U1 snRNP determines mRNA length and regulates isoform expression.

U1 snRNP (U1), in addition to its splicing role, protects pre-mRNAs from drastic premature termination by cleavage and polyadenylation (PCPA) at cryptic polyadenylation signals (PASs) in introns. Here, a high-throughput sequencing strategy of differentially expressed transcripts (HIDE-seq) mapped PCPA sites genome wide in divergent organisms. Surprisingly, whereas U1 depletion terminated most nascent gene transcripts within ~1 kb, moderate functional U1 level decreases, insufficient to inhibit splicing, dose-dependently shifted PCPA downstream and elicited mRNA 3' UTR shortening and proximal 3' exon switching characteristic of activated immune and neuronal cells, stem cells, and cancer. Activated neurons' signature mRNA shortening could be recapitulated by U1 decrease and antagonized by U1 overexpression. Importantly, we show that rapid and transient transcriptional upregulation inherent to neuronal activation physiology creates U1 shortage relative to pre-mRNAs. Additional experiments suggest cotranscriptional PCPA counteracted by U1 association with nascent transcripts, a process we term telescripting, ensuring transcriptome integrity and regulating mRNA length.

Engaging primary care professionals in OECD's international PaRIS survey: a documentary analysis.

Healthcare professionals have first-hand experience with patients in clinical practice and the dynamics in the healthcare system, which can be of great value in the design, implementation, data analysis and dissemination of research study results. Primary care professionals are particularly important as they provide first contact, accessible, coordinated, comprehensive and continuous people-focused care. However, in-depth examination of the engagement of health professionals in health system research and planning activities-how professionals are engaged and how this varies across national contexts- is limited, particularly in international initiatives. There is a need to identify gaps in the planning of engagement activities to inform the design and successful implementation of future international efforts to improve the responsiveness of health systems to the changing needs of patients and professionals. The aim of this study was to explore how primary care professionals were engaged in the design and implementation plans of an international health policy study led by the Organisation for Economic Co-operation and Development (OECD). The OECD's international PaRIS survey measures and disseminates information on patient-reported outcome and experience measures (PROMs and PREMs) of people living with chronic conditions who are managed in primary care. A documentary analysis of 17 written national implementation plans (country roadmaps) was conducted between January and June 2023. Two reviewers independently performed the screening and data abstraction and resolved disagreements by discussion. We reported the intended target primary care professionals, phase of the study, channel of engagement, level of engagement, and purpose of engagement. All 17 countries aimed to engage primary care professionals in the execution plans for the international PaRIS survey. While organisations of primary care professionals, particularly of family doctors, were the most commonly targeted group, variation was found in the timing of engagement activities during the different phases of the study and in the level of engagement, ranging from co-development (half of the countries co-developed the survey together with primary care professionals) to one-off consultations with whom. International guidance facilitated the participation of primary care professionals. Continuous collaborative efforts at the international and national levels can foster a culture of engagement with primary care organisations and individual professionals and enhance meaningful engagement of primary care professionals.

Spatiotemporal Mineral Phase Evolution and Arsenic Retention in Microfluidic Models of Zerovalent Iron-Based Water Treatment.

Arsenic (As) is a toxic element, and elevated levels of geogenic As in drinking water pose a threat to the health of several hundred million people worldwide. In this study, we used microfluidics in combination with optical microscopy and X-ray spectroscopy to investigate zerovalent iron (ZVI) corrosion, secondary iron (Fe) phase formation, and As retention processes at the pore scale in ZVI-based water treatment filters. Two 250 µm thick microchannels filled with single ZVI and quartz grain layers were operated intermittently (12 h flow/12 h no-flow) with synthetic groundwater (pH 7.5; 570 µg/L As(III)) over 13 and 49 days. Initially, lepidocrocite (Lp) and carbonate green rust (GRC) were the dominant secondary Fe-phases and underwent cyclic transformation. During no-flow, lepidocrocite partially transformed into GRC and small fractions of magnetite, kinetically limited by Fe(II) diffusion or by decreasing corrosion rates. When flow resumed, GRC rapidly and nearly completely transformed back into lepidocrocite. Longer filter operation combined with a prolonged no-flow period accelerated magnetite formation. Phosphate adsorption onto Fe-phases allowed for downstream calcium carbonate precipitation and, consequently, accelerated anoxic ZVI corrosion. Arsenic was retained on Fe-coated quartz grains and in zones of cyclic Lp-GRC transformation. Our results suggest that intermittent filter operation leads to denser secondary Fe-solids and thereby ensures prolonged filter performance.

