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Context Osteopathic manipulative treatment (OMT) has been established as a beneficial and noninvasive treatment option for multiple conditions. With the total number of osteopathic providers tripling and the subsequent increase in osteopathic physician representation, we would expect the clinical use of OMT to increase accordingly. Objectives To that end, we evaluated the utilization and reimbursement of OMT services among Medicare beneficiaries. Methods Current procedural terminology (CPT) codes 98925 to 98929 were accessed from the Center for Medicare and Medicaid Services (CMS) from 2000 to 2019. These codes indicate OMT treatment, 98925 (1–2 body regions treated), 98926 (3–4 body regions treated), 98927 (5–6 body regions treated), 98928 (7–8 body regions treated), and 98929 (9–10 body regions treated). Monetary reimbursement from Medicare was adjusted for inflation, and total code volume was scaled to codes per 10,000 beneficiaries to account for the increase in Medicare enrollment. Results Overall OMT utilization declined between 2000 and 2019 by 24.5%. A significant downward trend in the utilization of CPT codes for OMT involving fewer body regions (98925–98927) was observed, and was contrasted by a slight upward trend in the use of codes for more body regions (98928, 98929). The adjusted sum reimbursement of all codes decreased by 23.2%. Lower value codes showed a higher rate of decline, whereas higher value codes changed less dramatically. Conclusions We conjecture that lower remuneration for OMT has disincentivized physicians financially and may have contributed to the overall decline in OMT utilization among Medicare patients, along with a decreased number of residencies offering specific training in OMT, and increased billing complexity. In considering the upward trend of higher-value code usage, it is possible that some physicians are increasing the comprehensiveness of their physical assessment and associated OMT to reduce the overall financial impact of reimbursement cuts.

Here, we find that cation exchange and metal deposition outcomes are insensitive to either synthetic approach or metal mixture. However, extent and composition of the added metals varies with both metal combination and synthetic approach.

Light driven hydrogen production from the water splitting reaction has the ability to reduce dependence on fossil fuels in a green energy future.

Some of the most devastating crop diseases and insect pests can be transmitted by wind over extremely long distances. These low-probability but high-impact events can have severe consequences for crop production and food security by causing epidemic outbreaks or devastating insect infestations in previously uninfected geographic areas. Two prominent examples that have recently caused substantial damage to agricultural production are novel strains of wheat rusts and desert locust swarm infestations. Whilst quantitative estimates of long-range atmospheric transport events can be obtained using meteorological transport simulations, the exact characteristics of three-dimensional spatiotemporal dynamics of crop pathogen transport and insect flight on extremely large spatial scales, over entire regions and continents, remain largely unknown. Here, we investigate the feasibility and usefulness of new advanced geospatial data visualization methods for studying extremely long-distance airborne transmission of crop pathogens and insect pests. We combine field surveillance data and a Lagrangian Particle Dispersion Model with novel techniques from computer graphics to obtain, for the first time, detailed three-dimensional visual insights into airborne crop pathogen and insect pest transport on regional and continental scales. Visual insights into long-distance dispersal of pests and pathogens are presented as a series of short 3D movies. We use interactive three-dimensional visual data analysis for explorative examination of long-range atmospheric transport events from a selection of outbreak and infestation sites in East Africa and South East Asia. The practical usefulness of advanced 3D visualization methods for improving risk estimates and early warning is discussed in the context of two operational crop disease and insect pest management systems (for wheat rusts and desert locusts). The tools and methods introduced here can be applied to other pathogens, pests, and geographical areas and can improve understanding of risks posed to agricultural production by crop disease and insect pest transmission caused by meteorological extreme events.

