bluuebunny/crossref_metadata_2025 huggingface dataset:
Tivantinib (ARQ 197) Exhibits Antitumor Activity by Directly Interacting with Tubulin and Overcomes ABC Transporter–Mediated Drug Resistance
Authors: Aoyama Aki , Katayama Ryohei , Oh-hara Tomoko , Sato Shigeo , Okuno Yasushi , Fujita Naoya
Published: October 2014

Tivantinib (ARQ197) was first reported as a highly selective inhibitor of c-MET and is currently being investigated in a phase III clinical trial. However, as recently reported by us and another group, tivantinib showed cytotoxic activity independent of cellular c-MET status and also disrupted microtubule dynamics. To investigate if tivantinib exerts its cytotoxic activity by disrupting microtubules, we quantified polymerized tubulin in cells and xenograft tumors after tivantinib treatment. Consistent with our previous report, tivantinib reduced tubulin polymerization in cells and in mouse xenograft tumors in vivo. To determine if tivantinib directly binds to tubulin, we performed an in vitro competition assay. Tivantinib competitively inhibited colchicine but not vincristine or vinblastine binding to purified tubulin. These results imply that tivantinib directly binds to the colchicine binding site of tubulin. To predict the binding mode of tivantinib with tubulin, we performed computer simulation of the docking pose of tivantinib with tubulin using GOLD docking program. Computer simulation predicts tivantinib fitted into the colchicine binding pocket of tubulin without steric hindrance. Furthermore, tivantinib showed similar IC50 values against parental and multidrug-resistant cells. In contrast, other microtubule-targeting drugs, such as vincristine, paclitaxel, and colchicine, could not suppress the growth of cells overexpressing ABC transporters. Moreover, the expression level of ABC transporters did not correlate with the apoptosis-inducing ability of tivantinib different from other microtubule inhibitor. These results suggest that tivantinib can overcome ABC transporter–mediated multidrug-resistant tumor cells and is potentially useful against various tumors. Mol Cancer Ther; 13(12); 2978–90. ©2014 AACR.
Real-Time Intravital Imaging Establishes Tumor-Associated Macrophages as the Extraskeletal Target of Bisphosphonate Action in Cancer
Authors: Junankar Simon , Shay Gemma , Jurczyluk Julie , Ali Naveid , Down Jenny , Pocock Nicholas , Parker Andrew , Nguyen Akira , Sun Shuting , Kashemirov Boris , McKenna Charles E. , Croucher Peter I. , Swarbrick Alexander , Weilbaecher Katherine , Phan Tri Giang , Rogers Michael J.
Published: October 2014

Recent clinical trials have shown that bisphosphonate drugs improve breast cancer patient survival independent of their antiresorptive effects on the skeleton. However, because bisphosphonates bind rapidly to bone mineral, the exact mechanisms of their antitumor action, particularly on cells outside of bone, remain unknown. Here, we used real-time intravital two-photon microscopy to show extensive leakage of fluorescent bisphosphonate from the vasculature in 4T1 mouse mammary tumors, where it initially binds to areas of small, granular microcalcifications that are engulfed by tumor-associated macrophages (TAM), but not tumor cells. Importantly, we also observed uptake of radiolabeled bisphosphonate in the primary breast tumor of a patient and showed the resected tumor to be infiltrated with TAMs and to contain similar granular microcalcifications. These data represent the first compelling in vivo evidence that bisphosphonates can target cells in tumors outside the skeleton and that their antitumor activity is likely to be mediated via TAMs.

Significance: Bisphosphonates are assumed to act solely in bone. However, mouse models and clinical trials show that they have surprising antitumor effects outside bone. We provide unequivocal evidence that bisphosphonates target TAMs, but not tumor cells, to exert their extraskeletal effects, offering a rationale for use in patients with early disease. Cancer Discov; 5(1); 35–42. ©2014 AACR.

See related commentary by Sterling, p. 14

This article is highlighted in the In This Issue feature, p. 1
Young Adults with Dyskinetic Cerebral Palsy Improve Subjectively on Pallidal Stimulation, but not in Formal Dystonia, Gait, Speech and Swallowing Testing
Authors: Koy Anne , Pauls K. Amande M. , Flossdorf Pia , Becker Johannes , Schönau Eckhard , Maarouf Mohammad , Liebig Thomas , Fricke Oliver , Fink Gereon R. , Timmermann Lars
Published: October 2014

Background: Pharmacological treatment of dyskinetic cerebral palsy (CP) is often ineffective. Data about outcome of deep brain stimulation (DBS) in these patients remains scarce. Methods: Eight patients with dyskinetic CP and DBS of the Globus Pallidus internus were investigated. Using pre- and postoperative videos the severity of dystonia and changes thereof during standardized settings (‘on') and after the stimulator had been switched off (‘off') were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Furthermore, subjective impression (SI) of the extent of postoperative change as well as gait (Leonardo Mechanograph® Gangway), speech (Frenchay Dysarthria) and swallowing performances (fiberoptic laryngoscopy) were assessed during ‘on' and ‘off'. Results: When comparing pre- and postoperative as well as ‘on' and ‘off', the BFMDRS and most of the gait, speech, and swallowing parameters did not differ significantly. In contrast, patients reported significant improvement of their SI postoperatively (3.1 on a 10-point-scale). Conclusion: Data show that our CP-patients did not benefit from GPi-DBS when tested formally for dystonia, gait, speech and swallowing. In stark contrast, these patients reported significant subjective improvement. Taken together, and in light of current unsatisfactory medical treatment options, our data suggest that further assessment of the effects of GPi-DBS in dyskinetic CP is warranted.
Putting Experimental Dynamics into the Field: The German ‘Ostfeldzug' and the Creation of Emergency Care Chains in Military Neurology and Neurological Surgery, 1941-1945
Authors: Stahnisch Frank W.
Published: October 2014

