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PURPOSE: To determine the relationship between abdominal hernia and obesity. Although obesity is frequently cited as a risk factor for abdominal hernia, few studies have confirmed this association (Menzo et al. Surg Obes Relat Dis 14:1221-1232. 10.1016/j.soard.2018.07.005, 2018). METHODS: A cross-sectional study of primary care ambulatory patients aged older than 16 years treated at UCLA Health from 01/01/2018 to 06/06/2023. Abdominal hernia was identified by clinic encounter ICD-10 codes (K40-K46). RESULTS: There were 41,703 hernias identified among 1,362,440 patients (306.1 per10,000) with a mean age of 62.5 ± 16.1 years, and 57.6% were men. Nearly half (44.7%) of all abdominal hernias were diaphragmatic. There was an approximately equal distribution of the ventral (28.7%) and inguinal (24.3%) hernia. Each hernia type had a different relationship with obesity: The odds of having a ventral hernia increased with BMI in both sexes: BMI 25-29.9 kg/m2 odds ratio (OR) = 1.65, (CI 1.56-1.74); BMI 30-39.9 kg/m2 OR = 2.42 (CI 2.29-2.56), BMI 40-49.9 kg/m2 OR = 2.28 (CI 2.05-2.54) and BMI >  = 50 kg/m2 OR = 2.54 (CI 2.03-3.17) all relative to normal BMI. In contrast, the odds of having an inguinal hernia decreased with obesity relative to normal weight [obesity (BMI 30-39.9 kg/m2): OR = 0.60 (CI 0.56-0.65)], morbid obesity (BMI 40-49.9 kg/m2): OR = 0.29 (CI 0.23-0.37). The OR for diaphragmatic hernia peaks with obesity in women and overweight status in men but was found to decrease with morbid obesity [OR = 1.18 (CI 1.07-1.30)]. There was no significant difference between men and women in the prevalence of femoral hernia (men: 0.7/per10,000, women: 0.9/per10,000, p = 0.19). CONCLUSIONS: The relationship between hernia and obesity is complex with some hernias decreasing in prevalence as obesity increases. Further research is needed to better understand this paradoxical relationship.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.

Obesity, and the associated metabolic syndrome, is a risk factor for increased disease severity with a variety of infectious agents, including influenza virus. Yet, the mechanisms are only partially understood. As the number of people, particularly children, living with obesity continues to rise, it is critical to understand the role of host status on disease pathogenesis. In these studies, we use a diet-induced obese ferret model and tools to demonstrate that, like humans, obesity resulted in notable changes to the lung microenvironment, leading to increased clinical disease and viral spread to the lower respiratory tract. The decreased antiviral responses also resulted in obese animals shedding higher infectious virus for a longer period, making them more likely to transmit to contacts. These data suggest that the obese ferret model may be crucial to understanding obesitys impact on influenza disease severity and community transmission and a key tool for therapeutic and intervention development for this high-risk population.

The generation of vascular stroma is essential for solid tumor growth and involves stimulatory and inhibiting factors as well as stromal components that regulate functions such as cellular adhesion, migration, and gene expression. In an effort to obtain a more integrated understanding of vascular stroma formation in breast carcinoma, we examined expression of the angiogenic factor vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF); the VPF/VEGF receptors flt-1 and KDR; thrombospondin-1, which has been reported to inhibit angiogenesis; and the stromal components collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin by mRNA in situ hybridization on frozen sections of 113 blocks of breast tissue from 68 patients including 28 sections of breast tissue without malignancy, 18 with in situ carcinomas, 56 with invasive carcinomas, and 8 with metastatic carcinomas. A characteristic expression profile emerged that was remarkably similar in invasive carcinoma, carcinoma in situ, and metastatic carcinoma, with the following characteristics: strong tumor cell expression of VPF/VEGF; strong endothelial cell expression of VPF/VEGF receptors; strong expression of thrombospondin-1 by stromal cells and occasionally by tumor cells; and strong stromal cell expression of collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin. The formation of vascular stroma preceded invasion, raising the possibility that tumor cells invade not into normal breast stroma but rather into a richly vascular stroma that they have induced. Similarly, tumor cells at sites of metastasis appear to induce the vascular stroma in which they grow. We conclude that a distinct pattern of mRNA expression characterizes the generation of vascular stroma in breast cancer and that the formation of vascular stroma may play a role not only in growth of the primary tumor but also in invasion and metastasis.

We report the total and differential cross sections for J/ψ photoproduction with the large acceptance GlueX spectrometer for photon beam energies from the threshold at 8.2 GeV up to 11.44 GeV and over the full kinematic range of momentum transfer squared, t. Such coverage facilitates the extrapolation of the differential cross sections to the forward (t=0) point beyond the physical region. The forward cross section is used by many theoretical models and plays an important role in understanding J/ψ photoproduction and its relation to the J/ψ-proton interaction. These measurements of J/ψ photoproduction near threshold are also crucial inputs to theoretical models that are used to study important aspects of the gluon structure of the proton, such as the gluon generalized parton distribution of the proton, the mass radius of the proton, and the trace anomaly contribution to the proton mass. We observe possible structures in the total cross section energy dependence and find evidence for contributions beyond gluon exchange in the differential cross section close to threshold, both of which are consistent with contributions from open-charm intermediate states.

Astroviruses cause a spectrum of diseases spanning asymptomatic infections to severe diarrhea, but little is understood about their pathogenesis. We previously determined that small intestinal goblet cells were the main cell type infected by murine astrovirus-1. Here, we focused on the host immune response to infection and inadvertently discovered a role for indoleamine 2,3-dioxygenase 1 (Ido1), a host tryptophan catabolizing enzyme, in the cellular tropism of murine and human astroviruses. We identified that Ido1 expression was highly enriched among infected goblet cells, and spatially corresponded to the zonation of infection. Because Ido1 can act as a negative regulator of inflammation, we hypothesized it could dampen host antiviral responses. Despite robust interferon signaling in goblet cells, as well as tuft cell and enterocyte bystanders, we observed delayed cytokine induction and suppressed levels of fecal lipocalin-2. Although we found Ido-/- animals were more resistant to infection, this was not associated with fewer goblet cells nor could it be rescued by knocking out interferon responses, suggesting that IDO1 instead regulates cell permissivity. We characterized IDO1-/- Caco-2 cells and observed significantly reduced human astrovirus-1 infection. Together this study highlights a role for Ido1 in astrovirus infection and epithelial cell maturation.

