Coherent elastic neutrino-nucleus scattering: Terrestrial and astrophysical applications

Coherent elastic neutrino-nucleus scattering (CE$\nu$NS) is a process in which neutrinos scatter on a nucleus which acts as a single particle. Though the total cross section is large by neutrino standards, CE$\nu$NS has long proven difficult to detect, since the deposited energy into the nucleus is $\sim$ keV. In 2017, the COHERENT collaboration announced the detection of CE$\nu$NS using a stopped-pion source with CsI detectors, followed up the detection of CE$\nu$NS using an Ar target. The detection of CE$\nu$NS has spawned a flurry of activities in high-energy physics, inspiring new constraints on beyond the Standard Model (BSM) physics, and new experimental methods. The CE$\nu$NS process has important implications for not only high-energy physics, but also astrophysics, nuclear physics, and beyond. This whitepaper discusses the scientific importance of CE$\nu$NS, highlighting how present experiments such as COHERENT are informing theory, and also how future experiments will provide a wealth of information across the aforementioned fields of physics

Coherent elastic neutrino-nucleus scattering: Terrestrial and astrophysical applications

Coherent elastic neutrino-nucleus scattering (CE$\nu$NS) is a process inwhich neutrinos scatter on a nucleus which acts as a single particle. Thoughthe total cross section is large by neutrino standards, CE$\nu$NS has longproven difficult to detect, since the deposited energy into the nucleus is$\sim$ keV. In 2017, the COHERENT collaboration announced the detection ofCE$\nu$NS using a stopped-pion source with CsI detectors, followed up thedetection of CE$\nu$NS using an Ar target. The detection of CE$\nu$NS hasspawned a flurry of activities in high-energy physics, inspiring newconstraints on beyond the Standard Model (BSM) physics, and new experimentalmethods. The CE$\nu$NS process has important implications for not onlyhigh-energy physics, but also astrophysics, nuclear physics, and beyond. Thiswhitepaper discusses the scientific importance of CE$\nu$NS, highlighting howpresent experiments such as COHERENT are informing theory, and also how futureexperiments will provide a wealth of information across the aforementionedfields of physics.<br

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

PolyCert: Polymorphic Self-optimizing Replication for In-Memory Transactional Grids

Part 6: Replication and CachingInternational audienceIn-memory NoSQL transactional data grids are emerging as an attractive alternative to conventional relational distributed databases. In these platforms, replication plays a role of paramount importance, as it represents the key mechanism to ensure data durability. In this work we focus on Atomic Broadcast (AB) based certification replication schemes, which have recently emerged as a much more scalable alternative to classical replication protocols based on active replication or atomic commit protocols. We first show that, among the existing AB-based certification protocols, no “one-fits-all” solution exists that achieves optimal performance in presence of heterogeneous workloads. Next, we present PolyCert, a polymorphic certification protocol that allows for the concurrent coexistence of different certification protocols, relying on machine-learning techniques to determine the optimal certification scheme on a per transaction basis. We design and evaluate two alternative oracles, based on parameter-free machine learning techniques that rely both on off-line and on-line training approaches. Our experimental results demonstrate the effectiveness of the proposed approach, highlighting that PolyCert is capable of achieving a performance extremely close to that of an optimal non-adaptive certification protocol in presence of non heterogeneous workloads, and significantly outperform any non-adaptive protocol when used with realistic, complex applications that generate heterogeneous workloads

JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression

BACKGROUND: Prostate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated as potential oncogenic drivers, the molecular programs contributing to prostate cancer progression are not fully understood. METHODS: We analyzed JUN expression in clinical prostate cancer samples across different stages and investigated its functional role in a Pten-deficient mouse model. We performed histopathological examinations, transcriptomic analyses and explored the senescence-associated secretory phenotype in the tumor microenvironment. RESULTS: Elevated JUN levels characterized early-stage prostate cancer and predicted improved survival in human and murine samples. Immune-phenotyping of Pten-deficient prostates revealed high accumulation of tumor-infiltrating leukocytes, particularly innate immune cells, neutrophils and macrophages as well as high levels of STAT3 activation and IL-1ß production. Jun depletion in a Pten-deficient background prevented immune cell attraction which was accompanied by significant reduction of active STAT3 and IL-1ß and accelerated prostate tumor growth. Comparative transcriptome profiling of prostate epithelial cells revealed a senescence-associated gene signature, upregulation of pro-inflammatory processes involved in immune cell attraction and of chemokines such as IL-1ß, TNF-a, CCL3 and CCL8 in Pten-deficient prostates. Strikingly, JUN depletion reversed both the senescence-associated secretory phenotype and senescence-associated immune cell infiltration but had no impact on cell cycle arrest. As a result, JUN depletion in Pten-deficient prostates interfered with the senescence-associated immune clearance and accelerated tumor growth. CONCLUSIONS: Our results suggest that JUN acts as tumor-suppressor and decelerates the progression of prostate cancer by transcriptional regulation of senescence- and inflammation-associated genes. This study opens avenues for novel treatment strategies that could impede disease progression and improve patient outcomes

International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol

Submitted by Raphael Belchior ([email protected]) on 2020-04-02T13:47:38Z No. of bitstreams: 1 CRIS-IGM - IAM - IFF - International prospective observational.pdf: 600810 bytes, checksum: 8e0c7389346277503afb09ceb41010da (MD5)Approved for entry into archive by Raphael Belchior ([email protected]) on 2020-04-02T14:05:08Z (GMT) No. of bitstreams: 1 CRIS-IGM - IAM - IFF - International prospective observational.pdf: 600810 bytes, checksum: 8e0c7389346277503afb09ceb41010da (MD5)Made available in DSpace on 2020-04-02T14:05:08Z (GMT). No. of bitstreams: 1 CRIS-IGM - IAM - IFF - International prospective observational.pdf: 600810 bytes, checksum: 8e0c7389346277503afb09ceb41010da (MD5) Previous issue date: 2019Social, Statistical and Environmental Sciences, RTI International, Durham, NC, USA.Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis.Centro Nacional de Diagnostico y Referencia, Complejo Nacional de Salud, Managua, Nicaragua.Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, GA, USA.Fundação Oswaldo Cruz. Presidência. Centro de Relações Internacionais em Saúde. Rio de Janeiro, RJ, Brasil.Fundación para la Alimentación y Nutrición de Centro América y Panamá (INCAP), Guatemala City, Guatemala.Section of Nutrition, Pediatrics, University of Colorado, Aurora, CO, USA.Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.Section of Nutrition, Pediatrics, University of Colorado, Aurora, CO, USA.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departmento de Virologia e Terapias Experimentais. Recife, PE, Brasil / School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.Director of Research Institute at Imbanaco Medical Center, Cali, Colombia.Social, Statistical and Environmental Sciences, RTI International, Durham, NC, USA.Programa de Pós-Graduação em Ciências da Saúde (PPGCS) da Universidade de Pernambuco, Microcephaly Epidemic Research Group, Recife, Brazil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.Ribeirão Preto Medical School, Ribeirão Preto, Brazil.Instituto de Medicina Tropical Alexander von Humboldt and Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru.Department of Pathobiological Sciences, University of Wisconsin, Madison, WI, USA.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, 38105, USA.Department of Epidemiology, Harvard Chan School of Public Health, Boston, MA, USA.Social, Statistical and Environmental Sciences, RTI International, Durham, NC, USA.Instituto de Medicina Tropical Alexander von Humboldt and Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru.University of Puerto Rico, San Juan, Puerto Rico.Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, GA, USA.University of Puerto Rico, San Juan, Puerto Rico.Maternal-Infant Studies Center (CEMI), San Juan, Puerto Rico.Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes