bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the motivation and performance of community health volunteers involved in the delivery of health programmes in Kampala, Uganda: a realist evaluation protocol
Authors: Vareilles Gaëlle , Pommier Jeanine , Kane Sumit , Pictet Gabriel , Marchal Bruno
Published: January 2015

Introduction

The recruitment of community health volunteers to support the delivery of health programmes is a well-established approach in many countries, particularly where health services are not readily available. However, studies on management of volunteers are scarce and current research on human resource management of volunteers faces methodological challenges. This paper presents the protocol of a realist evaluation that aims at identifying the factors influencing the performance of community health volunteers involved in the delivery of a Red Cross immunisation programme in Kampala (Uganda) with a specific focus on motivation.

Methods and analysis

The realist evaluation cycle structures the protocol. To develop the theoretical basis for the evaluation, the authors conducted interviews and reviewed the literature on community health volunteers’ performance, management and organisational behaviour. This led to the formulation of the initial programme theory, which links the intervention inputs (capacity-building strategies) to the expected outcomes (positive work behaviour) with mechanisms that point in the direction of drivers of motivation. The contextual elements include components such as organisational culture, resource availability, etc. A case study design will be adopted. We define a case as a Red Cross branch, run by a programme manager, and will select two cases at the district level in Kampala. Mixed methods will be used in data collection, including individual interviews of volunteers, participant observation and document review. The thematic analysis will be based on the initial programme theory and will seek for context-mechanism-outcome configurations. Findings from the two cases will be compared.

Discussion

We discuss the scope for applying realist evaluation and the methodological challenges we encountered in developing this protocol.

Ethics and dissemination

The study was approved by the Ethical Committee at Rennes University Hospital, France. Results will be published in scientific journals, and communicated to respondents and relevant institutions.
The POPPY Research Programme protocol: investigating opioid utilisation, costs and patterns of extramedical use in Australia
Authors: Degenhardt Louisa , Blanch Bianca , Gisev Natasa , Larance Briony , Pearson Sallie
Published: January 2015

Introduction

Opioid prescribing is increasing in many countries. In Australia, there is limited research on patterns of prescribing and access, or the outcomes associated with this use. The aim of this research programme is to use national dispensing data to estimate opioid use and costs, including problematic or extramedical use in the Australian population.

Methods and analysis

In a cohort of persons dispensed at least one opioid in 2013, we will estimate monthly utilisation and costs of prescribed opioids, overall and according to individual opioid formulations and strengths. In a cohort of new opioid users, commencing therapy between 1 July 2009 and 31 December 2013, we will examine patterns of opioid use including initiation of therapy, duration of treatment and concomitant use of opioids and other prescribed medicines. We will also examine patterns of extramedical opioid use based on indicators including excess dosing, use of more than one opioid concomitantly, doctor/pharmacy shopping and accelerated time to prescription refill.

Ethics and dissemination

This protocol was approved by the NSW Population and Health Services Ethics Committee (March 2014) and data access approved by the Department of Human Services External Review Evaluation Committee (June 2014). This will be one of the first comprehensive Australian studies with the capability to investigate individual patterns of use and track extramedical use. In the first instance our analysis will be based on 5 years of dispensing data but will be expanded with ongoing annual data updates. This research has the capability to contribute significantly to pharmaceutical policy within Australia and globally. In particular, the trajectory of extramedical prescription-opioid use has been the subject of limited research to date. The results of this research will be published widely in general medical, pharmacoepidemiology, addiction and psychiatry journals.
Protocol of a longitudinal cohort study on physical activity behaviour in physically disabled patients participating in a rehabilitation counselling programme: ReSpAct
Authors: Alingh Rolinde A , Hoekstra Femke , van der Schans Cees P , Hettinga Florentina J , Dekker Rienk , van der Woude Lucas H V
Published: January 2015

Introduction

Stimulating physical activity behaviour in persons with a physical disability is important, especially after discharge from rehabilitation. A tailored counselling programme covering both the period of the rehabilitation treatment and the first months at home seems on the average effective. However, a considerable variation in response is observed in the sense that some patients show a relevant beneficial response while others show no or only a small response on physical activity behaviour. The Rehabilitation, Sports and Active lifestyle (ReSpAct) study aims to estimate the associations of patient and programme characteristics with patients’ physical activity behaviour after their participation in a tailored counselling programme.

Methods and analysis

A questionnaire-based nationwide longitudinal prospective cohort study is conducted. Participants are recruited from 18 rehabilitation centres and hospitals in The Netherlands. 2000 participants with a physical disability or chronic disease will be followed during and after their participation in a tailored counselling programme. Programme outcomes on physical activity behaviour and patient as well as programme characteristics that may be associated with differences in physical activity behaviour after programme completion are being assessed. Data collection takes place at baseline and 14, 33 and 52 weeks after discharge from rehabilitation.

Ethics and dissemination

The study protocol has been approved by the Medical Ethics Committee of the University Medical Centre Groningen and at individual participating institutions. All participants give written informed consent. The study results will provide new insights into factors that may help explain the differences in physical activity behaviour of patients with a physical disability after they have participated in the same physical activity and sports stimulation programme. Thereby, it will support healthcare professionals to tailor their guidance and care to individual patients in order to stimulate physical activity after discharge in a more efficient and effective way.

