bluuebunny/crossref_metadata_2025_split huggingface dataset:
Institutional Change and Ethics Management in the EU's College of Commissioners
Authors: Cini Michelle 
Published: January 2013

Research Highlights and Abstract This article makes the following contribution: It identifies a gap in theoretical work on gradual institutional change by highlighting the importance of ‘reluctant agency’ that is, agents who do not oppose change outright, but are reluctant to agree to anything more than minimal reforms. It demonstrates the importance of the interplay of internal and external factors in explanations of gradual institutional change. It provides an empirical account of the evolution of the EU Commissioners' ethics regime since 1999. It identifies institutional change in the EU Commissioners' ethics regime as taking the form of a ‘layering’ process. It shows how institutional change in the EU Commissioners' ethics regime can be explained using a framework comprising political context, institutional characteristics and change agency (drawing on the work of Mahoney and Thelen). This article comprises a theory-informed case study of the European Commissioners' ethics regime. Conceptualising the evolution of the regime since 1999 as a process of gradual institutional change, it asks how the Commissioners' ethics regime continued to evolve incrementally after its inception, and what form that evolution took. Drawing on a recent theory of gradual institutional change (Mahoney and Thelen's), the article argues that the evolution of the Commissioners' ethics regime has involved a ‘layering’ process which has resulted from the Commission's changing position within the EU system (political context) and the extent of the Commission's control over the reform process (institutional characteristics). External change agents (the European Parliament and NGOs) are crucial, but so too is the Commission itself, which engages only reluctantly, in a risk-averse manner, in the on-going reform of the regime.
Predictive value of combined cervicovaginal cytokines and gestational age at sampling for intra‐amniotic infection in preterm premature rupture of membranes
Authors: Ryu Aeli , Park Kyo Hoon , Oh Kyung Joon , Lee Sung Youn , Jeong Eun Ha , Park Jeong Woo 
Published: January 2013

AbstractObjectiveTo determine whether interleukin (IL)‐1β, IL‐6, and IL‐8 in cervicovaginal fluid, alone or in combination with clinical risk factors, could predict intra‐amniotic infection in women with preterm premature rupture of membranes (PPROM).DesignA prospective cohort study.SettingUniversity teaching hospital.PopulationWomen with singleton pregnancies presenting PPROM between 20 and 35 weeks of gestation (n = 76).MethodsCervicovaginal fluid samples were collected for IL‐1β, IL‐6, and IL‐8 measurements immediately before amniocentesis. Amniotic fluid obtained by amniocentesis was cultured and the white blood cell count was determined. Clinical risk factors analyzed included demographics and gestational age. Cervicovaginal concentrations of cytokines were measured using a multiplex bead array assay.Main outcome measureA positive amniotic fluid culture.ResultsThe prevalence of a positive amniotic fluid culture was 46.1% (35/76). Stepwise multivariate regression analysis yielded a model using cervicovaginal IL‐6 and gestational age at sampling with the area under the curve (AUC) of 0.807 for predicting intra‐amniotic infection. The AUC for this model was significantly higher than either parameter retained in this model but no differences were observed between the AUC of this model based on non‐invasive variables, and amniotic fluid white blood cell count using invasive amniocentesis for the prediction of intra‐amniotic infection.ConclusionsAmong measured cytokines, the combination of cervicovaginal IL‐6 and gestational age appears to be best in predicting intra‐amniotic infection and allows for a considerably better accuracy than the use of either factor alone. Overall, this combination performed as well as amniotic fluid WBC count for predicting intra‐amniotic infection.
Important surgical measures and techniques at cesarean hysterectomy for placenta previa accreta
Authors: Matsubara Shigeki , Kuwata Tomoyuki , Usui Rie , Watanabe Takashi , Izumi Akio , Ohkuchi Akihide , Suzuki Mitsuaki , Nakata Manabu 
Published: January 2013

