bluuebunny/crossref_metadata_2025 huggingface dataset:
A molecular update on pseudohypoaldosteronism type II
Authors: Pathare Ganesh , Hoenderop Joost G. J. , Bindels René J. M. , San-Cristobal Pedro
Published: October 2013

The DCT (distal convoluted tubule) is the site of microregulation of water reabsorption and ion handling in the kidneys, which is mainly under the control of aldosterone. Aldosterone binds to and activates mineralocorticoid receptors, which ultimately lead to increased sodium reabsorption in the distal part of the nephron. Impairment of mineralocorticoid signal transduction results in resistance to aldosterone and mineralocorticoids, and, therefore, causes disturbances in electrolyte balance. Pseudohypoaldosteronism type II (PHAII) or familial hyperkalemic hypertension (FHHt) is a rare, autosomal dominant syndrome characterized by hypertension, hyperkalemia, metabolic acidosis, elevated or low aldosterone levels, and decreased plasma renin activity. PHAII is caused by mutations in the WNK isoforms (with no lysine kinase), which regulate the Na-Cl and Na-K-Cl cotransporters (NCC and NKCC2, respectively) and the renal outer medullary potassium (ROMK) channel in the DCT. This review focuses on new candidate genes such as KLHL3 and Cullin3, which are instrumental to unraveling novel signal transductions pathways involving NCC, to better understand the cause of PHAII along with the molecular mechanisms governing the pathophysiology of PHAII and its clinical manifestations.
Whole person-evoked fMRI activity patterns in human fusiform gyrus are accurately modeled by a linear combination of face- and body-evoked activity patterns
Authors: Kaiser Daniel , Strnad Lukas , Seidl Katharina N. , Kastner Sabine , Peelen Marius V.
Published: October 2013

Visual cues from the face and the body provide information about another's identity, emotional state, and intentions. Previous neuroimaging studies that investigated neural responses to (bodiless) faces and (headless) bodies have reported overlapping face- and body-selective brain regions in right fusiform gyrus (FG). In daily life, however, faces and bodies are typically perceived together and are effortlessly integrated into the percept of a whole person, raising the possibility that neural responses to whole persons are qualitatively different than responses to isolated faces and bodies. The present study used fMRI to examine how FG activity in response to a whole person relates to activity in response to the same face and body but presented in isolation. Using multivoxel pattern analysis, we modeled person-evoked response patterns in right FG through a linear combination of face- and body-evoked response patterns. We found that these synthetic patterns were able to accurately approximate the response patterns to whole persons, with face and body patterns each adding unique information to the response patterns evoked by whole person stimuli. These results suggest that whole person responses in FG primarily arise from the coactivation of independent face- and body-selective neural populations.
Selective Disruption of Rb–Raf-1 Kinase Interaction Inhibits Pancreatic Adenocarcinoma Growth Irrespective of Gemcitabine Sensitivity
Authors: Treviño José G. , Verma Monika , Singh Sandeep , Pillai Smitha , Zhang Dongyu , Pernazza Daniele , Sebti Said M. , Lawrence Nicholas J. , Centeno Barbara A. , Chellappan Srikumar P.
Published: October 2013

Inactivation of the retinoblastoma (Rb) tumor suppressor protein is widespread in human cancers. Inactivation of Rb is thought to be initiated by association with Raf-1 (C-Raf) kinase, and here we determined how RRD-251, a disruptor of the Rb–Raf-1 interaction, affects pancreatic tumor progression. Assessment of phospho-Rb levels in resected human pancreatic tumor specimens by immunohistochemistry (n = 95) showed that increased Rb phosphorylation correlated with increasing grade of resected human pancreatic adenocarcinomas (P = 0.0272), which correlated with reduced overall patient survival (P = 0.0186). To define the antitumor effects of RRD-251 (50 μmol/L), cell-cycle analyses, senescence, cell viability, cell migration, anchorage-independent growth, angiogenic tubule formation and invasion assays were conducted on gemcitabine-sensitive and -resistant pancreatic cancer cells. RRD-251 prevented S-phase entry, induced senescence and apoptosis, and inhibited anchorage-independent growth and invasion (P < 0.01). Drug efficacy on subcutaneous and orthotopic xenograft models was tested by intraperitoneal injections of RRD-251 (50 mg/kg) alone or in combination with gemcitabine (250 mg/kg). RRD-251 significantly reduced tumor growth in vivo accompanied by reduced Rb phosphorylation and lymph node and liver metastasis (P < 0.01). Combination of RRD-251 with gemcitabine showed cooperative effect on tumor growth (P < 0.01). In conclusion, disruption of the Rb–Raf-1 interaction significantly reduces the malignant properties of pancreatic cancer cells irrespective of their gemcitabine sensitivity. Selective targeting of Rb–Raf-1 interaction might be a promising strategy targeting pancreatic cancer. Mol Cancer Ther; 12(12); 2722–34. ©2013 AACR.
Microtubule Dynamics Control Tail Retraction in Migrating Vascular Endothelial Cells
Authors: Ganguly Anutosh , Yang Hailing , Zhang Hong , Cabral Fernando , Patel Kamala D.
Published: October 2013

