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This study resolves a significant impediment to taxonomy of the Neotropical endemic hematophagous candirus by providing the first high-resolution, CT-based osteological descriptions of type and non-type specimens of Paracanthopoma parva, type species of the genus. We also describe the distinctive new species Paravandellia alleynei based on specimens that were previously misidentified as Parac. parva in the only taxonomic study of that species since its 1935 description. Paracanthopoma parva is distinguished from all nominal congeners by its parietosupraoccipital and caudal skeleton morphology and by various meristics, including numbers of median premaxillary teeth, vertebrae, and procurrent and principal caudal-fin rays. Paravandellia alleynei differs from both nominal congeners (Parav. oxyptera, and Parav. phaneronema) by the unique morphology of its maxilla, mesethmoid, and opercular apparatus, relative position of the pelvic- and anal-fin origins, orientation of the opercular odontodes, and by various meristics, including numbers of vertebrae, median premaxillary teeth, medial teeth on premaxilla, branchiostegal rays, opercular and interopercular odontodes, distal claw-like premaxillary teeth, dorsal-fin rays, and dentary teeth. This is the first species of Paravandellia recognized from Guyana and the Essequibo River basin. It is currently known only from two type specimens from the lower Essequibo River basin and 43 non-type specimens from the upper Branco River basin. By providing the first skeletal observations for type specimens of the type species Paracanthopoma parva and for topotypic specimens of all three nominal species of Paravandellia, we clarify and confirm the diagnosis of Parac. parva, and establish a robust foundation for ongoing taxonomic revisions of these two small-sized and species-poor, yet trans-continentally distributed genera, both of which contain considerable unrecognized diversity. This article is protected by copyright. All rights reserved.

Background Guidelines recommend atezolizumab plus nab-paclitaxel (A + nP) for first-line treatment of unresectable, locally advanced, or metastatic triple-negative breast cancer expressing programmed death-ligand 1 (PD-L1) on tumor-infiltrating immune cells (IC), based on IMpassion130. We report the final overall survival (OS) and safety of that study as per the prespecified analysis plan. Patients and methods Patients were randomized to nP 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) with atezolizumab 840 mg (A + nP) or placebo (P + nP; days 1 and 15), until progression or unacceptable toxicity. Coprimary endpoints were progression-free survival [intention-to-treat (ITT) and PD-L1 IC-positive populations] and OS (tested hierarchically in the ITT population and, if significant, in the PD-L1 IC-positive population). Results Each arm comprised 451 patients; 666 (73.8%) had died by the final OS analysis cut-off (median follow-up, 18.8 months; interquartile range, 8.9-34.7 months). Median OS in the ITT population was 21.0 months [95% confidence interval (CI), 19.0-23.4 months] with A + nP, and 18.7 months (95% CI, 16.9-20.8 months) with P + nP [stratified hazard ratio (HR), 0.87; 95% CI, 0.75-1.02; P = 0.077]. Exploratory analysis in the PD-L1 IC-positive population showed a median OS of 25.4 months (95% CI, 19.6-30.7 months) with A + nP (n = 185) and 17.9 months (95% CI, 13.6-20.3 months) with P + nP (n = 184; stratified HR, 0.67; 95% CI, 0.53-0.86). Safety outcomes were consistent with previous analyses and the known toxicity profiles of each agent. Immune-mediated adverse events of special interest were reported in 58.7% and 41.6% of patients treated with A + nP and P + nP, respectively. Conclusion Although the OS benefit in the ITT population was not statistically significant, precluding formal testing, clinically meaningful OS benefit was observed with A + nP in PD-L1 IC-positive patients, consistent with prior interim analyses. This combination remained safe and tolerable with longer follow-up.

