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The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously considered the idea of pre-asthma in relation to allergic asthma and considered that, in addition to the need to improve population health via multiple measures, including reduction of exposure to allergens and pollutants and avoidance of obesity, there are several possible specific means to reduce asthma development in those most at risk (pre- asthma). The most obvious is allergen immunotherapy (AIT), which when given for allergic rhinitis (AR) has reasonable evidence to support asthma prevention in children (2) but also needs further study as primary prevention. In this second paper we explore the possibilities for similar actions in late onset eosinophilic asthma.
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Carbon monoxide (CO) is a poisonous gas produced by incomplete combustion of carbon-based fuels that is linked to mortality and morbidity. Household air pollution from burning fuels on poorly ventilated stoves can lead to high concentrations of CO in homes. There are few datasets available on household concentrations of CO in urban areas of sub-Saharan African countries. CO was measured every minute over 24 h in a sample of homes in Nairobi, Kenya. Data on household characteristics were gathered by questionnaire. Metrics of exposure were summarised and analysis of temporal changes in concentration was performed. Continuous 24-h data were available from 138 homes. The mean (SD), median (IQR) and maximum 24-h CO concentration was 4.9 (6.4), 2.8 (1.0-6.3) and 44 ppm, respectively. 50% of homes had detectable CO concentrations for 847 min (14h07m) or longer during the 24-h period, and 9% of homes would have activated a CO-alarm operating to European specifications. An association between a metric of total CO exposure and self-reported exposure to vapours >15 h per week was identified, however this were not statistically significant after adjustment for the multiple comparisons performed. Mean concentrations were broadly similar in homes from a more affluent area and an informal settlement. A model of typical exposure suggests that cooking is likely to be responsible for approximately 60% of the CO exposure of Nairobi schoolchildren. Household CO concentrations are substantial in Nairobi, Kenya, despite most homes using gas or liquid fuels. Concentrations tend to be highest during the evening, probably associated with periods of cooking. Household air pollution from cooking is the main source of CO exposure of Nairobi schoolchildren. The public health impacts of long-term CO exposure in cities in sub-Saharan Africa may be considerable and should be studied further.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Monóxido de Carbono , Monóxido de Carbono/análisis , Contaminación del Aire Interior/análisis , Contaminación del Aire Interior/estadística & datos numéricos , Kenia , Humanos , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Ciudades , Vivienda , Salud Pública , Culinaria , Composición Familiar , Exposición a Riesgos Ambientales/estadística & datos numéricosRESUMEN
Lower-limb wearable robots designed to assist people in everyday activities must reliably recover from any momentary confusion about what the user is doing. Such confusion might arise from momentary sensor failure, collision with an obstacle, losing track of gait due to an out-of-distribution stride, etc. Systems that infer a user's walking condition from angle measurements using Bayesian filters (e.g., extended Kalman filters) have been shown to accurately track gait across a range of activities. However, due to the fundamental problem structure and assumptions of Bayesian filter implementations, such estimators risk becoming 'lost' with little hope of a quick recovery. In this paper, we 1) introduce a Monte Carlo-based metric to quantify the robustness of pattern-tracking gait estimators, 2) propose strategies for improving tracking robustness, and 3) systematically evaluate them against this new metric using a publicly available gait biomechanics dataset. Our results, aggregating 2,700 trials of simulated walking of 10 able-bodied subjects under random perturbations, suggest that drastic improvements in robustness (from 8.9% to 99%) are possible using relatively simple modifications to the estimation process without noticeably degrading estimator accuracy.
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Robotic ankle exoskeletons have been shown to reduce human effort during walking. However, existing ankle exoskeleton control approaches are limited in their ability to apply biomimetic torque across diverse tasks outside of the controlled lab environment. Energy shaping control can provide task-invariant assistance without estimating the user's state, classifying task, or reproducing pre-defined torque trajectories. In previous work, we showed that an optimally task-invariant energy shaping controller implemented on a knee-ankle exoskeleton reduced the effort of certain muscles for a range of tasks. In this paper, we extend this approach to the sensor suite available at the ankle and present its implementation on a commercially-available, bilateral ankle exoskeleton. An experiment with three healthy subjects walking on a circuit and on a treadmill showed that the controller can approximate biomimetic profiles for varying terrains and task transitions without classifying tasks or switching control modes.