OBJECTIVES: To correlate preoperative imaging of fecaliths with what is seen in surgical specimens. BACKGROUND: Early studies considered radiological findings of appendicoliths as a contraindication for nonoperative treatment of appendicitis. There is no standard definition for what is labeled as an appendicolith radiologically and little is known about the pathological correlates of these lesions. METHODS: A single center, retrospective study of a consecutive series of adult patients who underwent appendectomy for acute appendicitis from March 2021 to February 2022 was performed. The primary outcome was concordance between preoperative cross-sectional imaging description of appendicolith with postoperative gross pathology description. Images were retrospectively reviewed by an independent radiologist, and the presence and characteristics of appendicoliths and appendices were examined. RESULTS: Of 88 cases of appendicitis, 86 were diagnosed preoperatively by computed tomography (CT) imaging. Appendicoliths were seen either on CT or pathology in 45 (51%) patients. Of these 45 patients, a total of 38 (84%) were identified radiographically, and 28 (62%) were identified on pathology. Of the 38 appendicoliths diagnosed on preoperative imaging, only 21 (55%) were confirmed pathologically. Additionally, of the 28 appendicoliths observed on pathology, only 21 (75%) were identified preoperatively on imaging. There was no appendiceal obstruction in 10 of the 40 cases (25%) in which retrospective radiological review identified appendicoliths. CONCLUSIONS: Discrepancies were observed between CT and pathology findings of appendicoliths. Not all appendicoliths seem to cause appendicitis. Because the presence of appendicolith influences the treatment decisions, there is a need to standardize their radiological diagnosis and better understand their pathophysiology.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic drastically altered children's activity patterns. Our goal was to investigate how COVID-19 affected demographics, injury characteristics, treatment patterns, follow-up, and outcomes in pediatric supracondylar humerus (SCH) fractures.MethodsThis was an Institutional Review Board-approved retrospective analysis of patients undergoing surgery for a SCH fracture from May to November 2019 (pre-COVID-19) and from May to November 2020 (during COVID-19) at 2 tertiary children's hospitals. Demographic information, injury characteristics, hospital course, and follow-up data were collected and compared.ResultsSCH fractures decreased by >50% from 2019 (149) to 2020 (72). Children in the 2020 cohort were younger (mean 5.2 y old) compared with 2019 (6.0 y old) ( P =0.019). Mechanism of injury was significantly different in 2020 ( P

BackgroundSmall bowel obstruction (SBO) is common and its management has evolved in recent years.Study designThe literature describing adhesive small bowel obstruction (aSBO) treatment was reviewed, and a formal systematic review was performed to identify publications reporting results of aSBO treatment without NGTs.ResultsThe annual rate of hospital admission for SBO in the US has increased, with 340,100 admissions in 2019 alone. SBO is usually treated with bowel rest, intravenous hydration and NGT placement. In recent years, water soluble contrast (WSC) has been used as a cathartic to simulate bowel function and may reduce hospital length of stay (HLOS) by 1.95 days (95%CI 0.56-3.3). There were 3 articles of the initial 1650 screened that reported outcomes of SBO treatment without NGTs. These articles included 759 patients, of whom 272 (36%) with aSBO were managed successfully without NGTs. When comparing outcomes to patients who did receive NGT decompression, there were no significant differences in operative rates (28.6% v 16.5%, risk ratio 1.34, 95% CI 1.0, 1.8). Mortality and rates of bowel resection were also not affected by NGT decompression (risk ratio 1.98, 95% CI 0.43, 9.10 and risk ratio 1.56, 95% CI 0.92, 2.65, respectively).ConclusionSBO is a common disease process with increasing annual incidence. Use of WSC stimulates the bowel and may reduce HLOS. Modern aSBO treatment protocols should include NGT decompression with consideration of WSC administration. Selection of patients for treatment without NGT decompression requires further investigation.

BACKGROUND: Recurrence after resection of metastatic sarcoma is common. The gangliosides GM2, GD2 and GD3 are strongly expressed across sarcoma subtypes. We hypothesised that generation of anti-ganglioside antibodies would control micrometastases and improve outcomes in sarcoma patients who were disease-free after metastasectomy. METHODS: We conducted a randomised phase II trial of the immunological adjuvant OPT-821 with a KLH-conjugated ganglioside vaccine targeting GM2, GD2 and GD3, versus OPT-821 alone in patients with metastatic sarcoma following complete metastasectomy. Patients received 10 subcutaneous injections at Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68 and 84 and were followed for evidence of recurrent disease. The primary end-point was relapse-free survival. Secondary end-points included overall survival and serologic response. RESULTS: A total of 136 patients were randomised, 68 to each arm. The mean age was 51.2, 52.2% were male, 90.4% had relapsed disease, 86.8% had high-grade tumours and 14% had ≥4 metastases resected. Histologies included leiomyosarcoma (33%), spindle cell sarcoma (14%), undifferentiated pleomorphic sarcoma (13%), osteosarcoma (10%), synovial sarcoma (9%), liposarcoma (9%) and others (12%). Most adverse events were Grade ≤2 (83.8% and 70.6% in the vaccine and adjuvant arms, respectively). The most common (≥20% of patients) were injection site reaction (89.7%), fatigue (44.1%) and pyrexia (27.9%) on the vaccine arm, and injection site reaction (69.1%) on the adjuvant only arm. The 1-year relapse-free survival rate (34.5% and 34.8% in the vaccine and OPT-821 monotherapy arm, respectively) did not differ between arms (P = 0.725). One-year overall survival rates were 93.1% and 91.5% in the vaccine and OPT-821 monotherapy arm, respectively (P = 0.578). Serologic responses at week 9 were more frequent on the vaccine arm (96.5% of patients) than in the adjuvant arm (32.8%), and the difference between groups was durable. CONCLUSIONS: A sustained serologic response to vaccination was induced with the vaccine, but no difference in recurrence-free or overall survival was observed between treatment arms. CLINICALTRIALS: gov identifier: NCT01141491.