Drugs that target microtubules are potent inhibitors of angiogenesis, but their mechanism of action is not well understood. To explore this, we treated human umbilical vein endothelial cells with paclitaxel, vinblastine, and colchicine and measured the effects on microtubule dynamics and cell motility. In general, lower drug concentrations suppressed microtubule dynamics and inhibited cell migration whereas higher concentrations were needed to inhibit cell division; however, surprisingly, large drug-dependent differences were seen in the relative concentrations needed to inhibit these two processes. Suppression of microtubule dynamics did not significantly affect excursions of lamellipodia away from the nucleus or prevent cells from elongating; but, it did inhibit retraction of the trailing edges that are normally enriched in dynamic microtubules, thereby limiting cell locomotion. Complete removal of microtubules with a high vinblastine concentration caused a loss of polarity that resulted in roundish, rather than elongated, cells, rapid but nondirectional membrane activity, and little cell movement. The results are consistent with a model in which more static microtubules stabilize the leading edge of migrating cells, whereas more dynamic microtubules locate to the rear where they can remodel and allow tail retraction. Suppressing microtubule dynamics interferes with tail retraction, but removal of microtubules destroys the asymmetry needed for cell elongation and directional motility. The prediction that suppressing microtubule dynamics might be sufficient to prevent angiogenesis was supported by showing that low concentrations of paclitaxel could prevent the formation of capillary-like structures in an in vitro tube formation assay. Mol Cancer Ther; 12(12); 2837–46. ©2013 AACR.
Effect of F8 B domain gene variants on synthesis, secretion, activity and stability of factor VIII protein
Authors: Pahl Saskia , Pavlova Anna , Driesen Julia , Oldenburg Johannes
Published: October 2013

The B domain of the coagulation factor (F)VIII comprises some unique characteristics. Though the B domain is important for processing, intracellular transport and secretion of FVIII protein, its role in the coagulation still remains unclear. This study aims to investigate the influence of 19 reported B domain variants on quantity and quality of expressed FVIII protein. F8 variants were transiently expressed in HEK293T cells. Media and cell lysates were collected after 72 hours. FVIII synthesis, relative secretion, activity and thermostability were analysed in comparison to FVIII wild-type. Eleven of 19 analysed B domain variants showed normal FVIII activity (FVIII:C), and antigen values (40–150 %). Eight variants exhibited a decreased FVIII:C, corresponding to a mild phenotype most likely due to impaired expression and secretion mechanism, reduced thermostability or combined mechanisms. One variant, p.His1066Tyr, showed markedly reduced FVIII antigen in cell lysate. The variants p.Asp845Glu, p.His998Gln, and p.Ala1610Ser revealed a significantly decreased relative secretion. Additionally, six B domain variants significantly reduced stability of FVIII. In conclusion, none of the analysed missense mutations was causative for a severe haemophilia A (HA) phenotype. Nevertheless, the mutations p.Asp845Glu, p.Pro947Arg, p.Glu1057Lys, p.His1066Tyr, p.Arg1126Trp, p.Arg1329His, p.Leu1481Pro, and p.Ala1610Ser resulted in decreased FVIII:C values that may explain mild HA phenotypes.
Novel antiplatelet drugs in clinical development
Authors: Ungerer Martin , Münch Götz
Published: October 2013

The clinical value of antiplatelet compounds strongly depends on the benefit-risk balance between their anti-thrombotic effects and the bleeding risk they incur. This ratio is especially important in the treatment of cerebro-vascular disease. Several novel compounds in clinical development hold promise to improve this benefit-risk ratio.
A novel natural mutation AαPhe98Ile in the fibrinogen coiled-coil affects fibrinogen function
Authors: Riedelová-Reicheltová Zuzana , Kotlín Roman , Suttnar Jiří , Geierová Věra , Riedel Tomáš , Májek Pavel , Dyr Jan Evangelista
Published: October 2013

The aim of this study was to investigate the structure and function of fibrinogen obtained from a patient with normal coagulation times and idiopathic thrombophilia. This was done by SDS-PAGE and DNA sequence analyses, scanning electron microscopy, fibrinopeptide release, fibrin polymerisation initiated by thrombin and reptilase, fibrinolysis, and platelet aggregometry. A novel heterozygous point mutation in the fibrinogen Aα chain, Phe98 to Ile, was found and designated as fibrinogen Vizovice. The mutation, which is located in the RGDF sequence (Aα 95–98) of the fibrinogen coiled-coil region, significantly affected fibrin clot morphology. Namely, the clot formed by fibrinogen Vizovice contained thinner and curled fibrin fibers with reduced length. Lysis of the clots prepared from Vizovice plasma and isolated fibrinogen were found to be impaired. The lysis rate of Vizovice clots was almost four times slower than the lysis rate of control clots. In the presence of platelets agonists the mutant fibrinogen caused increased platelet aggregation. The data obtained show that natural mutation of Phe98 to Ile in the fibrinogen Aα chain influences lateral aggregation of fibrin protofibrils, fibrinolysis, and platelet aggregation. They also suggest that delayed fibrinolysis, together with the abnormal fibrin network morphology and increased platelet aggregation, may be the direct cause of thrombotic complications in the patient associated with pregnancy loss.
Pharmacological modulation of procoagulant microparticles improves haemodynamic dysfunction during septic shock in rats
Authors: Boisramé-Helms Julie , Delabranche Xavier , Degirmenci Su-Emmanuelle , Zobairi Fatiha , Berger Asael , Meyer Grégory , Burban Mélanie , Mostefai Hadj-Ahmed , Levy Bruno , Toti Florence , Meziani Ferhat
Published: October 2013

