Mining poses significant and potentially underestimated risks to tropical forests worldwide. In Brazil's Amazon, mining drives deforestation far beyond operational lease boundaries, yet the full ...extent of these impacts is unknown and thus neglected in environmental licensing. Here we quantify mining-induced deforestation and investigate the aspects of mining operations, which most likely contribute. We find mining significantly increased Amazon forest loss up to 70 km beyond mining lease boundaries, causing 11,670 km
of deforestation between 2005 and 2015. This extent represents 9% of all Amazon forest loss during this time and 12 times more deforestation than occurred within mining leases alone. Pathways leading to such impacts include mining infrastructure establishment, urban expansion to support a growing workforce, and development of mineral commodity supply chains. Mining-induced deforestation is not unique to Brazil; to mitigate adverse impacts of mining and conserve tropical forests globally, environmental assessments and licensing must considered both on- and off-lease sources of deforestation.
Mining regions undergo abrupt and extensive land use change, the impacts of which pose management challenges for mining companies and regulatory agencies. In this study we investigated 20 years of ...land use change in Brazil's Iron Quadrangle (QF) mining region. We classified remote sensing images to produce land use maps and conducted a Land Change analysis to investigate the causes and consequences of observed changes. The QF underwent extensive land use change between 1990 and 2010, including deforestation, plantation expansion, urbanization and mine expansion. Comparing our results with those of surrounding non-mining landscapes illustrated important differences. For example, QF contained additional highly profitable land uses, including mining and plantation forestry, which were driven by globalized markets for mineral resources. This finding suggests processes of land use change within mining regions are distinct from those found elsewhere and, as such, land management policies should reflect this. We also hypothesized four generalizations regarding these processes: 1) the direct footprints of mining expands over time, 2) the offsite footprints of mining are extensive and also often expanding, 3) the direct and indirect land used by mines causes environmental and social impacts, some of which are not captured by current management approaches, and 4) the footprints of mining (and associated impacts) are driven by global factors, many of which are uncontrollable by local land holders and regional land management plans and policies. We describe and discuss these generalizations, drawing on published evidence from other mining regions to illustrate both their generality and implications for land management.
•Mining regions undergo abrupt and extensive land use change (LUC).•A Land Change analysis was used to investigate LUC in Brazil's Iron Quadrangle (QF).•Processes of LUC within the QF were distinct from those in non-mining regions.•Some similarities between the QF and other mining regions were also evident.•Four generalisations were identified to help guide land management in mining regions.
The gut microbiota in patients with inflammatory bowel disease are perturbed in both composition and function. The vaginal microbiome and its role in the reproductive health of women with ...inflammatory bowel disease is less well described. We aim to compare the vaginal microbiota of women with inflammatory bowel disease to healthy controls. Women with inflammatory bowel disease enrolled in a longitudinal cohort study provided self-collected vaginal swabs. Healthy controls underwent provider-collected vaginal swabs at routine gynecologic exams. All participants completed surveys on health history, vulvovaginal symptoms and gastrointestinal symptoms, if applicable. Microbiota were characterized by sequencing the V4 region of the 16S rRNA gene. Associations between patient characteristics and microbial community composition were evaluated by PERMANOVA and Principal Components Analysis. Lactobacillus dominance of the microbial community was compared between groups using chi-square and Poisson regression. The cohort included 54 women with inflammatory bowel disease (25 Ulcerative colitis, 25 Crohn's Disease) and 26 controls. A majority, 72 (90%) were White; 17 (31%) with inflammatory bowel disease and 7 (27%) controls were postmenopausal. The composition of the vaginal microbiota did not vary significantly by diagnosis or severity of inflammatory bowel disease but did vary by menopausal status (p = 0.042). There were no significant differences in Shannon Diversity Index between healthy controls and women with IBD in premenopausal participants. There was no difference in proportion of Lactobacillus dominance according to diagnosis in premenopausal participants. A subgroup of postmenopausal women with Ulcerative colitis showed a significant higher alpha diversity and a lack of Lactobacillus dominance in the vaginal microbiome. Menopausal status had a larger impact on vaginal microbial communities than inflammatory bowel disease diagnosis or severity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, Monte Carlo simulations were created to investigate the distribution of Raman signals in tissue phantoms and to validate the arctk code that was used. The aim was to show our code is ...capable of replicating experimental results in order to use it to advise similar future studies and to predict the outcomes. The experiment performed to benchmark our code used large volume liquid tissue phantoms to simulate the scattering properties of human tissue. The scattering agent used was Intralipid (IL), of various concentrations, filling a small quartz tank. A thin sample of PTFE was made to act as a distinct layer in the tank; this was our Raman signal source. We studied experimentally, and then reproduced