Synthesis, Characterization, and Non-Covalent Interactions of Palladium(II)-Amino Acid Complexes.

The reaction of palladium(II) acetate with acyclic amino acids in acetone/water yields square planar bis-chelated palladium amino acid complexes that exhibit interesting non-covalent interactions. In all cases, complexes were examined by multiple spectroscopic techniques, especially HRMS (high resolution mass spectrometry), IR (infrared spectroscopy), and 1H NMR (nuclear magnetic resonance) spectroscopy. In some cases, suitable crystals for single crystal X-ray diffraction were able to be grown and the molecular structure was obtained. The molecular geometries of the products are discussed. Except for the alanine complex, all complexes incorporate water molecules into the extended lattice and exhibit N-H···O and/or O···(HOH)···O hydrogen bonding interactions. The non-covalent interactions are discussed in terms of the extended lattice structures exhibited by the structures.

Geostatistical model of the spatial distribution of arsenic in groundwaters in Gujarat State, India.

Geogenic arsenic contamination in groundwaters poses a severe health risk to hundreds of millions of people globally. Notwithstanding the particular risks to exposed populations in the Indian sub-continent, at the time of writing, there was a paucity of geostatistically based models of the spatial distribution of groundwater hazard in India. In this study, we used logistic regression models of secondary groundwater arsenic data with research-informed secondary soil, climate and topographic variables as principal predictors generate hazard and risk maps of groundwater arsenic at a resolution of 1 km across Gujarat State. By combining models based on different arsenic concentrations, we have generated a pseudo-contour map of groundwater arsenic concentrations, which indicates greater arsenic hazard (> 10 µg/L) in the northwest, northeast and south-east parts of Kachchh District as well as northwest and southwest Banas Kantha District. The total number of people living in areas in Gujarat with groundwater arsenic concentration exceeding 10 µg/L is estimated to be around 122,000, of which we estimate approximately 49,000 people consume groundwater exceeding 10 µg/L. Using simple previously published dose-response relationships, this is estimated to have given rise to 700 (prevalence) cases of skin cancer and around 10 cases of premature avoidable mortality/annum from internal (lung, liver, bladder) cancers-that latter value is on the order of just 0.001% of internal cancers in Gujarat, reflecting the relative low groundwater arsenic hazard in Gujarat State.

Unexpected Abundance and Diversity of Phototrophs in Mats from Morphologically Variable Microbialites in Great Salt Lake, Utah.

Microbial mat communities are associated with extensive (∼700 km2) and morphologically variable carbonate structures, termed microbialites, in the hypersaline Great Salt Lake (GSL), Utah. However, whether the composition of GSL mat communities covaries with microbialite morphology and lake environment is unknown. Moreover, the potential adaptations that allow the establishment of these extensive mat communities at high salinity (14% to 17% total salts) are poorly understood. To address these questions, microbial mats were sampled from seven locations in the south arm of GSL representing different lake environments and microbialite morphologies. Despite the morphological differences, microbialite-associated mats were taxonomically similar and were dominated by the cyanobacterium Euhalothece and several heterotrophic bacteria. Metagenomic sequencing of a representative mat revealed Euhalothece and subdominant Thiohalocapsa populations that harbor the Calvin cycle and nitrogenase, suggesting they supply fixed carbon and nitrogen to heterotrophic bacteria. Fifteen of the next sixteen most abundant taxa are inferred to be aerobic heterotrophs and, surprisingly, harbor reaction center, rhodopsin, and/or bacteriochlorophyll biosynthesis proteins, suggesting aerobic photoheterotrophic (APH) capabilities. Importantly, proteins involved in APH are enriched in the GSL community relative to that in microbialite mat communities from lower salinity environments. These findings indicate that the ability to integrate light into energy metabolism is a key adaptation allowing for robust mat development in the hypersaline GSL.IMPORTANCE The earliest evidence of life on Earth is from organosedimentary structures, termed microbialites, preserved in 3.481-billion-year-old (Ga) rocks. Phototrophic microbial mats form in association with an ∼700-km2 expanse of morphologically diverse microbialites in the hypersaline Great Salt Lake (GSL), Utah. Here, we show taxonomically similar microbial mat communities are associated with morphologically diverse microbialites across the lake. Metagenomic sequencing reveals an abundance and diversity of autotrophic and heterotrophic taxa capable of harvesting light energy to drive metabolism. The unexpected abundance of and diversity in the mechanisms of harvesting light energy observed in GSL mat populations likely function to minimize niche overlap among coinhabiting taxa, provide a mechanism(s) to increase energy yield and osmotic balance during salt stress, and enhance fitness. Together, these physiological benefits promote the formation of robust mats that, in turn, influence the formation of morphologically diverse microbialite structures that can be imprinted in the rock record.