Zusammenfassung Hintergrund Mangelernährung bei hospitalisierten Patienten ist ein relevantes Problem unterschätzten Ausmaßes mit negativen Auswirkungen auf das Überleben und den Behandlungserfolg bei einer Vielzahl von chirurgischen Krankheitsbildern. Zwischen dem in Leitlinien definierten Versorgungsanspruch und der klinischen Realität besteht oftmals eine Diskrepanz. Hauptursache ist die mangelhafte Etablierung ernährungsmedizinischer Strukturen als integraler Bestandteil der Regelversorgung im klinischen Alltag. Die notwendige Weiterentwicklung dieser Strukturen ist durch knappe Ressourcen, aber möglicherweise im Einzelfall auch durch mangelndes Problembewusstsein erschwert, sodass Praxisrelevanz und Machbarkeit im Hinblick auf die örtlichen Gegebenheiten die entscheidenden Kriterien für eine nachhaltige Verbesserung sind. Methoden Dargestellt wird am Beispiel eines Großklinikums, welche institutionellen und prozeduralen Maßnahmen zur Implementierung einer ernährungsmedizinischen Gesamtstrategie durchgeführt werden mussten. Es wird in die zugrunde liegende ernährungsmedizinische Methodik eingeführt sowie anhand von 4 Projekten die konkrete Implementierung im klinischen Alltag veranschaulicht. Ergebnisse Mit der hier vorgestellten Systematik konnten an einem Großklinikum innerhalb eines Jahreszeitraumes die Strukturen geschaffen werden, um Malnutrition im stationären Setting zu erfassen, eine ernährungsmedizinische Komplexbehandlung durchführen zu können und durch fortlaufende und zukünftige Projektinitiativen die Ernährungssituation hospitalisierter Patienten fortlaufend zu verbessern. Zusammenfassung Die hier dargestellte, am Universitätsklinikum Bonn erfolgreich eingeführte ernährungsmedizinische Gesamtstrategie kann als Modellerfahrung für Kliniken dienen, die eine Verbesserung der ernährungsmedizinischen Versorgungslage und damit der Behandlungsqualität bei ihren Patienten erwirken wollen.

This descriptive cohort study describes the pilot project of a novel partnership between a university college of nursing and 2 low-income housing organizations serving older adults. The partnership allowed for the creation of onsite primary care clinics eliminating transportation as a barrier to care. Data from intake visits and medical record audits indicated this patient population had a higher prevalence of health disparities, such as more chronic conditions, medications, depression, anxiety, and isolation, than the general United States population older than 65 years. Further research is needed to understand patients’ decision to engage or not engage in services.

Based on the control-value theory of achievement emotions, the study examines elementary school students’ science performance and control-value beliefs (self-concept, intrinsic and achievement valu...

The swelling and solvation of 100-200 nm thin films of a diblock copolymer consisting of a short poly(methyl methacrylate) (PMMA) block and a long poly(N-isopropylacrylamide) (PNIPAM) block are investigated in mixed water/methanol vapors. The processes are followed in real time using spectral reflectance (SR), time-of-flight neutron reflectometry (ToF-NR), and Fourier transform infrared (FT-IR) spectroscopy, applying two neutron scattering contrast variation sequences. After hydration in pure water vapor, the vapor composition (relative to a flow rate of 1 L/min ≙ 100%) is changed to 70% water (D2O/H2O) and 30% methanol (CH3OH/CD3OH). Upon the mixed vapor stimulus, a two-step response is found, in which an initially enhanced swelling of the films is followed by a contraction. Differences in the solvent exchange kinetics found in ToF-NR experiments coincide with characteristic changes in the FT-IR spectra. While the initially enhanced swelling of the films is driven by the absorption of methanol, the film contraction is related to the release of both solvents, with almost no further change in solvent composition. In analogy to the coil-to-globule transition encountered in the polymer solution, these film response characteristics are attributed to the cononsolvency behavior of PNIPAM in water/methanol mixtures.

BACKGROUND The effect of macronutrient composition on total energy expenditure (TEE) remains controversial, with divergent findings among studies. One source of heterogeneity may be study duration, as physiological adaptation to lower carbohydrate intake may require 2 to 3 wk. OBJECTIVE We tested the hypothesis that the effects of carbohydrate [expressed as % of energy intake (EI)] on TEE vary with time. METHODS The sample included trials from a previous meta-analysis and new trials identified in a PubMed search through 9 March 2020 comparing lower- and higher-carbohydrate diets, controlled for EI or body weight. Three reviewers independently extracted data and reconciled discrepancies. Effects on TEE were pooled using inverse-variance-weighted meta-analysis, with between-study heterogeneity assessed using the I2 statistic. Meta-regression was used to quantify the influence of study duration, dichotomized at 2.5 wk. RESULTS The 29 trials ranged in duration from 1 to 140 d (median: 4 d) and included 617 participants. Difference in carbohydrate between intervention arms ranged from 8% to 77% EI (median: 30%). Compared with reported findings in the prior analysis (I2 = 32.2%), we found greater heterogeneity (I2 = 90.9% in the reanalysis, 81.6% in the updated analysis). Study duration modified the diet effect on TEE (P

