bluuebunny/crossref_metadata_2025 huggingface dataset:
NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models
Authors: Charych Deborah H. , Hoch Ute , Langowski John L. , Lee Steve R. , Addepalli Murali K. , Kirk Peter B. , Sheng Dawei , Liu Xiaofeng , Sims Paul W. , VanderVeen Laurie A. , Ali Cherie F. , Chang Thomas K. , Konakova Marina , Pena Rhoneil L. , Kanhere Rupesh S. , Kirksey Yolanda M. , Ji Chunmei , Wang Yujun , Huang Jicai , Sweeney Theresa D. , Kantak Seema S. , Doberstein Stephen K.
Published: February 2016

Purpose: Aldesleukin, recombinant human IL2, is an effective immunotherapy for metastatic melanoma and renal cancer, with durable responses in approximately 10% of patients; however, severe side effects limit maximal dosing and thus the number of patients able to receive treatment and potential cure. NKTR-214 is a prodrug of conjugated IL2, retaining the same amino acid sequence as aldesleukin. The IL2 core is conjugated to 6 releasable polyethylene glycol (PEG) chains. In vivo, the PEG chains slowly release to generate active IL2 conjugates.

Experimental Design: We evaluated the bioactivity and receptor binding of NKTR-214 and its active IL2 conjugates in vitro; the tumor immunology, tumor pharmacokinetics, and efficacy of NKTR-214 as a single agent and in combination with anti–CTLA-4 antibody in murine tumor models. Tolerability was evaluated in non-human primates.

Results: In a murine melanoma tumor model, the ratio of tumor-killing CD8+ T cells to Foxp3+ regulatory T cells was greater than 400 for NKTR-214 compared with 18 for aldesleukin, supporting preferential activation of the IL2 receptor beta over IL2 receptor alpha, due to the location of PEG molecules. NKTR-214 provides a 500-fold greater exposure of the tumor to conjugated IL2 compared with aldesleukin. NKTR-214 showed efficacy as a single agent and provided durable immunity that was resistant to tumor rechallenge in combination with anti–CTLA-4 antibody. NKTR-214 was well tolerated in non-human primates.

Conclusions: These data support further evaluation of NKTR-214 in humans for a variety of tumor types, adding to the repertoire of potent and potentially curative cancer immunotherapies. Clin Cancer Res; 22(3); 680–90. ©2016 AACR.
The β3 Adrenergic Receptor Agonist BRL37344 Exacerbates Atrial Structural Remodeling Through iNOS Uncoupling in Canine Models of Atrial Fibrillation
Authors: Wang Xiaobing , Wang Ruifeng , Liu Guangzhong , Dong Jingmei , Zhao Guanqi , Tian Jingpu , Sun Jiayu , Jia Xiuyue , Wei Lin , Wang Yuping , Li Weimin
Published: February 2016

Background/Aims: The role of the β3-adrenergic receptor (β3-AR) agonist BRL37344 in atrial fibrillation (AF) structural remodeling and the underlying mechanisms as a therapeutic target were investigated. Methods: Four groups of dogs were evaluated: sham, pacing, β3-AR agonist BRL37344 (β3-AGO), and β3-AR antagonist L748337 (β3-ANT) groups. Dogs in the pacing, β3-AGO and β3-ANT groups were subjected to rapid atrial pacing for four weeks. Atrial structure and function, AF inducibility and duration, atrial myocyte apoptosis and interstitial fibrosis were assessed. Atrial superoxide anions were evaluated by fluorescence microscopy and colorimetric assays. Cardiac nitrate+nitrite levels were used to assess nitric oxide (NO) production. Protein and mRNA expression of β3-AR, neuronal NO synthase (nNOS), inducible NO synthase (iNOS), endothelial NO synthase (eNOS) and guanosine triphosphate cyclohydrolase-1 (GCH-1) as well as tetrahydrobiopterin (BH4) levels were measured. Results: β3-AR was up-regulated in AF. Stimulation of β3-AR significantly increased atrial myocyte apoptosis, fibrosis and atrial dilatation, resulting in increased AF induction and prolonged duration. These effects were attenuated by β3-ANT. Moreover, β3-AGO reduced BH4 and NO production and increased superoxide production, which was inhibited by the specific iNOS inhibitor, 1400w β3-AGO also increased iNOS but decreased eNOS and had no effect on nNOS expression in AF. Conclusions: β3-AR stimulation resulted in atrial structural remodeling by increasing iNOS uncoupling and related oxidative stress. β3-AR up-regulation and iNOS uncoupling might be underlying AF therapeutic targets.
Spermine inhibits Endoplasmic Reticulum Stress - induced Apoptosis: a New Strategy to Prevent Cardiomyocyte Apoptosis
Authors: Wei Can , Wang Yuehong , Li Meixiu , Li Hongzhu , Lu Xiaoxiao , Shao Hongjiang , Xu Changqing
Published: February 2016

