Search

Abstract Background The COVID-19 pandemic exposed several health disparities experienced by underserved and Latino/a communities, including inequitable access to COVID-19 testing. Objective and Goals To describe the utilization of a community-driven and culturally-tailored testing model on COVID-19 testing in an underserved Latino/a community in San Diego. Methods The Community-driven Optimization of COVID-19 testing to Reach and Engage Underserved Areas for Testing Equity (CO-CREATE) project implemented a community co-designed COVID-19 testing program in partnership with a Federally Qualified Health Center in a US/Mexico border community. Results Between May 2021 and March 2023, 24, 422 COVID-19 PCR tests were administered to 13,253 individuals, among whom 93% percent identified as Latino/a, 57% spoke Spanish in the home, and 38% resided in our target community adjacent to the US/Mexico border, San Ysidro. Based on a subset of available county testing data, CO-CREATE accounted for nearly 12% of all COVID-19 tests reported for San Ysidro residents. Over the course of the project, we estimated that nearly 17% of all San Ysidro residents were tested for COVID-19 through the CO-CREATE project. Conclusion These findings highlight the success and reach of this culturally responsive and community co-designed COVID-19 testing program, within a Latino/a border community. Future public health interventions should focus on identifying testing barriers and design appropriate strategies to ensure equitable access to resources and testing uptake for all community members.

Abstract There is an urgent need to monitor the mental health of large populations, especially during crises such as the COVID-19 pandemic, to timely identify the most at-risk subgroups and to design targeted prevention campaigns. We therefore developed and validated surveillance indicators related to suicidality: the monthly number of hospitalisations caused by suicide attempts and the prevalence among them of five known risks factors. They were automatically computed analysing the electronic health records of fifteen university hospitals of the Paris area, France, using natural language processing algorithms based on artificial intelligence. We evaluated the relevance of these indicators conducting a retrospective cohort study. Considering 2,911,920 records contained in a common data warehouse, we tested for changes after the pandemic outbreak in the slope of the monthly number of suicide attempts by conducting an interrupted time-series analysis. We segmented the assessment time in two sub-periods: before (August 1, 2017, to February 29, 2020) and during (March 1, 2020, to June 31, 2022) the COVID-19 pandemic. We detected 14,023 hospitalisations caused by suicide attempts. Their monthly number accelerated after the COVID-19 outbreak with an estimated trend variation reaching 3.7 (95%CI 2.1–5.3), mainly driven by an increase among girls aged 8–17 (trend variation 1.8, 95%CI 1.2–2.5). After the pandemic outbreak, acts of domestic, physical and sexual violence were more often reported (prevalence ratios: 1.3, 95%CI 1.16–1.48; 1.3, 95%CI 1.10–1.64 and 1.7, 95%CI 1.48–1.98), fewer patients died (p = 0.007) and stays were shorter (p

Abstract Background The SARS CoV‐2 pandemic disrupted healthcare systems. We compared the cancer stage for new breast cancers (BCs) before and during the pandemic. Methods We performed a retrospective multicenter cohort study on the data warehouse of Greater Paris University Hospitals (AP‐HP). We identified all female patients newly referred with a BC in 2019 and 2020. We assessed the timeline of their care trajectories, initial tumor stage, and treatment received: BC resection, exclusive systemic therapy, exclusive radiation therapy, or exclusive best supportive care (BSC). We calculated patients' 1‐year overall survival (OS) and compared indicators in 2019 and 2020. Results In 2019 and 2020, 2055 and 1988, new BC patients underwent cancer treatment, and during the two lockdowns, the BC diagnoses varied by −18% and by +23% compared to 2019. De novo metastatic tumors (15% and 15%, p = 0.95), pTNM and ypTNM distributions of 1332 cases with upfront resection and of 296 cases with neoadjuvant therapy did not differ (p = 0.37, p = 0.3). The median times from first multidisciplinary meeting and from diagnosis to treatment of 19 days (interquartile 11–39 days) and 35 days (interquartile 22–65 days) did not differ. Access to plastic surgery (15% and 17%, p = 0.08) and to treatment categories did not vary: tumor resection (73% and 72%), exclusive systemic therapy (13% and 14%), exclusive radiation therapy (9% and 9%), exclusive BSC (5% and 5%) (p = 0.8). Among resected patients, the neoadjuvant therapy rate was lower in 2019 (16%) versus 2020 (20%) (p = 0.02). One‐year OS rates were 99.3% versus 98.9% (HR = 0.96; 95% CI, 0.77–1.2), 72.6% versus 76.6% (HR = 1.28; 95% CI, 0.95–1.72), 96.6% versus 97.8% (HR = 1.09; 95% CI, 0.61–1.94), and 15.5% versus 15.1% (HR = 0.99; 95% CI, 0.72–1.37), in the treatment groups. Conclusions Despite a decrease in the number of new BCs, there was no tumor stage shift, and OS did not vary.

Abstract Background Acute myocardial infarction (AMI) is one of the major cardiac complications in patients hospitalized in the intensive care unit (ICU) for non-cardiac disease. A better knowledge of ischemic and bleeding risks in these patients is needed to identify those most likely to benefit from specific cardiac management. We therefore assessed the incidence and predictors of a composite outcome of severe ischemic event (AMI recurrence, ischemic stroke), major bleeding, or all-cause death in this setting. Methods In this multicenter retrospective study, all consecutive adult patients admitted for non-cardiac disease to four French university hospital ICUs between January 2012 and December 2018 who had an AMI with obstructive coronary artery disease (OCAD) during the ICU stay were considered for inclusion. AMI with OCAD was defined as an elevated cardiac troponin value associated with at least one sign (clinical, electrocardiographic, or echocardiographic) suggestive of myocardial ischemia and presence of OCAD on coronary angiography. The primary endpoint was in-hospital occurrence of the composite outcome. Results Ninety-six patients [median age 69 years, 22 women (23%), 59 with sepsis (61%), 35 with ST elevation (37%), median sequential organ failure assessment (SOFA) of 8 on the day of AMI] were included. The median peak cardiac troponin value was 131 (IQR 44–303) times the upper reference limit. Dual antiplatelet, therapeutic anticoagulation, and early mechanical reperfusion therapies were administered in 61 (64%), 68 (71%), and 47 (49%) patients, respectively. The composite outcome occurred in 48 (50%) patients. Severe ischemic events occurred in 17 (18%) patients and major bleeding in 26 (27%) patients; 26 patients (27%) died in the hospital. AMI management was not significantly different in patients with and without the composite outcome. A history of arterial hypertension (HR 2.05, 95% CI 1.01–4.16) and high SOFA score at the time of AMI (HR 1.07, 95% CI 1.00–1.15) were independent risk factors for the composite outcome. Conclusions Patients who have an AMI with OCAD during an ICU stay for non-cardiac disease are at risk of a composite outcome of severe ischemia, major bleeding, and death. A history of arterial hypertension and high SOFA scores were independent hazards for poor prognosis. Graphical Abstract

Abstract Turner syndrome (TS; ORPHA 881) is a rare condition in which all or part of one X chromosome is absent from some or all cells. It affects approximately one in every 1/2500 liveborn girls. The most frequently observed karyotypes are 45,X (40–50%) and the 45,X/46,XX mosaic karyotype (15–25%). Karyotypes with an X isochromosome (45,X/46,isoXq or 45,X/46,isoXp), a Y chromosome, X ring chromosome or deletions of the X chromosome are less frequent. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins) is to provide health professionals with information about the optimal management and care for patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Growth and Developmental Endocrine disorders, is available from the French Health Authority website. Turner Syndrome is associated with several phenotypic conditions and a higher risk of comorbidity. The most frequently reported features are growth retardation with short adult stature and gonadal dysgenesis. TS may be associated with various congenital (heart and kidney) or acquired diseases (autoimmune thyroid disease, celiac disease, hearing loss, overweight/obesity, glucose intolerance/type 2 diabetes, dyslipidemia, cardiovascular complications and liver dysfunction). Most of the clinical traits of TS are due to the haploinsufficiency of various genes on the X chromosome, particularly those in the pseudoautosomal regions (PAR 1 and PAR 2), which normally escape the physiological process of X inactivation, although other regions may also be implicated. The management of patients with TS requires collaboration between several healthcare providers. The attending physician, in collaboration with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are designed to provide such support.

Introduction Antiphospholipid syndrome (APS) is an autoimmune disease characterised by thrombosis (arterial, venous or small vessel) or obstetrical events and persistent antiphospholipid antibodies (aPL), according to the Sydney classification criteria. Many studies have performed cluster analyses among patients with primary APS and associated autoimmune disease, but none has focused solely on primary APS. We aimed to perform a cluster analysis among patients with primary APS and asymptomatic aPL carriers without any autoimmune disease, to assess prognostic value.Methods In this multicentre French cohort study, we included all patients with persistent APS antibodies (Sydney criteria) measured between January 2012 and January 2019. We excluded all patients with systemic lupus erythematosus or other systemic autoimmune diseases. We performed hierarchical cluster analysis on the factor analysis of mixed data coordinates results with baseline patient characteristics to generate clusters.Results We identified four clusters: cluster 1, comprising ‘asymptomatic aPL carriers’, with low risk of events during follow-up; cluster 2, the ‘male thrombotic phenotype’, with older patients and more venous thromboembolic events; cluster 3, the ‘female obstetrical phenotype’, with obstetrical and thrombotic events; and cluster 4, ‘high-risk APS’, which included younger patients with more frequent triple positivity, antinuclear antibodies, non-criteria manifestations and arterial events. Regarding survival analyses, asymptomatic aPL carriers relapsed less frequently than the others, but no other differences in terms of relapse rates or deaths were found between clusters.Conclusions We identified four clusters among patients with primary APS, one of which was ‘high-risk APS’. Clustering-based treatment strategies should be explored in future prospective studies.

Abstract Background From this retrospective study, we aimed to (1) describe the prevalence and characteristics of non-criteria features in primary antiphospholipid syndrome (p-APS) and (2) determine their prognostic value. Methods This retrospective French multicenter cohort study included all patients diagnosed with p-APS (Sydney criteria) between January 2012 and January 2019. We used Kaplan-Meier and adjusted Cox proportional hazards models to compare the incidence of relapse in p-APS with and without non-criteria manifestations. Results One hundred and seventy-nine patients with p-APS were included during the study time, with a median age of 52.50 years [39.0; 65.25] and mainly women (n = 112; 62.6%). Among them, forty-three patients (24.0%) presented at least one non-criteria manifestation during the follow-up: autoimmune cytopenias (n = 17; 39.5%), Libman Sachs endocarditis (n = 5; 11.6%), APS nephropathy (n = 4; 9.3%), livedo reticularis (n = 8; 18.6%), and neurological manifestations (n = 12; 27.9%). In comparison to p-APS without any non-criteria manifestations (n = 136), p-APS with non-criteria features had more arterial thrombosis (n = 24; 55.8% vs n = 48; 35.3%; p = 0.027) and more frequent pre-eclampsia (n = 6; 14.3% vs n = 4; 3.1%; p = 0.02). The prevalence of triple positivity was significantly increased in patients with non-criteria features (n = 20; 47.6% vs n = 25; 19.8%; p = 0.001). Patients with p-APS and non-criteria manifestations (n = 43) received significantly more additional therapies combined with vitamin K antagonists and/or antiaggregants. Catastrophic APS (CAPS) tended to be more frequent in p-APS with non-criteria features (n = 2; 5.1% vs none; p = 0.074). The p-APS with non-criteria manifestations had significantly increased rates of relapse (n = 20; 58.8% vs 33; 33.7%; p = 0.018) in bivariate analysis, but in survival analyses, the hazard ratio (HR) of relapse was not significantly different between the two groups (HR at 1.34 [0.67; 2.68]; p = 0.40). Conclusions The presence of non-criteria features is important to consider, as they are associated with particular clinical and laboratory profiles, increased risk of relapse, and need for additional therapies. Prospective studies are necessary to better stratify the prognosis and the management of p-APS.

Metaphors are ubiquitous in natural language; in fact, no language without metaphors is known. But can we construct a language without metaphors? An issue that is particularly relevant to this question is the relation between metaphor and simile. Some argue that metaphors are a type of (elided) simile, whereas others claim that the two phenomena differ in kind. Ideally, a way to settle the dispute would be to find a language that contains similes but not metaphors. There is no such actual language. But two science fiction authors have attempted to conceive of and describe just such a language. David Brin, in The Uplift War, creates birdlike aliens, whose language is claimed to have similes but not metaphors. However, Brin reproduces utterances of these aliens, in which he reflects their avian nature; and he often does so by metaphor. China Miéville, in Embassytown, also creates aliens whose language is claimed to have similes but not metaphors. However, these similes are frozen, and are actually idioms: they have a fixed, conventional meaning. Later on, the aliens acquire metaphors, and only then do they begin to have, in addition, novel similes. Hence, both Brin and Miéville fail: the former constructs a language that has both similes and metaphors, whereas the other constructs a language that initially has neither, and later acquires both simultaneously. Science fiction authors are, after all, humans, and are bound by the constraints of human languages. Hence, their failure to construct a language that contains similes but not metaphors tells us that the two phenomena are fundamentally very close. To the extent that it is possible to construct a language without metaphors, it appears that it would have to do without similes too.

Abstract Background Echocardiographic parameters have been poorly investigated for estimating cardiovascular risk in patients with sepsis and new-onset atrial fibrillation. We aim to assess the prevalence of transesophageal echocardiographic abnormalities and their relationship with cardiovascular events in mechanically ventilated patients with sepsis and new-onset atrial fibrillation. Methods In this prospective multicenter pilot study, left atrial/left atrial appendage (LA/LAA) dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were assessed using an initial transesophageal echocardiographic study, which was repeated after 48–72 h to detect LA/LAA thrombus formation. The study outcome was a composite of cardiovascular events at day 28, including arterial thromboembolic events (ischemic stroke, non-cerebrovascular arterial thromboembolism, LA/LAA thrombus), major bleeding, and all-cause death. Results The study population comprised 94 patients (septic shock 63%; 35% women; median age 69 years). LA/LAA dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were detected in 17 (19%), 22 (24%), and 27 (29%) patients, respectively. At day 28, the incidence of cardiovascular events was 46% (95% confidence interval [CI]: 35 to 56). Arterial thromboembolic events and major bleeding occurred in 7 (7%) patients (5 ischemic strokes, 1 non-cerebrovascular arterial thromboembolism, 2 left atrial appendage thrombi) and 18 (19%) patients, respectively. At day 28, 27 patients (29%) died. Septic shock (hazard ratio [HR]: 2.36; 95% CI 1.06 to 5.29) and left ventricular systolic dysfunction (HR: 2.06; 95% CI 1.05 to 4.05) were independently associated with cardiovascular events. Conclusions Transesophageal echocardiographic abnormalities are common in mechanically ventilated patients with sepsis and new-onset atrial fibrillation, but only left ventricular systolic dysfunction was associated with cardiovascular events at day 28.

