bluuebunny/crossref_metadata_2025 huggingface dataset:
Deploying time investigation of automotive active hood lift mechanism with different design parameters of hinge part
Authors: Lee Tae-Hoon , Yoon Gun-Ha , Choi Seung-Bok
Published: April 2016

This article investigates the change in deploying time of an active hood lift mechanism of a passenger vehicle activated by a gunpowder actuator. Especially, in this work, the deploying time is investigated by changing the principal design parameters of the hinge part of the hood mechanism. After briefly introducing the working principle of the active hood lift mechanism operated by the gunpowder actuator, the governing dynamic equations of the active hood lift mechanism are formulated for deploying motion. Subsequently, using the governing equations of motion, the response time for deploying the hood lift mechanism is investigated by changing several geometric locations such as the location of actuator. Then, a comparison is made of the total response time to completely deploy the hood lift mechanism with the existing conventional hood lift mechanism and the proposed active hood lift mechanism. In addition, the workable driving speed of the proposed active hood lift mechanism is compared with the conventional one by changing the powder volume of the actuator.
‘The martyr of dawn’: Femicide in Jordanian media
Authors: Mahadeen Ebtihal
Published: April 2016

This study aims to address the gap in Arab media scholarship on the representation of gender-based violence. Despite the prevalence and normalisation of gender-based violence in Jordan, no scholarly engagements exist that unpack the role of the media in fostering this social acceptance. This paper aims to critically analyse the media’s role by adopting a comparative approach to two types of femicide which have made headlines in the country: the first, a single mega murder which occurred in December 2013, and the second, a number of so-called honour crimes which occurred in 2008–2014. It argues that while both are manifestations of sexual violence, Jordanian media approach these femicides in wildly different ways and rank their victims differently. Drawing on criminological engagements with victimology, homicide and the media, the paper reveals the implicit assumptions and practices of Jordanian news media. This analysis is located within its Jordanian context, where violence against women, and even so-called honour crimes, are normalised.
Incidence and long-term outcomes of adult patients with diabetic ketoacidosis admitted to intensive care: A retrospective cohort study
Authors: Ramaesh Aksha
Published: April 2016

Aims

Diabetic ketoacidosis is a life-threatening but avoidable complication of diabetes mellitus often managed in intensive care units. The risk of emergency hospital readmission in patients surviving an intensive care unit episode of diabetic ketoacidosis is unknown. We aimed to report the cumulative incidence of emergency hospital readmission and costs in all patients surviving an intensive care unit episode of diabetic ketoacidosis in Scotland.

Methods

We used a national six-year cohort of survivors of first diabetic ketoacidosis admissions to Scottish intensive care units (1 January 2005–31 December 2010) identified in the Scottish Intensive Care Society Audit Group registry linked to acute hospital and death records (follow-up censored 31 December 2010). Diabetic ketoacidosis-related emergency readmissions were identified using International Classification of Disease-10 codes.

Results

During the study period, 386 patients were admitted to intensive care units in Scotland with diabetic ketoacidosis (admission rate 1.5/100,000 Scottish population). Median age was 44 (IQR 29–56); 51% male; 55% required no organ support on admission. Mortality after intensive care unit admission was 8% at 30 days, 18% at one year, and 35% at five years. A total of 349 patients survived their first intensive care unit diabetic ketoacidosis admission [mean (SD) age 42.5 (18.1) years; 50.4% women; 46.1% required ≥1 organ support]. Following hospital discharge, cumulative incidence of 90-day, one-year, and five-year diabetic ketoacidosis readmission (all-cause readmission) was 13.8% (31.8%), 29.7% (58.9%) and 46.4% (82.6%).

Discussion

Diabetic ketoacidosis in patients requiring intensive care unit admission is associated with high risk of long-term mortality and high hospital costs. An understanding of the precipitating causes of diabetic ketoacidosis in patients admitted to intensive care units may allow patients who are at high risk to be targeted, potentially reducing future morbidity and the substantial burden that diabetic ketoacidosis currently places on the healthcare system.
Classic cases revisited: Oscar the cat and predicting death
Authors: Szawarski Piotr
Published: April 2016

Uncertainty, although inherent in medicine, is rarely discussed in spite of being ubiquitous. Communication of uncertainty is poor due to anxiety associated with it, yet one could argue that lack of such disclosure could undermine trust, lead to perception of deceit, alter decision making and in some cases could invalidate the consent process. Predictions concerning end of life are particularly difficult and may lead to excessive or insufficient medical interventions. Acknowledging uncertainty when prognosticating outcomes, and in particular death, may help in facilitating patient-centred care in context of a critical illness.
Effects of functional shirts with different fiber compositions on thermoregulation in well-trained runners
Authors: Herten Anne , Csapo Robert , Kofler Philipp , Bottoni Giuliamarta , Hasler Michael , Bechtold Thomas , Nachbauer Werner
Published: April 2016

