nils-herrmann/clean_scirepeval huggingface dataset:
Simvastatin in the Acute Respiratory Distress Syndrome.
Venue: The New England journal of medicine

There are in vitro, animal and phase 2 studies suggesting that statins may be beneficial in the acute respiratory distress syndrome (ARDS) This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS.  In this multicentre, allocation concealed, double blind clinical trial, patients with an onset of ARDS within the previous 48 hours were randomized in a 1:1 ratio to receive enteral simvastatin 80mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator free days to day 28. Secondary outcomes included number of non pulmonary organ failure free days to day 28, mortality at 28 days and safety.  The study recruited 540 patients with 259 patients allocated to simvastatin and 281 patients to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between study groups in mean SD) ventilator free days (12.6+ 9.9 with simvastatin and 11.5+ 10.4 with placebo, P 0.21) non pulmonary organ failure free days (19.4+ 11.1 with simvastatin and 17.8+ 11.7 with placebo, P 0.11) or in 28 day mortality (22.0% with simvastatin and 26.8% with placebo, P 0.23) There was no difference in the incidence of severe adverse events between the groups.  Simvastatin therapy, while safe and with minimal adverse effects, did not improve clinical outcomes in patients with ARDS. (Funded by the UK National Institute for Health Research Efficacy and Confidential: Destroy when review is complete. Submitted to the New England Journal of Medicine
Acute respiratory distress syndrome.
Venue: Clinical medicine

Acute respiratory distress syndrome is a common cause of acute respiratory failure that is underdiagnosed both inside and outside of intensive care units. Progression to the most severe forms of the syndrome confers a mortality rate greater than 40% and is associated with often severe functional disability and psychological sequelae in survivors. While there are no disease modifying pharmacotherapies for the syndrome, this progression may be prevented through the institution of quality improvement measures that minimise iatrogenic injury associated with acute severe illness.
[Acute respiratory distress syndrome]
Venue: Medicina

Acute respiratory distress syndrome (ARDS) is an acute respiratory failure produced by an inflammatory edema secondary to increased lung capillary permeability. This causes alveolar flooding and subsequently deep hypoxemia, with intrapulmonary shunt as its most important underlying mechanism. Characteristically, this alteration is unresponsive to high FIO2 and only reverses with end expiratory positive pressure (PEEP) Pulmonary infiltrates on CXR and CT are the hallmark, together with decreased lung compliance. ARDS always occurs within a week of exposition to a precipitating factor; most frequently pneumonia, shock, aspiration of gastric contents, sepsis, and trauma. In CT scan, the disease is frequently inhomogeneous, with gravitational infiltrates coexisting with normal density areas and also with hyperaerated parenchyma. Mortality is high (30 60% especially in ARDS associated with septic shock and neurocritical diseases. The cornerstone of therapy lies in the treatment of the underlying cause and in the use mechanical ventilation which, if inappropriately administered, can lead to ventilator induced lung injury. Tidal volume 6 ml/kg of ideal body weight to maintain an end inspiratory (plateau) pressure 30 cm H2O "protective ventilation" is the only variable consistently associated with decreased mortality. Moderate to high PEEP levels are frequently required to treat hypoxemia, yet no specific level or titration strategy has improved outcomes. Recently, the use of early prone positioning in patients with PaO2/FIO2 150 was associated with increased survival. In severely hypoxemic patients, it may be necessary to use adjuvants of mechanical ventilation as recruitment maneuvers, pressure controlled modes, neuromuscular blocking agents, and extracorporeal membrane oxygenation. Fluid restriction appears beneficial.
Current incidence and outcome of the acute respiratory distress syndrome
Venue: Current opinion in critical care

This article discusses recently published articles reporting the incidence and outcome of patients with the acute respiratory distress syndrome (ARDS) This is a difficult task since there is a marked variability regarding the methodology of the few, large epidemiological, and observational studies on ARDS.  The review will mainly focus on publications from the past 18 months. We have reviewed new epidemiological studies reporting population based incidence of ARDS. Also, we have reviewed the data on survival reported in observational and randomized controlled trials, discussed how the current ARDS definition modifies the true incidence of ARDS, and briefly mentioned recent approaches that appear to improve ARDS outcome.  On the basis of current evidence, it seems that the incidence and overall hospital mortality of ARDS has not changed substantially in the last decade. Independent of the definition used for identification of ARDS patients, reported population based incidence of ARDS is an order of magnitude lower in Europe than in the USA. Current hospital mortality of combined moderate and severe ARDS reported in observational studies is greater than 40%
Low Tidal Volume Ventilation Use in Acute Respiratory Distress Syndrome*
Venue: Critical care medicine

