bluuebunny/crossref_metadata_2025 huggingface dataset:
Do goals lead to outcomes or can it be the other way around?: Causal ordering of mastery goals, metacognitive strategies, and achievement
Authors: King Ronnel B. , McInerney Dennis M.
Published: February 2016

Background

Goal theory research has mostly focused on the unidirectional effects of goals on learning strategies and academic achievement. Reciprocal relationships have mostly been neglected.

Aims

The primary aim of this study was to examine the reciprocal relations and causal ordering of mastery goals, metacognitive strategy use, and academic achievement.

Sample

A total of 8,773 secondary students drawn from three cohorts in Hong Kong participated in the study.

Results

We found that mastery goals and metacognitive strategy use exhibited reciprocal effects. Interestingly, and contrary to previous research, academic achievement was shown to predict mastery goal adoption and metacognitive strategy use but not the other way around. Results of the model were shown to be invariant across students of different genders, year levels, and school bands. Implications for goal theory research are discussed.
The G‐protein biased partial κ opioid receptor agonist 6′‐GNTI blocks hippocampal paroxysmal discharges without inducing aversion
Authors: Zangrandi Luca , Burtscher Johannes , MacKay James P , Colmers William F , Schwarzer Christoph
Published: February 2016

Background and Purpose

With a prevalence of 1–2%, epilepsies belong to the most frequent neurological diseases worldwide. Although antiepileptic drugs are available since several decades, the incidence of patients that are refractory to medication is still over 30%. Antiepileptic effects of κ opioid receptor (κ receptor) agonists have been proposed since the 1980s. However, their clinical use was hampered by dysphoric side effects. Recently, G‐protein biased κ receptor agonists were developed, suggesting reduced aversive effects.

Experimental Approach

We investigated the effects of the κ receptor agonist U‐50488H and the G‐protein biased partial κ receptor agonist 6′‐GNTI in models of acute seizures and drug‐resistant temporal lobe epilepsy and in the conditioned place avoidance (CPA) test. Moreover, we performed slice electrophysiology to understand the functional mechanisms of 6′‐GNTI.

Key Results

As previously shown for U‐50488H, 6′‐GNTI markedly increased the threshold for pentylenetetrazole‐induced seizures. All treated mice displayed reduced paroxysmal activity in response to U‐50488H (20 mg·kg−1) or 6′‐GNTI (10–30 nmoles) treatment in the mouse model of intra‐hippocampal injection of kainic acid. Single cell recordings on hippocampal pyramidal cells revealed enhanced inhibitory signalling as potential mechanisms causing the reduction of paroxysmal activity. Effects of 6′‐GNTI were blocked in both seizure models by the κ receptor antagonist 5′‐GNTI. Moreover, 6′‐GNTI did not induce CPA, a measure of aversive effects, while U‐50488H did.

Conclusions and Implications

Our data provide the proof of principle that anticonvulsant/antiseizure and aversive effects of κ receptor activation can be pharmacologically separated in vivo.
Oceanic island biogeography through the lens of the general dynamic model: assessment and prospect
Authors: Borregaard Michael K. , Amorim Isabel R. , Borges Paulo A. V. , Cabral Juliano S. , Fernández‐Palacios José M. , Field Richard , Heaney Lawrence R. , Kreft Holger , Matthews Thomas J. , Olesen Jens M. , Price Jonathan , Rigal Francois , Steinbauer Manuel J. , Triantis Konstantinos A. , Valente Luis , Weigelt Patrick , Whittaker Robert J.
Published: February 2016

The general dynamic model of oceanic island biogeography (GDM) has added a new dimension to theoretical island biogeography in recognizing that geological processes are key drivers of the evolutionary processes of diversification and extinction within remote islands. It provides a dynamic and essentially non‐equilibrium framework generating novel predictions for emergent diversity properties of oceanic islands and archipelagos. Its publication in 2008 coincided with, and spurred on, renewed attention to the dynamics of remote islands. We review progress, both in testing theGDM's predictions and in developing and enhancing ecological–evolutionary understanding of oceanic island systems through the lens of theGDM. In particular, we focus on four main themes: (i) macroecological tests using a space‐for‐time rationale; (ii) extensions of theory to islands following different patterns of ontogeny; (iii) the implications ofGDMdynamics for lineage diversification and trait evolution; and (iv) the potential for downscalingGDMdynamics to local‐scale ecological patterns and processes within islands. We also consider the implications of theGDMfor understanding patterns of non‐native species diversity. We demonstrate the vitality of the field of island biogeography by identifying a range of potentially productive lines for future research.
Peer Rejection, Victimization, and Relational Self‐System Processes in Adolescence: Toward a Transactional Model of Stress, Coping, and Developing Sensitivities
Authors: Zimmer‐Gembeck Melanie J.
Published: February 2016

Rejection and victimization by peers are significant stressors in the lives of many teenagers; both are highly salient and associated with developing symptoms of depression and anxiety. Conversely, emotional maladjustment can result in even more rejection and victimization over time. Given that rejection or victimization and emotional maladjustment mutually influence each other over time, researchers have asked why this occurs and how events unfold in adolescents’ lives. In this article, I describe relational self‐system processes, including perceptions of peer relationships, sensitivity to rejection, attributions of cause, perceived control, and coping responses. I conclude with ideas for research and ways to apply the findings.
A randomized controlled clinical trial comparing small buccal dehiscence defects around dental implants treated with guided bone regeneration or left for spontaneous healing
Authors: Jung Ronald E. , Herzog Milan , Wolleb Karin , Ramel Christian F. , Thoma Daniel S. , Hämmerle Christoph H. F.
Published: February 2016

Purpose

The aim of the present randomized controlled clinical study was to test whether small bony dehiscence defects (≤5 mm) left to heal spontaneously result in the same clinical and radiological outcome as defects treated with guided bone regeneration (GBR).

