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Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.
We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
We read with interest the recent editorial, “The Hennepin Ketamine Study,” by Dr. Samuel Stratton commenting on the research ethics, methodology, and the current public controversy surrounding this study.1 As researchers and investigators of this study, we strongly agree that prospective clinical research in the prehospital environment is necessary to advance the science of Emergency Medical Services (EMS) and emergency medicine. We also agree that accomplishing this is challenging as the prehospital environment often encounters patient populations who cannot provide meaningful informed consent due to their emergent conditions. To ensure that fellow emergency medicine researchers understand the facts of our work so they may plan future studies, and to address some of the questions and concerns in Dr. Stratton’s editorial, the lay press, and in social media,2 we would like to call attention to some inaccuracies in Dr. Stratton’s editorial, and to the lay media stories on which it appears to be based.
Ho JD, Cole JB, Klein LR, Olives TD, Driver BE, Moore JC, Nystrom PC, Arens AM, Simpson NS, Hick JL, Chavez RA, Lynch WL, Miner JR. The Hennepin Ketamine Study investigators’ reply. Prehosp Disaster Med. 2019;34(2):111–113
OBJECTIVES/SPECIFIC AIMS: We aimed to develop an assay to measure new protein synthesis after Antisense Oligonucleotide treatment, which we hypothesized to be the earliest biochemical identification of RNA-targeting therapy efficacy. METHODS/STUDY POPULATION: We treated 2 transgenic animal models expressing proteins implicated in neurodegenerative disease: human tau protein (hTau) and human superoxide dismutase 1 (hSOD1), with ASO against these mRNA transcripts. Animals received isotope-labeled 13C6-Leucine via drinking water to label newly synthesized proteins. We assayed target protein synthesis and concentration after ASO treatment to determine the earliest identification of ASO target engagement. RESULTS/ANTICIPATED RESULTS: hTau ASO treatment in transgenic mice lowered hTau protein concentration 23 days post-treatment in cortex (95% CI: 0.05%–64.0% reduction). In the same tissue, we observed lowering of hTau protein synthesis as early as 13 days (95% CI: 29.4%–123%). In hSOD1 transgenic rats, we observed lowering of 13C6-leucine-labeled hSOD1 in the cerebrospinal fluid 30 days after ASO treatment compared with inactive ASO control (95% CI: 12.0%–48.4%). DISCUSSION/SIGNIFICANCE OF IMPACT: In progressive neurodegenerative diseases, it is crucial to develop measurements that identify treatment efficacy early to improve patient outcomes. These data support the use of stable isotope labeling of amino acids to measure new protein synthesis as an early pharmacodynamics measurement for therapies that target RNA and inhibit the translation of proteins.
Mental health support in Sierra Leone is sparse, and qualitative research into the feasibility of implementing psychological interventions is equally underdeveloped. Following the 2014 Ebola virus disease outbreak, South London and Maudsley NHS Trust were commissioned to develop a psychological intervention that UK clinicians could train national staff with minimal psychological experience to deliver to their peers. Following the completion of the stepped care, group-based cognitive–behavioural therapy intervention, qualitative interviews were conducted with the national team to identify key barriers and enablers to implementation of and engagement with this intervention. This article describes the key themes that came out of those interviews, and discusses the implications of these findings for future clinical teams.
A previously unresearched Early Bronze Age dagger-grave found in 1989 at Racton, West Sussex, is profiled here through a range of studies. The dagger, the only grave accompaniment, is of the ‘transitional’ Ferry Fryston type, this example being of bronze rather than copper. Bayesian analysis of relevant radiocarbon dates is used to refine the chronology of the earliest bronze in Britain. While the Ferry Fryston type was current in the earlier half of the twenty-second century bc, the first butt-riveted bronze daggers did not emerge until the second half. The Racton dagger is also distinguished by its elaborate rivet-studded hilt, an insular innovation with few parallels.
The excavated skeleton was that of a senior male, buried according to the appropriate rites of the time. Isotopic profiling shows an animal-protein rich diet that is typical for the period, but also the likelihood that he was brought up in a region of older silicate sedimentary rocks well to the west or north west of Racton. He had suffered injury at or close to the time of death; a slice through the distal end of his left humerus would have been caused by a fine-edged blade, probably a dagger. Death as a result of combat-contested leadership is explored in the light of other injuries documented among Early Bronze Age burials. Codified elite-level combat could help to explain the apparent incongruity between the limited efficacy of early dagger forms and their evident weapon-status.
Angle/action based distribution function (DF) models can be optimised based on how well they reproduce observations thus revealing the current matter distribution in the Milky Way. Gaia data combined with data from other surveys, e.g. the RAVE/TGAS sample, and its full selection function will greatly improve their accuracy.