via
simulations, the variation in Raman signal strength in a transmission geometry as a function of the optical properties of the scattering agent and the location of the Raman material in the volume. We have also found that a direct linear extrapolation of scattering coefficients between concentrations of Intralipid is an incorrect assumption at lower concentrations when determining the optical properties. By combining experimental and simulation results, we have calculated different estimates of these scattering coefficients. The results of this study give insight into light propagation and Raman transport in scattering media and show how the location of maximum Raman signal varies as the optical properties change. The success of arctk in reproducing observed experimental signal behaviour will allow us in future to inform the development of noninvasive cancer screening applications (such as breast and prostate cancers)
in vivo
.
Monte Carlo modelling of Raman spectroscopy in tissue phantoms to validate code and provide insight into the optical properties of Intralipid.
•Global demand for steel drives extensive land-use change.•Steel production is correlated with mine expansion and plantation expansion.•Land-use changes directly impacts native vegetation.•Plantation ...expansion indirectly decreased native forest regrowth rates.•Mine expansion indirectly increased regional deforestation pressures.
Global demand for minerals is often considered an insignificant driver of land-use change because mines are small. We (1) investigated evidence supporting a link between global demand for steel and land-use change in Brazil's Iron Quadrangle, and (2) quantified the extent of land-use change and associated impacts on native vegetation. Historic land-use change was quantified using Landsat TM, relationships between demand for steel and land-use change were investigated using a simple linear model, and future scenarios were simulated using a calibrated land-use change model. Results support our hypothesis that global demand for steel drives extensive land-use change in the Iron Quadrangle, where increased steel production was correlated with increased iron ore production and mine expansion, and with increased charcoal production and plantation expansion. The direct impacts of mining on native vegetation were disproportionate to their relatively small spatial extent, while direct impacts of plantations were spatially extensive, as were their impacts on surrounding native vegetation. Additionally, evidence of two indirect impacts emerged during 1990–2010. Plantation expansion decreased native forest regrowth, while competition for land between mining companies and urban developers increased deforestation pressures. In combination, global demand for steel affected the majority of land in the Iron Quadrangle; however, many impacts were poorly captured by current land management approaches. Similar processes may operate in other mining regions, where global demand for minerals drives production of multiple resources (non-renewable and renewable) and thus extensive land-use change.
Viral meningitis is increasingly recognised, but little is known about the frequency with which it occurs, or the causes and outcomes in the UK. We aimed to determine the incidence, causes, and ...sequelae in UK adults to improve the management of patients and assist in health service planning.
We did a multicentre prospective observational cohort study of adults with suspected meningitis at 42 hospitals across England. Nested within this study, in the National Health Service (NHS) northwest region (now part of NHS England North), was an epidemiological study. Patients were eligible if they were aged 16 years or older, had clinically suspected meningitis, and either underwent a lumbar puncture or, if lumbar puncture was contraindicated, had clinically suspected meningitis and an appropriate pathogen identified either in blood culture or on blood PCR. Individuals with ventricular devices were excluded. We calculated the incidence of viral meningitis using data from patients from the northwest region only and used these data to estimate the population-standardised number of cases in the UK. Patients self-reported quality-of-life and neuropsychological outcomes, using the EuroQol EQ-5D-3L, the 36-Item Short Form Health Survey (SF-36), and the Aldenkamp and Baker neuropsychological assessment schedule, for 1 year after admission.