Life on Earth anticipates recurring 24-hour environmental cycles via genetically encoded molecular clocks active in all mammalian organs. Communication between these clocks controls circadian homeostasis. Intertissue communication is mediated, in part, by temporal coordination of metabolism. Here, we characterize the extent to which clocks in different organs control systemic metabolic rhythms, an area that remains largely unexplored. We analyzed the metabolome of serum from mice with tissue-specific expression of the clock gene Bmal1. Having functional hepatic and muscle clocks can only drive a minority (13%) of systemic metabolic rhythms. Conversely, limiting Bmal1 expression to the central pacemaker in the brain restores rhythms to 57% of circulatory metabolites. Rhythmic feeding imposed on clockless mice resulted in a similar rescue, indicating that the central clock mainly regulates metabolic rhythms via behavior. These findings explicate the circadian communication between tissues and highlight the importance of the central clock in governing those signals. P.P. was funded by the Wenner-Gren Foundation; the Foundation Blanceflor Boncompagni Ludovisi, née Bildt; and the Tore Nilsson Foundation for Medical Science. Funding for P.S.-C. was provided by the National Institutes of Health (NIH) (AG053592 and DK114652), a Novo Nordisk Foundation Challenge Grant, and Institut National de la Sante et la Recherche Medicale (U1233 INSERM, France). Research in the S.A.B. laboratory is supported partially by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 787041), the Government of Cataluña (SGR grant), the Government of Spain (MINECO), the La Marató/TV3 Foundation, the Foundation Lilliane Bettencourt, the Spanish Association for Cancer Research (AECC), and the Worldwide Cancer Research Foundation (WCRF). The IRB Barcelona is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). P.M.C. acknowledges funding from MICINN-RTI2018-096068, ERC-2016-AdG-741966, LaCaixa-HEALTH-HR17-00040, MDA, UPGRADE-H2020-825825, AFM, DPP-Spain, Fundació La Marató TV3-80/19-202021, MWRF, María-de-Maeztu Program for Units of Excellence to UPF (MDM-2014-0370), and the Severo- Ochoa Program for Centers of Excellence to CNIC (SEV-2015-0505). T.S. was supported by a Japan Society for the Promotion of Science (JSPS) fellowship. C.M.G. was funded by European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 749869. T.M. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754510. P.-S.W. is supported by grant RYC2019-026661-I funded by MCIN/ AEI/10.13039/501100011033 and by “ESF Investing in your future.” We acknowledge predoctoral fellowships to M.C. from the NIH (GM117942), the American Heart Association (17PRE33410952), and the UCI School of Medicine Behrens Research Excellence Award. The work of S.C. and P.B. was, in part, supported by NIH grant NIH GM123558. Sí

OBJECTIVE To estimate the financial burden to the U.S. Army of suicide by enlisted Soldiers during their first year of service. METHODS This analysis included new Army enlisted Soldiers who started initial entry training from October 2012 through September 2016 and subsequently died by suicide within their first year of service. Outpatient and inpatient direct medical, direct nonmedical, recruiting, and training costs to the Army were calculated. RESULTS During the 48-month observational study period, 29 Soldiers died by suicide within their respective first year of service. The described financial costs accrued by the Army as a result of these deaths were $152,271-with an average of $6,091 per healthcare utilizer. Recruiting and training costs were $1,115,860 for all suicide cases. CONCLUSION Average direct cost per healthcare utilizer increased during a Soldier's first year of service. This may be associated with the transition through different phases of training and to the first operational duty station. PUBLIC HEALTH IMPLICATIONS Results obtained through this cost-of-illness analysis may serve as baseline metrics to inform future cost-effectiveness studies.