The association between the workload of general practitioners and patient experiences with care: results of a cross-sectional study in 33 countries.

BACKGROUND: The workload of general practitioners (GPs) and dissatisfaction with work have been increasing in various Western countries over the past decades. In this study, we evaluate the relation between the workload of GPs and patients' experiences with care. METHODS: We collected data through a cross-sectional survey among 7031 GPs and 67,873 patients in 33 countries. Dependent variables are the patient experiences on doctor-patient communication, accessibility, continuity, and comprehensiveness of care. Independent variables concern the workload measured as the GP-reported work hours per week, average consultation times, job satisfaction (an indicator of subjective workload), and the difference between the workload measures of every GP and the average in their own country. Finally, we evaluated interaction effects between workload measures and what patients find important in a country and the presence of a patient-list system. Relationships were determined through multilevel regression models. RESULTS: Patients of GPs who are happier with their work were found to experience better communication, continuity, access, and comprehensiveness. When GPs are more satisfied compared to others in their country, patients also experience better quality. When GPs work more hours per week, patients also experience better quality of care, but not in the area of accessibility. A longer consultation time, also when compared to the national average, is only related to more comprehensive care. There are no differences in the relationships between countries with and without a patient list system and in countries where patients find the different quality aspects more important. CONCLUSIONS: Patients experience better care when their GP has more work hours, longer consultation times, and especially, a higher job satisfaction.

Increased HIV in Greater Kinshasa Urban Health Zones: Democratic Republic of Congo (2017-2018).

BACKGROUND: Diagnosis of people living with HIV (PLHIV) is the first step toward achieving the new Fast Track Strategy to end AIDS by 2030: 95-95-95. However, reaching PLHIV is especially difficult in resource-limited settings such as the Democratic Republic of Congo (DRC), where reliable prevalence data is lacking. This study evaluated the prevalence of HIV in patients in the urban Kinshasa area. METHODS: Individuals seeking healthcare were tested for HIV between February 2017 and July 2018 at existing Kinshasa urban clinics. The study was conducted in two phases. Case finding was optimized in a pilot study phase using a modified cell phone-based Open\Data Kit (ODK) collection system. HIV prevalence was then determined from data obtained between March-July of 2018 from 8320 individuals over the age of 18 years receiving care at one of 47 clinics in Kinshasa. RESULTS: The prevalence of HIV in our study was 11.0% (95% CI 10.3-11.6%) overall and 8.14% in the subset of N = 1240 participants who were healthy mothers seeking prenatal care. These results are in sharp contrast to President's Emergency Plan for AIDS Relief (PEPFAR) estimates of 2.86%, but are consistent with data from surrounding countries. CONCLUSION: While this data is sub-national and reflects an urban healthcare setting, given the large population of Kinshasa and rapidly changing age demographics, the results suggest that HIV prevalence in the DRC is substantially higher than previously reported.

Individual, institutional, and scientific environment factors associated with questionable research practices in the reporting of messages and conclusions in scientific health services research publications.