Trial registration number

NTR3961.
Predictors of infection from dog bite wounds: which patients may benefit from prophylactic antibiotics?
Authors: Tabaka Meg E , Quinn James V , Kohn Michael A , Polevoi Steven K
Published: January 2015

Objectives

To determine a current infection rate of dog bite wounds and predictors of wounds at risk for infection that may benefit from prophylactic antibiotics.

Methods

A prospective multicentre observational study was conducted over 4.5 years. At the time of treatment Emergency Physicians completed a structured data form evaluating patient, wound and treatment characteristics of patients with dog bite wounds. Patients were followed up at 30 days to assess for infection. Predictor variables were analysed with univariate analysis, using either χ2, parametric or nonparametric methods where appropriate. Significant variables and those with important interactions on univariate analysis were considered in a logistic regression (LR) analysis.

Results

495 patients with dog bites were enrolled and 345 had complete follow-up. Eighteen patients (5.2%, 95% CI 3.1% to 8.1%) had bites that became infected. On univariate analysis, only puncture wounds were found to be significantly associated with infection RR 2.8 (95% CI 1.2 to 6.9). However, location and wound closure met criteria for entry into the model having important interactions; facial wounds had a higher risk of infection than anticipated but were also more likely to be closed (p < 0.0001). A LR model considering puncture wounds, wound closure and wound location found that puncture wounds (OR 4.1 [95% CI 1.4 to 11.7]) and wound closure (OR 3.1 [95% CI 1.03 to 9.0]) were independent predictors of infection. The incidence of infection in wounds that were not punctured or closed during treatment was only 2.6% (95% CI 0.7% to 6.5%).

Conclusions

Puncture wounds or wounds closed during treatment are dog bite wounds at a high risk of infection and should be considered for treatment with prophylactic antibiotics.
Systematic analysis of missed colorectal cancer cases and common pitfalls in diagnosis
Authors: Vaughan-Shaw P G , Aung M , Knight H , Williams T , Borley N R , Wheeler J M D
Published: January 2015

Background

Missed colorectal cancer on endoscopic or radiological investigations may delay diagnosis and impact outcome. This study audits incidence of previous investigations in patients with colorectal cancer, considers outcome in ‘missed’ cancer cases and examines the diagnostic pathway in the derived case series to identify common pitfalls in diagnosis.

Methods

Patients diagnosed with colorectal cancer in 2011 at a single National Health Service (NHS) Trust were reviewed. Incidence of endoscopic and radiological investigations in the 3 years preceding diagnosis and outcome data were collected. Cases of prior investigation not leading to diagnosis were considered ‘missed’ cancers and survival compared with ‘detected’ cases. The diagnostic pathway in each ‘missed’ case was reviewed.

Results

395 colorectal cancer cases were studied. Eighteen (4.6%) patients underwent previous investigation including colonoscopy (n=4), flexible sigmoidoscopy (n=5), barium enema (n=5) and diagnostic abdominal CT scan (n=12), median 708 days prior to diagnosis. Previous investigation predicted reduced overall and disease-free survival (HR 2.07, p=0.04 and HR 2.66, p<0.0001), after age and gender adjustment. Ten different categories termed ‘pitfalls’ were derived from analysis of the diagnostic pathway. These included CT scanning for abdominal pain without further investigation (n=7), rectosigmoid cancer following a previous diagnosis of diverticular disease (n=4) and incomplete diagnostic investigations without adequate follow-up (n=3).

Conclusions

A proportion of patients diagnosed with colorectal cancer have previously been investigated for gastrointestinal symptoms and survival appears reduced in these patients. Regular audit and analysis of previous investigations can identify common pitfalls in diagnosis, which should be used to inform training and improve practice.
Republished: The wire anchor loop traction (WALT) maneuver
Authors: Effendi Khaled , Sacho Raphael Hillel , Belzile François , Marotta Thomas R
Published: January 2015

Crossing the neck of large complex intracranial aneurysms for the purposes of stent deployment can be challenging using standard over the wire techniques. We describe a novel yet simple technique for straightening out the loop formed within a large intracranial aneurysm, which is often required in order to cross the aneurysm neck into the distal branch. Both the microcatheter and microwire are initially introduced into the distal vasculature, followed by withdrawal of the microwire to a point parallel to the distal exiting branch. The microcatheter and microwire are then gently withdrawn and a series of maneuvers to gradually reduce the loop is performed, obviating the need for distal purchase in the form of a stent, balloon, or coil, which have previously been described to maintain distal purchase.
Numerical investigation of the geomechanical response of adjacent backfilled stopes
Authors: Falaknaz Nooshin , Aubertin Michel , Li Li
Published: January 2015

Backfilling of mine stopes helps provide a safe workplace underground. The interaction between the backfill and surrounding rock mass has to be evaluated to ensure the secure application of backfill. This critical issue has led to much research on the stress state in single (isolated) backfilled stopes. However, the stress distribution in multiple openings that interact with each other has not yet been investigated as thoroughly. In this paper, the authors are using numerical simulations to evaluate the response of two adjacent backfilled stopes created in sequence, with a new assumption that is based on an explicit relationship between Poisson’s ratio and the internal friction angle of the backfill; as shown here, the use of this relationship can significantly modify the stress state in backfilled stopes. The simulation results, presented in terms of stresses, displacements, and strains, illustrate the influence of different parameters including backfill strength, pillar width, stope depth, rock mass stiffness, natural stress state, and excavation and filling sequence. Complementary aspects are also considered. A discussion follows on some of the characteristics and limitations of this investigation.
Bayesian updating for one-dimensional consolidation measurements
Authors: Kelly Richard , Huang Jinsong
Published: January 2015

