bluuebunny/crossref_metadata_2025 huggingface dataset:
An evaluation of the effectiveness of a ‘Five Ways to Well‐being’ group run with people with learning disabilities
Authors: Mahoney‐Davies Gerwyn , Dixon Clare , Tynan Hannah , Mann Sian
Published: November 2016

Accessible summary

The Five Ways to Well‐being is a document produced by the government which gives advice about things people can do to improve how they feel. These five things are being with people, being active, noticing things around you, to keep learning and giving to others.

We taught a group of adults with learning disabilities how to do these five things. We had ten sessions which lasted 2 h each.

We did not find that people felt better after the ten sessions, but we did find that they noticed more things around them which may help improve their well‐being. People found the group useful.

Background: The ‘Five Ways to Well‐being’ document presents five ways in which people in the general population may be able to improve their well‐being. This study evaluates the use of a ‘Five Ways to Well‐being’ group in a population of people with learning disabilities.

Materials and Methods: Twelve participants who attend a day support service engaged in a ten‐week group programme based on the Five Ways to Well‐being. Scores on the Rosenberg Self‐Esteem Scale and Short Warwick‐Edinburgh Mental Well‐being Scale provided a baseline, and scores at the first, middle and final session were entered into repeated measures analysis of variance or nonparametric equivalents.

Results: Scores suggest there was no difference between baseline and final session on either of these scales (P > 0.05). There was a significant difference between baseline and final session on a clinician‐devised measure of well‐being of the aims of the group (F(2,18) = 3.6, P = 0.049), and this effect is likely to be carried by an increase in the group's use of mindfulness skills. Qualitative feedback suggests that the group was useful and prompted changes in participants' well‐being.

Conclusions: Participants found the group useful, and scores suggest an increase in mindfulness practice, but there is no evidence that running a Five Ways to Well‐being group with people with learning disabilities will improve their well‐being. However, this was not a clinical group of people with mental health concerns, and conclusions cannot be made about the usefulness of the model in this population.
MONEY AND INFLATION IN INDIA: EVIDENCE FROM P‐STAR MODEL
Authors: Paul Sunil , Rather Sartaj Rasool , Ramachandran M.
Published: November 2016

This study uses P‐star model to examine the role of money in explaining inflation in India. In particular, we compare the performance of traditional Phillips curve approach against P‐star model in forecasting inflation. Moreover, the study estimates P‐star model using the alternative measures of money such as simple sum and Divisia M3, to examine the relevance of aggregation theoretic monetary aggregates in explaining inflation. The empirical results indicate that P‐star model with real money gap has an edge over traditional Phillips curve approach in forecasting inflation. More importantly, we found that the P‐star model estimated with Divisia real money gap performs better than its simple sum counterpart. These empirical findings suggest that the changes in real money gap play a crucial role in explaining inflation in India.
Collateral blood flow in different cerebrovascular hierarchy provides endogenous protection in cerebral ischemia
Authors: Luo Chuanming , Liang Fengyin , Ren Huixia , Yao Xiaoli , Liu Qiang , Li Mingyue , Qin Dajiang , Yuan Ti‐Fei , Pei Zhong , Su Huanxing
Published: November 2016

Collateral blood flow as vascular adaptions to focal cerebral ischemia is well recognized. However, few studies directly investigate the dynamics of collateral vessel recruitment in vivo and little is known about the effect of collateral blood flow in different cerebrovascular hierarchy on the neuropathology after focal ischemic stroke. Here, we report that collateral blood flow is critically involved in blood vessel compensations following regional ischemia. We occluded a pial arteriole using femtosecond laser ablating under the intact thinned skull and documented the changes of collateral flow around the surface communication network and between the surface communication network and subsurface microcirculation network using in vivo two photon microscopy imaging. Occlusion of the pial arteriole apparently increased the diameter and collateral blood flow of its leptomeningeal anastomoses, which significantly reduced the cortical infarction size. This result suggests that the collateral flow via surface communicating network connected with leptomeningeal anastomoses could greatly impact on the extent of infarction. We then further occluded the target pial arteriole and all of its leptomeningeal anastomoses. Notably, this type of occlusion led to reversals of blood flow in the penetrating arterioles mainly proximal to the occluded pial arteriole in a direction from the subsurface microcirculation network to surface arterioles. Interesting, the cell death in the area of ischemic penumbra was accelerated when we performed occlusion to cease the reversed blood flow in those penetrating arterioles, suggesting that the collateral blood flow from subsurface microcirculation network exerts protective roles in delaying cell death in the ischemic penumbra. In conclusion, we provide the first experimental evidence that collateral blood vessels at different cerebrovascular hierarchy are endogenously compensatory mechanisms in brain ischemia.
Antidepressant‐like effects of fenofibrate in mice via the hippocampal brain‐derived neurotrophic factor signalling pathway
Authors: Jiang Bo , Wang Ying‐Jie , Wang Hao , Song Lu , Huang Chao , Zhu Qing , Wu Feng , Zhang Wei
Published: November 2016

Background and Purpose

Depression is a neuropsychiatric disorder accompanied by a decrease in the brain‐derived neurotrophic factor (BDNF) signalling cascade in the hippocampus. Fenofibrate is a selective agonist of PPAR‐α. In this study, we investigated the antidepressant‐like effects of fenofibrate in C57BL/6J mice.

