bluuebunny/crossref_metadata_2025 huggingface dataset:
Placing Transport Workers on the Agenda: The Conflicting Logics of Governing Mobility on Bishkek's Marshrutkas
Authors: Rekhviashvili Lela , Sgibnev Wladimir
Published: June 2018

Transport workers are conspicuously absent from both mobilities and urban studies literature. This paper therefore starts out with a double critique. First, transport workers, primarily drivers, are largely disregarded in mobilities and urban transport research. Second, the literature we find on transport workers—mostly based in empirical settings in the global South—remains outside recent and ongoing debates in critical urban transport studies. Providing empirical insights from post‐Soviet Central Asia, this paper strives to close these gaps and delve into the struggles and cleavages that structure informal transport workers’ positions and livelihoods. We argue that the diverse and contradictory logics that govern urban mobility affect the livelihoods and working conditions of informal transport workers, as well as their choices and motivations. These, in turn, significantly shape mobility provision, in terms of urban transport's (lack of) affordability, accessibility, convenience and safety.
Hospital care for viral gastroenteritis in socio‐economic and geographical context in Sweden 2006–2013
Authors: Lind Johannes , Schollin Ask Lina , Juarez Sol , Hjern Anders
Published: June 2018

Aim

We investigated socio‐economic and geographical determinants of hospital care for viral gastroenteritis in young children.

Method

This is a register‐based study in a national birth cohort of 752 078 children 0–5 years of age in Sweden during 2006–2012. Hazard ratios (HR) of time to first admission and first episode of outpatient emergency department (ED) care with a diagnosis of viral gastroenteritis were estimated with Cox regression.

Results

The adjusted HRs for hospital admission with a diagnosis of viral gastroenteritis were increased when the mother was below 25 years at the birth of the child, 1.30 (95% CI: 1.24–1.35), had a short (<=9 years) education, 1.18 (95% CI: 1.12–1.23), a psychiatric disorder, 1.34 (95% CI: 1.30–1.39), and/or when parents were born outside Europe, 1.23 (95% CI: 1.18–1.29). In contrast, the disposable income of the family was only marginally associated with such hospital admissions. The pattern of HRs for outpatient ED hospital care was similar. Hospital care incidences for viral gastroenteritis differed considerably between Swedish counties.

Conclusion

Parental indicators associated with a lower level of health literacy increase the risk for hospital care due to gastroenteritis in young children. Information about oral rehydration should be provided in ways that are accessible to these parents.
Connexins in the control of vasomotor function
Authors: Pogoda K. , Kameritsch P. , Mannell H. , Pohl U.
Published: June 2018

Vascular endothelial cells, as well as smooth muscle cells, show heterogeneity with regard to their receptor expression and reactivity. For the vascular wall to act as a functional unit, the various cells’ responses require integration. Such an integration is not only required for a homogeneous response of the vascular wall, but also for the vasomotor behaviour of consecutive segments of the microvascular arteriolar tree. As flow resistances of individual sections are connected in series, sections require synchronization and coordination to allow effective changes of conductivity and blood flow. A prerequisite for the local coordination of individual vascular cells and different sections of an arteriolar tree is intercellular communication. Connexins are involved in a dual manner in this coordination. (i) By forming gap junctions between cells, they allow an intercellular exchange of signalling molecules and electrical currents. In particular, the spread of electrical currents allows for coordination of cell responses over longer distances. (ii) Connexins are able to interact with other proteins to form signalling complexes. In this way, they can modulate and integrate individual cells' responses also in a channel‐independent manner. This review outlines mechanisms allowing the vascular connexins to exert their coordinating function and to regulate the vasomotor reactions of blood vessels both locally, and in vascular networks. Wherever possible, we focus on the vasomotor behaviour of small vessels and arterioles which are the main vessels determining vascular resistance, blood pressure and local blood flow.
Prospective evaluation of the impact of covert hepatic encephalopathy on quality of life and sleep in cirrhotic patients
Authors: Labenz C. , Baron J. S. , Toenges G. , Schattenberg J. M. , Nagel M. , Sprinzl M. F. , Nguyen‐Tat M. , Zimmermann T. , Huber Y. , Marquardt J. U. , Galle P. R. , Wörns M.‐A.
Published: June 2018

Background

Minimal hepatic encephalopathy (HE) and HE grade 1 (HE1) according to the West Haven criteria have recently been grouped as one entity named—covert HE‐ (CHE). Data regarding the impact of CHE on health‐related quality of life (HRQoL) and sleep quality are controversial.

Aim

First, to determine whether CHE affects HRQoL and sleep quality of cirrhotic patients and second, whether minimal HE (MHE) and HE1 affect HRQoL and sleep quality to a comparable extent.

Methods

A total of 145 consecutive cirrhotic patients were enrolled. HE1 was diagnosed clinically according to the West Haven criteria. Critical flicker frequency and the Psychometric Hepatic Encephalopathy Score were used to detect MHE. Chronic Liver Disease Questionnaire (CLDQ) was used to assess HRQoL and Pittsburgh Sleep Quality Index (PSQI) was applied to assess sleep quality.

