bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the wisdom of the crowds to find critical errors in biomedical ontologies: a study of SNOMED CT
Authors: Mortensen Jonathan M , Minty Evan P , Januszyk Michael , Sweeney Timothy E , Rector Alan L , Noy Natalya F , Musen Mark A
Published: October 2014

Objectives The verification of biomedical ontologies is an arduous process that typically involves peer review by subject-matter experts. This work evaluated the ability of crowdsourcing methods to detect errors in SNOMED CT (Systematized Nomenclature of Medicine Clinical Terms) and to address the challenges of scalable ontology verification.

Methods We developed a methodology to crowdsource ontology verification that uses micro-tasking combined with a Bayesian classifier. We then conducted a prospective study in which both the crowd and domain experts verified a subset of SNOMED CT comprising 200 taxonomic relationships.

Results The crowd identified errors as well as any single expert at about one-quarter of the cost. The inter-rater agreement (κ) between the crowd and the experts was 0.58; the inter-rater agreement between experts themselves was 0.59, suggesting that the crowd is nearly indistinguishable from any one expert. Furthermore, the crowd identified 39 previously undiscovered, critical errors in SNOMED CT (eg, ‘septic shock is a soft-tissue infection’).

Discussion The results show that the crowd can indeed identify errors in SNOMED CT that experts also find, and the results suggest that our method will likely perform well on similar ontologies. The crowd may be particularly useful in situations where an expert is unavailable, budget is limited, or an ontology is too large for manual error checking. Finally, our results suggest that the online anonymous crowd could successfully complete other domain-specific tasks.

Conclusions We have demonstrated that the crowd can address the challenges of scalable ontology verification, completing not only intuitive, common-sense tasks, but also expert-level, knowledge-intensive tasks.
Toward a science of learning systems: a research agenda for the high-functioning Learning Health System
Authors: Friedman Charles , Rubin Joshua , Brown Jeffrey , Buntin Melinda , Corn Milton , Etheredge Lynn , Gunter Carl , Musen Mark , Platt Richard , Stead William , Sullivan Kevin , Van Houweling Douglas
Published: October 2014

Objective The capability to share data, and harness its potential to generate knowledge rapidly and inform decisions, can have transformative effects that improve health. The infrastructure to achieve this goal at scale—marrying technology, process, and policy—is commonly referred to as the Learning Health System (LHS). Achieving an LHS raises numerous scientific challenges.

Materials and methods The National Science Foundation convened an invitational workshop to identify the fundamental scientific and engineering research challenges to achieving a national-scale LHS. The workshop was planned by a 12-member committee and ultimately engaged 45 prominent researchers spanning multiple disciplines over 2 days in Washington, DC on 11–12 April 2013.

Results The workshop participants collectively identified 106 research questions organized around four system-level requirements that a high-functioning LHS must satisfy. The workshop participants also identified a new cross-disciplinary integrative science of cyber-social ecosystems that will be required to address these challenges.

Conclusions The intellectual merit and potential broad impacts of the innovations that will be driven by investments in an LHS are of great potential significance. The specific research questions that emerged from the workshop, alongside the potential for diverse communities to assemble to address them through a ‘new science of learning systems’, create an important agenda for informatics and related disciplines.
Data standards to support health information exchange between poison control centers and emergency departments
Authors: Del Fiol Guilherme , Crouch Barbara Insley , Cummins Mollie R
Published: October 2014

Objective Poison control centers (PCCs) routinely collaborate with emergency departments (EDs) to provide care for poison-exposed patients. During this process, a significant amount of information is exchanged between EDs and PCCs via telephone, leading to important inefficiencies and safety vulnerabilities. In the present work, we identified and assessed a set of data standards to enable a standards-based health information exchange process between EDs and PCCs.

Materials and methods Based on a reference model for PCC–ED health information exchange, we (1) mapped PCC–ED information exchange events to clinical documents specified in the Health Level Seven (HL7) Consolidated Clinical Document Architecture (C-CDA) Standard, and (2) mapped information types routinely exchanged in PCC–ED telephone conversations to C-CDA sections.

Results Four C-CDA document types were necessary to support the PCC–ED information exchange process: History & Physical Note, Consultation Note, Progress Note, and Discharge Summary. Information types that are commonly exchanged between PCCs and EDs can be reasonably well represented within these C-CDA documents.

Conclusions A standards-based health information exchange process between PCCs and EDs appears to be feasible given a set of clinical data standards that are required for EHR certification in the USA, although the proposed approach still needs to be validated in actual system implementations. Such a process has the potential to improve the safety and efficiency of PCC–ED communication, ultimately resulting in improved patient care outcomes.
An ECG changed the life of a young boy: a case of arrhythmogenic right ventricular dysplasia
Authors: Altun Ibrahim , Akin Fatih , Sahin Cem , Beydilli Halil
Published: October 2014

Arrhythmogenic right ventricular dysplasia (ARVD) is a progressive condition with the right ventricular myocardium being replaced by fibrofatty tissue. It is a hereditary disorder mostly caused by desmosome gene mutations. The prevalence of arrhythmogenic right ventricular cardiomyopathy is about 1/1000–5000. Clinical presentation is usually related to ventricular tachycardias, syncope, presyncope or ventricular fibrillation leading to cardiac arrest, mostly in young people and athletes. We report a case of a 17-year-old boy from Turkey, who was referred to our cardiology department for an ECG, required of him prior to joining a football team.
Endovascular revascularization results in IMS III: intracranial ICA and M1 occlusions
Authors: Tomsick Thomas A , Yeatts Sharon D , Liebeskind David S , Carrozzella Janice , Foster Lydia , Goyal Mayank , von Kummer Ruediger , Hill Michael D , Demchuk Andrew M , Jovin Tudor , Yan Bernard , Zaidat Osama O , Schonewille Wouter , Engelter Stefan , Martin Renee , Khatri Pooja , Spilker Judith , Palesch Yuko Y , Broderick Joseph P
Published: October 2014

Background

Interventional Management of Stroke III did not show that combining IV recombinant tissue plasminogen activator (rt-PA) with endovascular therapies (EVTs) is better than IV rt-PA alone.

