bluuebunny/crossref_metadata_2025 huggingface dataset:
Closed-list proportional representation in Russia
Authors: Moraski Bryon
Published: January 2013

This work considers how a ruling party in an increasingly authoritarian regime utilizes legislative electoral system changes. It argues that the placement of former district deputies on the list of Russia’s ruling party after the move to a PR-only system reflected an interest in expanding its presence in the countryside as well as the attractiveness of the ruling party to the former district deputies themselves. It submits that both the party’s willingness to place former district deputies on its list and the willingness of the deputies to accept positions should vary by previous party affiliations, yielding predictable patterns in the aggregate. In terms of list ranking, it finds that the ruling party’s district deputies received significantly better placement than previously independent deputies, but not better placement than district deputies who made the list but had competed under a different party label in the previous election.
Deliberative research as a tool to make value judgements
Authors: Burchardt Tania
Published: January 2013

The purpose of deliberation as a research technique (as opposed to policymaking or public consultation) is distinctive: to uncover the public’s informed, considered and collective view on a normative question. Such questions often arise in relation to research on poverty and inequality, where there is a need to justify the thresholds and concepts adopted on a deeper basis than convention alone can offer. But can deliberative research provide the answer, and if so in what circumstances? By comparing deliberative research to more traditional methods, such as in-depth interviewing, attitudinal surveys, ethnography and participatory approaches, this article reveals that deliberative designs involve a number of assumptions, including a strong fact/value distinction, an emphasis on ‘outsider’ expertise and a view of participants as essentially similar to each other rather than defined by socio-demographic differences. Using an example of deliberative research in which the author was involved, developing a list of ‘capabilities’ for monitoring inequalities in Britain, it also demonstrates that normative decisions permeate the design and implementation of deliberative research in practice. Thus, while deliberative research has the potential to provide uniquely considered, insightful and well-justified answers to the problem of defining a collective position on key questions in social science, it is currently under-theorised as an approach, and transparency at all stages of the process is essential to avoid the charge of simply reflecting the researchers’ implicit values.
Controllable pitch propeller actuating mechanism, modelling and simulation
Authors: Martelli Michele , Figari Massimo , Altosole Marco , Vignolo Stefano
Published: January 2013

This article focuses on the mathematical model of the pitch control mechanism for a marine controllable pitch propeller, with the aim of describing the dynamic behaviour of this kind of system and its influence on ship performance. Too great a load on the blades can result in high pressures in the actuating system, response delays and control system problems, which are ultimately responsible for most mechanism failures. The behaviour of the controllable pitch propeller actuating mechanism is considered in terms of blade position, oil pressures inside the controllable pitch propeller hub and magnitudes of the forces acting on the blades. In the proposed mathematical model, the forces acting on the propeller blade are evaluated taking into account the yaw motion of the ship, the propeller speed (including shaft accelerations and decelerations) and the turning of the blade during the pitch change. On the basis of the introduced procedure, a controllable pitch propeller numerical model as part of an overall propulsion and manoeuvrability simulator representing the dynamic behaviour of a twin-screw fast vessel is developed. The aim of this work is to represent the ship propulsion dynamics through time-domain simulation, based on which the designers can develop and test several design options, in order to avoid possible machinery overloads with their consequent failures and to obtain the best possible ship performances. In this aspect, the controllable pitch propeller model is an essential design tool.
Lessons Learned From the Implementation of a Time-Limited, Large-Scale Nicotine Replacement Therapy Giveaway Program in New York City
Authors: Davis Karen A. , Coady Micaela H. , Mbamalu Ijeoma G. , Sacks Rachel , Kilgore Elizabeth A.
Published: January 2013

Since 2006, the New York City (NYC) Department of Health and Mental Hygiene has conducted the Nicotine Patch and Gum Program (NPGP) in collaboration with 311, NYC’s non-emergency information line. In two prior years, the program was conducted in collaboration with the New York State (NYS) Smokers’ Quitline and with community-based organizations. The NPGP is an annual, brief, population-based nicotine replacement therapy (NRT) giveaway for NYC residents, complementing the NYS Quitline’s year-round NRT distribution program. Since 2006, 168,000 smokers have enrolled, with the largest number of enrollees in 2010 (n = 40,000) and the smallest number in 2009 (n = 28,000). A 2003 program evaluation demonstrated that smokers who received NRT through the NPGP had higher quit rates than smokers who did not receive NRT; these results were replicated in 2006 and 2008. Lessons learned from implementing the NPGP include: 1) time-limited NRT interventions are important complements to year-round NRT distribution; 2) expanding NRT distribution to light smokers increases treatment reach; and 3) employing multiple enrollment mechanisms, including telephone and online options, extends program reach to diverse groups of smokers. The NPGP provides a model for other jurisdictions considering implementing time-limited, population-based NRT programs as a complementary strategy to enhance ongoing tobacco control efforts.
Cognitive-Behavioral Therapy for an Indian Adolescent With Depression
Authors: Sondhi Roshni , Gulgulia Shagun , Shriharsh Vandana
Published: January 2013