After a geotechnical design has been developed, it is common to monitor performance during construction using the observational method by Peck (published in 1969). The observational method is a process where data are collected and geotechnical models updated, allowing timely decisions to be made with respect to risk and opportunity by asset owners or contractors. The observational method is similar to the mathematical formulation for Bayesian updating of material parameters based on measurements. A proof of concept study has been performed to assess the potential for Bayesian updating to be combined with the observational method to allow timely and accurate decision-making during construction of embankments on soft soils. The method was able to converge to an accurate solution prior to 50% consolidation assuming small measurement errors. It is also demonstrated that confidence in the predicted settlement is relatively low at the prior “design” stage and rapidly increases with three or four measurements spaced over time during the posterior “construction” phase.
Endurance training alters basal erythrocyte MCT-1 contents and affects the lactate distribution between plasma and red blood cells in T2DM men following maximal exercise
Authors: Opitz David , Lenzen Edward , Opiolka Andreas , Redmann Melanie , Hellmich Martin , Bloch Wilhelm , Brixius Klara , Brinkmann Christian
Published: January 2015

Chronic elevated lactate levels are associated with insulin resistance in patients with type 2 diabetes mellitus (T2DM). Furthermore, lactacidosis plays a role in limiting physical performance. Erythrocytes, which take up lactate via monocarboxylate transporter (MCT) proteins, may help transport lactate within the blood from lactate-producing to lactate-consuming organs. This study investigates whether cycling endurance training (3 times/week for 3 months) alters the basal erythrocyte content of MCT-1, and whether it affects lactate distribution kinetics in the blood of T2DM men (n = 10, years = 61 ± 9, body mass index = 31 ± 3 kg/m2) following maximal exercise (WHO step-incremental cycle ergometer test). Immunohistochemical staining indicated that basal erythrocyte contents of MCT-1 protein were up-regulated (+90%, P = 0.011) post-training. Erythrocyte and plasma lactate increased from before acute exercise (= resting values) to physical exhaustion pre- as well as post-training (pre-training: +309%, P = 0.004; +360%, P < 0.001; post-training: +318%, P = 0.008; +300%, P < 0.001), and did not significantly decrease during 5 min recovery. The lactate ratio (erythrocytes:plasma) remained unchanged after acute exercise pre-training, but was significantly increased after 5 min recovery post-training (compared with the resting value) (+22%, P = 0.022). The results suggest an increased time-delayed influx of lactate into erythrocytes following an acute bout of exercise in endurance-trained diabetic men.
Short-Term Prediction of Marine Sensor Data with Fuzzy Clustering
Authors: O'Mara Aidan , Shahriar Md. Sumon
Published: January 2015

In predicting water quality variables in the short term, a novel technique using fuzzy pattern similarity-based fuzzy clustering has been proposed. The experimental results show that the proposed method outperforms than existing similar methods for sea water temperature and conductivity data sets from a marine sensor network for environmental monitoring. The short-term prediction of water quality variables has immense benefit in aquaculture and fisheries industries for decision-making purposes.
High Gain and High CMRR Two-Stage Folded Cascode OTA with Nested Miller Compensation
Authors: Akbari Meysam , Hashemipour Omid
Published: January 2015

By using Gm-C compensation (GCC) technique, a two-stage recycling folded cascode (FC) operational transconductance amplifier (OTA) is designed. The proposed configuration consists of recycling structure, positive feedback and feed-forward compensation path. In comparison with the typical folded cascode CMOS Miller amplifier, this design has higher DC gain, unity-gain frequency (UGF), slew rate and common mode rejection ratio (CMRR). The presented OTA is simulated in 0.18-μm CMOS technology and the simulation results confirm the theoretical analyses. Finally, the proposed amplifier has a 111 dB open-loop DC gain, 20 MHz UGF and 145 dB CMRR @ 1.2 V supply voltage while the power consumption is 400 μW which makes it suitable for low-voltage applications.
Experimental and Numerical Studies on Lateral-Torsional Buckling of GJ Structural Steel Beams Under a Concentrated Loading Condition
Authors: Yang Bo , Xiong Gang , Ding Kang , Nie Shidong , Zhang Weifu , Hu Ying , Dai Guoxin
Published: January 2015