Exploring highly connected networks of qubits is invaluable for implementing various quantum algorithms and simulations. All-to-all connectivity allows for entangling qubits with reduced gate depth. On trapped ion quantum processors, the shared motional degree of freedom is routinely used to simultaneously entangle over a dozen qubits with high fidelity in the Mølmer-Sørensen gate. Here, we demonstrate the first implementation of a Mølmer-Sørensen-like interaction in circuit quantum electrodynamics through assisted by a shared photonic mode and Rabi driven qubits, which relaxes restrictions on qubit frequencies during fabrication and supports scalability. We achieve a two-qubit entangled state with maximum state fidelity or 97% in 310 ns and a three-qubit GHZ state with fidelity 90.5% in 217 ns, and a four-qubit GHZ state with 66% fidelity. The four-qubit gate is limited by shared resonator losses and the spread of qubit-resonator couplings, which must be addressed for high fidelity operations. Exploring highly connected networks of qubits is invaluable for implementing various quantum algorithms and simulations as it allows for entangling qubits with reduced circuit depth. Here, we demonstrate a multi-qubit STAR (Sideband Tone Assisted Rabi driven) gate. Our scheme is inspired by the ion qubit Mølmer-Sørensen gate and is mediated by a shared photonic mode and Rabi-driven superconducting qubits, which relaxes restrictions on qubit frequencies during fabrication and supports scalability. We achieve a two-qubit gate with maximum state fidelity of 95% in 310 ns, a three-qubit gate with state fidelity 90.5% in 217 ns, and a four-qubit gate with state fidelity 66% in 200 ns. Furthermore, we develop a model of the gate that show the four-qubit gate is limited by shared resonator losses and the spread of qubit-resonator couplings, which must be addressed to reach high-fidelity operations.

As superconducting quantum processors increase in complexity, techniques to overcome constraints on frequency crowding are needed. The recently developed method of laser-annealing provides an effective post-fabrication method to adjust the frequency of superconducting qubits. Here, we present an automated laser-annealing apparatus based on conventional microscopy components and demonstrate preservation of highly coherent transmons. In addition, we perform noise spectroscopy to investigate the change in defect features, in particular, two-level system defects, after laser-annealing. Finally, we present a local heating model as well as demonstrate aging stability for laser-annealing on the wafer scale. Our work constitutes an important step toward both understanding the underlying physical mechanism and scaling up laser-annealing of superconducting qubits.

OBJECTIVE: In a large multisite cohort of Veterans who underwent Roux-en-Y gastric bypass (RYGB) or laparoscopic sleeve gastrectomy (LSG), initiation of (ie, incident) and persistence of (ie, continuation of preoperative) depression treatment are compared with matched nonsurgical controls. BACKGROUND: Bariatric surgery has been associated with short-term improvements in depression but less is known about longer term outcomes. METHODS: In a retrospective cohort study, we matched 1713 Veterans with depression treatment who underwent bariatric surgery in Veterans Administration bariatric centers from fiscal year 2001 to 2016 to 15,056 nonsurgical controls using sequential stratification and examined the persistence of depression treatment via generalized estimating equations. Incidence of depression treatment was compared using Cox regression models between 2227 surgical patients and 20,939 matched nonsurgical controls without depression treatment at baseline. RESULTS: In surgical patients with depression treatment at baseline, the use of postsurgical depression treatment declined over time for both surgical procedures, but postsurgical patients had greater use of depression treatment at 5 years [RYGB: odds ratio=1.24, 95% confidence interval (CI): 1.04-1.49; LSG: odds ratio=1.27, 95% CI: 1.04-1.56] compared with controls. Among those without depression treatment at baseline, bariatric surgery was associated with a higher incidence of depression treatment compared with matched controls (RYGB: hazard ratio=1.34, 95% CI: 1.17-1.53; LSG: hazard ratio at 1-5 years=1.27, 95% CI: 1.10-1.47). CONCLUSIONS: Bariatric surgery was associated with a greater risk of postoperative incident depression treatment and greater persistence of postoperative depression treatment. Depression may worsen for some patients after bariatric surgery, so clinicians should carefully monitor their patients for depression postoperatively.

Continuous quantum error correction has been found to have certain advantages over discrete quantum error correction, such as a reduction in hardware resources and the elimination of error mechanisms introduced by having entangling gates and ancilla qubits. We propose a machine learning algorithm for continuous quantum error correction that is based on the use of a recurrent neural network to identify bit-flip errors from continuous noisy syndrome measurements. The algorithm is designed to operate on measurement signals deviating from the ideal behavior in which the mean value corresponds to a code syndrome value and the measurement has white noise. We analyze continuous measurements taken from a superconducting architecture using three transmon qubits to identify three significant practical examples of non-ideal behavior, namely auto-correlation at temporal short lags, transient syndrome dynamics after each bit-flip, and drift in the steady-state syndrome values over the course of many experiments. Based on these real-world imperfections, we generate synthetic measurement signals from which to train the recurrent neural network, and then test its proficiency when implementing active error correction, comparing this with a traditional double threshold scheme and a discrete Bayesian classifier. The results show that our machine learning protocol is able to outperform the double threshold protocol across all tests, achieving a final state fidelity comparable to the discrete Bayesian classifier.

The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases within the National Institutes of Health established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants that could potentially affect the transmission, virulence, and resistance to infection- and vaccine-induced immunity. The SAVE programme is a critical data-generating component of the US Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines and therapeutics, and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models and notable findings facilitated by this collaborative approach and identify future challenges. This programme is a template for the response to rapidly evolving pathogens with pandemic potential by monitoring viral evolution in the human population to identify variants that could reduce the effectiveness of countermeasures.

BackgroundLeukocytosis is a rise in white blood cell (WBC) count and clinical outcomes of moderate to severe leukocytosis in trauma patients have not been described. We hypothesized that trauma patients with severe leukocytosis (SL; ≥40.0 × 109 leukocytes/L) have higher rates of in-hospital complications and mortality than those with moderate leukocytosis (ML; 25.0-39 × 109 leukocytes/L).MethodsWe performed a retrospective analysis (2010-2017) on trauma patients developing ML or SL at a single Level-I trauma center. A multivariable logistic regression analysis for risk factors were performed.ResultsFrom 15,807 trauma admissions, 332 (2.1%) had ML or SL. Of these, 308 (92.8%) were ML and 24 (7.2%) were SL. Patients with ML and SL reached their peak WBC count in 1 and 10 days after admission respectively (p

The storage and processing of quantum information are susceptible to external noise, resulting in computational errors. A powerful method to suppress these effects is quantum error correction. Typically, quantum error correction is executed in discrete rounds, using entangling gates and projective measurement on ancillary qubits to complete each round of error correction. Here we use direct parity measurements to implement a continuous quantum bit-flip correction code in a resource-efficient manner, eliminating entangling gates, ancillary qubits, and their associated errors. An FPGA controller actively corrects errors as they are detected, achieving an average bit-flip detection efficiency of up to 91%. Furthermore, the protocol increases the relaxation time of the protected logical qubit by a factor of 2.7 over the relaxation times of the bare comprising qubits. Our results showcase resource-efficient stabilizer measurements in a multi-qubit architecture and demonstrate how continuous error correction codes can address challenges in realizing a fault-tolerant system.

