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The nuclear dependence of the inclusive inelastic electron scattering cross section (the EMC effect) has been measured for the first time in B10 and B11. Previous measurements of the EMC effect in A≤12 nuclei showed an unexpected nuclear dependence; B10 and B11 were measured to explore the EMC effect in this region in more detail. Results are presented for Be9, B10, B11, and C12 at an incident beam energy of 10.6 GeV. The EMC effect in the boron isotopes was found to be similar to that for Be9 and C12, yielding almost no nuclear dependence in the EMC effect in the range A=4-12. This represents important new data supporting the hypothesis that the EMC effect depends primarily on the local nuclear environment due to the cluster structure of these nuclei.

BackgroundThe United States Chronic Thromboembolic Pulmonary Hypertension Registry (US-CTEPH-R) was designed to characterize the demographic characteristics, evaluation, clinical course, and outcomes of surgical and nonsurgical therapies for patients with chronic thromboembolic pulmonary hypertension.Research questionWhat are the differences in baseline characteristics and 1-year outcomes between operated and nonoperated subjects?Study design and methodsThis study describes a multicenter, prospective, longitudinal, observational registry of patients newly diagnosed (< 6 months) with CTEPH. Inclusion criteria required a mean pulmonary artery pressure ≥ 25 mm Hg documented by right heart catheterization and radiologic confirmation of CTEPH. Between 2015 and 2018, a total of 750 patients were enrolled and followed up biannually until 2019.ResultsMost patients with CTEPH (87.9%) reported a history of acute pulmonary embolism. CTEPH diagnosis delays were frequent (median, 10 months), and most patients reported World Health Organization functional class 3 status at enrollment with a median mean pulmonary artery pressure of 44 mm Hg. The registry cohort was subdivided into Operable patients undergoing pulmonary thromboendarterectomy (PTE) surgery (n = 566), Operable patients who did not undergo surgery (n = 88), and those who were Inoperable (n = 96). Inoperable patients were older than Operated patients; less likely to be obese; have a DVT history, non-type O blood group, or thrombophilia; and more likely to have COPD or a history of cancer. PTE resulted in a median pulmonary vascular resistance decline from 6.9 to 2.6 Wood units (P < .001) with a 3.9% in-hospital mortality. At 1-year follow-up, Operated patients were less likely treated with oxygen, diuretics, or pulmonary hypertension-targeted therapy compared with Inoperable patients. A larger percentage of Operated patients were World Health Organization functional class 1 or 2 at 1 year (82.9%) compared with the Inoperable (48.2%) and Operable/No Surgery (56%) groups (P < .001).InterpretationDifferences exist in the clinical characteristics between patients who exhibited operable CTEPH and those who were inoperable, with the most favorable 1-year outcomes in those who underwent PTE surgery.Clinical trial registrationClinicalTrials.gov; No.: NCT02429284; URL: www.clinicaltrials.gov.

We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the solar system, exploring the transient optical sky, and mapping the Milky Way. LSST will be a large, wide-field ground-based system designed to obtain repeated images covering the sky visible from Cerro Pachón in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg 2 field of view, a 3.2-gigapixel camera, and six filters (ugrizy) covering the wavelength range 320-1050 nm. The project is in the construction phase and will begin regular survey operations by 2022. About 90% of the observing time will be devoted to a deep-wide-fast survey mode that will uniformly observe a 18,000 deg 2 region about 800 times (summed over all six bands) during the anticipated 10 yr of operations and will yield a co-added map to r ∼27.5. These data will result in databases including about 32 trillion observations of 20 billion galaxies and a similar number of stars, and they will serve the majority of the primary science programs. The remaining 10% of the observing time will be allocated to special projects such as Very Deep and Very Fast time domain surveys, whose details are currently under discussion. We illustrate how the LSST science drivers led to these choices of system parameters, and we describe the expected data products and their characteristics.

BackgroundRare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.MethodsWe did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses.FindingsA locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity.InterpretationThis is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials.FundingUK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR.