1126 patients were enrolled between Sept 30, 2011, and Sept 30, 2014. 638 (57%) patients had meningitis: 231 (36%) cases were viral, 99 (16%) were bacterial, and 267 (42%) had an unknown cause. 41 (6%) cases had other causes. The estimated annual incidence of viral meningitis was 2·73 per 100 000 and that of bacterial meningitis was 1·24 per 100 000. The median length of hospital stay for patients with viral meningitis was 4 days (IQR 3–7), increasing to 9 days (6–12) in those treated with antivirals. Earlier lumbar puncture resulted in more patients having a specific cause identified than did those who had a delayed lumbar puncture. Compared with the age-matched UK population, patients with viral meningitis had a mean loss of 0·2 quality-adjusted life-years (SD 0·04) in that first year.
Viruses are the most commonly identified cause of meningitis in UK adults, and lead to substantial long-term morbidity. Delays in getting a lumbar puncture and unnecessary treatment with antivirals were associated with longer hospital stays. Rapid diagnostics and rationalising treatments might reduce the burden of meningitis on health services.
Meningitis Research Foundation and UK National Institute for Health Research.
Exome Sequencing of Familial Bipolar Disorder Goes, Fernando S; Pirooznia, Mehdi; Parla, Jennifer S ...
Archives of general psychiatry,
06/2016, Letnik:
73, Številka:
6
Journal Article
Recenzirano
Odprti dostop
IMPORTANCE: Complex disorders, such as bipolar disorder (BD), likely result from the influence of both common and rare susceptibility alleles. While common variation has been widely studied, rare ...variant discovery has only recently become feasible with next-generation sequencing. OBJECTIVE: To utilize a combined family-based and case-control approach to exome sequencing in BD using multiplex families as an initial discovery strategy, followed by association testing in a large case-control meta-analysis. DESIGN, SETTING, AND PARTICIPANTS: We performed exome sequencing of 36 affected members with BD from 8 multiplex families and tested rare, segregating variants in 3 independent case-control samples consisting of 3541 BD cases and 4774 controls. MAIN OUTCOMES AND MEASURES: We used penalized logistic regression and 1-sided gene-burden analyses to test for association of rare, segregating damaging variants with BD. Permutation-based analyses were performed to test for overall enrichment with previously identified gene sets. RESULTS: We found 84 rare (frequency <1%), segregating variants that were bioinformatically predicted to be damaging. These variants were found in 82 genes that were enriched for gene sets previously identified in de novo studies of autism (19 observed vs. 10.9 expected, P = .0066) and schizophrenia (11 observed vs. 5.1 expected, P = .0062) and for targets of the fragile X mental retardation protein (FMRP) pathway (10 observed vs. 4.4 expected, P = .0076). The case-control meta-analyses yielded 19 genes that were nominally associated with BD based either on individual variants or a gene-burden approach. Although no gene was individually significant after correction for multiple testing, this group of genes continued to show evidence for significant enrichment of de novo autism genes (6 observed vs 2.6 expected, P = .028). CONCLUSIONS AND RELEVANCE: Our results are consistent with the presence of prominent locus and allelic heterogeneity in BD and suggest that very large samples will be required to definitively identify individual rare variants or genes conferring risk for this disorder. However, we also identify significant associations with gene sets composed of previously discovered de novo variants in autism and schizophrenia, as well as targets of the FRMP pathway, providing preliminary support for the overlap of potential autism and schizophrenia risk genes with rare, segregating variants in families with BD.
Photothermal therapy using nanoparticles is a promising new approach for the treatment of cancer. The principle is to utilise plasmonic nanoparticle light interaction for efficient heat conversion. ...However, there are many hurdles to overcome before it can be accepted in clinical practice. One issue is a current poor characterization of the thermal dose that is distributed over the tumour region and the surrounding normal tissue. Here, we use Monte Carlo simulations of photon radiative transfer through tissue and subsequent heat diffusion calculations, to model the spatial thermal dose in a skin cancer model. We validate our heat rise simulations against experimental data from the literature and estimate the concentration of nanorods in the tumor that are associated with the heat rise. We use the cumulative equivalent minutes at 43 °C (CEM43) metric to analyse the percentage cell kill across the tumour and the surrounding normal tissue. Overall, we show that computer simulations of photothermal therapy are an invaluable tool to fully characterize thermal dose within tumour and normal tissue.
Antenatal Care (ANC) during pregnancy can play an important role in the uptake of evidence-based services vital to the health of women and their infants. Studies report positive effects of ANC on use ...of facility-based delivery and perinatal mortality. However, most existing studies are limited to cross-sectional surveys with long recall periods, and generally do not include population-based samples.
This study was conducted within the Health and Demographic Surveillance System (HDSS) of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) in Matlab, Bangladesh. The HDSS area is divided into an icddr,b service area (SA) where women and children receive care from icddr,b health facilities, and a government SA where people receive care from government facilities. In 2007, a new Maternal, Neonatal, and Child Health (MNCH) program was initiated in the icddr,b SA that strengthened the ongoing maternal and child health services including ANC. We estimated the association of ANC with facility delivery and perinatal mortality using prospectively collected data from 2005 to 2009. Using a before-after study design, we also determined the role of ANC services on reduction of perinatal mortality between the periods before (2005 - 2006) and after (2008-2009) implementation of the MNCH program.
Antenatal care visits were associated with increased facility-based delivery in the icddr,b and government SAs. In the icddr,b SA, the adjusted odds of perinatal mortality was about 2-times higher (odds ratio (OR) 1.91; 95% confidence intervals (CI): 1.50, 2.42) among women who received ≤1 ANC compared to women who received ≥3 ANC visits. No such association was observed in the government SA. Controlling for ANC visits substantially reduced the observed effect of the intervention on perinatal mortality (OR 0.64; 95% CI: 0.52, 0.78) to non-significance (OR 0.81; 95% CI: 0.65, 1.01), when comparing cohorts before and after the MNCH program initiation (Sobel test of mediation P < 0.001).
ANC visits are associated with increased uptake of facility-based delivery and improved perinatal survival in the icddr,b SA. Further testing of the icddr,b approach to simultaneously improving quality of ANC and facility delivery care is needed in the existing health system in Bangladesh and in other low-income countries to maximize health benefits to mothers and newborns.
Aneuploidy is frequently detected in human cancers and is implicated in carcinogenesis. Pharmacologic targeting of aneuploidy is an attractive therapeutic strategy, as this would preferentially ...eliminate malignant over normal cells. We previously discovered that CDK2 inhibition causes lung cancer cells with more than two centrosomes to undergo multipolar cell division leading to apoptosis, defined as anaphase catastrophe. Cells with activating KRAS mutations were especially sensitive to CDK2 inhibition. Mechanisms of CDK2-mediated anaphase catastrophe and how activated KRAS enhances this effect were investigated. Live-cell imaging provided direct evidence that following CDK2 inhibition, lung cancer cells develop multipolar anaphase and undergo multipolar cell division with the resulting progeny apoptotic. The siRNA-mediated repression of the CDK2 target and centrosome protein CP110 induced anaphase catastrophe of lung cancer cells. In contrast, CP110 overexpression antagonized CDK2 inhibitor-mediated anaphase catastrophe. Furthermore, activated KRAS mutations sensitized lung cancer cells to CDK2 inhibition by deregulating CP110 expression. Thus, CP110 is a critical mediator of CDK2 inhibition-driven anaphase catastrophe. Independent examination of murine and human paired normal-malignant lung tissues revealed marked upregulation of CP110 in malignant versus normal lung. Human lung cancers with KRAS mutations had significantly lower CP110 expression as compared with KRAS wild-type cancers. Thus, a direct link was found between CP110 and CDK2 inhibitor antineoplastic response. CP110 plays a mechanistic role in response of lung cancer cells to CDK2 inhibition, especially in the presence of activated KRAS mutations.
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