The impact of different doses of vitamin A supplementation on male and female mortality. A randomised trial from Guinea-Bissau

<p>Abstract</p> <p>Background</p> <p>Vitamin A supplementation (VAS) given to children between 6 months and 5 years of age is known to reduce mortality in low-income countries. We have previously observed that girls benefit more from a lower dose of VAS than the one recommended by WHO, the effect being strongest if diphtheria-tetanus-pertussis vaccine (DTP) was the most recent vaccination. We aimed to test these observations.</p> <p>Methods</p> <p>During national immunisations days in Guinea-Bissau, West Africa, combining oral polio vaccination and VAS, we randomised 8626 children between 6 months and 5 years of age to receive the dose of VAS recommended by WHO or half this dose. Mortality rate ratios (MRRs) were assessed after 6 and 12 month.</p> <p>Results</p> <p>The overall mortality rate among participants was lower than expected. There was no significant difference in mortality at 6 months and 12 months of follow up between the low dose VAS group and the recommended dose VAS group. The MRRs were 1.23 (0.60-2.54) after 6 months and 1.17 (0.73-1.87) after 12 months. This tendency was similar in boys and girls. The low dose was not associated with lower mortality in girls if the most recent vaccine was DTP (MRR = 0.60 (0.14-2.50) after 6 months).</p> <p>Conclusion</p> <p>Our sample size does not permit firm conclusions since mortality was lower than expected. We could not confirm a beneficial effect of a lower dose of VAS on mortality in girls.</p> <p>Trial registration</p> <p>The study was registered under clinicaltrials.gov, number <a href="http://www.clinicaltrials.gov/ct2/show/NCT00168636">NCT00168636</a></p

Observations of interplanetary dust by the Juno magnetometer investigation

One of the Juno magnetometer investigation's star cameras was configured to search for unidentified objects during Juno's transit en route to Jupiter. This camera detects and registers luminous objects to magnitude 8. Objects persisting in more than five consecutive images and moving with an apparent angular rate of between 2 and 18,000 arcsec/s were recorded. Among the objects detected were a small group of objects tracked briefly in close proximity to the spacecraft. The trajectory of these objects demonstrates that they originated on the Juno spacecraft, evidently excavated by micrometeoroid impacts on the solar arrays. The majority of detections occurred just prior to and shortly after Juno's transit of the asteroid belt. This rather novel detection technique utilizes the Juno spacecraft's prodigious 60 sq. m of solar array as a dust detector and provides valuable information on the distribution and motion of interplanetary (greater than a micron) dust. Plain Language Summary: The Juno magnetometer investigation uses star cameras co-located with the magnetic sensors at the outer end of one of Juno's solar arrays. These cameras compare images with an onboard star catalog to determine the orientation of the sensors in inertial space. They also serendipitously recorded multiple images of small particles excavated from the spacecraft by high-velocity dust impacts. We trace their trajectories back in time to demonstrate that they evolved from the spacecraft. This allows us to use the vast collecting area of Juno's solar arrays (60 sq. m)as a novel dust detector, sensitive to particles with a mass range never before measured in situ

One vaccine to counter many diseases? Modeling the economics of oral polio vaccine against child mortality and COVID-19

INTRODUCTION: Recent reviews summarize evidence that some vaccines have heterologous or non-specific effects (NSE), potentially offering protection against multiple pathogens. Numerous economic evaluations examine vaccines\u27 pathogen-specific effects, but less than a handful focus on NSE. This paper addresses that gap by reporting economic evaluations of the NSE of oral polio vaccine (OPV) against under-five mortality and COVID-19. MATERIALS AND METHODS: We studied two settings: (1) reducing child mortality in a high-mortality setting (Guinea-Bissau) and (2) preventing COVID-19 in India. In the former, the intervention involves three annual campaigns in which children receive OPV incremental to routine immunization. In the latter, a susceptible-exposed-infectious-recovered model was developed to estimate the population benefits of two scenarios, in which OPV would be co-administered alongside COVID-19 vaccines. Incremental cost-effectiveness and benefit-cost ratios were modeled for ranges of intervention effectiveness estimates to supplement the headline numbers and account for heterogeneity and uncertainty. RESULTS: For child mortality, headline cost-effectiveness was $650 per child death averted. For COVID-19, assuming OPV had 20$23,000-65,000 if it were administered simultaneously with a COVID-19 vaccine \u3c200 days into a wave of the epidemic. If the COVID-19 vaccine availability were delayed, the cost per averted death would decrease to $2600-6100. Estimated benefit-to-cost ratios vary but are consistently high. DISCUSSION: Economic evaluation suggests the potential of OPV to efficiently reduce child mortality in high mortality environments. Likewise, within a broad range of assumed effect sizes, OPV (or another vaccine with NSE) could play an economically attractive role against COVID-19 in countries facing COVID-19 vaccine delays. FUNDING: The contribution by DTJ was supported through grants from Trond Mohn Foundation (BFS2019MT02) and Norad (RAF-18/0009) through the Bergen Center for Ethics and Priority Setting

