bluuebunny/crossref_metadata_2025 huggingface dataset:
Demographic Differences in Disruptive Mood Dysregulation Disorder Symptoms in ADHD, Autism, and General Population Samples
Authors: Mayes Susan D. , Calhoun Susan L. , Waxmonsky James G. , Kokotovich Cari , Baweja Raman , Lockridge Robin , Bixler Edward O.
Published: August 2016

Objective: Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) disruptive mood dysregulation disorder (DMDD) is a controversial new diagnosis. No studies have investigated DMDD symptoms (irritable-angry mood and temper outbursts) and demographics in general population and psychiatric samples. Method: Maternal ratings of DMDD symptoms and diagnoses, age, gender, IQ, race, and parent occupation were analyzed in general population ( n = 665, 6-12 years) and psychiatric samples ( n = 2,256, 2-16 years). Results: Percentage of school-age children with DMDD symptoms were 9% general population, 12% ADHD-I, 39% ADHD-C, and 43% autism. Male, nonprofessional parent, and autism with IQ > 80 were associated with increasing DMDD symptoms, but demographics together explained only 2% to 3% of the DMDD score variance. Conclusion: Demographics contributed little to the presence of DMDD symptoms in all groups, whereas oppositional defiant disorder (ODD) explained most of the variance. Almost all children with DMDD symptoms had ODD suggesting that DMDD may not be distinct from ODD.
Adult ADHD Self-Report Scale: Comprehensive Psychometric Study in a Spanish SUD Sample
Authors: Lozano Óscar M. , Carmona José , Muñoz-Silva Alicia , Fernández-Calderón Fermín , Díaz-Batanero Carmen , Sanchez-Garcia Manuel
Published: August 2016

Objective: The purpose of this study is to provide reliability and validity evidence of the Adult Self-Report Scale (ASRS) scores on different versions and scoring procedures in a Spanish substance use disorder (SUD) sample. Method: The sample was made up of 170 outpatients diagnosed with SUD. The ASRS, the Mini-International Neuropsychiatric Interview (MINI), and the Substance Dependence Severity Scale were administered. Results: The results of the confirmatory factor analysis (CFA) showed adequate fit to the structure proposed by the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) in the 18-item version. On the screening scale, best fit was found for a model with two correlated factors (inattention and hyperactivity). The exploratory factor analysis (EFA) showed that the ADHD items converge and are differentiated from symptoms of withdrawal. The regression analyses showed that severity of dependence is explained by the ASRS scores. Conclusion: Both versions of the ASRS showed adequate psychometric properties. The polytomous or dichotomous score is relevant in patient classification.
Are Some Countries More Prone to Pressure Evaluators Than Others? Comparing Findings From the United States, United Kingdom, Germany, and Switzerland
Authors: Pleger Lyn , Sager Fritz , Morris Michael , Meyer Wolfgang , Stockmann Reinhard
Published: August 2016

Pressure on evaluators has been investigated recently by surveys in the USA, the UK, Germany, and Switzerland. This study compares the results of those studies regarding pressure on evaluators in different countries. The findings suggest that independence of evaluations does not exist for many respondents. Moreover, the person who commissioned the evaluator for evaluation is identified by all studies as the primary influencing stakeholder in the evaluation process. In terms of differences, Germany seems to be more prone to pressure on evaluators. However, German evaluators do not show stronger tendencies to surrender to pressure than the other countries’ respondents. We suggest that this pattern may be explained by the strong state tradition in Germany as opposed to the U.S. and Switzerland, in conjunction with evaluators’ profession-based, principled resistance to such pressure.
“It comes down to just how human someone can be”: A qualitative study with young people from refugee backgrounds about their experiences of Australian mental health services
Authors: Valibhoy Madeleine C. , Kaplan Ida , Szwarc Josef
Published: August 2016

While much literature documents the mental health needs of young people from refugee backgrounds, and the barriers they face in accessing mental health services, researchers have yet to document the perspectives of service users from this population about their contacts with clinicians and services. We therefore individually interviewed 16 young people (aged 18–25 years) who were refugees about their experiences of seeing mental health professionals. Participants were born in 9 different countries and had lived in Australia for an average of 5.2 years. They placed most emphasis on in-session factors, and particularly on interpersonal considerations. Among the main themes identified via thematic analysis were the practitioner's sensitivity to the young person's cultural background and to the stressors affecting him or her, including traumatic refugee experiences, and the therapeutic relationship—especially the qualities of trust, understanding, respect, and a caring connection. The participants had diverse reactions to treatment strategies. They emphasised the role of their preconceptions around mental health services, and called for systematic mental health awareness-raising for young people from refugee backgrounds. Implications for research, policy, and practice are discussed with a focus on findings that may guide efforts to improve service acceptability, accessibility, and effectiveness. In particular, there is a need for practitioners to attend to their clients' experiences of sessions, to adopt an attuned, contextualised, systemic approach, and especially to take a nuanced approach to cultural sensitivity.
Epidemiology of Flexor Tendon Injuries of the Hand in a Northern Finnish Population
Authors: Manninen M. , Karjalainen T. , Määttä J. , Flinkkilä T.
Published: August 2016

Background:

Flexor tendon injuries cause significant morbidity in working-age population. The epidemiology of these injuries in adult population is not well known. The aim of this study was to describe the epidemiology of flexor tendon injuries in a Northern Finnish population.

Material and Methods:

Data on flexor tendon injuries, from 2004 to 2010, were retrieved from patient records from four hospitals, which offer surgical repair of the flexor tendon injuries in a well-defined area in Northern Finland. The incidence of flexor tendon injury as well as the gender-specific incidence rates was calculated. Mechanism of injury, concomitant nerve injuries, and re-operations were also recorded.

Results:

The incidence rate of flexor tendon injury was 7.0/100,000 person-years. The incidence was higher in men and inversely related to age. The most common finger to be affected was the fifth digit. In 37% of injuries also digital nerve was affected. The most common finger to have simultaneous digital nerve injury was the thumb.

Conclusion:

Flexor tendon laceration is a relatively rare injury. It predominantly affects working-aged young males and frequently includes a nerve injury, which requires microsurgical skills from the surgeon performing the repair. This study describes epidemiology of flexor tendon injuries and therefore helps planning the surgical and rehabilitation services needed to address this entity.
Carceral framing of human rights in Russian prisons
Authors: Piacentini Laura , Katz Elena
Published: August 2016

This paper introduces to punishment and society scholarship a new carceral framing of human rights in Russian prisons. Russian imprisonment remains elusive to prison scholars and ethnographers around the world. Moreover, on the subject of prisoners’ rights specifically, the scholarship is dominated by legal discourse. The empirical and theoretical scholarship that has developed over the last twenty years has argued that Russian imprisonment is exceptional in the study of world penal systems with the research seeking to gain a sense of this exceptionality through looking at the inertial legacies of Gulag penal culture on present day punishment forms. This article attempts to challenge this claim and will argue that specifically in the area of human rights, Russia has followed a not dissimilar carceral formation to Western prisons. Through an interrogation of the cultural, political and historical factors underpinning how rights are framed in Russian prisons the article suggests that human rights are operationalised as a lever for legal and penal control. This is a significant new finding in the study of Russian imprisonment because of the questions that arise around penal resilience, how rights and penal power develop through discourse and how global penal norms converge across jurisdictions.
Factors Associated With Black Men’s Preference for Health Information
Authors: Parker Lauren J. , Hunte Haslyn , Ohmit Anita , Thorpe Roland J.
Published: August 2016

Black men are less likely to seek routine health care examinations or preventative care compared with their racial/ethnic and gender counterparts. Because of Black men’s limited engagement with the health system, Black men’s preference to receive health information is unclear. Guided by a revised version of the Andersen Healthcare Utilization Model, the aim of the study is to examine factors associated with Black men’s preference for informal or formal health information. Findings from the study demonstrate that financial barriers to care (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.43-0.98) and higher income (OR = 2.44, 95% CI = 1.49-4.00) were most predictive of using a formal source for health information. Furthermore, age (OR = 1.02, 95% CI = 1.01-1.03) and having a college education (OR = 0.44, 95% CI = 0.26-0.76) were associated with using a formal place for health information. Interestingly, health care discrimination was not associated with preferred source or place for health information. Results from the study suggest that predisposing and enabling factors are most salient to the use of formal sources of health information among Black men.
Role of microglia in embryonic neurogenesis
Authors: Tong Chih Kong , Vidyadaran Sharmili
Published: August 2016

Microglia begin colonizing the developing brain as early as embryonic day 9, prior to the emergence of neurons and other glia. Their ontogeny is also distinct from other central nervous system cells, as they derive from yolk sac hematopoietic progenitors and not neural progenitors. In this review, we feature these unique characteristics of microglia and assess the spatiotemporal similarities between microglia colonization of the central nervous system and embryonic neurogenesis. We also infer to existing evidence for microglia function from embryonic through to postnatal neurodevelopment to postulate roles for microglia in neurogenesis.
Original Research: ACE2 activator associated with physical exercise potentiates the reduction of pulmonary fibrosis
Authors: Prata Luana O , Rodrigues Carolina R , Martins Jéssica M , Vasconcelos Paula C , Oliveira Fabrício Marcus S , Ferreira Anderson J , Rodrigues-Machado Maria da Glória , Caliari Marcelo V
Published: August 2016

