bluuebunny/crossref_metadata_2025 huggingface dataset:
Proprietary costs of intellectual capital reporting: Malaysian evidence
Authors: Kamardin Hasnah , Abu Bakar Robiah , Ishak Rokiah
Published: August 2015

Purpose

– The purpose of this paper is to examine the relationship between intellectual capital (IC) performance (value-added intellectual coefficient (VAIC)) and company characteristics with IC disclosure (ICD) in Malaysian listed companies.

Design/methodology/approach

– Sample of the study is 68 biggest Malaysian companies listed in Malaysian Stock Exchange based on market capitalization in year 2006. The paper follows the classification of ICD by Huang et al. (2007), with three broad IC categories in 45 items. Content analysis was used to collect the IC information from the annual reports. Regression analysis was conducted for VAIC and its components. Log linear analysis was also conducted to cater the possible misspecification in the model.

Findings

– Results of the study show that VAIC is negatively related to ICD. Further classification of VAIC shows that intellectual capital efficiency and human capital efficiency are negatively related to ICD whilst structural capital efficiency is not related to ICD. Company size and leverage are found to be positively related to ICD.

Research limitations/implications

– Negative association between VAIC and ICD suggests that companies reduce ICD for competitive advantage reason which supports the proprietary cost theory. The findings of the study may provide some evidence to regulators to enhance the reporting practices of IC for the benefits of users of financial reporting in making relevant decisions. The focus should be given on the reporting of human capital items.

Originality/value

– This is the first paper to use IC framework by Huang et al. (2007). Consistency of findings with other studies using different IC framework can be compared for the choice of IC framework in future studies.
Foregrounding the role of relationships in reform
Authors: Liou Yi-Hwa , Daly Alan J. , Brown Chris , del Fresno Miguel
Published: August 2015

Purpose

– The role of relationships in the process of leadership and change is central, yet the social aspect of the work of reform is often background in favor of more technical approaches to improvement. Therefore, the purpose of this paper is to argue that social network theory and analysis provides a useful theory and set of tools to unpack the complex social work of leadership.

Design/methodology/approach

– In this paper the authors begin by reviewing social network theory in education to date. The authors identify strengths and gap areas and use findings and data from existing social network studies of educational leadership to highlight major concepts.

Findings

– Along with empirical examples, the paper proposes four important strands of social network analysis for future research in educational leadership: multiplex networks; multi-mode networks; longitudinal networks; and real time networks.

Originality/value

– This paper builds on recent scholarship using social network analysis in educational leadership and suggests that social network theory and methods provides unique and important analytic purchase in the study of educational leadership.
17‐(allylamino)‐17‐demethoxygeldanamycin drives Hsp70 expression but fails to improve morphological or functional recovery in injured skeletal muscle
Authors: Baumann Cory W , Otis Jeffrey S
Published: August 2015

The stress inducible 70 kDa heat shock protein (Hsp70) is instrumental to efficient morphological and functional recovery following skeletal muscle injury because of its roles in protein quality control and molecular signalling. Therefore, in attempt to improve recovery, Hsp70 expression was increased with 17‐(allylamino)‐17‐demethoxygeldanamycin (17‐AAG) prior to and following an intramuscular injection of barium chloride (BaCl2) into the tibialis anterior (TA) of healthy young mice. To assess recovery, regenerating fibre cross‐sectional area (CSA) of the TA and in vivo peak isometric torque produced by the anterior crural muscles (TA, extensor digitorum longus and extensor hallucis muscles) were analyzed for up to 3 weeks after the injury. Because treatment of 17‐AAG and Hsp70 are known to influence inflammatory and myogenic signalling, tumor necrosis factor‐α (TNF‐α) and myogenin content were also assessed. This study reports that 17‐AAG was effective at up‐regulating Hsp70 expression, increasing content fivefold in the uninjured muscle. However, this significant increase in Hsp70 content did not enhance morphological or functional recovery following the injury, as the return of regenerating fibre CSA and in vivo peak isometric torque did not differ compared to that of the injured muscle from the vehicle treated mice. Treatment with 17‐AAG also altered TNF‐α and myogenin content, increasing both to a greater extent after the injury. Together, these findings demonstrate that although 17‐AAG may alter molecular makers of regeneration, it does not improve recovery following BaCl2‐induced skeletal muscle injury in healthy young mice.
Targeting the platelet‐derived growth factor signalling in cardiovascular disease
Authors: Hu Weining , Huang Yu
Published: August 2015

Over 40 years of studies on platelet‐derived growth factors (PDGFs) and their receptors, the molecular mechanisms and functional roles of PDGFs in the development of embryos and human diseases, especially in cancer, are gradually being unravelled. PDGF‐BB was approved by the United States Food and Drug Administration for promoting wound healing, while imatinib, which selectively inhibits tyrosine kinase activity of PDGF receptors (PDGFR), has been prescribed to treat patients with gastrointestinal stromal tumor and chronic eosinophilic leukaemia. However, much less often have these drugs been studied in relation to cardiovascular diseases. This brief review mainly describes the role of PDGF signalling in cardiovascular pathogenesis such as atherosclerosis, pulmonary arterial hypertension, diabetes, angiogenesis and inflammation with an emphasis on how PDGFs function in these situations and what components might serve as potential therapeutic targets against cardio‐metabolic dysfunction.
Microvascular resistance in response to iodinated contrast media in normal and functionally impaired kidneys
Authors: Kurihara Osamu , Takano Masamichi , Uchiyama Saori , Fukuizumi Isamu , Shimura Tetsuro , Matsushita Masato , Komiyama Hidenori , Inami Toru , Murakami Daisuke , Munakata Ryo , Ohba Takayoshi , Hata Noritake , Seino Yoshihiko , Shimizu Wataru
Published: August 2015

