bluuebunny/crossref_metadata_2025 huggingface dataset:
Voluntary Disclosure and Information Asymmetry: Evidence from the 2005 Securities Offering Reform
Authors: SHROFF NEMIT , SUN AMY X. , WHITE HAL D. , ZHANG WEINING
Published: August 2013

In 2005, the Securities and Exchange Commission enacted the Securities Offering Reform (Reform), which relaxes “gun‐jumping” restrictions, thereby allowing firms to more freely disclose information before equity offerings. We examine the effect of the Reform on voluntary disclosure behavior before equity offerings and the associated economic consequences. We find that firms provide significantly more preoffering disclosures after the Reform. Further, we find that these preoffering disclosures are associated with a decrease in information asymmetry and a reduction in the cost of raising equity capital. Our findings not only inform the debate on the market effect of the Reform, but also speak to the literature on the relation between voluntary disclosure and information asymmetry by examining the effect of quasi‐exogenous changes in voluntary disclosure on information asymmetry, and thus a firm's cost of capital.
Critique and Political Argumentation
Authors: Finlayson Alan
Published: August 2013

If political philosophy begins with Plato then it begins with anxiety over linguistic ambiguity – with an attempt to establish fixed definitions of words and to assign the right of rule to those best able to contain and order meaning. In the present day philosophers and social scientists remain deeply interested in language – but where Plato wanted to regulate the form and content of stories, substitute private dialogue for public speech and ban the unruly art of writing, contemporary philosophers are generally concerned with the establishment of public reason, specification of the principles that might govern our societal communications and explication of the uses, effects and histories of particular kinds of language.
Clinical features of patients with invasive thymoma: A retrospective analysis of 61 cases
Authors: Imai Hisao , Kaira Kyoichi , Yoshino Reiko , Sato Koji , Shimizu Kimihiro , Kawashima Osamu , Tanaka Shigebumi , Mori Masatomo
Published: August 2013

Aim

Invasive thymomas are rare tumours of the anterior mediastinum. These tumours' clinical features have been the subject of much controversy. Therefore, it is necessary to elucidate the optimal management of invasive thymomas.

Patients and Methods

A total of 61 patients with invasive thymoma were retrospectively reviewed.

Results

The study group comprised 38 males (62.3 per cent) and 23 females (37.7 per cent), with a median age of 55 years (range: 28–79 years). According to the Masaoka staging, 31 patients had stage II disease (50.8 per cent), 21 patients had stage III disease (34.4 per cent), four patients had stage IVa disease (6.6 per cent) and five patients had stage IVb disease (8.2 per cent). A statistically‐significant difference in the survival rate was observed between stages II and III (P < 0.001) and between III and IV (P < 0.001). Complete resection was performed in 43 patients (70.5 per cent). Patients who underwent complete resection showed significantly better prognosis than those with incomplete resection (P < 0.001) and inoperable/biopsy (P < 0.001). After initial treatment, a total of 20 patients (32.8 per cent) relapsed. The recurrence rates in stages II, III and IV were 3.2 per cent, 66.7 per cent and 55.5 per cent, respectively. Treatment for recurrence was performed in all 20 patients.

Conclusion

The outcome of invasive thymoma was correlated with the Masaoka stage and the extent of tumour resection. Salvage treatment for recurrent thymoma might give a moderate response rate and improve survival. A large‐scale study is warranted for evaluating the role of the multimodality therapeutic approach in patients with invasive thymoma.
Aetiology and treatment of spontaneous renal subcapsular effusion
Authors: He Qun , Xia Ming , Zhang Ji‐Wei , Wang Hai‐Tao , Wang Jian‐Jun
Published: August 2013

Aim

The aim of the present study was to investigate the diagnosis and treatment of spontaneous renal subcapsular effusion.

Patients and Methods

From May 2003 to December 2010, 14 patients with spontaneous renal subcapsular effusion were treated at our department. Subcapsular renal aspiration and drainage was performed in four patients, and effusion drainage and renal capsulotomy plus omentum wrapping was performed in 10 patients, among whom laparoscopic surgery was carried out in two cases.

Results

Fever was controlled within 3–5 days after aspiration or open surgical drainage plus omental wrapping. Renal subcapsular effusion disappeared after the second and third attempts of aspiration in three cases. In the other 11 cases, subcapsular effusion disappeared approximately 7–26 days after a single aspiration with continuous drainage or open surgical drainage plus omental wrapping (including two cases of laparoscopic surgery). No recurrence was observed during follow up (ranging from 6 months to 6 years).

Conclusion

Spontaneous renal subcapsular effusion is an inflammatory exudate of the renal parenchyma of undetermined aetiology. One of the possible causes is allergic disease of the renal vessels. Satisfactory therapeutic outcomes can be achieved by aspiration drainage or renal subcapsular effusion plus omental wrapping (including laparoscopic surgery), together with the administration of antibiotics and glucocorticoids.
Conflicting patterns of DNA barcoding and taxonomy in the cicada genus Tettigettalna from southern Europe (Hemiptera: Cicadidae)
Authors: Nunes Vera L. , Mendes Raquel , Marabuto Eduardo , Novais Bruno M. , Hertach Thomas , Quartau José A. , Seabra Sofia G. , Paulo Octávio S. , Simões Paula C.
Published: August 2013

