bluuebunny/crossref_metadata_2025 huggingface dataset:
Age and sex relationship with flow-mediated dilation in healthy children and adolescents
Authors: Hopkins Nicola D. , Dengel Donald R. , Stratton Gareth , Kelly Aaron S. , Steinberger Julia , Zavala Hanan , Marlatt Kara , Perry Daniel , Naylor Louise H. , Green Daniel J.
Published: August 2015

Flow-mediated dilation (FMD) is a noninvasive technique used to measure conduit artery vascular function. Limited information is available on normative FMD values in healthy children and adolescents. The objective of this study was to assess relationships between age and sex with FMD across childhood and adolescence. Nine hundred and seventy-eight asymptomatic children (12 ± 3 yr, range 6–18 yr, 530 male) underwent ultrasonic brachial artery assessment before and after 5 min of forearm ischemia. Sex differences in FMD and baseline artery diameter were assessed using mixed linear models. Baseline artery diameter was smaller in females than males [2.96 mm (95% CI: 2.92–3.00) vs. 3.24 mm (3.19–3.28), P < 0.001] and increased with age across the cohort ( P < 0.001). Diameter increased between ages 6 and 17 yr in males [from 2.81 mm (2.63, 3.00) to 3.91 mm (3.68, 4.14)] but plateaued at age 12 yr in females. Males had a lower FMD [7.62% (7.33–7.91) vs. 8.31% (7.95–8.66), P = 0.024], specifically at ages 17 and 18 yr. There was a significant effect of age on FMD ( P = 0.023), with a reduction in FMD apparent postpuberty in males. In conclusion, the brachial artery increases structurally with age in both sexes; however, there are sex differences in the timing and rate of growth, in line with typical sex-specific adolescent growth patterns. Males have a lower FMD than females, and FMD appears to decline with age; however, these findings are driven by reductions in FMD as males near maturity. The use of age- and sex-specific FMD data may therefore not be pertinent in childhood and adolescence.
Stimulus-induced up states in the dorsal pallium of a weakly electric fish
Authors: Elliott S. Benjamin , Maler Leonard
Published: August 2015

We investigated the response of putative novelty-detecting neurons in the pallium of an electric fish to electrosensory and acoustic stimuli. Extracellular and whole cell patch recordings were made from neurons in the dorsal pallial nucleus (DD) of Apteronotus leptorhynchus. DD neurons were typically quiescent and exhibited hyperpolarized resting membrane potentials. Stimulation induced, with a variable long latency, rapid though transient depolarization and spike discharge. The transition between resting and depolarized/spiking states resembled the transition to Up states seen in mammalian telencephalic neurons.
Interpreting the electrophysiological power spectrum
Authors: Gao Richard
Published: August 2015

Recent experimental findings suggest that there may be rich physiological information embedded within the power spectrum of neurophysiological recordings, which, in addition to power in specific oscillatory frequencies, can be extracted with the appropriate model. This article reviews previous empirical and modeling results, as well as the canonical power law model that is often used to describe the power spectrum. In addition, a modified power law model with parameters estimating synaptic and spiking contributions is proposed.
Hydration: Knowledge, Attitudes, and Practices of UK Dietitians
Authors: Douglas Pauline , Ball Lauren , McGuffin Lynn , Laur Celia , Crowley Jennifer , Rajput-Ray Minha , Gandy Joan , Ray Sumantra
Published: August 2015

Aim. The aim of this study was to investigate dietitians’ knowledge, attitudes, and practices (KAP) regarding hydration and patient care. Methods. A cross-sectional online survey was administered to UK dietitians via the British Dietetic Association monthly newsletter and included 18 items on hydration knowledge (n=8), attitudes (n=4), and practices (n=6). KAP scores were calculated by adding the total number of correct knowledge responses and by ranking attitude and practice responses on a Likert scale. Results. 97 dietitians completed the online survey and displayed varying levels of KAP regarding hydration and patient care. The mean unweighted scores were knowledge 5.0 (±1.3) out of 8; attitude 13.9 (±1.3) out of 16; practice 14.9 (±2.6) out of 24. Dietitians appeared to be guided by clinical reasoning and priorities for nutrition care. Conclusions. There may be scope to further assess and potentially enhance the KAP of dietitians regarding hydration and patient care. Innovative approaches to hydration promotion are warranted and may include focusing on dietitians’ personal hydration status, increasing communication with other healthcare professionals, and partnering with patients to take a proactive role in hydration monitoring.
Correcting Air-Pressure Data Collected by MEMS Sensors in Smartphones
Authors: Kim Na-Young , Kim Yong-Hyuk , Yoon Yourim , Im Hyo-Hyuc , Choi Reno K. Y. , Lee Yong Hee
Published: August 2015

We present a novel correction method for air-pressure data collected by microelectromechanical pressure sensors embedded in Android-based smartphones, in order to render them usable as meteorological data. The first step of the proposed correction method involves removing the mechanically derived outliers existing beyond the physical limits and those existing outside 3σ, as well as a reduction to the mean sea level pressure using the altitude data from digital elevation models. The second correction step involves classifying data by location and linear-regression analysis utilizing the temperature and humidity sensed by the smartphone to reduce correction errors by performing the analysis according to personalized settings. Air-pressure data obtained from smartphones is subject to several influential factors, depending on the users’ external environment. However, once corrected for spatial location, temperature, and humidity and for individual users after a comprehensive quality control, the corrected air-pressure data was highly reliable as an auxiliary resource for automatic weather stations.
Evaluation of Antidiarrheal Activity of Methanolic Extract ofMaranta arundinaceaLinn. Leaves
Authors: Rahman Md. Khalilur , Chowdhury Md. Ashraf Uddin , Islam Mohammed Taufiqual , Chowdhury Md. Anisuzzaman , Uddin Muhammad Erfan , Sumi Chandra Datta
Published: August 2015

