bluuebunny/crossref_metadata_2025 huggingface dataset:
Clarifying the Impact of Polycomb Complex Component Disruption in Human Cancers
Authors: Yamamoto Yukiya , Abe Akihiro , Emi Nobuhiko
Published: February 2014

The dysregulation of proper transcriptional control is a major cause of developmental diseases and cancers. Polycomb proteins form chromatin-modifying complexes that transcriptionally silence genome regions in higher eukaryotes. The BCL6 corepressor (BCOR) complex comprises ring finger protein 1B (RNF2/RING1B), polycomb group ring finger 1 (PCGF1), and lysine-specific demethylase 2B (KDM2B) and is uniquely recruited to nonmethylated CpG islands, where it removes histone H3K36me2 and induces repressive histone H2A monoubiquitylation. Germline BCOR mutations have been detected in patients with oculofaciocardiodental and Lenz microphthalmia syndromes, which are inherited conditions. Recently, several variants of BCOR and BCOR-like 1 (BCORL1) chimeric fusion transcripts were reported in human cancers, including acute promyelocytic leukemia, bone sarcoma, and hepatocellular carcinoma. In addition, massively parallel sequencing has identified inactivating somatic BCOR and BCORL1 mutations in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia, medulloblastoma, and retinoblastoma. More importantly, patients with AML and MDS with BCOR mutations exhibit poor prognosis. This perspective highlights the detection of BCOR mutations and fusion transcripts of BCOR and BCORL1 and discusses their importance for diagnosing cancer subtypes and estimating the treatment responses of patients. Furthermore, this perspective proposes the need for additional functional studies to clarify the oncogenic mechanism by which BCOR and BCORL1 are disrupted in cancers, and how this may lead to the development of novel therapeutics. Mol Cancer Res; 12(4); 479–84. ©2014 AACR.
Autophagy-Dependent Production of Secreted Factors Facilitates Oncogenic RAS-Driven Invasion
Authors: Lock Rebecca , Kenific Candia M. , Leidal Andrew M. , Salas Eduardo , Debnath Jayanta
Published: February 2014

The tumor-promoting functions of autophagy are primarily attributed to its ability to promote cancer cell survival. However, emerging evidence suggests that autophagy plays other roles during tumorigenesis. Here, we uncover that autophagy promotes oncogenic RAS-driven invasion. In epithelial cells transformed with oncogenic RAS, depletion of autophagy-related genes suppresses invasion in three-dimensional culture, decreases cell motility, and reduces pulmonary metastases in vivo. Treatment with conditioned media from autophagy-competent cells rescues the invasive capacity of autophagy-deficient cells, indicating that these cells fail to secrete factors required for RAS-driven invasion. Reduced autophagy diminishes the secretion of the promigratory cytokine interleukin-6 (IL-6), which is necessary to restore invasion of autophagy-deficient cells. Moreover, autophagy-deficient cells exhibit reduced levels of matrix metalloproteinase 2 and WNT5A. These results support a previously unrecognized function for autophagy in promoting cancer cell invasion via the coordinate production of multiple secreted factors.

Significance: Our results delineate a previously unrecognized function for autophagy in facilitating oncogenic RAS-driven invasion. We demonstrate that an intact autophagy pathway is required for the elaboration of multiple secreted factors favoring invasion, including IL-6. Cancer Discov; 4(4); 466–79. ©2014 AACR.

This article is highlighted in the In This Issue feature, p. 377
Categorizing Intraoperative Complications of Retrograde Intrarenal Surgery
Authors: Oguz Ural , Resorlu Berkan , Ozyuvali Ekrem , Bozkurt Omer Faruk , Senocak Cagri , Unsal Ali
Published: February 2014

Purpose: To review our intraoperative complications of retrograde intrarenal surgery (RIRS) for kidney calculi and stratify these complications according to the modified Satava classification system (SCS). Patients and Methods: 230 patients (119 males, 111 females) who underwent RIRS because of kidney calculi were analyzed. We documented and stratified the intraoperative complications according to the modified SCS. There are four grades for this classification: grade 1 complications include events without consequences for patients; grade 2a complications include events that could be treated with endoscopic surgery intraoperatively; grade 2b complications include events which were treated with endoscopic treatment in another session, and grade 3 describes the events requiring laparoscopic or open surgery. Results: Mean age was 39.1 years (range 1-78). The stone-free rate after one session was 81%. Intraoperative complications were recorded in 30.4% of the patients. According to the modified SCS, grade 1 complications were documented in 15.9%, grade 2a complications were documented in 5.6%, and grade 2b complications were documented in 8.9% of the patients. Grade 3 complications were not detected in any of the patients. Conclusion: In our opinion, the modified SCS can facilitate patients to understand the safety of this surgery and can make it easier to compare the results of different institutes and surgeons.
Intravascular Hemolysis, Vascular Endothelial Cell Activation and Thrombophilia in Splenectomized Patients with Hemoglobin E/β-Thalassemia Disease
Authors: Atichartakarn Vichai , Chuncharunee Suporn , Archararit Napaporn , Udomsubpayakul Umaporn , Aryurachai Katcharin
Published: February 2014

The relationship between asplenia and thrombophilia in β-thalassemia disease patients is not yet completely understood. One hundred and ten adult hemoglobin (Hb) E/β-thalassemia (E/β-Thal) disease outpatients, dichotomized according to the presence or absence of the spleen, were prospectively studied for evidence of intravascular hemolysis (IVH) and vascular endothelial cell (EC) activation. Biomarkers of IVH (serum cell-free Hb), EC [soluble E-selectin (sE-selectin) and soluble vascular cell adhesion molecule 1 (sVCAM-1)], platelet and EC [soluble P-selectin (sP-selectin)], inflammation [high-sensitivity C-reactive protein (hs-CRP)], and coagulation [thrombin-antithrombin complexes (TAT)] activation, as well as other selected blood tests were determined. The 61 splenectomized patients had a more severe hemolytic disease and higher levels of cell-free Hb and ferritin (p = 0.003), sE-selectin, sP-selectin, hs-CRP, and TAT (p < 0.05). However, serum levels of sVCAM-1 were not different between the two groups. The findings suggested IVH and EC activation. Together with chronic iron overload and chronic low-grade inflammation activation, the findings extend our understanding of the mechanism of thrombophilia in splenectomized E/β-Thal disease patients.
The Contested Fifth Liquid in Malayalam: A Window into the Lateral-Rhotic Relationship in Dravidian Languages
Authors: Punnoose Reenu , Khattab Ghada , Al-Tamimi Jalal
Published: February 2014

Apart from Tamil, Malayalam is the only Dravidian language that still retains a fifth liquid in its inventory (denoted as /ʐ/), a sound that can be traced back to Proto-Dravidian. The phonetic and phonological status of this sound has been the subject of considerable debate, both in terms of its rhotic versus lateral status and its phonetic realisation. Studies to date have been impressionistic, so this is the first acoustic study of all five liquids in Malayalam. Production data from 8 male speakers reveal that while /ʐ/ is realised as a central post-alveolar approximant, its ambiguous phonotactic patterning and mixed acoustic profile are contributors to its mixed identity. An understanding of the complex patterning of this sound, which straddles the rhotic/lateral divide, requires an appreciation of the role of secondary acoustic resonance in distinguishing members of a crowded liquid system and in preventing a /ʐ/-/ɭ/ merger.
Zinc Induces Apatite and Scholzite Formation during Dentin Remineralization
Authors: Osorio R. , Osorio E. , Cabello I. , Toledano M.
Published: February 2014

The aim of this study was to ascertain whether zinc may improve the repair ability of demineralized dentin. Dentin disks were demineralized by phosphoric acid during 15 s and immersed in artificial saliva, remineralizing solution, a zinc chloride solution and a zinc oxide solution. Dentin specimens were analyzed after 24 h and 1 month of storage. Surface morphology was assessed by atomic force and scanning electron microscopy, mechanical properties were analyzed by nanohardness testing in a TriboIndenter, and chemical changes at the surfaces were determined by X-ray diffraction, Raman and energy-dispersive elemental analyses. After phosphoric acid application, dentin was only partially demineralized. Demineralized dentin was remineralized after 24 h of storage in any of the tested solutions (nanohardness increased and hydroxylapatite formation was detected by Raman). Remineralization was maintained up to 1 month in dentin stored in remineralizing solution, zinc chloride and zinc oxide. Zinc and phosphate were important for hydroxylapatite homeostasis. Scholzite formation was encountered in dentin stored in zinc-containing solutions. Zinc might allow to reach the balance between dentin demineralization and remineralization processes.
Prospective, Multicenter, Phase II Study on Reducing the Dosage of Idarubicin and FLAG for Patients Younger than 65 Years with Resistant Acute Myeloid Leukemia: A Comparison with a Higher Dosage Trial
Authors: Kim Hawk , Lee Je-Hwan , Joo Young-Don , Bae Sung Hwa , Lee Jung-Hee , Kim Dae-Young , Lee Won-Sik , Ryoo Hun-Mo , Jo Jae-Cheol , Park Jae-Hoo , Lee Kyoo-Hyung ,   and CoOperative Study Group A for Hematology (COSAH)
Published: February 2014

We previously assessed continuous infusion (CI) of fludarabine and cytarabine plus idarubicin (CI-FLAG1) for patients under 65 years of age with resistant acute myeloid leukemia. Induction chemotherapy consisted of idarubicin (IDA) plus fludarabine and cytarabine (ARAC) as a 24-hour CI. In response to induction, 31.6% of patients achieved complete remission (CR) and in 68.4% the treatment failed. We concluded that CI-FLAG1 carried a high risk of toxicity and reduced CI-FLAG doses were recommended. Therefore, we revised the protocol (CI-FLAG2) by reducing the dose of IDA and ARAC. In total, 38 and 68 patients were enrolled into CI-FLAG1 and CI-FLAG2, respectively. When comparing outcomes between CI-FLAG1 and CI-FLAG2, there were no differences in terms of the CR rate (p = 0.306) and the overall response rate (ORR; p = 0.206). The treatment failure patterns were different between CI-FLAG1 and CI-FLAG2. The median overall survival showed only a trend towards longer survival in CI-FLAG2 (p = 0.074). Among intermediate-risk patients, there were high response rates favoring CI-FLAG2 in terms of the CR rate (p = 0.108), the ORR (p = 0.031), and overall survival (p = 0.033). This represented a relatively improved response rate compared to our previous study. There was decreased aplasia with dose reductions at the expense of increased resistance. A reduced dose of CI-FLAG might be most beneficial for intermediate-risk groups.
Perceptual Learning of Phonetic Information That Indicates Morphological Structure
Authors: Barden Katharine , Hawkins Sarah
Published: February 2014

