A Pilot Randomized, Controlled Trial of an In-Home Drinking Water Intervention Among HIV + Persons

Although immunocompromised persons may be at increased risk for gastrointestinal illnesses, no trials investigating drinking water treatment and gastrointestinal illness in such patients have been published. Earlier results from San Francisco suggested an association (OR 6.76) between tap water and cryptosporidiosis among HIV + persons. The authors conducted a randomized, triple-blinded intervention trial of home water treatment in San Francisco, California, from April 2000 to May 2001. Fifty HIV-positive patients were randomized to externally identical active (N = 24) or sham (N = 26) treatment devices. The active device contained a filter and UV light; the sham provided no treatment. Forty-five (90%) of the participants completed the study and were successfully blinded. Illness was measured using \u27highly credible gastrointestinal illness\u27 (HCGI), a previously published measure. There were 31 episodes of HCGI during 1,797 person-days in the sham group and 16 episodes during 1,478 person-days in the active group. The adjusted relative risk was 3.34 (95% CI: 0.99-11.21) times greater in those with the sham device. The magnitude of the point estimate of the risk, its consistency with recently published observational data, and its relevance for drinking water choices by immunocompromised individuals support the need for larger trials

20 years of research on the Alcator C-Mod tokamak

The object of this review is to summarize the achievements of research on the Alcator C-Mod tokamak [Hutchinson et al., Phys. Plasmas 1, 1511 (1994) and Marmar, Fusion Sci. Technol. 51, 261 (2007)] and to place that research in the context of the quest for practical fusion energy. C-Mod is a compact, high-field tokamak, whose unique design and operating parameters have produced a wealth of new and important results since it began operation in 1993, contributing data that extends tests of critical physical models into new parameter ranges and into new regimes. Using only high-power radio frequency (RF) waves for heating and current drive with innovative launching structures, C-Mod operates routinely at reactor level power densities and achieves plasma pressures higher than any other toroidal confinement device. C-Mod spearheaded the development of the vertical-target divertor and has always operated with high-Z metal plasma facing components—approaches subsequently adopted for ITER. C-Mod has made ground-breaking discoveries in divertor physics and plasma-material interactions at reactor-like power and particle fluxes and elucidated the critical role of cross-field transport in divertor operation, edge flows and the tokamak density limit. C-Mod developed the I-mode and the Enhanced Dα H-mode regimes, which have high performance without large edge localized modes and with pedestal transport self-regulated by short-wavelength electromagnetic waves. C-Mod has carried out pioneering studies of intrinsic rotation and demonstrated that self-generated flow shear can be strong enough in some cases to significantly modify transport. C-Mod made the first quantitative link between the pedestal temperature and the H-mode's performance, showing that the observed self-similar temperature profiles were consistent with critical-gradient-length theories and followed up with quantitative tests of nonlinear gyrokinetic models. RF research highlights include direct experimental observation of ion cyclotron range of frequency (ICRF) mode-conversion, ICRF flow drive, demonstration of lower-hybrid current drive at ITER-like densities and fields and, using a set of novel diagnostics, extensive validation of advanced RF codes. Disruption studies on C-Mod provided the first observation of non-axisymmetric halo currents and non-axisymmetric radiation in mitigated disruptions. A summary of important achievements and discoveries are included.United States. Dept. of Energy (Cooperative Agreement DE-FC02-99ER54512)United States. Dept. of Energy (Cooperative Agreement DE-FG03-94ER-54241)United States. Dept. of Energy (Cooperative Agreement DE-AC02-78ET- 51013)United States. Dept. of Energy (Cooperative Agreement DE-AC02-09CH11466)United States. Dept. of Energy (Cooperative Agreement DE-FG02-95ER54309)United States. Dept. of Energy (Cooperative Agreement DE-AC02-05CH11231)United States. Dept. of Energy (Cooperative Agreement DE-AC52-07NA27344)United States. Dept. of Energy (Cooperative Agreement DE-FG02- 97ER54392)United States. Dept. of Energy (Cooperative Agreement DE-SC00-02060