Results

Covert HE was detected in 59 (40.7%) patients (MHE: n = 40; HE1: n = 19). Multivariate analysis identified CHE (P < 0.001) and female gender (P = 0.006) as independent predictors of reduced HRQoL (CLDQ total score). CHE (P = 0.021), low haemoglobin (P = 0.024) and female gender (P = 0.003) were identified as independent predictors of poor sleep quality (PSQI total score). Results of CLDQ and PSQI were comparable in patients with HE1 and MHE (CLDQ: 4.6 ± 0.9 vs 4.5 ± 1.2, P = 0.907; PSQI: 11.3 ± 3.8 vs 9.9 ± 5.0, P = 0.3).

Conclusion

Covert HE was associated with impaired HRQoL and sleep quality. MHE and HE1 affected both outcomes to a comparable extent supporting the use of CHE as a clinically useful term for patients with both entities of HE in clinical practice.
The Work of Anthropology Reconsidered: Career Diversity and the Future of Doctoral Education
Authors: Lyon Sarah
Published: June 2018

In recent years, discussion about the training and job placement of PhD students in the humanities and social sciences has increasingly been informed by broader conversations about the crisis in higher education and the persistent decline in the availability of tenure‐track academic jobs. This article analyzes 28 semi‐structured interview transcripts from the Society for Applied Anthropology's Oral History Project to explore how one group of anthropologists experience and value their livelihood pursuits and how diverse career paths impact scholarly identities within broader political economic contexts. Specifically, it explores three central themes: First, rather than viewing nonacademic work as entirely separate from their scholarly pursuits, many of the interviewed anthropologists described a flexible career trajectory shaped through repeated pivots between academic and practicing spheres. Second, the anthropologists identified multiple ways in which their nonacademic work was shaped by their unique anthropological insights and how, in turn, their work as practicing anthropologists enhanced and even deepened their scholarly engagement. Third, the interviewed anthropologists acknowledged the multiple challenges they faced in pursuing work beyond the tenure track. The manuscript ends by considering how we might build on these insights into anthropological career diversity in order to profitably rethink the purpose and form of doctoral education within our discipline.
Medical cannabis: aligning use to evidence‐based medicine approach
Authors: Bar‐Lev Schleider Lihi , Abuhasira Ran , Novack Victor
Published: June 2018

During the past decade we have been witnessing a rise in medical cannabis use, yet the evidence for the safety and efficacy of the various cannabinoid compounds is scarce. The State of Israel has always been at the forefront of clinical and translational research in support of Evidence Based Medicine. With respect to cannabis Israel has created a medical and regulatory environment that enables clinical studies with cannabis which may lead to improved Evidence Based use of these compounds. This opinion paper discusses selected studies into the safety and effects of cannabis derived products.
Use of antipsychotics and risk of breast cancer: a Danish nationwide case–control study
Authors: Pottegård Anton , Lash Timothy L. , Cronin‐Fenton Deirdre , Ahern Thomas P. , Damkier Per
Published: June 2018

Aims

Some antipsychotics increase prolactin levels, which might increase the risk of breast cancer. Existing evidence is conflicting and based on sparse data, especially for the increasingly used second‐generation antipsychotics. We conducted a nationwide case–control study of the association between antipsychotic use and incident breast cancer.

Methods

From the Danish Cancer Registry, we identified women with a first‐time diagnosis of breast cancer 2000–2015 (n = 60 360). For each case, we age‐matched 10 female population controls. Using conditional logistic regression, we calculated odds ratios (ORs) for breast cancer associated with use of antipsychotics. We stratified antipsychotics by first‐ and second‐generation status and by ability to induce elevation of prolactin.

Results

In total, 4951 cases (8.1%) and 47 643 controls (7.9%) had ever used antipsychotics. Long‐term use (≥10 000 mg olanzapine equivalents) was associated with breast cancer, with an adjusted OR of 1.18 [95% confidence interval (CI), 1.06, 1.32]. A weak dose–response pattern was seen, with ORs increasing to 1.27 (95% CI 1.01, 1.59) for ≥50 000 mg olanzapine equivalents. Associations were similar for first‐ and second‐generation antipsychotics (ORs 1.17 vs. 1.11), but also for nonprolactin inducing‐antipsychotics (OR 1.17). Stratifying by oestrogen receptor status, positive associations were seen for oestrogen receptor‐positive cancers (long‐term use: OR 1.29; 95% CI 1.13, 1.47) while no associations were observed for oestrogen receptor‐negative cancers.

Conclusions

Overall, our results do not suggest a clinically important association between antipsychotic use and risk of breast cancer. The importance of drug‐induced prolactin elevation is unclear but may lead to a slightly increased risk of oestrogen receptor‐positive breast cancer.
Effects of cannabidiol plus naltrexone on motivation and ethanol consumption
Authors: Viudez‐Martínez Adrián , García‐Gutiérrez María S , Fraguas‐Sánchez Ana Isabel , Torres‐Suárez Ana Isabel , Manzanares Jorge
Published: June 2018

Background and Purpose

The aim of this study was to explore if the administration of naltrexone together with cannabidiol (CBD) may improve the efficacy in reducing alcohol consumption and motivation rather than any of the drugs given separately.

Experimental Approach

The effects of low doses of naltrexone (0.7 mg·kg−1, p.o.) and/or CBD (20 mg·kg−1·day−1, s.c.) on ethanol consumption and motivation to drink were evaluated in the oral‐ethanol self‐administration paradigm in C57BL/6 mice. Gene expression analyses of the opioid μ receptor (Oprm1) in the nucleus accumbens (NAc), tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and the 5‐HT1A receptor in the dorsal raphe nucleus (DR) were carried out by real‐time PCR. The role of 5‐HT1A receptors in the ethanol reduction induced by the administration of CBD + naltrexone was analysed by using the 5‐HT1A receptor antagonist WAY100635 (0.3 mg·kg−1, i.p.).

Key Results

The administration of CBD + naltrexone significantly reduced motivation and ethanol intake in the oral self‐administration procedure in a greater proportion than the drugs given alone. Only the combination of both drugs significantly reduced Oprm1, TH and 5‐HT1A gene expressions in the NAc, VTA and DR respectively. Interestingly, the administration of WAY100635 significantly blocked the actions of CBD + naltrexone but had no effects by itself.

Conclusion and Implications

The combination of low doses of CBD plus naltrexone were more effective than either CBD or naltrexone alone at reducing ethanol consumption and the motivation to drink. These effects appear to be mediated, at least in part, by 5‐HT1A receptors.
A long‐acting FGF21 alleviates hepatic steatosis and inflammation in a mouse model of non‐alcoholic steatohepatitis partly through an FGF21‐adiponectin‐IL17A pathway
Authors: Bao Lichen , Yin Jun , Gao Wen , Wang Qun , Yao Wenbing , Gao Xiangdong
Published: June 2018

Background and Purpose

Non‐alcoholic steatohepatitis (NASH) is the most severe form of non‐alcoholic fatty liver disease and is a serious public health problem around the world. There are currently no approved treatments for NASH. FGF21 has recently emerged as a promising drug candidate for metabolic diseases. However, the disadvantages of FGF21 as a clinically useful medicine include its short plasma half‐life and poor drug‐like properties. Here, we have explored the effects of PsTag600‐FGF21, an engineered long‐acting FGF21 fusion protein, in mice with NASH and describe some of the underlying mechanisms.

Experimental Approach

A long‐acting FGF21 was prepared by genetic fusion with a 600 residues polypeptide (PsTag600). We used a choline‐deficient high‐fat diet‐induced model of NASH in mice. The effects on body weight, insulin sensitivity, inflammation and levels of hormones and metabolites were studied first. We further investigated whether PsTag600‐FGF21 attenuated inflammation through the Th17‐IL17A axis and the associated mechanisms.

Key Results

PsTag600‐FGF21 dose‐dependently reduced body weight, blood glucose, and insulin and lipid levels and reversed hepatic steatosis. PsTag600‐FGF21 enhanced fatty acid activation and mitochondrial β‐oxidation in the liver. The profound reduction in hepatic inflammation in NASH mice following PsTag600‐FGF21 was associated with inhibition of IL17A expression in Th17 cells. Furthermore, PsTag600‐FGF21 depended on adiponectin to exert its suppression of Th17 cell differentiation and IL17A expression.

Conclusions and Implications

Our data have uncovered some of the mechanisms by which PsTag600‐FGF21 suppresses hepatic inflammation and further suggest that PsTag600‐FGF21 could be an effective approach in NASH treatment.
Quantitative systems pharmacology analysis of drug combination and scaling to humans: the interaction between noradrenaline and vasopressin in vasoconstriction
Authors: Yin Anyue , Yamada Akihiro , Stam Wiro B , van Hasselt Johan G C , van der Graaf Piet H
Published: June 2018

Background and Purpose

Development of combination therapies has received significant interest in recent years. Previously, a two‐receptor one‐transducer (2R‐1T) model was proposed to characterize drug interactions with two receptors that lead to the same phenotypic response through a common transducer pathway. We applied, for the first time, the 2R‐1T model to characterize the interaction of noradrenaline and arginine‐vasopressin on vasoconstriction and performed inter‐species scaling to humans using this mechanism‐based model.

Experimental Approach

Contractile data were obtained from in vitro rat small mesenteric arteries after exposure to single or combined challenges of noradrenaline and arginine‐vasopressin with or without pretreatment with the irreversible α‐adrenoceptor antagonist, phenoxybenzamine. Data were analysed using the 2R‐1T model to characterize the observed exposure–response relationships and drug–drug interaction. The model was then scaled to humans by accounting for differences in receptor density.

Key Results

With receptor affinities set to published values, the 2R‐1T model satisfactorily characterized the interaction between noradrenaline and arginine‐vasopressin in rat small mesenteric arteries (relative standard error ≤20%), as well as the effect of phenoxybenzamine. Furthermore, after scaling the model to human vascular tissue, the model also adequately predicted the interaction between both agents on human renal arteries.

Conclusions and Implications

The 2R‐1T model can be of relevance to quantitatively characterize the interaction between two drugs that interact via different receptors and a common transducer pathway. Its mechanistic properties are valuable for scaling the model across species. This approach is therefore of significant value to rationally optimize novel combination treatments.
Apolipoprotein E favours the blunting by high‐fat diet of prostacyclin receptor activation in the mouse aorta
Authors: Cheng Yanhua , Vanhoutte Paul M , Leung Susan W S
Published: June 2018

Background and Purpose

NO‐mediated, endothelium‐dependent relaxations of isolated arteries are blunted by ageing and high‐fat diets, as well as by apolipoprotein E deletion. The present study was designed to test the hypothesis that apolipoprotein E deletion impairs endothelium‐dependent responses to prostacyclin (IP) receptor activation.

Experimental Approach

Five‐week‐old ApoE+/+ and ApoE−/− mice were fed normal chow or high‐fat diet for 29 weeks. The aortae were isolated for the measurements of isometric tension in Halpern–Mulvany myographs. Levels of proteins were assessed by Western blotting and immunofluorescence, and cyclic nucleotide levels by elisa.

Key Results

The IP receptor agonist, iloprost, induced endothelium‐, NO‐synthase‐ and IP‐dependent relaxations in aortae of young ApoE+/+ mice. High‐fat diet favoured activation of thromboxane receptors by iloprost, causing contraction. Apolipoprotein E was present in aortae of ApoE+/+ mice, especially in endothelium. Its presence was augmented by high‐fat diet. Its deletion potentiated iloprost‐induced relaxations in aortae of young mice and prevented the blunting of this response by high‐fat diet. Levels of cAMP were higher, but those of cGMP were lower in the aorta of ApoE−/− than in ApoE+/+ mice of the same age. The levels of IP receptor protein were not different between ApoE+/+ and ApoE−/− mice.

Conclusions and Implications

Iloprost induced an endothelium‐dependent relaxation in the aorta of young healthy mice which involved both the cGMP and cAMP pathways. This response was blunted by prolonged exposure to a high‐fat diet. Apolipoprotein E deletion potentiated relaxations to IP receptor activation, independently of age and diet.
Intravenous immunoglobulin treatment in multiple sclerosis: A prospective, rater‐blinded analysis of relapse rates during pregnancy and the postnatal period
Authors: Winkelmann Alexander , Rommer Paulus Stefan , Hecker Michael , Zettl Uwe Klaus
Published: June 2018

Background

Multiple sclerosis (MS) affects predominantly young women. Currently available disease‐modifying drugs have neither been approved during pregnancy nor nursing.

Aims

Evaluating the effect of treatment with intravenous immunoglobulin (IVIg) in MS patients with desire to have a baby.

Methods

In all, 70 MS patients were either treated with IVIg before conception, during first trimester of pregnancy and 12 months postnatal (group I, n = 38) or started IVIg after delivery for 12 months (group II, n = 23) or were untreated (group III, n = 9). Relapse rates and disease progression were analyzed.

Results

Pre‐gestational relapse rates differed between groups. Lowest relapse rates were observed during late pregnancy, followed by an elevated relapse rate after delivery compared to the pre‐pregnancy year and the first trimester. Only in group I, the postnatal relapse rate did not exceed the relapse rate before conception. IVIg treatment did not influence disease progression after delivery.

Conclusions

In MS patients, IVIg treatment during and/or after delivery is an option to reduce the incidence of relapses during pregnancy and the postnatal period. Surprisingly, untreated patients becoming pregnant showed an increase in the relapse rate in the first trimester compared with the pre‐gestational period. How alterations of hormone status during pregnancy affect disease activity in MS has to be further investigated.
Spatial relationship between climatic diversity and biodiversity conservation value
Authors: Wang Junjun , Wu Ruidong , He Daming , Yang Feiling , Hu Peijun , Lin Shiwei , Wu Wei , Diao Yixin , Guo Yang
Published: June 2018

Capturing the full range of climatic diversity in a reserve network is expected to improve the resilience of biodiversity to climate change. Therefore, a study on systematic conservation planning for climatic diversity that explicitly or implicitly hypothesizes that regions with higher climatic diversity support greater biodiversity is needed. However, little is known about the extent and generality of this hypothesis. We used the case of Yunnan, southwest China, to quantitatively classify climatic units and modeled 4 climatic diversity indicators, including the variety (VCU), rarity (RCU), endemism (ECU) of climatic units, and a composite index of climatic diversity (CICD). We used 5 schemes that reliably identify priority conservation areas (PCAs) to identify areas with high biodiversity conservation value. We then investigated the spatial relationships between the 4 climatic diversity indicators and the results of the 5 PCA schemes and assessed the representation of climatic diversity within the existing nature reserves. The CICD was the best indicator of areas with high conservation value, followed by ECU and RCU. Contrary to conventional knowledge, VCU was not positively associated with biodiversity conservation value. The rarer or more endemic climatic units tended to have higher reserve coverage than the more common units. However, only 28 units, covering 10.5% of the land in Yunnan, had >17% of their areas protected. In addition to climatic factors, topography and human disturbances also significantly affected the relationship between climatic diversity and biodiversity conservation value. Our results suggest that climatic diversity can be an effective surrogate for establishing a more robust reserve network under climate change in Yunnan. Our study improves understanding of the relationship between climatic diversity and biodiversity and helps build an evidence‐based foundation for systematic conservation planning that targets climatic diversity in response to climate change.
Bacterial meningitis as a cause of death in lung transplant donors: Early outcomes in recipients
Authors: Grewal Harpreet S. , Highland Kristin B. , McCurry Kenneth , Akindipe Olufemi , Budev Marie , Mehta Atul C.
Published: June 2018

Background

Lung transplant remains an established treatment for end‐stage lung disease, but limited organ availability remains a major barrier and contributor to waitlist mortality.1 Only 20% of available organs are considered suitable for lung transplantation (Am J Transplant, 16, 2016 and 141; Thorac Surg Clin, 25, 2015 and 35). Successful lung transplantation has been reported from donors infected with bacterial or fungal organisms, but there is a paucity of evidence regarding the use of donors with bacterial meningitis (Transplant Proc, 32, 2000 and 75; Transplantation, 64, 1997 and 365; Ann Thorac Surg, 86, 2008 and 1554).