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Immune dysregulation is heavily implicated in Parkinson's disease (PD) but the role of Natural Killer (NK) cells has not been well characterised. Accumulating evidence indicates the immune response peaks early in the disease, hence this study focused on characterising NK cells in recently diagnosed PD. PBMCs were obtained from PD cases (< 2 years duration) and age-matched controls and immunophenotyped using flow cytometry. We found an increased proportion and number of NK cells (CD3-CD56+), mature cytotoxic NK cells (CD3-CD16 + CD56dim), and NK cells expressing the activation marker, NKG2D. This implies NK cells are activated in the earliest stages of PD.
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Enfermedad de Parkinson , Humanos , Células Asesinas Naturales , Citometría de Flujo , Antígeno CD56RESUMEN
In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.
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PURPOSE: Pressures related to the COVID-19 pandemic have created the need to develop innovative ways to deliver mental health care, especially for urgent needs. After the launch of a pediatric Emergency Department (ED) Virtual Care service, we aimed to evaluate pediatric ED physicians' experiences with the use of ED virtual care for mental health assessments. METHODS: This mixed-methods study was conducted at a pediatric academic health center in Ontario, Canada. Pediatric ED physicians who conducted ED virtual mental health assessments from May to December 2020 were eligible. Participants completed a 22-question novel survey and were invited to participate in a focus group. Descriptive and thematic analyses were used to analyze the data. RESULTS: Twenty-nine physicians provided mental health services through the ED virtual care platform. Twenty-five physicians (86% response rate) completed the survey and 3 (10%) participated in a focus group. While many agreed that virtual care benefits patients (67%), key barriers identified included time constraints, lack of mental health clinician support, and uncertainty around the pediatric ED physicians' role in these types of assessments. Despite these barriers, physicians recognized the potential benefit of the ED virtual care service for mental health assessments and were largely amenable to improving this process should mental health support be available. CONCLUSIONS: While many physicians agreed that there is a potential benefit of the ED virtual care platform for urgent mental health assessments, time constraints and lack of confidence in providing satisfactory virtual mental health care with minimal mental health support limited its acceptability. These findings can inform the future implementation of mental health services using an innovative virtual ED platform.
RéSUMé: OBJECTIF: Les pressions liées à la pandémie de COVID-19 ont créé le besoin de développer des moyens innovants pour fournir des soins de santé mentale, en particulier pour les besoins urgents. Après le lancement d'un service de soins virtuels aux urgences pédiatriques, nous avons cherché à évaluer les expériences des médecins des urgences pédiatriques avec l'utilisation des soins virtuels aux urgences pour les évaluations de la santé mentale. MéTHODOLOGIE: Cette étude à méthodes mixtes a été menée dans un centre universitaire de santé pédiatrique en Ontario, au Canada. Les médecins pédiatriques qui ont effectué des évaluations virtuelles de la santé mentale aux urgences de mai à décembre 2020 étaient admissibles. Les participants ont rempli une enquête inédite de 22 questions et ont été invités à participer à un groupe de discussion. Des analyses descriptives et thématiques ont été utilisées pour analyser les données. RéSULTATS: Vingt-neuf médecins ont fourni des services de santé mentale par le biais de la plateforme de soins virtuels des urgences. Vingt-cinq médecins (taux de réponse de 86 %) ont répondu au sondage et trois (10 %) ont participé à un groupe de discussion. Si beaucoup s'accordent à dire que les soins virtuels sont bénéfiques pour les patients (67 %), les principaux obstacles identifiés sont les contraintes de temps, le manque de soutien des cliniciens en santé mentale et l'incertitude quant au rôle des urgentistes pédiatriques dans ces types d'évaluations. Malgré ces obstacles, les médecins ont reconnu l'avantage potentiel du service de soins virtuels de l'urgence pour les évaluations de la santé mentale et étaient largement disposés à améliorer ce processus si un soutien en santé mentale était disponible. CONCLUSIONS: Bien que de nombreux médecins s'accordent à dire que la plateforme de soins virtuels des urgences présente un avantage potentiel pour les évaluations urgentes de la santé mentale, les contraintes de temps et le manque de confiance dans la prestation de soins de santé mentale virtuels satisfaisants avec un soutien minimal en matière de santé mentale ont limité son acceptabilité. Ces résultats peuvent éclairer la mise en Åuvre future des services de santé mentale à l'aide d'une plateforme virtuelle d'urgence innovante.