DNA barcodes have great potential to assist in species identification, especially when high taxonomical expertise is required. We investigated the utility of the 5′ mitochondrial cytochrome c oxidase I (COI) region to discriminate between 13 European cicada species. These included all nine species currently recognized under the genus Tettigettalna, from which seven are endemic to the southern Iberian Peninsula. These cicadas have species‐specific male calling songs but are morphologically very similar. Mean COI divergence between congeners ranged from 0.4% to 10.6%, but this gene was proven insufficient to determine species limits within genus Tettigettalna because a barcoding gap was absent for several of its species, that is, the highest intraspecific distance exceeded the lowest interspecific distance. The genetic data conflicted with current taxonomic classification for T. argentata and T. mariae. Neighbour‐joining and Bayesian analyses revealed that T. argentata is geographically structured (clades North and South) and might constitute a species complex together with T. aneabi and T. mariae. The latter diverges very little from the southern clade of T. argentata and shares with it its most common haplotype. T. mariae is often in sympatry with T. argentata but it remains unclear whether introgression or incomplete lineage sorting may be responsible for the sharing of haplotypes. T. helianthemi and T. defauti also show high intraspecific variation that might signal hidden cryptic diversity. These taxonomic conflicts must be re‐evaluated with further studies using additional genes and extensive morphological and acoustic analyses.
Modulation of murine gastric vagal afferent mechanosensitivity by neuropeptide W
Authors: Li H. , Kentish S. J. , Kritas S. , Young R. L. , Isaacs N. J. , O'Donnell T. A. , Blackshaw L. A. , Wittert G. A. , Page A. J.
Published: August 2013

Aim

Neuropeptide W (NPW) is an endogenous ligand for the receptors GPR7 and GPR8 and is involved in central regulation of energy homeostasis. NPW in the periphery is found in gastric gastrin (G) cells. In the stomach, energy intake is influenced by vagal afferent signals, so we aimed to determine the effect of NPW on mechanosensitive gastric vagal afferents under different feeding conditions.

Methods

Female C57BL/6 mice (N > 10 per group) were fed a standard laboratory diet (SLD), high‐fat diet (HFD) or were food restricted. The relationship between NPW immunopositive cells and gastric vagal afferent endings was determined by anterograde tracing and NPW immunohistochemistry. An in vitro gastro‐oesophageal preparation was used to determine the functional effects of NPW on gastric vagal afferents. Expression of NPW in the gastric mucosa and GPR7 in whole nodose ganglia was determined by quantitative RT‐PCR (QRT‐PCR). The expression of GPR7 in gastric vagal afferent neurones was determined by retrograde tracing and QRT‐PCR.

Results

Neuropeptide W immunoreactive cells were found in close proximity to traced vagal afferents. NPW selectively inhibited responses of gastric vagal tension receptors to stretch in SLD but not HFD or fasted mice. In the nodose ganglia, GPR7 mRNA was specifically expressed in gastric vagal afferent neurones. In fasted mice gastric mucosal NPW and nodose GPR7, mRNA was reduced compared with SLD. A HFD had no effect on gastric NPW mRNA, but down‐regulated nodose GPR7 expression.

Conclusion

Neuropeptide W modulates gastric vagal afferent activity, but the effect is dynamic and related to feeding status.
Mechanisms of cytolysin‐induced cell damage – a role for auto‐ and paracrine signalling
Authors: Skals M. , Praetorius H. A.
Published: August 2013

Cytolysins inflict cell damage by forming pores in the plasma membrane. The Na+ conductivity of these pores results in an ion influx that exceeds the capacity of the Na+/K+‐pump to extrude Na+. This net load of intracellular osmolytes results in swelling and eventual lysis of the attacked cell. Many nucleated cells have the capacity to reduce the potential damage of pore‐forming proteins, whereas erythrocytes have been regarded as essentially defenceless against cytolysin‐induced cell damage. This review addresses how autocrine/paracrine signalling and the cells intrinsic volume regulation markedly influence the fate of the cell after membrane insertion of cytolysins. Moreover, it regards the various steps that may explain the relative large degree of diversity between cell types and species as well as highlights some of the current gaps in the mechanistic understanding of cytolysin‐induced cell injury.
Aspirin for treatment of lithium‐associated sexual dysfunction in men: randomized double‐blind placebo‐controlled study
Authors: Saroukhani Sepideh , Emami‐Parsa Morteza , Modabbernia Amirhossein , Ashrafi Mandana , Farokhnia Mehdi , Hajiaghaee Reza , Akhondzadeh Shahin
Published: August 2013

Objectives

The aim of the present study was to assess the effect of aspirin on lithium‐related sexual dysfunction in men with stable bipolar affective disorder (BAD).

Methods

In a randomized, double‐blind, placebo‐controlled study, 32 men with stable BAD who had been on lithium maintenance therapy randomly received aspirin (240 mg/day) or placebo for six weeks. The International Index for Erectile Function (IIEF) was used to assess sexual symptoms at baseline, Week 3, and Week 6. Depressive and mania symptoms and plasma lithium concentrations were assessed at baseline and Week 6. Side effects were assessed using a checklist.

Results

Thirty patients (15/group) completed the study. Baseline and endpoint lithium concentrations and mania and depressive symptoms did not differ significantly between the two groups. Significant effects of time × treatment interaction were observed for total score [Greenhouse–Geisser: F(1.410,39.466) = 6.084, p = 0.010] and erectile function [Greenhouse–Geisser: F(1.629,45.602) = 7.250, p = 0.003]. By Week 6, patients in the aspirin group showed significantly greater improvement in the total (63.9% improvement from the baseline) and erectile function domain (85.4% improvement from the baseline) scores than the placebo group (14.4% and 19.7% improvement from the baseline, p‐values = 0.002 and 0.001, respectively). By Week 6, 12 (80%) patients in the aspirin group and three (20%) patients in the placebo group met the criteria of minimal clinically important change [χ2(1) = 10.800, p = 0.001]. Other IIEF domains also showed significant improvement at the end of the trial. The frequency of side effects was similar between the two groups.

