bluuebunny/crossref_metadata_2025 huggingface dataset:
HOW SHOULD RURAL FINANCIAL COOPERATIVES BE BEST ORGANIZED? EVIDENCE FROM ETHIOPIA
Authors: A. ABAY Kibrom , KORU Bethelhem , ABATE Gashaw Tadesse , BERHANE Guush
Published: May 2018

What is the optimal size and composition of Rural Financial Cooperatives (RFCs)? With this broad question in mind, we characterize alternative formation of RFCs and their implications in improving rural households’ access to financial services, including savings, credit and insurance services. We find that some features of RFCs have varying implications for delivering various financial services (savings, credit and insurance). We find that the size of RFCs exhibits nonlinear relationship with the various financial services RFCs provide. We also show that compositional heterogeneity among members (including diversity in wealth) is associated with higher access to credit services, while this has little implication on households’ savings behavior. Similarly, social cohesion among members is strongly associated with higher access to financial services. These empirical descriptions suggest that the optimal size and composition of RFCs may vary across the domains of financial services they are designed to facilitate. These pieces of evidence provide some suggestive insights on how to ensure financial inclusion among smallholders, a pressing agenda and priority of policy makers in developing countries, including Ethiopia. The results also provide some insights into rural microfinance operations which are striving to satisfy members’ demand for financial services.
Serotonergic regulation of insulin secretion
Authors: Cataldo Bascuñan L. R. , Lyons C. , Bennet H. , Artner I. , Fex M.
Published: May 2018

The exact physiological role for the monoamine serotonin (5‐HT) in modulation of insulin secretion is yet to be fully understood. Although the presence of this monoamine in islets of Langerhans is well established, it is only with recent advances that the complex signalling network in islets involving 5‐HT is being unravelled. With more than fourteen different 5‐HT receptors expressed in human islets and receptor‐independent mechanisms in insulin‐producing β‐cells, our understanding of 5‐HT's regulation of insulin secretion is increasing. It is now widely accepted that failure of the pancreatic β‐cell to release sufficient amounts of insulin is the main cause of type 2 diabetes (T2D), an ongoing global epidemic. In this context, 5‐HT signalling may be of importance. In fact, 5‐HT may serve an essential role in regulating the release of insulin and glucagon, the two main hormones that control glucose and lipid homoeostasis. In this review, we will discuss past and current understanding of 5‐HT's role in the endocrine pancreas.
Inguinoscrotal hernia containing the urinary bladder successfully repaired using laparoscopic transabdominal preperitoneal repair technique: A case report
Authors: Tazaki Tatsuya , Sasaki Masaru , Kohyama Mohei , Sugiyama Yoichi , Uegami Shinnosuke , Shintakuya Ryuta , Imamura Yuji , Nakamitsu Atsushi
Published: May 2018

We report herein a patient with an inguinoscrotal hernia containing the urinary bladder. The hernia was safely repaired using the laparoscopic transabdominal preperitoneal repair technique. A 76‐year‐old man was admitted to our hospital with abdominal pain, vomiting, and diarrhea. His scrotum was swollen to fist size. Abdominal CT showed herniation of the sigmoid colon and the bladder into the right inguinal region, and his abdominal pain was attributed to incarceration of the sigmoid colon; this was manually reduced. About 1 month later, we performed transabdominal preperitoneal repair. After the direct hernial orifice was identified, the bladder was noted to be sliding from the medial side of the hernia; this was reduced. Peeling on the medial side was carried out to the middle of the abdominal wall, and the myopectineal orifice was covered with mesh. The patient was discharged on postoperative day 1.
Effects of rearing system on meat quality, fatty acid and amino acid profiles of Hu lambs
Authors: Chai Jianmin , Diao Qiyu , Zhao Jiangchao , Wang Haichao , Deng Kaidong , Qi Minli , Nie Mingfei , Zhang Naifeng
Published: May 2018

To determine the effects of early rearing system on meat quality traits, fatty acid and amino acid profiles of meat, 48 Hu lambs were selected and randomly divided into four treatments: control lambs were ewe‐reared from birth to 60 days of age (ER), while treatment lambs were segregated from their dams at 10, 20 and 30 days of age, then artificially reared with milk replacer until 60 days of age (EW10, EW20 and EW30, respectively). All lambs had no access to the milk replacer or their dams from 61 to 90 days. Creep feed was supplied ad libitum to all lambs from 15 to 90 days of age. Artificially reared lambs (EW10, EW20 and EW30) had higher (p < .05) creep feed intake, average daily gain, slaughter weight, hot carcass weight, meat ether extract content, bright meat color (lightness and yellowness) than ewe‐reared lambs. The content of unsaturated fatty acids and monounsaturated fatty acids in EW10 and EW20 were greater (p < .05) than that in ER, whereas the proportions of saturated fatty acids in EW10 and EW20 were lower than that in ER (p < .05). The percentages of C18:0, C18:2, C18:3 and the ratio of polyunsaturated fatty acids and saturated fatty acids of artificially reared lambs were greater than ewe‐reared lambs (p < .05). The meat proportions of leucine, alanine and proline were higher (p < .05) in artificially reared lambs than ewe‐reared ones. Finally, the artificially reared system increased meat production and changed the fatty acid and amino acid profiles of meat, and it would be appropriate to rear Hu lambs artificially from 10 days with milk replacer.
Determinants of CSR Reporting and Assurance: An Analysis of Top Cooperative and Mutual Organisations
Authors: Bollas‐Araya Helena María , Polo‐Garrido Fernando , Seguí‐Mas Elies
Published: May 2018

