bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis of sessile serrated adenomas/polyps using endocytoscopy (with videos)
Authors: Mori Yuichi , Kudo Shin‐ei , Ogawa Yushi , Wakamura Kunihiko , Kudo Toyoki , Misawa Masashi , Hayashi Takemasa , Katagiri Atsushi , Miyachi Hideyuki , Inoue Haruhiro , Oka Shiro , Matsuda Takahisa
Published: January 2016

Sessile serrated adenomas/polyps (SSA/P) are considered to be precursors of colorectal cancers. They therefore need to be distinguished from hyperplastic polyps, and should be treated similarly to adenomas. Various endoscopic classifications for discriminating SSA/P have recently been proposed and validated, including the ‘Type II‐O’ pit pattern in magnifying chromoendoscopy and the ‘varicose microvascular vessel’ in narrow‐band imaging. However, there is currently no diagnostic consensus on the endoscopic appearance of SSA/P. Endocytoscopy (EC) is an emerging modality with diagnostic potential for SSA/P. EC is a type of a contact light microscopy, which allows in vivo visualization of cells and nuclei facilitating precise, real‐time pathological prediction. SSA/P show oval gland lumens with small round nuclei in EC, indirectly reflecting the pathological features. EC has shown a sensitivity of 83.3% and a specificity of 97.8% for the diagnosis of SSA/P. EC is also a promising tool for the diagnosis of SSA/P with cytological dysplasia because of its ability to detect morphological changes in nuclei, which is the most important factor determining the presence of dysplasia in the lesion. However, clinical data validating the usefulness of EC are lacking, and further studies are required.
Encoding and decoding time in neural development
Authors: Toma Kenichi , Wang Tien‐Cheng , Hanashima Carina
Published: January 2016

The development of a multicellular organism involves time‐dependent changes in molecular and cellular states; therefore ‘time’ is an indispensable mathematical parameter of ontogenesis. Regardless of their inextricable relationship, there is a limited number of events for which the output of developmental phenomena primarily uses temporal cues that are generated through multilevel interactions between molecules, cells, and tissues. In this review, we focus on neural stem cells, which serve as a faithful decoder of temporal cues to transmit biological information and generate specific output in the developing nervous system. We further explore the identity of the temporal information that is encoded in neural development, and how this information is decoded into various cellular fate decisions.
Timing mechanisms in neuronal pathfinding, synaptic reorganization, and neuronal regeneration
Authors: Ivakhnitskaia Evguenia , Hamada Kana , Chang Chieh
Published: January 2016

Precise temporal control of neuro differentiation and post‐differentiation events are necessary for the creation of appropriate wiring diagram in the brain. To make advances in the treatment of neurodevelopmental and neurodegenerative disorders, and traumatic brain injury, it is important to understand these mechanisms. Caenorhabditis elegans has emerged as a revolutionary tool for the study of neural circuits due to its genetic homology to vertebrates and ease of genetic manipulation. microRNA (miRNA), a ubiquitous class of small non‐coding RNA, that inhibits the expression of target genes, has emerged as an important timing control molecule through research conducted on C. elegans. This review will focus on the temporal control of neurodifferentiation and post‐differentiation events exerted by two conserved miRNAs, lin‐4 and let‐7. We summarize recent findings on the role of lin‐4 as a timing regulator controlling transition of sequential events in neuronal pathfinding and synaptic remodeling, and the role of let‐7 as a timing regulator that limits the regeneration potential of post‐differentiated AVM neurons as they age.
The 2011 flood event in the Mekong Delta: preparedness, response, damage and recovery of private households and small businesses
Authors: Chinh Do Thi , Bubeck Philip , Dung Nguyen Viet , Kreibich Heidi
Published: January 2016

Floods frequently cause substantial economic and human losses, particularly in developing countries. For the development of sound flood risk management schemes that reduce flood consequences, detailed insights into the different components of the flood risk management cycle, such as preparedness, response, flood impact analyses and recovery, are needed. However, such detailed insights are often lacking: commonly, only (aggregated) data on direct flood damage are available. Other damage categories such as losses owing to the disruption of production processes are usually not considered, resulting in incomplete risk assessments and possibly inappropriate recommendations for risk management. In this paper, data from 858 face‐to‐face interviews among flood‐prone households and small businesses in Can Tho city in the Vietnamese Mekong Delta are presented to gain better insights into the damage caused by the 2011 flood event and its management by households and businesses.
Cultural issues in post‐disaster reconstruction: the case of Typhoon Morakot in Taiwan
Authors: Lin Jen‐Jen , Lin Wan‐I
Published: January 2016