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COVID-19 , Médicos , Humanos , Niño , Salud Mental , Pandemias , COVID-19/epidemiología , Servicio de Urgencia en Hospital , Médicos/psicología , OntarioRESUMEN
BACKGROUND: Much has been written about the state and persistent lack of progress regarding gender equity and the commonly referenced phenomenon of a 'leaking pipeline'. This framing focuses attention on the symptom of women leaving the workforce, rather than the well-documented contributing factors of hindered recognition, advancement, and financial opportunities. While attention shifts to identifying strategies and practices to address gender inequities, there is limited insight into the professional experiences of Canadian women, specifically in the female-dominated healthcare sector. METHODS: We conducted a survey of 420 women working across a range of roles within healthcare. Frequencies and descriptive statistics were calculated for each measure as appropriate. For each respondent, two composite Unconscious Bias (UCB) scores were created using a meaningful grouping approach. RESULTS: Our survey results highlight three key areas of focus to move from knowledge to action, including (1) identifying the resources, structural factors, and professional network elements that will enable a collective shift towards gender equity; (2) providing women with access to formal and informal opportunities to develop the strategic relational skills required for advancement; and (3) restructuring social environments to be more inclusive. Specifically, women identified that self-advocacy, confidence building, and negotiation skills were most important to support development and leadership advancement. CONCLUSIONS: These insights provide systems and organizations with practical actions they can take to support women in the health workforce amid a time of considerable workforce pressure.
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Atención a la Salud , Sector de Atención de Salud , Humanos , Femenino , Canadá , Fuerza Laboral en Salud , Encuestas y CuestionariosRESUMEN
Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma. However asthma prevention has been less studied. Currently there is a concept of pre- diabetes which allows a reduction in full blown diabetes if diet and exercise are undertaken. Similar predictive states are found in Alzheimer's and Parkinson's diseases. In this paper we explore the possibilities for asthma prevention, both at population level and also investigate the possibility of defining a state of pre-asthma, in which intensive treatment could reduce progression to asthma. Since asthma is a heterogeneous condition, this paper is concerned with allergic asthma. A subsequent one will deal with late onset eosinophilic asthma.
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Task-specific, trajectory-based control methods commonly used in exoskeletons may be appropriate for individuals with paraplegia, but they overly constrain the volitional motion of individuals with remnant voluntary ability (representing a far larger population). Human-exoskeleton systems can be represented in the form of the Euler-Lagrange equations or, equivalently, the port-controlled Hamiltonian equations to design control laws that provide task-invariant assistance across a continuum of activities/environments by altering energetic properties of the human body. We previously introduced a port-controlled Hamiltonian framework that parameterizes the control law through basis functions related to gravitational and gyroscopic terms, which are optimized to fit normalized able-bodied joint torques across multiple walking gaits on different ground inclines. However, this approach did not have the flexibility to reproduce joint torques for a broader set of activities, including stair climbing and stand-to-sit, due to strict assumptions related to input-output passivity, which ensures the human remains in control of energy growth in the closed-loop dynamics. To provide biomimetic assistance across all primary activities of daily life, this paper generalizes this energy shaping framework by incorporating vertical ground reaction forces and global planar orientation into the basis set, while preserving passivity between the human joint torques and human joint velocities. We present an experimental implementation on a powered knee-ankle exoskeleton used by three able-bodied human subjects during walking on various inclines, ramp ascent/descent, and stand-to-sit, demonstrating the versatility of this control approach and its effect on muscular effort.