Circulating microparticles play a pro-inflammatory and procoagulant detrimental role in the vascular dysfunction of septic shock. It was the objective of this study to investigate mechanisms by which a pharmacological modulation of microparticles could affect vascular dysfunction in a rat model of septic shock. Septic or sham rats were treated by activated protein C (aPC) and resuscitated during 4 hours. Their microparticles were harvested and inoculated to another set of healthy recipient rats. Haemodynamic parameters were monitored, circulating total procoagulant microparticles assessed by prothrombinase assay, and their cell origin characterised. Mesenteric resistance arteries, aorta and heart were harvested for western blotting analysis. We found that a) the amount and phenotype of circulating microparticles were altered in septic rats with an enhanced endothelial, leucocyte and platelet contribution; b) aPC treatment significantly reduced the generation of leucocyte microparticles and norepinephrine requirements to reach the mean arterial pressure target in septic rats; c) Microparticles from untreated septic rats, but not from aPC-treated ones, significantly reduced the healthy recipients’ mean arterial pressure; d) Microparticle thromboxane content and aPC activity were significantly increased in aPC-treated septic rats. In inoculated naïve recipients, microparticles from aPC-treated septic rats prompted reduced NF-κB and cyclooxygenase-2 arterial activation, blunted the generation of pro-inflammatory iNOS and secondarily increased platelet and endothelial microparticles. In conclusion, in this septic shock model, increased circulating levels of procoagulant microparticles led to negative haemodynamic outcomes. Pharmacological treatment by aPC modified the cell origin and levels of circulating microparticles, thereby limiting vascular inflammation and favouring haemodynamic improvement.
Mandatory contrast-enhanced venography to detect deep-vein thrombosis (DVT) in studies of DVT prophylaxis: upsides and downsides
Authors: Hirsh Jack , Ginsberg Jeffrey S. , Chan Noel , Guyatt Gordon , Eikelboom John W.
Published: October 2013

The introduction of venography into patient care was a major advance because it was the first accurate method for the diagnosis of DVT. Compression ultrasound has since become the preferred test for patients with suspected DVT because, unlike venography, it is simple, non-invasive and widely available. Venography has facilitated the development and approval of new anticoagulants and remains widely used as an efficacy outcome in trials of venous thromboembolism prevention. Most thrombi detected by screening venography are, however, small and unimportant for patients. In order to calculate the trade-off between an asymptomatic thrombus and a bleed we require an estimate of the number of asymptomatic thrombi that must be prevented to avoid a patient-important thrombus. A credible estimate of this ratio is not available. Therefore when used as a measure of efficacy in trials of thromboprophylaxis, venography has limitations for comparing the relative effects of alternative antithrombotic agents on outcomes important to patients.
Epicardial Ablation of Ventricular Tachycardia in Ischemic Heart Disease
Authors: Sarkozy Andrea , Tokuda Michifumi , Tedrow Usha B. , Sieria Juan , Michaud Gregory F. , Couper Gregory S. , John Roy , Stevenson William G.
Published: October 2013

Background—

Epicardial approaches have increased ablation success in nonischemic cardiomyopathy, but the use for postinfarction ventricular tachycardias (VT) is less clear. We report the findings for epicardial VT ablation in postinfarct patients.

Methods and Results—

Records of 444 consecutive patients with VT because of prior infarction referred for 600 catheter ablation procedures were reviewed. Epicardial procedures were performed in the electrophysiology laboratory in 56 (13%) patients using percutaneous (43 patients) or surgical (13 patients) epicardial access. In 7 patients, epicardial ablation was performed surgically in the operating room. In the electrophysiology laboratory epicardial VT targets were identified in 38 (68%) patients and epicardial ablation abolished ≥1 VT in 27 patients (6% of the total study population); inducibility was not tested after ablation in 4, and VT remained inducible in 7 patients. No ablation was performed in 18 (32%) patients because of no accessible epicardial target or a complication. Major complications occurred in 8 (14%) of the 57 electrophysiology laboratory procedures. After the first procedure any VT recurred in 21 (54%) of 39 patients who had epicardial ablation compared with 164 (47%) of 347 endocardial-only ablation patients (
P
=0.35).