Conclusion

Aspirin effectively improves lithium‐related sexual dysfunction in men with stable BAD.
Genetic susceptibility to anthracycline‐related congestive heart failure in survivors of haematopoietic cell transplantation
Authors: Armenian Saro H. , Ding Yan , Mills George , Sun Canlan , Venkataraman Kalyanasundaram , Wong Florence Lennie , Neuhausen Susan L. , Senitzer David , Wang Shirong , Forman Stephen J. , Bhatia Smita
Published: August 2013

Haematopoietic cell transplantation (HCT) survivors are at increased risk for developing congestive heart failure (CHF), primarily due to pre‐HCT exposure to anthracyclines. We examined the association between the development of CHF after HCT and polymorphisms in 16 candidate genes involved in anthracycline metabolism, iron homeostasis, anti‐oxidant defence, and myocardial remodelling. A nested case‐control study design was used. Cases (post‐HCT CHF) were identified from 2950 patients who underwent HCT between 1988 and 2007 at City of Hope and had survived ≥1 year. This cohort formed the sampling frame for selecting controls (without CHF) matched on: age, race/ethnicity, cumulative anthracycline exposure, stem cell source (allogeneic, autologous), and length of follow‐up. Seventy‐seven cases with pre‐HCT germline DNA and 178 controls were genotyped. Multivariate analysis revealed that the odds of CHF was higher in females [Odds Ratio (OR) = 2·9, P < 0·01], individuals with pre‐HCT chest radiation (OR = 4·7, P = 0·05), hypertension (OR = 2·9, P = 0·01), and with variants of genes coding for the NAD(P)H‐oxidase subunit RAC2 (rs13058338, 7508T→A; OR = 2·8, P < 0·01), HFE (rs1799945, 63C→G; OR = 2·5, P = 0·05) or the doxorubicin efflux transporter ABCC2 (rs8187710, 1515G→A; OR = 4·3, P < 0·01). A combined (clinical and genetic) CHF predictive model performed better [area under the curve (AUC), 0·79] than the genetic (AUC = 0·67) or the clinical (AUC = 0·69) models alone.
Union Campaigns as Countermovements: Mobilizing Immigrant Workers in France and the United Kingdom
Authors: Tapia Maite , Turner Lowell
Published: August 2013

In this article, we compare recent innovative union campaigns: the ‘sans papiers’ campaign in France and the ‘Justice for Cleaners’ campaign in the United Kingdom, both based on a sustained grass‐roots mobilization of immigrant workers. Rather than focusing on the ‘usual suspect’ explanatory factors, such as contrasting national settings, union power structures or traditions, our cross‐national comparison highlights important underlying similarities in unions' strategic responses to a growing precarious immigrant workforce. In the absence of established channels of representation, both unions decided to act like social movements fighting for social protection. Using Polanyi's framework, we view both case studies as examples of countermovements against heightened levels of global liberalization and precarious employment.
Exposed evaporite diapirs and minibasins above a canopy in central Sverdrup Basin, Axel Heiberg Island, Arctic Canada
Authors: Harrison J. C. , Jackson M. P. A.
Published: August 2013

Axel Heiberg Island (Arctic Archipelago, northern Nunavut, Canada) contains the thickest Mesozoic section in Sverdrup Basin (11 km). The ca. 370‐km‐long island is second only to Iran in its concentration of exposed evaporite diapirs. Forty‐six diapirs of Carboniferous evaporites and associated minibasins are excellently exposed on the island. Regional anticlines, which formed during Paleogene Eurekan orogeny, trend roughly north on a regular ca. 20‐km wavelength and probably detach on autochthonous Carboniferous Otto Fiord Formation evaporites comprising halite overlain by thick anhydrite. In contrast, a 60‐km‐wide area, known as the wall‐and‐basin structure (WABS) province, has bimodal fold trends and irregular (<10 km) wavelengths. Here, crooked, narrow diapirs of superficially gypsified anhydrite crop out in tight anticline cores, which are separated by wider synclinal minibasins. We interpret the WABS province to detach on a shallow, partly exposed canopy of coalesced allochthonous evaporite sheets. Surrounding strata record a salt‐tectonic history spanning the Late Triassic (Norian) to the Paleogene. Stratigraphic thinning against diapirs and spectacular angular unconformities indicate mild regional shortening in which diapiric roof strata were bulged up and flanking strata steepened. This bulging culminated in the Hauterivian, when diapiric evaporites broke out and coalesced to form a canopy. As the inferred canopy was buried, it yielded second‐generation diapirs, which rose between minibasins subsiding into the canopy. Consistent high level emplacement suggests that all exposed diapirs inside the WABS area rose from the canopy. In contrast, diapirs along the WABS margins were sourced in autochthonous salt as first‐generation diapirs. Apart from the large diapir‐flanking unconformities, Jurassic‐Cretaceous depositional evidence of salt tectonics also includes submarine debris flows and boulder conglomerates shed from at least three emergent diapirs. Extreme local relief, tectonic slide blocks, steep talus fans and subaerial debris flows suggest that many WABS diapirs continue to rise today. The Axel Heiberg canopy is one of only three known exposed evaporite canopies, each inferred or known at a different structural level: above the canopy (Axel Heiberg), through the canopy (Great Kavir) and beneath a possible canopy (Sivas).
Glutathione S‐transferase omega‐2 polymorphism Asn142Asp modifies the risk of age‐related cataract in smokers and subjects exposed to ultraviolet irradiation
Authors: Stamenkovic Miroslav , Radic Tanja , Stefanovic Ivan , Coric Vesna , Sencanic Ivan , Pljesa‐Ercegovac Marija , Matic Marija , Jaksic Vesna , Simic Tatjana , Savic‐Radojevic Ana
Published: August 2013

Background

Glutathione S‐transferase omega‐1 and 2 have a unique range of enzymatic activities, including the regeneration of ascorbate by their dehydroascorbate reductase activities. Because these enzymes could have a protective role from oxidative damage in the lens, the question of whether the two coding glutathione S‐transferase omega polymorphisms confer the risk of age‐related cataract was addressed.