Facial Hemangiomas are often recommended to be removed exclusively in the operating room under general anesthesia, especially for children under the age of 4. Assumed parental and patient anxiety and possible blood loss pushes surgeons away from attempting excision under local anesthesia.A review was conducted to assess the outcomes of children who underwent excision of facial hemangiomas under local anesthesia alone by 1 plastic surgeon with a minimum of 3 months follow-up. Complications and hemangioma recurrence were recorded. A survey was given 3 to 6 months after treatment to assess parental satisfaction, anxiety, and thought process about anesthesia.Eighteen children (9 males and 9 females) underwent in-office excision between 2020 and 2021. The mean age of this cohort was 12 months ( ranging 2-52 m). The average facial hemangioma size was 2.088 cm (ranging 1.0-3.2 cm). Ten patients experienced complete resolution (56%) at 12-month follow-up. There were no hospitalizations or cases of significant (10 mL) blood loss, infection, dehiscence, hematoma, or scar hypertrophy. The average level of parental anxiety before the procedure was 3.3/10, and 1.6/10 after the procedure. Total 13/14 parents gave 4/4 ratings for satisfaction with the quality of care, team responsiveness, pain management, and management of expectations.Facial hemangioma removal under local anesthesia alone is a safe and feasible alternative treatment method for patients younger than 4 years of age.

Osteoarthritis (OA) of the knee is thought to lead to a loss of lumbar lordosis (LL) as a compensation for knee flexion contracture. Changes in sagittal alignment are not limited to the lumbar spine and involve a complex interplay of alignment of the hip, pelvis, and spine. While spine–hip interactions have been previously explored, the influence of knee OA sagittal alignment parameters on spinopelvic alignment and global sagittal balance remains unexplored. Standing radiological examination using EOS biplanar radiography was examined in 108 patients with knee OA. Whole-body sagittal alignment parameters (thoracic kyphosis, LL, pelvic incidence, pelvic tilt [PT], femoropelvic angle [FPA], femoral tilt angle [FTA], tibial tilt angle, and knee flexion angle [KFA]) and global balance parameters (sagittal vertical axis [SVA] and odontoid hip axis [OD-HA] angle) were measured three dimensionally (3D). The correlation coefficients among all parameters were assessed. A multiple stepwise linear regression model was built to investigate the direct association between SVA or OD-HA angle (dependent variables) and sagittal alignment parameters and demographic data (independent variables). Significant correlations between KFA, FPA, FTA, SVA, and OD-HA angle were found. FTA was correlated with LL and FPA. The FTA was the most influential predictor of both global sagittal balance parameters (p

To perform a retrospective characterization of one-star reviews of ophthalmologists on Yelp.com and to increase understanding of patient complaints on Yelp.com.A search was performed for reviews on Yelp.com using the keyword "ophthalmologist" for the top 8 most population-dense metropolitan areas in the United States. One-star reviews were collected and classified as procedural or nonprocedural. Complaints were also categorized as clinical, nonclinical, or both. Clinical complaints cited issues such as complications, reoperations, uncontrolled pain, misdiagnosis, unclear treatment plan, etc. Nonclinical complaints included comments such as physician bedside manner, other staff interpersonal manner, wait time, brevity of appointment time, etc.5,532 total reviews were assessed, of which 477 (9%) one-star reviews were included in the study for analysis. These reviews amounted to 1,120 distinct complaints. 287 (26%) were clinical in nature and 833 (74%) were nonclinical. Technical incompetence or error (50: 4%), unsatisfactory results (46: 4%), and complications (43: 4%) represented the most common clinical complaints while office staff interpersonal manner (182: 16%), wait time (174: 16%), and physician interpersonal manner (141: 13%) were the most common nonclinical complaints. Refractive surgery was the most frequently mentioned subspecialty (89: 8%). Patients undergoing an ophthalmic procedure (surgery, injection, etc.) wrote 64 reviews that resulted in 193 (17%) complaints. Nonprocedural patients wrote 413 reviews that resulted in 927 (83%) complaints. Compared with procedural reviews, nonprocedural reviews were less likely to include a clinical complaint (rate ratio, 0.3:The majority of one-star reviews of ophthalmologists included in this study were nonclinical. Complaints referencing a procedural episode were more likely to include a clinical component in the review. In the era of intense medical consumerism and increased physician and health care institution competition for patient acquisition and retention, the characterization of excessively negative reviews allows identification of potential areas of concern for patients that use online review sites such as Yelp.com.

A soldier’s first year of military service is a critical period of transition where the risk of suicidal behavior may be increased. This study described time to initial suicide attempts and death b...