This study aimed to investigate the effects of two functional sport shirts with different fiber compositions (polyester: 100% polyester vs polyester–lyocell combination: 67%–33%) on thermoregulation and wearing comfort during treadmill walking at an average intensity under moderate environmental conditions. It was hypothesized that the hydrophilic lyocell fibers would benefit sweat evaporation and, thus, provide a superior cooling effect. Using a repeated-measures study design, core, surface and between skin-and-shirt temperatures were measured in 11 men while wearing either the polyester or polyester–lyocell shirt. Additionally, sweat loss, heart rate and subjective perception of comfort were determined. In spite of significantly greater sweat production, relative humidity was lower with the polyester–lyocell shirt. In the later phases of the walking intervention, the temperatures were consistently higher with polyester–lyocell, although between-shirt differences failed to reach significance. These results suggest that greater water retention limits the thermoregulatory efficiency of cellulosic fibers when excessive sweat production occurs.
Scrotal emergencies
Authors: Williams Sarah Anne , Menezes Pravin
Published: April 2016

A common presentation to GPs is by patients with symptoms of scrotal pain, swelling and erythema. Some of these conditions have a benign cause, and therefore, can be managed in primary care. Other causes require urgent referral to secondary services for further investigation and management. The aim of this article is to enable GPs to be able to identify scrotal emergencies based on clinical presentation and examination findings. This will allow appropriate and timely referrals to be made, which will optimise patient care and subsequent outcomes. We discuss common presentations and their management based on suspected diagnosis.
Stem cell-based therapies in inflammatory bowel disease: promises and pitfalls
Authors: Duran Natalie E. , Hommes Daniel W.
Published: April 2016

Inflammatory bowel disease (IBD) is a chronic, often relapsing, condition that deeply impacts the quality of life for many patients. Although there have been significant advances in medical treatments, a large proportion of patients become refractory to available therapeutic options. Stem-cell therapy through hematopoietic stem cells (HSCs) or mesenchymal stem (stromal) cells (MSCs) is a promising therapeutic option for severe refractory cases especially when surgery is not feasible. In HSC transplantation, the objective is to destroy the ‘autoreactive’ immune cells responsible for disease chronicity, and to re-establish gut tolerance to gut microbes. In perianal Crohn’s disease (CD), the objective is to deposit MSCs locally in fistulizing tracts to down-regulate the local immune response and induce wound healing. Results from upcoming and ongoing clinical trials will set the path of these novel therapeutic options that have the capability to successfully treat severe refractory Crohn’s patients.
Investigating the therapeutic role and molecular biology of curcumin as a treatment for glioblastoma
Authors: Rodriguez Gregor A. , Shah Ashish H. , Gersey Zachary C. , Shah Sumedh S. , Bregy Amade , Komotar Ricardo J. , Graham Regina M.
Published: April 2016

Objectives:

Despite the aggressive standard of care for patients with glioblastoma multiforme, survival rates typically do not exceed 2 years. Therefore, current research is focusing on discovering new therapeutics or rediscovering older medications that may increase the overall survival of patients with glioblastoma. Curcumin, a component of the Indian natural spice, turmeric, also known for its antioxidant and anti-inflammatory properties, has been found to be an effective inhibitor of proliferation and inducer of apoptosis in many cancers. The goal of this study was to investigate the expanded utility of curcumin as an antiglioma agent.

Methods:

Using the PubMed MeSH database, we conducted a systematic review of the literature to include pertinent studies on the growth inhibitory effects of curcumin on glioblastoma cell lines based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results:

A total of 19 in vitro and five in vivo studies were analyzed. All of the studies indicated that curcumin decreased glioblastoma cell viability through various pathways (i.e. decrease in prosurvival proteins such as nuclear factor κB, activator protein 1, and phosphoinositide 3 kinase, and upregulation of apoptotic pathways like p21, p53, and executor caspase 3). Curcumin treatment also increased animal survival compared with control groups.

Conclusions:

Curcumin inhibits proliferation and induces apoptosis in certain subpopulations of glioblastoma tumors, and its ability to target multiple signaling pathways involved in cell death makes it an attractive therapeutic agent. As such, it should be considered as a potent anticancer treatment. Further experiments are warranted to elucidate the use of a bioavailable form of curcumin in clinical trials.
Differences between invasive lobular and invasive ductal carcinoma of the breast: results and therapeutic implications
Authors: Barroso-Sousa Romualdo , Metzger-Filho Otto
Published: April 2016

Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer (BC): ILC differs from invasive ductal carcinoma (IDC) in its clinicopathological characteristics and responsiveness to systemic therapy. From the clinical standpoint, data suggest that ILC derives a distinct benefit from systemic therapy compared to IDC. In addition, comprehensive molecular analyses have been reported for ILCs, confirming that these tumors have specific genomic profiles compared to IDC. Despite these differences, clinical trials and practical clinical guidelines tend to treat BC as a single entity. Here we discuss these clinical and molecular data and their therapeutic implications.
Context Moderates Affirmation Effects on the Ethnic Achievement Gap
Authors: Protzko John , Aronson Joshua
Published: April 2016

We attempted to replicate a self-affirmation intervention that produced a 40% reduction in the academic achievement gap among at-risk students. The intervention was designed as a protection against stereotype threat—, which creates stress and suppresses the performance, engagement, and learning of students stereotyped as intellectually inferior. In previous research, Black and Hispanic students who engaged in a values-affirmation exercise significantly improved their academic performance over the course of a school semester. We attempted to replicate these salutary effects in both an inner-city school and a more wealthy suburban school—contexts not tested in the original research. Despite employing the same materials, we found no effect of the affirmation on academic performance. We discuss these results in terms of the possibility that negatively stereotyped students benefit most from self-affirmations in environments where their numbers portray them neither as clearly “majority” nor minority.
Medical management of gastrinoma in a cat
Authors: Lane Michael , Larson Jeanne , Hecht Silke , Tolbert M Katherine
Published: April 2016

Case summary

A 7-year-old male castrated domestic short-haired cat was evaluated for a 4 week history of intermittent vomiting, ptyalism, lethargy and weight loss. Serum biochemistry revealed mild mixed hepatopathy. Abdominal ultrasonography identified multiple heterogeneous hepatic masses and a linear, hyperechoic focus with associated reverberation artifact in the wall of the stomach consistent with a gastric ulcer. Serum gastrin concentrations were markedly increased. Cytologic interpretation of a fine-needle aspirate of the hepatic masses was consistent with neuroendocrine neoplasia, and a diagnosis of gastrinoma was established. Deterioration of the cat’s condition, despite at-home acid-suppressant therapy, led to hospitalization. The cat was initially stabilized with intravenous crystalloid fluid therapy, maropitant, pantoprazole and octreotide. A continuous radiotelemetric intragastric pH monitoring system was used to monitor the response of intragastric pH to therapy. Long-term therapy was continued with omeprazole (orally q12h), octreotide (subcutaneously q8h) and thrice-weekly toceranib administered orally. Toceranib therapy led to gastrointestinal upset and was discontinued. Gastric ulceration resolved within 8 weeks, and palliation of clinical signs was achieved for approximately 5 months.

Relevance and novel information

Including this report, only six cases of feline gastrinoma have been reported in the veterinary literature. Little is known regarding non-surgical therapy, and octreotide has not been previously reported for medical management of feline gastrinoma. Results of intragastric pH monitoring and clinical improvement suggest that medical therapy using octreotide and proton pump inhibitors represents a novel therapeutic option for cats with gastrinoma where surgical excision is not feasible.
Ethnic enclaves revisited: Effects on earnings of migrant workers in China
Authors: Zhang Chunni , Xie Yu
Published: April 2016

Among rural-to-urban migrants, migrant workers from the same origins tend to concentrate in the same workplaces. When this concentration in a workplace is sufficiently dense, we may consider it a native-place enclave. According to extensive literature on US immigrants, enclave participation may improve the economic well-being of immigrants. This study borrows the same reasoning to evaluate whether or not working in a native-place enclave affects earnings of migrant workers in urban China. We pay particular attention to heterogeneity, not only in how migrants who work in an enclave may differ from those who choose to work in the open economy, but also in varying earnings returns to enclave participation across different groups of migrant workers. Using data from a 2010 survey of migrant workers in the Pearl River Delta and the Yangtze River Delta, we match enclave workers and non-enclave workers with the same propensity to work in an enclave and then compare their earnings differences. We find a positive average earnings return to enclave participation, although this effect is smaller than that resulting from a naïve comparison. Moreover, we find that migrants with a high propensity to work in an enclave benefit more from enclave participation than those with a low propensity. Our findings generally support the enclave thesis and its role in internal migration in China.
Academic achievement as status competition: Intergenerational transmission of positional advantage among Taiwanese and American students
Authors: Tam Tony
Published: April 2016