This case study describes the treatment of an adolescent male, referred to as ML, who presented with a significant decline in academic performance coupled with a difficulty in coping with parental pressure. A formal assessment revealed the signs of moderate depression with anxiety features, especially on the dimensions of tension and guilt proneness. He was treated with 12 sessions of cognitive-behavioral therapy (CBT) along with group sessions of family therapy and interpersonal therapy. ML’s progress throughout treatment is detailed in this case study report. Results lend support to the body of case series studies attesting to the efficacy of CBT for use with adolescents with depression and anxiety, further implicating the importance of the role played by the parents in the conceptualization, maintenance, as well as treatment of the adolescent.
Intravascular Ultrasound-Guided Inferior Vena Cava Filter Placement Using a Single-Puncture Technique in 99 Patients
Authors: Gunn Andrew J. , Iqbal Shams I. , Kalva Sanjeeva P. , Walker T. Gregory , Ganguli Suvranu , Salazar Gloria M. , Oklu Rahmi , Wicky Stephan
Published: January 2013

Purpose:

To assess the feasibility and safety of intravascular ultrasound (IVUS) to guide inferior vena cava (IVC) filter placement using a single venous puncture technique.

Materials and Methods:

Medical records of all patients who had IVC filters placed under IVUS guidance between January 1, 2005 and December 31, 2011 were retrospectively reviewed for pertinent history, results, and complications. All filters were placed using a single venous puncture technique.

Results:

Filters were successfully placed within the IVC in 94% of the patients with 6 malpositioned filters (4 in the iliac veins and 2 in the suprarenal IVC). Complications included groin hematoma (4%), deep venous thrombosis at the site of vascular access (2%), and filter tilt >15° along the long axis of the IVC (2%).

Conclusions:

The IVUS-guided IVC filter placement using a single venous puncture technique is technically feasible and safe when compared to case series using a double venous puncture technique.
A Proposed Workshop Curriculum for Students to Responsibly Engage Cultural Conflict in Community-Based Service Learning
Authors: Tharp D. Scott
Published: January 2013

Service-learning opportunities provide interactive experiences between diverse communities and students in order to achieve, among various goals, thoughtful learning about issues of cultural inequality and social power. Service learning has notable benefits for those who participate along with legitimate concerns about the risk of these experiences reinforcing problematic attitudes and behaviors related to systems of dominance and subordination. Given the popularity of service-learning initiatives within higher education, the literature regarding diversity and service learning is reviewed to offer a pilot workshop curriculum that addresses common gaps through intentional focus on social forces that perpetuate inequality, introspection on social location, and skills for identifying and addressing cultural conflict utilizing both transformative education and diversity education best practices. Assessment of the pilot workshop curriculum showed statistically significant growth related to awareness of culturally based values, cultural reflection, and imposition of values onto others.
Early Outcomes of Darunavir- and/or Raltegravir-Based Antiretroviral Therapy in Children with Multidrug-Resistant HIV at a Pediatric Center in Botswana
Authors: Kirk Brianna L. , Gomila Andres , Matshaba Mogomotsi , Marape Marape , Joel Dipesalema R. , Anabwani Gabriel , Tolle Michael A.
Published: January 2013

Background:

Data on the use of ritonavir-boosted darunavir (DRV/r) and/or raltegravir (RAL) in resource-limited settings are rare and there is currently no published data regarding their use among African children. Botswana has recently made DRV/r and RAL available for patients failing second-line antiretroviral therapy (ART).

Methods:

Retrospective chart review of 4 multidrug-resistant pediatric patients on DRV/r- and/or RAL-based regimens. Viral load, CD4 count, adherence by pill count, and World Health Organization (WHO) clinical stage prior to and after switch to DRV/r- and/or RAL-based regimen were assessed. Antiretroviral therapy history, duration of virologic failure, and time to viral suppression were also noted. Genotypic resistance assays reviewed for mutations present prior to switch.

Results:

All patients achieved viral suppression, showed improved/stable CD4 counts, and obtained or maintained WHO clinical treatment stage I, even after long-standing virologic/immunologic failure.

Conclusions:

Well tolerated by and effective in our patients, DRV/r and RAL provide potentially lifesaving ART options for children and adolescents in resource-limited settings failing ART due to ritonavir-boosted lopinavir (LPV/r) resistance.
The Making and Re-making of Winsor McCay’s Gertie (1914)
Authors: Nathan David L , Crafton Donald
Published: January 2013

In addition to creating legendary comics like Little Nemo in Slumberland, Winsor McCay was a pioneer of animation. His Gertie (1914) was the first American masterpiece of animated film. Two versions are known to have existed: the original in which McCay appeared on the vaudeville stage with an animated dinosaur named Gertie projected on screen, and a later one that contained a live-action prologue and epilogue filmed and distributed by William Fox’s Box Office Attractions Company. The Fox version is still extant as original nitrate prints, but McCay’s vaudeville version was lost. However, an examination of 334 of McCay’s original drawings reveals that near the end of the vaudeville version there was a ‘Curtain Call’ sequence not included in the Fox version. Fifteen drawings from the lost segment allowed its reconstruction by the Gertie Project applying digital technology. The authors have dated Gertie’s vaudeville chronology more precisely and have demonstrated McCay’s animation techniques, including his ‘split system’, by decoding his original annotations. The authors examine the filmmaker’s claim that he had made 10,000 drawings for Gertie. The resulting historic analysis of a milestone in silent film animation discusses the artistic mastery of Winsor McCay, issues of historical authenticity, and the archival implications of digital reconstruction.
Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia
Authors: Musallam Khaled M. , Taher Ali T. , Cappellini Maria Domenica , Sankaran Vijay G.
Published: January 2013

Recent molecular studies of fetal hemoglobin (HbF) regulation have reinvigorated the field and shown promise for the development of clinical HbF inducers to be used in patients with β-thalassemia and sickle cell disease. However, while numerous promising inducers of HbF have been studied in the past in β-thalassemia patient populations, with limited success in some cases, no universally effective agents have been found. Here we examine the clinical studies of such inducers in an attempt to systematically review the field. We examine trials of agents, including 5-azacytidine, hydroxyurea, and short-chain fatty acids. This review highlights the heterogeneity of clinical studies done on these agents, including both the patient populations examined and the study end points. By examining the published studies of these agents, we hope to provide a resource that will be valuable for the design of future studies of HbF inducers in β-thalassemia patient populations.
Fine and coarse particulate air pollution in relation to respiratory health in Sweden
Authors: Willers Saskia M. , Eriksson Charlotta , Gidhagen Lars , Nilsson Mats E. , Pershagen Göran , Bellander Tom
Published: January 2013

Health effects have repeatedly been associated with residential levels of air pollution. However, it is difficult to disentangle effects of long-term exposure to locally generated and long-range transported pollutants, as well as to exhaust emissions and wear particles from road traffic. We aimed to investigate effects of exposure to particulate matter fractions on respiratory health in the Swedish adult population, using an integrated assessment of sources at different geographical scales.

The study was based on a nationwide environmental health survey performed in 2007, including 25 851 adults aged 18–80 years. Individual exposure to particulate matter at residential addresses was estimated by dispersion modelling of regional, urban and local sources. Associations between different size fractions or source categories and respiratory outcomes were analysed using multiple logistic regression, adjusting for individual and contextual confounding.

Exposure to locally generated wear particles showed associations for blocked nose or hay fever, chest tightness or cough, and restricted activity days with odds ratios of 1.5–2 per 10-μg·m−3increase. Associations were also seen for locally generated combustion particles, which disappeared following adjustment for exposure to wear particles.

In conclusion, our data indicate that long-term exposure to locally generated road wear particles increases the risk of respiratory symptoms in adults.
Thenar oxygen saturation during weaning from mechanical ventilation: an observational study
Authors: Gruartmoner Guillem , Mesquida Jaume , Masip Jordi , Martínez Maria L. , Villagra Ana , Baigorri Francisco , Pinsky Michael R. , Artigas Antonio
Published: January 2013

Our aim was to determine whether thenar tissue oxygen saturation (StO2), measured by noninvasive near-infrared spectroscopy, and its changes derived from an ischaemic challenge are associated with weaning outcome.

Our study comprised a prospective observational study in a 26-bed medical–surgical intensive care unit. Patients receiving mechanical ventilation for >48 h, and considered ready to wean by their physicians underwent a 30-min weaning trial.StO2was measured continuously on the thenar eminence. A transient vascular occlusion test was performed prior to and at the end of the 30-min weaning trial, in order to obtainStO2deoxygenation and reoxygenation rates, and estimated local oxygen consumption.

37 patients were studied. Patients were classified as weaning success (n=24) or weaning failure (n=13). No significant demographic, respiratory or haemodynamic differences were observed between the groups at inclusion. Patients who failed the overall weaning process showed a significant increase in deoxygenation and in local oxygen consumption from baseline to 30 min of weaning trial, whereas no significant changes were observed in the weaning success group.

Failure to wean from mechanical ventilation was associated with higher relative increases in deoxygenation after 30 min of spontaneous ventilation.
Impact of bronchiectasis and trapped air on quality of life and exacerbations in cystic fibrosis
Authors: Tepper Leonie A. , Utens Elisabeth M.W.J. , Caudri Daan , Bos Aukje C. , Gonzalez-Graniel Karla , Duivenvoorden Hugo J. , van der Wiel Els C.W. , Quittner Alexandra L. , Tiddens Harm A.W.M.
Published: January 2013

Cystic fibrosis (CF) is primarily characterised by bronchiectasis and trapped air on chest computed tomography (CT). The revised Cystic Fibrosis Questionnaire respiratory symptoms scale (CFQ-R RSS) measures health-related quality of life.

To validate bronchiectasis, trapped air and CFQ-R RSS as outcome measures, we investigated correlations and predictive values for pulmonary exacerbations. CF patients (aged 6–20 years) underwent CT, CFQ-R RSS and 1-year follow-up. Bronchiectasis and trapped air were scored using the CF-CT scoring system. Correlation coefficients and backward multivariate modelling were used to identify predictors of pulmonary exacerbations.

