bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the current radiofrequency ablation systems using axiomatic design theory
Authors: Zhang Bing , Moser Michael AJ , Luo Yigang , Zhang Edwin M , Zhang Wenjun
Published: April 2014

This article evaluates current radiofrequency ablation systems using axiomatic design theory. Due to its minimally invasive procedure, short-time hospital stay, low cost, and tumour metastasis treatment, the radiofrequency ablation technique has been playing an important role in tumour treatment in recent decades. Although the radiofrequency ablation technique has many advantages, some issues still need to be addressed. Among these issues, the two most important are as follows: (1) the size of tumours to be removed (has to be larger than 3 cm in diameter) and (2) cleanness of the removal. Many device solutions have been proposed to address the two issues. However, there is a lack of knowledge regarding the systematic evaluation of these solutions. This article evaluates these systems in terms of their solution principles (or simply called conceptual design in general product design theory) using a design theory called axiomatic design theory. In addition, with the axiomatic design theory, a better conceptual design in terms of its feasibility to cope with incomplete target tissue necrosis from the large size of tumours has been found. The detailed analysis and simulation of the new conceptual design are conducted using finite element approach. The results in this article are proved by the information of animal experiments and clinical practices obtained from the literature. This study thus contributes to the current knowledge to further developments in radiofrequency ablation systems and procedure guidelines for physicians to perform the radiofrequency ablation operation more effectively.
Lupus flares in two established end-stage renal disease patients with on-line hemodiafiltration during pregnancy – case series
Authors: Althaf MM , Abdelsalam MS , Alfurayh OI
Published: April 2014

Many patients with established end-stage renal disease on maintenance dialysis as a result of lupus nephritis are young females in their reproductive years. We report two such patients dialyzed with on-line hemodiafiltration who developed reactivation of lupus disease activity only when they conceived after initial systemic lupus erythematosus burnout. We believe that the flare was triggered by both efficient dialysis and hormonal changes during pregnancy. The flares were treated with oral corticosteroids with an excellent response. Both patients had live births but delivered preterm.
Measuring serum levels of high-mobility group box 1 by enzyme-linked immunosorbent assay does not identify bacterial infections in patients with systemic lupus erythematosus
Authors: Tang Kuo-Tung , Hsieh Tsu-Yi , Chen Yi-Ming , Hsieh Chia-Wei , Chen Yi-Hsing , Chen Der-Yuan
Published: April 2014

Introduction

studies have shown that high-mobility group box 1 (HMGB1) may play a role in the propagation of inflammatory response in infectious and autoimmune diseases. However, its utility in the differentiation between infections and disease flares in systemic lupus erythematosus (SLE) patients has not been investigated.

Methods

we prospectively recruited 38 hospitalized patients from Taiwan with SLE. Among them, 13 patients suffered from superimposed bacterial infections while the other 25 patients experienced disease flares. SLE disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Serum levels of HMGB1 were measured by an enzyme-linked immunosorbent assay (ELISA). Additionally, serum levels of high-sensitivity C-reactive protein (hsCRP) were determined among 34 of the SLE patients.

Results

there was no significant difference between the serum HMGB1 levels in SLE patients with disease flares and patients with bacterial infections. Among SLE patients with disease flares, serum HMGB1 levels were significantly higher in patients with mild to moderate flares (3.53 ng/ml) compared to those with severe flares (1.72 ng/ml, p < 0.05). For identifying bacterial infections in patients with SLE, the area under the receiver operating characteristic (ROC) curve was 0.705 (95% CI: 0.524–0.848) for hsCRP and 0.497 (95% CI: 0.331–0.663) for HMGB1. The best cutoff value for hsCRP was 1.07 mg/dl for detection of bacterial infections in SLE patients, with a sensitivity of 75% and a specificity of 68%.

Conclusion

the determination of serum HMGB1 level is not useful in the differentiation between disease flares and bacterial infections in SLE patients.
Views on Sex and Sex Education Among Gang-Involved Latino Youth in the United States
Authors: Kassab Veronica A. , Acevedo-Polakovich Ignacio D. , Grzybowski Megan M. , Stout Stacy , Richards Allyn E. , Barnett Miya L. , Guerra-Morales Aileen , Bell Katrina M. , Crider Elizabeth A. , Beck Kara L. , Brookins-Fisher Jodi , Alfaro Mario , Saxena Suchita R.
Published: April 2014

Although gang-involved Latino youth in the United States are uniquely at risk of adverse consequences from sexual behavior, little research is available that can guide those who wish to develop interventions to reduce sexual risk among these youth. To facilitate the development of effective interventions, we identified cultural and contextual factors that influence sexual behavior and sex education among gang-involved Latino youth in one U.S. community. By analyzing transcripts from interviews and focus groups with three different groups of key stakeholders—gang-experienced Latino youth, the parents of gang-experienced Latino youth, and the personnel of a program providing comprehensive human services for gang-involved Latino youth—we identified three domains to be considered in developing sexual risk-reduction interventions for gang-involved U.S. Latino youth. The focus of our discussion is on the implications of these findings for future development or adaptation of interventions.
Patient-Centered Care or Cultural Competence
Authors: Nielsen Lisa Seto , Angus Jan E. , Howell Doris , Husain Amna , Gastaldo Denise
Published: April 2014

