify new, druggable therapeutic targets, and they allow comparison of prion synaptotoxic pathways with those involved in other neurodegenerative diseases.

Background: Cognitive training (CT) aims to develop a range of skills, like attention and decision-making, through targeted training of core cognitive functions. While CT can target context specific skills, like movement anticipation, much CT is domain general, focusing on core abilities (e.g., selective attention) for transfer to a range of real-world tasks, such as spotting opponents. Commercial CT (CCT) devices are highly appealing for athletes and coaches due to their ease of use and eye-catching marketing claims. The extent to which this training transfers to performance in the sporting arena is, however, unclear. Therefore, this paper sought to provide a systematic review of evidence for beneficial training effects of CCT devices and evaluate their application to sport.Methods: An extensive search of electronic databases (PubMed, PsychInfo, GoogleScholar, and SportDiscus) was conducted to identify peer-reviewed evidence of training interventions with commercially available CT devices. Forty-three studies met the inclusion criteria and were retained for quality assessment and synthesis of results. Seventeen studies assessed transfer effects beyond laboratory cognitive tests, but only 1 directly assessed transfer to a sporting task.Results: The review of evidence showed limited support for far transfer benefits from CCT devices to sporting tasks, mainly because studies did not target the sporting environment. Additionally, a number of methodological issues with the CCT literature were identified, including small sample sizes, lack of retention tests, and limited replication of findings by researchers independent of the commercial product. Therefore, evidence for sporting benefits is currently limited by the paucity of representative transfer tests and a focus on populations with health conditions.Conclusions: Currently there is little direct evidence that the use of CCT devices can transfer to benefits for sporting performance. This conclusion, however, stems more from a lack of experimental studies in the sporting field and a lack of experimental rigor, rather than convincing null effects. Subsequently, there is an opportunity for researchers to develop more reliable findings in this area through systematic assessment in athletic populations and major methodological improvements.

Biodiversity forecasts are important for conservation, management, and evaluating how well current models characterize natural systems. While the number of forecasts for biodiversity is increasing, there is little information available on how well these forecasts work. Most biodiversity forecasts are not evaluated to determine how well they predict future diversity, fail to account for uncertainty, and do not use time-series data that captures the actual dynamics being studied. We addressed these limitations by using best practices to explore our ability to forecast the species richness of breeding birds in North America. We used hindcasting to evaluate six different modeling approaches for predicting richness. Hindcasts for each method were evaluated annually for a decade at 1,237 sites distributed throughout the continental United States. All models explained more than 50% of the variance in richness, but none of them consistently outperformed a baseline model that predicted constant richness at each site. The best practices implemented in this study directly influenced the forecasts and evaluations. Stacked species distribution models and “naive” forecasts produced poor estimates of uncertainty and accounting for this resulted in these models dropping in the relative performance compared to other models. Accounting for observer effects improved model performance overall, but also changed the rank ordering of models because it did not improve the accuracy of the “naive” model. Considering the forecast horizon revealed that the prediction accuracy decreased across all models as the time horizon of the forecast increased. To facilitate the rapid improvement of biodiversity forecasts, we emphasize the value of specific best practices in making forecasts and evaluating forecasting methods.