Contrast‐induced nephropathy (CIN) is considered to result from intrarenal vasoconstriction, and occurs more frequently in impaired than in normal kidneys. It was hypothesized that iodinated contrast media would markedly change renal blood flow and vascular resistance in functionally impaired kidneys. Thirty‐six patients were enrolled (32 men; mean age, 75.3 ± 7.6 years) undergoing diagnostic coronary angiography and were divided into two groups based on the presence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min per 1.73 m2 (CKD and non‐CKD groups, n = 18 in both). Average peak velocity (APV) and renal artery resistance index (RI) were measured by Doppler flow wire before and after administration of the iodinated contrast media. The APV and the RI were positively and inversely correlated with the eGFR at baseline, respectively (APV, R = 0.545, P = 0.001; RI, R = −0.627, P < 0.001). Mean RI was significantly higher (P = 0.015) and APV was significantly lower (P = 0.026) in the CKD than in the non‐CKD group. Both APV (P < 0.001) and RI (P = 0.002) were significantly changed following contrast media administration in the non‐CKD group, but not in the CKD group (APV, P = 0.258; RI, P = 0.707). Although renal arterial resistance was higher in patients with CKD, it was not affected by contrast media administration, suggesting that patients with CKD could have an attenuated response to contrast media.
Cyclo‐Gly‐Pro, a cyclic dipeptide, attenuates nociceptive behaviour and inflammatory response in mice
Authors: Ferro Jamylle Nunes de Souza , de Aquino Fernanda Lima Torres , de Brito Renan Guedes , dos Santos Priscila Laíse , Quintans Jullyana de Souza Siqueira , de Souza Lucas Costa , de Araújo Almair Ferreira , Diaz Bruno Lourenço , Lucca‐Júnior Waldecy , Quintans‐Júnior Lucindo José , Barreto Emiliano
Published: August 2015

The present study aimed to investigate the antinociceptive and anti‐inflammatory effects of the cyclic dipeptide cyclo‐Gly‐Pro (CGP) in mice. Antinociceptive activity was assessed by employing different pain models, such as formalin test, acetic acid‐induced writhing, hot plate test, and carrageenan‐induced hyperalgesia, in mice. The number of c‐Fos‐immunoreactive cells in the periaqueductal gray (PAG) was evaluated in CGP‐treated mice. Anti‐inflammatory activity was evaluated using paw oedema induced by carrageenan, compound 48/80, serotonin, and prostaglandin E2 (PGE2) and analyzed by plethysmometry. Quantitation of myeloperoxidase (MPO) in the paw was carried out to analyze the presence of neutrophils in the tissue. Intraperitoneal injection of CGP produced a significant inhibition in both neurogenic and inflammatory phases of formalin‐induced pain. The antinociceptive effect of CGP, evaluated in the acetic acid‐induced writhing test, was detected for up to 6 h after treatment. Further, in the hot plate test, antinociceptive behaviour was evoked by CGP, and this response was inhibited by naloxone. Animals treated with CGP did not present changes in motor performance. In CGP‐treated mice there was an increase in the number of c‐Fos‐positive neurons in the periaqueductal gray. In another set of experiments, CGP attenuated the hyperalgesic response induced by carrageenan. Furthermore, CGP also reduced the carrageenan‐increased MPO activity in paws. In addition, CGP also reduced the paw oedema evoked by compound 48/80, serotonin, and PGE2. Taken together, these results may support a possible therapeutic application of the cyclic dipeptide cyclo‐Gly‐Pro toward alleviating nociception and damage caused by inflammation conditions.
Banking Structure, Marketization, and Small Business Development: Regional Evidence From China
Authors: Hasan Iftekhar , Kobeissi Nada , Wang Haizhi , Zhou Mingming
Published: August 2015

This paper provides an empirical examination of the regional banking structures in China and their effects on entrepreneurial activity. Using a panel of 27 provinces and four directly controlled municipalities from 1997 through 2008, we find that the presence of large banking institutions negatively correlates with small business development in local markets and that this negative relation is driven mainly by participation of large banks in the short‐term loan market. Rural banking institutions, in contrast, are found to promote regional entrepreneurial activity. Moreover, large state banks facilitate small business development in concentrated markets. When we interact measures of banking financing by state banks and rural banking institutions with a set of provincial‐level marketization indexes, we find that extensive marketization, factor market development and sophistication of legal frameworks mitigate the negative effect of large state banks on small business development. In provinces with advanced market development, efficient factor markets and favourable institutional settings, the positive effect of rural banking institutions on small business growth is even stronger.
Successful radiotherapy in postoperative recurrence of a primary mediastinal yolk sac tumor: A case report
Authors: Sakaguchi Masakuni , Maebayashi Toshiya , Aizawa Takuya , Ishibashi Naoya , Fukushima Shoko , Saito Tsutomu
Published: August 2015