The interstitial lung diseases are poorly understood and there are currently no studies evaluating the association of physical exercise with an ACE2 activator (DIZE) as a possible treatment for this group of diseases. We evaluate the effects of pharmacological treatment with an angiotensin-converting enzyme 2 activator drug, associated with exercise, on the pulmonary lesions induced by bleomycin. From the 96 male Balb/c mice used in the experiment, only 49 received 8 U/kg of bleomycin (BLM, intratracheally). The mice were divided into control (C) and bleomycin (BLM) groups, sedentary and trained (C-SED, C-EXE, BLM-SED, BLM-EXE), control and bleomycin and also sedentary and trained treated with diminazene (C-SED/E, C-EXE/E, BLM-SED/E, BLM-EXE/E). The animals were trained five days/week, 1 h/day with 60% of the maximum load obtained in a functional capacity test, for four weeks. Diminazene groups were treated (1 mg/kg, by gavage) daily until the end of the experiment. The lungs were collected 48 h after the training program, set in buffered formalin and investigated by Gomori’s trichrome, immunohistochemistry of collagen type I, TGF-β1, beta-prolyl-4-hydroxylase, MMP-1 and -2. The BLM-EXE/E group obtained a significant increase in functional capacity, reduced amount of fibrosis and type I collagen, decreased expression of TGF-β1and beta-prolyl-4-hydroxylase and an increase of metalloproteinase −1, −2 when compared with the other groups. The present research shows, for the first time, that exercise training associated with the activation of ACE2 potentially reduces pulmonary fibrosis.
Wireless communication architectures based on data aggregation for internal monitoring of large-scale wind turbines
Authors: Ahmed Mohamed A. , Kim Young-Chon
Published: August 2016

Wireless networks are regarded as a promising candidate for condition monitoring systems of large-scale wind turbines due to the design flexibility, easy deployment, and reduced installation cost. This article investigates different data aggregation approaches of wireless-based architectures for the internal monitoring of a large-scale wind turbine. The main objective is to construct a wireless internal network inside the wind turbine nacelle, for collecting sensing data from different parts and transmitting the data to a remote control center through a wireless external network that serves the turbine towers of the wind farm. The proposed wireless network architectures consist of wireless sensor nodes, coordinator nodes, and a front-end device. The designs of the wireless-based architectures involve choices of physical components, sensor types, sampling rate, and data rate. Wi-Fi is a promising technology that is considered for the wind turbine internal network in this work. Through simulations, the network performance is evaluated with regard to end-to-end delay for different data aggregation approaches of wireless-based architectures.
Routing for context-addressable messages using Predefined Concept Connection Map in delay tolerant network
Authors: Schoeneich Radosław Olgierd
Published: August 2016

This article presents methods of nodes discovery and message routing for a context-based addressing in Delay and Disruptive Tolerant Networks. The context-based addressing is the novel way of descriptive addressing that is based on ontology model. The context-based addressing enables description of each node by a set of concepts. The main idea of this article is to present the method of the addressees discovery that uses specialized graph composed of concepts. It is called Predefined Concept Connection Map. The Predefined Concept Connection Map describes physical communication abilities between context-based addressed nodes. In this article, ns-2 simulations are presented. They are based on specially designed simulation model which supports context-based address assigned for each Delay and Disruptive Tolerant Network node.
Exploring obstacles to critical care trials in the UK: A qualitative investigation
Authors: Pattison Natalie , Arulkumaran Nishkantha , Humphreys Sally , Walsh Tim
Published: August 2016

Background

Clinical trials in critical care are often resource-intense, with many unique challenges. Barriers to effective recruitment and implementation of study intervention have not been explored in a UK context.

Aim

To identify facilitating factors and barriers to enrolling patients into critical care clinical trials within the UK from clinician’s perspectives.

Methods

A qualitative interview study was undertaken on behalf of the National Institute of Health Research critical care specialty group, in which research active clinicians across different Clinical Research Networks were interviewed. A loosely structured interview schedule was used, based on themes generated from the literature associated with accessing critical care trials. Research teams (critical care doctors, research nurses, and trial coordinators) from hospitals from each Clinical Research Network were contacted to try to achieve representation across the UK.

Results

Interviews were carried out across nine UK Clinical Research Networks with a range of doctors and research nurses. All hospitals were teaching hospitals with varying research nurse numbers and allocated consultant research sessions. There were a range of six to nine ongoing clinical trials in critical care for each centre representative interviewed. Data were analysed using framework analysis, and six final themes were identified related to factors associated with: centre, unit, resources, study, clinician, and patient/family. The most commonly cited barrier to conducting clinical trials was related to resources, namely insufficient human and financial resources, leading to staff and study recruitment difficulties. Clinical uncertainty and equipoise regarding comparative merits of trials were challenging in terms of engaging critical care teams. A number of patient and family factors added complexities in terms of recruitment; however, refusal rates were generally reported as low.