AbstractFor cesarean hysterectomy with placenta previa accreta, “universally achievable” measures are required. We propose eight measures: (i) placement of intra‐iliac arterial occlusion balloon catheters; (ii) placement of ureter stents; (iii) “holding the cervix” to identify the site to be transected; (iv) uterine fundal incision; (v) avoidance of uterotonics; (vi) “M cross double ligation” for ligating the ovarian ligament; (vii) “filling the bladder” to identify the bladder separation site and “opening the bladder” for placenta previa accreta with bladder invasion; and (viii) to continue to clamp the medial side of the parametrium or the cervix or employment of the “double edge pick‐up” to ligate it. These eight measures are simple, easy, effective, and thus “universally achievable”.
Stable purse‐string suturing using an anterior esophagotomy for reconstruction with a circular stapler during laparoscopic total gastrectomy
Authors: Kong Seong‐Ho , Suh Yunsuhk , Kwon Sebastianus , Lee Hyuk‐Joon , Kim Hyung‐Ho , Yang Han‐Kwang 
Published: January 2013

AbstractIntroductionDuring a laparoscopic total gastrectomy, the combined process of purse‐string suture placement and anvil insertion of a circular stapler is one of the most difficult steps in the reconstruction. We have developed a stable and reliable technique in which purse‐string suture placement and anvil insertion using anterior esophagotomy precede complete transection of the esophagus.MethodsThe procedure involves tying the distal esophagus, insufflating the esophagus via a nasogastric tube, anterior wall purse‐string suture, anterior esophagotomy, posterior wall purse‐string suture, anvil insertion, fastening purse‐string suture, and transecting the esophagus. The technique has been employed in nine patients since April 2011.ResultsEight of the nine gastrectomies were for patients with stage IA early gastric cancer and one was for a patient with medically intractable bleeding from multiple polyps. Three were men and six were women. Average BMI was 25.2 ± 5.3 (range, 16.3–33.9). Mean operation time was 276.2 ± 56.3 min (range, 215.0–395.0 min) and the mean duration for anvil insertion was 29.8 ± 7.0 min (range, 23.0–46.0 min). There were no intraoperative or postoperative anastomosis‐related complications or mortality.ConclusionOur method of anvil insertion of a circular stapler can be a good option for safe and reliable esophagojejunostomy during a laparoscopic total gastrectomy.
Clinical outcomes of laparoscopic surgery for transverse and descending colon cancers in a community setting
Authors: Matsuda Takeru , Fujita Hirofumi , Kunimoto Yukihiro , Kimura Taisei , Hayashi Tomomi , Maeda Toshiyuki , Yamakawa Junichi , Mizumoto Takuya , Ogino Kazunori 
Published: January 2013

AbstractIntroductionThe feasibility, safety and oncological outcomes of laparoscopic surgery for transverse and descending colon cancers in a community hospital setting were evaluated.MethodsTwenty‐six patients with transverse or descending colon cancers who underwent laparoscopic surgery at our hospital were included in this retrospective analysis (group A). Their outcomes were compared with those of 71 patients who underwent laparoscopic surgery for colon cancer at other tumor sites (group B).ResultsThere were no significant differences between the two groups in terms of operative time, estimated blood loss, postoperative hospital stay and morbidity rate. Extended lymphadenectomy was performed more frequently and the number of harvested lymph nodes was significantly higher in group B than in group A. However, no recurrence developed in group A, while recurrence occurred in four patients from group B. The 3‐year disease‐free survival rates were 100% for group A and 93.5% for group B. The 3‐year overall survival rates were 100% for group A and 91.6% for group B.ConclusionsLaparoscopic surgery for transverse and descending colon cancers can be performed safely with oncological validity in a community hospital setting, provided there is careful selection of the patients and adequate lymphadenectomy considering the clinical stage of their disease.
Predicted heart rate effect of inhaled PF‐00610355, a long acting β‐adrenoceptor agonist, in volunteers and patients with chronic obstructive pulmonary disease
Authors: Diderichsen Paul Matthias , Cox Eugène , Martin Steven W. , Cleton Adriaan , Ribbing Jakob 
Published: January 2013