The literature about Chinese attitudes toward death and dying contains frequent references to strong taboos against open discussion about death; consequently, there is an assumption that dying at home is not the preferred option. This focused ethnographic study examined the palliative home care experiences of 4 Chinese immigrants with terminal cancer, their family caregivers, and home care nurses and key informant interviews with 11 health care providers. Three main themes emerged: (1) the many facets of taboo; (2) discursive tensions between patient-centered care and cultural competence; and (3) rethinking language barriers. Thus, training on cultural competence needs to move away from models that portray cultural beliefs as shared, fixed patterns, and take into account the complicated reality of everyday care provision at end of life in the home.
Force Perception, Effort, Strength, and Dynamic Muscle Function in Cancer-Related Fatigue
Authors: Platt Alexandra , Gross James , Davis Mellar P.
Published: April 2014

There are several kinesthetic parameters that can be used to measure fatigue including strength, endurance, sense of effort, perception of force exerted, and tapping speed. We developed a protocol and tested the feasibility of correlating subjective fatigue with kinesthetic parameters in a small group of patients with cancer having fatigue and in controls. Accrual was limiting. We discuss the limitations and potential modifications in the procedure, which may allow improved accrual and the rationale behind performing such a study.
Parental Power, Prestige, and Acceptance as Predictors of Young Adults’ Psychological Adjustment in Gilgit-Baltistan, Pakistan
Authors: Najam Najma , Hussain Sadiq , Kanwal Rabia Hussain , Malik Farah , Kausar Rukhsana
Published: April 2014

One hundred four 18- through 36-year-old students ( M = 22.6 years, 44% men) were recruited from Karakoram International University, Gilgit city, Pakistan. The adult version of the Parental Power–Prestige Questionnaire was administered to participants along with short forms of the adult Parental Acceptance–Rejection Questionnaire for mothers and for fathers, the adult version of the Personality Assessment Questionnaire and the Gender Inequality Scale. Results showed that perceived paternal and maternal acceptance were significantly correlated with the young adults’ psychological adjustment. Neither power nor prestige was significantly correlated with adjustment. Hierarchical regression analysis indicated that both perceived paternal and maternal acceptance independently predicted offspring’s psychological adjustment, while perceived parental power and prestige failed to predict their psychological adjustment. Perceived parental power and prestige were also evaluated as possible moderators in the relationship between paternal and maternal acceptance and psychological adjustment, but findings were not significant.
Effects of Parental Power/Prestige and Acceptance on the Psychological Adjustment of Turkish Youth
Authors: Börkan Bengü , Erkman Fatoş , Keskiner Pınar
Published: April 2014

The moderator role of perceived parental power and prestige in relation to perceived parental acceptance and adolescents’ psychological adjustment was analyzed in this study. The sample consisted of 306 adolescents (45% males) within the age range of 16 through 20 years ( M = 17.23). Measures used were the child versions of Parental Acceptance–Rejection Questionnaire for mothers and fathers, the youth version of Parental Power–Prestige Questionnaire, and the youth version of Personality Assessment Questionnaire. Results showed that both maternal acceptance and paternal acceptance were significantly correlated with youth’s psychological adjustment, regardless of sex. Neither power nor prestige was significantly correlated with psychological adjustment. Power and prestige were, however, correlated with maternal acceptance among females, but not among males. In addition, parental prestige was negatively correlated with paternal acceptance among females. After controlling for the effects of age, hierarchical multiple regression showed that only perceived maternal acceptance made a unique contribution to the psychological adjustment of females, and only perceived paternal acceptance made a unique contribution to the adjustment of males. However, interpersonal power moderated the relationship between perceived maternal acceptance and females’ psychological adjustment.
Reassessing Descriptive Representation by Women and Men of Color
Authors: Lien Pei-te
Published: April 2014

This research uses the concept of intersectionality to help improve understanding of the relationship between race and gender as it pertains to the jurisdictional context of elective offices held by Blacks, Latinos, Asian-Americans, and American-Indians at the subnational level. Utilizing an enhanced version of a comprehensive data set associated with the Gender and Multicultural Leadership Project, we document more substantial evidence of ethnoracial descriptive representation in state and local offices than previously known as well as important variations by race, gender, level/type of office, and their intersections. To help disentangle the paradoxical position of political women of color, we discuss with three scenarios implications of jurisdictional context on building electoral coalitions across race or gender by women of color.
Measuring State Highway Sustainability
Authors: Chen Can
Published: April 2014

Sustainability is vital to the future of America’s transportation infrastructure. Achieving a sustainable highway system contributes to overall transportation development. This article focuses on the development of a sustainability index that can be used to measure and benchmark state highway transportation systems. The index was derived from a principal components analysis (PCA) of 2007 U.S. state highway systems data. Seventeen variables measuring four dimensions of highway sustainability were utilized to derive a composite index. This study finds a wide variation in highway sustainability across the U.S. states and regions. The PCA-based index provides a simple and robust measure of state highway sustainability, enables benchmarking and tracking state highway performance, and helps states identify viable strategies for addressing the challenges toward a sustainable highway transportation system.
Relationship Between the pH of Enema Solutions and Intestinal Damage in Rabbits
Authors: Zhang Feng , Li Xia , Xu Xujuan , Cai Duanying , Zhang Jianguo
Published: April 2014