Conclusion

Flexibility in funding and employment by research teams enables continuity of studies and staff. Innovative measures to incentivise research nurses and clinical teams can help recruit more patients into trials. Research teams are highly committed to providing cover to recruit critical care trials, and a significant effort to anticipate barriers is undertaken; these endeavours are summarised to provide guidance for other teams wishing to address any potential difficulties.
Dural arteriovenous fistula of the craniocervical junction manifesting as cerebellar haemorrhage
Authors: Inamasu Joji , Tanaka Riki , Nakahara Ichiro , Hirose Yuichi
Published: August 2016

We report a rare case of dural arteriovenous fistula at the craniocervical junction manifesting as cerebellar haemorrhage, which posed a diagnostic challenge for physicians. A 77-year-old woman with no history of arterial hypertension presented to our Emergency Department with dizziness, and imaging studies revealed a small cerebellar haemorrhage. She was diagnosed with hypertensive intracerebral haemorrhage and conservatively treated. Four months later, she developed subarachnoid haemorrhage, and imaging studies revealed dural arteriovenous fistula at the left C1 dural sleeve. Disruption of a distended cerebellar vein due to venous hypertension by dural arteriovenous fistula was considered to be responsible for intracerebral haemorrhage and subarachnoid haemorrhage. Dural arteriovenous fistula was cured following surgical ligation of a feeding artery and a draining vein. The present case was educational in that effort to identify the cause of bleeding using vascular imaging studies may be important in patients with seemingly typical hypertensive intracerebral haemorrhage, particularly in those without a past history of arterial hypertension.
Fetal development of the corpus callosum: Insights from a 3T DTI and tractography study in a patient with segmental callosal agenesis
Authors: Scola Elisa , Sirgiovanni Ida , Avignone Sabrina , Cinnante Claudia Maria , Biffi Riccardo , Fumagalli Monica , Triulzi Fabio
Published: August 2016

Commissural embryology mechanisms are not yet completely understood. The study and comprehension of callosal dysgenesis can provide remarkable insights into embryonic or fetal commissural development. The diffusion tensor imaging (DTI) technique allows the in vivo analyses of the white-matter microstructure and is a valid tool to clarify the disturbances of brain connections in patients with dysgenesis of the corpus callosum (CC). The segmental callosal agenesis (SCAG) is a rare partial agenesis of the corpus callosum (ACC). In a newborn with SCAG the DTI and tractography analyses proved that the CC was made of two separate segments consisting respectively of the ventral part in the genu and body of the CC, connecting the frontal lobes, and the dorsal part in the CC splenium and the attached hippocampal commissure (HC), connecting the parietal lobes and the fornix. These findings support the embryological thesis of a separated origin of the ventral and the dorsal parts of the CC.
Thinking about measuring Augé’s non-places with Big Data
Authors: Bauder Michael
Published: August 2016

Augé describes non-places as quantifiable and measureable physical space, but does not give an appropriate measure to do so. This contribution thinks about using crowd-harvested photo data, a specific kind of Big Data, to measure non-places in the context of tourism by giving a theory based discussion on Augé’s non-places, photography as key element of “doing” tourism, and the selection processes of photography and uploading photos. Solely using theoretical thoughts and propositional logic, this contribution indicates that it could be possible to do so. Yet, there are plenty of empirical studies needed in order to verify the built hypothesis.
Net neutrality, Facebook, and India’s battle to #SaveTheInternet
Authors: Mukerjee Subhayan
Published: August 2016

In August 2013, Facebook, in a partnership with a few other companies, launched Internet.org —a new service that aimed to bring low cost and subsidized access to a few selected Internet services to developing countries in Asia and Africa. Ever since its announcement, and subsequent roll-out in India in 2015, activists around the world, and particularly in India, have decried the service on grounds of it violating net neutrality. This article traces the manner in which this contentious issue has unfolded in India, primarily in the Indian social media in 2015, leading up to the Telecom Regulatory Authority of India banning the service and upholding net neutrality in February 2016.
Protein Losing Enteropathy After Cardiac Transplantation Successfully Treated by Stent Implantation
Authors: Devanagondi Rajiv , Suntharos Patcharapong , Boyle Gerard J. , Prieto Lourdes R.
Published: August 2016

Protein losing enteropathy (PLE) is a severe consequence of Fontan physiology that sometimes requires heart transplantation for definitive treatment. We describe transplant refractory PLE in a patient with heterotaxia and complex systemic and hepatic venous connections, successfully treated by transcatheter relief of multiple venous obstructions.
Development and Validation of the Self-Conscious Emotion Regulatory Efficacy Scale (SCERES)
Authors: Wu Yan , Liang Qimin , Li Bi
Published: August 2016

Self-conscious emotion regulatory efficacy is very important in regulating and mediating psychosocial function. We developed the Self-Conscious Emotion Regulatory Efficacy Scale (SCERES) to assess self-efficacy in managing shame/embarrassment, guilt, envy, and pride, and tested it using a sample of 674 university students from mainland China. Exploratory and confirmatory factor analyses were conducted to determine the structure of the SCERES. Its internal consistency and stability were evaluated by examining composite and test–retest reliability. Construct validity was also examined. The results showed that the SCERES has good psychometric properties and can be considered a reliable and valid instrument for the measurement of self-conscious emotion regulatory efficacy.
Sport-Related National Pride in East and West Germany, 1992-2008
Authors: Meier Henk Erik , Mutz Michael
Published: August 2016