Conclusions—

Epicardial ablation is potentially useful in ≥6% of the postinfarction VT population, but the number could be substantially greater because more than two thirds of patients selected for epicardial mapping after failed ablation had an epicardial VT target. Successful epicardial ablation of a VT was not predictable from infarct location or other patient characteristics.
Positron Emission Tomography/Computed Tomographic and Magnetic Resonance Imaging in a Murine Model of Progressive Atherosclerosis Using
64
Cu-Labeled Glycoprotein VI-Fc
Authors: Bigalke Boris , Phinikaridou Alkystis , Andia Marcelo E. , Cooper Margaret S. , Schuster Andreas , Schönberger Tanja , Griessinger Christoph M. , Wurster Thomas , Onthank David , Ungerer Martin , Gawaz Meinrad , Nagel Eike , Botnar Rene M.
Published: October 2013

Background—

Plaque erosion leads to exposure of subendothelial collagen, which may be targeted by glycoprotein VI (GPVI). We aimed to detect plaque erosion using
64
Cu-labeled GPVI-Fc (fragment crystallized).

Methods and Results—

Four-week-old male apolipoprotein E–deficient (ApoE
−/−
) mice (n=6) were fed a high-fat diet for 12 weeks. C57BL/6J wild-type (WT) mice served as controls (n=6). Another group of WT mice received a ligation injury of the left carotid artery (n=6) or sham procedure (n=4). All mice received a total activity of ≈12 MBq
64
Cu-GPVI-Fc by tail vein injection followed by delayed (24 hours) positron emission tomography using a NanoPET/computed tomographic scanner (Mediso, Hungary; Bioscan, USA) with an acquisition time of 1800 seconds. Seventy-two hours after positron emission tomography/computed tomography, all mice were scanned 2 hours after intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-specific MR contrast agent. MRI was performed on a 3-T clinical scanner (Philips Healthcare, Best, The Netherlands). In ApoE
−/−
mice, the
64
Cu-GPVI-Fc uptake in the aortic arch was significantly higher compared with WT mice (ApoE
−/−
: 13.2±1.5 Bq/cm
3
versus WT mice: 5.1±0.5 Bq/cm
3
;
P
=0.028).
64
Cu-GPVI-Fc uptake was also higher in the injured left carotid artery wall compared with the intact right carotid artery of WT mice and as a trend compared with sham procedure (injured: 20.7±1.3 Bq/cm
3
versus intact: 2.3±0.5 Bq/cm
3
;
P
=0.028 versus sham: 12.7±1.7 Bq/cm
3
;
P
=0.068). Results were confirmed by ex vivo histology and in vivo MRI with elastin-specific MR contrast agent that measures plaque burden and vessel wall remodeling. Higher R1 relaxation rates were found in the injured carotid wall with a T1 mapping sequence (injured: 1.44±0.08 s
−1
versus intact: 0.91±0.02 s
−1
;
P
=0.028 versus sham: 0.97±0.05 s
−1
;
P
=0.068) and in the aortic arch of ApoE
−/−
mice compared with WT mice (ApoE
−/−
: 1.49±0.05 s
−1
versus WT: 0.92±0.04 s
−1
;
P
=0.028).

Conclusions—

64
Cu-GPVI-Fc positron emission tomographic imaging allows identification of exposed subendothelial collagen in injured WT and high-fat diet–fed ApoE
−/−
mice.
Practical Linguistic Steganography using Contextual Synonym Substitution and a Novel Vertex Coding Method
Authors: Chang Ching-Yun , Clark Stephen
Published: October 2013

Linguistic steganography is concerned with hiding information in natural language text. One of the major transformations used in linguistic steganography is synonym substitution. However, few existing studies have studied the practical application of this approach. In this article we propose two improvements to the use of synonym substitution for encoding hidden bits of information. First, we use the Google n-gram corpus for checking the applicability of a synonym in context, and we evaluate this method using data from the SemEval lexical substitution task and human annotated data. Second, we address the problem that arises from words with more than one sense, which creates a potential ambiguity in terms of which bits are represented by a particular word. We develop a novel method in which words are the vertices in a graph, synonyms are linked by edges, and the bits assigned to a word are determined by a vertex coding algorithm. This method ensures that each word represents a unique sequence of bits, without cutting out large numbers of synonyms, and thus maintains a reasonable embedding capacity.
What’s New About Muslim Ismaili Transnationalism? Comparing Business Practices in British East Africa, Colonial Mozambique and Contemporary Angola
Authors: Trovão Susana Salvaterra , Batoréu Filomena
Published: October 2013

Abstract

The way in which the history of colonialism might link up with the formation of postcolonial migrant identities remains insufficiently examined. Through a comparison between transnational business practices of Khoja Ismaili Muslim settled in the British and Portuguese colonial territories of East Africa and in contemporary Angola, the present paper aims to discuss the impact of colonial experiences in the configuration of postcolonial business cultures. Articulating several guiding empirical questions, we will attempt to show that the continuing centrality of the nation-states in which Ismaili transnational economic activities are embedded, the notion of a disadvantageous network closure, concomitant with the importance of face-to-face contacts, the mutual trust and understanding sustained through personal relations, and the tendency for national loyalty to prevail over religious belonging (whenever any potential conflict between the two exists) constitute crucial dimensions of an accumulated colonial knowledge which is significant in the analysis of the Ismaili competitive advantage in postcolonial Africa. This argument will be developed on the basis of a multi-sited ethnographic research. The U.K. and Portugal emerged as a strategic passage for our encounters with East African Ismailis from former British and Portuguese colonial territories. The current Angolan context, absent from the available literature, was selected as a postcolonial term of comparison.
Comparing Peer Reviews: The Universal Periodic Review of the UN Human Rights Council and the African Peer Review Mechanism
Authors: McMahon Edward R. , Busia Kojo , Ascherio Marta
Published: October 2013