AimTo assess the cardiovascular effects of a new inhaled long‐acting β‐adrenoceptor agonist PF‐00610355 in COPD patients.MethodsThirteen thousand and sixty‐two heart rate measurements collected in 10 clinical studies from 579 healthy volunteers, asthma and COPD patients were analyzed. The relationship between heart rate profiles and predicted plasma concentration profiles, patient status, demographics and concomitant medication was evaluated using non‐linear mixed‐effects models. The median heart rate increase in COPD patients for doses of PF‐00610355 up to 280 μg once daily was simulated with the final pharmacokinetic/pharmacodynamic (PKPD) model.ResultsAn Emax model accounting for delayed on‐and off‐set of the PF‐00610355‐induced change in heart rate was developed. The predicted potency in COPD patients was three‐fold lower compared with healthy volunteers, while no difference in maximum drug effect was identified. Simulations suggested a maximum placebo‐corrected increase of 2.7 (0.90–4.82) beats min−1 in COPD patients for a PF‐00610355 dose of 280 μg once daily, with 19% subjects experiencing a heart rate increase of more than 20 beats min−1 compared with 8% in the placebo group.ConclusionsThis PKPD analysis supports the clinical observation that no relevant effects of PF‐00610355 on heart rate in COPD patients should be expected for doses up to 280 μg once daily.
Dendritic cells phenotype fitting under hypoxia or lipopolysaccharide; adenosine 5′-triphosphate-binding cassette transporters far beyond an efflux pump
Authors: Lloberas N , Rama I , Llaudó I , Torras J , Cerezo G , Cassis L , Franquesa M , Merino A , Benitez-Ribas D , Cruzado J M , Herrero-Fresneda I , Bestard O , Grinyó J M 
Published: January 2013

SummaryThis study examines adenosine 5′-triphosphate-binding cassette (ABC) transporters as a potential therapeutic target in dendritic cell (DC) modulation under hypoxia and lipopolysaccharide (LPS). Functional capacity of dendritic cells (DCs) (mixed lymphocyte reaction: MLR) and maturation of iDCs were evaluated in the presence or absence of specific ABC-transporter inhibitors. Monocyte-derived DCs were cultured in the presence of interleukin (IL)-4/granulocyte–macrophage colony-stimulating factor (GM-CSF). Their maturation under hypoxia or LPS conditions was evaluated by assessing the expression of maturation phenotypes using flow cytometry. The effect of ABC transporters on DC maturation was determined using specific inhibitors for multi-drug resistance (MDR1) and multi-drug resistance proteins (MRPs). Depending on their maturation status to elicit T cell alloresponses, the functional capacity of DCs was studied by MLR. Mature DCs showed higher P-glycoprotein (Pgp) expression with confocal microscopy. Up-regulation of maturation markers was observed in hypoxia and LPS-DC, defining two different DC subpopulation profiles, plasmacytoid versus conventional-like, respectively, and different cytokine release T helper type 2 (Th2) versus Th1, depending on the stimuli. Furthermore, hypoxia-DCs induced more B lymphocyte proliferation than control-iDC (56% versus 9%), while LPS-DCs induced more CD8-lymphocyte proliferation (67% versus 16%). ABC transporter-inhibitors strongly abrogated DC maturation [half maximal inhibitory concentration (IC50): P-glycoprotein inhibition using valspodar (PSC833) 5 μM, CAS 115104-28-4 (MK571) 50 μM and probenecid 2·5 μM], induced significantly less lymphocyte proliferation and reduced cytokine release compared with stimulated-DCs without inhibitors. We conclude that diverse stimuli, hypoxia or LPS induce different profiles in the maturation and functionality of DC. Pgp appears to play a role in these DC events. Thus, ABC-transporters emerge as potential targets in immunosuppressive therapies interfering with DCs maturation, thereby abrogating innate immune response when it is activated after ischaemia.
Inhibition of Pref‐1 (preadipocyte factor 1) by oestradiol in adolescent girls with anorexia nervosa is associated with improvement in lumbar bone mineral density
Authors: Faje Alexander T. , Fazeli Pouneh K. , Katzman Debra , Miller Karen K. , Breggia Anne , Rosen Clifford J. , Mendes Nara , Misra Madhusmita , Klibanski Anne 
Published: January 2013