Most members of Taiwan's indigenous communities live in areas that are prone to natural disasters. Yet, due to their marginalised cultural, economic and political status, each time such calamities strike, any assistance they receive is usually provided without considering their actual needs. The areas hardest hit by Typhoon Morakot in August 2009 were the indigenous villages in the southern and eastern parts of the island. After the initial emergency relief efforts had been completed, there remained the highly challenging task of reconstruction and the resettlement of those who lost their homes and livelihoods. This paper examines the cultural conflicts that arose during the reconstruction process, with special emphasis on the participation of Taiwan's indigenous communities and their capacity for resilience. It was found that community participation and identification are key issues in effective disaster governance.
The Four Cs of disaster partnering: communication, cooperation, coordination and collaboration
Authors: Martin Eric , Nolte Isabelle , Vitolo Emma
Published: January 2016

Public, nonprofit and private organisations respond to large‐scale disasters domestically and overseas. Critics of these assistance efforts, as well as those involved, often cite poor interorganisational partnering as an obstacle to successful disaster response. Observers frequently call for ‘more’ and ‘better’ partnering. We found important qualitative distinctions existed within partnering behaviours. We identified four different types of interorganisational partnering activities often referred to interchangeably: communication, cooperation, coordination and collaboration—the Four Cs. We derived definitions of the Four Cs from the partnering literature. We then tested them in a case study of the response to the 2010 Haiti earthquake. We suggest that the Four Cs are distinct activities, that organisations are typically strong or weak in one or more for various reasons, and that the four terms represent a continuum of increased interorganisational embeddedness in partnering activities.
Vulnerability to typhoon hazards in the coastal informal settlements of Metro Manila, the Philippines
Authors: Morin Véronique M. , Ahmad Mokbul Morshed , Warnitchai Pennung
Published: January 2016

In many low‐ and middle‐income countries informal communities—also termed slum and squatter areas—have become a dominant and distinct form of urban settlement, with ever increasing populations. Such communities are often located in areas of high hazard exposure and frequently affected by disasters. While often recognised as one of the highest ‘at risk’ populations, this paper will argue that informal settlers have been directly and indirectly excluded from many formal mechanisms, thereby increasing their vulnerability to disaster events. Household surveys were conducted across several frequently flooded informal coastal communities in Metro Manila, the Philippines, following a major typhoon and storm surge disaster. The study revealed a large level of diversity in socio‐economic vulnerability, although all households faced similar levels of physical exposure and physical vulnerability. Disaster risk reduction policies and responses need to better integrate informal settlement areas and recognise the diversity within these communities.
‘Are you prepared?’ Representations and management of floods in Lomanikoro, Rewa (Fiji)
Authors: Nolet Emilie
Published: January 2016

The islands of Fiji, in the Western Pacific, are exposed to a wide range of natural hazards. Tropical storms and associated floods are recurring natural phenomena, but it has been regularly alleged that Fijians lack preparation, over‐rely on state assistance in post‐disaster situations or engage in risky behaviours that aggravate the negative impact of floods. Risk reduction strategies, which are now implemented by government authorities and international organisations, heavily promote the principle of ‘community preparedness’. Both community awareness programmes and capacity‐building programmes are conducted throughout the country in the most vulnerable communities. This paper analyses how the inhabitants of Lomanikoro village, in the low areas of the Rewa Delta, perceive and manage existing flood risks. It examines social and cultural factors that contribute to shape risk response locally—in particular, why villagers may be reluctant to adopt some recommended preparedness measures and resettle in higher, safer zones.
The Indian Ocean tsunami and private donations to NGOs
Authors: Kim Youngwan , Nunnenkamp Peter , Bagchi Chandreyee
Published: January 2016

Non‐governmental organisations (NGOs) are widely believed to raise their flag in humanitarian hotspots with a strong media presence in order to attract higher private donations. We assess this hypothesis by comparing the changes in donations between US‐based NGOs with and without aid operations in the four countries most affected by the tsunami in the Indian Ocean in 2004. Simple before‐after comparisons tend to support the hypothesis that ‘flying the flag’ helps attract higher private donations. However, performing a difference‐in‐difference‐in‐differences (DDD) approach, we find only weak indications that private donors systematically and strongly preferred NGOs with operations in the region. Extended specifications of the baseline regressions reveal that our major findings are robust. NGO heterogeneity matters in some respects, but the DDD results hold when accounting for proxies of the NGOs’ reputation and experience.
Assessing climate change and health vulnerability at the local level: Travis County, Texas
Authors: Prudent Natasha , Houghton Adele , Luber George
Published: January 2016

