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The physics of a rotary wing in forward flight are highly complex, particularly when flow separation is involved. The purpose of this work is to assess the role of three-dimensional (3-D) vortex dynamics, with a focus on Coriolis forces, in the evolution of vortices in the reverse flow region of a rotating wing. High-fidelity numerical simulations were performed to recreate the flow about a representative rotating wing in forward flight. A vorticity transport analysis was performed to quantify and compare the magnitudes of 2-D flow physics, vortex tilting and Coriolis effects in the resulting flow fields. Three-dimensional vortex dynamics was found to have a very small impact on the growth and behaviour of vortices in the reverse flow region; in fact, the rate of vortex growth was successfully modelled using a simple 2-D vortex method. The small role of 3-D physics was attributed to the Coriolis and vortex tilting terms being approximately equal and opposite to one another. This ultimately lead to vortex behaviour that more closely resembled a surging wing as opposed to a conventional rotating wing, a feature unique to the reverse flow region.
Peripheral low-grade inflammation in depression is increasingly seen as a therapeutic target. We aimed to establish the prevalence of low-grade inflammation in depression, using different C-reactive protein (CRP) levels, through a systematic literature review and meta-analysis.
We searched the PubMed database from its inception to July 2018, and selected studies that assessed depression using a validated tool/scale, and allowed the calculation of the proportion of patients with low-grade inflammation (CRP >3 mg/L) or elevated CRP (>1 mg/L).
After quality assessment, 37 studies comprising 13 541 depressed patients and 155 728 controls were included. Based on the meta-analysis of 30 studies, the prevalence of low-grade inflammation (CRP >3 mg/L) in depression was 27% (95% CI 21–34%); this prevalence was not associated with sample source (inpatient, outpatient or population-based), antidepressant treatment, participant age, BMI or ethnicity. Based on the meta-analysis of 17 studies of depression and matched healthy controls, the odds ratio for low-grade inflammation in depression was 1.46 (95% CI 1.22–1.75). The prevalence of elevated CRP (>1 mg/L) in depression was 58% (95% CI 47–69%), and the meta-analytic odds ratio for elevated CRP in depression compared with controls was 1.47 (95% CI 1.18–1.82).
About a quarter of patients with depression show evidence of low-grade inflammation, and over half of patients show mildly elevated CRP levels. There are significant differences in the prevalence of low-grade inflammation between patients and matched healthy controls. These findings suggest that inflammation could be relevant to a large number of patients with depression.
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of olaratumab (Lartruvo®), Eli Lilly & Company Limited, to submit evidence for the clinical and cost effectiveness of this drug, in combination with doxorubicin, for advanced soft tissue sarcoma (STS) not amenable to surgery or radiotherapy, as part of the Institute's Single Technology Appraisal. The Peninsula Technology Assessment Group critically reviewed the submitted evidence.
Clinical effectiveness was derived from an open-label, randomized controlled trial, JGDG. The economic analysis was based on a partitioned survival model with a time horizon of 25 years. The perspective was of the UK National Health Service (NHS) and Personal Social Services. Costs and benefits were discounted at 3.5 percent per year. The company's evidence was submitted in anticipation that olaratumab would be considered as an alternative to doxorubicin, which has been used as a first-line treatment for advanced STS. To improve the cost effectiveness of olaratumab, the company offered a discount through a Commercial Access Agreement with the NHS England.
In the company's submission, the mean base-case and probabilistic incremental cost-effectiveness ratios (ICERs) for olaratumab plus doxorubicin versus doxorubicin alone were GBP 46,076 (USD 61,403) and GBP 47,127 (USD 62,804) per quality-adjusted life-year (QALY) gained, respectively; the probability of this treatment being cost effective at the willingness-to-pay threshold of GBP 50,000 (USD 66,632) per QALY gained, applicable to end-of-life treatments, was 0.54. The respective estimates in our analysis were approximately GBP 60,000 (USD 79,959) per QALY gained, and the probability of cost-effectiveness was 0.21. The increase in the ICERs was primarily due to differences in extrapolation of overall survival, and drug administration costs.
Based on the available evidence, olaratumab in combination with doxorubicin improves the survival of patients with advanced STS. However, this treatment is unlikely to be cost-effective. Olaratumab is now recommended for use within the Cancer Drugs Fund.
To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.
To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.
Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.
Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.
Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis.
We report baseline neuropsychological findings from a longitudinal, population-based study of first-episode psychosis, which followed up cases from index admission to 10 years. At the 10-year follow up patients were classified as treatment responsive or TR after reconstructing their entire case histories. Of 145 cases with neuropsychological data at baseline, 113 were classified as treatment responsive, and 32 as TR at the 10-year follow-up.