Continental carbonate facies of a Neoproterozoic panglaciation, north-east Svalbard

The Marinoan panglaciation (ca 650 to 635 Ma) is represented in north-east Svalbard by the 130 to 175 m thick Wilsonbreen Formation which contains syn-glacial carbonates in its upper 100 m. These sediments are now known to have been deposited under a CO2-rich atmosphere, late in the glaciation, and global climate models facilitate testing of proposed analogues. Precipitated carbonates occur in four of the seven facies associations identified: Fluvial Channel (including stromatolitic and intraclastic limestones in ephemeral stream deposits); Dolomitic Floodplain (dolomite-cemented sand and siltstones, and microbial dolomites); Calcareous Lake Margin (intraclastic dolomite and wave-rippled or aeolian siliciclastic facies); and Calcareous Lake (slump-folded and locally re-sedimented rhythmic/stromatolitic limestones and dolomites associated with ice-rafted sediment). There is no strong cyclicity, and modern analogues suggest that sudden changes in lake level may exert a strong control on facies geometry. Both calcite and dolomite in stromatolites and rhythmites display either primary or early diagenetic replacive growth. Oxygen isotope values (−12 to +15‰VPDB) broadly covary with δ13C. High δ13C values of +3·5 to +4·5‰ correspond to equilibration with an atmosphere dominated by volcanically degassed CO2 with δ13C of −6 to −7‰. Limestones have consistently negative δ18O values, while rhythmic and playa dolomites preserve intermediate compositions, and dolocretes possess slightly negative to strongly positive δ18O signatures, reflecting significant evaporation under hyperarid conditions. Inferred meltwater compositions (−8 to −15·5‰) could reflect smaller Rayleigh fractionation related to more limited cooling than in modern polar regions. A common pseudomorph morphology is interpreted as a replacement of ikaite (CaCO3·H2O), which may also have been the precursor for widespread replacive calcite mosaics. Local dolomitization of lacustrine facies is interpreted to reflect microenvironments with fluctuating redox conditions. Although differing in (palaeo)latitude and carbonate abundance, the Wilsonbreen carbonates provide strong parallels with the McMurdo Dry Valleys of Antarctica

Microphysiologic Human Tissue Constructs Reproduce Autologous Age-Specific BCG and HBV Primary Immunization <i>in vitro</i>

Current vaccine development disregards human immune ontogeny, relying on animal models to select vaccine candidates targeting human infants, who are at greatest risk of infection worldwide, and receive the largest number of vaccines. To help accelerate and de-risk development of early-life effective immunization, we engineered a human age-specific microphysiologic vascular-interstitial interphase, suitable for pre-clinical modeling of distinct age-targeted immunity in vitro. Our Tissue Constructs (TCs) enable autonomous extravasation of monocytes that undergo rapid self-directed differentiation into migratory Dendritic Cells (DCs) in response to adjuvants and licensed vaccines such as Bacille Calmette-Guérin (BCG) or Hepatitis B virus Vaccine (HBV). TCs contain a confluent human endothelium grown atop a tri-dimensional human extracellular matrix substrate, employ human age-specific monocytes and autologous non heat-treated plasma, and avoid the use of xenogenic materials and exogenous cytokines. Vaccine-pulsed TCs autonomously generated DCs that induced single-antigen recall responses from autologous naïve and memory CD4+ T lymphocytes, matching study participant immune-status, including BCG responses paralleling donor PPD status, BCG-induced adenosine deaminase (ADA) activity paralleling infant cohorts in vivo, and multi-dose HBV antigen-specific responses as demonstrated by lymphoproliferation and TCR sequencing. Overall, our microphysiologic culture method reproduced age- and antigen-specific recall responses to BCG and HBV immunization, closely resembling those observed after a birth immunization of human cohorts in vivo, offering for the first time a new approach to early pre-clinical selection of effective age-targeted vaccine candidates.</p

