bluuebunny/crossref_metadata_2025 huggingface dataset:
Midline Cervical Cleft: Review of an Uncommon Entity
Authors: Puscas Liana
Published: April 2015

Introduction. Midline cervical cleft is a rare congenital malformation which nonetheless has a classic presentation. This study presents one of the largest single series of new patients with MCC and provides an exhaustive review and catalogue of publications from the international literature.Materials and Methods. Retrospective chart review performed in two academic medical centers and literature review performed with primary verification of all quoted references.Results. Ten patients with MCC were identified (8 boys and 2 girls). All patients presented with the classic findings of this congenital anomaly, and the length of the skin defect correlated with an increase in the patient’s age. Surgical excision was complete in all cases. Thorough international literature review yielded only 195 verifiable previously reported cases.Conclusions. This is one of the largest series of new patients with midline cervical cleft presented in the world literature. Although rare (with less than 200 cases published to date) this entity does have a reliable presentation that should lead to rapid and accurate diagnosis. Complete surgical excision at an early age is appropriate since the anomaly increases in length commensurate with the patient’s age.
Dynamic Compression of the Spinal Cord by Paraspinal Muscles following Cervical Laminectomy: Diagnosis Using Flexion-Extension MRI
Authors: Evans Linton T. , Lollis S. Scott
Published: April 2015

Introduction. Flexion-extension, or kinematic, MRI has been used to identify dynamic spondylotic spinal cord compression not seen with traditional static MRI. The use of kinematic MRI to diagnose postoperative complications, specifically dynamic compression, is not as well documented. The authors describe a case of dynamic spinal cord compression by the paraspinal muscles causing worsening myelopathy following cervical laminectomy. This was only diagnosed with flexion-extension MRI.Methods. The patient was a 90-year-old male presenting to the neurosurgery clinic with functional decline and cervical spondylotic myelopathy.Results. A multilevel laminectomy was performed. Following surgery the patient had progressive weakness and worsening myelopathy. No active cord compression was seen on multiple MRIs obtained in a neutral position, and flexion-extension X-rays did not show instability. A kinematic MRI demonstrated dynamic compression of the spinal cord only during neck extension, by the paraspinal muscles. To relieve the compression, the patient underwent an instrumented fusion, with cross-links used to buttress the paraspinal muscles away from the cord. This resulted in neurologic improvement.Conclusions. We describe a novel case of spinal cord compression by paraspinal muscles following cervical laminectomy. In individuals with persistent myelopathy or delayed neurologic decline following posterior decompression, flexion-extension MRI may prove useful in diagnosing this potential complication.
Design of a Novel W-Sinker RF LDMOS
Authors: Xu Xiangming , Yu Han , Huang Jingfeng , Wang Chun , Ji Wei , Zhou Zhengliang , Cai Ying , Wang Yong , Li Pingliang , Wang Peng-Fei , Zhang David Wei
Published: April 2015

A novel RF LDMOS device structure and corresponding manufacturing process are presented in this paper. Deep trench W-sinker (tungsten sinker) is employed in this technology to replace the traditional heavily doped diffusion sinker which can shrink chip size of the LDMOS transistor by more than 30% and improve power density. Furthermore, the W-sinker structure reduces the parasitic resistance and inductance and improves thermal conductivity of the device as well. Combined with the adoption of the techniques, like grounded shield, step gate oxide, LDD optimization, and so forth, an advanced technology for RF LDMOS based on conventional 0.35 μm CMOS technology is well established. AnF+Apower amplifier product with frequency range of 1.8–2.1 GHz is developed for the application of 4G LTE base station and industry leading performance is achieved. The qualification results show that the device reliability and ruggedness can also meet requirement of the application.
Autologous Advanced Tenon Grafting Combined with Conjunctival Flap in Scleromalacia after Pterygium Excision
Authors: Lee Jong Soo , Shin Min Kyu , Park Jong Ho , Park Young Min , Song Margaret
Published: April 2015

Purpose. To evaluate the efficacy of autologous tenon grafting combined with conjunctival flap as a treatment for scleromalacia or scleral thinning after pterygium excision without any additional donor graft tissue. Methods. Twenty-six cases underwent autologous advanced tenon grafting combined with sliding or rotating conjunctival flap for scleromalacia after pterygium surgery ranging from 2 years to 30 years. The extent of scleral defect measured from 2.0 mm to 6.8 mm in diameter. The cosmetic outcome was defined as complete resolution of scleromalacia or completely conjunctival reepithelialization and firm adhesion between subtenon and scleral tissue over scleral thinning without significant complications. Results. All cases achieved the covering of conjunctival and tenon or subtenon tissue over scleromalacia or scleral thinning with this procedure. Preoperative pain, inflammation, and choroidal exposure disappeared after surgery. Immediate postoperative complications, such as large wound dehiscence or reopening of the scleral wound, did not occur in any of the patients. There were no significant clinical complications during the mean postoperative follow-up period of 14.17 months in all cases. Conclusions. We obtained excellent outcome with fewer complications after autologous advanced tenon graft and conjunctival flap, without an additional donor graft, in scleromalacia or scleral thinning caused by previous pterygium excision.
Group DSalmonellaUrinary Tract Infection in an Immunocompetent Male
Authors: Jehangir Asad , Poudel Dilli , Fareedy Shoaib Bilal , Salman Ahmed , Qureshi Anam , Jehangir Qasim , Alweis Richard
Published: April 2015