Background: The interconnections between the history of neurology and neurological surgery with the development of modern, technological warfare are a vastly under-researched area of medical history. The main objectives of this paper are hence to contribute to the understanding and analysis of a major case example from World War II. Materials: The article's research is based on work at the Bundesarchiv in Koblenz, the Max Planck Gesellschaft in Berlin, and literature regarding the Fuehrungsstab der Luftwaffe, undertaken as part of a larger scale project on the history of the neurosciences and psychiatry in the first half of the 20th century. Summary: The current article focuses particularly on the Ostfeldzug of the Wehrmacht and the creation of emergency care chains in military neurology and neurological surgery. Its results show how major German neurologists, such as Otfrid Foerster, Wilhelm Toennis, Georg Merrem and Klaus Joachim Zuelch have contributed to the development of emergency care chains in military neurology. Key Messages: In conclusion, despite the atrocities and often-inhumane ways through which knowledge was gathered in contemporary military neurology, a better understanding of modern neurology can be gained from a critical assessment of the history of military neurology during World War II.
Bispectral Index and Lower Margin Amplitude of the Amplitude-Integrated Electroencephalogram in Neonates
Authors: Werther Tobias , Olischar Monika , Giordano Vito , Czaba Christine , Waldhoer Thomas , Berger Angelika , Pollak Arnold , Deindl Philipp
Published: October 2014

Background: The lower margin amplitude (LMA) of the amplitude-integrated electroencephalogram (aEEG) is suppressed in neonates during deep sedation, a feature that is attributed to the bispectral index (BIS) in adults. Objective: We compare the BIS and the LMA of the aEEG in neonates. Methods: Thirty neurologically healthy neonates between 37 and 44 weeks postmenstrual age were included in this study. Twenty patients received sedoanalgesic therapy for various reasons. BIS and aEEG recordings were performed simultaneously. The digital data were imported in the numerical software environment Matlab®. The LMA of the aEEG was computed on a 1-min time scale and synchronized with the BIS data. The correlation between the time-dependent variables BIS and LMA was estimated using the Spearman rank correlation index. Results: The median correlation between BIS and LMA was 0.3. Inclusion of recordings of high signal quality only into analysis improved the median correlation index to 0.6. Conclusions: We found a light-to-moderate correlation between BIS and LMA in our study cohort and a good correlation in the subgroup with high signal quality.
Minimal versus Definitive Surgery in Managing Peptic Ulcer Bleeding: A Population-Based Cohort Study
Authors: Sverdén Emma , Sondén Anders , Leinsköld Ted , Lagergren Jesper , Lu Yunxia
Published: October 2014

Objective: To compare radical surgery with a minimal approach for peptic ulcer bleeding in relation to survival. Design: A Swedish nationwide population-based cohort study from 1987-2008 compared survival after minimal surgery and definitive surgery. The cohort was also stratified into calendar year before and after the year 2000 for subgroup analyses. Data were collected from the Swedish Patient Register. The two surgical groups were matched based on the propensity score to mimic a randomized trial design. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounders. Results: 4,163 patients were included. There were no differences in survival in patients who underwent definitive surgical procedures compared to those who underwent minimal surgery for a bleeding peptic ulcer during the full study period. Using minimal surgery group as the reference, the HRs for death in the definitive surgery group within 30 days, 90 days, 1 year, and 5 years were 0.87 (95% CI 0.72-1.05), 0.93 (0.80-1.09), 1.00 (95% CI 0.87-1.14), and 1.05 (95% CI 0.95-1.16), respectively. The corresponding HRs during the calendar period after the year 2000 were 1.05 (95% CI 0.65-1.69), 1.18 (95% CI 0.81-1.73), 1.17 (0.84-1.62), and 1.27 (95% CI 0.99-1.63), respectively. Conclusion: This study found no worse overall survival after minimal surgery compared to more extensive surgery for refractory peptic ulcer bleeding, and indicated better long-term survival in the minimal surgery group during the more recent study period. A minimal approach is probably sufficient in most cases.
Atherogenic Risk Factors and Hearing Thresholds
Authors: Frederiksen Thomas Winther , Ramlau-Hansen Cecilia Høst , Stokholm Zara Ann , Brødsgaard Grynderup Matias , Hansen Åse Marie , Lund Søren Peter , Medom Vestergaard Jesper , Kristiansen Jesper , Bonde Jens Peter , Kolstad Henrik Albert
Published: October 2014