Mutations in succinate dehydrogenase B (SDHB) enhance neutrophil survival independent of HIF-1α expression.

status: publishe

Snowball Earth climate dynamics and Cryogenian geology-geobiology

Geological evidence indicates that grounded ice sheets reached sea level at all latitudes during two long-lived Cryogenian (58 and ≥5 My) glaciations. Combined uranium-lead and rhenium-osmium dating suggests that the older (Sturtian) glacial onset and both terminations were globally synchronous. Geochemical data imply that CO2 was 102 PAL (present atmospheric level) at the younger termination, consistent with a global ice cover. Sturtian glaciation followed breakup of a tropical supercontinent, and its onset coincided with the equatorial emplacement of a large igneous province. Modeling shows that the small thermal inertia of a globally frozen surface reverses the annual mean tropical atmospheric circulation, producing an equatorial desert and net snow and frost accumulation elsewhere. Oceanic ice thickens, forming a sea glacier that flows gravitationally toward the equator, sustained by the hydrologic cycle and by basal freezing and melting. Tropical ice sheets flow faster as CO2 rises but lose mass and become sensitive to orbital changes. Equatorial dust accumulation engenders supraglacial oligotrophic meltwater ecosystems, favorable for cyanobacteria and certain eukaryotes. Meltwater flushing through cracks enables organic burial and submarine deposition of airborne volcanic ash. The subglacial ocean is turbulent and well mixed, in response to geothermal heating and heat loss through the ice cover, increasing with latitude. Terminal carbonate deposits, unique to Cryogenian glaciations, are products of intense weathering and ocean stratification. Whole-ocean warming and collapsing peripheral bulges allow marine coastal flooding to continue long after ice-sheet disappearance. The evolutionary legacy of Snowball Earth is perceptible in fossils and living organisms

PTF1 J071912.13+485834.0: An outbursting AM CVn system discovered by a synoptic survey

We present extensive photometric and spectroscopic observations of PTF1 J071912.13+485834.0, an outbursting AM CVn system discovered by the Palomar Transient Factory (PTF). AM CVn systems are stellar binaries with some of the smallest separations known and orbital periods ranging from 5 to 65 minutes. They are believed to be composed of a white dwarf accretor and a (semi)-degenerate He-rich donor and are considered to be the helium equivalents of Cataclysmic Variables. We have spectroscopically and photometrically identified an orbital period of 26.77 \pm 0.02 minutes for PTF1 J071912.13+485834.0 and found a super-outburst recurrence time of greater than 65 days along with the presence of "normal" outbursts - rarely seen in AM CVn systems but well known in super-outbursting Cataclysmic Variables. We present a long-term light curve over two super-cycles as well as high cadence photometry of both outburst and quiescent stages, both of which show clear variability. We also compare both the outburst and quiescent spectra of PTF1 J071912.13+485834.0 to other known AM CVn systems, and use the quiescent phase-resolved spectroscopy to determine the origin of the photometric variability. Finally, we draw parallels between the different subclasses of SU UMa-type Cataclysmic Variables and outbursting AM CVn systems. We conclude by predicting that the Palomar Transient Factory may more than double the number of outbursting AM CVn systems known, which would greatly increase our understanding of AM CVn systems.Comment: 11 pages, 10 figures; accepted to Ap

