Frequency and phenotype associations of rare variants in 5 monogenic cerebral small vessel disease genes in 200,000 UK Biobank participants

BACKGROUND AND OBJECTIVES: Based on previous case reports and disease-based cohorts, a minority of patients with cerebral small vessel disease (cSVD) have a monogenic cause, with many also manifesting extracerebral phenotypes. We investigated the frequency, penetrance, and phenotype associations of putative pathogenic variants in cSVD genes in the UK Biobank (UKB), a large population-based study. METHODS: We used a systematic review of previous literature and ClinVar to identify putative pathogenic rare variants in CTSA, TREX1, HTRA1, and COL4A1/2. We mapped phenotypes previously attributed to these variants (phenotypes-of-interest) to disease coding systems used in the UKB's linked health data from UK hospital admissions, death records, and primary care. Among 199,313 exome-sequenced UKB participants, we assessed the following: the proportion of participants carrying ≥1 variant(s); phenotype-of-interest penetrance; and the association between variant carrier status and phenotypes-of-interest using a binary (any phenotype present/absent) and phenotype burden (linear score of the number of phenotypes a participant possessed) approach. RESULTS: Among UKB participants, 0.5% had ≥1 variant(s) in studied genes. Using hospital admission and death records, 4%–20% of variant carriers per gene had an associated phenotype. This increased to 7%–55% when including primary care records. Only COL4A1 variant carrier status was significantly associated with having ≥1 phenotype-of-interest and a higher phenotype score (OR = 1.29, p = 0.006). DISCUSSION: While putative pathogenic rare variants in monogenic cSVD genes occur in 1:200 people in the UKB population, only approximately half of variant carriers have a relevant disease phenotype recorded in their linked health data. We could not replicate most previously reported gene-phenotype associations, suggesting lower penetrance rates, overestimated pathogenicity, and/or limited statistical power

Emergency and critical care services in Tanzania: a survey of ten hospitals.

While there is a need for good quality care for patients with serious reversible disease in all countries in the world, Emergency and Critical Care tends to be one of the weakest parts of health systems in low-income countries. We assessed the structure and availability of resources for Emergency and Critical Care in Tanzania in order to identify the priorities for improving care in this neglected specialty. Ten hospitals in four regions of Tanzania were assessed using a structured data collection tool. Quality was evaluated with standards developed from the literature and expert opinion. Important deficits were identified in infrastructure, routines and training. Only 30% of the hospitals had an emergency room for adult and paediatric patients. None of the seven district and regional hospitals had a triage area or intensive care unit for adults. Only 40% of the hospitals had formal systems for adult triage and in less than one third were critically ill patients seen by clinicians more than once daily. In 80% of the hospitals there were no staff trained in adult triage or critical care. In contrast, a majority of equipment and drugs necessary for emergency and critical care were available in the hospitals (median 90% and 100% respectively. The referral/private hospitals tended to have a greater overall availability of resources (median 89.7%) than district/regional hospitals (median 70.6). Many of the structures necessary for Emergency and Critical Care are lacking in hospitals in Tanzania. Particular weaknesses are infrastructure, routines and training, whereas the availability of drugs and equipment is generally good. Policies to improve hospital systems for the care of emergency and critically ill patients should be prioritised

De seditionibus libri sex : rationibus et exemplis ex omni doctrinarum et authorum genere locupletati /

ColofónMarca tip. en colofón. (U.B., Marcas tipográficas)El ej. BHR/B-050-083 (1) enc. junto con: "D. Conradi Bruni ... opera tria... ; De caeremoniis libri sex", formando un vol. facticio"CCPB000003529CCSXVI B-2528BHR/B-050-083 (1)Perg.FDH 46084Hª del Derecho/N 104 (1)a6, b4, A-Z6, a-f6, g