Compared with 257 community controls, both case groups showed baseline deficits in three composite neuropsychological scores, derived from principal component analysis: verbal intelligence and fluency, visuospatial ability and executive function, and verbal memory and learning (p values⩽0.001). Compared with treatment responders, TR cases showed deficits in verbal intelligence and fluency, both in the extended psychosis sample (t = −2.32; p = 0.022) and in the schizophrenia diagnostic subgroup (t = −2.49; p = 0.017). Similar relative deficits in the TR cases emerged in sub-/sensitivity analyses excluding patients with delayed-onset treatment resistance (p values<0.01–0.001) and those born outside the UK (p values<0.05).
Verbal intelligence and fluency are impaired in patients with TR psychosis compared with those who respond to treatment. This differential is already detectable – at a group level – at the first illness episode, supporting the conceptualisation of TR psychosis as a severe, pathogenically distinct variant, embedded in aberrant neurodevelopmental processes.
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.
This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.
A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.
Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.
The effectiveness of Early Intervention in Psychosis (EIP) services for individuals with a first episode of psychosis (FEP) could be thwarted by high rates of early disengagement.
To investigate which factors predict disengagement with EIP services.
Using data from a naturalistic cohort of 786 EIP clients in East Anglia (UK), we investigated the association between sociodemographic and clinical predictors and disengagement using univariable and multivariable Cox proportional hazards models.
Over half (54.3%) of our sample were discharged before receiving 3 years of EIP care, with 92 (11.7%) participants discharged due to disengagement. Milder negative symptoms, more severe hallucinations, not receiving an FEP diagnosis, polysubstance use and being employed were associated with greater disengagement.
Our findings highlight heterogeneous reasons for disengagement with EIP services. For some patients, early disengagement may hinder efforts to sustain positive long-term EIP outcomes. Efforts to identify true FEP cases and target patients with substance use problems and more severe positive symptoms may increase engagement.
The heat-assisted magnetic recording (HAMR) head–disk interface is a unique operating environment that combines nanoscale spacings, high shear rates, high-temperature gradients, and high optical fluxes in a mass-produced device. One of the greatest challenges is to develop materials for the head–disk interface that enable the required head–media spacing while also providing reliability. Traditional head–disk interface materials, engineered and optimized for conventional magnetic recording hard-disk drives, are challenged to provide the needed performance at the high temperatures that HAMR involves. We review some of the primary materials used in conventional magnetic recording, how high temperatures challenge their performance, and some of the current understanding and strategies to develop a reliable HAMR head–disk interface.
This study compared the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme portfolio of research with the united Kingdom (UK) burden of disease, as measured by Disability-Adjusted Life Years (DALYs).
Design: Cross-sectional study.
Setting: The HTA Programme cohort included all funded applications (n = 363) received by the HTA Programme during the period 1 April 2011 to 31 March 2016. The sample contained primary research and evidence syntheses, all purely methodological studies were excluded since these are not comparable to the other study types.
Main Outcome Measure: Proportion of spend for each of the twenty-one Health Research Classification System (HRCS) health categories were compared with burden of disease in the UK calculated using 2015 DALY data from the Institute for Health Metrics and Evaluation (IHME) Global Health Data Exchange (GHDx).
The funded HTA Programme projects totalled about GBP397million research spend, which broadly reflected the UK DALY burden. Overall, there was less than 5 percent difference between the actual and predicted programme spend based on the burden of disease in the UK in most instances (seventeen out of the twenty-one HRCS Health Categories).
The largest categories of apportioned spend were Cancer (accounting for 12.1 percent of portfolio), and Mental Health (11.8 percent of portfolio) which particularly reflected the 9.8 percent burden of disease to the UK. Most notable deviations from DALY, where spend was lower than disease burden, were in the Cancer, Cardiovascular and Musculoskeletal categories; which may reflect the importance of other, notably charity, funding.
The HTA Programme spend broadly aligns with burden of disease as measured using DALYs. Discrepancies were expected owing to the programme remit and its approach to commissioning research to address market failure particularly in areas that are not already well supported by research charities or industry. Regular review of DALY data during research prioritisation and commissioning allows the HTA Programme to identify and address shortfalls in disease areas and to balance its portfolio.
Uncertainty (i.e., variable payoffs with unknown probabilities) brings together a number of features of the authors' argument. It leads to present bias, even for completely rational agents with time-consistent preferences. As an evolutionary product of Pleistocene climate instability, humans possess broad adaptations to environmental uncertainty, giving rise to key features of the behavioral constellation of deprivation (BCD).