It is commonly assumed that international sport reinforces feelings of national pride and national identity. Using large-scale survey data from Germany, covering the period between 1992 and 2008, some unresolved key questions surrounding sportive nationalism are addressed. We examine the relative importance of sport as a source of national pride, analyze the sociodemographics of sportive nationalism, and describe its long-term development in East and West Germany after reunification. Results reveal that sport is an increasingly important source of pride in Germany. Sportive nationalism is more common among younger generations, males, and individuals with lower socioeconomic status. Prevailing differences between East and West Germany document persistent socialization effects of former sport-centered identity politics. Among East Germans, sport is more important for general national pride, and sportive nationalism is much more equally distributed between various social groups (with regard to age, gender, education). From 1992 to 2008, however, a trend toward convergence between East and West Germans is also demonstrated.
Postschool Services and Postschool Outcomes for Individuals With Mild Intellectual Disability
Authors: Bouck Emily C. , Chamberlain Courtney
Published: August 2016

Understanding the relationship between services and outcomes is important for students with disabilities. While research exists regarding relationships between services and supports provided in school and adult life outcomes for students with disabilities, less attention is paid to the supports and services provided after students exit high school. This study was a secondary data analysis of the National Longitudinal Transition Study−2 (NLTS2) to explore the postschool experiences and services received by individuals with mild intellectual disability and to understand the relationship between receipt of postschool services and postschool outcomes. The main findings for this secondary analysis were the lack of postschool services and supports provided to individuals with mild intellectual disability, and a lack of benefit in terms of postschool outcomes if postschool services were received.
Evidence-Based Parenting Interventions to Promote Secure Attachment
Authors: Wright Barry , Edginton Elizabeth
Published: August 2016

Various interventions are used in clinical practice to address insecure or disorganized attachment patterns and attachment disorders. The most common of these are parenting interventions, but not all have a robust empirical evidence base. We undertook a systematic review of randomized trials comparing a parenting intervention with a control, where these used a validated attachment instrument, in order to evaluate the clinical and cost-effectiveness of interventions aiming to improve attachment in children with severe attachment problems (mean age <13 years). This article aims to inform clinicians about the parenting interventions included in our systematic review that were clinically effective in promoting secure attachment. For completeness, we also briefly discuss other interventions without randomized controlled trial evidence, identified in Patient Public Involvement workshops and expert groups at the point our review was completed as being used or recommended. We outline the key implications of our findings for clinical practice and future research.
Global Health Simulation During Residency
Authors: Rosenman Jane R. , Fischer Philip R. , Arteaga Grace M. , Hulyalkar Manasi , Butteris Sabrina M. , Pitt Michael B.
Published: August 2016

Resident participation in international health electives (IHEs) has been shown to be beneficial, yet not all residents have the opportunity to participate. We sought to determine whether participating in simulated global health cases, via the standardized Simulation Use for Global Away Rotations (SUGAR) curriculum, was useful for all pediatric residents, not merely those planning to go on an IHE. Pediatric residents in our program took part in 2 SUGAR cases and provided feedback via an online survey. Thirty-six of 40 residents participated (90%); 72% responded to the survey. Three of 10 residents not previously planning to work in resource-limited settings indicated participation in SUGAR made them more likely to do so. Nearly all residents (88%) felt SUGAR should be part of the residency curriculum. All felt better prepared for working cross-culturally. While designed to prepare trainees for work in resource-limited settings, SUGAR may be beneficial for all residents.
Using Critical Race Theory to Explore Race-Based Conversations Through a Critical Family Book Club
Authors: Johnson Lamar L.
Published: August 2016

Stemming from my personal encounter with what I consider a racial affliction imposed by a White female teacher, I provide a glimpse of my racial narrative as a young Black male to illustrate a reference point for thinking through how racism functions in homes and schools. It touches on the importance of race-based conversations within school and out of school spaces. In this article, I illustrate the creation of a “critical” relationship between parents, youth, and educators in that I used a critical family book club as a mechanism for engaging parents and students in discussions about race and racism. Drawing from interviews, memos, field notes, and other forms of research data, I analyze participants’ experiences with race, racism, and power. I conclude with the pedagogical possibilities of enacting critical race pedagogy and critical family book clubs in K–12 spaces.
Incidental Finding of a Right Coronary Artery to Coronary Sinus Fistula in an Adult Transthoracic Echocardiogram
Authors: Rodriguez Joleen Duarte
Published: August 2016

Congenital coronary artery fistula (CAF) is a rare anomaly of the heart presenting in 0.002% of the general population. This case study presents an adult patient with an undiagnosed heart murmur and symptoms of chest pain, fatigue, and lightheadedness that demonstrated an incidental finding of CAF diagnosed by transthoracic echocardiography. Transthoracic echocardiography revealed an aneurysmal, tortuous right coronary artery terminating in a dilated coronary sinus. Sonographic findings were compared with angiography and computed tomography. This study highlights the potential of transthoracic echocardiography to assess heart structure and physiology and detect a CAF.
Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes
Authors: Nasrallah Rabab , Fast Eva M. , Solaimani Parham , Knezevic Kathy , Eliades Alexia , Patel Rahima , Thambyrajah Roshana , Unnikrishnan Ashwin , Thoms Julie , Beck Dominik , Vink Chris S. , Smith Aileen , Wong Jason , Shepherd Mairi , Kent David , Roychoudhuri Rahul , Paul Fabian , Klippert Julia , Hammes Annette , Willnow Thomas , Göttgens Bertie , Dzierzak Elaine , Zon Leonard I. , Lacaud George , Kouskoff Valerie , Pimanda John E.
Published: August 2016