The article presents my research in psychoanalytic psychopathology on the psychic etiology of psychosis, carried out between 2012 and 2020 at Universidade Federal Fluminense (Volta Redonda, Brazil). In Brazil, patients with various mental disorders rely on the Brazilian Unified Health System which aimed at treatment and psychosocial rehabilitation services. These services are called Psychosocial Care Centers (CAPS). There is an innovation in mental health treatment because they replace the treatment model for mental disorders directed only at hospital admissions. The clinical treatment of mental disorders in CAPS is organized into unique therapeutic projects. It is characterized by a multidisciplinary team in an open, non-hospital environment, close to the patient’s place of residence. Since 1996, the SUS-Brazil diagnostic guidelines are used to conduct epidemiological studies, formulate public policies on mental health, and establish its funding for the mental health network. These manuals ignore the presence of etiological factors of a psychological nature and exclude the theoretical framework in the definition of disorders. The absence of consideration of etiological factors and the exclusion of theoretical frameworks is evident in the way the DSM-5 defines the spectrum of schizophrenia, resulting in the predominance of schizophrenia in the clarification of psychotic disorders and, consequently, in the weakening of the classic category of psychosis. My research aims to contribute to psychosis by examining the role of delusion in the onset of psychosis, triggering events, and stabilizing the psychotic structure. This article aims to present the hypothesis of the psychic etiology of psychosis from the contributions of Sigmund Freud. This theorizing is significant as it introduces the hypothesis of loss, restitution, and recovery into the psychiatric lexicon of the opposition between schizophrenia and paranoia. To this end, this article exhibits a survey of Freudian references to emphasize the construction of an original theory of psychosis, where: 1) The consideration of the functioning of drives is relevant in isolating psychic etiology from its triggers; 2) A redefinition of the concept of delusion signals the originality of the Freudian theory of the stabilization of psychoses: delusion is defined as a psychic effort of recovery, an attempt at reaching a cure.

O Diabetes Mellitus (DM) afeta 415 milhões de indivíduos no mundo e 14,3 milhões no Brasil. Sabe-se que alimentos ricos em fibras alimentares têm papel fundamental no controle da glicemia sanguínea. Avaliar a influência do conhecimento sobre a importância da ingestão de fibras e sua frequência de consumo no controle do DM. A população foi composta por diabéticos tipo 2 que frequentam uma Unidade de Saúde Escola de Itajaí/SC. A coleta de dados foi realizada por entrevista contendo questões referentes às características socioeconômicas, conhecimentos e frequência de consumo de fibras. O controle do DM foi avaliado através da Hemoglobina Glicada (HbA1c). A população constituiu-se de 22 pessoas, sendo a maioria do sexo feminino (n=15; 68%), com idade média de 60 (±9,3) anos, e com no máximo 9 (±3,4) anos de estudo. A média de consumo semanal de legumes e saladas foi de oito porções (± 4,5), enquanto as frutas foram citadas em 14 vezes na semana e os cereais integrais, sete vezes. Quando questionados sobre a capacidade das fibras de prevenir e tratar o diabetes, 86% (n=19) dos pacientes concordaram com a afirmação. Encontrou-se tempo médio de diagnóstico de 9 (± 7) anos e média de HbA1c de 8% (± 2). Observou-se conhecimento insuficiente a respeito de fibras alimentares, mesmo sabendo da importância de consumi-las adequadamente, visto que a ingestão de legumes e saladas, de frutas e de cereais integrais foi avaliada como insuficiente, podendo tal fato estar relacionado com renda, ausência de cuidado com a saúde e tempo de diagnóstico.

Tuberkulose (TB) ist eine der haufigsten Infektionskrankheit weltweit. Hier berichten wir uber einen 20-jahrigen Fluchtling aus Somalia, der sich zunachst mit rechtsseitigem Oberbauchschmerz, Erbrechen, Gewichtsverlust und Ikterus bei Verdacht auf eine Cholezystitis in unserer Klinik vorstellte. Im Rahmen der weiteren Diagnostik stellte sich eine Pylorusstenose dar, die – wie auch die Cholestase – durch komprimierende peripankreatische Lymphknotenpakete verursacht wurde. In einer zytologischen Untersuchung der Lymphknoten wurden eine verkasende Nekrose und Tuberkulosebakterien nachgewiesen.