Experimental Approach

The antidepressant‐like effects of fenofibrate were first identified in the forced swim test (FST) and tail suspension test (TST), and then assessed in the chronic social defeat stress (CSDS) model. The changes in the hippocampal BDNF signalling pathway and adult hippocampal neurogenesis after CSDS and fenofibrate treatment were further investigated. A PPAR‐α inhibitor, cannabinoid system inhibitors and BDNF signalling inhibitors were also used to determine the antidepressant mechanisms of fenofibrate.

Key Results

Fenofibrate administration exhibited antidepressant‐like effects in the FST and TST without affecting the locomotor activity of mice. Chronic fenofibrate treatment also prevented the depressive‐like symptoms induced by CSDS. Moreover, fenofibrate restored the CSDS‐induced decrease in the hippocampal BDNF signalling cascade and adult hippocampal neurogenesis. The antidepressant‐like effects of fenofibrate could be blocked by a PPAR‐α inhibitor and BDNF signalling inhibitors.

Conclusions and Implications

Taken together, these results suggest that fenofibrate has antidepressant‐like effects mediated through the promotion of the hippocampal BDNF signalling cascade.
Revisiting the links between bone remodelling and osteocytes: insights from across phyla
Authors: Currey John D. , Dean Mason N. , Shahar Ron
Published: November 2016

We question two major tenets of bone biology: that the primary role of remodelling is to remove damage in the bone (so‐called damage‐driven remodelling) and that osteocytes are the only strain‐sensing orchestrators of this process. These concepts are distilled largely from research on model mammal species, but in fact, there are a number of features of various bones, from mammalian and non‐mammalian species, that do not accord with these ‘rules’. Here, we assemble a variety of examples, ranging from species that lack osteocytes but that still seem capable of remodelling their bones, to species with osteocytic bones that do not remodel, and to instances of inter‐species, inter‐bone and/or intra‐bone variation in bone remodelling that show that this purported repair process is not always where the ‘rules’ tell us it should be. This collection of points argues that our understanding of the advantages, roles and primary drivers of remodelling are inadequate and biased to quite a small phylogenetic cross section of the species that possess bone. We suggest a variety of new directions for bone research that would provide us with a better understanding of bone remodelling, tying together the interests of comparative biologists, palaeontologists and medical researchers.
Edge effects on dung beetle assemblages in an Andean mosaic of forest and coffee plantations
Authors: Villada‐Bedoya Sebastián , Cultid‐Medina Carlos A. , Escobar Federico , Guevara Roger , Zurita Gustavo
Published: November 2016

In landscapes dominated by agriculture, conspicuous edges often occur between landscape elements. However, there is disagreement about the existence and intensity of edge effects, and information about species‐specific responses remains scarce. Studying such edge effects can help elucidate functional landscape connectivity and contribute to agricultural management. We, therefore, assessed whether sun‐grown coffee represents a barrier to dung beetles in an Andean agricultural landscape. We also evaluated whether the response to edge effects differs among species. We found that diversity and abundance tend to decrease from forest to sun‐grown coffee and that there are sharp increases in species turnover at the forest–coffee edge. We detected several different species‐specific responses to the forest–coffee edge, suggesting differences in the mobility of the species (or spillover) and in the degree of penetration that takes place from forest patches to sun‐grown coffee plantations. This study demonstrates that the sun‐grown coffee matrix constitutes a barrier to forest species and suggests that the forest–coffee ecotone is more complex than expected. Our results support the notion that the conservation value of native forest patches in agricultural scenarios depends on the functional connectivity of forest units in the landscape to maximize the opportunities species have to disperse through the agricultural matrix.
Metazoan parasites of African annual killifish (Nothobranchiidae): abundance, diversity, and their environmental correlates
Authors: Nezhybová Veronika , Reichard Martin , Blažek Radim , Ondračková Markéta
Published: November 2016

Estimates of biodiversity and its global patterns are affected by parasite richness and specificity. Despite this, parasite communities are largely neglected in biodiversity estimates, especially in the tropics. We studied the parasites of annual killifish of the genus Nothobranchius that inhabit annually desiccating pools across the African savannah and survive the dry period as developmentally arrested embryos. Their discontinuous, non‐overlapping generations make them a unique organism in which to study natural parasite fauna. We investigated the relationship between global (climate and altitude) and local (pool size, vegetation, host density and diversity, and diversity of potential intermediate hosts) environmental factors and the community structure of killifish parasites. We examined metazoan parasites from 21 populations of four host species (Nothobranchius orthonotus, N. furzeri, N. kadleci, and N. pienaari) across a gradient of aridity in Mozambique. Seventeen parasite taxa were recorded, with trematode larval stages (metacercariae) being the most abundant taxa. The parasites recorded were both allogenic (life cycle includes non‐aquatic host; predominantly trematodes) and autogenic (cycling only in aquatic hosts; nematodes). The parasite abundance was highest in climatic regions with intermediate aridity, while parasite diversity was associated with local environmental characteristics and positively correlated with fish species diversity and the amount of aquatic vegetation. Our results suggest that parasite communities of sympatric Nothobranchius species are similar and dominated by the larval stages of generalist parasites. Therefore, Nothobranchius serve as important intermediate or paratenic hosts of parasites, with piscivorous birds and predatory fish being their most likely definitive hosts.
Barriers to dispersal of rain forest butterflies in tropical agricultural landscapes
Authors: Scriven Sarah A. , Beale Colin M. , Benedick Suzan , Hill Jane K.
Published: November 2016