Key Points

ENG regulatory elements target hemogenic mesoderm and hemogenic endothelium. Hemogenic progenitors can be enriched using these elements as molecular probes to discover novel regulators of hematopoiesis.
FastProject: a tool for low-dimensional analysis of single-cell RNA-Seq data
Authors: DeTomaso David , Yosef Nir
Published: August 2016

Background

A key challenge in the emerging field of single-cell RNA-Seq is to characterize phenotypic diversity between cells and visualize this information in an informative manner. A common technique when dealing with high-dimensional data is to project the data to 2 or 3 dimensions for visualization. However, there are a variety of methods to achieve this result and once projected, it can be difficult to ascribe biological significance to the observed features. Additionally, when analyzing single-cell data, the relationship between cells can be obscured by technical confounders such as variable gene capture rates.

Results

To aid in the analysis and interpretation of single-cell RNA-Seq data, we have developed FastProject, a software tool which analyzes a gene expression matrix and produces a dynamic output report in which two-dimensional projections of the data can be explored. Annotated gene sets (referred to as gene ‘signatures’) are incorporated so that features in the projections can be understood in relation to the biological processes they might represent. FastProject provides a novel method of scoring each cell against a gene signature so as to minimize the effect of missed transcripts as well as a method to rank signature-projection pairings so that meaningful associations can be quickly identified. Additionally, FastProject is written with a modular architecture and designed to serve as a platform for incorporating and comparing new projection methods and gene selection algorithms.

Conclusions

Here we present FastProject, a software package for two-dimensional visualization of single cell data, which utilizes a plethora of projection methods and provides a way to systematically investigate the biological relevance of these low dimensional representations by incorporating domain knowledge.
Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons
Authors: Hilinski William C. , Bostrom Jonathan R. , England Samantha J. , Juárez-Morales José L. , de Jager Sarah , Armant Olivier , Legradi Jessica , Strähle Uwe , Link Brian A. , Lewis Katharine E.
Published: August 2016

Background

Alterations in neurotransmitter phenotypes of specific neurons can cause imbalances in excitation and inhibition in the central nervous system (CNS), leading to diseases. Therefore, the correct specification and maintenance of neurotransmitter phenotypes is vital. As with other neuronal properties, neurotransmitter phenotypes are often specified and maintained by particular transcription factors. However, the specific molecular mechanisms and transcription factors that regulate neurotransmitter phenotypes remain largely unknown.

Methods

In this paper we use single mutant, double mutant and transgenic zebrafish embryos to elucidate the functions of Lmx1ba and Lmx1bb in the regulation of spinal cord interneuron neurotransmitter phenotypes.

Results

We demonstrate that lmx1ba and lmx1bb are both expressed in zebrafish spinal cord and that lmx1bb is expressed by both V0v cells and dI5 cells. Our functional analyses demonstrate that these transcription factors are not required for neurotransmitter fate specification at early stages of development, but that in embryos with at least two lmx1ba and/or lmx1bb mutant alleles there is a reduced number of excitatory (glutamatergic) spinal interneurons at later stages of development. In contrast, there is no change in the numbers of V0v or dI5 cells. These data suggest that lmx1b-expressing spinal neurons still form normally, but at least a subset of them lose, or do not form, their normal excitatory fates. As the reduction in glutamatergic cells is only seen at later stages of development, Lmx1b is probably required either for the maintenance of glutamatergic fates or to specify glutamatergic phenotypes of a subset of later forming neurons. Using double labeling experiments, we also show that at least some of the cells that lose their normal glutamatergic phenotype are V0v cells. Finally, we also establish that Evx1 and Evx2, two transcription factors that are required for V0v cells to acquire their excitatory neurotransmitter phenotype, are also required for lmx1ba and lmx1bb expression in these cells, suggesting that Lmx1ba and Lmx1bb act downstream of Evx1 and Evx2 in V0v cells.

Conclusions

Lmx1ba and Lmx1bb function at least partially redundantly in the spinal cord and three functional lmx1b alleles are required in zebrafish for correct numbers of excitatory spinal interneurons at later developmental stages. Taken together, our data significantly enhance our understanding of how spinal cord neurotransmitter fates are regulated.
Employment chances of immigrants and their children in Germany: does sense of personal control matter?
Authors: Thum-Thysen Anna
Published: August 2016

Labour market integration is a social process suggesting that personality traits are relevant. This paper explores whether immigrants with a higher belief in their ability to control outcomes tend to be more likely to be employed. This trait is known in psychology as the locus of control (LOC). I employ a model framework that allows LOC to depend on a set of observable determining variables. Results indicate that sense of personal control is correlated with employment probability and that there is a risk that immigrants and their children tend to have a more externalized LOC. Mother’s education is a key factor correlated with the sense of personal control.
Eosinophils, probiotics, and the microbiome
Authors: Rosenberg Helene F , Masterson Joanne C , Furuta Glenn T
Published: August 2016