Methods

rs4925 (Ala140Asp) of glutathione S‐transferase omega‐1 and rs156697 (Asn142Asp) of glutathione S‐transferase omega‐2 polymorphisms in 100 patients with age‐related cataract and 130 controls were assessed.

Results

Presence of one mutant GSTO1*Asp or GSTO2*Asp allele did not contribute independently towards the risk of cataract; however, homozygous carriers of GSTO1*Asp/GSTO2*Asp haplotype demonstrated 3.42‐fold enhanced risk of cataract development (95% confidence interval = 0.84–13.93; P = 0.086). When GSTO genotype was analysed in association with smoking or professional exposure to ultraviolet irradiation, carriers of at least one mutant GSTO2*Asp allele had increased risk of cataract development in comparison with individuals with wild‐type GSTO2*Asn/Asn with no history of smoking or ultraviolet exposure (odds ratio = 6.89, 95% confidence interval = 1.81–16.21, P = 0.005; odds ratio = 4.10, 95% confidence interval = 1.23–13.74, P = 0.022, respectively). Regarding the distribution of particular glutathione S‐transferase omega genotype and cataract type, the highest frequency of mutant GSTO2*Asp allele was found in patients with nuclear cataract.

Conclusion

The results indicate that mutant GSTO2*Asp genotype is associated with increased risk of age‐related cataract in smokers and ultraviolet‐exposed subjects, suggesting a role of inefficient ascorbate regeneration in cataract development.
Prevalence of dry eye syndrome in an adult population
Authors: Hashemi Hassan , Khabazkhoob Mehdi , Kheirkhah Ahmad , Emamian Mohammad Hassan , Mehravaran Shiva , Shariati Mohammad , Fotouhi Akbar
Published: August 2013

Background

To determine the prevalence of dry eye syndrome in the general 40‐ to 64‐year‐old population of Shahroud, Iran.

Design

Population‐based cross‐sectional study.

Participants

Through cluster sampling, 6311 people were selected and 5190 participated. Assessment of dry eye was done in a random subsample of 1008 people.

Methods

Subjective assessment for dry eye syndrome was performed using Ocular Surface Disease Index questionnaire. In addition, the following objective tests of dry eye syndrome were employed: Schirmer test, tear break‐up time, and fluorescein and Rose Bengal staining using the Oxford grading scheme.

Main Outcome Measures

Those with an Ocular Surface Disease Index score ≥23 were considered symptomatic, and dry eye syndrome was defined as having symptoms and at least one positive objective sign.

Results

The prevalence of dry eye syndrome was 8.7% (95% confidence interval 6.9–10.6). Assessment of signs showed an abnormal Schirmer score in 17.8% (95% confidence interval 15.5–20.0), tear break‐up time in 34.2% (95% confidence interval 29.5–38.8), corneal fluorescein staining (≥1) in 11.3% (95% confidence interval 8.5–14.1) and Rose Bengal staining (≥3 for cornea and/or conjunctiva) in 4.9% (95% confidence interval 3.4–6.5). According to the Ocular Surface Disease Index scores, 18.3% (95% confidence interval 15.9–20.6) had dry eye syndrome symptoms. The prevalence of dry eye syndrome was significantly higher in women (P = 0.010) and not significantly associated with age (P = 0.291). The objective dry eye syndrome signs significantly increased with age.

Conclusions

Based on the findings, the prevalence of dry eye syndrome in the studied population is in the mid‐range. The prevalence is higher in women. Also, objective tests tend to turn abnormal at higher age. Pterygium is associated with dry eye syndrome and increased its symptoms.
Counterfactuals and Causal Models: Introduction to the Special Issue
Authors: Sloman Steven A.
Published: August 2013

Judea Pearl won the 2010 Rumelhart Prize in computational cognitive science due to his seminal contributions to the development of Bayes nets and causal Bayes nets, frameworks that are central to multiple domains of the computational study of mind. At the heart of the causal Bayes nets formalism is the notion of a counterfactual, a representation of something false or nonexistent. Pearl refers to Bayes nets as oracles for intervention, and interventions can tell us what the effect of action will be or what the effect of counterfactual possibilities would be. Counterfactuals turn out to be necessary to understand thought, perception, and language. This selection of papers tells us why, sometimes in ways that support the Bayes net framework and sometimes in ways that challenge it.
Structural Counterfactuals: A Brief Introduction
Authors: Pearl Judea
Published: August 2013

Recent advances in causal reasoning have given rise to a computational model that emulates the process by which humans generate, evaluate, and distinguish counterfactual sentences. Contrasted with the “possible worlds” account of counterfactuals, this “structural” model enjoys the advantages of representational economy, algorithmic simplicity, and conceptual clarity. This introduction traces the emergence of the structural model and gives a panoramic view of several applications where counterfactual reasoning has benefited problem areas in the empirical sciences.
Predicting Global Patterns in Mangrove Forest Biomass
Authors: Hutchison James , Manica Andrea , Swetnam Ruth , Balmford Andrew , Spalding Mark
Published: August 2013