This article compares the intergenerational transmission of relative/positional advantage for the academic achievement of secondary school students in Taiwan and the USA. Although any monotonic transformation of rank order is a valid measure of positional status, we use ‘the average number of competitors excluded’ as the index of positional status (PSI) because it is a ratio-scale metric easy to interpret and universally comparable—even among different variables and achievement test scores based on completely different tests. A PSI analysis of two large-scale national surveys of secondary school students (TEPS and NELS) shows that parental education plays a much stronger role than family income in both societies. Most important, parental education and income effects on the PSI are statistically indistinguishable between the two societies, despite very substantial differences in the institution of secondary education, including the screening and allocation of secondary students for higher education. This resemblance is especially striking given the large cross-national variation in the same PSI-based measures of intergenerational transmission of positional advantage among Organisation for Economic Co-operation and Development (OECD) countries.
Developmental idealism, body weight and shape, and marriage entry in transitional China
Authors: Xu Hongwei
Published: April 2016

New trends toward later and less marriages are emerging in post-reform China. Previous research has examined the changing individual-level socioeconomic and demographic characteristics shaping marriage entry in Chinese adults. Employing a cultural model known as developmental idealism, this study argues that a new worldview specifying an ideal body type has become popular in the West and that this new worldview has been exported to China. This new part of the developmental idealism package is likely stratified by gender, has a stronger impact on women than on men, and has likely penetrated urban areas more than rural areas. Drawing on the 1991–2009 longitudinal data from the China Health and Nutrition Survey, this study employs discrete-time logit models to estimate the relationships between various body types and the transition to first marriage in Chinese young adults aged 18 to 30 years. Body weight status and body shape are measured by body mass index and waist-to-hip ratio, respectively, and further divided into categories of underweight, normal, and obese. Regression results indicate that larger values of body mass index and waist-to-hip ratio were associated with delayed entry into first marriage in urban women, whereas being overweight or obese was associated with accelerated transition to first marriage in rural men. Not only were these associations statistically significant, but their strengths were substantively remarkable. Findings from this study suggest that both body weight and body shape have important implications for marital success, independent of individual-level socioeconomic and demographic characteristics, and contribute to evolving gender and rural–urban disparities, as China is undergoing a rapid nutrition transition.
Political capital and intergenerational mobility: Evidence from elite college admissions in China
Authors: Yang Wenhui , Chen Ling
Published: April 2016

In this article, we examine the intergenerational influence of political capital on educational attainment. Most previous researchers have focused on the centrality of political cadres to the redistribution of resources in transitional economies, yet the intergenerational mobility of these cadres has rarely been discussed. We use data from the 2010 Chinese College Student Survey to investigate the effects of cadre parent status on children’s admission to elite colleges in China. The results reveal that the children of cadre parents are more likely to attend elite colleges. According to the results of China’s standardized college entrance examinations, the children of cadre parents are not innately more intelligent than the children of non-cadre parents. However, children with cadre parents are more likely to attend elite senior high schools, which increases their likelihood of gaining entrance to elite colleges.
The Geriatric Driver
Authors: Ikpeze Tochukwu C. , Elfar John C.
Published: April 2016

The increase in the growth of the elderly population in the past 2 decades has been paralleled by an increase in the number of active elderly drivers. Consequentially, this growth has been accompanied by a rise in fatal road-related accidents. Due to age-related fragility, elderly drivers are more susceptible to injuries and death following a road-related accident. The increased risk of accidents has become a growing public health issue and has led to certain guidelines and restrictions for elderly drivers. Moreover, the cognitive and physiological decline that exacerbates with age has encouraged preventative measures aimed at optimizing their ability to operate motor vehicles. Some of these include yearly vision, cognitive, motor, and mental assessment tests. Results obtained from these tests may help suggest when an elderly driver becomes unsuitable to drive.
Fostering Stakeholders Trust through CSR Reporting: An Analytical Focus
Authors: Verma Priyanka , Singh Anupam
Published: April 2016

Corporate social responsibility (CSR) is a buzzword worldwide. In today’s globalized world, one of the great challenges faced by firms is integration of CSR in business. Stakeholders require a lot more from companies than merely pursuing growth and profitability. They demand information about economic, social and environmental performances of the companies. Previous studies in developed countries have confirmed that a true and sincere corporate communication leads to the building of stakeholders’ trust. There is, however, a dearth of such studies in developing countries such as India. This study is an attempt to bridge the gap by conducting an exploratory study on how the top management of a company reports CSR. Using the technique of content analysis, this article assessed the extent and nature of CSR reporting by Indian companies. We used multiple regression analysis to evaluate how well a set of predictors explain the social disclosure practices of Indian firms. The results indicated that there is no significant relationship between a firm’s profitability and its corporate social disclosure (CSD). However, a firm’s ownership (private sector or public sector) has influence on CSD practices. The findings also suggest that firm size has a positive association with CSD under the community development theme. This implies that large companies with public visibility favour community development. Finally, the study ends with a conclusion that has strong managerial implications: sincere and honest social reporting can harness a better relationship with all stakeholders.
Parent Income–Based Gaps in Schooling
Authors: Ziol-Guest Kathleen M. , Lee Kenneth T. H.
Published: April 2016

