Search

We examine the heterogeneity of text-based behavioral interventions in a series of 5 preregistered studies across one in-person and 10 online panels, with over 11000 respondents in total. We observe large heterogeneity across settings and paradigms. Model the heterogeneity we introduce a framework that measures typically omitted moderators: Fluid Intelligence, Attentiveness, Crystallized Intelligence, and Experience. Variation in these factors are associated with different effect sizes and explain variations across samples. Moderators are associated with effect sizes through two paths, with the intensity of the manipulation and with the effect of the manipulation directly. Our results motivate observing these moderators and provide a theoretical and empirical framework for understanding and predicting varying effect sizes in the social sciences.

Background Community active case finding (ACF) for tuberculosis was widely implemented in Europe and North America between 1940 and 1970, when incidence was comparable to many present-day high-burden countries. Using an interrupted time series analysis, we analysed the effect of the 1957 Glasgow mass chest X-ray campaign to inform contemporary approaches to screening. Methods and findings Case notifications for 1950 to 1963 were extracted from public health records and linked to demographic data. We fitted Bayesian multilevel regression models to estimate annual relative case notification rates (CNRs) during and after a mass screening intervention implemented over 5 weeks in 1957 compared to the counterfactual scenario where the intervention had not occurred. We additionally estimated case detection ratios and incidence. From 11 March 1957 to 12 April 1957, 714,915 people (622,349 of 819,301 [76.0%] resident adults [greater than or equal to]15 years) were screened with miniature chest X-ray; 2,369 (0.4%) were diagnosed with tuberculosis. Pre-intervention (1950 to 1956), pulmonary CNRs were declining at 2.3% per year from a CNR of 222/100,000 in 1950. With the intervention in 1957, there was a doubling in the pulmonary CNR (RR: 1.95, 95% uncertainty interval [UI] [1.81, 2.11]) and 35% decline in the year after (RR: 0.65, 95% UI [0.59, 0.71]). Post-intervention (1958 to 1963) annual rates of decline (5.4% per year) were greater (RR: 0.77, 95% UI [0.69, 0.85]), and there were an estimated 4,599 (95% UI [3,641, 5,683]) pulmonary case notifications averted due to the intervention. Effects were consistent across all city wards and notifications declined in young children (0 to 5 years) with the intervention. Limitations include the lack of data in historical reports on microbiological testing for tuberculosis, and uncertainty in contributory effects of other contemporaneous interventions including slum clearances, introduction of BCG vaccination programmes, and the ending of postwar food rationing. Conclusions A single, rapid round of mass screening with chest X-ray (probably the largest ever conducted) likely resulted in a major and sustained reduction in tuberculosis case notifications. Synthesis of evidence from other historical tuberculosis screening programmes is needed to confirm findings from Glasgow and to provide insights into ongoing efforts to successfully implement ACF interventions in today's high tuberculosis burden countries and with new screening tools and technologies., Author(s): Peter MacPherson 1,2,3,*, Helen R. Stagg 4, Alvaro Schwalb 4,5, Hazel Henderson 3, Alice E. Taylor 3, Rachael M. Burke 2, Hannah M. Rickman 2,6, Cecily Miller 7, Rein [...]

ObjectiveCardiac Allograft Vasculopathy (CAV), a process of vascular damage accelerated by antibody-mediated rejection (AMR), is one of the leading causes of cardiac transplant failure. Proteasome inhibitors (PIs) are utilized to treat AMR, however PI-associated toxicity limits their therapeutic utility. Novel immunoproteasome inhibitors (IPIs) have higher specificity for immune cells and have not been investigated for AMR in cardiac transplant patients. We sought to evaluate IPI effect on AMR in a murine cardiac transplant model.MethodsFully MHC mismatched C57BL/6 to huCD52Tg heterotopic heart transplantations were performed. Recipients were treated with alemtuzumab (10 µg, IP) on days −2, −1, 2, and 4 and anti-CD25mAb (PC61, 100 µg, IP) on day 7 to accelerate AMR with or without IPI (ONX-0914,15 mg/kg, SQ), administered on transplant day and three times a week thereafter.ResultsAnimals without IPI gradually developed post-transplant donor-specific antibody (DSA) and showed a significantly elevated DSA level compared to animals receiving IPI. (TFXM 48.86 vs. 14.17; p = 0.0291, BFXM 43.53 vs. 6.114; p = 0.0031). Accordingly, H&E staining of allograft showed reduced evidence of AMR with IPI compared to controls (P = 0.0410). Notably, increased mortality was observed in the IPI treated group.ConclusionThis study demonstrated the ability of ONYX-0914, an IPI, to control post-transplant DSA production and the AMR development in a heart transplant model. However, IPI-resistant DSA production was also observed and increased mortality with IPI therapy raises concerns about potential toxicity. Further investigation is warranted to assess the utility and potential risk associated with the use of IPI as a post-transplant maintenance immunosuppression.