Humans and elephants as treefall drivers in African savannas

Humans have played a major role in altering savanna structure and function, and growing land-use pressure will only increase their influence on woody cover. Yet humans are often overlooked as ecological components. Both humans and the African elephant Loxodonta africana alter woody vegetation in savannas through removal of large trees and activities that may increase shrub cover. Interactive effects of both humans and elephants with fire may also alter vegetation structure and composition. Here we capitalize on a macroscale experimental opportunity – brought about by the juxtaposition of an elephant-mediated landscape, human-utilized communal harvesting lands and a nature reserve fenced off from both humans and elephants – to investigate the influence of humans and elephants on height-specific treefall dynamics. We surveyed 6812 ha using repeat, airborne high resolution Light Detection and Ranging (LiDAR) to track the fate of 453 685 tree canopies over two years. Human-mediated biennial treefall rates were 2–3.5 fold higher than the background treefall rate of 1.5% treefall ha–1, while elephant-mediated treefall rates were 5 times higher at 7.6% treefall ha–1 than the control site. Model predictors of treefall revealed that human or elephant presence was the most important variable, followed by the interaction between geology and fire frequency. Treefall patterns were spatially heterogeneous with elephant-driven treefall associated with geology and surface water, while human patterns were related to perceived ease of access to wood harvesting areas and settlement expansion. Our results show humans and elephants utilize all height classes of woody vegetation, and that large tree shortages in a heavily utilized communal land has transferred treefall occurrence to shorter vegetation. Elephant- and human-dominated landscapes are tied to interactive effects that may hinder tree seedling survival which, combined with tree loss in the landscape, may compromise woodland sustainability.Andrew Mellon Foundation; Council for Scientific and Industrial Research (CSIR) Strategic Research Panel; Dept of Science and Technology (DST); Avatar Alliance Foundation; Margaret A. Cargill Foundation; David and Lucile Packard Foundation; Gordon and Betty Moore Foundation; Grantham Foundation for the Protection of the Environment; W. M. Keck Foundation; John D. and Catherine T. MacArthur Foundation; Exxaro Chairman's Fund; Applied Centre for Climate and Earth System Science; DST/NRF Centre of Excellence in Tree Health Biotechnology; NRF Innovation Scholarship [UID: 95030].http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1600-05872018-11-30hj2017Geography, Geoinformatics and Meteorolog

Fuelwood extraction intensity drives compensatory regrowth in African savanna communal lands

Woody biomass remains the primary energy source for domestic use in the developing world, raising concerns about woodland sustainability. Yet woodland regenerative capacity and the adaptive response of harvesters to localised fuelwood shortages are often underestimated or unaccounted for in fuelwood supply–demand models. Here, we explore the rates and patterns of height‐specific woody vegetation structural dynamics in three communal lands in a semiarid savanna in South Africa. Using repeat, airborne light detection and ranging, we measured height‐specific change in woody vegetation structure, and the relative influence of geology, fire, and ease of access to fuelwood. Monitoring 634,284 trees canopies over 4 years revealed high compensatory growth, particularly in the high wood extraction communal land: 34.1% of trees increased in height >1 m. Vegetation structural patterns were associated with ease of access to the communal land but were mediated by wood extraction intensity. In these communal lands, vegetation structural dynamics show rapid woody thickening as a response to repeat harvesting. However, loss of height in vegetation structure did not follow a gradient of wood extraction intensity. We propose a conceptual framework to better understand change in vegetation structural metrics and the paradoxical phenomenon of high growth in high wood extraction scenarios. We also show coadaptive responses of humans and woody vegetation to fuelwood harvesting in human–environment systems through patterns of regrowth response relative to ease of access to fuelwood resources.LiDAR data collection was funded by the Andrew Mellon Foundation, the Council for Scientific and Industrial Research (CSIR) Strategic Research Panel and the Department of Science and Technology (DST). The CAO has been made possible by grants and donations from the Avatar Alliance Foundation, Margaret A. Cargill Foundation, David and Lucile Packard Foundation, Gordon and Betty Moore Foundation, Grantham Foundation for the Protection of the Environment, W. M. Keck Foundation, John D. and Catherine T. MacArthur Foundation, Andrew Mellon Foundation, Mary Anne Nyburg Baker and G. Leonard Baker Jr, and William R. Hearst III. B. F. N. E. is supported by the Exxaro Chairman's Fund. P. J. M. is funded by the DST/NRF Centre of Excellence in Tree Health Biotechnology and an NRF Innovation Scholarship (grant UID: 95030).http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1099-145X2020-01-30hj2018Geography, Geoinformatics and Meteorolog

What lies beneath : detecting sub-canopy changes in savanna woodlands using a three-dimensional classification method