BackgroundThe decision for withholding and withdrawing of life-sustaining treatments (LSTs) in COVID-19 patients is currently based on a collegial and mainly clinical assessment. In the context of a global pandemic and overwhelmed health system, the question of LST decision support for COVID-19 patients using prognostic biomarkers arises.MethodsIn a multicenter study in 24 French hospitals, 2878 COVID-19 patients hospitalized in medical departments from 26 February to 20 April 2020 were included. In a propensity-matched population, we compared the clinical, biological, and management characteristics and survival of patients with and without LST decision using Student's t-test, the chi-square test, and the Cox model, respectively.ResultsAn LST was decided for 591 COVID-19 patients (20.5%). These 591 patients with LST decision were secondarily matched (1:1) based on age, sex, body mass index, and cancer history with 591 COVID-19 patients with no LST decision. The patients with LST decision had significantly more cardiovascular diseases, such as high blood pressure (72.9 vs. 66.7%, p = 0.02), stroke (19.3 vs. 11.1%, p < 0.001), renal failure (30.4 vs. 17.4%, p < 0.001), and heart disease (22.5 vs. 14.9%, p < 0.001). Upon admission, LST patients were more severely attested by a qSOFA score ≥2 (66.5 vs. 58.8%, p = 0.03). Biologically, LST patients had significantly higher values of D-dimer, markers of heart failure (BNP and NT-pro-BNP), and renal damage (creatinine) (p < 0.001). Their evolutions were more often unfavorable (in-hospital mortality) than patients with no LST decision (41.5 vs. 10.3%, p < 0.001). By combining the three biomarkers (D-dimer, BNP and/or NT-proBNP, and creatinine), the proportion of LST increased significantly with the number of abnormally high biomarkers (24, 41.3, 48.3, and 60%, respectively, for none, one, two, and three high values of biomarkers, trend p < 0.01).ConclusionThe concomitant increase in D-dimer, BNP/NT-proBNP, and creatinine during the admission of a COVID-19 patient could represent a reliable and helpful tool for LST decision. Circulating biomarker might potentially provide additional information for LST decision in COVID-19.

BackgroundTakotsubo syndrome is an acute cardiac condition involving sudden, transient apical ballooning of the left ventricle of the heart that may be triggered by emotional stress and some non-cardiac conditions. Its diagnosis is based on clinical presentation, electrocardiogram, cardiac imaging and biomarkers.Case SummaryHere, we present a novel and original case report of a patient presenting very soon in the post-partum period with an unusual form of Takotsubo syndrome without clinical symptoms of cardiac disease and accompanied by HELLP syndrome. The overall dynamics of the changes in troponin I, troponin T and NT-proBNP levels after delivery were generally similar, but the amount of troponin I was much greater than that of troponin T and troponin I was already elevated before delivery. NT-proBNP levels peaked around the same time as the troponins and the peak concentration was within the same range as that of troponin I.DiscussionOur findings indicate that assaying circulating cardiac biomarkers, especially troponin I and NT-proBNP, may be a useful complement to non-invasive cardiac imaging including transthoracic echocardiography and cardiovascular magnetic resonance imaging, in the diagnosis of Takotsubo syndrome. They illustrate the importance of cardiac biomarkers in assisting diagnosis of this disease.

INTRODUCCIÓN La mayoría de los estudios publicados en 2019 sobre el diagnóstico y tratamiento de la insuficiencia cardiaca (IC) en revistas internacionales de alto impacto se centran en tratamientos farmacológicos. Esto incluye iniciar la administración de sacubitrilo-valsartán durante la hospitalización índice, así como los beneficios derivados de los inhibidores del SGLT2, los cuales reducen la mortalidad cardiovascular y la IC. No obstante, la mayoría de estos estudios, dirigidos a un amplio número de lectores, no caracterizan importantes problemas de índole local. Para mejorar el tratamiento de la IC, se deben incorporar las particularidades de los diferentes países miembros de la Sociedad Europea de Cardiología (ESC), incorporación y diseminación que puede lograrse a través de las Revistas de las Sociedades Nacionales de Cardiología (NSCJ). Durante el Congreso de la ESC de 2019, la Red de Editores de la ESC auspició esta iniciativa para fomentar la divulgación de la investigación cardiológica que publican las NSCJ resumiendo en un artículo de revisión las evidencias recopiladas en áreas seleccionadas. Los miembros de la Red de Editores de la ESC se decantaron por publicaciones en el campo de la IC como primer tema de esta revisión. Epidemiología Las disparidades existentes en la prevalencia de factores de riesgo, la carga de...

Background: Microthrombosis and large-vessel thrombosis are the main triggers of COVID-19 worsening. The optimal anticoagulant regimen in COVID-19 patients hospitalized in medical wards remains unknown.Objectives: To evaluate the effects of intermediate-dose vs. standard-dose prophylactic anticoagulation (AC) among patients with COVID-19 hospitalized in medical wards.Methods and results: We used a large French multicentric retrospective study enrolling 2,878 COVID-19 patients hospitalized in medical wards. After exclusion of patients who had an AC treatment before hospitalization, we generated a propensity-score-matched cohort of patients who were treated with intermediate-dose or standard-dose prophylactic AC between February 26 and April 20, 2020 (intermediate-dose, n = 261; standard-dose prophylactic anticoagulation, n = 763). The primary outcome of the study was in-hospital mortality; this occurred in 23 of 261 (8.8%) patients in the intermediate-dose group and 74 of 783 (9.4%) patients in the standard-dose prophylactic AC group (p = 0.85); while time to death was also the same in both the treatment groups (11.5 and 11.6 days, respectively, p = 0.17). We did not observe any difference regarding venous and arterial thrombotic events between the intermediate dose and standard dose, respectively (venous thrombotic events: 2.3 vs. 2.4%, p=0.99; arterial thrombotic events: 2.7 vs. 1.2%, p = 0.25). The 30-day Kaplan–Meier curves for in-hospital mortality demonstrate no statistically significant difference in in-hospital mortality (HR: 0.99 (0.63–1.60); p = 0.99). Moreover, we found that no particular subgroup was associated with a significant reduction in in-hospital mortality.Conclusion: Among COVID-19 patients hospitalized in medical wards, intermediate-dose prophylactic AC compared with standard-dose prophylactic AC did not result in a significant difference in in-hospital mortality.

The Editors’ Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices. Keywords: Editorial ethics, Scientific Process, Authorship, Accountability, Scientific journals, Journals

Background: Handwriting is an essential part of human communication. Its successful development is decisive for its personal and academic future. One of its most important components is the grip of the pen, of which there are 5 standard variants. The correct calligraphic education has a very important role in the generation of writing habits and a better legibility. Methods: In a cross-sectional study of correlation between variables, the aim was to correlate calligraphic education with many variables. The data was collected with a survey and a calligraphic test. Results: The sample consisted of 80 subjects between the ages of 18-30. No statistically significant correlation was found between legibility and years of calligraphic education, gender, age, dominant hand, GPA and preferred font. The only significant correlation was found between legibility and the use of one standard grips of the pen and an alternative (p=0.01). Discussion: 77.5% of the subjects had good legibility in the calligraphic test and no correlation was found between legibility and most of the variables on the study. However, the association between legibility and the use of the standard grips was found, in comparison with people that do not use one of those grips. Conclusions: Handwriting legibility is a multi-factor influenced skill, and calligraphic education during childhood is decisive to develop it properly. Nevertheless, the study showed no association between the length of the education and legibility, and a correlation between the use of an alternative pen grip and a worse result in the calligraphic test.