Green manure crops must produce high biomass to supply biological N, increase organic matter and control weeds. The objectives of our study were to assess above-ground biomass productivity and weed suppression of clover (Trifolium spp.) green manures in an organic soybean [Glycine max (L.) Merr.]-winter wheat (Triticum aestivum L.)-corn (Zea mays L.) rotation in eastern Nebraska in three cycles (2011–12, 2012–13, 2013–14). Treatments were green manure species [red clover (T. pratense L.) and white clover (T. repens L.)] undersown into winter wheat in March and green manure mowing regime (one late summer mowing or no mowing). We measured wheat productivity and grain protein at wheat harvest, and clover and weed above-ground biomass as dry matter (DM) at wheat harvest, 35 days after wheat harvest, in October and in April before clover termination. Winter wheat grain yields and grain protein were not affected by undersown clovers. DM was higher for red than for white clover at most sampling times. Red clover produced between 0.4 and 5.5 Mg ha−1 in the fall and 0.4–5.2 Mg ha−1 in the spring. White clover produced between 0.1 and 2.5 Mg ha−1 in the fall and 0.2–3.1 Mg ha−1 in the spring. Weed DM was lower under red clover than under white clover at most sampling times. In the spring, weed DM ranged from 0.0 to 0.6 Mg ha−1 under red clover and from 0.0 to 3.1 Mg ha−1 under white clover. Mowing did not consistently affect clover or weed DM. For organic growers in eastern Nebraska, red clover undersown into winter wheat can be a productive green manure with good weed suppression potential.
We studied neuroinflammation in individuals with late-life, depression, as a
risk factor for dementia, using [11C]PK11195 positron emission
tomography (PET). Five older participants with major depression and 13
controls underwent PET and multimodal 3T magnetic resonance imaging (MRI),
with blood taken to measure C-reactive protein (CRP). We found significantly
higher CRP levels in those with late-life depression and raised
[11C]PK11195 binding compared with controls in brain regions
associated with depression, including subgenual anterior cingulate cortex,
and significant hippocampal subfield atrophy in cornu ammonis 1 and
subiculum. Our findings suggest neuroinflammation requires further
investigation in late-life depression, both as a possible aetiological
factor and a potential therapeutic target.
This work provides new insights into human responses to and perceptions of sea-level rise at a time when the landscapes of north-west Europe were radically changing. These issues are investigated through a case study focused on the Channel Islands. We report on the excavation of two sites, Canal du Squez in Jersey and Lihou (GU582) in Guernsey, and the study of museum collections across the Channel Islands. We argue that people were drawn to this area as a result of the dynamic environmental processes occurring and the opportunities these created. The evidence suggests that the area was a particular focus during the Middle Mesolithic, when Guernsey and Alderney were already islands and while Jersey was a peninsula of northern France. Insularisation does not appear to have created a barrier to occupation during either the Middle or Final Mesolithic, indicating the appearance of lifeways increasingly focused on maritime voyaging and marine resources from the second half of the 9th millennium BC onwards.
This paper examines the relationship between the presence of symmetry and the Acheulean biface within a predominantly British Lower Palaeolithic context. There has been a long-standing notion within Palaeolithic studies that Acheulean handaxes are symmetrical and become increasingly so as time progress as a reflection of increasing hominin cognitive and behavioural complexity. Specifically, the presence of symmetry within Acheulean handaxes is often seen as one of the first examples of material culture being used to mediate social relationships. However, this notion has never been satisfactorily tested against a large data set. This paper seeks to address the issue by conducting an analysis of some 2680 bifaces across a chronological and geographical span. The results from the sample presented here are that symmetrical bifaces do not appear to have a particularly strong presence in any assemblage and do not appear to increase as time progress. These results have significant implications for modern researchers assessing the cognitive and behavioural complexities of Acheulean hominins.
Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism contributes to the development of depression (major depressive disorder, MDD), but it is unclear whether neural effects observed in healthy individuals are sustained in MDD.
To investigate BDNF Val66Met effects on key regions in MDD neurocircuitry: amygdala, anterior cingulate, middle frontal and orbitofrontal regions.
Magnetic resonance imaging scans were acquired in 79 persons with MDD (mean age 49 years) and 74 healthy volunteers (mean age 50 years). Effects on surface area and cortical thickness were examined with multiple comparison correction.
People who were Met allele carriers showed reduced caudal middle frontal thickness in both study groups. Significant interaction effects were found in the anterior cingulate and rostral middle frontal regions, in which participants in the MDD group who were Met carriers showed the greatest reduction in surface area.
Modulatory effects of the BDNF Val66Met polymorphism on distinct subregions in the prefrontal cortex in MDD support the neurotrophin model of depression.