BACKGROUND: Health Services Research findings (HSR) reported in scientific publications may become part of the decision-making process on healthcare. This study aimed to explore associations between researcher's individual, institutional, and scientific environment factors and the occurrence of questionable research practices (QRPs) in the reporting of messages and conclusions in scientific HSR publications. METHODS: We employed a mixed-methods study design. We identified factors possibly contributing to QRPs in the reporting of messages and conclusions through a literature review, 14 semi-structured interviews with HSR institutional leaders, and 13 focus-groups amongst researchers. A survey corresponding with these factors was developed and shared with 172 authors of 116 scientific HSR publications produced by Dutch research institutes in 2016. We assessed the included publications for the occurrence of QRPs. An exploratory factor analysis was conducted to identify factors within individual, institutional, and environmental domains. Next, we conducted bivariate analyses using simple Poisson regression to explore factors' association with the number of QRPs in the assessed HSR publications. Factors related to QRPs with a p-value < .30 were included in four multivariate models tested through a multiple Poisson regression. RESULTS: In total, 78 (45%) participants completed the survey (51.3% first authors and 48.7% last authors). Twelve factors were included in the multivariate analyses. In all four multivariate models, a higher score of "pressure to create societal impact" (Exp B = 1.28, 95% CI [1.11, 1.47]), was associated with higher number of QRPs. Higher scores on "specific training" (Exp B = 0.85, 95% CI [0.77-0.94]) and "co-author conflict of interest" (Exp B = 0.85, 95% CI [0.75-0.97]) factors were associated with a lower number of QRPs. Stratification between first and last authors indicated different factors were related to the occurrence of QRPs for these groups. CONCLUSION: Experienced pressure to create societal impact is associated with more QRPs in the reporting of messages and conclusions in HSR publications. Specific training in reporting messages and conclusions and awareness of co-author conflict of interests are related to fewer QRPs. Our results should stimulate awareness within the field of HSR internationally on opportunities to better support reporting in scientific HSR publications.

An expert-based mapping of healthcare system strategies to support rational drug prescribing in primary care across 13 European countries.

BACKGROUND: Irrational prescribing has received increasing attention among policy-makers to improve drug safety and effectiveness while avoiding economic waste. The policies intended to rationalise prescribing have been grouped by WHO under a taxonomy, classifying them into two types of strategies - (1) targeted approaches (micro level) and (2) system-oriented approaches (macro level). The extent to which countries implement strategies and the existing types is currently unknown. This paper explores the following research question via expert opinions: to what extent have European countries implemented strategies to support rational prescribing (targeted and system oriented) and what are the types implemented? METHODS: We assessed the available information on policies intended to promote rational prescribing. We used the WHO taxonomy to explore our research question as the basis for a standardised questionnaire. The data were collected between August 2018 and April 2019. The questionnaire consisted of questions that solicited the opinion of experts on the implementation of prescribing control mechanisms in primary care in their respective countries. Experts were identified through the literature and relevant networks. The questionnaire was sent to 17 identified country experts from 17 different countries; 15 responded and 13 were used in our analysis. Answers were validated through follow-up correspondence, interviews and presentation at an OECD meeting. RESULTS: Expert-reported data shows that all 13 countries included in our study have several mechanisms in place for enhancing rational prescribing in primary care. All approaches were reported to have been implemented in at least two countries. We identified two groups of countries, namely a small group of countries (n = 3) with fewer mechanisms in place and a larger group of countries (n = 10) with a large number of strategies with accompanying instruments at both the micro and macro levels. CONCLUSIONS: The data reported by the experts suggests that all 13 countries included in our study have several mechanisms in place for enhancing rational prescribing in primary care on both the micro and macro levels. With respect to the extent of mechanisms being in place, two groups of countries were identified. This initial mapping of strategies forms a basis for more in-depth research to be able to assess the impact of bundles of strategies on system and targeted level on rational drug prescribing in primary care in Europe.

Arsenic and Other Geogenic Contaminants in Groundwater - A Global Challenge.

Groundwater is a much safer and more dependable source of drinking water than surface water. However, natural (geogenic) hazardous elements can contaminate groundwater and lead to severe health problems in consumers. Arsenic concentrations exceeding the WHO drinking water guideline of 10 µg/L globally affect over 220 million people and can cause arsenicosis (skin lesions and cancers). Fluoride, while preventing caries at low concentrations, has detrimental effects when above the WHO drinking water guideline of 1.5 mg/L and puts several hundred million people at risk of dental and skeletal fluorosis. In this article, we report on the geochemistry and occurrence of arsenic and fluoride in groundwater and on the development of global and regional risk maps that help alert governments and water providers to take appropriate mitigation measures for the provision of safe drinking water. We then summarize research on the removal of arsenic and fluoride from drinking water, focusing on adapted technologies for water treatment. Finally, we discuss the applicability of various measures in a larger context and future challenges in reaching the goal of access to safe drinking water for all.

Hepatitis C virus surveillance and identification of human pegivirus 2 in a large Cameroonian cohort.