Immune checkpoint inhibitors (ICI) have constituted a paradigm shift in the management of patients with cancer. Their administration is associated with a new spectrum of immune-related toxicities that can affect any organ. In patients treated with ICI, cardiovascular toxicities, particularly myocarditis, occur with a low incidence (

Background Coronavirus disease 2019 (COVID‐19) is a respiratory disease associated with thrombotic outcomes with coagulation and endothelial disorders. Based on that, several anticoagulation guidelines have been proposed. We aimed to determine whether anticoagulation therapy modifies the risk of developing severe COVID‐19. Methods and Results Patients with COVID‐19 initially admitted in medical wards of 24 French hospitals were included prospectively from February 26 to April 20, 2020. We used a Poisson regression model, Cox proportional hazard model, and matched propensity score to assess the effect of anticoagulation on outcomes (intensive care unit admission or in‐hospital mortality). The study enrolled 2878 patients with COVID‐19, among whom 382 (13.2%) were treated with oral anticoagulation therapy before hospitalization. After adjustment, anticoagulation therapy before hospitalization was associated with a better prognosis with an adjusted hazard ratio of 0.70 (95% CI, 0.55–0.88). Analyses performed using propensity score matching confirmed that anticoagulation therapy before hospitalization was associated with a better prognosis, with an adjusted hazard ratio of 0.43 (95% CI, 0.29–0.63) for intensive care unit admission and adjusted hazard ratio of 0.76 (95% CI, 0.61–0.98) for composite criteria intensive care unit admission or death. In contrast, therapeutic or prophylactic low‐ or high‐dose anticoagulation started during hospitalization were not associated with any of the outcomes. Conclusions Anticoagulation therapy used before hospitalization in medical wards was associated with a better prognosis in contrast with anticoagulation initiated during hospitalization. Anticoagulation therapy introduced in early disease could better prevent COVID‐19–associated coagulopathy and endotheliopathy, and lead to a better prognosis.

The considerable progress made in the field of cancer treatment has led to a dramatic improvement in the prognosis of patients with cancer. However, toxicities resulting from these treatments represent a cost that can be harmful to short‐ and long‐term outcomes. Adverse events affecting the cardiovascular system are one of the greatest challenges in the overall management of patients with cancer, as they can compromise the success of the optimal treatment against the tumor. Such adverse events are associated not only with older chemotherapy drugs such as anthracyclines but also with many targeted therapies and immunotherapies. Recognizing this concern, several American and European governing societies in oncology and cardiology have published guidelines on the cardiovascular monitoring of patients receiving potentially cardiotoxic cancer therapies, as well as on the management of cardiovascular toxicities. However, the low level of evidence supporting these guidelines has led to numerous discrepancies, leaving clinicians without a consensus strategy to apply. A cardio‐oncology expert panel from the French Working Group of Cardio‐Oncology has undertaken an ambitious effort to analyze and harmonize the most recent American and European guidelines to propose roadmaps and decision algorithms that would be easy for clinicians to use in their daily practice. In this statement, the experts addressed the cardiovascular monitoring strategies for the cancer drugs associated with the highest risk of cardiovascular toxicities, as well as the management of such toxicities.

Background It is unclear whether HIV infection affects the long‐term prognosis after an acute coronary syndrome (ACS). The objective of the current study was to compare rates of major adverse cardiac and cerebrovascular events after a first ACS between people living with HIV (PLHIV) and HIV‐uninfected (HIV−) patients, and to identify determinants of cardiovascular prognosis. Methods and Results Consecutive PLHIV and matched HIV− patients with a first episode of ACS were enrolled in 23 coronary intensive care units in France. Patients were matched for age, sex, and ACS type. The primary end point was major adverse cardiac and cerebrovascular events (cardiac death, recurrent ACS, recurrent coronary revascularization, and stroke) at 36‐month follow‐up. A total of 103 PLHIV and 195 HIV− patients (mean age, 49 years [SD, 9 years]; 94.0% men) were included. After a mean of 36.6 months (SD, 6.1 months) of follow‐up, the risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV− patients (17.8% and 15.1%, P=0.22; multivariable hazard ratio [HR], 1.60; 95% CI, 0.67–3.82 [P=0.29]). Recurrence of ACS was more frequent among PLHIV (multivariable HR, 6.31; 95% CI, 1.32–30.21 [P=0.02]). Stratified multivariable Cox models showed that HIV infection was the only independent predictor for ACS recurrence. PLHIV were less likely to stop smoking (47% versus 75%; P=0.01) and had smaller total cholesterol decreases (–22.3 versus –35.0 mg/dL; P=0.04). Conclusions Although the overall risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV− individuals, PLHIV had a higher rate of recurrent ACS. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00139958.

Background: Electronic nicotine delivery systems (ENDS), or vaping, usage has become increasingly popular and generally has a positive perception by the public. However, ENDS are known to contain harmful chemicals and teratogens that induce numerous health consequences to both the pregnant mother and fetus. Despite this, physician knowledge and discussion of ENDS with their pregnant patients remains limited. The main objective of this study was to assess the knowledge of Obstetrics and Gynecology (OBGYN) providers regarding the safety and usage of ENDS in pregnancy. A secondary objective was to understand providers’ practices to increase patient education and awareness of the effects of ENDS on pregnant women and developing fetuses. Methods: A 40-question online anonymous survey was developed for this study. The survey aimed at assessing OBGYN providers’ understanding of the usage of ENDS and potential harms. The questionnaire was distributed to OBGYN providers in the Midwest and South of the United States of America. Results: One Hundred and four respondents completed the survey (95% response rate). While 96% of providers investigated alcohol and tobacco use during prenatal visits, only 44% routinely inquired about ENDS use. Most providers noted that they had received no formal education about ENDS usage and 55% of providers reported an insufficient understanding of vaping. Conclusions: These results demonstrate that providers lack the education and knowledge about ENDS usage in pregnancy. This is concerning as ENDS usage is rapidly increasing in the United States of America. It is essential to develop educational resources for providers about the risks of vaping and incorporate questions ENDS usage into the social history, especially in pregnancy.

Although 18–45-year-old (y-o) patients represent a significant proportion of patients hospitalized for COVID-19, data concerning the young population remain scarce. The Critical COVID France (CCF) study was an observational study including consecutive patients hospitalized for COVID-19 in 24 centers between 26 February and 20 April 2020. The primary composite outcome included transfer to the intensive care unit (ICU) or in-hospital death. Secondary outcomes were cardiovascular (CV) complications. Among 2868 patients, 321 (11.2%) patients were in the 18–45-y-o range. In comparison with older patients, young patients were more likely to have class 2 obesity and less likely to have hypertension, diabetes and dyslipidemia. The primary outcome occurred less frequently in 18–45-y-o patients in comparison with patients > 45 years old (y/o) (16.8% vs. 30.7%, p < 0.001). The 18–45-y-o patients presented with pericarditis (2.2% vs. 0.5%, p = 0.003) and myocarditis (2.5% vs. 0.6%, p = 0.002) more frequently than patients >45 y/o. Acute heart failure occurred less frequently in 18–45-y-o patients (0.9% vs. 7.2%, p < 0.001), while thrombotic complications were similar in young and older patients. Whereas both transfer to the ICU and in-hospital death occurred less frequently in young patients, COVID-19 seemed to have a particular CV impact in this population.

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship -emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors’ Network of the European Society of Cardiology.

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship -emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors’ Network of the European Society of Cardiology.