Mechanical enemas can lead to intestinal mucosal injuries and bowel barrier damage, presenting as electrolyte disturbances and functional intestinal disorders. Most researchers believe that the mechanism of injury is related to osmolality, volume and temperature of the solution, infusion pressure, and the composition of the enema tube. We hypothesized that the pH of the enema solution may also contribute to intestinal damage. We administered enema solutions—normal saline, soapsuds, or vinegar (neutral, alkaline, or acidic solutions, respectively)—to three groups of rabbits ( n = 20 per group). The solutions were standardized for volume and temperature and the soapsuds and vinegar solutions were adjusted to be isotonic with normal saline or deionized water. We also included a control group ( n = 20) in which the enema tubes were inserted but no solution was administered. We biopsied 3 sites (rectum and distal and proximal colon). Damage to intestinal mucosa was observed by light microscopy and transmission electron microscopy. In order to explore the detection of damage using noninvasive methods, cyclooxygenase (COX)-2 gene expression was measured in the exfoliated cells gathered from postenema defecation. Epithelial loss, inflammatory reaction, and cellular microstructure damage was increased in the vinegar and soapsuds groups. Also, exfoliated cells in these groups had higher COX-2 expression than the normal saline group. The acidic and alkaline enema solutions thus caused more severe damage to the intestinal mucosa compared to the neutral liquid, supporting our hypothesis. Further, the detection of COX-2 expression shows promise as a noninvasive method for estimating enema-induced damage.
Start, stop, and continue: Preliminary insight into the appeal of self-injury e-communities
Authors: Lewis Stephen P , Michal Natalie J
Published: April 2014

Nonsuicidal self-injury e-communication has gained heightened empirical and public interest. This is the first study to examine possible motives for nonsuicidal self-injury e-communication. A total of 68 nonsuicidal self-injury e-community members responded to open-ended questions concerning reasons for starting, temporarily stopping, and continuing nonsuicidal self-injury e-communication. Results from a thematic analysis indicated that being motivated to obtain support, get nonsuicidal self-injury help, help others, and better understand nonsuicidal self-injury represented motives for starting nonsuicidal self-injury e-communication. For some, negative interactions and accessing triggering material contributed to e-communication stoppage; these individuals continued e-communication to get support and help. Implications for research and e-outreach are discussed.
Mothers, household managers, and productive workers: The International Labor Organization and Women in Development
Authors: Boris Eileen
Published: April 2014

Focused on the International Labor Organization (ILO), this article historicizes the concept of ‘women in developing countries’ by looking at its own development through use by women researchers and others within the ILO context. It traces the construction of ‘women in developing countries’ as a distinct category of woman worker. In doing so, it advances the understanding of the very terms of policy that we take for granted, contextualizing a category that has managed to both justify first-world non-governmental organization (NGO) intervention and reflect the aspirations of women in the Global South for better lives. In capturing this tension, it suggests that we must complicate our analysis of global policymaking for, about, and by women. I begin to redirect attention from trends in the literature that either celebrate the generation who developed the Women in Development (WID) approach or critique their projects as hopelessly modernist. My goal is to underscore the institutional settings in which the contested terms of ‘women’ and ‘development’ became linked. What began as a definition of otherness, an objectification of a group defined by policymakers, turned into a subject position through which women activists within the ILO and on the ground in ‘Third-World’ nations demanded resources – and, as would become evident in conventions on home-based work, gained recognition as workers.
A clash of modernities: Developing a new value-based framework to understand the mismatch between production and consumption
Authors: Wikström Solveig , Jönsson Håkan , Decosta Patrick L’Espoir
Published: April 2014

This study addresses the enduring problem of the mismatch between firms’ offerings and consumers’ desires. It combines the general framework of modernity theory with the concept of regimes and uses the food area as the empirical context. Our cultural analytical study of consumers’ and firms’ articulation of values of food and meal demonstrates that firms are largely entrenched in the modern era, characterized by rationality, resource efficiency, and progress as means to improve human lives by providing more and better products. The consumers, on the other hand, have shifted to the late modern era, identified by risk aversion, local production, naturalism, hedonism, and a focus on identity and everyday life. The study concludes that the dichotomy in values and the structural constraints inherent within the contemporary food system explain much of the mismatch between firms and consumers in the Swedish food market. Another reason is that firms have difficulties to respond to new consumer demands. Our results are summarized in a conceptual model of differences in values between firms and consumers. They provide guidelines on how firms can rethink the present structure and better understand consumers.
The Use of Unregulated Staff: Time for Regulation?
Authors: Duffield Christine M. , Twigg Di E. , Pugh Judith D. , Evans Gemma , Dimitrelis Sofia , Roche Michael A.
Published: April 2014