Corporate social responsibility (CSR) has greatly influenced business communication. CSR reporting has become the main tool through which organisations worldwide communicate their economic, social and environmental performance. Just as this practice is consolidated, the need for credible information in this area is critical. As a result, some companies subject their CSR reports to an assurance process. Several studies have analysed CSR reporting and assurance among stock companies, but few authors have developed a non‐stock firm perspective. Given the shortage of prior research, we analyse these practices, focusing on cooperative and mutual organisations because, as social enterprises, they have a special link with CSR, and they represent another kind of firm with different transaction costs. By combining statistical and content analysis methods, we aim to identify the determinants that influence the adoption of CSR reporting and assurance, the choice of assuror and the quality of assurance statements. The findings reveal that size is positively but non‐linearly related to reporting, while country and sector significantly affect the adoption of reporting and assurance. Assurance statements substantially differ across providers and their quality depends on size, sector and assuror, exhibiting interactions between size and assuror and between sector and assuror.
The pharmacokinetics, pharmacodynamics and tolerability of PUR0200, a novel tiotropium formulation, in chronic obstructive pulmonary disease
Authors: Singh Dave , Ravi Arjun , Kane Katie , Schmalbach Tess , Hava David L.
Published: May 2018

Aims

PUR0200 is a tiotropium bromide formulation engineered with the iSPERSE dry powder delivery technology. PUR0200 is being developed as a bioequivalent alternative to tiotropium bromide, delivered using Spiriva® HandiHaler® (HH). We investigated the bronchodilator effects, pharmacokinetics and safety of PUR0200 in patients with chronic obstructive pulmonary disease (COPD).

Methods

This was a randomized, placebo‐controlled, crossover study using different PUR0200 doses and the comparator tiotropium HH. In vitro aerodynamic particle size distribution (aPSD) characterization of PUR0200 and tiotropium HH are presented. The main endpoints included forced expiratory volume in 1 s (FEV1) trough and (0–24 h) and pharmacokinetic parameters.

Results

The increased fine‐particle fraction of PUR0200 demonstrated by testing using the next‐generation impactor increased the proportion of drug available for lung deposition compared with the tiotropium HH. There was a numerical dose–response effect for PUR0200 on FEV1, with 3 μg demonstrating a lower effect than higher doses. The placebo‐adjusted mean (95% confidence interval) increases from baseline at 24 h postdose were 150 ml (100–200), 210 ml (160–270) and 200 ml (140–250) for 3 μg, 6 μg and 9 μg doses of PUR0200, respectively. Tiotropium HH (18 μg) caused a mean 169 ml (standard deviation 157ml) improvement in trough FEV1, which was not significantly different to the PUR0200 effects at any of the tested doses.

Conclusions

PUR0200 treatment caused bronchodilation in COPD patients that was similar in magnitude to that caused by tiotropium HH. This enabled a similar clinical effect on lung function to be achieved with PUR0200 using a lower metered dose of tiotropium compared with tiotropium HH.
Interaction betweenABCG2 421C>Apolymorphism and valproate in their effects on steady‐state disposition of lamotrigine in adults with epilepsy
Authors: Klarica Domjanović Iva , Lovrić Mila , Trkulja Vladimir , Petelin‐Gadže Željka , Ganoci Lana , Čajić Ivana , Božina Nada
Published: May 2018

Aims

To investigate the impact of glucuronidation enzyme (UGT1A4*3 142T>G, UGT1A4*2 70C>A, UGT2B7 –161C>T) and transporter (MDR1/ABCB1 1236C>T, ABCG2 421C>A) polymorphisms on steady‐state disposition of lamotrigine and on the lamotrigine–valproate interaction.

Methods

Adults with epilepsy on lamotrigine monotherapy (n = 131) or lamotrigine + valproate treatment (n = 74) were genotyped and steady‐state lamotrigine and valproate morning troughs were determined as a part of routine therapeutic drug monitoring.

Results

No effect ofUGTandMDR1/ABCB1polymorphisms was observed. In the entire cohort,ABCG2 421Aallele had no effect however an interaction between the variant allele and valproate was observed: (i) in lamotrigine‐only patients, variant allele (vs. wild type homozygosity) was independently (adjustments: age, sex, body mass index, lamotrigine dose, other polymorphisms) associated with mildly lower lamotrigine troughs [geometric means ratio (GMR) = 0.76, 95% confidence interval (CI) 0.59–0.98], whereas in lamotrigine + valproate patients it was associated with higher troughs (GMR = 1.72, 95%CI 1.14–2.62); (ii) valproate cotreatment was overall associated with markedly higher troughsvs. lamotrigine monotherapy (GMR = 3.49, 95%CI 2.73–4.44), but more so in variant allele carriers (GMR = 5.24, 95%CI 3.38–8.15) than in wild type homozygotes (GMR = 2.32, 95%CI 1.89–2.83); (iii) variant allele effects in two treatment subsets and valproate effects in two genotype subsets differed by 2.36‐fold (95%CI 1.39–3.67); (iv) increase in lamotrigine troughs associated with increasing valproate troughs was greater in variant allele carriers than in wild type homozygotes, i.e. variant allele effect increased with increasing valproate troughs.