Low tidal volume ventilation lowers mortality in the acute respiratory distress syndrome. Previous studies reported poor low tidal volume ventilation implementation. We sought to determine the rate, quality, and predictors of low tidal volume ventilation use. Retrospective cross sectional study. One academic and three community hospitals in the Chicago region. A total of 362 adults meeting the Berlin Definition of acute respiratory distress syndrome consecutively admitted between June and December 2013. Seventy patients (19.3% were treated with low tidal volume ventilation (tidal volume 6.5 mL/kg predicted body weight) at some time during mechanical ventilation. In total, 22.2% of patients requiring an FIO2 greater than 40% and 37.3% of patients with FIO2 greater than 40% and plateau pressure greater than 30 cm H2O received low tidal volume ventilation. The entire cohort received low tidal volume ventilation 11.4% of the time patients had acute respiratory distress syndrome. Among patients who received low tidal volume ventilation, the mean (SD) percentage of acute respiratory distress syndrome time it was used was 59.1% (38.2% and 34% waited more than 72 hours prior to low tidal volume ventilation initiation. Women were less likely to receive low tidal volume ventilation, whereas sepsis and FIO2 greater than 40% were associated with increased odds of low tidal volume ventilation use. Four attending physicians (6.2% initiated low tidal volume ventilation within 1 day of acute respiratory distress syndrome onset for greater than or equal to 50% of their patients, whereas 34 physicians (52.3% never initiated low tidal volume ventilation within 1 day of acute respiratory distress syndrome onset. In total, 54.4% of patients received a tidal volume less than 8 mL/kg predicted body weight, and the mean tidal volume during the first 72 hours after acute respiratory distress syndrome onset was never less than 8 mL/kg predicted body weight. More than 12 years after publication of the landmark low tidal volume ventilation study, use remains poor. Interventions that improve adoption of low tidal volume ventilation are needed.
A Pathophysiologic Approach to Biomarkers in Acute Respiratory Distress Syndrome
Venue: Disease markers

Acute respiratory distress syndrome (ARDS) is an acute onset hypoxic condition with radiographic bilateral lung infiltration. It is characterized by an acute exudative phase combining diffuse alveolar damage and lung edema followed by a later fibroproliferative phase. Despite an improved understanding of ARDS pathobiology, our ability to predict the development of ARDS and risk stratify patients with the disease remains limited. Biomarkers may help to identify patients at the highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. After a short description of ARDS pathobiology, here, we review the scientific evidence that supports the value of various ARDS biomarkers with regard to their major biological roles in ARDS associated lung injury and/or repair. Ongoing research aims at identifying and characterizing novel biomarkers, in order to highlight relevant mechanistic explorations of lung injury and repair, and to ultimately develop innovative therapeutic approaches for ARDS patients. This review will focus on the pathophysiologic, diagnostic, and therapeutic implications of biomarkers in ARDS and on their utility to ultimately improve patient care.
VectorH: Taking SQL on Hadoop to the Next Level
Venue: SIGMOD Conference

Actian Vector in Hadoop (VectorH for short) is a new SQL on Hadoop system built on top of the fast Vectorwise analytical database system. VectorH achieves fault tolerance and storage scalability by relying on HDFS, and extends the state of the art in SQL on Hadoop systems by instrumenting the HDFS replication policy to optimize read locality. VectorH integrates with YARN for workload management, achieving a high degree of elasticity. Even though HDFS is an append only filesystem, and VectorH supports (update averse) ordered tables, trickle updates are possible thanks to Positional Delta Trees (PDTs) a differential update structure that can be queried efficiently. We describe the changes made to single server Vectorwise to turn it into a Hadoop based MPP system, encompassing workload management, parallel query optimization and execution, HDFS storage, transaction processing and Spark integration. We evaluate VectorH against HAWQ, Impala, SparkSQL and Hive, showing orders of magnitude better performance.
Hybrid central upwind finite volume schemes for solving the Euler and Navier Stokes equations
Venue: Comput. Math. Appl.

A novel method based on the hybridization of central schemes and upwind schemes is proposed for finite volume discretization of the Euler and NavierStokes equations on multi blocked structured grids. The developed methodology takes the advantages of the low diffusion characteristic from an improved central scheme and the discontinuity capturing capability from a characteristic based upwind scheme. A simple and efficient improvement to the scalar dissipation and matrix dissipation model for the central scheme is suggested to enhance the accuracy of the existing methods. The resulting hybrid schemes are as compact as the underlying finite volume methods and therefore easy to implement. Numerical results for a wide range of flow conditions demonstrate the method simultaneously obtains the desired accuracy and sharp, oscillation free shock transition for both the inviscid and viscous simulation.
Characteristic boundary conditions for magnetohydrodynamics: The Brio Wu shock tube