Leonardo Kapural,1 Jim Melton,2 Billy Kim,3 Priyesh Mehta,4 Abindra Sigdel,5 Alexander Bautista,6 Erika A Petersen,7 Konstantin V Slavin,8,9 John Eidt,10 Jiang Wu,11 Said Elshihabi,12 Jason Matthew Schwalb,13 H Edward Garrett Jr,14 Elias Veizi,15 Giancarlo Barolat,16 Ravi R Rajani,17 Peter C Rhee,18 Maged Guirguis,19 Nagy Mekhail20 1Carolinas Pain Institute and Center for Clinical Research, Winston-Salem, NC, USA; 2Department of Vascular Surgery, Cardiovascular Health Clinic, Oklahoma City, OK, USA; 3Department of Vascular Surgery, The Surgical Clinic, Nashville, TN, USA; 4Department of Pain Medicine, Meta Medical Research Institute, Dayton, OH, USA; 5Department of Surgery, University of Louisville, Louisville, KY, USA; 6Department of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY, USA; 7Department of Neurosurgery, University of Arkansas, Little Rock, AR, USA; 8Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL, USA; 9Department of Neurology, Jesse Brown VA Medical Center, Chicago, IL, USA; 10Department of Vascular Surgery, Baylor Scott and White Heart and Vascular Hospital Dallas, Dallas, TX, USA; 11Department of Anesthesiology & Pain Medicine, University of Washington Medical Center, Seattle, WA, USA; 12Department of Neurosurgery, Legacy Brain & Spine Surgical Center, Atlanta, GA, USA; 13Department of Neurosurgery, Henry Ford Medical Group, Detroit, MI, USA; 14Department of Vascular Surgery, University of Tennessee-Memphis, Memphis, TN, USA; 15Department of Pain Medicine, VA Northeast OH Healthcare System, Cleveland, OH, USA; 16Department of Neurosurgery, Barolat Neuroscience, Presbyterian/St Luke’s Medical Center, Denver, CO, USA; 17Department of Vascular Surgery, Emory University and Grady Memorial Hospital, Atlanta, GA, USA; 18Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; 19Department of Interventional Pain Management, Ochsner Health System, New Orleans, LA, USA; 20Department of Pain Management, Cleveland Clinic, Cleveland, OH, USACorrespondence: Leonardo Kapural, Carolinas Pain Institute and Center for Clinical Research, 145 Kimel Park Dr #330, Winston-Salem, NC, 27103, USA, Email lkapuralmd@gmail.comPurpose: This multicenter, randomized, double-blinded, active sham-controlled pivotal study was designed to assess the efficacy and safety of high-frequency nerve block treatment for chronic post-amputation and phantom limb pain.Patients and Methods: QUEST enrolled 180 unilateral lower-limb amputees with severe post-amputation pain, 170 of whom were implanted with the Altius device, were randomized 1:1 to active-sham or treatment groups and reached the primary endpoint. Responders were those subjects who received ≥ 50% pain relief 30 min after treatment in ≥ 50% of their self-initiated treatment sessions within the 3-month randomized period. Differences between the active treatment and sham control groups as well as numerous secondary outcomes were determined.Results: At 30-min, (primary outcome), 24.7% of the treatment group were responders compared to 7.1% of the control group (p=0.002). At 120-minutes following treatment, responder rates were 46.8% in the Treatment group and 22.2% in the Control group (p=0.001). Improvement in Brief Pain Inventory interference score of 2.3 ± 0.29 was significantly greater in treatment group than the 1.3 ± 0.26-point change in the Control group (p = 0.01). Opioid usage, although not significantly different, trended towards a greater reduction in the treatment group than in the control group. The incidence of adverse events did not differ significantly between the treatment and control groups.Conclusion: The primary outcomes of the study were met, and the majority of Treatment patients experienced a substantial improvement in PAP (regardless of meeting the study definition of a responder). The significant in PAP was associated with significantly improved QOL metrics, and a trend towards reduced opioid utilization compared to Control. These data indicate that Altius treatment represents a significant therapeutic advancement for lower-limb amputees suffering from chronic PAP.Keywords: post-amputation pain, phantom limb pain, neuromodulation, peripheral nerve stimulation, high-frequency nerve block