Key steps in the functionalization of an unactivated arene often involve its dihaptocoordination by a transition metal followed by insertion into the C-H bond. However, rarely are the η2-arene and aryl hydride species in measurable equilibrium. In this study, the benzene/phenyl hydride equilibrium is explored for the {WTp(NO)(PBu3)} (Bu = n-butyl; Tp = trispyrazoylborate) system as a function of temperature, solvent, ancillary ligand, and arene substituent. Both face-flip and ring-walk isomerizations are identified through spin-saturation exchange measurements, which both appear to operate through scission of a C-H bond. The effect of either an electron-donating or electron-withdrawing substituent is to increase the stability of both arene and aryl hydride isomers. Crystal structures, electrochemical measurements, and extensive NMR data further support these findings. Static density functional theory calculations of the benzene-to-phenyl hydride landscape suggest a single linear sequence for this transformation involving a sigma complex and oxidative cleavage transition state. Static DFT calculations also identified an η2-coordinated benzene complex in which the arene is held more loosely than in the ground state, primarily through dispersion forces. Although a single reaction pathway was identified by static calculations, quasiclassical direct dynamics simulations identified a network of several reaction pathways connecting the η2-benzene and phenyl hydride isomers, due to the relatively flat energy landscape.

Sickle cell disease (SCD) patients require urgent red cell exchange (RCE) procedures for acute chest syndrome (ACS), demanding a coordinated effort of multiple clinical services. Execution of RCE is a multistep process from the time the procedure is requested to the time the procedure is initiated. A retrospective review of patients with SCD requiring urgent RCE for ACS and stroke from 2012 to 2017 was performed at a centralized hemapheresis service covering a multihospital healthcare system. A total of 30 urgent RCE procedures performed on 28 patients were evaluated. The time required for red blood cell (RBC) preparation was the longest step in the process (median 3.8 hours). Furthermore, RBC preparation time was longer for sickle cell patients with RBC alloimmunization compared with nonalloimmunized patients (8.6 vs 3.8 hours, P = .03). One mortality event occurred in Ab- group. This study identified potentially modifiable factors, which impact the time to implementation of RCE in one service area. It highlights the importance of a structured and coordinated approach for the efficient and timely delivery of this vital treatment modality.

The exceptionally π-basic metal fragments {MoTp-(NO)(DMAP)} and {WTp(NO)(PMe(3))} (Tp = tris(pyrazolyl)borate; DMAP = 4-(N,N-dimethylamino)pyridine) form thermally stable η(2)-coordinated complexes with a variety of electron-deficient arenes. The tolerance of substituted arenes with fluorine-containing electron withdrawing groups (EWG; −F, −CF(3), −SF(5)) is examined for both the molybdenum and tungsten systems. When the EWG contains a π bond (nitriles, aldehydes, ketones, ester), η(2) coordination occurs predominantly on the nonaromatic functional group. However, complexation of the tungsten complex with trimethyl orthobenzoate (PhC(OMe)(3)) followed by hydrolysis allows access to an η(2)-coordinated arene with an ester substituent. In general, the tungsten system tolerates sulfur-based withdrawing groups well (e.g., PhSO(2)Ph, MeSO(2)Ph), and the integration of multiple electron-withdrawing groups on a benzene ring further enhances the π-back-bonding interaction between the metal and aromatic ligand. While the molybdenum system did not form stable η(2)-arene complexes with the sulfones or ortho esters, it was capable of forming rare examples of stable η(2)-coordinated arene complexes with a range of fluorinated benzenes (e.g., fluorobenzene, difluorobenzenes). In contrast to what has been observed for the tungsten system, these complexes formed without interference of C–H or C–F insertion.