Materials and methods

Twenty‐two patients who received at least one implant with a small bony dehiscence defect were enrolled in the study. If the defect height was ≤5 mm, the site was randomly assigned to either the spontaneous healing (SH) group or the GBR group. In the SH group, the defect was left without any treatment. In the GBR group, the defects around the implants were grafted with deproteinized bovine bone mineral (DBBM) and covered with a native collagen membrane. Clinical and radiographic measurements were performed 6 months after implant placement with a reentry surgery and at the time of crown insertion and the subsequent follow‐up appointments at 3, 6, 12 and 18 months after loading. For statistical analyses, the mixed linear model was applied for the clinical and radiographic measurements observed around the implants. Simple comparisons of the location of the measurements in the two independent groups are performed with the Mann–Whitney U‐test. In addition, the mixed model assumptions were checked.

Results

The implant and crown survival rate 18 months after loading was 100%, revealing no serious biologic or prosthetic complication. The mean changes of the buccal vertical bone height between implant placement and reentry surgery after 6 months revealed a small bone loss of −0.17 ± 1.79 mm (minimum −4 mm and maximum 2.5 mm) for the SH group and a bone gain of 1.79 ± 2.24 mm (minimum of −2.5 mm and maximum of 5 mm) for the GBR group, respectively (P = 0.017). Radiographic measurements demonstrated a slight bone loss of −0.39 ± 0.49 mm for the SH group and a stable bone level of 0.02 ± 0.48 mm for GBR group after 18 months. All peri‐implant soft tissue parameters revealed healthy tissues with no difference between the two groups.

Conclusion

Small bony dehiscence defects left for spontaneous healing demonstrated high implant survival rates with healthy and stable soft tissues. However, they revealed more vertical bone loss at the buccal aspect 6 months after implant insertion and also more marginal bone loss between crown insertion and 18 months after loading compared to sites treated with GBR.
Usefulness of rhinomanometry in the identification and treatment of patients with obstructive sleep apnoea: an algorithm for predicting the relationship between nasal resistance and continuous positive airway pressure. a retrospective study
Authors: Hueto J. , Santaolalla F. , Sanchez‐del‐Rey A. , Martinez‐Ibargüen A.
Published: February 2016

Objectives

We tried to assess the relationship between nasal resistance measured by rhinomanometry and the pressure used in CPAP.

Design

Retrospective medical case series review, January 2004 to December 2014.

Setting

Tertiary care academic medical centre.

Participants

Thirty‐eight patients (m = 56.55 years; male = 90.5%) with CPAP settings ≤8 and 39 patients (m = 57.49 years; male = 74.9%) with pressure settings ≥12.

Main outcome measures

Study variables were BMI, neck circumference, Epworth Sleepiness Scale score, nasopharyngeal examination and computerised anterior active rhinomanometry, sitting and supine, in basal conditions and after intranasal administration of oxymetazoline (0.05%). Nocturnal polysomnography was performed to calculate the apnoea–hypopnoea index without and with CPAP to analyse the effectiveness of the treatment.

Results

BMI and resistance in supine position after vasoconstriction at 150 Pa were useful variables to predict the pressure setting that should be used. We obtained an equation to calculate the probability that a patient requires a pressure >12 cm H2O as a function of their BMI and total nasal airflow at 150 pascal in supine position after vasoconstriction.

Conclusions

Rhinomanometry is useful to predict the impact of structural nasal modifications on the positive pressure to support decision‐making in relation to surgery.
Impact of Bias Magnification on Supply Chain Costs: The Mitigating Role of Forecast Sharing
Authors: Sanders Nada R. , Graman Gregory A.
Published: February 2016

The impact of forecast error magnification on supply chain cost has been well documented. Unlike past studies that measure forecast error in terms of forecast standard deviation, our study extends research to consider the impact of forecast bias, and the complex interaction between these variables. Simulating a two‐stage supply chain using realistic cost data we test the impact of bias magnification comparing two scenarios: one with forecast sharing between retailer and supplier, and one without. We then corroborate findings via survey data. Results show magnification of forecast bias to have a considerably greater impact on supply chain cost than magnification of forecast standard deviation. Particularly damaging is high bias in the presence of high forecast standard deviation. Forecast sharing is found to mitigate the impact of forecast error, however, primarily at higher levels of forecast standard deviation. At low levels of forecast standard deviation the benefits are not significant suggesting that engaging in such mitigation strategies may be less effective when there is little opportunity for improvement in accuracy. Furthermore, forecast sharing is found to be much less effective against high levels of bias. This is an important finding as managers often deliberately bias their forecasts and underscores the importance of exercising caution even with forecast sharing, particularly for forecasts that have inherently large errors. The findings provide a deeper understanding of the impact of forecast errors, suggest limitations of forecast sharing, and offer implications for research and practice alike.
Project Portfolio Selection: A Newsvendor Approach
Authors: Hu Qiaohai (Joice) , Szmerekovsky Joseph
Published: February 2016

We consider the problem of balancing the penalties associated with budgetary slack (being underbudget) and cost overruns in the project portfolio selection problem by addressing randomness in project costs and making individual project budgets decision variables. Setting the budget for a single project is shown to be analogous to the newsvendor problem. For related versions of the project portfolio selection problem we provide optimal and heuristic procedures. Numerical experiments are used to test the procedures and provide managerial guidelines. We show project budgets should be set so that each project in the portfolio has the same probability of running over budget, it is better to have a larger number of projects with less than ideal funding compared to a smaller number of projects with ideal funding, and substantial opportunities to select more projects with a higher expected profit are available if an aggregate portfolio budget is used.
Subclinical Left Ventricular Longitudinal and Radial Systolic Dysfunction in Children and Adolescents with Type 1 Diabetes Mellitus
Authors: Altun Gürkan , Babaoğlu Kadir , Binnetoğlu Köksal , Özsu Elif , Yeşiltepe Mutlu Rahime G. , Hatun Şükrü
Published: February 2016

Introduction: There are few studies of subclinical systolic dysfunctions in children and adolescents with type 1 diabetes mellitus (DM), and so the available data are limited. The aim of this study was to determine early echocardiographic signs of LV systolic dysfunction in children and adolescents with type 1 DM using two‐dimensional speckle tracking echocardiography (2DSTE). Material and Methods: The study included 84 children and adolescents with type 1 DM and 32 sex‐, age‐, and body mass index–matched healthy subjects. The LV functions were assessed using conventional echocardiography, tissue Doppler imaging, and 2DSTE. Results: The results showed LV diastolic dysfunction as reflected by significantly increased A‐wave velocity, decreased E/A ratio, and increased early filling deceleration time in the patients with diabetes (P = 0.02, P = 0.029, and P = 0.04; respectively). Compared with the control group, patients with diabetes showed significantly lower values for longitudinal systolic strain and strain rate in most segments of the LV; for radial strain values of the LV; for lateral circumferential strain and posterior and anterolateral circumferential strain rate of the LV; and for global longitudinal and radial strain of the LV. Global longitudinal and radial strain values of the LV were significantly lower among patients with poor glycemic control than in the control group. Conclusion: In addition to diastolic dysfunction, LV longitudinal and radial function was found to be impaired in asymptomatic children and adolescents with type 1 DM who have normal LV ejection fraction by 2DSTE. Glycemic control may be the main risk factor for alteration of myocardial function.
Blood Parasite Infection Intensity Covaries with Risk‐Taking Personality in Male Carpetan Rock Lizards (Iberolacerta cyreni)
Authors: Horváth Gergely , Martín José , López Pilar , Garamszegi László Zsolt , Bertók Péter , Herczeg Gábor
Published: February 2016

Identifying evolutionary and developmental mechanisms underlying consistent between‐individual differences in behaviour is the main goal in ‘animal personality studies’. Here, we explored whether activity and risk‐taking varied consistently between individuals and correlated to various – potentially fitness linked – male traits in Carpetan rock lizards (Iberolacerta cyreni). Lizards showed significant consistency within both behaviours, implying the presence of activity and risk‐taking personalities. However, there were no correlation between activity and risk‐taking, neither on the between‐ nor on the within‐individual levels, implying the absence of a behavioural syndrome. We found a strong link between the intensity of blood parasite (Haemogregarinidae) infection and risk‐taking: lizards with higher infection intensity took more risk. While we cannot distinguish cause from causative in the parasite intensity – risk‐taking correlation – our results are in line with the asset protection hypothesis predicting that individuals with lower future reproductive value should focus on the current reproductive event and take higher risk.
Anastomosis of the medial digital artery in a mare following traumatic laceration
Authors: Isgren C. M. , Milner P. I.
Published: February 2016

A 7‐year‐old Warmblood mare presented with blood loss from a laceration of the medial digital artery sustained in the field. The mare was initially managed conservatively by pressure bandaging but the bleeding did not stop. After a blood transfusion the mare underwent arterial repair under general anaesthesia and was initially managed in a cast post operatively. Doppler ultrasonography 4 days post operatively confirmed effective blood flow distal to the arterial anastomosis and the mare was discharged from the hospital. At 6 months follow‐up the owner reported that the mare was sound at the trot with an excellent cosmetic outcome of the surgical site.
Mib1 modulates dynamin 2 recruitment via Snx18 to promote Dll1 endocytosis for efficient Notch signaling
Authors: Okano Makoto , Matsuo Hiromi , Nishimura Yuya , Hozumi Katsuto , Yoshioka Saho , Tonoki Ayako , Itoh Motoyuki
Published: February 2016