Background Metastatic triple-negative breast cancer (mTNBC) is incurable. A key treatment goal is providing palliation while maintaining patients' health-related quality of life (HRQoL). IMpassion130 demonstrated progression-free survival benefit with atezolizumab + nab-paclitaxel (A + nP) versus placebo + nab-paclitaxel (Pl + nP) in first-line treatment of mTNBC patients with programmed death-ligand 1 positive (PD-L1+) tumors. We report data on patient-reported outcomes (PROs), which capture patient perspectives of treatment. Patients and methods Patients with untreated advanced or mTNBC received atezolizumab (840 mg) or placebo every 2 weeks in combination with nab-paclitaxel (100 mg/m2) on days 1, 8, and 15 of each 28-day cycle until progression or intolerance. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and its Breast Cancer Module (QLQ-BR23) on day 1 of each cycle, at end of treatment, and every 4 weeks during 1 year of follow-up. Time-to-deterioration (TTD) in HRQoL (first ≥10-point decrease from baseline lasting two cycles) was a secondary end point. Exploratory end points included TTD in functioning and mean and mean change from baseline scores in HRQoL, functioning, and disease- and treatment-related symptoms. Results Baseline completion of PROs was 92% (QLQ-C30) and 89% (QLQ-BR23) and remained >80% through cycle 20 in intent-to-treat (ITT) and PD-L1+ patients. No differences between arms in median TTD in PD-L1+ patients were observed for HRQoL {hazard ratio (HR) 0.94 [95% confidence interval (CI) 0.69–1.28]} or physical [HR 1.02 (95% CI 0.76–1.37)] or role [HR 0.77 (95% CI 0.57–1.04)] functioning. Mean baseline scores for A + nP versus Pl + nP for HRQoL (67.5 versus 65.0) and physical (82.8 versus 79.4) and role (73.7 versus 71.7) functioning were comparable between arms and throughout the course of treatment, with no clinically meaningful (≥10 point) changes from baseline until patients discontinued treatment. No differences in clinically meaningful worsening in treatment symptoms (fatigue, diarrhea, or nausea/vomiting) were observed between arms. Results in ITT patients were similar. Conclusions A + nP as first-line treatment for mTNBC delayed progression without compromising patients' day-to-day functioning or HRQoL or worsening treatment symptoms. ClinicalTrial.gov Identifier NCT02425891

Objective: To assess current management of diverticulitis in Switzerland.Methods: Prospective observational study of diverticulitis management and outcomes in surgical departments over a 3-month time period. Hospital category was graded according to the Swiss Medical Association (FMH) as: U: University; A: Cantonal; B: Regional; P: Private.Results: 75 participating hospitals treated 1,015 patients, among whom 214 patients (21%) had elective sigmoid resections in 49 hospitals. Indication for elective resection were recurrent diverticulitis, previous complicated diverticulitis, fistulas, and stenosis. Surgeries were performed completely laparoscopically in 185 cases (86%) and required conversion to open in 19 cases (9%). Overall postoperative complication rate was 18% (n = 39) and no mortality was observed. Operation time, surgeons experience and hospital stay differed considerably between hospital categories.Conclusions: Elective sigmoid resection for diverticulitis in Switzerland was mainly performed laparoscopically with low postoperative morbidity. Different practices and outcomes between institutions were observed.

BACKGROUND AND OBJECTIVES: Prescription opioid (PO) use disorder is a national public health crisis. Distress tolerance and alexithymia are two separate but related components of emotion regulation that are known to impact substance use disorders. No studies to date, however, have examined the role of distress tolerance and alexithymia in PO use disorder. Thus, the current study examined the association between distress tolerance, alexithymia, and specific motivations for PO use. METHODS: Participants were non-treatment seeking individuals with current PO use disorder (N = 81; average age = 35.0). Assessments included the Distress Tolerance Scale, Toronto Alexithymia Scale, and the Inventory of Drug Taking Situations.(16,28,29) RESULTS: The findings indicate that distress tolerance mediated the association between alexithymia and PO use in negative situations. Specifically, distress tolerance mediated the association between alexithymia and unpleasant emotions, testing personal control, and conflict with others. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The results provide novel information regarding emotional states that may contribute to PO use and are malleable intervention targets. Additionally, this study adds to existing literature exploring the relationship between distress tolerance and substance use and is the first to expand upon the connection between alexithymia and distress tolerance in an opioid using population. Implications for clinical practice and future research are discussed.