Phenotypes of athletic performance and exercise capacity are complex traits influenced by both genetic and environmental factors. This update on the panel of genetic markers (DNA polymorphisms) associated with athlete status summarises recent advances in sports genomics research, including findings from candidate gene and genome-wide association (GWAS) studies, meta-analyses, and findings involving larger-scale initiatives such as the UK Biobank. As of the end of May 2023, a total of 251 DNA polymorphisms have been associated with athlete status, of which 128 genetic markers were positively associated with athlete status in at least two studies (41 endurance-related, 45 power-related, and 42 strength-related). The most promising genetic markers include the AMPD1 rs17602729 C, CDKN1A rs236448 A, HFE rs1799945 G, MYBPC3 rs1052373 G, NFIA-AS2 rs1572312 C, PPARA rs4253778 G, and PPARGC1A rs8192678 G alleles for endurance; ACTN3 rs1815739 C, AMPD1 rs17602729 C, CDKN1A rs236448 C, CPNE5 rs3213537 G, GALNTL6 rs558129 T, IGF2 rs680 G, IGSF3 rs699785 A, NOS3 rs2070744 T, and TRHR rs7832552 T alleles for power; and ACTN3 rs1815739 C, AR ≥21 CAG repeats, LRPPRC rs10186876 A, MMS22L rs9320823 T, PHACTR1 rs6905419 C, and PPARG rs1801282 G alleles for strength. It should be appreciated, however, that elite performance still cannot be predicted well using only genetic testing.

Improvisation is a fundamental aspect of musicianship and an important pursuit in music education. Children in music classes throughout the world are engaged with improvisation in a variety of modes and settings. Whether singing, physically moving, or playing an instrument, the act of improvising in front of others may raise one's self-consciousness, potentially leading to feelings of fear and anxiety. We wish to share guiding principles for improvisation to alleviate many of the associated fears. The establishment of a classroom improvisation culture may breed willful participation and acceptance. When willful participation and acceptance become habitual, the goal of establishing a safe space for students to explore their musical creativity is more readily achieved. A manifestation of the guiding principles is shared in the form of two model improvisation experiences for the general music classroom.

Disrupted in schizophrenia 1 (DISC1) is a multi-functional scaffolding protein that has been associated with neuropsychiatric disease. The role of DISC1 is to assemble protein complexes that promote neural development and signaling, hence tight control of the concentration of cellular DISC1 in neurons is vital to brain function. Using structural and biochemical techniques, we show for we believe the first time that not only is DISC1 turnover elicited by the ubiquitin proteasome system (UPS) but that it is orchestrated by the F-Box protein, FBXW7. We present the structure of FBXW7 bound to the DISC1 phosphodegron motif and exploit this information to prove that disruption of the FBXW7-DISC1 complex results in a stabilization of DISC1. This action can counteract DISC1 deficiencies observed in neural progenitor cells derived from induced pluripotent stem cells from schizophrenia patients with a DISC1 frameshift mutation. Thus manipulation of DISC1 levels via the UPS may provide a novel method to explore DISC1 function.

Shared research infrastructure that is globally distributed and widely accessible has been a hallmark of the networking community. We present a vision for a future mid-scale distributed research infrastructure aimed at enabling new types of discoveries. The “lessons learned” from constructing and operating the Global Environment for Network Innovations (GENI) infrastructure are the basis for our attempt to project future concepts and solutions. Our aim is to engage the community to contribute new ideas and to inform funding agencies about future research directions.

This paper explores whether a diversity and inclusion strategy focused on using modern intelligence tests can assist public safety organizations in hiring a talented diverse workforce. Doing so may offer strategies for mitigating the issues of systematic racism with which these occupations have historically struggled. Past meta-analytic research shows that traditional forms of intelligence tests, which are often used in this sector, have not consistently demonstrated predictive validity but have negatively impacted Black candidates. As an alternative, we examine a modern intelligence test that consists of novel unfamiliar cognitive problems that test takers must solve without relying on their prior experience. Across six studies of varying public safety jobs (e.g., police, firefighter) in different organizations, we found a pattern of results that supports the criterion-related validity of the modern intelligence test. In addition to consistently predicting job performance and training success, the modern intelligence test also substantially mitigated the observed Black–White group differences. The implications of these findings are discussed in terms of how to alter the legacy of I/O psychology and human resource fields when it comes to our impact on facilitating employment opportunities for Black citizens, particularly in public safety positions.

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention-mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P

Skeletal muscle is a heterogenous and metabolically active tissue, the composition of which is associated with multiple traits. The aim of the study was to determine whether there are additional health and exercise-related traits associated with muscle fiber composition in athletes and non-athletes. This study recruited 164 Russian participants (51 endurance and 48 power athletes; 65 controls). Vastus lateralis muscle fiber composition was assessed by immunohistochemistry. Slow-twitch muscle fiber percentage (STMF%) was significantly greater in endurance than power athletes and non-athletes, and in non-athlete females than males. STMF% was positively associated with athletes’ training frequency, non-athletes’ and endurance athletes’ age, endurance athletes’ competition level and chest depth, and power athletes’ training age. STMF% was negatively associated with diastolic blood pressure in power athletes and with systolic blood pressure and reaction time in non-athletes. In all participants, STMF% was positively associated with age, tolerance to long distance exercise, chest depth and fracture incidence, and negatively with systolic blood pressure and resting heart rate. Age, sex and training frequency explained 10.6% and 13.2% of the variance in STMF% in endurance and power athletes, respectively. This is one of the most comprehensive studies involving athletes and untrained subjects and provides novel information concerning associations of increased STMF percentage with lower resting heart rate, better tolerance to long distances, faster reaction time and larger chest depth. On the other hand, the increased percentage of fast-twitch muscle fibers was associated with rare fracture incidence.

David Singer,1 Lindsay GS Bengtson,2 Caitlin Elliott,2 Ami R Buikema,2 Jessica Franchino-Elder1 1Health Economics and Outcomes Research, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 2Health Economics and Outcomes Research, Optum, Eden Prairie, MN, USACorrespondence: David SingerBoehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USATel +1-203-791-6409Email David_2.singer@Boehringer-Ingelheim.comBackground: Chronic obstructive pulmonary disease (COPD) is often managed with inhaled long-acting muscarinic antagonists (LAMAs), yet real-world data on healthcare resource utilization (HRU) by inhaler type are lacking. This study compared HRU after LAMA initiation with a soft mist inhaler (SMI) versus a dry powder inhaler (DPI).Patients and Methods: Inclusion criteria were COPD diagnosis, age ≥ 40 years, LAMA initiation (index date = first LAMA SMI or DPI claim 9/1/14— 6/30/18), and Medicare Advantage enrollment 1 year pre-index (baseline) to ≥ 30 days post-index (follow-up). Patients were followed to the earliest of discontinuation, switch, disenrollment, 1 year, or study end (7/31/18). Exclusion criteria were asthma, cystic fibrosis, or lung cancer diagnoses, unavailable demographics, multiple index LAMAs, or baseline LAMA use. Cohorts (SMI or DPI) were balanced on baseline characteristics using inverse probability of treatment weighting. Outcomes included per patient per month (PPPM) COPD-related HRU encounters, and exacerbations (defined as moderate [ambulatory visit with corticosteroid or antibiotic within ± 7 days] or severe [emergency visit or inpatient admission]); and 30-day readmissions following COPD-related hospitalizations.Results: After weighting, cohorts (SMI [n=5360] and DPI [n=22,880]) were similar in age (72 and 73 years, respectively), gender (both 52% female), and COPD severity score (31.3 and 31.5, respectively). Cohorts had similar counts of follow-up HRU encounters. However, the SMI cohort had fewer (mean ± standard deviation) COPD-related exacerbations (0.054± 0.082 vs DPI cohort 0.059± 0.088 PPPM, p< 0.001) overall. Moreover, the SMI cohort had fewer severe exacerbations (0.030± 0.058 vs DPI: 0.034± 0.065 PPPM, p< 0.001). Hospitalizations among SMI patients had a lower adjusted odds of readmission versus hospitalizations among DPI patients (odds ratio: 0.656, 95% confidence interval= 0.460, 0.937; p=0.020).Conclusion: SMI initiators had significantly fewer COPD-related exacerbations than DPI initiators. In addition, lower odds of readmissions were observed following COPD-related hospitalizations among the SMI cohort, as compared with the DPI cohort.Keywords: chronic obstructive pulmonary disease, COPD, long-acting muscarinic antagonist, LAMA, soft mist inhaler, SMI, dry powder inhaler, DPI, healthcare resource utilization, readmissions, exacerbations