The hydrogen isotopes deuterium (D) and tritium (T) have become essential tools in chemistry, biology and medicine1. Beyond their widespread use in spectroscopy, mass spectrometry and mechanistic and pharmacokinetic studies, there has been considerable interest in incorporating deuterium into drug molecules1. Deutetrabenazine, a deuterated drug that is promising for the treatment of Huntington's disease2, was recently approved by the United States' Food and Drug Administration. The deuterium kinetic isotope effect, which compares the rate of a chemical reaction for a compound with that for its deuterated counterpart, can be substantial1,3,4. The strategic replacement of hydrogen with deuterium can affect both the rate of metabolism and the distribution of metabolites for a compound5, improving the efficacy and safety of a drug. The pharmacokinetics of a deuterated compound depends on the location(s) of deuterium. Although methods are available for deuterium incorporation at both early and late stages of the synthesis of a drug6,7, these processes are often unselective and the stereoisotopic purity can be difficult to measure7,8. Here we describe the preparation of stereoselectively deuterated building blocks for pharmaceutical research. As a proof of concept, we demonstrate a four-step conversion of benzene to cyclohexene with varying degrees of deuterium incorporation, via binding to a tungsten complex. Using different combinations of deuterated and proteated acid and hydride reagents, the deuterated positions on the cyclohexene ring can be controlled precisely. In total, 52 unique stereoisotopomers of cyclohexene are available, in the form of ten different isotopologues. This concept can be extended to prepare discrete stereoisotopomers of functionalized cyclohexenes. Such systematic methods for the preparation of pharmacologically active compounds as discrete stereoisotopomers could improve the pharmacological and toxicological properties of drugs and provide mechanistic information related to their distribution and metabolism in the body.

Teratoid hepatoblastoma (HB) is a variant of mixed HB described as having a mixture of heterologous components. A 3-year-old boy presented for a liver transplant evaluation due to persistent HB. His liver was biopsied as well as a perirenal mass. Histologic examination demonstrated elements of yolk sac tumor and review of original resection showed a neuroendocrine component. This unique combination of histology has not been reported before in HB. Also, this case presents a unique diagnostic challenge as it presented with a metastasis containing yolk sac elements. Recognition and awareness of this histologic variant are important to accurately identify metastatic lesions.