Method

The Cleveland Clinic lung transplant database was retrospectively reviewed for patients between January 1998 and December 2014. Post‐transplantation outcomes collected included graft dysfunction, infectious complications, and survival.

Results

The recipients were identified as having lungs from donors with bacterial meningitis. All recipients remained free of infectious organisms responsible for bacterial meningitis related in the donor. Severe primary graft dysfunction (PGD) was not seen in these recipients.

Conclusion

In our study, lung transplantation from increased risk donors with bacterial meningitis was not associated with an increased risk of early infectious complications in recipients. Donors with bacterial meningitis should be considered for lung donation and may expand the donor pool safely.
Three‐dimensional transthoracic echocardiographic identification of individual cusps of the pulmonary valve: Potential misidentification by the two‐dimensional technique
Authors: Elsayed Mahmoud , Hsiung Ming C. , Nanda Navin C. , Alratroot Ahmad , Turaga Naga Sai Shravan
Published: June 2018

We demonstrate the incremental value of live/real time three‐dimensional transthoracic echocardiography (3DTTE) over the two‐dimensional modality in the identification of all three cusps of the pulmonary valve in patients in whom only two leaflets could be detected by the latter technique. This was because of the ability of 3DTTE to view the cusps enface permitting assessment of relationship to one another and the surrounding cardiac structures. In addition, 3DTTE showed not only the potential errors that can occur in pulmonary valve cusp identification when the two‐dimensional modality is used alone but also how some of these errors can be avoided by paying attention to the surrounding structures.
Transesophageal ultrasonography during orthotopic liver transplantation: Show me more
Authors: Vetrugno Luigi , Barnariol Federico , Bignami Elena , Centonze Grazia D. , De Flaviis Adelisa , Piccioni Federico , Auci Elisabetta , Bove Tiziana
Published: June 2018

The first perioperative transesophageal echocardiography (TEE) guidelines published 21 years ago were mainly addressed to cardiac anesthesiologists. TEE has since expanded its role outside this setting and currently represents an invaluable tool to assess chamber sizes, ventricular hypertrophy, and systolic, diastolic, and valvular function in patients undergoing orthotopic liver transplantation (OLT). Right‐sided microemboli, right ventricular dysfunction, and patent foramen ovale (PFO) are the most common intra‐operative findings described during OLT. However, left ventricular outflow tract obstruction and left ventricular ballooning syndrome are more difficult to recognize and less frequent. Transesophageal ultrasonography (TEU) during OLT is also underused. Its applications are as follows: (1) assistance in the difficult placement of pulmonary arterial catheters; (2) help with catheterization of great vessels for external veno‐venous bypass placement; (3) intra‐operative evaluation of surgical liver anastomosis patency, if feasible, through the liver window; and (4) intra‐operative investigation of “acute hypoxemia” due to pulmonary and cardiac issues using trans‐esophageal lung ultrasound (TELU). The aims of this review are as follows: (1) to summarize the uses of TEE and TEU throughout all phases of OLT, and (2) to describe other new feasible applications.
Chronic fluoxetine treatment accelerates kindling epileptogenesis in mice independently of 5‐HT2A receptors
Authors: Li Crystal , Silva Juliana , Ozturk Ezgi , Dezsi Gabriella , O'Brien Terence J. , Renoir Thibault , Jones Nigel C.
Published: June 2018

Patients with epilepsy often have mood disorders, and these are commonly treated with antidepressant drugs. Although these drugs are often successful in mitigating depressive symptoms, how they affect the epileptogenic processes has been little studied. Recent evidence has demonstrated that treatment with selective serotonin reuptake inhibitor (SSRI) antidepressant drugs adversely promotes epileptogenesis, which may be of great concern considering the number of patients exposed to these drugs. This study investigated 5‐HT2A receptor signaling as a potential mechanism driving the pro‐epileptogenic effects of the prototypical SSRI fluoxetine. Male homozygous 5‐HT2A receptor knockout mice or wild‐type littermates (n = 9‐14/group) were treated with continuous fluoxetine (10 mg kg−1d−1, sc) or vehicle and subjected to electrical kindling of the amygdala. Compared to vehicle, fluoxetine treatment accelerated kindling epileptogenesis (P < .001), but there was no effect of genotype (P = .75), or any treatment x genotype interaction observed (P = .90). Of interest, fluoxetine treatment increased afterdischarge thresholds in both genotypes (P = .007). We conclude that treatment with fluoxetine promotes epileptogenesis in mice, but this effect is not mediated by 5‐HT2A receptors. This suggests that antidepressants may accelerate the onset of acquired epilepsy in patients who have experienced epileptogenic cerebral insults.
Comorbid epilepsy in autism spectrum disorder: Implications of postnatal inflammation for brain excitability
Authors: Lewis Megan Leigh , Kesler Mitchell , Candy Sydney A. , Rho Jong M. , Pittman Quentin J.
Published: June 2018

Objective

In different cohorts, 5%‐30% of individuals with autism spectrum disorder (ASD) also have epilepsy. The high co‐occurrence of these disorders suggests that a common mechanistic link may exist. The underlying pathophysiology of this comorbidity remains unknown. To investigate the mechanism(s) involved in the pathogenesis of ASD and epilepsy, we developed and validated a novel mouse model that concurrently exhibits hallmark features of both disorders.