Fragmentation of natural habitats can be detrimental for species if individuals fail to cross habitat boundaries to reach new locations, thereby reducing functional connectivity. Connectivity is crucial for species shifting their ranges under climate change, making it important to understand factors that might prevent movement through human‐modified landscapes. In tropical regions, rain forests are being fragmented by agricultural expansion, potentially isolating populations of highly diverse forest‐dependent species. The likelihood of crossing habitat boundaries is an important determinant of species dispersal through fragmented landscapes, and so we examined movement across rain forest‐oil palm plantation boundaries on Borneo by using relatively mobile nymphalid butterflies as our model study taxon. We marked 1666 individuals from 65 species, and 19 percent (100/527) of recaptured individuals crossed the boundary. Boundary crossing was relatively frequent in some species, and net movement of individuals was from forest into plantation. However, boundary crossing from forest into plantation was detected in less than 50 percent (12/28) of recaptured species and was dominated by small‐sized butterfly species whose larval host plants occurred within plantations. Thus, while oil palm plantations may be relatively permeable to some species, they may act as barriers to the movement of forest‐dependent species (i.e., species that require rain forest habitat to breed), highlighting the importance of maintaining forest connectivity for conserving rain forest species.
New Directions and Challenges in Preventing Conduct Problems in Early Childhood
Authors: Shaw Daniel S. , Taraban Lindsay E.
Published: November 2016

In this article, we review advances in developing and preventing conduct problems in early childhood and identify challenges. Among the topics we address are expanding the targets of prevention programs beyond improving parenting skills, implementing family‐based interventions during early childhood for families living in impoverished communities, making greater use of community platforms that serve young children at risk for early conduct problems, and incorporating techniques such as motivational interviewing to improve families’ engagement in nontraditional mental health settings.
Maternal Support of Children's Early Numerical Concept Learning Predicts Preschool and First‐Grade Math Achievement
Authors: Casey Beth M. , Lombardi Caitlin M. , Thomson Dana , Nguyen Hoa Nha , Paz Melissa , Theriault Cote A. , Dearing Eric
Published: November 2016

The primary goal in this study was to examine maternal support of numerical concepts at 36 months as predictors of math achievement at 4½ and 6‐7 years. Observational measures of mother–child interactions (n = 140) were used to examine type of support for numerical concepts. Maternal support that involved labeling the quantities of sets of objects was predictive of later child math achievement. This association was significant for preschool (d = .45) and first‐grade math (d = .49), controlling for other forms of numerical support (identifying numerals, one‐to‐one counting) as well as potential confounding factors. The importance of maternal support of labeling set sizes at 36 months is discussed as a precursor to children's eventual understanding of the cardinal principle.
Urinary iodine excretion (UIE) estimated by iodine/creatinine ratio from spot urine in Chinese school‐age children
Authors: Chen Wen , Li Xiang , Guo Xiaohui , Shen Jun , Tan Long , Lin Laixiang , Wu Yalan , Wang Wei , Wang Wenqiang , Bian Jianchao , Zhang Wanqi
Published: November 2016

Objective

To assess the validity of urinary iodine excretion (UIE) estimated by urinary iodine/creatinine ratio (UI/Cr) from spot urines in Chinese school‐age children.

Design

A cross‐sectional survey was performed in which twice‐repeated collections of 24‐h urine, and spot urine samples were obtained within 1 month.

Measurements

Urinary iodine concentration (UIC), urinary creatinine concentration (UCr), urine volume (Uvol) of spot and 24‐h urine samples were measured. Measured 24‐h UIE was calculated from 24‐h UIC multiplied by 24‐h Uvol, while the estimated 24‐h UIE was calculated from spot UI/Cr multiplied by 24‐h urinary creatinine excretion (24‐h UCrE).

Results

No significant difference was observed in 24‐h Uvol between two repeated collections (P = 0·70), while spot UIC, 24‐h UIC, spot UI/Cr and measured 24‐h UIE were significantly different (P < 0·05). The estimated 24‐h UIE was 247 (136–431) μg/day in the first collection, lower than the measured 24‐h UIE of 329 (183–536) μg/day (P < 0·001), while no significant difference was observed (P = 0·30) in the second sampling as the estimated 24‐h UIE was 355 (168–624) μg/day and the measured 24‐h UIE 350 (181–615) μg/day. The spot UIC (r = 0·57, P < 0·001), spot UI/Cr (r = 0·63, P < 0·001) and the estimated 24‐h UIE (r = 0·83, P < 0·001) were strongly correlated with the measured 24‐h UIE in the first collection. Likewise, in the second sampling, spot UIC (r = 0·60, P < 0·001), spot UI/Cr (r = 0·72, P < 0·001) and the estimated 24‐h UIE (r = 0·89, P < 0·001) were also correlated with measured 24‐h UIE. The Bland–Altman results indicated 95% of subjects were expected to locate within the limits of agreement (LOA), but showed an underestimation of the urinary iodine excretion by the estimated 24‐h UIE. In addition, moderate‐to‐good agreement was found for the estimated and measured 24‐h UIE, with kappa values of 0·55 and 0·66.