Background/Aims: Endoplasmic reticulum stress (ERS) plays an important role in the progression of acute myocardial infarction (AMI), in part by mediating apoptosis. Polyamines, including putrescine, spermidine, and spermine, are polycations with anti-oxidative, anti-aging, and cell growth-promoting activities. This study aimed to determine the mechanisms by which spermine protects against ERS-induced apoptosis in rats following AMI. Methods and Results: AMI was established by ligation of the left anterior descending coronary artery (LAD) in rats, and exogenous spermine was administered by intraperitoneal injection (2.5 mg/ml daily for 7 days pre-AMI). Spermine treatment limited infarct size, attenuated cardiac troponin I and creatinine kinase-MB release, improved cardiac function, and decreased ERS and apoptosis related protein expression. Isolated cardiomyocytes subjected to hypoxia showed significant increase in reactive oxygen species (ROS) and the expression of apoptosis and ERS related proteins; these effects occurred through PERK and eIF2α phosphorylation. The addition of spermine attenuated cardiomyocyte apoptosis, suppressed the production of ROS, and inhibited ERS related pathways. Conclusions: Spermine was an effective pre-treatment strategy to attenuate cardiac ERS injury in rats, and the cardioprotective mechanism occurring through inhibition of ROS production and down regulation of the PERK-eIF2α pathway. These findings provide a novel target for the prevention of apoptosis in the setting of AMI.
Apoptosis of THP-1 Macrophages Induced by Pseudohypericin-Mediated Sonodynamic Therapy Through the Mitochondria-Caspase Pathway
Authors: Zheng Xiufeng , Wu Jinrong , Shao Qun , Li Xuesong , Kou Jiayuan , Zhu Xing , Zhong Zhaoyu , Jiang Yueqing , Liu Zhongni , Li Hongxia , Tian Ye , Yang Liming
Published: February 2016

Background/Aims: Pseudohypericin (P-HY) and its congener hypericin are the major hydroxylated phenanthroperylenediones present in Hypericum species. Our previous study indicated that hypericin was able to function as a sonosensitizer. The potential use of P-HY as a sonosensitizer for sonodynamic therapy (SDT) requires further exploration. Thus, this study aimed to investigate the effects of P-HY-SDT on THP-1 macrophages. Methods: THP-1 macrophages were incubated with P-HY, and cell viability was measured using a CCK-8 assay. Fluorescence microscopy assessed the intracellular reactive oxygen species (ROS), mitochondrial membrane potential (∆Ψm) and mitochondrial permeability transition pore (mPTP) opening. Apoptotic and necrotic cell levels were measured by the flow cytometry analysis. Western blots were employed to assay BAX, Cytochrome C expression and apoptosis-related proteins. Results: P-HY-SDT induced THP-1 macrophage apoptosis. The levels of ROS were significantly increased in the SDT group, resulting in both mPTP opening and ∆Ψm loss, which led to apoptosis. In addition, the translocation of BAX, release of Cytochrome C and the upregulated expression of apoptosis-related proteins after P-HY-SDT were observed, all of which were reversed by N-acetyl cysteine (NAC). Conclusion: P-HY-SDT induced THP-1 macrophage apoptosis through the mitochondria-caspase pathway via ROS generation, the translocation of BAX and the release of Cytochrome C to regulate the mPTP opening.
Genital Lichen Sclerosus in Male Patients: A New Treatment with Polydeoxyribonucleotide
Authors: Zucchi Alessandro , Cai Tommaso , Cavallini Giorgio , D'Achille Giuseppe , Pastore Antonio Luigi , Franco Giorgio , Lepri Luca , Costantini Elisabetta
Published: February 2016

Lichen sclerosus (LS) is an inflammatory and chronic disease that causes itching, pain, dysuria, urinary retention, dyspareunia and sexual dysfunction, in both men and women. The first line pharmacological treatment is based on the use of topical steroids, which have proved their efficacy in 60-70% of cases but with a high rate of relapses in time (50-80% of the patients of both sexes). The purpose of our non-randomised prospective pilot study was to evaluate the efficacy and tolerability of a new loco regional therapy with polydeoxyribonucleotides (PDRN) in the treatment of male genital LS. PDRN is an healing and anti-dystrophic drug with anti-inflammatory effects, through the reduction of cytokine. Twenty one male patients suffering from genital LS were recruited. All the patients were submitted to treatment using loco-regional intradermal injections with PDRN. Dermatology Life Quality Index (DLQI), International Index of Erectile Function (IIEF-5) and PGI-I questionnaires were administered at baseline and at the end of treatment in order to evaluate the results of this treatment. The statistical evaluation of the data obtained with the DLQI questionnaire showed a marked improvement of the overall conditions in terms of quality of life, with an average change of scores from 15 to 4 (p < 0.0001). PGI-I questionnaire showed that 80% of the patients treated considered their post-treatment conditions as ‘improved'. There was no significant change in terms of sexual function according to the IIEF questionnaire (p = 0.189). The results obtained show the excellent tolerability and the therapeutic efficacy of PDRN, with clear improvement of the local symptoms and of the quality of life.
The Contribution of Diffusion Tensor Imaging to Quantitative Assessment on Multilevel Cervical Spondylotic Myelopathy
Authors: Ying Jinwei , Zhou Xiaojun , Zhu Minyu , Zhou Yang , Huang Kelun , Zhou Beibei , Teng Honglin
Published: February 2016