A woman in her 60s was evaluated for anterior chest pain. Computed tomography (CT) revealed a 50 mm mass with irregular contrast enhancement in the anterior mediastinum. α‐fetoprotein (AFP) level was elevated to 1188 ng/mL. A germ cell tumor was diagnosed, mostly comprising of a yolk sac tumor (YST). Two courses of chemotherapy with cisplatin (CDDP) and etoposide (VP16) were administered and surgical tumor resection was then performed. The final diagnosis was YST. CDDP and VP16 were continued postoperatively; however, because the AFP level increased about six months after surgery, the chemotherapy regimen was altered to bleomycin and CPT‐11. As the AFP again increased and a CT scan revealed tumor re‐enlargement, recurrent YST was diagnosed and radiotherapy was administered. The patient received a total of 60 Gy (2 Gy per fraction). The tumor started to shrink during radiotherapy and AFP levels decreased. By one month post‐radiotherapy, AFP levels had normalized and the tumor had disappeared. As of six years after radiotherapy, the patient remains alive without recurrence. Mediastinal YSTs are rare, and treatment usually includes surgery and preoperative and postoperative chemotherapy with cisplatin‐based regimens. Successful treatment with radiotherapy has occasionally been reported. Our patient showed recurrence of a YST after surgery and chemotherapy, but achieved long‐term survival after radiotherapy. Few patients with YST have undergone radiotherapy, but this approach was successful in our patient. In cases of postoperative recurrent YST resistant to chemotherapy, radiotherapy, together with salvage surgery, may offer a valuable option.
Effects of Common Data Errors in Electronic Health Records on Emergency Department Operational Performance Metrics: A Monte Carlo Simulation
Authors: Ward Michael J. , Self Wesley H. , Froehle Craig M.
Published: August 2015

Objectives

The objective was to estimate how data errors in electronic health records (EHRs) can affect the accuracy of common emergency department (ED) operational performance metrics.

Methods

Using a 3‐month, 7,348‐visit data set of electronic time stamps from a suburban academic ED as a baseline, Monte Carlo simulation was used to introduce four types of data errors (substitution, missing, random, and systematic bias) at three frequency levels (2, 4, and 7%). Three commonly used ED operational metrics (arrival to clinician evaluation, disposition decision to exit for admitted patients, and ED length of stay for admitted patients) were calculated and the proportion of ED visits that achieved each performance goal was determined.

Results

Even small data errors have measurable effects on a clinical organization's ability to accurately determine whether it is meeting its operational performance goals. Systematic substitution errors, increased frequency of errors, and the use of shorter‐duration metrics resulted in a lower proportion of ED visits reported as meeting the associated performance objectives. However, the presence of other error types mitigated somewhat the effect of the systematic substitution error. Longer time‐duration metrics were found to be less sensitive to data errors than shorter time‐duration metrics.

Conclusions

Infrequent and small‐magnitude data errors in EHR time stamps can compromise a clinical organization's ability to determine accurately if it is meeting performance goals. By understanding the types and frequencies of data errors in an organization's EHR, organizational leaders can use data management best practices to better measure true performance and enhance operational decision‐making.
Complications associated with secondary orbital implantations
Authors: Sundelin Karin C , Dafgård Kopp Eva M E
Published: August 2015

Purpose

To evaluate complications associated with secondary procedures for orbital implants.

Methods

A retrospective review was made of the records of patients who had undergone a secondary orbital implantation at a tertiary referral centre at St Erik Eye Hospital in Stockholm, Sweden, from 1998 up to and including the first half of 2009. Implant‐related complications were noted as was demographic and surgical background data. The regional ethics committee in Stockholm gave its approval for this study.

Results

Seventy‐one patients had received a secondary orbital implant at the eye hospital. Implant‐related complications were noted in 24 patients (34%), and 20 patients required reoperation/s (28%). There were five types of complications: migration of the implant (13%), insufficient orbital volume (10%), exposure/extrusion/infection (8%), mechanical obstruction (1%) and socket oedema (1%). Analyses of sizes and types of implants, wrapping and surgical techniques did not reveal any specific factor that resulted in an increased number of complications. However, there was an indication that aluminium oxide might be associated with fewer complications (2/11 = 18%).

Conclusion

Our results show that secondary orbital implantations have high complication rates and that further surgery is needed in more than a quarter of cases. It is important to consider these facts when planning to insert secondary implants and to provide patients with accurate information about the procedure and possible outcomes.
Social Class, Economic Inequality, and the Convergence of Policy Preferences: Evidence from 24 Modern Democracies
Authors: Andersen Robert , Curtis Josh
Published: August 2015

Using data from the World Values Survey and national‐level indicators for 24 modern democracies, we assess the influence of social class and economic inequality on preferences for government responsibility. We improve on previous research by using multilevel models that account for differences in attitudes both within (i.e., over time) and across countries. Our findings are consistent with the economic self‐interest hypothesis. Specifically, working class individuals, who tend to gain the most from government intervention because of their low and often more precarious economic position, are more likely than others to support government intervention. We also find a positive relationship between national‐level income inequality and support for government intervention. As income inequality rises, its social ills tend to be more pervasive, resulting in public opinion becoming more supportive of governments taking responsibility for their citizens. We further demonstrate that inequality moderates the relationship between social class and attitudes. Although the effect of income inequality is positive for all social classes, attitudes across social classes become more similar as inequality rises.