A 62-year-old male with past medical history of benign prostatic hyperplasia presented to the emergency department with complaints of decreased urinary flow, inability to fully empty his bladder, and gross hematuria. Physical examination was unremarkable. Urinalysis revealed large amount of blood and more than 700 white blood cells suggesting a urinary tract infection. Urine culture grew group DSalmonellagreater than 100,000 colony-forming units per mL. He was prescribed 6 weeks of trimethoprim/sulfamethoxazole and had resolution of symptoms. Retrospectively, he reported a 3-day history of watery diarrhea about a week prior to onset of urinary symptoms that was presumed to be the hematogenous source in this case. Urinary tract infection from nontyphoidalSalmonella(NTS) is rare and is usually associated with immunosuppression, chronic diseases, such as diabetes or structural abnormalities of the genitourinary tract. Genitourinary tract abnormalities previously reported in the literature that predispose to nontyphoidalSalmonellaurinary tract infection include nephrolithiasis, chronic pyelonephritis, retrovesicular fistula, urethrorectal fistula, hydrocele, and post-TURP. We present an exceedingly uncommon case of 62-year-old male with group DSalmonellaurinary tract infection predisposed by his history of benign prostatic hyperplasia.
Comparing the Coronal Seal of Different Thicknesses of MTA with Gutta‐Percha after Post Space Preparation
Authors: Frough Reyhani Mohammad , Yavari Hamidreza , Ghasemi Negin , Rahimi Saeed , Soroush Barhaghi Mohammad Hosien , Mokhtari Hadi , Sarikhani Payman
Published: April 2015

Introduction. The aim of this study was to compare the coronal seal of different thicknesses of MTA with gutta‐percha after post space preparation. Materials and Methods. A total of 50 maxillary central incisors randomly divided into 5 experimental groups (n = 8). After preparation of the root canals with step back technique, in groups 1 and 2, post spaces were prepared and 4 or 5 mm gutta‐percha remained in the apical, respectively. In groups 3, 4, and 5, there was 1‐2 and 3 mm MTA in the apical, respectively. The ten teeth serve as control groups. The teeth were connected to a bacterial microleakage evaluation system. The study period was 120 days and the samples were evaluated on ten‐day intervals; Meier‐Kaplan technique was used for estimation of the mean time of microleakage to occur. Log‐rank test was used for comparison of microleakage. Results. Number of samples exhibiting microleakage in MTA was less than those of gutta‐percha at all intervals. Means of days with no microleakage were maximum and minimum with 3 mm MTA and 4 mm gutta‐percha, respectively. Conclusion. Obturation of root canals using the MTA technique provides a proper seal with the minimum thickness of MTA in teeth requiring post space preparation.
A Multicenter, Phase II, Randomized, Noncomparative Clinical Trial of Radiation and Temozolomide with or without Vandetanib in Newly Diagnosed Glioblastoma Patients
Authors: Lee Eudocia Q. , Kaley Thomas J. , Duda Dan G. , Schiff David , Lassman Andrew B. , Wong Eric T. , Mikkelsen Tom , Purow Benjamin W. , Muzikansky Alona , Ancukiewicz Marek , Huse Jason T. , Ramkissoon Shakti , Drappatz Jan , Norden Andrew D. , Beroukhim Rameen , Weiss Stephanie E. , Alexander Brian M. , McCluskey Christine S. , Gerard Mary , Smith Katrina H. , Jain Rakesh K. , Batchelor Tracy T. , Ligon Keith L. , Wen Patrick Y.
Published: April 2015

Purpose: Vandetanib, a tyrosine kinase inhibitor of KDR (VEGFR2), EGFR, and RET, may enhance sensitivity to chemotherapy and radiation. We conducted a randomized, noncomparative, phase II study of radiation (RT) and temozolomide with or without vandetanib in patients with newly diagnosed glioblastoma (GBM).

Experimental Design: We planned to randomize a total of 114 newly diagnosed GBM patients in a ratio of 2:1 to standard RT and temozolomide with (76 patients) or without (38 patients) vandetanib 100 mg daily. Patients with age ≥ 18 years, Karnofsky performance status (KPS) ≥ 60, and not on enzyme-inducing antiepileptics were eligible. Primary endpoint was median overall survival (OS) from the date of randomization. Secondary endpoints included median progression-free survival (PFS), 12-month PFS, and safety. Correlative studies included pharmacokinetics as well as tissue and serum biomarker analysis.

Results: The study was terminated early for futility based on the results of an interim analysis. We enrolled 106 patients (36 in the RT/temozolomide arm and 70 in the vandetanib/RT/temozolomide arm). Median OS was 15.9 months [95% confidence interval (CI), 11.0–22.5 months] in the RT/temozolomide arm and 16.6 months (95% CI, 14.9–20.1 months) in the vandetanib/RT/temozolomide (log-rank P = 0.75).