Background/Aims: This study aimed at assessing the feasibility of diffusion tensor imaging (DTI) in multilevel cervical spondylotic myelopathy (MCSM) and quantifying the association between DTI parameters and neuronal status as a whole. Methods: Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were obtained from 32 patients with MCSM and 21 healthy volunteers at each level. The extent of cervical cord compression was evaluated by maximum spinal cord compression (MSCC). The DTI parameters were correlated with myelopathy severity based on modified Japanese Orthopedic Association (mJOA) score in comparison with anatomic morphological and signal changes on MRI. Results: There were significant differences in the DTI values between the patients and those in the control group (p < 0.001). The general mean FA values correlated with mJOA scores strongly (r = 0.507, p = 0.003), even more than MSCC (r = -0.361, p = 0.042); however, such an association was not detected between ADC values and clinical findings (p > 0.05). Conclusion: DTI shows a higher potential to quantitatively evaluate the whole neurological deficits of patients with MCSM. It helps us better understand the minor pathological changes within the spinal cord at an earlier stage than abnormal signal changes on MRI.
Impact of Alzheimer's Disease in Nine Asian Countries
Authors: Yang Yuan-Han , Meguro Kenichi , Kim Sang-Yun , Shim Yong-Soo , Yu Xin , Chen Christopher Li-Hsian , Wang Huali , Lam Linda , Senanarong Vorapun , Dominguez Jacqueline , Lu Pei-yuan , Lin Yu-Te , Hu Chaur-Jong , Chiu Pai-Yi , Fuh Jong-Ling , Wang Wen-Fu , Yu Bao-Cheng , Li Tao , Wang Ming-Wei , Situmeang Rocksy Fransisca V. , Jang Jae-Won , Zhang Jing , Chan Wai-Chi , Zhou Yu-Ying , Lou Hui-ling , Zhang Li , Ye Min , Chen Xu
Published: February 2016

Background: Asia will soon have the majority of demented patients in the world. Objective: To assess dementia using a uniform data system to update the current status of dementia in Asia. Methods: A uniformed data set was administered in Taiwan, China, Hong Kong, Korea, Japan, Philippines, Thailand, Singapore, and Indonesia to gather data with regard to Alzheimer's disease (AD) and its related issues for these countries. Results: In total, 2,370 AD patients and their caregivers were recruited from 2011 to 2014. The demographic characteristics of these patients and the relationships between patients and caregivers were different among individuals in these countries (p < 0.001). Of note, the family history for having dementia was 8.2% for females in contrast to 3.2% for males. Conclusion: Our study highlighted the differences in dementia assessment and care in developing versus developed countries. Greater effort with regard to studying dementia, especially in developing countries, is necessary.
Androgen Receptor Genotype in Humans and Susceptibility to Endocrine Disruptors
Authors: Lundberg Giwercman Yvonne
Published: February 2016

Although animal studies have raised concern that the influence of endocrine-disrupting compounds would obstruct the development of the male reproductive system, in general, exposure levels far above those found in humans have been needed to induce reproductive toxicity in animal models. Human data are inconclusive and have evoked the question whether endocrine-disrupting compounds can have any impact on hormonal function and thus health consequences when natural hormones are present. Indeed, many contaminants with hormone-like activity are much less potent than endogenous hormones themselves: 17β-oestradiol was, for instance, estimated to be 17,000 times more potent than o,p′-DDT. However, humans are exposed to a multitude of agents, and when present in sufficient number and concentration, they might in principle act collected on the actions of endogenous hormones. Whether such effects will be physiologically relevant is still not known. Nevertheless, in the worst-case scenario, there are no threshold levels below which there are no effects at all, and one target molecule is the androgen receptor. This mini review focuses on the androgen receptor gene, its link with classical endocrine disruptors and smoking, and how common genetic variants in the androgen receptor gene may influence physiological outcomes.
Silodosin, an α1A-Adrenoceptor Antagonist, May Ameliorate Ischemia-Induced Bladder Denervation and Detrusor Dysfunction by Improving Bladder Blood Flow
Authors: Goi Yoshiaki , Tomiyama Yoshitaka , Maruyama Itaru , Tatemichi Satoshi , Maruyama Kazuyasu , Kobayashi Mamoru , Nomiya Masanori , Yamaguchi Osamu
Published: February 2016

Background/Aims: This study was performed to investigate the detailed mechanism underlying the effects of the selective α1A-adrenoceptor antagonist, silodosin, on bladder function in a rat model of atherosclerosis-induced chronic bladder ischemia (CBI). Methods: The CBI model was prepared by balloon endothelial injury of the bilateral iliac arteries in male rats. Using an osmotic pump, the CBI rats received either silodosin or vehicle alone subcutaneously for 8 weeks. Rats received a 2% cholesterol diet throughout the experiment. Bladder blood flow (BBF) was measured. Immunohistochemical staining was performed to determine the nerve distribution and nerve growth factor expression in the bladder. Bladders were used for muscle strip contraction analysis. The expression levels of muscarinic M2 and M3 receptors were measured. Results: Silodosin abrogated the decrease in BBF in CBI rats. Silodosin prevented the decrease in nerve distribution and increase in nerve growth factor expression in the CBI model. Bladder contractile response was reduced in the CBI group. Silodosin ameliorated the effect on the bladder contractile response. The level of muscarinic M3 receptor mRNA present in the bladder of CBI rats was increased by silodosin. Conclusion: The results of this study suggest that silodosin ameliorates the denervation of the bladder and effects on detrusor contractile function under ischemic conditions by restoring BBF.
Chemopreventive Effects of Alpha Lipoic Acid on Obesity-Related Cancers
Authors: Moon Hyun-Seuk
Published: February 2016