Objective

To report efficacy and safety results for EVT of intracranial internal carotid artery (ICA) and middle cerebral artery trunk (M1) occlusion.

Methods

Five revascularization methods for persistent occlusions after IV rt-PA treatment were evaluated for prespecified primary and secondary endpoints, after accounting for differences in key baselines variables using propensity scores. Revascularization was scored using the arterial occlusive lesion (AOL) and the modified Thrombolysis in Cerebral Ischemia (mTICI) scores.

Results

EVT of 200 subjects with intracranial ICA or M1 occlusion resulted in 81.5% AOL 2–3 recanalization, in addition to 76% mTICI 2–3 and 42.5% mTICI 2b–3 reperfusion. Adverse events included symptomatic intracranial hemorrhage (SICH) (8.0%), vessel perforations (1.5%), and new emboli (14.9%). EVT techniques used were standard microcatheter n=51; EKOS n=14; Merci n=77; Penumbra n=39; Solitaire n=4; multiple n=15. Good clinical outcome was associated with both TICI 2–3 and TICI 2b–3 reperfusion. Neither modified Rankin scale (mRS) 0–2 (28.5%), nor 90-day mortality (28.5%), nor asymptomatic ICH (36.0%) differed among revascularization methods after propensity score adjustment for subjects with intracranial ICA or M1 occlusion.

Conclusions

Good clinical outcome was associated with good reperfusion for ICA and M1 occlusion. No significant differences in efficacy or safety among revascularization methods were demonstrated after adjustment. Lack of high-quality reperfusion, adverse events, and prolonged time to treatment contributed to lower-than-expected mRS 0–2 outcomes and study futility compared with IV rt-PA.

Trial registration number

NCT00359424.
Stochastic dynamics for the solutions of a modified Holling–Tanner model with random perturbation
Authors: Liu Zhenjie
Published: October 2014

In this paper, we consider a stochastic nonautonomous predator–prey model with modified Leslie–Gower and Holling II schemes in the presence of environmental forcing. The deterministic model is the modified Holling–Tanner model which is an extension of the classical Leslie–Gower model. We show that there is a unique positive solution to the stochastic system for any positive initial value. Sufficient conditions for strong persistence in mean and extinction to the stochastic system are established.
Nullification of Torus knots and links
Authors: Ernst Claus , Montemayor Anthony
Published: October 2014

It is known that a knot/link can be nullified, i.e. can be made into the trivial knot/link, by smoothing some crossings in a projection diagram of the knot/link. The minimum number of such crossings to be smoothed in order to nullify the knot/link is called the nullification number. In this paper we investigate the nullification numbers of a particular knot family, namely the family of torus knots and links.
The Rationality of Punishment — Measuring the Severity of Crimes: An AHP-Based Orders-of-Magnitude Approach
Authors: Saaty Thomas L. , Özdemir Müjgan Sağır , Shang Jennifer S.
Published: October 2014

We propose an innovative AHP-based model to assess the severity of the harms a criminal commits to society in a comprehensive and coherent way. Different from the traditional approach of structuring alternatives into one level, we organize the alternatives into multiple levels of that hierarchy. This arrangement and evaluation of alternatives differs from one criterion to another, which adds to the sophistication of the task when assessing numerous heterogeneous criminal activities. Structuring multifaceted decisions with the proposed model enables us to better deal with its inherent complexity. Our approach can systematically tackle problems of widespread orders of magnitude of criteria and alternatives. When the sizes are actually very small or very large, the accuracy of rating alternatives one at a time is very low. With the proposed method, we are able to obtain priorities with greater precision.
Contribution to the study of the effect of the interspecificity on a two nutrients competition model
Authors: Borsali Fethi , Yadi Karim
Published: October 2014

We consider a model of the exploitative competition of two micro-organisms for two complementary nutrients in a chemostat and take into account the interspecific interaction. The growth functions occurring in the model are of general type and the interaction functions are monotonic and positive. By the mean of the Thieme–Zhao theorem, we establish conditions for uniform persistence of the model.
Report of a debate on Snowden's actions by ACM members
Authors: Adams A. A.
Published: October 2014

In 2012 Edward Snowden starting releasing a cache of computer files to a small number of journalists, which he claimed to have copied from servers at the US' National Security Agency (NSA). The NSA have disputed the context or interpretation of some of the material published by the journalists, but have confirmed that Snowden had previously worked at the agency as an employee of an external firm Booz Hamilton. The result of Snowden's revelations have included a large scale debate about the activities of both the US' NSA and their partner agency in the UK (Government Communications Headquarters) in monitoring the communications of individuals and organisations worldwide.