Conclusions: The addition of vandetanib at a dose of 100 mg daily to standard chemoradiation in patients with newly diagnosed GBM or gliosarcoma was associated with potential pharmacodynamic biomarker changes and was reasonably well tolerated. However, the regimen did not significantly prolong OS compared with the parallel control arm, leading to early termination of the study. Clin Cancer Res; 21(16); 3610–8. ©2015 AACR.
Regulator of Chromosome Condensation 2 Identifies High-Risk Patients within Both Major Phenotypes of Colorectal Cancer
Authors: Bruun Jarle , Kolberg Matthias , Ahlquist Terje C. , Røyrvik Ellen C. , Nome Torfinn , Leithe Edward , Lind Guro E. , Merok Marianne A. , Rognum Torleiv O. , Bjørkøy Geir , Johansen Terje , Lindblom Annika , Sun Xiao-Feng , Svindland Aud , Liestøl Knut , Nesbakken Arild , Skotheim Rolf I. , Lothe Ragnhild A.
Published: April 2015

Purpose: Colorectal cancer has high incidence and mortality worldwide. Patients with microsatellite instable (MSI) tumors have significantly better prognosis than patients with microsatellite stable (MSS) tumors. Considerable variation in disease outcome remains a challenge within each subgroup, and our purpose was to identify biomarkers that improve prediction of colorectal cancer prognosis.

Experimental Design: Mutation analyses of 42 MSI target genes were performed in two independent MSI tumor series (n = 209). Markers that were significantly associated with prognosis in the test series were assessed in the validation series, followed by functional and genetic explorations. The clinical potential was further investigated by immunohistochemistry in a population-based colorectal cancer series (n = 903).

Results: We identified the cell-cycle gene regulator of chromosome condensation 2 (RCC2) as a cancer biomarker. We found a mutation in the 5′ UTR region of RCC2 that in univariate and multivariate analyses was significantly associated with improved outcome in the MSI group. This mutation caused reduction of protein expression in dual luciferase gene reporter assays. siRNA knockdown in MSI colon cancer cells (HCT15) caused reduced cell proliferation, cell-cycle arrest, and increased apoptosis. Massive parallel sequencing revealed few RCC2 mutations in MSS tumors. However, weak RCC2 protein expression was significantly associated with poor prognosis, independent of clinical high-risk parameters, and stratifies clinically important patient subgroups with MSS tumors, including elderly patients (>75 years), stage II patients, and those with rectal cancer.

Conclusions: Impaired RCC2 affects functional and clinical endpoints of colorectal cancer. High-risk patients with either MSI or MSS tumors can be identified with cost-effective routine RCC2 assays. Clin Cancer Res; 21(16); 3759–70. ©2015 AACR.
Significance of Polypyrimidine Tract–Binding Protein 1 Expression in Colorectal Cancer
Authors: Takahashi Hidekazu , Nishimura Junichi , Kagawa Yoshinori , Kano Yoshihiro , Takahashi Yusuke , Wu Xin , Hiraki Masayuki , Hamabe Atsushi , Konno Masamitsu , Haraguchi Naotsugu , Takemasa Ichiro , Mizushima Tsunekazu , Ishii Masaru , Mimori Koshi , Ishii Hideshi , Doki Yuichiro , Mori Masaki , Yamamoto Hirofumi
Published: April 2015

Polypyrimidine tract–binding protein (PTBP1) is an RNA-binding protein with various molecular functions related to RNA metabolism and a major repressive regulator of alternative splicing, causing exon skipping in numerous alternatively spliced pre-mRNAs. Here, we have investigated the role of PTBP1 in colorectal cancer. PTBP1 expression levels were significantly overexpressed in cancerous tissues compared with corresponding normal mucosal tissues. We also observed that PTBP1 expression levels, c-MYC expression levels, and PKM2:PKM1 ratio were positively correlated in colorectal cancer specimens. Moreover, PTBP1 expression levels were positively correlated to poor prognosis and lymph node metastasis. In analyses of colorectal cancer cells using siRNA for PTBP1, we observed that PTBP1 affects cell invasion, which was partially correlated to CD44 splicing, and this correlation was also confirmed in clinical samples. PTBP1 expression also affected anchorage-independent growth in colorectal cancer cell lines. PTBP1 expression also affected cell proliferation. Using time-lapse imaging analysis, PTBP1 was implicated in prolonged G2–M phase in HCT116 cells. As for the mechanism of prolonged G2–M phase in HCT116 siPTBP1 cells, Western blotting revealed that PTBP1 expression level was correlated to CDK11p58 expression level, which was reported to play an important role on progression to complete mitosis. These findings indicated that PTBP1 is a potential therapeutic target for colorectal cancer. Mol Cancer Ther; 14(7); 1705–16. ©2015 AACR.
Celiac Disease and the Gluten-Free Diet: Consequences and Recommendations for Improvement
Authors: Theethira Thimmaiah G. , Dennis Melinda
Published: April 2015

Background: Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically susceptible individuals. CD-related enteropathy leads to multiple nutritional deficiencies involving macro- and micronutrients. Currently, medical nutrition therapy consisting of the gluten-free diet (GFD) is the only accepted treatment for CD. Key Messages: The GFD is the cornerstone of treatment for CD. Prior published studies have concluded that maintenance of the GFD results in improvement of the majority of nutritional deficiencies. In the past, counseling for CD focused mainly on the elimination of gluten in the diet. However, the GFD is not without its inadequacies; compliance to the GFD may result in certain deficiencies such as fiber, B vitamins, iron, and trace minerals. Paucity of fortified gluten-free foods may be responsible for certain deficiencies which develop on the GFD. Weight gain and obesity have been added to the list of nutritional consequences while on the GFD and have been partially attributed to hypercaloric content of commercially available gluten-free foods. Follow-up of patients diagnosed with CD after starting the GFD has been reported to be irregular and, hence, less than ideal. Conclusions: Monitoring of the nutritional status using blood tests and use of appropriate gluten-free supplementation are integral components in the management of CD. The ideal GFD should be nutrient-dense with naturally gluten-free foods, balanced with macro- and micronutrients, reasonably priced, and easily accessible. Rotation of the pseudo-cereals provides a good source of complex carbohydrates, protein, fiber, fatty acids, vitamins and minerals. Fortification/enrichment of commonly consumed gluten-free commercial grain products should be encouraged. Dietitians specializing in CD play a critical role in the education and maintenance of the GFD for patients with CD.
Videocapsule Endoscopy in Celiac Disease: Indications and Timing
Authors: Rondonotti Emanuele , Paggi Silvia
Published: April 2015

Background: Because of its technical characteristics (i.e. 8-fold magnification, capability to inspect the entire small bowel) and minimal invasiveness, videocapsule endoscopy (VCE) has been proposed as a useful tool for managing patients with celiac disease (CD). Key Messages: Although VCE has been found to be highly sensitive and specific in identifying CD endoscopic markers, it is still inadequate to replace esophagogastroduodenoscopy (EGD) with biopsies in the diagnosis of CD. Nevertheless, it represents a reliable alternative in patients unable or unwilling to undergo EGD. Up to now, available studies have failed to identify any correlation between the length of small bowel involvement and the severity of symptoms. The available evidence on the use of VCE in diagnosing CD in equivocal cases (patients with positive serology and negative or nonspecific histology or those with negative serology and histologically proven villous atrophy) is limited, and its role is still under discussion. In CD patients not improving on gluten-free diet, a complete workup is necessary. In patients with nonresponsive (NRCD) or refractory CD (RCD), VCE has been shown to be able not only to detect significant findings, driving further management, but also to rule out major complications. Nevertheless, in this setting, the inability of VCE to take tissue samples and the risk of capsule retention can represent major limitations. Conclusions: At the present time, for diagnostic purposes, VCE can be proposed only in patients unable or unwilling to undergo EGD, whereas it could be useful in some equivocal cases. Conversely, there is no room for VCE either to estimate the length of the small bowel affected by villous atrophy or to follow up patients improving on gluten-free diet. In patients with NRCD or RCD, VCE can play a role, but it should be combined with other diagnostic techniques.
Refractory Celiac Disease: Epidemiology and Clinical Manifestations
Authors: Malamut Georgia , Cellier Christophe
Published: April 2015

A small subset of celiac disease (CD) patients becomes refractory to a gluten-free diet with persistent malabsorption and intestinal villous atrophy. This is a rare (probably less than 2% of adult CD patients), but serious disorder, with a high risk of progression to an overt T-cell lymphoma. Diagnosis of this condition defined as refractory CD (RCD) is made after exclusion of other small bowel diseases with villous atrophy. RCD has been subdivided into two subgroups according to the normal (RCDI) or abnormal phenotype of intraepithelial lymphocytes (RCDII). Whereas RCDI is hardly distinguishable from active noncompliant CD, RCDII has a severe clinical presentation and a very poor prognosis. We precisely describe below the different types of RCD and propose diagnostic and therapeutic guidelines for its clinical management.
Celiac Disease Screening in Southern and East Asia
Authors: Makharia Govind K.
Published: April 2015

Until 1970s, celiac disease (CD) was considered to be an uncommon disease except in Western Europe. The global epidemiology of CD continues to evolve with improvement in the diagnostic tests, simplification of the diagnostic criteria and increase in awareness about the disease. The Asian region is currently at the crossroads of the frontier of knowledge and awareness of CD. In many Asian nations, CD is still considered to be either nonexistent or very rare. A notable exception is India, where CD has been well recognized, especially in the northern part, and 2 population-based studies have revealed a prevalence of 0.3-1.04%. Initial reports from Malaysia, China, Japan and Singapore suggest the existence of CD in these countries. Furthermore, a meta-analysis of the predisposing factors predicts a high probability of occurrence of CD in fair numbers in China. There are no formal reports on CD from Malaysia, Indonesia, Korea, Taiwan and many other nations in this region. With the impending CD epidemic in Asia, there are many challenges. Some of the efforts which are required include determination of prevalence of CD across the region, spreading of awareness among physicians and patients, training of dieticians for proper counseling and supervision of patients, creation of gluten-free food infrastructure in the food supply and creation of patient advocacy organizations. Although the absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years/decades. It is thus appropriate that the medical community across Asia define the extent of the problem and get prepared to handle the impending CD epidemic.
Motility Alterations in Celiac Disease and Non-Celiac Gluten Sensitivity
Authors: Pinto-Sanchez Maria Ines , Bercik Premysl , Verdu Elena F.
Published: April 2015