Summary Background Immunotherapy in combination with chemotherapy has shown promising efficacy across many different tumour types. We report the prespecified second interim overall survival analysis of the phase 3 IMpassion130 study assessing the efficacy and safety of atezolizumab plus nab-paclitaxel in patients with unresectable, locally advanced or metastatic triple-negative breast cancer. Methods In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 246 academic centres and community oncology practices in 41 countries, patients aged 18 years or older, with previously untreated, histologically documented, locally advanced or metastatic triple-negative breast cancer, and Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) using a permuted block method (block size of four) and an interactive voice–web response system. Randomisation was stratified by previous taxane use, liver metastases, and PD-L1 expression on tumour-infiltrating immune cells. Patients received atezolizumab 840 mg or matching placebo intravenously on day 1 and day 15 of every 28-day cycle and nab-paclitaxel 100 mg/m2 of body surface area intravenously on days 1, 8, and 15 until progression or unacceptable toxicity. Investigators, patients, and the funder were masked to treatment assignment. Coprimary endpoints were investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1 and overall survival, assessed in the intention-to-treat population and in patients with PD-L1 immune cell-positive tumours (tumours with ≥1% PD-L1 expression). The final progression-free survival results were previously reported at the first interim overall survival analysis. The prespecified statistical testing hierarchy meant that overall survival in the subgroup of PD-L1 immune cell-positive patients could only be formally tested if overall survival was significantly different between the treatment groups in the intention-to-treat population. This study is registered with ClinicalTrials.gov , NCT02425891 . Findings Between June 23, 2015, and May 24, 2017, 902 patients were enrolled, of whom 451 were randomly assigned to receive atezolizumab plus nab-paclitaxel and 451 were assigned to receive placebo plus nab-paclitaxel (the intention-to-treat population). Six patients from each group did not receive treatment. At the second interim analysis (data cutoff Jan 2, 2019), median follow-up was 18·5 months (IQR 9·6–22·8) in the atezolizumab group and 17·5 months (8·4–22·4) in the placebo group. Median overall survival in the intention-to-treat patients was 21·0 months (95% CI 19·0–22·6) with atezolizumab and 18·7 months (16·9–20·3) with placebo (stratified hazard ratio [HR] 0·86, 95% CI 0·72–1·02, p=0·078). In the exploratory overall survival analysis in patients with PD-L1 immune cell-positive tumours, median overall survival was 25·0 months (95% CI 19·6–30·7) with atezolizumab versus 18·0 months (13·6–20·1) with placebo (stratified HR 0·71, 0·54–0·94]). As of Sept 3, 2018 (the date up to which updated safety data were available), the most common grade 3–4 adverse events were neutropenia (38 [8%] of 453 patients in the atezolizumab group vs 36 [8%] of 437 patients in the placebo group), peripheral neuropathy (25 [6%] vs 12 [3%]), decreased neutrophil count (22 [5%] vs 16 [4%]), and fatigue (17 [4%] vs 15 [3%]). Treatment-related deaths occurred in two ( Interpretation Consistent with the first interim analysis, this second interim overall survival analysis of IMpassion130 indicates no significant difference in overall survival between the treatment groups in the intention-to-treat population but suggests a clinically meaningful overall survival benefit with atezolizumab plus nab-paclitaxel in patients with PD-L1 immune cell-positive disease. However, this positive result could not be formally tested due to the prespecified statistical testing hierarchy. For patients with PD-L1 immune cell-positive metastatic triple-negative breast cancer, atezolizumab plus nab-paclitaxel is an important therapeutic option in a disease with high unmet need. Funding F Hoffmann-La Roche and Genentech.

Recent international studies on the impact of the COVID-19 pandemic on mental health motivated the writing of this article. The article presents the preliminary results of the research conducted by me at the Laboratory of Fundamental Psychopathology in Studies on Subjectivity and Humanitarian Emergencies, of the Graduate Program in Psychology at the Federal University of Rio de Janeiro (UFRJ, Brazil). There were five months of theoretical survey of the theme based on the following research problem: what is the impact of social isolation and uncertainty about the future, on the functioning of the self in psychosis? The purpose of the article is to expose the results of the first phase of research on the topic, which consisted of a systematic review of the scientific literature on the topic of humanitarian emergencies, locating pandemics in this classification and specifically asking about the impact of COVID-19 on disorders related to the functioning of the self in psychosis, I finally maintain the relevance of developing a clinical protocol for the psychological approach of these situations, within the framework of the impacts of the COVID-19 pandemic about subjective functioning.

Background Although beta‐blockers are recommended following myocardial infarction (MI), the benefits of long‐term treatment have not been established. The study's aim was to evaluate beta‐blocker efficacy by dose in 1‐year post‐MI survivors. Methods and Results The OBTAIN (Outcomes of Beta‐Blocker Therapy After Myocardial Infarction) registry included 7057 patients with acute MI, with 6077 one‐year survivors. For this landmark analysis, beta‐blocker dose status was available in 3004 patients and analyzed by use (binary) and dose at 1 year after MI. Doses were classified as no beta‐blocker and >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target doses used in randomized clinical trials. Age was 63 to 64 years, and approximately two thirds were men. Median follow‐up duration was 1.05 years (interquartile range, 0.98–1.22). When analyzed dichotomously, beta‐blocker therapy was not associated with improved survival. When analyzed by dose, propensity score analysis showed significantly increased mortality in the no–beta‐blocker group (hazard ratio,1.997; 95% CI, 1.118–3.568; P 0% to 12.5% group (hazard ratio, 1.817; 95% CI, 1.094–3.016; P 25% to 50% group (hazard ratio, 1.764; 95% CI, 1.105–2.815; P 12.5% to 25% dose group. The mortality in the full‐dose group was not significantly higher (hazard ratio, 1.196; 95% CI, 0.687–2.083). In subgroup analyses, only history of congestive heart failure demonstrated significant interaction with beta‐blocker effects on survival. Conclusions This analysis suggests that patients treated with >12.5% to 25% of the target dose used in prior randomized clinical trials beyond 1 year after MI may have enhanced survival compared with no beta‐blocker and other beta‐blocker doses. A new paradigm for post‐MI beta‐blocker therapy is needed that addresses which patients should be treated, for how long, and at what dose.