Methods

We utilized inbred BTBR T+ Itpr3tf/J (BTBR) mice that exhibit the core behavioral characteristics of ASD (ie, impaired sociability, altered vocalizations, and restricted interests). BTBR mice received a lipopolysaccharide (LPS) or sterile saline injection at postnatal day (P)7, P14, or P21. Cytokine expression was analyzed for interleukin (IL)‐1β, IL‐10, IL‐6, and tumor necrosis factor α in brain tissue of P7 and adult BTBR mice. Adult BTBR mice were behaviorally analyzed for seizure susceptibility, sociability, communication deficits, and motor stereotypies, and monitored using chronic video‐electroencephalography (EEG).

Results

Adult male and female BTBR mice treated at P7‐P14 with LPS were more sensitive to pentylenetetrazol‐induced seizures than saline‐treated controls. ASD‐like behaviors and hippocampal cytokine levels were unchanged between P7 LPS‐treated BTBR mice and controls. EEG recordings from the dorsal hippocampus revealed a significant increase in number and frequency of seizures over the 4‐week recording period (P60‐P88) in BTBR mice postnatally treated with LPS at P7. These results indicate the presence of a comorbid epileptic phenotype in BTBR mice.

Significance

These findings suggest that an early postnatal immune challenge can increase brain excitability in adult BTBR mice and reveal an underlying epilepsy phenotype. This novel animal model may enable the elucidation of specific molecular alterations that are associated with the concurrent presentation of ASD and epilepsy, which could facilitate the development of targeted therapies for individuals affected by this comorbidity.
Bayesian estimation of partial population continuity using ancient DNA and spatially explicit simulations
Authors: Silva Nuno Miguel , Rio Jeremy , Kreutzer Susanne , Papageorgopoulou Christina , Currat Mathias
Published: June 2018

The retrieval of ancient DNA from osteological material provides direct evidence of human genetic diversity in the past. Ancient DNA samples are often used to investigate whether there was population continuity in the settlement history of an area. Methods based on the serial coalescent algorithm have been developed to test whether the population continuity hypothesis can be statistically rejected by analysing DNA samples from the same region but of different ages. Rejection of this hypothesis is indicative of a large genetic shift, possibly due to immigration occurring between two sampling times. However, this approach is only able to reject a model of full continuity model (a total absence of genetic input from outside), but admixture between local and immigrant populations may lead to partial continuity. We have recently developed a method to test for population continuity that explicitly considers the spatial and temporal dynamics of populations. Here, we extended this approach to estimate the proportion of genetic continuity between two populations, using ancient genetic samples. We applied our original approach to the question of the Neolithic transition in Central Europe. Our results confirmed the rejection of full continuity, but our approach represents an important step forward by estimating the relative contribution of immigrant farmers and of local hunter‐gatherers to the final Central European Neolithic genetic pool. Furthermore, we show that a substantial proportion of genes brought by the farmers in this region were assimilated from other hunter‐gatherer populations along the way from Anatolia, which was not detectable by previous continuity tests. Our approach is also able to jointly estimate demographic parameters, as we show here by finding both low density and low migration rate for pre‐Neolithic hunter‐gatherers. It provides a useful tool for the analysis of the numerous ancient DNA data sets that are currently being produced for many different species.
Standing repair of a proximal, incomplete, articular fracture of the third metatarsal bone
Authors: Cillán‐García E. , Reardon R. J. M. , Schiavo S. , Fordham T. , Elce Y. A.
Published: June 2018

A 5‐year‐old National Hunt Thoroughbred mare presented with sudden onset left hindlimb lameness after race training on the gallops. Clinical examination revealed a marked painful reaction over the proximal metatarsal region but no other obvious abnormalities were detected. Survey radiographs at the yard did not reveal any abnormalities. Nuclear scintigraphic examination 3 days after injury revealed focal marked increased radiopharmaceutical uptake in the proximal metatarsal region. Subsequent radiography revealed an incomplete, articular fracture of the proximal left third metatarsal bone. Repair of the fracture using 3 × 4.5 mm cortical screws placed in lag fashion was performed under standing sedation following perineural analgesia. Follow‐up radiographs demonstrated progressive healing of the fracture. The mare returned to race training 8 months after the fracture was repaired and raced successfully 12 months post injury.
Life Quality of University Students From Immigrant Families in the United States
Authors: Bakhtiari Farin , Benner Aprile D. , Plunkett Scott W.
Published: June 2018

The numbers of university students from immigrant families have been increasing in the United States, yet little research exists on factors influencing their life quality. Self‐report data were collected from 2,210 students from one university in California. Direct effects of four contextual stressors (i.e., ethnic discrimination, parent–child cultural conflict, family disengagement, and family financial stress) were examined in relation to life quality. Also, the potential moderating and mediating role of perceived stress was examined, as well as the potential moderating role of students' generational status. The results provided strong support for mediation, showing contextual stressors influenced students' life quality through their perceived stress. Some evidence was found for moderation, showing the complex role of perceived stress. Generational status did not play a moderating role.
Exploring Financial Burdens of Student Loan Holders in the United States
Authors: Lee Jae Min , Kim Kyoung Tae , Hong Eunice Jihyun
Published: June 2018