Conclusion

This study is first to indicate a potentially relevant interaction betweenABCG2 421C>Apolymorphism and valproate in their effects on lamotrigine disposition.
Risk Factors for Valproic Acid‐induced Hyperammonaemia in Chinese Paediatric Patients with Epilepsy
Authors: Zhu Xu , Li Xinlin , Zhang Ti , Zhao Limei
Published: May 2018

This study was aimed at identifying genetic and non‐genetic risk factors for valproic acid (VPA)‐induced hyperammonaemia in Chinese paediatric patients with epilepsy. A total of 210 epileptic patients, treated with VPA as monotherapy, were enrolled and classified into hyperammonaemia and control groups according to their blood ammonia level (cut‐off value 50 μmol/L). Serum concentrations of VPA and its major metabolites were simultaneously determined by ultrahigh‐performance liquid chromatography–tandem mass spectrometry. Six single nucleotide polymorphisms in the candidate genes, CYP2C9, CYP2A6, CYP2B6 and CPS1, were analysed by a matrix‐assisted laser desorption ionization‐time of flight mass spectrometry method or nested PCR. Significant differences in age, aspartate transaminase level and the incidence of liver injury were observed between patients of hyperammonaemia and control groups. Genotype distributions of CYP2C9*3, CYP2A6*4 and CPS1 4217C>A allelic variants were also significantly different between the two groups. According to multiple regression analysis, a significant negative correlation was detected between age and the blood ammonia level, while liver injury, the concentration–dose ratio (CDR) of VPA and 2‐propyl‐4‐pentenoic acid (4‐ene VPA), and the presence of CYP2A6*4 or CPS1 4217C>A showed positive correlations with the blood ammonia level. In addition, the risk factors for hyperammonaemia identified by logistic regression analysis were as follows: a younger age (odds ratio [OR] = 0.85; 95% confidence interval [CI] = 0.76–0.96; p = 0.007), occurrence of liver injury (OR = 4.60; 95% CI = 1.27–16.74; p = 0.021), higher CDR of 4‐ene VPA (OR = 1.08; 95% CI = 1.03–1.14; p = 0.001), and carrying mutant alleles of CYP2C9*3 (OR = 3.42; 95% CI = 1.15–10.19; p = 0.028), CYP2A6*4 (OR = 3.23; 95% CI = 1.40–7.48; p = 0.006) and CPS1 4217C>A (OR = 3.25; 95% CI = 1.52–6.94; p = 0.002). Our findings indicated that multiple genetic and non‐genetic risk factors that were identified can be used to predict the development of VPA‐induced hyperammonaemia in Chinese paediatric patients with epilepsy.
Why do college students continue to use mobile learning? Learning involvement and self‐determination theory
Authors: Yang Shuiqing , Zhou Shasha , Cheng Xiaoying
Published: May 2018

Retaining learners and facilitating their continuance are critical for the mobile learning providers and educators. Drawing on stimulus‐organism‐response framework and self‐determination theory, this study examines factors that affect college students' mobile learning continuance by considering the self‐determination needs and learning involvement. A research model was developed and empirically tested against data collected from 309 college students who are the mobile learning users of an online education platform in China. The results of structural equation modeling analysis showed that perceived learning support, self‐management of learning and peer influence significantly influence affective learning involvement, which in turn positively affect mobile learning continuance intention. In addition, perceived learning support and peer influence also significantly influence cognitive learning involvement, which further determine mobile learning continuance intention. Theoretical and practical implications of these findings are also discussed.
I follow, therefore I lead: A longitudinal study of leader and follower identity and leadership in the marines
Authors: Peters Kim , Haslam S. Alexander
Published: May 2018

It is acknowledged that identity plays an important role in a person's leadership development. To date, however, there has been little consideration of the possibility – suggested by the social identity perspective – that individuals who identify as followers may be especially likely to emerge as leaders. We test this possibility in a longitudinal sample of recruit commandos in the Royal Marines. Recruits rated their identification with leader and follower roles five times over the course of their 32‐week training programme. Recruits’ leadership and followership were evaluated by their commanders, and their leadership was assessed by their peers. Analysis indicated that while recruits who identified as leaders received higher leadership ratings from their commanders, recruits who identified – and were perceived – as followers emerged as leaders for their peers. These findings suggest that follower and leader identities underpin different aspects of leadership and that these are differentially recognized by others.
A review of predation as a limiting factor for bird populations in mesopredator‐rich landscapes: a case study of the UK
Authors: Roos Staffan , Smart Jennifer , Gibbons David W. , Wilson Jeremy D.
Published: May 2018

The impact of increasing vertebrate predator numbers on bird populations is widely debated among the general public, game managers and conservationists across Europe. However, there are few systematic reviews of whether predation limits the population sizes of European bird species. Views on the impacts of predation are particularly polarised in the UK, probably because the UK has a globally exceptional culture of intensive, high‐yield gamebird management where predator removal is the norm. In addition, most apex predators have been exterminated or much depleted in numbers, contributing to a widely held perception that the UK has high numbers of mesopredators. This has resulted in many high‐quality studies of mesopredator impacts over several decades. Here we present results from a systematic review of predator trends and abundance, and assess whether predation limits the population sizes of 90 bird species in the UK. Our results confirm that the generalist predators Red Fox (Vulpes vulpes) and Crows (Corvus coroneandC. cornix) occur at high densities in the UK compared with other European countries. In addition, some avian and mammalian predators have increased numerically in the UK during recent decades. Despite these high and increasing densities of predators, we found little evidence that predation limits populations of pigeons, woodpeckers and passerines, whereas evidence suggests that ground‐nesting seabirds, waders and gamebirds can be limited by predation. Using life‐history characteristics of prey species, we found that mainly long‐lived species with high adult survival and late onset of breeding were limited by predation. Single‐brooded species were also more likely to be limited by predation than multi‐brooded species. Predators that depredate prey species during all life stages (i.e. from nest to adult stages) limited prey numbers more than predators that depredated only specific life stages (e.g. solely during the nest phase). The Red Fox and non‐native mammals (e.g. the American MinkNeovison vison) were frequently identified as numerically limiting their prey species. Our review has identified predator–prey interactions that are particularly likely to result in population declines of prey species. In the short term, traditional predator‐management techniques (e.g. lethal control or fencing to reduce predation by a small number of predator species) could be used to protect these vulnerable species. However, as these techniques are costly and time‐consuming, we advocate that future research should identify land‐use practices and landscape configurations that would reduce predator numbers and predation rates.
Long non‐coding RNA NEAT1 promoted ovarian cancer cells’ metastasis through regulation of miR‐382‐3p/ROCK1 axial
Authors: Liu Yangcheng , Wang Yong , Fu Xinming , Lu Zhi
Published: May 2018