Lipid biomarkers are valuable proxies for reconstructing paleoclimate and paleoenvironmental changes as well as human impact. However, little attention has been paid on evaluating how the combination of biomarkers can be used to reconstruct various aspects of local paleoenvironmental conditions. This study presents a suite of lipid biomarker records from a sediment core from Lake Höglwörth, southern Germany, covering the past 400 years. Compound-specific hydrogen isotopic compositions (δD) of terrestrial n-alkanes (n-C29-alkane) and n-alkanoic acids (n-C30-acid) indicate minor changes in isotopic composition of precipitation. The δD of n-C22-acid is interpreted to record the isotopic composition of the lake water and evaporative enrichment, which drops after 1700 CE, coinciding with the construction of a mill and the related rerouting of a creek into Lake Höglwörth. The δD of n-C25-alkane is also enriched but decoupled from the reconstructed isotopic composition of precipitation and lake water. Therefore, we suggest that δD of n-C25-alkane reflects the leaf water isotopic composition of Sphagnum, which is present in the catchment and undergoes transpirative enrichment. Both short-chain compounds have become more enriched over the last century, maybe related to increasing temperature associated with anthropogenic climate warming. The faecal biomarkers record the changes in human population, partly related to the history of the local Monastery, the World Wars I and II as well as the intensive farming after the mid-20th century. Polycyclic aromatic hydrocarbons (PAHs) reveal a significant change in combustion activities associated with human activities such as the industrial revolution, biomass burning, and environmental cleanup as well as the implementation of emission standards. Our study demonstrates that the combination of plant wax compounds, faecal biomarkers, and PAHs from lacustrine sediment serves as a valuable tool to reconstruct and distinguish various aspects of paleoclimate and paleoenvironmental changes including human impacts.

Researchers and practitioners in marketing, economics, and public policy often use preference elicitation tasks to forecast real-world behaviors. These tasks typically ask a series of similarly structured questions. The authors posit that every time a respondent answers an additional elicitation question, two things happen: (1) they provide information about some parameter(s) of interest, such as their time preference or the partworth for a product attribute, and (2) the respondent increasingly “adapts” to the task—that is, using task-specific decision processes specialized for this task that may or may not apply to other tasks. Importantly, adaptation comes at the cost of potential mismatch between the task-specific decision process and real-world processes that generate the target behaviors, such that asking more questions can reduce external validity. The authors used mouse and eye tracking to trace decision processes in time preference measurement and conjoint choice tasks. Respondents increasingly relied on task-specific decision processes as more questions were asked, leading to reduced external validity for both related tasks and real-world behaviors. Importantly, the external validity of measured preferences peaked after as few as seven questions in both types of tasks. When measuring preferences, less can be more.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb). Following infection, immune responses to Mtb antigens can be measured using the tuberculin skin test or an interferon-γ release assay. The gain of Mtb immunoreactivity, a change from a negative to a positive tuberculin skin test or interferon-γ release assay result, is called conversion and has long been used as a measure of Mtb exposure. However, the loss of immunoreactivity (reversion; a positive followed by a negative result) has often been overlooked. Instead, in clinical and epidemiological circles, Mtb immunoreactivity is commonly considered to persist lifelong and confer a lifetime of disease risk. We present a critical review, describing the evidence for reversion from cohort studies, ecological studies and studies of TB progression risk. We outline the inconsistent reasons why reversion has been dismissed from common understanding and present evidence demonstrating that, just as conversion predominantly indicates prior exposure to Mtb antigens, so its opposite, reversion, suggests the reduction or absence of exposure (endogenous or exogenous). Mtb immunoreactivity is dynamic in both individuals and populations and this is why it is useful for stratifying short-term TB progression risk. The neglect of reversion has shaped TB research and policy at all levels, influencing clinical management and skewing Mtb infection risk estimation and transmission modelling, leading to an underestimation of the contribution of re-exposure to the burden of TB, a serious oversight for an infectious disease. More than a century after it was first demonstrated, it is time to incorporate reversion into our understanding of the natural history of TB.