Diarrhea is one of the most common causes for thousands of deaths every year. Therefore, identification of new source of antidiarrheal drugs becomes one of the most prominent focuses in modern research. Our aim was to investigate the antidiarrheal and cytotoxic activities of methanolic extract ofMaranta arundinacealinn. (MEMA) leaves in rats and brine shrimp, respectively. Antidiarrheal effect was evaluated by using castor oil-induced diarrhea, enteropooling, and gastrointestinal motility tests at 200 mg/kg and 400 mg/kg body weight in rats where the cytotoxic activity was justified using brine shrimp lethality bioassay at different concentrations of MEMA. The extract showed considerable antidiarrheal effect by inhibiting 42.67% and 57.75% of diarrheal episode at the doses of 200 and 400 mg/kg, respectively. MEMA also significantlyp<0.01reduced the castor oil-induced intestinal volume (2.14 ± 0.16 to 1.61 ± 0.12 mL) in enteropooling test as well as intestinal transit (33.00 to 43.36%) in GI motility test, compared to their respective control. These observed effects are comparable to that of standard drug loperamide (5 mg/kg). On the other hand, in brine shrimp lethality test after 24 h, surviving brine shrimp larvae were counted and LD50was assessed. Result showed that MEMA was potent against brine shrimp with LD50value of 420 µg/mL. So the highest dose of 400 µg/mL of MEMA was not toxic to mice. So these results indicate that bioactive compounds are present in methanolic extract ofMaranta arundinacealeaves including significant antidiarrheal activity and could be accounted for pharmacological effects.
Effects of TCMC on Transformation of Good Health Status to Suboptimal Health Status: A Nested Case-Control Study
Authors: Wang Tian , Chen Jieyu , Sun Xiaomin , Xiang Lei , Zhou Lin , Li Fei , Lin Changsong , Jiang Pingping , Wu Shengwei , Xiao Ya , Cheng Jingru , Luo Ren , Liu Yanyan , Zhao Xiaoshan
Published: August 2015

To explore the effects of traditional Chinese medicine constitution (TCMC) on transformation of good health status to suboptimal health status (SHS), we conducted a nested case-control study among college students in China. During the 18-month mean follow-up time, 543 cases of SHS (42.7%) occurred in 1273 healthy students. There was a significant (P=0.000) and marked reduction in SHMS V1.0 total score in the case group at the 18-month follow-up (69.32 ± 5.45) compared with baseline (78.60 ± 4.70), but there was no significant change in the control group. Conditional logistic regression analysis showed that respondents reporting Yin-deficiency and Qi-deficiency were, respectively, 2.247 and 2.198 times more likely to develop SHS, while tendency to Yin-deficiency and tendency to Damp-heat were, respectively, 1.642 and 1.506 times more likely to develop SHS. However, the Balanced Constitution was a significant protective factor (OR 0.649;P<0.05). Altogether, these findings demonstrate that Yin-deficiency, Qi-deficiency, tendency to Yin-deficiency, and tendency to Damp-heat appeared to induce a change in health status to SHS, while the Balanced Constitution seemed to restrain this change. We conclude that regulating the unbalanced TCMC (such as Yin-deficiency and Qi-deficiency) may prevent a healthy status developing into SHS or lead to the regression of SHS.
Low-Frequency Variability of the Yellow Sea Cold Water Mass Identified from the China Coastal Waters and Adjacent Seas Reanalysis
Authors: Li Xuewei , Wang Xidong , Chu Peter C. , Zhao Dongliang
Published: August 2015

This study uses the China Coastal Waters and Adjacent Seas Reanalysis (CORA) data to investigate the interannual and decadal variability of the Yellow Sea cold water mass (YSCWM) and its relationship to climate indices including the Arctic Oscillation (AO), El Niño/Southern Oscillation (ENSO), and Pacific Decadal Oscillation (PDO). On the interannual timescale, the strong correlation between winter PDO and the YSCWM may indicate the dominant effect of winter PDO on the YSCWM through the modulation of local heat flux and wind stress. It is also found that the local wind stress and heat flux in summer have little impact on the interannual variability of the YSCWM. On the decadal time scale, the YSCWM is associated with winter AO and winter PDO. Winter AO mainly controls local heat flux, modulating the decadal variability of the YSCWM. In contrast, winter PDO is strongly connected with winter heat flux and wind stress to modulate the decadal variability of the YSCWM. In summer, for three climate factors, ENSO is the dominant factor controlling the decadal variability of the YSCWM.
Research on Cold Core Eddy Change and Phytoplankton Bloom Induced by Typhoons: Case Studies in the South China Sea
Authors: Shang Xiao-dong , Zhu Hai-bin , Chen Gui-ying , Xu Chi , Yang Qi
Published: August 2015

The effects of 8 typhoons which passed by coldcore eddy (CCE) areas in the South China Sea (SCS) from 1997 to 2009 were observed and evaluated. The changes in the preexisting CCE acted upon by typhoons were described by eddy kinetic energy (EKE) and eddy available gravitational potential energy (EAGPE). The mechanical energy of CCE was estimated from a two-layer reduced gravity model. Comparing with the scenario that typhoon passes by the region without CCEs, the preexisting CCE area plays an important role in the increase of chlorophyll-a (chl-a) concentration in the CCEs impacted by the typhoons. The preexisting chl-a in CCE is about 25%~45% (8%~25%) of postexisting chl-a in CCE for higher (slower) transit speed typhoons. If the EAGPE of CCE increases greatly after typhoon passing by with slow transit speed, so does the chl-a in the CCE area. The EKE (EAGPE) changes of the preexisting CCE are in the order of O(1014~1015 J). EKE and EAGPE of CCE are dominantly enhanced by typhoon with slow transit speed (<3 m/s) and the posttyphoon EAGPE is always larger than posttyphoon EKE for 8 cases. The maximum EAGPE change of the preexisting CCE reaches5.11×1015 J, which was induced by typhoon Hagibis.
Sexual and Reproductive Health: Knowledge, Attitude, and Perceptions among Young Unmarried Male Residents of Delhi
Authors: Meena Jitendra Kumar , Verma Anjana , Kishore Jugal , Ingle Gopal Krishan
Published: August 2015

Context. Men play a significant role in all spheres of domestic life including reproduction. Youth is a period of critical development and ignoring sexual and reproductive health (SRH) needs of young men ought to have wider social and health consequences.Aims and Objectives. To assess the knowledge, attitude, and perceptions regarding SRH among young unmarried men (18–25 years).Settings and Design. A semiqualitative study conducted across four health centers (2 rural, 2 urban) across Delhi.Materials and Methods. Focus group discussions (FGDs) were held among sixty-four participants regarding various aspects of SRH.Data Analysis. The data generated were analyzed using free listing and thematic content analysis along with simple quantitative proportions for different variable groups.Results. Good knowledge regarding HIV/AIDS was observed though found poor regarding other STIs/RTIs. Inadequate knowledge and negative attitude towards SRH and condom use were observed among rural participants. Peer group and mass media were the commonest SRH information sources among rural and urban participants, respectively.Conclusions. Poor SRH knowledge, perceptions, and available nonformal, unreliable information sources expose young men to poor SRH outcomes. Early, comprehensive SRH information provision can have life-long protective benefits to them and their partners.
Prediction of Moderate and Heavy Rainfall in New Zealand Using Data Assimilation and Ensemble
Authors: Yang Yang , Andrews Phillip , Carey-Smith Trevor , Uddstrom Michael , Revell Mike
Published: August 2015

This numerical weather prediction study investigates the effects of data assimilation and ensemble prediction on the forecast accuracy of moderate and heavy rainfall over New Zealand. In order to ascertain the optimal implementation of state-of-the-art 3Dvar and 4Dvar data assimilation techniques, 12 different experiments have been conducted for the period from 13 September to 18 October 2010 using the New Zealand limited area model. Verification has shown that an ensemble based on these experiments outperforms all of the individual members using a variety of metrics. In addition, the rainfall occurrence probability derived from the ensemble is a good predictor of heavy rainfall. Mountains significantly affect the performance of this ensemble which provides better forecasts of heavy rainfall over the South Island than over the North Island. Analysis suggests that underestimation of orographic lifting due to the relatively low resolution of the model (~12 km) is a factor leading to this variability in heavy rainfall forecast skill. This study indicates that regional ensemble prediction with a suitably fine model resolution (≤5 km) would be a useful tool for forecasting heavy rainfall over New Zealand.
Fuzzy Collaborative Clustering-Based Ranking Approach for Complex Objects
Authors: Liu Shihu , Chen Xiaozhou , Moughal Tauqir Ahmed , Yu Fusheng
Published: August 2015

This paper makes a discussion on the ranking problem of complex objects where each object is composed of some patterns described by individual attribute information as well as the relational information between patterns. This paper presents a fuzzy collaborative clustering-based ranking approach for this kind of ranking problem. In this approach, a referential object is employed to guide the ranking process. To achieve the final ranking result, fuzzy collaborative clustering is carried on the patterns in the referential object by using the collaborative information obtained from each ranked object. Since the collaborative information of ranking objects is represented by cluster centers and/or partition matrices, we give two forms of the proposed approach. With the aid of fuzzy collaborative clustering, the ranking results can be obtained by comparing the difference of the referential object before and after collaboration with respect to ranking objects. One can find that this proposed ranking approach is totally different from the previous ranking methods because of its completely collaborative clustering mechanism. Moreover, some synthetic examples show that our proposed ranking algorithm is valid.
A Study of Coupling Parameter Estimation Implemented by 4D-Var and EnKF with a Simple Coupled System
Authors: Han Guijun , Wu Xinrong , Zhang Shaoqing , Liu Zhengyu , Navon Ionel Michael , Li Wei
Published: August 2015

Coupling parameter estimation (CPE) that uses observations to estimate the parameters in a coupled model through error covariance between variables residing in different media may increase the consistency of estimated parameters in an air-sea coupled system. However, it is very challenging to accurately evaluate the error covariance between such variables due to the different characteristic time scales at which flows vary in different media. With a simple Lorenz-atmosphere and slab ocean coupled system that characterizes the interaction of two-timescale media in a coupled “climate” system, this study explores feasibility of the CPE with four-dimensional variational analysis and ensemble Kalman filter within a perfect observing system simulation experiment framework. It is found that both algorithms can improve the representation of air-sea coupling processes through CPE compared to state estimation only. These simple model studies provide some insights when parameter estimation is implemented with a coupled general circulation model for improving climate estimation and prediction initialization.
Genipin Cross-Linked Chitosan-Polyvinylpyrrolidone Hydrogels: Influence of Composition and Postsynthesis Treatment on pH Responsive Behaviour
Authors: Nwosu Chinyelumndu Jennifer , Hurst Glenn Adam , Novakovic Katarina
Published: August 2015

Understanding the factors that influence the pH responsive behaviour of biocompatible cross-linked hydrogel networks is essential when aiming to synthesise a mechanically stable and yet stimuli responsive material suitable for various applications including drug delivery and tissue engineering. In this study the behaviour of intelligent chitosan-polyvinylpyrrolidone-genipin cross-linked hydrogels is examined as a function of their composition and postsynthesis treatment. Hydrogels are synthesised with varying amounts of each component (chitosan, polyvinylpyrrolidone, and genipin) and their response in a pH 2 buffer is measured optically. The influence of postsynthesis treatment on stability and smart characteristics is assessed using selected hydrogel samples synthesised at 30, 40, and 50°C. After synthesis, samples are exposed to either continuous freezing or three freeze-thaw cycles resulting in increased mechanical stability for all samples. Further morphological and mechanical characterisations have aided the understanding of how postsynthesis continual freezing or freeze-thaw manipulation affects network attributes.
Diffusion Filters for Variational Data Assimilation of Sea Surface Temperature in an Intermediate Climate Model
Authors: Zhang Xuefeng , Li Dong , Chu Peter C. , Zhang Lianxin , Li Wei
Published: August 2015

Sequential, adaptive, and gradient diffusion filters are implemented into spatial multiscale three-dimensional variational data assimilation (3DVAR) as alternative schemes to model background error covariance matrix for the commonly used correction scale method, recursive filter method, and sequential 3DVAR. The gradient diffusion filter (GDF) is verified by a two-dimensional sea surface temperature (SST) assimilation experiment. Compared to the existing DF, the new GDF scheme shows a superior performance in the assimilation experiment due to its success in extracting the spatial multiscale information. The GDF can retrieve successfully the longwave information over the whole analysis domain and the shortwave information over data-dense regions. After that, a perfect twin data assimilation experiment framework is designed to study the effect of the GDF on the state estimation based on an intermediate coupled model. In this framework, the assimilation model is subject to “biased” initial fields from the “truth” model. While the GDF reduces the model bias in general, it can enhance the accuracy of the state estimation in the region that the observations are removed, especially in the South Ocean. In addition, the higher forecast skill can be obtained through the better initial state fields produced by the GDF.
Fallopia japonica, a Natural Modulator, Can Overcome Multidrug Resistance in Cancer Cells
Authors: Eid Safaa Yehia , El-Readi Mahmoud Zaki , Ashour Mohamed Lotfy , Wink Michael
Published: August 2015

Resistance of cancer cells to chemotherapy is controlled by the decrease of intracellular drug accumulation, increase of detoxification, and diminished propensity of cancer cells to undergo apoptosis. ATP-binding cassette (ABC) membrane transporters with intracellular metabolic enzymes contribute to the complex and unresolved phenomenon of multidrug resistance (MDR). Natural products as alternative medicine have great potential to discover new MDR inhibitors with diverse modes of action. In this study, we characterized several extracts of traditional Chinese medicine (TCM) plants (N= 16) for their interaction with ABC transporters, cytochrome P3A4 (CYP3A4), and glutathione-S-transferase (GST) activities and their cytotoxic effect on different cancer cell lines.Fallopia japonica(FJ) (Polygonaceae) shows potent inhibitory effect on CYP3A4 P-glycoprotein activity about 1.8-fold when compared to verapamil as positive control. FJ shows significant inhibitory effect (39.81%) compared with the known inhibitor ketoconazole and 100 μg/mL inhibited GST activity to 14 μmol/min/mL. FJ shows moderate cytotoxicity in human Caco-2, HepG-2, and HeLa cell lines; IC50values were 630.98, 198.80, and 317.37 µg/mL, respectively. LC-ESI-MS were used to identify and quantify the most abundant compounds, emodin, polydatin, and resveratrol, in the most active extract of FJ. Here, we present the prospect of usingFallopia japonicaas natural products to modulate the function of ABC drug transporters. We are conducting future study to evaluate the ability of the major active secondary metabolites ofFallopia japonicato modulate MDR and their impact in case of failure of chemotherapy.
Generalized Linguistic Hesitant Intuitionistic Fuzzy Hybrid Aggregation Operators
Authors: Yang Wei , Shi Jiarong , Pang Yongfeng
Published: August 2015

Some hybrid aggregation operators have been developed based on linguistic hesitant intuitionistic fuzzy information. The generalized linguistic hesitant intuitionistic fuzzy hybrid weighted averaging (GLHIFHWA) operator and the generalized linguistic hesitant intuitionistic fuzzy hybrid geometric mean (GLHIFHGM) operator are defined. Some special cases of the new aggregation operators are studied and many existing aggregation operators are special cases of the new operators. A new multiple attribute decision making method based on the new aggregation operators is proposed and a practical numerical example is presented to illustrate the feasibility and practical advantages of the new method.
A Molecular Portrait of High-Grade Ductal Carcinoma In Situ
Authors: Abba Martin C. , Gong Ting , Lu Yue , Lee Jaeho , Zhong Yi , Lacunza Ezequiel , Butti Matias , Takata Yoko , Gaddis Sally , Shen Jianjun , Estecio Marcos R. , Sahin Aysegul A. , Aldaz C. Marcelo
Published: August 2015

Ductal carcinoma in situ (DCIS) is a noninvasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer whereas others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome, and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty-two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM, and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor-intrinsic subtypes, proliferative, immune scores, and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like, or ERBB2+) displayed signatures characteristic of activated Treg cells (CD4+/CD25+/FOXP3+) and CTLA4+/CD86+ complexes indicative of a tumor-associated immunosuppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly, ncRNA and methylation profiles reproduce changes observed postinvasion. Among the most significant findings, we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a preinvasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer. Cancer Res; 75(18); 3980–90. ©2015 AACR.
Unraveling Psychomotor Slowing in Bipolar Disorder
Authors: Morsel Anne M. , Temmerman Anke , Sabbe Bernard , Hulstijn Wouter , Morrens Manuel
Published: August 2015

Background/Aims: In addition to affective and cognitive symptomatology, psychomotor deficits are known to be present in bipolar disorder (BD). Psychomotor functioning includes all of the processes necessary for completing a movement, from planning to initiation and execution. While these psychomotor symptoms have been studied extensively in schizophrenia and major depressive disorder, only simple measures have been conducted in BD. The present study examines psychomotor functioning in BD. Methods: Twenty-two euthymic BD patients and 21 healthy controls performed three computerized copying tasks varying in cognitive load. Movement times (MT), reflecting fine motor processing, and initiation times (IT), reflecting cognitive processing of visual-spatial information, were separately measured in each group. Results: The BD patients had longer IT but not MT in the simplest task and the opposite pattern of longer MT but not IT in the complex task. However, when controlling for residual mood symptoms, the MT were no longer significantly slower in the BD group. Conclusions: The longer MT and IT in BD reflect overall psychomotor slowing. Specifically, the results provide evidence for cognitive slowing in BD. In addition, the longer MT in the complex task reflect a slowed motor component of movement when the cognitive load is high and when depressive symptoms are present. These findings extend the current knowledge of the nature of psychomotor slowing in BD and may have important prognostic implications for patients.
Low Treatment Adherence in Pubertal Children Treated with Thyroxin or Growth Hormone
Authors: Lass Nina , Reinehr Thomas
Published: August 2015

Background: Treatment outcome depends largely on treatment adherence (TA). However, studies analyzing TA in chronic endocrine diseases are scarce and controversial in childhood. Patients and Methods: We studied TA in 103 children treated subcutaneously with growth hormone (GH) and 97 children treated orally with thyroxin. TA was calculated based on the prescription refill rates. The number of GH injections was recorded by an autoinjector device in 23 children treated with GH. Results: The correlation between recorded TA and calculated TA based on prescription refill rates was very good (p < 0.001, r = 0.83). TA was lower (p < 0.01) in pubertal children compared to prepubertal children and in children self-administering their medication compared to those whose drug was administered by their parents, both in GH- and thyroxin-treated children. Overall, 67% of the pubertal children treated with GH and 58% of the pubertal children treated with thyroxin missed at least 1 dose per week. TA was higher (p < 0.001) in children with thyroxin treatment compared to children treated with recombinant human GH (8 vs. 26% missed >3 doses/week). Discussion: Puberty and self-administration of drugs were negative predictors of TA. Therefore, in puberty, prevention and treatment efforts should be undertaken to improve TA, especially when adolescents administer their drugs themselves.
Gene Therapy for Retinal Disease: What Lies Ahead
Authors: MacLaren Robert E.
Published: August 2015

Gene therapy in simple terms can be defined as a medical treatment that exerts its effects using molecules of DNA or RNA within cells. Most traditional drugs act by mechanisms that include binding to cell surface receptors, inhibiting enzymes in intracellular pathways or by modifying transcription. These approaches rely to some extent on a normal genetic make-up of the cell in the final common pathway, which raises significant challenges in diseases that are caused by specific gene mutations. An alternative gene therapy approach to change the behaviour of cells at the most fundamental level by one single genetic modification is therefore potentially very powerful and wide ranging. This paper presents an overview of retinal gene therapy at the current time and highlights the future therapeutic potential for a number of diseases that are currently incurable.
Potential Clinical Use of Kisspeptin
Authors: Prague Julia K. , Dhillo Waljit S.
Published: August 2015

Over the last 10 years, kisspeptins - peptide products of varying lengths encoded by the KISS1 gene - have been found to be key regulators of normal reproductive function throughout life in animals and humans. By activating the kisspeptin receptor [previously known as orphan G protein-coupled receptor 54 (GPR54)], they elicit an effect on the central gonadotropin-releasing hormone neurons. Administration of kisspeptin by either the subcutaneous or intravenous route potently stimulates endogenous gonadotropin hormone release in healthy men and women as well as in animals. Kisspeptin also stimulates endogenous release of gonadotropins in subfertile as well as healthy volunteers, and therefore it has potential as a novel therapeutic agent in reproductive disorders. Further human studies have shown that chronic, high-dose administration of kisspeptin causes desensitisation with rapid subsequent suppression of the hypothalamic-pituitary-gonadal axis, and therefore high-dose long-acting analogues may have a clinical role in treating sex hormone-dependent malignancies. By further elucidating the intricacies and mechanisms of the kisspeptin signalling system, and the tissues it acts on during different phases of the reproductive timeline (including during puberty, fertility, pregnancy and menopause), pharmacologic analogues could become clinically useful.
Deletion or inhibition of Fc gamma receptor 2B (CD32) prevents FVIII-specific activation of memory B cells in vitro
Authors: Vollack Nadine , Hornung Marcus von , Kalippke Katy , Kutzschbach Julia , Trummer Arne , Ganser Arnold , Tiede Andreas , Werwitzke Sonja
Published: August 2015