Notch signaling regulates normal development and tissue homeostasis. Ligand endocytosis plays critical roles in Notch signaling activation. Endocytic proteins such as epsin and dynamin participate in Notch ligand activity by mediating Notch ligand endocytosis. The ubiquitin ligase Mib1 also plays essential roles in Notch signaling via Notch ligand ubiquitination. However, the molecular links between Mib1 and endocytic proteins have not been fully defined. Here, we show that Mib1 is involved in dynamin 2 recruitment to Dll1 and that Snx18, which interacts with dynamin 2, modestly regulates Dll1 endocytosis. Furthermore, the ubiquitin ligase activity of Mib1 is induced by Notch ligand–receptor interactions. Mib1 promotes the interaction between dynamin 2 and Snx18 in an ubiquitin ligase activity‐dependent manner. These results suggest that Mib1 modulates dynamin recruitment by regulating the interaction between Snx18 and dynamin 2, thereby helping to ensure the efficient signaling activity of Notch ligands.
Do Infants Recognize Engagement in Social Interactions? The Case of Face‐to‐Face Conversation
Authors: Gustafsson Erik , Brisson Julie , Mailloux Dominique , Mainville Marc , Beaulieu Christelle , Sirois Sylvain
Published: February 2016

This study explores 12‐month‐olds' understanding of face‐to‐face conversation, a key contextual structure associated with engagement in a social interaction. Using a violation‐of‐expectations paradigm, we habituated infants to a “face‐to‐face” conversation, and in a test phase compared their looking times between “back‐to‐back” (conceptually novel) and “face‐to‐face” (conceptually familiar) conversations, while simultaneously manipulating perceptual familiarity in a 2 × 2 factorial design. We also analyzed dynamic changes in pupil dilation, which are considered a reliable measure of cognitive load that may index processing of social interactions. Infants looked relatively longer at perceptual changes (new speaker positions) but not at conceptual change (back‐to‐back conversation), suggesting that face‐to‐face conversation may not elicit particular expectations, and so may not carry any particular conceptual significance. Moreover, on the first test trial, larger pupil dilation was observed for familiar conditions, suggesting that familiarity with perceptual features could enhance processing of conversations. Thus, this study undermines assertions regarding infants' conceptual understanding of the social signals underlying engagement. Infants may rather recognize such signals through their perceptual familiarity and associated positive feelings. This may then increase their engagement when observing and participating in others' collaborative activities, in turn allowing for the development of knowledge regarding others' intentions.
Needs assessment for master of nursing programmes among Bangladesh nurses
Authors: Lee T.W. , Kim H.S. , Kim S. , Chu S.H. , Kim M.S , Lee S.J. , Lim S. , Jeon Y. , Park H.J. , Anowar M.N. , Begum T.
Published: February 2016

Aim

This study aimed to assess the intent to enrol in a master of nursing programme among Bangladesh nurses, identify preferred programme options and measure the association among intent to enrol in the programme, clinical competency and job satisfaction.

Background

Personal and professional aspects of potential students pursuing graduate education are beneficial in devising educational strategies. However, considering the pressing needs for higher nursing education, there are no masters of nursing programmes in Bangladesh.

Methods

This study used a descriptive correlational design. Nurses working in Bangladesh public sector were recruited to participate in a self‐administered survey (n = 260). The questionnaire consisted of perception of job satisfaction, clinical competency and the need for educational options, including the intent to enrol in a master of nursing programme, preferred specialty area, curriculum content and career goals after graduation. Data were analysed using descriptive statistics and point‐biserial correlation.

Results

Ninety per cent of the respondents reported that they intended to enrol in a master of nursing programme. Intention was significantly correlated with clinical competency but not with job satisfaction. The most preferred specialty areas were nursing management and education. Half of the respondents responded that teaching at nursing schools was a career goal after graduation.

Discussion

The results of the needs assessment for the programme reflected the unique interest and priorities of the current status of Bangladesh.

Conclusions

The results indicate a strong motivation to enrol in a master of nursing programme, confidence in clinical competence and high demand for programme in nursing management and education. These findings should be considered to design the programme in order to meet the interest of Bangladesh nurses.

Implications for nursing and health policy

Educational needs assessments should take precedence to ensure the best possible educational outcome and to produce competent nurses who will contribute in achieving the Millennium Development Goals of Bangladesh.
Implementation of protected mealtimes in the subacute setting: stepped wedge cluster trial protocol
Authors: Porter Judi , Haines Terry , Truby Helen
Published: February 2016

Aim

This protocol paper describes a study that aims to determine if protected mealtimes implementation closes the energy deficit of 1900 kJ between estimated requirements and actual energy intake of hospitalized adults in the subacute setting.

Background

Protected mealtimes, a strategy developed to address the prevalence of malnourished hospitalized adults, aims to minimize unavoidable and unnecessary interruptions at mealtimes. It has been implemented widely with limited high‐quality studies as to its effect.

Design

A pragmatic stepped wedge cluster trial. Primary outcomes are daily energy and protein intake.

Methods

Funding was awarded in October 2014. In this study, protected mealtimes implementation will occur across each cluster (ward) chosen at random. A waiver of consent has been endorsed, enabling all patients to receive the intervention. Patients excluded from outcome evaluation will be those receiving end of life care and patients who are nil by mouth. The selection of patients for outcome evaluation will also occur randomly. Sample size, randomization, statistical analysis and contamination issues consider the reporting guidelines of the CONSORT statement: extension to cluster randomized trials.