40 children and 32 adolescents were included. CF-CT bronchiectasis (r = -0.38, p<0.001) and CF-CT trapped air (r = -0.35, p = 0.003) correlated with CFQ-R RSS. Pulmonary exacerbations were associated with: bronchiectasis (rate ratio 1.10, 95% CI 1.02–1.19; p = 0.009), trapped air (rate ratio 1.02, 95% CI 1.00–1.05; p = 0.034) and CFQ-R RSS (rate ratio 0.95, 95% CI 0.91–0.98; p = 0.002). The CFQ-R RSS was an independent predictor of pulmonary exacerbations (rate ratio 0.96, 95% CI 0.94–0.97; p<0.001).

Bronchiectasis, trapped air and CFQ-R RSS were associated with pulmonary exacerbations. The CFQ-R RSS was an independent predictor. This study further validated bronchiectasis, trapped air and CFQ-R RSS as outcome measures in CF.
Species richness, distribution and genetic diversity of Caenorhabditis nematodes in a remote tropical rainforest
Authors: Félix Marie-Anne , Jovelin Richard , Ferrari Céline , Han Shery , Cho Young Ran , Andersen Erik C , Cutter Asher D , Braendle Christian
Published: January 2013

Background

In stark contrast to the wealth of detail about C. elegans developmental biology and molecular genetics, biologists lack basic data for understanding the abundance and distribution of Caenorhabditis species in natural areas that are unperturbed by human influence.

Methods

Here we report the analysis of dense sampling from a small, remote site in the Amazonian rain forest of the Nouragues Natural Reserve in French Guiana.

Results

Sampling of rotting fruits and flowers revealed proliferating populations of Caenorhabditis, with up to three different species co-occurring within a single substrate sample, indicating remarkable overlap of local microhabitats. We isolated six species, representing the highest local species richness for Caenorhabditis encountered to date, including both tropically cosmopolitan and geographically restricted species not previously isolated elsewhere. We also documented the structure of within-species molecular diversity at multiple spatial scales, focusing on 57 C. briggsae isolates from French Guiana. Two distinct genetic subgroups co-occur even within a single fruit. However, the structure of C. briggsae population genetic diversity in French Guiana does not result from strong local patterning but instead presents a microcosm of global patterns of differentiation. We further integrate our observations with new data from nearly 50 additional recently collected C. briggsae isolates from both tropical and temperate regions of the world to re-evaluate local and global patterns of intraspecific diversity, providing the most comprehensive analysis to date for C. briggsae population structure across multiple spatial scales.

Conclusions

The abundance and species richness of Caenorhabditis nematodes is high in a Neotropical rainforest habitat that is subject to minimal human interference. Microhabitat preferences overlap for different local species, although global distributions include both cosmopolitan and geographically restricted groups. Local samples for the cosmopolitan C. briggsae mirror its pan-tropical patterns of intraspecific polymorphism. It remains an important challenge to decipher what drives Caenorhabditis distributions and diversity within and between species.
Ammonia production by human faecal bacteria, and the enumeration, isolation and characterization of bacteria capable of growth on peptides and amino acids
Authors: Richardson Anthony J , McKain Nest , Wallace R John
Published: January 2013

Background

The products of protein breakdown in the human colon are considered to be detrimental to gut health. Amino acid catabolism leads to the formation of sulfides, phenolic compounds and amines, which are inflammatory and/or precursors to the formation of carcinogens, including N-nitroso compounds. The aim of this study was to investigate the kinetics of protein breakdown and the bacterial species involved.

Results

Casein, pancreatic casein hydrolysate (mainly short-chain peptides) or amino acids were incubated in vitro with suspensions of faecal bacteria from 3 omnivorous and 3 vegetarian human donors. Results from the two donor groups were similar. Ammonia production was highest from peptides, followed by casein and amino acids, which were similar. The amino acids metabolized most extensively were Asp, Ser, Lys and Glu. Monensin inhibited the rate of ammonia production from amino acids by 60% (P = 0.001), indicating the involvement of Gram-positive bacteria. Enrichment cultures were carried out to investigate if, by analogy with the rumen, there was a significant population of asaccharolytic, obligately amino acid-fermenting bacteria (‘hyper-ammonia-producing’ bacteria; HAP) in the colon. Numbers of bacteria capable of growth on peptides or amino acids alone averaged 3.5% of the total viable count, somewhat higher than the rumen. None of these were HAP, however. The species enriched included Clostridium spp., one of which was C. perfringens, Enterococcus, Shigella and Escherichia coli.

Conclusions

Protein fermentation by human faecal bacteria in the absence of sugars not only leads to the formation of hazardous metabolic products, but also to the possible proliferation of harmful bacteria. The kinetics of protein metabolism were similar to the rumen, but HAP bacteria were not found.
Brain activity underlying auditory perceptual learning during short period training: simultaneous fMRI and EEG recording
Authors: de Souza Ana Cláudia Silva , Yehia Hani Camille , Sato Masa-aki , Callan Daniel
Published: January 2013

Background

There is an accumulating body of evidence indicating that neuronal functional specificity to basic sensory stimulation is mutable and subject to experience. Although fMRI experiments have investigated changes in brain activityafterrelative tobeforeperceptual learning, brain activityduringperceptual learning has not been explored. This work investigated brain activity related to auditory frequency discrimination learning using a variational Bayesian approach for source localization, during simultaneous EEG and fMRI recording. We investigated whether the practice effects are determined solely by activity in stimulus-driven mechanisms or whether high-level attentional mechanisms, which are linked to the perceptual task, control the learning process.