Both income inequality and the achievement test score gap between high- and low-income children increased dramatically in the United States beginning in the 1970s. Recent work by Chetty, Hendren, Kline, Saez, and Turner (2014) suggests that, unlike the test score gap, the gap in college enrollment is essentially constant. This article takes a longer historical view and investigates trends in income-based gaps in a number of schooling attainment measures using data from two cohorts of the National Longitudinal Survey of Youth (NLSY79 and NLSY97) as well as 31 birth cohorts from the Panel Study of Income Dynamics (PSID). Findings support Chetty and colleagues’ conclusion of little change in college enrollment for their cohorts but show significant increases in college enrollment gaps between Chetty and colleagues’ and prior cohorts in both the PSID and the NLSY. We further find strong evidence of growing gaps in college completion. In contrast, gaps in high school graduation have fallen, which provide at least one optimistic sign of catching up among low-income individuals. The net result of these trends is to produce a modestly increasing gap in completed schooling between children growing up in low- and high-income families.
“Hot, Black Leather, Whip”
Authors: Heldman Caroline , Frankel Laura Lazarus , Holmes Jennifer
Published: April 2016

This article employs a content analysis to investigate whether and how the violent woman archetype in action film changed from 1960 to 2014. We find a trend toward hypersexualized female action leads (FALs), starting in the 2000s. This trend is in line with the broader social trends of hypersexualization during this period, evidenced in a variety of other media sources. We then combine these findings with existing research to discuss the likely affects on viewers’ attitudes and beliefs. We suggest that the trend toward hypersexualizing FALs has harmful public health affects and is part of a broader cultural backlash against gender equity. Public Health Significance Statement: This study finds a trend toward hypersexualization of female protagonists in action cinema that contributes to the cultural normalization of female objectification. This normalization has been linked to clinical depression, habitual body monitoring, diet restriction, symptoms of anorexia and bulimia, social physique anxiety, shame about bodily functions, inhibited cognitive functioning, diminished motor skills, diminished sexual pleasure, lower self-esteem, diminished personal efficacy, and lower overall well-being for women.
The Impact of Class and Sexuality-Based Stereotyping on Rape Blame
Authors: Spencer Bettina
Published: April 2016

In order to investigate whether stereotypes about sexuality can impact perceptions of sexual assault, participants read a scenario that described a situation in which a woman reported being raped. The woman’s socioeconomic status (SES) was varied, so that she appeared to be of low or high-SES. Following the vignette, participants completed explicit measures that assessed victim blame, attitudes toward rape victims, and perceived promiscuity. Participants also answered an open-ended question that was coded for minimizing and maximizing language. Last, participants completed an “attitude survey” that measured classist attitudes. It was hypothesized that participants who read about the low-SES woman would show more rape blame, display more negative attitudes about rape victims, respond to the open-ended question with more minimizing language, and perceive her as being more promiscuous. It was also predicted that these explicit measures would be positively correlated and that the language measure would be moderated by participants’ classism. Results supported these hypotheses. Participants who read about the low-SES survivor showed more negative attitudes, believed her to be more culpable, and more promiscuous. The explicit measures were positively correlated. Additionally, participants differed in linguistic minimization and maximization, such that participants who were low in classism were more likely to maximize the low-SES target’s experience, whereas participants who were high in classism were more likely to minimize the low-SES target’s experience. Taken together, these results suggest that low-SES women are stereotyped as being promiscuous and that this stereotype affects how they may be blamed after cases of sexual assault. Public Health Significance Statement: The results of this study suggest that low-socioeconomic status (SES) survivors of assault are more likely to be blamed and found culpable for the assault than high-SES women. These attitudes correlate with stereotypes about low-SES women’s sexuality.
Digital Imaging Capability for Caries Detection
Authors: Winand C. , Shetty A. , Senior A. , Ganatra S. , De Luca Canto G. , Alsufyani N. , Flores-Mir C. , Pachêco-Pereira C.
Published: April 2016

The objective of this study was to identify the diagnostic capability of photostimulable phosphor plates (PSPs) and direct digital sensors (DDSs) in the detection of interproximal caries. Studies were identified that evaluated the diagnostic capability of PSPs and DDSs in detecting interproximal caries in human teeth, in both dentin and enamel. Histologic sections were the gold standard. This systematic review searched several electronic databases. In addition, Google Scholar and reference lists of the finally included studies were screened. QUADAS-2 was applied to evaluate the risk of bias among included studies. Six studies were finally included; 4 of which were considered homogeneous enough to conduct a meta-analysis. The meta-analysis evaluated 668 interproximal human tooth surfaces. All studies used extracted human teeth ranging from no caries present to caries into dentin. Each tooth was radiographed by both PSP and DDS technologies and then submitted for histologic analysis as the gold standard. Meta-analysis showed that intraoral digital imaging is of high specificity but low sensitivity in the detection of interproximal caries. The sensitivity and specificity for different studies with PSPs varied substantially from 15% to 54% and from 84% to 100%, respectively. Direct sensor analysis sensitivity and specificity ranged from 16% to 56% and from 90% to 100%, respectively. Newer PSP and DDS technologies had statistically significant higher sensitivities, yet the differences in diagnostic capabilities between the older and newer technologies were clinically insignificant. Both digital systems were excellent in identifying surfaces without caries (specificity) but were not sensitive enough to reliably identify interproximal surfaces with caries. Clinicians must therefore remain vigilant in performing a careful clinical examination and other diagnostic tests rather than relying solely on radiographic imaging to diagnose interproximal caries.