QUESTION : Increasing population pressure, socio-economic development and associated natural resource use in savannas are resulting in large-scale land cover changes, which can be mapped using remote sensing. Is a three-dimensional (3D) woody vegetation structural classification applied to LiDAR (Light Detection and Ranging) data better than a 2D analysis to investigate change in fine-scale woody vegetation structure over 2 yrs in a protected area (PA) and a communal rangeland (CR)? LOCATION : Bushbuckridge Municipality and Sabi Sand Wildtuin, NE South Africa. METHODS : Airborne LiDAR data were collected over 3 300 ha in April 2008 and 2010. Individual tree canopies were identified using object-based image analysis and classified into four height classes: 1–3, 3–6, 6–10 and >10 m. Four structural metrics were calculated for 0.25-ha grid cells: canopy cover, number of canopy layers present, cohesion and number of height classes present. The relationship between top-of-canopy cover and sub-canopy cover was investigated using regression. Gains, losses and persistence (GLP) of cover at each height class and the four structural metrics were calculated. GLP of clusters of each structural metric (calculated using LISA – Local Indicators of Spatial Association – statistics) were used to assess the changes in clusters of eachmetric over time. RESULTS : Top-of-canopy cover was not a good predictor of sub-canopy cover. The number of canopy layers present and cohesion showed gains and losseswith persistence in canopy cover over time, necessitating the use of a 3D classification to detect fine-scale changes, especially in structurally heterogeneous savannas. Trees >3 min height showed recruitment and gains up to 2.2 times higher in the CR where they are likely to be protected for cultural reasons, but losses of up to 3.2-foldmore in the PA, possibly due to treefall caused by elephant and/or fire. CONCLUSION : Land use has affected sub-canopy structure in the adjacent sites, with the low intensity use CR showing higher structural diversity. A 3D classification approach was successful in detecting fine-scale, short-term changes between land uses, and can thus be used as amonitoring tool for savannawoody vegetation structure. Remove selectedThe Carnegie Airborne Observatory is made possible by the Avatar Alliance Foundation, Margaret A. Cargill Foundation, John D. and Catherine T. MacArthur Foundation, Grantham Foundation for the Protection of the Environment, W.M. Keck Foundation, Gordon and Betty Moore Foundation, Mary Anne Nyburg Baker and G. Leonard Baker Jr. and William R. Hearst III. Application of the CAO data in South Africa is made possible by the Andrew Mellon Foundation and the endowment of the Carnegie Institution for Science.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1654-109X2016-07-31hb201

Biomass increases go under cover : woody vegetation dynamics in South African rangelands