Abstract

The Universal Periodic Review Mechanism (UPR) of the UN Human Rights Council and the African Peer Review Mechanism (APRM) reflect a growing trend in international organizations to utilize peer review processes to assess and improve member state governance and human rights performance. The two mechanisms are distinct in many ways. For example, the APRM undertakes a more in-depth and rigorous examination of a broader range of issues. Both review mechanisms, however, also have similarities e.g. they emphasize follow-up and actions to be taken as a result of the reviews and are products of a consensus decision-making process based on voluntary engagement. They represent an evolutionary process by which international norms can be integrated in a national context.
The Return of the Natives: Asian Diaspora Issues and Dilemmas – The Case of India
Authors: Varshney Deepanjana
Published: October 2013

Abstract

The research paper probes into the reverse migrants’ psychological dimensions and provides insights on their motivational dynamics. Key demographic variables are taken into consideration and the respondents’ perception towards own life cycle stage, the foreign country and the home country provides salient insights on the reverse migration literature. I have, in this empirical paper, correlated demographic variables with select reverse migration factors and have offered plausible reasons and underlying forces behind the return of Indian expatriates abroad. I present the argument in my paper that the underlying causes for return migration are the same globally irrespective of the country of present residence.
New species and new records of Ampithoidae (Peracarida: Amphipoda) from Australian Waters
Authors: HUGHES LAUREN E. , PEART RACHAEL A.
Published: October 2013

Forty-eight species from the algal dwelling family Ampithoidae are recorded from five genera Ampithoe, Cymadusa, Paragrubia, Peramphithoe, and Plumithoe. New distribution records are provided for 18 species including five new records from Australian waters and an additional 18 new species are described. Twenty-two Ampithoe, 23 Cymadusa, six Paragrubia, two Peramphithoe, and one Plumithoe species are now known from Australian waters. The generic concepts of both Cymadusa and Paragrubia are revised to accommodate the new species diversity within the Ampithoidae. The new species are: Ampithoe mantissa; A. prolata; Cymadusa botulus; C. drummondae; C. euclidius; C. hadros; C. hallex; C. hentyana; C. jubata; C. lumanus; C. platys; C. priscileo; Paragrubia apoorei; P. cassini; P. dongara; P. dwyeri; P. springthorpei and Peramphithoe bungareei.
An Analysis of Registered Clinical Trials in Otolaryngology from 2007 to 2010: ClinicalTrials.gov
Authors: Witsell David L. , Schulz Kristine A. , Lee Walter T. , Chiswell Karen
Published: October 2013

Objective

To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity.

Study Design

Database analysis.

Setting

Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010.

Methods

Data extraction from ClinicalTrials.gov was done using MeSH and non‐MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD‐9 codes for otolaryngology and non‐otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi‐square tests were used to explore differences between groups.

Results

A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints.

Conclusions

Analysis of otolaryngology‐related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology‐associated conditions in our tertiary health system exceeds research activity within the field.
Alternative redo sternotomy in a patient with tracheostoma and patent grafts
Authors: Uehara Kyokun , Minakata Kenji , Funamoto Masaki , Yamazaki Kazuhiro , Marui Akira , Sakata Ryuzo
Published: October 2013

We describe a redo mitral valve replacement operation in a 71-year-old man with a tracheostoma and patent bypass grafts to the coronary arteries. Preoperative investigations revealed that the patent right internal thoracic artery graft ran directly under the sternum just anterior to the ascending aorta, and a saphenous vein graft was adhering to a surgical wire. To prevent injury to the patent grafts and cardiac structures, and to avoid communication with the tracheostoma, the redo procedure was performed via an anterior minithoracotomy combined with a low T-shaped partial sternotomy. The reoperation was successfully completed without any complications.
Sumatriptan/naproxen sodium for the acute treatment of probable migraine without aura: A randomized study
Authors: Silberstein Stephen , McDonald Susan A , Goldstein Jerome , Aurora Sheena , Lener Shelly E , White Jonathan , Runken Michael C , Saiers Jane , Derosier Frederick , Lipton Richard B
Published: October 2013

Objective

Probable migraine is a common, disabling migraine subtype fulfilling all but one of the diagnostic criteria for migraine. This study was conducted to evaluate the efficacy and tolerability of sumatriptan/naproxen sodium for the acute treatment of probable migraine without aura.

Methods

Patients treated a headache of probable migraine without aura when pain was moderate or severe with sumatriptan/naproxen sodium ( n = 222 intent-to-treat (ITT)) or placebo ( n = 221 ITT/complete case analysis a ) in this randomized, double-blind, parallel-group study.