We created a measure to help comprehend population vulnerability to potential flooding and excessive heat events using health, built environment and social factors. Through principal component analysis (PCA), we created non‐weighted sum index scores of literature‐reviewed social and built environment characteristics. We created baseline poor health measures using 1999–2005 age‐adjusted cardiovascular and combined diabetes and hypertension mortality rates to correspond with social–built environment indices. We mapped US Census block groups by linked age‐adjusted mortality and a PCA‐created social–built environment index. The goal was to measure flooding and excessive heat event vulnerability as proxies for population vulnerability to climate change for Travis County, Texas. This assessment identified communities where baseline poor health, social marginalisation and built environmental impediments intersected. Such assessments may assist targeted interventions and improve emergency preparedness in identified vulnerable communities, while fostering resilience through the focus of climate change adaptation policies at the local level.
Of timelines and timeliness: lessons from Typhoon Haiyan in early disaster response
Authors: Santiago J. Sedfrey S. , Manuela Wilfred S. , Tan Marion Lara L. , Sañez Siegfried Kiel , Tong Aldo Zelig U.
Published: January 2016

Typhoon Haiyan struck the Philippines on 8 November 2013 with maximum sustained winds of 235 kilometres per hour, adversely affecting at least 11 million people and displacing some 673,000 in the central regions of the country. The disaster clearly overwhelmed the Philippine government despite its seemingly well‐crafted disaster management plan. Using timelines of different organisations, this paper identifies gaps in the government's response, mainly due to its failure in coordinating and managing relief operations, which adversely affected its effectiveness and efficiency in the delivery of critical goods and services following the disaster. The paper also demonstrates how non‐governmental organisations (NGOs), the United Nations, foreign governments and other organisations provided assistance, mainly through aid niching, to cover the government's shortcomings. The paper recommends a paradigm shift in the government's disaster response by integrating collaborative arrangements between government agencies and NGOs, and giving local governments the lead role, with the national government as support, in disaster planning and response.
Public perceptions and attitudes to biological risks: Saudi Arabia and regional perspectives
Authors: Alshehri Saud Ali , Rezgui Yacine , Li Haijiang
Published: January 2016

Saudi Arabia has experienced frequent occurrences of biological disasters due to a wide range of generator factors, including natural disasters and epidemics. A national survey (n=1,164) was conducted across 13 regions of Saudi Arabia to examine public perceptions to the risk of a biological disaster. The primary results reveal: (a) a degree of knowledge about biological threats such as SARS and H5N1 flu, despite the lack of individual experience with disasters; (b) age, gender, education and faith are positively related to the perception of biological risk; and (c) a number of important community resilience factors exist, including faith, education and willingness. This study concludes that the development of adapted resilience strategies in disaster management can be achieved through public education and training involving cooperation with official organisations and religious authorities in the country to increase public awareness, knowledge and skills in mitigating biological threats.
Efficacy and safety of LY2963016 insulin glargine in patients with type 1 and type 2 diabetes previously treated with insulin glargine
Authors: Hadjiyianni I. , Dahl D. , Lacaya L. B. , Pollom R. K. , Chang C. L. , Ilag L. L.
Published: January 2016

The safety and efficacy of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, were assessed in subgroups of patients with type 1 (T1D, n = 452) or type 2 diabetes (T2D, n = 299) reporting prestudy IGlar treatment in 52‐week open‐label (ELEMENT‐1) and 24‐week double‐blind (ELEMENT‐2) studies. At randomization, patients transitioned from their prestudy IGlar to equivalent doses of LY IGlar or IGlar. Primary efficacy (change in glycated haemoglobin from baseline to 24 weeks), other efficacy and select safety outcomes of LY IGlar were compared with those of IGlar. Continuous data were analysed using analysis of covariance, categorical data by Fisher's exact test, and treatment comparisons for hypoglycaemia by Wilcoxon test. No statistically significant treatment differences were identified for efficacy and safety outcomes except for weight change (T1D), overall incidence of detectable insulin antibodies (T2D), and serious adverse events (T2D). These differences were neither consistently observed across both studies nor observed in the total study populations, and their magnitude suggests they were not clinically meaningful. LY IGlar and IGlar show similar efficacy and safety profiles in patients reporting prestudy IGlar treatment.
Effect of ranolazine on glycaemic control in patients with type 2 diabetes treated with either glimepiride or metformin
Authors: Pettus J. , McNabb B. , Eckel R. H. , Skyler J. S. , Dhalla A. , Guan S. , Jochelson P. , Belardinelli L. , Henry R. H.
Published: January 2016

Aim

To report the results of two phase III trials assessing the efficacy of ranolazine for glycaemic control in patients with type 2 diabetes on metformin or glimepiride background therapy.