Utilisant les données de World Values Survey et indicateurs de niveau national, nous évaluons l'influence de la classe sociale et l'inégalité économique sur les préférences en matière de responsabilité du gouvernement dans 24 démocraties modernes. Notre analyse se améliore sur la recherche précédente en utilisant des modèles à plusieurs niveaux qui tiennent compte des différences dans les attitudes au sein (ce est à dire, au fil du temps) et entre les pays. Nos résultats sont cohérents avec l'hypothèse d'auto‐ intérêt économique. Par exemple, les travailleurs ‐ qui ont tendance à bénéficier plus quand le gouvernement intervient dans l’économie en raison de leurs faibles revenus et souvent position plus précaire ‐ sont plus susceptibles que d'autres à un soutien responsabilité du gouvernement. Nous constatons également une relation positive entre l'inégalité des revenus au niveau national et le soutien à l'intervention du gouvernement. Comme l'inégalité des revenus se élève—et ses maux sociaux ont tendance à être plus répandue—l'opinion publique devient plus favorable des gouvernements assument la responsabilité de citoyens. Tout aussi important, cependant, nous démontrons également que la relation entre la social classe et les préférences pour la responsabilisation du gouvernement diffèrent par la quantité de l'inégalité des revenus dans un pays. Bien que l'effet de l'inégalité des revenus est positif pour toutes les classes sociales, les différences dans les attitudes de la classes sociale convergent que l'inégalité augmente.
Six‐year incidence of visually significant age‐related cataract: the Chennai eye disease incidence study
Authors: Panday Manish , George Ronnie , Asokan Rashima , Ve Ramesh Satyamangalam , Velumuri Lokapavani , Choudhari Nikhil S , Boddupalli Sachi Devi , Sunil Govindan T , Vijaya Lingam
Published: August 2015

Background

The aim of this study is to report the 6‐year incidence of age‐related cataract in a population‐based study.

Design

The design used is a population‐based cohort study.

Participants

A cohort of 2484 phakic subjects, aged 40 years and above at baseline, from a south Indian population was included in the study.

Methods

Bilateral phakics with visual acuity of 6/12 or better and cataract less than N2, C2 and P2 on the Lens Opacities Classification System II at baseline were included. Subjects with glaucoma and corneal or retinal diseases were excluded. Incident visually significant cataract was defined as visual acuity of less than 6/18 with a corresponding one grade or greater change in Lens Opacities Classification System II or history of having undergone cataract surgery with evidence of pseudophakia or aphakia at the 6‐year follow‐up.

Main Outcome Measures

Six‐year incidence of visually significant cataract and associated risk factors data were collected.

Results

Incident visually significant cataract at 6 years was seen in 158 subjects (6.36%, 95% CI: 5.40–7.32, phakics:pseudophakics/aphakics 70:88). Incidence was higher in the rural cohort as compared with the urban cohort (P < 0.001). Incidence increased with age and was highest in the ≥70 years age group (odds ratio (OR):31.23, 95% CI: 15.20–64.16, P < 0.001). Other associated risk factors included illiteracy (OR 1.75, 95% CI: 1.17–2.61, P = 0.007) and smoking (OR 1.77, 95% CI: 1.08–2.88, P = 0.02).

Conclusions

A significant proportion of the population developed visually significant age‐related cataract at 6 years. Incident visually significant cataract was significantly greater for the rural cohort between 50 and 69 years old.
Projective Blue‐Noise Sampling
Authors: Reinert Bernhard , Ritschel Tobias , Seidel Hans‐Peter , Georgiev Iliyan
Published: August 2015

We propose projective blue‐noise patterns that retain their blue‐noise characteristics when undergoing one or multiple projections onto lower dimensional subspaces. These patterns are produced by extending existing methods, such as dart throwing and Lloyd relaxation, and have a range of applications. For numerical integration, our patterns often outperform state‐of‐the‐art stochastic and low‐discrepancy patterns, which have been specifically designed only for this purpose. For image reconstruction, our method outperforms traditional blue‐noise sampling when the variation in the signal is concentrated along one dimension. Finally, we use our patterns to distribute primitives uniformly in 3D space such that their 2D projections retain a blue‐noise distribution.
Caesarean delivery and the risk of offspring overweight and obesity over the life course: a systematic review and bias‐adjusted meta‐analysis
Authors: Sutharsan R. , Mannan M. , Doi S. A. , Mamun A. A.
Published: August 2015

A causal role of Caesarean delivery (CD) on developing overweight and obesity in the life course of offspring has been postulated. However, the true strength of this association is not clear and the potential for confounding has not been adequately addressed. A systematic review and meta‐analysis were conducted to evaluate the strength of this association, this time using a bias‐adjusted model in addition to conventional methods. Our search yielded 32 estimates from 14 publications (n = 261 000) for meta‐analysis. The pooled analysis of seven estimates (n = 194 463) demonstrated a trend only towards a risk increase (RR = 1.15; 95% CI:0.94, 1.40) in overweight and obesity combined (ow+ob) due to CD in early childhood (0–5 years) and a similar trend was observed for mid‐childhood and adolescence (5–18 years). In adulthood, a moderate increase in risk for ow+ob due to CD was observed (n = 30 200) (RR = 1.28; 95% CI 1.02, 1.34). Results for obesity and overweight separately were stronger for obesity and demonstrated a decreasing effect across the three life stages. Conventional methods of analysis suggested less uncertainty than we report and publication bias assessment was strongly suggestive of a bias in favour of positive studies. The current analysis therefore suggests that the small effects seen with CD in this and previous meta‐analyses are probably a cumulative consequence of several biases we have outlined, including confounding effect and publication bias.
Intersphincteric completion proctectomy with omentoplasty for chronic presacral sinus after low anterior resection for rectal cancer
Authors: Musters G. D. , Borstlap W. A. , Bemelman W. A. , Buskens C. J. , Tanis P. J.
Published: August 2015

Aim

This study aimed to determine the clinical outcome of salvage surgery without restoring continuity for symptomatic chronic presacral sinus after low anterior resection (LAR) for rectal cancer.