Internationally, shortages in the nursing workforce, escalating patient demands, and financial constraints within the health system have led to the growth of unlicensed nursing support workers. Recently, in relation to the largest publicly funded health system (National Health Service), it was reported that extensive substitution of registered nurses with unskilled nursing support workers resulted in inadequate patient care, increased morbidity and mortality rates, and negative nurse outcomes. We argue that it is timely to consider regulation of nursing support workers with their role and scope of practice clearly defined. Further, the addition of these workers in a complementary model of care (rather than substitutive model) should also be explored in future research, in terms of impact on patient and nurse outcomes.
The emerging role of epigenetics in cardiovascular disease
Authors: Abi Khalil Charbel
Published: April 2014

There is a worldwide epidemic of cardiovascular diseases causing not only a public health issue but also accounting for trillions of dollars of healthcare expenditure. Studies pertaining to epidemiology, pathophysiology, molecular biology, gene identification and genetic linkage maps have been able to lay a strong foundation for both the diagnosis and treatment of cardiovascular medicine. Although the concept of ‘epigenetics’ is not recent, the term in current usage is extended from the initial concept of ‘controlling developmental gene expression and signaling pathways in undifferentiated zygotes’ to include heritable changes to gene expression that are not from differences in the genetic code. The impact of epigenetics in cardiovascular disease is now emerging as an important regulatory key player at different levels from pathophysiology to therapeutics. This review focuses on the emerging role of epigenetics in major cardiovascular medicine specialties such as coronary artery disease, heart failure, cardiac hypertrophy and diabetes.
Teacher Education in Ghana
Authors: Asare Kwame Bediako , Nti Seth Kofi
Published: April 2014

In an era when quality education is a concern for education-focused international organizations and dominates national debates, teacher quality must equally be a priority. The central role of the teacher requires that teacher education must be of the highest quality toward achieving any educational agenda. This article provides a synopsis and adds to the currency of contemporary teacher education efforts in Ghana. It presents key teacher training institutions in Ghana and highlights the structure of teacher preparation, type of teacher training pursued, and pathways to teacher development in Ghana. It examines how the question of approaches teacher educators use in training student-teachers can or cannot lead to the development of critical thinking skills, which are vital to promoting teacher effectiveness. We advocate that universities, colleges, Teacher Education Division of the Ghana Education Service, and all bodies involved in teacher education in Ghana join forces to chart new content and, emphatically, approaches to teaching teachers-in-training that can promote critical thinking skills in teachers. With the increased private sector participation, we initiate a debate as to the need to ensure uniformity in teacher quality standards in Ghana.
A conditional knockout mouse model reveals endothelial cells as the principal and possibly exclusive source of plasma factor VIII
Authors: Fahs Scot A. , Hille Matthew T. , Shi Qizhen , Weiler Hartmut , Montgomery Robert R.
Published: April 2014

Key Points

Endothelial cells are the predominant (and possibly exclusive) source of coagulation factor VIII. Hepatocytes do not contribute to plasma FVIII production.
On the topology and wt-distance on metric type spaces
Authors: Hussain Nawab , Saadati Reza , Agrawal Ravi P
Published: April 2014

Recently, Khamsi and Hussain (Nonlinear Anal. 73:3123-3129, 2010) discussed a natural topology defined on any metric type space and noted that this topology enjoys most of the metric topology like properties. In this paper, we define topologically complete type metrizable space and prove that being of metrizability type is preserved under a countable Cartesian product and establish the fact that any

G
δ

set in a complete metric type space is a topologically metrizable type space. Next, we introduce the concept of wt-distance on a metric type space and prove some fixed point theorems in a partially ordered metric type space with some weak contractions induced by the wt-distance.

MSC:47H09, 47H10.
Canadian physicians’ responses to cross border health care
Authors: Runnels Vivien , Labonté Ronald , Packer Corinne , Chaudhry Sabrina , Adams Owen , Blackmer Jeff
Published: April 2014

Background

The idea for this survey emanated from desk research and two meetings for researchers that discussed medical tourism and out-of-country health care, which were convened by some of the authors of this article (VR, CP and RL).

Methods

A Cross Border Health Care Survey was drafted by a number of the authors and administered to Canadian physicians via the Canadian Medical Association’s e-panel. The purpose of the survey was to gain an understanding of physicians’ experiences with and views of their patients acquiring health care out of country, either as medical tourists (paying out-of-pocket for their care) or out-of-country care patients funded by provincial/territorial public health insurance plans. Quantitative and qualitative results of the survey were analyzed.

Results

631 physicians responded to the survey. Diagnostic procedures were the top-ranked procedure for patients either as out-of-country care recipients or medical tourists. Respondents reported that the main reason why patients sought care abroad was because waiting times in Canada were too long. Some respondents were frustrated with a lack of information about out-of-country procedures upon their patients’ return to Canada. The majority of physician respondents agreed that it was their responsibility to provide follow-up care to medical travellers on return to Canada, although a substantial minority disagreed that they had such a responsibility.

Conclusions

Cross-border health care, whether government-sanctioned (out-of-country-care) or patient-initiated (medical tourism), is increasing in Canada. Such flows are thought likely to increase with aging populations. Government-sanctioned outbound flows are less problematic than patient-initiated flows but are constrained by low approval rates, which may increase patient initiation. Lack of information and post-return complications pose the greatest concern to Canadian physicians. Further research on both types of flows (government-sanctioned and patient-initiated), and how they affect the Canadian health system, can contribute to a more informed debate about the role of cross-border health care in the future, and how it might be organized and regulated.
HMG-CoA reductase expression in primary colorectal cancer correlates with favourable clinicopathological characteristics and an improved clinical outcome
Authors: Bengtsson Erik , Nerjovaj Pashtrik , Wangefjord Sakarias , Nodin Björn , Eberhard Jakob , Uhlén Mathias , Borgquist Signe , Jirström Karin
Published: April 2014

Background

An association between tumor-specific HMG-CoA reductase (HMGCR) expression and good prognosis has previously been demonstrated in breast and ovarian cancer. In this study, the expression, clinicopathological correlates and prognostic value of HMGCR expression in colorectal cancer was examined.

Findings

Immunohistochemical expression of HMGCR was assessed in tissue microarrays with primary tumours from 557 incident cases of colorectal cancer in the Malmö Diet and Cancer Study. Pearson’s Chi Square test was applied to explore the associations between HMGCR expression and clinicopathological factors and other investigative biomarkers. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the relationship between HMGCR expression and cancer-specific survival (CSS) according to negative vs positive HMGCR expression.

A total number of 535 (96.0%) tumours were suitable for analysis, of which 61 (11.4%) were HMGCR negative. Positive cytoplasmic HMGCR expression was associated with distant metastasis-free disease at diagnosis (p = 0.002), lack of vascular invasion (p = 0.043), microsatellite-instability (p = 0.033), expression of cyclin D1 (p = <0.001) and p21 (p = <0.001). Positive HMGCR expression was significantly associated with a prolonged CSS in unadjusted Cox regression analysis in the entire cohort (HR = 1.79; 95% CI 1.20-2.66) and in Stage III-IV disease (HR = 1.71; 95% CI 1.09-2.68), but not after adjustment for established clinicopathological parameters.

Conclusions

Findings from this prospective cohort study demonstrate that HMGCR is differentially expressed in colorectal cancer and that positive expression is associated with favourable tumour characteristics and a prolonged survival in unadjusted analysis. The utility of HMGCR as a predictor of response to neoadjuvant or adjuvant statin treatment in colorectal cancer merits further study.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2115647072103464.
Foot orthoses for adults with flexible pes planus: a systematic review
Authors: Banwell Helen A , Mackintosh Shylie , Thewlis Dominic
Published: April 2014

Background

Foot orthoses are widely used in the management of flexible pes planus, yet the evidence to support this intervention has not been clearly defined. This systematic review aimed to critically appraise the evidence for the use of foot orthoses for flexible pes planus in adults.

Methods

Electronic databases (Medline, CINAHL, Cochrane, Web of science, SportDiscus, Embase) were systematically searched in June 2013 for randomised controlled, controlled clinical and repeated measure trials where participants had identified flexible pes planus using a validated and reliable measure of pes planus and the intervention was a rigid or semi‐rigid orthoses with the comparison being a no‐orthoses (shoes alone or flat non‐posted insert) condition. Outcomes of interest were foot pain, rearfoot kinematics, foot kinetics and physical function.

Results

Of the 2,211 articles identified by the searches, 13 studies met the inclusion criteria; two were randomised controlled trials, one was a controlled trial and 10 were repeated measure studies. Across the included studies, 59 relevant outcome measures were reported with 17 calculated as statistically significant large or medium effects observed with use of foot orthoses compared to the no orthoses condition (SMD range 1.13 to ‐4.11).

Conclusions

No high level evidence supported the use of foot orthoses for flexible pes planus. There is good to moderate level evidence that foot orthoses improve physical function (medial‐lateral sway in standing (level II) and energy cost during walking (level III)). There is low level evidence (level IV) that foot orthoses improve pain, reduce rearfoot eversion, alter loading and impact forces; and reduce rearfoot inversion and eversion moments in flexible pes planus. Well‐designed randomised controlled trials that include appropriate sample sizes, clinical cohorts and involve a measure of symptom change are required to determine the efficacy of foot orthoses to manage adult flexible pes planus.
Identifying and prioritizing industry-level competitiveness factors: evidence from pharmaceutical market
Authors: Shabaninejad Hosein , Mehralian Gholamhossein , Rashidian Arash , Baratimarnani Ahmad , Rasekh Hamid Reza
Published: April 2014

Background

Pharmaceutical industry is knowledge-intensive and highly globalized, in both developed and developing countries. On the other hand, if companies want to survive, they should be able to compete well in both domestic and international markets. The main purpose of this paper is therefore to develop and prioritize key factors affecting companies’ competitiveness in pharmaceutical industry. Based on an extensive literature review, a valid and reliable questionnaire was designed, which was later filled up by participants from the industry. To prioritize the key factors, we used the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS).