GJ structural steel has been applied in many high-rise buildings and large-span structures, such as New CCTV Building and Beijing Olympic Stadium (Birds Nest). However, the design methods of GJ structural steel members are not covered by the current design codes. This paper describes the lateral-torsional buckling behavior of welded sections based on a series of flexural tests performed on H-sections fabricated from GJ structural steel plates. Six steel beams were tested under a concentrated loading condition. It was observed from the experimental tests that lateral-torsional buckling controlled the final failure modes. Numerical simulations of the experimental tests were conducted as well. The numerical simulation results agreed well with the test data. Parametric study was conducted after the validation of the numerical model. Finally, both the experimental test and parametric study results were compared with multiple design codes, including Chinese steel structure design codes (GB50017-2003, GB50017-201X), Eurocode (EC3) and American code (ANSI/AISC360-10). The comparisons indicate that GB50017-201X can predict appropriate flexural strengths of GJ structural steel beams. Also, it is found that the predictions of EC3 are too conservative, while for certain cases ANSI/AISC360-10 predictions are too high for the design flexural strength of GJ structural steel beams.
Development of a Customized Wireless Sensor System for Large-Scale Spatial Structures and Its Applications in Two Cases
Authors: Shen Yanbin , Yang Pengcheng , Luo Yaozhi
Published: January 2015

In this paper, a customized wireless sensor system (WSS) for structural health monitoring is developed toward large-scale spatial structures. Spatial structures are widely used in large public buildings which generally house thousands of people, therefore the safety of the buildings is a major concern for structural engineers. One of the characteristics of spatial structures is their steel construction and the material is homogeneous throughout. So the strain is commonly the most distinct parameter to indicate status of the structure. Another characteristic of spatial structures is their large-area scale, which brings problem for traditional wired monitoring systems, so an effective wireless sensor network (WSN) for structural monitoring is in urgent demand. Considering those features, the WSS development mainly focused on the sensor selection, hardware design and network customization. In this paper, a vibrating wire sensor is selected for strain measurement because of its stable, durable and anti-electromagnetic properties. For other parameters measurement, some commercial sensor products with digital signal output are adopted. Following the principle of modularization and extendibility, the hardware design is mainly based on the realization of several functional modules. All along, energy efficiency and measurement accuracy are the core design objective. The WSN is classified into four different types of topologies from basic to complex ones. They all have the common working mechanism, namely the collected data transfers via several relay from sensor nodes to sink nodes. Different types of networks are to be customized according to the configuration and scale of different structures. Finally, two typical applications are discussed in detail to verify the feasibility of the system. It can be concluded that the customized WSS is effective and durable, and well satisfies the requirement of structural status monitoring for large-scale spatial structures. Collected data have also shown that the structural stress variation is obvious under the effect of construction process and some other factors.
Bulk irreducibles of the modular group
Authors: Le Bruyn Lieven
Published: January 2015

As the 3-string braid group B3 and the modular group Γ are both of wild representation type one cannot expect a full classification of all their finite dimensional simple representations. Still, one can aim to describe 'most' irreducible representations by constructing for each d-dimensional irreducible component X of the variety iss n(Γ) classifying the isomorphism classes of semi-simple n-dimensional representations of Γ an explicit minimal étale rational map 𝔸d → X having a Zariski dense image. Such rational dense parametrizations were obtained for all components when n < 12 in [5]. The aim of the present paper is to establish such parametrizations for all finite dimensions n.
A Decision Model for the Evaluation and Selection of Cloud Computing Services: A First Step Towards a More Sustainable Perspective
Authors: Walterbusch Marc , Martens Benedikt , Teuteberg Frank
Published: January 2015

In this paper, we present a decision model for evaluating and selecting Cloud Computing Services. A strong focus is put on the economic, environmental and social perspectives which are subsumed under the term 'sustainable information systems management'. The model supports decision makers in comprehensively evaluating relevant cost types. We seek to formulate a realistic model by applying a combination of deductive and inductive steps to reveal the core characteristics of Cloud Computing Services and their economic, environmental and social impacts. For the construction of the pricing model and the determination of carbon emission costs, we drew on several theoretical and practical sources. The quality of the model is confirmed on the one hand by expert interviews and on the other hand by the outcomes of a simulation study including two scenarios and a statistical evaluation. The presented research results clarify the need to consider more than the economic dimension — including factors and attributes of sustainable information systems management — in evaluating and selecting Cloud Computing Services.
Testing against second-order stochastic dominance of multiple distributions
Authors: Zhang Jianling , Zhang Zhongzhan , Wang Weizhen
Published: January 2015

Second-order stochastic dominance plays an important role in reliability and various branches of economics such as finance and decision-making under risk, and statistical testing for the stochastic dominance is often useful in practice. In this paper, we present a test of stochastic equality under the constraint of second-order stochastic dominance based on the theory of empirical processes. The asymptotic distribution of the test statistic is obtained, and a simple method to compute the critical value is derived. Simulation results and real data examples are presented to illustrate the proposed test method.
Searching for majority with k-tuple queries
Authors: De Marco Gianluca , Kranakis Evangelos
Published: January 2015

Diagnosing the quality of components in fault-tolerant computer systems often requires numerous tests with limited resources. It is usually the case that repeated tests on a selected, limited number of components are performed and the results are taken into account so as to infer a diagnostic property of the computer system as a whole. In this paper we abstract fault-tolerant testing as the following problem concerning the color of the majority in a set of colored balls. Given a set of balls each colored with one of two colors, the majority problem is to determine whether or not there is a majority in one of the two colors. In case there is such a majority, the aim is to output a ball of the majority color, otherwise to declare that there is no majority. We propose algorithms for solving the majority problem by repeatedly testing only k-tuple queries. Namely, successive answers of an oracle (which accepts as input only k-tuples) to a sequence of k-tuple queries are assembled so as to determine whether or not the majority problem has a solution. An issue is to design an algorithm which minimizes the number of k-tuple queries needed in order to solve the majority problem on any possible input of n balls. In this paper we consider three querying models: Output, Counting, and General, reflecting the amount and type of information provided by the oracle on each test for a k-tuple.
PREDICTION OF FRICTIONAL AND WEAR BEHAVIOR OF ALUMINIUM MATRIX COMPOSITES BY ARTIFICIAL NEURAL NETWORK
Authors: KAMBLE VIKRAM G. , KAMBLE SAGAR G. , K. D. RAMESH
Published: January 2015