Objective Atrial fibrillation (AF) is one of the most common side effects of ibrutinib, a drug that has dramatically improved the prognosis of chronic B-cell malignancies such as chronic lymphocytic leukaemia (CLL). The true incidence of ibrutinib-related AF (IRAF) is not well known and its therapeutic management poses unique challenges especially due to the inherent risk of bleeding. We aimed to determine the incidence and predictors of IRAF, and to analyse its management and outcome.Methods A standardised monitoring was applied at two cardio-oncology clinics in consecutive patients referred before and during ibrutinib therapy. The primary endpoint was the incidence of IRAF. The excess of AF incidence with ibrutinib was studied by comparing the incidence of IRAF with the expected incidence of AF in general population and in patients with CLL not exposed to ibrutinib.Results 53 patients were included. The incidence of IRAF was 38% at 2 years and the risk was 15-fold higher than the AF risk in both the general population and patients with CLL not exposed to ibrutinib (p

Autosomal dominant hypercholesterolemia (ADH) is a human disorder characterized phenotypically by isolated high-cholesterol levels. Mutations in the low density lipoprotein receptor (LDLR), APOB, and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes are well known to be associated with the disease. To characterize the genetic background associated with ADH in France, the three ADH-associated genes were sequenced in a cohort of 120 children and 109 adult patients. Fifty-one percent of the cohort had a possible deleterious variant in LDLR, 3.1% in APOB, and 1.7% in PCSK9. We identified 18 new variants in LDLR and 2 in PCSK9. Three LDLR variants, including two newly identified, were studied by minigene reporter assay confirming the predicted effects on splicing. Additionally, as recently an in-frame deletion in the APOE gene was found to be linked to ADH, the sequencing of this latter gene was performed in patients without a deleterious variant in the three former genes. An APOE variant was identified in three patients with isolated severe hypercholesterolemia giving a frequency of 1.3% in the cohort. Therefore, even though LDLR mutations are the major cause of ADH with a large mutation spectrum, APOE variants were found to be significantly associated with the disease. Furthermore, using structural analysis and modeling, the identified APOE sequence changes were predicted to impact protein function.

Background: Gemcitabine is a nucleoside analog, widely used either alone or in combination, for the treatment of multiple cancers. However, gemcitabine may also be associated with cardiovascular adverse-drug-reactions (CV-ADR). Methods: First, we searched for all cases of cardiotoxicity associated with gemcitabine, published in MEDLINE on 30 May 2019. Then, we used VigiBase, the World Health Organization’s global database of individual case safety reports, to compare CV-ADR reporting associated with gemcitabine against the full database between inception and 1 April 2019. We used the information component (IC), an indicator value for disproportionate Bayesian reporting. A positive lower end of the 95% credibility interval for the IC (IC025) ≥ 0, is deemed significant. Results: In VigiBase, 46,898 reports were associated with gemcitabine on a total of 18,908,940 in the full database. Gemcitabine was associated with higher reporting for myocardial ischemia (MI, n: 119), pericardial diseases (n: 164), supraventricular arrhythmias (SVA, n: 308) and heart failure (HF, n: 484) versus full database with IC025 ranging between 0.40 and 2.81. CV-ADR were associated with cardiovascular death in up to 17% of cases. Conclusion: Treatment with gemcitabine is associated with potentially lethal CV-ADRs, including MI, pericardial diseases, SVA and HF. These events should be considered in patient care and clinical trial design.

Variants in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and progeroid syndromes. Cardiovascular laminopathic involvement is classically described as cardiomyopathy in striated muscle laminopathies, and arterial wall dysfunction and/or valvulopathy in lipodystrophic and/or progeroid laminopathies. We report unexpected cardiovascular phenotypes in patients with LMNA-associated lipodystrophies, illustrating the complex multitissular pathophysiology of the disease and the need for specific cardiovascular investigations in affected patients. A 33-year-old woman was diagnosed with generalized lipodystrophy and atypical progeroid syndrome due to the newly identified heterozygous LMNA p.(Asp136Val) variant. Her complex cardiovascular phenotype was associated with atherosclerosis, aortic valvular disease and left ventricular hypertrophy with rhythm and conduction defects. A 29-year-old woman presented with a partial lipodystrophy syndrome and a severe coronary atherosclerosis which required a triple coronary artery bypass grafting. She carried the novel heterozygous p.(Arg60Pro) LMNA variant inherited from her mother, affected with partial lipodystrophy and dilated cardiomyopathy. Different lipodystrophy-associated LMNA pathogenic variants could target cardiac vasculature and/or muscle, leading to complex overlapping phenotypes. Unifying pathophysiological hypotheses should be explored in several cell models including adipocytes, cardiomyocytes and vascular cells. Patients with LMNA-associated lipodystrophy should be systematically investigated with 24-h ECG monitoring, echocardiography and non-invasive coronary function testing.

I propose a classification of dispositions according to two parameters: (i) whether their argument is a causer, and (ii) whether they are (almost) always realized or only sometimes realized. This results in a four way distinction, which I represent as the Square of Disposition. Each cell of this square corresponds to a different type of disposition; I show that each such type is expressed by a distinct linguistic expression. This correspondence between philosophy-based and linguistics-based distinctions shows the potential usefulness of linguistic considerations in philosophical debates.

Metaphor abounds in both sign and spoken languages. However, in sign languages, languages in the visual-manual modality, metaphors work a bit differently than they do in spoken languages. In this paper we explore some of the ways in which metaphors in sign languages differ from metaphors in spoken languages. We address three differences: (a) Some metaphors are very common in spoken languages yet are infelicitous in sign languages; (b) Body-part terms are possible in very specific types of metaphors in sign languages, but are not so restricted in spoken languages; (c) Similes in some sign languages are dispreferred in predicative positions in which metaphors are fine, in contrast to spoken languages where both can appear in these environments. We argue that these differences can be explained by two seemingly unrelated principles: the Double Mapping Constraint (Meir, 2010), which accounts for the interaction between metaphor and iconicity in languages, and Croft’s (2003) constraint regarding the autonomy and dependency of elements in metaphorical constructions. We further argue that the study of metaphor in the signed modality offers novel insights concerning the nature of metaphor in general, and the role of figurative speech in language.

Thermal sensors (TS) are essential for achieving optimized performance and reliability in the era of nanoscale microprocessor and system on chip (SoC). Compiling with the low-power and small die area of the mobile computing, the presented TS supports a wide range of sampling frequencies with an optimized power envelope. The TS supports up to 45 K samples/s, low average power consumption, as low as 20 μW, and small core Si area of 0.013 mm2. Advanced circuit techniques are used in order to overcome process variability, ensuring inaccuracy lower than ±2 °C without any calibration. All this makes the presented thermal sensor a cost-effective, low-power solution for 22 nm nanoscale digital process technology.

No abstract available DOI: http://dx.doi.org/10.5564/mjia.v0i8-9.125 The Mongolian Journal of International Affairs; Number 8-9, 2002, Pages 12-23

Anorexigenics are compounds capable of reducing or suppressing appetite. Their three main types act on different neurotransmitters, either norepinephrine, serotonin or a combination of both. Among the drugs that act on norepinephrine are fenproporex, amfepramone and clobenzorex. Derivatives of the thyroid hormone triiodothyronine have also been associated with weight loss and used as a controversial treatment for obesity, despite their known cardiovascular side effects. Recent data suggest a possible vasodilating effect for these four substances that might be beneficial in a subset of patients. Herein we performed a systematic review of the literature (with emphasis on recent reports) to determine the implications and mechanisms of the vasodilating effects of some anorectics, specifically fenproporex, clobenzorex, amfepramone and triiodothyronine. Data analysis showed these four drugs to be vasodilating agents for rat aortic rings. The different mechanisms of action include endothelium-dependent vasodilation via activation of the NO-cGMP-PKG pathway and the opening of calcium-activated potassium channels. The finding of vasodilating activity indicates a potential role for some anorexigenic drugs in the treatment of obesity in hypertensive patients. Further in vivo studies are needed to test the clinical benefits of these four drugs.