Understanding spatial variation in carbon storage in natural habitats is critical for climate change mitigation efforts such as REDD. Terrestrial forests are being mapped with increasing accuracy, but the distribution of ``blue carbon'' in marine ecosystems remains poorly understood. We reviewed the literature to obtain field data on carbon storage and fluxes in mangroves world‐wide. Using this material we developed a climate‐based model for potential mangrove above‐ground biomass (AGB) with almost four times the explanatory power of the only previous published model. From this model, we present the first ever global map of potential mangrove AGB and estimate a total global mangrove AGB of 2.83 Pg, with an average of 184.8 t ha−1. Data on other carbon stocks and fluxes confirm the importance of mangroves in carbon accounting. The map highlights the high variability in mangrove AGB and indicates areas that should be prioritised for mangrove conservation and restoration.
Alemtuzumab induction in simultaneous pancreas and kidney transplantation
Authors: Zachariah Mareena , Gregg Austin , Schold Jesse , Magliocca Joseph , Kayler Liise K.
Published: August 2013

Background

Alemtuzumab (AZ) is a monoclonal anti‐CD52 antibody used as an induction agent in organ transplantation. Few studies have analyzed this agent in the context of simultaneous kidney–pancreas transplantation (SPKT).

Methods

We examined US registry data of SPKT recipient outcomes from January 2002 to October 2009 stratified by induction agent including AZ, other T‐cell–depleting agents combined (T cell), IL2 receptor blockade (IL‐2RAb), and no induction (none).

Results

Of 6860 SPKT recipients, induction therapy was AZ in 10%, T cell in 49%, IL‐2RAb in 18%, and none in 22%. On multivariate analysis, there were no significant differences in overall patient survival, pancreas or renal allograft survival, or delayed renal graft function for the three induction groups compared with no induction. Rehospitalization within six months of transplantation occurred more often with AZ (51%) T cell (52%), and IL‐2RAB (45%) compared with none (41%; p < 0.0001). On multivariate analysis, there was a significant higher odds of six‐month rehospitalization with AZ (aOR 1.40, 95%CI 1.14–1.71), IL‐2RAb (aOR 1.20, 95%CI 1.01–1.42–1.20), and other T‐cell–depleting agents (aOR 1.50, 95%CI 1.31–1.73) compared with none. Median length of stay was significantly shorter in the AZ (8 d) compared with the IL‐2RAb (9 d), T cell (10 d), and none (10 d) groups (p < 0.0001).

Conclusions

There are no differences in patient, pancreas or renal allograft survival using AZ induction. AZ may confer an advantage in the perioperative period as evidenced by a decreased hospital length of stay. However, this benefit may be lost due to more frequent rehospitalizations.
How the imaging investigation of EAST syndrome points towards the future of radiological multi‐parametric phenotyping of a genetic disease
Authors: Stivaros Stavros
Published: August 2013

This commentary is on the original article by Cross et al. on pages 846–856 of this issue.
Vocational rehabilitation services and employment outcomes for adults with cerebral palsy in the United States
Authors: Huang I‐Chun , Holzbauer Jerome J , Lee Eun‐Jeong , Chronister Julie , Chan Fong , O'neil John
Published: August 2013

Aim

The aim of this study was to examine the relationship between vocational rehabilitation services provided and work outcomes among people with cerebral palsy (CP), taking in to account demographic characteristics.

Method

From the US Department of Education Rehabilitation Service Administration Case Service Report (RSA‐911) database, data from 3162 individuals with CP (1820 males [57.6%] and 1342 females [42.4% age range 16–54y) whose cases were closed in 2009, were used in this study. A total of 1567 cases (49.6%) were closed with clients being categorized as ‘successful employment’ and 1595 cases (50.4%) were closed with clients being classified as unemployed.

Results

Multivariate logistic regression was used to examine the relationship between services provided and work outcomes with regard to demographic characteristics. Males aged between 26 and 54 years old with higher education attainment were more likely to be employed. Individuals receiving disability benefits were less likely to be employed. After controlling for the effect of demographic and work disincentive variables, five vocational rehabilitation services significantly predicted employment outcomes (p<0.05), including (1) on‐the‐job training; (2) job placement assistance; (3) on‐the‐job support; (4) maintenance services; and (5) rehabilitation technology.

Interpretation

Medical and health professionals need to be aware of vocational rehabilitation agencies as a resource for providing medical, psychological, educational, and vocational interventions for adults with CP to help them maximize their employability, to address their much needed work adjustment skills, to establish independent living, and to eventually reach their full potential in participation in society.
Hemiconvulsion‐hemiplegia syndrome: new insights from neuroimaging
Authors: Abernethy Laurence J
Published: August 2013

This commentary is on the original article by Barcia et al. on pages 1150–1158 of this issue.
The potential for motivational interviewing to improve outcomes in the management of diabetes and obesity in paediatric and adult populations: a clinical review
Authors: Christie D. , Channon S.
Published: August 2013

Having good intentions to engage in healthy behaviours, to change our lives in a positive direction and make substantial, lasting changes may not always translate into actions or behaviour that is maintained. Motivational Interviewing is a directive person‐centred approach designed to explore ambivalence and activate motivation for change [Miller WR, Rollnick S. Motivational Interviewing: Preparing People to Change Addictive Behaviour. London: Guilford Press, 1991]. A key component of a motivational interviewing conversation is to acknowledge that clients have every right to make no change. It uses a guiding communication style which invites people to consider their own situation and find their own solutions to situations that they identify as problematic that are preventing change. Motivational Interviewing was first introduced in adult health addiction services in the early 1980s. It has developed in the physical health specialties, and in the last 20 years or so attention has turned to the potential of Motivational Interviewing in the paediatric setting and the challenges of using it in families with children at differing ages and developmental stages. This article summarizes studies published from 2006 to 2011 of Motivational Interviewing in individuals across the lifespan with type 1 and type 2 diabetes and obesity.
Lipoproteins and Hedgehog signalling – possible implications for the adrenal gland function
Authors: Swierczynska Marta M. , Lamounier‐Zepter Valéria , Bornstein Stefan R. , Eaton Suzanne
Published: August 2013

Background

Metabolic syndrome is a common metabolic disorder that is associated with an increased risk of type 2 diabetes and cardiovascular diseases. Disturbances in adrenal steroid hormone production significantly contribute to the development of this disorder. Therefore, it is extremely important to fully understand the mechanisms governing adrenal gland function, both in physiological and pathological conditions.