Abraham Lincoln was fond of saying “killing the dog does not cure the bite” when referring to problems and their persnickety pervasiveness. When thinking about the problems facing the industrial and organizational (I-O) psychology profession, there is no greater source of frustration than the gap between a scientist's findings and the application of those findings to practice. In recent years, organizations such as the White House Behavioral Sciences unit, the Society for Human Resource Management (SHRM) Foundation in partnership with The Economist Intelligence Unit, and many others have explored the gap between research and practice and have highlighted every major derailer, from delays associated with peer-reviewed publication cycles to a lacking infrastructure for bringing science to practitioners. In 2014, the SHRM Foundation even went so far as to implement a strategy based on driving research directly to practitioners through executive round table forums. Despite the best efforts to identify strategies for closing the gap, many organizations have failed to find the optimal means for bringing I-O psychology research to the masses of human resource (HR) practitioners and, in many cases, even I-O psychology practitioners dealing with significant organizational issues.
Although there is an impressive body of research on the U.S. Congress, there has been limited discussion about the central role race plays in the organization of this political institution. While some scholars have documented Congress’ racist past, less is known about the present significance of race in the federal legislature. Throughout the day, African Americans routinely nod to one another in the halls of the Capitol, and consider the Black nod as a common cultural gesture. However, data from over sixty in-depth interviews suggest there is an additional layer of meaning to the Black nod in Congress. From the microlevel encounters, I observed and examined, I interpret the nod as more than a gesture that occurs in a matter of seconds between colleagues or even among perfect strangers in the halls of Congress. The Black nod encompasses and is shaped by labor organized along racial lines, a history of racial subordination, and powerful perceptions of race in the post-Civil-Rights era on the meso-, and macrolevels. Using this interpretive foundation, this article will show how the nod is an adaptive strategy of Black staffers that renders them visible in an environment where they feel socially invisible. The nod becomes an external expression of their racialized professional identity. I argue that the congressional workplace is a raced political institution and that the microlevel encounters I observed delineate and reproduce its racial boundaries. This article represents perhaps the first sociological study of Congress and provides an unprecedented view into its inner workings and the social dimensions that organize workplace relationships.
Issues in traditional cross-section sampling of paintings and other cultural artifacts with a scalpel, such as crumbling, delamination and paint compression, can deter conservators from sampling fragile paint layers. Often, such sampling carries the risk of causing further damage from a scalpel, which outweighs the benefits of scientific investigation. Here, we show that femtosecond lasers offer a viable alternative to obtaining cross-sections with minimal damage to the surrounding artwork. A Regenerative Ti:Sapphire amplifier system with a pulse duration of 70 femtoseconds, a few milliwatts of average power and a repetition rate of 1 kHz (1000 pulses/sec) was used for the study. Tests were performed on oil paintings ranging in age from the 19th century to late 20th century. Effective settings were determined to be 2 mW of power at a speed of 10mm/sec using an 800nm laser. Preliminary results suggest femtosecond lasers could be a viable alternative for obtaining paint cross-sections when traditional sampling methods cause unnecessary damage to fragile materials.
To investigate an outbreak of Burkholderia cepacia complex and describe the measures that revealed the source.
A 629-bed, tertiary-care, pediatric hospital in Houston, Texas.
Pediatric patients without cystic fibrosis (CF) hospitalized in the pediatric and cardiovascular intensive care units.
We investigated an outbreak of B. cepacia complex from February through July 2016. Isolates were evaluated for molecular relatedness with repetitive extragenic palindromic polymerase chain reaction (rep-PCR); specific species identification and genotyping were performed at an independent laboratory. The investigation included a detailed review of all cases, direct observation of clinical practices, and respiratory surveillance cultures. Environmental and product cultures were performed at an accredited reference environmental microbiology laboratory.
Overall, 18 respiratory tract cultures, 5 blood cultures, 4 urine cultures, and 3 stool cultures were positive in 24 patients. Among the 24 patients, 17 had symptomatic infections and 7 were colonized. The median age of the patients was 22.5 months (range, 2–148 months). Rep-PCR typing showed that 21 of 24 cases represented the same strain, which was identified as a novel species within the B. cepacia complex. Product cultures of liquid docusate were positive with an identical strain of B. cepacia complex. Local and state health departments, as well as the CDC and FDA, were notified, prompting a multistate investigation.
Our investigation revealed an outbreak of a unique strain of B. cepacia complex isolated in clinical specimens from non-CF pediatric patients and from liquid docusate. This resulted in a national alert and voluntary recall by the manufacturer.