BACKGROUND:Oral anticoagulation therapy is increasingly used for the prevention and treatment of thromboembolic complications in various clinical situations. Nowadays, education programs for patients treated with anticoagulants constitute an integrated component of their management. However, such programs are usually based on the healthcare providers' perceptions of what patients should know, rather than on patients' preferences. OBJECTIVE:To investigate patients' viewpoints on educational needs and preferred modalities of information delivery. METHODS:We conducted an observational study based on a self-administered questionnaire. To explore several profiles of patients, the study was designed for enrolling patients in two settings: during outpatient consultations in a cardiology department (Saint Antoine Hospital, Paris, France) and in community pharmacies throughout France. RESULTS:Of the 371 patients who completed the questionnaire, 187 (50.4%) were recruited during an outpatient consultation and 184 (49.6%) were recruited in community pharmacies. 84.1% of patients were receiving a vitamin K antagonist and 15.6% a direct oral anticoagulant. Patients ranked 16 of 21 (76.2%) questionnaire items on information about their treatment as important or essential; information on adverse effects of treatment was the highest ranked domain (mean score 2.38, 95% CI 2.30-2.46). Pharmacists (1.69, 1.58-1.80), nurses (1.05, 0.95-1.16), and patient associations (0.36, 0.29-0.44), along with group sessions (0.85, 0.75-0.95), the internet (0.77, 0.67-0.88), and delivery of material at the patient's home (1.26, 1.14-1.38), were ranked poorly in terms of delivering educational material. CONCLUSION:This study revealed substantial discrepancies between patient preferences and current educational programs. These findings should be useful for tailoring future educational programs that are better adapted to patients, with a potential associated enhancement of their effectiveness.

Disclosure of potential conflicts of interest (COI) is used by biomedical journals to guarantee credibility and transparency of the scientific process. Conflict of interest disclosure, however, is not systematically nor consistently dealt with by journals. Recent joint editorial efforts paved the way towards the implementation of uniform vehicles for COI disclosure. This paper provides a comprehensive editorial perspective on classical COI-related issues. New insights into the current COI policies and practices among European Society of Cardiology National Cardiovascular Journals, as derived from a cross-sectional survey using a standardised questionnaire, are discussed. Keywords: Conflict of interest, Disclosure, Editorial ethics, Journals

The Ribonuclease A Superfamily is composed of cationic peptides that are secreted by immune cells and epithelial tissues. Although their physiological roles are unclear, several members of the vertebrate Ribonuclease A Superfamily demonstrate antimicrobial and immune modulation activities. The objective of this review is to provide an overview of the published literature on the Ribonuclease A Superfamily with an emphasis on each peptide’s regulation, antimicrobial properties, and immunomodulatory functions. As additional insights emerge regarding the mechanisms in which these ribonucleases eradicate invading pathogens and modulate immune function, these ribonucleases may have the potential to be developed as a novel class of therapeutics for some human diseases.

Microfabricated semiconductor devices are becoming increasingly relevant for detection of biological and chemical components. The integration of active biological materials together with sensitive transducers offers the possibility of generating highly sensitive, specific, selective and reliable biosensors. This paper presents the fabrication of a sensitive, fully depleted (FD), electrolyte-insulator-semiconductor field-effect transistor (EISFET) made with a silicon-on-insulator (SOI) wafer of a thin 10-30 nm active SOI layer. Initial results are presented for device operation in solutions and for bio-sensing. Here we report the first step towards a high volume manufacturing of a CMOS-based biosensor that will enable various types of applications including medical and enviro nmental sensing.

To understand gene function, genetic analysis uses large perturbations such as gene deletion, knockdown or over-expression. Large perturbations have drawbacks: they move the cell far from its normal working point, and can thus be masked by off-target effects or compensation by other genes. Here, we offer a complementary approach, called noise genetics. We use natural cell-cell variations in protein level and localization, and correlate them to the natural variations of the phenotype of the same cells. Observing these variations is made possible by recent advances in dynamic proteomics that allow measuring proteins over time in individual living cells. Using motility of human cancer cells as a model system, and time-lapse microscopy on 566 fluorescently tagged proteins, we found 74 candidate motility genes whose level or localization strongly correlate with motility in individual cells. We recovered 30 known motility genes, and validated several novel ones by mild knockdown experiments. Noise genetics can complement standard genetics for a variety of phenotypes.

Regulation of proteins across the cell cycle is a basic process in cell biology. It has been difficult to study this globally in human cells due to lack of methods to accurately follow protein levels and localizations over time. Estimates based on global mRNA measurements suggest that only a few percent of human genes have cell-cycle dependent mRNA levels. Here, we used dynamic proteomics to study the cell-cycle dependence of proteins. We used 495 clones of a human cell line, each with a different protein tagged fluorescently at its endogenous locus. Protein level and localization was quantified in individual cells over 24h of growth using time-lapse microscopy. Instead of standard chemical or mechanical methods for cell synchronization, we employed in-silico synchronization to place protein levels and localization on a time axis between two cell divisions. This non-perturbative synchronization approach, together with the high accuracy of the measurements, allowed a sensitive assay of cell-cycle dependence. We further developed a computational approach that uses texture features to evaluate changes in protein localizations. We find that 40% of the proteins showed cell cycle dependence, of which 11% showed changes in protein level and 35% in localization. This suggests that a broader range of cell-cycle dependent proteins exists in human cells than was previously appreciated. Most of the cell-cycle dependent proteins exhibit changes in cellular localization. Such changes can be a useful tool in the regulation of the cell-cycle being fast and efficient.