Knowledge Transfer Statement: This study will help clinicians make an evidence-based decision when deciding which digital radiography system to use when evaluating interproximal caries. Time, patient radiation safety, cost, and image quality are factors to be considered. The performance of the different available digital imaging systems was compared with the current gold standard—a histologic analysis—via meta-analysis.
A thrombopoietin receptor antagonist is capable of depleting myelofibrosis hematopoietic stem and progenitor cells
Authors: Wang Xiaoli , Haylock David , Hu Cing Siang , Kowalczyk Wioleta , Jiang Tianbo , Qiu Jiajing , Mosoyan Goar , He Wu , Marshall Netonia , Mascarenhas John , Tarasova Anna , Brody Joshua , Winkler David , Hoffman Ronald
Published: April 2016

Key Points

Treatment of MF CD34+ cells with a TPO receptor antagonist selectively depletes MF HSCs and HPCs. Agents that target the TPO receptor represent potentially new approaches for the treatment of MF patients.
Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype
Authors: Toubiana Julie , Okada Satoshi , Hiller Julia , Oleastro Matias , Lagos Gomez Macarena , Aldave Becerra Juan Carlos , Ouachée-Chardin Marie , Fouyssac Fanny , Girisha Katta Mohan , Etzioni Amos , Van Montfrans Joris , Camcioglu Yildiz , Kerns Leigh Ann , Belohradsky Bernd , Blanche Stéphane , Bousfiha Aziz , Rodriguez-Gallego Carlos , Meyts Isabelle , Kisand Kai , Reichenbach Janine , Renner Ellen D. , Rosenzweig Sergio , Grimbacher Bodo , van de Veerdonk Frank L. , Traidl-Hoffmann Claudia , Picard Capucine , Marodi Laszlo , Morio Tomohiro , Kobayashi Masao , Lilic Desa , Milner Joshua D. , Holland Steven , Casanova Jean-Laurent , Puel Anne
Published: April 2016

Key Points

AD STAT1 GOF is the most common genetic cause of inherited CMC and is not restricted to a specific age or ethnic group. STAT1 GOF underlies a variety of infectious and autoimmune features, as well as carcinomas and aneurysms associated with a poor outcome.
Matriptase activation connects tissue factor–dependent coagulation initiation to epithelial proteolysis and signaling
Authors: Le Gall Sylvain M. , Szabo Roman , Lee Melody , Kirchhofer Daniel , Craik Charles S. , Bugge Thomas H. , Camerer Eric
Published: April 2016

The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.
How I treat patients with a history of heparin-induced thrombocytopenia
Authors: Warkentin Theodore E. , Anderson Julia A. M.
Published: April 2016

Heparin-induced thrombocytopenia (HIT) is a relatively common prothrombotic adverse drug reaction of unusual pathogenesis that features platelet-activating immunoglobulin G antibodies. The HIT immune response is remarkably transient, with heparin-dependent antibodies no longer detectable 40 to 100 days (median) after an episode of HIT, depending on the assay performed. Moreover, the minimum interval from an immunizing heparin exposure to the development of HIT is 5 days irrespective of the patient’s previous heparin exposure status or history of HIT. This means that short-term heparin reexposure can be safely performed if platelet-activating antibodies are no longer detectable at reexposure baseline and is recommended when heparin is the clear anticoagulant of choice, such as for cardiac or vascular surgery. The risk of recurrent HIT 1 to 2 weeks after heparin reexposure is ∼2% to 5% and is attributable to formation of delayed-onset (or autoimmune-like) HIT antibodies that activate platelets even in the absence of pharmacologic heparin. Some studies suggest that longer-term heparin reexposure (eg, for chronic hemodialysis) may also be reasonable. However, for other antithrombotic indications that involve patients with a history of HIT (eg, treatment of venous thromboembolism or acute coronary syndrome), preference should be given to non-heparin agents such as fondaparinux, danaparoid, argatroban, bivalirudin, or one of the new direct-acting oral anticoagulants as appropriate.
Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study
Authors: de Rooij Jasmijn D. E. , Masetti Riccardo , van den Heuvel-Eibrink Marry M. , Cayuela Jean-Michel , Trka Jan , Reinhardt Dirk , Rasche Mareike , Sonneveld Edwin , Alonzo Todd A. , Fornerod Maarten , Zimmermann Martin , Pigazzi Martina , Pieters Rob , Meshinchi Soheil , Zwaan C. Michel , Locatelli Franco
Published: April 2016

