Long-term abstinence from developmental cocaine exposure alters Arc/Arg3.1 modulation in the rat medial prefrontal cortex

Cocaine is a psychostimulant whose abuse causes a social and economic burden for our society. Most of the published literature deals with acute effects of cocaine or short-term abstinence in adult animals but much less information exists on neuroplastic changes following long-term abstinence. We have recently shown that the long-term abstinence following developmental exposure to cocaine results in increased Activity-Regulated Cytoskeletal- associated protein (Arc/Arg3.1) expression in the crude synaptosomal fraction (Giannotti et al. Int J Neuropsychopharmacology 7(4):625-634, 2014). Given that Arc/Arg3.1 localizes not only at active synapse but also in the nucleus (Okuno et al. Cell 149:886-898, 2012; Korb et al. Nat Neurosci 16:874-883 2013; Bloomer et al. Brain Res 1153:20-33 2007), we investigated Arc/Arg3.1 protein levels in the whole homogenate and the nuclear fraction of animals exposed to cocaine during adolescence. We observed the increased expression of Arc/Arg3.1 in both the fractions, suggesting that up-regulation of Arc/Arg3.1 protein may be partly due to the increased nuclear expression of Arc/Arg3.1 in the medial prefrontal cortex (mPFC) of rats sacrificed at postnatal day 90, following 48 days of abstinence. This effect seems to cause reduced Gria1 transcription. We also found reduced expression of fragile X mental retardation gene (FMR1) which normally inhibits Arc/Arg3.1 translation together with reduced expression of Ubiquitin-protein ligase E3A (Ube3a) that normally causes Arc/Arg3.1 protein degradation via ubiquitination. Further, we found increased expression of metabotropic glutamate receptor 5 (GRM5) which is also involved in the regulation of Arc/Arg3.1 expression. Taken together, our findings show that abstinence from developmental exposure to cocaine is associated with alterations in the finely tuned mechanisms that regulate Arc/Arg3.1 expression

Coherent spin valve phenomena and electrical spin injection in ferromagnetic/semiconductor/ferromagnetic junctions

Coherent quantum transport in ferromagnetic/ semiconductor/ ferromagnetic junctions is studied theoretically within the Landauer framework of ballistic transport. We show that quantum coherence can have unexpected implications for spin injection and that some intuitive spintronic concepts which are founded in semi-classical physics no longer apply: A quantum spin-valve (QSV) effect occurs even in the absence of a net spin polarized current flowing through the device, unlike in the classical regime. The converse effect also arises, i.e. a zero spin-valve signal for a non-vanishing spin-current. We introduce new criteria useful for analyzing quantum and classical spin transport phenomena and the relationships between them. The effects on QSV behavior of spin-dependent electron transmission at the interfaces, interface Schottky barriers, Rashba spin-orbit coupling and temperature, are systematically investigated. While the signature of the QSV is found to be sensitive to temperature, interestingly, that of its converse is not. We argue that the QSV phenomenon can have important implications for the interpretation of spin-injection in quantum spintronic experiments with spin-valve geometries.Comment: 15 pages including 11 figures. To appear in PR

Mapping child growth failure across low- and middle-income countries

Childhood malnutrition is associated with high morbidity and mortality globally1. Undernourished children are more likely to experience cognitive, physical, and metabolic developmental impairments that can lead to later cardiovascular disease, reduced intellectual ability and school attainment, and reduced economic productivity in adulthood2. Child growth failure (CGF), expressed as stunting, wasting, and underweight in children under five years of age (0�59 months), is a specific subset of undernutrition characterized by insufficient height or weight against age-specific growth reference standards3�5. The prevalence of stunting, wasting, or underweight in children under five is the proportion of children with a height-for-age, weight-for-height, or weight-for-age z-score, respectively, that is more than two standard deviations below the World Health Organization�s median growth reference standards for a healthy population6. Subnational estimates of CGF report substantial heterogeneity within countries, but are available primarily at the first administrative level (for example, states or provinces)7; the uneven geographical distribution of CGF has motivated further calls for assessments that can match the local scale of many public health programmes8. Building from our previous work mapping CGF in Africa9, here we provide the first, to our knowledge, mapped high-spatial-resolution estimates of CGF indicators from 2000 to 2017 across 105 low- and middle-income countries (LMICs), where 99 of affected children live1, aggregated to policy-relevant first and second (for example, districts or counties) administrative-level units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the ambitious World Health Organization Global Nutrition Targets to reduce stunting by 40 and wasting to less than 5 by 2025. Large disparities in prevalence and progress exist across and within countries; our maps identify high-prevalence areas even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where the highest-need populations reside, these geospatial estimates can support policy-makers in planning interventions that are adapted locally and in efficiently directing resources towards reducing CGF and its health implications. © 2020, The Author(s)