Background: It has been generally accepted that being overweight or obese is a risk factor for several types of cancers, including breast, thyroid, colon, pancreatic and liver. In fact, people who are obese have more fat tissues that can produce hormones, such as insulin or estrogen, which may cause cancer cells to grow. Alpha lipoic acid (ALA) is anorganosulfur compound derived from octanoic acid, which is produced in animals normally, and is essential for aerobic metabolism. Summary: Studies in both in vitro cells and in vivo animal models have shown that ALA inhibits the initiation and promotion stages of carcinogenesis, suggesting that ALA has considerable attention as a chemopreventive agent. This brief review collects the scattered data available in the literature concerning ALA and highlights its anti-cancer properties, intermediary metabolism and exploratory implications. Key Messages: Based on scientific evidences so far, ALA might be useful agents in the management or chemoprevention of obesity-related cancers.
Relation of Nailfold Capillaries and Autoantibodies to Mortality in Patients With Raynaud Phenomenon
Authors: Mueller Markus , Gschwandtner Michael E. , Gamper Jutta , Giurgea Georgiana-Aura , Charwat-Resl Silvia , Kiener Hans P. , Smolen Josef S. , Perkmann Thomas , Koppensteiner Renate , Schlager Oliver
Published: February 2016

Background—

In incipient Raynaud phenomenon, nailfold capillaroscopy and autoantibody tests are obtained to screen for an emerging connective tissue disease. Whether the presence of abnormal nailfold capillaries and autoantibodies are related to mortality in patients with incipient Raynaud phenomenon is not known.

Methods and Results—

In 2958 consecutive patients (78% women, median age 45 years) with incipient Raynaud phenomenon without previously known connective tissue disease, nailfold capillaroscopy and laboratory tests for antinuclear antibodies (ANA) and ANA subsets were obtained at initial presentation. During a median follow-up period of 9.3 years, 227 women (9.9% of female patients) and 129 men (20% of male patients) with Raynaud phenomenon died. In comparison with a demographically matched standard population, survival was poorer in patients with Raynaud phenomenon (log-rank test
P
<0.0001). In patients with Raynaud phenomenon, mortality was higher in men than in women (
P
<0.0001, Cox proportional hazards model). In women, the presence of abnormal nailfold capillaries, ANA, and anti–Scl-70 antibodies were related to an increase in all-cause mortality. The conjoint presence of abnormal nailfold capillaries and autoantibodies was associated with the highest mortality rates. In men, abnormal nailfold capillaries, and ANA and ANA subsets, as well, were not related to survival. In both sexes, patients’ age and serum creatinine were associated with mortality.

Conclusions—

In Raynaud phenomenon, male sex, age, and serum creatinine are related to mortality. Abnormal nailfold capillaries and autoantibodies are associated with an increase in all-cause mortality in female patients, but not in male patients with Raynaud phenomenon.
Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease
Authors: Tonelli Marcello , Karumanchi S. Ananth , Thadhani Ravi
Published: February 2016

Patients with chronic kidney disease and end-stage renal disease are at 5- to 10-fold higher risk for developing cardiovascular disease (CVD) than age-matched controls. Clinically, CVD in this population manifests as coronary artery disease, arrhythmias, stroke, or congestive heart failure. Beyond the traditional risk factors (eg, diabetes mellitus and hypertension), uremia-specific factors that arise from accumulating toxins also contribute to the pathogenesis of CVD. In this review, we summarize the literature on the epidemiology of both traditional and uremia-related CVD and focus on postulated mechanisms of the latter. In the context of current and emerging diagnostics and therapies for CVD, we highlight what we interpret as major gaps in the medical management of this growing population that need to be addressed with targeted epidemiological and translational research. Finally, we describe the global challenges associated with the recognition and management of uremia-related CVD in developed and developing nations.
It’s just between girls: Negotiating the postfeminist gaze in women’s ‘looking talk’
Authors: Riley Sarah , Evans Adrienne , Mackiewicz Alison
Published: February 2016

Feminists have argued that women’s bodies, appearance, and subjectivity are formed through a multitude of regulatory dispositif and disciplinary apparatus. One such disciplinary technique has been “looking”, evidenced in work on the male gaze, disciplinary power, misrecognition, objectification, and indirect social aggression. But there remains a significant gap in the role of women’s looking in subject formation, particularly within the context of a postfeminist sensibility. To address this gap a poststructuralist informed discourse analysis was performed on interviews with 44 white heterosexual British women (aged 18–36). Four discourses deployed by the participants when talking about looking between women were identified. These discourses were as follows: judgemental looking between women is pervasive; judgement is consumption oriented; women’s looks are prioritised over men’s, foregrounding a female gaze; and appearance is the vehicle to recognition. We conclude by highlighting the importance of a postfeminist gaze for understanding women’s subjectivities, and how looking works in a postfeminist context to maintain regulation, anxiety, surveillance, and judgement.
Youth Heterotopias in Precarious Times
Authors: Pechtelidis Yannis
Published: February 2016

Under the structural restraints of the current financial, social and political crisis, I examine the case of a collectivity of students in Greece as an alternative small-scale form of political and cultural action, and I explore its dynamics and limits. I claim that the ‘collectivity’ is a form of heterotopia, that is, a specific social and cultural space, which somehow reflects and at the same time distorts, unsettles or inverts other spaces. In particular, I seek to uncover the rituals, practices and mentalities produced by the participants of this youth cultural space, and to understand how new subjectivities and collectivities come into being. In this context, I discuss some of the relevant literature on youth political participation. Furthermore, I illustrate the debate about ‘autonomy’ and ‘hegemony’ within social and political theory today.
Aesthetics of Youth Scenes
Authors: Ferreira Vitor Sérgio
Published: February 2016

