bluuebunny/crossref_metadata_2025_split huggingface dataset:
Negative urodynamic testing in women with stress incontinence
Authors: Liversidge Kylie , Guzmán Rojas Rodrigo , Kamisan Atan Ixora , Dietz Hans Peter 
Published: December 2014

IntroductionA minority of women with a subjective complaint of stress urinary incontinence will have negative urodynamic stress incontinence (USI) findings.AimTo test clinical and ultrasound measures as predictors of an unexpected absence of USI. We hypothesised that unexpectedly negative USI would be more common in young women with good pelvic floor and urethral function.MethodsA retrospective study analysing 398 data sets from women attending a urogynaecology clinic for evaluation of lower urinary tract and pelvic floor dysfunction. Clinical, urodynamic and translabial ultrasound data were tested as possible predictors of negative USI findings.ResultsWomen with unexpectedly negative USI findings were younger, had less anterior compartment prolapse and had a higher maximum urethral pressure. Measures of pelvic floor muscle function were not predictive.ConclusionsWomen with unexpectedly negative USI are younger and have better urethral function, but voluntary pelvic floor muscle function seems unrelated to this phenomenon.
Prognostic significance of metabolic tumor burden by positron emission tomography/computed tomography in patients with relapsed/refractory diffuse large B‐cell lymphoma
Authors: Tateishi Ukihide , Tatsumi Mitsuaki , Terauchi Takashi , Ando Kiyoshi , Niitsu Nozomi , Kim Won Seog , Suh Cheolwon , Ogura Michinori , Tobinai Kensei 
Published: December 2014

The aim of the present study was to investigate the feasibility of measuring metabolic tumor burden using [F‐18] fluorodeoxyglucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) in patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL) treated with bendamustine–rituximab. Because the standardized uptake value is a critical parameter of tumor characterization, we carried out a phantom study of 18F‐FDG PET/CT to ensure quality control for 28 machines in the 24 institutions (Japan, 17 institutions; Korea, 7 institutions) participating in our clinical study. Fifty‐five patients with relapsed or refractory DLBCL were enrolled. The 18F‐FDG PET/CT was acquired before treatment, after two cycles, and after the last treatment cycle. Treatment response was assessed after two cycles and after the last cycle using the Lugano classification. Using this classification, remission was complete in 15 patients (27%) and incomplete in 40 patients (73%) after two cycles of therapy, and remission was complete in 32 patients (58%) and incomplete in 23 patients (42%) after the last treatment cycle. The percentage change in all PET/CT parameters except for the area under the curve of the cumulative standardized uptake value–volume histogram was significantly greater in complete response patients than in non‐complete response patients after two cycles and the last cycle. The Cox proportional hazard model and best subset selection method revealed that the percentage change of the sum of total lesion glycolysis after the last cycle (relative risk, 5.24; P = 0.003) was an independent predictor of progression‐free survival. The percent change of sum of total lesion glycolysis, calculated from PET/CT, can be used to quantify the response to treatment and can predict progression‐free survival after the last treatment cycle in patients with relapsed or refractory DLBCL treated with bendamustine–rituximab.
Long‐term efficacy and safety of canagliflozin over 104 weeks in patients aged 55–80 years with type 2 diabetes
Authors: Bode B. , Stenlöf K. , Harris S. , Sullivan D. , Fung A. , Usiskin K. , Meininger G. 
Published: December 2014