AbstractObjectiveAdolescents with anorexia nervosa (AN) are amenorrheic and have decreased bone mass accrual and low bone mineral density (BMD). The regulation of mesenchymal stem cell differentiation is an important factor governing bone formation. Preadipocyte factor 1 (Pref‐1), an inhibitor of adipocyte and osteoblast differentiation, is elevated in states of oestrogen deficiency. In this study, we aim to (i) investigate effects of transdermal oestradiol on Pref‐1 in adolescent girls with AN, and (ii) examine associations of changes in Pref‐1 with changes in lumbar BMD and bone turnover markers.DesignAdolescent girls with AN and normal‐weight controls were studied cross‐sectionally. Girls with AN were examined longitudinally in a double‐blind study and received transdermal oestradiol (plus cyclic medroxyprogesterone) or placebo for 12 months.PatientsSixty‐nine girls (44 with AN, 25 normal‐weight controls) 13–18 years were studied at baseline; 22 AN girls were followed prospectively.MeasurementsPref‐1 levels, bone formation and resorption markers, and BMD.ResultsPref‐1 levels decreased in girls with AN after treatment with transdermal oestradiol compared with placebo (−0·015 ± 0·016 vs 0·060±0·026 ng/ml, P = 0·01), although at baseline, levels did not differ in AN vs controls (0·246 ± 0·015 vs 0·267 ± 0·022 ng/ml). Changes in Pref‐1 over 12 months correlated inversely with changes in lumbar BMD (r = −0·48, P = 0·02) and positively with changes in CTX (r = 0·73, P = 0·006).ConclusionsFor the first time, we show that Pref‐1 is negatively regulated by oestradiol in adolescent girls with AN. Inhibition of Pref‐1 may mediate the beneficial effects of transdermal oestradiol replacement on BMD in girls with AN.
Does differential response make a difference: examining domestic violence cases in child protection services
Authors: Alaggia Ramona , Gadalla Tahany M. , Shlonsky Aron , Jenney Angelique , Daciuk Joanne 
Published: January 2013

AbstractLarge numbers of domestic violence (DV) cases on child protection caseloads have necessitated the development of practices that address both DV and child safety. The first step in this process is to gain an understanding of the differences between DV‐involved cases and other forms of maltreatment. The implementation of a differential response service model in Ontario offered an opportunity to compare risk assessment ratings, service outcomes and recurrence and to identify pathways of DV cases through child protection services (CPS). A sample (n = 785) of child protection investigations over a 4‐month period was examined. Of these investigations, 26% cases were DV referred; 87% of the DV victims were mothers; perpetrating partners were mostly absent from investigations; non‐white families were more often investigated for DV than white families; and DV cases were more likely to remain open for ongoing CPS. Only one‐third of DV‐exposed children were assessed as having been harmed and most community referrals were made for the victim parent. Mothers were the primary target of investigation, remaining in CPS for extended service provision although recurrence rates were lower than found in other investigations. Results are discussed to inform investigative procedures, assessment and service response to more adequately respond to children and families when DV is present.
The use of local anaesthesia in haemorrhoidal banding: a randomized controlled trial
Authors: Kwok H. C. K. , Noblett S. E. , Murray N. E. A. , Merrie A. E. H. , Hayes J. L. , Bissett I. P. 
Published: January 2013

AbstractAimRubber band ligation is a common office procedure for the treatment of symptomatic haemorrhoids. It can be associated with pain and vasovagal symptoms. The effect of local anaesthetic use during banding was studied.MethodA single‐blinded randomized controlled trial was carried out in the colorectal outpatient clinic. Patients presenting with symptomatic haemorrhoids suitable for banding were prospectively recruited and randomized to undergo the procedure with local anaesthetic or without (control). Submucosal bupivacaine was injected immediately after banding just proximal to the site. Vasovagal symptoms were assessed at the time of banding and pain scores (visual analogue scale) were recorded at the conclusion of the procedure, after 15 min, and on leaving the clinic.ResultsSeventy‐two patients (40 local anaesthetic injection, group 1; 32 no injection, group 2) were recruited. The mean ages were 50 and 54 years respectively, the median duration of symptoms was 12 months in each group and the median number of haemorrhoids banded was three in each group. The mean pain score on leaving the clinic was 2.6 (95% CI 2.1, 3.1) in group 1 and 4.1 (95% CI 3.3, 5.0) (P = 0.04) in group 2. There were no complications related to local anaesthetic use. No significant difference in vasovagal symptoms was found (P = 0.832).ConclusionLocal anaesthetic injection at the time of banding is simple and safe. It may reduce patient discomfort following banding of haemorrhoids.
Conformational changes of recombinant Ca2+–ATPase studied by reaction‐induced infrared difference spectroscopy
Authors: Kumar Saroj , Li Chenge , Montigny Cédric , le Maire Marc , Barth Andreas 
Published: January 2013