Anthropogenic activities have exerted strong influence on ecosystems worldwide, particularly since 1950 CE. The local impact of past human activities often started much earlier and deserves detailed study. Here, we present an environmental record from a 278 cm long sedimentary core from Lake Höglwörth (Bavaria, Germany). Sedimentological and geochemical parameters indicate that the organic-rich bottom sediments of the record consist of peat that formed prior to 870-160+140 CE, when lake sediments started to accumulate. After 870-160+140 CE, distinct shifts in lithology, elemental composition, and the biological record are visible and are interpreted to result from the construction of a monastery on the lake peninsula in 1125 CE and/or the damming of the lake. From 1120±120 to 1240-120+110 CE, the lake environment was relatively stable. This period was followed by enhanced deforestation that led to a more open landscape and soil erosion, visible in increased allochthonous input from 1240-120+110 to 1380-110+90 CE. This was accompanied by high aquatic productivity and bottom or interstitial water anoxia from 1310-120+100 to 1470-100+90 CE, possibly triggered by increased nutrient availability. Enhanced allochthonous input and a substantial shift in the aquatic community can be assigned to the construction of a flour mill and related rerouting of a small creek in 1701 CE. High aquatic productivity and bottom or interstitial water anoxia after 1960±10 CE correspond to recent eutrophication resulting from accelerated local anthropogenic activities. The sedimentary record from Lake Höglwörth exemplarily demonstrates that anthropogenic activities have had substantial environmental impacts on aquatic environments during the past millennium.

Relaxed Si1−xGex layers on Si(001) serve as virtual substrates for strained Si or Ge layers. However, plastically relaxed layers inevitably contain misfit and threading dislocations, negatively affecting devices. Deposition of a SiGe layer on the backside of the substrate introduces a dislocation reservoir at the wafer edge that can reduce the threading dislocation density (TDD) of Si0.98Ge0.02/Si layers, as these preexisting dislocations start gliding toward the wafer center upon reaching the critical thickness. Here, we show that this low-strain system can be used effectively to study dislocation glide kinetics. In agreement with the literature, dislocation glide is a thermally activated process with an activation energy of 2.12–2.16 eV. Near the critical thickness, relaxation is sluggish and inefficient due to the linear dependence of the glide velocity on excess stress. At lower growth rates, dislocations from the edge reservoir are activated in a lower density due to the increase in the critical thickness through partial strain relaxation by already activated dislocations. Contrary to common models, here, the lowest possible growth rate is not essential for minimizing the TDD. Instead, a careful balance between low and high growth rates is beneficial. Overcoming the initial sluggish and inefficient relaxation phase is critical while also avoiding accumulation of strain energy, and, therefore, the activation of dislocation sources. Only in a later stage of buffer growth, the growth rate should be reduced to a minimum. With this method, the TDD of strain relaxed Si0.84Ge0.16 layers is reduced to 7 × 104 cm−2. [ABSTRACT FROM AUTHOR]