Conclusions

The methods selected will ensure that the research is of high quality with conclusions useful and relevant for translation into practice settings. The study does not aim to assess whether the intervention is sustainable beyond the study period, rather it will establish whether the removal of known barriers to intervention uptake enables high fidelity with the intervention. As a result we will have a greater understanding of the nutritional consequences of protected mealtimes in subacute care.
Multiscale partitioning of small mammal β‐diversity provides novel insights into the Quaternary faunal history of Qinghai–Tibetan Plateau and Hengduan Mountains
Authors: Wen Zhixin , Yang Qisen , Quan Qing , Xia Lin , Ge Deyan , Lv Xue
Published: February 2016

Aim

To assess the validity of four hypothesized drivers (Quaternary climate, niche conservatism, contemporary climate, spatial configuration) of small mammal beta diversity in the Qinghai–Tibetan Plateau (QTP) and the Hengduan Mountains (HDM).

Location

QTP and HDM of China.

Methods

We partitioned the beta diversity of small mammals in QTP and HDM into the spatial turnover and nestedness components at the regional (longitudinal/latitudinal zones) and grid (1° × 1°) scales. Regional beta diversity was evaluated by calculating the multiple‐site dissimilarities and the distance‐dissimilarity relationships. We examined the relative effects of geographical distance, environmental difference, habitat diversity, geographical isolation and Quaternary climate stability on the beta diversity patterns.

Results

The overall beta diversity in all longitudinal/latitudinal zones of both regions was primarily driven by spatial turnover, longitudinal nestedness patterns were almost non‐existent in QTP. Turnover was stronger in the latitudinal direction of QTP and in the longitudinal direction of HDM, which corresponded to the general topography of each region. At the grid scale, higher turnover was primarily concentrated in mountainous areas. Turnover was highly correlated with geographical distance and environmental difference in both regions, and geographical isolation was another strong predictor of turnover in HDM. Habitat diversity independently explained most of the variation in nestedness of HDM.

Main conclusions

Spatial turnover is the primary cause of the small mammal beta diversity in QTP and HDM. Three non‐exclusive mechanisms including the historic effect of past glaciation, contemporary climate and spatial configuration of the landscape might act in combination to shape the beta diversity patterns in QTP and HDM, particularly the directional patterns. Our results challenge the prevailing view that the current distribution of QTP fauna is primarily explained by westward post‐glacial recolonization, and support the alternative idea that QTP retained considerable refugia and even centres of origin during the Quaternary glaciations.
A New Combined Parameter to Predict Premature Ventricular Complexes Induced Cardiomyopathy: Impact and Recognition of Epicardial Origin
Authors: HAMON DAVID , BLAYE‐FELICE MARIE SADRON , BRADFIELD JASON S. , CHAACHOUI NAJIA , TUNG RODERICK , ELAYI CLAUDE S. , VASEGHI MARMAR , DHANJAL TARVINDER S. , BOYLE NOEL G. , MAURY PHILIPPE , SHIVKUMAR KALYANAM , LELLOUCHE NICOLAS
Published: February 2016

Predict the Impact of PVC on Myocardial Function

Introduction

Reversible premature ventricular complexes‐induced cardiomyopathy (PVC‐CMP) is a well‐described, multi‐factorial entity. Single predictors, such as PVC burden or QRS duration, may not apply equally to all patients in contemporary unselected populations including patients with structural heart disease (SHD) or with particular origin such as epicardial (EPI) PVC. We sought to evaluate clinical criteria associated with PVC‐CMP notably focusing on the EPI origin impact and ECG recognition and the value of a new composite predictor of PVC‐CMP, the PVC‐CMP‐Index.

Methods and Results

We studied 107 consecutive patients (69 men; mean age = 56 ± 16 years) with frequent PVC (23.1 ± 11.5%) referred for PVC ablation. Thirty‐six patients (33.6%) had an underlying SHD and 25 patients (23.4%) an EPI PVC origin. After a mean follow‐up of 22.7 ± 15.3 months, 72.9% achieved a long‐term successful ablation and 54.2% had PVC‐CMP. PVC‐CMP prevalence was significantly higher in patients with an EPI compared to endocardial PVC focus (84.0% vs. 45.1%, respectively, P < 0.001). EPI PVC origin (OR = 68.7 IC95% [3.5–1363], P = 0.005), as well as SHD (OR = 12.3 IC95% [1.6–92.6], P = 0.015), was independent predictor of PVC‐CMP. While PVC burden (AUC = 0.78) or PVC‐QRS width (AUC = 0.68) independently predicted PVC‐CMP, the PVC‐CMP‐Index (values ≥39) defined as: PVC burden (0–1) × PVC‐QRS width (milliseconds) × a constant C (1.28 for SHD or 2 for ECG suggesting EPI origin based on our ECG 3‐step algorithm), highly correlated with PVC‐CMP (AUC = 0.91, sensitivity = 93%, specificity = 80%).