ACM SIGCAS makes an Award each year called the "Making a Difference Award". Typically this has gone to a researcher in computer ethics or a practitioner or researcher in some other field of computer science whose work has had a significant socially beneficial impact. In 2013 some members of SIGCAS engaged in an online debate about whether Snowden would be a worth recipient of this award. The arguments put forth in this debate illuminate the divided opinions regarding Snowden's actions in the general population are also present in the computer ethics community. A distillation of the arguments put forward are presented in this piece without individual attribution to the commenters.
The NSA and Edward Snowden
Authors: Verble Joseph
Published: October 2014

This paper examines the case and background of Edward Snowden, the history and purpose of the National Security Agency (NSA), legality and American public opinion and its aftermath.
Cardiovascular parameters in a mixed-sex swine study of severe decompression sickness treated with the emulsified perfluorocarbon Oxycyte
Authors: Mahon R. T. , Cronin W. A. , Bodo M. , Tirumala S. , Regis D. P. , Auker C. R.
Published: October 2014

Intravenous perfluorocarbons (PFC) have reduced the effects of decompression sickness (DCS) and improved mortality rates in animal models. However, concerns for the physiological effects of DCS combined with PFC therapy have not been examined in a balanced mixed-sex population. Thirty-two (16 male, 16 female) instrumented and sedated juvenile Yorkshire swine were exposed to 200 feet of seawater (fsw) for 31 min of hyperbaric air. Pulmonary artery pressure (PAP), cardiac output (CO), and systemic arterial pressure (SAP) were monitored before (control) and after exposure. Animals were randomized to treatment with Oxycyte (5 ml/kg; Oxygen Biotherapeutics, Inc., Morrisville, NC) vs. saline (control) with 100% oxygen administered upon DCS onset; animals were observed for 90 min. Parameters recorded and analyzed included PAP, CO, and SAP. In all animals PAP began to rise prior to cutis marmorata (CM) onset, the first sign of clinical DCS, generally peaking after CM onset. Female swine, compared with castrated males, had a more rapid onset of CM (7.30 vs. 11.46 min postsurfacing) and earlier onset to maximal PAP (6.41 vs. 9.69 min post-CM onset). Oxycyte therapy was associated with a sustained PAP elevation above controls in both sexes (33.41 vs. 25.78 mmHg). Significant pattern differences in PAP, CO, and SAP were noted between sexes and between therapeutic groups. There were no statistically significant differences in survival or paralysis between the PFC and control groups during the 48-h observation period. In conclusion, Oxycyte therapy for DCS is associated with a prolonged PAP increase in swine. These species and sex differences warrant further exploration.
Cortical substrates of the effects of caffeine and time-on-task on perception of effort
Authors: de Morree Helma M. , Klein Christoph , Marcora Samuele M.
Published: October 2014

Caffeine intake results in a decrease in perception of effort, but the cortical substrates of this perceptual effect of caffeine are unknown. The aim of this randomized counterbalanced double-blind crossover study was to investigate the effect of caffeine on the motor-related cortical potential (MRCP) and its relationship with rating of perceived effort (RPE). We also investigated whether MRCP is associated with the increase in RPE occurring over time during submaximal exercise. Twelve healthy female volunteers performed 100 intermittent isometric knee extensions at 61 ± 5% of their maximal torque 1.5 h after either caffeine (6 mg/kg) or placebo ingestion, while RPE, vastus lateralis electromyogram (EMG), and MRCP were recorded. RPE and MRCP amplitude at the vertex during the first contraction epoch (0–1 s) were significantly lower after caffeine ingestion compared with placebo ( P < 0.05) and were significantly higher during the second half of the submaximal intermittent isometric knee-extension protocol compared with the first half ( P < 0.05). No significant effects of caffeine and time-on-task were found for EMG amplitude and submaximal force output variables. The covariation between MRCP and RPE across both caffeine and time-on-task ( r10 = −0.335, P < 0.05) provides evidence in favor of the theory that perception of effort arises from neurocognitive processing of corollary discharges from premotor and motor areas of the cortex. Caffeine seems to reduce perception of effort through a reduction in the activity of cortical premotor and motor areas necessary to produce a submaximal force, and time-on-task has the opposite effect.
Adenosine A2A Receptors Intrinsically Regulate CD8+ T Cells in the Tumor Microenvironment
Authors: Cekic Caglar , Linden Joel
Published: October 2014

Adenosine A2A receptor (A2AR) blockade enhances innate and adaptive immune responses. However, mouse genetic studies have shown that A2AR deletion does not inhibit the growth of all tumor types. In the current study, we showed that growth rates for ectopic melanoma and bladder tumors are increased in Adora2a−/− mice within 2 weeks of tumor inoculation. A2AR deletion in the host reduced numbers of CD8+ T cells and effector–memory differentiation of all T cells. To examine intrinsic functions in T cells, we generated mice harboring a T-cell–specific deletion of A2AR. In this host strain, tumor-bearing mice displayed increased growth of ectopic melanomas, decreased numbers of tumor-associated T cells, reduced effector–memory differentiation, and reduced antiapoptotic IL7Rα (CD127) expression on antigen-experienced cells. Intratumoral pharmacologic blockade similarly reduced CD8+ T-cell density within tumors in wild-type hosts. We found that A2AR-proficient CD8+ T cells specific for melanoma cells displayed a relative survival advantage in tumors. Thus, abrogating A2AR signaling appeared to reduce IL7R expression, survival, and differentiation of T cells in the tumor microenvironment. One implication of these results is that the antitumor effects of A2AR blockade that can be mediated by activation of cytotoxic T cells may be overcome in some tumor microenvironments as a result of impaired T-cell maintenance and effector–memory differentiation. Thus, our findings imply that the efficacious application of A2AR inhibitors for cancer immunotherapy may require careful dose optimization to prevent activation-induced T-cell death in tumors. Cancer Res; 74(24); 7239–49. ©2014 AACR.
The Role of Genome Sequencing in Personalized Breast Cancer Prevention
Authors: Sieh Weiva , Rothstein Joseph H. , McGuire Valerie , Whittemore Alice S.
Published: October 2014