Regulation of gut motility is complex and involves neuromuscular, immune and environmental mechanisms. It is well established that patients with celiac disease (CD) often display gut dysmotility. Studies have shown the presence of disturbed esophageal motility, altered gastric emptying, and dysmotility of the small intestine, gallbladder and colon in untreated CD. Most of these motor abnormalities resolve after a strict gluten-free diet, suggesting that mechanisms related to the inflammatory condition and disease process are responsible for the motor dysfunction. Motility abnormalities are also a hallmark of functional bowel disorders such as irritable bowel syndrome (IBS), where it has been proposed as underlying mechanism for symptom generation (diarrhea, constipation, bloating). Non-celiac gluten sensitivity (NCGS) is a poorly defined entity, mostly self-diagnosed, that presents clinically with IBS symptoms in the absence of specific celiac markers. Patients with NCGS are believed to react symptomatically to wheat components, and some studies have proposed the presence of low-grade inflammation in these patients. There is little information regarding the functional characterization of these patients before and after a gluten-free diet. A study suggested the presence of altered gastrointestinal transit in NCGS patients who also have a high prevalence of nonspecific anti-gliadin antibodies. Results of an ongoing clinical study in NCGS patients with positive anti-gliadin antibodies before and after a gluten-free diet will be discussed. Elucidating the mechanisms for symptom generation in NCGS patients is important to find new therapeutic alternatives to the burden of imposing a strict gluten-free diet in patients who do not have CD.
Endothelial Dimethylarginine Dimethylaminohydrolase 1 Is an Important Regulator of Angiogenesis but Does Not Regulate Vascular Reactivity or Hemodynamic Homeostasis
Authors: Dowsett Laura , Piper Sophie , Slaviero Anna , Dufton Neil , Wang Zhen , Boruc Olga , Delahaye Matthew , Colman Lucy , Kalk Eliza , Tomlinson James , Birdsey Graeme , Randi Anna M. , Leiper James
Published: April 2015

Background—

Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthesis and a risk factor for cardiovascular disease. Dimethylarginine dimethylaminohydrolase (DDAH) enzymes are responsible for ADMA breakdown. It has been reported that endothelial DDAH1 accounts for the majority of ADMA metabolism. However, we and others have shown strong DDAH1 expression in a range of nonendothelial cell types, suggesting that the endothelium is not the only site of metabolism. We have developed a new endothelium-specific DDAH1 knockout mouse (DDAH1
En−/−
) to investigate the significance of endothelial ADMA in cardiovascular homeostasis.

Methods and Results—

DDAH1 deletion in the DDAH1
En−/−
mouse was mediated by Tie-2 driven Cre expression. DDAH1 deletion was confirmed through immunocytochemistry, whereas Western blotting showed that DDAH1 remained in the kidney and liver, confirming expression in nonendothelial cells. Plasma ADMA was unchanged in DDAH1
En−/−
mice, and cultured aortas released amounts of ADMA to similar to controls. Consistent with these observations, vasoreactivity ex vivo and hemodynamics in vivo were unaltered in DDAH1
En−/−
mice. In contrast, we observed significantly impaired angiogenic responses both ex vivo and in vivo.

Conclusions—

We demonstrate that endothelial DDAH1 is not a critical determinant of plasma ADMA, vascular reactivity, or hemodynamic homeostasis. DDAH1 is widely expressed in a range of vascular and nonvascular cell types; therefore, the additive effect of DDAH1 expression in multiple organ systems determines plasma ADMA concentrations. Endothelial deletion of DDAH1 profoundly impairs the angiogenic capacity of endothelial cells, indicating that intracellular ADMA is a critical determinant of endothelial cell response.
hERG Potassium Channel Blockade by the HCN Channel Inhibitor Bradycardic Agent Ivabradine
Authors: Melgari Dario , Brack Kieran E. , Zhang Chuan , Zhang Yihong , El Harchi Aziza , Mitcheson John S. , Dempsey Christopher E. , Ng G. André , Hancox Jules C.
Published: April 2015

Background

Ivabradine is a specific bradycardic agent used in coronary artery disease and heart failure, lowering heart rate through inhibition of sinoatrial nodal
HCN
‐channels. This study investigated the propensity of ivabradine to interact with

KCNH
2

‐encoded human Ether‐à‐go‐go–Related Gene (
hERG
) potassium channels, which strongly influence ventricular repolarization and susceptibility to torsades de pointes arrhythmia.

Methods and Results

Patch clamp recordings of
hERG
current (I
h

ERG

) were made from
hERG
expressing cells at 37°C. I
h

ERG

was inhibited with an
IC
50
of 2.07 μmol/L for the
hERG
1a isoform and 3.31 μmol/L for coexpressed
hERG
1a/1b. The voltage and time‐dependent characteristics of I
h

ERG

block were consistent with preferential gated‐state‐dependent channel block. Inhibition was partially attenuated by the N588K inactivation‐mutant and the S624A pore‐helix mutant and was strongly reduced by the Y652A and F656A S6 helix mutants. In docking simulations to a MthK‐based homology model of
hERG
, the 2 aromatic rings of the drug could form multiple π‐π interactions with the aromatic side chains of both Y652 and F656. In monophasic action potential (
MAP
) recordings from guinea‐pig Langendorff‐perfused hearts, ivabradine delayed ventricular repolarization and produced a steepening of the
MAPD
90
restitution curve.

Conclusions

Ivabradine prolongs ventricular repolarization and alters electrical restitution properties at concentrations relevant to the upper therapeutic range. In absolute terms ivabradine does not discriminate between
hERG
and
HCN
channels: it inhibits I
h

ERG

with similar potency to that reported for native I
f
and
HCN
channels, with S6 binding determinants resembling those observed for
HCN
4. These findings may have important implications both clinically and for future bradycardic drug design.
“Femininity without Feminism”
Authors: Mun Soo-Hyun
Published: April 2015

This article contributes to the debate between the merits of the ‘politics of presence’ versus the ‘politics of ideas’ by examining the case of the first female Korean president, Park Geun-Hye. On the one hand, Park did not represent ‘the ideas’ of feminist politics. While her gender identity was widely propagated and accepted, it did not transform into deliberate identity-based politics. On the other hand, she contributed to the elevation of women’s social status through various unintended consequences, although Park’s ‘femininity without feminism’ inevitably led to the negligence of gender politics in her government. Indeed, Park’s existence, rather than her intention, stimulated the debate on the role and status of women in Korean society and enabled the rise of a number of first females in various sectors. In sum, the ‘politics of presence’ was triggered even without overt political measures.
Traffic noise affects colouration but not calls in the European treefrog (Hyla arborea)
Authors: Troïanowski Mathieu , Condette Camille , Mondy Nathalie , Dumet Adeline , Lengagne Thierry
Published: April 2015

In terrestrial habitats, traffic noise is responsible for chronic noise exposure and impacts both signal detection and acoustic signal structure. Several species are known to adapt their call structures to cope with noise. However, compromised hearing affects more than acoustic communication, and noise should be consider as a stress factor that can also alter visual communication in the case of carotenoid-based signals. Here, we experimentally investigated the impact of traffic noise on the expression of secondary sexual signals in the European treefrog, Hyla arborea. Treefrogs use multimodal communication in the sexual selection process (mating calls and vocal sac colouration). We found that treefrogs seem unable to adjust their call structure. Nonetheless, males showed a significant decrease in colouration intensity. Our findings highlight for the first time the negative effect of traffic noise on colour signals. This suggests that anthropogenic noise could affect a wider range of species than previously thought.
Phylogenetic relationships of the species and biogeography of the characid genus Oligosarcus Günther, 1864 (Ostariophysi, Characiformes, Characidae)
Authors: RIBEIRO ALEXANDRE CUNHA , MENEZES NAÉRCIO AQUINO
Published: April 2015

The characid genus Oligosarcus consists of 20 described species distributed throughout most of South American river basins below 14º south latitude. This study focus on the phylogenetic relationships of the species of Oligosarcus based on the analysis of osteological characters to provide data to discuss the biogeographic history of the genus. The analysis resulted in a single most parsimonious tree with 152 steps (CI= 0.355 and RI= 0.600). The 18 included Oligosarcus species were hierarchically organized into 17 clades. A minimal age of 15 Ma for the genus is suggested based on the putatively cladogenetic event represented by the continued shortening of the Eastern Cordillera that established the eastern boundary of the modern central Andean plateau and was responsible for cladogenesis between the common ancestor of O. schindleri + O. bolivianus versus the remaining congeners. There is a pronounced disjunction in the upland species distribution by the lowland areas of the Chaco-Pantanal basin. This indicates that upland habitats (headwater streams) are preferential habitats for a set of species including O. argenteus, O. bolivianus, O. brevioris, O. paranensis, O. perdido, O. pintoi, O. planaltinae, O. brevioris, and O. schindleri. Fragmentation of populations of O. pintoi and O. perdido are at least 2.5 Ma old, since the origin of the upper Paraguay depression clearly promoted the present-day observed disjunction in the distribution of these species. The lowland Oligosarcus species are all included in a single clade but the obtained results suggest that fragmentation of upland versus lowland components of the genus was not causally related to a single vicariant event. The available fossil record of Oligosarcus indicates that the genus already occurred in the coastal plain at about 2.3 to 1.25 Ma. The sister-group relationship between O. hepsetus and O. longirostris provided additional evidences of the so-called historical affinities between the SE Brazilian coastal plain and the Rio Iguaçu drainage basin.
A new species of Magnimyiolia Shiraki (Diptera: Tephritidae: Trypetinae) and new records of Acanthonevrini from India
Authors: SINGH SHAKTI KUMAR , DAVID K. J. , KUMAR DINESH , RAMAMURTHY V. V.
Published: April 2015

A new species of the subfamily Trypetinae, Magnimyiolia perennifascia Singh & David, sp. nov. (Trypetini) is described from India. Two species of subfamily Phytalmiinae, Ectopomyia baculigera Hardy and Ptilona conformis Zia (Acanthonevrini) are recorded for the first time from India. An updated key to Oriental species of Magnimyiolia Shiraki is provided.
Clinical accuracy of a low cost portable blood pressure device in pregnancy and pre-eclampsia: the Nissei DS-400
Authors: de Greeff Annemarie , Shennan Andrew H
Published: April 2015

Hypertensive disorders of pregnancy cause significant maternal morbidity and mortality worldwide, particularly in developing countries. This study evaluated the accuracy of the Nissei DS-400, a low cost blood pressure (BP) device, in pregnancy according to the British Hypertension Society protocol. Forty-five pregnant women (15 with pre-eclampsia), were recruited from a large teaching hospital. Nine sequential same-arm BP measurements were taken from each woman by trained observers, alternating between mercury sphygmomanometry and the device. The Nissei DS-400 achieved the highest accuracy grade (A/A) in all subjects ( n = 45) and in pregnancy alone ( n = 30). The mean difference ± standard deviation between the standard and the device in pregnancy were −1.0 ± 5.1 mmHg and −1.1 ± 5.0 mmHg for systolic and diastolic BP, respectively, and −2.6 ± 5.9 mmHg and –3.4 ± 5.8 mmHg in all subjects. The Nissei-DS 400 can be recommended for clinical use in pregnancy and has potential as a good screening tool for pre-eclampsia in low resource settings.
Understanding the Implementation of Medicaid and Medicare: Social Construction and Historical Context
Authors: Piatak Jaclyn S.
Published: April 2015

This article examines the history and formation of Medicare and Medicaid to determine how America’s two major public health insurance programs came to have such vastly different implementation structures. Drawing upon theories of social construction and path dependence, findings show how the programs were set on divergent paths. This article also explores how the intergovernmental nature of Medicaid has promoted inequities, both between programs and among recipients across states. The findings show how social construction can influence the policy tool chosen and how the implementation structure impacts the individuals whom these programs are intended to serve for years to come.
Stigma as a Barrier to Substance Abuse Treatment Among Those With Unmet Need: An Analysis of Parenthood and Marital Status
Authors: Stringer Kristi L. , Baker Elizabeth H.
Published: April 2015

Substance use (SU) stigma is one factor contributing to unmet need for SU treatment. Additionally, theory suggests that women and single parents who use substances experience enhanced stigma because they do not adhere to normative social expectations. This study examines differences in perceived stigma by gender and parenthood among those with unmet need for SU treatment using the 2003-2010 National Survey of Drug Use and Health ( N = 1,474). Results indicate that women are more likely to report stigma as a barrier to treatment compared with men, though the interaction between gender and parenthood is not significant. We find that married parents report the highest level of stigma. We situate our findings in past health-related stigma research. We suggest that these results shed a light on stigma, particularly as it relates to family status, as a contributing factor to differences regarding SU treatment utilization. Finally, we raise a provocative question concerning social status and anticipated stigma.
Miniaturized versus conventional cardiopulmonary bypass and acute kidney injury after cardiac surgery
Authors: Chew STH , Ng RRG , Liu W , Goh SG , Caleb MG , Ti LK
Published: April 2015

Introduction:

Acute kidney injury (AKI) is a serious complication after coronary artery bypass grafting (CABG). There are conflicting reports whether a miniaturized cardiopulmonary bypass (MCPB) system is associated with a lower AKI incidence compared with conventional cardiopulmonary bypass (CCPB). It is unknown if AKI risk factors differ between the two groups. We assessed if MCPB decreases AKI after CABG and compared the risk factors between both groups.

Methods:

Sixty-eight Asian patients presenting for elective CABG at a tertiary heart centre were enrolled. They were randomly assigned to MCPB (n=34) or CCPB group (n=34) and followed up in a single-blinded, prospective, randomized, controlled trial. The primary outcome was Acute Kidney Injury Network stage 1 AKI.

Results:

The AKI incidence was 21.5% and was not significantly different between patients undergoing MCPB versus CCPB (21.9% versus 21.2%, p=0.948). The first CPB haematocrit was independently associated with AKI in the MCPB group (Relative Risk [RR]=0.484, 95% Confidence Interval [CI]=0.268-0.876, p=0.016); post-operative blood loss and inflammation were independently associated with AKI in the CCPB group (RR=1.005, 95%CI=1.003-1.007, p<0.001; RR=1.018, 95%CI=1.010-1.028, p<0.001).

Conclusion:

The MCPB system is not associated with a lower incidence of AKI in Asian patients undergoing CABG. Risk factors for AKI differed between patients using the MCPB and CCPB systems.
A comparison of remote therapy, face to face therapy and an attention control intervention for people with aphasia: a quasi-randomised controlled feasibility study
Authors: Woolf Celia , Caute Anna , Haigh Zula , Galliers Julia , Wilson Stephanie , Kessie Awurabena , Hirani Shashi , Hegarty Barbara , Marshall Jane
Published: April 2015

Objective:

To test the feasibility of a randomised controlled trial comparing face to face and remotely delivered word finding therapy for people with aphasia.

Design:

A quasi-randomised controlled feasibility study comparing remote therapy delivered from a University lab, remote therapy delivered from a clinical site, face to face therapy and an attention control condition.

Setting:

A University lab and NHS outpatient service.

Participants:

Twenty-one people with aphasia following left hemisphere stroke.

Interventions:

Eight sessions of word finding therapy, delivered either face to face or remotely, were compared to an attention control condition comprising eight sessions of remotely delivered supported conversation. The remote conditions used mainstream video conferencing technology.

Outcome measures:

Feasibility was assessed by recruitment and attrition rates, participant observations and interviews, and treatment fidelity checking. Effects of therapy on word retrieval were assessed by tests of picture naming and naming in conversation.

Results:

Twenty-one participants were recruited over 17 months, with one lost at baseline. Compliance and satisfaction with the intervention was good. Treatment fidelity was high for both remote and face to face delivery (1251/1421 therapist behaviours were compliant with the protocol). Participants who received therapy improved on picture naming significantly more than controls (mean numerical gains: 20.2 (remote from University); 41 (remote from clinical site); 30.8 (face to face); 5.8 (attention control); P <.001). There were no significant differences between groups in the assessment of conversation.

Conclusions:

Word finding therapy can be delivered via mainstream internet video conferencing. Therapy improved picture naming, but not naming in conversation.
Randomized controlled clinical trial evaluating multiplex polymerase chain reaction for pathogen identification and therapy adaptation in critical care patients with pulmonary or abdominal sepsis
Authors: Tafelski Sascha , Nachtigall Irit , Adam Thomas , Bereswill Stefan , Faust Jana , Tamarkin Andrey , Trefzer Tanja , Deja Maria , Idelevich Evgeny A , Wernecke Klaus-Dieter , Becker Karsten , Spies Claudia
Published: April 2015

Objective

To determine whether a multiplex polymerase chain reaction (PCR)-based test could reduce the time required for initial pathogen identification in patients in an intensive care unit (ICU) setting.