Modern technologies require materials with unusual combination of properties that cannot be met by conventional metal alloys, ceramic, etc. In our work, we prepared the samples of metal alloys such as Al 356- TiB 2. Processing of samples is done by artificial neural network (ANN) which is one of the promising fields of research in predicting experimental results. In our investigation we worked on grain size analysis, micro hardness, regression analysis, friction test, wear test and microstructure analysis of samples to describe the materials properties of Al 356- TiB 2.
Development of an Unmanned Helicopter for Vertical Replenishment
Authors: Wang Fei , Liu Peidong , Zhao Shiyu , Chen Ben M. , Phang Swee King , Lai Shupeng , Pang Tao , Wang Biao , Cai Chenxiao , Lee Tong H.
Published: January 2015

This paper presents an intelligent and robust guidance, navigation and control solution for a rotary-wing UAV to carry out an autonomous cargo transportation mission between two moving platforms. Different from the conventional GPS/INS-only navigation scheme, this solution also integrates sophisticated Lidar and vision systems capable of precisely locating cargo loading and unloading positions. Besides, another complementary GPS/INS system is set up on the moving platforms with communication to the unmanned helicopter so that the controlled UAV is able to follow the dynamic platforms with good tracking performance. The whole system has been successfully implemented, and with its superb performance the Unmanned Systems Research Group from the National University of Singapore won the first place in the final round of the rotary-wing category competition of the 2nd AVIC Cup — International UAV Innovation Grand Prix 2013.
Atrial natriuretic peptide inhibits cell cycle activity of embryonic cardiac progenitor cells via its NPRA receptor signaling axis
Authors: Hotchkiss Adam , Feridooni Tiam , Baguma-Nibasheka Mark , McNeil Kathleen , Chinni Sarita , Pasumarthi Kishore B. S.
Published: January 2015

The biological effects of atrial natriuretic peptide (ANP) are mediated by natriuretic peptide receptors (NPRs), which can either activate guanylyl cyclase (NPRA and NPRB) or inhibit adenylyl cyclase (NPRC) to modulate intracellular cGMP or cAMP, respectively. During cardiac development, ANP serves as an early maker of differentiating atrial and ventricular chamber myocardium. As development proceeds, expression of ANP persists in the atria but declines in the ventricles. Currently, it is not known whether ANP is secreted or the ANP-NPR signaling system plays any active role in the developing ventricles. Thus the primary aims of this study were to 1) examine biological activity of ANP signaling systems in embryonic ventricular myocardium, and 2) determine whether ANP signaling modulates proliferation/differentiation of undifferentiated cardiac progenitor cells (CPCs) and/or cardiomyocytes. Here, we provide evidence that ANP synthesized in embryonic day (E)11.5 ventricular myocytes is actively secreted and processed to its biologically active form. Notably, NPRA and NPRC were detected in E11.5 ventricles and exogenous ANP stimulated production of cGMP in ventricular cell cultures. Furthermore, we showed that exogenous ANP significantly decreased cell number and DNA synthesis of CPCs but not cardiomyocytes and this effect could be reversed by pretreatment with the NPRA receptor-specific inhibitor A71915. ANP treatment also led to a robust increase in nuclear p27 levels in CPCs compared with cardiomyocytes. Collectively, these data provide evidence that in the developing mammalian ventricles ANP plays a local paracrine role in regulating the balance between CPC proliferation and differentiation via NPRA/cGMP-mediated signaling pathways.
Intracellular Ca2+ release from endoplasmic reticulum regulates slow wave currents and pacemaker activity of interstitial cells of Cajal
Authors: Zhu Mei Hong , Sung Tae Sik , O'Driscoll Kate , Koh Sang Don , Sanders Kenton M.
Published: January 2015