Key Points

NUP98/KDM5A, CBFA2T3/GLIS2, KMT2A-rearrangements, and monosomy 7 are associated with poor outcome; RBM15/MKL1 and others fare better. Screening for NUP98/KDM5A, RBM15/MKL1, CBFA2T3/GLIS2, and KMT2A rearrangements combined with conventional karyotyping is advisable.
Sequence-based prediction of protein-protein interactions using weighted sparse representation model combined with global encoding
Authors: Huang Yu-An , You Zhu-Hong , Chen Xing , Chan Keith , Luo Xin
Published: April 2016

Background

Proteins are the important molecules which participate in virtually every aspect of cellular function within an organism in pairs. Although high-throughput technologies have generated considerable protein-protein interactions (PPIs) data for various species, the processes of experimental methods are both time-consuming and expensive. In addition, they are usually associated with high rates of both false positive and false negative results. Accordingly, a number of computational approaches have been developed to effectively and accurately predict protein interactions. However, most of these methods typically perform worse when other biological data sources (e.g., protein structure information, protein domains, or gene neighborhoods information) are not available. Therefore, it is very urgent to develop effective computational methods for prediction of PPIs solely using protein sequence information.

Results

In this study, we present a novel computational model combining weighted sparse representation based classifier (WSRC) and global encoding (GE) of amino acid sequence. Two kinds of protein descriptors, composition and transition, are extracted for representing each protein sequence. On the basis of such a feature representation, novel weighted sparse representation based classifier is introduced to predict protein interaction class. When the proposed method was evaluated with the PPIs data of S. cerevisiae, Human and H. pylori, it achieved high prediction accuracies of 96.82, 97.66 and 92.83 % respectively. Extensive experiments were performed for cross-species PPIs prediction and the prediction accuracies were also very promising.

Conclusions

To further evaluate the performance of the proposed method, we then compared its performance with the method based on support vector machine (SVM). The results show that the proposed method achieved a significant improvement. Thus, the proposed method is a very efficient method to predict PPIs and may be a useful supplementary tool for future proteomics studies.
Comparative effectiveness of β-lactam versus vancomycin empiric therapy in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia
Authors: Wong Davie , Wong Titus , Romney Marc , Leung Victor
Published: April 2016

Background

Vancomycin may be inferior to β-lactams for the empiric treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We compared empiric β-lactams to vancomycin to assess clinical outcomes in patients with MSSA bacteremia.

Methods

We conducted a retrospective cohort study of adult inpatients with their first episode of MSSA bacteremia at two tertiary care hospitals in Vancouver, Canada, between 2007 and 2014. Exposure was either empiric β-lactam with or without vancomycin or vancomycin monotherapy. All patients received definitive treatment with cloxacillin or cefazolin. The primary outcome was 28-day mortality. Secondary outcomes were 90-day mortality, duration of bacteremia, and hospital length-of-stay. Outcomes were adjusted using multivariable logistic regression.

Results

Of 669 patients identified, 255 met inclusion criteria (β-lactam = 131, vancomycin = 124). Overall 28-day mortality was 7.06 % (n = 18). There were more cases of infective endocarditis in the β-lactam than in the vancomycin group [24 (18.3 %) vs 12 (9.7 %), p = 0.05]. Adjusted mortality at 28 days was similar between the two groups (OR 0.85; 95 % CI 0.27–2.67). The duration of bacteremia was longer in the vancomycin group (97.1 vs 70.7 h, p = 0.007). Transition to cloxacillin or cefazolin occurred within a median of 68.3 h in the vancomycin group.

Conclusions

Empiric β-lactams was associated with earlier clearance of bacteremia by a median of 1 day compared to vancomycin. Future prospective studies are needed to confirm our findings.
Foot health education provision for people with rheumatoid arthritis–an online survey of UK podiatrists' perceptions
Authors: Graham Andrea S , Williams Anita E
Published: April 2016

Background

Patient education supports general disease self‐management and in relation to foot problems, it is recommended as a key intervention for people with rheumatoid arthritis (RA). Further, it is known what the foot health educational (FHE) needs are in relation to their experiences of foot problems. Podiatrists are the key health professionals who provide the management of RA‐related foot pathology and this includes the delivery of FHE. However, we do not know what is currently provided and what podiatrists' perceptions are of this intervention. It is possible that there is a difference between what is provided and what patients need in order to maximise their foot health benefits and hence this may contribute to the persistence of foot problems and symptoms. This study primarily aims to define what UK podiatrists' perceptions of FHE are in relation to; what is delivered, how it is delivered, and the timing of its delivery, in the context of its' accessibility. The secondary aim is to identify any influence of the participants' gender, age and duration of professional qualification on their responses.