Results

Sumatriptan/naproxen sodium was more effective than placebo with respect to the co-primary efficacy endpoints two-hour pain-free response (29% sumatriptan/naproxen sodium vs 11% placebo, p < 0.001) and two- to 24-hour sustained pain-free response (24% sumatriptan/naproxen sodium vs 9% placebo, p < 0.001). Sumatriptan/naproxen sodium was significantly more effective than placebo with respect to the secondary efficacy endpoints of pain-free response four hours postdose ( p < 0.001), pain-free response maintained one to two hours postdose ( p = 0.034) and two to four hours postdose ( p < 0.001), headache relief four hours postdose ( p < 0.001), headache relief maintained two to four hours postdose ( p = 0.015), sustained headache relief two through 24 hours postdose ( p = 0.002), and rescue medication use ( p < 0.001); but not productivity scores. The most common adverse events were dizziness (4% sumatriptan/naproxen sodium,<1% placebo), dry mouth (2% sumatriptan/naproxen sodium, <1% placebo), and nausea (2% sumatriptan/naproxen sodium, <1% placebo).

Conclusion

Sumatriptan/naproxen sodium is effective in the acute treatment of probable migraine as demonstrated by higher rates of freedom from pain and restoration of function.
Comparative efficacy of triptans for the abortive treatment of migraine: A multiple treatment comparison meta-analysis
Authors: Thorlund Kristian , Mills Edward J , Wu Ping , Ramos Elodie , Chatterjee Anjan , Druyts Eric , Goadsby Peter J
Published: October 2013

Background

Migraine is the most common neurological condition in developed countries. The abortive treatment of migraine attacks is important both for quality of life and costs associated with illness. Triptans, serotonin 5-HT1B/1D receptor agonists, effectively relieve the pain, disability, and associated symptoms of migraine while improving health-related quality of life. Although a number of direct head-to-head triptan comparisons have been made, data for all possible permutations are not available, and unlikely to ever be so, although in clinical practice such information would be useful.

Objective

We aimed to determine the relative efficacy of all available triptans to abort migraine headache among patients with previous adequate response to migraine treatments.

Methods

We included only double-blinded randomized clinical trials comparing triptans to either placebo or another triptan. Our primary outcomes were pain-free response at two hours and 24-hour sustained pain-free response, and our secondary outcomes were headache response at two hours and 24-hour sustained headache response. We used Bayesian multiple treatment comparison meta-analyses of seven triptans used in adult patients to abort migraine attacks. We applied a random-effects analysis with meta-regression adjusting for dose. Results are reported as odds ratios with 95% credible intervals.

Results

We included data from 74 randomized clinical trials. All triptans were significantly superior to placebo for all outcomes, with the exception of naratriptan for 24-hour sustained pain-free response. Eletriptan consistently yielded the highest treatment effect estimates. For the two-hour endpoints, eletriptan was statistically significantly superior to sumatriptan, almotriptan, naratriptan, and frovatriptan for at least one of the two outcomes. Rizatriptan yielded the second highest treatment effects followed by zolmitriptan. For the 24-hour endpoints, eletriptan was statistically significantly superior to sumatriptan, rizatriptan, almotriptan, and naratriptan for at least one of the two outcomes. Frovatriptan data were not available at that endpoint. Further, the probability that eletriptan is the most likely of all triptans to produce a favorable outcome was 68% for pain-free response at two hours, and 54% for 24-hour sustained pain-free response.

Conclusion

Triptans appear to offer differing treatment effects. In the populations studied eletriptan was most likely to produce pain-free responses that were sustained.
Longitudinal prostate-specific antigen reference ranges: Choosing the underlying model of age-related changes
Authors: Simpkin Andrew J , Metcalfe Chris , Martin Richard M , Lane J Athene , Donovan Jenny L , Hamdy Freddie C , Neal David E , Tilling Kate
Published: October 2013

Serial measurements of prostate-specific antigen (PSA) are used as a biomarker for men diagnosed with prostate cancer following an active monitoring programme. Distinguishing pathological changes from natural age-related changes is not straightforward. Here, we compare four approaches to modelling age-related change in PSA with the aim of developing reference ranges for repeated measures of PSA. A suitable model for PSA reference ranges must satisfy two criteria. First, it must offer an accurate description of the trend of PSA on average and in individuals. Second, it must be able to make accurate predictions about new PSA observations for an individual and about the entire PSA trajectory for a new individual.
When celebrity athletes are ‘social movement entrepreneurs’: A study of the role of elite runners in run-for-peace events in post-conflict Kenya in 2008
Authors: Wilson Brian , Van Luijk Nicolien , Boit Michael K
Published: October 2013

This paper reports findings from a study of the role played by high-profile Kenyan runners in the organization of Run-for-Peace events that took place in response to election-related violence in Kenya in late 2007 and early 2008. Acknowledging concerns expressed by some sociologists of sport about the role of celebrity athletes in the sport for development and peace movement, we suggest that in the particular contexts we studied, high-profile athletes played a crucial role in the organization of reconciliation events. Informed by interviews with former and current elite Kenyan runners and others involved in the organization of these events, we argue that the apparent effectiveness of the athletes in mobilizing resources, pursuing political opportunities and devising a collective action frame was possible because of the extant positioning of the athletes in the impacted communities, the active involvement in and personal investment of the athletes in the outcome of the peace-promoting activities, and the unique pre-Olympic moment in which the events took place. In doing so, we differentiate between celebrity athletes who are a ‘presence’ at sport for development and peace events, and those who might be considered ‘social movement entrepreneurs’. We conclude the paper by describing how strands of social movement theory were helpful in guiding our analysis of high-profile athletes and peace promotion, and with suggestions for future research pertaining to sport-related reconciliation movements.
Students’ Expectations and Motivation for Service-Learning in Public Relations
Authors: Muturi Nancy , An Soontae , Mwangi Samuel
Published: October 2013