Familiarity with a talker or accent can facilitate speech perception, but little is known about the acoustic-phonetic knowledge that is acquired during exposure to an unfamiliar talker, particularly with respect to how a talker realises grammatical and prosodic distinctions. The present experiment used relatively natural stimuli and tasks to investigate listeners' adaptation to a phonetic variant that is systematically associated with a morphological context, specifically the English /ri:/ prefix. Results showed that listeners who had previously been exposed to the atypical variant in /ri:/ prefixes in stories scored higher than control listeners in an intelligibility-in-noise task that included instances of the atypical variant. Perceptual learning was partly specific to the /ri:/ prefix, though there was weak generalisation of learning to word-initial /ri:/ syllables that were not prefixes. These results emphasise the value of developing context-sensitive, probabilistic models of speech perception which include multiple, parallel levels of representation.
Fine Needle Aspiration Cytology Diagnosis of Tailgut Cyst: A Rare Entity
Authors: Siddiqui Farhan Asif , Chopra Rajan , Al-Marzooq Yusef
Published: February 2014

Background: Tailgut cyst is a rare tumor believed to originate from small portions of the embryonic tailgut, which normally disappear in early fetal development. It is often misdiagnosed due to the general unfamiliarity with this entity and also because of its clinical presentation similar to other more common diseases such as perianal fistulas and abscesses. Case: The authors take this opportunity to report a case of tailgut cyst in a 21-year-old Saudi female. The patient had presented with painful low back swelling, which had been gradually increasing in size. The case was diagnosed by fine needle aspiration cytology (FNAC) as tailgut cyst and later confirmed by histopathology. Conclusion: Tailgut cysts are congenital cystic hamartomatous lesions, which are rare in occurrence. They are generally benign, but malignancy has also been reported, which is even rarer in occurrence. FNAC is an effective diagnostic tool, which if applied appropriately can be used for the early detection of rarer lesions such as tailgut cyst.
Oversights, Confusions and Misinterpretations Related to Self-Care and Medication in Diabetic and Renal Patients
Authors: Mira José J. , Ortiz Lidia , Lorenzo Susana , Royuela Catalina , Vitaller Julián , Pérez-Jover Virtudes
Published: February 2014

Objective: To analyse information about the errors made by diabetic and renal patients based on information provided by professionals (general practitioners, specialists, and nurses) and the patients themselves. Subjects and Methods: A descriptive study was carried out by interviewing 199 patients and 60 professionals from the Spanish provinces of Alicante and Madrid. The interview explored the frequencies and types of oversights, confusions, and misinterpretations and the factors that contributed to them. Results: Among the 199 patients, 59 (29.5%) and 42 (70%) of the 60 professionals considered that patients frequently made errors that affected the success of their treatment. There were no differences in the frequency of the reported errors based on gender (p = 0.7), educational level (p = 0.9), or marital status (p = 0.5). The most commonly reported errors were taking the wrong medication (n = 70; 35%) and mixing up medicines (n = 15; 7.5%). Diabetics who had not been adequately informed, compared to renal patients, reported a higher number of errors (p = 0.02). Conclusions: Patient errors were frequent because of communication failures and confusions. Diabetic patients had a higher chance of committing an error than renal patients. Patient education must include clear and personalized instructions for improving self-care and reducing risks when using medicines.
Dietary Acid Intake and Kidney Disease Progression in the Elderly
Authors: Kanda Eiichiro , Ai Masumi , Kuriyama Renjiro , Yoshida Masayuki , Shiigai Tatsuo
Published: February 2014

Background/Aims: Non-volatile acid is produced by metabolism of organic sulfur in dietary protein, and promotes kidney damage. We investigated the role of dietary acid load, in terms of net endogenous acid production (NEAP), in chronic kidney disease (CKD) progression. Methods: 217 CKD patients on low-protein diet with a normal serum bicarbonate level were enrolled in this retrospective cohort study in Japan. The primary outcome was 25% decline in estimated glomerular filtration rate (eGFR) or start of dialysis. Their NEAP was measured every 3 months. The patients were categorized into four groups on the basis of quartiles of NEAP every 3 months. The groups were treated as time-dependent variables. Results: The average age (SD) was 70.6 (7.1) years; eGFR 23.5 (14.2) ml/min/1.73 m2. Analysis using extended Cox models for the NEAP groups adjusted for baseline characteristics (referring to group 1 showing the lowest NEAP) showed that high NEAP was associated with a high risk of CKD progression; group 2, adjusted hazard ratio (HR) 3.930 (95% confidence interval (CI) 1.914, 8.072); group 3, adjusted HR 4.740 (95% CI 2.196, 10.288); group 4, adjusted HR 4.303 (95% CI 2.103, 8.805). Logistic regression analysis adjusted for baseline characteristics showed that the occurrence of hypoalbuminemia or hyperkalemia was associated with low serum bicarbonate level and the presence of complications at baseline, but not with NEAP. Conclusion: In elderly CKD patients, our findings suggest that high NEAP is independently associated with CKD progression. The decrease in NEAP may be an effective kidney-protective therapy.
From Normal Development to Disease: The Biochemistry and Regulation of GLI2
Authors: McCleary-Wheeler Angela L.
Published: February 2014

GLI2 is an oncogene encoding a unique transcription factor with both repressor and activator functions. Vitally important in development, it is also thought to be necessary for homeostasis of adult cells. However, deregulation of the GLI2 protein can result in detrimental effects to an organism, such as congenital defects or cancer. Historically deemed an activator and effector molecule of the Hedgehog signaling pathway, GLI2 has since been shown to be a critical effector of other signaling pathways, thus positioning itself as a potent mediator of signaling crosstalk. While GLI2 activity can be modulated by a variety of signaling influences, its regulation at the gene level is less understood. Indeed, gene mutations in GLI2 have been reported, but these generally led to developmental defects and are less commonly identified in tumors as being a cause of its deregulation. While the biological importance of GLI2 overexpression in a multitude of unrelated cancers has been well established, questions about the mechanisms leading to aberrant expression have remained largely unanswered. Furthering our understanding of both the transcriptional regulation of the GLI2 gene and the target genes regulated by GLI2 may identify novel therapeutic targets for cancer treatment.
The Reimbursement and Cost of Acute Kidney Injury: A UK Hospital Perspective
Authors: Kolhe Nitin V. , Eldehni Mohamed T. , Selby Nicholas M. , McIntyre Christopher W.
Published: February 2014

Background: Despite the great interest in acute kidney injury (AKI), there have been very few studies that examined the economic impact and costing methodologies of AKI. We aimed to examine the cost and income of AKI in hospitalised patients over a period of 1 year using the NHS costing system related to that year. Methods: A total of 627 patients discharged between January 2008 and December 2008 with AKI were identified by International Classification of Disease 10 codes (ICD-10). Basic demographic data were collected using the hospital electronic records, and the severity of AKI was classified according to the Acute Kidney Injury Network (AKIN) classification. We calculated the total income and isolated the AKI income related to AKI-specific finished consultant episodes. Then we conducted a patient level costing exercise using relative value units (RVU) to compare the cost of AKI to the actual income. Results: The total spell income for all patients was GBP 1,954,922.7; the mean total income per patient was GBP 3,752.3 (95% CI 3,594.6-3,903.9). AKIN stage 3 generated significantly higher total spell and AKI income. The estimated overall cost of treating AKI was higher than the AKI income to the Primary Care Trust (GBP 1,984,543.9 vs. 1,755,395). Conclusion: AKIN stage 3 has a significant economic impact when compared with AKIN stages 1 and 2. The move towards a patient level costing using RVU could be a more efficient way to match cost and income.
Combined Intracranial Pressure Monitoring and Cerebrospinal Fluid Infusion Study to Guide Management of Slit Ventricle Syndrome
Authors: Hart Michael Gavin , Czosnyka Marek , Czosnyka Zofia Helena , Fernandes Helen Marie
Published: February 2014

Introduction: Slit ventricle syndrome remains a complex entity presenting a considerable challenge to treat successfully. This study aims to demonstrate the application of dual intracranial pressure (ICP) and infusion studies together with the novel shunt occlusion test in both a diagnostic and therapeutic role. Case Report: An 8-year-old child had aqueduct stenosis treated with a ventriculoperitoneal shunt (medium-pressure valve). The presentation was of headaches with papilloedema. Imaging with both computed tomography and magnetic resonance imaging revealed slit ventricles. Initially a shunt exploration revealed distal obstruction that was treated together with insertion of a paediatric strata II regular valve; however, the child continued to deteriorate. Overnight ICP monitoring revealed dramatically raised ICP with poor compensatory reserve. Intra-operative infusion study revealed a shunt that was patent distally but with proximal obstruction. A subtemporal decompression ipsilateral to the shunt was performed together with adjustment of the paediatric strata II regular valve to 2.5 in order to prevent overdrainage. This led to normalisation of ICP, resolution of papilloedema and symptomatic improvement. Discussion: We demonstrate how combined ICP monitoring and shunt infusion studies can be used to help guide management. Unilateral subtemporal decompressions and preventing shunt overdrainage can result in normalisation of ICP and cerebrospinal fluid dynamics.
Projections of Trends in Overweight in the Elderly Population in Germany until 2030 and International Comparison
Authors: Westphal Christina , Doblhammer Gabriele
Published: February 2014

Background/Aims: To project the numbers of pre-obese (BMI 25-29.99 kg/m²) and obese (BMI > 30 kg/m²) men and women aged 50+ in Germany until 2030 and to compare our estimates with actual figures from four European countries and the USA. Estimates are based on six scenarios encompassing improvements as well as worsenings of current trends. Methods: We used pooled data from 1999 to 2009 of the German Microcensus (n = 1,472,547). Using multinomial logistic regression models we estimated age-specific probabilities of pre-obesity and obesity and applied them to the 12th population projection of the Federal Statistical Office. Results: We project overall increases in absolute numbers of pre-obesity ranging between 14.2 and 18.2 million. However, the prevalence of pre-obesity is likely to decrease slightly. In contrast, absolute and relative numbers of obesity are projected to increase, ranging between 7.2 and 15.8 million. The international comparison revealed that pre-obesity prevalences will remain among the highest in Germany, while obesity is projected to fall below current levels of the UK or the USA. Conclusion: Pre-obesity and, particularly, obesity are likely to become a more prominent health issue in Germany in the near future which could have large repercussions for the public health system.
Methodological Issues in Cohort Studies That Relate Sodium Intake to Cardiovascular Disease Outcomes
Authors: Cobb Laura K. , Anderson Cheryl A.M. , Elliott Paul , Hu Frank B. , Liu Kiang , Neaton James D. , Whelton Paul K. , Woodward Mark , Appel Lawrence J.
Published: February 2014

Background—

The results of cohort studies relating sodium (Na) intake to blood pressure–related cardiovascular disease (CVD) are inconsistent. To understand whether methodological issues account for the inconsistency, we reviewed the quality of these studies.