Chad Moretz,1 Beth Hahn,1 John White,2 Alyssa Goolsby Hunter,2 Breanna Essoi,2 Caitlin Elliott,2 Riju Ray3 1US Value Evidence & Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA; 2Optum, Eden Prairie, MN, USA; 3US Medical Affairs, GlaxoSmithKline, Research Triangle Park, NCCorrespondence: Beth HahnGSK, 5 Moore Drive, Research Triangle Park, Durham, NC, USATel +1 919 274 0660Email beth.a.hahn@gsk.comBackground: Long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) provide greater improvements in lung function and symptoms than inhaled corticosteroid (ICS)/LABA in patients with chronic obstructive pulmonary disease (COPD). This study evaluated symptom burden and Global Initiative for Obstructive Lung Disease (GOLD) categorization among patients who recently initiated umeclidinium/vilanterol (UMEC/VI; LAMA/LABA) or fluticasone propionate/salmeterol (FP/SAL; ICS/LABA) single-inhaler dual therapy.Methods: COPD-diagnosed Medicare Advantage enrollees aged ≥ 65 years were identified from the Optum Research Database (ORD). Eligible patients had ≥ 1 pharmacy claim for UMEC/VI or FP/SAL in the 6-month period before sample identification, with no evidence of triple therapy (ICS/LAMA/LABA), asthma, or lung cancer. Symptom burden was assessed via cross-sectional surveys using the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scale. Patients were classified into GOLD categories using patient-reported symptoms and claims-based exacerbation history. Treatment groups were balanced on potential confounders using inverse probability of treatment weighting (IPTW). CAT and mMRC scores were analyzed with generalized linear regression models using IPTW propensity scores.Results: The final analytic sample included 789 respondents (UMEC/VI: N=392; FP/SAL: N=397). Approximately 66% patients were classified as GOLD B when assessing symptoms with CAT and mMRC together, or CAT alone; more patients were classified as GOLD A (∼ 40%) than GOLD B (∼ 36%) using mMRC alone. Proportions of patients in each GOLD group were similar between treatment cohorts. Post-IPTW multivariable modeling showed similar symptom burden between treatment groups.Conclusion: After controlling for baseline characteristics, symptom burden was similar between patients receiving UMEC/VI or FP/SAL. GOLD classification using mMRC produced more conservative results compared with CAT, potentially underestimating patient symptoms. Many patients receiving FP/SAL were classified as GOLD A or B, despite GOLD recommending non-ICS-containing therapy in these patients. These findings support the need for routine assessment of symptoms in patients with COPD.Keywords: COPD, fluticasone propionate/salmeterol, umeclidinium/vilanterol, CAT, mMRC, GOLD group

These days, smartphones are popular commodities among students in high school and college. Students carry their devices all the time, so why not use such a popular electronic device to measure physical quantities such as "g" in physics labs? In this work, we report a "multiple tasking" method, a measurement technique that we came up with, for this very purpose. The method is simple: A person holds a ball using one hand and prepares to activate a recording function using another hand. Then the person drops the metal ball and starts the voice memo simultaneously. The time the ball takes to reach the floor is measured by reviewing the sound amplitude recorded, and the magnitude of "g" is calculated from the time. The error due to the auditory reaction time alone could be about 0.15 s, but we could measure the time in a 0.02-s range at 95% confidence level. A "using sound" technique to measure "g" was introduced before, but given that triggers such as a latch or something equivalent could introduce larger errors due to the device resolutions, we came up with our own.