Method

Out of a prospective cohort of 46 patients with chronic presacral sinus (> 1 year after LAR), 27 underwent completion proctectomy with omentoplasty between January 2005 and July 2014.

Results

The initial treatment for rectal cancer included neoadjuvant radiotherapy in 26 (96%) patients. Besides a chronic presacral sinus, a secondary fistula was present in 15 (56%) patients. Definitive salvage surgery was performed after a median of 40 (12–350) months from the primary resection. The median hospital stay after single‐ and multiple‐stage salvage surgery was 11 and 17 days. Postoperative complications occurred in 44% of patients. The re‐intervention rate was 33% with a range of 1–10 interventions per patient. During a median follow‐up of 20 (4–45) months from salvage surgery, healing of the chronic presacral sinus occurred in 78% of patients, with a healing rate after single‐ and multiple‐stage procedures of 88% and 64% respectively (P = 0.19).

Conclusion

Patients with a symptomatic chronic presacral sinus after LAR for rectal cancer, in whom restoration of continuity is not intended, can be effectively managed by completion proctectomy with complete debridement of the sinus and fistula tracts followed by an omentoplasty to fill the presacral cavity, preferably as a single‐stage procedure.
Laparoscopic salvage lateral pelvic lymph node dissection for locally recurrent rectal cancer
Authors: Akiyoshi T. , Nagata J. , Nagasaki T. , Konishi T. , Fujimoto Y. , Nagayama S. , Fukunaga Y. , Ueno M.
Published: August 2015

Aim

The lateral pelvic lymph nodes are one of the major sites and sources of local recurrence (LR) after surgery for rectal cancer. Salvage lateral pelvic lymph node dissection (LPLD) is potentially curative, but the value of laparoscopic surgery in such cases is unknown. Our aim was to report the technical details of laparoscopic salvage LPLD for LR at these nodes after rectal cancer surgery.

Method

The study was based on nine patients who underwent laparoscopic salvage LPLD for LR at the lateral pelvic lymph nodes after surgery for rectal cancer. The safety and feasibility of this procedure were determined.

Results

The median operation time was 381 min and the median estimated blood loss was 130 ml. There were no conversions. Adjacent structures removed en bloc were the pelvic plexus in four patients, the internal iliac artery in seven patients and the seminal vesicle in one patient. The median number of metastatic lymph nodes was 1 (range 1–11).

Conclusion

Our novel technique of laparoscopic salvage LPLD for LR at the lateral pelvic lymph nodes is safe and feasible.
Coronary events in obese hemodialysis patients before and after renal transplantation
Authors: De Lima Jose Jayme G. , Gowdak Luis Henrique W. , de Paula Flavio J. , Muela Henrique Cotchi S. , David‐Neto Elias , Bortolotto Luiz A.
Published: August 2015

We examined the impact of obesity (BMI ≥30 kg/m2, n = 357) on prognosis in 1696 hemodialysis (HD) patients before and after renal transplantation (TX). End‐points were coronary events, composite cardiovascular (CV) events, and death. Obese HD patients were older (55.9 ± 9.2 vs. 54.2 ± 11), had more diabetes (54% vs. 40%), dyslipidemia (49% vs. 30%), altered myocardial scan (38% vs. 31%), myocardial infarction (MI) (16% vs. 10%), coronary intervention (11% vs. 7%), higher total cholesterol (186 ± 52 vs. 169 ± 47), and triglycerides (219 ± 167 vs. 144 ± 91). Obese undergoing TX had more dyslipidemia (46% vs. 31%), angina (23% vs. 14%), MI (18% vs. 5%), increased total cholesterol (185 ± 56 vs. 172 ± 48), and triglycerides (237 ± 190 vs. 149 ± 100). Obesity was independently associated with coronary events (log‐rank = 0.008, HR 2.55% CI 1.27–5.11) and death (log‐rank 0.046, HR 1.52, % CI 1.007–2.30) in TX but not in HD. Obese HD patients had more risk factors and ischemic heart disease, but these characteristics did not interfere with prognosis. In TX patients, obesity predicts coronary events and death.
Intraepidermal nerve‐fibre density as a biomarker of the course of neuropathy in patients with Type 2 diabetes mellitus
Authors: Divisova S. , Vlckova E. , Srotova I. , Kincova S. , Skorna M. , Dusek L. , Dubovy P. , Bednarik J.
Published: August 2015

Aims

This paper aims to investigate whether intraepidermal nerve‐fibre density (IENFD) may be used as a marker of the course of neuropathy in patients with Type 2 diabetes mellitus.

Methods

Skin biopsies from the distal leg were serially evaluated in a group of 30 patients with Type 2 diabetes mellitus (median age 60 years, 17 men) with a short duration of diabetes (< 3 years) and good glucose control, and in 23 age‐ and sex‐matched controls. The time intervals between biopsies were > 2 years (median 33.8 months). Eighteen patients with Type 2 diabetes mellitus had symptoms or signs of distal symmetrical diabetic polyneuropathy, 12 had no neuropathy.