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health

Burden of Neurological Disorders across the US from 1990-2017: A Global Burden of Disease Study

Importance: Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US. Objective: To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017. Design, Setting, and Participants: This is a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus. Exposures: Any of the 14 listed neurological diseases. Main Outcome and Measure: Absolute numbers in detail by age and sex and age-standardized rates (with 95 uncertainty intervals) were calculated. Results: The 3 most burdensome neurological disorders in the US in terms of absolute number of DALYs were stroke (3.58 95% uncertainty interval UI], 3.25-3.92] million DALYs), Alzheimer disease and other dementias (2.55 95% UI, 2.43-2.68 million DALYs), and migraine (2.40 95% UI, 1.53-3.44 million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population. Exceptions for this trend included traumatic brain injury incidence (-29.1% 95% UI, -32.4% to -25.8%); spinal cord injury prevalence (-38.5% 95% UI, -43.1% to -34.0%); meningitis prevalence (-44.8% 95% UI, -47.3% to -42.3%), deaths (-64.4% 95% UI, -67.7% to -50.3%), and DALYs (-66.9% 95% UI, -70.1% to -55.9%); and encephalitis DALYs (-25.8% 95% UI, -30.7% to -5.8%). The different metrics of age-standardized rates varied between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus. Conclusions and Relevance: There is a large and increasing burden of noncommunicable neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in particular neurological disorders across the US states. The information reported in this article can be used by health care professionals and policy makers at the national and state levels to advance their health care planning and resource allocation to prevent and reduce the burden of neurological disorders.. © 2021 American Medical Association. All rights reserved

Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems

BackgroundHuman immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico.MethodsWe performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017.ResultsAll countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries-apart from Ecuador-across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups-the median age group among decedents ranged from 30 to 45years of age at the municipality level in Brazil, Colombia, and Mexico in 2017.ConclusionsOur subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths.Peer reviewe

Search for strong gravity in multijet final states produced in pp collisions at √s=13 TeV using the ATLAS detector at the LHC

A search is conducted for new physics in multijet final states using 3.6 inverse femtobarns of data from proton-proton collisions at √s = 13TeV taken at the CERN Large Hadron Collider with the ATLAS detector. Events are selected containing at least three jets with scalar sum of jet transverse momenta (HT) greater than 1TeV. No excess is seen at large HT and limits are presented on new physics: models which produce final states containing at least three jets and having cross sections larger than 1.6 fb with HT > 5.8 TeV are excluded. Limits are also given in terms of new physics models of strong gravity that hypothesize additional space-time dimensions

The performance of the jet trigger for the ATLAS detector during 2011 data taking

The performance of the jet trigger for the ATLAS detector at the LHC during the 2011 data taking period is described. During 2011 the LHC provided proton–proton collisions with a centre-of-mass energy of 7 TeV and heavy ion collisions with a 2.76 TeV per nucleon–nucleon collision energy. The ATLAS trigger is a three level system designed to reduce the rate of events from the 40 MHz nominal maximum bunch crossing rate to the approximate 400 Hz which can be written to offline storage. The ATLAS jet trigger is the primary means for the online selection of events containing jets. Events are accepted by the trigger if they contain one or more jets above some transverse energy threshold. During 2011 data taking the jet trigger was fully efficient for jets with transverse energy above 25 GeV for triggers seeded randomly at Level 1. For triggers which require a jet to be identified at each of the three trigger levels, full efficiency is reached for offline jets with transverse energy above 60 GeV. Jets reconstructed in the final trigger level and corresponding to offline jets with transverse energy greater than 60 GeV, are reconstructed with a resolution in transverse energy with respect to offline jets, of better than 4 % in the central region and better than 2.5 % in the forward direction

Measurement of jet charge in dijet events from √s = 8 TeV pp collisions with the ATLAS detector

The momentum-weighted sum of the charges of tracks associated to a jet is sensitive to the charge of the initiating quark or gluon. This paper presents a measurement of the distribution of momentum-weighted sums, called jet charge, in dijet events using 20.3 fb−¹ of data recorded with the ATLAS detector at √s = 8 TeV in pp collisions at the LHC. The jet charge distribution is unfolded to remove distortions from detector effects and the resulting particle-level distribution is compared with several models. The pT dependence of the jet charge distribution average and standard deviation are compared to predictions obtained with several leading-order and next-to-leading-order parton distribution functions. The data are also compared to different Monte Carlo simulations of QCD dijet production using various settings of the free parameters within these models. The chosen value of the strong coupling constant used to calculate gluon radiation is found to have a significant impact on the predicted jet charge. There is evidence for a pT dependence of the jet charge distribution for a given jet flavor. In agreement with perturbative QCD predictions, the data show that the average jet charge of quark-initiated jets decreases in magnitude as the energy of the jet increases