Results

Recently, Sonic hedgehog has emerged as an important regulator of adrenal development, with a possible role in adult gland homeostasis. Recent work of our group shows that lipoproteins are important regulators of Hedgehog signaling; they act as carriers for the spread of Hedgehog proteins, but also contain lipid(s) that inhibit the pathway.

Conclusions

We propose that lipoproteins may affect Sonic hedgehog signaling in the adult adrenal gland at multiple levels. Understanding the interplay between lipoprotein metabolism and adrenal Hedgehog signaling may improve our understanding of how adrenal gland disorders contribute to the metabolic syndrome.
Exercise as a therapeutic tool to prevent mitochondrial degeneration in nonalcoholic steatohepatitis
Authors: Gonçalves Inês O. , Oliveira Paulo J. , Ascensão António , Magalhães José
Published: August 2013

Nonalcoholic fatty liver disease, encompassing hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, is a significant health problem associated with modern lifestyle, based on caloric overconsumption and physical inactivity. Although the mechanisms associated with progression from the ‘benign’ steatosis toNASHare still elusive, mitochondrial dysfunction seems to play an important role in this degenerative process. Degeneration of mitochondrial function duringNASHhas been associated with impaired β‐oxidation, oxidative phosphorylation and increased reactive oxygen species production, contributing to hepatocyte death and inflammatory response. Despite the fact that several therapeutic approaches can be used in the context ofNASH, including insulin‐sensitizing agents, anti‐obesity drugs, lipid‐lowering drugs or mitochondrial‐targeted drugs, dietary and physical activity are still the most effective strategies. In fact, active lifestyles decrease insulin resistance and body weight and result in decreased histological signs of liver injury. In fatty liver, physical activity prevents the disease progression through mitochondrial adaptations, namely by increasing cytochrome c content, enzyme activities and fatty acid oxidation, which are lost after some days of physical inactivity. However, less is known about the effect of physical activity onNASH‐associated mitochondrial dysfunction. After a brief characterization ofNASHand its association with liver mitochondrial (dys)function, the present review addresses the impact of physical (in)activity onNASHand, particularly, the possible contribution of active lifestyles to the modulation of liver mitochondrial dysfunction.
Acoustic recording as a non‐invasive method to detect larval infestation of Cosmopolites sordidus
Authors: Vinatier Fabrice , Vinatier Claude
Published: August 2013

The banana weevil, Cosmopolites sordidus (Germar) (Coleoptera: Curculionidae), is a major pest of banana cropping systems, as larvae bore into the corm of banana plants and damage the insertion points of primary roots, leading to plant snapping and toppling. Plant infestation by the banana weevil is assessed only via invasive techniques, such as plant cutting that highlights larval tunnels. We present here a non‐invasive technique based on a bioacoustic sensor with a band‐pass filter to detect larval activity inside banana corm. On the basis of a test under controlled conditions, we observed that the range of larval activity was between 1.4 and 2.6 kHz. Pulses lasted ca. 168 ms and were separated by intervals of 300 ms. The technique enables detection of more than 90% of infested suckers. The use of this technique to understand larval development of banana weevil is discussed.
Long‐term safety and tolerability of romiplostim in patients with primary immune thrombocytopenia: a pooled analysis of 13 clinical trials
Authors: Rodeghiero Francesco , Stasi Roberto , Giagounidis Aristoteles , Viallard Jean‐François , Godeau Bertrand , Pabinger Ingrid , Cines Douglas , Liebman Howard , Wang Xuena , Woodard Paul
Published: August 2013

Background and objectives

Thrombopoietin receptor agonists (TPOra) are the only treatments for immune thrombocytopenia (ITP) for which evidence of efficacy and safety from randomized, placebo‐controlled trials is available. We sought to determine the long‐term tolerability of the TPOra romiplostim, with a particular focus on thrombosis, bleeding, bone marrow (BM) reticulin, neoplasms/haematological malignancies and fatal events.

Methods

Data from 13 romiplostim clinical trials in which 653 patients with ITP received romiplostim for up to 5 yr (921.5 patient‐years) were pooled; subject incidence rates and exposure‐adjusted event rates (per 100 patient‐years) were calculated.

Results

The rate of thrombotic events (6% of patients, 7.5 events per 100 patient‐years) did not appear to increase over time; 9 events were associated with platelet counts >400 × 109/L and 10 with romiplostim doses exceeding current recommendations. Serious and grade ≥3 bleeding each occurred in approximately 8% of patients (~11 events per 100 patient‐years). Adverse events of BM reticulin were recorded for 12 patients (1.8%, 1.3 events per 100 patient‐years, confirmed by bone biopsy in ten patients) and BM collagen for one patient (0.2%, 0.1 event per 100 patient‐years, confirmed by trichrome staining). Neoplasms and haematological malignancies occurred in 2.1% and 0.8% of patients, respectively (2.2 and 0.7 events per 100 patient‐years). Fatal events occurred in 3.7% of patients (2.6 events per 100 patient‐years, four events treatment‐related).