Conclusions

Estimated 24‐h UIE by UI/Cr ratio from spot urine could represent a valid and reliable alternative for measured 24‐h UIE in estimating iodine excretion in children.
Differential Impairment of Thalamocortical Structural Connectivity in Amyotrophic Lateral Sclerosis
Authors: Zhang Jiu‐Quan , Ji Bing , Zhou Chao‐Yang , Li Long‐Chuan , Li Zhi‐Hao , Hu Xiao‐Ping , Hu Jun
Published: November 2016

Aims

The thalamus is a major relay station that modulates input from many cortical areas and a filter for sensory input and is involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). However, it still remains unclear whether all thalamocortical networks are affected or whether there is selective vulnerability. In this study, we aimed to study the selective vulnerability of different thalamocortical structural connections in ALS and to test the hypothesis of a specific impairment in motor‐related thalamocortical connectivity.

Methods

Diffusion tensor imaging (DTI) tractography was used to identify thalamocortical structural pathways in 38 individuals with ALS and 35 gender/age‐matched control subjects. Thalami of both groups were parcellated into subregions based on local patterns of thalamocortical connectivity. DTI measures of these distinct thalamocortical connections were derived and compared between groups.

Results

The analysis of probabilistic tractography showed that the structural connectivity between bilateral pre/primary motor cortices and associated thalamic subregions was specifically impaired in patients with ALS, while the other thalamocortical connections remained relatively intact. In addition, fractional anisotropy values of the impaired thalamocortical motor pathway were inversely correlated with the disease duration.

Conclusion

Our findings provide direct evidence for selective impairment of the thalamocortical structural connectivity in ALS.
Creating an integrated care model for childhood obesity: a randomized pilot study utilizing telehealth in a community primary care setting
Authors: Fleischman A. , Hourigan S. E. , Lyon H. N. , Landry M. G. , Reynolds J. , Steltz S. K. , Robinson L. , Keating S. , Feldman H. A. , Antonelli R. C. , Ludwig D. S. , Ebbeling C. B.
Published: November 2016

In an integrated care model, involving primary care providers (PCPs) and obesity specialists, telehealth may be useful for overcoming barriers to treating childhood obesity. We conducted a pilot study comparing body mass index (BMI) changes between two arms (i) PCP in‐person clinic visits plus obesity specialist tele‐visits (
PCP visits + specialist tele‐visits) and (ii) PCP in‐person clinic visits only (
PCP visits only), with ongoing tele‐consultation between PCPs and obesity specialists for both arms. Patients (N = 40, 10–17 years, BMI ≥ 95th percentile) were randomized to Group 1 or 2. Both groups had PCP visits every 3 months for 12 months. Using a cross‐over protocol, Group 1 had PCP visits + specialist tele‐visits during the first 6 months and PCP visits only during the second 6 months, and Group 2 followed the opposite sequence. Each of 12 tele‐visits was conducted by a dietitian or psychologist with a patient and parent. Retention rates were 90% at 6 months and 80% at 12 months. BMI (z‐score) decreased more for Group 1 (started with PCP visits + specialist tele‐visits) vs. Group 2 (started with PCP visits only) at 3 months (−0.11 vs. −0.05, P = 0.049) following frequent tele‐visits. At 6 months (primary outcome), BMI was lower than baseline within Group 1 (−0.11, P = 0.0006) but not Group 2 (−0.06, P = 0.08); however, decrease in BMI at 6 months did not differ between groups. After crossover, BMI remained lower than baseline for Group 1 and dropped below baseline for Group 2. An integrated care model utilizing telehealth holds promise for treating children with obesity.
Aligning science and policy to achieve evolutionarily enlightened conservation
Authors: Cook Carly N. , Sgrò Carla M.
Published: November 2016

There is increasing recognition among conservation scientists that long‐term conservation outcomes could be improved through better integration of evolutionary theory into management practices. Despite concerns that the importance of key concepts emerging from evolutionary theory (i.e., evolutionary principles and processes) are not being recognized by managers, there has been little effort to determine the level of integration of evolutionary theory into conservation policy and practice. We assessed conservation policy at 3 scales (international, national, and provincial) on 3 continents to quantify the degree to which key evolutionary concepts, such as genetic diversity and gene flow, are being incorporated into conservation practice. We also evaluated the availability of clear guidance within the applied evolutionary biology literature as to how managers can change their management practices to achieve better conservation outcomes. Despite widespread recognition of the importance of maintaining genetic diversity, conservation policies provide little guidance about how this can be achieved in practice and other relevant evolutionary concepts, such as inbreeding depression, are mentioned rarely. In some cases the poor integration of evolutionary concepts into management reflects a lack of decision‐support tools in the literature. Where these tools are available, such as risk‐assessment frameworks, they are not being adopted by conservation policy makers, suggesting that the availability of a strong evidence base is not the only barrier to evolutionarily enlightened management. We believe there is a clear need for more engagement by evolutionary biologists with policy makers to develop practical guidelines that will help managers make changes to conservation practice. There is also an urgent need for more research to better understand the barriers to and opportunities for incorporating evolutionary theory into conservation practice.
Occurrence and concentrations of isothiazolinones in detergents and cosmetics in Switzerland
Authors: Garcia‐Hidalgo Elena , Sottas Virginie , von Goetz Natalie , Hauri Urs , Bogdal Christian , Hungerbühler Konrad
Published: November 2016

Background

In recent years, the frequency of contact allergy to isothiazolinones has increased alarmingly in Europe, but only limited data are available on concentrations of isothiazolinones in consumer products.