AimsThe long‐term efficacy and safety of canagliflozin, a sodium glucose co‐transporter 2 inhibitor, was evaluated over 104 weeks in patients aged 55–80 years with type 2 diabetes mellitus (T2DM) inadequately controlled on a stable antihyperglycaemic agent regimen.MethodsIn this randomized, double‐blind, phase III study, patients received canagliflozin 100 or 300 mg or placebo once daily during a 26‐week core period (N = 714) and a 78‐week extension period (n = 624). Efficacy endpoints at week 104 included change from baseline in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and systolic blood pressure, and percent change from baseline in body weight and fasting plasma lipids. Safety was assessed by adverse event (AE) reports.ResultsAt week 104, canagliflozin 100 and 300 mg were associated with reductions in HbA1c versus placebo (−0.32 and −0.43% vs 0.17%, respectively; overall mean baseline, 7.7%) and more patients achieved HbA1c <7.0% with canagliflozin 100 and 300 mg than with placebo (35.8 and 41.9% vs 20.3%, respectively). Reductions in FPG, body weight and systolic blood pressure, and increases in high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol (LDL‐C) were seen with canagliflozin compared with placebo. The overall incidence rates of AEs over 104 weeks were 88.0, 89.8 and 86.1% with canagliflozin 100 and 300 mg and placebo, respectively; serious AE rates were low across treatment groups. The incidence rates of urinary tract infections, genital mycotic infections and osmotic diuresis– and volume depletion–related AEs were higher with canagliflozin than with placebo.ConclusionCanagliflozin improved glycaemic control, reduced body weight and systolic blood pressure, and was generally well tolerated in patients aged 55–80 years with T2DM over 104 weeks.
The clinical pharmacology profile of the new antiepileptic drug perampanel: A novel noncompetitive AMPA receptor antagonist
Authors: Patsalos Philip N. 
Published: December 2014

SummaryThe clinical pharmacology profile of a drug critically determines its therapeutics, and this review summarizes the characteristics associated with the antiepileptic drug (AED) perampanel. A PubMed literature search was performed for perampanel. Congress abstract data are included where necessary and Eisai Ltd provided access to unpublished data on file. After oral ingestion, perampanel is rapidly absorbed and peak plasma concentrations occur 0.5–2.5 h later; its bioavailability is ~100%. Although the rate of perampanel absorption is slowed by food co‐ingestion, the extent absorbed remains unchanged; therefore, perampanel can be administered without regard to meal times. The pharmacokinetics of perampanel are linear and predictable over the clinically relevant dose range (2–12 mg); perampanel is 95% protein‐bound to albumin and α1‐acid glycoprotein. Perampanel is extensively metabolized (>90%) in the liver, primarily by cytochrome P450 (CYP) 3A4, to various pharmacologically inactive metabolites. In healthy volunteers, the apparent terminal half‐life is ~105 h, whereas the calculated effective half‐life is 48 h. These half‐life values allow for once‐daily dosing, which will aid patient compliance and in the event of a missed dose, will have minimal impact on seizure control. In healthy volunteers prescribed carbamazepine, half‐life decreases to 25 h. Clearance values are not significantly different in adolescents (~13.0 ml/min) and the elderly (~10.5 ml/min) compared with adults (10.9 ml/min). Perampanel has minimal propensity to cause pharmacokinetic interactions. However, it is the target of such interactions and CYP3A4‐inducing AEDs enhance its clearance; this can be used to advantage because dose titration can be faster and thus optimum therapeutic outcome can be achieved sooner. Perampanel 12 mg, but not 4 or 8 mg, enhances the metabolism of the progesterone component of the oral contraceptive pill, necessitating the need for an additional reliable contraceptive method. Overall, perampanel has a favorable clinical pharmacology profile, which should aid its clinical use.
Long‐term seizure outcome in 211 patients with focal cortical dysplasia
Authors: Fauser Susanne , Essang Charles , Altenmüller Dirk‐Matthias , Staack Anke Maren , Steinhoff Bernhard J. , Strobl Karl , Bast Thomas , Schubert‐Bast Susanne , Stephani Ulrich , Wiegand Gert , Prinz Marco , Brandt Armin , Zentner Josef , Schulze‐Bonhage Andreas 
Published: December 2014