BACKGROUND: Histologic and molecular differences between primary breast cancer and their subsequent metastases are well-established. Characterization of this heterogeneity may provide important information for both diagnosis and prognosis. Tissue donation via autopsy can aid in characterizing the microenvironment and understanding organ tropism. We describe the implementation, results, and challenges of a cohesive program of post-mortem tissue procurement in patients with breast cancer. METHODS: Prior to formalization of the program, three autopsies were performed without specific operating procedures. In 2016, formal input from patients, their families, clinicians, and pathology technicians helped to operationalize a formal tissue donation program. Ten autopsies have been performed to date. Demographic and clinical data were collected for these patients through retrospective chart reviews. When available, primary tumor tissue and any prior metastasis which were biopsied or surgically resected were acquired from clinical archives at our institution, or requested from outside facilities for future analyses. RESULTS: Between October 2011 and April 2019, autopsies were performed on 1 male and 9 female patients. Time from primary to metastatic disease was an average of 4 years. The median age at the time of death was 56 years (range 37-73). The average time from diagnosis of metastatic disease to consent to autopsy was 30 months. Although the majority of patients died outside the hospital (70%), the mean time between death and the start of autopsy was 4.7 hours. Samples of metastatic tissue were collected in all patients postmortem. There was an average of 16 samples collected from various sites that included both normal and metastatic tissue. The most common sites were the liver (80%), lung (70%), and lymph nodes (70%). Immunohistochemical analysis of metastatic tumors revealed intrapatient heterogeneity in ER, HER2 and Ki67 staining. TABLE 1: CLINICAL COURSE OF PATIENTSN=10 patientsPatients (%)Age at Diagnosis, years (median)46.7 (24.9-57.8)GenderFemale9 (90)Male1 (10)AJCC stage at initial presentationStage 13 (30)Stage 23 (30)Stage 33 (30)Stage 41 (10)Molecular SubtypesHR+/HER 2-6 (60)HR+/HER 2+2 (20)HR-/HER 2-2 (20)HR-/HER 2+0 (0)Time from initial diagnosis to metastatic disease, years (median)4.3 (0-12.8)Tissue of Metastases Obtained While AliveYes4 (40)No6 (60)Median age at time of death, years56.5 (37-73)Total Survival (dx to death), years (median)7.7Metastatic Survival (mets to death), years (median)3.3 TABLE 2: POST MORTEM TISSUE DONATION PROGRAMTime from Metastatic Diagnosis to Consent for Autopsy, months (median)30.3Time from Consent for Autopsy to Death, months (median)10.25Location of DeathHome5 (50)Hospital3 (30)Inpatient Hospice Facility2 (20)Time from death to starting autopsy, hours (median)4.68Time to complete autopsy, hours (median) N=72.82Number of Samples Collected During Autopsy (median)16.2 (3-27)Sites for Metastatic Tissue Procurement Postmortem8 (80)Liver7 (70)Lung7 (70)Lymph Nodes4 (40)Brain4 (40)Ascitic Fluid3 (30)Bone2 (20)Adrenal2 (20)Pericardium2 (20)Pleural Effusion1 (10)Chest Wall1 (10)Gall Bladder1 (10) CONCLUSION: Post-mortem tissue donation programs allow procurement of tissue that would otherwise be inaccessible in the living patient. Histological examination and immunohistochemical assessment of key biomarkers will be used to further characterize the tissue collected ante-mortem and post-mortem. This data combined with the clinical history and longitudinal specimens will help us better understand how intra- and inter-tumor heterogeneity play a role in the clinical course of breast cancer. Also, as we establish the program, we will identify barriers that need to be addressed in order to optimize the process. Citation Format: Tara Hyder, Lori Miller, Jennifer M Atkinson, Zoe Wecht, Ashuvinee Elangovan, Kai Ding, Nolan Priedigkeit, Zheqi Li, Tiantong Liu, Laura Savariau, Fangyuan Chen, Oscar Lopez, Dayne Ashman, Daniel Geisler, Jacob A Smith, Rachel Jankowitz, Priscilla F McAuliffe, Shannon Puhalla, Humberto E Trejo Bittar, Jeffrey S Nine, Peter C Lucas, Adam Brufsky, Steffi Oesterreich, Adrian V Lee, Margaret Rosenzweig. Implementation of a breast cancer post-mortem tissue donation program [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-21-02.

Expressed throughout the body, the circadian clock system achieves daily metabolic homeostasis at every level of physiology, with clock disruption associated with metabolic disease (1, 2). Molecular clocks present in the brain, liver, adipose, pancreas and skeletal muscle each contribute to glucose homeostasis (3). However, it is unclear; 1) which organ clocks provide the most essential contributions, and 2) if these contributions depend on inter-organ communication. We recently showed that the liver clock alone is insufficient for most aspects of daily liver glucose handling and requires connections with other clocks (4). Considering the pathways that link glucose metabolism between liver and skeletal muscle, we sought to test whether a clock connection along this axis is important. Using our previous published methodology for tissue-specific rescue of Bmal1 in vivo (4, 5), we now show that in the absence of feeding-fasting cycles, liver and muscle clocks are not sufficient for systemic glucose metabolism, nor do they form a functional connection influencing local glucose handling or daily transcriptional rhythms in each tissue. However, the introduction of a daily feeding-fasting rhythm enables a synergistic state between liver and muscle clocks that leads to restoration of systemic glucose tolerance. These findings reveal limited autonomous capabilities of liver and muscle clocks and highlight the need for inter-organ clock communication for glucose homeostasis which involves at least two peripheral metabolic organs.