Objectives

To examine the current frequency of isothiazolinones [methylisothiazolinone (MI), methylchloroisothiazolinone (MCI), benzisothiazolinone (BIT), and octylisothiazolinone (OIT)] in a wide array of detergents and cosmetics relevant for the Swiss population.

Methods

By means of a market survey, the occurrence of isothiazolinones was investigated in 1948 consumer products. Of these, 88 products were analysed by liquid chromatography–high‐resolution mass spectrometry after ultrasonic extraction.

Results

Only 7.6% of all cosmetics contained isothiazolinones, but the prevalence in detergents was much higher (42.9%). The measured concentration ranges in detergents were 4.3–10, 3.5–279, 3.8–186 and 7.9 ppm (one product only) for MI, MCI, BIT, and OIT, respectively. For cosmetics, these were 1.3–133 and 4.8 ppm (one product only) for MI and MCI, respectively.

Conclusions

Our study has shown that high concentrations of isothiazolinones (including MI) can be found in a large variety of products, in particular in detergents. Therefore, the safe use of these preservatives should be re‐evaluated by including detergents in the exposure assessment.
Identification of specific EBUS sonographic characteristics for predicting benign mediastinal lymph nodes
Authors: Ayub Irfan Ismail , Mohan Anant , Madan Karan , Hadda Vijay , Jain Deepali , Khilnani G. C. , Guleria Randeep
Published: November 2016

Objective

Reliable differentiation of benign from malignant mediastinal lymphadenopathy is important, especially in countries with a high tuberculosis burden. We hypothesized that specific sonographic features on endobronchial ultrasonography (EBUS) may differentiate benign from malignant nodes. In this study, the sonographic features of non‐malignant and malignant nodes were compared.

Methods

This was a retrospective analysis of patients with intrathoracic lymphadenopathy who underwent EBUS‐guided transbronchial needle aspiration (TBNA). Sonographic features such as nodal size, margin (distinct or indistinct), echogenicity (heterogeneous or homogeneous), and presence or absence of calcification, a central hilar structure, coagulation necrosis sign, and nodal conglomeration were recorded and compared in the 2 groups.

Results

During the study period, a diagnosis of tuberculosis (n = 71), sarcoidosis (n = 63), and malignancy (n = 36) was made in 170 patients by EBUS‐TBNA. A total of 312 lymph node stations were examined. Presence of central hilar structure (15.6% versus 4%, P = .03) and the presence of nodal conglomeration (27.5% versus 8%, P < .01) were significantly higher in benign nodes. Further, logistic regression analysis revealed that the presence of well‐defined nodal margins, the presence of central hilar structure, and the presence of conglomeration of lymph nodes were independent predictive factors for the diagnosis of benign mediastinal lymphadenopathy.

Conclusion

Sonographic features of well‐defined margins, presence of central hilar structure, and presence of nodal conglomeration in the lymph nodes on EBUS are predictive of benign disease.
Visceral fat is strongly associated with post‐transplant diabetes mellitus and glucose metabolism 1 year after kidney transplantation
Authors: von Düring Marit Elizabeth , Jenssen Trond , Bollerslev Jens , Åsberg Anders , Godang Kristin , Hartmann Anders
Published: November 2016

Body composition after kidney transplantation is linked to glucose metabolism, and impaired glucose metabolism is associated with increased risk of cardiovascular events and death. One year after transplantation, we examined 150 patients for post‐transplant diabetes performing oral glucose tolerance tests and body composition measurements including visceral adipose tissue (VAT) content from dual‐energy X‐ray absorptiometry scans. We found that glucose metabolism was generally improved over the first year post‐transplant, and that the levels of VAT and percentage VAT of total body fat mass (VAT%totBFM) were lowest in those with normal glucose tolerance and highest in those with post‐transplant diabetes mellitus. In a multivariable linear regression analysis, 87.4% of the variability in fasting glucose concentration was explained by insulin resistance (P<.001, HOMA‐IR index), beta cell function (P<.001, HOMA‐beta), VAT%totBFM (P=.007), and body mass index (BMI; P=.015; total model P<.001), while insulin resistance (P<.001) and beta cell function (P<.001) explained 31.9% of the variability in 2‐hour glucose concentration in a multivariable model (total model P<.001). VAT was associated with glucose metabolism to a larger degree than BMI. In conclusion, VAT is associated with hyperglycemia one year after kidney transplantation, and insulin resistance and beta cell function estimates are the most robust markers of glucose metabolism.
Cost and clinical outcome of islet transplantation in Norway 2010‐2015
Authors: Schive Simen W. , Foss Aksel , Sahraoui Afaf , Kloster‐Jensen Kristine , Hafsahl Geir , Kvalheim Gunnar , Lundgren Torbjørn , von Zur‐Mühlen Bengt , Felldin Marie , Rafael Ehab , Lempinen Marko , Korsgren Olle , Jenssen Trond G. , Mishra Vinod , Scholz Hanne
Published: November 2016