The objective of this study was to evaluate the influence of atherogenic risk factors on hearing thresholds. In a cross-sectional study we analyzed data from a Danish survey in 2009-2010 on physical and psychological working conditions. The study included 576 white- and blue-collar workers from children's day care units, financial services and 10 manufacturing trades. Associations between atherogenic risk factors (blood lipids, glycosylated hemoglobin, smoking habits, body mass index (BMI), and ambulatory blood pressure) and hearing thresholds were analyzed using multiple linear regression models. Adjusted results suggested associations between smoking, high BMI and triglyceride level and low high-density lipoprotein level and increased low-frequency hearing thresholds (average of pure-tone hearing thresholds at 0.25, 0.5 and 1 kHz). Furthermore, an increasing load of atherogenic risk factors seemed associated with increased low-frequency hearing thresholds, but only at a borderline level of statistical significance. Associations were generally strongest with hearing levels of the worst hearing ear. We found no statistically significant associations between atherogenic risk factors and high-frequency hearing thresholds (average of pure-tone hearing thresholds at 4, 6 and 8 kHz).
Thrombelastography Maximal Clot Strength Could Predict One-Year Functional Outcome in Patients with Ischemic Stroke
Authors: Yao Xiaoying , Dong Quan , Song Yeping , Wang Yanqing , Deng Ye , Li Yansheng
Published: October 2014

Background: Elevated maximal clot strength, measured by thrombelastography (TEG) maximum amplitude (MA) has been associated with a higher risk for ischemic events in patients with coronary artery diseases. However, it has not been investigated in patients with cerebrovascular diseases. In the current study, we aimed to evaluate the predictive ability of TEG-MA in assessing the risk for ischemic event recurrence and the functional outcome after index ischemic stroke. Methods: This was a prospective observational study. Consecutive eligible patients with acute ischemic stroke were included and followed up for one year. Patients were stratified into tertile groups based on MA levels. TEG-hypercoagulability was deﬁned as an MA of ≥69 mm. Ischemic events were defined as a composite of ischemic stroke, myocardial infarction, or vascular death (excluding hemorrhagic death). The functional outcome was evaluatewd by modified Rankin Scale (mRS). Unfavorable functional outcome was defined as mRS ≥2. Results: Two hundred and eleven patients were enrolled with 27 lost to follow-up at one year contact. At baseline, 38 (18.0%) patients were TEG-hypercoagulopathy after the treatment of antiplatelets. Patients with higher tertile of MA were more likely to be females, and had lower hemoglobin levels, higher platelet counts, higher fibrinogen levels, higher white blood cell counts, as well as higher ESR and hsCRP levels. Patients in the third tertile group were more likely to have intracranial artery stenosis and large-vessel subtype stroke than those in the other two groups. Higher tertile of MA was also related to stroke severity in acute phase (higher NIHSS scores on admission and longer in-hospital stay). At one year of follow-up, a higher percentage of unfavorable functional outcome and a non-significant trend of higher ischemic event rate were observed in higher MA tertile groups. Multivariate logistic analysis revealed that higher MA level (OR = 1.192, p = 0.022) was an independent predictor for unfavorable one-year functional outcome. Other independent predictors included old age (OR = 1.119, p = 0.001), diabetes mellitus (DM) (OR = 4.280, p = 0.014), previous ischemic stroke/TIA history (OR = 4.953, p = 0.008), and higher NIHSS scores on admission (OR = 1.437, p = 0.001). Conclusions: We found that higher TEG-MA levels could predict an unfavorable functional outcome after index ischemic stroke. Further, large-scale studies are required to investigate the relationship between MA levels and risk of recurrent ischemic events in ischemic stroke patients.
Self-Citation Rate and Impact Factor in Ophthalmology
Authors: Mimouni Michael , Segal Ori
Published: October 2014

Purpose: To analyze the self-citation rate (SCR) of ophthalmology journals, determine its possible effect on a journal's impact factor (IF) and compare the SCR of subspecialty journals versus general ophthalmology journals. Method: A retrospective consecutive study of ophthalmology journals listed in the Journal Citations Report (JCR) 2013. We retrieved these parameters from each journal's report: IF, total citations, self-citations, SCR and IF without self-citations (corrected IF). Results: A significant correlation was detected between the number of self-citations and publications (R2 = 86.3, p = 0.000). Subspecialty journals had a significantly higher SCR than general journals (p = 0.017). No significant difference was found in terms of IF and corrected IF between general and subspecialty journals (p = 0.260 and p = 0.108, respectively). No significant correlation between IF and SCR was detected (p = 0.099). The corrected IF was inversely correlated with SCR (R2 = -32.6, p = 0.013). An inverse correlation was detected between SCR and IF in the 29 ophthalmology journals with the lowest IF (R2 = -57.3, p = 0.001). Conclusion: Unlike other fields of medicine, the IF of an ophthalmology journal does not correlate with its SCR. Self-citation is found more often in journals with a low corrected IF and is inversely correlated with IF in the bottom half.
Feasibility of Neonatal Pulse Wave Velocity and Association with Maternal Hemoglobin A1c
Authors: Chen Sharon , Chetty Shilpa , Lowenthal Alexander , Evans Jasmine M. , Vu Chau , Stauffer Katie J. , Lyell Deirdre , Selamet Tierney Elif Seda
Published: October 2014