The aesthetic expressions produced and reproduced within post-war spectacular youth (sub)cultures used to be seen as a display of resistance to and subversion of ‘social order’, perceived as opressive of youth life experiences and chances. Under the traditional subculturalist paradigm, both artefacts or performances were subsumed to the class status of their young practicioners and seen as ideological expression of their dominated and disadvantadged social position. Nowadays, however, the stylistic resources used in youth scenes has taken on new meanings for which the concept of resistance is not enough and/or adequate to explain. Therefore, departing from a post-subcultural approach, this essay intends to highlight the social changes recently occurred in the political culture of spectacular youth scenes and, consequently, to contribute to overcome resistance as nuclear concept on the debate, relocating it towards the concept of existence. Following this idea, and to close this essay, I suggest the concept of arts of existence as analytical point of view on the new expressiveness of the aesthetics of contemporary youth scenes. Inspired in Foucault, that concept allows to go further in the understanding of youth scenes aesthetics as arts of a good living (in the consumption sphere), and arts of making a living (in the production sphere).
Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors
Authors: Kaimakis Polynikis , de Pater Emma , Eich Christina , Solaimani Kartalaei Parham , Kauts Mari-Liis , Vink Chris S. , van der Linden Reinier , Jaegle Martine , Yokomizo Tomomasa , Meijer Dies , Dzierzak Elaine
Published: February 2016

Key Points

A new Gata2 reporter indicates that all HSCs express Gata2 and corroborates findings that Gata2 is not required for generation of all HPCs. Isolatable non–Gata2-expressing HPCs show less potency and a distinct genetic program, thus having implications for reprogramming strategies.
Treatable traits: toward precision medicine of chronic airway diseases
Authors: Agusti Alvar , Bel Elisabeth , Thomas Mike , Vogelmeier Claus , Brusselle Guy , Holgate Stephen , Humbert Marc , Jones Paul , Gibson Peter G. , Vestbo Jørgen , Beasley Richard , Pavord Ian D.
Published: February 2016

Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airway diseases that have a high personal and social impact. They likely represent a continuum of different diseases that may share biological mechanisms (i.e.endotypes), and present similar clinical, functional, imaging and/or biological features that can be observed (i.e.phenotypes) which require individualised treatment. Precision medicine is defined as “treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations”. In this Perspective, we propose a precision medicine strategy for chronic airway diseases in general, and asthma and COPD in particular.
Hypertension and diabetes in Africa: design and implementation of a large population-based study of burden and risk factors in rural and urban Malawi
Authors: Crampin Amelia Catharine , Kayuni Ndoliwe , Amberbir Alemayehu , Musicha Crispin , Koole Olivier , Tafatatha Terence , Branson Keith , Saul Jacqueline , Mwaiyeghele Elenaus , Nkhwazi Lawrence , Phiri Amos , Price Alison Jane , Mwagomba Beatrice , Mwansambo Charles , Jaffar Shabbar , Nyirenda Moffat Joha
Published: February 2016

Background

The emerging burden of cardiovascular disease and diabetes in sub-Saharan Africa threatens the gains made in health by the major international effort to combat infectious diseases. There are few data on distribution of risk factors and outcomes in the region to inform an effective public health response. A comprehensive research programme is being developed aimed at accurately documenting the burden and drivers of NCDs in urban and rural Malawi; to design and test intervention strategies. The programme includes population surveys of all people aged 18 years and above, linking individuals with newly diagnosed hypertension and diabetes to healthcare and supporting clinical services. The successes, challenges and lessons learnt from the programme to date are discussed.

Results

Over 20,000 adults have been recruited in rural Karonga and urban Lilongwe. The urban population is significantly younger and wealthier than the rural population. Employed urban individuals, particularly males, give particular recruitment challenges; male participation rates were 80.3 % in the rural population and 43.6 % in urban, whilst female rates were 93.6 and 75.6 %, respectively. The study is generating high quality data on hypertension, diabetes, lipid abnormalities and risk factors.

Conclusions

It is feasible to develop large scale studies that can reliably inform the public health approach to diabetes, cardiovascular disease and other NCDs in Sub-Saharan Africa. It is essential for studies to capture both rural and urban populations to address disparities in risk factors, including age structure. Innovative approaches are needed to address the specific challenge of recruiting employed urban males.
Brief electrical stimulation after facial nerve transection and neurorrhaphy: A randomized prospective animal study
Authors: Mendez Adrian , Seikaly Hadi , Biron Vincent L. , Zhu Lin Fu , Côté David W. J.
Published: February 2016

Background

Recent studies have examined the effects of brief electrical stimulation (BES) on nerve regeneration, with some suggesting that BES accelerates facial nerve recovery. However, the facial nerve outcome measurement in these studies has not been precise or accurate. The objective of this study is to assess the effect of BES on accelerating facial nerve functional recovery from a transection injury in the rat model.

Methods

A prospective randomized animal study using a rat model was performed. Two groups of 9 rats underwent facial nerve surgery. Both group 1 and 2 underwent facial nerve transection and repair at the main trunk of the nerve, with group 2 additionally receiving BES on post-operative day 0 for 1 h using an implantable stimulation device. Primary outcome was measured using a laser curtain model, which measured amplitude of whisking at 2, 4, and 6 weeks post-operatively.

Results

At week 2, the average amplitude observed for group 1 was 4.4°. Showing a statistically significant improvement over group 1, the group 2 mean was 14.0° at 2 weeks post-operatively ( p = 0.0004). At week 4, group 1 showed improvement having an average of 9.7°, while group 2 remained relatively unchanged with an average of 12.8°. Group 1 had an average amplitude of 13.63° at 6-weeks from surgery. Group 2 had a similar increase in amplitude with an average of 15.8°. There was no statistically significant difference between the two groups at 4 and 6 weeks after facial nerve surgery.

