bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of a risk stratification tool for fall-related injury in a state-wide cohort
Authors: McCoy Thomas H , Castro Victor M , Cagan Andrew , Roberson Ashlee M , Perlis Roy H
Published: February 2017

Objective

A major preventable contributor to healthcare costs among older individuals is fall-related injury. We sought to validate a tool to stratify such risk based on readily available clinical data, including projected medication adverse effects, using state-wide medical claims data.

Design

Sociodemographic and clinical features were drawn from health claims paid in the state of Massachusetts for individuals aged 35–65 with a hospital admission for a period spanning January–December 2012. Previously developed logistic regression models of hospital readmission for fall-related injury were refit in a testing set including a randomly selected 70% of individuals, and examined in a training set comprised of the remaining 30%. Medications at admission were summarised based on reported adverse effect frequencies in published medication labelling.

Setting

The Massachusetts health system.

Participants

A total of 68 764 hospitalised individuals aged 35–65 years.

Primary Measures

Hospital readmission for fall-related injury defined by claims code.

Results

A total of 2052 individuals (3.0%) were hospitalised for fall-related injury within 90 days of discharge, and 3391 (4.9%) within 180 days. After recalibrating the model in a training data set comprised of 48 136 individuals (70%), model discrimination in the remaining 30% test set yielded an area under the receiver operating characteristic curve (AUC) of 0.74 (95% CI 0.72 to 0.76). AUCs were similar across age decades (0.71 to 0.78) and sex (0.72 male, 0.76 female), and across most common diagnostic categories other than psychiatry. For individuals in the highest risk quartile, 11.4% experienced fall within 180 days versus 1.2% in the lowest risk quartile; 57.6% of falls occurred in the highest risk quartile.

Conclusions

This analysis of state-wide claims data demonstrates the feasibility of predicting fall-related injury requiring hospitalisation using readily available sociodemographic and clinical details. This translatable approach to stratification allows for identification of high-risk individuals in whom interventions are likely to be cost-effective.
Practising evidence-based medicine (EBM): a descriptive analysis of medical students’ whole-task EBM assignments
Authors: Maggio Lauren A , Capdarest-Arest Nicole
Published: February 2017

Researchers have suggested whole-task learning activities to practice and teach evidence-based medicine (EBM); however, limited description exists of their use in EBM curricula. This article describes medical students' execution of a whole-task EBM assignment and characterises themes emerging from assignment submissions. Between 2013 and 2015, Stanford University's paediatric clerkship students completed a whole-task EBM assignment based on a patient encounter. The assignment captured students' efforts to perform all EBM steps and describe their patient scenario and future knowledge needs strategies. Assignments were analysed using descriptive statistics and qualitative description. 123 students completed the assignment. Students formulated therapy (n=76), prognosis (n=18), diagnosis (n=15), harm (n=9) and aetiology (n=2) questions, and used a single (n=58) or multiple information resources (n=57). Based on evidence appraisal, 95 students indicated that the found evidence would inform future practice while 16 were sceptical of its conclusivity. 65 learners wanted to share evidence with colleagues; 33 with patients and families. To meet future knowledge needs, learners suggested using a structured approach (eg, PICO (patient, intervention, comparison and outcome); n=58), reading more primary literature (n=22) and creating question logs (n=21). This article provides a glimpse into students' EBM process and demonstrates the feasibility of whole-task activities for use in EBM training. Findings related to students’ clinical uncertainty and information sharing raise questions about coverage of these topics in current EBM training and suggest that further investigation is warranted.
Coaching and mentoring team members
Authors: Aylott Anne‐Marie Svendsen
Published: February 2017

A challenge for anyone working in veterinary practice is helping to grow and develop the skill‐set of the team around them. Here, Anne‐Marie Svendsen Aylott explains how coaching and mentoring can be used to help develop talent within the veterinary team.
When the client is away
Authors: Coghlan Simon
Published: February 2017

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.

In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘When the client is away’, was submitted and is discussed by Simon Coghlan. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue.

The series is being coordinated by Steven McCulloch, a practising vet with a PhD in the ethics of veterinary policy. It aims to provide a framework that will help practitioners find solutions when facing similar dilemmas.
Comments on the dilemma in the January issue: Brachycephalic dogs and honesty with clients
Authors: Hargreaves Robin
Published: February 2017

In the dilemma discussed in the January issue of In Practice, a colleague had been interviewed on local radio to discuss the health problems associated with brachycephalic breeds. Among other things, they had stated that vets should not promote the ownership of these dogs. One of their clients, a pug owner, now refuses to see the vet and books an appointment with you. You share your colleague's views on brachycephalic breeds. What would you do? (IP, January 2017, vol 39, pp 45‐46). Anne Fawcett said that a compassionate vet would identify and address welfare issues with these breeds and communicate them sensitively to the owner. The welfare issues should be addressed without being biased by your own conflict of interest. Ideally, the client should walk away feeling like they have had an opportunity to be heard and be more aware of the signs of brachycephalic obstructive airway syndrome to look out for in their pug.
A snake in the grass
Authors: Trefor Rhiannon , Varma Murali
Published: February 2017

Clinical question

A 77-year-old man presented with haematuria. Cystoscopy revealed a papillary tumour in the trigone region of the bladder. A TURBT was performed. Review the high-quality, interactive digital Aperio slide athttp://virtualacp.com/JCPCases/jclinpath-2016-204015and consider your diagnosis.

What is your diagnosis?

Urothelial carcinoma pTa

Urothelial carcinoma pT1

Metastatic carcinoma

Prostatic adenocarcinoma

Prostatic polyp
Analysis of longitudinal momentum distribution data of 26–29P isotopes in stripping reactions
Authors: Kumar Ravinder , Singh Pardeep , Kumar Rajiv
Published: February 2017

The orbital occupancy of the stripped proton in the phosphors isotopes with mass number 26–29 have been determined through the analysis of longitudinal momentum distributions (LMDs) of [Formula: see text] core fragments coming from [Formula: see text] and [Formula: see text] stripping reactions at high energies. It has been found that the probability of occupying [Formula: see text]-orbital by the stripped proton is 40–60%, 30–50%, 30–50% and 0–20% in [Formula: see text] isotopes, respectively. The effects of Coulomb barrier for the possibility of halo structure in proton-rich nuclei has also been examined and found that it decreases the chance of possessing halo structure in proton-rich nuclei.
STOCHASTIC ANALYSIS OF A DETERMINISTIC AND SEASONALLY-FORCED SEI MODEL FOR IMPROVED DISEASE SPREAD SIMULATION
Authors: SOHAIL AYESHA , LI ZHI WU , IFTIKHAR MEHWISH , MOHAMED MABRUKA , BÉG O. ANWAR
Published: February 2017

The geographic distribution of different viruses has developed widely, giving rise to an escalating number of cases during the past two decades. The deterministic Susceptible, Exposed, Infectious (SEI) models can demonstrate the spatio-temporal dynamics of the diseases and have been used extensively in modern mathematical and mechano-biological simulations. This article presents a functional technique to model the stochastic effects and seasonal forcing in a reliable manner by satisfying the Lipschitz criteria. We have emphasized that the graphical portrayal can prove to be a powerful tool to demonstrate the stability analysis of the deterministic as well as the stochastic modeling. Emphasis is made on the dynamical effects of the force of infection. Such analysis based on the parametric sweep can prove to be helpful in predicting the disease spread in urban as well as rural areas and should be of interest to mathematical biosciences researchers.
DEMYSTIFYING ABSORPTIVE CAPACITY: FOCUS ON FIRM SIZE AND EMPLOYEE EMPOWERMENT
Authors: NOWAK RADOSLAW
Published: February 2017

This project investigates the impact of contextual factors on the relationship between potential and realised absorptive capacity. The paper proposes that a firm’s size negatively affects this relationship, thus hindering the firm’s ability to create and exploit new knowledge. Nonetheless, as the paper posits, large firms can alleviate this negative effect of size by increasing a level of employee empowerment. The empirical analysis, based on the data collected from over 370 employees at 71 hospitals located in the United States, confirms main assumptions of the proposed model. The study considers key implications for strategy research as well as for managerial practices.
STRATEGIC PLANNING, PERFORMANCE AND INNOVATIVE CAPABILITIES OF NON-FAMILY MEMBERS IN FAMILY BUSINESSES
Authors: FAHED-SREIH JOSIANE , EL-KASSAR ABDUL-NASSER
Published: February 2017

Drawing upon the resource-based view and agency theories of family businesses, this study examines the role of strategic planning in developing non-family members’ innovative capabilities and the effect of strategic planning on family businesses’ performance mediated by those capabilities. It was found that strategic planning positively affects the business’ performance, it helps non-family members develop their innovative capabilities which have a positive effect on the performance of the business mediating the relationship between strategic planning and performance.

A survey was distributed to Lebanese family businesses for data collection. This study contributes to theory and practice; it suggests more fields of studies and helps family firms’ owners in improving the business’ performance.
ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice
Authors: Weerasekera Lakshini , Rudnicka Caroline , Sang Qing-Xiang , Curran Joanne E. , Johnson Matthew P. , Moses Eric K. , Göring Harald H. H. , Blangero John , Hricova Jana , Schlaich Markus , Matthews Vance B.
Published: February 2017

Obesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with insulin resistance, which may ultimately culminate in type 2 diabetes (T2D). We sought to ascertain whether the human metalloproteinase A Disintegrin and Metalloproteinase 19 (ADAM19) correlates with parameters of the metabolic syndrome in humans and mice. To determine the potential novel role of ADAM19 in the metabolic syndrome, we first conducted microarray studies on peripheral blood mononuclear cells from a well-characterised human cohort. Secondly, we examined the expression of ADAM19 in liver and gonadal white adipose tissue using an in vivo diet induced obesity mouse model. Finally, we investigated the effect of neutralising ADAM19 on diet induced weight gain, insulin resistance in vivo, and liver TNF-α levels. Significantly, we show that, in humans, ADAM19 strongly correlates with parameters of the metabolic syndrome, particularly BMI, relative fat, HOMA-IR, and triglycerides. Furthermore, we identified that ADAM19 expression was markedly increased in the liver and gonadal white adipose tissue of obese and T2D mice. Excitingly, we demonstrate in our diet induced obesity mouse model that neutralising ADAM19 therapy results in weight loss, improves insulin sensitivity, and reduces liver TNF-α levels. Our novel data suggest that ADAM19 is pro-obesogenic and enhances insulin resistance. Therefore, neutralisation of ADAM19 may be a potential therapeutic approach to treat obesity and T2D.
Long-Term Use and Perceived Benefits of Goal-Oriented Attentional Self-Regulation Training in Chronic Brain Injury
Authors: Loya Fred , Novakovic-Agopian Tatjana , Binder Deborah , Rossi Annemarie , Rome Scott , Murphy Michelle , Chen Anthony J. -W.
Published: February 2017

Primary Objective. To investigate the long-term use and perceived benefit(s) of strategies included in Goal-Oriented Attentional Self-Regulation (GOALS) training (Novakovic-Agopian et al., 2011) by individuals with acquired brain injury (ABI) and chronic executive dysfunction. Research Design. Longitudinal follow-up of training. Methods and Procedures. Sixteen participants with chronic ABI participated in structured telephone interviews 20 months (range 11 to 31 months) following completion of GOALS training. Participants responded to questions regarding the range of strategies they continued to utilize, perceived benefit(s) of strategy use, situations in which strategy use was found helpful, and functional changes attributed to training. Results. Nearly all participants (94%) reported continued use of at least one trained strategy in their daily lives, with 75% of participants also reporting improved functioning resulting from training. However, there was considerable variability with respect to the specific strategies individuals found helpful as well as the perceived impact of training on overall functioning. Conclusions. GOALS training shows promising long-term benefits for individuals in the chronic phase of brain injury. Identifying individual- and injury-level factors that account for variability in continued strategy use and the perceived long-term benefits of training will help with ongoing intervention development.
Vitamin D Status and Its Association with Parathyroid Hormone Concentration in Brazilians
Authors: Martins Juliana Sálvio , Palhares Magda de Oliveira , Teixeira Octávio Cury Mayrink , Gontijo Ramos Mariana
Published: February 2017

Vitamins are organic compounds that play a vital role in the control of metabolic processes. The D complex is considered a nutrient with a hormonal action and has an important participation in the constant maintenance of serum and extracellular calcium levels. The present study aims to analyze the results of 105.588 vitamin D (25(OH)D) measurements obtained from a database from a clinical analysis laboratory in Brazil, between the years of 2011 and 2013. The values of 25(OH)D were correlated with age, gender, and values of PTH. The results show a high prevalence of values of 25(OH)D considered inadequate, characterizing 76% of the studied population. It was observed that 26,5% of the individuals had deficiency and 49,5% had insufficiency of vitamin D. It was also shown that there was a negative correlation between 25(OH)D and PTH levels. In conclusion, this study is in accordance with others that show a high prevalence of vitamin D deficiency in different populations and alerts us for the importance of these measurements and analysis in clinical practice and as a base for diagnosis and treatment of hypovitaminosis.
MHD Flow of Micropolar Fluid over an Oscillating Vertical Plate Embedded in Porous Media with Constant Temperature and Concentration
Authors: Sheikh Nadeem Ahmad , Ali Farhad , Khan Ilyas , Saqib Muhammad , Khan Arshad
Published: February 2017

The present analysis represents the MHD flow of micropolar fluid past an oscillating infinite vertical plate embedded in porous media. At the plate, free convections are caused due to the differences in temperature and concentration. Therefore, the combined effect of radiative heat and mass transfer is taken into account. Partial differential equations are used in the mathematical formulation of a micropolar fluid. The system of dimensional governing equations is reduced to dimensionless form by means of dimensional analysis. The Laplace transform technique is applied to obtain the exact solutions for velocity, temperature, and concentration. In order to highlight the flow behavior, numerical computation and graphical illustration are carried out. Furthermore, the corresponding skin friction and wall couple stress are calculated.
A Non-Convex Partition of Unity and Stress Analysis of a Cracked Elastic Medium
Authors: Hong Won-Tak
Published: February 2017

A stress analysis using a mesh-free method on a cracked elastic medium needs a partition of unity for a non-convex domain whether it is defined explicitly or implicitly. Constructing such partition of unity is a nontrivial task when we choose to create a partition of unity explicitly. We further extend the idea of the almost everywhere partition of unity and apply it to linear elasticity problem. We use a special mapping to build a partition of unity on a non-convex domain. The partition of unity that we use has a unique feature: the mapped partition of unity has a curved shape in the physical coordinate system. This novel feature is especially useful when the enrichment function has polar form, f(r,θ)=rλg(θ), because we can partition the physical domain in radial and angular directions to perform a highly accurate numerical integration to deal with edge-cracked singularity. The numerical test shows that we obtain a highly accurate result without refining the background mesh.
Preclinical Development of a Nontoxic Oral Formulation of Monoethanolamine, a Lipid Precursor, for Prostate Cancer Treatment
Authors: Saxena Roopali , Yang Chunhua , Rao Mukkavilli , Turaga Ravi Chakra , Garlapati Chakravarthy , Gundala Sushma Reddy , Myers Kimberly , Ghareeb Ahmed , Bhattarai Shristi , Kamalinia Golnaz , Bristi Sangina , Su Dan , Gadda Giovanni , Rida Padmashree C.G. , Cantuaria Guilherme H. , Aneja Ritu
Published: February 2017

Purpose: Most currently available chemotherapeutic agents target rampant cell division in cancer cells, thereby affecting rapidly dividing normal cells resulting in toxic side-effects. This nonspecificity necessitates identification of novel cellular pathways that are reprogrammed selectively in cancer cells and can be exploited to develop pharmacologically superior and less toxic therapeutics. Despite growing awareness on dysregulation of lipid metabolism in cancer cells, targeting lipid biosynthesis is still largely uncharted territory. Herein, we report development of a novel nontoxic orally deliverable anticancer formulation of monoethanolamine (Etn) for prostate cancer by targeting the Kennedy pathway of phosphatidylethanolamine (PE) lipid biosynthesis.

Experimental Design: We first evaluated gastrointestinal tract stability, drug–drug interaction liability, pharmacokinetic, and toxicokinetic properties of Etn to evaluate its suitability as a nontoxic orally deliverable agent. We next performed in vitro and in vivo experiments to investigate efficacy and mechanism of action.

Results: Our data demonstrate that Etn exhibits excellent bioavailability, gastrointestinal tract stability, and no drug–drug interaction liability. Remarkably, orally fed Etn inhibited tumor growth in four weeks by approximately 67% in mice bearing human prostate cancer PC-3 xenografts without any apparent toxicity. Mechanistically, Etn exploits selective overexpression of choline kinase in cancer cells, resulting in accumulation of phosphoethanolamine (PhosE), accompanied by downregulation of HIF-1α that induces metabolic stress culminating into cell death.

Conclusions: Our study provides first evidence for the superior anticancer activity of Etn, a simple lipid precursor formulation, whose nontoxicity conforms to FDA-approved standards, compelling its clinical development for prostate cancer management. Clin Cancer Res; 23(14); 3781–93. ©2017 AACR.
Results from a Phase I/II Open-Label, Dose-Finding Study of Pralatrexate and Oral Bexarotene in Patients with Relapsed/Refractory Cutaneous T-cell Lymphoma
Authors: Duvic Madeleine , Kim Youn H. , Zinzani Pier Luigi , Horwitz Steven M.
Published: February 2017

Purpose: Pralatrexate is a folic acid analogue metabolic inhibitor similar to methotrexate, which has shown tolerability and efficacy with an overall response rate of 45% in a phase I dose deescalation study of patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL).

Experimental Design: The object of this phase I/II open-label, multicenter clinical trial was to determine the MTD and recommended dose of pralatrexate plus oral bexarotene in 34 patients with relapsed/refractory CTCL who had failed prior systemic therapies. Pralatrexate was administered by intravenous push at 15 mg/m2 given weekly 3 weeks out of 4 weeks with daily oral bexarotene (150 or 300 mg/m2), levothyroxine, atorvastatin, folate, and with B12 every 2 months.

Results: At the MTD of 15 mg/m2 bexarotene and 15 mg/m2 pralatrexate, the response rate was 60% [4 complete responses (CR), 14 partial responses (PR)], the maximum observed response duration was 28.9+ months, and duration of response for 4 CRs ranged from 9.0 to 28.3 months. The median progression-free survival was 12.8 months (0.5–29.9). Mucositis was the most common adverse event.

Conclusions: The combination of pralatrexate (15 mg/m2) and oral bexarotene (150 mg/m2) is active with high response rates and minimal toxicity for cutaneous T-cell lymphomas. Clin Cancer Res; 23(14); 3552–6. ©2017 AACR.
PARP Inhibitor Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression
Authors: Jiao Shiping , Xia Weiya , Yamaguchi Hirohito , Wei Yongkun , Chen Mei-Kuang , Hsu Jung-Mao , Hsu Jennifer L. , Yu Wen-Hsuan , Du Yi , Lee Heng-Huan , Li Chia-Wei , Chou Chao-Kai , Lim Seung-Oe , Chang Shih-Shin , Litton Jennifer , Arun Banu , Hortobagyi Gabriel N. , Hung Mien-Chie
Published: February 2017

Purpose: To explore whether a cross-talk exists between PARP inhibition and PD-L1/PD-1 immune checkpoint axis, and determine whether blockade of PD-L1/PD-1 potentiates PARP inhibitor (PARPi) in tumor suppression.

Experimental Design: Breast cancer cell lines, xenograft tumors, and syngeneic tumors treated with PARPi were assessed for PD-L1 expression by immunoblotting, IHC, and FACS analyses. The phospho-kinase antibody array screen was used to explore the underlying mechanism of PARPi-induced PD-L1 upregulation. The therapeutic efficacy of PARPi alone, PD-L1 blockade alone, or their combination was tested in a syngeneic tumor model. The tumor-infiltrating lymphocytes and tumor cells isolated from syngeneic tumors were analyzed by CyTOF and FACS to evaluate the activity of antitumor immunity in the tumor microenvironment.

Results: PARPi upregulated PD-L1 expression in breast cancer cell lines and animal models. Mechanistically, PARPi inactivated GSK3β, which in turn enhanced PARPi-mediated PD-L1 upregulation. PARPi attenuated anticancer immunity via upregulation of PD-L1, and blockade of PD-L1 resensitized PARPi-treated cancer cells to T-cell killing. The combination of PARPi and anti-PD-L1 therapy compared with each agent alone significantly increased the therapeutic efficacy in vivo.

Conclusions: Our study demonstrates a cross-talk between PARPi and tumor-associated immunosuppression and provides evidence to support the combination of PARPi and PD-L1 or PD-1 immune checkpoint blockade as a potential therapeutic approach to treat breast cancer. Clin Cancer Res; 23(14); 3711–20. ©2017 AACR.
Lipid Nanoparticle–Mediated Delivery of Anti-miR-17 Family Oligonucleotide Suppresses Hepatocellular Carcinoma Growth
Authors: Huang Xinqiang , Magnus Jill , Kaimal Vivek , Karmali Priya , Li Jian , Walls Marlena , Prudente Rene , Sung Eric , Sorourian Mehran , Lee Robin , Davis Scott , Yang Xia , Estrella Heather , Lee Edmund C. , Chau B. Nelson , Pavlicek Adam , Zabludoff Sonya
Published: February 2017

Hepatocellular carcinoma (HCC) is one of the most common human malignancies with poor prognosis and urgent unmet medical need. Aberrant expression of multiple members of the miR-17 family are frequently observed in HCC, and their overexpression promotes tumorigenic properties of HCC cells. However, whether pharmacologic inhibition of the miR-17 family inhibits HCC growth remains unknown. In this study, we validated that the miR-17 family was upregulated in a subset of HCC tumors and cell lines and its inhibition by a tough decoy inhibitor suppressed the growth of Hep3B and HepG2 cells, which overexpress the miR-17 family. Furthermore, inhibition of the miR-17 family led to a global derepression of direct targets of the family in all three HCC cell lines tested. Pathway analysis of the deregulated genes indicated that the genes associated with TGFβ signaling pathway were highly enriched in Hep3B and HepG2 cells. A miR-17 family target gene signature was established and used to identify RL01-17(5), a lipid nanoparticle encapsulating a potent anti-miR-17 family oligonucleotide. To address whether pharmacologic modulation of the miR-17 family can inhibit HCC growth, RL01-17(5) was systemically administrated to orthotopic Hep3B xenografts. Suppression of Hep3B tumor growth in vivo was observed and tumor growth inhibition correlated with induction of miR-17 family target genes. Together, this study provides proof-of-concept for targeting the miR-17 family in HCC therapy. Mol Cancer Ther; 16(5); 905–13. ©2017 AACR.
Anatomopathological findings in captive-raised red-winged tinamou (Rhynchotus rufescens)
Authors: Momo Claudia , Garrido Eduardo , Werther Karin
Published: February 2017

A perdiz (Rhynchotus rufescens) membro da família Tinamidae é uma ave que apresenta relativa facilidade à adaptação ao cativeiro. É considerada apta à produção de carne de boa qualidade, com ótima conversão alimentar. Essas características a torna interessante para produção comercial. Visando conhecer as principais afecções que acometem essas aves, foram analisados achados macro e microscópicos de 114 perdizes que vieram a óbito ao longo de 12 anos, entre 1994 e 2006 provenientes de criatório experimental, mantidas em dois diferentes tipos de recintos. Os exames anatomopatológicos revelaram que os sistemas mais acometidos foram o urinário e o digestório. No primeiro, a gota úrica foi o principal achado, seguida da amiloidose e parasitismo pelo trematoda Paratanaisia confusa. No sistema digestório, foi observada a presença de corpo estranho e parasitismo por Capillaria penidoi em esôfago e inglúvio. As aves mantidas em alojamento com piso natural apresentaram maior parasitismo, enquanto as que foram mantidas em recinto com piso de concreto e palha apresentaram maior quantidade de corpos estranhos no sistema gastrointestinal, caquexia e amiloidose. O objetivo deste trabalho foi descrever os principais achados anatomopatológicos em perdizes criadas em cativeiro, correlacionando-os com o tipo de recinto adotado.
When Blue-Collars Feel Blue
Authors: Lemogne Cédric , Meneton Pierre , Wiernik Emmanuel , Quesnot Ariane , Consoli Silla M. , Ducimetière Pierre , Nabi Hermann , Empana Jean-Philippe , Hoertel Nicolas , Limosin Frédéric , Goldberg Marcel , Zins Marie
Published: February 2017

Background—

The association of psychological variables with cardiovascular health might depend on socioeconomic status. We examined the moderating effect of occupational grade on the association between depression and incident cardiac events among middle-aged workers from the GAZEL cohort.

Methods and Results—

A total of 10 541 participants (7855 men, mean age: 47.8±3.5 years) free of cardiovascular diseases completed the Center of Epidemiologic Studies Depression scale in 1993. Age, sex, and occupational grade (low, medium, and high) were obtained from company records. Classical cardiovascular risk factors were self-reported. All participants were followed-up for medically certified cardiac events from January 1994 to December 2014. Associations between baseline variables and incident cardiac events were estimated with hazard ratios and 95% confidence intervals computed in Cox regressions. After a median follow-up of 21 years, 592 (5.6%) participants had a cardiac event. There was a significant interaction between depression and occupational grade in both age- and sex-adjusted (
P
=0.008) and multiadjusted (
P
=0.009) models. This interaction was mainly explained by an association between depression and incident cardiac events that prevailed among participants of low occupational grade (3.71 versus 1.96 events per 1000 person-years among those depressed versus nondepressed, multiadjusted hazard ratios [95% confidence intervals], 1.99 [1.12–3.48]).

Conclusions—

From a research perspective, these results may account for previous conflicting results and constitute an impetus for reanalyzing previous data sets, taking into account the moderating role of socioeconomic status. From a clinical perspective, they urge clinicians and policy makers to consider depressive symptoms and low socioeconomic status as synergistic cardiovascular risk factors.
ORAI1 Activates Proliferation of Lymphatic Endothelial Cells in Response to Laminar Flow Through Krüppel-Like Factors 2 and 4
Authors: Choi Dongwon , Park Eunkyung , Jung Eunson , Seong Young Jin , Hong Mingu , Lee Sunju , Burford James , Gyarmati Georgina , Peti-Peterdi Janos , Srikanth Sonal , Gwack Yousang , Koh Chester J. , Boriushkin Evgenii , Hamik Anne , Wong Alex K. , Hong Young-Kwon
Published: February 2017

Rationale:

Lymphatic vessels function to drain interstitial fluid from a variety of tissues. Although shear stress generated by fluid flow is known to trigger lymphatic expansion and remodeling, the molecular basis underlying flow-induced lymphatic growth is unknown.