Conclusion

We developed a new index, which incorporates PVC burden, QRS width, and presence of SHD or suspected EPI origin that best predicted PVC‐CMP.
Renalase attenuates hypertension, renal injury and cardiac remodelling in rats with subtotal nephrectomy
Authors: Yin Jianyong , Lu Zeyuan , Wang Feng , Jiang Zhenzhen , Lu Limin , Miao Naijun , Wang Niansong
Published: February 2016

Chronic kidney disease is associated with higher risk of cardiovascular complication and this interaction can lead to accelerated dysfunction in both organs. Renalase, a kidney‐derived cytokine, not only protects against various renal diseases but also exerts cardio‐protective effects. Here, we investigated the role of renalase in the progression of cardiorenal syndrome (CRS) after subtotal nephrectomy. Sprague–Dawley rats were randomly subjected to sham operation or subtotal (5/6) nephrectomy (STNx). Two weeks after surgery, sham rats were intravenously injected with Hanks' balanced salt solution (sham), and STNx rats were randomly intravenously injected with adenovirus‐β‐gal (STNx+Ad‐β‐gal) or adenovirus‐renalase (STNx+Ad‐renalase) respectively. After 4 weeks of therapy, Ad‐renalase administration significantly restored plasma, kidney and heart renalase expression levels in STNx rats. We noticed that STNx rats receiving Ad‐renalase exhibited reduced proteinuria, glomerular hypertrophy and interstitial fibrosis after renal ablation compared with STNx rats receiving Ad‐β‐gal; these changes were associated with significant decreased expression of genes for fibrosis markers, proinflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components. At the same time, systemic delivery of renalase attenuated hypertension, cardiomyocytes hypertrophy and cardiac interstitial fibrosis; prevented cardiac remodelling through inhibition of pro‐fibrotic genes expression and phosphorylation of extracellular signal‐regulated kinase (ERK)‐1/2. In summary, these results indicate that renalase protects against renal injury and cardiac remodelling after subtotal nephrectomy via inhibiting inflammation, oxidative stress and phosphorylation of ERK‐1/2. Renalase shows potential as a therapeutic target for the prevention and treatment of CRS in patients with chronic kidney disease.
Determinants of Bargaining Satisfaction Across Policy Domains in the European Union Council of Ministers
Authors: Arregui Javier
Published: February 2016

This research is about the extent to which the policy outcomes in the European Union (EU) decision‐making process represent the policy preferences defended by Member States. Few studies have systematically analysed bargaining satisfaction within the Council. This research uses as a measure of bargaining satisfaction the salient weighted distance between a Member State's policy preference and the decision outcome. This is the first analysis to frame EU Member States' satisfaction using the content of the issues and distinguishing among policy domains. The analysis also includes a substantive number of cases from the post‐2004 enlargement. The empirical analysis shows, in contrast to previous work, that the level of variation of fulfilment in the decision‐making within the Council is considerable across policy domains. The main determinants of bargaining satisfaction are related to both structural and agency factors.
Randomized clinical trial of the safety and efficacy of sitagliptin and metformin co‐administered to Chinese patients with type 2 diabetes mellitus
Authors: Ji Linong , Han Ping , Wang Xiaoyue , Liu Jingdong , Zheng Shaoxiong , Jou Ying‐Ming , O'Neill Edward A , Golm Gregory T , Engel Samuel S , Kaufman Keith D , Shankar R Ravi
Published: February 2016

Introduction

The results of a clinical trial to evaluate the efficacy and safety of initial combination therapy with sitagliptin and metformin in Chinese patients with type 2 diabetes and inadequate glycemic control are reported here.

Materials and Methods

This was a multicenter, randomized, double‐blind, placebo‐controlled, parallel group, 24‐week clinical trial carried out in China. Patients (n = 744) with type 2 diabetes and inadequate glycemic control (glycated hemoglobin ≥7.5 and ≤11.0%) who were either drug‐naïve or washed out of previous therapy were randomized in equal ratios to sitagliptin 100 mg once daily (q.d.; S100), metformin 500 mg twice daily (b.i.d.; M1000), metformin 850 mg b.i.d. (M1700), sitagliptin 50 mg b.i.d. plus metformin 500 mg b.i.d. (S100/M1000), sitagliptin 50 mg b.i.d. plus metformin 850 mg b.i.d. (S100/M1700), or placebo.

Results

The mean baseline glycated hemoglobin in randomized patients was 8.7%. Least squares mean changes from baseline in glycated hemoglobin were −0.59% (placebo), −0.99% (S100), −1.29% (M1000), −1.56% (M1700), −1.67% (S100/M1000) and −1.83% (S100/M1700) (P < 0.05 for each active group vs placebo, for S100/M1700 and S100/M1000 vs S100, and for S100/M1000 vs M1000). All treatments were generally well‐tolerated. The overall incidence of hypoglycemia (symptomatic or asymptomatic) was higher in the two co‐administration groups (S100/M1700 and S100/M1000) compared with the placebo. The incidence of symptomatic hypoglycemia was low, and similar, across all treatment groups. The incidences of gastrointestinal adverse events were generally higher in high‐dose metformin groups than in the placebo group.