This study examined the profile of student loan holders in the United States. Data were extracted from the pooled dataset of the 2010 and 2013 Survey of Consumer Finances. The sample included 2,161 households with outstanding student loans. The analyses focused on: (1) amount of the outstanding balance of the student loan; (2) loan payment‐to‐income ratio, and (3) loan delinquency. Factors that were positively related to the amount of student loan debt included: education, income, and homeownership. Factors that were positively related to the loan payment‐to‐income ratio included: age, education, presence of children between aged 18 and 25, net worth, and self‐employment. In regard to loan delinquency, households with credit constraints were more likely to be delinquent on their student loans. Interestingly, education, net worth, and homeownership were negatively related to being delinquent on student loans.
Continued Barriers Affecting Hispanic Families’ Dietary Patterns
Authors: Villegas Elizabeth , Coba‐Rodriguez Sarai , Wiley Angela R.
Published: June 2018

Obesity and changing dietary patterns continue to be concerning issues among Hispanic immigrant families. Using consumer acculturation theory, the researchers conducted three focus groups with 19 mothers to examine changing behaviors (postimmigration) that affect healthy eating habits. Using a priori codes and data displays, the analysis revealed that mothers: (i) realize family food consumption needs to be healthier; (ii) recognize as barriers food availability, time constraints, and shopping practices; and (iii) link financial constraints and children's preferences to unhealthy eating. Findings suggest continued investigation of the complex factors impacting changing lifestyles, plus exploration of innovative, behavioral interventions to support immigrant families, is needed.
The Relationship Between Student Loan Debt and Financial Wellness
Authors: Henager Robin , Wilmarth Melissa J.
Published: June 2018

With the rising cost of tuition, the burden of student loans on individuals and families is increasing. Using data from the National Financial Capability Study (NFCS), the researchers analyzed the relationship between financial wellness and the presence of student loan debt. Results from ordered logistic regression showed that holding a student loan was negatively related to financial wellness, but having a college degree (as compared to having a high school degree) was positively associated with financial wellness. It is important for a student to understand this and weigh the decision to borrow for college considering the costs and benefits.
Secondary Teacher Education Program Redesign as a Community of Practice
Authors: Hales Patrick D. , Kampmann Jennifer , Stremmel Andrew
Published: June 2018

A recurring problem in university teacher education programs is the lack of connection between what teacher candidates do in coursework and what they practice in classroom field placements. This article describes the efforts of the secondary teacher education program (STEP) faculty in the College of Education and Human Sciences at South Dakota State University to redesign their coursework and field experiences into a residency program to better address the development of teacher candidates and needs of school districts. The authors reflect upon their efforts using a Communities of Practice framework. There are implications in the redesign process for teacher education programs hoping to address similar situations for the benefit of the teacher candidate, the universities, and the school districts.
Spatial and temporal differences in life history parameters of Rastrineobola argentea (Pellegrin, 1904) in the Lake Victoria basin in relation to fishing intensity
Authors: Mangeni‐Sande R. , Taabu‐Munyaho A. , Ogutu‐Ohwayo R. , Nkalubo W. , Natugonza V. , Nakiyende H. , Nyamweya C. S. , Muwanika V. B.
Published: June 2018

The small pelagic cyprinid, Rastrineobola argentea (Pellegrin), commonly known as dagaa, accounted for 60% of the total fish biomass and 40% of the commercial catches in Lake Victoria in 2015. However, some aspects of the biology of species (from which management interventions are based) have changed since 1970s; and yet harvest regulations have remained the same. In this study, spatial and temporal variations in life history traits of dagaa in the northern portion of Lake Victoria were examined in relation to fishing intensity to offer guidance on possible adjustments in managing the fishery. The mean standard length halved, whilst the length at 50% maturity (Lm50) reduced by 27%, between the 1970s and 2015; however, the decline in Lm50 was more pronounced in males than females. Data collected between 2014 and 2015 showed that immature individuals are largely harvested from inshore and mid‐island areas, whilst most of the fishes caught in open water areas are largely mature irrespective of the size of the gear used. The causes of the changes in these biological aspects, and the need for policy adjustment, are discussed in the context of changes in fishing pressure.
Association between the interannual variation in the oceanic environment and catch rates of bigeye tuna (Thunnus obesus) in the Atlantic Ocean
Authors: Lan Kuo‐Wei , Lee Ming‐An , Chou Chin‐Pei , Vayghan Ali Haghi
Published: June 2018