Background: Use of non-invasive peripheral arterial tonometry to assess arterial stiffness has not been studied in neonates. Perinatal factors impact childhood vascular health, but the effect in neonates remains to be examined. Objectives: To examine the feasibility of pulse wave velocity (PWV) among healthy term neonates, and to evaluate the effects of perinatal factors on neonatal PWV. Methods: Pregnant women with singleton gestation presenting for routine care were enrolled. Postnatally, PWV measurements of their neonates were obtained using an arterial tonometer. A variability index was calculated for each PWV measurement. Intra- and inter-observer reproducibility were illustrated with Bland-Altman plots. Medical records were reviewed. Relationships between neonatal PWV and perinatal factors were examined. Results: PWV measurements were attempted in 76 neonates and successfully obtained in 67 (88%). Using PWV measurements with a variability index ≤0.25 (48 neonates), the intra-class coefficient was 0.69. The mean differences (limits of agreement) for intra- and inter-rater reproducibility were 0.02 (-3.64 to 3.60) and 0.34 (-2.23 to 2.39), respectively. Median neonatal PWV was 2.80 m/s (range 0.60-8.40). Neonates of mothers with HgbA1c ≥6% had significantly higher PWV than neonates of mothers with HgbA1c <6% (4.12 m/s, 95% CI 3.22-5.02, vs. 2.78 m/s, 95% CI 2.28-3.28, p = 0.02). Conclusions: Neonatal PWV using peripheral arterial tonometry is feasible and reproducible when using measurements with a variability index ≤0.25. Neonates of mothers with increased HgbA1c had higher PWV, suggesting an effect of maternal hyperglycemia on neonatal vasculature. The long-term implications of this finding warrant further investigation.
Frequent Hemodialysis Fistula Infectious Complications
Authors: Lok Charmaine E. , Sontrop Jessica M. , Faratro Rose , Chan Christopher T. , Zimmerman Deborah Lynn
Published: October 2014

Background: Few studies have examined if infectious arteriovenous access complications vary with the cannulation technique and whether this is modified by dialysis frequency. We compared the infection rate between fistulas cannulated using buttonhole versus stepladder techniques for patients treated with short daily (SDH) or nocturnal hemodialysis at home (NHD). We also compared patients receiving conventional intermittent hemodialysis (CIHD) using stepladder cannulation. Methods: Data were prospectively collected from 631 patients dialyzed with a fistula from 2001 to 2010 (Toronto and Ottawa, Canada). We compared the person-time incidence rate of bacteremia and local fistula infections using the exact binomial test. Results: Forty-six (7.3%) patients received SDH (≥5 sessions/week, 2-4 h/session), 128 (20.3%) NHD (≥4 sessions/week, ≥5 h/session) and 457 (72%) CIHD (3 sessions/week, ≤4 h/session). Fifty percent of SDH and 72% of NHD patients used the buttonhole technique. There were 39 buttonhole-related bacteremias (rate: 0.196/1,000 fistula days) and at least 2 local buttonhole site infections. Staphylococcus aureus accounted for 85% of the bacteremias. There were 5 (13%) infection-related hospitalizations and 3 (10%) serious metastatic infections, including fistula loss. In comparison, there was 1 possible fistula-related infection in CIHD during follow-up (rate: 0.002/1,000 fistula days). Conclusions: The rate of buttonhole-related infections was high among patients on frequent hemodialysis and more than 50 times greater than that among patients on CIHD with the stepladder technique. Most bacteremias were due to S. aureus - with serious consequences. The risks and benefits of buttonhole cannulation require individual consideration with careful monitoring, prophylaxis and management.
Evaluation of a Novel Brachial Cuff-Based Oscillometric Method for Estimating Central Systolic Pressure in Hemodialysis Patients
Authors: Sarafidis Pantelis A. , Georgianos Panagiotis I. , Karpetas Antonios , Bikos Athanasios , Korelidou Linda , Tersi Maria , Divanis Dimitrios , Tzanis Georgios , Mavromatidis Konstantinos , Liakopoulos Vassilios , Zebekakis Pantelis E. , Lasaridis Anastasios , Protogerou Athanase D.
Published: October 2014

Background/Aims: Elevated wave reflections and arterial stiffness, as well as ambulatory blood pressure (BP) are independent predictors of cardiovascular risk in end-stage-renal-disease. This study is the first to evaluate in hemodialysis patients the validity of a new ambulatory oscillometric device (Mobil-O-Graph, IEM, Germany), which estimates aortic BP, augmentation index (AIx) and pulse wave velocity (PWV). Methods: Aortic SBP (aSBP), heart rate-adjusted AIx (AIx(75)) and PWV measured with Mobil-O-Graph were compared with the values from the most widely used tonometric device (Sphygmocor, ArtCor, Australia) in 73 hemodialysis patients. Measurements were made in a randomized order after 10 min of rest in the supine position at least 30 min before a dialysis session. Brachial BP (mercury sphygmomanometer) was used for the calibration of Sphygmocor's waveform. Results: Sphygmocor-derived aSBP and AIx(75) did not differ from the relevant Mobil-O-Graph measurements (aSBP: 136.3 ± 19.6 vs. 133.5 ± 19.3 mm Hg, p = 0.068; AIx(75): 28.4 ± 9.3 vs. 30.0 ± 11.8%, p = 0.229). The small difference in aSBP is perhaps explained by a relevant difference in brachial SBP used for calibration (146.9 ± 20.4 vs. 145.2 ± 19.9 mm Hg, p = 0.341). Sphygmocor PWV was higher than Mobil-O-Graph PWV (10.3 ± 3.4 vs. 9.5 ± 2.1 m/s, p < 0.01). All 3 parameters estimated by Mobil-O-Graph showed highly significant (p < 0.001) correlations with the relevant measurements of Sphygmocor (aSBP, r = 0.770; AIx(75), r = 0.400; PWV, r = 0.739). The Bland-Altman Plots for aSBP and AIx(75) showed acceptable agreement between the two devices and no evidence of systemic bias for PWV. Conclusion: As in other populations, acceptable agreement between Mobil-O-Graph and Sphygmocor was evident for aSBP and AIx(75) in hemodialysis patients; PWV was slightly underestimated by Mobil-O-Graph.
Calculated Antibiosis of Acute Cholangitis and Cholecystitis
Authors: Bornscheuer Till , Schmiedel Stefan
Published: October 2014