Islet transplantation is a minimally invasive β‐cell replacement strategy. Islet transplantation is a reimbursed treatment in Norway. Here, we summarize the cost and clinical outcome of 31 islet transplantations performed at Oslo University Hospital (OUS) from January 2010 to June 2015. Patients were retrospectively divided into three groups. Thirteen patients received either one or two islet transplantation alone (ITA), while five patients received islet transplantation after previous solid organ transplantation. For the group receiving 2 ITA, Kaplan‐Meier estimates show an insulin independence of 20% more than 4 years after their last transplantation. An estimated 70% maintain at least partial graft function, defined as fasting C‐peptide >0.1 nmol L−1, and 47% maintain a HbA1c below 6.5% or 2 percent points lower than before ITA. For all groups combined, we estimate that 44% of the patients have a 50% reduction in insulin requirement 4 years after the initial islet transplantation. The average cost for an islet transplantation procedure was 347 297±60 588 NOK, or 35 424±6182 EUR, of which isolation expenses represent 34%. We hereby add to the common pool of growing experience with islet transplantation and also describe the cost of the treatment at our center.
Impact of insurance status on heart transplant wait‐list mortality for patients with left ventricular assist devices
Authors: Emani Sitaramesh , Tumin Dmitry , Foraker Randi E. , Hayes Don , Smith Sakima A.
Published: November 2016

Objectives

To test the hypotheses that receipt of Medicaid or Medicare (versus private insurance or self‐pay) and low socioeconomic status (SES) leads to increased mortality and lower chances of transplantation among heart transplant (HTx) candidates with bridge to transplant left ventricular assist devices (BTT LVADs).

Background

Survival while awaiting HTx has improved with the use of BTT LVADs. However, it is unknown whether benefits extend uniformly across patient groups based on insurance status.

Methods

Data from the United Network of Organ Sharing (UNOS) registry between 2006 and 2015 were examined for first‐time HTx candidates ≥18 and <65 years who had LVAD support while wait‐listed. Multivariable survival analysis was conducted on competing outcomes of mortality and time to transplant stratified by insurance source at the time of listing. Additional covariates included demographic information and SES.

Results

A total of 4626 patients met inclusion criteria, with 3353 being used for multivariable analysis. A majority of patients (68%) underwent HTx during the study period. BTT LVAD wait‐list mortality was found to be greater among Medicaid beneficiaries vs. private insurance (SHR 1.57, P<.05) and did not diminish with the inclusion of neighborhood SES. Transplantation as an outcome demonstrated no difference by insurance status.

Conclusion

Medicaid insurance status is associated with worse survival on the HTx wait‐list among patients with BTT LVADs, although access to transplant was not different among insurance groups. The disparity is not reflective of SES in general and therefore points to other barriers inherent to Medicaid beneficiaries.
Centralized versus Decentralized Competition for Price and Lead‐Time Sensitive Demand
Authors: Pekgün Pelin , Griffin Paul M. , Keskinocak Pınar
Published: November 2016

We study two firms that compete on price and lead‐time decisions in a common market. We explore the impact of decentralizing these decisions, as made by the marketing and production departments, respectively, with either marketing or production as the leader. We compare scenarios in which none, one, or both of the firms are decentralized to see whether decentralization can be the equilibrium strategy. We find that under intense price competition, with intensity characterized by the underlying parameters of market demand, firms may suffer from a decentralized structure, particularly under high flexibility induced by high capacity, where revenue‐based sales incentives motivate sales/marketing to make aggressive price cuts that often erode profit margins. In contrast, under intense lead‐time competition, a decentralized strategy with marketing as the leader can not only result in significantly higher profits, but also be the equilibrium strategy. Moreover, decentralization may no longer lead to lower prices or longer lead‐times if the production department chooses capacity along with lead‐time.
GLUT1 deficiency: progress in unraveling its genetic basis
Authors: Van Karnebeek Clara D M
Published: November 2016

This commentry is on the original article by Liu et al. on pages 1295–1302 of this issue.
Towards a better understanding of fatigue experienced by adults with cerebral palsy
Authors: Morgan Prue
Published: November 2016

This commentary is on the original article by McPhee et al. on pages 367–373 of this issue.
Quantitative echocardiographic measures in the assessment of single ventricle function post‐Fontan: Incorporation into routine clinical practice
Authors: Rios Rodrigo , Ginde Salil , Saudek David , Loomba Rohit S. , Stelter Jessica , Frommelt Peter
Published: November 2016

Background

Quantitative echocardiographic measurements of single ventricular (SV) function have not been incorporated into routine clinical practice.

Methods

A clinical protocol, which included quantitative measurements of SV deformation (global circumferential and longitudinal strain and strain rate), standard deviation of time to peak systolic strain, myocardial performance index (MPI), dP/dT from an atrioventricular valve regurgitant jet, and superior mesenteric artery resistance index, was instituted for all patients with a history of Fontan procedure undergoing echocardiography. All measures were performed real time during clinically indicated studies and were included in clinical reports.

Results

A total of 100 consecutive patients (mean age = 11.95±6.8 years, range 17 months–31.3 years) completed the protocol between September 1, 2014 to April 29, 2015. Deformation measures were completed in 100% of the studies, MPI in 93%, dP/dT in 55%, and superior mesenteric artery Doppler in 82%. The studies were reviewed to assess for efficiency in completing the protocol. The average time for image acquisition was 27.4±8.8 (range 10–62 minutes). The average time to perform deformation measures was 10.8±5.5 minutes (range 5‐35 minutes) and time from beginning of imaging to report completion was 53.4±13.7 minutes (range 27–107 minutes). There was excellent inter‐observer reliability when deformation indices were blindly repeated. Patients with a single left ventricle had significantly higher circumferential strain and strain rate, longitudinal strain and strain rate, and dP/dT compared to a single right ventricle. There were no differences in quantitative indices of ventricular function between patients <10 vs. >10 years post‐Fontan.