Conclusions

This is the first study to use an implantable stimulator for serial BES following neurorrhaphy in a validated animal model. Results suggest performing BES after facial nerve transection and neurorrhaphy at the main trunk of the facial nerve is associated with accelerated whisker movement in a rat model compared with a control group.
Upper airway obstruction due to a change in altitude: First report in fifty years
Authors: Butskiy Oleksandr , Anderson Donald W.
Published: February 2016

Background

Air travel mostly causes minor ear, nose and throat complaints. We describe a second report in literature of airway obstruction caused by a drop in atmospheric pressure during a routine commercial flight.

Case presentation

A 54-year-old male was referred to a head and neck surgeon with a 2 cm left submandibular mass that would enlarge during commercial flights. As the plane gained elevation, the mass would grow and cause him to become stridorous and short of breath. The shortness of breath and stridor would only resolve upon landing of the plane. A CT scan showed a large air sac extending from the larynx at the level of the true vocal cords up to the angle of the mandible. Based on the history and the CT findings a diagnosis of a laryngocele was made. The laryngocele was excised using an external approach, resolving the patient's difficulty with flying.

Conclusion

This article reports a rare case of upper airway obstruction caused by atmospheric pressure changes during air travel. The reported case is of significance as only a few uncomplicated laryngoceles have been reported to cause airway distress in the literature. This report highlights the epidemiology, presentation, complication and management of laryngoceles.
Estimating snow water equivalent over long mountain transects using snowmobile-mounted ground-penetrating radar
Authors: Holbrook W. Steven , Miller Scott N. , Provart Matthew A.
Published: February 2016

The water balance in alpine watersheds is dominated by snowmelt, which provides infiltration, recharges aquifers, controls peak runoff, and is responsible for most of the annual water flow downstream. Accurate estimation of snow water equivalent (SWE) is necessary for runoff and flood estimation, but acquiring enough measurements is challenging due to the variability of snow accumulation, ablation, and redistribution at a range of scales in mountainous terrain. We have developed a method for imaging snow stratigraphy and estimating SWE over large distances from a ground-penetrating radar (GPR) system mounted on a snowmobile. We mounted commercial GPR systems (500 and 800 MHz) to the front of the snowmobile to provide maximum mobility and ensure that measurements were taken on pristine snow. Images showed detailed snow stratigraphy down to the ground surface over snow depths up to at least 8 m, enabling the elucidation of snow accumulation and redistribution processes. We estimated snow density (and thus SWE, assuming no liquid water) by measuring radar velocity of the snowpack through migration focusing analysis. Results from the Medicine Bow Mountains of southeast Wyoming showed that estimates of snow density from GPR ([Formula: see text]) were in good agreement with those from coincident snow cores ([Formula: see text]). Using this method, snow thickness, snow density, and SWE can be measured over large areas solely from rapidly acquired common-offset GPR profiles, without the need for common-midpoint acquisition or snow cores.
3D ground-penetrating radar imaging of ice complex deposits in northern East Siberia
Authors: Schennen Stephan , Tronicke Jens , Wetterich Sebastian , Allroggen Niklas , Schwamborn Georg , Schirrmeister Lutz
Published: February 2016

Ice complex deposits are characteristic, ice-rich formations in northern East Siberia and represent an important part in the arctic carbon pool. Recently, these late Quaternary deposits are the objective of numerous investigations typically relying on outcrop and borehole data. Many of these studies can benefit from a 3D structural model of the subsurface for upscaling their observations or for constraining estimations of inventories, such as the local carbon stock. We have addressed this problem of structural imaging by 3D ground-penetrating radar (GPR), which, in permafrost studies, has been primarily used for 2D profiling. We have used a 3D kinematic GPR surveying strategy at a field site located in the New Siberian Archipelago on top of an ice complex. After applying a 3D GPR processing sequence, we were able to trace two horizons at depths below 20 m. Taking available borehole and outcrop data into account, we have interpreted these two features as interfaces of major lithologic units and derived a 3D cryostratigraphic model of the subsurface. Our data example demonstrated that a 3D surveying and processing strategy was crucial at our field site and showed the potential of 3D GPR to image geologic structures in complex ice-rich permafrost landscapes.
Reasons for choosing to specialise in psychiatry: differences between core psychiatry trainees and consultant psychiatrists
Authors: Denman Melissa , Oyebode Femi , Greening Jayne
Published: February 2016

Aims and method

This questionnaire study aimed to investigate the reasons for choosing to specialise in psychiatry in a sample of consultant psychiatrists and core trainee psychiatrists from within the West Midlands.

Results

Five reasons were significantly different between the core trainees and consultant psychiatrists. ‘Emphasis on the patient as a whole’ was identified as the most important reason for choosing to specialise for both core trainees and consultants. Six additional reasons were shared within the top ten ‘very important’ reasons, although their actual ranking varies.

Clinical implications

Some of the reasons for choosing to specialise in psychiatry were shown to significantly differ between core trainees and consultants. Numerous key driving factors have remained important over time for both groups, whereas other reasons have been replaced with a shift of importance towards lifestyle and humanitarian factors for core trainees. Consequently, it may be advisable not to use the reasons that consultants gave for choosing psychiatry when thinking about how to attract today's prospective psychiatrists.
Debating personal health budgets
Authors: Alakeson Vidhya , Boardman Jed , Boland Billy , Crimlisk Helen , Harrison Charlotte , Iliffe Steve , Khan Masood , O'Shea Rory , Patterson Janet
Published: February 2016

Personal health budgets (PHBs) were piloted in the National Health Service (NHS) in England between 2009 and 2012 and were found to have greater positive effects on quality of life and psychological well-being for those with mental health problems than commissioned service, as well as reducing their use of unplanned care. The government intends to extend PHBs in England for long-term conditions, including mental health, from April 2015. Given the importance of engaging clinicians in the next phase of PHB development, we provide an overview of the approach, synthesise the evidence from the national pilot and debate some of the opportunities and challenges. Balancing individual choice and recovery with concerns for risk, equity and the sustainability of existing community services is the central tension underpinning this innovation in mental health service delivery.
In-patient rehabilitation: clinical outcomes and cost implications
Authors: Bunyan Mel , Ganeshalingam Yogesh , Morgan Ehab , Thompson-Boy Donvé , Wigton Rebekah , Holloway Frank , Tracy Derek K.
Published: February 2016

Aims and method

A retrospective evaluation was undertaken of the clinical and economic effectiveness of three in-patient rehabilitation units across one London National Health Service trust. Information on admission days and costs 2 years before and 2 years after the rehabilitation placement, length of rehabilitation placement and the discharge pathway was collected on 22 service users.

Results

There were statistically significant reductions in hospital admission days in the 2 years following rehabilitation compared with the 2 years before, further reflected in significantly lower bed costs. Longer length of rehabilitation placement was correlated with fewer admission days after the placement. A substantial proportion of the sample went into more independent living, some with no further admissions at follow-up.

Clinical implications

The findings suggest that in-patient rehabilitation is both clinically and cost effective: if benefits are sustained they will offset the cost of the rehabilitation placement.
Betrayals
Authors: Zinsser Judith P.
Published: February 2016

The career and writings of the philosophe Emilie Du Châtelet (1706–49) have recently been accorded their proper significance in the historical narratives of eighteenth-century philosophy and science. However, despite the best efforts of historians and biographers, the contrary image of the marquise as Voltaire's promiscuous mistress and a dabbler in physics and mathematics remains seductively popular, and Nancy Mitford's 1957 Voltaire in Love and Elisabeth Badinter's Emilie, Emilie: L'ambition féminine au XVIIIe siècle of 1983 continue to be recommended as the most authoritative accounts of Du Châtelet's life. This article gives a brief historiography of writings on the marquise into the twentieth century and then considers Mitford's and Badinter's sexualized portrayals. It also speculates on the reasons for the continuing popularity of these outdated, skewed interpretations.

La carrière et les écrits de la « philosophe » Emilie Du Châtelet (1706–49) ont récemment trouvé la place qui leur est due dans l'histoire de la philosophie et des sciences au dix-huitième siècle. Cependant, malgré tous les efforts des historiens et des biographes, la représentation de la marquise en maîtresse volage de Voltaire et en dilettante qui se piquait de physique et de mathématiques reste toujours aussi séduisante et répandue. La biographie de Nancy Mitford, Voltaire amoureux, qui date de 1957, et celle d'Elisabeth Badinter, Emilie, Emilie: L'ambition féminine au XVIIIe siècle, de 1983, continuent à être considérées comme les ouvrages biographiques les plus fiables. Notre essai présente une courte historiographie des écrits sur la marquise au vingtième siècle et remet en question les portraits passablement érotiques de Mitford et de Badinter. Nous réfléchissons également aux raisons pour lesquelles ces interprétations infidèles et désuètes continuent à être aussi populaires.
Royal Agents and Templar Confessions in the Bailliage of Rouen
Authors: Field Sean L.
Published: February 2016

Through a close examination of the two extant documents generated by the Templar arrests and interrogations in the bailliage of Rouen, this article sheds new light on the way Philip IV's agents there interpreted their mandates in the uncertain atmosphere of the week following October 13, 1307. These crucial documents (reedited in appendices) are uniquely revealing, because they were produced entirely by the king's secular agents: the bailli of Rouen and the knights empowered to act in the arrest and questioning of seven Templars in the bailliage. When considered in tandem these documents show how audaciously the king's men moved to obtain, record, and compile confessions to the ostensibly ecclesiastical crime of heresy.

Cet article propose une analyse minutieuse des deux documents qui subsistent de l'arrestation et des interrogatoires des templiers dans le bailliage de Rouen, pour apporter un nouvel éclairage sur la façon dont les agents de Philippe IV, dans l'incertitude qui domina au cours de la semaine suivant le 13 octobre 1307, ont interprété les ordres royaux. Ces documents cruciaux, réédités en annexes, constituent des sources uniques, particulièrement révélatrices, parce qu'ils furent produits par les seuls agents séculiers du roi, en l'occurrence le bailli de Rouen et les chevaliers mandatés pour procéder à l'arrestation et à l'interrogation de sept templiers dans le bailliage. Considérés ensemble, ces textes montrent avec quelle audace les hommes du roi agirent pour obtenir, enregistrer et mettre en forme les aveux du crime d'hérésie, dont la nature était clairement ecclésiastique.
“Entrepreneurial Nobles” Or “Aristocratic Serfs”?
Authors: Fitch Nancy
Published: February 2016

This article examines the changing nature of aristocratic land acquisitions in central France in the centuries before the outbreak of revolution in 1789. It shows how nobles bought up or confiscated peasant land to engross large estates. Since their acquisition rarely altered the legal status of such lands, aristocrats surprisingly were among those responsible for paying the bulk of the feudal dues at the end of the Old Regime (and were probably the major beneficiaries when the French Revolution abolished them). These “entrepreneurial” nobles often blended new kinds of industry with traditional forms of agriculture; they also increasingly deprived peasants of land and grazing rights. By exploring changing patterns in aristocratic landholding, this article shows how the nobility in central France contributed both to the development of capitalism and industrialization in France and to rising peasant anger at the beginning of the French Revolution.