Recombinant Ca2+–ATPase was expressed in Saccharomyces cerevisiae with a biotin‐acceptor domain linked to its C–terminus by a thrombin cleavage site. We obtained 200 μg of ~ 70% pure recombinant sarcoendoplasmic reticulum Ca2+–ATPase isoform 1a (SERCA1a) from a 6–L yeast culture. The catalytic cycle of SERCA1a was followed in real time using rapid scan FTIR spectroscopy. Different intermediate states (Ca2E1P and Ca2E2P) of the recombinant protein were accumulated using different buffer compositions. The difference spectra of their formation from Ca2E1 had the same spectral features as those from the native rabbit SERCA1a. The enzyme‐specific activity for the active enzyme fraction in both samples was also similar. The results show that the recombinant protein obtained from the yeast‐based expression system has similar structural and dynamic properties as native rabbit SERCA1a. It is now possible to apply this expression system together with IR spectroscopy to the investigation of the role of individual amino acids.
Synergistic effects of antibodies against high‐mobility group box 1 and tumor necrosis factor‐α antibodies on d‐(+)‐galactosamine hydrochloride/lipopolysaccharide‐induced acute liver failure
Authors: Wang Wei , Sun Li , Deng Yonghao , Tang Jie 
Published: January 2013

High‐mobility group box 1 (HMGB1) protein is released into the serum after tissue damage, and serves as a warning signal to enhance the inflammatory response. Acute liver injury is one of the diseases that starts with tissue damage and ends with systemic inflammation. We used d‐(+)‐galactosamine hydrochloride (d‐GalN)/lipopolysaccharide (LPS)‐treated mice as an acute liver injury model to explore the functions of HMGB1 in more detail. HMGB1 is released into the serum at a very early stage of d‐GalN/LPS‐induced acute liver injury. It upregulates the expression of tumor necrosis factor‐α (TNF‐α), interleukin‐6, inducible nitric oxide synthase, and tissue factor. TNF‐α and HMGB1 form a positive feedback loop to amplify the downstream signals. mAbs against HMGB1 and TNF‐α have synergistic effects in protecting mice from d‐GalN/LPS‐induced acute liver failure. The results suggest that HMGB1 is a key mediator in d‐GalN/LPS‐induced acute liver injury. Tissue damage and cell necrosis shortly after administration of d‐GalN and LPS lead to early HMGB1 release, and HMGB1 acts synergistically with TNF‐α to promote pathological processes in acute liver failure.
Identification of a highly reactive substrate peptide for transglutaminase 6 and its use in detecting transglutaminase activity in the skin epidermis
Authors: Fukui Mina , Kuramoto Katsuma , Yamasaki Risa , Shimizu Yoshitaka , Itoh Miho , Kawamoto Tadafumi , Hitomi Kiyotaka 
Published: January 2013

Mammalian transglutaminases (TGs) are a family of enzymes that catalyze the formation of covalent crosslinks between glutamine and lysine residues in proteins. These catalytic reactions play roles in several essential biological processes, including blood coagulation, skin formation, and stabilization of the extracellular matrix. Among the members of this family, factor XIII and TGs 1–5 have been characterized well, but very little is known about the novel members TG6 and TG7. Recently, however, autoantibodies against TG6 were found in a patient with gluten ataxia, a disease caused by enzymatically modified gluten‐derived peptides in neuronal cells. To characterize the possible physiological functions of TG6, in this study we screened a phage‐displayed random peptide library to find highly reactive glutamine donor substrate peptides. From several candidate peptides, one sequence, designated Y25, appeared to have the highest reactivity. The Y25 sequence also has apparent isozyme specificity when evaluated by incorporation of the labeled glutamine acceptor substrate as a fusion protein with glutathione‐S‐transferase. Also, the sequence retained high reactivity as well as the isozyme specificity in the peptide form. Analyses with the biotin‐labeled and fluorescence‐labeled peptides showed TG6 to be an active enzyme and react to specific substrates in the skin, which is consistent with the results of the expression pattern of its transcripts.