Methods and Results—

We reviewed cohort studies that examined the association between Na and CVD. We then identified methodological issues with greatest potential to alter the direction of association (reverse causality, systematic error in Na assessment), some potential to alter the direction of association (residual confounding, inadequate follow-up), and the potential to yield false null results (random error in Na assessment, insufficient power). We included 26 studies with 31 independent analyses. Of these, 13 found direct associations between Na and CVD, 8 found inverse associations, 2 found J-shaped associations, and 8 found null associations only. On average there were 3 to 4 methodological issues per study. Issues with greater potential to alter the direction of association were present in all but 1 of the 26 studies (systematic error, 22; reverse causality, 16). Issues with lesser potential to alter the direction of association were present in 18 studies, whereas those with potential to yield false null results were present in 23.

Conclusions—

Methodological issues may account for the inconsistent findings in currently available observational studies relating Na to CVD. Until well-designed cohort studies in the general population are available, it remains appropriate to base Na guidelines on the robust body of evidence linking Na with elevated blood pressure and the few existing general population trials of the effects of Na reduction on CVD.
Trends in Cause of Death After Percutaneous Coronary Intervention
Authors: Spoon Daniel B. , Psaltis Peter J. , Singh Mandeep , Holmes David R. , Gersh Bernard J. , Rihal Charanjit S. , Lennon Ryan J. , Moussa Issam D. , Simari Robert D. , Gulati Rajiv
Published: February 2014

Background—

The impact of changing demographics on causes of long-term death after percutaneous coronary intervention (PCI) remains incompletely defined.

Methods and Results—

We evaluated trends in cause-specific long-term mortality after index PCI performed at a single center from 1991 to 2008. Deaths were ascertained by scheduled prospective surveillance. Cause was determined via telephone interviews, medical records, autopsy reports, and death certificates. Competing-risks analysis of cause-specific mortality was performed using 3 time periods of PCI (1991–1996, 1997–2002, and 2003–2008). Final follow-up was December 31, 2012. A total of 19 077 patients survived index PCI hospitalization, of whom 6988 subsequently died (37%, 4.48 per 100 person-years). Cause was determined in 6857 (98.1%). Across 3 time periods, there was a 33% decline in cardiac deaths at 5 years after PCI (incidence: 9.8%, 7.4%, and 6.6%) but a 57% increase in noncardiac deaths (7.1%, 8.5%, and 11.2%). Only 36.8% of deaths in the recent era were cardiac. Similar trends were observed regardless of age, extent of coronary disease, or PCI indication. After adjustment for baseline variables, there was a 50% temporal decline in cardiac mortality but no change in noncardiac mortality. The decline in cardiac mortality was driven by fewer deaths from myocardial infarction/sudden death (
P
<0.001) but not heart failure (
P
=0.85). The increase in noncardiac mortality was primarily attributable to cancer and chronic diseases (
P
<0.001).

Conclusions—

This study found a marked temporal switch from predominantly cardiac to predominantly noncardiac causes of death after PCI over 2 decades. The decline in cardiac mortality was independent of changes in baseline clinical characteristics. These findings have implications for patient care and clinical trial design.
Examining the Association of Olmesartan and Other Angiotensin Receptor Blockers With Overall and Cause-Specific Mortality
Authors: Lin Jou-Wei , Chang Chia-Hsuin , Caffrey James L. , Wu Li-Chiu , Lai Mei-Shu
Published: February 2014

Concerns about an increased cardiovascular risk with the angiotensin receptor blocker, olmesartan, prompted the current study to examine associations between olmesartan and other angiotensin receptor blockers with overall and cause-specific mortalities. We collected patients who started to use losartan, valsartan, irbesartan, candesartan, telmisartan, and olmesartan between January 1, 2004, and December 31, 2009, from Taiwan’s National Health Insurance claims database. Prescribed drug types, dosage, and other clinical information were collected. Overall mortality and cause-specific mortality were ascertained through linkages with Taiwan’s National Death Registry. Two follow-up analyses, labeled intention-to-treat and as-treated, were conducted. A Cox proportional hazard regression model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) using losartan as the reference group. A total of 690 463 subjects were included, with a mean follow-up ranging from a low of 2.8 years for olmesartan to a high of 4.1 years for irbesartan. Subjects who began with valsartan had a modest but significantly increased risk of overall mortality (HR, 1.04; 95% CI, 1.02–1.06) compared with losartan. Irbesartan (HR, 0.96; 95% CI, 0.94–0.99), candesartan (HR, 0.95; 95% CI, 0.92–0.99), telmisartan (HR, 0.93; 95% CI, 0.90–0.96), and olmesartan (HR, 0.93; 95% CI, 0.88–0.97) were associated with a slightly lower overall mortality risk than losartan. The analysis indicates that the differences in mortality risk among individual angiotensin receptor blockers were only marginal and thus less likely to be clinically important. Although uncontrolled confounding might still exist, olmesartan does not seem to increase cardiovascular risk compared with losartan.
Augmentation Pressure Is Influenced by Ventricular Contractility/Relaxation Dynamics
Authors: Fok Henry , Guilcher Antoine , Li Ye , Brett Sally , Shah Ajay , Clapp Brian , Chowienczyk Phil
Published: February 2014