This study is based on a survey of public relations students and examines their attitudes, expectations, and motivations for participating in curriculum-infused service-learning projects. Results indicate that prior participation does not influence attitudes or expectations, but motivation to participate in the project was significantly associated with positive attitude and higher expectations. Students’ expectations, which include social and professional growth, and psychological and altruistic gratification through community contributions, indicate a need for discipline-focused service-learning programs and for a focus on civic engagement given the role of public relations in relationship building and in strategically addressing social issues that impact society.
Being Leaders for Socially Just Education
Authors: Baldev Satyen , Choi Timothy , Mahmood Bushra , Oslinker Richelle , Sumrein Faten , Waqar Aminah , White Carolyne J.
Published: October 2013

Radically democratic citizen-action-in-the-world requires teachers who are committed to the emergence of such citizens in their classrooms. In addition, commitment alone is insufficient. Teachers must have access to the power to realize their commitment within the overwhelming constraints of neoliberalism. This article illuminates our communal becoming as teacher leaders within a course that utilizes both informative and transformative pedagogy to invite us to view political action newly. This militant pedagogy inspires us to be empowered citizens who craft powerful contexts that call forth new ways of being and acting to incite futures that were not going to happen without collective action.
Automated determination of metastases in unstructured radiology reports for eligibility screening in oncology clinical trials
Authors: Petkov Valentina I , Penberthy Lynne T , Dahman Bassam A , Poklepovic Andrew , Gillam Chris W , McDermott James H
Published: October 2013

Enrolling adequate numbers of patients that meet protocol eligibility criteria in a timely manner is critical, yet clinical trial accrual continues to be problematic. One approach to meet these accrual challenges is to utilize technology to automatically screen patients for clinical trial eligibility. This manuscript reports on the evaluation of different automated approaches to determine the metastatic status from unstructured radiology reports using the Clinical Trials Eligibility Database Integrated System (CTED). The study sample included all patients (N = 5,523) with radiologic diagnostic studies (N = 10,492) completed in a two-week period. Eight search algorithms (queries) within CTED were developed and applied to radiology reports. The performance of each algorithm was compared to a reference standard which consisted of a physician’s review of the radiology reports. Sensitivity, specificity, positive, and negative predicted values were calculated for each algorithm. The number of patients identified by each algorithm varied from 187 to 330 and the number of true positive cases confirmed by physician review ranged from 171 to 199 across the algorithms. The best performing algorithm had sensitivity 94%, specificity 100%, positive predictive value 90%, negative predictive value 100%, and accuracy of 99%. Our evaluation process identified the optimal method for rapid identification of patients with metastatic disease through automated screening of unstructured radiology reports. The methods developed using the CTED system could be readily implemented at other institutions to enhance the efficiency of research staff in the clinical trials eligibility screening process.
Lung Decortication and Lobectomy in a Child With Unrepaired Tetralogy of Fallot
Authors: Sethi Brijindera Singh , Gupta Kushant , Chauhan Sandeep , Choudhary Shiv Kumar
Published: October 2013

Patients with uncorrected tetralogy of Fallot (TOF) have been reported as undergoing emergency noncardiac surgeries such as cesarean section, brain abscess drainage, and major abdominal surgery. The uncorrected TOF group presents a great challenge with issues related to long-term effects of chronic hypoxemia and decreased pulmonary blood flow modifying patient physiology. We report a rare case of a child with uncorrected TOF with necrotizing streptococcal pneumonia complicated by empyema and bronchopleural fistula. The child successfully underwent lung decortication and right middle lobectomy in the first stage followed by an intracardiac repair (ICR) 15 days later. This staged approach was directed at controlling the infective focus, improving the pulmonary status, and following it up with a definitive ICR electively.
Bicuspid Aortic Valves Experience Increased Strain as Compared to Tricuspid Aortic Valves
Authors: Szeto Kai , Pastuszko Peter , Álamo Juan C. del , Lasheras Juan , Nigam Vishal
Published: October 2013

Objective:

To determine whether the leaflets of bicuspid aortic valve (BAV) experience increased strain when compared to tricuspid aortic valve (TAV) leaflets.

Background:

The population at highest risk of aortic valve calcification (AVC) are individuals with BAVs. Currently, efforts to medically treat AVC are hampered by a limited understanding of the biomechanical forces involved in the molecular pathogenesis of AVC.

Methods:

Surgically created BAVs and control TAVs were placed into a left heart simulator. Strains were calculated by comparing the distances between points on the aortic valve (AoV) leaflet during various time points during a simulated cardiac cycle.