BackgroundMost people living with dementia want to remain living in their own homes and are supported to do so by family carers. No interventions have consistently demonstrated improvements to people with dementia's life quality, functioning, or other indices of living as well as possible with dementia. We have co-produced, with health and social care professionals and family carers of people with dementia, a new intervention (NIDUS-family). To our knowledge, NIDUS-family is the first manualised intervention that can be tailored to personal goals of people living with dementia and their families and is delivered by facilitators without clinical training. The intervention utilizes components of behavioural management, carer support, psychoeducation, communication and coping skills training, enablement, and environmental adaptations, with modules selected to address dyads' selected goals. We will evaluate the effect of NIDUS-family and usual care on goal attainment, as measured by Goal Attainment Scaling (GAS) rated by family carers, compared to usual care alone at 12-month follow-up. We will also determine whether NIDUS-family and usual care is more cost-effective than usual care alone over 12 months.MethodsA randomised, two-arm, single-masked, multi-site clinical trial involving 297 people living with dementia-family carer dyads. Dyads will be randomised 2:1 to receive the NIDUS-family intervention with usual care (n = 199) or usual care alone (n = 98). The intervention group will be offered, over 1 year, via 6-8 video call or telephone sessions (or face to face if COVID-19 restrictions allow in the recruitment period) in the initial 6 months, followed by telephone follow-ups every 1-2 months to support implementation, with a trained facilitator.DiscussionIncreasing the time lived at home by people living with dementia is likely to benefit lives now and in the future. Our intervention, which we adapted to include remote delivery prior to trial commencement due to the COVID-19 pandemic, aims to address barriers to living as well and as independently as possible that distress people living with dementia, exacerbate family carer(s) stress, negatively affect relationships, lead to safety risks, and frequently precipitate avoidable moves to a care home.Trial registrationInternational Standard Randomised Controlled Trials Number ISRCTN11425138 . Registered on 7 October 2019.

Continuous quantum error correction has been found to have certain advantagesover discrete quantum error correction, such as a reduction in hardwareresources and the elimination of error mechanisms introduced by havingentangling gates and ancilla qubits. We propose a machine learning algorithmfor continuous quantum error correction that is based on the use of a recurrentneural network to identify bit-flip errors from continuous noisy syndromemeasurements. The algorithm is designed to operate on measurement signalsdeviating from the ideal behavior in which the mean value corresponds to a codesyndrome value and the measurement has white noise. We analyze continuousmeasurements taken from a superconducting architecture using three transmonqubits to identify three significant practical examples of non-ideal behavior,namely auto-correlation at temporal short lags, transient syndrome dynamicsafter each bit-flip, and drift in the steady-state syndrome values over thecourse of many experiments. Based on these real-world imperfections, wegenerate synthetic measurement signals from which to train the recurrent neuralnetwork, and then test its proficiency when implementing active errorcorrection, comparing this with a traditional double threshold scheme and adiscrete Bayesian classifier. The results show that our machine learningprotocol is able to outperform the double threshold protocol across all tests,achieving a final state fidelity comparable to the discrete Bayesianclassifier.

BackgroundChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia.MethodsData from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.ResultsIn a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; P

The generation of vascular stroma is essential for solid tumor growth and involves stimulatory and inhibiting factors as well as stromal components that regulate functions such as cellular adhesion, migration, and gene expression. In an effort to obtain a more integrated understanding of vascular stroma formation in breast carcinoma, we examined expression of the angiogenic factor vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF); the VPF/VEGF receptors flt-1 and KDR; thrombospondin-1, which has been reported to inhibit angiogenesis; and the stromal components collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin by mRNA in situ hybridization on frozen sections of 113 blocks of breast tissue from 68 patients including 28 sections of breast tissue without malignancy, 18 with in situ carcinomas, 56 with invasive carcinomas, and 8 with metastatic carcinomas. A characteristic expression profile emerged that was remarkably similar in invasive carcinoma, carcinoma in situ, and metastatic carcinoma, with the following characteristics: strong tumor cell expression of VPF/VEGF; strong endothelial cell expression of VPF/VEGF receptors; strong expression of thrombospondin-1 by stromal cells and occasionally by tumor cells; and strong stromal cell expression of collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin. The formation of vascular stroma preceded invasion, raising the possibility that tumor cells invade not into normal breast stroma but rather into a richly vascular stroma that they have induced. Similarly, tumor cells at sites of metastasis appear to induce the vascular stroma in which they grow. We conclude that a distinct pattern of mRNA expression characterizes the generation of vascular stroma in breast cancer and that the formation of vascular stroma may play a role not only in growth of the primary tumor but also in invasion and metastasis.

The misuse of genomic information has generated considerable concern in American Indian and Alaska Native communities. To understand how issues of genomic research misuse are understood by the public this article focuses on the case brought against Arizona State University by the Havasupai Indian Tribe. To understand how the Havasupai was being framed in the print media, this article examines newspaper articles (N=59) from when the story broke in 2004 until 2019. Our findings suggest that news media rarely engaged the concept of sovereignty and framed the story as an issue of research and scientific ethics.