Conclusions

Romiplostim is the TPOra for which the longest duration of safety data is available. Our data demonstrate that long‐term romiplostim treatment is well tolerated, with no new safety signals, even in patients treated for up to 5 yr.
Therapeutic superiority and safety of combined hydroxyurea with recombinant human erythropoietin over hydroxyurea in young β‐thalassemia intermedia patients
Authors: Elalfy Mohsen S. , Adly Amira A. M. , Ismail Eman A. , Elhenawy Yasmine I. , Elghamry Islam R.
Published: August 2013

Objective

To assess the efficacy and safety of combined hydroxyurea (HU) and recombinant human erythropoietin (rHuEPO) in β‐thalassemia intermedia (TI) patients compared with single HU therapy.

Methods

An interventional prospective randomized study registered in the ClinicalTrials.gov (NCT01624038) was performed on 80 TI patients (≤18 yr) divided into group A (40 patients received combined HU and rHuEPO) and group B (40 patients received single HU therapy). Baseline serum EPO levels were measured, and both groups were followed up for a mean period of 1 yr with regular assessment of transfusion requirements, blood pressure, ferritin, liver and renal functions, hemoglobin, and HbF. Quality of life (QoL) was assessed at the start and end of the study.

Results

Transfusion frequency and index were significantly decreased, while QoL was increased in group A compared with group B where 85% of patients showed improvement on combined therapy compared with 50% of patients on HU. Hemoglobin and HbF were significantly increased in both TI groups; however, this was more evident in group A than in group B. Also, 37.5% of patients in group A became transfusion‐independent compared with 15% in group B. EPO levels were negatively related to increments of hemoglobin and HbF. Splenectomized patients and those with initial HbF% >40% had the best response to combined therapy. No serious adverse events necessitating discontinuation of therapy in both groups.

Conclusions

HU was effective in management of TI; however, combination with rHuEPO gave a superior therapeutic effect resulting in the best clinical and hematological responses without adverse events.
BCR‐ABL1 molecular remission after 90Y‐epratuzumab tetraxetan radioimmunotherapy in CD22+Ph+B‐ALL: proof of principle
Authors: Chevallier Patrice , Bodet‐Milin Caroline , Robillard Nelly , Eugene Thomas , Menard Audrey , Le Houerou Claire , Guillaume Thierry , Delaunay Jacques , Escoffre‐Barbe Martine , Wegener William A. , Goldenberg David M. , Kraeber‐Bodéré Francoise
Published: August 2013

Although targeted therapies are used increasingly in hematologic malignancies, we are unaware of any prior studies of radioimmunotherapy (RAIT) in B‐acute lymphoblastic leukemia (ALL), even though this radiosensitive tumor expresses CD22, potentially a good target for this approach. Here, we report a patient with Philadelphia chromosome‐positive B‐ALL in third relapse who received RAIT with 90yttrium (90Y)‐labeled anti‐CD22 epratuzumab tetraxetan. Seven weeks after initiating therapy, the patient achieved a BCR‐ABL1 molecular remission documented by RT‐qPCR, which is now continuing at 6 months while awaiting an allogeneic hematopoietic stem cell transplant. 90Y‐Epratuzumab tetraxetan may be a promising therapeutic option for CD22+ B‐ALL patients.
Apoptotic signal molecules in skin biopsies of cutaneous lupus erythematosus: analysis using tissue microarray
Authors: Toberer Ferdinand , Sykora Jaromir , Göttel Daniel , Hartschuh Wolfgang , Werchau Siegfried , Enk Alexander , Joos Stefan , Krammer Peter H. , Kuhn Annegret
Published: August 2013

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease. Different pathogenetic mechanisms, including the accumulation of apoptotic keratinocytes in CLE, have been reported. Therefore, we investigated whether CLE and other inflammatory skin diseases differ with regard to the epidermal expression of molecules that are crucial for the initiation and regulation of apoptosis. In this study, 241 skin biopsies from patients with CLE, psoriasis (PSO), lichen planus (LP) and healthy controls (HCs) were analysed immunohistochemically using the tissue microarray (TMA) technique. The TUNEL assay and anti‐activated caspase‐3 antibodies revealed a significant increase of apoptotic keratinocytes in CLE lesions compared with HCs. Furthermore, we detected a significant increase in the epidermal expression of CD95 in CLE specimens compared with PSO, LP and HCs. These data suggest that the accumulation of apoptotic keratinocytes in CLE might be due to the increased epidermal expression of CD95, resulting in increased activity of the extrinsic apoptotic pathway in the disease.
α‐Synuclein as an intrinsically disordered monomer – fact or artefact?
Authors: Coelho‐Cerqueira Eduardo , Carmo‐Gonçalves Phelippe , Sá Pinheiro Anderson , Cortines Juliana , Follmer Cristian
Published: August 2013

Fibrillization of the protein α‐synuclein (α‐syn) is a hallmark of Parkinson's disease and other α‐synucleinopathies. The well‐established idea that α‐syn is a natively disordered monomer prone to forming fibrils was recently challenged by data showing that the protein mostly exists in vitro and in vivo as helically folded tetramers that are resistant to fibrillization. These apparently conflicting findings may be reconciled by the idea that α‐syn exists as a disordered monomer in equilibrium with variable amounts of dynamic oligomeric species. In this context, varying the approaches used for protein purification, such as the method used to lyse cells or the inclusion of denaturing agents, could dramatically perturb this equilibrium and hence alter the relative abundance of the disordered monomer. In the present study, we investigated how the current methods for α‐syn purification affect the structure and oligomeric state of the protein, and we discuss the main pitfalls associated with the production of recombinant α‐syn in Escherichia coli. We demonstrate that α‐syn was expressed in E. coli as a disordered monomer independent of both the cell lysis method and the use of heating/acidification for protein purification. In addition, we provide convincing evidence that the disordered monomer exists in equilibrium with a dynamic dimer, which is not an artefact of the cross‐linking protocol as previously suggested. Unlike the helically folded tetramer, α‐syn dimer is prone to fibrillate and thus it may be an interesting target for anti‐fibrillogenic molecules.