Results

The results revealed that human capital and macro-level policies were two key factors placed at the highest rank in respect of their effects on the competitiveness considering the industry-level in pharmaceutical area.

Conclusion

This study provides fundamental evidence for policymakers and managers in pharma context to enable them formulating better polices to be proactively competitive and responsive to the markets’ needs.
Philadelphia chromosome-positive acute lymphoblastic leukemia with extramedullary and meningeal relapse after allogeneic hematopoietic stem cell transplantation that was successfully treated with dasatinib
Authors: Kondo Toshinori , Tasaka Taizo , Matsumoto Kana , Matsumoto Rui , Koresawa Lisa , Sano Fuminori , Tokunaga Hirotoshi , Matsuhashi Yoshiko , Nakanishi Hidekazu , Morita Kunihiko , Wada Hideho , Sugihara Takashi
Published: April 2014

Central nervous system (CNS) relapse is a critical issue while treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). A 58-year-old woman with Ph-positive ALL who relapsed after bone marrow transplantation for meningeal leukemia was treated with high-dose methotrexate, which resulted in remission. She underwent allogeneic cord blood transplantation followed by reduced intensity conditioning chemotherapy with imatinib; however, she experienced CNS relapse and developed an extramedullary mass on the right side of the temporal region. We treated 40 mg of dasatinib once daily, which had to be temporarily discontinued because she developed grade 2 pleural effusion and grade 2 hematemesis. After reinitiation of dasatinib, the extramedullary mass disappeared and meningeal leukemia ameliorated almost immediately. With 40 mg dasatinib administered once daily, its trough level and cerebrospinal fluid (CSF) concentration were 32 ng/mL and below the sensitivity threshold of 1 ng/mL, respectively. Treatment was continued, and the patient remained in complete remission until she died of pneumonia 7 years after the initial diagnosis of ALL. Dasatinib can be an effective treatment for Ph-positive ALL with CNS relapse. Although the concentration in the CSF seems low, it may be sufficient to exert anti-leukemic effects in the human CNS.
Promoter hypermethylation of tumor suppressor genes correlates with tumor grade and invasiveness in patients with urothelial bladder cancer
Authors: Bilgrami Shumaila M , Qureshi Sohail A , Pervez Shahid , Abbas Farhat
Published: April 2014

Purpose

To investigate the promoter methylation status at selected loci which encode for key proteins involved in apoptosis, DNA repair, cell cycle control and progression in urothelial cell carcinoma of bladder and compare the findings from tissue samples with that of plasma.

Methods

Total genomic DNA was isolated from 43 non-muscle invasive (low grade) and 33 muscle invasive (high grade) urothelial bladder cancer samples along with 10 control cases of normal bladder mucosa. Promoter methylation status was investigated for RASSF1A, APC, MGMT, CDKN2A and CDKN2B genes using real-time methylation-specific PCR with SYBR® green. Plasma samples from 16 patients with muscle invasive high grade bladder cancer were also subjected to similar analyses.

Results

Promoter hypermethylation was frequently observed in RASSF1A, APC and MGMT gene promoters (p-value < 0.001). The methylation was more prominent in the muscle invasive high grade bladder cancer when compared to non-muscle invasive low grade group (p-value < 0.001) and normal bladder mucosa (p-value < 0.05). The RNA expression of RASSF1A, APC and MGMT was also found to be decreased in the muscle-invasive high grade bladder cancer when compared to the non muscle invasive low grade group (p-value < 0.05). RASSF1A, MGMT and CDKN2A showed comparable results when data from 16 plasma samples was compared to the corresponding tissue samples.

Conclusion

Our results suggest that epigenetic silencing of RASSF1A, APC and MGMT genes is strongly associated with invasive high grade urothelial bladder cancer. Thus, status of promoter methylation has the potential to serve as valuable tool for assessing aggressiveness of urothelial cell carcinoma of bladder.
In situ experimental techniques to study the mechanical behavior of materials using X-ray synchrotron tomography
Authors: Singh Sudhanshu S , Williams Jason J , Hruby Peter , Xiao Xianghui , De Carlo Francesco , Chawla Nikhilesh
Published: April 2014

In situ X-ray synchrotron tomography is an excellent technique for understanding deformation behavior of materials in 4D (the fourth dimension here is time). However, performing in situ experiments in synchrotron is challenging, particularly in regard to the design of the mechanical testing stage. Here, we report on several in situ testing methods developed by our group in collaboration with Advanced Photon source at Argonne National Laboratory used to study the mechanical behavior of materials. The issues associated with alignment during mechanical testing along with the improvements made to the in situ mechanical testing devices, over time, are described. In situ experiments involving corrosion-fatigue and stress corrosion cracking in various environments are presented and discussed. These include fatigue loading of metal matrix composites (MMCs), corrosion-fatigue, and stress corrosion cracking of Al 7075 alloys.
Angiotensin II-Induced Protein Kinase D Activates the ATF/CREB Family of Transcription Factors and Promotes StAR mRNA Expression
Authors: Olala Lawrence O. , Choudhary Vivek , Johnson Maribeth H. , Bollag Wendy B.
Published: April 2014