Methods

In two double‐blind trials we randomized 431 and 442 patients with type 2 diabetes to ranolazine 1000 mg twice daily versus placebo added to either glimepiride (glimepiride add‐on study) or metformin background therapy (metformin add‐on study). Patients receiving ranolazine added to metformin had their metformin dose halved (with the addition of a metformin‐matched placebo) relative to the placebo group to correct for a metformin‐ranolazine pharmacokinetic interaction. The primary endpoint of the trials was the change from baseline in glycated haemoglobin (HbA1c) at week 24.

Results

When added to glimepiride, ranolazine caused a 0.51% least squares mean [95% confidence interval (CI) 0.71, 0.32] decrease from baseline in HbA1c at 24 weeks relative to placebo and roughly doubled the proportion of patients achieving an HbA1c of <7% (27.1 vs 14.1%; p = 0.001). When added to metformin background therapy, there was no significant difference in the 24‐week HbA1c change from baseline [placebo‐corrected LS mean difference −0.11% (95% CI −0.31, 0.1)].

Conclusions

Compared with placebo, addition of ranolazine in patients with type 2 diabetes treated with glimepiride, but not metformin, significantly reduced HbA1c over 24 weeks. The decreased dose of metformin used in the metformin add‐on study complicates the interpretation of this trial. Whether an effective regimen of ranolazine added to metformin for glycaemic control can be identified remains unclear.
Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase‐4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24‐week multicentre, randomized, double‐blind, placebo‐controlled phase III trial
Authors: Hong S. , Park C.‐Y. , Han K. A. , Chung C. H. , Ku B. J. , Jang H. C. , Ahn C. W. , Lee M.‐K. , Moon M. K. , Son H. S. , Lee C. B. , Cho Y.‐W. , Park S.‐W.
Published: January 2016

We assessed the 24‐week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase‐4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were −0.94% [least‐squares (LS) mean −1.22, −0.65] and −1.21 mmol/l (−1.72, −0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo‐controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM.
Changes in soil organic carbon fractions after afforestation with xerophytic shrubs in theTenggerDesert,northernChina
Authors: Li X. J. , Li X. R. , Wang X. P. , Yang H. T.
Published: January 2016

Afforestation is an important means of controlling desertification and of restoring vegetation on land that has become desert. The procedure leads to changes in the dynamics of organic carbon (C) in the soil as xerophytic shrubs are established, but the dynamics are still poorly understood, partly because of the lack of long‐term observations. Progressive measures to bind sand dunes along the route of theBaotou–Lanzhou railway on the south eastern edge of theTenggerDesert inChina, which were begun in 1956, provide the opportunity to study such changes. We sampled the topsoil (0–10 cm) from 10 sites that represent a chronosequence and vary in age from 1 to 57 years since sand‐binding measures and afforestation were begun. These measures evidently trapped increasing amounts of clay and silt, and with them increased the concentrations of both available phosphorus (P) and available potassium (K). By analysing the organicCin the samples we have been able to describe quantitatively the changes in severalCfractions over time. We found that totalC, its light and heavy fractions, dissolvedCand microbialCall increase slowly at first after afforestation, then more rapidly, and then at a decreasing rate. They seem to be examples of logistic growth and could be described by logistic equations. The light fraction increased faster than the totalC, as did the microbialCduring the first 19 years. The lightCfraction was the most sensitive for identifying changes in soilCafter afforestation. Over the full 57 years, the contributions of the light and microbial fractions to totalCincreased, while those of the heavy fraction and dissolvedCdecreased. Our results suggest that the proportion ofCin labile pools increased, but the proportion in stable pools decreased, which would increase the risk of substantial losses ofCcaused by potential global warming and human‐induced disturbances.
The Role of Embedded Individual Values, Belief and Attitudes and Spiritual Capital in Shaping Everyday Postsecular Organizational Culture
Authors: Stokes Peter , Baker Christopher , Lichy Jessica
Published: January 2016

This paper investigates the values, beliefs and attitudes (VBA) held by individual employees within business environments which motivate and shape behavior in the workplace, and the extent to which VBA reveal roots and drivers linked to spiritual capital (and associated capitals). Building on early authorial work (Baker, Stokes, Lichy, Atherton, 2011), and referring to literature from theology and religion, as well as business organization and management, the paper discusses the critical and dialectical relationship between different forms of capital (for example, social, human, economic), modernistic, ‘hard’ cultures and issues of managerialism and alternative critical, ‘soft’ frameworks and sources of ethics and values – and their impact on the business setting. It will do this primarily by proposing a new typological model showing the dynamic and potentially progressive interplay between spiritual, human, bridging and linking forms of social capital within corporate and public settings and explores their implications for management. This typological model is derived from original research using in‐depth semi‐structured interviews from three different organizations in North West England and North Wales, to determine the extent to which notions of the postsecular and spiritual capital may operate in workplaces.
All That We Know Dariusz Jemielniak Common knowledge? An ethnography of Wikipedia. (Stanford University Press 2014)
Authors: Bourne Dorota Joanna
Published: January 2016