The peripartal cow experiences a rapid change in calcium metabolism at the onset of lactation. Research has focused on understanding how mammary-derived factors, such as serotonin (5HT) and parathyroid hormone like hormone (PTHLH), aid in coordinating these calcemic adaptations to lactation. Therefore, the aim of our study was to determine how induced subclinical hypocalcemia influences physiological responses, specifically the 5HT-PTHLH-Ca axis, in lactating and nonlactating dairy cows to elucidate the potential contribution of the mammary gland. Twelve nonlactating, nonpregnant (NL) multiparous Holstein cows and 12 early-lactation (EL) multiparous Holstein cows received either (1) a continuous 24-h intravenous solution of 0.9% NaCl or (2) 5% ethylene glycol tetraacetic acid (EGTA) solution in 0.9% NaCl (n = 6 EL, n = 6 NL per treatment) with the aim of maintaining blood ionized calcium (iCa) less than 1.0 mM. Mammary gland biopsies were taken immediately after and 48 h after termination of infusion. Blood was sampled hourly during infusion and 4, 8, 12, 24, 48, and 72 h after termination of infusion. Infusion of EGTA successfully decreased blood iCa concentrations. However, EL EGTA-infused cows required increased rates of EGTA infusion to maintain iCa below 1.0 mM. Circulating and mammary serotonin concentrations were increased in EL relative to NL cows, with no difference as a result of EGTA infusion. Mammary PTHLH expression was increased in EL cows, with highest expression observed in EL EGTA-infused cows. Collectively, these data demonstrate the robust adaptations EL cows have to maintain Ca homeostasis and the supporting roles 5HT and PTHLH may play.

An amendment to this paper has been published and can be accessed via the original article.

Simple Summary Blood samples from patients with pancreatic diseases have been analysed to identify predictive RNA-based variants. These variants are not subject to changes in the environment, as is the case for gene expression or metabolic. The variants served together with CA19-9 as input to deep learning for a cohort of 268 patients with pancreatic diseases. Of these patients, 183 patients had pancreatic cancer and 85 from chronic pancreatitis. Among others, we were able to define a set of variants, which were able to differentiate resected pancreatic cancer from chronic pancreatitis with an area under the curve of (AUC) of 96%. Due to the ease of our approach and the wide availability of the used method, it will have a broad impact on the clinical routine. Suspicious patients are only subjected to a blood draw of 2.5 mL blood, and the specimen can then be sent at room temperature to a specialised laboratory. Abstract For optimal pancreatic cancer treatment, early and accurate diagnosis is vital. Blood-derived biomarkers and genetic predispositions can contribute to early diagnosis, but they often have limited accuracy or applicability. Here, we seek to exploit the synergy between them by combining the biomarker CA19-9 with RNA-based variants. We use deep sequencing and deep learning to improve differentiating pancreatic cancer and chronic pancreatitis. We obtained samples of nucleated cells found in peripheral blood from 268 patients suffering from resectable, non-resectable pancreatic cancer, and chronic pancreatitis. We sequenced RNA with high coverage and obtained millions of variants. The high-quality variants served as input together with CA19-9 values to deep learning models. Our model achieved an area under the curve (AUC) of 96% in differentiating resectable cancer from pancreatitis using a test cohort. Moreover, we identified variants to estimate survival in resectable cancer. We show that the blood transcriptome harbours variants, which can substantially improve noninvasive clinical diagnosis.

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564

Background Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. Results 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). Conclusions The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.

Traditional neuroimage analysis pipelines involve computationally intensive, time-consuming optimization steps, and thus, do not scale well to large cohort studies with thousands or tens of thousands of individuals. In this work we propose a fast and accurate deep learning based neuroimaging pipeline for the automated processing of structural human brain MRI scans, replicating FreeSurfer's anatomical segmentation including surface reconstruction and cortical parcellation. To this end, we introduce an advanced deep learning architecture capable of whole brain segmentation into 95 classes. The network architecture incorporates local and global competition via competitive dense blocks and competitive skip pathways, as well as multi-slice information aggregation that specifically tailor network performance towards accurate segmentation of both cortical and sub-cortical structures. Further, we perform fast cortical surface reconstruction and thickness analysis by introducing a spectral spherical embedding and by directly mapping the cortical labels from the image to the surface. This approach provides a full FreeSurfer alternative for volumetric analysis (in under 1 minute) and surface-based thickness analysis (within only around 1h runtime). For sustainability of this approach we perform extensive validation: we assert high segmentation accuracy on several unseen datasets, measure generalizability and demonstrate increased test-retest reliability, and high sensitivity to group differences in dementia., Comment: Submitted to NeuroImage