Background: The aim of this article is to present the most recent suggestions for the therapy of acute cholangitis and cholecystitis based on a review of the current literature. Methods: We performed a systematic literature search in the Medline, PubMed, and Google Scholar databases using the keywords mentioned above. This article is strongly influenced by the publication of the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07, TG13) in 2007 and 2013. These were the first practical guidelines targeting diagnosis and treatment of acute cholangitis and cholecystitis. These guidelines are based on the best published evidence and a consensus conference of international experts in the field. Results and Conclusion: Acute cholangitis and acute cholecystitis are common conditions that may result in progressively severe infection and death when not treated appropriately. Beside supportive therapy and antiobstructive measures, therapy with antimicrobial agents is an important component in the management of affected patients. Here, we discuss the use of antimicrobial agents that are suitable for the first-line management of these infections. Empirical therapy depends upon the knowledge of local microbial epidemiology and patient-specific factors affecting the selection of appropriate agents.
Predialysis NTproBNP Predicts Magnitude of Extracellular Volume Overload in Haemodialysis Patients
Authors: Nongnuch Arkom , Panorchan Kwanpeemai , Davenport Andrew
Published: October 2014

Introduction: Increased natriuretic peptides are associated with increased cardiovascular and all-cause mortality for haemodialysis (HD) patients. However, debate continues whether these biomarkers are increased by extracellular water (ECW) excess and can be used to aid clinical assessment of volume status and help determine target weight. Methods: We measured N terminal probrain natriuretic peptide (NT-proBNP) predialysis in 375 stable haemodialysis outpatients with corresponding pre and postdialysis multifrequency bioelectrical impedance assessments (MFBIA) of (ECW)/total body water (TBW). Results: Median age 64 (51-75), 63.9% male, 42.9% diabetic, 43.2% Caucasoid, 14.4% with a history of myocardial infarction, 8.4% coronary artery bypass surgery, dialysis vintage 28.2 (12.3-55.5) months. Median predialysis NT-proBNP 283 (123-989) pmol/l, and predialysis ECW/TBW ratio 0.397 ± 0.029. On multivariate analysis, predialysis log NT-proBNP was associated with predialysis systolic blood pressure (β 0.007, p = 0.000), weight (β −0.008, p = 0.001), valvular heart disease (β 0.342, p = 0.015, ECW/TBW (β 1.3, p = 0.019) and log CRP (β 0.145, p = 0.037). Dividing patients into NTproBNP quartiles, %ECW/TBW and relative ECW overhydration were significantly greater for the highest quartile vs. lowest (40.5 ± 4.1 vs. 39.0 ± 1.1, and 1.51 ± 1.24 vs. 0.61 ± 0.69 l, respectively, p < 0.001). Conclusion: In this study, predialysis NTproBNP values were associated with direct assessments of the extracellular volume excess measured by MFBIA and systolic arterial blood pressure. This suggests that predialysis NTproBNP values can potentially be used to aid clinical assessment of volume status in dialysis patients to determine target weight.
Autoimmune Hepatitis with Multiple Sclerosis and Graves Disease: Coincidence or Association
Authors: Nadhem Omar N. , Al Janabi Mohammed , Omer Abdel Rahman , Wan Bang
Published: October 2014

Autoimmune hepatitis (AIH) is a generally progressive, chronic hepatitis of unknown cause that occurs in children and adults of all ages. It is associated with a variety of autoimmune conditions like thyroid disorders (Hashimoto and Graves disease), celiac disease and multiple sclerosis (MS). We report the case of a 61-year-old woman with MS (untreated) and a history of Graves disease who presented with fatigue and right upper quadrant abdominal pain. She was admitted to our hospital for evaluation. Clinical and laboratory workup revealed AIH. She was successfully treated with prednisone and azathioprine, with complete clinical and laboratory improvement. However, to our knowledge there have been only a few reports of a possible association between AIH and untreated MS.
A Case of Inflammatory Generalized Type of Peeling Skin Syndrome Possibly Caused by a Homozygous Missense Mutation of CDSN
Authors: Kawakami Hiroshi , Uchiyama Masaki , Maeda Tatsuo , Tsunoda Takahiko , Mitsuhashi Yoshihiko , Tsuboi Ryoji
Published: October 2014

A 54-year-old Japanese woman had repetitive superficial skin peeling and ensuing erythematous changes in the sites since infancy. Her parents had a consanguineous marriage, and she was the only individual affected in her family tree. The erythematous changes seemed to worsen in the summer. Histologically, hyperkeratosis and splitting of the epidermis within the stratum corneum was noted, and electron microscopy revealed shedding of corneal cells in the horny layer and normal-looking corneodesmosomes. Gene analysis revealed a homozygous missense mutation at c.1358G>A in CDSN. Electron microscopic examination of the length and number of corneodesmosomes revealed statistically significant shortness and sparsity in the affected individual (mean ± SD 386.2 ± 149.5 nm) compared with that of an age- and site-matched control (406.6 ± 182.3 nm). We speculate that this size shrinkage of corneodesmosomes might be the result of a missense mutation of CDSN and that this could be one of the factors contributing to the pathological process of skin peeling.
Architectural Correlates of Myocardial Conduction
Authors: Fry Christopher H. , Gray Rosaire P. , Dhillon Paramdeep S. , Jabr Rita I. , Dupont Emmanuel , Patel Pravina M. , Peters Nicholas S.
Published: October 2014

Background—

We tested the hypothesis that alterations to action potential conduction velocity (CV) and conduction anisotropy in left ventricular hypertrophy are associated with topographical changes to gap-junction coupling and intracellular conductance by measuring these variables in the same preparations.