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INTRODUCTION: South Africa's evolving burden of disease is challenging due to a persistent infectious disease, burgeoning obesity, most notably among women and rising rates of non-communicable diseases (NCDs). With two thirds of women presenting at their first antenatal visit either overweight or obese in urban South Africa (SA), the preconception period is an opportunity to optimise health and offset transgenerational risk of both obesity and NCDs. METHODS AND ANALYSIS: Bukhali is the first individual randomised controlled trial in Africa to test the efficacy of a complex continuum of care intervention and forms part of the Healthy Life Trajectories Initiative (HeLTI) consortium implementing harmonised trials in Canada, China, India and SA. Starting preconception and continuing through pregnancy, infancy and childhood, the intervention is designed to improve nutrition, physical and mental health and health behaviours of South African women to offset obesity-risk (adiposity) in their offspring. Women aged 18-28 years (n=6800) will be recruited from Soweto, an urban-poor area of Johannesburg. The primary outcome is dual-energy X-ray absorptiometry derived fat mass index (fat mass divided by height2) in the offspring at age 5 years. Community health workers will deliver the intervention randomly to half the cohort by providing health literacy material, dispensing a multimicronutrient supplement, providing health services and feedback, and facilitating behaviour change support sessions to optimise: (1) nutrition, (2) physical and mental health and (3) lay the foundations for healthier pregnancies and early child development. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Human Ethics Research Committee University of the Witwatersrand, Johannesburg, South Africa (M1811111), the University of Toronto, Canada (19-0066-E) and the WHO Ethics Committee (ERC.0003328). Data and biological sample sharing policies are consistent with the governance policy of the HeLTI Consortium (https://helti.org) and South African government legislation (POPIA). The recruitment and research team will obtain informed consent. TRIAL REGISTRATION: This trial is registered with the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za) on 25 March 2019 (identifier: PACTR201903750173871). PROTOCOL VERSION: 20 March 2022 (version #4). Any protocol amendments will be communicated to investigators, Institutional Review Board (IRB)s, trial participants and trial registries.
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Estado de Salud , Salud Mental , Niño , Preescolar , Agentes Comunitarios de Salud , Femenino , Humanos , Masculino , Obesidad/prevención & control , Embarazo , SudáfricaRESUMEN
Decreasing soil cadmium (Cd) is one method of removing Cd from the food chain. Phosphorus (P) fertilisers are a major source of Cd inputs into soil. Stopping P fertiliser should theoretically decrease Cd inputs and soil Cd accumulation, but there are few field data to show if this occurs. We examined three long-term grazed pasture trials in New Zealand (Ballantrae, Winchmore and Whatawhata) where P fertiliser had been applied (from 10 to 100 kg P ha-1 yr-1) for up to six years and then stopped for 10 to 26 years. Stopping P fertiliser applications reduced soil Cd concentrations at Winchmore and Whatawhata where P had been applied at ≥34 kg P ha-1 yr-1. No reductions occurred below this rate nor at Ballantrae where only 10 years post P-application data were available. Decreases were ascribed to moderate rainfall (1630 mm at Whatawhata and 740 mm rainfall plus 770 mm irrigation at Winchmore) that enhanced Cd leaching and may have been aided at Winchmore by a decrease in soil pH over time (0.4 units). However, because stopping P fertiliser inputs may quickly impair pasture production, additional strategies may be required to decrease soil Cd quickly.
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Fertilizantes , Contaminantes del Suelo , Cadmio/análisis , Fertilizantes/análisis , Nueva Zelanda , Fosfatos , Suelo , Contaminantes del Suelo/análisisRESUMEN
Augmenting the physical strength of a human operator during unpredictable human-directed (volitional) movements is a relevant capability for several proposed exoskeleton applications, including mobility augmentation, manual material handling, and tool operation. Unlike controllers and augmentation systems designed for repetitive tasks (e.g., walking), we approach physical strength augmentation by a task-agnostic method of force amplification-using force/torque sensors at the human-machine interface to estimate the human task force, and then amplifying it with the exoskeleton. We deploy an amplification controller that is integrated into a complete whole-body control framework for controlling exoskeletons that includes human-led foot transitions, inequality constraints, and a computationally efficient prioritization. A powered lower-body exoskeleton is used to demonstrate behavior of the control framework in a lab environment. This exoskeleton can assist the operator in lifting an unknown backpack payload while remaining fully backdrivable.
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Structured protocols offer a transparent and systematic way to elicit and combine/aggregate, probabilistic predictions from multiple experts. These judgements can be aggregated behaviourally or mathematically to derive a final group prediction. Mathematical rules (e.g., weighted linear combinations of judgments) provide an objective approach to aggregation. The quality of this aggregation can be defined in terms of accuracy, calibration and informativeness. These measures can be used to compare different aggregation approaches and help decide on which aggregation produces the "best" final prediction. When experts' performance can be scored on similar questions ahead of time, these scores can be translated into performance-based weights, and a performance-based weighted aggregation can then be used. When this is not possible though, several other aggregation methods, informed by measurable proxies for good performance, can be formulated and compared. Here, we develop a suite of aggregation methods, informed by previous experience and the available literature. We differentially weight our experts' estimates by measures of reasoning, engagement, openness to changing their mind, informativeness, prior knowledge, and extremity, asymmetry or granularity of estimates. Next, we investigate the relative performance of these aggregation methods using three datasets. The main goal of this research is to explore how measures of knowledge and behaviour of individuals can be leveraged to produce a better performing combined group judgment. Although the accuracy, calibration, and informativeness of the majority of methods are very similar, a couple of the aggregation methods consistently distinguish themselves as among the best or worst. Moreover, the majority of methods outperform the usual benchmarks provided by the simple average or the median of estimates.