Background: There is uncertainty about the benefits of using genome-wide sequencing to implement personalized preventive strategies at the population level, with some projections suggesting little benefit. We used data for all currently known breast cancer susceptibility variants to assess the benefits and harms of targeting preventive efforts to a population subgroup at highest genomic risk of breast cancer.

Methods: We used the allele frequencies and effect sizes of 86 known breast cancer variants to estimate the population distribution of breast cancer risks and evaluate the strategy of targeting preventive efforts to those at highest risk. We compared the efficacy of this strategy with that of a “best-case” strategy based on a risk distribution estimated from breast cancer concordance in monozygous twins, and with strategies based on previously estimated risk distributions.

Results: Targeting those in the top 25% of the risk distribution would include approximately half of all future breast cancer cases, compared with 70% captured by the best-case strategy and 35% based on previously known variants. In addition, current evidence suggests that reducing exposure to modifiable nongenetic risk factors will have greatest benefit for those at highest genetic risk.

Conclusions: These estimates suggest that personalized breast cancer preventive strategies based on genome sequencing will bring greater gains in disease prevention than previously projected. Moreover, these gains will increase with increased understanding of the genetic etiology of breast cancer.

Impact: These results support the feasibility of using genome-wide sequencing to target the women who would benefit from mammography screening. Cancer Epidemiol Biomarkers Prev; 23(11); 2322–7. ©2014 AACR.
TFAP2E Methylation Status and Prognosis of Patients with Radically Resected Colorectal Cancer
Authors: Park Seong Joon , Kim Seung-mi , Hong Yong Sang , Lee Jae-Lyun , Kim Jeong-Eun , Kim Kyu-pyo , Hong Seung-Mo , Jin Dong-Hoon , Kim Chan Wook , Yoon Yong Sik , Park In Ja , Lim Seok-Byung , Yu Chang Sik , Kim Jin Cheon , Kim Tae Won
Published: October 2014

Objectives: This study investigates the clinical significance of the gene encoding AP-2ε (TFAP2E) in colorectal cancer (CRC) patients undergoing curative resection. Methods: A single-institution cohort of 248 patients who underwent curative resection of stage I/II/III CRCs between March and December 2004 was enrolled, and 193 patients whose tumors were available for the determination of the TFAP2E methylation status were included in the analysis. Results: TFAP2E hypermethylation was detected in 112 patients (58%) and was significantly associated with distally located CRCs, low pathologic T stage (T1/T2), and stage I tumors. After a median follow-up of 86.3 months, the patients with TFAP2E hypermethylation tended to show better relapse-free survival (RFS) and overall survival (OS) than the patients with TFAP2E hypomethylation (5-year RFS rate: 90 vs. 80%, p = 0.063; 6-year OS rate: 88 vs. 80%, p = 0.083). Multivariate analysis showed that the pathologic nodal stage and TFAP2E methylation status were independent prognostic factors for RFS and OS, and they remained significant factors in the subgroup analysis that included 154 patients with stage II/III CRCs who had received adjuvant chemotherapy. Conclusions: TFAP2E hypermethylation is associated with good clinical outcomes and may be considered as an independent prognostic factor in patients with curatively resected CRCs. © 2014 S. Karger AG, Basel
Different and Shared Brain Volume Abnormalities in Late- and Early-Onset Schizophrenia
Authors: Egashira Kazuteru , Matsuo Koji , Mihara Toshinari , Nakano Masayuki , Nakashima Mami , Watanuki Toshio , Matsubara Toshio , Watanabe Yoshifumi
Published: October 2014

The differences in clinical characteristics between late- (LOS) and early-onset schizophrenia (EOS) are well documented. However, very little is known about the neural mechanisms underlying these differences. Here, we compared morphometric abnormalities between patients with EOS and those with LOS. A total of 22 patients with LOS, 24 patients with EOS and 41 healthy control subjects were included in this magnetic resonance imaging study. Brain images were analyzed using DARTEL preprocessing for voxel-based morphometry in SPM8. We tested a main effect of diagnosis in the whole-brain analysis and compared the results among the three groups. We also carried out correlation analyses between regional volumes and clinical variables. Patients with LOS showed larger gray matter (GM) volume of the left precuneus compared with healthy subjects and patients with EOS. Patients with LOS and EOS showed decreased GM volumes in the right insula, left superior temporal gyrus and left orbitofrontal gyrus compared with healthy subjects. A longer duration of illness was associated with reduced GM volume in the temporal pole in patients with EOS. Our findings may help improve our understanding of schizophrenia pathophysiology and shed light on the different and shared neurobiological underpinnings of LOS and EOS.
Prism Adaptation and Perceptual Skill Learning Deficits in Early-Stage Parkinson's Disease
Authors: Sato Eigo , Onitsuka Toshiaki , Ninomiya Hideaki , Nakamura Itta , Kanba Shigenobu
Published: October 2014

