Characterization of the ZFX family of transcription factors that bind downstream of the start site of CpG island promoters

Our study focuses on a family of ubiquitously expressed human C₂H₂ zinc finger proteins comprised of ZFX, ZFY and ZNF711. Although their protein structure suggests that ZFX, ZFY and ZNF711 are transcriptional regulators, the mechanisms by which they influence transcription have not yet been elucidated. We used CRISPR-mediated deletion to create bi-allelic knockouts of ZFX and/or ZNF711 in female HEK293T cells (which naturally lack ZFY). We found that loss of either ZFX or ZNF711 reduced cell growth and that the double knockout cells have major defects in proliferation. RNA-seq analysis revealed that thousands of genes showed altered expression in the double knockout clones, suggesting that these TFs are critical regulators of the transcriptome. To gain insight into how these TFs regulate transcription, we created mutant ZFX proteins and analyzed them for DNA binding and transactivation capability. We found that zinc fingers 11–13 are necessary and sufficient for DNA binding and, in combination with the N terminal region, constitute a functional transactivator. Our functional analyses of the ZFX family provides important new insights into transcriptional regulation in human cells by members of the large, but under-studied family of C₂H₂ zinc finger proteins

The Evolving Activity of the Dynamically Young Comet C/2009 P1 (Garradd)

We used the UltraViolet-Optical Telescope on board Swift to observe the dynamically young comet C/2009 P1 (Garradd) from a heliocentric distance of 3.5 AU pre-perihelion until 4.0 AU outbound. At 3.5 AU pre-perihelion, comet Garradd had one of the highest dust-to-gas ratios ever observed, matched only by comet Hale-Bopp. The evolving morphology of the dust in its coma suggests an outburst that ended around 2.2 AU pre-perihelion. Comparing slit-based measurements and observations acquired with larger fields of view indicated that between 3 AU and 2 AU pre-perihelion a significant extended source started producing water in the coma. We demonstrate that this source, which could be due to icy grains, disappeared quickly around perihelion. Water production by the nucleus may be attributed to a constantly active source of at least 75 km$^2$, estimated to be more than 20 percent of the surface. Based on our measurements, the comet lost $4x10^{11}$ kg of ice and dust during this apparition, corresponding to at most a few meters of its surface.Even though this was likely not Garradd's first passage through the inner solar system, the activity of the comet was complex and changed significantly during the time it was observed

Suicidal behavior in individuals accused or convicted of child sex abuse or indecent image offenses: systematic review of prevalence and risk factors

Objective An emerging body of research indicates that child sex abuse (CSA) offenders are at high risk of suicide when their offenses come to light and that those accused of accessing indecent images of children (IIOC) are at particular risk. Methods We conducted a systematic review and narrative synthesis on suicide rates and risk factors in this population of offenders. A keyword search of bibliographic databases (PsycINFO, Ovid, MEDLINE, Embase, PILOTS, SCIE, the Cochrane Central Register of Controlled Trials [CENTRAL] and CINAHL) was conducted. Results Eighteen articles were included in the review, with eleven studies meeting criteria for quality assessment. The risk of suicide in perpetrators of CSA and IIOC might be over 100 times that of the general population, although estimates vary widely between studies. Several complex, interlinking factors were identified as associated with risk, including shame, unique demographic characteristics of the offenders, absence of prior criminal contact, and the impact of a criminal investigation. Conclusions The review identified factors that may have practical, clinical, and operational implications in the prevention of suicide in CSA and IIOC perpetrators. Exploring the impact of the investigation itself on suicide risk, including potential operational strategies and clinical input to reduce risk, should be a priority

Quantification of annual settlement growth in rural mining areas using machine learning

Studies on annual settlement growth have mainly focused on larger cities or incorporated data rarely available in, or applicable to, sparsely populated areas in sub-Saharan Africa, such as aerial photography or night-time light data. The aim of the present study is to quantify settlement growth in rural communities in Burkina Faso affected by industrial mining, which often experience substantial in-migration. A multi-annual training dataset was created using historic Google Earth imagery. Support vector machine classifiers were fitted on Landsat scenes to produce annual land use classification maps. Post-classification steps included visual quality assessments, majority voting of scenes of the same year and temporal consistency correction. Overall accuracy in the four studied scenes ranged between 58.5% and 95.1%. Arid conditions and limited availability of Google Earth imagery negatively affected classification accuracy. Humid study sites, where training data could be generated in proximity to the areas of interest, showed the highest classification accuracies. Overall, by relying solely on freely and globally available imagery, the proposed methodology is a promising approach for tracking fast-paced population dynamics in rural areas where population data is scarce. With the growing availability of longitudinal high-resolution imagery, including data from the Sentinel satellites, the potential applications of the methodology presented will further increase in the futur

How do disease control measures impact spatial predictions of schistosomiasis and hookworm? The example of predicting school-based prevalence before and after preventive chemotherapy in Ghana

BACKGROUND: Schistosomiasis and soil-transmitted helminth infections are among the neglected tropical diseases (NTDs) affecting primarily marginalized communities in low- and middle-income countries. Surveillance data for NTDs are typically sparse, and hence, geospatial predictive modeling based on remotely sensed (RS) environmental data is widely used to characterize disease transmission and treatment needs. However, as large-scale preventive chemotherapy has become a widespread practice, resulting in reduced prevalence and intensity of infection, the validity and relevance of these models should be re-assessed. METHODOLOGY: We employed two nationally representative school-based prevalence surveys of Schistosoma haematobium and hookworm infections from Ghana conducted before (2008) and after (2015) the introduction of large-scale preventive chemotherapy. We derived environmental variables from fine-resolution RS data (Landsat 8) and examined a variable distance radius (1-5 km) for aggregating these variables around point-prevalence locations in a non-parametric random forest modeling approach. We used partial dependence and individual conditional expectation plots to improve interpretability. PRINCIPAL FINDINGS: The average school-level S. haematobium prevalence decreased from 23.8% to 3.6% and that of hookworm from 8.6% to 3.1% between 2008 and 2015. However, hotspots of high-prevalence locations persisted for both diseases. The models with environmental data extracted from a buffer radius of 2-3 km around the school location where prevalence was measured had the best performance. Model performance (according to the R2 value) was already low and declined further from approximately 0.4 in 2008 to 0.1 in 2015 for S. haematobium and from approximately 0.3 to 0.2 for hookworm. According to the 2008 models, land surface temperature (LST), modified normalized difference water index (MNDWI), elevation, slope, and streams variables were associated with S. haematobium prevalence. LST, slope, and improved water coverage were associated with hookworm prevalence. Associations with the environment in 2015 could not be evaluated due to low model performance. CONCLUSIONS/SIGNIFICANCE: Our study showed that in the era of preventive chemotherapy, associations between S. haematobium and hookworm infections and the environment weakened, and thus predictive power of environmental models declined. In light of these observations, it is timely to develop new cost-effective passive surveillance methods for NTDs as an alternative to costly surveys, and to focus on persisting hotspots of infection with additional interventions to reduce reinfection. We further question the broad application of RS-based modeling for environmental diseases for which large-scale pharmaceutical interventions are in place

dCas9-based epigenome editing suggests acquisition of histone methylation is not sufficient for target gene repression.

Distinct epigenomic profiles of histone marks have been associated with gene expression, but questions regarding the causal relationship remain. Here we investigated the activity of a broad collection of genomically targeted epigenetic regulators that could write epigenetic marks associated with a repressed chromatin state (G9A, SUV39H1, Krüppel-associated box (KRAB), DNMT3A as well as the first targetable versions of Ezh2 and Friend of GATA-1 (FOG1)). dCas9 fusions produced target gene repression over a range of 0- to 10-fold that varied by locus and cell type. dCpf1 fusions were unable to repress gene expression. The most persistent gene repression required the action of several effector domains; however, KRAB-dCas9 did not contribute to persistence in contrast to previous reports. A 'direct tethering' strategy attaching the Ezh2 methyltransferase enzyme to dCas9, as well as a 'recruitment' strategy attaching the N-terminal 45 residues of FOG1 to dCas9 to recruit the endogenous nucleosome remodeling and deacetylase complex, were both successful in targeted deposition of H3K27me3. Surprisingly, however, repression was not correlated with deposition of either H3K9me3 or H3K27me3. Our results suggest that so-called repressive histone modifications are not sufficient for gene repression. The easily programmable dCas9 toolkit allowed precise control of epigenetic information and dissection of the relationship between the epigenome and gene regulation

Industrial mining and HIV risk: evidence from 39 mine openings across 16 countries in sub-Saharan Africa