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Agregación de Datos , Testimonio de Experto , Procesos de Grupo , Juicio , Modelos Estadísticos , Concienciación , Teorema de Bayes , Predicción/métodos , Humanos , Psicología/métodos , Opinión Pública , Investigadores/psicología , Estudiantes/psicologíaRESUMEN
The simple Goldman-Hodgkin-Katz model for resting-state membrane potentials has been generalized to provide a new nonlinear theoretical model for action potentials in perfused axons. Our minimalistic model appeals naturally to physically based electrodiffusion principles to describe electric-current densities inside sodium and potassium-ion channels whereas the 1952 Hodgkin-Huxley model describes such current densities in an ad hoc way. Although the two models share similar schemes for the kinetics of ion-channel gating, our relaxation times for channel gating are simpler, being independent of membrane potential. Like the theoretical model of Hodgkin and Huxley, based primarily on experimental data at [Formula: see text], our dynamical system behaves as a 4-dimensional resonator exhibiting subthreshold oscillations. Although our present analysis refers to experiments at [Formula: see text], re-parameterizations of this model should permit consideration of action potentials at alternative temperatures. The predicted speed of propagating action potentials in giant axons of squid at [Formula: see text] is in excellent agreement with the Hodgkin-Huxley experimental value at [Formula: see text]. In cases where our model predictions differ from those of the Hodgkin-Huxley model, new experiments will be required to determine which model is more accurate.
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Axones , Canales de Potasio , Potenciales de Acción , Axones/metabolismo , Potenciales de la Membrana , Sodio/metabolismoRESUMEN
Constipation is a common but not a universal feature in early PD, suggesting that gut involvement is heterogeneous and may be part of a distinct PD subtype with prognostic implications. We analysed data from the Parkinson's Incidence Cohorts Collaboration, composed of incident community-based cohorts of PD patients assessed longitudinally over 8 years. Constipation was assessed with the MDS-UPDRS constipation item or a comparable categorical scale. Primary PD outcomes of interest were dementia, postural instability and death. PD patients were stratified according to constipation severity at diagnosis: none (n = 313, 67.3%), minor (n = 97, 20.9%) and major (n = 55, 11.8%). Clinical progression to all three outcomes was more rapid in those with more severe constipation at baseline (Kaplan-Meier survival analysis). Cox regression analysis, adjusting for relevant confounders, confirmed a significant relationship between constipation severity and progression to dementia, but not postural instability or death. Early constipation may predict an accelerated progression of neurodegenerative pathology.
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Pastures are the most widespread land use, globally. The Winchmore trials were established in 1948-1949 in Canterbury, New Zealand and examined either different rates of phosphorus (P) fertiliser on the same irrigation schedule (Fertiliser trial), or different irrigation scheduling at the same rate of P application (Irrigation trial). About 96,000 records of soil chemistry and physical data and pasture yield and botanical composition are available along with nearly 7000 soil samples. These data have been used in 475 publications that have explored topics as diverse as: improvements in sheep, dairy and deer production; the efficacy and scheduling of irrigation; improvements in pasture and crop production; agronomic and environmental soil and water research; and entomology. In addition to above topics, these data are invaluable for calibrating models to predict long-term issues like the accumulation of soil carbon or contaminants like cadmium and informing policy on climate change and agricultural practices. The data and soil samples are available for use and may yet yield discoveries, unforeseen 70 years ago.