Woody biomass dynamics are an expression of ecosystem function, yet biomass estimates do not provide information on the spatial distribution of woody vegetation within the vertical vegetation subcanopy. We demonstrate the ability of airborne light detection and ranging (LiDAR) to measure aboveground biomass and subcanopy structure, as an explanatory tool to unravel vegetation dynamics in structurally heterogeneous landscapes. We sampled three communal rangelands in Bushbuckridge, South Africa, utilised by rural communities for fuelwood harvesting. Woody biomass estimates ranged between 9 Mg ha-1 on gabbro geology sites to 27 Mg ha-1 on granitic geology sites. Despite predictions of woodland depletion due to unsustainable fuelwood extraction in previous studies, biomass in all the communal rangelands increased between 2008 and 2012. Annual biomass productivity estimates (10–14% p.a.) were higher than previous estimates of 4% and likely a significant contributor to the previous underestimations of modelled biomass supply. We show that biomass increases are attributable to growth of vegetation <5 m in height, and that, in the high wood extraction rangeland, 79% of the changes in the vertical vegetation subcanopy are gains in the 1-3m height class. The higher the wood extraction pressure on the rangelands, the greater the biomass increases in the low height classes within the subcanopy, likely a strong resprouting response to intensive harvesting. Yet, fuelwood shortages are still occurring, as evidenced by the losses in the tall tree height class in the high extraction rangeland. Loss of large trees and gain in subcanopy shrubs could result in a structurally simple landscape with reduced functional capacity. This research demonstrates that intensive harvesting can, paradoxically, increase biomass and this has implications for the sustainability of ecosystem service provision. The structural implications of biomass increases in communal rangelands could be misinterpreted as woodland recovery in the absence of three-dimensional, subcanopy information.S1 Dataset. Biomass model data. Data include 2012 LiDAR-derived average height and canopy cover extraction metrics, as well as field-work based allometry. Each line item is per 25 m x 25 m grid cell. Metadata are included in the dataset.S2 Dataset. Biomass and subcanopy data. Data include 2008 and 2012 biomass estimates derived from biomass models as well as % subcanopy returns for voxel data for the height class categories: 1-3m, 3-5m, 5-10m and >10m. Each line item is per 25 m x 25 m grid cell. Data are organized per land extraction category into separate worksheets. Metadata are included in the dataset.S3 Dataset. Biomass changes (Mg ha-1) in relation to relative height and canopy cover change. Data include biomass change estimates (2008–2012), percentage height and canopy cover changes for each 25 m x 25 m grid cell. Each height class (relative to height in 2008) are shown on separate worksheets. Metadata are included in the dataset.S1 Fig. Site-specific biomass model residuals. The residual spread demonstrates heteroskedasticity with increasing biomass fitted values for rangelands with a) high, b) intermediate and c) low extraction pressure.S2 Fig. Biomass changes (%) relative to height-specific change in subcanopy returns (%). Height categories are: 1–3 m, 3–5 m, 5–10 m and >10 m.The Carnegie Airborne Observatory (CAO) is made possible by the Avatar Alliance Foundation, Margaret A. Cargill Foundation, John D. and Catherine T. MacArthur Foundation, Grantham Foundation for the Protection of the Environment, W. M. Keck Foundation, Gordon and Betty Moore Foundation, Mary Anne Nyburg Baker and G. Leonard Baker, Jr., and William R. Hearst III. Application of the CAO data in South Africa is made possible through the Andrew Mellon Foundation and the endowment of the Carnegie Institution for Science, the Council for Scientific and Industrial Research (CSIR), and the South African Department of Science and Technology (grant agreement DST/ CON 0119/2010, Earth Observation Application Development in Support of SAEOS). CSIR coauthors are supported by the European Union’s Seventh Framework Programme (FP7/2007-2013, grant agreement n°282621, AGRICAB). PJM acknowledges funding from the National Research Foundation (NRF: SFH1207203615). Additionally, PJM and ETFW acknowledge the DST-NRF Centre of Excellence in Tree Health Biotechnology (CTHB) and, PJM and BFNE, the Applied Centre for Climate and Earth Systems Science (ACCESS). BFNE acknowledges financial support from Exxaro.http://www.plosone.orgam201

The Value of Rents and the Likelihood of Conflicts

This paper extends the prey--predator model of Grossman and Kim (1995) to analyze the relation between the value of the contested rent and the emergence of a conflict. We show that an increase in the value of the rent makes the conflict equilibrium more likely. We also analyze the case where the valuation of the rent is different for the two players. We find, for example, that a conflict equilibrium may occur even though the predator has an important disadvantage in warfare. That's when its valuation of the rent is sufficiently high compare to that of the prey

Cost-consciousness among Swiss doctors: a cross-sectional survey

BACKGROUND: Knowing what influences physicians attitudes toward health care costs is an important matter, because most health care expenditures are the results of doctors' decisions. Many decisions regarding medical tests and treatments are influenced by factors other than the expected benefit to the patient, including the doctor's demographic characteristics and concerns about cost and income. METHODS: Doctors (n = 1184) in Geneva, Switzerland, answered questions about their cost-consciousness, practice patterns (medical specialty, public.vs. private sector, number of patients per week, time spent with a new patient), work satisfaction, and stress from uncertainty. General linear models were used to identify independent risk factors of higher cost-consciousness. RESULTS: Most doctors agreed that trying to contain costs was their responsibility ("agree" or "totally agree": 90%) and that they should take a more prominent role in limiting the use of unnecessary tests (92%); most disagreed that doctors are too busy to worry about costs (69%) and that the cost of health care is only important if the patient has to pay for it out-of-pocket (88%). In multivariate analyses, cost-consciousness was higher among doctors in the public sector, those who saw fewer patients per week, who were most tolerant of uncertainty, and who were most satisfied with their work. CONCLUSION: Thus even in a setting with very high health care expenditures, doctors' stated cost-consciousness appeared to be generally high, even though it was not uniformly distributed among them