Structured digital abstract

aplha-Syn and aplha-Syn bind by cross-linking study (View interaction)

aplha-Syn and aplha-Syn bind by detection by mass spectrometry (1, 2)

aplha-Syn and aplha-Syn bind by molecular sieving (View interaction)

aplha-Syn and aplha-Syn bind by circular dichroism (View interaction)
Identification of key amino acid residues in the catalytic mechanism of diaminopropionate ammonialyase from Salmonella typhimurium
Authors: Kalyani Josyula N. , Bisht Shveta , Lakshmikanth Mariyanna , Murthy Mathur R. N. , Savithri Handanahal S.
Published: August 2013

Diaminopropionate ammonialyase (DAPAL), a fold‐type II pyridoxal 5′‐phosphate‐dependent enzyme, catalyzes the α,β‐elimination of diaminopropionate (DAP) to pyruvate and ammonia. DAPAL was able to utilize both d‐ and l‐DAP as substrates with almost equal efficiency. Mutational analysis of functionally important residues such as Thr385, Asp125 and Asp194 was carried out to understand the mechanism by which the isomers are hydrolyzed. Further, the putative residues involved in the formation of disulfide bond Cys271 and Cys299 were also mutated. T385S, T385D sDAPAL were as active with dl‐DAP as substrate as sDAPAL, whereas the later exhibited a threefold increase in catalytic efficiency with d‐Ser as substrate. Further analysis of these mutants suggested that DAPAL might follow an anti‐E2 mechanism of catalysis that does not involve the formation of a quinonoid intermediate. Of the two mutants of Asp125, D125E showed complete loss of activity with d‐DAP as substrate, whereas the reaction with l‐DAP was not affected significantly, demonstrating that Asp125 was essential for abstraction of protons from the d‐isomer. By contrast, mutational analysis of Asp194 showed that the residue may not be directly involved in proton abstraction from l‐DAP. sDAPAL does not form a disulfide bond in solution, although the position of Cys299 and Cys271 in the modeled structure of sDAPAL favored the formation of a disulfide bond. Further, unlike eDAPAL, sDAPAL could be activated by monovalent cations. Mutation of the cysteine residues showed that Cys271 may be involved in coordinating the monovalent cation, as observed in the case of other fold‐type II enzymes.
Differential effects of thapsigargin analogues on apoptosis of prostate cancer cells
Authors: Dubois Charlotte , Vanden Abeele Fabien , Sehgal Pankaj , Olesen Claus , Junker Steffen , Christensen Søren B. , Prevarskaya Natalia , Møller Jesper V.
Published: August 2013

The inhibition of sarcoplasmic reticulum Ca2+‐ATPase (SERCA) by thapsigargin (Tg) and Tg‐type analogues is considered to trigger cell death by activation of apoptotic pathways. Some of these analogues may be useful as antineoplastic agents after appropriate targeting as peptide conjugated prodrugs to cancer cells. With this in mind, this study evaluates the effect on LNCaP androgen‐sensitive cancer cells of thapsigargin substituted with 12‐aminododecanoyl linkers and Leu (Leu‐8ADT), aspartate (Asp‐8ADT) or Boc‐8ADT. Our results show that both Leu‐8ADT and Asp‐8ADT result in rapid ER calcium depletion and an influx of calcium across the plasma membrane by activation of store‐operated calcium entry. By contrast, ER Ca2+ depletion by Boc‐8ADT is a very slow process that does not perceptibly increase cytosolic Ca2+ and activate store‐operated calcium entry, because the inhibition of SERCA with this compound is very slow. Nevertheless, we find that Boc‐8ADT is a more efficient inducer of apoptosis than both Tg and Leu‐8ADT. Compared with Tg and the other analogues, apoptosis induced by Asp‐8ADT is very modest, although this compound also activates store‐operated calcium entry and at high concentrations (1 μm) causes severe morphological changes, reflecting decreased cell viability. We conclude that many factors need to be considered for optimization of these compounds in antineoplastic drug design. Among these ER stress induced by Ca2+ endoplasmic reticulum mobilization seems particularly important, whereas the early cytosolic increase of Ca2+ concentration preceding the executive phase of apoptosis appears to be of no, or little, consequence for a subsequent apoptotic effect.
Fatigue performance and fatigue damage parameter estimation of spot welded joints of aluminium alloys 6111‐T4 and 5754
Authors: Shi Y. , Guo H.
Published: August 2013

In the present study, fatigue behaviours of spot welded joints of aluminium alloys 6111‐T4 and 5754 have been experimentally investigated. Fatigue results indicate that fatigue strength of spot weld primarily depends on specimen loading type and gauge thickness. Effects of base material and load ratio on fatigue resistance of welded specimen are insignificant. An equivalent stress based fatigue damage parameter is derived to consolidate empirical data and develop predictive capabilities for automobile designers. The fatigue damage parameter defined in this study is proven effective in consolidating a large amount of fatigue data into a narrow band and is especially suitable for the comparative fatigue strength evaluation of components and specimens.