There is currently substantial interest in the therapeutic properties of probiotic microorganisms as recent research suggests that oral administration of specific bacterial strains may reduce inflammation and alter the nature of endogenous microflora in the gastrointestinal tract. Eosinophils are multifunctional tissue leukocytes, prominent among the resident cells of the gastrointestinal mucosa that promote local immunity. Recent studies with genetically altered mice indicate that eosinophils not only participate in maintaining gut homeostasis, but that the absence of eosinophils may have significant impact on the nature of the endogenous gut microflora and responses to gut pathogens, notably Clostridium difficile. Furthermore, in human subjects, there is an intriguing relationship between eosinophils, allergic inflammation, and the nature of the lung microflora, notably a distinct association between eosinophil infiltration and detection of bacteria of the phylum Actinobacteria. Among topics for future research, it will be important to determine whether homeostatic mechanisms involve direct interactions between eosinophils and bacteria or whether they involve primarily eosinophil-mediated responses to cytokine signaling in the local microenvironment. Likewise, although is it clear that eosinophils can and do interact with bacteria in vivo, their ability to discern between pathogenic and probiotic species in various settings remains to be explored.
Genome-Wide DNA Methylation Analysis Reveals Epigenetic Dysregulation of MicroRNA-34A in TP53-Associated Cancer Susceptibility
Authors: Samuel Nardin , Wilson Gavin , Lemire Mathieu , Id Said Badr , Lou Youliang , Li Weili , Merino Diana , Novokmet Ana , Tran James , Nichols Kim E. , Finlay Jonathan L. , Choufani Sanaa , Remke Marc , Ramaswamy Vijay , Cavalli Florence M.G. , Elser Christine , Meister Lynn , Taylor Michael D. , Tabori Uri , Irwin Meredith , Weksberg Rosanna , Wasserman Jonathan D. , Paterson Andrew D. , Hansford Jordan R. , Achatz Maria Isabel W. , Hudson Thomas J. , Malkin David
Published: August 2016

Purpose

Although the link between mutant TP53 and human cancer is unequivocal, a significant knowledge gap exists in clinically actionable molecular targets in Li-Fraumeni syndrome (LFS), a highly penetrant cancer predisposition syndrome associated with germline mutations in TP53. This study surveyed the epigenome to identify functionally and clinically relevant novel genes implicated in LFS.

Patients and Methods

We performed genome-wide methylation analyses of peripheral blood leukocyte DNA in germline TP53 mutation carriers (n = 72) and individuals with TP53 wild type in whom histologically comparable malignancies developed (n = 111). Targeted bisulfite pyrosequencing was performed on a validation cohort of 30 TP53 mutation carriers and 46 patients with TP53 wild type, and candidate sites were evaluated in primary tumors from patients with LFS across multiple histologic tumor types.

Results

In 183 patients, distinct DNA methylation signatures were associated with deleterious TP53 mutations in peripheral blood leukocytes. TP53-associated DNA methylation marks occurred in genomic regions that harbored p53 binding sites and in genes encoding p53 pathway proteins. Moreover, loss-of-function TP53 mutations were significantly associated with differential methylation at the locus encoding microRNA miR-34A, a key component of the p53 regulatory network (adjusted P < .001), and validated in an independent patient cohort (n = 76, P < .001). Targeted bisulfite pyrosequencing demonstrated that miR-34A was inactivated by hypermethylation across many histologic types of primary tumors from patients with LFS. Moreover, miR-34A tumor hypermethylation was associated with decreased overall survival in a cohort of 29 patients with choroid plexus carcinomas, a characteristic LFS tumor (P < .05).

Conclusion

Epigenetic dysregulation of miR-34A may comprise an important path in TP53-associated cancer predisposition and represents a therapeutically actionable target with potential clinical relevance.
Cost-Effectiveness Analysis of Elective Neck Dissection in Patients With Clinically Node-Negative Oral Cavity Cancer
Authors: Acevedo Joseph R. , Fero Katherine E. , Wilson Bayard , Sacco Assuntina G. , Mell Loren K. , Coffey Charles S. , Murphy James D.
Published: August 2016

Purpose

Recently, a large randomized trial found a survival advantage among patients who received elective neck dissection in conjunction with primary surgery for clinically node-negative oral cavity cancer compared with those receiving primary surgery alone. However, elective neck dissection comes with greater upfront cost and patient morbidity. We present a cost-effectiveness analysis of elective neck dissection for the initial surgical management of early-stage oral cavity cancer.

Methods

We constructed a Markov model to simulate primary, adjuvant, and salvage therapy; disease recurrence; and survival in patients with T1/T2 clinically node-negative oral cavity squamous cell carcinoma. Transition probabilities were derived from clinical trial data; costs (in 2015 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollar per quality-adjusted life-year (QALY), were calculated with incremental cost-effectiveness ratios less than $100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty.