SummaryObjectiveFocal cortical dysplasia (FCD) is currently recognized as the most common cause of neocortical pharmacoresistant epilepsy. Epilepsy surgery has become an increasingly successful treatment option. Herein, the largest patient cohort reported to date is analyzed regarding long‐term outcome and factors relevant for long‐term seizure control.MethodsTwo hundred eleven children and adults undergoing epilepsy surgery for histologically proven FCD and a follow‐up period of 2–12 years were analyzed regarding the longitudinal course of seizure control, effects of FCD type, localization, magnetic resonance imaging (MRI), timing of surgery, and postoperative antiepileptic treatment.ResultsAfter 1 year, Engel class I outcome was achieved in 65% of patients and the percentage of seizure‐free patients remained stable over the following (up to 12) years. Complete resection of the assumed epileptogenic area, lower age at surgery, and unilobar localization were positive prognostic indicators of long‐term seizure freedom. Seizure recurrence was 12% after the first year, whereas 8% achieved late seizure freedom either following additional introduction of antiepileptic drugs (AEDs) (4%), a reoperation (2%), or a running down phenomenon (2%). Thirty‐nine percent of patients had a reduction of AED from polytherapy to monotherapy or a complete cessation of AED treatment. Late seizure relapse was seen in nine patients during reduction of AEDs (i.e., in 12% of all patients with AED tapering); in four of them seizures persisted after reestablishment of antiepileptic medication.SignificancePostoperative long‐term seizure outcome was favorable in patients with FCD and remained stable in 80% of patients after the first postoperative year. Several preoperative factors revealed to be predictive for the postoperative outcome and may help in the preoperative counseling of patients with FCD and in the selection of ideal candidates for epilepsy surgery.
Diagnostic practice of psychogenic nonepileptic seizures (PNES) in the pediatric setting
Authors: Wichaidit Bianca T. , Østergaard John R. , Rask Charlotte U. 
Published: December 2014

SummaryObjectiveNo formal guidelines for diagnosing psychogenic nonepileptic seizures (PNES) in children exist, and little is known about the clinical practice of diagnosing PNES in the pediatric setting. We therefore performed a national survey as a first step to document pediatricians’ current diagnostic practice for PNES.MethodsA questionnaire was distributed to all pediatricians (n = 64) working in the field of neuropediatrics and/or social pediatrics in the Danish hospital setting to uncover their use of terminology and of the International Classification of Diseases, 10th Revision (ICD‐10) codes as well as their clinical diagnostic approach to pediatric PNES. The questionnaire included questions on 18 history and 24 paroxysmal event characteristics.ResultsThe response rate was 95% (61/64). There was no consensus on which terminology and diagnostic codes to use. Five history characteristics (psychosocial stressors/trauma, sexual abuse, paroxysmal events typically occur in stressful situations, no effect of antiepileptic drugs, and physical abuse) and six paroxysmal event characteristics (resisted eyelid opening, avoidance/guarding behavior, paroxysmal events occur in the presence of others, closed eyes, rarely injury related to paroxysmal event, and absence of postictal change) were agreed to be very predictive of PNES by at least 50% of the pediatricians. Supplementary diagnostic tests such as blood chemistry measurements (e.g., blood glucose or acute phase reactants; i.e., white blood cell count and C‐reactive protein) and electrocardiography were inconsistently used. Only 49% of the respondents reported to use video‐electroencephalography (VEEG) frequently as part of their diagnostic procedure.SignificanceTo our knowledge, this is the first national survey that offers a systematic insight into the diagnostic practices for children with PNES in the hospital setting. The results demonstrate a need for clinical guidelines to improve and systematize the diagnostic approach for PNES in children.
Muscarinic excitation of parvalbumin‐positive interneurons contributes to the severity of pilocarpine‐induced seizures
Authors: Yi Feng , DeCan Evan , Stoll Kurt , Marceau Eric , Deisseroth Karl , Lawrence J. Josh 
Published: December 2014