This article presents a review of an ethnography of Wikipedia by professor Dariusz Jemielniak: Common Knowledge? An Ethnography of Wikipedia published in 2014 by Stanford University Press. Following an introductory discussion on Wikipedia's importance in today's society and academic literature, the main content and structure of the book are outlined together with the key points raised by Jemielniak in each chapter. Limitations of the book and some critical comments on this work are presented in the third section. The article ends with the conclusions regarding overall contribution of the book and its potential readership.
50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate
Authors: Cavus Idil , Widi Gabriel A. , Duckrow Robert B. , Zaveri Hitten , Kennard Jeremy T. , Krystal John , Spencer Dennis D.
Published: January 2016

Objective

The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure.

Methods

Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation–associated glutamate concentrations, basal zero‐flow levels, and stimulated seizures were examined.

Results

Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation‐induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R2 = 0.81, p = 0.001). The evoked‐seizure group had lower basal glutamate levels than the no‐seizure group (p = 0.04), with no stimulation‐induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no‐seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation‐induced glutamate efflux.

Significance

Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated glutamate increase was related to elevation in basal interictal glutamate, suggesting a common mechanism, possibly impaired glutamate metabolism. Divergent mechanisms may exist for seizure induction and increased glutamate in patients with epilepsy. These data highlight the potential risk of 50 Hz stimulation in patients with epilepsy.
Technical aspects of pediatric epilepsy surgery: Report of a multicenter, multinational web‐based survey by the ILAE Task Force on Pediatric Epilepsy Surgery
Authors: Cukiert Arthur , Rydenhag Bertil , Harkness William , Cross J. Helen , Gaillard William D. ,   the Task Force for Pediatric Epilepsy Surgery for the ILAE Commissions of Pediatrics and Surgical Therapies
Published: January 2016

Surgical techniques may vary extensively between centers. We report on a web‐based survey aimed at evaluating the current technical approaches in different centers around the world performing epilepsy surgery in children. The intention of the survey was to establish technical standards. A request was made to 88 centers to complete a web‐based survey comprising 51 questions. There were 14 questions related to general issues, 13 questions investigating the different technical aspects for children undergoing epilepsy surgery, and 24 questions investigating surgical strategies in pediatric epilepsy surgery. Fifty‐two centers covering a wide geographic representation completed the questionnaire. The median number of resective procedures per center per year was 47. Some important technical practices appeared (>80% of the responses) such as the use of prophylactic antibiotics (98%), the use of high‐speed drills for bone opening (88%), nonresorbable material for bone flap closure (85%), head fixation (90%), use of the surgical microscope (100%), and of free bone flaps. Other questions, such as the use of drains, electrocorticography (ECoG) and preoperative withdrawal of valproate, led to mixed, inconclusive results. Complications were noted in 3.8% of the patients submitted to cortical resection, 9.9% hemispheric surgery, 5% callosotomy, 1.8% depth electrode implantation, 5.9% subdural grids implantation, 11.9% hypothalamic hamartoma resection, 0.9% vagus nerve stimulation (VNS), and 0.5% deep brain stimulation. There were no major differences across regions or countries in any of the subitems above. The present data offer the first overview of the technical aspects of pediatric epilepsy surgery worldwide. Surprisingly, there seem to be more similarities than differences. That aside many of the evaluated issues should be examined by adequately designed multicenter randomized controlled trials (RCTs). Further knowledge on these technical issues might lead to increased standardization and lower costs in the future, as well as definitive practice guidelines.
Distinct white matter integrity in glutamic acid decarboxylase and voltage‐gated potassium channel‐complex antibody‐associated limbic encephalitis
Authors: Wagner Jan , Schoene‐Bake Jan‐Christoph , Witt Juri‐Alexander , Helmstaedter Christoph , Malter Michael P. , Stoecker Winfried , Probst Christian , Weber Bernd , Elger Christian E.
Published: January 2016

Objective

Autoantibodies against glutamic acid decarboxylase (GAD) and the voltage‐gated potassium channel (VGKC) complex are associated with distinct subtypes of limbic encephalitis regarding clinical presentation, response to therapy, and outcome. The aim of this study was to investigate white matter changes in these two limbic encephalitis subtypes by means of diffusion tensor imaging (DTI).

Methods

Diffusion data were obtained in 14 patients with GAD antibodies and 16 patients with VGKC‐complex antibodies and compared with age‐ and gender‐matched control groups. Voxelwise statistical analysis was carried out using tract‐based spatial statistics. The results were furthermore compared with those of 15 patients with unilateral histologically confirmed hippocampal sclerosis and correlated with verbal and figural memory performance.