Mapping male circumcision for HIV prevention efforts in sub-Saharan Africa

Background HIV remains the largest cause of disease burden among men and women of reproductive age in sub-Saharan Africa. Voluntary medical male circumcision (VMMC) reduces the risk of female-to-male transmission of HIV by 50–60%. The World Health Organization (WHO) and Joint United Nations Programme on HIV/AIDS (UNAIDS) identified 14 priority countries for VMMC campaigns and set a coverage goal of 80% for men ages 15–49. From 2008 to 2017, over 18 million VMMCs were reported in priority countries. Nonetheless, relatively little is known about local variation in male circumcision (MC) prevalence. Methods We analyzed geo-located MC prevalence data from 109 household surveys using a Bayesian geostatistical modeling framework to estimate adult MC prevalence and the number of circumcised and uncircumcised men aged 15–49 in 38 countries in sub-Saharan Africa at a 5 × 5-km resolution and among first administrative level (typically provinces or states) and second administrative level (typically districts or counties) units. Results We found striking within-country and between-country variation in MC prevalence; most (12 of 14) priority countries had more than a twofold difference between their first administrative level units with the highest and lowest estimated prevalence in 2017. Although estimated national MC prevalence increased in all priority countries with the onset of VMMC campaigns, seven priority countries contained both subnational areas where estimated MC prevalence increased and areas where estimated MC prevalence decreased after the initiation of VMMC campaigns. In 2017, only three priority countries (Ethiopia, Kenya, and Tanzania) were likely to have reached the MC coverage target of 80% at the national level, and no priority country was likely to have reached this goal in all subnational areas. Conclusions Despite MC prevalence increases in all priority countries since the onset of VMMC campaigns in 2008, MC prevalence remains below the 80% coverage target in most subnational areas and is highly variable. These mapped results provide an actionable tool for understanding local needs and informing VMMC interventions for maximum impact in the continued effort towards ending the HIV epidemic in sub-Saharan Africa

Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies: A Mendelian Randomization Analysis.

IMPORTANCE: Human genetic studies have indicated that plasma lipoprotein(a) (Lp[a]) is causally associated with the risk of coronary heart disease (CHD), but randomized trials of several therapies that reduce Lp(a) levels by 25% to 35% have not provided any evidence that lowering Lp(a) level reduces CHD risk. OBJECTIVE: To estimate the magnitude of the change in plasma Lp(a) levels needed to have the same evidence of an association with CHD risk as a 38.67-mg/dL (ie, 1-mmol/L) change in low-density lipoprotein cholesterol (LDL-C) level, a change that has been shown to produce a clinically meaningful reduction in the risk of CHD. DESIGN, SETTING, AND PARTICIPANTS: A mendelian randomization analysis was conducted using individual participant data from 5 studies and with external validation using summarized data from 48 studies. Population-based prospective cohort and case-control studies featured 20 793 individuals with CHD and 27 540 controls with individual participant data, whereas summarized data included 62 240 patients with CHD and 127 299 controls. Data were analyzed from November 2016 to March 2018. EXPOSURES: Genetic LPA score and plasma Lp(a) mass concentration. MAIN OUTCOMES AND MEASURES: Coronary heart disease. RESULTS: Of the included study participants, 53% were men, all were of white European ancestry, and the mean age was 57.5 years. The association of genetically predicted Lp(a) with CHD risk was linearly proportional to the absolute change in Lp(a) concentration. A 10-mg/dL lower genetically predicted Lp(a) concentration was associated with a 5.8% lower CHD risk (odds ratio [OR], 0.942; 95% CI, 0.933-0.951; P = 3 × 10-37), whereas a 10-mg/dL lower genetically predicted LDL-C level estimated using an LDL-C genetic score was associated with a 14.5% lower CHD risk (OR, 0.855; 95% CI, 0.818-0.893; P = 2 × 10-12). Thus, a 101.5-mg/dL change (95% CI, 71.0-137.0) in Lp(a) concentration had the same association with CHD risk as a 38.67-mg/dL change in LDL-C level. The association of genetically predicted Lp(a) concentration with CHD risk appeared to be independent of changes in LDL-C level owing to genetic variants that mimic the relationship of statins, PCSK9 inhibitors, and ezetimibe with CHD risk. CONCLUSIONS AND RELEVANCE: The clinical benefit of lowering Lp(a) is likely to be proportional to the absolute reduction in Lp(a) concentration. Large absolute reductions in Lp(a) of approximately 100 mg/dL may be required to produce a clinically meaningful reduction in the risk of CHD similar in magnitude to what can be achieved by lowering LDL-C level by 38.67 mg/dL (ie, 1 mmol/L)