Background: Skill learning deficits in Parkinson's disease (PD) at an early stage are not well known, and findings in behavioral studies with mirror reading and prism adaptation tasks are mixed. Moreover, skill learning over several days in PD patients has not been studied. Methods: A total of 12 nondemented early-stage PD patients and 12 age-matched normal control subjects participated in this study. The Wechsler Memory Scale-Revised (WMS-R) was applied to all subjects to assess declarative memory. The mirror reading task of horizontally presented kana letters and the reversed vision task using a prism were performed throughout 3 consecutive days. Results: For the mirror reading skill, the early-stage PD patients showed significantly increased mirror reading time on days 2 and 3. For the prism adaptation, the PD patients performed significantly more slowly in reversed vision than the normal controls, specifically at blocks 1 and 2, over 3 days. The WMS-R subscores did not show a significant correlation with the reaction times in reversed vision or with the mirror reading times. Conclusions: Using two tasks with different modalities, the present study revealed visuomotor adaptation deficits and acquisition/retention deficits, especially in the later phase of perceptual skill learning, in early-stage PD patients.
Bcl1 Polymorphism of the Glucocorticoid Receptor Gene and Treatment Response to Milnacipran and Fluvoxamine in Japanese Patients with Depression
Authors: Takahashi Hitoshi , Yoshida Keizo , Higuchi Hisashi , Kamata Mitsuhiro , Inoue Kazuyuki , Suzuki Toshio , Ishigooka Jun
Published: October 2014

Background: Polymorphisms in the glucocorticoid receptors (GRs) have been widely studied with rather less emphasis on relating their differences with possible pharmacological treatment outcomes. The purpose of this study was to investigate whether Bcl1 polymorphisms of GRs are associated with the antidepressant effect of milnacipran, a serotonin noradrenaline reuptake inhibitor (SNRI), and fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), in Japanese patients with depression. Methods: Patients were prescribed either milnacipran (n = 98) or fluvoxamine (n = 95). The severity of depression was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) at 0, 1, 2, 4 and 6 weeks of treatment. Results: Both agents were similarly effective in reducing MADRS scores in 6 weeks. In all subjects receiving milnacipran or fluvoxamine, our data showed no significant interaction between Bcl1 polymorphisms and therapeutic effects. However, when milnacipran- and fluvoxamine-treated subjects were analyzed independently, patients with G allele in Bcl1 polymorphism had a significantly better response to fluvoxamine than those with C/C genotype. On the other hand, no significant relationship was found between treatment response to milnacipran and Bcl1 polymorphism. Conclusion: Bcl1 polymorphism may be one of the genetic factors in predicting treatment response to SSRI but not SNRI in Japanese patients with depression.
Augmentation of Antipsychotics with Electroconvulsive Therapy in Treatment-Resistant Schizophrenia Patients with Dominant Negative Symptoms: A Pilot Study of Effectiveness
Authors: Pawełczyk Tomasz , Kołodziej-Kowalska Emilia , Pawełczyk Agnieszka , Rabe-Jabłońska Jolanta
Published: October 2014

Objectives: The aim of the study was to determine the effectiveness of the augmentation of antipsychotics (AP) with electroconvulsive therapy (ECT) in treatment-resistant schizophrenia (TRS) patients with dominant negative symptoms. Methods: The study encompassed 34 patients aged 21-55 years, 47.1% of whom were female, who were diagnosed with TRS. Each patient underwent a course of ECT sessions combined with AP medications which had previously been found to be ineffective. Prior to ECT and within 3 days after the final ECT session, the participants were evaluated on the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia and the Clinical Global Impression scales. Results: Augmentation of AP therapy with ECT led to a significant decrease in symptom severity in TRS patients with dominant negative symptoms, 58.8% of whom demonstrated at least a 25% decrease in the total PANSS score. The greatest reductions were observed in the general and positive PANSS subscales (mean ± SD: 11.35 ± 7.43 and 6.79 ± 5.23 patients), and the least significant in the negative symptoms subscale (5.03 ± 4.36 patients). Conclusion: Augmentation of AP therapy with ECT in a group of TRS patients with dominant negative symptoms induced a significant decrease in symptom severity. The greatest reductions were obtained in general and positive symptoms and the least in negative symptoms.
A New Needle Holder Facilitating Palm Grip Suturing
Authors: Frimand Rönnow Carl-Fredrik , Jeppsson Bengt , Thorlacius Henrik
Published: October 2014

Purpose: The finger grip and the palm grip are the most common needle holder grips for hand suturing in surgery. The major advantages of the palm grip are an increased versatility and the possibility to apply controlled force. However, there is a risk for a potential loss of precision and uncontrolled movement of the needle when disengaging the ratchet mechanism of the palmed instrument. The purpose of this study was to develop a new needle holder, referred to as the Frimand needle holder (FNH), and evaluate surgeons' perception of it. It was designed to overcome the above-mentioned disadvantages, hence facilitating palm and finger grip suturing. Moreover, we evaluated suture precision and attitudes related to the use of the finger grip and the palm grip. Methods: Thirty-two surgeons performed sutures utilizing both the palm grip and the finger grip on postmortem porcine skin and small bowels, comparing the FNH to a standard Crile-Wood needle holder (CWNH). The participants assessed the FNH on an evaluation form. Precision was determined by letting the surgeons perform 20 sutures utilizing the finger grip and the palm grip on a polyurethane pad with premarked insert and exit sites. The distance between the designated exit site and the real exit site defined precision and was measured with a digital sliding dimension scale. Results: We found that 28 (88%) of the 32 surgeons use the palm grip to some extent, and 31 surgeons (97%) experienced an advantage when suturing with the FNH using the palm grip. Twenty-four (75%) of the 32 surgeons would prefer to suture with the FNH instead of the CWNH. There was no significant difference in precision between the finger grip and the palm grip. Conclusion: This study presents a new needle holder facilitating palm grip suturing. A majority of the participants preferred the new FNH over the standard CWNH for hand suturing.
Central Adrenal Insufficiency Could Not Be Confirmed by Measurement of Basal Serum DHEAS Levels in Pubertal Children
Authors: Vaiani Elisa , Maceiras Mercedes , Chaler Eduardo , Lazzati Juan Manuel , Chiavero M. , Novelle Claudia , Rivarola Marco , Belgorosky Alicia
Published: October 2014