Results

Our base-case model found that over a lifetime the addition of elective neck dissection to primary surgery reduced overall costs by $6,000 and improved effectiveness by 0.42 QALYs compared with primary surgery alone. The decrease in overall cost despite the added neck dissection was a result of less use of salvage therapy. On one-way sensitivity analysis, the model was most sensitive to assumptions about disease recurrence, survival, and the health utility reduction from a neck dissection. Probabilistic sensitivity analysis found that treatment with elective neck dissection was cost effective 76% of the time at a willingness-to-pay threshold of $100,000/QALY.

Conclusion

Our study found that the addition of elective neck dissection reduces costs and improves health outcomes, making this a cost-effective treatment strategy for patients with early-stage oral cavity cancer.
Vitamin D Receptor Down-Regulation Is Associated With Severity of Albuminuria in Type 2 Diabetes Patients
Authors: Yi Bin , Huang Jing , Zhang Wei , Li Ai Mei , Yang Shi Kun , Sun Jian , Wang Jian Wen , Li Yan Chun , Zhang Hao
Published: August 2016

Context:

Inflammation plays an important role in albuminuria in type 2 diabetes mellitus (T2DM). The vitamin D receptor (VDR) has potent anti-inflammatory activities.

Objective:

To investigate the correlation between VDR expression and albuminuria in T2DM.

Design/Setting/Patients:

Renal biopsies from T2DM patients with albuminuria (n = 8) and nondiabetic subjects (n = 4) were compared for VDR expression by immunohistochemistry. Recruited T2DM patients (n = 242; estimated glomerular filtration rate > 60 mL/min/1.73 m2) were divided into three groups based on urinary albumin-to-creatinine ratio (uACR): normal albuminuria (uACR < 30 mg/g; n = 85), microalbuminuria (30 mg/g ≤ uACR < 300 mg/g; n = 84), and macroalbuminuria (uACR ≥ 300 mg/g; n = 73), with healthy individuals (n = 72) as controls. Peripheral blood mononuclear cells (PBMCs) from these subjects were analyzed for VDR mRNA (n = 314), TNF-α mRNA (n = 314), microRNA (miR)-346 (n = 120; 30 for each group), and VDR protein (n = 80; 20 for each group). PBMCs from randomly selected subjects (n = 6 for each group) were cultured ex vivo to evaluate the effect of TNF-α on miR-346 and VDR, and miR-346-mediated VDR suppression was further explored in HK2 cells.

Results:

VDR expression was down-regulated in PBMCs and renal tubular epithelial cells from T2DM patients with albuminuria. VDR mRNA and protein levels were both negatively correlated with uACR, and VDR mRNA was inversely correlated with TNF-α and miR-346 in PBMCs from T2DM patients. TNF-α reduced VDR while inducing miR-346 in cultured PBMCs. TNF-α suppressed VDR by up-regulating miR-346 in HK2 cells.

Conclusions:

VDR down-regulation in PBMCs is independently associated with the severity of albuminuria in T2DM. TNF-α suppression of VDR in PBMCs and HK2 cells is mediated by miR-346.
Salivary Testosterone Levels and Health Status in Men and Women in the British General Population: Findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)
Authors: Clifton S. , Macdowall W. , Copas A. J. , Tanton C. , Keevil B. G. , Lee D. M. , Mitchell K. R. , Field N. , Sonnenberg P. , Bancroft J. , Mercer C. H. , Wallace A. M. , Johnson A. M. , Wellings K. , Wu F. C. W.
Published: August 2016

Context:

Salivary T (Sal-T) measurement by liquid chromatography–tandem mass spectroscopy resents the opportunity to examine health correlates of Sal-T in a large-scale population survey.

Objective:

This study sought to examine associations between Sal-T and health-related factors in men and women age 18–74 years.

Design and Setting:

Morning saliva samples were obtained from participants in a cross-sectional probability-sample survey of the general British population (Natsal-3). Self-reported health and lifestyle questions were administered as part of a wider sexual health interview.

Participants:

Study participants included 1599 men and 2123 women.

Methods:

Sal-T was measured using liquid chromatography–tandem mass spectroscopy. Linear regression was used to examine associations between health factors and mean Sal-T.

Results:

In men, mean Sal-T was associated with a range of health factors after age adjustment, and showed a strong independent negative association with body mass index (BMI) in multivariable analysis. Men reporting cardiovascular disease or currently taking medication for depression had lower age-adjusted Sal-T, although there was no association with cardiovascular disease after adjustment for BMI. The decline in Sal-T with increasing age remained after adjustment for health-related factors. In women, Sal-T declined with increasing age; however, there were no age-independent associations with health-related factors or specific heath conditions with the exception of higher Sal-T in smokers.

Conclusions:

Sal-T levels were associated, independently of age, with a range of self-reported health markers, particularly BMI, in men but not women. The findings support the view that there is an age-related decline in Sal-T in men and women, which cannot be explained by an increase in ill health. Our results demonstrate the potential of Sal-T as a convenient measure of tissue androgen exposure for population research.