Augmentation pressure (AP), the increment in aortic pressure above its first systolic shoulder, is thought to be determined mainly by pressure wave reflection but could be influenced by ventricular ejection characteristics. We sought to determine the mechanism by which AP is selectively reduced by nitroglycerin (NTG). Simultaneous measurements of aortic pressure and flow were made at the time of cardiac catheterization in 30 subjects (11 women; age, 61±13 years [mean±SD]) to perform wave intensity analysis and calculate forward and backward components of AP generated by the ventricle and arterial tree, respectively. Measurements were made at baseline and after NTG given systemically (800 μg sublingually, n=20) and locally by intracoronary infusion (1 μg/min; n=10). Systemic NTG had no significant effect on first shoulder pressure but reduced augmentation (and central pulse pressure) by 12.8±3.1 mm Hg (
P
<0.0001). This resulted from a reduction in forward and backward wave components of AP by 7.0±2.4 and 5.8±1.3 mm Hg, respectively (each
P
<0.02). NTG had no significant effect on the ratio of amplitudes of either backward/forward waves or backward/forward compression wave energies, suggesting that effects on the backward wave were largely secondary to those on the forward wave. Time to the forward expansion wave was reduced (
P
<0.05). Intracoronary NTG decreased AP by 8.3±3.6 mm Hg (
P
<0.05) with no significant effect on the backward wave. NTG reduces AP and central pulse pressure by a mechanism that is, at least in part, independent of arterial reflections and relates to ventricular contraction/relaxation dynamics with enhanced myocardial relaxation.
Relationship of Wall-to-Lumen Ratio of Retinal Arterioles With Clinic and 24-Hour Blood Pressure
Authors: Salvetti Massimo , Agabiti Rosei Claudia , Paini Anna , Aggiusti Carlo , Cancarini Anna , Duse Sarah , Semeraro Francesco , Rizzoni Damiano , Agabiti Rosei Enrico , Muiesan Maria Lorenza
Published: February 2014

Wall-to-lumen ratio of retinal arterioles might serve as an in vivo parameter of vascular damage. We analyzed the impact of brachial clinic blood pressure (BP), of central BP, and of 24-hour BP on wall-to-lumen ratio (WLR) of retinal arterioles. In 295 subjects (147 men; age range, 22–72 years; mean age, 54±7 years), WLR of retinal arterioles was assessed in vivo using scanning laser Doppler flowmetry. In addition, clinic and 24-hour BP values were measured. Central hemodynamics was assessed by pulse wave analysis. In treated patients with essential hypertension (n=100), a higher WLR (0.29±0.18 versus 0.23±0.13;
P
=0.009) was observed in comparison with normotensive individuals (n=119); no significant differences were observed between treated and untreated hypertensive patients (0.29±0.18 versus 0.28±0.18;
P
=0.7). WLR of retinal arterioles was significantly related to clinic systolic (
r
=0.18;
P
=0.002) and pulse pressure (
r
=0.20;
P
=0.001), to 24-hour systolic (
r
=0.25;
P
=0.0001) and pulse pressure (
r
=0.17;
P
=0.005), and to central systolic (
r
=0.16;
P
=0.006) and pulse pressure (
r
=0.18;
P
=0.002). Multiple regression analysis revealed that only mean systolic 24-hour BP was independently associated with an increased WLR of retinal arterioles. In this large group of hypertensive patients and normotensive individuals, 24-hour systolic BP seems to be the strongest determinant of increased WLR of retinal arterioles.
Entering the Forbidden Zone
Authors: Janse Ronald
Published: February 2014

Over the past 7 years or so, the World Bank has expanded its rule of law agenda by moving into the area of criminal justice reform. This turn to criminal justice reform, however obvious it may be from a development perspective, was — and still is — a controversial step. This is because the World Bank, like most other multilateral development banks, is prohibited by its basic legal document, the Articles of Agreement, from interfering in the political affairs of its members. It must make its decisions on the basis of economic considerations only. Following the 2011 World Development Report, which made the case for World Bank involvement in criminal justice, in early 2012 the Bank’s legal vice presidency released the Legal Note on Bank Involvement in the Criminal Justice Sector and a Staff Guidance Note: World Bank Support for Criminal Justice Activities. This paper shows how the Legal Note and the Guidance Note, by offering new interpretations of the World Bank’s mandate and of the criminal justice sector, seek to incorporate criminal justice reform within the World Bank’s governance agenda. It argues that the interpretation offered by these documents is unconvincing in addressing the two components of the political prohibition clause, being the injunction to decide on the basis of economic considerations only and the prohibition on political interference. As a result, the Legal Note does not entirely succeed in its mission to provide ‘…a general legal framework for determining which interventions by the Bank in this sector would fall within the World Bank’s mandate under its Articles of Agreement’. This paper concludes by suggesting that some of the loose ends in the Legal Note and the Guidance Note can be explained by the purpose of this new legal interpretation of the mandate, which is not so much to provide a consistent legal argument, but rather — and above all — to play [to] constituencies with different interests and maintain the myth of a common understanding of the World Bank’s mandate and mission.
The ILO Regular Supervisory System: A Model in Crisis?
Authors: Maupain Francis
Published: February 2014