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Glaciers provide cold, turbid runoff to many mountain streams in the late summer and buffer against years with low snowfall. The input of glacial meltwater to streams maintains unique habitats and support a diversity of stream flora and fauna. In western Canada, glaciers are anticipated to retreat by 60-80% by the end of the century, and this retreat will invoke widespread changes in mountain ecosystems. We used a space-for-time substitution along a gradient of glacierization in western Canada to develop insights into changes that may occur in glaciated regions over the coming decades. Here we report on observed changes in physical (temperature, turbidity), and chemical (dissolved and total nutrients) characteristics of mountain streams and the associated shifts in their diatom communities during de-glacierization. Shifts in habitat characteristics across gradients include changes in nutrient concentrations, light penetration, temperatures, and flow, all of which have led to distinct changes in diatom community composition. Importantly, glacial-fed rivers were 3-5 °C cooler than rivers without glacial contributions. Declines in glacial meltwater contribution to streams resulted in shifts in the timing of nutrient fluxes and lower concentrations of total phosphorus (TP), soluble reactive phosphorus (SRP), and higher dissolved inorganic nitrogen (DIN) and light penetration. The above set of conditions were linked to the overgrowth of the benthic diatom Didymosphenia geminata. These changes in stream condition and D. geminata colony development primarily occurred in streams with marginal (2-5%) to no glacier cover. Our data support a hypothesis that climate-induced changes in river hydrochemistry and physical condition lead to a phenological mismatch that favors D. geminata bloom development.
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Diatomeas , Ríos , Canadá , Ecosistema , Cubierta de Hielo , Calidad del AguaRESUMEN
BACKGROUND: HIV remains a major public health issue, especially in Eastern and Southern Africa. Pre-exposure prophylaxis is highly effective when adhered to, but its effectiveness is limited by cost, user acceptability and uptake. The cost of a non-inferiority phase III trial is likely to be prohibitive, and thus, it is essential to select the best possible drug, dose and schedule in advance. The aim of this study, the Combined HIV Adolescent PrEP and Prevention Study (CHAPS), is to investigate the drug, dose and schedule of pre-exposure prophylaxis (PrEP) required for the protection against HIV and the acceptability of PrEP amongst young people in sub-Saharan Africa, and hence to inform the choice of intervention for future phase III PrEP studies and to improve strategies for PrEP implementation. METHODS: We propose a mixed-methods study amongst young people aged 13-24 years. The first component consists of qualitative research to identify the barriers and motivators towards the uptake of PrEP amongst young people in South Africa, Uganda and Zimbabwe. The second component is a randomised clinical trial (ClinicalTrials.gov NCT03986970, June 2019) using a novel ex vivo HIV challenge method to investigate the optimal PrEP treatment (FTC-TDF vs FTC-TAF), dose and schedule. We will recruit 144 amongst HIV-negative uncircumcised men aged 13-24 years from voluntary male medical circumcision clinics in two sites (South Africa and Uganda) and randomise them into one of nine arms. One group will receive no PrEP prior to surgery; the other arms will receive either FTC-TDF or FTC-TAF, over 1 or 2 days, and with the final dose given either 6 or 20 h prior to surgery. We will conduct an ex vivo HIV challenge on their resected foreskin tissue. DISCUSSION: This study will provide both qualitative and quantitative results to help decide the optimum drug, dose and schedule for a future phase III trial of PrEP. The study will also provide crucial information on successful strategies for providing PrEP to young people in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT03986970 . Registered on 14 June 2019.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Adolescente , Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Sudáfrica , Uganda , ZimbabweRESUMEN
The potential role for serological tests in the current COVID-19 pandemic has generated very considerable recent interest across many sectors worldwide, inter alia pathologists seeking additional weapons for their armoury of diagnostic tests; epidemiologists seeking tools to gain seroprevalence data that will inform improved models of the spread of disease; research scientists seeking tools to study the natural history of COVID-19 disease; vaccine developers seeking tools to assess vaccine efficacy in clinical trials; and companies and governments seeking tools to aid return-to-work decision-making. However, much of the local debate to date has centred on questions surrounding whether regulatory approval processes are limiting access to serological tests, and has not paused to consider the intrinsically limiting impact of underlying fundamental biology and immunology on where and how different COVID-19 serological tests can usefully be deployed in the response to the current pandemic. We review, from an immunological perspective, recent experimental evidence on the time-dependency of adaptive immune responses following SARS-CoV-2 infection and the impact of this on the sensitivity and specificity of COVID-19 antibody tests made at different time points post infection. We interpret this scientific evidence in terms of mooted clinical applications for current COVID-19 antibody tests in identifying acute infections, in confirming recent or past infections at the individual and population level, and in detecting re-infection and protective immunity. We conclude with guidance on where current COVID-19 antibody tests can make a genuine impact in the pandemic.