Development of inhibitory antibodies against factor VIII (FVIII) is a severe complication of replacement therapy in haemophilia A. Patients with inhibitors are treated with high FVIII doses in the context of immune tolerance therapy (ITT). Data from haemophilia A mouse model suggest that high FVIII concentrations prevent the formation of antibody secreting cells (ASCs) from memory B cells (MBCs) by inducing apoptosis. Fc gamma receptor 2B (CD32) is an important regulator of B cell function, mediating inhibitory signals after cross-linking with the B cell receptor. Here, the role of CD32 in the regulation of FVIII-specific MBCs was investigated using F8-/- and F8-/-CD32-/- knockout mice and monoclonal antibodies (mAbs). The initial immune response was similar between F8-/- and F8-/-CD32-/- mice, including concentration of anti-FVIII antibodies and number of FVIII-specific ASCs in spleen and bone marrow. In contrast, formation of ASCs from MBCs upon rhFVIII re-stimulation in vitro was abolished in F8-/-CD32-/- mice, whereas FVIII/anti-FVIII immune complexes significantly enhanced ASC formation in F8-/- mice. Inhibition of CD32 by mAbs or F(ab)2 fragments prevented ASC formation in a dose-dependent manner. Transfer of B cell-depleted splenocytes using CD45R (B220) depletion from CD32-competent mice did not restore ASC formation in F8-/-CD32-/- cells confirming that CD32 is required on B cells. We conclude that CD32 is a crucial regulator of FVIII-specific B cells and is required for the differentiation of MBCs into ASCs. Inhibition of CD32 could potentially improve the efficacy of FVIII in the context of ITT.
Fibrillar cellular fibronectin supports efficient platelet aggregation and procoagulant activity
Authors: Maurer Eric , Schaff Mathieu , Receveur Nicolas , Bourdon Catherine , Mercier Luc , Nieswandt Bernhard , Dubois Christophe , Jandrot-Perrus Martine , Goetz Jacky G. , Lanza François , Gachet Christian , Mangin Pierre H.
Published: August 2015

The ability of cellular fibronectin, found in the vessel wall in a fibrillar conformation, to regulate platelet functions and trigger thrombus formation remains largely unknown. In this study, we evaluated how parietal cellular fibronectin can modulate platelet responses under flow conditions. A fibrillar network was formed by mechanically stretching immobilised dimeric cellular fibronectin. Perfusion of anticoagulated whole blood over this surface resulted in efficient platelet adhesion and thrombus growth. The initial steps of platelet adhesion and activation, as evidenced by filopodia extension and an increase in intracellular calcium levels (419 ± 29 nmol/l), were dependent on integrins α5β1 and αIIbβ3. Subsequent thrombus growth was mediated by these integrins together with the GPIb-V-IX complex, GPVI and Toll-like receptor 4. The involvement of Toll-like receptor 4 could be conveyed via its binding to the EDA region of cellular fibronectin. Upon thrombus formation, the platelets became procoagulant and generated fibrin as revealed by video-microscopy. This work provides evidence that fibrillar cellular fibronectin is a strong thrombogenic surface which supports efficient platelet adhesion, activation, aggregation and procoagulant activity through the interplay of a series of receptors including integrins α5β1 and αIIbβ3, the GPIb-V-IX complex, GPVI and Toll-like receptor 4.
Deletion of
capn4
Protects the Heart Against Endotoxemic Injury by Preventing ATP Synthase Disruption and Inhibiting Mitochondrial Superoxide Generation
Authors: Ni Rui , Zheng Dong , Wang Qiang , Yu Yong , Chen Ruizhen , Sun Tao , Wang Wang , Fan Guo-Chang , Greer Peter A. , Gardiner Richard B. , Peng Tianqing
Published: August 2015

Background—

Our recent study has demonstrated that inhibition of calpain by transgenic overexpression of calpastatin reduces myocardial proinflammatory response and dysfunction in endotoxemia. However, the underlying mechanisms remain to be determined. In this study, we used cardiomyocyte-specific
capn4
knockout mice to investigate whether and how calpain disrupts ATP synthase and induces mitochondrial superoxide generation during endotoxemia.

Methods and Results—

Cardiomyocyte-specific
capn4
knockout mice and their wild-type littermates were injected with lipopolysaccharides. Four hours later, calpain-1 protein and activity were increased in mitochondria of endotoxemic mouse hearts. Mitochondrial calpain-1 colocalized with and cleaved ATP synthase-α (ATP5A1), leading to ATP synthase disruption and a concomitant increase in mitochondrial reactive oxygen species generation during lipopolysaccharide stimulation. Deletion of
capn4
or upregulation of ATP5A1 increased ATP synthase activity, prevented mitochondrial reactive oxygen species generation, and reduced proinflammatory response and myocardial dysfunction in endotoxemic mice. In cultured cardiomyocytes, lipopolysaccharide induced mitochondrial superoxide generation that was prevented by overexpression of mitochondria-targeted calpastatin or ATP5A1. Upregulation of calpain-1 specifically in mitochondria sufficiently induced superoxide generation and proinflammatory response, both of which were attenuated by ATP5A1 overexpression or mitochondria-targeted superoxide dismutase mimetics.

Conclusions—

Cardiomyocyte-specific
capn4
knockout protects the heart against lipopolysaccharide-induced injury in endotoxemic mice. Lipopolysaccharides induce calpain-1 accumulation in mitochondria. Mitochondrial calpain-1 disrupts ATP synthase, leading to mitochondrial reactive oxygen species generation, which promotes proinflammatory response and myocardial dysfunction during endotoxemia. These findings uncover a novel mechanism by which calpain mediates myocardial dysfunction in sepsis.
Clipping and Coiling of Unruptured Intracranial Aneurysms Among Medicare Beneficiaries, 2000 to 2010
Authors: Jalbert Jessica J. , Isaacs Abby J. , Kamel Hooman , Sedrakyan Art
Published: August 2015

Background and Purpose—

Endovascular coiling therapy is increasingly popular for obliteration of unruptured intracranial aneurysms, but older patients face higher procedural risks and shorter periods during which an untreated aneurysm may rupture causing subarachnoid hemorrhage (SAH). We assessed trends in clipping and coiling of unruptured intracranial aneurysms, outcomes after clipping and coiling of unruptured intracranial aneurysms, and in SAH among Medicare beneficiaries.

Methods—

Using 2000 to 2010 Medicare Provider Analysis and Review data, we identified 2 cohorts of patients admitted electively for clipping or coiling of an unruptured aneurysm: (1) utilization cohort (2000–2010): patients ≥65 years enrolled ≥1 month in a given year and (2) outcomes cohort (2001–2010): patients ≥66 years of age enrolled in Medicare for ≥1 year. We calculated rates of clipping, coiling, and SAH per 100 000 Medicare beneficiaries. We tested for trends in the risk of in-hospital mortality and complications, discharge destination, 30-day mortality, 30-day readmissions, and length of hospitalization.

Results—

Characteristics of patients undergoing clipping (n=4357) or coiling (n=7942) did not change appreciably. Overall, 30-day mortality, in-hospital complications, and 30-day readmissions decreased, generally reaching their lowest levels in 2008 to 2010 (1.6%, 25.0%, and 14.5% for clipping and 1.5%, 13.8%, and 11.0% for coiling, respectively). Procedural treatment rates per 100 000 beneficiaries increased from 1.4 in 2000 to 6.0 in 2010, driven mainly by increased use of coiling but SAH rates did not decrease.

Conclusions—

Although outcomes tended to improve over time, increased preventative treatment of unruptured intracranial aneurysms among Medicare beneficiaries did not result in a population-level decrease in SAH rates.
The Relative Dating of the Eden Narrative Gen *2-3
Authors: Bührer Walter
Published: August 2015

The present study investigates the methodological presuppositions inherent in a relative dating of Old Testament texts. Using Gen 1-3 as a test case, this study examines one of the most crucial texts in classical Pentateuchal scholarship. Recently, European scholars have tended to assume a late dating for the non-Priestly Eden narrative, an evaluation yielded through comparison with Priestly, Deuteronomic-Deuteronomistic, and late wisdom texts. However, given the lack of distinct textual reference to Priestly texts, the investigation argues that Gen 2-3 constitutes a pre-Priestly composition. In addition, no conclusive evidence indicates either Deuteronomic-Deuteronomistic or late wisdom texts influenced Gen 2-3; in fact, the lexical comparisons commonly adduced are not as conclusive as often believed.
A Short Note on Hos 3:1a
Authors: Moon Joshua N.
Published: August 2015

While often translated to describe the current living situation of the woman whom Hosea is to marry, the grammar of Hos 3:1a properly describes her current status based upon past actions.
Minor Pausal Forms and their Function
Authors: Revell E. J.
Published: August 2015

Minor pausal forms do not attract much attention from Biblical grammarians. They are briefly described by some, ignored by others (including, as far as I can determine, ehll). No specific function has ever been attributed to these forms. It is generally assumed that the accent marked on them engenders the features which justify the name ‘minor’ pausal forms. This paper describes these forms comprehensively, It shows that their most common function is to mark the end of the first of a pair of structures which are treated together as a semantic unit. It further shows that the syntax of the forms justifies the use of the term ‘minor’. The less common function of the forms confirms that they are used in situations in which a pausal form is appropriate, but which are not sufficiently prominent to support a standard pausal form.
Patriarchy, Spirituality, and Power
Authors: Cleveland Emma Kathryn
Published: August 2015

The reorganization of Akan society in the early 1300’s-1400, the subsequent formation of Asante in 1701, and the introduction of the trans-Atlantic slave trade in the former Gold Coast created new social, economic, and political conditions which initiated a change in the status, mobility, and role of women. Societal restrictions were placed upon female title-holders through language and spiritual taboos which prohibited them from sacred spaces and shrines. Akan cosmology and spirituality were monopolized as a tool for the acquisition of authority. A desire for the accumulation of wealth and power reconceptualised masculine identities as military victories began to be associated with manliness and honor. Patriarchal systems of governance were later established, specifically the institutions of chieftaincy and kingship, which were key contributors to the deterioration of political positions for females, for example, the Queen Mother. As the dominant political organizations, these institutions have seemingly functioned to shape the experiences of Ghanaian women throughout the history of Asante. This paper argues that the significance of women in the realm of politics and cultural affairs in Akan society were effectively lessened as a result of patriarchy, the manipulation of spirituality, and the influence of militaristic ideals.
Changes for Diplomacy under the Lens of Feminist Neo-Institutional Theory: The Case of Australia
Authors: Rossetti Sonia
Published: August 2015

Gender and cultural diversity have not been thoroughly studied in the literature devoted to the diplomatic system. The fundamental reason behind this gender blindness reflects the presumption that institutions are gender-neutral. Feminist literature has longed argued that gender has effects in political life and recent engagement with neo-institutionalist literature has analysed how institutions rebalance the structure/agency scale, pushing for a better understanding of the co-constitutive nature of politics. This article uses feminist neo-institutional theory to analyse whether recent internal and external changes to diplomatic practice are affecting formal and informal rules of diplomacy and improving women’s agency within diplomatic institutions.
Dryinidae of the Eastern Palaearctic region (Hymenoptera: Chrysidoidea)
Authors: OLMI MASSIMO , XU ZAIFU
Published: August 2015

An updated revision of Eastern Palaearctic Dryinidae is presented. Six subfamilies, 17 genera and 160 species are treated. Descriptions, geographic distribution, known hosts, natural enemies and type material of each species are presented, together with illustrations of the main morphological characters and keys to the subfamilies, genera and species. Complete lists of references concerning the Eastern Palaearctic Dryinidae and their hosts are given. The lectotype is designated for Anteon flaviscapus Jansson, 1950. A new combination is proposed for Mirodryinus olmii (Móczár, 1983), comb. nov. (from Radiimancus Móczár). The following new records are reported: Aphelopus prolatus Mita & Olmi, 2014 and Gonatopus formicicolus Richards, 1939 from Sweden; Aphelopus querceus Olmi, 1984, Aphelopus serratus Richards, 1939 and Anteon reticulatum Kieffer, 1905 from Bulgaria; Gonatopus nigricans (R. Perkins, 1905) from Solomon Islands; Haplogonatopus oratorius (Westwood, 1833) from Germany and Sweden.
The Impact of the Temperature Inversion Breakup on the Exchange of Heat and Mass in an Idealized Valley: Sensitivity to the Radiative Forcing
Authors: Leukauf Daniel , Gohm Alexander , Rotach Mathias W. , Wagner Johannes S.
Published: August 2015

The breakup of a nocturnal temperature inversion during daytime is studied in an idealized valley by means of high-resolution numerical simulations. Vertical fluxes of heat and mass are strongly reduced as long as an inversion is present; hence it is important to understand the mechanisms leading to its removal. In this study breakup times are determined as a function of the radiative forcing. Further, the effect of the nocturnal inversion on the vertical exchange of heat and mass is quantified. The Weather Research and Forecasting Model is applied to an idealized quasi-two-dimensional valley. The net shortwave radiation is specified by a sine function with amplitudes between 150 and 850 W m−2 during daytime and at zero during the night. The valley inversion is eroded within 5 h for the strongest forcing. A minimal amplitude of 450 W m−2 is required to reach the breakup, in which case the inversion is removed after 11 h. Depending on the forcing amplitude, between 10% and 57% of the energy provided by the surface sensible heat flux is exported out of the valley during the whole day. The ratio of exported energy to provided energy is approximately 1.6 times as large after the inversion is removed as before. More than 5 times the valley air mass is turned over in 12 h for the strongest forcing, whereas the mass is turned over only 1.3 times for 400 W m−2.
Subsidence Warming as an Underappreciated Ingredient in Tropical Cyclogenesis. Part I: Aircraft Observations
Authors: Kerns Brandon W. , Chen Shuyi S.
Published: August 2015

The development of a compact warm core extending from the mid-upper levels to the lower troposphere and related surface pressure falls leading to tropical cyclogenesis (TC genesis) is not well understood. This study documents the evolution of the three-dimensional thermal structure during the early developing stages of Typhoons Fanapi and Megi using aircraft dropsonde observations from the Impact of Typhoons on the Ocean in the Pacific (ITOP) field campaign in 2010. Prior to TC genesis, the precursor disturbances were characterized by warm (cool) anomalies above (below) the melting level (~550 hPa) with small surface pressure perturbations. Onion-shaped skew T–logp profiles, which are a known signature of mesoscale subsidence warming induced by organized mesoscale convective systems (MCSs), are ubiquitous throughout the ITOP aircraft missions from the precursor disturbance to the tropical storm stages. The warming partially erodes the lower-troposphere (850–600 hPa) cool anomalies. This warming results in increased surface pressure falls when superposed with the upper-troposphere warm anomalies associated with the long-lasting MCSs/cloud clusters. Hydrostatic pressure analysis suggests the upper-level warming alone would not result in the initial sea level pressure drop associated with the transformation from a disturbance to a TC. As Fanapi and Megi intensify into strong tropical storms, aircraft flight-level (700 hPa) and dropsonde data reveal that the warm core extends down to 850–600 hPa and has some characteristics of subsidence warming similar to the eyes of mature TCs.