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LUX-ZEPLIN (LZ) is a second-generation direct dark matter experiment with spin-independent WIMP-nucleon scattering sensitivity above 1.4×10–48 cm2 for a WIMP mass of 40GeV/c2 and a 1000 days exposure. LZ achieves this sensitivity through a combination of a large 5.6 t fiducial volume, active inner and outer veto systems, and radio-pure construction using materials with inherently low radioactivity content. The LZ collaboration performed an extensive radioassay campaign over a period of six years to inform material selection for construction and provide an input to the experimental background model against which any possible signal excess may be evaluated. The campaign and its results are described in this paper. We present assays of dust and radon daughters depositing on the surface of components as well as cleanliness controls necessary to maintain background expectations through detector construction and assembly. Finally, examples from the campaign to highlight fixed contaminant radioassays for the LZ photomultiplier tubes, quality control and quality assurance procedures through fabrication, radon emanation measurements of major sub-systems, and bespoke detector systems to assay scintillator are presented.

LUX-ZEPLIN (LZ) is a second-generation direct dark matter experiment with spin-independent WIMP-nucleon scattering sensitivity above 1.4×10–48 cm2 for a WIMP mass of 40GeV/c2 and a 1000 days exposure. LZ achieves this sensitivity through a combination of a large 5.6 t fiducial volume, active inner and outer veto systems, and radio-pure construction using materials with inherently low radioactivity content. The LZ collaboration performed an extensive radioassay campaign over a period of six years to inform material selection for construction and provide an input to the experimental background model against which any possible signal excess may be evaluated. The campaign and its results are described in this paper. We present assays of dust and radon daughters depositing on the surface of components as well as cleanliness controls necessary to maintain background expectations through detector construction and assembly. Finally, examples from the campaign to highlight fixed contaminant radioassays for the LZ photomultiplier tubes, quality control and quality assurance procedures through fabrication, radon emanation measurements of major sub-systems, and bespoke detector systems to assay scintillator are presented.

Deep underground environments are ideal for low background searches due to the attenuation of cosmic rays by passage through the earth. However, they are affected by backgrounds from \\(\\)-rays emitted by \\(^40\\)K and the \\(^238\\)U and \\(^232\\)Th decay chains in the surrounding rock. The LUX-ZEPLIN (LZ) experiment will search for dark matter particle interactions with a liquid xenon TPC located within the Davis campus at the Sanford Underground Research Facility, Lead, South Dakota, at the 4,850-foot level. In order to characterise the cavern background, in-situ \\(\\)-ray measurements were taken with a sodium iodide detector in various locations and with lead shielding. The integral count rates (0--3300~keV) varied from 596~Hz to 1355~Hz for unshielded measurements, corresponding to a total flux in the cavern of \\(1.90.4\\)~\\(~\\)cm\\(^-2\\)s\\(^-1\\). The resulting activity in the walls of the cavern can be characterised as \\(22060\\)~Bq/kg of \\(^40\\)K, \\(2915\\)~Bq/kg of \\(^238\\)U, and \\(133\\)~Bq/kg of \\(^232\\)Th.

Making informed future decisions about solar radiation modification (SRM; also known as solar geoengineering)—approaches such as stratospheric aerosol injection (SAI) that would cool the climate by reflecting sunlight—requires projections of the climate response and associated human and ecosystem impacts. These projections, in turn, will rely on simulations with global climate models. As with climate-change projections, these simulations need to adequately span a range of possible futures, describing different choices, such as start date and temperature target, as well as risks, such as termination or interruptions. SRMmodeling simulations to date typically consider only a single scenario, often with some unrealistic or arbitrarily chosen elements (such as starting deployment in 2020), and have often been chosen based on scientific rather than policy-relevant considerations (e.g., choosing quite substantial cooling specifically to achieve a bigger response). This limits the ability to compare risks both between SRM and non-SRM scenarios and between different SRM scenarios. To address this gap, we begin by outlining some general considerations on scenario design for SRM. We then describe a specific set of scenarios to capture a range of possible policy choices and uncertainties and present corresponding SAI simulations intended for broad community use.

Abstract Background A national crisis of opioid-related morbidity, mortality, and misuse has led to initiatives to address the appropriate role of opioids to treat pain. Deployment of a guideline from the Centers for Disease Control and Prevention to reduce the risks of opioid therapy has raised substantial clinical and public policy challenges. The agency anticipated implementation challenges and committed to reevaluating the guideline for intended and unintended effects on clinician and patient outcomes. Observations A multidisciplinary expert panel met to review the influence of the core recommendations of the guideline on pain management practices, principally regarding the estimated 5 to 8 million Americans with chronic pain currently on opioids. The panel identified implementation challenges, including application of dosage ceilings and prescription duration guidance, failure to appreciate the importance of patient involvement in decisions to taper or discontinue opioids, barriers to diagnosis and treatment of opioid use disorder, and impeded access to recommended comprehensive, multimodal pain care. Furthermore, policy-making and regulatory bodies may misapply guideline recommendations without flexibility and, sometimes, without full awareness of what the guideline contains. Conclusions and Relevance The panel largely supported the guideline, endorsing its focal points of safety and comprehensive assessment and monitoring. To mitigate clinical and policy challenges identified with implementing the guideline, the panel discussed areas where viewpoints diverged and arrived at consensus proposals. The target audience includes the leaders and institutions that create policy and influence guideline implementation to include regulatory agencies, legislators, public and private payers, and health care systems.

Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a neurons promote male aggression and form synaptic contacts with OA neurons. By restricting the monoamine neuron target population, we show that three previously identified OA-Fru(M) neurons involved in behavioral choice are among the Gr32a-OA connections. Our findings demonstrate that octopaminergic neuromodulatory neurons function as early as a second-order step in this chemosensory-driven male social behavior pathway.

Sepsis is a heterogeneous syndrome and phenotypes have been proposed using clinical data. Less is known about the contribution of protein biomarkers to clinical sepsis phenotypes and their importance for treatment effects in randomized trials of resuscitation. The objective is to use both clinical and biomarker data in the Protocol-Based Care for Early Septic Shock (ProCESS) randomized trial to determine sepsis phenotypes and to test for heterogeneity of treatment effect by phenotype comparing usual care to protocolized early, goal-directed therapy(EGDT). In this secondary analysis of a subset of patients with biomarker sampling in the ProCESS trial (n = 543), we identified sepsis phenotypes prior to randomization using latent class analysis of 20 clinical and biomarker variables. Logistic regression was used to test for interaction between phenotype and treatment arm for 60-day inpatient mortality. Among 543 patients with severe sepsis or septic shock in the ProCESS trial, a 2-class model best fit the data (p = 0.01). Phenotype 1 (n = 66, 12%) had increased IL-6, ICAM, and total bilirubin and decreased platelets compared to phenotype 2 (n = 477, 88%, p < 0.01 for all). Phenotype 1 had greater 60-day inpatient mortality compared to Phenotype 2 (41% vs 16%; p < 0.01). Treatment with EGDT was associated with worse 60-day inpatient mortality compared to usual care (58% vs. 23%) in Phenotype 1 only (p-value for interaction = 0.05). The 60-day inpatient mortality was similar comparing EGDT to usual care in Phenotype 2 (16% vs. 17%). We identified 2 sepsis phenotypes using latent class analysis of clinical and protein biomarker data at randomization in the ProCESS trial. Phenotype 1 had increased inflammation, organ dysfunction and worse clinical outcomes compared to phenotype 2. Response to EGDT versus usual care differed by phenotype.

Past work has suggested that perception of object distances in natural scenes depends on the environmental surroundings, even when the physical object distance remains constant. The cue bases for such effects remain unclear and are difficult to study systematically in real-world settings, given the challenges in manipulating large environmental features reliably and efficiently. Here, we used rendered scenes and crowdsourced data collection to address these challenges. In 4 experiments involving 452 participants, we investigated the effect of room width and depth on egocentric distance judgments. Targets were placed at distances of 2–37 meters in rendered rooms that varied in width (1.5–40 meters) and depth (6–40 meters). We found large and reliable effects of room width: Average judgments for the farthest targets in a 40-meter-wide room were between 16–33% larger than for the same target distances seen in a 1.5-meter-wide hallway. Egocentric distance cues and focal length were constant across room widths, highlighting the role of environmental context in judging distances in natural scenes. Obscuring the fine-grained ground texture, per se, is not primarily responsible for the width effect, nor does linear perspective play a strong role. However, distance judgments tended to decrease when doors and/or walls obscured more distant regions of the scene. We discuss how environmental features may be used to calibrate relative distance cues for egocentric distance judgments.

Background This is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock. Methods Patient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L). Results Totally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08–3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01–6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79–37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54–30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p  = 0.016) and surviving to hospital discharge ( p  = 0.019). Conclusion In the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency.

This double-blind, randomized, controlled trial evaluated rosiglitazone, metformin, and glyburide as an initial treatment in patients with type 2 diabetes. Rosiglitazone reduced the risk of treatment failure (the primary outcome) by 32% as compared with metformin and by 63% as compared with glyburide. The potential risks, benefits, and costs of these medications should all be considered to help inform the choice of pharmacotherapy for patients with type 2 diabetes. In patients with type 2 diabetes, rosiglitazone reduced the risk of treatment failure by 32% as compared with metformin and by 63% as compared with glyburide. The attainment and maintenance of near-normal glycemia reduces the risk of long-term complications of diabetes. 1 – 3 Despite lifestyle and pharmacologic interventions, glucose levels increase over time in type 2 diabetes, probably as a consequence of declining β-cell function. 4 The progressive nature of type 2 diabetes makes it difficult to maintain target levels of glycated hemoglobin with traditional glucose-lowering agents 5 , 6 and generally necessitates the escalation of drug doses and the use of combination therapies or insulin. 7 Thiazolidinediones reduce insulin resistance by sensitizing muscle, liver, and adipose tissue to insulin 8 and delay progression to type 2 diabetes in patients with glucose . . .