Interstitial cells of Cajal (ICC) provide pacemaker activity in gastrointestinal muscles that underlies segmental and peristaltic contractions. ICC generate electrical slow waves that are due to large-amplitude inward currents resulting from anoctamin 1 (ANO1) channels, which are Ca2+-activated Cl− channels. We investigated the hypothesis that the Ca2+ responsible for the stochastic activation of ANO1 channels during spontaneous transient inward currents (STICs) and synchronized activation of ANO1 channels during slow wave currents comes from intracellular Ca2+ stores. ICC, obtained from the small intestine of Kit +/copGFP mice, were studied under voltage and current clamp to determine the effects of blocking Ca2+ uptake into stores and release of Ca2+ via inositol 1,4,5-trisphosphate (IP3)-dependent and ryanodine-sensitive channels. Cyclocpiazonic acid, thapsigargin, 2-APB, and xestospongin C inhibited STICs and slow wave currents. Ryanodine and tetracaine also inhibited STICs and slow wave currents. Store-active compounds had no direct effects on ANO1 channels expressed in human embryonic kidney-293 cells. Under current clamp, store-active drugs caused significant depolarization of ICC and reduced spontaneous transient depolarizations (STDs). After block of ryanodine receptors with ryanodine and tetracaine, repolarization did not restore STDs. ANO1 expressed in ICC has limited access to cytoplasmic Ca2+ concentration, suggesting that pacemaker activity depends on Ca2+ dynamics in restricted microdomains. Our data from studies of isolated ICC differ somewhat from studies on intact muscles and suggest that release of Ca2+ from both IP3 and ryanodine receptors is important in generating pacemaker activity in ICC.
Calcium-binding protein, spermatid-specific 1 is expressed in human salivary glands and contains an anti-inflammatory motif
Authors: St. Laurent Chris D. , St. Laurent Katherine E. , Mathison Ron D. , Befus A. Dean
Published: January 2015

Salivary glands are involved in the production and exocrine and endocrine secretion of biologically active proteins, polypeptides, and hormones involved in growth and differentiation, homeostasis, and digestion. We have previously studied the prohormone submandibular rat 1 (SMR1), product of the Vcsa1 gene, which is highly expressed in the testes and salivary glands of rats, and can be cleaved to produce polypeptides with analgesic, erectile function, and anti-inflammatory activities. Humans lack the Vcsa1 gene, but homologous sequences and functions for analgesia and erectile function exist in the human genes Prol1, SMR3a, and SMR3b located on the human chromosomal region close to where Vcsa1 lies in the rat. Here we show the human protein calcium-binding protein spermatid-specific 1 (CABS1) contains a similar sequence to the anti-inflammatory sequence in rat SMR1, thus CABS1 may be another human gene with homologous function to Vcsa1. Using Western blot and PCR, we discovered that the human protein CABS1, previously thought to only be expressed in the testes, is also expressed in the salivary glands and lung, in a tissue-specific manner. Peptides derived from CABS1 were tested in an in vivo mouse model of lipopolysaccharide (LPS)-induced neutrophilia and an ex vivo rat model of antigen-induced intestinal anaphylaxis and significantly reduced both neutrophil accumulation in bronchoalveolar lavage fluid and antigen-induced ileal contractions, respectively. Thus human CABS1 has a peptide motif homologous to the anti-inflammatory peptide sequence of rat SMR1. Whether this similarity of CABS1 extends to the neuroendocrine regulation of the anti-inflammatory activity seen for SMR1 remains to be determined.
IGF-2R-Gαqsignaling and cardiac hypertrophy in the low-birth-weight lamb
Authors: Wang Kimberley C. W. , Tosh Darran N. , Zhang Song , McMillen I. Caroline , Duffield Jaime A. , Brooks Doug A. , Morrison Janna L.
Published: January 2015

The cardiac insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy in a heterotrimeric G protein receptor-coupled manner involving αq (Gαq) or αs (Gαs). We have previously shown increased left ventricular weight and cardiac IGF-2 and IGF-2R gene expression in low-birth-weight (LBW) compared with average-birth-weight (ABW) lambs. Here, we have investigated the cardiac expression of IGF-2 gene variants, the degree of histone acetylation, and the abundance of proteins in the IGF-2R downstream signaling pathway in ABW and LBW lambs. Samples from the left ventricle of ABW and LBW lambs were collected at 21 days of age. There was increased phospho-CaMKII protein with decreased HDAC 4 abundance in the LBW compared with ABW lambs. There was increased GATA 4 and decreased phospho-troponin I abundance in LBW compared with ABW lambs, which are markers of pathological cardiac hypertrophy and impaired or reduced contractility, respectively. There was increased histone acetylation of H3K9 at IGF-2R promoter and IGF-2R intron 2 differentially methylated region in the LBW lamb. In conclusion, histone acetylation of IGF-2R may lead to increased IGF-2R mRNA expression and subsequently mediate Gαqsignaling early in life via CaMKII, resulting in an increased risk of left ventricular hypertrophy and cardiovascular disease in adult life.
A comparison of physiological and transcriptome responses to water deprivation and salt loading in the rat supraoptic nucleus
Authors: Greenwood Michael P. , Mecawi Andre S. , Hoe See Ziau , Mustafa Mohd Rais , Johnson Kory R. , Al-Mahmoud Ghada A. , Elias Lucila L. K. , Paton Julian F. R. , Antunes-Rodrigues Jose , Gainer Harold , Murphy David , Hindmarch Charles C. T.
Published: January 2015