ObjectiveTo evaluate survival outcomes associated with perioperative allogeneic red blood cell transfusion (RBCT) in patients with pancreatic ductal adenocarcinoma undergoing surgery.MethodsPubMed, Embase, Cochrane, and Web of Science Core Collection were queried for English-language articles until May 28, 2020. Studies evaluating long-term outcomes of RBCT compared with no transfusion in adults with pancreatic ductal adenocarcinoma undergoing pancreatectomy were included. E-value sensitivity analysis assessed the potential for unmeasured confounders to overcome these findings.ResultsOf 4379 citations, 5 retrospective cohort studies were included. Three studies reported shorter recurrence-free survival by 1 to 5 months with RBCT. Two studies found shorter disease-specific survival by 5 to 13 months with RBCT. Overall survival was reduced by 5 to 7 months with RBCT in 3 studies. All multivariable findings associated with RBCT could be readily overcome unmeasured confounding on sensitivity analysis. Confounding in baseline characteristics resulted in high risk of bias.ConclusionsImprecision, unmeasured confounding, small effect sizes, and overall low quality of the available literature result in uncertainty regarding the effect of transfusion on recurrence-free survival, disease-specific survival, and overall survival in patients undergoing surgery for pancreatic cancer. Randomized trials are needed to determine if there is a causal relationship between transfusion and survival after pancreatic resection.

BackgroundTrauma care providers often face a dilemma regarding anticoagulation therapy initiation in patients with traumatic brain injury owing to the associated risks of traumatic brain injury progression. The aims of this study were the following: (1) to describe the current practice of anticoagulation therapy in traumatic brain injury patients and their outcomes and (2) to identify factors associated with the progression of traumatic brain injury after anticoagulation therapy.MethodsIn this multicenter prospective observational study, we included computed tomography-proven traumatic brain injury patients who received anticoagulation therapy within 30 days of hospital admission. Our primary outcome was the incidence of clinically significant progression of traumatic brain injury after anticoagulation therapy initiation.ResultsA total of 168 patients were enrolled more than 22 months. Atrial fibrillation and venous thromboembolism were the most common pre-injury and postinjury anticoagulation therapy indications, respectively. Overall, 16 patients (9.6%) experienced clinically significant traumatic brain injury progression after anticoagulation therapy, out of which 9 (5.4%) patients subsequently required neurosurgical interventions. Between patients with clinical progression of traumatic brain injury and patients who showed no such progression, there were no significant differences in the baseline demographics and severity of traumatic brain injury. However, anticoagulation therapy was initiated significantly earlier in patients of the deterioration group than those of the no-deterioration group (4.5 days vs 11 days, P = .015). In a multiple logistic regression model, patients who received anticoagulation therapy later after injury had significantly lower risk of clinically significant traumatic brain injury progression (odds ratio: 0.915 for each day, 95% confidence interval: 0.841-0.995, P = .037).ConclusionOur results suggest that early anticoagulation therapy is associated with higher risk of traumatic brain injury progression, thus a balance between bleeding and thromboembolic risks should be carefully evaluated in each case before initiating anticoagulation therapy.

We present a transmission spectrum for the warm (500-600 K) sub-Neptune HD 3167c obtained using the Hubble Space Telescope Wide Field Camera 3 infrared spectrograph. We combine these data, which span the 1.125-1.643 μm wavelength range, with broadband transit measurements made using Kepler/K2 (0.6-0.9 μm) and Spitzer/IRAC (4-5 μm). We find evidence for absorption by at least one of H2O, HCN, CO2, and CH4 (Bayes factor 7.4; 2.5σ significance), although the data precision does not allow us to unambiguously discriminate between these molecules. The transmission spectrum rules out cloud-free hydrogen-dominated atmospheres with metallicities ≤100 solar at >5.8σ confidence. In contrast, good agreement with the data is obtained for cloud-free models assuming metallicities >700 solar. However, for retrieval analyses that include the effect of clouds, a much broader range of metallicities (including subsolar) is consistent with the data, due to the degeneracy with cloud-top pressure. Self-consistent chemistry models that account for photochemistry and vertical mixing are presented for the atmosphere of HD 3167c. The predictions of these models are broadly consistent with our abundance constraints, although this is primarily due to the large uncertainties on the latter. Interior structure models suggest that the core mass fraction is >40%, independent of a rock or water core composition, and independent of atmospheric envelope metallicity up to 1000 solar. We also report abundance measurements for 15 elements in the host star, showing that it has a very nearly solar composition.

HD 106315 and GJ 9827 are two bright, nearby stars that host multiple super-Earths and sub-Neptunes discovered by K2 that are well suited for atmospheric characterization. We refined the planets' ephemerides through Spitzer transits, enabling accurate transit prediction required for future atmospheric characterization through transmission spectroscopy. Through a multiyear high-cadence observing campaign with Keck/High Resolution Echelle Spectrometer and Magellan/Planet Finder Spectrograph, we improved the planets' mass measurements in anticipation of Hubble Space Telescope transmission spectroscopy. For GJ 9827, we modeled activity-induced radial velocity signals with a Gaussian process informed by the Calcium II H&K lines in order to more accurately model the effect of stellar noise on our data. We measured planet masses of Mb = 4.87 ± 0.37 M⊕, Mc = 1.92 ± 0.49 M⊕, and Md = 3.42 ± 0.62 M⊕. For HD 106315, we found that such activity radial velocity decorrelation was not effective due to the reduced presence of spots and speculate that this may extend to other hot stars as well (Teff > 6200 K). We measured planet masses of Mb = 10.5 ± 3.1 M⊕ and Mc = 12.0 ± 3.8 M⊕. We investigated all of the planets' compositions through comparison of their masses and radii to a range of interior models. GJ 9827 b and GJ 9827 c are both consistent with a 50/50 rock-iron composition, GJ 9827 d and HD 106315 b both require additional volatiles and are consistent with moderate amounts of water or hydrogen/helium, and HD 106315 c is consistent with a ∼10% hydrogen/helium envelope surrounding an Earth-like rock and iron core.

Case Presentation: A 28-year-old female presented to the emergency department complaining of right lower abdominal pain. A contrast-enhanced computed tomography (CT) was done, which showed a 15-centimeter right adnexal cyst with adjacent “whirlpool sign” concerning for right ovarian torsion. Transvaginal pelvic ultrasound (US) revealed a hemorrhagic cyst in the right adnexa, with duplex Doppler identifying arterial and venous flow in both ovaries. Laparoscopic surgery confirmed right ovarian torsion with an attached cystic mass, and a right salpingo-oophorectomy was performed given the mass was suspicious for malignancy.Discussion: Ultrasound is the test of choice for diagnosis of torsion due to its ability to evaluate anatomy and perfusion. When ovarian pathology is on the patient’s right, appendicitis is high in the differential diagnosis, and CT may be obtained first. Here we describe a case where CT first accurately diagnosed ovarian torsion by demonstrating the whirlpool sign, despite an US that showed arterial flow to the ovary. Future studies should determine whether CT alone is sufficient to diagnose or exclude ovarian torsion.