SummaryObjectiveA common rodent model in epilepsy research employs the muscarinic acetylcholine receptor (mAChR) agonist pilocarpine, yet the mechanisms underlying the induction of pilocarpine‐induced seizures (PISs) remain unclear. Global M1 mAChR (M1R) knockout mice are resistant to PISs, implying that M1R activation disrupts excitation/inhibition balance. Parvalbumin‐positive (PV) inhibitory neurons express M1Rs, participate in cholinergically induced oscillations, and can enter a state of depolarization block (DB) during epileptiform activity. Here, we test the hypothesis that pilocarpine activation of M1Rs expressed on PV cells contributes to PISs.MethodsCA1 PV cells in PV‐CRE mice were visualized with a floxed YFP or hM3Dq‐mCherry adeno‐associated virus, or by crossing PV‐CRE mice with the RosaYFP reporter line. To eliminate M1Rs from PV cells, we generated PV‐M1knockout (KO) mice by crossing PV‐CRE and floxed M1 mice. Action potential (AP) frequency was monitored during application of pilocarpine (200 μm). In behavioral experiments, locomotion and seizure symptoms were recorded in wild‐type (WT) or PV‐M1KO mice during PISs.ResultsPilocarpine significantly increased AP frequency in CA1 PV cells into the gamma range. In the continued presence of pilocarpine, a subset (5/7) of PV cells progressed to DB, which was mimicked by hM3Dq activation of Gq‐receptor signaling. Pilocarpine‐induced depolarization, AP firing at gamma frequency, and progression to DB were prevented in CA1 PV cells of PV‐M1KO mice. Finally, compared to WT mice, PV‐M1KO mice were associated with reduced severity of PISs.SignificancePilocarpine can directly depolarize PV+ cells via M1R activation, but a subset of these cells progress to DB. Our electrophysiologic and behavioral results suggest that this mechanism is active during PISs, contributing to a collapse of PV‐mediated γ‐aminobutyric acid (GABA)ergic inhibition, dysregulation of excitation/inhibition balance, and increased susceptibility to PISs.
Abietic acid inhibits UVB‐induced MMP‐1 expression in human dermal fibroblast cells through PPARα/γ dual activation
Authors: Jeon Youngsic , Jung Yujung , Youm Jong‐Kyung , Kang Ki Sung , Kim Yong Kee , Kim Su‐Nam 
Published: December 2014

AbstractPeroxisome proliferator‐activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand‐activated transcription factors and consist of three isotypes: PPARα, PPARβ/δ and PPARγ. PPARs are expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, these receptors are highly studied in dermato‐endocrine research, and their ligands are targets for the treatment of various skin disorders, such as photoageing and chronological ageing of skin. Intensive studies have revealed that PPARα/γ functions in photoageing and age‐related inflammation by regulating matrix metalloproteinases (MMPs) via nuclear factor‐kappa B (NF‐κB) and activator protein‐1 (AP‐1). However, the detailed mechanism of PPARα/γ's role in photoageing has not yet been elucidated. In this study, we confirmed that abietic acid (AA) is a PPARα/γ dual ligand and significantly decreased UVB‐induced MMP‐1 expression by downregulating UVB‐induced MAPK signalling and downstream transcription factors, subsequently reducing IκBα degradation and blocking NF‐κB p65 nuclear translocation in Hs68 human dermal fibroblast cells. Treatment of cells with AA and GW6471 or bisphenol A diglycidyl ether (BADGE), PPARα or PPARγ antagonists, respectively, reversed the effect on UVB‐induced MMP‐1 expression and inflammatory signalling pathway activation. Taken together, our data suggest that AA acts as a PPARα/γ dual activator to inhibit UVB‐induced MMP‐1 expression and age‐related inflammation by suppressing NF‐κB and the MAPK/AP‐1 pathway and can be a useful agent for improving skin photoageing.
Frequent co‐inactivation of the SWI/SNF subunits SMARCB1, SMARCA2 and PBRM1 in malignant rhabdoid tumours
Authors: Rao Qiu , Xia Qiu‐yuan , Wang Zi‐yu , Li Li , Shen Qin , Shi Shan‐shan , Wang Xuan , Liu Biao , Wang Yan‐fen , Shi Qun‐li , Ma Heng‐hui , Lu Zhen‐feng , He Yan , Zhang Ru‐song , Yu Bo , Zhou Xiao‐jun 
Published: December 2014

AimsMalignant rhabdoid tumours (MRTs) are highly aggressive malignancies of early infancy characterized by inactivation of SMARCB1, a core member of the SWI/SNF chromatin‐remodelling complex. The aim of this study was to explore the status of multiple key subunits of the SWI/SNF complex in MRTs.Methods and resultsWe screened the key subunits of the SWI/SNF complex, including SMARCB1, SMARCA2, PBRM1, SMARCA4, and ARID1A, in four MRTs by immunohistochemistry, sequencing, and fluorescence in‐situ hybridization (FISH). Complete loss of SMARCB1, SMARCA2 and PBRM1 expression and corresponding mutations in the same genes were observed in all cases. The mutations included seven missense, three same‐sense, four frameshift and two truncating mutations. FISH revealed heterozygous deletion of SMARCB1 in one case, and monoploidy of chromosome 22, which harbours SMARCB1, in another case. Furthermore, trisomy of chromosome 9, which harbours SMARCA2, was observed in two cases. Abnormality of PBRM1 was not found in any case.ConclusionsWe report, for the first time, co‐inactivation and frequent mutations of SMARCB1, SMARCA2 and PBRM1 in MRTs. Multiple subunit abnormalities of the SWI/SNF complex potentially act together to contribute to the tumorigenesis of MRTs, which provides unique insights into this disease.
Stability of coagulation proteins in lyophilized plasma
Authors: Jennings I. , Kitchen D. P. , Woods T. A. L. , Kitchen S. , Preston F. E. , Walker I. D. 
Published: December 2014