Results

The results of fMRI analyses revealed significant attention and learning related activity in left and right superior temporal gyrus STG as well as the left inferior frontal gyrus IFG. Current source localization of simultaneously recorded EEG data was estimated using a variational Bayesian method. Analysis of current localized to the left inferior frontal gyrus and the right superior temporal gyrus revealed gamma band activity correlated with behavioral performance.

Conclusions

Rapid improvement in task performance is accompanied by plastic changes in the sensory cortex as well as superior areas gated by selective attention. Together the fMRI and EEG results suggest that gamma band activity in the right STG and left IFG plays an important role during perceptual learning.
Deficiency in four and one half LIM domain protein 2 (FHL2) aggravates liver fibrosis in mice
Authors: Huss Sebastian , Stellmacher Christian , Goltz Diane , Khlistunova Inna , Adam Alexander C , Trebicka Jonel , Kirfel Jutta , Büttner Reinhard , Weiskirchen Ralf
Published: January 2013

Background

Four and one half LIM domain protein 2 (FHL2) has been reported to be a key regulator in many cellular processes being associated with fibrogenesis such as cell migration and contraction. Moreover, hepatic FHL2 is involved in regulation pathways mediating proliferation and cell death machineries. We here investigated the role of FHL2 in the setting of experimental and clinical liver fibrosis.

Methods

FHL2−/− and wild type (wt) mice were challenged with CCl4. Fibrotic response was assessed by quantitative real time PCR (qRT-PCR) of fibrotic marker genes, measurement of hydroxyproline content and histological methods. Murine FHL2−/− and hepatic stellate cells (HSC) were isolated and investigated via immunofluorescence. Human fibrotic and normal liver samples were analysed immunohistochemically using antibodies directed against FHL2.

Results

FHL2−/− mice displayed aggravated liver fibrosis compared to wt mice. However, immunofluorescence revealed no significant morphological changes in cultured FHL2−/− and wt myofibroblasts (MFB). In human liver samples, FHL2 was strongly expressed both in the nucleus and cytoplasm in MFB of fibrotic livers. In contrast, FHL2 expression was absent in normal liver tissue.

Conclusions

Deficiency of FHL2 results in aggravation of murine liver fibrosis. In human liver samples, FHL2 is expressed in activated HSCs and portal fibroblasts in human fibrotic livers, pointing to a central role of FHL2 for human hepatic fibrogenesis as well.
Calcification of coronary arteries and abdominal aorta in relation to traditional and novel risk factors of atherosclerosis in hemodialysis patients
Authors: Pencak Przemysław , Czerwieńska Beata , Ficek Rafał , Wyskida Katarzyna , Kujawa-Szewieczek Agata , Olszanecka-Glinianowicz Magdalena , Więcek Andrzej , Chudek Jerzy
Published: January 2013

Background

Process of accelerated atherosclerosis specific for uremia increases cardiovascular risk in patients with chronic kidney disease (CKD) and may be influenced by the different structure of arteries. The study assesses the influence of traditional and novel risk factors on calcification of coronary arteries (CAC) and abdominal aorta (AAC) in hemodialysis patients (HD).

Methods

CAC and AAC were assessed by CT in 104 prevalent adult HD and 14 apparently healthy subjects with normal kidney function (control group). Mineral metabolism parameters, plasma levels of FGF-23, MGP, osteoprotegerin, osteopontin, fetuin-A, CRP, IL-6 and TNF-α were measured.

Results

CAC and AAC (calcification score ≥ 1) were found in 76 (73.1%) and 83 (79.8%) HD respectively, more frequent than in the control group. In 7 HD with AAC no CAC were detected. The frequency and severity of calcifications increased with age. Both CAC and AAC were more frequently detected in diabetics (OR = 17.37 and 13.00, respectively). CAC score was significantly greater in males. CAC and AAC scores were correlated significantly with pack-years of smoking and plasma osteoprotegrin levels. However the independent contribution of plasma osteoprotegerin levels was not confirmed in multiple regression analysis. Age (OR = 1.13) and hemodialysis vintage (OR = 1.14) were the independent risk factor favoring the occurrence of CAC; while age (OR = 1.20) was the only predictor of AAC occurrence in HD.

Conclusions

1. AAC precedes the occurrence of CAC in HD patients. 2. The exposition to uremic milieu and systemic chronic microinflammation has more deteriorative effect on the CAC than the AAC.
Effect of dabrafenib on melanoma cell lines harbouring the BRAF
V600D/R
mutations
Authors: Gentilcore Giusy , Madonna Gabriele , Mozzillo Nicola , Ribas Antoni , Cossu Antonio , Palmieri Giuseppe , Ascierto Paolo A
Published: January 2013

Background

Conventional therapeutic agents are largely unsatisfactory into the treatment of malignant melanoma. Recently, an innovative approach based on inhibitors of the mutated BRAF gene (which represents the most prevalent alteration in melanoma patients) appears very promising from the clinical point of view. On this regard, a new compound, dabrafenib (GSK2118436), has been demonstrated to be effective in patients carrying the BRAFV600E/K mutations. We here tested dabrafenib for its capability to inhibit cell growth on primary melanoma cell lines, established from patients' tumour tissues and carrying the BRAFV600D/R mutations.