Conclusions

In Chinese patients with type 2 diabetes, initial combination therapy with sitagliptin and metformin was generally well‐tolerated, and provided improvement in glycemic control.
Estimation of energy expenditure using prediction equations in overweight and obese adults: a systematic review
Authors: Madden A. M. , Mulrooney H. M. , Shah S.
Published: February 2016

Background

Estimates of energy requirements are needed in weight management and are usually determined using prediction equations. The objective of these two systematic reviews was to identify which equations based on simple anthropometric and demographic variables provide the most accurate and precise estimates of (1) resting energy expenditure (REE) and (2) total energy expenditure (TEE) in healthy obese adults.

Methods

Systematic searches for relevant studies in healthy adults with body mass index (BMI) ≥25 kg m−2 and published in English were undertaken using Cinahl, Cochrane Library, OpenGrey, PubMed and Web of Science (completed March 2014). Search terms included metabolism, calorimetry, obesity and prediction equations. Data extraction, study appraisal and synthesis followed guidelines from PRISMA (Preferred Reporting Items for Systematic reviews and Meta‐Analyses).

Results

From 243 REE papers and 254 TEE papers identified, 21 and four studies, respectively, met the inclusion criteria. (1) The most accurate REE predictions varied with BMI subgroup: WHO (weight and height) ≥25 and ≥30 kg m−2; Mifflin 30–39.9 kg m−2; Henry ≥40 kg m−2. The most precise REE predictions were obtained using Mifflin in BMI 30–39.9 and ≥40 kg m−2, where approximately 75% of predictions were within 10% of measured REE. (2) No accurate or precise predictions of TEE were identified.

Conclusions

No single prediction equation provides accurate and precise REE estimates in all obese adults. Mifflin equations are recommended in this population, although errors exceed 10% in 25% of those assessed. There is no evidence to support the use of prediction equations in estimating TEE in obesity.
Electron microscopic time‐lapse visualization of surface pore filtration on particulate matter trapping process
Authors: SANUI RYOKO , HANAMURA KATSUNORI
Published: February 2016

A scanning electron microscope (SEM) was used to dynamically visualize the particulate matter (PM) trapping process on diesel particulate filter (DPF) walls at a micro scale as ‘time‐lapse’ images corresponding to the increase in pressure drop simultaneously measured through the DPF. This visualization and pressure drop measurement led to the conclusion that the PM trapping in surface pores was driven by PM bridging and stacking at constricted areas in porous channels. This caused a drastic increase in the pressure drop during PM accumulation at the beginning of the PM trapping process. The relationship between the porous structure of the DPF and the depth of the surface pore was investigated in terms of the porosity distribution and PM penetration depth near the wall surface with respect to depth. The pressure drop calculated with an assumed surface pore depth showed a good correspondence to the measured pressure drop.
Dual‐specificity phosphatase 26 (DUSP26) stimulates Aβ42 generation by promoting amyloid precursor protein axonal transport during hypoxia
Authors: Jung Sunmin , Nah Jihoon , Han Jonghee , Choi Seon‐Guk , Kim Hyunjoo , Park Jaesang , Pyo Ha‐Kyung , Jung Yong‐Keun
Published: February 2016

Amyloid beta peptide (Aβ) is a pathological hallmark of Alzheimer's disease (AD) and is generated through the sequential cleavage of amyloid precursor protein (APP) by β‐ and γ‐secretases. Hypoxia is a known risk factor for AD and stimulates Aβ generation by γ‐secretase; however, the underlying mechanisms remain unclear. In this study, we showed that dual‐specificity phosphatase 26 (DUSP26) regulates Aβ generation through changes in subcellular localization of the γ‐secretase complex and its substrate C99 under hypoxic conditions. DUSP26 was identified as a novel γ‐secretase regulator from a genome‐wide functional screen using a cDNA expression library. The phosphatase activity of DUSP26 was required for the increase in Aβ42 generation through γ‐secretase, but this regulation did not affect the amount of the γ‐secretase complex. Interestingly, DUSP26 induced the accumulation of C99 in the axons by stimulating anterograde transport of C99‐positive vesicles. Additionally, DUSP26 induced c‐Jun N‐terminal kinase (JNK) activation for APP processing and axonal transport of C99. Under hypoxic conditions, DUSP26 expression levels were elevated together with JNK activation, and treatment with JNK inhibitor SP600125, or the DUSP26 inhibitor NSC‐87877, reduced hypoxia‐induced Aβ generation by diminishing vesicle trafficking of C99 to the axons. Finally, we observed enhanced DUSP26 expression and JNK activation in the hippocampus of AD patients. Our results suggest that DUSP26 mediates hypoxia‐induced Aβ generation through JNK activation, revealing a new regulator of γ‐secretase‐mediated APP processing under hypoxic conditions.

image

We propose the role of phosphatase dual‐specificity phosphatase 26 (DUSP26) in the selective regulation of Aβ42 production in neuronal cells under hypoxic stress. Induction of DUSP26 causes JNK‐dependent shift in the subcellular localization of γ‐secretase and C99 from the cell body to axons for Aβ42 generation. These findings provide a new strategy for developing new therapeutic targets to arrest AD progression.
Anorexia is Associated with Stress‐Dependent Orexigenic Responses to Exogenous Neuropeptide Y
Authors: Yi J. , Delp M. S. , Gilbert E. R. , Siegel P. B. , Cline M. A.
Published: February 2016