Results

At first skin biopsy, IENFD was normal in all controls and in patients without neuropathy (mean 9.5 and 7.9 fibres/mm, respectively) compared with abnormal IENFD in 77.8% in patients with polyneuropathy (mean 3.4 fibres/mm). The annual rate of intraepidermal nerve‐fibre (IENF) loss expressed as a percentage of the first IENFD value in patients with diabetic polyneuropathy was significantly higher [mean (se), 11.95 (3.82)%] compared with controls [1.92 (1.81)%, P < 0.001] and similar to patients without polyneuropathy [12.16 (4.38)%]. The rate of IENF loss did not correlate with degree of glucose control.

Conclusions

The annual rate of IENF loss in patients with Type 2 diabetes mellitus was several times higher than that of healthy participants, irrespective of the presence of signs or symptoms of diabetic polyneuropathy at initial evaluation. The change in IENFD is not linear and should be expressed as a proportion of initial IENFD to serve as a marker of the course of diabetic neuropathy.
Factors predicting parents' adaptation when supporting their young adult during a first‐episode psychosis
Authors: Morin Marie‐Helene , St‐Onge Myreille
Published: August 2015

Aim

The objective is to identify the factors that predict how well parents will adapt when supporting their adult child experiencing a FEP.

Methods

The study was conducted in Quebec city with 58 parents and stepparents who received services from a specialized clinic for treating psychotic illnesses in the early stages. Participants filled in four measuring instruments during a standardized telephone interview. Based on the model being proposed, bivariate analyses and linear regression models were carried out to identify factors that predict how parents will adapt.

Results

The analyses allowed us to determine that the factors revealing the severity of the illness and the vulnerability of the young person predict the negative aspects of the parents' experience (R2 = 0.39, P ≤ 0.000), whereas the personal factors related to the parents themselves essentially predict the positive aspects (R2 = 0.51, P ≤ 0.001). The empowerment can be predicted by the combined effect of the positive aspects of the parents' experience and their coping strategies, more specifically those related to family intervention (R2 = 0.60, P ≤ 0.001), whereas the parents' social functioning is linked to their active participation in a family association (R2= 0.14, P ≤ 0.006).

Conclusion

This study contributes to how we think of parents' adaptation as it suggests a model that takes the positive aspects into account, associated with the role of support, along with family intervention strategies offered by social workers. Adaptation that is conceptualized using two dependent variables, empowerment and social functioning, allows to identify intervention targets that will be beacons of hope for both the parents and the young people with psychosis, while encouraging early intervention and partnership practices between services and family members.
Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase
Authors: Latagliata Roberto , Montagna Chiara , Porrini Raffaele , Di Veroli Ambra , Leonetti Sabrina Crescenzi , Niscola Pasquale , Ciccone Fabrizio , Spadea Antonio , Breccia Massimo , Maurillo Luca , Rago Angela , Spirito Francesca , Cedrone Michele , De Muro Marianna , Montanaro Marco , Andriani Alessandro , Bagnato Antonino , Montefusco Enrico , Alimena Giuliana
Published: August 2015

At present, very few data are available on deferasirox (DFX) in the treatment of patients with Philadelphia‐negative myeloproliferative neoplasms in fibrotic phase (FP‐MPN) and transfusion dependence. To address this issue, a retrospective analysis of 28 patients (22 male and 6 female) with FP‐MPN and iron overload secondary to transfusion dependence was performed, based on patients enrolled in the database of our regional cooperative group who received treatment with DFX. DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1–43.1) with median ferritin values of 1415 ng/mL (IR 1168–1768). Extra‐hematological toxicity was reported in 16 of 28 patients (57.1%), but only two patients discontinued treatment due to toxicity. Among 26 patients evaluable for response (≥6 months of treatment), after a median treatment period of 15.4 months (IR 8.1–22.3), 11 patients (42.3%) achieved a stable and consistent reduction in ferritin levels <1000 ng/mL. As for hematological improvement, 6 of 26 patients (23%) showed a persistent (>3 months) rise of Hb levels >1.5 g/dL, with disappearance of transfusion dependence in four cases. Treatment with DFX is feasible and effective in FP‐MPN with iron overload. Moreover, in this setting, an erythroid response can occur in a significant proportion of patients.
A high BMI is a risk factor in younger patients with de novo acute myelogenous leukemia
Authors: Crysandt Martina , Kramer Michael , Ehninger Gerhard , Bornhäuser Martin , Berdel Wolfgang E. , Serve Hubert , Röllig Christoph , Kaifie Andrea , Jost Edgar , Brummendorf Tim H. , Wilop Stefan
Published: August 2015

Overweight and obese patients have an increased risk to develop several malignancies and, additionally, body mass index (BMI) impacts on outcome in several solid tumors. However, little is known for AML. We analyzed a cohort of 3526 patients with AML treated in three prospective multicenter trials within the German Study Alliance Leukemia. In multivariate analyses, we identified BMI as an independent risk factor for both DFS (HR 1.014, P = 0.0217) and OS (HR 1.015, P < 0.0036). Interestingly, overweight and obesity seemed to be a risk factor predominantly in patients with de novo AML younger than 65 yr with intermediate risk and adverse cytogenetics. Overweight with a BMI ≥25 kg/m² best discriminated the worse outcome and led to an absolute reduction in long‐term survival of 5–7% in the group of all younger patients (3‐yr OS 39.9% vs. 47.3%; 10‐yr OS 28.7% vs. 33.8%, P = 0.0002). Additionally, response to induction therapy was significantly reduced in these patients (76.9% vs. 82.8%, P < 0.0001). Thus, in younger patients with de novo AML, overweight and obesity are risk factors for impaired response to induction therapy, DFS and OS. This effect is, in part but not fully, explained by dose reduction such as dose‐capping at a body surface area of 2 m².
A novel dopamine transporter transgenic mouse line for identification and purification of midbrain dopaminergic neurons reveals midbrain heterogeneity
Authors: Apuschkin Mia , Stilling Sara , Rahbek‐Clemmensen Troels , Sørensen Gunnar , Fortin Guillaume , Herborg Hansen Freja , Eriksen Jacob , Trudeau Louis‐Eric , Egerod Kristoffer , Gether Ulrik , Rickhag Mattias
Published: August 2015