Aldosterone synthesis is initiated upon the transport of cholesterol from the outer to the inner mitochondrial membrane, where the cholesterol is hydrolyzed to pregnenolone. This process is the rate-limiting step in acute aldosterone production and is mediated by the steroidogenic acute regulatory (StAR) protein. We have previously shown that angiotensin II (AngII) activation of the serine/threonine protein kinase D (PKD) promotes acute aldosterone production in bovine adrenal glomerulosa cells, but the mechanism remains unclear. Thus, the purpose of this study was to determine the downstream signaling effectors of AngII-stimulated PKD activity. Our results demonstrate that overexpression of the constitutively active serine-to-glutamate PKD mutant enhances, whereas the dominant-negative serine-to-alanine PKD mutant inhibits, AngII-induced StAR mRNA expression relative to the vector control. PKD has been shown to phosphorylate members of the activating transcription factor (ATF)/cAMP response element binding protein (CREB) family of leucine zipper transcription factors, which have been shown previously to bind the StAR proximal promoter and induce StAR mRNA expression. In primary glomerulosa cells, AngII induces ATF-2 and CREB phosphorylation in a time-dependent manner. Furthermore, overexpression of the constitutively active PKD mutant enhances the AngII-elicited phosphorylation of ATF-2 and CREB, and the dominant-negative mutant inhibits this response. Furthermore, the constitutively active PKD mutant increases the binding of phosphorylated CREB to the StAR promoter. Thus, these data provide insight into the previously reported role of PKD in AngII-induced acute aldosterone production, providing a mechanism by which PKD may be mediating steroidogenesis in primary bovine adrenal glomerulosa cells.
Evidence That Estrogen Hastens Epiphyseal Fusion and Cessation of Longitudinal Bone Growth by Irreversibly Depleting the Number of Resting Zone Progenitor Cells in Female Rabbits
Authors: Nilsson Ola , Weise Martina , Landman Ellie B.M. , Meyers Jodi L. , Barnes Kevin M. , Baron Jeffrey
Published: April 2014

With age, growth plate cartilage undergoes programmed senescence, eventually causing cessation of bone elongation and epiphyseal fusion. Estrogen accelerates this developmental process. We hypothesized that senescence occurs because progenitor cells in the resting zone are depleted in number and that estrogen acts by accelerating this depletion. To test this hypothesis, juvenile ovariectomized rabbits received injections of estradiol cypionate or vehicle for 5 weeks, and then were left untreated for an additional 5 weeks. Exposure to estrogen accelerated the normal decline in growth plate height and in the number of proliferative and hypertrophic chondrocytes. Five weeks after discontinuation of estrogen treatment, these structural parameters remained advanced, indicating an irreversible advancement in structural senescence. Similarly, transient estrogen exposure hastened epiphyseal fusion. Estrogen also caused a more rapid decline in functional parameters of growth plate senescence, including growth rate, proliferation rate, and hypertrophic cell size. However, in contrast to the structural parameters, once the estrogen treatment was discontinued, the growth rate, chondrocyte proliferation rate, and hypertrophic cell size all normalized, suggesting that estrogen has a reversible, suppressive effect on growth plate function. In addition, estrogen accelerated the normal loss of resting zone chondrocytes with age. This decrease in resting zone cell number did not appear to be due to apoptosis. However, it was maintained after the estrogen treatment stopped, suggesting that it represents irreversible depletion. The findings are consistent with the hypothesis that estrogen causes irreversible depletion of progenitor cells in the resting zone, thus irreversibly accelerating structural senescence and hastening epiphyseal fusion. In addition, estrogen reversibly suppresses growth plate function.
Framing Incremental Expansions to Public Health Insurance Systems: The Case of Canadian Pharmacare
Authors: Daw Jamie R. , Morgan Steven G. , Collins Patricia A. , Abelson Julia
Published: April 2014

Canada is the only country in the world to offer universal comprehensive public health insurance that excludes outpatient prescription medicines. Few scholars have attempted to explain this policy puzzle. We study media coverage of prescription drug financing from 1990 to 2010 to elucidate how the policy problem and potential solutions have been framed in media discourse and identify the actors that have dominated media texts. We confirm previous analyses that have revealed the significant role played by policy elites in media coverage of health reform debates. We also find that proposed expansions to public coverage are presented as a financial liability that could “crowd out” the existing (and popular) public insurance program. Within the context of a predominantly public funded system, framing of incremental expansion reorients away from values and toward discourse related to costs — both of the current system and of potential reforms. This may reflect a strategic narrative used by actors to maintain “silos of values” for coverage for prescription medicines versus those for other services. This has significant implications for the motivation for reform among the electorate and politicians alike, and for the extent to which policy developments, if they occurred, would legitimately reflect societal values for health financing.
Genetic studies in Drosophila and humans support a model for the concerted function of CISD2, PPT1 and CLN3 in disease
Authors: Jones Melanie A. , Amr Sami , Ferebee Aerial , Huynh Phung , Rosenfeld Jill A. , Miles Michael F. , Davies Andrew G. , Korey Christopher A. , Warrick John M. , Shiang Rita , Elsea Sarah H. , Girirajan Santhosh , Grotewiel Mike
Published: April 2014