Background: Central adrenal insufficiency (CAI) is due to a decrease of CRH and/or ACTH secretion. ACTH-dependent dehydroepiandrosterone sulphate (DHEAS) has been postulated as a possible marker of adrenal function in adult patients. Aims: To evaluate the usefulness of basal serum DHEAS determination to diagnose CAI in pubertal patients with a suspected diagnosis of CAI. Methods: Ninety-four pubertal patients suspected of having CAI were divided into two groups according to sufficient (group 1) or insufficient (group 2) low-dose ACTH test serum cortisol response. Concordance with low (<2.5th percentile) or normal (≥2.5th percentile) basal serum DHEAS levels for age and sex, respectively, was analysed. Results: Fifty patients (53.2%) in group 1 and 44 (46.8%) in group 2 were included. The median value of serum DHEAS levels in group 2 (0.7 µmol/l, interquartile range 0.44-1.49) was significantly lower than in group 1 (2.13 µmol/l, interquartile range 0.87-3.5; p < 0.03). Nevertheless, serum basal DHEAS levels as a diagnostic marker of CAI showed 39% sensitivity and 80% specificity. Conclusion: In pubertal patients, basal serum DHEAS levels do not seem to be a useful tool to diagnose either sufficiency or insufficiency of secondary adrenal function.
EN-RAGE
Authors: Ligthart Symen , Sedaghat Sanaz , Ikram M. Arfan , Hofman Albert , Franco Oscar H. , Dehghan Abbas
Published: October 2014

Objective—

Inflammation plays a key role in atherosclerosis. We hypothesized that novel inflammatory markers may predict the risk of coronary heart disease (CHD).

Approach and Results—

We investigated the association of 16 inflammatory biomarkers with the risk of CHD in a random subset of 839 CHD-free individuals in a prospective population-based cohort study. A Bonferroni corrected
P
value of 3.1×10
−3
was used as a threshold of statistical significance. The mean age at baseline was 72.8 years. During a median follow-up of 10.6 years, 99 cases of incident CHD were observed. Among all inflammatory biomarkers, neutrophil-derived human s100a12 (extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE]) showed the strongest association with the risk of CHD (
P
value 2.0×10
−3
). After multivariable adjustment for established cardiovascular risk factors, each standard deviation increase in the natural log-transformed EN-RAGE was associated with 30% higher risk of incident CHD (hazard ratio, 1.30; 95% confidence interval, 1.06–1.59). Further adjustment for previously studied inflammatory markers did not attenuate the association. Excluding individuals with prevalent type 2 diabetes mellitus, impaired kidney function, or individuals using antihypertensive medication did not change the effect estimates. Cause-specific hazard ratios suggested a stronger association between EN-RAGE and CHD mortality compared with stable CHD.

Conclusions—

Our results highlight EN-RAGE as an inflammatory marker for future CHD in a general population, beyond traditional CHD risk factors and inflammatory markers.
Elastin-Derived Peptides Are New Regulators of Thrombosis
Authors: Kawecki Charlotte , Hézard Nathalie , Bocquet Olivier , Poitevin Gaël , Rabenoelina Fanja , Kauskot Alexandre , Duca Laurent , Blaise Sébastien , Romier Béatrice , Martiny Laurent , Nguyen Philippe , Debelle Laurent , Maurice Pascal
Published: October 2014

Objective—

Elastin is the major structural extracellular matrix component of the arterial wall that provides the elastic recoil properties and resilience essential for proper vascular function. Elastin-derived peptides (EDP) originating from elastin fragmentation during vascular remodeling have been shown to play an important role in cell physiology and development of cardiovascular diseases. However, their involvement in thrombosis has been unexplored to date. In this study, we investigated the effects of EDP on (1) platelet aggregation and related signaling and (2) thrombus formation. We also characterized the mechanism by which EDP regulate thrombosis.

Approach and Results—

We show that EDP, derived from organo-alkaline hydrolysate of bovine insoluble elastin (kappa-elastin), decrease human platelet aggregation in whole blood induced by weak and strong agonists, such as ADP, epinephrine, arachidonic acid, collagen, TRAP, and U46619. In a mouse whole blood perfusion assay over a collagen matrix, kappa-elastin and VGVAPG, the canonical peptide recognizing the elastin receptor complex, significantly decrease thrombus formation under arterial shear conditions. We confirmed these results in vivo by demonstrating that both kappa-elastin and VGVAPG significantly prolonged the time for complete arteriole occlusion in a mouse model of thrombosis and increased tail bleeding times. Finally, we demonstrate that the regulatory role of EDP on thrombosis relies on platelets that express a functional elastin receptor complex and on the ability of EDP to disrupt plasma von Willebrand factor interaction with collagen.