Methods and Results—

Left ventricular papillary muscles were excised from aortic-banded or sham-operated guinea-pig hearts. With intracellular stimulating and recording microelectrodes, CV was measured in 3 dimensions with simultaneous conductance mapping with subthreshold stimuli and correlated with quantitative histomorphometry of myocardial architecture and connexin 43 distribution. In hypertrophied myocardium, CV in the longitudinal axis was smaller and transverse velocity was greater compared with control; associated with similar differences of intracellular conductance, consistent with more cell contacts per cell (5.7±0.2 versus 8.1±0.5; control versus hypertrophy), and more intercalated disks mediating side-to-side coupling (8.2±0.2 versus 10.2±0.4 per cell). Intercalated disk morphology and connexin 43 immunolabelling were not different in hypertrophy. Hypertrophied preparations showed local submillimeter (≈250 μm) regions with slow conduction and low intracellular conductance, which, although not affecting CV on the millimeter scale, were consistent with discontinuities from increased microscopical connective tissue content.

Conclusions—

With myocardial hypertrophy, altered longitudinal and transverse CV, and greater nonuniformity of CV anisotropy correspond to changes of intracellular conductance. These are associated with alteration of myocardial architecture, specifically the topography of cell–cell coupling and gap-junction connectivity.
The “Vietnam Legion”: West German Psychological Warfare against East German Propaganda in the 1960s
Authors: Busch Peter
Published: October 2014

Studies in the wake of the “cultural turn” in diplomatic history have shown that propaganda and public diplomacy were key aspects of Western Cold War strategy. This article expands recent literature by focusing on propaganda practices at the grassroots level, making use of West and East German archival records to trace information campaigns in relation to the Vietnam War. In addition to explaining the organization of East German propaganda campaigns, the article explores the methods used by the psychological warfare section of West Germany’s Ministry of Defense. This section maintained an unofficial network that helped publish “camouflaged propaganda” at home as well as in France and Great Britain. Germany’s Nazi past was an important aspect of East Germany’s campaign that accused West Germany of having deployed a “Vietnam Legion.” Interestingly, Germany’s Nazi legacy also cast a shadow over the methods West German psychological warfare experts relied on to counter East German accusations.
The Neural Correlates of Speech Motor Sequence Learning
Authors: Segawa Jennifer A. , Tourville Jason A. , Beal Deryk S. , Guenther Frank H.
Published: October 2014

Speech is perhaps the most sophisticated example of a species-wide movement capability in the animal kingdom, requiring split-second sequencing of approximately 100 muscles in the respiratory, laryngeal, and oral movement systems. Despite the unique role speech plays in human interaction and the debilitating impact of its disruption, little is known about the neural mechanisms underlying speech motor learning. Here, we studied the behavioral and neural correlates of learning new speech motor sequences. Participants repeatedly produced novel, meaningless syllables comprising illegal consonant clusters (e.g., GVAZF) over 2 days of practice. Following practice, participants produced the sequences with fewer errors and shorter durations, indicative of motor learning. Using fMRI, we compared brain activity during production of the learned illegal sequences and novel illegal sequences. Greater activity was noted during production of novel sequences in brain regions linked to non-speech motor sequence learning, including the BG and pre-SMA. Activity during novel sequence production was also greater in brain regions associated with learning and maintaining speech motor programs, including lateral premotor cortex, frontal operculum, and posterior superior temporal cortex. Measures of learning success correlated positively with activity in left frontal operculum and white matter integrity under left posterior superior temporal sulcus. These findings indicate speech motor sequence learning relies not only on brain areas involved generally in motor sequencing learning but also those associated with feedback-based speech motor learning. Furthermore, learning success is modulated by the integrity of structural connectivity between these motor and sensory brain regions.
Changing the Topic
Authors: Allan Rutger J.
Published: October 2014

Abstract

In Ancient Greek, topics can be expressed as intra-clausal constituents but they can also precede or follow the main clause as extra-clausal constituents. Together, these various topic expressions constitute a coherent system of complementary pragmatic functions. For a comprehensive account of topic organization, therefore, a limited focus on the clause proper is insufficient. In this paper, I will argue that it is possible to distinguish five different structural positions in which topic constituents may appear in Ancient Greek. These are: (i) Theme, (ii) clause-initial, (iii) postverbal in Setting, (iv) postverbal in main clause and (v) Tail. Each of these positions in the sentence is associated with a specific pragmatic function: Resumed Topic, Contrastive/New Topic, Given Topic or clarification of Given Topic. In linguistic theory, topic and focus are often seen as independent aspects of information structure instead of complementary functions. It is, therefore, attractive to posit two separate sets of constructional templates: on the one hand, a topic set comprising the aforementioned topic constructions and, on the other hand, a focus set containing two (narrow and broad) focus-constructions. This results in a flexible system in which the word order of each sentence is determined by a combination of a focus construction plus one or more topic constructions.
The Starting Points of Human Understanding
Authors: Goris Wouter
Published: October 2014