Long non‐coding RNA (lncRNA) are extensively involved in various malignant tumors, including ovarian cancer (OC). In the present study, we focused on the expression and function of nuclear enriched abundant transcript 1 (NEAT1) in OC cells’ metastasis. We demonstrated that NEAT1 was upregulated in OC tissue specimens and cell lines. In addition, we revealed that depression of NEAT1 inhibited OC cells’ metastasis and the expression of Rho associated coiled‐coil containing protein kinase 1 (ROCK1), which is a metastasis‐related gene. Using online predictive software and a series of luciferase assays, we demonstrated that both NEAT1 and ROCK1 were the targets of microRNA‐382‐3p (miR‐382‐3p) and share similar microRNA responding elements (MRE). Furthermore, we illustrated that NEAT1 and miR‐382‐3p inhibited each other in a reciprocal manner. Finally, through antisense experiments we demonstrated that NEAT1 promoted ROCK1‐mediated metastasis by functioning as a ceRNA of miR‐382‐3p. In summary, the findings of this study revealed that NEAT1 promoted OC cells’ metastasis through regulating the miR‐382‐3p/ROCK1 axial. The present study might provide a new target for treating OC.
Synergy between peroxisome proliferator‐activated receptor γ agonist and radiotherapy in cancer
Authors: Huang Guodong , Yin Limei , Lan Jie , Tong Ruizhan , Li Mengqian , Na Feifei , Mo Xianming , Chen Chong , Xue Jianxin , Lu You
Published: May 2018

Angiogenesis and inflammation are crucial processes through which the tumor microenvironment (TME) influences tumor progression. In this study, we showed that peroxisome proliferator‐activated receptor γ (PPARγ) is not only expressed in CT26 and 4T1 tumor cell lines but also in cells of TME, including endothelial cells and tumor‐associated macrophages (TAM). In addition, we showed that rosiglitazone may induce tumor vessel normalization and reduce TAM infiltration. Additionally, 4T1 and CT26 tumor‐bearing mice treated with rosiglitazone in combination with radiotherapy showed a significant reduction in lesion size and lung metastasis. We reported that a single dose of 12 Gy irradiation strongly inhibits local tumor angiogenesis. Secretion of C‐C motif chemokine ligand 2 (CCL2) in response to local irradiation facilitates the recruitment of migrating CD11b+ myeloid monocytes and TAM to irradiated sites that initiate vasculogenesis and enable tumor recurrence after radiotherapy. We found that rosiglitazone partially decreases CCL2 secretion by tumor cells and reduces the infiltration of CD11b+ myeloid monocytes and TAM to irradiated tumors, thereby delaying tumor regrowth after radiotherapy. Therefore, combination of the PPARγ agonist rosiglitazone with radiotherapy enhances the effectiveness of radiotherapy to improve local tumor control, decrease distant metastasis risks and delay tumor recurrence.
Peripapillary vessel density changes in Leber's hereditary optic neuropathy: a new biomarker
Authors: Balducci Nicole , Cascavilla Maria Lucia , Ciardella Antonio , La Morgia Chiara , Triolo Giacinto , Parisi Vincenzo , Bandello Francesco , Sadun Alfredo A , Carelli Valerio , Barboni Piero
Published: May 2018

Importance

The contribution of the microvascular supply to the pathogenesis of Leber's hereditary optic neuropathy (LHON) is poorly understood.

Background

We aimed at measuring the peripapillary capillary vessel density (VD) using optical coherence tomography angiography (OCT‐A) at different stages of LHON.

Design

Prospective, cross‐sectional, multicenter, observational study.

Participants

Twenty‐two LHON patients divided in four groups: unaffected mutation carriers (LHON‐u); early sub‐acute stage (LHON‐e); late sub‐acute stage (LHON‐l); chronic stage (LHON‐ch).

Methods

OCT‐A scans centred on the optic disc were obtained by spectral domain OCT system.

Main Outcome Measures

VD, retinal nerve fibre layer (RNFL) and ganglion cell‐inner plexiform layer (GC‐IPL) thickness were compared between groups.

Results

Significant VD changes were detected in every sector (P < 0.0001). In LHON‐e, the VD was reduced in the temporal sector compared with LHON‐u and in the temporal and inferotemporal sectors compared with controls. In LHON‐l, VD was reduced in whole, temporal, superotemporal and inferotemporal sectors compared with LHON‐u and controls. In LHON‐ch, the VD was reduced in all sectors compared to the other groups. An asynchronous pattern emerged in the temporal sector with VD changes occurring earlier than RNFL thickness changes and together with GC‐IPL thinning.