Case Presentation: A 28-year-old female presented to the emergency department complaining of right lower abdominal pain. A contrast-enhanced computed tomography (CT) was done, which showed a 15-centimeter right adnexal cyst with adjacent “whirlpool sign” concerning for right ovarian torsion. Transvaginal pelvic ultrasound (US) revealed a hemorrhagic cyst in the right adnexa, with duplex Doppler identifying arterial and venous flow in both ovaries. Laparoscopic surgery confirmed right ovarian torsion with an attached cystic mass, and a right salpingo-oophorectomy was performed given the mass was suspicious for malignancy.Discussion: Ultrasound is the test of choice for diagnosis of torsion due to its ability to evaluate anatomy and perfusion. When ovarian pathology is on the patient’s right, appendicitis is high in the differential diagnosis, and CT may be obtained first. Here we describe a case where CT first accurately diagnosed ovarian torsion by demonstrating the whirlpool sign, despite an US that showed arterial flow to the ovary. Future studies should determine whether CT alone is sufficient to diagnose or exclude ovarian torsion.

We present a transmission spectrum for the warm (500-600 K) sub-Neptune HD 3167c obtained using the Hubble Space Telescope Wide Field Camera 3 infrared spectrograph. We combine these data, which span the 1.125-1.643 μm wavelength range, with broadband transit measurements made using Kepler/K2 (0.6-0.9 μm) and Spitzer/IRAC (4-5 μm). We find evidence for absorption by at least one of H2O, HCN, CO2, and CH4 (Bayes factor 7.4; 2.5σ significance), although the data precision does not allow us to unambiguously discriminate between these molecules. The transmission spectrum rules out cloud-free hydrogen-dominated atmospheres with metallicities ≤100 solar at >5.8σ confidence. In contrast, good agreement with the data is obtained for cloud-free models assuming metallicities >700 solar. However, for retrieval analyses that include the effect of clouds, a much broader range of metallicities (including subsolar) is consistent with the data, due to the degeneracy with cloud-top pressure. Self-consistent chemistry models that account for photochemistry and vertical mixing are presented for the atmosphere of HD 3167c. The predictions of these models are broadly consistent with our abundance constraints, although this is primarily due to the large uncertainties on the latter. Interior structure models suggest that the core mass fraction is >40%, independent of a rock or water core composition, and independent of atmospheric envelope metallicity up to 1000 solar. We also report abundance measurements for 15 elements in the host star, showing that it has a very nearly solar composition.

BackgroundSince its release in 2015, the hoverboard has been associated with injuries in children and adolescents. However, its public health implications have yet to be explored in the orthopedic literature across multiple centers.Purpose/questionsWe sought to assess the nature of orthopedic injuries and the use of clinical resources related to the hoverboard at four high-volume, regional pediatric hospitals.MethodsDepartmental databases of emergency department (ED) consultations and urgent orthopedic clinic (UC) visits were queried for hoverboard injuries. A retrospective medical record review was performed for patients presenting over a 3-month period at four institutions. Data on demographics, injuries, clinical course, and resource use were analyzed. The frequency of hoverboard-related consultations was compared to those for monkey bar-related injuries at the primary study institution.ResultsEighty-nine patients with orthopedic hoverboard injuries presented to the ED and/or UC in the study period. Hoverboard injuries represented 2.2% of orthopedic ED consultations at the primary institution, compared to 1.5% for monkey bar injuries. Sixty-nine out of 89 (77.5%) total injuries involved the upper extremity, including 47 (52.8%) distal radius fractures, the most common hoverboard-related diagnosis. All but one injury (97.8%) underwent radiography, and eight (9%) required surgery. No patients reported wearing protective gear at the time of their injury.ConclusionsHoverboards were associated with a variety of pediatric orthopedic injuries and required the use of significant resources in the ED, UC, and operating room. These data may represent a starting point for further prospective multi-center studies and public health efforts toward prevention of hoverboard injuries.

Lessons learnedThe results from the liposarcoma cohort of SARC024 confirm previously published data and do not support the routine use of regorafenib in this patient population. Continued exploration of novel therapies, including combination approaches, is warranted for a patient population in whom limited treatment options exist.BackgroundRegorafenib is a multitargeted kinase inhibitor with a kinase profile overlapping, but distinct from, pazopanib, an agent approved for recurrent and metastatic non-gastrointestinal stromal tumor (GIST), non-adipocytic soft tissue sarcoma. We conducted a randomized, phase II study of regorafenib versus placebo in refractory liposarcoma patients.MethodsPatients with advanced or metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive regorafenib 160 mg or placebo once daily (3 weeks on, 1 week off). Patients with well-differentiated liposarcoma only were excluded. Crossover for placebo was allowed upon progression. The primary endpoint was progression-free survival (PFS), according to RECIST version 1.1.ResultsForty-eight subjects with liposarcoma (34 dedifferentiated, 12 myxoid/round cell, 2 pleomorphic) were enrolled. Median PFS was 1.87 (95% confidence interval [CI], 0.92-3.67) months for regorafenib versus 2.07 (95% CI, 1.64-3.44) months for placebo; stratified hazard ratio [HR], 0.85 (95% CI, 0.46, 1.58), p = .62. No responses were seen on regorafenib. One PR was observed on placebo. Median overall survival was 6.46 (95% CI, 4.16-23.48) months for regorafenib and 4.89 (95% CI, 3.02-9.77) months for placebo, stratified HR, 0.66 (95% CI, 0.31-1.40), p = .28). Treatment-related adverse events were similar to the known safety profile of regorafenib.ConclusionRegorafenib did not appear to improve PFS in treatment-refractory liposarcoma. No new significant safety signals were observed.