The prevalence of chronic hepatitis C virus (HCV) and the presence of human pegivirus 2 (HPgV-2) have not been examined in Cameroon, although HCV has been associated with HPgV-2 infections previously. Herein we aimed to characterize the burden and genetic diversity of HCV and the presence of HPgV-2 in Cameroon. Retrospective plasma specimens collected from N = 12 369 consenting subjects in South Cameroon from 2013 to 2016 were included in the study. The majority (97.1%) of participants were patients seeking health care. All specimens were screened for HCV using the Abbott RealTime HCV viral load assay and positive specimens with remaining volume were also screened for HPgV-2 antibodies on the Abbott ARCHITECT instrument, followed by molecular characterization. Overall, HCV RNA was detected in 305 (2.47%; 95% CI: 2.21%-2.75%) specimens. Notably, the prevalence of HCV RNA was 9.09% amongst participants over age 40 and 3.81% amongst males. Phylogenetic classification of N = 103 HCV sequences identified genotypes 1 (19.4%), 2 (15.5%) and 4 (65.1%) within the study cohort. Amongst HCV RNA-positive specimens, N = 28 (10.6%; 95% CI: 7.44%-14.90%) specimens also had detectable HPgV-2 antibodies. Of these, N = 2 viremic HPgV-2 infections were confirmed by sequencing and shared 93-94 median % identity with strains found on other continents. This is the first study to determine the prevalence of chronic HCV in Cameroon, and the discovery of HPgV-2 in this study cohort expands the geography of HPgV-2 to the African continent, indicating a widespread distribution exists.

Figure Interpretation Assessment Tool-Health (FIAT-health) 2.0: from a scoring instrument to a critical appraisal tool.

BACKGROUND: Statistics are frequently used in health advocacy to attract attention, but are often misinterpreted. The Figure Interpretation Assessment Tool-Health (FIAT-Health) 1.0 was developed to support systematic assessment of the interpretation of figures on health and health care. This study aimed to test and evaluate the FIAT-Health 1.0 amongst its intended user groups, and further refine the tool based on our results. METHODS: Potential users (N = 32) were asked to assess one publicly reported figure using the FIAT-Health 1.0, and to justify their assessments and share their experience in using the FIAT-Health. In total four figures were assessed. For each figure, an expert on the specific topic (N = 4) provided a comparative assessment. The consistency of the answers was calculated, and answers to the evaluation questions were qualitatively analysed. A qualitative comparative analysis of the justifications for assessment by the experts and potential users was made. Based on the results, a new version of the FIAT-Health was developed and tested by employees (N = 27) of the National Institute for Public Health and the Environment (RIVM), and approved by the project's advisory group. In total sixty-three participants contributed. RESULTS: Potential users using the FIAT-Health 1.0 and experts gave similar justifications for their assessments. The justifications provided by experts aligned with the items of the FIAT-Health. Seventeen out of twenty-six dichotomous questions were consistently answered by the potential users. Numerical assessment questions showed inconsistencies in how potential users responded. In the evaluation, potential users most frequently mentioned that thanks to its structured approach, the FIAT-Health contributed to their awareness of the main characteristics of the figure (n = 14), but they did find the tool complex (n = 11). The FIAT-Health 1.0 was revised from a scoring instrument into a critical appraisal tool: the FIAT-Health 2.0, which was tested and approved by employees of the RIVM and the advisory group. CONCLUSION: The tool was refined according to the results of the test and evaluation, transforming the FIAT-Health from a quantitative scoring instrument into an online qualitative appraisal tool that has the potential to aid the better interpretation and public reporting of statistics on health and healthcare.

Retardation of arsenic transport through a Pleistocene aquifer.

Groundwater drawn daily from shallow alluvial sands by millions of wells over large areas of south and southeast Asia exposes an estimated population of over a hundred million people to toxic levels of arsenic. Holocene aquifers are the source of widespread arsenic poisoning across the region. In contrast, Pleistocene sands deposited in this region more than 12,000 years ago mostly do not host groundwater with high levels of arsenic. Pleistocene aquifers are increasingly used as a safe source of drinking water and it is therefore important to understand under what conditions low levels of arsenic can be maintained. Here we reconstruct the initial phase of contamination of a Pleistocene aquifer near Hanoi, Vietnam. We demonstrate that changes in groundwater flow conditions and the redox state of the aquifer sands induced by groundwater pumping caused the lateral intrusion of arsenic contamination more than 120 metres from a Holocene aquifer into a previously uncontaminated Pleistocene aquifer. We also find that arsenic adsorbs onto the aquifer sands and that there is a 16-20-fold retardation in the extent of the contamination relative to the reconstructed lateral movement of groundwater over the same period. Our findings suggest that arsenic contamination of Pleistocene aquifers in south and southeast Asia as a consequence of increasing levels of groundwater pumping may have been delayed by the retardation of arsenic transport.