Conclusions and Relevance

Significant peripapillary miscrovascular changes were detected over the different stages of LHON. Studying the vascular network separately from fibres revealed that microvascular changes in the temporal sector preceded the changes of RNFL and mirrored the GC‐IPL changes. Measurements of the peripapillary vascular network may become a useful biomarker to monitor the disease process, evaluate therapeutic efficacy and elucidate pathophysiology.
Pallister‐Killian syndrome: Review of fetal phenotype
Authors: Thakur S. , Gupta R. , Tiwari B. , Singh N. , Saxena K.K.
Published: May 2018

Pallister‐Killian syndrome is a multi‐system sporadic disorder with developmental delay. It is a rare chromosomal abnormality involving supernumerary isochormosome 12p. The disorder exhibits tissue specific mosaicism. The first prenatal diagnosis of PKS was reported in 1985 after ultrasound detection of fetal anomalies. Since this observation, there have been about 62 reports of fetuses with PKS. In this review, we cover the prenatal aspects of PKS.
Land‐use trade‐offs between tree biodiversity and crop production in the Atlantic Forest
Authors: Marcilio‐Silva Vinícius , Marques Márcia C. M. , Cavender‐Bares Jeannine
Published: May 2018

Trade‐offs in ecosystem services (ES) have received increasing attention because provisioning services often come at the expense of biodiversity loss. When land‐use patterns are not maximally efficient relative to productivity, provisioning services, such as crop production, can often be increased without losing biodiversity. The Atlantic Forest (AF) encompasses dense, mixed, and seasonal forests and has high levels of endemism and anthropogenic threat. We examined trade‐offs between biodiversity and crop production in the AF to provide insights into land‐use management decisions. We developed a biodiversity metric that combines information on tree species richness, evolutionary distinctiveness, and rarity at the local level. We examined the extent to which the nature of ES trade‐offs differ among the 3 forest types. We assessed how annual deforestation rates and land management practices affect biodiversity and agricultural revenues. Finally, we tested whether it is possible to achieve the same total regional revenue without reducing biodiversity by improving local management practices. The 3 forest types had similar patterns in ES trade‐offs, although within mixed forest patterns differed. Biodiversity appeared to be more sensitive to land‐use change than crop revenues. Certain crops yielded up to 10 times higher values in some sites. Enhanced crop productivity may increase revenues without reducing biodiversity. Our results showed that to enhance human well‐being without further conversion of AF, maximizing crop productivity is needed . Increasing efficiency of management outcomes by maintaining higher biodiversity and increasing provisioning services depends on knowledge of forest type, the comparative advantage of planting crops in the best places, and preserving species in a balanced manner across forests.
Spatial Semantics, Cognition, and Their Interaction: A Comparative Study of Spatial Categorization in English and Korean
Authors: Yun Hongoak , Choi Soonja
Published: May 2018

This study has two goals. First, we present much‐needed empirical linguistic data and systematic analyses on the spatial semantic systems in English and Korean, two languages that have been extensively compared to date in the debate on spatial language and spatial cognition. We conduct our linguistic investigation comprehensively, encompassing the domains of tight‐ and loose‐fit as well as containment and support relations. The current analysis reveals both cross‐linguistic commonalities and differences: From a common set of spatial features, each language highlights a subset of those features for its principal categorization, and those primary features are importantly different between English and Korean: English speakers categorize events predominantly by containment and support relations (and do so with prepositions), whereas Korean speakers categorize them by tight‐fit and loose‐fit relations (and do so with verbs), with a further distinction of containment and support within the loose‐fit relation. The analysis also shows that the tight‐fit domain is more cross‐linguistically diverse in categorization than is the loose‐fit domain. Second, we test the language data against the nonlinguistic categorization results reported in Choi and Hattrup (2012). The results show a remarkable degree of convergence between the patterns predicted from the current linguistic analysis and those found in C&H's nonlinguistic study and thus provide empirical and strong evidence for an influence of language on nonlinguistic spatial cognition. At the same time, the study reveals areas where the two systems closely interact with each other as well as those where one is independent from the other. Taking both parts of the study together, we identify the specific roles that language and spatial perception/cognition play in spatial categorization.
Clinical characteristics and validation of bronchiectasis severity score systems for post‐tuberculosis bronchiectasis
Authors: Wang Hong , Ji Xiao‐Bin , Li Cheng‐Wei , Lu Hai‐Wen , Mao Bei , Liang Shuo , Cheng Ke‐Bin , Bai Jiu‐Wu , Martinez‐Garcia Miguel Angel , Xu Jin‐Fu
Published: May 2018

Introduction

Lung damage related to tuberculosis is a major contributor to the etiology of bronchiectasis in China. It is unknown whether bronchiectasis severity score systems are applicable in these cases.

Objectives

To evaluate the clinical characteristics and validation of bronchiectasis severity score systems for post‐tuberculosis bronchiectasis.

Methods

The study enrolled 596 bronchiectasis patients in Shanghai Pulmonary Hospital between January 2011 and December 2012. The data for calculating FACED and bronchiectasis severity index (BSI) scores along with mortality, readmission, and exacerbation outcomes were collected and analyzed within a follow‐up period with a median length of 48 months (interquartile range 43‐54 months).