Lessons learnedThe results from the liposarcoma cohort of SARC024 confirm previously published data and do not support the routine use of regorafenib in this patient population. Continued exploration of novel therapies, including combination approaches, is warranted for a patient population in whom limited treatment options exist.BackgroundRegorafenib is a multitargeted kinase inhibitor with a kinase profile overlapping, but distinct from, pazopanib, an agent approved for recurrent and metastatic non-gastrointestinal stromal tumor (GIST), non-adipocytic soft tissue sarcoma. We conducted a randomized, phase II study of regorafenib versus placebo in refractory liposarcoma patients.MethodsPatients with advanced or metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive regorafenib 160 mg or placebo once daily (3 weeks on, 1 week off). Patients with well-differentiated liposarcoma only were excluded. Crossover for placebo was allowed upon progression. The primary endpoint was progression-free survival (PFS), according to RECIST version 1.1.ResultsForty-eight subjects with liposarcoma (34 dedifferentiated, 12 myxoid/round cell, 2 pleomorphic) were enrolled. Median PFS was 1.87 (95% confidence interval [CI], 0.92-3.67) months for regorafenib versus 2.07 (95% CI, 1.64-3.44) months for placebo; stratified hazard ratio [HR], 0.85 (95% CI, 0.46, 1.58), p = .62. No responses were seen on regorafenib. One PR was observed on placebo. Median overall survival was 6.46 (95% CI, 4.16-23.48) months for regorafenib and 4.89 (95% CI, 3.02-9.77) months for placebo, stratified HR, 0.66 (95% CI, 0.31-1.40), p = .28). Treatment-related adverse events were similar to the known safety profile of regorafenib.ConclusionRegorafenib did not appear to improve PFS in treatment-refractory liposarcoma. No new significant safety signals were observed.

Healthy sexual function among women service members/veterans (SM/Vs) is associated with higher quality of life, lower incidence and severity of mental health diagnoses, higher relationship satisfaction, and less frequent suicidal ideation. Although trauma exposure has been established as a predictor of poor sexual function and satisfaction in women SM/Vs, no study to date has examined whether specific trauma types, such as military sexual trauma (MST), increase risk for sexual issues. Moreover, the possible mechanisms of this association have not been explored. The current study examined whether posttraumatic stress disorder (PTSD) and depression symptom clusters mediated the association of trauma type and sexual function and satisfaction in 426 trauma-exposed women SM/Vs. Two hundred seventy participants (63.4%) identified MST as their index trauma. Path analyses demonstrated that MST was related to poorer sexual function and lower satisfaction relative to the other traumas (χ2[28, N = 426] = 43.3, p = 0.03, CFI = 1.00, TLI = 0.99, and RMSEA = 0.04), and this association was mediated by higher non-somatic depressive symptoms and PTSD symptom clusters of anhedonia and negative alterations in cognition and mood (NACM). Causality cannot be inferred due to the cross-sectional nature of the data. However, our findings suggest that interventions aimed at decreasing sexual issues among female SM/Vs with MST should target depressogenic symptoms, whether the origin is depression or PTSD. Longitudinal research exploring the etiological processes that contribute to sexual dysfunction among those with MST is needed.

Healthy sexual function among women service members/veterans (SM/Vs) is associated with higher quality of life, lower incidence and severity of mental health diagnoses, higher relationship satisfaction, and less frequent suicidal ideation. Although trauma exposure has been established as a predictor of poor sexual function and satisfaction in women SM/Vs, no study to date has examined whether specific trauma types, such as military sexual trauma (MST), increase risk for sexual issues. Moreover, the possible mechanisms of this association have not been explored. The current study examined whether posttraumatic stress disorder (PTSD) and depression symptom clusters mediated the association of trauma type and sexual function and satisfaction in 426 trauma-exposed women SM/Vs. Two hundred seventy participants (63.4%) identified MST as their index trauma. Path analyses demonstrated that MST was related to poorer sexual function and lower satisfaction relative to the other traumas (χ2[28, N = 426] = 43.3, p = 0.03, CFI = 1.00, TLI = 0.99, and RMSEA = 0.04), and this association was mediated by higher non-somatic depressive symptoms and PTSD symptom clusters of anhedonia and negative alterations in cognition and mood (NACM). Causality cannot be inferred due to the cross-sectional nature of the data. However, our findings suggest that interventions aimed at decreasing sexual issues among female SM/Vs with MST should target depressogenic symptoms, whether the origin is depression or PTSD. Longitudinal research exploring the etiological processes that contribute to sexual dysfunction among those with MST is needed.

BackgroundOpioid analgesics are often prescribed to manage pain after bariatric surgery, which may develop into chronic prescription opioid use (CPOU) in opioid-naïve patients. Bariatric surgery may affect opioid use in those with or without presurgical CPOU.ObjectiveTo compare CPOU persistence and incidence in a large multisite cohort of veterans undergoing bariatric surgery (open Roux-en-Y gastric bypass, laparoscopic RYGB, or laparoscopic sleeve gastrectomy) and matched nonsurgical controls.SettingVeterans Administration hospitals.MethodsIn a retrospective cohort study, we matched 1117 surgical patients with baseline CPOU to 9531 nonsurgical controls, and 2822 surgical patients without CPOU at baseline to 26,392 nonsurgical controls using sequential stratification. CPOU persistence in veterans with baseline CPOU was estimated using generalized estimating equations by procedure type. CPOU incidence in veterans without baseline CPOU was estimated in Cox regression models by procedure type because postoperative pain, complications, and absorption may differ by procedure.ResultsIn veterans with baseline CPOU, postsurgical CPOU declined over time for each surgical procedure; these trends did not differ between surgical patients and nonsurgical controls. In veterans without baseline CPOU, compared with nonsurgical controls, bariatric patients had higher CPOU incidence within 5 years after open Roux-en-Y gastric bypass (hazard ratio = 1.19; 95% confidence interval: 1.06-1.34) or laparoscopic open Roux-en-Y gastric bypass (hazard ratio = 1.22, 95% confidence interval: 1.06-1.41). Veterans undergoing laparoscopic sleeve gastrectomy had higher CPOU incidence 1 to 5 years after surgery (hazard ratio = 1.28; 95% confidence interval: 1.05-1.56) than nonsurgical controls.ConclusionsBariatric surgery was associated with greater risk of CPOU incidence in patients without baseline CPOU but was not associated with greater CPOU persistence.