Conclusion

Advanced quantitative assessment of SV function post‐Fontan can be consistently and efficiently performed real time during clinically indicated echocardiograms with excellent reliability.
Antibiotic resistance in healthcare‐related and nosocomial spontaneous bacterial peritonitis
Authors: Lutz Philipp , Nischalke Hans Dieter , Krämer Benjamin , Goeser Felix , Kaczmarek Dominik J. , Schlabe Stefan , Parcina Marijo , Nattermann Jacob , Hoerauf Achim , Strassburg Christian P. , Spengler Ulrich
Published: November 2016

Background

Spontaneous bacterial peritonitis (SBP) can be life threatening in patients with liver cirrhosis. In contrast to community‐acquired SBP, no standard treatment has been established for healthcare‐related and nosocomial SBP.

Materials and methods

We prospectively collected healthcare‐related and nosocomial SBP cases from March 2012 till February 2016 at the Department of Internal Medicine I of the University of Bonn and analysed the prevalence of antibiotic resistance among the isolated bacteria. SBP was diagnosed according to international guidelines. Ciprofloxacin, ceftriaxone and meropenem were used as reference substance for resistance to quinolones, third‐generation cephalosporins and carbapenems, respectively.

Results

Ninety‐two SBP episodes in 86 patients were identified: 63 episodes (69%) were nosocomial. Escherichia coli, Klebsiella species, enterococci and streptococci were most frequently isolated. Frequencies of these microorganisms were comparable for healthcare‐related and nosocomial SBP (14% vs. 11%, 14% vs. 8%, 14% vs. 5% and 10% vs. 6%, respectively). In general, antibiotic resistance was higher in isolates from nosocomial than from healthcare‐related SBP (50% vs. 18% for quinolones, 30% vs. 11% for piperacillin–tazobactam; P > 0·05), but comparable concerning third‐generation cephalosporins (30% vs. 33%). All microorganisms were sensitive to carbapenems apart from nosocomial infections with Enterococcus faecium (n = 3) and Candida albicans (n = 1) due to intrinsic resistance or lack of microbiological efficacy, respectively. No multidrug‐resistant microorganisms were detected. Resistance to initial antibiotic treatment affected 30‐day survival negatively (18% vs. 68%; P = 0·002).

Conclusion

Resistance to initial antibiotic treatment was associated with increased mortality. With resistance to cephalosporins being frequent, piperacillin–tazobactam or carbapenems might be preferred as treatment of SBP.
Association between complete response and outcomes in transplant‐eligible myeloma patients in the era of novel agents
Authors: van de Velde Helgi , Londhe Anil , Ataman Ozlem , Johns Helen L. , Hill Stephen , Landers Emma , Berlin Jesse A.
Published: November 2016

Objectives

Achieving complete response (CR) has been linked to improved progression‐free (PFS) and overall (OS) survival in myeloma. A meta‐analysis was conducted to investigate whether this holds true in the era of novel agents (bortezomib, lenalidomide, thalidomide).

Methods

A total of 24 studies in newly diagnosed patients undergoing autologous stem cell transplantation (ASCT) that reported associations between responses and long‐term outcomes (PFS/OS rates post‐ASCT by response, or hazard ratios with 95% confidence intervals from Cox models) were identified and analyzed.

Results

Achievement of CR vs. <CR post‐ASCT reduced risk of progression/death by 38% [risk ratio (RR): 0.62, P < 0.0001]; risk of death was 41% lower (RR: 0.59, P < 0.0001). Subgroup meta‐analyses showed significant PFS risk reduction with CR post‐ASCT with novel (RR: 0.32, P < 0.006) and non‐novel (RR: 0.72, P < 0.0001) agents, and corresponding OS risk reduction with novel (RR: 0.33, P = 0.0013) and non‐novel (RR: 0.64, P < 0.0001) agents. Risk reduction was greater with novel vs. non‐novel agents (PFS: P = 0.047; OS: P = 0.058).

Conclusions

Achieving CR during first‐line therapy remains important in the novel‐agent era; magnitude of association between achieving CR and outcomes appears higher for CR obtained using novel vs. non‐novel agents.
Modelling idiopathic Parkinson disease as a complex illness can inform incidence rate in healthy adults: the PREDIGT score
Authors: Schlossmacher Michael G. , Tomlinson Julianna J. , Santos Goncalo , Shutinoski Bojan , Brown Earl G. , Manuel Douglas , Mestre Tiago
Published: November 2016