Abstract

The present article discusses the notion of πρῶτον νοητόν in the Didaskalikos, where this notion indicates a cognitive primacy exclusively related to human understanding. It is argued that, due to the enrichment of Platonic doctrine with Stoic motives in this treatise, a dual starting point is ascribed here to human cognition. Both the πρῶτον νοητόν and the φυσικὴ ἔννοια function as such. The πρῶτον νοητόν is the primary object of a decarnate νόησις, the φυσικὴ ἔννοια our present reminiscence of this decarnate νόησις. The recognition of a genetic perspective in the Didaskalikos enables us to resolve the interpretative difficulties related to the restrictive expression οὐκ ἄνευ τοῦ ἐπιστηµονικοῦ λόγου, which characterizes the judgement of the πρῶτα νοητά by νόησις. Among the procedures employed to arrive at the starting points of human cognition are ‘analysis’ and ‘induction’. These specimina of an ‘investigation from below’ (κάτωθεν) contribute to the complex rhythm of the Didaskalikos. The tradition inaugurated by the treatise, i.e. the search for first known objects of human understanding in Greek, Arabic, and Latin philosophy, is accompanied by a tension between the empirical and the transcendental, which is used in the Didaskalikos to argue for the necessity of a Platonic frame, and consequently re-activated in all attempts to free the search for first known objects of human understanding from a Platonic ontology.
Refuge characteristics and preferences of Psammobates oculifer in semi-arid savanna
Authors: Keswick Toby , Hofmeyr Margaretha
Published: October 2014

The availability of suitable refuges to buffer temperature extremes may be a critical determinant in the distribution of arid-zone ectotherms. We studied refuge selection of Kalahari tent tortoises over five seasons in two vegetation types to assess how seasonal climate change, vegetation type, and the size difference between sexes influence refuge selection. Plant refuges accounted for 78% and mammal burrows for 22% of refuges used. Burrow use did not differ between vegetation types or sexes but its use increased exponentially with maximum temperature, indicating that mammal burrows may be an essential resource to protect small-bodied tortoises against summer heat. Kalahari tent tortoises preferred grass refuges to other growth forms, whether shrubs or grasses were dominant in the habitat. Tall grass was selected in excess of availability, by males and females in both vegetation types, probably because it was denser than short grass and provided better protection against heat and predators. The increased use of short grass refuges in colder months may be linked to thermal needs because this growth form allowed P. oculifer to bask in filtered sunlight whilst being in cover. Females made greater use than males did of short grass refuges, perhaps because their larger size necessitated longer exposure to sunlight. Body size differences also explain why males required wider and denser refuges than females did to protect them against environmental hazards. Our results underscore the complexities of refuge selection by an arid-zone ectotherm and the role it may play in their distribution.
Surveys on populations of green frogs (Pelophylax) of Western Tuscany sites with molecular and morphometric methods
Authors: Tognarelli Giulia , Zuffi Marco A.L. , Marracci Silvia , Ragghianti Matilde
Published: October 2014

The water frogs of western Tuscany (Italy) belong to the L-E hybridogenetic system, and comprise one parental species and its hybrid. A stringent morphological approach for discriminating the Italian hybrids from non-hybrids has yet to be established. In this work, using the molecular marker RrS1, we have determined the hybrid versus non-hybrid status of 43 water frogs collected from two sampling sites (“Fiume Morto Vecchio” and “Padule di Bientina”). At “Fiume Morto Vecchio” we determined 25 non-hybrids and nine hybrids and in “Padule di Bientina” we determined eight hybrids and one non-hybrid individual. All individuals of these two frog populations were analyzed morphologically. We used the derived residuals from regression analysis of all normally distributed morphological parameters on callus internus length (snout to vent length, tibia length, head width, distance nostril eye, first toe length and body mass) to build sex independent variables in discriminant analysis providing a valid contribution to morphologically distinguish hybrids from non-hybrid green frogs in Italy.
Does intraspecific and intersexual attraction or avoidance influence newt abundance estimates based on fish funnel trap records?
Authors: Rödel Mark-Oliver , Demtröder Sebastian , Fuchs Claire , Petrich Diana , Pfisterer Friedrich , Richter Andreas , Stolpe Clemens , Voß Ramona , Ripperger Simon Peter , Mayer Frieder , Dittrich Carolin , Thein Jürgen
Published: October 2014

We experimentally investigated whether intraspecific and intersexual attraction (or avoidance) by chemical signals may bias newt trapping success. We installed commercially available fish funnel traps which are often used in newt monitoring studies. We tested if capture rates differed between traps with or without newts. One experimental trap set comprised five traps, one trap being empty and four traps containing one male or female Lissotriton vulgaris or Ichthyosaura alpestris, respectively. Capture rates of newts of neither species nor sex was significantly affected by the presence of a particular newt species or sex in the traps, compared to control traps without newts. Trapping success thus seems not to be biased beyond random effects.
The origins of moral judgment
Authors: Joyce Richard
Published: October 2014

Is human morality a biological adaptation? And, if so, should this fact have any substantial impact on the ethical inquiry of how we should live our lives? In this paper I will address both these questions, though will not attempt definitively to answer either. Regarding the former, my goal is to clarify the question and identify some serious challenges that arise for any attempt to settle the matter one way or the other. Regarding the latter, my ambitions here are restricted to some brief critical comments on one recent attempt to answer the question in the affirmative.
The neuroscience of social relations. A comparative-based approach to empathy and to the capacity of evaluating others’ action value
Authors: Ferrari Pier F.
Published: October 2014