Results

The study enrolled 101 post‐tuberculosis bronchiectasis patients and 495 non‐tuberculosis bronchiectasis patients. Compared with non‐post‐tuberculosis bronchiectasis, post‐tuberculosis bronchiectasis patients experienced less bilateral bronchiectasis (P = .004), a higher frequency of right upper lobe involvement (P < .001) and showed the cylindrical type more often (P < .001). Follow‐up data indicated that both scoring systems were able to predict 48(43–54) month mortality in post‐tuberculosis patients as assessed by the area under the receiver operator characteristic curve (AUC) (FACED AUC = 0.81, BSI AUC = 0.70), but they did not predict readmission (FACED and BSI = 0.56) or exacerbation (FACED and BSI = 0.52) well.

Conclusions

There are apparent differences on radiologic features between bronchiectasis patients with and without history of pulmonary tuberculosis. Both FACED and BSI can predict mortality in post‐tuberculosis bronchiectasis.
Barriers to and enablers of diabetic retinopathy screening attendance: a systematic review of published and grey literature
Authors: Graham‐Rowe E. , Lorencatto F. , Lawrenson J. G. , Burr J. M. , Grimshaw J. M. , Ivers N. M. , Presseau J. , Vale L. , Peto T. , Bunce C. , J Francis J.
Published: May 2018

Aims

To identify and synthesize studies reporting modifiable barriers/enablers associated with retinopathy screening attendance in people with Type 1 or Type 2 diabetes, and to identify those most likely to influence attendance.

Methods

We searched MEDLINE, EMBASE, PsycINFO, Cochrane Library and the ‘grey literature’ for quantitative and qualitative studies to February 2017. Data (i.e. participant quotations, interpretive summaries, survey results) reporting barriers/enablers were extracted and deductively coded into domains from the Theoretical Domains Framework; with domains representing categories of theoretical barriers/enablers proposed to mediate behaviour change. Inductive thematic analysis was conducted within domains to describe the role each domain plays in facilitating or hindering screening attendance. Domains that were more frequently coded and for which more themes were generated were judged more likely to influence attendance.

Results

Sixty‐nine primary studies were included. We identified six theoretical domains [‘environmental context and resources’ (75% of included studies), ‘social influences’ (51%), ‘knowledge’ (51%), ‘memory, attention, decision processes’ (50%), ‘beliefs about consequences’ (38%) and ‘emotions’ (33%)] as the key mediators of diabetic retinopathy screening attendance. Examples of barriers populating these domains included inaccurate diabetic registers and confusion between routine eye care and retinopathy screening. Recommendations by healthcare professionals and community‐level media coverage acted as enablers.

Conclusions

Across a variety of contexts, we found common barriers to and enablers of retinopathy screening that could be targeted in interventions aiming to increase screening attendance.
P465L‐PPARγ mutation confers partial resistance to the hypolipidaemic action of fibrates
Authors: Rodriguez‐Cuenca Sergio , Carobbio Stefania , Barceló‐Coblijn Gwendolyn , Prieur Xavier , Relat Joana , Amat Ramon , Campbell Mark , Dias Ana Rita , Bahri Myriam , Gray Sarah L. , Vidal‐Puig Antonio
Published: May 2018

Aims

Familial partial lipodystrophic syndrome 3 (FPLD3) is associated with mutations in the transcription factor PPARγ. One of these mutations, the P467L, confers a dominant negative effect. We and others have previously investigated the pathophysiology associated with this mutation using a humanized mouse model that recapitulates most of the clinical symptoms observed in patients who have been phenotyped under different experimental conditions. One of the key clinical manifestations observed, both in humans and mouse models, is the ectopic accumulation of fat in the liver. With this study we aim to dissect the molecular mechanisms that contribute to the excessive accumulation of lipids in the liver and characterize the negative effect of this PPARγ mutation on the activity of PPARα in vivo when activated by fibrates.

Material and Methods

P465L‐PPAR mutant and wild‐type mice were divided into 8 experimental groups, 4 different conditions per genotype. Briefly, mice were fed a chow diet or a high‐fat diet (HFD 45% Kcal from fat) for a period of 28 days and treated with WY14643 or vehicle for five days before culling. At the end of the experiment, tissues and plasma were collected. We performed extensive gene expression, fatty acid composition and histological analysis in the livers. The serum collected was used to measure several metabolites and to perform basic lipoprotein profile.

Results

P465L mice showed increased levels of insulin and free fatty acids (FFA) as well as increased liver steatosis. They also exhibit decreased levels of very low density lipoproteins (VLDL) when fed an HFD. We also provide evidence of impaired expression of a number of well‐established PPARα target genes in the P465L mutant livers.

Conclusion

Our data demonstrate that P465L confers partial resistance to the hypolipidemic action of fibrates. These results show that the fatty liver phenotype observed in P465L mutant mice is not only the consequence of dysfunctional adipose tissue, but also involves defective liver metabolism. All in all, the deleterious effects of P465L‐PPARγ mutation may be magnified by their collateral negative effect on PPARα function.
Left atrial compression and right ventricular outflow tract diameter on echocardiography are independently associated with exercise capacity in patients with large hiatal hernia
Authors: Naoum Christopher , Kritharides Leonard , Falk Gregory L. , Martin David , Yiannikas John
Published: May 2018

Introduction

Large hiatal hernia (HH) is often associated with left atrial (LA) compression, anteroposterior cardiac compression (manifesting as reduced right ventricular outflow tract (RVOT) diameter), and left ventricular (LV) compression (manifesting as systolic paradoxical outward motion (LV‐PM) of the posterobasal LV segment). Exercise impairment, also common in this population, improves following HH surgery. We aimed to identify echocardiographic parameters independently associated with exercise impairment due to HH‐mediated cardiogenic compression.