Objective:

We aimed to gain a better understanding of the mechanism by which laminar shear stress activates lymphatic proliferation.

Methods and Results:

Primary endothelial cells from dermal blood and lymphatic vessels (blood vascular endothelial cells and lymphatic endothelial cells [LECs]) were exposed to low-rate steady laminar flow. Shear stress–induced molecular and cellular responses were defined and verified using various mutant mouse models. Steady laminar flow induced the classic shear stress responses commonly in blood vascular endothelial cells and LECs. Surprisingly, however, only LECs showed enhanced cell proliferation by regulating the vascular endothelial growth factor (VEGF)-A, VEGF-C, FGFR3, and p57/CDKN1C genes. As an early signal mediator, ORAI1, a pore subunit of the calcium release–activated calcium channel, was identified to induce the shear stress phenotypes and cell proliferation in LECs responding to the fluid flow. Mechanistically, ORAI1 induced upregulation of Krüppel-like factor (KLF)-2 and KLF4 in the flow-activated LECs, and the 2 KLF proteins cooperate to regulate VEGF-A, VEGF-C, FGFR3, and p57 by binding to the regulatory regions of the genes. Consistently, freshly isolated LECs from
Orai1
knockout embryos displayed reduced expression of KLF2, KLF4, VEGF-A, VEGF-C, and FGFR3 and elevated expression of p57. Accordingly, mouse embryos deficient in
Orai1
,
Klf2
, or
Klf4
showed a significantly reduced lymphatic density and impaired lymphatic development.

Conclusions:

Our study identified a molecular mechanism for laminar flow–activated LEC proliferation.
Genesis of the Cube: The Design and Deployment of an HDLA-Based Performance and Research Facility
Authors: Lyon Eric , Caulkins Terence , Blount Denis , Ico Bukvic Ivica , Nichols Charles , Roan Michael , Upthegrove Tanner
Published: February 2017

The Cube is a recently built facility that features a high-density loudspeaker array. The Cube is designed to support spatial computer music research and performance, art installations, immersive environments, scientific research, and all manner of experimental formats and projects. We recount here the design process, implementation, and initial projects undertaken in the Cube during the years 2013–2015.
Don’t Rush to Rehabilitate: A Remark on Koeneman and Zeijlstra 2014
Authors: Heycock Caroline , Sundquist John D.
Published: February 2017

Koeneman and Zeijlstra (2014) aim to rehabilitate the strong version of the Rich Agreement Hypothesis (RAH), according to which there is a bidirectional implication between “rich” agreement morphology in the verbal system and movement of the finite verb to a functional head above vP but below the C system (V-to-I movement). We show that one of the clearest empirical arguments raised in the literature against the strong RAH—the persistence of V-to-I movement in Early Modern Danish—is not addressed by any of the counterarguments raised by Koeneman and Zeijlstra and therefore still stands as evidence against the rehabilitated generalization and theory.
×Polascontria (Cactaceae), a nothogenus that represents the gene flow between Escontria and Polaskia
Authors: CRUZ-ZAMORA YURIDIA , CRUZ-GARCÍA FELIPE , OROZCO-ARROYO GREGORIO , REYES-SANTIAGO JERÓNIMO , MARTÍNEZ-CASTILLA LEÓN P. , WEGIER ANA , VÁZQUEZ-SANTANA SONIA
Published: February 2017

Hybridization represents an important mechanism in the diversification of Cactaceae where interspecific barriers are poorly developed. Putative hybrids with an intermediate phenotype between the columnar cacti Escontria chiotilla and Polaskia chichipe were observed in Oaxaca, Mexico. The putative hybrids grow sympatrically with their parents, sharing pollinators and overlapping flowering periods. On the basis of morphological, genetic and molecular studies, we show that a gene flow occurs between E. chiotilla and P. chichipe. Morphological and genetic similarities were used to carry out phenetic analyses, which allowed us to separate the two taxa and the potential hybrids, and cluster them into discrete groups with a high degree of consistency. We also generate artificial hybrids by hand-pollination crosses. These hybrids indicate that there are partial pre- and postzygotic barriers between E. chiotilla and P. chichipe. Backcrosses between parents and hybrids produced viable seeds, suggesting that there is a high potential of introgression with both parents. Taken together, we propose that hybrids observed in the field are the product of cross-pollination between E. chiotilla and P. chichipe. Thus, gene flow between both genera can explain why the genetic independence of these taxa has not kept them reproductively isolated. A complete description and illustrations of a new intergeneric hybrid are provided.
Discovery of the genus Claraeola Aczél in Iran with the description of two new species (Diptera: Pipunculidae)
Authors: MOTAMEDINIA BEHNAM , KEHLMAIER CHRISTIAN , MOKHTARI AZIZOLLAH , RAKHSHANI EHSAN , GILASIAN EBRAHIM
Published: February 2017

The genus Claraeola Aczél is recorded from Iran for the first time. Two new species, Claraeola parnianae Motamedinia & Kehlmaier sp. nov. and Claraeola khorshidae Motamedinia & Kehlmaier sp. nov., are described and illustrated. An updated identification key to the Western Palaearctic species of the genus Claraeola is provided. Both species were characterized morphologically and by DNA barcoding of the mitochondrial COI gene.
Resisting Throughput Pressures
Authors: Oh Hyeyoung
Published: February 2017