Patients' perception of communication at the interface between primary and secondary care: a cross-sectional survey in 34 countries.

BACKGROUND: Poor communication between general practitioners (GPs) and medical specialists can lead to poorer quality, and continuity, of care. Our study aims to assess patients' perceptions of communication at the interface between primary and secondary care in 34 countries. It will analyse, too, whether this communication is associated with the organisation of primary care within a country, and with the characteristics of GPs and their patients. METHODS: We conducted a cross-sectional survey among patients in 34 countries. Following a GP consultation, patients were asked two questions. Did they take to understand that their GP had informed medical specialists about their illness upon referral? And, secondly, did their GP know the results of the treatment by a medical specialist? We used multi-response logistic multilevel models to investigate the association of factors related to primary care, the GP, and the patient, with the patients' perceptions of communication at the interface between primary and secondary care. RESULTS: In total, 61,931 patients completed the questionnaire. We found large differences between countries, in both the patients' perceptions of information shared by GPs with medical specialists, and the patients' perceptions of the GPs' awareness of the results of treatment by medical specialists. Patients whose GPs stated that they 'seldom or never' send referral letters, also less frequently perceived that their GP communicated with their medical specialists about their illness. Patients with GPs indicating they 'seldom or never' receive feedback from medical specialists, indicated less frequently that their GP would know the results of treatment by a medical specialist. Moreover, patients with a personal doctor perceived higher rates of communication in both directions at the interface between primary and secondary care. CONCLUSION: Generally, patients perceive there to be high rates of communication at the interface between primary and secondary care, but there are large differences between countries. Policies aimed at stimulating personal doctor arrangements could, potentially, enhance the continuity of care between primary and secondary care.

Statistics in Dutch policy debates on health and healthcare.

BACKGROUND: The notion of 'fact-free politics' is debated in Europe and the United States of America and has particular relevance for the use of evidence to underpin health and healthcare policies. To better understand how evidence on health and healthcare is used in the national policy-making process in the Netherlands, we explore how different statistics are used in various policy debates on health and healthcare in the Dutch government and parliament. METHODS: We chose eight ongoing policy debates as case studies representing the subject categories of morbidity, lifestyle, healthcare expenditure and healthcare outcomes, including (1) breast cancer screening rates, prevalence and incidence, (2) dementia prevalence and incidence, (3) prevalence of alcohol use by pregnant women, (4) mobility and school sports participation in children, (5) costs of smoking, (6) Dutch national healthcare expenditure, (7) hospital mortality rates, and (8) bedsore prevalence. Using selected keywords for each policy debate case, we performed a document search to identify documentation of the debates (2014-2016) on the websites of the Dutch government and parliament. We retrieved 163 documents and examined the policy debate cases through a content analyses approach. RESULTS: Sources of the statistics used in policy debates were primarily government funded. We identified two distinct functions, i.e. rhetorical and managerial use of statistics. The function of the debate is rhetorical when the specific statistic is used for agenda-setting or to convince the reader of the importance of a topic. The function of the debate is managerial when statistics determine planning, monitoring or evaluation of policy. When evaluating a specific policy, applied statistics were mostly the result of routine or standardised data collection. When policy-makers use statistics for a managerial function, the policy debate mirrors terms derived from scientific debates. CONCLUSION: While statistics used for rhetorical functions do not seem to invite critical reflection, when the function of the debate is managerial, i.e. to plan, monitor or evaluate healthcare, their construction does receive attention. Considering the current role of statistics in rhetorical and managerial debates, there is a need to be cautious of too much leniency towards the technocratic process in exchange for the democratic debate.

Prediction Modeling and Mapping of Groundwater Fluoride Contamination throughout India.

For about the past eight decades, high concentrations of naturally occurring fluoride have been detected in groundwater in different parts of India. The chronic consumption of fluoride in high concentrations is recognized to cause dental and skeletal fluorosis. We have used the random forest machine-learning algorithm to model a data set of 12 600 groundwater fluoride concentrations from throughout India along with spatially continuous predictor variables of predominantly geology, climate, and soil parameters. Despite only surface parameters being available to describe a subsurface phenomenon, this has produced a highly accurate prediction map of fluoride concentrations exceeding 1.5 mg/L at 1 km resolution throughout the country. The most affected areas are the northwestern states/territories of Delhi, Gujarat, Haryana, Punjab, and Rajasthan and the southern states of Andhra Pradesh, Karnataka, Tamil Nadu, and Telangana. The total number of people at risk of fluorosis due to fluoride in groundwater is predicted to be around 120 million, or 9% of the population. This number is based on rural populations and accounts for average rates of groundwater consumption from nonmanaged sources. The new fluoride hazard and risk maps can be used by authorities in conjunction with detailed groundwater utilization information to prioritize areas in need of mitigation measures.