In the present paper we develop and test a characteristic based boundary condition (BC) scheme for the compressible magnetohydrodynamic equations, as the extension of a characteristic gasdynamics BC model. We use a Harten Yee finite volume scheme for the spatial discretization of the domain, and a TVD Backward Euler time integrator for the sake of robustness. First we verify that the scheme works correctly for gasdynamic initial conditions (i.e. when B 0 comparing with both analytical and experimental data. We then test the BC scheme with the Brio and Wu shock tube for two different types of boundaries: an open end and solid walls. We present a comparison between results obtained with the zeroth order extrapolated BC scheme and the characteristic scheme developed. For a solid wall condition, we found discrepancies between both schemes when perturbations in the transverse magnetic field component (By) reach the boundaries. Also for the open end condition some discrepancies appear between the characteristic and extrapolated schemes, presenting the latter some instabilities. The results obtained with the characteristic scheme are smoother but presented a different wave pattern, which we believe is physical.
Specimen agnostic guided wave inspection using recursive feedback
Venue: 2016 IEEE International Ultrasonics Symposium (IUS)

Lamb waves, a configuration of guided waves are often applied to the inspection of plate like structures. Their complex, multi modal nature makes them well suited to the inspection of different defects. Control over their propagation direction allows the engineer to increase inspection distance and prospectively locate the defect. Schemes already exist, but they require knowledge of material and its dispersion curves. If the material composition is not known, or external factors are effecting its speed of sound then these schemes may not be appropriate. The recursive feedback algorithm can be used to enhance guided waves in a single direction without a priori knowledge. In recursive feedback, a guided wave is generated using the first element of an array transducer. Over several subsequent iterations, this guided wave is reinforced by re transmitting recorded out of plane displacements. In this work, recursive feedback has been applied to two inspection problems; a contaminated kissing bond and a plate with a defect. With the kissing bond, it is shown that the the contamination can be identified as the A0 mode of generated waves are absorbed. In the defective plate, the defect direction is identified by a 10 dB increase in reflected energy when the guided waves are enhanced in one direction.
Identification of novel macrolides with antibacterial, anti inflammatory and type I and III IFN augmenting activity in airway epithelium
Venue: The Journal of antimicrobial chemotherapy

Exacerbations of asthma and COPD are triggered by rhinoviruses. Uncontrolled inflammatory pathways, pathogenic bacterial burden and impaired antiviral immunity are thought to be important factors in disease severity and duration. Macrolides including azithromycin are often used to treat the above diseases, but exhibit variable levels of efficacy. Inhaled corticosteroids are also readily used in treatment, but may lack specificity. Ideally, new treatment alternatives should suppress unwanted inflammation, but spare beneficial antiviral immunity.  In the present study, we screened 225 novel macrolides and tested them for enhanced antiviral activity against rhinovirus, as well as anti inflammatory activity and activity against Gram positive and Gram negative bacteria. Primary bronchial epithelial cells were grown from 10 asthmatic individuals and the effects of macrolides on rhinovirus replication were also examined. Another 30 structurally similar macrolides were also examined.  The oleandomycin derivative Mac5, compared with azithromycin, showed superior induction (up to 5 fold, EC50 5 11 mM) of rhinovirus induced type I IFNb, type III IFNl1 and type III IFNl2/3 mRNA and the IFN stimulated genes viperin and MxA, yet had no effect on IL 6 and IL 8 mRNA. Mac5 also suppressed rhinovirus replication at 48 h, proving antiviral activity. Mac5 showed antibacterial activity against Gram positive Streptococcus pneumoniae; however, it did not have any antibacterial properties compared with azithromycin when used against Gram negative Escherichia coli (as a model organism) and also the respiratory pathogens Pseudomonas aeruginosa and non typeable Haemophilus influenzae. Further non toxic Mac5 derivatives were identified with various anti inflammatory, antiviral and antibacterial activities.  The data support the idea that macrolides have antiviral properties through a mechanism that is yet to be ascertained. We also provide evidence that macrolides can be developed with anti inflammatory, antibacterial and antiviral activity and show surprising versatility depending on the clinical need.
Open arms, conflicted hearts: nurse practitioner's attitudes towards working with lesbian, gay and bisexual patients.
Venue: Journal of clinical nursing