Methods

Three melanoma cell lines were tested: M257 wild-type BRAF, LCP BRAFV600R and WM266 BRAFV600D. The MTT assays were performed using standardized approaches. To evaluate the inhibition of MAPK pathway and the consequent inhibition of cellular proliferation, the phosphorylation of ERK was examined by Western Blot analysis performed on total protein extracts from cell lines after treatment with dabrafenib.

Results

Our experiments demonstrated an effective action of Dabrafenib (GSK2118436) and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations.

Conclusion

These results could be helpful to enlarge the number of melanoma patients who may benefit of a more effective targeted treatment.
Study protocol: the effect of whole body vibration on acute unilateral unstable lateral ankle sprain- a biphasic randomized controlled trial
Authors: Baumbach Sebastian Felix , Fasser Mariette , Polzer Hans , Sieb Michael , Regauer Markus , Mutschler Wolf , Schieker Matthias , Blauth Michael
Published: January 2013

Background

Ankle sprains often result in ankle instability, which is most likely caused by damage to passive structures and neuromuscular impairment. Whole body vibration (WBV) is a neuromuscular training method improving those impaired neurologic parameters. The aim of this study is to compare the current gold standard functional treatment to functional treatment plus WBV in patients with acute unilateral unstable inversion ankle sprains.

Methods/Design

60 patients, aged 18–40 years, presenting with an isolated, unilateral, acute unstable inversion ankle sprain will be included in this bicentric, biphasic, randomized controlled trial. Samples will be randomized by envelope drawing. All patients will be allowed early mobilization and pain-dependent weight bearing, limited functional immobilization by orthosis, PRICE, NSARDs as well as home and supervised physiotherapy. Supervised physical therapy will take place twice a week, for 30 minutes for a period of 6 weeks, following a standardized intervention protocol. During supervised physical therapy, the intervention group will perform exercises similar to those of the control group, on a side-alternating sinusoidal vibration platform. Two time-dependent primary outcome parameters will be assessed: short-term outcome after six weeks will be postural control quantified by the sway index; mid-term outcome after one year will be assessed by subjective instability, defined by the presence of giving-way attacks. Secondary outcome parameters include: return to pre-injury level of activities, residual pain, recurrence, objective instability, energy/coordination, Foot and Ankle Disability Index and EQ 5D.

Discussion

This is the first trial investigating the effects of WBV in patients with acute soft tissue injury. Inversion ankle sprains often result in ankle instability, which is most likely due to damage of neurological structures. Due to its unique, frequency dependent, influence on various neuromuscular parameters, WBV is a promising treatment method for patients with acute unstable inversion ankle sprains.

Trial registration

NCT01702597
Focal cryosurgical ablation of the prostate: a single institute’s perspective
Authors: Hale Zachary , Miyake Makito , Palacios Diego Aguilar , Rosser Charles J
Published: January 2013

Background

With the stage migration of prostate cancer witnessed in the late 1990’s and early 2000’s along with the persistent morbidities associated with prostatectomy and radiation therapy, the concept of focal prostate cancer treatment remains quite attractive. Herein we evaluate the tolerability and non-oncologic outcomes of a highly select cohort of men that underwent focal cryoablation of the prostate for the treatment of localized prostate cancer.

Methods

Pre-operatively, erectile function was assessed by SHIM questionnaire while voiding symptoms were assessed by AUA symptom score. Twenty-six highly select patients (23 low-risk prostate cancer and 3 intermediate-risk prostate cancer) with documented minimal disease on saturation prostate biopsy underwent focal cryoablation of the prostate (24 hemi-ablation and 2 subtotal ablation). Subsequently, serum PSAs were obtained every 3 months for 2 years and then every 6 months thereafter. PSA failure was defined as an increase of 0.50 ng/ml over nadir. Mean follow-up was 19.1 months. Subjective assessment of erectile function and voiding was assessed post-operatively at each visit.

Results

Based on our PSA failure definition, 11.5% (3 patients) of the cohort experienced biochemical failure. In two of the three patients, localized disease was detected on subsequent transrectal ultrasound guided biopsy. These two patients went on to have favorable PSA nadirs after undergoing conventional definitive therapy (one patient had external beam radiation and one patient had whole gland cryoablation). Within the study cohort, 27% (7 patients) reported new post-operative erectile dysfunction requiring therapy while no patients reported new post-operative urinary incontinence or worsening of voiding symptoms.

Conclusion

These preliminary results add to the expanding body of literature that the minimally invasive focal cryosurgical ablation of the prostate is a safe procedure with few side effects. The true extent of cancer control remains in question, but in highly select patients, favorable PSA kinetics have been demonstrated. If confirmed by further studies with long-term follow-up, this treatment approach could have a profound effect on prostate cancer management.
The characteristics of patient safety culture in Japan, Taiwan and the United States
Authors: Fujita Shigeru , Seto Kanako , Ito Shinya , Wu Yinghui , Huang Chiu-Chin , Hasegawa Tomonori
Published: January 2013

Background

Quality and safety issues are receiving growing attention. Patient safety culture (PSC) plays an important role in patient safety. The characteristics of PSC in various countries, each with a different set of values, have not been determined sufficiently. The aim of this study is to investigate the characteristics of PSC in Japan, Taiwan and the U.S.