Improving interpretation of publically reported statistics on health and healthcare: the Figure Interpretation Assessment Tool (FIAT-Health).

BACKGROUND: Policy-makers, managers, scientists, patients and the general public are confronted daily with figures on health and healthcare through public reporting in newspapers, webpages and press releases. However, information on the key characteristics of these figures necessary for their correct interpretation is often not adequately communicated, which can lead to misinterpretation and misinformed decision-making. The objective of this research was to map the key characteristics relevant to the interpretation of figures on health and healthcare, and to develop a Figure Interpretation Assessment Tool-Health (FIAT-Health) through which figures on health and healthcare can be systematically assessed, allowing for a better interpretation of these figures. METHODS: The abovementioned key characteristics of figures on health and healthcare were identified through systematic expert consultations in the Netherlands on four topic categories of figures, namely morbidity, healthcare expenditure, healthcare outcomes and lifestyle. The identified characteristics were used as a frame for the development of the FIAT-Health. Development of the tool and its content was supported and validated through regular review by a sounding board of potential users. RESULTS: Identified characteristics relevant for the interpretation of figures in the four categories relate to the figures' origin, credibility, expression, subject matter, population and geographical focus, time period, and underlying data collection methods. The characteristics were translated into a set of 13 dichotomous and 4-point Likert scale questions constituting the FIAT-Health, and two final assessment statements. Users of the FIAT-Health were provided with a summary overview of their answers to support a final assessment of the correctness of a figure and the appropriateness of its reporting. CONCLUSIONS: FIAT-Health can support policy-makers, managers, scientists, patients and the general public to systematically assess the quality of publicly reported figures on health and healthcare. It also has the potential to support the producers of health and healthcare data in clearly communicating their data to different audiences. Future research should focus on the further validation of the tool in practice.

Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection.

Hepatitis C virus (HCV) and human pegivirus (HPgV), formerly GBV-C, are the only known human viruses in the Hepacivirus and Pegivirus genera, respectively, of the family Flaviviridae. We present the discovery of a second pegivirus, provisionally designated human pegivirus 2 (HPgV-2), by next-generation sequencing of plasma from an HCV-infected patient with multiple bloodborne exposures who died from sepsis of unknown etiology. HPgV-2 is highly divergent, situated on a deep phylogenetic branch in a clade that includes rodent and bat pegiviruses, with which it shares <32% amino acid identity. Molecular and serological tools were developed and validated for high-throughput screening of plasma samples, and a panel of 3 independent serological markers strongly correlated antibody responses with viral RNA positivity (99.9% negative predictive value). Discovery of 11 additional RNA-positive samples from a total of 2440 screened (0.45%) revealed 93-94% nucleotide identity between HPgV-2 strains. All 12 HPgV-2 RNA-positive cases were identified in individuals also testing positive for HCV RNA (12 of 983; 1.22%), including 2 samples co-infected with HIV, but HPgV-2 RNA was not detected in non-HCV-infected individuals (p<0.0001), including those singly infected by HIV (p = 0.0075) or HBV (p = 0.0077), nor in volunteer blood donors (p = 0.0082). Nine of the 12 (75%) HPgV-2 RNA positive samples were reactive for antibodies to viral serologic markers, whereas only 28 of 2,429 (1.15%) HPgV-2 RNA negative samples were seropositive. Longitudinal sampling in two individuals revealed that active HPgV-2 infection can persist in blood for at least 7 weeks, despite the presence of virus-specific antibodies. One individual harboring both HPgV-2 and HCV RNA was found to be seronegative for both viruses, suggesting a high likelihood of simultaneous acquisition of HCV and HPgV-2 infection from an acute co-transmission event. Taken together, our results indicate that HPgV-2 is a novel bloodborne infectious virus of humans and likely transmitted via the parenteral route.

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

OBJECTIVE: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. METHODS: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. RESULTS: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.