An international, multidisciplinary research group is proposing the “NICA-BRIDGE” drilling project, within the framework of the International Continental Scientific Drilling Program (ICDP). The project goal is to conduct scientific drilling in Lake Nicaragua and Lake Managua (Nicaragua, Central America) to obtain long lacustrine sediment records to (a) extend the neotropical paleoclimate record back to the Pliocene, making it one of the longest continental tropical climate archives in the world, and to (b) provide geological data on the long-term complex interplay among tectonics, volcanism, sea-level dynamics, climate change, and biosphere. The lakes are the two largest in Central America, and they are located in a trench-parallel half graben that hosts the volcanic front, which developed during or prior to the Pliocene, as a consequence of subduction-related tectonic activity. The lakes are uniquely suited for multidisciplinary scientific investigation as their long, continuous sediment records (several Myr) will facilitate the study of (1) terrestrial and marine basin development at the southern Central American margin, (2) alternating lacustrine and marine environments in response to tectonic and climatic changes, (3) the longest record of tropical climate proxies, (4) the evolution of (and transition between) the Miocene to Pliocene/Pleistocene and Pleistocene to present volcanic arcs, which were separated by slab rollback, (5) the significance of the lakes as hot spots for endemism, and (6) the Great American Biotic Interchange at this strategic location, i.e., the N–S and reverse migration of fauna after the land bridge between the Americas was established. The planned ICDP project offers an opportunity to explore these topics through continent-based seismological, volcanological, paleoclimatological, paleoecological, and paleoenvironmental studies, combined with an International Ocean Discovery Program (IODP) drill project to explore its oceanic continuation. In preparation of this drilling project, an ICDP workshop was held in Montelimar, Nicaragua, on 2–5 March 2020 to develop drilling strategies and refine scientific questions, objectives, and hypotheses. The workshop was organized and hosted by the principal investigators and the Instituto Nicaragüense de Estudios Territoriales (INETER), with funding from the ICDP. Forty-five researchers from 12 countries participated in the workshop, including representatives from ICDP. During the workshop, previous research data on the study lakes, including new recent surveys, were reviewed, and a three-phase strategy for the proposed research was developed. The aim of Phase 0 is to complement the pre-site surveys where we identified the need for further data. In Phase I, with ICDP support, we will obtain sediment cores ∼ 100 m long, which will allow us to investigate many of the scientific questions. Based on the data from those drill cores, coring locations will be identified for a future Phase II, which we envisage as a combined ICDP/IODP project to collect deep drill cores in the lakes and the offshore Sandino Basin in order to extend Phase I results to much deeper time. The Sandino Basin is the oceanic continuation of the depression in which the studied lakes are located, and complementary marine drilling will improve the understanding of the evolution of this complex margin.

We contribute transcriptomic data for two species of Ostracoda, an early-diverged group of small-sized pancrustaceans. Data include new reference transcriptomes for two asexual non-marine species (Dolerocypris sinensis and Heterocypris aff. salina), as well as single-specimen transcriptomic data that served to analyse gene expression across four developmental stages in D. sinensis. Data are evaluated by computing gene expression profiles of the different developmental stages which consistently placed eggs and small larvae (at the stage of instar A-8) similar to each other, and apart from adults which were distinct from all other developmental stages but closest to large larvae (instar A-4). We further evaluated the transcriptomic data with two newly sequenced low-coverage genomes of the target species. The new data thus document the feasibility of obtaining reliable transcriptomic data from single specimens – even eggs – of these small metazoans.

Eukaryotic RNA polymerase II (Pol II) contains a tail-like, intrinsically disordered carboxy-terminal domain (CTD) comprised of heptad-repeats, that functions in coordination of the transcription cycle and in coupling transcription to co-transcriptional processes. The CTD repeat number varies between species and generally increases with genome size, but the reasons for this are unclear. Here, we show that shortening the CTD in human cells to half of its length does not generally change pre-mRNA synthesis or processing in cells. However, CTD shortening decreases the duration of promoter-proximal Pol II pausing, alters transcription of putative enhancer elements, and delays transcription activation after stimulation of the MAP kinase pathway. We suggest that a long CTD is required for efficient enhancer-dependent recruitment of Pol II to target genes for their rapid activation.