Midbrain dopaminergic (DAergic) neurons are a heterogeneous cell group, composed of functionally distinct cell populations projecting to the basal ganglia, prefrontal cortex and limbic system. Despite their functional significance, the midbrain population of DAergic neurons is sparse, constituting only 20 000–30 000 neurons in mice, and development of novel tools to identify these cells is warranted. Here, a bacterial artificial chromosome mouse line [Dat1‐enhanced green fluorescent protein (eGFP)] from the Gene Expression Nervous System Atlas (GENSAT) that expresses eGFP under control of the dopamine transporter (DAT) promoter was characterized. Confocal microscopy analysis of brain sections showed strong eGFP signal reporter in midbrain regions and striatal terminals that co‐localized with the DAergic markers DAT and tyrosine hydroxylase (TH). Thorough quantification of co‐localization of the eGFP reporter signal with DAT and TH in the ventral midbrain showed that a vast majority of eGFP‐expressing neurons are DAergic. Importantly, expression profiles also revealed DAergic heterogeneity when comparing substantia nigra and ventral tegmental area. Dat1‐eGFP mice showed neither change in synaptosomal DA uptake nor altered levels of DAT and TH in both striatum and midbrain. No behavioural difference between Dat1‐eGFP and wild‐type was found, suggesting that the strain is not aberrant. Finally, cell populations highly enriched in DAergic neurons can be obtained from postnatal mice by fluorescence‐activated cell sorting and the sorted neurons can be cultured in vitro. The current investigation demonstrates that eGFP expression in this mouse line is selective for DAergic neurons, suggesting that the Dat1‐eGFP mouse strain constitutes a promising tool for delineating new aspects of DA biology.
Simultaneous depletion of Atm and Mdl rebalances cytosolic Fe‐S cluster assembly but not heme import into the mitochondrion of Trypanosoma brucei
Authors: Horáková Eva , Changmai Piya , Paris Zdeněk , Salmon Didier , Lukeš Julius
Published: August 2015

ABC transporter mitochondrial 1 (Atm1) and multidrug resistance‐like 1 (Mdl) are mitochondrial ABC transporters. Although Atm1 was recently suggested to transport different forms of glutathione from the mitochondrion, which are used for iron‐sulfur (Fe‐S) cluster maturation in the cytosol, the function of Mdl remains elusive. In Trypanosoma brucei, we identified one homolog of each of these genes, TbAtm and TbMdl, which were downregulated either separately or simultaneously using RNA interference. Individual depletion of TbAtm and TbMdl led to limited growth defects. In cells downregulated for TbAtm, the enzymatic activities of the Fe‐S cluster proteins aconitase and fumarase significantly decreased in the cytosol but not in the mitochondrion. Downregulation of TbMdl did not cause any change in activities of the Fe‐S proteins. Unexpectedly, the simultaneous downregulation of TbAtm and TbMdl did not result in any growth defect, nor were the Fe‐S cluster protein activities altered in either the cytosolic or mitochondrial compartments. Additionally, TbAtm and TbMdl were able to partially restore the growth of the Saccharomyces cerevisiae Δatm1 and Δmdl2 null mutants, respectively. Because T. brucei completely lost the heme b biosynthesis pathway, this cofactor has to be obtained from the host. Based on our results, TbMdl is a candidate for mitochondrial import of heme b, which was markedly decreased in both TbMdl and TbAtm + TbMdl knockdowns. Moreover, the levels of heme a were strongly decreased in the same knockdowns, suggesting that TbMdl plays a key role in heme a biosynthesis, thus affecting the overall heme homeostasis in T. brucei.
The dynamic blood–brain barrier
Authors: Keaney James , Campbell Matthew
Published: August 2015

With the endothelium as its central unit, the blood–brain barrier (BBB) is a complex multicellular structure separating the central nervous system (CNS) from the systemic circulation. Disruption of the BBB has now been implicated in a multitude of acute and chronic CNS disorders indicating the potentially devastating effects of BBB breakdown on brain function. However, the healthy BBB is not an impermeable wall, but rather a communication ‘centre’, responding to and passing signals between the CNS and blood. New studies are identifying BBB‐specific transport pathways that tightly regulate the entry and exit of molecules to and from the brain. They are revealing a highly plastic barrier in which dynamic changes in BBB components like paracellular tight junction complexes can contribute to BBB maintenance. Here, we provide a succinct overview of the current state‐of‐play in BBB research and summarize novel findings into BBB regulation in homeostatic regulation of the brain.
A kinetic model for the prevalence of mono‐ over poly‐pupylation
Authors: Regev Ofir , Roth Ziv , Korman Maayan , Khalaila Isam , Gur Eyal
Published: August 2015