The right to strike has always been of fundamental importance to both workers and employers at the national level. However, the globalization of production has instilled it with renewed significance for their organizations at the international level. Beyond this fundamental substantive issue, there is also an equally fundamental institutional issue at stake for the International Labour Organization (ILO). This is the so-called “regular supervisory system”, which combines two complementary types of review and assessment of the action Members have taken to meet their obligations under ratified Conventions: an objective and impartial review conducted by the Committee of Experts on the Application of Conventions and Recommendations; and a more political and moral review exercised through the Conference Committee on the Application of Conventions and Recommendations. In June 2012, the effectiveness of this system was called into question when employers criticized the historical interpretations of ILO Convention 87 on Freedom of Association as building up a detailed and expansive right to strike, and retaliated by blocking the adoption of the proposed list of cases to be examined by the Conference Committee. For the first time in its existence, the Applications Committee and the Conference found themselves unable to fulfil what is considered to be the ILO’s core function. This crisis is unlikely to be just a passing episode. This paper considers how this crisis might be avoided or resolved. By unearthing the deep and bifurcated roots of this twin crisis of political support and of systemic sustainability, it suggests that any durable solution to the crisis needs to take into account a dual objective: first, rebuilding a tripartite compact around the supervisory system; and second, restoring institutional balance foreseen in the ILO Constitution.
Sovereign Immunity v. Redress for War Crimes: The Judgment of the International Court of Justice in the Case Concerning Jurisdictional Immunities of the State (Germany v. Italy)
Authors: Negri Stefania
Published: February 2014

Abstract

In the judgment delivered in the case concerning Jurisdictional Immunities of the State (Germany v. Italy), the International Court of Justice held that under the present state of international customary law State immunity encompasses all acta jure imperii, regardless of whether they are unlawful. Following the ruling that States are entitled to jurisdictional immunities before foreign courts even if their sovereign acts amount to violations of peremptory norms, the Court found that Italy had violated Germany’s immunity from jurisdiction and enforcement. In rendering such a conservative judgment, the Court missed a double opportunity: to contribute to the development of international law by interpreting the rule on sovereign immunity in harmony with international human rights law and its dynamics, and to finally serve justice for the victims of war crimes.
A Critical History of Internet Activism and Social Protest in Malaysia, 1998-2011
Authors: Postill John
Published: February 2014

Abstract

This article asks two related questions. First, to what extent has internet activism shaped social protest in Malaysia from the late 1990s to the present? Second, what can the history of internet activism and social protest in Malaysia tell us, if anything, about the 2011 global wave of protests? To address these questions I distinguish three key moments in Malaysia’s eventful history of internet activism and social protest, namely the 1998-1999 reformasi movement, the electoral ‘tsunami’ of 2008 (in which the ruling coalition lost its two-thirds majority), and the Bersih 2.0 rallies of 2011. I argue that Bersih 2.0 is best explained as both the latest episode in a series of uniquely Malaysian techno-political events and as a local variant of the global wave of protests of 2011 – a wave in which hackers, online journalists, and technology lawyers, as well as ordinary citizens using digital media, played an important part. The article ends with a summary and with suggestions for further research.
A taxonomic revision of Pterisanthes (Vitaceae) in Thailand and a new Thai record for Pterisanthes cissioides
Authors: Trias-Blasi Anna , Chayamarit Kongkanda , Teerawatananon Atchara , Parnell John A.N.
Published: February 2014

A revision of Pterisanthes in Thailand is presented with three species: P. eriopoda, P. polita and P. cissioides. Pterisanthes cissioides Blume is newly recorded for Thailand. A description and illustration are provided. Full typification is presented for all species and synonyms and lectotypes are selected for five names. Distribution maps are presented.
A review of the genus Rhipidia Meigen from China, with descriptions of seven new species (Diptera, Limoniidae)
Authors: ZHANG XIAO , LI YAN , YANG DING
Published: February 2014

The genus Rhipidia Meigen, 1818 from China is reviewed. Twenty-one species are presented, of which seven species, Rhipidia (Rhipidia) bilobata sp. nov., R. (R.) flava sp. nov., R. (R.) lobifera sp. nov., R. (R.) longa sp. nov., R. (R.) sejuga sp. nov., R. (R.) shennongjiensis sp. nov., and R. (R.) spinosa sp. nov., are described as new to science, and one species, R. (R.) reductispina Savchenko, 1983, is recorded from China for the first time. A key to the species of the genus Rhipidia from China is given.
Redefinition of Cosmolaelaps Berlese (Acari: Laelapidae) and description of five new species from Brazil
Authors: MOREIRA GRAZIELLE FURTADO , KLOMPEN HANS , MORAES GILBERTO JOSÉ DE
Published: February 2014