In recent years, quickly discharging patients has become a collective goal at hospitals, as excessive medical workups and extended hospital stays have been associated with unnecessary healthcare spending. Physicians, however, frequently encounter numerous barriers when trying to discharge patients. Presenting ethnographic and interview data collected from September 2010 to September 2013, this paper examines one of the most difficult discharge cases physicians encounter on the internal medicine service at a U.S. teaching hospital: resistant patients—patients and families who refuse to leave the hospital. As physicians try to discharge resistant patients, they are met with conflicting financial and professional incentives. Drawing from the sociological literature on professions, managerialism, and consumerism, I analyze the strategies physicians develop to manage these difficult discharge cases.
Diagnostic Performance of Narrow Band Imaging for Laryngeal Cancer: A Systematic Review and Meta‐analysis
Authors: Sun Changling , Han Xue , Li Xiaoying , Zhang Yayun , Du Xiaodong
Published: February 2017

Objective

To evaluate the performance of narrow band imaging (NBI) for the diagnosis of laryngeal cancer and to compare the diagnostic value of NBI with that of white light endoscopy.

Data Sources

PubMed, Embase, Cochrane Library, and CNKI databases.

Review Methods

Data analyses were performed with Meta‐DiSc. The updated Quality Assessment of Diagnostic Accuracy Studies–2 tool was used to assess study quality and potential bias. Publication bias was assessed with the Deeks’s asymmetry test. The protocol used in this article has been published on PROSPERO and is in accordance with the PRISMA checklist. The registry number for this study is CRD42015025866.

Results

Six studies including 716 lesions were included in this meta‐analysis. The pooled sensitivity, specificity, and diagnostic odds ratio for the NBI diagnosis of laryngeal cancer were 0.94 (95% confidence interval [95% CI]: 0.91‐0.96), 0.89 (95% CI: 0.85‐0.92), and 142.12 (95% CI: 46.42‐435.15), respectively, and the area under receiver operating characteristics curve was 0.97. Among the 6 studies, 3 evaluated the diagnostic value of white light endoscopy, with a sensitivity of 0.81 (95% CI: 0.76‐0.86), a specificity of 0.92 (95% CI: 0.88‐0.95), and a diagnostic odds ratio of 33.82 (95% CI: 14.76‐77.49). The evaluation of heterogeneity, calculated per the diagnostic odds ratio, gave an I2 of 66%. No marked publication bias (P =. 84) was detected in this meta‐analysis.

Conclusion

The sensitivity of NBI is superior to white light endoscopy, and the potential value of NBI needs to be validated in future studies.
Chronicity of Voice‐Related Health Care Utilization in the General Medicine Community
Authors: Cohen Seth M. , Lee Hui‐Jie , Roy Nelson , Misono Stephanie
Published: February 2017

Objectives

To examine voice‐related health care utilization of patients in the general medical community without otolaryngology evaluation and explore factors associated with prolonged voice‐related health care.

Study Design

Retrospective cohort analysis.

Setting

Large, national administrative US claims database.

Subjects and Methods

Patients with voice disorders perInternational Classification of Diseases, Ninth Revision, Clinical Modification(ICD‐9‐CM) codes from January 1, 2010, to December 31, 2012, seen by a general medical physician, and who did not see an otolaryngologist in the subsequent year were included. Voice‐related health care utilization, patient demographics, comorbid conditions, and index laryngeal diagnosis were collected. Logistic regression with variable selection was performed to evaluate the association between predictors and ≥30 days of voice‐related health care use.

Results

In total, 46,205 unique voice‐disordered patients met inclusion criteria. Of these patients, 8.5%, 10.0%, and 12.5% had voice‐related health care use of ≥90, ≥60, and ≥30 days, respectively. Of the ≥30‐day subset, 80.3% and 68.5%, respectively, had ≥60 and ≥90 days of voice‐related health care utilization. The ≥30‐day subset had more general medicine and nonotolaryngology specialty physician visits, more prescriptions and procedures, and 4 times the voice‐related health care costs compared with those in the <30‐day subset. Age, sex, employment status, initial voice disorder diagnosis, and comorbid conditions were related to ≥30 days of voice‐related health care utilization.

Conclusions

Thirty days of nonotolaryngology‐based care for a voice disorder may represent a threshold beyond which patients are more likely to experience prolonged voice‐related health care utilization. Specific factors were associated with extended voice‐related health care.
Effect of combined opioid receptor and α2-adrenoceptor blockade on anxiety and electrically evoked startle responses
Authors: Vo Lechi , Drummond Peter D
Published: February 2017