To explore nurse practitioner's attitudes towards working with lesbian, gay and bisexual patients.  Literature suggests that lesbians, gay men and bisexuals have significant health disparities compared to heterosexuals. Although the reasons are multifactorial, research suggests that attitudes of healthcare providers (HCPs) may be a contributing factor in both accessing and receiving care. There is currently no literature exploring the attitudes of the approximately 300,000 nurse practitioners in the United States. Thus, nurse practitioners strengths and challenges in providing care to sexual minorities are unknown.  As part of a larger study, Corbin Strauss' grounded theory methodology was used to explore the attitudes towards lesbian, gay and bisexual patients among primary care nurse practitioners in NYC.  Data were collected via individual semi structured interviews with nurse practitioners currently in practice in primary or outpatient care in NYC (n 19) Data were evaluated using the three step constant comparison method.  Nurse practitioners in this study had varied, often overlapping and sometimes conflicting, attitudes about working with lesbian, gay and bisexual patients. The main theme identified was 'open arms, conflicted hearts' with three major subthemes feeling at home, struggling to maintain professionalism and finding comfort under the umbrella of diversity.  Nurse practitioner participants in this study had varied attitudes about working with lesbian, gay and bisexual patients, ranging from open, confident and comfortable to ambivalent, cautious and unsure about working with lesbian, gay and bisexual patients generally and specifically regarding the health needs of this population.  This study highlights the inadequate didactic and clinical preparation most nurse practitioners feel they have to care for lesbian, gay and bisexual patients. There is a need for increased education for registered nurses and nurse practitioners regarding lesbian, gay and bisexual culture, their unique healthcare needs, as well as the role of stigma and marginalisation in caring for vulnerable populations.
A nurse led sexual rehabilitation intervention after radiotherapy for gynecological cancer
Venue: Supportive Care in Cancer

PurposeAlthough vaginal dilator use after combined pelvic radiation therapy and brachytherapy (RT/BT) is recommended to prevent vaginal shortening and stenosis, women fail to use them and experience sexual problems. A nurse led sexual rehabilitation intervention targeting sexual recovery and vaginal dilatation was developed. Its feasibility was investigated during a prospective, longitudinal, observational pilot study.MethodsFour oncology nurses were specifically trained to conduct the intervention. Gynecologic cancer patients treated with RT/BT were assessed using (i) questionnaires on frequency of dilator use (monthly) sexual functioning, and sexual distress (at baseline and 1, 6, and 12 months) and psychological and relational distress (at 1, 6, and 12 months) (ii) semi structured interviews (between 6 and 12 months) and (iii) consultation recordings (a random selection of 21 of all consults).ResultsTwenty participants were 26 71 years old (mean 40) Eight participants discontinued participation after 3 to 9 months. At 6 months after RT, 14 out of 16 (88 and at 12 months 9 out of 12 (75 participants dilated regularly, either by having sexual intercourse or by using dilators. Sexual functioning improved between 1 and 6 months after RT, with further improvement at 12 months. Most participants reported that the intervention was helpful and the nurses reported having sufficient expertise and counseling skills.ConclusionsAccording to the pilot results, the intervention was feasible and promising for sexual rehabilitation and regular dilator use after RT. Its (cost )effectiveness will be investigated in a randomized controlled trial.
Assuring the Proper Analytical Performance of Measurement Procedures for Immunosuppressive Drug Concentrations in Clinical Practice: Recommendations of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology Immunosuppressive Drug Scientific Committee
Venue: Therapeutic drug monitoring

Monitoring immunosuppressive drugs (ISDs) in blood or plasma is still a key therapeutic drug monitoring (TDM) application in clinical settings. Narrow target ranges and severe side effects at drug underexposure or overexposure make accurate and precise measurements a must. This overview prepared by the Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology is intended to serve as a summary and guidance document describing the current state of the art in the TDM of ISDs.
Toxicology Strategies for Drug Discovery: Present and Future.
Venue: Chemical research in toxicology

Attrition due to nonclinical safety represents a major issue for the productivity of pharmaceutical research and development (R&D) organizations, especially during the compound optimization stages of drug discovery and the early stages of clinical development. Focusing on decreasing nonclinical safety related attrition is not a new concept, and various approaches have been experimented with over the last two decades. Front loading testing funnels in Discovery with in vitro toxicity assays designed to rapidly identify unfavorable molecules was the approach adopted by most pharmaceutical R&D organizations a few years ago. However, this approach has also a non negligible opportunity cost. Hence, significant refinements to the "fail early, fail often" paradigm have been proposed recently to reflect the complexity of accurately categorizing compounds with early data points without taking into account other important contextual aspects, in particular efficacious systemic and tissue exposures. This review provides an overview of toxicology approaches and models that can be used in pharmaceutical Discovery at the series/lead identification and lead optimization stages to guide and inform chemistry efforts, as well as a personal view on how to best use them to meet nonclinical safety related attrition objectives consistent with a sustainable pharmaceutical R&D model. The scope of this review is limited to small molecules, as large molecules are associated with challenges that are quite different. Finally, a perspective on how several emerging technologies may impact toxicity evaluation is also provided.