Methods

A cross-sectional survey was conducted in Japan and Taiwan using the Hospital Survey on PSC (HSOPS) questionnaire developed by the U.S. Agency for Healthcare Research and Quality (AHRQ). Data from Japan and Taiwan were also compared with the U.S. “2010 HSOPS Comparative Database” provided by AHRQ.

Results

Valid response rates in Japan, Taiwan and the U.S. were 66.5% (6,963/10,466), 85.7% (10,019/11,692) and 35.2% (291,341/827,424), respectively. The proportion of respondents with some experience of event reporting during the past 12 months was highest in Japan. In general, U.S. healthcare workers were likely to evaluate their PSC higher than that in Japan or Taiwan. The attitude of continuous improvement in Japan and event reporting of near misses in Taiwan were rated as low. In the U.S., staffing was rated as high.

Conclusions

The results suggest that PSC varies among different countries, and the cultural setting of each country should be given special consideration in the development of effective intervention plans to improve PSC. Additional investigations with improved methodology and a common protocol are required to accurately compare PSCs among countries.
Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde
Authors: He Yinghong , Rank Gerhard , Zhang Miaomiao , Ju Junyi , Liu Ronghua , Xu Zhen , Brown Fiona , Cerruti Loretta , Ma Chi , Tan Renxiang , Jane Stephen M , Zhao Quan
Published: January 2013

Background

Pharmacologic reactivation of fetal hemoglobin expression is a promising strategy for treatment of sickle cell disease and β-thalassemia. The objective of this study was to investigate the effect of the methyl transferase inhibitor adenosine-2’,3’-dialdehyde (Adox) on induction of human fetal hemoglobin (HbF) in K562 cells and human hematopoietic progenitor cells.

Methods

Expression levels of human fetal hemoglobin were assessed by northern blot analysis and Real-time PCR. HbF and adult hemoglobin (HbA) content were analyzed using high-performance liquid chromatography (HPLC). DNA methylation levels on human gamma-globin gene promoters were determined using Bisulfite sequence analysis. Enrichment of histone marks on genes was assessed by chromosome immunoprecipitation (ChIP).

Results

Adox induced γ-globin gene expression in both K562 cells and in human bone marrow erythroid progenitor cells through a mechanism potentially involving inhibition of protein arginine methyltransferase 5 (PRMT5).

Conclusions

The ability of methyl transferase inhibitors such as Adox to efficiently reactivate fetal hemoglobin expression suggests that these agents may provide a means of reactivating fetal globin expression as a therapeutic option for treating sickle cell disease and β-thalassemia.
A closed form unwrapping method for a spherical omnidirectional view sensor
Authors: Chong Nguan Soon , Kho Yau Hee , Dennis Wong Mou Ling
Published: January 2013

This article proposes a novel method of image unwrapping for spherical omnidirectional images acquired through a non-single viewpoint (NSVP) omnidirectional sensor. It has three key steps i.e. (1) calibrate the camera to obtain parameters describing the spherical omnidirectional sensor, (2) map world points onto mirror points and, subsequently, onto image points, and (3) set up the projection plane for the final image unwrapping. Based on the projection plane selected, the algorithm is able to produce three common forms of unwrapping, namely cylindrical panoramic, cuboid panoramic, and ground plane view using closed form mapping equations. The motivation for developing this technique is to address the complexity in using a NSVP omnidirectional sensor and ultimately encouraging its application in robotics field. One of the main advantages of a NSVP omnidirectional sensor is that the mirror can often be obtained at a lower price as compared to the single viewpoint counterpart.
Fasting substrate oxidation in relation to habitual dietary fat intake and insulin resistance in non-diabetic women: a case for metabolic flexibility?
Authors: Carstens Madelaine T , Goedecke Julia H , Dugas Lara , Evans Juliet , Kroff Jacolene , Levitt Naomi S , Lambert Estelle V
Published: January 2013

Background

Metabolic flexibility described as “the capacity of the body to match fuel oxidation to fuel availability” has been implicated in insulin resistance. We examined fasting substrate oxidation in relation to dietary macronutrient intake, and markers of insulin resistance in otherwise healthy women, with and without a family history of diabetes mellitus (FH DM).

Methods

We measured body composition (dual x-ray absorptiometry), visceral and subcutaneous adipose tissue area (VAT, SAT, using Computerised Tomography), fasting [glucose], [insulin], [free fatty acids], [blood lipids], insulin resistance (HOMA-IR), resting energy expenditure (REE), respiratory exchange ratio(RER) and self-reported physical activity in a convenience sample of 180 women (18-45 yrs). A food frequency questionnaire was used to assess energy intake (EI) and calculate the RER: Food Quotient (FQ) ratio. Only those with EI:REE (1.05 -2.28) were included (N=140). Insulin resistance was defined HOMA-IR (>1.95).