OBJECTIVES: The aim of this study was to assess the impact of natural resource extraction projects on HIV transmission risks in local communities in sub-Saharan Africa. DESIGN: Difference-in-differences design using repeated cross-sectional data from around newly opened mines. METHODS: We combined data on mine openings with HIV data from the Demographic and Health Surveys (DHS). Using logistic regression models, we compared HIV related indicators between mining (i.e. up to 10 km distance from the mine) and comparison (i.e. 10-50 km) areas before and after mine opening to identify their impact on HIV prevalence, sexual behavior and HIV knowledge. RESULTS: A total of 33,086 individuals across 39 mine openings were analyzed. Adjusting for baseline differences and temporal trends in the study regions, mine opening increased the odds of HIV infection almost two-fold (odds ratio (OR): 1.93, 95% confidence interval (CI): 1.19-3.14). Strongest effects were seen in high-prevalence countries and in the 20-29 years age group. In mining communities around operational mines there was a tendency towards lower HIV knowledge (OR: 0.81, 95% CI: 0.63-1.04). New mine openings increased the odds of risky sexual behaviors, such as having multiple sex partners (OR: 1.61, 95% CI: 1.02-2.55), high-risk sexual partners (OR: 1.45, 95% CI: 1.03-2.05) and unprotected sex with high-risk partners (OR: 1.77, 95% CI: 1.18-2.67). CONCLUSION: The findings suggest that in our sample of households surrounding industrial mines, HIV infection risks substantially increase upon mine opening. Existing strategies for addressing mining-related risks for HIV transmission seem to be insufficient. Further efforts for mitigating and monitoring impacts of mines are needed. Video Abstract: http://links.lww.com/QAD/C557

Short-term effects of national-level natural resource rents on life expectancy: a cross-country panel data analysis

While a substantial amount of literature addresses the relationship between natural resources and economic growth, relatively little is known regarding the relationship between natural resource endowment and health at the population level. We construct a 5-year cross-country panel to assess the impact of natural resource rents on changes in life expectancy at birth as a proxy indicator for population health during the period 1970-2015. To estimate the causal effects of interest, we use global commodity prices as instrumental variables for natural resource rent incomes in two-stage-least squares regressions. Controlling for country and year fixed effects, we show that each standard deviation increase in resource rents results in life expectancy increase of 6.72% (CI: 2.01%, 11.44%). This corresponds to approximately one additional year of life expectancy gained over five years. We find a larger positive effect of rents on life expectancy in sub-Saharan Africa (SSA) compared to other world regions. We do not find short-term effects of rents on economic growth, but show that increases in resource rents result in sizeable increases in government revenues in the short run, which likely translate into increased spending across government sectors. This suggests that natural resources can help governments finance health and other development-oriented programs needed to improve population health

Automation of procedure writing for the RLWTF

In August of 1997, the Radioactive Liquid Waste Treatment Facility (RLWTF) at Los Alamos National Laboratory (LANL) recognized the need to re-engineer document management business process. All nuclear facilities at LANL are required to ensure that both the latest approved revision of controlled documents and any changes to those documents are available to operating personnel at all times. The Nuclear Materials Technology (NMT) Division was also re-engineering its document management business processes and searching for a solution. Both groups contacted several internal and external organizations in search of potential software solutions in use that would meet requirements. This report describes the objectives and features required by the software package, the choice of Procedure Design as the software package, and its implementation

Impact of mining projects on water and sanitation infrastructures and associated child health outcomes: a multi-country analysis of Demographic and Health Surveys (DHS) in sub-Saharan Africa

BACKGROUND: Access to improved water and sanitation infrastructures are key determinants of health. The sub-Saharan African region in particular is lagging behind the ambitious goal of the 2030 Agenda for Sustainable Development to ensure universal access to improved and reliable water and sanitation for all (Sustainable Development Goal (SDG) 6). Large mining projects can promote economic growth and hence investments in water and sanitation infrastructures, but at the same time lead to rapid population growth and environmental degradation. In turn, these changes can pose risks and opportunities for child health (SDG 3). In this study we aim to quantify the impacts of mining projects on access to water and sanitation infrastructure as well as diarrhea and malnutrition among children using data from 131 Demographic and Health Surveys from sub-Saharan Africa. RESULTS: From a sample of around 1.2 million households, data within the proximity of 52 mine-panels were selected for longitudinal analyses, resulting in 41,896 households and 32,112 children. Improvements in access to modern water and sanitation infrastructures after mine opening were much larger in households near mining sites than in comparison areas located further away (adjusted relative risk ratio (aRRR) water: 18.60, 95 % confidence interval (CI): 13.08-26.46 and aRRR sanitation: 2.56, 95 % CI: 1.32-4.99). However, these associations were weaker among poorer households. In areas close to the mining sites, stunting and underweight prevalence decreased more strongly upon mine opening (adjusted odds ratio (aOR) stunting: 0.62, 95 % CI: 0.43-0.90; aOR underweight: 0.55, 95 % CI: 0.36-0.84). No differential changes were seen for wasting and diarrhea. Large impact heterogeneity was observed both within and across countries. CONCLUSIONS: Our results suggest that the opening of mines is associated with improvements in access to modern water and sanitation infrastructures (SDG 6) as well as in some health outcomes (SDG 3). However, the large impact heterogeneity suggests that the assessment and management of mining-related impacts on communities should have an increased equity-focus, in order to "leave no one behind" in the work towards the 2030 Agenda for Sustainable Development. Overall, the findings of this study underscore that the resource extraction sector has the potential to make positive and substantial contributions towards achieving the SDGs