Salt loading (SL) and water deprivation (WD) are experimental challenges that are often used to study the osmotic circuitry of the brain. Central to this circuit is the supraoptic nucleus (SON) of the hypothalamus, which is responsible for the biosynthesis of the hormones, arginine vasopressin (AVP) and oxytocin (OXT), and their transport to terminals that reside in the posterior lobe of the pituitary. On osmotic challenge evoked by a change in blood volume or osmolality, the SON undergoes a function-related plasticity that creates an environment that allows for an appropriate hormone response. Here, we have described the impact of SL and WD compared with euhydrated (EU) controls in terms of drinking and eating behavior, body weight, and recorded physiological data including circulating hormone data and plasma and urine osmolality. We have also used microarrays to profile the transcriptome of the SON following SL and remined data from the SON that describes the transcriptome response to WD. From a list of 2,783 commonly regulated transcripts, we selected 20 genes for validation by qPCR. All of the 9 genes that have already been described as expressed or regulated in the SON by osmotic stimuli were confirmed in our models. Of the 11 novel genes, 5 were successfully validated while 6 were false discoveries.
Attenuated muscle metaboreflex-induced pressor response during postexercise muscle ischemia in renovascular hypertension
Authors: Spranger Marty D. , Kaur Jasdeep , Sala-Mercado Javier A. , Machado Tiago M. , Krishnan Abhinav C. , Alvarez Alberto , O'Leary Donal S.
Published: January 2015

During dynamic exercise, muscle metaboreflex activation (MMA; induced via partial hindlimb ischemia) markedly increases mean arterial pressure (MAP), and MAP is sustained when the ischemia is maintained following the cessation of exercise (postexercise muscle ischemia, PEMI). We previously reported that the sustained pressor response during PEMI in normal individuals is driven by a sustained increase in cardiac output (CO) with no peripheral vasoconstriction. However, we have recently shown that the rise in CO with MMA is significantly blunted in hypertension (HTN). The mechanisms sustaining the pressor response during PEMI in HTN are unknown. In six chronically instrumented canines, hemodynamic responses were observed during rest, mild exercise (3.2 km/h), MMA, and PEMI in the same animals before and after the induction of HTN [Goldblatt two kidney, one clip (2K1C)]. In controls, MAP, CO and HR increased with MMA (+52 ± 6 mmHg, +2.1 ± 0.3 l/min, and +37 ± 7 beats per minute). After induction of HTN, MAP at rest increased from 97 ± 3 to 130 ± 4 mmHg, and the metaboreflex responses were markedly attenuated (+32 ± 5 mmHg, +0.6 ± 0.2 l/min, and +11 ± 3 bpm). During PEMI in HTN, HR and CO were not sustained, and MAP fell to normal recovery levels. We conclude that the attenuated metaboreflex-induced HR, CO, and MAP responses are not sustained during PEMI in HTN.
Cross-talk between insulin and IGF-1 receptors in the cortical collecting duct principal cells: implication for ENaC-mediated Na+reabsorption
Authors: Ilatovskaya Daria V. , Levchenko Vladislav , Brands Michael W. , Pavlov Tengis S. , Staruschenko Alexander
Published: January 2015

Insulin and IGF-1 are recognized as powerful regulators of the epithelial Na+channel (ENaC) in the aldosterone-sensitive distal nephron. As previously described, these hormones both acutely increase ENaC activity in freshly isolated split open tubules and cultured principal cortical collecting duct cells. The present study was aimed at differentiating the effects of insulin and IGF-1 on Na+transport in immortalized mpkCCDcl4cells and defining their interrelations. We have shown that both insulin and IGF-1 applied basolaterally, but not apically, enhanced transepithelial Na+transport in the mpkCCDcl4cell line with EC50values of 8.8 and 14.5 nM, respectively. Insulin treatment evoked phosphorylation of both insulin and IGF-1 receptors, whereas the effects of IGF-1 were more profound on its own receptor rather than the insulin receptor. AG-1024 and PPP, inhibitors of IGF-1 and insulin receptor tyrosine kinase activity, diminished insulin- and IGF-1-stimulated Na+transport in mpkCCDcl4cells. The effects of insulin and IGF-1 on ENaC-mediated currents were found to be additive, with insulin likely stimulating both IGF-1 and insulin receptors. We hypothesize that insulin activates IGF-1 receptors in addition to its own receptors, making the effects of these hormones interconnected.
Mechanisms of angiotensin II stimulation of NCC are time-dependent in mDCT15 cells
Authors: Ko Benjamin , Mistry Abinash , Hanson Lauren , Mallick Rickta , Hoover Robert S.
Published: January 2015

Angiotensin II (ANG II) increases thiazide-sensitive sodium-chloride cotransporter (NCC) activity both acutely and chronically. ANG II has been implicated as a switch that turns WNK4 from an inhibitor of NCC into an activator of NCC, and ANG II's effect on NCC appears to require WNK4. Chronically, ANG II stimulation of NCC results in an increase in total and phosphorylated NCC, but the role of NCC phosphorylation in acute ANG II actions is unclear. Here, using a mammalian cell model with robust native NCC activity, we corroborate the role that ANG II plays in WNK4 regulation and clarify the role of Ste20-related proline alanine-rich kinase (SPAK)-induced NCC phosphorylation in ANG II action. ANG II was noted to have a biphasic effect on NCC, with a peak increase in NCC activity in the physiologic range of 10−11M ANG II. This effect was apparent as early as 15 min and remained sustained through 120 min. These changes correlated with significant increases in NCC surface protein expression. Knockdown of WNK4 expression sharply attenuated the effect of ANG II. SPAK knockdown did not affect ANG II action at early time points (15 and 30 min), but it did attenuate the response at 60 min. Correspondingly, NCC phosphorylation did not increase at 15 or 30 min, but increased significantly at 60 min. We therefore conclude that within minutes of an increase in ANG II, NCC is rapidly trafficked to the cell surface in a phosphorylation-independent but WNK4-dependent manner. Then, after 60 min, ANG II induces SPAK-dependent phosphorylation of NCC.
Utricular afferents: morphology of peripheral terminals
Authors: Huwe J. A. , Logan G. J. , Williams B. , Rowe M. H. , Peterson E. H.
Published: January 2015