Lake Petén Itzá (Guatemala) possesses one of the longest lacustrine sediment records in the northern Neotropics, which enabled study of paleoclimate variability in the region during the last ∼400 000 years. We used geochemical (Ti, Ca/(Ti+Fe) and Mn/Fe) and mineralogical (carbonates, gypsum, quartz, clay) data from sediment core PI-2 to infer past changes in runoff, lake evaporation, organic matter sources and redox conditions in the water column, caused by hydrological changes in the northern Neotropics during Marine Isotope Stages (MISs) 3–2. From 59 to 39 cal ka BP climate conditions were relatively wet, and the lake was marked by higher primary productivity and anoxic bottom waters. This wet environment was interrupted for two periods of possible low water level at 52 and 46 cal ka BP, when our data suggest higher evaporation, high terrestrial organic matter input and persistent oxic conditions. Between 39 and 23 cal ka BP, evaporation and input of terrestrial organic matter increased considerably, lake level declined, and lake bottom waters generally became oxic. These conditions reversed during the Last Glacial Maximum (23.5–18.0 cal ka BP), when runoff and lake productivity increased, and rising lake level caused bottom waters to again become anoxic. Comparison of our hydrologic proxy data with sea surface temperature anomalies between the eastern Pacific and the Caribbean suggests that changes in the intensity of the Caribbean Low-Level Jet (CLLJ) may have influenced long-term changes in runoff during MISs 3–2. Higher intensity of the CLLJ during the onset of MIS 3 and the LGM might have led to greater runoff into the lake, whereas the MIS 3–2 transition experienced a weaker CLLJ and consequently less runoff. A refined, high-resolution age–depth model for the PI-2 sediment core enabled us to identify millennial-scale Greenland interstadials (GIs) 14–2, Greenland stadials (GSs) 14–2 and Heinrich stadials (HSs) 5–1. In general, HSs and GSs were characterized by drier conditions. In contrast to GSs and HSs, GIs were characterized by greater runoff and overall wetter conditions, with the most pronounced GI peaks between 40 and 30 cal ka BP. Whereas GSs 9, 8, 7 and 6 began with abrupt increases in evaporation and ended with gradual increases in humidity, GSs 11 and 10 showed reversed patterns. The Lake Petén Itzá paleohydrology record, along with other regional paleoclimate records, led us to conclude that shifts in the position of the Intertropical Convergence Zone (ITCZ) altered moisture delivery to the lake on millennial timescales. During GSs and HSs, high evaporation from Petén Itzá (dry climate conditions) was associated with a more southerly position of the ITCZ, whereas wetter GIs prevailed during a more northerly ITCZ position. Although abrupt millennial-scale shifts in ITCZ and hydroclimate between GSs/HSs and GIs can be linked to instabilities in the Atlantic Meridional Overturning Circulation (AMOC), longer-term changes were additionally influenced by changes in atmospheric convection linked to modulations of the CLLJ in response to ΔSST between the equatorial Pacific and tropical Atlantic.

(1) Background: To improve the quality of emergency care for children, the Hessian Ministry for Social Affairs and Integration offered paediatric simulation-based training (SBT) for all children’s hospitals in Hesse. We investigated the quality of paediatric life support (PLS) in simulated paediatric resuscitations before and after SBT. (2) Methods: In 2017, a standardised, high-fidelity, two-day in-house SBT was conducted in 11 children’s hospitals. Before and after SBT, interprofessional teams participated in two study scenarios (PRE and POST) that followed the same clinical course of apnoea and cardiac arrest with a shockable rhythm. The quality of PLS was assessed using a performance evaluation checklist. (3) Results: 179 nurses and physicians participated, forming 47 PRE and 46 POST interprofessional teams. Ventilation was always initiated. Before SBT, chest compressions (CC) were initiated by 87%, and defibrillation by 60% of teams. After SBT, all teams initiated CC (p = 0.012), and 80% defibrillated the patient (p = 0.028). The time to initiate CC decreased significantly (PRE 123 ± 11 s, POST 76 ± 85 s, p = 0.030). (4) Conclusions: The quality of PLS in simulated paediatric cardiac arrests with shockable rhythm was poor in Hessian children’s hospitals and improved significantly after SBT. To improve children’s outcomes, SBT should be mandatory for paediatric staff and concentrate on the management of shockable rhythms.