Graphene-based photodetectors have attracted attention for realizing optoelectronic devices including photodetectors. We report a graphene field effect transistor on silicon for broadband light detection from the ultraviolet to near-infrared region, which is compatible with the silicon technology and does not need a complicated fabrication process. The photodetectors show an improved responsivity. Specifically, fabricated graphene photodetectors shows a photo-responsivity of ~980 A/W at room temperature. These results provide a promising for the development of graphene-based optoelectronic applications with the broadband photodetection from the ultraviolet to near-infrared region.

Peritraumatic distress and anxiety sensitivity are associated with complications in bereavement, including posttraumatic stress and prolonged grief reactions. The extent to which these factors interact to contribute to bereavement-related distress, however, remains unclear. This study investigates whether anxiety sensitivity moderates the association between peritraumatic reactions and posttraumatic stress and prolonged grief symptoms in a sample of young adults with a history of bereavement due to sudden, unexpected deaths. Participants were 606 undergraduate students recruited from two US universities. Results suggest that peritraumatic emotional and physical distress and anxiety sensitivity are all independently associated with both posttraumatic stress and prolonged grief reactions. Furthermore, the association between peritraumatic distress and prolonged grief, but not posttraumatic stress, is moderated by anxiety sensitivity. These findings point to several potentially important, clinically modifiable factors associated with a variety of bereavement-related mental health problems among a vulnerable group of grievers.

Objective Evaluation of nutritional status and consumption frequency of inflammatory and anti-inflammatory food by patients with inflammatory bowel diseases. Methods An observational study of the patients assisted by the interdisciplinary inflammatory bowel diseases ambulatory of UNIVALI-SC. The nutritional status of patients was evaluated and each patient was categorized according to his/her body max index and also through a research questionnaire of the individual social-economy situation, life habits, and inflammatory and anti-inflammatory food consumption in a determinate period of time. Results Out of the 65 patients, 57% had Crohn’s disease and 43% had ulcerative colitis. According to the disease activity, 71% were in remission and 29% in activity. Of the sample, 57% were classified as overweight. It was not possible to correlate nutritional status and type of inflammatory bowel diseases, nutritional status and income or nutritional status and level of education. The most inflammatory foods were beef (65%) and coffee (60%), while the anti-inflammatory ones were garlic (75%), olive oil (54%), and sweet potatoes (23%). There was no association between the most consumed inflammatory and anti-inflammatory food and body max index. Conclusion According to the results, most of the patients were overweight. The most commonly consumed inflammatory foods were beef and coffee and the anti-inflammatory ones were garlic, olive oil, and sweet potatoes. RESUMO Objetivo Avaliar o estado nutricional e a frequência de consumo de alimentos inflamatórios e anti-inflamatórios por portadores de doenças inflamatórias intestinais. Metodologia Estudo transversal com indivíduos assistidos pelo ambulatório interdisciplinar de doenças inflamatórias intestinais da UNIVALI-SC. Avaliados por meio do estado nutricional e classificados de acordo com o índice de massa corporal, bem como através de um questionário contendo dados socioeconômicos, hábitos de vida e frequência do consumo de alimentos inflamatórios e anti-inflamatórios. Resultados Dos 65 pacientes, 57% eram portadores de doença de Crohn e 43% de retocolite ulcerativa. De acordo com a atividade da doença, 71% encontravam-se em remissão e 29% em atividade. Da amostra, 57% foram classificados como acima do peso. Não foi possível correlacionar estado nutricional e o tipo de doenças inflamatórias intestinais, estado nutricional e renda ou estado nutricional e escolaridade. Os alimentos inflamatórios mais consumidos foram carne de gado (65%) e café (60%), já os anti-inflamatórios foram alho (75%), azeite de oliva (54%) e batata doce (23%). Não houve associação entre os alimentos inflamatórios e anti-inflamatórios mais consumidos e o índice de massa corporal. Conclusão Segundo os resultados, observou-se que a maioria dos pacientes apresentava excesso de peso. Os alimentos inflamatórios mais consumidos foram carne de gado e café e os anti-inflamatórios foram alho, azeite de oliva e batata doce.