Results

We found widespread changes of fractional anisotropy and all diffusivity parameters in GAD‐associated limbic encephalitis, whereas no changes were found in VGKC‐complex–associated limbic encephalitis. The changes observed in the GAD group were even more extensive when compared against those of the hippocampal sclerosis group, although the disease duration was markedly shorter in patients with GAD antibodies. Correlation analysis revealed areas with a trend toward a negative correlation of diffusivity parameters with figural memory performance located mainly in the right temporal lobe in the GAD group as well.

Significance

The present study provides further evidence that, depending on the associated antibody, limbic encephalitis features clearly distinct imaging characteristics by showing widespread white matter changes in GAD‐associated limbic encephalitis and preserved white matter integrity in VGKC‐complex–associated limbic encephalitis. Furthermore, our results contribute to a better understanding of the specific pathophysiologic properties in these two subforms of limbic encephalitis by revealing that patients with GAD antibodies show widespread affections of white matter across various regions of the brain. In contrast to this, the inflammatory process seems to be more localized in VGKC‐complex–associated limbic encephalitis, primarily affecting mesiotemporal gray matter.
Autosomal dominant cortical tremor, myoclonus, and epilepsy (ADCME) in a unique south Indian community
Authors: Mahadevan Radha , Viswanathan Natarajan , Shanmugam Ganesan , Sankaralingam Saravanan , Essaki Bobby , Chelladurai Rachel P.
Published: January 2016

Autosomal dominant cortical tremor, myoclonus, and epilepsy (ADCME)/familial adult onset myoclonic epilepsy (FAME) is a nonprogressive disorder characterized by (1) distal tremors that are usually precipitated by posture and action; (2) stimulus‐sensitive myoclonus that is predominantly seen in the upper limb and is precipitated by photic stimuli, fatigue, emotional stress, and sleep deprivation; (3) seizures that were predominantly of the generalized tonic–clonic type that showed significant response to antiepileptic drugs (AEDs). ADCME has been reported worldwide with different genetic loci in Japanese families (8q23.3‐q24.1), Italian families (2p11.1‐q12.2), a French family (5p15.3.1‐p15.1), and a Thai family (3q26.32‐q28). ADCME has not been reported in South India and is still not recognized as an independent entity under the International League Against Epilepsy (ILAE). We report 241 patients with ADCME identified belonging to 48 families. The 48 families are domiciled in two southern districts of Tamilnadu in India, belonging to a community called “Nadar” whose nativity is confined to these southern districts, with reported unique genetic characteristics. This study is reported for the presentation of this rare disease in a unique ethnic group, and is the largest single report on ADCME worldwide.
Gene flow from an adaptively divergent source causes rescue through genetic and demographic factors in two wild populations of Trinidadian guppies
Authors: Fitzpatrick Sarah W. , Gerberich Jill C. , Angeloni Lisa M. , Bailey Larissa L. , Broder Emily D. , Torres‐Dowdall Julian , Handelsman Corey A. , López‐Sepulcre Andrés , Reznick David N. , Ghalambor Cameron K. , Chris Funk W.
Published: January 2016

Genetic rescue, an increase in population growth owing to the infusion of new alleles, can aid the persistence of small populations. Its use as a management tool is limited by a lack of empirical data geared toward predicting effects of gene flow on local adaptation and demography. Experimental translocations provide an ideal opportunity to monitor the demographic consequences of gene flow. In this study we take advantage of two experimental introductions of Trinidadian guppies to test the effects of gene flow on downstream native populations. We individually marked guppies from the native populations to monitor population dynamics for 3 months before and 26 months after gene flow. We genotyped all individuals caught during the first 17 months at microsatellite loci to classify individuals by their genetic ancestry: native, immigrant, F1 hybrid, F2 hybrid, or backcross. Our study documents a combination of demographic and genetic rescue over multiple generations under fully natural conditions. Within both recipient populations, we found substantial and long‐term increases in population size that could be attributed to high survival and recruitment caused by immigration and gene flow from the introduction sites. Our results suggest that low levels of gene flow, even from a divergent ecotype, can provide a substantial demographic boost to small populations, which may allow them to withstand environmental stochasticity.
Control of helminth parasites in juvenile horses
Authors: Reinemeyer C. R. , Nielsen M. K.
Published: January 2016