SummaryIntroductionExternal quality assessment (EQA) is an important component of quality assurance for laboratory tests of haemostasis. Lyophilization of plasma confers stability of labile clotting factors, allowing valid comparison of results between participating centres. However, elevated ambient temperatures in some geographical areas could affect the stability of lyophilized samples in transit.MethodsThe effect on lyophilized plasma samples of consistent elevated temperature with respect to haemostasis tests was determined in a single centre. The temperature to which packages were exposed during transit was also monitored.ResultsSurvey packages were exposed to average temperatures up to 31.9 °C and maximum temperatures up to 39.7 °C over delivery periods between 1 and 8 weeks. In‐house studies revealed samples to be stable over a 6‐week period at a constant 30 °C, and only small changes were observed for samples exposed to 37 °C for 4 weeks. 6‐week storage at 37 °C was associated with average changes of up to 15% in factor assay activity.ConclusionLyophilized EQA material employed in UK NEQAS surveys is stable under conditions encountered for the majority of participants, but in cases of delayed delivery of samples, the effect of temperature on sample integrity must be considered when assessing laboratory performance.
Star CEOs or Political Connections? Evidence from China's Publicly Traded Firms
Authors: Conyon Martin J. , He Lerong , Zhou Xin 
Published: December 2014

AbstractThis paper studies China's “star CEOs” defined as members of the National People's Congress (NPC) or the National Committee of the Chinese People's Political Consultative Conference (CPPCC) and “politically connected” CEOs who have previous government or military experience. We evaluate the effect of “star CEOs” and “politically connected” CEOs on firm performance and CEO compensation. We find that announcement date returns, CEO compensation and incentives are all higher in firms that appoint “star CEOs”. However, the mechanism explaining these various premiums is largely political connectedness of these star CEOs. Our study finds only modest evidence that star‐CEO status directly determines firm performance. Our analysis strongly suggests that compensation and performance premiums are mostly driven by CEO political connections, as opposed to CEO talent/star effects.
Bergmann meets Scholander: geographical variation in body size and insulation in the koala is related to climate
Authors: Briscoe Natalie J. , Krockenberger Andrew , Handasyde Kathrine A. , Kearney Michael R. 
Published: December 2014

AbstractAimBody size often varies clinally, with dominant explanations centred on how body size influences heat exchange (e.g. Bergmann's rule). However, for endotherms, pelage properties can also dramatically alter heat exchange – a point emphasized by Scholander in the 1950s but which has received little attention in biogeographical analyses. Here, we investigate how geographical variation in both body size and fur properties of the koala (Phascolarctos cinereus) is related to climate.LocationEastern Australia.MethodsWe measured head length and fur depths of koala museum specimens from across its geographical range, and quantified the relationship between fur depth and insulation. We used linear regression and regression tree analyses to test for associations between morphological traits and climate variables relating to four hypotheses: heat conservation (Bergmann's rule), heat dissipation, fasting endurance/survival of extremes, and productivity.ResultsBoth body size and fur depth of koalas decrease substantially towards the tropics. Consistent with Scholander's view, fur properties showed stronger associations with climate than body size. Males, the larger sex, had shorter fur than females in hot environments but not in more temperate regions, suggesting that shorter fur compensates for sexual size dimorphism. While fur depth and male body size were more strongly associated with variables relating to heat dissipation, female body size was most strongly associated with minimum temperatures.Main conclusionsBody size interacts strongly with other traits, such as fur properties, to influence how animals experience climate. Our results emphasize how the consideration of geographical variation in suites of functionally related traits can provide important insight into how species persist across broad environmental gradients.