Methods

Patients with a large HH (>30% intra‐thoracic stomach, n = 163) referred for cardiac evaluation were included. Echocardiographic parameters were retrospectively analyzed in relation to HH‐related LA compression severity and the presence of LV‐PM. Echocardiographic parameters independently associated with exercise capacity were identified by multivariable analysis.

Results

Mean baseline metabolic equivalents were reduced (70 ± 28% predicted). Moderate–severe LA compression and LV‐PM were present in 91 of 163 (56%) and 65 of 162 (40%) patients, respectively. Patients with moderate–severe LA compression and LV‐PM had decreased LA and LV dimensions. Moderate–severe LA compression was also associated with reduced RVOT diameter while LV‐PM predicted a greater reduction in LV volumes. LA compression and RVOT diameter were independently associated with baseline exercise capacity and increased following HH surgery performed in a subgroup (n = 72, LA diameter: 14 ± 5 vs 20 ± 4 mm/m2; RVOT diameter: 17 ± 3 vs 19 ± 3 mm/m2, P < .001 for both). Conversely, LV‐PM was not independently associated with exercise capacity.

Conclusion

Hiatal hernia‐related cardiac compression reduces LA and RVOT dimensions. These parameters are independently associated with baseline exercise capacity and improve following HH surgery. LV‐PM is associated with decreased LV volumes but not exercise capacity in this population.
Can cardiovascular MRI be used to more definitively characterize cardiac masses initially identified using echocardiography?
Authors: Rathi Vikas K. , Czajka Anna T. , Thompson Diane V. , Doyle Mark , Tewatia Tarun , Yamrozik June , Williams Ronald B. , Biederman Robert W. W.
Published: May 2018

In diagnosing cardiac and paracardiac masses, cardiac MRI (CMR) has gained acceptance as the gold standard. CMR has been observed to be superior to echocardiography in characterizing soft‐tissue structures and, specifically, in classifying cardiac masses. The aim of our study was to evaluate the association between mortality and cardiac or paracardiac masses initially identified by echocardiography (ECHO) and confirmed by CMR. Between January 2002 and August 2007, a total of 158 patients underwent both ECHO and CMR for the evaluation of cardiac masses that were equivocal or undefined by ECHO. The primary study endpoints were 5‐year all‐cause mortality and 5‐year cardiac mortality. Causes of death as of April 1, 2015 were obtained from medical records or the National Death Index. Patients were analyzed according to mass type determined by CMR using the Kruskal–Wallis test, Kaplan–Meier curves, and the log‐rank test. Over a mean duration of follow‐up of 10.4 ± 2.9 years (range: 0.01–12 years) post‐CMR, the overall all‐cause mortality rate was 25.9% (41/158). Median age at death was 76 years and there were 21 females (51.2%). Mortality rates in the different classifications of cardiac masses by CMR were as follows: 20% (1/5) in patients with a Nondiagnostic CMR; 20% (1/5) in Other Diagnoses; 17.9% (7/39) in No Masses (includes Normal Anatomical Variants); 16.7% (3/18) in Benign Masses; 23.8% (15/63) in Fat; 50% (5/10) in Thrombus; and 61.5% (8/13) in Malignant Mass. The mean survival time in patients with No Mass (n = 39) was not significantly longer than patients with any type of cardiac mass (n = 114) (P = .16). No significant difference was found in age at death between patients when grouped by CMR classification (P = .40). However, among CMR‐confirmed masses, there were some significant differences by mass classification type (P = .006). During the follow‐up period, 26% (41/158) of patients died and 22% (9/41) of the deaths were cardiovascular related; there was no significant difference in mean survival times with respect to cause of mortality (P = .23). In patients with cardiac masses, dually confirmed by ECHO and CMR, significant differences in survival time were observed based upon CMR classified type of mass while CMR was instrumental in obviating invasive biopsy.
Interactions between insulin and diet on striatal dopamine uptake kinetics in rodent brain slices
Authors: Patel Jyoti C. , Stouffer Melissa A. , Mancini Maria , Nicholson Charles , Carr Kenneth D. , Rice Margaret E.
Published: May 2018

Diet influences dopamine transmission in motor‐ and reward‐related basal ganglia circuitry. In part, this reflects diet‐dependent regulation of circulating and brain insulin levels. Activation of striatal insulin receptors amplifies axonal dopamine release in brain slices, and regulates food preference in vivo. The effect of insulin on dopamine release is indirect, and requires striatal cholinergic interneurons that express insulin receptors. However, insulin also acts directly on dopamine axons to increase dopamine uptake by promoting dopamine transporter (DAT) surface expression, counteracting enhanced dopamine release. Here, we determined the functional consequences of acute insulin exposure and chronic diet‐induced changes in insulin on DAT activity after evoked dopamine release in striatal slices from adult ad‐libitum fed (AL) rats and mice, and food‐restricted (FR) or high‐fat/high‐sugar obesogenic (OB) diet rats. Uptake kinetics were assessed by fitting evoked dopamine transients to the Michaelis‐Menten equation and extracting Cpeak and Vmax. Insulin (30 nm) increased both parameters in the caudate putamen and nucleus accumbens core of AL rats in an insulin receptor‐ and PI3‐kinase‐dependent manner. A pure effect of insulin on uptake was unmasked using mice lacking striatal acetylcholine, in which increased Vmax caused a decrease in Cpeak. Diet also influenced Vmax, which was lower in FR vs. AL. The effects of insulin on Cpeak and Vmax were amplified by FR but blunted by OB, consistent with opposite consequences of these diets on insulin levels and insulin receptor sensitivity. Overall, these data reveal acute and chronic effects of insulin and diet on dopamine release and uptake that will influence brain reward pathways.
Behavioural state‐specific neurons in the mouse medulla involved in sleep‐wake switching
Authors: Sakai Kazuya
Published: May 2018