Unresectable locally advanced or metastatic triple-negative (hormone-receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)-paclitaxel may enhance the anticancer activity of atezolizumab.In this phase 3 trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel; patients continued the intervention until disease progression or an unacceptable level of toxic effects occurred. Stratification factors were the receipt or nonreceipt of neoadjuvant or adjuvant taxane therapy, the presence or absence of liver metastases at baseline, and programmed death ligand 1 (PD-L1) expression at baseline (positive vs. negative). The two primary end points were progression-free survival (in the intention-to-treat population and PD-L1-positive subgroup) and overall survival (tested in the intention-to-treat population; if the finding was significant, then it would be tested in the PD-L1-positive subgroup).Each group included 451 patients (median follow-up, 12.9 months). In the intention-to-treat analysis, the median progression-free survival was 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months with placebo plus nab-paclitaxel (hazard ratio for progression or death, 0.80; 95% confidence interval [CI], 0.69 to 0.92; P=0.002); among patients with PD-L1-positive tumors, the median progression-free survival was 7.5 months and 5.0 months, respectively (hazard ratio, 0.62; 95% CI, 0.49 to 0.78; P0.001). In the intention-to-treat analysis, the median overall survival was 21.3 months with atezolizumab plus nab-paclitaxel and 17.6 months with placebo plus nab-paclitaxel (hazard ratio for death, 0.84; 95% CI, 0.69 to 1.02; P=0.08); among patients with PD-L1-positive tumors, the median overall survival was 25.0 months and 15.5 months, respectively (hazard ratio, 0.62; 95% CI, 0.45 to 0.86). No new adverse effects were identified. Adverse events that led to the discontinuation of any agent occurred in 15.9% of the patients who received atezolizumab plus nab-paclitaxel and in 8.2% of those who received placebo plus nab-paclitaxel.Atezolizumab plus nab-paclitaxel prolonged progression-free survival among patients with metastatic triple-negative breast cancer in both the intention-to-treat population and the PD-L1-positive subgroup. Adverse events were consistent with the known safety profiles of each agent. (Funded by F. Hoffmann-La Roche/Genentech; IMpassion130 ClinicalTrials.gov number, NCT02425891 .).

Our objective was to investigate the association between herbal/botanic supplement use and perceived quality of life (QoL), cancer recurrence, and all-cause mortality in colon cancer patients.Patients (n = 453) newly diagnosed with stage II adenocarcinoma of the colon between 2009 and 2011 were recruited from the North Carolina Central Cancer Registry. Data including demographic variables, herbal medicine use and frequency, lifestyle, diet, cancer treatment, and QoL were collected by interviews at diagnosis (baseline) and 1 and 2 y after diagnosis. Mortality information was obtained via the National Death Index. The Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and Medical Outcomes Short Form 12 (SF-12) were used to evaluate QoL.At baseline, herbal/botanic supplement users were more likely to have a healthier lifestyle than non-users, including more physical activity (P 0.01), more fruit and vegetable consumption (P = 0.01), less smoking (P 0.01), and less energy intake from fat (P = 0.02). After adjustment for potential confounders, no significant association was found between herbal/botanic supplement use and QoL assessed by FACT-C and SF-12. Similarly, herbal/botanic supplement use was not associated with the risk of recurrence, all-cause mortality or the combined.In this study, patients with stage II colon cancer using herbal/botanic supplements had no significant improvement in their QoL and no difference in odds of colon cancer recurrence and all-cause mortality over 2 y after diagnosis compared with those who did not use herbs/botanicals. Further studies are warranted to confirm the findings and to focus on types of herbal/botanic supplements.

International audience; The relationship between childhood trauma and dissociative experiences is widely acknowledged. However, the association between emotion regulation difficulties (ERD), anxiety/depression and dissociation in adolescents and young adults with cumulative maltreatment (CM) remains unclear. The present study examined the role of ERD at both intrapersonal and interpersonal levels and anxiety/depression symptoms in the development of psychoform or somatoform dissociation in adolescents and young adults with CM. We assessed 58 participants with CM and 55 participants without childhood trauma history between the age of 12 and 22 years old. Participants completed self-reports of ERD, anxiety/depression, psychoform dissociation and somatoform dissociation. The results revealed that adolescents and young adults exposed to CM displayed high levels of psychoform and somatoform dissociation, ERD and anxiety/depression symptoms. It was also found that intrapersonal and interpersonal ERD predicted psychoform dissociation, whereas anxiety/depression predicted somatoform dissociation in adolescents and young adults with CM. Intrapersonal and interpersonal ERD and anxiety/depression are therapy targets for clinical interventions in adolescents and young adults with CM and dissociative symptoms.

Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. Aims In the present study, we assessed the role of ghrelin – GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. Main methods and key findings Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the amplitude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin amplified the increases in calcium transient changes evoked by isoproterenol. Significance Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors.