bluuebunny/crossref_metadata_2025 huggingface dataset:
Anterior surface opacification of intraocular lenses after Descemet's stripping automated endothelial keratoplasty
Authors: Ní Mhéalóid Áine , Fulcher Tim , O'Keefe Michael
Published: December 2015

Descemet's stripping automated endothelial keratoplasty (DSAEK) is today recognised as the surgical procedure of choice for corneal endothelial dysfunction.1The triple procedure (either staged or combined), whereby cataract surgery can be performed at the same time as endothelial keratoplasty, is well suited for patients with Fuch's endothelial dystrophy with decreased vision due to endothelial guttata, early stromal oedema and cataract formation.2Recognised complications of DSAEK include donor graft detachment/dislocation, primary graft failure and pupillary block by air.2–4Intraocular lens (IOL) opacification is a complication that is becoming apparent in patients who have undergone DSAEK and, to date, no definitive mechanism of such opacification has been discovered. Primary postoperative optic opacification of hydrophilic acrylic IOL designs has been attributed to the formation of calcium phosphate deposits.5 6This has led to changes in lens designs, manufacturing processes and packaging.7Secondary calcification is thought to be caused by environmental factors unrelated to the IOL model, such as breakdown of the blood–aqueous barrier.8In this report, four cases of IOL anterior surface opacification are described in patients who required both cataract surgery and DSAEK. Only one case had cataract surgery and DSAEK performed concurrently, with the remainder having DSAEK performed at variable timeframes after cataract surgery.
Juvenile spondyloarthropathy: an important clinical lesson to remember
Authors: Sridharan Radhika , Ngiu Chai Soon , Shaharir Syahrul Sazliyana , Mohamed Said Mohd Shahrir
Published: December 2015

Spondyloarthropathy (SpA) is a group of inflammatory conditions that include spondylitis, sacroiliitis, asymmetrical peripheral arthritis and enthesitis. This condition is known as juvenile SpA when the diagnosis is made in patients up to 16 years of age. Enthesitis is a highly specific feature that occurs more often in juvenile SpA than in the adult form. In contrast to adult onset SpA, the initial manifestation of juvenile SpA rarely presents as inflammatory back pain. Peripheral arthritis is the more common presenting feature. We report a case of a 12-year-old boy who presented with a 1-year history of progressive low back pain, gluteal pain and thigh pain. There were no clinical symptoms of arthropathy of the distal extremities. MRI of the whole spine was performed twice, which, unfortunately, was unyielding. Finally, MRI of the sacroiliac joints revealed asymmetric sacroiliitis as well as enthesitis of the hips and pelvis. Further laboratory data showed negative rheumatoid factor and positive human leucocyte antigen (HLA) B27. A diagnosis of juvenile SpA with sacroiliitis and enthesitis was made. The imaging characteristics of juvenile SpA are highlighted.
Locally advanced adenocarcinoma of the rectum presenting with necrotising fasciitis of the perineum: successful management with early aggressive surgery and multimodal therapy
Authors: Ferreira Luís , Alexandrino Henrique , Leite Júlio Soares , Castro Sousa Francisco
Published: December 2015

Colorectal cancer is a common malignant neoplasm and its treatment usually involves surgery associated, in some cases, depending on the staging, with chemoradiotherapy. Necrotising fasciitis of the perineum is a highly lethal infection of the perineum, perirectal tissues and genitals, requiring emergency surgical debridement, broad-spectrum antibiotics and control of sepsis. We present the case of a 59-year-old man with necrotising fasciitis of the perineum as the first clinical manifestation of locally advanced adenocarcinoma of the rectum, in which successful management consisted of early and aggressive surgical debridement, followed by multimodal therapy with curative intent. 2 years and 6 months after surgery the patient is well, with no evidence of local or systemic relapse.
Relative associations between depression and anxiety on adverse cardiovascular events: does a history of coronary artery disease matter? A prospective observational study
Authors: Pelletier Roxanne , Bacon Simon L , Arsenault André , Dupuis Jocelyn , Laurin Catherine , Blais Lucie , Lavoie Kim L
Published: December 2015

Objectives

To assess whether depression and anxiety increase the risk of mortality and major adverse cardiovascular events (MACE), among patients with and without coronary artery disease (CAD).

Design and setting, and patients

DECADE (Depression Effects on Coronary Artery Disease Events) is a prospective observational study of 2390 patients referred at the Montreal Heart Institute. Patients were followed for 8.8 years, between 1998 and 2009. Depression and anxiety were assessed using a psychiatric interview (Primary Care Evaluation of Mental Disorders, PRIME-MD). Outcomes data were obtained from Quebec provincial databases.

Main outcome measures

All-cause mortality and MACE.

Results

After adjustment for covariates, patients with depression were at increased risks of all-cause mortality (relative risk (RR)=2.84; 95% CI 1.25 to 6.49) compared with patients without depression. Anxiety was not associated with increased mortality risks (RR=0.86; 95% CI 0.31 to 2.36). When patients were stratified according to CAD status, depression increased the risk of mortality among patients with no CAD (RR=4.39; 95% CI 1.12 to 17.21), but not among patients with CAD (RR=2.32; 95% CI 0.78 to 6.88). Neither depression nor anxiety was associated with MACE among patients with or without CAD.

Conclusions and relevance

Depression, but not anxiety, was an independent risk factor for all-cause mortality in patients without CAD. The present study contributes to a better understanding of the relative and unique role of depression versus anxiety among patients with versus without CAD.
Inequalities in physical comorbidity: a longitudinal comparative cohort study of people with severe mental illness in the UK
Authors: Reilly Siobhan , Olier Ivan , Planner Claire , Doran Tim , Reeves David , Ashcroft Darren M , Gask Linda , Kontopantelis Evangelos
Published: December 2015

Objectives

Little is known about the prevalence of comorbidity rates in people with severe mental illness (SMI) in UK primary care. We calculated the prevalence of SMI by UK country, English region and deprivation quintile, antipsychotic and antidepressant medication prescription rates for people with SMI, and prevalence rates of common comorbidities in people with SMI compared with people without SMI.

Design

Retrospective cohort study from 2000 to 2012.

Setting

627 general practices contributing to the Clinical Practice Research Datalink, a UK primary care database.

Participants

Each identified case (346 551) was matched for age, sex and general practice with 5 randomly selected control cases (1 732 755) with no diagnosis of SMI in each yearly time point.

Outcome measures

Prevalence rates were calculated for 16 conditions.

Results

SMI rates were highest in Scotland and in more deprived areas. Rates increased in England, Wales and Northern Ireland over time, with the largest increase in Northern Ireland (0.48% in 2000/2001 to 0.69% in 2011/2012). Annual prevalence rates of all conditions were higher in people with SMI compared with those without SMI. The discrepancy between the prevalence of those with and without SMI increased over time for most conditions. A greater increase in the mean number of additional conditions was observed in the SMI population over the study period (0.6 in 2000/2001 to 1.0 in 2011/2012) compared with those without SMI (0.5 in 2000/2001 to 0.6 in 2011/2012). For both groups, most conditions were more prevalent in more deprived areas, whereas for the SMI group conditions such as hypothyroidism, chronic kidney disease and cancer were more prevalent in more affluent areas.

Conclusions

Our findings highlight the health inequalities faced by people with SMI. The provision of appropriate timely health prevention, promotion and monitoring activities to reduce these health inequalities are needed, especially in deprived areas.
Trends in hospital admissions and surgical procedures for degenerative lumbar spine disease in England: a 15-year time-series study
Authors: Sivasubramaniam Vinothan , Patel Hitesh C , Ozdemir Baris A , Papadopoulos Marios C
Published: December 2015

Objectives

Low back pain (LBP), from degenerative lumbar spine disease, represents a significant burden on healthcare resources. Studies worldwide report trends attributable to their country's specific demographics and healthcare system. Considering England's specific medico-socioeconomic conditions, we investigate recent trends in hospital admissions and procedures for LBP, and discuss the implications for the allocation of healthcare resources.

Design

Retrospective cohort study using Hospital Episode Statistics data relating to degenerative lumbar spine disease in England, between 1999 and 2013. Regression models were used to analyse trends.

Outcome measures

Trends in the number of admissions and procedures for LBP, mean patient age, gender and length of stay.

Results

Hospital admissions and procedures have increased significantly over the study period, from 127.09 to 216.16 and from 24.5 to 48.83 per 100 000, respectively, (p<0.001). The increase was most marked in the oldest age groups with a 1.9 and 2.33-fold increase in admissions for patients aged 60–74 and ≥75 years, respectively, and a 2.8-fold increase in procedures for those aged ≥60 years. Trends in hospital admissions were characterised by a widening gender gap, increasing mean patient age, and decreasing mean hospital stay (p<0.001). Trends in procedures were characterised by a narrowing gender gap, increasing mean patient age (p=0.014) and decreasing mean hospital stay (p<0.001). Linear regression models estimate that each hospital admission translates to 0.27 procedures, per 100 000 (95% CI 0.25 to 0.30, r 0.99, p<0.001; r, Pearson's correlation coefficient). Hospital admissions are increasing at 3.5 times the rate of surgical procedures (regression gradient 7.63 vs 2.18 per 100 000/year).

Conclusions

LBP represents a significant and increasing workload for hospitals in England. These trends demonstrate an increasing demand for specialists involved in the surgical and non-surgical management of this disease, and highlight the need for services capable of dealing with the increased comorbidity burden associated with an ageing patient group.
Bloodstream infections, antibiotic resistance and the practice of blood culture sampling in Germany: study design of a Thuringia-wide prospective population-based study (AlertsNet)
Authors: Karch André , Schmitz Roland P , Rißner Florian , Castell Stefanie , Töpel Sandra , Jakob Matthias , Brunkhorst Frank M , Mikolajczyk Rafael T
Published: December 2015

Introduction

Bloodstream infections are a major cause of death worldwide; blood culture (BC) sampling remains the most important tool for their diagnosis. Current data suggest that BC rates in German hospitals are considerably lower than recommended; this points to shortfalls in the application of microbiological analyses. Since early and appropriate BC diagnostics are associated with reduced case fatality rates and a shorter duration of antimicrobial therapy, a multicomponent study for the improvement of BC diagnostics was developed.

Methods and analysis

An electronic BC registry established for the German Federal state of Thuringia is the structural basis of this study. The registry includes individual patient data (microbiological results and clinical data) and institutional information for all clinically relevant positive BCs at the participating centres. First, classic result quality indicators for bloodstream infections (eg, sepsis rates) will be studied using Poisson regression models (adjusted for institutional characteristics) in order to derive relative ranks for feedback to clinical institutions. Second, a target value will be established for the process indicator BC rate. On the basis of this target value, recommendations will be made for a given combination of institutional characteristics as a reference for future use in quality control. An interventional study aiming at the improvement of BC rates will be conducted thereafter. On the basis of the results of a survey in the participating institutions, a targeted educational intervention will be developed. The success of the educational intervention will be measured by changes in the process indicator and the result indicators over time using a pre–post design.

Ethics and dissemination

Ethics approval was obtained from the Ethics committee of the University Hospital Jena and from the Ethics committee of the State Chamber of Physicians of Thuringia. Findings of AlertsNet will be disseminated through public media releases and publications in peer-reviewed journals.

Trial registration number

DRKS00004825.
Estimating the probability of demonstrating vaccine efficacy in the declining Ebola epidemic: a Bayesian modelling approach
Authors: Camacho Anton , Eggo Rosalind M , Funk Sebastian , Watson Conall H , Kucharski Adam J , Edmunds W John
Published: December 2015

Objectives

We investigate the chance of demonstrating Ebola vaccine efficacy in an individually randomised controlled trial implemented in the declining epidemic of Forécariah prefecture, Guinea.

Methods

We extend a previously published dynamic transmission model to include a simulated individually randomised controlled trial of 100 000 participants. Using Bayesian methods, we fit the model to Ebola case incidence before a trial and forecast the expected dynamics until disease elimination. We simulate trials under these forecasts and test potential start dates and rollout schemes to assess power to detect efficacy, and bias in vaccine efficacy estimates that may be introduced.

Results

Under realistic assumptions, we found that a trial of 100 000 participants starting after 1 August had less than 5% chance of having enough cases to detect vaccine efficacy. In particular, gradual recruitment precludes detection of vaccine efficacy because the epidemic is likely to go extinct before enough participants are recruited. Exclusion of early cases in either arm of the trial creates bias in vaccine efficacy estimates.

Conclusions

The very low Ebola virus disease incidence in Forécariah prefecture means any individually randomised controlled trial implemented there is unlikely to be successful, unless there is a substantial increase in the number of cases.
Breast carcinoma and phyllodes tumour: a case series
Authors: Sin Eliza I-Lin , Wong Chow Yin , Yong Wei Sean , Ong Kong Wee , Madhukumar Preetha , Tan Veronique Kiak Mien , Thike Aye Aye , Tan Puay Hoon , Tan Benita Kiat Tee
Published: December 2015

Malignant transformation of the epithelial component of phyllodes tumours (PT) is rare and only reported in literature as sporadic cases of carcinoma associated with PTs. We report the clinicopathological characteristics of in situ and invasive carcinoma coexisting with PT in 10 patients treated in our institution over an 11-year period from 1992 to 2012. Ten patients with coexisting PT and in situ or invasive carcinoma were identified from our records. Six had carcinoma found within the PT. All were female with a median age of 47 (43–72) years. One patient had a history of PT in the same breast while another had a history of PT in the same breast as well as invasive ductal carcinoma in the contralateral breast. The rest did not have any risk factors of breast cancer. Five patients had a preoperative core needle biopsy performed with the report of a fibroepithelial lesion. The rest of the patients had surgery upfront for their breast masses. Two patients who had ER/PR positive invasive carcinoma received adjuvant hormonal therapy. Patients were followed up for a mean of 3.6 years (9 months–10 years) and all patients were alive and recurrence free. PT associated with carcinoma is rare, and we present a series of cases that add to the limited current literature. It is often difficult to detect the presence of the carcinomatous component preoperatively. Hence, close examination of resected PT specimens must be carried out to allow prompt detection of any associated carcinomas, however rare, such that adequate treatment can be given.
Astragaloside IV protects cardiomyocytes from anoxia/reoxygenation injury by upregulating the expression of Hes1 protein
Authors: Huang Huang , Lai Songqing , Wan Qing , Qi Wanghong , Liu Jichun
Published: December 2015

Astragaloside IV (ASI), a traditional Chinese medicine, is a main active ingredient of Astragalus membranaceus. Many clinical studies have found that ASI protects cardiomyocytes in cardiovascular diseases, but the underlying mechanisms remain obscure. The aim of this study was to investigate the molecular mechanisms responsible for the protective effects of ASI in cardiomyocytes from anoxia/reoxygenation (A/R) injury. According to the previous studies, we hypothesized that the cardioprotective effects of ASI against A/R injury might be associated with Notch1/Hes1 signaling pathway. In this study, neonatal rat primary cardiomyocytes were preconditioned with ASI prior to A/R injury. Our results showed that ASI effectively increased the cell viability, decreased the content of MDA, decreased the activities of CPK and LDH, increased the activities of GSH-Px and SOD, and reduced the reactive oxygen species (ROS) generation and the loss of mitochondrial membrane potential (Δψm). ASI inhibited the mitochondrial permeability transition pore (mPTP) opening and activation of caspase-3, and finally decreased the cell apoptosis in cardiomyocytes. Furthermore, ASI upregulated Hes1 protein expression. However, pretreatment with DAPT, a Notch1 inhibitor, effectively attenuated the cardioprotective effects of ASI against A/R injury, except MDA, SOD, GSH-Px, and the ROS generation. Taken together, we demonstrated that ASI could protect against A/R injury via the Notch1/Hes1 signaling pathway.
Implementation of Microplane Model Into Three-Dimensional Beam Element for Shape Memory Alloys
Authors: Poorasadion Saeid , Arghavani Jamal , Naghdabadi Reza , Sohrabpour Saeed
Published: December 2015

In this study, a three-dimensional (3D) beam element based on Timoshenko beam theory is introduced for shape memory alloys (SMAs). Employing the microplane approach, we use a 3D SMA constitutive model extended from a 1D model proposed by Brinson. The SMA model is implemented into a user-defined subroutine (UMAT) in the nonlinear finite element software ABAQUS/Standard. Results of numerical examples show reasonable agreement with experimental data in proportional and non-proportional loadings. Furthermore, several applications (staple, spring, structure) are simulated and the results are compared with those of continuum elements. According to the results, the 3D SMA beam element can be used in the design and analysis of various SMA applications.
Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells
Authors: Li Ziqing , Li Chaohong , Zhou Yuhuan , Chen Weishen , Luo Guotian , Zhang Ziji , Wang Haixing , Zhang Yangchun , Xu Dongliang , Sheng Puyi
Published: December 2015

Advanced glycation end products (AGEs) disturb bone remodeling during aging, and this process is accelerated in diabetes. However, their role in modulation of osteoclast-induced bone resorption is controversial, with some studies indicating that AGEs enhance bone resorption and others showing the opposite effect. We determined whether AGEs present at different stages of osteoclast differentiation affect bone resorption differently. Based on increased levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK), we identified day 4 of induction as the dividing time of cell fusion stage and mature stage in RAW264.7 cell-derived osteoclast-like cells (OCLs). AGE-modified BSA (50–400 μg/ml) or control BSA (100 μg/ml) was then added at the beginning of each stage. Results showed that the presence of AGEs at the cell fusion stage reduced pit numbers, resorption area, and CTSK expression. Moreover, expression of receptor activator of nuclear factor-κB (RANK) as well as the number of TRAP-positive cells, nuclei per OCL, actin rings, and podosomes also decreased. However, the presence of AGEs at the mature stage enlarged the resorption area markedly and increased pit numbers slightly. Intriguingly, only the number of nuclei per OCL and podosomes increased. These data indicate that AGEs biphasically modulate bone resorption activity of OCLs in a differentiation stage-dependent manner. AGEs at the cell fusion stage reduce bone resorption dramatically, mainly via suppression of RANK expression in osteoclast precursors, whereas AGEs at the mature stage enhance bone resorption slightly, most likely by increasing the number of podosomes in mature OCLs.
Handedness and index finger movements performed on a small touchscreen
Authors: Aoki Tomoko , Rivlis Gil , Schieber Marc H.
Published: December 2015

Many studies of right/left differences in motor performance related to handedness have employed tasks that use arm movements or combined arm and hand movements rather than movements of the fingers per se, the well-known exception being rhythmic finger tapping. We therefore explored four simple tasks performed on a small touchscreen with relatively isolated movements of the index finger. Each task revealed a different right/left performance asymmetry. In a step-tracking Target Task, left-handed subjects showed greater accuracy with the index finger of the dominant left hand than with the nondominant right hand. In a Center-Out Task, right-handed subjects produced trajectories with the nondominant left hand that had greater curvature than those produced with the dominant right hand. In a continuous Circle Tracking Task, slips of the nondominant left index finger showed higher jerk than slips of the dominant right index finger. And in a continuous Complex Tracking Task, the nondominant left index finger showed shorter time lags in tracking the relatively unpredictable target than the dominant right index finger. Our findings are broadly consistent with previous studies indicating left hemisphere specialization for dynamic control and predictable situations vs. right hemisphere specialization for impedance control and unpredictable situations, the specialized contributions of the two hemispheres being combined to different degrees in the right vs. left hands of right-handed vs. left-handed individuals.
PLAC8 Localizes to the Inner Plasma Membrane of Pancreatic Cancer Cells and Regulates Cell Growth and Disease Progression through Critical Cell-Cycle Regulatory Pathways
Authors: Kaistha Brajesh P. , Lorenz Holger , Schmidt Harald , Sipos Bence , Pawlak Michael , Gierke Berthold , Kreider Ramona , Lankat-Buttgereit Brigitte , Sauer Melanie , Fiedler Lisa , Krattenmacher Anja , Geisel Bettina , Kraus Johann M. , Frese Kristopher K. , Kelkenberg Sabine , Giese Nathalia A. , Kestler Hans A. , Gress Thomas M. , Buchholz Malte
Published: December 2015

Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumors and is generally strongly resistant to currently available chemo- and/or radiotherapy regimens, including targeted molecular therapies. Therefore, unraveling the molecular mechanisms underlying the aggressive behavior of pancreatic cancer is a necessary prerequisite for the development of novel therapeutic approaches. We previously identified the protein placenta-specific 8 (PLAC8, onzin) in a genome-wide search for target genes associated with pancreatic tumor progression and demonstrated that PLAC8 is strongly ectopically expressed in advanced preneoplastic lesions and invasive human PDAC. However, the molecular function of PLAC8 remained unclear, and accumulating evidence suggested its role is highly dependent on cellular and physiologic context. Here, we demonstrate that in contrast to other cellular systems, PLAC8 protein localizes to the inner face of the plasma membrane in pancreatic cancer cells, where it interacts with specific membranous structures in a temporally and spatially stable manner. Inhibition of PLAC8 expression strongly inhibited pancreatic cancer cell growth by attenuating cell-cycle progression, which was associated with transcriptional and/or posttranslational modification of the central cell-cycle regulators CDKN1A, retinoblastoma protein, and cyclin D1 (CCND1), but did not impact autophagy. Moreover, Plac8 deficiency significantly inhibited tumor formation in genetically engineered mouse models of pancreatic cancer. Together, our findings establish PLAC8 as a central mediator of tumor progression in PDAC and as a promising candidate gene for diagnostic and therapeutic targeting. Cancer Res; 76(1); 96–107. ©2015 AACR.
Establishment and Characterization of an In Vitro Model of Ovarian Cancer Stem-like Cells with an Enhanced Proliferative Capacity
Authors: Ishiguro Tatsuya , Sato Ai , Ohata Hirokazu , Ikarashi Yoshinori , Takahashi Ryou-u , Ochiya Takahiro , Yoshida Masayuki , Tsuda Hitoshi , Onda Takashi , Kato Tomoyasu , Kasamatsu Takahiro , Enomoto Takayuki , Tanaka Kenichi , Nakagama Hitoshi , Okamoto Koji
Published: December 2015

The establishment of cancer stem-like cell (CSC) culture systems may be instrumental in devising strategies to fight refractory cancers. Inhibition of the Rho kinase ROCK has been shown to favorably affect CSC spheroid cultures. In this study, we show how ROCK inhibition in human serous ovarian cancer (SOC) cells can help establish a CSC system, which illuminates cancer pathophysiology and its treatment in this setting. In the presence of a ROCK kinase inhibitor, spheroid cultures of SOC cells expressed characteristic CSC markers including ALDH1A1, CD133, and SOX2, along with differentiation and tumorigenic capabilities in mouse xenograft models of human SOC. High expression levels of ALDH, but not CD133, correlated with spheroid formation CSC marker expression and tumor forming capability. In clinical specimens of SOC, high levels of ALDH1A1 correlated with advanced stage and poor prognosis. Pharmacologic or genetic blockade of ALDH blocked cell proliferation and reduced expression of SOX2, the genetic ablation of which abolished spheroid formation, whereas SOX2 overexpression inhibited ALDH1A1 expression and blocked spheroid proliferation. Taken together, our findings illustrated a new method to culture human ovarian CSC, and they defined a reciprocal regulatory relationship between ALDH1A1 and SOX2, which impacts ovarian CSC proliferation and malignant progression. Cancer Res; 76(1); 150–60. ©2015 AACR.
Molecular Pathways: Targeting Cancer Stem Cells Awakened by Chemotherapy to Abrogate Tumor Repopulation
Authors: Chan Keith Syson
Published: December 2015

Cytotoxic chemotherapy remains the first-line therapy for many advanced solid tumors; hence, understanding the underlying mechanisms to overcome chemoresistance remains a top research priority. In the clinic, chemotherapy is administered in multiple cycles that are spaced out to allow the recovery or repopulation of normal tissues and tissue stem cells between treatment cycles. However, residual surviving cancer cells and cancer stem cells can also repopulate tumors during the gap periods between chemotherapy cycles. Tumor repopulation is a phenomenon that has not been well studied; it is often overlooked due to current customized experimental study strategies. Recent findings reveal an alarming role for dying cells targeted by chemotherapy in releasing mitogens to stimulate active repopulation of quiescent cancer stem cells. Therefore, new therapeutic options to abrogate tumor repopulation will provide new avenues to improve chemotherapeutic response and clinical outcome. Clin Cancer Res; 22(4); 802–6. ©2015 AACR.
Profiling Non–Small Cell Lung Cancer: From Tumor to Blood
Authors: Tsui Dana W.Y. , Berger Michael F.
Published: December 2015

Circulating cell-free tumor DNA has shown great promise for noninvasive genomic profiling to guide the administration of targeted therapies in non–small cell lung cancer. With advancements in molecular technology, it is now possible to interrogate multiple clinically actionable genetic drivers in the blood with a single assay. Clin Cancer Res; 22(4); 790–2. ©2015 AACR.

See related article by Paweletz et al., p. 915
Use of Calcium Channel Blockers is Associated with Mortality in Patients with Chronic Kidney Disease
Authors: Haider Dominik G. , Sauter Thomas , Lindner Gregor , Masghati Salome , Peric Slobodan , Friedl Alexander , Wolzt Michael , Hörl Walter H. , Soleiman Afschin , Exadaktylos Aristomenis , Fuhrmann Valentin
Published: December 2015

Background/Aims: The use of antihypertensive medicines has been shown to reduce proteinuria, morbidity, and mortality in patients with chronic kidney disease (CKD). A specific recommendation for a class of antihypertensive drugs is not available in this population, despite the pharmacodynamic differences. We have therefore analysed the association between antihypertensive medicines and survival of patients with chronic kidney disease. Methods: Out of 2687 consecutive patients undergoing kidney biopsy a cohort of 606 subjects with retrievable medical therapy was included into the analysis. Kidney function was assessed by glomerular filtration rate (GFR) estimation at the time point of kidney biopsy. Main outcome variable was death. Results: Overall 114 (18.7%) patients died. In univariate regression analysis the use of alpha-blockers and calcium channel antagonists, progression of disease, diabetes mellitus (DM) type 1 and 2, arterial hypertension, coronary heart disease, peripheral vascular disease, male sex and age were associated with mortality (all p<0.05). In a multivariate Cox regression model the use of calcium channel blockers (HR 1.89), age (HR 1.04), DM type 1 (HR 8.43) and DM type 2 (HR 2.17) and chronic obstructive pulmonary disease (HR 1.66) were associated with mortality (all p < 0.05). Conclusion: The use of calcium channel blockers but not of other antihypertensive medicines is associated with mortality in primarily GN patients with CKD.
Prelemniscal Radiations: A New Reliable Landmark of the Thalamic Nucleus Ventralis Intermedius Location?
Authors: Lefranc Michel , Carron Romain , Regis Jean
Published: December 2015

Background: The thalamic nucleus ventralis intermedius (Vim nucleus) is the main surgical target for the management of intractable tremor. The Vim nucleus cannot be reliably located with routine stereotactic imaging, and so targeting relies on indirect coordinates. Objective: We propose to investigate if colored fractional anisotropy (FA) mapping can help to locate the Vim nucleus by identifying its borders, particularly the prelemniscal radiations (Raprl) that lie below and behind the nucleus. Method: We retrospectively reviewed the colored FA maps for 18 consecutive patients having undergone gamma knife stereotactic Vim thalamotomy for disabling tremor. Results: The Raprl were easily located on colored FA maps and enabled the identification of the lower and posterior borders of the Vim nucleus in all patients. In the medial plane, the mean distance ± SD between the Raprl and Vim nucleus was 0.77 ± 1.19 mm (range: 0.1-3.3). The Raprl were located 1.35 ± 1.33 mm (range: 0.2-3.9) behind the Vim nucleus and 1.99 ± 1.23 mm (range: 0.7-4.4) below it. The mean vector distance ± SD between the Vim nucleus and the Raprl was 3 ± 1.38 mm (range: 1.25-5.2). Conclusion: The Raprl can be easily seen on colored FA maps and constitute a reliable landmark for the borders of the Vim nucleus.
Influence of Varying Assessment Parameters on the Diagnostic Accuracy of Magnetic Resonance Imaging in the Local Staging of Prostate Cancer
Authors: Umbehr Martin H. , Lüscher Martin , Hunziker Roger , Falkner Florian , Wild Peter J. , Poyet Cédric , Seifert Burkhardt , Müntener Michael
Published: December 2015

Introduction: There is a broad variability in the accuracy levels of MRI with regard to the local staging of prostate cancer (PCa). Methods: A prospective analysis was conducted in patients with localized PCa with MRI of the prostate before radical prostatectomy. MRI and pathology findings were independently reviewed and reported based on a standardized map of the prostate with 16 regions of interest (ROIs). Diagnostic accuracy analysis of the MRI was performed using varying prostate-subpart sizes and varying cutoffs for the radiological probability for PCa presence. Results: Seventy four patients were included. Using varying cutoff probabilities and varying sizes of prostate-subparts resulted in a broad range of sensitivity (6-88%) and specificity (38-100%). Lower probabilities of PCa presence and larger prostate-subparts resulted in higher sensitivity but lower specificity and vice versa. Best diagnostic performance was achieved by using prostate sextants and at least moderate probabilities for PCa presence; mean sensitivity and specificity were 38% (95% CI 13-75) and 95% (95% CI 88-98). Conclusion: The use of varying assessment parameters strongly affects the diagnostic accuracy of MRI in the local staging of PCa. Hence, precise and standardized reporting regarding these parameters is important. In our study, using at least moderate probabilities for PCa presence on MRI and prostatic sextants as ROI size was associated with best diagnostic performance.
Evaluation of Respiratory Muscle Strength and Pulmonary Function in Patients with Charcot-Marie-Tooth Disease Type 2
Authors: Garcez Catarina Andrade , Neves Eduardo Luis Aquino , Melo Saulo Maia D''avila , Nunes Paula Santos , Barreto Lidiane Carine Lima , Costa Iandra Maria Pinheiro , Souza Cynthia Coelho , Rezende Rejane Lenier , Araújo Adriano Antunes de Souza
Published: December 2015

The aim of this study was to evaluate the pulmonary condition in a large family with Charcot-Marie-Tooth disease type 2 (CMT2). Eighteen participants diagnosed with CMT2 and 20 healthy individuals were evaluated by spirometry and maximal expiratory and maximal inspiratory pressures (MEP and MIP, respectively). Clinical disability was measured with CMT neuropathy score (CMTNS; range 0-36). One control group (CG) comprising 20 individuals, matched for age, sex and body mass index, were used for comparison. Eight patients were female (44.5%) and 10 patients were male (55.5%); mean age was 31.8 years (range 11-79) and CMTNS range was 6-26. Differences between CMT2 and CG in the spirometry and respiratory muscle strength were statistically significant for all dimensions. There were significant correlations between CMTNS and MIP (Pearson = -0.581) and MEP (Pearson = -0.5090). The results of this study show that patients with CMT, in spite of not showing clinical signs of advanced respiratory impairment, may present subclinical respiratory changes. The respiratory comprise in the CMT disease can be silent and insidious without presenting characteristic clinical signals.
Functional Genetic Variants of PPARγ and PPARα Encoding Peroxisome Proliferator-Activated Receptors and Susceptibility to Ischemic Stroke in Chinese Han Population
Authors: Tong Yeqing , Cai Li , Han ShengHong , Lu Qing , Guan Xuhua , Ying Xiaoxv , Hou Shuangyi , Zhan Fanxian , Cheng Jin-quan , Liu Jiafa
Published: December 2015

Background: PPARγ and PPARα belong to a receptor family of ligand-activated transcription factors involved in the regulation of inflammation, cellular glucose uptake, protection against atherosclerosis and endothelial cell function. Through these effects, they might be involved with the ischemic stroke (IS). Methods: One thousand two hundred ninety-six subjects from the Chinese Han Population were chosen to assess the nature of the functional polymorphisms of PPARs and any links with IS. Multivariate logistic regression analysis was used to examine the association between PPARγ and PPARα genotypes and a diagnosis of IS. Results: Pro/Ala carriage may be associated with the decreased risk of IS in Hans (OR 0.542, 95% CI 0.346-0.850). The 162Val allele frequency at the DNA-binding region of PPARα was extremely rare in Chinese Han population. Conclusions: PPARγ 12Pro/Ala resulting in an amino acid exchange in N-terminal sequence may be an independent protective factor for IS in the Chinese Han population. However, more populations are warranted to validate our findings.
Assessment of Estradiol Response after Depot Triptorelin Administration in Girls with Central Precocious Puberty
Authors: Freire Analía Verónica , Gryngarten Mirta Graciela , Ballerini María Gabriela , Arcari Andrea Josefina , Escobar María Eugenia , Bergadá Ignacio , Ropelato María Gabriela
Published: December 2015

Background: Estradiol at baseline or after a classical gonadotropin-releasing hormone test did not reflect ovarian steroidogenesis in central precocious puberty (CPP) girls. Aims: To evaluate estradiol response to depot triptorelin, both at start and during therapy to determine how active ovarian steroidogenesis is at pubertal stage and under therapy. Methods: A prospective study was performed in 43 CPP girls. Serum luteinizing hormone and follicle-stimulating hormone at 3 h (LH-3h, FSH-3h) and estradiol at 24 h (E2-24h) after injection of depot triptorelin 3.75 mg were measured, at first dose and at 3, 6, 12, 18 and 24 months of treatment. Results: E2-24h after depot triptorelin was >100 pg/ml after the first dose. Estradiol response (E2-24h) fell to levels <14 pg/ml in 78 out of 82 follow-up visits along 2 years of therapy. Concomitantly, LH-3h and FSH-3h were <4.0 and <6.3 IU/l, respectively. In 4 patients with inadequate treatment, E2-24h, LH-3h and FSH-3h rose to pubertal values similar to those observed at first dose. Conclusion: Estradiol (<14 pg/ml) assessment 24 h after depot triptorelin administration is a reliable and simple manner to confirm ovarian suppression in CPP girls during treatment.
Screening for and Estimating the Prevalence of Essential Tremor: A Random-Digit Dialing-Based Study in the New York Metropolitan Area
Authors: Louis Elan D. , Factor-Litvak Pam
Published: December 2015

Background: There are nearly no published screening instruments for essential tremor (ET). This is a remarkable fact, given its high prevalence. Here, we assess the validity of a screening questionnaire and hand-drawn spirals and also estimate the prevalence of ET in a community sample. Methods: Four hundred nineteen study subjects living in a geographically defined area in the New York metropolitan area were contacted using a random digit telephone dialing scheme. Seven tremor screening questions were administered and each subject drew 2 spirals. A movement disorders neurologist assigned ET diagnoses based on neurological examination. Results: The spirals were a more sensitive test than the screening questions (73.7 vs. 26.3%); specificities of the 2 tests were similar (95.5 vs. 96.8%). The combination of both tests was not superior to the use of spirals alone. The positive predictive value of the spiral test was 43.8%. The crude prevalence of ET, 19 of 419 (4.53%, 95% CI 2.92-6.97), increased with age (p = 0.049). Conclusions: A screening spiral was more sensitive than a screening questionnaire for ET and was moderately sensitive. Nearly one-half of subjects who screened positive had ET; therefore, when screening a population, one can expect the number of true positives and false positives to be roughly equivalent.
Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion
Authors: Choi Bo-Ryoung , Kim Dong-Hee , Back Dong Bin , Kang Chung Hwan , Moon Won-Jin , Han Jung-Soo , Choi Dong-Hee , Kwon Kyoung Ja , Shin Chan Young , Kim Bo-Ram , Lee Jongmin , Han Seol-Heui , Kim Hahn Young
Published: December 2015

Background and Purpose—

Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion.