Chicken lines that have been divergently selected for either low (LWS) or high (HWS) body weight at 56 days of age for more than 57 generations have different feeding behaviours in response to a range of i.c.v. injected neurotransmitters. The LWS have different severities of anorexia, whereas the HWS become obese. Previously, we demonstrated that LWS chicks did not respond, whereas HWS chicks increased food intake, after central injection of neuropeptide Y (NPY). The present study aimed to determine the molecular mechanisms underlying the loss of orexigenic function of NPY in LWS. Chicks were divided into four groups: stressed LWS and HWS on day of hatch, and control LWS and HWS. The stressor was a combination of food deprivation and cold exposure. On day 5 post‐hatch, each chick received an i.c.v. injection of vehicle or 0.2 nmol of NPY. Only the LWS stressed group did not increase food intake in response to i.c.v. NPY. Hypothalamic mRNA abundance of appetite‐associated factors was measured at 1 h post‐injection. Interactions of genetic line, stress and NPY treatment were observed for the mRNA abundance of agouti‐related peptide (AgRP) and synaptotagmin 1 (SYT1). Intracerebroventricular injection of NPY decreased and increased AgRP and SYT1 mRNA, respectively, in the stressed LWS and increased AgRP mRNA in stressed HWS chicks. Stress was associated with increased NPY, orexin receptor 2, corticotrophin‐releasing factor receptor 1, melanocortin receptor 3 (MC3R) and growth hormone secretagogue receptor expression. In conclusion, the loss of responsiveness to exogenous NPY in stressed LWS chicks may be a result of the decreased and increased hypothalamic expression of AgRP and MC3R, respectively. This may induce an intensification of anorexigenic melanocortin signalling pathways in LWS chicks that block the orexigenic effect of exogenous NPY. These results provide insights onto the anorexic condition across species, and especially for forms of inducible anorexia such as human anorexia nervosa.
In ovo testosterone treatment reduces long‐term survival of female pigeons: a preliminary analysis after nine years of monitoring
Authors: Matson K. D. , Riedstra B. , Tieleman B. I.
Published: February 2016

Early exposure to steroid hormones, as in the case of an avian embryo exposed yolk testosterone, can impact the biology of an individual in different ways over the course of its life. While many early‐life effects of yolk testosterone have been documented, later‐life effects remain poorly studied. We followed a cohort of twenty captive pigeons hatched in 2005. Half of these birds came from eggs with experimentally increased concentrations of testosterone; half came from control eggs. Preliminary results suggest non‐random mortality during the birds’ first nine years of life. Hitherto, all males have survived, and control females have survived better than testosterone‐treated ones. Despite inherent challenges, studies of later‐life consequences of early‐life exposure in longer‐lived species can offer new perspectives that are precluded by studies of immediate outcomes or shorter‐lived species.
Potential market size and impact of hepatitis C treatment in low‐ and middle‐income countries
Authors: Woode M. E. , Abu‐Zaineh M. , Perriëns J. , Renaud F. , Wiktor S. , Moatti J.‐P.
Published: February 2016

The introduction of direct‐acting antiviral agents (DAAs) has made hepatitis C infection curable in the vast majority of cases and the elimination of the infection possible. Although initially too costly for large‐scale use, recent reductions in DAA prices in some low‐ and middle‐income countries (LaMICs) has improved the prospect of many people having access to these drugs/medications in the future. This article assesses the pricing and financing conditions under which the uptake of DAAs can increase to the point where the elimination of the disease in LaMICs is feasible. A Markov simulation model is used to study the dynamics of the infection with the introduction of treatment over a 10‐year period. The impact on HCV‐related mortality and HCV incidence is assessed under different financing scenarios assuming that the cost of the drugs is completely paid for out‐of‐pocket or reduced through either subsidy or drug price decreases. It is also assessed under different diagnostic and service delivery capacity scenarios separately for low‐income (LIC), lower‐middle‐income (LMIC) and upper‐middle‐income countries (UMIC). Monte Carlo simulations are used for sensitivity analyses. At a price of US$ 1680 per 12‐week treatment duration (based on negotiated Egyptian prices for an all oral two‐DAA regimen), most of the people infected in LICs and LMICs would have limited access to treatment without subsidy or significant drug price decreases. However, people in UMICs would be able to access it even in the absence of a subsidy. For HCV treatment to have a significant impact on mortality and incidence, a significant scaling‐up of diagnostic and service delivery capacity for HCV infection is needed.
Safety and efficacy of sofosbuvir‐containing regimens in hepatitis C‐infected patients with impaired renal function
Authors: Saxena Varun , Koraishy Farrukh M. , Sise Meghan E. , Lim Joseph K. , Schmidt Monica , Chung Raymond T. , Liapakis Annmarie , Nelson David R. , Fried Michael W. , Terrault Norah A. ,   HCV‐TARGET
Published: February 2016

Background & Aims

Renal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF‐containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR).

Methods

HCV‐TARGET database is a multicentre, longitudinal ‘real‐world’ treatment cohort.

Results

A total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4–6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m2. Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post‐transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400–1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82–83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV‐free regimens. Patients with baseline eGFR≤30 and eGFR 31–45 had similar frequencies of efficacy and safety outcomes.

Conclusions

Sustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m2) treated with SOF‐containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF‐containing regimens.