Results

The Insulin Resistant (IR) group had higher energy, carbohydrate and protein intakes (p < 0.05) and lower PA levels than Insulin Sensitive (IS) group (P < 0.001), but there were no differences in RER or RER:FQ between groups. However, nearly 50% of the variance in HOMA-IR was explained by age, body fat %, VAT, RER:FQ and FH DM (adjusted R2 = 0.50, p < 0.0001). Insulin-resistant women, and those with FH DM had a higher RER:FQ than their counterparts (p < 0.01), independent of body fat % or distribution.

Conclusion

In these apparently healthy, weight-stable women, insulin resistance and FH DM were associated with lower fat oxidation in relation to dietary fat intake, suggesting lower metabolic flexibility.
Bee venom acupuncture for the treatment of chronic low back pain: study protocol for a randomized, double-blinded, sham-controlled trial
Authors: Seo Byung-Kwan , Lee Jun-Hwan , Sung Won-Suk , Song Eun-Mo , Jo Dae-Jean
Published: January 2013

Background

Chronic non-specific low back pain is the most common medical problem for which patients seek complementary and alternative medical treatment, including bee venom acupuncture. However, the effectiveness and safety of such treatments have not been fully established by randomized clinical trials. The aim of this study is to determine whether bee venom acupuncture is effective for improving pain intensity, functional status and quality of life of patients with chronic non-specific low back pain.

Methods/design

This study is a randomized, double-blinded, sham-controlled clinical trial with two parallel arms. Fifty-four patients between 18 and 65 years of age with non-radicular chronic low back pain experiencing low back pain lasting for at least the previous three months and ≥4 points on a 10-cm visual analog scale for bothersomeness at the time of screening will be included in the study. Participants will be randomly allocated into the real or sham bee venom acupuncture groups and treated by the same protocol to minimize non-specific and placebo effects. Patients, assessors, acupuncturists and researchers who prepare the real or sham bee venom acupuncture experiments will be blinded to group allocation. All procedures, including the bee venom acupuncture increment protocol administered into predefined acupoints, are designed by a process of consensus with experts and previous researchers according to the Standards for Reporting Interventions in Clinical Trials of Acupuncture. Bothersomeness measured using a visual analogue scale will be the primary outcome. Back pain-related dysfunction, pain, quality of life, depressive symptoms and adverse experiences will be measured using the visual analogue scale for pain intensity, the Oswestry Disability Index, the EuroQol 5-Dimension, and the Beck’s Depression Inventory. These measures will be recorded at baseline and 1, 2, 3, 4, 8 and 12 weeks.

Discussion

The results from this study will provide clinical evidence on the efficacy and safety of bee venom acupuncture in patients with chronic non-specific low back pain.

Trial registration

This study is registered with the United States National Institutes of Health Clinical Trials Registry: NCT01491321
Recommendations for the management of tyrosinaemia type 1
Authors: de Laet Corinne , Dionisi-Vici Carlo , Leonard James V , McKiernan Patrick , Mitchell Grant , Monti Lidia , de Baulny Hélène Ogier , Pintos-Morell Guillem , Spiekerkötter Ute
Published: January 2013

The management of tyrosinaemia type 1 (HT1, fumarylacetoacetase deficiency) has been revolutionised by the introduction of nitisinone but dietary treatment remains essential and the management is not easy. In this review detailed recommendations for the management are made based on expert opinion, published case reports and investigational studies as the evidence base is limited and there are no prospective controlled studies.

The added value of this paper is that it summarises in detail current clinical knowledge about HT1 and makes recommendations for the management.
Identification of anti-inflammatory and other biological activities of 3-carboxamide, 3-carbohydrazide and ester derivatives of gatifloxacin
Authors: Sultana Najma , Arayne M Saeed , Naz Asia , Mesaik M Ahmed
Published: January 2013

Background

Seventeen 1,4-dihydroquinoline-3-carboxamide and 1,4-dihydroquinoline-3-carbohydrazide derivatives of gatifloxacin have been prepared with a facile one step synthesis aiming to improve antibacterial, antifungal and immunological activities. The methodology allows the introduction of a variety of substituents such as amines, alcohol, phenol, amides and alkyl halides into the core structure of gatifloxacin.

Results

The analog N-(3-aminophenyl)-1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxamide has been identified as a potentially excellent anti-inflammatory agent, which exhibited highly potent effects on the oxidative burst activity of whole blood phagocytes (IC50 <12.5 μg mL-1), neutrophils (IC50 <0.1 μg mL-1) and macrophages phagocytes (IC50 <3.1 μg mL-1) as well as potent T-cell proliferation inhibitory effect (IC50 3.7 μg mL-1) while having comparable antibacterial activity to gatifloxacin. Another analog, 1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-N-phenyl-1,4-dihydroquinoline-3-carbohydrazide has tremendous T-cell proliferation inhibitory effect IC50 <3.1 μg mL-1 as compared to prednisolone, whereas, 3,5-dihydroxyphenyl1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate and 2-hydroxyphenyl-1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate envision good inhibitory activity on T-cells proliferation (IC50 6.8 & 8.8 μg mL-1 respectively).

Conclusions

The structural modification at carboxylic group has resulted in improved anti-inflammatory activities with comparable antibacterial activity to gatifloxacin. We believe that C3 structural modifications of gatifloxacin are definitely important in bringing major immunomodulatory changes in these compounds.