Results:

The fused leaflets of BAVs experience significantly more strain during systole when compared to TAVs. Specifically, BAVs experience 24% strain ( P < .0001) in the radial direction, parallel to the direction of blood flow, as compared to TAVs. There was peak difference of 4% ( P < .001) in the circumferential direction.

Discussion:

Based upon the data presented here, we are in the process of identifying how increased strain activates calcification-associated pathways in AoV cells. Future studies will examine whether these stretch responsive pathways can be blocked to inhibit calcification of BAVs.
Functional characterisation of three members of the Vitis viniferaL. carotenoid cleavage dioxygenase gene family
Authors: Lashbrooke Justin G , Young Philip R , Dockrall Samantha J , Vasanth Krishnan , Vivier Melané A
Published: October 2013

Background

In plants, carotenoids serve as the precursors to C13-norisoprenoids, a group of apocarotenoid compounds with diverse biological functions. Enzymatic cleavage of carotenoids catalysed by members of the carotenoid cleavage dioxygenase (CCD) family has been shown to produce a number of industrially important volatile flavour and aroma apocarotenoids including β-ionone, geranylacetone, pseudoionone, α-ionone and 3-hydroxy-β-ionone in a range of plant species. Apocarotenoids contribute to the floral and fruity attributes of many wine cultivars and are thereby, at least partly, responsible for the “varietal character”. Despite their importance in grapes and wine; carotenoid cleavage activity has only been described for VvCCD1 and the mechanism(s) and regulation of carotenoid catabolism remains largely unknown.

Results

Three grapevine-derived CCD-encoding genes have been isolated and shown to be functional with unique substrate cleavage capacities. Our results demonstrate that the VvCCD4a and VvCCD4b catalyse the cleavage of both linear and cyclic carotenoid substrates. The expression ofVvCCD1,VvCCD4aandVvCCD4bwas detected in leaf, flower and throughout berry development.VvCCD1expression was constitutive, whereasVvCCD4aexpression was predominant in leaves andVvCCD4bin berries. A transgenic population with a 12-fold range ofVvCCD1expression exhibited a lack of correlation betweenVvCCD1expression and carotenoid substrates and/or apocarotenoid products in leaves, providing proof that thein plantafunction(s) of VvCCD1 in photosynthetically active tissue is distinct from thein vitroactivities demonstrated. The isolation and functional characterisation of VvCCD4a and VvCCD4b identify two additional CCDs that are functional in grapevine.

Conclusions

Taken together, our results indicate that the three CCDs are under various levels of control that include gene expression (spatial and temporal), substrate specificity and compartmentalisation that act individually and/or co-ordinately to maintain carotenoid and volatile apocarotenoid levels in plants. Altering the expression ofVvCCD1in a transgenic grapevine population illustrated the divergence between thein vitroenzyme activity and thein plantaactivity of this enzyme, thereby contributing to the efforts to understand how enzymatic degradation of carotenoids involved in photosynthesis occurs. The identification and functional characterisation of VvCCD4a and VvCCD4b suggest that these enzymes are primarily responsible for catalysing the cleavage of plastidial carotenoids.
Questionnaire-based study to assess the association between management practices and mastitis within tie-stall and free-stall dairy housing systems in Switzerland
Authors: Gordon Paz F , van den Borne Bart HP , Reist Martin , Kohler Samuel , Doherr Marcus G
Published: October 2013

Background

Prophylactic measures are key components of dairy herd mastitis control programs, but some are only relevant in specific housing systems. To assess the association between management practices and mastitis incidence, data collected in 2011 by a survey among 979 randomly selected Swiss dairy farms, and information from the regular test day recordings from 680 of these farms was analyzed.

Results

The median incidence of farmer-reported clinical mastitis (ICM) was 11.6 (mean 14.7) cases per 100 cows per year. The median annual proportion of milk samples with a composite somatic cell count (PSCC) above 200,000 cells/ml was 16.1 (mean 17.3) %. A multivariable negative binomial regression model was fitted for each of the mastitis indicators for farms with tie-stall and free-stall housing systems separately to study the effect of other (than housing system) management practices on the ICM and PSCC events (above 200,000 cells/ml). The results differed substantially by housing system and outcome. In tie-stall systems, clinical mastitis incidence was mainly affected by region (mountainous production zone; incidence rate ratio (IRR) = 0.73), the dairy herd replacement system (1.27) and farmers age (0.81). The proportion of high SCC was mainly associated with dry cow udder controls (IRR = 0.67), clean bedding material at calving (IRR = 1.72), using total merit values to select bulls (IRR = 1.57) and body condition scoring (IRR = 0.74). In free-stall systems, the IRR for clinical mastitis was mainly associated with stall climate/temperature (IRR = 1.65), comfort mats as resting surface (IRR = 0.75) and when no feed analysis was carried out (IRR = 1.18). The proportion of high SSC was only associated with hand and arm cleaning after calving (IRR = 0.81) and beef producing value to select bulls (IRR = 0.66).

Conclusions

There were substantial differences in identified risk factors in the four models. Some of the factors were in agreement with the reported literature while others were not. This highlights the multifactorial nature of the disease and the differences in the risks for both mastitis manifestations. Attempting to understand these multifactorial associations for mastitis within larger management groups continues to play an important role in mastitis control programs.