Cet article étudie l'évolution des acquisitions aristocratiques de terrains en France centrale pendant les siècles avant la Révolution de 1789. Il montre comment les nobles ont acheté ou confisqué les terres paysannes afin de les réunir en de grands domaines. Puisque ces achats n'ont que rarement modifié le statut juridique de ces terres, les aristocrates étaient obligés à payer la majeure partie de la cotisation féodale à la fin de l'ancien régime. Souvent ces nobles « entreprenants » mélangeaient de nouveaux types d'industrie avec les formes traditionnelles de l'agriculture; en même temps, ils ont de plus en plus privé les paysans de terres et de droits de pâturage. En explorant les nouvelles habitudes de l'aristocratie foncière, cet article montrera comment la noblesse de la France centrale a contribué au développement du capitalisme et de l'industrialisation en France et à la colère paysanne au début de la Révolution française.
Degradation of Peroxynitrite by Simple, Recyclable Selenolanes
Authors: Kumar Pavitra V , Singh Beena G , Kunwar Amit , Iwaoka Michio , Priyadarsini K Indira
Published: February 2016

Two cyclic organoselenium compounds, DHS (trans-3,4-dihydroxy-1-selenolane) and MAS (3-amino-1-selenolane) were examined for their reaction with peroxynitrite. Both DHS and MAS scavenge peroxynitrite with rate constants of the order of 103 M−1 s−1. Additionally the two compounds efficiently react with carbonate (CO3•−) radical (formed by reaction of peroxynitrite with carbon dioxide) by one-electron oxidation and their selenoxides convert the nitrite formed by peroxynitrite reduction to nitrate. Even though the reactivity of DHS/MAS was fairly the same with peroxynitrite and its derived radicals, they differ in their ability to protect plasmid pBR322 DNA and CHO cells from peroxynitrite induced toxicity. To understand this, analysis of crucial products formed during peroxynitrite reaction was carried out. On reaction with peroxynitrite, both the compounds were converted to their corresponding selenoxide, identified and estimated by NMR and HPLC. Comparing the relative yields of the selenoxides, it has been confirmed that DHS produced significantly higher amount of selenoxide than MAS. The selenoxide can be regenerated back to the parent compound, either by thiols or by nitrite. Based on these results it is concluded that formation of stable and recyclable selenoxide makes selenolanes, a novel class of selenium compounds as antioxidants for peroxynitrite degradation.
COMPUTATION OF SOIL-CEMENT COLLISION WALL OF METAL STRUCTURES PIT IN THE CONSTRUCTION OF SUBWAY
Authors: Дыба Владимир , Dyba Vladimir , Орлова Ю , Orlova Yu
Published: February 2016

Authors develop the method of computation of soil-cement collision wall by the first limit state. The method of calculation of the stability of the pit and the calculation of limiting the depth of pit are offered.
APPROXIMATE ANALYTICAL SOLUTION OF MIXED PROBLEM OF SOIL ELASTICITY AND PLASTICITY THEORY AND ITS EXPERIMENTAL JUSTIFICATION
Authors: Подтелков Василий , Podtelkov Vasiliy , Богомолова Оксана , Bogomolova Oksana , Павлов Дмитрий , Pavlov Dmitriy , Богомолов Александр , Bogomolov Aleksandr , Ермаков Олег , Ermakov Oleg
Published: February 2016

The paper presents the basic correlations of the approximate analytical solution of mixed problem of soil elasticity and plasticity theory as well as the examples of the comparison of numeric values of the experiments’ results aimed at determining the load-bearing capacity of foundation beds and the form and dimensions of plastic strain ranges with the results obtained on its basis.
NUMERICAL SIMULATION OF THE PROCESS OF GEOTHERMAL LOW-POTENTIAL GROUND ENERGY EXTRACTION
Authors: Захаров Александр , Zakharov Aleksandr , Пономарев Андрей , Ponomarev Andrey
Published: February 2016

The aim of our research is to study the interaction of energy foundations with the ground mass and to develop methods for their construction on the example of the city of Perm. Field studies of ground were carried out in a specially chosen pilot site to determine temperature distribution in the ground mass, change of ground-water level and physical-mechanical and thermal-physical characteristics of the ground mass. The diagrams of depth temperature distribution in the ground and its seasonal variations were obtained on the results of monitoring, and also the average groundwater level. To carry out numerical simulation, software-complex “GeoStudio” was selected. Its basic differential equation is the fundamental heat conduction equation with an internal heat source. The purpose of the numerical simulation was quantitative evaluation of the thermal energy extracted from different energy foundations under soil conditions in the city of Perm. By results of the spent numerical experiments the equations of regress and nomographs dependences of size of received thermal energy on geometrical parameters of the projected power bases to hydro-geological and climatic conditions of the Perm region are constructed
Study of clay-soil with core stamp
Authors: Ляшенко Павел , Lyashenko Pavel , Ляшенко Евгений , Lyashenko Evgeniy
Published: February 2016

Static sensing of a ground rod stamp with a constant low speed of movement allows you to determine the value of step microstructural heterogeneities of the soil and to assess the values of the elastic and inelastic parts of the soil deformation