Conclusions—

These results highlight the complex nature of the mechanisms governing thrombus formation and reveal an unsuspected regulatory role for circulating EDP in thrombosis.
Brachial Flow-Mediated Dilation and Incident Atrial Fibrillation
Authors: O’Neal Wesley T. , Efird Jimmy T. , Yeboah Joseph , Nazarian Saman , Alonso Alvaro , Heckbert Susan R. , Soliman Elsayed Z.
Published: October 2014

Objective—

It is unknown whether endothelial dysfunction precedes atrial fibrillation (AF) development. The objective of this study was to examine the association of brachial flow-mediated dilation (FMD) with incident AF.

Approach and Results—

A total of 2936 participants (mean age, 61±9.9 years; 50% women; 66% nonwhites) from the Multi-Ethnic Study of Atherosclerosis with available ultrasound brachial FMD measurements who were free of baseline AF were included in this analysis. Baseline (2000–2002) FMD was computed from the percentage difference (%FMD) in brachial artery diameter and maximum diameter during measured vasodilator response. AF was ascertained from hospitalization data including Medicare claims during a median follow-up of 8.5 years. Probability-weighted Cox proportional-hazards regression was used to compute hazard ratios and 95% confidence intervals for the association between FMD as a continuous variable (%FMD values per 1-SD increase) and incident AF. Incident AF was detected in 137 (4.7%) participants. Those with %FMD values below the sex-specific median value (median %FMD; men, 3.6%; women, 4.2%; incidence rate per 1000 person-years, 7.3; 95% confidence interval, 5.9–9.0) were more likely to develop AF than people whose %FMD values were above the median value (incidence rate per 1000 person-years, 4.5; 95% confidence interval, 3.4–5.8; log-rank
P
=0.0043). In a multivariable Cox regression analysis, each 1-SD increase in %FMD values (SD, 2.8%) was associated with less incident AF (hazard ratio, 0.84; 95% confidence interval, 0.70–0.99). These results were consistent across subgroups stratified by age, sex, and race/ethnicity.

Conclusions—

Smaller brachial FMD values are associated with higher rates of AF, suggesting a role for endothelial dysfunction in AF pathogenesis.
Loss of β-Catenin Promotes Chondrogenic Differentiation of Aortic Valve Interstitial Cells
Authors: Fang Ming , Alfieri Christina M. , Hulin Alexia , Conway Simon J. , Yutzey Katherine E.
Published: October 2014

Objective—

The Wnt/β-catenin signaling pathway has been implicated in human heart valve disease and is required for early heart valve formation in mouse and zebrafish. However, the specific functions of Wnt/β-catenin signaling activity in heart valve maturation and maintenance in adults have not been determined previously.

Approach and Results—

Here, we show that Wnt/β-catenin signaling inhibits Sox9 nuclear localization and proteoglycan expression in cultured chicken embryo aortic valves. Loss of β-catenin in vivo in mice, using
Periostin
(
Postn
)
Cre
–mediated tissue-restricted loss of β-catenin (
Ctnnb1
) in valvular interstitial cells, leads to the formation of aberrant chondrogenic nodules and induction of chondrogenic gene expression in adult aortic valves. These nodular cells strongly express nuclear Sox9 and Sox9 downstream chondrogenic extracellular matrix genes, including
Aggrecan
,
Col2a1
, and
Col10a1
. Excessive chondrogenic proteoglycan accumulation and disruption of stratified extracellular matrix maintenance in the aortic valve leaflets are characteristics of myxomatous valve disease. Both in vitro and in vivo data demonstrate that the loss of Wnt/β-catenin signaling leads to increased nuclear expression of Sox9 concomitant with induced expression of chondrogenic extracellular matrix proteins.

Conclusions—

β-Catenin limits Sox9 nuclear localization and inhibits chondrogenic differentiation during valve development and in adult aortic valve homeostasis.
Unnatural History of Tetralogy of Fallot
Authors: Cuypers Judith A.A.E. , Menting Myrthe E. , Konings Elisabeth E.M. , Opić Petra , Utens Elisabeth M.W.J. , Helbing Willem A. , Witsenburg Maarten , van den Bosch Annemien E. , Ouhlous Mohamed , van Domburg Ron T. , Rizopoulos Dimitris , Meijboom Folkert J. , Boersma Eric , Bogers Ad J.J.C. , Roos-Hesselink Jolien W.
Published: October 2014

Background—

Prospective data on long-term survival and clinical outcome beyond 30 years after surgical correction of tetralogy of Fallot are nonexistent.

Methods and Results—

This longitudinal cohort study consists of the 144 patients with tetralogy of Fallot who underwent surgical repair at <15 years of age between 1968 and 1980 in our center. They are investigated every 10 years. Cumulative survival (data available for 136 patients) was 72% after 40 years. Late mortality was due to heart failure and ventricular fibrillation. Seventy-two of 80 eligible survivors (90%) participated in the third in-hospital investigation, consisting of ECG, Holter, echocardiography, cardiopulmonary exercise testing, N-terminal pro-brain natriuretic peptide measurement, cardiac magnetic resonance (including dobutamine stress testing), and the Short Form-36 questionnaire. Median follow-up was 36 years (range, 31–43 years). Cumulative event-free survival was 25% after 40 years. Subjective health status was comparable to that in the normal Dutch population. Although systolic right and left ventricular function declined, peak exercise capacity remained stable. There was no progression of aortic root dilation. A previous shunt operation, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality (hazard ratio, 2.9, 1.1, and 2.5, respectively). An increase in QRS duration and a deterioration of exercise tolerance and ventricular dysfunction did not predict mortality. Insertion of a transannular patch was a predictor for late arrhythmias (hazard ratio, 4.0; 95% confidence interval, 1.2–13.4).