Method

An online survey of UK HCPC registered podiatrists was used to capture quantitative data in relation to the perceived; aims, content, methods and effectiveness, timing and barriers to FHE provision to people with RA. Data was analysed to assess significant associations between the participant responses and their gender, age and duration of professional qualification. Free text comments were analysed using thematic analysis.

Results

43 podiatrists across the UK completed the survey. The majority of participants stated that, they provided FHE and agreed with its overall aims. The most common methods of delivery that were perceived to be most effective were: verbal, written and website based information. The best times at which to deliver FHE were thought to be at the point of diagnosis of RA and at any available opportunity of health care delivery. The majority of participants thought they had enough knowledge and access to information resources to effectively deliver FHE, but half of the participants felt that consultation duration limited their ability to do so. Gender and duration of professional qualification influenced participants' perceptions of FHE.

Conclusion

The importance and content of FHE for people with RA has been defined, but time limitations are seen to restrict its delivery. The development of an education needs analysis tool to facilitate efficient identification of patients FHE needs could enable timely and tailored delivery of FHE to people with RA.
The trans-well coculture of human synovial mesenchymal stem cells with chondrocytes leads to self-organization, chondrogenic differentiation, and secretion of TGFβ
Authors: Kubosch Eva Johanna , Heidt Emanuel , Bernstein Anke , Böttiger Katharina , Schmal Hagen
Published: April 2016

Background

Synovial mesenchymal stem cells (SMSC) possess a high chondrogenic differentiation potential, which possibly supports natural and surgically induced healing of cartilage lesions. We hypothesized enhanced chondrogenesis of SMSC caused by the vicinity of chondrocytes (CHDR).

Methods

Human SMSC and CHDR interactions were investigated in an in-vitro trans-well monolayer coculture over a time period of up to 21 days. Protein expression was analyzed using histology, immunostaining, or enzyme-linked immunosorbent assay. Additionally, mRNA expression was assessed by quantitative PCR.

Results

After 7 days, phase-contrast microscopy revealed cell aggregation of SMSC in coculture with CHDR. Afterwards, cells formed spheres and lost adherence. However, this phenomenon was not observed when culturing SMSC alone. Fluorescence labeling showed concurrent collagen type II expression. Addition of transforming growth factor beta (TGFβ) to the cocultures induced SMSC aggregation in less time and with higher intensity. Additionally, alcian blue staining demonstrated enhanced glycosaminoglycan expression around SMSC aggregates after 1 and 2 weeks. Although TGFβ mRNA was expressed in all SMSC, the protein was measured with constantly increasing levels over 21 days only in supernatants of the cocultures. Considering the enhanced mRNA levels following supplementation with TGFβ, a positive feedback mechanism can be supposed. In line with the development of a chondrogenic phenotype, aggrecan mRNA expression increased after 7 and 14 days in the cocultures with and without TGFβ. Coculture conditions also amplified collagen type II mRNA expression after 2 weeks without and already after 1 week with TGFβ. There was no difference in collagen type I and type X expression between SMSC alone and the coculture with CHDR. Expression of both collagens increased following addition of TGFβ. mRNA data correlated with the intensity of immunofluorescence staining.

Conclusions

Paracrine effects of CHDR induce a chondrogenic phenotype in SMSC possibly mimicking joint homeostasis. Coculture approaches may lead to a better understanding of cellular interactions with potential implications for cartilage repair procedures.
A training programme involving automatic self-transcending meditation in late-life depression: preliminary analysis of an ongoing randomised controlled trial - RETRACTED
Authors: Vasudev Akshya , Arena Amanda , Burhan Amer M. , Ionson Emily , Hirjee Hussein , Maldeniya Pramudith , Wetmore Stephen , Newman Ronnie I.
Published: April 2016

Late-life depression affects 2–6% of seniors aged 60 years and above. Patients are increasingly embracing non-pharmacological therapies, many of which have not been scientifically evaluated. This study aimed to evaluate a category of meditation, automatic self-transcending meditation (ASTM), in alleviating symptoms of depression when augmenting treatment as usual (NCT02149810). The preliminary results of an ongoing single-blind randomised controlled trial comparing a training programme involving ASTM with a wait-list control indicate that a 12-week ASTM programme may lead to significantly greater reductions in depression and anxiety severity. As such, ASTM may be an effective adjunctive therapy in the treatment of late-life depression.