Parasite control in juvenile horses remains a substantial challenge for veterinary practitioners and their clients. This age group is at risk for various types of parasitic disease because their worm burdens tend to be larger and more diverse than in mature horses. This contrast is largely attributable to marked differences in relative levels of acquired immunity. Frequent, perennial anthelmintic treatment is not a sustainable approach for parasite control in this age group, but the simple, surveillance‐based parasite control strategies recommended for mature horses are not appropriate for juveniles either. Maneuvering through the early years of a horse's life requires up‐to‐date knowledge about biology and epidemiology of the parasite species in play as well as local evidence regarding the anthelmintic resistance status of each herd. This article provides an overview of the most important helminth parasites to target in a control programme for juvenile horses, and highlights how the target species change as horses age. Young foals (<2 months) are exposed toStrongyloides westeriandParascarisspp., whereas the primary target parasite in foals between age 2 months and weaning isParascarisspp. Beyond weaning, the focus shifts away from ascarids, and the targets instead are strongyles and tapeworms.Gasterophilusspp. andOxyuris equiare also discussed.
RANK as a therapeutic target in cancer
Authors: González‐Suárez Eva , Sanz‐Moreno Adrián
Published: January 2016

The RANK signaling pathway has emerged as a new target in breast cancer as receptor activator of nuclear factor κB ligand (RANKL) and its receptor RANK mediate the pro‐tumorigenic role of progesterone in the mammary gland. Thousands of cancer patients worldwide are already taking RANKL inhibitors for the management of bone metastasis, given the relevance of this pathway in osteoclastogenesis and bone resorption. RANK signaling also has multiple divergent effects in immunity and inflammation, both in the generation of active immune responses and in the induction of tolerance: it is required for lymph node organogenesis, thymic medullary epithelial development and self‐tolerance, and regulates activation of several immune cells and inflammatory processes. The RANK pathway interferes with mammary epithelial differentiation and mediates the major proliferative response of mammary epithelium to progesterone and progesterone‐driven expansion of mammary stem cells; it also controls hair follicle and epidermal stem cell homeostasis, pointing to RANK as a key regulator of epithelial stemness. Here we revisit the main functions of RANK signaling in bone remodeling, immune cells and epithelial differentiation. We also discuss the mechanistic evidence that supports its pleiotropic effects on cancer: from bone metastasis to immune and cancer‐cell‐dependent effects.
Structural basis of substrate specificity in porcine RNase 4
Authors: Liang Shutian , Acharya K. Ravi
Published: January 2016

RNase 4, a member of the RNase A superfamily with substrate preference for uridine, has roles in host defence, angiogenesis and neurodegenerative diseases. It also exhibits the highest interspecies amino acid sequence similarity amongst RNase A family members. However, compared to other members of the RNase A family, including eosinophil‐derived neurotoxin, eosinophil cationic protein and angiogenin, little is known about the molecular basis of substrate specificity in RNase 4. Here we report high to medium resolution structures of native porcine RNase 4 (PL3), a ‘substrate‐specificity’ determining mutant D80A and their respective complexes with deoxyuridine 5′‐monophosphate (dUMP) and deoxycytidine 5′‐monophosphate (dCMP). These structures provide insight into the structural basis of the uridine versus cytosine substrate specificity in RNase 4: in the D80A mutant (D80A•dCMP), the side chain of Arg101 is positioned further away from the substrate‐binding pocket due to the loss of the Asp80 side chain, reducing the repulsion force on the less favoured dCMP from Arg101 and allowing the ligand to occupy the binding pocket. This can also explain the observation that the ligand in the D80A•dCMP complex is stabilized only by a small number of hydrogen bonds. Compared to the previously reported structure of the human RNase 4•2′‐deoxyuridine 3′‐phosphate complex, the structure of PL3•dUMP complex shows additional hydrogen bonds between the ligand and the protein. In addition, the interaction between Arg101 and the dUMP ligand is absent. These observed differences are probably the result of the flexibility and different ‘positioning’ of the phosphate group among the mononucleotide ligands.

Database

The atomic coordinates and structure factors for PL3 (5AR6), D80A (5ARJ), PL3∙dUMP (5ARK) and D80A∙dCMP (5ARL) complexes have been deposited with the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ, USA (http://www.rcsb.org/).
Kinetic and structural characterization of amyloid‐β peptide hydrolysis by human angiotensin‐1‐converting enzyme
Authors: Larmuth Kate M. , Masuyer Geoffrey , Douglas Ross G. , Schwager Sylva L. , Acharya K. Ravi , Sturrock Edward D.
Published: January 2016