Methods—

Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury.

Results—

Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration.

Conclusions—

White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia.
The Contributions of the Inter-American Court of Human Rights to the Development of Transitional Justice
Authors: Ceia Eleonora Mesquita
Published: December 2015

Transitional justice refers to the set of judicial and non-judicial measures adopted by different countries in order to confront their dictatorial past. In practice, countries adopt different transitional policies according to their own political, legal, social, historical, and cultural traditions. This applies, for example, to Latin American countries, some of which enacted amnesty laws currently in force, while others tried and convicted those responsible for human rights violations. In this process, the Inter-American Court of Human Rights has contributed significantly to the progress of transitional justice. Through its jurisprudence, the Court has enshrined fundamental principles related to transitional justice. In addition, it has helped Latin American countries overcome jurisprudential positions and revoke national laws that contradict international human rights standards. This article examines the contribution of the Inter-American Court of Human Rights to the development of transitional justice, with an emphasis on the case of Brazil. Ultimately, it assesses the impact of selected court jurisprudence on Brazil in order to identify the quality of the existing dialogue on transitional justice between the Inter-American Court of Human Rights and the Brazilian Supreme Federal Court.
The Genocide Convention as a Human Rights Treaty: The Possible Contribution of the Inter-American Court of Human Rights to the Jurisprudence of the International Court of Justice
Authors: Frisso Giovanna M.
Published: December 2015

This article reflects upon the potential contribution of the jurisprudence of the Inter-American Court of Human Rights (iachr) to international law. This is done through an analysis of the debates related to two aspects of the 2007 judgment of the International Court of Justice (icj) on the application of the Genocide Convention, judgment which has received a great amount of criticism, in part because the approaches adopted by the icj differ from those adopted by human rights courts. The jurisprudence of the iachr has been used to illustrate these differences and to articulate the challenges that they pose to an understanding of the international legal system as a unified system. This article argues that due consideration of the jurisprudence of the iachr could have strengthened the persuasive force of the icj judgment, because it would have required the icj to clearly indicate the arguments relied on for choosing one of the different, and sometimes contradictory, approaches.
The Realist and Rhetorical Dimensions of the Protection of Religious Feelings in Russia
Authors: Antonov Mikhail , Samokhina Ekaterina
Published: December 2015

The authors examine how the Russian judiciary formulates legal policies when adjudicating cases in which religious beliefs are concerned. First, the authors describe the framework within which their research on this matter is conducted, basing it on the theory of legal argumentation. Applying this framework to the investigation of Russian court practice has enabled the authors to discover important features, which they argue are characteristic of legal reasoning of the judiciary in this category of cases. In particular, the authors note that, at least until the present, the Russian Constitutional Court has chosen to abstain from crafting principles of legal policy regarding religious issues. Furthermore, in religious cases, the Russian judiciary—by and large—does not follow the jurisprudence of the ecthr, and the Russian Supreme Court has no clear-cut policy in handling these cases. In such a situation, ordinary judges choose individual strategies. These are indispensable insomuch as fidelity to the letter of the law is inadequate for adjudicating such cases. Russian court practice (from 1997 on) in religious cases can be more easily understood from this perspective than it can in the light of presumed political influence.
Accession of the Russian Federation to the World Trade Organization: A New Player Joins the Trade Game
Authors: Van der Borght Kim
Published: December 2015

To date, no country has taken longer to join the World Trade Organization than the Russian Federation despite the fact that the ussr (of which the Russian Federation is the legal successor) participated in the drafting conference of the Charter to the International Trade Organization, i.e., the original source of the rules of the General Agreement on Tariffs and Trade and the later wto.

While the ussr never joined the ito, Russia finally joined the wto in 2012, eighteen years after its first application had been made. The reasons for the lengthy accession process were partially economic, as the wto was established to remove trade impediments; however, the context also was highly politicized. The economic aspects of the wto accession process are the concessions made to existing members. These entail removing the cover offered to domestic producers by opening up to international competition. This process also has political aspects, as domestic lobbies representing economic sectors likely to suffer from an increasingly competitive international environment seek compensation. The politicization is facilitated by a custom contra legem in wto decision-making procedures that gives a de facto veto to existing members. Georgia used this to reassert its position on South Osetiia and Abkhaziia. China brought a border dispute into the process, and the us entangled the process in a broad-ranging debate linked to human rights.

In joining the wto, a dual process of domestic and international negotiations results in the final package of commitments to which an acceding member needs to agree as it joins the wto. Part of our focus in this article will be on key economic and political obligations that the Russian Federation took upon itself by becoming a member of the wto.
Names Given to the Offspring of Animals in Modern Turkish and its Dialects
Authors: Bayraktar Nesrin
Published: December 2015

The analysis revealed that the names employed for baby animals are abundant in modern Turkish and its dialects. Frequently, young animals are labelled according to their age, sex, and even whether they have given birth. A hyponymy relationship was observed in regards the groups of animals (e.g. enik “dogs and cats”; cücük “domestic fowls”). Finally, in coining names for animal offspring, +Ak/+(V)k, a derivative suffix appeared to be frequently employed. This study presented a general tendency in Modern Turkish to name young animals.