In mammals, an integrated network of molecular oscillators drives daily rhythms of tissue-specific homeostatic processes. This network is required for maintaining health and can be compromised by physiological aging, disease, and lifestyle choices. However, critical elements and properties of this network, such as key signaling nodes, the mechanisms of communication, and how physiological coherence is maintained, remain undefined. To dissect this system, we constructed a minimal clock network comprising only two nodes: the peripheral epidermal clock and the central brain clock. We observe that communication between the brain and epidermal clock is sufficient for wild-type core clock activity and specific homeostatic processes in the epidermis, yet full daily physiology requires input from other clock nodes. Moreover, our results show that the epidermal clock selectively suppresses or interprets systemic signals to ensure coherence of specific homeostatic processes, such as the cell cycle, identifying a previously-unrecognized gatekeeper role for this peripheral clock. This novel approach for dissecting a tissue’s daily physiology reveals the specific rhythmic processes controlled by secondary tissues and niche components, opening the possibility of identifying the sources of age-related circadian disruption and potentially developing therapeutic interventions.

The gut microbiome influences cognition and behavior in mammals, yet its metabolic impact on the brain is only starting to be defined. Using metabolite profiling of antibiotics-treated mice, we reveal the microbiome as a key input controlling circadian metabolic cycles in the brain. Intra and inter-region analyses characterise the influence of the microbiome on the suprachiasmatic nucleus, containing the central clockwork, as well as the hippocampus and cortex, regions involved in learning and behavior.

There is a growing interest in the science uniquely enabled by observations in the MeV range, particularly in light of multi-messenger astrophysics. The Compton Pair (ComPair) telescope, a prototype of the AMEGO Probe-class concept, consists of four subsystems that together detect and characterize gamma rays in the MeV regime. A double-sided strip silicon Tracker gives a precise measure of the first Compton scatter interaction and tracks pair-conversion products. A novel cadmium zinc telluride (CZT) detector with excellent position and energy resolution beneath the Tracker detects the Compton-scattered photons. A thick cesium iodide (CsI) calorimeter contains the high-energy Compton and pair events. The instrument is surrounded by a plastic anti-coincidence (ACD) detector to veto the cosmic-ray background. In this work, we will give an overview of the science motivation and a description of the prototype development and performance.

Background Numerous reports have demonstrated the disproportionate impact that COVID-19 has had on vulnerable populations. Our purpose is to describe our health care system’s response to this impact. Methods We convened a Workgroup with the goal to mitigate the impact of COVID-19 on the most medically vulnerable people in Springfield, Massachusetts, USA, particularly those with significant social needs. We did this through (1) identifying vulnerable patients in high-need geographic areas, (2) developing and implementing a needs assessment/outreach tool tailored to meet cultural, linguistic and religious backgrounds, (3) surveying pharmacies for access to medication delivery, (4) gathering information about sources of food delivery, groceries and/or prepared food, (5) gathering information about means of travel, and (6) assessing need for testing. We then combined these six elements into a patient-oriented branch and a community outreach/engagement branch. Conclusions Our highly intentional and methodical approach to patient and community outreach with a strong geographic component has led to fruitful efforts in COVID-19 mitigation. Our patient-level outreach engages our health centers’ clinical teams, particularly community health workers, and is providing the direct benefit of material and service resources for our at-risk patients and their families. Our community efforts leveraged existing relationships and created new partnerships that continue to inform us—healthcare entities, healthcare employees, and clinical teams—so that we can grow and learn in order to authentically build trust and engagement.

One of the controversial methodological topics in the social and behavioral sciences is the (ab)use of Likert Scale items, Likert-type items and ranked ordered response categories. The debate is whether parametric tests can be legitimately conducted on technically ordinal response categories that are represented with numbers. Participants answered survey questions on moral disengagement, where we changed the intervals of seven response categories and tested whether assigning numbers made any difference in two separate studies. The results showed that participants’ ratings were not significantly different with or without numbers. Participants tend to covertly superimpose numbers where none were provided. Also, there were no significant interactions between assignment of numbers and ‘intervalness’. However, ratings were significantly different between two key interval groups. Knowing the assumptions of respondents to these Likert items even without numbers could inform researchers especially if parametric tests are to be conducted.