Bacteria belonging to the phyla Actinobacteria and Nitrospira possess proteasome cores homologous to the eukaryotic 20S proteasome particle. In these bacteria, the cytoplasmic signal for proteasomal degradation is a small protein termed Pup (prokaryotic ubiquitin‐like protein). PafA, the only known Pup ligase, conjugates Pup to lysine side chains of target proteins. In contrast to the eukaryotic ubiquitin‐proteasome system, where poly‐ubiquitin chains are the principal tags for proteasomal degradation, mono‐Pup moieties are almost exclusively observed in vivo and are sufficient as degradation tags. Although Pup presents lysines, raising the possibility of poly‐Pup chain assembly, these do not predominate. At present, the factors promoting the distinct predominance of mono‐ over poly‐pupylation remain poorly understood. To address this issue, we conducted a detailed biochemical analysis characterizing the pupylation of model proteins in vitro. We found that Pup can indeed serve as a pupylation target for PafA either in its free form or when already conjugated to proteins, thus allowing for the formation of poly‐Pup chains. However, our results indicate that pupylation of an already pupylated protein is unlikely to occur due to low affinity of PafA for such species. This alone prevents predominance of poly‐ over mono‐pupylation in vitro. This effect is likely to be magnified in vivo by the combination of PafA kinetics with the high abundance of non‐pupylated proteins. Overall, this work provides a kinetic explanation for the prevalence of mono‐ rather than poly‐pupylation in vivo, and sheds light on PafA substrate specificity.
Soluble extracellular matrix metalloproteinase inducer (EMMPRIN, EMN) regulates cancer‐related cellular functions by homotypic interactions with surface CD147
Authors: Knutti Nadine , Kuepper Michael , Friedrich Karlheinz
Published: August 2015

EMMPRIN (extracellular matrix metalloproteinase inducer) is a widely expressed glycoprotein and a member of the immunoglobulin superfamily which exists in both a membrane‐spanning and a soluble form. Homotypic interactions of EMMPRIN underlie its multiple roles in normal development and pathological situations such as viral infections, Alzheimer's disease and cancer. This study employed a recombinant soluble, fully glycosylated EMMPRIN domain (rhsEMN) as a tool to characterize the structural basis of EMMPRIN‐EMMPRIN receptor (EMNR) contacts and their functional effects on MCF‐7 breast carcinoma cells. rhsEMN did not form dimers in solution but bound to surface EMMPRIN (EMN) on MCF‐7 cells with high affinity and was readily internalized. The interaction interface for the homotypic contact was localized to the N‐terminal Ig domain. rhsEMN exerted a stimulatory effect on proliferation of MCF‐7 cells whereas it reduced cell migration in a dose‐dependent manner. These effects were accompanied by an upregulation of endogenous EMMPRIN as well as of matrix metalloproteinase‐14 (MMP‐14), a membrane‐bound protease involved in the extracellular release of soluble EMMPRIN, indicating a regulatory feedback mechanism. The proliferation‐promoting activity of rhsEMN was mimicked by a novel functional antibody directed to EMMPRIN, underscoring that crosslinking of cell surface EMMPRIN (EMNR) is crucial for eliciting intracellular signalling. Addressing malignancy‐related signal transduction in HEK‐293 cells, we could show that rhsEMN triggers the oncogenic Wnt pathway.
Supporting Student Learning Outcomes Through Service Learning
Authors: Bettencourt Michelle
Published: August 2015

Because of the current emphasis on accountability at the elementary, secondary, and postsecondary levels across all content areas, accreditation agencies, administrators, program designers, course developers, faculty, and students have increasingly focused on stating and measuring student learning outcomes and documenting the relationship between learning activities and achievement of those outcomes. In the three‐way service‐learning partnership made up of the student, the faculty member, and the community partner, student learning is sometimes vaguely defined, often simply assumed to occur, and usually only indirectly assessed. In addition, the extent to which course‐specific learning outcomes are supported during service learning is also unclear. Using action research and the DEAL model for critical reflection, this study measured university‐level, Intermediate Spanish learners’ attainment of course‐specific and non‐course‐specific learning outcomes. Analysis of oral reflective journals, surveys, focus group responses, and interviews indicated that students’ service learning experiences supported most course‐specific learning outcomes and also offered learning opportunities in other unexpected areas.
An Analysis of Spanish L2 Learners' Orientation Through Activity Theory
Authors: Tocaimaza‐Hatch C. Cecilia
Published: August 2015

Orientation is defined as the way in which individuals view a task and the means they devise to fulfill it (Appel & Lantolf, 1994; Roebuck, 2000). This study investigated the orientation of twelve learners enrolled in a fourth‐semester Spanish L2 university course through the analysis of their interactions during a collaborative text‐reconstruction task and in their post‐activity reflections on their participation. Viewed through the lens of activity theory (Appel & Lantolf, 1994; Wertsch, 1998), learners' behavior and reflections presented an account of their orientation that was rooted in their motives, needs, and goals and materialized in concrete action during the task. Findings demonstrated that (a) learners' orientation changed at various times during the activity depending on how their individual goals were met by the social setting (e.g., how helpful their partner was in completing the task) and (b) learners' reflections exposed information that was not apparent in activity (e.g., dissatisfaction with the task) but essential for language practitioners who seek to understand learners' goals, needs, and overall orientation toward language learning. Pedagogical implications address the implementation of orientation assessment forms in the L2 classroom.