The environmental processes associated with variability in the catch rates of bigeye tuna in the Atlantic Ocean are largely unexplored. This study used generalized additive models (GAMs) fitted to Taiwanese longline fishery data from 1990 to 2009 and investigated the association between environmental variables and catch rates to identify the processes influencing bigeye tuna distribution in the Atlantic Ocean. The present findings reveal that the year (temporal factor), latitude and longitude (spatial factors), and major regular longline target species of albacore catches are significant for the standardization of bigeye tuna catch rates in the Atlantic Ocean. The standardized catch rates and distribution of bigeye tuna were found to be related to environmental and climatic variation. The model selection processes showed that the selected GAMs explained 70% of the cumulative deviance in the entire Atlantic Ocean. Regarding environmental factors, the depth of the 20 degree isotherm (D20) substantially contributed to the explained deviance; other important factors were sea surface temperature (SST) and sea surface height deviation (SSHD). The potential fishing grounds were observed with SSTs of 22–28°C, a D20 shallower than 150 m and negative SSHDs in the Atlantic Ocean. The higher predicted catch rates were increased in the positive northern tropical Atlantic and negative North Atlantic Oscillation events with a higher SST and shallow D20, suggesting that climatic oscillations affect the population abundance and distribution of bigeye tuna.
Engaging youth in research planning, design and execution: Practical recommendations for researchers
Authors: Hawke Lisa D. , Relihan Jacqueline , Miller Joshua , McCann Emma , Rong Jessica , Darnay Karleigh , Docherty Samantha , Chaim Gloria , Henderson Joanna L.
Published: June 2018

Context

Engaging youth as partners in academic research projects offers many benefits for the youth and the research team. However, it is not always clear to researchers how to engage youth effectively to optimize the experience and maximize the impact.

Objective

This article provides practical recommendations to help researchers engage youth in meaningful ways in academic research, from initial planning to project completion. These general recommendations can be applied to all types of research methodologies, from community action‐based research to highly technical designs.

Results

Youth can and do provide valuable input into academic research projects when their contributions are authentically valued, their roles are clearly defined, communication is clear, and their needs are taken into account. Researchers should be aware of the risk of tokenizing the youth they engage and work proactively to take their feedback into account in a genuine way. Some adaptations to regular research procedures are recommended to improve the success of the youth engagement initiative.

Conclusions

By following these guidelines, academic researchers can make youth engagement a key tenet of their youth‐oriented research initiatives, increasing the feasibility, youth‐friendliness and ecological validity of their work and ultimately improve the value and impact of the results their research produces.
How do adolescents with cerebral palsy participate? Learning from their personal experiences
Authors: Wintels Sophie Catharina , Smits Dirk‐Wouter , van Wesel Floryt , Verheijden Johannes , Ketelaar Marjolijn ,   the PERRIN PiP Study Group
Published: June 2018

Background

Participation in society can be difficult for adolescents with cerebral palsy (CP). Information is often based on quantitative studies, and little is known about their personal participation experiences.

Objective

The aim of this study was to examine the participation experiences of adolescents (aged 12‐17 years) with CP.

Methods

A qualitative participatory research method was used. Twenty‐three semi‐structured open interviews were conducted with 13 male and 10 female adolescents (mean age 15 years) with CP. An interview checklist was developed jointly with adolescents with CP. This checklist ensured that the adolescents reflected on various participation areas, that is school, sports, health care and work. The analysis was based on principles of grounded theory.

Findings

From the adolescents’ experiences, 4 key categories were identified. One concerned participation, as such, expressed as “My participation experiences,” including experiences, thoughts and feelings while participating in daily life. Three other categories concerned factors that influence participation experiences, expressed as “My disability,” “Me as a person” and “My environment.” These 4 categories together formed a model showing the interactions and dynamics of participation according to adolescents with CP.

Conclusion

Adolescents with CP expressed their participation experiences, including various important influencing factors. This study conceptualized these experiences into a dynamic model. This experience‐based participation model may provide new, personalized perspectives for practice, for instance in rehabilitation, but also for schools and sports (or sports clubs) attended by adolescents. Focusing on personal and environmental factors might be the key to successful participation.
What do stakeholders expect from patient engagement: Are these expectations being met?
Authors: Boudes Mathieu , Robinson Paul , Bertelsen Neil , Brooke Nicholas , Hoos Anton , Boutin Marc , Geissler Jan , Sargeant Ify
Published: June 2018

Background

Meaningful patient engagement (PE) in medicines development and during the life cycle of a product requires all stakeholders have a clear understanding of respective expectations.

Objective

A qualitative survey was undertaken to understand stakeholder expectations.

Design

The survey explored 4 themes from the perspective of each stakeholder group: meaning, views, expectations and priorities for PE. Participants were grouped into 7 categories: policymakers/regulators; health‐care professionals (HCPs); research funders; payers/purchasers/HTA; patients/patient representatives; pharmaceutical/life sciences industry; and academic researchers.

Results

Fifty‐nine interviews were conducted across a range of geographies, PE experience and job seniority/role. There was consensus across stakeholders on meaning of PE; importance of promoting PE to a higher level than currently; need for a more structured process and guidance. There was little consensus on stakeholder expectations and roles. Policymakers/regulators were expected by others to drive PE, create a framework and facilitate PE, provide guidelines of good practice and connect stakeholders, but this expectation was not shared by the policymakers/regulators group. HCPs were seen as the link between patients and other stakeholders, but HCPs did not necessarily share this view.

Discussion and conclusions

Despite broad stakeholder categories, clear themes emerged: there is no “leader”; no stakeholder has a clear view on how to meaningfully engage with patients; there are educational gaps; and a structure and guidance for PE is urgently required. Given the diversity of stakeholders, there needs to be multistakeholder collaborative leadership. Effective collaboration requires consensus on roles, responsibilities and expectations to synergize efforts to deliver meaningful PE in medicines life cycle.