Wheat stem rust epidemics caused by the obligate pathogenic fungus Puccinia graminis f.sp. tritici have historically driven severe yield losses on all wheat growing continents and, after many decades of control, stem rust is re-emerging as a disease of concern. In 1998, a highly virulent race able to overcome 90% of world wheat cultivars, Ug99, was identified in Uganda. Since initial detection, the pathogen has evolved many new variants and spread to many countries. The original variant spread from East Africa to the Middle East with three years between detection in Ethiopia and subsequent detection in Yemen. In 2014, another Ug99 variant (TTKTT), with one of the most complex virulence profiles, was detected in Kenya. This variant also spread from East Africa to the Middle East, but with only one year between detection in Ethiopia and subsequent detection in Iraq. Here we investigate potential airborne migration routes to account for the rapid spread of TTKTT in East Africa and beyond to the Middle East by using an integrated model combining the outputs from a meteorology-driven fungal spore dispersion model with epidemiological models to account for seasonal availability of susceptible crops and conditions for spore release and infectivity. We find viable pathways in the 2018/19 season that incorporate critical stepping-stone locations in Yemen or Saudi Arabia, but only in the presence of newly irrigated regions in Ethiopia. Our results indicate the potential and increasing importance of irrigated wheat areas in Ethiopia, Yemen and Saudi Arabia for inter-regional stem rust movements. Future movement of stem rust races out of East Africa is considered likely as irrigated areas expand. Targeted surveillance and the use of mitigation strategies including the use of durable resistant varieties in regions of irrigation are required to reduce the risks of enhanced dispersal of stem rust to other regions.

Investigation of weapons noise exposure outdoors necessitates including the impact of ground reflections. When analyzing the reflections’ impact on A-weighted equivalent level (LAeq), the contribution of the reflected waveform to the total level can often be acceptably modeled using a Friedlander equation-based source model and an ideal reflection based on the measurement geometry. However, the Friedlander model does not adequately model the negative phase of a gunshot waveform, making it inaccurate for locations where the waveform of the direct blast and the waveform of the reflection begin to overlap temporally. This merging of the waveforms for locations where the direct and ground-reflected path length difference is relatively small also makes it difficult to separate the waveforms and calculate the reflected wave’s contribution to noise exposure. As such, this paper investigates different approaches to estimating the contribution of the ground reflected wave to the LAeq, using direct and reflected waveforms in regions where they are well separated and then adjusting timing and amplitude for different geometries where merging takes place. Results reveal regions where the ground reflection contributes negligibly or even negatively to the total LAeq, which is not predicted by the Friedlander model nor by simple energy-addition approaches. [Work supported by Air Force Research Laboratory through Ball Aerospace Technology Corporation.]

Aims The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. Methods and results In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94–30.02, P = 8.05e−11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31–24.87, P, Graphical Abstract Truncating variants in ALPK3 are a cause of 1–2% of autosomal dominant hypertrophic cardiomyopathy and are associated with a phenotype characterized by extensive fibrosis and a predominantly concentric or apical pattern of left ventricular hypertrophy without left ventricular outflow tract obstruction. (A) Main phenotype characteristics and outcomes. ALPK3tv, alpha-protein kinase 3-truncating variants; CK, creatine kinase; HCM, hypertrophic cardiomyopathy; ICD, implantable cardioverter–defibrillator; LVH, left ventricular hypertrophy; LVSD, left ventricular systolic dysfunction; SCD, sudden cardiac death. (B) Cardiac magnetic resonance imaging showing the prevalent phenotype of severe mid to apical hypertrophy and extensive late gadolinium enhancement in three patients. Left to right: 4-chamber view end-diastole cine image, 4-chamber view late gadolinium enhancement image, short axis late gadolinium enhancement image. (C) Kaplan–Meier analysis comparing incidence of an outcome of heart failure death and transplant between ALP3tv patients, sarcomere positive and sarcomere negative. SARC+: sarcomere positive; SARC−: sarcomere negative.