The superlative quantifiers, at least and at most, are commonly assumed to have the same truth-conditions as the comparative quantifiers more than and fewer than. However, as Geurts & Nouwen (2007) have demonstrated, this is wrong, and several theories have been proposed to account for them. In this paper we propose that superlative quantifiers are illocutionary operators; specifically, they modify meta-speech acts. Meta speech-acts are operators that do not express a speech act, but a willingness to make or refrain from making a certain speech act. The classic example is speech act denegation, e.g. I don't promise to come, where the speaker is explicitly refraining from performing the speech act of promising What denegations do is to delimit the future development of conversation, that is, they delimit future admissible speech acts. Hence we call them meta-speech acts. They are not moves in a game, but rather commitments to behave in certain ways in the future. We formalize the notion of meta speech acts as commitment development spaces, which are rooted graphs: The root of the graph describes the commitment development up to the current point in conversation; the continuations from the root describe the admissible future directions. We define and formalize the meta-speech act GRANT, which indicates that the speaker, while not necessarily subscribing to a proposition, refrains from asserting its negation. We propose that superlative quantifiers are quantifiers over GRANTs. Thus, Mary petted at least three rabbits means that the minimal number n such that the speaker GRANTs that Mary petted n rabbits is n = 3. In other words, the speaker denies that Mary petted two, one, or no rabbits, but GRANTs that she petted more. We formalize this interpretation of superlative quantifiers in terms of commitment development spaces, and show how the truth conditions that are derived from it are partly entailed and partly conversationally implicated. We demonstrates how the theory accounts for a wide variety of phenomena regarding the interpretation of superlative quantifiers, their distribution, and the contexts in which they can be embedded.ReferencesBolinger, D. 1978. ‘Yes-No Questions are not Alternative Questions’. In H. Hiz (ed.) ‘Questions’, Dordrecht: Reidel.Borkin, A. 1971. ‘Polarity Items in Questions’. In ‘Papers from the 7th Regional Meeting of the Chicago Linguistic Society’, 53–62.Bott, L. & Noveck, I. A. 2004. ‘Some Utterances are Underinformative: The Onset and Time Course of Scalar Inferences’. Journal of Memory and Language 51, no. 3: 437–457.http://dx.doi.org/10.1016/j.jml.2004.05.006Brasoveanu, A. 2009. ‘Modified Numerals as Post-Suppositions’. In ‘Proceedings of the 17th Amsterdam Colloquium’, .Büring, D. 2007. ‘The least “at least" can do’. In ‘Proceedings of WCCFL 26’, 114–20. Somerville, MA: Cascadilla Press.Chierchia, G. 2004. ‘Scalar Implicatures, Polarity Phenomena and the Syntax/Pragmatics Interface’. In A. Belletti (ed.) ‘Structures and Beyond’, 39–103. Oxford: Oxford University Press.Cohen, A. 2010. ‘Epistemic Modals as Speech Act Modifiers’. Paper presented at Sentence Types, Sentence Moods and Illocutionary Forces: An International Conference to Honor Manfred Bierwisch, ZAS, Berlin.Coniglio, M. 2011. Die Syntax der deutschen Modalpartikeln. Berlin: Akademie-Verlag.Cummins, C. & Katsos, N. 2010. ‘Comparative and Superlative Quantifiers: Pragmatic Effects of Comparison Type’. Journal of Semantics 27: 271–305.http://dx.doi.org/10.1093/jos/ffq006Fodor, J. 1975. The Language of Thought. Cambridge, Massachusetts: Harvard University Press.Geurts, B. & Nouwen, R. 2007. ‘At Least et al.: The Semantics of Scalar Modifiers’. Language 83, no. 3: 533–559.http://dx.doi.org/10.1353/lan.2007.0115Geurts, B., Katsos, N., Cummins, C., Moons, J. & Noordman, L. 2010. ‘Scalar Quantifiers: Logic, Acquisition, and Processing’. Language and Cognitive Processes 5, no. 1: 244–253.Hacohen, A., Kozlowski, D. & Cohen, A. 2011a. ‘The Truth Shall Make You Slow: Superlative Quantifiers as Illocutionary Operators’. Presented at the Experimental Pragmatics Conference, Barcelona.Hacohen, A., Kozlowski, D. & Cohen, A. 2011b. ‘Superlative Quantifiers as Speech Act Modifiers: Experimental Evidence’. Presented at a workshop on The Proper Use of Quantification in Ordinary Language, Ljubljana.Hare, R. M. 1970. ‘Meaning and speech acts’. The Philosophical Review 79: 3–24.http://dx.doi.org/10.2307/2184066Horn, L. R. 1972. On the Semantic Properties of Logical Operators in English. Ph.D. thesis, University of California, Los Angeles.Kadmon, N. 1987. On Unique and Non-Unique Reference and Asymmetric Quantification. Ph.D. thesis, University of Massachusetts at Amherst.Kadmon, N. & Landman, F. 1993. ‘Any’. Linguistics and Philosophy 16: 353–422.http://dx.doi.org/10.1007/BF00985272Karttunen, L. 1977. ‘Syntax and semantics of questions’. Linguistics and Philosophy 1: 3–44.http://dx.doi.org/10.1007/BF00351935Kay, P. 1992. ‘At Least’. In A. Lehrer & E. F. Kittay (eds.) ‘Frames, Fields, and Contrasts: New Essays in Semantic and Lexical Organization’, 309–331. Hillsdayle, NJ: Lawrence Erlbaum Associates.Keenan, E. L. & Stavi, J. 1986. ‘A Semantic Characterization of Natural Language Determiners’. Linguistics and Philosophy 9, no. 3: 253–326.http://dx.doi.org/10.1007/BF00630273Krifka, M. 1991. ‘Some Remarks on Polarity Items’. In D. Zaefferer (ed.) ‘Semantic Universals and Universal Semantics’, 150–189. Berlin/New York: Foris.Krifka, M. 1995. ‘The Semantics and Pragmatics of Polarity Items’. Linguistic Analysis 25: 209–257.Krifka, M. 1999a. ‘At Least Some Determiners Aren’t Determiners’. In K. Turner (ed.) ‘The Semantics/Pragmatics Interface from Different Points of View’, 257–291. Amsterdam: Elsevier.Krifka, M. 1999b. ‘Quantification into Question Acts’. In ‘Proceedings of Semantics and Linguistic Theory 9’, Cornell: CLC Publications.Krifka, M. 2001. ‘Quantification into Question Acts’. Natural Language Semantics 9: 1–40.http://dx.doi.org/10.1023/A:1017903702063Krifka, M. to appear. ‘Embedding Speech Acts’.Lakoff, R. 1969. ‘Some Reasons Why There Can’t Be Any Some-Any Rule’. Language 45, no. 3: 608–615.http://dx.doi.org/10.2307/411442Lyons, J. 1977. Semantics. Cambridge: Cambridge University Press.Nilsen, Øystein. 2007. ‘At Least—Free Choice and Lowest Utility’. Talk given at the ESSLLI Workshop On Quantifier Modification, Dublin.http://www.let.uu.nl/~Rick.Nouwen/qm/nilsen.pdf.Nouwen, R. 2009. ‘The Semantics of Minimal Requirements’. Paper presented at the 7th Conference on Semantics and Modelisation (JSM09), Paris.Noveck, I. 2001. ‘When Children are More Logical than Adults: Experimental Investigations of Scalar Implicature’. Cognition 78: 165–188.http://dx.doi.org/10.1016/S0010-0277(00)00114-1Pope, E. 1972. Questions and Answers in English. Ph.D. thesis, Massachusetts Institute of Technology.Roelofsen, F. & van Gool, S. 2009. ‘Disjunctive Questions, Intonation, and Highlighting’. In M. Aloni & K. Schulz (eds.) ‘Proceedings of the Seventeenth Amsterdam Colloquium’, .Schlenker, P. 2002. ‘A Plea for Monsters’. Linguistics and Philosophy 26: 29–120.http://dx.doi.org/10.1023/A:1022225203544Searle, J. R. 1969. Speech Acts: An Essay in the Philosophy of Language. Cambridge: Cambridge University Press.Shapira, R. 2010. ‘Surveying the Evaluative Sense of Superlative Quantifiers When Embedded as Conditional Antecedents’. Guided research paper, Ben-Gurion University of the Negev.Sweetser, E. 1996. ‘Reasoning, Mappings, and Meta-Metaphorical Conditionals’. In M. Shibatani & S. Thompson (eds.) ‘Grammatical Constructions: Their Form and Meaning’, Oxford: Oxford University Press.von Fintel, K. & Iatridou, S. 2005. ‘What to Do if You Want to Go to Harlem: Anankastic Conditionals and Related Matters’. Ms., Massachusetts Institute of Technology.von Stechow, A., Krasikova, S. & Penka, D. 2005. ‘Anankastic conditionals’. Ms., University of Tubingen.