The utricle provides critical information about spatiotemporal properties of head movement. It comprises multiple subdivisions whose functional roles are poorly understood. We previously identified four subdivisions in turtle utricle, based on hair bundle structure and mechanics, otoconial membrane structure and hair bundle coupling, and immunoreactivity to calcium-binding proteins. Here we ask whether these macular subdivisions are innervated by distinctive populations of afferents to help us understand the role each subdivision plays in signaling head movements. We quantified the morphology of 173 afferents and identified six afferent classes, which differ in structure and macular locus. Calyceal and dimorphic afferents innervate one striolar band. Bouton afferents innervate a second striolar band; they have elongated terminals and the thickest processes and axons of all bouton units. Bouton afferents in lateral (LES) and medial (MES) extrastriolae have small-diameter axons but differ in collecting area, bouton number, and hair cell contacts (LES >> MES). A fourth, distinctive population of bouton afferents supplies the juxtastriola. These results, combined with our earlier findings on utricular hair cells and the otoconial membrane, suggest the hypotheses that MES and calyceal afferents encode head movement direction with high spatial resolution and that MES afferents are well suited to signal three-dimensional head orientation and striolar afferents to signal head movement onset.
Redistribution of neural phase coherence reflects establishment of feedforward map in speech motor adaptation
Authors: Sengupta Ranit , Nasir Sazzad M.
Published: January 2015

Despite recent progress in our understanding of sensorimotor integration in speech learning, a comprehensive framework to investigate its neural basis is lacking at behaviorally relevant timescales. Structural and functional imaging studies in humans have helped us identify brain networks that support speech but fail to capture the precise spatiotemporal coordination within the networks that takes place during speech learning. Here we use neuronal oscillations to investigate interactions within speech motor networks in a paradigm of speech motor adaptation under altered feedback with continuous recording of EEG in which subjects adapted to the real-time auditory perturbation of a target vowel sound. As subjects adapted to the task, concurrent changes were observed in the theta-gamma phase coherence during speech planning at several distinct scalp regions that is consistent with the establishment of a feedforward map. In particular, there was an increase in coherence over the central region and a decrease over the fronto-temporal regions, revealing a redistribution of coherence over an interacting network of brain regions that could be a general feature of error-based motor learning in general. Our findings have implications for understanding the neural basis of speech motor learning and could elucidate how transient breakdown of neuronal communication within speech networks relates to speech disorders.
Sinus Venosus Atrial Septal Defect as a Cause of Palpitations and Dyspnea in an Adult: A Diagnostic Imaging Challenge
Authors: Donovan Michael S. , Kassop David , Liotta Robert A. , Hulten Edward A.
Published: January 2015

Sinus venosus atrial septal defects (SV-ASD) have nonspecific clinical presentations and represent a diagnostic imaging challenge. Transthoracic echocardiography (TTE) remains the initial diagnostic imaging modality. However, detection rates have been as low as 12%. Transesophageal echocardiography (TEE) improves diagnostic accuracy though it may not detect commonly associated partial anomalous pulmonary venous return (PAPVR). Cardiac magnetic resonance (CMR) imaging provides a noninvasive, highly sensitive and specific imaging modality of SV-ASD. We describe a case of an adult male with exercise-induced, paroxysmal supraventricular tachycardia who presented with palpitations and dyspnea. Despite nondiagnostic imaging results on TTE, CMR proved to be instrumental in visualizing a hemodynamically significant SV-ASD with PAPVR that ultimately led to surgical correction.
Severe IgG4-Related Disease in a Young Child: A Diagnosis Challenge
Authors: Corujeira Susana , Ferraz Catarina , Nunes Teresa , Fonseca Elsa , Vaz Luísa Guedes
Published: January 2015

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome that can appear with multiple organ involvement, typically with tumor-like swelling, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, and elevated serum IgG4 concentrations. We report the case of a 22-month-old female child with failure to thrive and recurrent respiratory tract infections since 8 months of age. Physical examination was normal except for pulmonary auscultation with bilateral crackles and wheezes. Laboratory tests revealed elevated erythrocyte sedimentation rate, and elevated serum IgG and IgG4 with polyclonal hypergammaglobulinemia. Thoracic CT and MRI showed multiple mediastinal lymphadenopathies and a nodular posterior mediastinal mass in right paratracheal location with bronchial compression. Initial fine needle aspiration biopsy was compatible with reactive lymphadenopathy but after clinical worsening a thoracoscopic partial resection of the mass was performed and tissue biopsy revealed lymphoplasmacytic infiltrate and increased number of IgG4-positive plasma cells and a ratio of IgG4/IgG positive cells above 40%. Glucocorticoids therapy was started with symptomatic improvement, reduction in the size of the mass, and decrease of serum IgG4 levels after 6 weeks. There are very few reports of IgG4-RD in children. Long-term follow-up is necessary to monitor relapses and additional organ involvement.