Fifty‐five years after the concept of dopamine replacement therapy was introduced, Parkinson disease (PD) remains an incurable neurological disorder. To date, no disease‐modifying therapeutic has been approved. The inability to predict PD incidence risk in healthy adults is seen as a limitation in drug development, because by the time of clinical diagnosis ≥ 60% of dopamine neurons have been lost. We have designed an incidence prediction model founded on the concept that the pathogenesis of PD is similar to that of many disorders observed in ageing humans, i.e. a complex, multifactorial disease. Our model considers five factors to determine cumulative incidence rates for PD in healthy adults: (i) DNA variants that alter susceptibility (D), e.g. carrying a LRRK2 or GBA risk allele; (ii) Exposure history to select environmental factors including xenobiotics (E); (iii) Gene–environment interactions that initiate pathological tissue responses (I), e.g. a rise in ROS levels, misprocessing of amyloidogenic proteins (foremost, α‐synuclein) and dysregulated inflammation; (iv) sex (or gender; G); and importantly, (v) time (T) encompassing ageing‐related changes, latency of illness and propagation of disease. We propose that cumulative incidence rates for PD (PR) can be calculated in healthy adults, using the formula: PR (%) = (E + D + I) × G × T. Here, we demonstrate six case scenarios leading to young‐onset parkinsonism (n = 3) and late‐onset PD (n = 3). Further development and validation of this prediction model and its scoring system promise to improve subject recruitment in future intervention trials. Such efforts will be aimed at disease prevention through targeted selection of healthy individuals with a higher prediction score for developing PD in the future and at disease modification in subjects that already manifest prodromal signs.
Amygdala mu‐opioid receptors mediate the motivating influence of cue‐triggered reward expectations
Authors: Lichtenberg Nina T. , Wassum Kate M.
Published: November 2016

Environmental reward‐predictive stimuli can retrieve from memory a specific reward expectation that allows them to motivate action and guide choice. This process requires the basolateral amygdala (BLA), but little is known about the signaling systems necessary within this structure. Here we examined the role of the neuromodulatory opioid receptor system in the BLA in such cue‐directed action using the outcome‐specific Pavlovian‐to‐instrumental transfer (PIT) test in rats. Inactivation of BLA mu‐, but not delta‐opioid receptors was found to dose‐dependently attenuate the ability of a reward‐predictive cue to selectively invigorate the performance of actions directed at the same unique predicted reward (i.e. to express outcome‐specific PIT). BLA mu‐opioid receptor inactivation did not affect the ability of a reward itself to similarly motivate action (outcome‐specific reinstatement), suggesting a more selective role for the BLA mu‐opioid receptor in the motivating influence of currently unobservable rewarding events. These data reveal a new role for BLA mu‐opioid receptor activation in the cued recall of precise reward memories and the use of this information to motivate specific action plans.
Steady‐state VEP responses to uncomfortable stimuli
Authors: O'Hare Louise
Published: November 2016

Periodic stimuli, such as op‐art, can evoke a range of aversive sensations included in the term visual discomfort. Illusory motion effects are elicited by fixational eye movements, but the cortex might also contribute to effects of discomfort. To investigate this possibility, steady‐state visually evoked responses (SSVEPs) to contrast‐matched op‐art‐based stimuli were measured at the same time as discomfort judgements. On average, discomfort reduced with increasing spatial frequency of the pattern. In contrast, the peak amplitude of the SSVEP response was around the midrange spatial frequencies. Like the discomfort judgements, SSVEP responses to the highest spatial frequencies were lowest amplitude, but the relationship breaks down between discomfort and SSVEP for the lower spatial frequency stimuli. This was not explicable by gross eye movements as measured using the facial electrodes. There was a weak relationship between the peak SSVEP responses and discomfort judgements for some stimuli, suggesting that discomfort can be explained in part by electrophysiological responses measured at the level of the cortex. However, there is a breakdown of this relationship in the case of lower spatial frequency stimuli, which remains unexplained.
Long‐term monitoring of cardiorespiratory patterns in drug‐resistant epilepsy
Authors: Goldenholz Daniel M. , Kuhn Amanda , Austermuehle Alison , Bachler Martin , Mayer Christopher , Wassertheurer Siegfried , Inati Sara K. , Theodore William H.
Published: November 2016

Objective

Sudden unexplained death in epilepsy (SUDEP) during inpatient electroencephalography (EEG) monitoring has been a rare but potentially preventable event, with associated cardiopulmonary markers. To date, no systematic evaluation of alarm settings for a continuous pulse oximeter (SpO2) has been performed. In addition, evaluation of the interrelationship between the ictal and interictal states for cardiopulmonary measures has not been reported.

Methods

Patients with epilepsy were monitored using video‐EEG, SpO2, and electrocardiography (ECG). Alarm thresholds were tested systematically, balancing the number of false alarms with true seizure detections. Additional cardiopulmonary patterns were explored using automated ECG analysis software.

Results

One hundred ninety‐three seizures (32 generalized) were evaluated from 45 patients (7,104 h recorded). Alarm thresholds of 80–86% SpO2 detected 63–73% of all generalized convulsions and 20–28% of all focal seizures (81–94% of generalized and 25–36% of focal seizures when considering only evaluable data). These same thresholds resulted in 25–146 min between false alarms. The sequential probability of ictal SpO2 revealed a potential common seizure termination pathway of desaturation. A statistical model of corrected QT intervals (QTc), heart rate (HR), and SpO2 revealed close cardiopulmonary coupling ictally. Joint probability maps of QTc and SpO2 demonstrated that many patients had baseline dysfunction in either cardiac, pulmonary, or both domains, and that ictally there was dissociation—some patients exhibited further dysfunction in one or both domains.

Significance

Optimal selection of continuous pulse oximetry thresholds involves a tradeoff between seizure detection accuracy and false alarm frequency. Alarming at 86% for patients that tend to have fewer false alarms and at 80% for those who have more, would likely result in a reasonable tradeoff. The cardiopulmonary findings may lead to SUDEP biomarkers and early seizure termination therapies.