Angiotensin‐1‐converting enzyme (ACE), a zinc metallopeptidase, consists of two homologous catalytic domains (N and C) with different substrate specificities. Here we report kinetic parameters of five different forms of human ACE with various amyloid beta (Aβ) substrates together with high resolution crystal structures of the N‐domain in complex with Aβ fragments. For the physiological Aβ(1–16) peptide, a novel ACE cleavage site was found at His14‐Gln15. Furthermore, Aβ(1–16) was preferentially cleaved by the individual N‐domain; however, the presence of an inactive C‐domain in full‐length somatic ACE (sACE) greatly reduced enzyme activity and affected apparent selectivity. Two fluorogenic substrates, Aβ(4–10)Q and Aβ(4–10)Y, underwent endoproteolytic cleavage at the Asp7‐Ser8 bond with all ACE constructs showing greater catalytic efficiency for Aβ(4–10)Y. Surprisingly, in contrast to Aβ(1–16) and Aβ(4–10)Q, sACE showed positive domain cooperativity and the double C‐domain (CC‐sACE) construct no cooperativity towards Aβ(4–10)Y. The structures of the Aβ peptide–ACE complexes revealed a common mode of peptide binding for both domains which principally targets the C‐terminal P2′ position to the S2′ pocket and recognizes the main chain of the P1′ peptide. It is likely that N‐domain selectivity for the amyloid peptide is conferred through the N‐domain specific S2′ residue Thr358. Additionally, the N‐domain can accommodate larger substrates through movement of the N‐terminal helices, as suggested by the disorder of the hinge region in the crystal structures. Our findings are important for the design of domain selective inhibitors as the differences in domain selectivity are more pronounced with the truncated domains compared to the more physiological full‐length forms.

Database

The atomic coordinates and structure factors for N‐domain ACE with Aβ peptides 4–10 (5AM8), 10–16 (5AM9), 1–16 (5AMA), 35–42 (5AMB) and (4–10)Y (5AMC) complexes have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ, USA (http://www.rcsb.org/).
Socially Responsible Investing by Universities and Colleges
Authors: Smith Janet Kiholm , Smith Richard L.
Published: January 2016

We analyze the socially responsible investing (SRI) practices of universities and colleges. Although SRI may align with an institution's mission and enhance its “brand,” these activities may also arise from agency problems. We find evidence of both effects. Consistent with branding effects, we find significant differences between independent and church‐affiliated schools, we find that highly selective and elite schools do not seek differentiation through SRI and are unlikely to sacrifice returns for SRI, and we find that Less Selective schools appear to regard costs of SRI as branding investments. Consistent with agency problems, attributes of investment committees bear on policy choices. For independent schools, larger committees and those where professional representation is low are likely to screen, allow sustainability considerations to influence investment choices, and vote proxies along SRI lines. “Social boards,” those with more alumni and less investments expertise, appear more oriented toward generating donations and less focused on investment policy.
Land cover change and carbon emissions over 100 years in an African biodiversity hotspot
Authors: Willcock Simon , Phillips Oliver L. , Platts Philip J. , Swetnam Ruth D. , Balmford Andrew , Burgess Neil D. , Ahrends Antje , Bayliss Julian , Doggart Nike , Doody Kathryn , Fanning Eibleis , Green Jonathan M. H. , Hall Jaclyn , Howell Kim L. , Lovett Jon C. , Marchant Rob , Marshall Andrew R. , Mbilinyi Boniface , Munishi Pantaleon K. T. , Owen Nisha , Topp‐Jorgensen Elmer J. , Lewis Simon L.
Published: January 2016

Agricultural expansion has resulted in both land use and land cover change (LULCC) across the tropics. However, the spatial and temporal patterns of such change and their resulting impacts are poorly understood, particularly for the presatellite era. Here, we quantify the LULCC history across the 33.9 million ha watershed of Tanzania's Eastern Arc Mountains, using geo‐referenced and digitized historical land cover maps (dated 1908, 1923, 1949 and 2000). Our time series from this biodiversity hotspot shows that forest and savanna area both declined, by 74% (2.8 million ha) and 10% (2.9 million ha), respectively, between 1908 and 2000. This vegetation was replaced by a fivefold increase in cropland, from 1.2 million ha to 6.7 million ha. This LULCC implies a committed release of 0.9 Pg C (95% CI: 0.4–1.5) across the watershed for the same period, equivalent to 0.3 Mg C ha−1 yr−1. This is at least threefold higher than previous estimates from global models for the same study area. We then used the LULCC data from before and after protected area creation, as well as from areas where no protection was established, to analyse the effectiveness of legal protection on land cover change despite the underlying spatial variation in protected areas. We found that, between 1949 and 2000, forest expanded within legally protected areas, resulting in carbon uptake of 4.8 (3.8–5.7) Mg C ha−1, compared to a committed loss of 11.9 (7.2–16.6) Mg C ha−1 within areas lacking such protection. Furthermore, for nine protected areas where LULCC data are available prior to and following establishment, we show that protection reduces deforestation rates by 150% relative to unprotected portions of the watershed. Our results highlight that considerable LULCC occurred prior to the satellite era, thus other data sources are required to better understand long‐term land cover trends in the tropics.