Wolfram syndrome (WFS) is a progressive neurodegenerative disease characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. WFS1 and WFS2 are caused by recessive mutations in the genes Wolfram Syndrome 1 (WFS1) and CDGSH iron sulfur domain 2 (CISD2), respectively. To explore the function of CISD2, we performed genetic studies in flies with altered expression of its Drosophila orthologue, cisd2. Surprisingly, flies with strong ubiquitous RNAi-mediated knockdown of cisd2 had no obvious signs of altered life span, stress resistance, locomotor behavior or several other phenotypes. We subsequently found in a targeted genetic screen, however, that altered function of cisd2 modified the effects of overexpressing the fly orthologues of two lysosomal storage disease genes, palmitoyl-protein thioesterase 1 (PPT1 in humans, Ppt1 in flies) and ceroid-lipofuscinosis, neuronal 3 (CLN3 in humans, cln3 in flies), on eye morphology in flies. We also found that cln3 modified the effects of overexpressing Ppt1 in the eye and that overexpression of cln3 interacted with a loss of function mutation in cisd2 to disrupt locomotor ability in flies. Follow-up multi-species bioinformatic analyses suggested that a gene network centered on CISD2, PPT1 and CLN3 might impact disease through altered carbohydrate metabolism, protein folding and endopeptidase activity. Human genetic studies indicated that copy number variants (duplications and deletions) including CLN3, and possibly another gene in the CISD2/PPT1/CLN3 network, are over-represented in individuals with developmental delay. Our studies indicate that cisd2, Ppt1 and cln3 function in concert in flies, suggesting that CISD2, PPT1 and CLN3 might also function coordinately in humans. Further, our studies raise the possibility that WFS2 and some lysosomal storage disorders might be influenced by common mechanisms and that the underlying genes might have previously unappreciated effects on developmental delay.
Cytokinesis defines a spatial landmark for hepatocyte polarization and apical lumen formation
Authors: Wang Ting , Yanger Kilangsungla , Stanger Ben Z. , Cassio Doris , Bi Erfei
Published: April 2014

By definition, all epithelial cells have apical-basal polarity, but it is unclear how epithelial polarity is acquired and how polarized cells engage in tube formation. Here, we show that hepatocyte polarization is linked to cytokinesis using the rat hepatocyte cell line Can 10. Before abscission, polarity markers are delivered to the site of cell division in a strict spatiotemporal order. Immediately after abscission, daughter cells remain attached through a unique disc-shaped structure, which becomes the site for targeted exocytosis, resulting in the formation of a primitive bile canaliculus (BC). Subsequently, oriented cell division and asymmetric cytokinesis occur at the BC midpoint, resulting in its equal partitioning into daughter cells. Finally, successive cycles of oriented cell division and asymmetric cytokinesis lead to the formation of a tubular bile canaliculus (tBC) shared by two rows of hepatocytes. These findings define a novel mechanism for cytokinesis-linked polarization and tube formation, which appears to be broadly conserved in diverse cell types.
GAS2-like proteins mediate communication between microtubules and actin through interaction with end-binding proteins
Authors: Stroud Matthew J , Nazgiewicz Alicja , McKenzie Edward A , Wang Yisu , Kammerer Richard A , Ballestrem Christoph
Published: April 2014

Crosstalk between the microtubule (MT) and actin cytoskeletons is fundamental to many cellular processes including cell polarisation and cell motility. Previous work has shown that members of the growth arrest specific 2 (GAS2) family mediate the crosstalk between filamentous actin (F-actin) and MTs, but the molecular basis remains unclear. By using fluorescence microscopy, we demonstrate that three members of this family, GAS2-like 1 (G2L1), GAS2-like 2 (G2L2), and GAS2-like 3 (G2L3) are differentially involved in mediating the crosstalk between F-actin and MTs. While all localise to actin and MTs, only the exogenous expression of G2L1 and G2L2 influenced MT stability, dynamics, and guidance along actin stress fibres. Biochemical analysis and live-cell imaging reveal that their functions are largely due to the association of these proteins with MT plus-end binding (EB) proteins that bind to SxIP/SxLP motifs located at G2L C-termini. Our findings lead to a model in which EB proteins play a key role in mediating actin-MT crosstalk.
Coordination Lamellar Nanofibers Consisting of N-(2-Hydroxydodecyl)-substituted Amino Acid and Divalent Copper Cation
Authors: Yamada Teppei , Minami Yusuke , Kimizuka Nobuo
Published: April 2014

Lamellar nanoribbons consisting of 1:2 complexes of divalent copper and N-(2-hydroxydodecyl)-l-alanine (l-AlaC12OH) and related N-(2-hydroxydodecyl)-substituted amino acid were newly developed. When racemic ligand was used, the lamellar size showed shrinkage and the stability of the fibrous nanostructures were enhanced, reflecting the spontaneous effective mixing of l and d complexes to form supramolecular racemic compounds.