The majority of participants (Cohen, Esposito, Fuller, and Khan) shared the concern that militant and violent adherents of radical political Islam – “jihadis,” for lack of a better term – may not only radicalize the West’s attitude toward western Muslims, but, more importantly, toward Islam as a whole. Indeed, the continuation of terrorism against western interests will likely result in either an American or a combined western future response – both political and military. The result of either action may be greater involvement by the United States in the greater Middle East, although, ironically, one needs to remember that it is the radicals who would, in fact, prefer that this country pull out of the region. Terrorism is also the cause of what some authors refer to as “Islamophobia,” a phenomenon that remains quite rare despite the events of 9/11. Though 2004 saw a greater number of anti-Jewish incidents reported in the United States than anti-Islamic incidents, one could assume that the jihadis would prefer to see anti-Muslim incidents carried out by Americans to increase. One reason for this could be that aberrant American actions, especially if they are blown out of proportion by media in the United States and abroad, will radicalize Muslims and cause the jihadis’ ranks to swell. Additionally, Cohen, Esposito, Fuller, and Khan also agreed upon the necessity for a broader interpretation of the meaning of ijtihad as a tool of modernization for the Muslim world. However, one of the other participants, Jan, formulated a traditionalist/fundamentalist position regarding ijtihad, viewing it as a tool that only the ulama can wield. He believes that mass and elite indoctrination along the lines of traditional orthodox Islam will bring about the establishment of a pan-Islamic state along the lines of a khilafah. Most of other participants disagreed with such a prognosis. Unfortunately, Esposito, Fuller, and Jan launched quite vitriolic and misplaced attacks against the supporters of Israel. They refer to them by different names: “pro-Likud Lobbies,” “extremists,” or supporters of the “Zionist state.” The topic of Arab-Israeli relations has little to do with the questions at hand: moderate Islam vs. radical Islam, and the future of political Islam. If Israel never existed, the extremists would identify other issues to fight about. Israel-bashers, fall prey – or are, indeed, intentional mouthpieces for – a conspiracy theory of the worst kind: an ideological canard, that the United States, or even the world, is run by the Jews. These modern simulacra certainly resemble something out of the Protocols of the Elders of Zion, a Czarist secret service (Okhrana) piece of anti-Semitic disinformation, or the vitriolic rhetoric of Der Sturmer, the Nazi propaganda weekly rag. Take Jan’s 2003 discussion of Husain Haqqani’s article in The Nation: … there are well-studded gems for pleasing [the] master of our destiny, the Zionists in the U.S… Realising Zionist power, the chief opportunist, General Musharraf, took the lead through covert promises of recognising Israel during his visit to the U.S.[2] The intellectual mercenaries are now trying to catch up with some confused mixture of rejecting Musharraf and accepting Israel ...

Question 1: Various commentators have frequently invoked the importance of moderate Muslims and the role that they can play in fighting extremism in the Muslim world. But it is not clear who is a moderate Muslim. The recent cancellation of Tariq Ramadan’s visa to the United States, the raids on several American Muslim organizations, and the near marginalization of mainstream American Muslims in North America pose the following question: If moderate Muslims are critical to an American victory in the war on terror, then why does the American government frequently take steps that undermine moderate Muslims? Perhaps there is a lack of clarity about who the moderate Muslims are. In your view, who are these moderate Muslims and what are their beliefs and politics? AC: I would like to say from the outset that I am neither a Muslim nor a sociologist. Therefore, my remarks should be taken as those of an interested and sympathetic outsider. I do not believe at all that the American government “undermines” moderate Muslims. The problem is more complicated. Many American officials abhor engagement in religion or the politics of religion. They believe that the American Constitution separates religion and state and does not allow them to make distinctions when it comes to different interpretations of Islam. For some of them, Salafiya Islam is as good as Sufi Islam. Others do not have a sufficient knowledge base to sort out the moderates from the radicals, identify the retrograde fundamentalists, or recognize modernizers who want political Islam to dominate. This is wrong. Radical ideologies have to do more with politics and warfare than religion, and, in some extreme cases, should not enjoy the constitutional protections of freedom of religion or free speech. There is a difference between propagating a faith and disseminating hatred, violence, or murder. The latter is an abuse and exploitation of faith for political ends, and should be treated as such. For example, the racist Aryan Nation churches were prosecuted and bankrupted by American NGOs and the American government. One of the problems is that the American government allows radical Muslims who support terrorism to operate with impunity in the United States and around the world, and does very little to support moderate Muslims, especially in the conflict zones. To me, moderate Muslims are those who do not view the “greater jihad” either as a pillar of faith or as a predominant dimension thereof. A moderate is one who is searching for a dialogue and a compromise with people who adhere to other interpretations of the Qur’an, and with those who are not Muslim. Amoderate Sunni, for example, will not support terror attacks on Shi`ahs or Sufis, or on Christians, Jews, or Hindus. Moderate Muslims respect the right of individuals to disagree, to worship Allah the way they chose, or not to worship – and even not to believe. Amoderate Muslim is one who is willing to bring his or her brother or sister to faith by love and logic, not by mortal threats or force of arms. Amoderate Muslim decries suicide bombings and terrorist “operations,” and abhors those clerics who indoctrinate toward, bless, and support such atrocities. The list of moderate Muslims is too long to give all or even a part of it here. Shaykh Muhammad Hisham Kabbani (chairman of the Islamic Supreme Council of America) and Sheikh Abdul Hadi Palazzi (secretarygeneral of the Rome-based Italian Muslim Association) come to mind. Ayatollah Ali Sistani may be a moderate, but I need to read more of his teachings. As the Wahhabi attacks against the Shi`ah escalate, Shi`i clerics and leaders are beginning to speak up. Examples include Sheikh Agha Jafri, a Westchester-based Pakistani Shi`ah who heads an organization called the Society for Humanity and Islam in America, and Tashbih Sayyed, a California-based Pakistani who serves as president of the Council for Democracy and Tolerance. I admire the bravery of Amina Wadud, a female professor of Islamic studies at Virginia Commonwealth University who led a mixed-gender Friday Islamic prayer service, according to Mona Eltahawy’s op-ed piece in The Washington Post on Friday, March 18, 2005 (“A Prayer Toward Equality”). Another brave woman is the co-founder of the Progressive Muslim Union of America, Sarah Eltantawi. And the whole world is proud of the achievements of Judge Shirin Ebadi, the Iranian human rights lawyer who was awarded the Nobel peace prize in 2003. There is a problem with the first question, however. It contains several assumptions that are debatable, to say the least, if not outright false. First, it assumes that Tariq Ramadan is a “moderate.” Nevertheless, there is a near-consensus that Ramadan, while calling for ijtihad, is a supporter of the Egyptian Ikhwan al-Muslimin [the Muslim Brotherhood] and comes from that tradition [he is the grandson of its founder, Hasan al-Banna]. He also expressed support for Yusuf al-Qaradawi (and all he stands for) on a BBC TVprogram, and is viewed as an anti-Semite. He also rationalizes the murder of children, though apparently that does not preclude the European Social Forum from inviting him to be a member. He and Hasan al-Turabi, the founder of the Islamic state in Sudan, have exchanged compliments. There are numerous reports in the media, quoting intelligence sources and ex-terrorists, that Ramadan associates with the most radical circles, including terrorists. In its decision to ban Ramadan, the United States Department of Homeland Security was guided by a number of issues, some of them reported in the media and others classified. This is sufficient for me to believe that Ramadan may be a security risk who, in the post-9/11 environment, could reasonably be banned from entering the United States.1 Second, the raids on “American Muslim organizations” are, in fact, a part of law enforcement operations. Some of these steps have had to do with investigations of terrorist activities, such as the alleged Libyan conspiracy to assassinate Crown Prince Abdullah of Saudi Arabia. Others focused on American Islamist organizations that were funding the terrorist activities of groups on the State Department’s terrorism watch list, such as Hamas. To say that these criminal investigations are targeting moderate Islam is like saying that investigating pedophile priests undermines freedom of religion in the United States. Finally, American Muslims are hardly marginalized. They enjoy unencumbered religious life and support numerous non-governmental organizations that often take positions highly critical of domestic and foreign policy – something that is often not the case in their countries of origin. There is no job discrimination – some senior Bush Administration officials, such as Elias A. Zerhouni, head of the National Institutes of Health (NIH), are Muslims. American presidents have congratulated Muslims on religious holidays and often invite Muslim clergymen to important state functions, such as the funeral of former president Ronald Reagan.

Abstract The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship - emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors´ Network of the European Society of Cardiology.