Methods

This double-blind, parallel-group randomized controlled trial** enrolled adults with suspected pulmonary or abdominal sepsis caused by an unknown pathogen. Both the intervention and control groups underwent the standard blood culture (BC) testing, but additional pathogen identification, based on the results of a LightCycler® SeptiFast PCR test, were provided in the intervention group.

Results

The study enrolled 37 patients in the control group and 41 in the intervention group. Baseline clinical and demographic characteristics were similar in both groups. The PCR-based test identified a pathogen in 10 out of 41 (24.4%) patients in the intervention group, with a mean duration from sampling to providing the information to the ICU of 15.9 h. In the control group, BC results were available after a significantly longer period (38.1 h).

Conclusion

The LightCycler® SeptiFast PCR test demonstrated a significant reduction in the time required for initial pathogen identification, compared with standard BC.
Confronting Farmer Suicides in India
Authors: Kaushal Akta
Published: April 2015

This article translates the realities and lifeworlds that encircle agrarian distress in India by mapping multiple affective responses from India’s middle classes to farmer suicides. Highlighting unheard voices first, specifically from the state of Punjab, it then analyzes discourses attempting to explain agrarian distress through farmer suicides. By mapping the contrasting terrain of multiple translations, the article seeks to reveal alternative ethico-political possibilities for responding to agrarian life and struggles.
Health geography II
Authors: Rosenberg Mark
Published: April 2015

Over the years, various observers of health geography have sought to ‘divide’ the sub-discipline mainly along theoretical lines or to argue for a broadening of its theoretical base. Paralleling the growing theoretical pluralism within health geography has been a growing methodological pluralism. As in other parts of human geography, health geographers have embraced historical research, quantitative and qualitative methods, and computer mapping and geographic information science (GIS). Analysing recent contributions by health geographers, the question I seek to answer is whether the growing theoretical and methodological pluralism has paradoxically led to increasing divisions in the topics of study based mainly, but not solely, on what methods are employed in the research. While there are topical overlaps (e.g. quantitative and qualitative studies of particular vulnerable groups), it is less obvious as to how research using one methodology is informing research using the other methodology.
Why do firms pay stock dividends: Is it just a stock split?
Authors: He Xi , Li Mingsheng , Shi Jing , Twite Garry
Published: April 2015

This paper examines why firms choose to pay stock dividends. Using a sample of listed Chinese firms we find that older, more profitable firms with lower leverage, higher levels of retained earnings, private ownership prior to listing, that invest more in fixed assets and operate in regions with lower shareholder protection are more likely to pay stock dividends. Consistent with stock dividends substituting for stock splits, our evidence indicates that the initiation of a stock dividend is associated with a significant positive market reaction and increased analyst following. These results suggest that firms use stock dividends to attract analysts’ attention. In addition, the positive announcement effect for stock dividends increases with the size of the split factor, suggesting that management use stock dividends to keep the firm’s stock price within its acceptable trading range.
After ideocracy and civil society
Authors: Hann Chris
Published: April 2015

Behind only that of Bronislaw Malinowski, the influence of the Central European polymaths Ernest Gellner and Karl Polanyi on socio-cultural anthropology in the 20th century was profound. Gellner and Polanyi also influenced much wider swathes of scholarship. They belong to different generations and were raised in quite different settings in Prague and Budapest respectively. What these thinkers have in common is a philosophy of history which posits the industrial revolution in northwest Europe as a radical rupture in Weltgeschichte. Polanyi’s ‘great transformation’, with its focus on the economy, corresponds to Gellner’s metaphor of the ‘big ditch’ and focus on a new polity. The cultural homogenization of the nation-state and the disembedding of the economy from society in the era of free trade are two sides of the same coin. This paper argues that these complementary models derive to a considerable degree from the scholars’ background on the margins of industrializing Europe, in the ruins of the Habsburg Empire.
What Bears Witness of the Failed Revolution?
Authors: Marzec Wiktor
Published: April 2015

This article investigates the rise of political antisemitism during the 1905–1907 Revolution in the Russian-controlled Kingdom of Poland. Extensive, diachronic discourse analysis of political leaflets reveals the role antisemitism played as a political device assisting the construction of new political identities and their dissemination through political mobilization. National Democracy and their labor branch, the National Workers Union, took the nation as the basic form of affiliation. The forging of such national unity, however, was difficult to engender among the workers owing to unique historical circumstances, the experience of exploitation, and longstanding socialist agitation. This process was aided, however, by the reference to a strong negative figure of the Other. When “nationalism began to hate,” antisemitism appeared to be an extremely effective mobilizing device, and the Jews started to act as a negative, constitutive point of reference for the construction of national unity among the Poles. The analysis of the mobilization process and focus on discourse as a main factor in shaping political identities demonstrates that National Democratic antisemitism was neither an automatic activation of already present popular anti-Jewish sentiments due to the rise of mass politics nor a sheer creation of nationalist ideologues. It was, rather, the logic of discourse that ushered in a need for a negatively evaluated outsider, Jews being easily invested in this place due to a particular sociodemographic conjuncture and older judeophobic tendencies.