Conclusions—

Although many patients needed a reoperation or developed arrhythmias, late mortality was low, and the clinical condition and subjective health status of most patients remained good. Previous shunt, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality.
The Singapore Ulama
Authors: Mostarom Tuty Raihanah
Published: October 2014

There is a common perception that Muslim religious leaders (ulama) in Singapore do not play any political role for the local Muslim community. Due to the seemingly close relationship between the government and grassroots Muslim organisations it is unsurprising that many presume that the activities of organisations such as the Islamic Religious Council of Singapore (MUIS) and the Singapore Islamic Scholars and Religious Teachers Association (PERGAS) are closely monitored by the government. As a result of this environment, the ulama in Singapore do not enter into the political arena. This article argues that the very act of keeping religion out of formal political life in Singapore is a conscious position taken by the local ulama and that in itself is a form of politics. Choosing not to do something is a political choice.
Reconfigurations of Islamic Authority in Malaysia
Authors: Shiozaki Yuki , Kushimoto Hiroko
Published: October 2014

The role and status of religious authority needs to be read into Malaysian political history over the past fifty years. During this period as the Malaysian state constructed its national identity and plotted its policy course, the role of Islam and religious leaders became an important point of debate. It is within this context that this article considers the independence and autonomy of Malaysian Muslim religious leaders. Traditional religious authority in Malaysia finds its underpinnings largely in the institutions of Islamic learning locally known as pondoks, which are a community of students of Islam under the directions of a religious leader, ulama (also often known as a Tok Guru). However as the state consolidated their control over these religious leaders whom were co-opted into the state apparatus, by employment and education at state universities, their social significance has been destabilized. In the wake of this compromised socio-political and religious position alternative sources of authoritative Islamic teachings have emerged in recent years such as the Tablighi Jamaʿat discussed in this article.
Khalwatiah Samman Tarekat in South Sulawesi, Indonesia (1920s–1998)
Authors: Ubaedillah Achmad
Published: October 2014

In order to interpret religious authority and its historical contours in Indonesia this article considers Sufi associations (Ind. tarekat) and the way that their religious leaders and followers understand their authority and the challenges to it. Particularly, this article will focus on the history of the Khalwatiah Sammān tarekat in South Sulawesi. Over the past two centuries the Khalwatiah Sammān and its growing membership have faced a long running opposition from formalist ulama whom take exception to their Islamic practices and interpretations. The opposition mounted against this tarekat and its adherent’s response to these attacks allows us to review the diverse ways that religious authority is understood and practiced in Indonesia.
The Culture of ‘Associational Leadership’ in the Hui Muslim Women’s Mosques of Central China
Authors: Shui Jingjun , Jaschok Maria
Published: October 2014

Women’s mosques and female Ahong (religious leaders) and their ‘Associational leadership’ style have made great contributions to Islamic religious practices and more generally Muslim communities in central China for over 300 years. This article investigates these issues through understanding the biographies of two leading female Ahong and considering their modes of operation and the relationships that they have with their community. New religious trends and a more open political context has allowed these religious leaders to develop and re-shape their authority. Importantly, female Ahong operate in distinctive ways through the cooperation with women’s mosque managers and committees to create and develop a unique female collective and ritual space for religious expression.
Morphological reassessment and molecular assessment of Sargassum (Fucales: Phaeophyceae) species from the Gulf of California, Mexico
Authors: ANDRADE-SORCIA GABRIELA , RIOSMENA-RODRIGUEZ RAFAEL , MUÑIZ-SALAZAR RAQUEL , LÓPEZ-VIVAS JUAN MANUEL , BOO GA HUN , LEE KYUNG MIN , BOO SUNG MIN
Published: October 2014

Systematic molecular studies have not been performed on ecologically important brown algae (Sargassum) in the Gulf of California, Mexico, where 42 specific and infraspecific names have been recorded within this genus. We conducted phylogenetic analyses of nuclear ribosomal ITS and mitochondrial cox1 and cox3 sequences, along with detailed morphological observations of Sargassum collected in the Gulf of California. We confirmed the presence of six species, five previously described—S. herporhizum, S. horridum, S. johnstonii, S. lapazeanum, and S. sinicola, as well as the newly described Sargassum ulixei sp. nov. which is characterized by terete primary axes arising from the stipe, lanceolate to elliptical sessile ecostate blades with smooth margins, cryptostomata, ellipsoidal vesicles with a short mucron, and cylindrical to ellipsoidal receptacles. The individual analyses and subsequent phylogenetic analysis recognized two groups previously described by Dawson, one as Sargassum and other as Horridum. Our studies suggest that the Gulf of California is a region with endemic Sargassum species, and is clearly distinguished from the Pacific side of Baja California, where recently introduced species are common. Based on phylogenetic relationships, we propose two geographical origins for the Sargassum from the Gulf of California: a first group originating from the proto-Gulf, related to species from the northern hemisphere (including five species); and a second group, containing S. sinicola, introduced when the southern end opened at a later stage.