The R3 component of the electrically evoked blink reflex may form part of a startle reaction. Acoustic startle responses are augmented by yohimbine, an α2-adrenoceptor antagonist that blocks α2-autoreceptors, and are potentiated by opioid receptor blockade. To investigate these influences on electrically evoked startle responses, 16 mg yohimbine, with (16 participants) or without 50 mg naltrexone (23 participants), was administered in separate double-blind placebo-controlled cross-over experiments. In each experiment, R3 (a probable component of the startle response) was examined before and after high-frequency electrical stimulation of the forearm, a procedure that initiates inhibitory pain controls. Anxiety and somatic symptoms were greater after yohimbine than placebo, and were potentiated by naltrexone. Pain ratings for the electrically evoked startle stimuli decreased after high-frequency electrical stimulation in the placebo session but remained stable after drug administration. Yohimbine with naltrexone, but not yohimbine alone, also blocked an inhibitory effect of high-frequency electrical stimulation on electrically evoked sharp sensations and R3. Together, the findings suggest that adding naltrexone to yohimbine potentiated anxiety and blocked inhibitory influences of high-frequency electrical stimulation on electrically evoked sensations and startle responses. Thus, opioid peptides could reduce activity in nociceptive and startle-reflex pathways, or inhibit crosstalk between these pathways. Failure of this inhibitory opioid influence might be important in chronically painful conditions that are aggravated by startle stimuli.
Endolymphatic Sac Tumor in Two Dogs
Authors: Barnes K. J. , Clear V. , Youmans K. , Hardcastle M. R. , Nelson N. , Petersen A. , Kiupel M.
Published: February 2017

Endolymphatic sac tumors (ELSTs) are rare neoplasms of the inner and middle ear described in humans. Diagnosis of such neoplasms is difficult and largely dependent on a combination of histologic, immunohistochemical, and clinical findings. Although the neoplastic cells lack cellular features of malignancy, these are clinically aggressive tumors that often invade the surrounding temporal bone. Here, we describe 2 dogs with middle ear masses that share morphologic, immunohistochemical, and clinical similarities with human ELSTs. Advanced imaging of the masses revealed evidence of aggressive behavior such as bony lysis of the temporal bone. Histologically, the neoplastic epithelial cells formed papillary structures, lacked mitotic figures, and had mild anisocytosis and anisokaryosis. The neoplastic cells were immunohistochemically positive for cytokeratin AE1/AE3 but were negative for chromogranin, synaptophysin, and thyroglobulin. Local invasion and bone destruction but no evidence of metastases suggest a clinical behavior similar to human ELSTs.
Stresses associated with multiple holes whose individual stresses interact
Authors: Khaja AA , Rowlands RE
Published: February 2017

The stress consequences of adding an auxiliary hole in the neighborhood of an original hole are determined from the load-induced thermal information when the geometric discontinuities are sufficiently close together that their respective stresses interact. The particular situation involves a smaller round hole near a larger round hole in a finite, isotropic tensile member where the holes are aligned in the direction of loading. Introducing a second hole reduces the stresses at each hole had it alone been present. The results correlate well with those from finite elements, strain gage and load equilibrium. The developed technology has relevance for isotropic, orthotropic or functionally graded materials.
A Qualitative Study of Challenges and Opportunities in Mobilizing Research Knowledge on Violence Against Women
Authors: Sibbald Shannon L. , MacGregor Jennifer C. D. , MacMillan Harriet L. , Wathen Nadine
Published: February 2017

Background

Effective delivery of interventions by health and social services requires research-based knowledge which identifies the causes and consequences of violence against women. Methods to effectively share new knowledge with violence against women decision-makers remain under studied.

Purpose

This paper examines how new research-based knowledge—namely, the lack of efficacy of health-care screening for exposure to intimate partner violence against women—is received by stakeholders in the violence against women field.

Methods

Data from 10 stakeholder group discussions ( N = 86) conducted during a knowledge-sharing forum were analyzed to assess how stakeholders responded to the new knowledge.

Results

Participant reactions ranged from full acceptance to significant resistance to the research findings. We suggest themes that help explain these reactions, including the context and content of our findings and their epistemological match to participants’ experiences and beliefs, and the perceived value of research evidence, compared to other forms of knowledge.

Conclusions

Violence against women is a complex psycho-social phenomenon, and people with an interest in this field bring diverse and even conflicting perspectives regarding its causes, consequences, and potential solutions.
Nutrition Support for Persistent Inflammation, Immunosuppression, and Catabolism Syndrome
Authors: Moore Frederick A. , Phillips Stuart M. , McClain Craig J. , Patel Jayshil J. , Martindale Robert G.
Published: February 2017

Despite tremendous advances in critical care, multiple‐organ failure continues to be a significant problem. However, in recent years, far fewer patients with multiple‐organ failure die early, but many experience ongoing immune dysregulation and are developing persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Most PICS patients are discharged to nonhome destinations, fail to rehabilitate, and succumb to indolent death. From a nutrition perspective, patients with PICS experience persistent inflammation‐induced cachexia despite evidenced‐based recommended intensive care unit nutrition support. Recent basic and translational research indicates that prolonged expansion of myeloid‐derived suppressor cells plays a central role in the pathogenesis of PICS. Myeloid‐derived suppressor cells express arginase 1, which depletes arginine, causing immunosuppression and impaired wound healing. This is the rationale for arginine supplementation in PICS. Other nutrition support recommendations for PICS are based on inferences made from other patient populations who experience similar persistent inflammation‐induced cachexia. These include patients with established cancers, major burns, and sarcopenia. These patients experience anabolic resistance, but studies show that this can be overcome by providing higher levels of protein and certain specific amino acids. Nutrition support guidelines recommend provision of >1.5 g/kg/d of protein and indicate that higher levels may be needed. Protein composition is also important. There is good evidence that leucine can promote anabolism in patients with cancer and sarcopenia. Finally, anabolic interventions—including intensive insulin, oxandrolone, propranolol, and resistance exercise—have proven to be effective in patients with major burns and are likely relevant in combating PICS cachexia.