One of the key questions in understanding human morality is how central are emotions in influencing our decisions and in our moral judgments. Theoretical work has proposed that empathy could play an important role in guiding our tendencies to behave altruistically or selfishly. Neurosciences suggest that one of the core elements of empathic behaviour in human and nonhuman primates is the capacity to internally mimic the behaviour of others, through the activation of shared motor representations. Part of the neural circuits involves parietal and premotor cortical regions (mirror system), in conjunction with other areas, such as the insula and the anterior cingulate cortex. Together with this embodied neural mechanism, there is a cognitive route in which individuals can evaluate the social situation without necessary sharing the emotional state of others. For example, several brain areas of the prefrontal cortex track the effects of one’s own behaviour and of the value of one’s own actions in social contexts. It is here proposed that, moral cognition could emerge as the consequence of the activity of emotional processing brain networks, probably involving mirror mechanisms, and of brain regions that, through abstract-inferential processing, evaluate the social context and the value of actions in terms of abstract representations. A comparative-based approach to the neurobiology of social relations and decision-making may explain how complex mental faculties, such as moral judgments, have their foundations in brain networks endowed with functions related to emotional and abstract-evaluation processing of goods. It is proposed that in primate evolution these brain circuits have been co-opted in the social domain to integrate mechanisms of self-reward, estimation of negative outcomes, with emotional engagement.
From Conflict to Consensus? Elite Integration and Democracy in Ghana
Authors: Osei Anja
Published: October 2014

The paper takes as its starting point Higley and Burton’s (2006) contention that no liberal democracy has ever evolved without a ‘consensually united elite’ which is structurally integrated and shares some general values. The fact that the evolution of a consensually united elite is a very rare event limits the prospects for the worldwide spread of liberal democracy. Ghana, however, could represent one of these rare cases. This paper looks at if and how an elite consensus on the “rules of the game” has emerged in the country and what the potential threats to this consensus are. It pays special attention to the social composition of elites and their patterns of interaction between elites (horizontal integration) as well as the relationship between elites and the wider population (vertical integration).
Global Networks and the Two Faces of Chinese National Oil Companies
Authors: de Graaff Nana
Published: October 2014

This paper investigates the patterns of transnational investments and alliances of Chinese state-owned oil companies since the mid-1990s and the social networks of their directors, taking the case ofcnpcand its listed subsidiary PetroChina as the example. Using Social Network Analysis, I will map how the oil companies and their directors are embedded in corporate and political networks both inside and outside China. The preliminary findings presented in this study show that with their overseas expansion,cnpcand PetroChina increasingly collaborate with other oil companies. Significantly, also forming what I have called ‘hybrid alliances’ with Western private oil majors. However, they remain wedded to a different role at home, where they are expected to adhere to priorities and values tightly knit to the state, such as supply security and social responsibilities. This duality is mirrored by the Chinese oil company directors who must maintain a balancing act between their ‘two faces’ of corporate managers, on the one hand, and commitments to party-state interests, on the other.
China’s Resource Demand and Market Opportunities in the Middle East: Policies and Operations in Iran and Iraq
Authors: Liu Dong
Published: October 2014

Following rapid economic development, China’s dependence on imported petroleum has been increasing at a pace. In order to prevent an energy shortage that would impede economic development, the Chinese government has come up with a strategy of nocs ‘going out’; this is as an important measure for securing energy safety at the beginning of twenty-first century. However, at a time when nationalization has become widespread among resource-rich countries, the only opportunities for Chinese nocs to implement the ‘going out’ policy are in politically fragile states. Against this background, Iran and Iraq became important ‘going out’ destinations of Chinese nocs. However, the contracts that Chinese nocs have signed with Iran and Iraq are service contracts. That is to say, by signing this kind of contract, the huge investments made by Chinese nocs in Iran and Iraq are not equal to their oil or gas interests and the Chinese nocs are also incapable of ensuring the oil and gas that they produce in both these resource-rich countries are exported to China. As a result, and due to the fact that the needs of the Chinese government with respect to securing stable energy imports, Chinese nocs’ decisions towards investing in Iran and Iraq, as well as the way they manage their projects in these two countries are driven purely by commercial considerations.
Chinese National Oil Companies in Ghana: The Cases of cnooc and Sinopec
Authors: Hardus Sarah
Published: October 2014

This article uses the case of Ghana to provide insight into the policies and strategies used by, as well as the cooperation between, Chinese state actors in their quest for natural resources in Africa. In 2007, Ghana discovered commercial quantities of oil. While the so-called Jubilee oilfield was initially divided amongst primarily Western oil companies, in 2010 the China National Offshore Oil Corporation partnered with Ghana’s national oil company to try and purchase a stake in Jubilee. Although this bid was rejected, later that year a second Chinese state-owned oil company, Sinopec, was able to access Ghana’s oil indirectly through an offtaker agreement, linked to a $3 billion dollar loan provided by the state-owned China Development Bank. The article uses these two cases to examine the level of coordination between the strategies of Chinese state actors in their attempts to access African natural resources. It shows that China’s national oil companies and policy banks operate in increasingly autonomous ways. This goes against the developmental state thesis, which argues that the Chinese state has full control over the overseas activities of its state actors. The article also shows that national political institutions in Africa can make use of and are able to influence Chinese resource deals, countering the notion of African passivity.