Background : Ten to fourteen percent of Ewing sarcoma (ES) study participants treated nationwide with IGF-1 receptor (IGF-1R)-targeted antibodies achieved tumor regression. Despite this success, low response rates and short response durations (approximately 7-weeks) have slowed the development of this therapy. Methods: We performed a meta-analysis of five phase-1b/2 ES-oriented trials that evaluated the anticancer activity of IGF-1R antibodies +/- mTOR inhibitors (mTORi). Our meta-analysis provided a head-to-head comparison of the clinical benefits of IGF-1R antibodies vs. the IGF-1R/mTOR-targeted combination. Available pretreatment clinical samples were semi-quantitatively scored using immunohistochemistry to detect proteins in the IGF-1R/PI3K/AKT/mTOR pathway linked to clinical response. Early PET/CT imaging, obtained within the first 2 weeks (median 10 days), were examined to determine if reduced FDG avidity was predictive of progression-free survival (PFS). Results: Among 56 ES patients treated at MD Anderson Cancer Center (MDACC) with IGF-1R antibodies, our analysis revealed a significant ~two-fold improvement in PFS that favored a combination of IGF-1R/mTORi therapy (1.6 vs. 3.3-months, p = 0.042). Low pIGF-1R in the pretreatment specimens was associated with treatment response. Reduced total-lesion glycolysis more accurately predicted the IGF-1R response than other previously reported radiological biomarkers. Conclusion: Synergistic drug combinations, and newly identified proteomic or radiological biomarkers of IGF-1R response, may be incorporated into future IGF-1R-related trials to improve the response rate in ES patients.

We present a transmission spectrum for the Neptune-size exoplanet HD 106315 cfrom optical to infrared wavelengths based on transit observations from theHubble Space Telescope/Wide Field Camera 3, K2, and Spitzer. The spectrum showstentative evidence for a water absorption feature in the $1.1 - 1.7\mu$mwavelength range with a small amplitude of 30 ppm (corresponding to just $0.8\pm 0.04$ atmospheric scale heights). Based on an atmospheric retrievalanalysis, the presence of water vapor is tentatively favored with a Bayesfactor of 1.7 - 2.6 (depending on prior assumptions). The spectrum is mostconsistent with either enhanced metallicity, high altitude condensates, orboth. Cloud-free solar composition atmospheres are ruled out at $>5\sigma$confidence. We compare the spectrum to grids of cloudy and hazy forward modelsand find that the spectrum is fit well by models with moderate cloud lofting orhaze formation efficiency, over a wide range of metallicities ($1 - 100\times$solar). We combine the constraints on the envelope composition with an interiorstructure model and estimate that the core mass fraction is $\gtrsim0.3$. Witha bulk composition reminiscent of that of Neptune and an orbital distance of0.15 AU, HD 106315 c hints that planets may form out of broadly similarmaterial and arrive at vastly different orbits later in their evolution.

As facial recognition systems (FRS) become widely available, a growing number of local governing bodies across the country have adopted these technologies. Without regulating how and when these technologies are used, the adoption of FRS by municipal governments has the potential to violate civil liberties and disproportionately harm marginalized groups. FRS may be an invaluable tool for law enforcement; however, best practices must be adopted to curb their misuse, specifically at the municipal level. We propose that cities considering procurement of FRS create an independent privacy advisory commission with a clear mandate, guaranteed cooperation from local government, technology expertise, and community stakeholder input.

Astroviruses are a global cause of pediatric diarrhea, but they are largely understudied, and it is unclear how and where they replicate in the gut. Using an in vivo model, here we report that murine astrovirus preferentially infects actively secreting small intestinal goblet cells, specialized epithelial cells that maintain the mucus barrier. Consequently, virus infection alters mucus production, leading to an increase in mucus-associated bacteria and resistance to enteropathogenic E. coli colonization. These studies establish the main target cell type and region of the gut for productive murine astrovirus infection. They further define a mechanism by which an enteric virus can regulate the mucus barrier, induce functional changes to commensal microbial communities, and alter host susceptibility to pathogenic bacteria.

BackgroundPrimary care physicians are challenged by the need to stay abreast of current research on a wide variety of topics in an environment of time constraints, evolving literature, and misinformation on health topics that are sometimes promulgated to the public.ObjectiveWe sought to identify and discuss common clinical situations encountered in primary care for which medical reversals have occurred.MethodsWe recently identified almost 400 medical practices that were used in clinical care before they were tested in well-done randomized controlled trials and subsequently were found to be ineffective or harmful.ResultsWe review several of these practices commonly used in family medicine, which include arthroscopy for osteoarthritis of the knee, opioids for common causes of pain, and aspirin and continuous positive airway pressure for the prevention of cardiovascular disease.ConclusionsAlthough these practices were implemented because of sound biologic plausibility or encouraging observational data, well done randomized controlled trials have failed to show evidence of effectiveness. These examples raise caution in introducing new clinical interventions into widespread clinical practice without sufficient high-quality evidence demonstrating efficacy.

K2-19b and c were among the first planets discovered by NASA's K2 mission and together stand in stark contrast with the physical and orbital properties of the solar system planets. The planets are between the size of Uranus and Saturn at 7.0 ± 0.2 R⊕ and 4.1 ± 0.2 R⊕, respectively, and reside a mere 0.1% outside the nominal 3:2 mean-motion resonance. They represent a different outcome of the planet formation process than the solar system, as well as the vast majority of known exoplanets. We measured the physical and orbital properties of these planets using photometry from K2, Spitzer, and ground-based telescopes, along with radial velocities from Keck/HIRES. Through a joint photodynamical model, we found that the planets have moderate eccentricities of e ≈ 0.20 and well-aligned apsides Δπ ≈ 0°. The planets occupy a strictly nonresonant configuration: the resonant angles circulate rather than librate. This defies the predictions of standard formation pathways that invoke convergent or divergent migration, both of which predict Δπ ≈ 180° and eccentricities of a few percent or less. We measured masses of M p,b = 32.4 ± 1.7 M⊕ and M p,c = 10.8 ± 0.6 M⊕. Our measurements, with 5% fractional uncertainties, are among the most precise of any sub-Jovian exoplanet. Mass and size reflect a planet's core/envelope structure. Despite having a relatively massive core of Mcore ≈ 15 M⊕, K2-19b is envelope-rich, with an envelope mass fraction of roughly 50%. This planet poses a challenge to standard models of core-nucleated accretion, which predict that cores ≈10 M⊕ will quickly accrete gas and trigger runaway accretion when the envelope mass exceeds that of the core.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.