Cosmolaelaps Berlese, 1903 was originally described as a subgenus of Laelaps Koch. More recently, this group has been treated at the generic level or as a subgenus of Hypoaspis Canestrini, 1885. One of the objectives of the present paper is to provide a detailed characterisation of Cosmolaelaps, here considered at the generic level, a group that was poorly characterised in its original description as well as in subsequent publications. It is most closely related to Stratiolaelaps Berlese, from which it can usually be distinguished by the presence of extra paired and unpaired setae on the opisthonotal region of the dorsal shield, as well as by not having hypertrophied chelicerae or corniculi. A total of 108 species belong to Cosmolaelaps, including the new species described here. Five other species may also belong to this genus, but the available published information does not allow their conclusive placement. The Brazilian fauna of Hypoaspidinae is poorly known, but Cosmolaelaps seems to be well represented in Brazil. Thus, the second objective of this paper is to describe five new species of Cosmolaelaps from that country, namely C. barbatus sp. nov., C. busolii sp. nov., C. confinisetarum sp. nov., C. jaboticabalensis sp. nov. and C. oliveirai sp. nov.
A new species of Cardiodactylus (Orthoptera: Grylloidea: Eneopterinae) from Singapore
Authors: TAN MING KAI , ROBILLARD TONY
Published: February 2014

Cardiodactylus is a speciose cricket genus belonging to the subfamily Eneopterinae. One new species of Cardiodactylus from Singapore is described: Cardiodactylus admirabilis Tan & Robillard n. sp. Acoustic analysis is also performed on the male calling song. A key to species of Eneopterinae from Singapore is provided.
Global Stochastic Tropical Cyclone Model Based on Principal Component Analysis and Cluster Analysis
Authors: Nakajo Sota , Mori Nobuhito , Yasuda Tomohiro , Mase Hajime
Published: February 2014

A global stochastic tropical cyclone model was developed as a means for preparing a large number of artificial tropical cyclone (TC) samples with different values for parameters such as track, minimum sea level pressure, and translation speed. In this paper, the model and the results of its verification are presented in detail. The proposed stochastic model is sensitive to approximations of the joint probability distribution functions (PDFs) of TC parameters and temporal correlations. A newly introduced accurate method for approximating joint PDFs by using principal component analysis and cluster analysis resulted in improved reproducibility of TC parameters. The simulation results were compared with historical observational data from the northwestern Pacific, southwestern Pacific, and North Atlantic Oceans. The grid-averaged mean values and distribution patterns of PDFs of TC parameters were in agreement with observational data.
Multivariate Minimum Residual Method for Cloud Retrieval. Part II: Real Observations Experiments
Authors: Auligné Thomas
Published: February 2014

In Part I of this two-part paper, the multivariate minimum residual (MMR) scheme was introduced to retrieve profiles of cloud fraction from satellite infrared radiances and identify clear observations. In this paper it is now validated with real observations from the Atmospheric Infrared Sounder (AIRS) instrument. This new method is compared with the cloud detection scheme presented earlier by McNally and Watts and operational at the European Centre for Medium-Range Weather Forecasts (ECMWF). Cloud-top pressures derived from both algorithms are comparable, with some differences at the edges of the synoptic cloud systems. The population of channels considered as clear is less contaminated with residual cloud for the MMR scheme. Further procedures, based on the formulation of the variational quality control, can be applied during the variational analysis to reduce the weight of observations that have a high chance of being contaminated by cloud. Finally, the MMR scheme can be used as a preprocessing step to improve the assimilation of cloud-affected infrared radiances.
Radar Data Assimilation in the Canadian High-Resolution Ensemble Kalman Filter System: Performance and Verification with Real Summer Cases
Authors: Chang Weiguang , Chung Kao-Shen , Fillion Luc , Baek Seung-Jong
Published: February 2014

An 80-member high-resolution ensemble Kalman filter (HREnKF) is implemented for assimilating radar observations with the Canadian Meteorological Center’s (CMC’s) Global Environmental Multiscale Limited-Area Model (GEM-LAM). This system covers the Montréal, Canada, region and assimilates radar data from the McGill Radar Observatory with 4-km data thinning. The GEM-LAM operates in fully nonhydrostatic mode with 58 hybrid vertical levels and 1-km horizontal grid spacing. As a first step toward full radar data assimilation, only radial velocities are directly assimilated in this study. The HREnKF is applied on three 2011 summer cases having different precipitation structures: squall-line structure, isolated small-scale structures, and widespread stratiform precipitation. The short-term (<2 h) accuracy of the HREnKF analyses and forecasts is examined.

In HREnKF, the ensemble spread is sufficient to cover the estimated error from innovations and lead to filter convergence. It results in part from a realistic initiation of HREnKF data assimilation cycle by using a Canadian regional EnKF system (itself coupled to a global EnKF) working at meso- and synoptic scales. The filter convergence is confirmed by the HREnKF background fields gradually approaching to radar observations as the assimilation cycling proceeds. At each analysis step, it is clearly shown that unobserved variables are significantly modified through HREnKF cross correlation of errors from the ensemble. Radar reflectivity observations are used to verify the improvements in analyses and short-term forecasts achievable by assimilating only radial velocities. Further developments of the analysis system are discussed.
Revenge of the Radical Right
Authors: Bustikova Lenka
Published: February 2014

What explains the success and failure of radical right parties over time and across countries? This article presents a new theory of the radical right that emphasizes its reactive nature and views it as backlash against the political successes of minorities and concessions extracted on their behalf. Unlike approaches that focus on competition between the extreme and mainstream parties, the theory stresses the dynamics between radical right and non-proximate parties that promote minority rights. Most notably, it derives the salience of identity issues in party politics from the polarization of the party system. The theory is tested with a new party-election-level dataset covering all post-communist democracies over the past 20 years. The results provide strong support for the theory and show that the rise and fall of radical right parties is shaped by the politics of minority accommodation.