The medullary reticular formation (RF) is involved in the maintenance of several vital physiological functions and level of vigilance. In this study, in nonanesthetised, head‐fixed mice, I examined the role of medullary RF neurons in the control of sleep‐wake states, that is, wakefulness (W), slow‐wave sleep (SWS) and paradoxical (or rapid eye movement) sleep (PS). I showed, for the first time, that the mouse medullary RF contains presumed SWS‐promoting, SWS‐on neurons that remain silent during W, display a sharp increase in discharge rate at sleep onset, and discharge tonically and selectively during SWS. In addition, I showed the presence in the medullary RF of both PS‐on and PS‐off neurons, which, respectively, commence discharging or cease firing selectively just prior to, and during, PS. PS‐off neurons were located in the raphe nuclei and ventral medulla, while PS‐on neurons were found in both the lateral part of the ventral gigantocellular reticular nucleus and the raphe nuclei, as were SWS‐on neurons. PS‐off and SWS‐on neurons appear to play an important role in both the W‐SWS and SWS‐PS switches, while PS‐on and PS‐off neurons play an important role in the PS‐W switch. The present findings on the trends in spike activity at the transitions from SWS to PS and from PS to W are in line with the reciprocal interaction hypothesis according to which PS occurs as a result of the cessation of discharge of PS‐off neurons, while PS ends as a result of the start of discharge of PS‐off neurons.
Molecular and cellular characterization of nicotinic acetylcholine receptor subtypes in the arcuate nucleus of the mouse hypothalamus
Authors: Calarco Cali A. , Li Zhiying , Taylor Seth R. , Lee Somin , Zhou Wenliang , Friedman Jeffrey M. , Mineur Yann S. , Gotti Cecilia , Picciotto Marina R.
Published: May 2018

Nicotine, acting through nicotinic acetylcholine receptors (nAChRs), increases the firing rate of both orexigenic agouti‐related peptide (AgRP) and anorexigenic pro‐opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC), yet nicotine and other nAChR agonists decrease food intake in mice. Viral‐mediated knockdown of the β4 nAChR subunit in all neuronal cell types in the ARC prevents the nicotinic agonist cytisine from decreasing food intake, but it is not known whether the β4 subunit is selectively expressed in anorexigenic neurons or how other nAChR subtypes are distributed in this nucleus. Using translating ribosome affinity purification (TRAP) on ARC tissue from mice with ribosomes tagged in either AgRP or POMC cells, we examined nAChR subunit mRNA levels using real‐time PCR. Both AgRP and POMC cells express a comparable panel of nAChR subunits with differences in α7 mRNA levels and a trend for difference in α4 levels, but no differences in β4 expression. Immunoprecipitation of assembled nAChRs revealed that the β4 subunit forms assembled channels with α3, β2 and α4, but not other subunits found in the ARC. Finally, using cell type‐selective, virally delivered small hairpin RNAs targeting either the β4 or α7 subunit, we examined the contribution of each subunit in either AgRP or POMC cells to the behavioural response to nicotine, refining the understanding of nicotinic regulation of this feeding circuit. These experiments identify a more complex set of nAChRs expressed in ARC than in other hypothalamic regions. Thus, the ARC appears to be a particular target of nicotinic modulation.
Resolving ambiguities in SUDEP classification
Authors: Devinsky Orrin , Bundock Elizabeth , Hesdorffer Dale , Donner Elizabeth , Moseley Brian , Cihan Esma , Hussain Fizza , Friedman Daniel
Published: May 2018

Objective

To examine the consistency of applying the Nashef et al (2012) criteria to classify sudden unexpected death in epilepsy (SUDEP).

Methods

We reviewed cases from the North American SUDEP Registry (n = 250) and Medical Examiner Offices (n = 1301: 698 Maryland, 457 New York City, 146 San Diego). Two epileptologists with expertise in SUDEP and epilepsy‐related mortality independently reviewed medical records, scene investigation, autopsy, and toxicology and assigned a SUDEP class.

Results

Major areas of disagreement arose between adjudicators concerned differentiating (1) Definite SUDEP Plus Comorbidity from Possible SUDEP and (2) Resuscitated (Near) SUDEP from SUDEP. In many cases, distinguishing between contributing and competing causes of death when trying to classify Definite SUDEP Plus Comorbidity versus Possible SUDEP is ambiguous and relies on judgement. Similarly, determining if an intervention was lifesaving or not (Resuscitated SUDEP or Not SUDEP), or if resuscitation merely delayed SUDEP (Resuscitated SUDEP or SUDEP) is often a judgement call and can differ between experienced adjudicators. Given these persisting ambiguities, we propose more explicit criteria for distinguishing these categories.

Significance

Accurate and consistent classification of cause of death among individuals with epilepsy remains a dire public health concern. SUDEP is likely underestimated in national health statistics. Greater standardization of criteria among epilepsy researchers, medical examiners, and epidemiologists to determine cause and classify death will lead to more accurate tracking of SUDEP and other epilepsy‐related mortalities.