Alcator C-Mod: research in support of ITER and steps beyond

This paper presents an overview of recent highlights from research on Alcator C-Mod. Significant progress has been made across all research areas over the last two years, with particular emphasis on divertor physics and power handling, plasma–material interaction studies, edge localized mode-suppressed pedestal dynamics, core transport and turbulence, and RF heating and current drive utilizing ion cyclotron and lower hybrid tools. Specific results of particular relevance to ITER include: inner wall SOL transport studies that have led, together with results from other experiments, to the change of the detailed shape of the inner wall in ITER; runaway electron studies showing that the critical electric field required for runaway generation is much higher than predicted from collisional theory; core tungsten impurity transport studies reveal that tungsten accumulation is naturally avoided in typical C-Mod conditions.United States. Department of Energy (DE-FC02-99ER54512-CMOD)United States. Department of Energy (DE-AC02-09CH11466)United States. Department of Energy (DE-FG02-96ER-54373)United States. Department of Energy (DE-FG02-94ER54235

2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

A healthy lifestyle is important in the prevention of CVD, the leading cause of morbidity and mortality worldwide. The intent of the Lifestyle Work Group (Work Group) was to evaluate evidence that particular dietary patterns, nutrient intake, and levels and types of physical activity can play a major role in CVD prevention and treatment through effects on modifiable CVD risk factors (ie, blood pressure [BP] and lipids). These ESs and recommendations may be used as appropriate in the management of hypercholesterolemia and hypertension. The target audience of the report is primary care providers

2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

A healthy lifestyle is important in the prevention of CVD, the leading cause of morbidity and mortality worldwide. The intent of the Lifestyle Work Group (Work Group) was to evaluate evidence that particular dietary patterns, nutrient intake, and levels and types of physical activity can play a major role in CVD prevention and treatment through effects on modifiable CVD risk factors (ie, blood pressure [BP] and lipids). These ESs and recommendations may be used as appropriate in the management of hypercholesterolemia and hypertension. The target audience of the report is primary care providers

Evidence for Transcript Networks Composed of Chimeric RNAs in Human Cells

The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5′ and 3′ transcriptional termini of 492 protein coding genes revealed that for 85% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric RNAs. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an RNA network

Lipid Composition of the Human Eye: Are Red Blood Cells a Good Mirror of Retinal and Optic Nerve Fatty Acids?

International audienceBACKGROUND: The assessment of blood lipids is very frequent in clinical research as it is assumed to reflect the lipid composition of peripheral tissues. Even well accepted such relationships have never been clearly established. This is particularly true in ophthalmology where the use of blood lipids has become very common following recent data linking lipid intake to ocular health and disease. In the present study, we wanted to determine in humans whether a lipidomic approach based on red blood cells could reveal associations between circulating and tissue lipid profiles. To check if the analytical sensitivity may be of importance in such analyses, we have used a double approach for lipidomics. METHODOLOGY AND PRINCIPAL FINDINGS: Red blood cells, retinas and optic nerves were collected from 9 human donors. The lipidomic analyses on tissues consisted in gas chromatography and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS). Gas chromatography did not reveal any relevant association between circulating and ocular fatty acids except for arachidonic acid whose circulating amounts were positively associated with its levels in the retina and in the optic nerve. In contrast, several significant associations emerged from LC-ESI-MS analyses. Particularly, lipid entities in red blood cells were positively or negatively associated with representative pools of retinal docosahexaenoic acid (DHA), retinal very-long chain polyunsaturated fatty acids (VLC-PUFA) or optic nerve plasmalogens. CONCLUSIONS AND SIGNIFICANCE: LC-ESI-MS is more appropriate than gas chromatography for lipidomics on red blood cells, and further extrapolation to ocular lipids. The several individual lipid species we have identified are good candidates to represent circulating biomarkers of ocular lipids. However, further investigation is needed before considering them as indexes of disease risk and before using them in clinical studies on optic nerve neuropathies or retinal diseases displaying photoreceptors degeneration

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants