bluuebunny/crossref_metadata_2025 huggingface dataset:
Tools in a clinical information system supporting clinical trials at a Swiss University Hospital
Authors: Weisskopf Michael , Bucklar Guido , Blaser Jürg
Published: August 2014

Background:

Issues concerning inadequate source data of clinical trials rank second in the most common findings by regulatory authorities. The increasing use of electronic clinical information systems by healthcare providers offers an opportunity to facilitate and improve the conduct of clinical trials and the source documentation. We report on a number of tools implemented into the clinical information system of a university hospital to support clinical research.

Methods:

In 2011/2012, a set of tools was developed in the clinical information system of the University Hospital Zurich to support clinical research, including (1) a trial registry for documenting metadata on the clinical trials conducted at the hospital, (2) a patient–trial–assignment–tool to tag patients in the electronic medical charts as participants of specific trials, (3) medical record templates for the documentation of study visits and trial-related procedures, (4) online queries on trials and trial participants, (5) access to the electronic medical records for clinical monitors, (6) an alerting tool to notify of hospital admissions of trial participants, (7) queries to identify potentially eligible patients in the planning phase as trial feasibility checks and during the trial as recruitment support, and (8) order sets to facilitate the complete and accurate performance of study visit procedures.

Results:

The number of approximately 100 new registrations per year in the voluntary trial registry in the clinical information system now matches the numbers of the existing mandatory trial registry of the hospital. Likewise, the yearly numbers of patients tagged as trial participants as well as the use of the standardized trial record templates increased to 2408 documented trial enrolments and 190 reports generated/month in the year 2013. Accounts for 32 clinical monitors have been established in the first 2 years monitoring a total of 49 trials in 16 clinical departments. A total of 15 months after adding the optional feature of hospital admission alerts of trial participants, 107 running trials have activated this option, including 48 out of 97 studies (49.5%) registered in the year 2013, generating approximately 85 alerts per month.

Conclusions:

The popularity of the presented tools in the clinical information system illustrates their potential to facilitate the conduct of clinical trials. The tools also allow for enhanced transparency on trials conducted at the hospital. Future studies on monitoring and inspection findings will have to evaluate their impact on quality and safety.
What does it mean to be a man? Psychosocial undercurrents in the voices of incarcerated (violent) Scottish teenage offenders
Authors: Holligan Chris , Deuchar Ross
Published: August 2014

This article explores connections between social strain, constructions and practices of masculinity and the prevalence of violence among a white working-class male demographic. The study’s evidence-base is qualitative research conducted in Scotland. It utilized life history interviews with a clinically significant sample of 40 incarcerated young male offenders convicted of violent crimes. Family, school and peer group ‘pressures’ coloured these young men’s trajectories to persistent violent reoffending. Their language highlights attachment and betrayal issues. Masculinity associated with Scottish history is a resource within Scotland which may impact on contemporary practices of masculinity. The article’s dominant thesis is that the young men’s violence reflects immersion in traumatic life histories. The masculinized cultures they encounter are likely to produce violence and limit opportunities which could help ameliorate attachment trauma.
Fanfare for the American
Authors: Billings Andrew , Angelini James R. , MacArthur Paul J. , Smith Lauren R. , Vincent John
Published: August 2014

Previous analyses have indicated strong tendencies for a host Olympic network to favor one’s home nation through enhanced clock-time, highlighting of star athletes from one’s home country, and more nuanced and positive dialogues. Analysis of NBC’s 2012 London Summer Olympic broadcast revealed significant differences between American and non-American athletes. Regarding athletic mentions, American athletes were more likely to be mentioned (55.8%) than all other athletes combined and composed 75% of the most-mentioned athletes within the broadcast. Regarding descriptions ascribed to the Olympians, American athletes were more likely to be depicted using subjective characterizations, disproportionately having their successes attributed to superior composure, commitment, intelligence, and consonance as well as having a greater level of comments pertaining to their modest/introverted nature. Conversely, non-American athletes were more likely to receive success attributions related to their superior experience and failures depicted as a lack of athletic skill—both largely objective measures.
Students and Social News
Authors: Rosengard Dana , Tucker-McLaughlin Mary , Brown Tim
Published: August 2014

The growth of new media is changing how news organizations publish their work, and the explosion of social networks is changing the way news consumers of all ages share information. As news outlets face an uncertain future and try to reach younger, newer audiences, the rapid growth of mobile devices means new opportunities to create, share, and consume news content. This study examines how young news consumers share and consume news content, specifically whether they are more likely to get news through social networks (Facebook and Twitter) or directly through news sources (news stations, newspapers, websites, and mobile apps). The findings here indicate that students may hear of news through social media, but rely on other internet sources to confirm it. Local news does not seem to carry as much weight with them, but they can be persuaded to pay attention to their college towns, if only for community news and information. The findings of this study could help producers of news content tailor their information to fit these new “publishing” formats to maintain (or perhaps increase) their audience.
Help Wanted
Authors: Wenger Debora , Owens Lynn , Thompson Patricia
Published: August 2014

Journalism outlets are moving quickly to embrace mobile technology as a means of gathering and disseminating news content. At the same time, journalism educators are ramping up to prepare their graduates for jobs that include the need for mobile skills. This mixed-methods research includes content analysis of more than 700 job postings from the Top 10 TV and newspaper companies in the United States, as well as interviews with news executives. The researchers found that a broad range of broadcast journalism positions require mobile skills, including producers, anchors, and reporters. Regardless of media platform, journalism employers want new hires to understand how to gather news with mobile devices, use them to interact with the social media audience, and how to format content appropriately for the medium. This research offers guidance to journalism programs looking to revise or create courses to provide graduates with these skill sets.
Level of A1C control and its predictors among Lebanese type 2 diabetic patients
Authors: Noureddine Hanan , Nakhoul Nancy , Galal Amal , Soubra Lama , Saleh Mounzer
Published: August 2014

Aim:

Lebanon is among the top 10 countries with the highest prevalence of diabetes in the Middle East region with estimates reaching as high as 16.6% in adults aged 20–79 years. The objective of this study was to assess the level of A1C control among a cohort of type 2 diabetic patients and factors associated with uncontrolled A1C.

Methods:

We carried out a retrospective observational study among type 2 diabetes mellitus patients attending an outpatient endocrinologist’s clinic between June 2008 and July 2012 in Beirut, Lebanon. Two groups were compared, based on their diabetic control (A1C < 7% and A1C ≥ 7%).

Results:

A total of 551 patients were included in this study, where 31.8% attained A1C control. Crude analyses showed that some factors were significantly associated with uncontrolled A1C, and these were long-standing diabetes, diabetes-related complications, uncontrolled blood pressure, lipid profile, as well as the use of metformin, sulfonylurea, or insulin. When multivariate analysis was carried out, the chances of having uncontrolled A1C were significantly higher among patients who developed neuropathy (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.11–3.90), had uncontrolled triglycerides (OR 1.98, 95% CI 1.33–2.94), used insulin (OR 4.52, 95% CI 2.32–8.83), and sulfonylureas (OR 2.88, 95% CI 1.88–4.40).

Conclusion:

Uncontrolled diabetes is more likely to exist in patients with neuropathy, uncontrolled triglycerides and those using insulin or sulfonylurea. Further research is needed to confirm the findings.
Olanzapine induced Q-Tc shortening
Authors: Shoja Shafti Saeed , Fallah Jahromi Parisa
Published: August 2014

Introduction

Prolongation of Q-Tc interval is commonly accepted as a surrogate marker for the ability of a drug to cause torsade de pointes. In the present study, safety of olanzapine versus risperidone was compared among a group of patients with schizophrenia to see the frequency of the electrocardiographic alterations induced by those atypical antipsychotics.

Method

Two hundred and sixty-eight female inpatients with schizophrenia entered in one of the two parallel groups to participate in an open study for random assignment to olanzapine ( n = 148) or risperidone ( n = 120). Standard 12-lead surface electrocardiogram (ECG) was taken from each patient at baseline, before initiation of treatment, and then at the end of management, just before discharge. The parameters that were assessed included heart rate (HR), P-R interval, QRS interval, Q-T interval (corrected = Q-Tc), ventricular activation time (VAT), ST segment, T wave, axis of QRS, and finally, interventricular conduction process.

Results

A total of 37.83% of cases in the olanzapine group and 30% in the risperidone group showed some Q-Tc changes; 13.51% and 24.32% of the patients in the olanzapine group showed prolongation and shortening of the Q-Tc, respectively, while changes in the risperidone group were restricted to only prolongation of Q-Tc. Comparison of means showed a significant increment in Q-Tc by risperidone ( p = 0.02). Also, comparison of proportions in the olanzapine group showed significantly more cases with shortening of Q-Tc versus its prolongation ( p = 0.01). No significant alterations with respect to other variables were evident.

Conclusion

Olanzapine and risperidone had comparable potentiality for induction of Q-Tc changes, while production of further miscellaneous alterations in ECG was more observable in the olanzapine group compared with the risperidone group. Also shortening of Q-Tc was specific to olanzapine.
Health-Related Quality of Life Among Online University Students
Authors: Maynard Pamela L. , Rohrer James E. , Fulton Lawrence
Published: August 2014

Background and Objectives: Online university students are a growing population whose health has received minimal attention. The purpose of this cross-sectional Internet survey was to identify risk factors for the health status among online university students. Methods: This online survey collected data from 301 online university students through a large, US-based participant pool and LinkedIn. Health status was measured using 3 elements of health-related quality of life (HRQOL): self-rated overall health (SRH), unhealthy days, and recent activity limitation days. All 3 measures were dichotomized. Results: The odds of poor SRH were higher for people who reported a body mass index in the overweight and obese categories (odds ratio [OR] = 2.99, P < .05) and for those who reported being smokers (OR = 2.52, P = .03). The odds of frequent unhealthy days were lower for those who made more than $35 000 compared with those who reported making less (OR = 0.50, P = .03) and those who exercised 4 or more times a week compared with those who exercised less (OR = 0.28, P < .05). The odds of frequent activity limitation were lower for those who reported an income of more than $35 000 (OR = 0.29, P = .04) and higher for persons who reported belonging to “other” race (OR = 14.75, P = .00). Conclusions: Universities might fruitfully target health promotion programs for online students who are low income, in disadvantaged racial groups, who are overweight, smoke, and who do not exercise.
Conceptual Frameworks and Research Models on Resilience in Leadership
Authors: Ledesma Janet
Published: August 2014

The purpose of this article was to discuss conceptual frameworks and research models on resilience theory. The constructs of resilience, the history of resilience theory, models of resilience, variables of resilience, career resilience, and organizational resilience will be examined and discussed as they relate to leadership development. The literature demonstrates that there is a direct relationship between the stress of the leader’s job and his or her ability to maintain resilience in the face of prolonged contact with adversity. This article discusses resilience theory as it relates to leadership development. The concept associated with resilience, which includes thriving and hardiness, is explored with the belief that resilient leaders are invaluable to the sustainability of an organization. In addition, the constructs of resilience and the history of resilience studies in the field of psychiatry, developmental psychopathy, human development, medicine, epidemiology, and the social sciences are examined. Survival, recovery, and thriving are concepts associated with resilience and describe the stage at which a person may be during or after facing adversity. The concept of “thriving” refers to a person’s ability to go beyond his or her original level of functioning and to grow and function despite repeated exposure to stressful experiences. The literature suggests a number of variables that characterize resilience and thriving. These variables include positive self-esteem, hardiness, strong coping skills, a sense of coherence, self-efficacy, optimism, strong social resources, adaptability, risk-taking, low fear of failure, determination, perseverance, and a high tolerance of uncertainty. These are reviewed in this article. The findings in this article suggest that those who develop leaders need to create safe environments to help emerging and existing leaders thrive as individuals and as organizational leaders in the area of resilience to impact productivity and sustainability.
Rasch Analysis of Lebanese Nurses’ Responses to the EIS Questionnaire
Authors: Clinton Michael , Alayan Nour , El-Alti Leila
Published: August 2014

This study examined the psychometric characteristics of a 32-item modified version of the Ethical Issues Scale (EIS). Data were collected from 59 registered nurses at the American University of Beirut Medical Centre (AUBMC). Data were analyzed using WINSTEPS Rasch analysis software. The four-category EIS rating scale needs modification for future studies in Lebanon. All EIS scale items need rewording prior to translation into Arabic to avoid confusion among Lebanese nurses. Principal component analysis (PCA) of residuals indicated the possible presence of additional dimensions. Additional EIS items are needed to improve targeting.
Big Five Measurement via Q-Sort
Authors: Fluckinger Chris D.
Published: August 2014

Socially desirable responding presents a difficult challenge in measuring personality. I tested whether a partially ipsative measure—a normatively scored Q-sort containing traditional Big Five items—would produce personality scores indicative of less socially desirable responding compared with Likert-based measures. Across both instructions to respond honestly and in the context of applying for a job, the Q-sort produced lower mean scores, lower intercorrelations between dimensions, and similar validity in predicting supervisor performance ratings to Likert. In addition, the Q-sort produced a more orthogonal structure (but not fully orthogonal) when modeled at the latent level. These results indicate that the Q-sort method did constrain socially desirable responding. Researchers and practitioners should consider Big Five measurement via Q-sort for contexts in which high socially desirable responding is expected.
Young Australians’ Attitudes to the Military and Military Service
Authors: Wadham Ben , Skrzypiec Grace , Slee Phillip
Published: August 2014

What are young Australians’ understandings of, and attitudes to, the military and military service? This article describes a pilot study of 320 young Australian university students’ attitudes to the military and military service during a time when Australia was engaged in the Afghanistan war. The main purpose of this study was to develop a survey instrument for further work in researching civil–military relations in Australia. Civil–military relations describe the complex set of relationships between the civil and military spheres. The role of the military, the relationship between the state and the military, the division of labor between civilian and military entities, foreign policy, and knowledge of military service are some of the fields that constitute a study of civil–military relations. This article reports on beliefs about, and attitudes to the specificities of military service and responses to the broader field of civil–military relations.
Current Physical and Mental Health of Former Collegiate Athletes
Authors: Kerr Zachary Y. , DeFreese J.D. , Marshall Stephen W.
Published: August 2014

Background:

There is a dearth of research on the current health of former collegiate athletes.

Purpose:

To examine the current health and related correlates in a cohort of former collegiate athletes who played in a diverse range of men’s and women’s sports with various levels of contact.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

Former collegiate athletes (N = 3657) were asked to complete an online questionnaire addressing sports history, medical history, and demographics. The questionnaire also included the Veterans RAND 12-Item Health Survey (VR-12), which yielded 2 composite scores for physical (PCS) and mental (MCS) health. The VR-12 PCS and MCS scores were compared with published US normative data using t tests and analyses of variance.

Results:

Mean PCS and MCS scores of the 797 respondents with complete data (21.9% of target sample; average, 14.5 years since last played collegiate sport) were 53.0 ± 6.1 and 51.7 ± 9.4, respectively. When stratified by age and sex, PCS and MCS scores were similar to normative scores in the United States. Lower PCS scores were associated with sustaining ≥3 concussions, playing in collision sports during college, and sustaining a career-ending injury (all, P < .001). No association was found between concussion and MCS scores ( P = .06). Among former collegiate athletes, prevalent medical conditions included anxiety (16.2%), hypercholesterolemia/high cholesterol (10.6%), and depression (10.4%). Additionally, 5.8% screened positive for alcohol dependence, and 5.8% screened positive for disordered eating (eg, binge eating, purging). These findings were more prevalent than those reported by the World Health Organization as representative of the US population. Conversely, there was a lower prevalence of depression, bipolar disorders, and attention deficit disorder, with or without hyperactivity (ADD/ADHD), than in the World Health Organization US population data sample.

Conclusion:

Former collegiate athletes appear similar to the general US population on many aspects of mental and physical health. However, observed health deficits associated with previous sports injuries warrant ongoing monitoring of the health and well-being of former collegiate athletes.
Prevalence of Osteochondritis Dissecans of the Capitellum in Young Baseball Players
Authors: Matsuura Tetsuya , Suzue Naoto , Iwame Toshiyuki , Nishio Susumu , Sairyo Koichi
Published: August 2014

Background:

Osteochondritis dissecans (OCD) of the capitellum is a well-recognized cause of elbow pain and disability in adolescent athletes. However, little is known about the prevalence of OCD in adolescent baseball players.

Purpose:

To determine the prevalence of OCD in baseball players aged 10 to 12 years based on ultrasonographic findings and to investigate the clinical characteristics of those with OCD lesions.

Study Design:

Descriptive epidemiology study.

Methods:

A total of 1040 players aged 10 to 12 years completed a questionnaire, ultrasound imaging, and radiographic examination to investigate OCD. Sonographic findings were classified into 5 grades (0, 1a, 1b, 2, and 3). Subjects with grade 1a, 1b, 2, or 3 were considered to have abnormal findings of the capitellum and were advised to undergo radiography. Radiographic and ultrasonographic findings were then compared. The prevalence of OCD was calculated, and differences by age and player position were determined.

Results:

Of the 1040 players, 33 (3.2%) had an abnormal finding on initial ultrasonography screening, and all 33 agreed to undergo radiography. Of them, 22 (66.7%) were found to have OCD of the capitellum on radiographs, giving an overall prevalence of 2.1%. Seven subjects (31.8%) had no history of elbow pain. Based on the radiographic classification, 20 subjects (90.9%) had stage I lesions. Analysis of OCD by age and player position revealed no significant differences.

Conclusion:

The prevalence of OCD of the capitellum was 2.1% in 1000 baseball players aged 10 to 12 years, with no differences in prevalence according to age or player position.
Study on self-lubricating coating prepared by electrospark deposition
Authors: Cao T. K. , Xiao Z. J.
Published: August 2014

It is still a matter to get thick self-lubricating coating with good tribological properties and strong bond. In the present work, Cu/BN coating was produced by electrospark deposition on mild steel. Chemical compatibility of Cu/BN/steel was analysed. The effects of the electric capacitance and deposition time on coating performance were studied, and the microscopic morphologies and structure of the coating were analysed. The results showed that there were no reactions in Cu/BN/steel. With the increase in capacitance, the surface roughness, friction coefficient and wear mass loss all increased. With the increase in deposition time, the surface roughness increased. Scanning electron microscope images showed that the lubricating coating is smooth, and thick coating (∼100 μm) was formed with metallurgical bond.
Functional characterization of the human dendritic cell immunodeficiency associated with the IRF8K108E mutation
Authors: Salem Sandra , Langlais David , Lefebvre François , Bourque Guillaume , Bigley Venetia , Haniffa Muzz , Casanova Jean-Laurent , Burk David , Berghuis Albert , Butler Karina M. , Leahy Timothy Ronan , Hambleton Sophie , Gros Philippe
Published: August 2014

Key Points

IRF8K108E mutation causes dendritic cell depletion, defective antigen presentation, and anergic T cells. IRF8K108E mutant protein is functionally null and shows defective nuclear targeting and increased proteasomal degradation.
Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis
Authors: Khor Sara , Beca Jaclyn , Krahn Murray , Hodgson David , Lee Linda , Crump Michael , Bremner Karen E , Luo Jin , Mamdani Muhammad , Bell Chaim M , Sawka Carol , Gavura Scott , Sullivan Terrence , Trudeau Maureen , Peacock Stuart , Hoch Jeffrey S
Published: August 2014

Background

Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.

Methods

We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG).

Results

Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087‒$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60–79 years old and $110,100/LYG for patients ≥80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age.

Conclusions

Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug.
Carbon nanotubes on nanoporous alumina: from surface mats to conformal pore filling
Authors: Fang Jinghua , Levchenko Igor , Han Zhao Jun , Yick Samuel , Ostrikov Kostya Ken
Published: August 2014

Control over nucleation and growth of multi-walled carbon nanotubes in the nanochannels of porous alumina membranes by several combinations of posttreatments, namely exposing the membrane top surface to atmospheric plasma jet and application of standard S1813 photoresist as an additional carbon precursor, is demonstrated. The nanotubes grown after plasma treatment nucleated inside the channels and did not form fibrous mats on the surface. Thus, the nanotube growth mode can be controlled by surface treatment and application of additional precursor, and complex nanotube-based structures can be produced for various applications. A plausible mechanism of nanotube nucleation and growth in the channels is proposed, based on the estimated depth of ion flux penetration into the channels.

PACS

63.22.Np Layered systems; 68. Surfaces and interfaces; Thin films and nanosystems (structure and non-electronic properties); 81.07.-b Nanoscale materials and structures: fabrication and characterization
Carbon nanotubes: properties, synthesis, purification, and medical applications
Authors: Eatemadi Ali , Daraee Hadis , Karimkhanloo Hamzeh , Kouhi Mohammad , Zarghami Nosratollah , Akbarzadeh Abolfazl , Abasi Mozhgan , Hanifehpour Younes , Joo Sang Woo
Published: August 2014

Current discoveries of different forms of carbon nanostructures have motivated research on their applications in various fields. They hold promise for applications in medicine, gene, and drug delivery areas. Many different production methods for carbon nanotubes (CNTs) have been introduced; functionalization, filling, doping, and chemical modification have been achieved, and characterization, separation, and manipulation of individual CNTs are now possible. Parameters such as structure, surface area, surface charge, size distribution, surface chemistry, and agglomeration state as well as purity of the samples have considerable impact on the reactivity of carbon nanotubes. Otherwise, the strength and flexibility of carbon nanotubes make them of potential use in controlling other nanoscale structures, which suggests they will have a significant role in nanotechnology engineering.
Cloning, secretory expression and characterization of recombinant β-mannanase from Bacillus circulans NT 6.7
Authors: Piwpankaew Yotthachai , Sakulsirirat Supa , Nitisinprasert Sunee , Nguyen Thu-Ha , Haltrich Dietmar , Keawsompong Suttipun
Published: August 2014

The mannanase gene of B. circulans NT 6.7 was cloned and expressed in an Escherichia coli expression system. The B. circulans NT 6.7 mannanase gene consists of 1,083 nucleotides encoding a 360-amino acid residue long polypeptide, belonging to glycoside hydrolase family 26. The full-length mannanase gene including its native signal sequence was cloned into the vector pET21d and expressed in E. coli BL21 (DE3). β-Mannanase activities in the culture supernatant and crude cell extract were 37.10 and 515 U per ml, respectively, with most of the activity in the cell extract attributed to the periplasmic fraction. In contrast, expression of mannanase was much lower when using the B. circulans NT 6.7 mannanase gene without its signal sequence. The optimum temperature of recombinant β-mannanase activity was 50°C and the optimum pH was 6.0. The enzyme was very specific for β-mannan substrates with a preference for galactomannan. Hydrolysis products of locust bean gum were various mannooligosaccharides including mannohexaose, mannopentaose, mannotetraose, mannotriose and mannobiose, while mannose could not be detected. In conclusion, this expression system is efficient for the secretory production of recombinant β-mannanase from B. circulans NT 6.7, which shows good characteristics for various applications.
Affinity purified anti-citrullinated protein/peptide antibodies target antigens expressed in the rheumatoid joint
Authors: Ossipova Elena , Cerqueira Cátia Fernandes , Reed Evan , Kharlamova Nastya , Israelsson Lena , Holmdahl Rikard , Nandakumar Kutty Selva , Engström Marianne , Harre Ulrike , Schett Georg , Catrina Anca I , Malmström Vivianne , Sommarin Yngve , Klareskog Lars , Jakobsson Per-Johan , Lundberg Karin
Published: August 2014

Introduction

A major subset of patients with rheumatoid arthritis (RA) is characterized by the presence of circulating autoantibodies directed to citrullinated proteins/peptides (ACPAs). These autoantibodies, which are commonly detected by using an enzyme-linked immunosorbent assay (ELISA) based on synthetic cyclic citrullinated peptides (CCPs), predict clinical onset and a destructive disease course. In the present study, we have used plasma and synovial fluids from patients with RA, for the affinity purification and characterization of anti-CCP2 reactive antibodies, with an aim to generate molecular tools that can be used in vitro and in vivo for future investigations into the pathobiology of the ACPA response. Specifically, this study aims to demonstrate that the surrogate marker CCP2 can capture ACPAs that bind to autoantigens expressed in vivo in the major inflammatory lesions of RA (that is, in the rheumatoid joint).

Methods

Plasma (n = 16) and synovial fluid (n = 26) samples were collected from RA patients with anti-CCP2 IgG levels of above 300 AU/mL. Total IgG was isolated on Protein G columns and subsequently applied to CCP2 affinity columns. Purified anti-CCP2 IgG was analyzed for reactivity and specificity by using the CCPlus® ELISA, in-house peptide ELISAs, Western blot, and immunohisto-/immunocytochemistry.

Results

Approximately 2% of the total IgG pool in both plasma and synovial fluid was CCP2-reactive. Purified anti-CCP2 reactive antibodies from different patients showed differences in binding to CCP2 and differences in binding to citrullinated peptides from α-enolase, vimentin, fibrinogen, and collagen type II, illustrating different ACPA fine-specificity profiles. Furthermore, the purified ACPA bound not only in vitro citrullinated proteins but, more importantly, in vivo-generated epitopes on synovial fluid cells and synovial tissues from patients with RA.

Conclusions

We have isolated ACPAs from plasma and synovial fluid and demonstrated that the CCP2 peptides, frequently used in diagnostic ELISAs, de facto act as surrogate antigens for at least four different, well-characterized, largely non-cross-reactive, ACPA fine specificities. Moreover, we have determined the concentration and proportion of CCP2-reactive IgG molecules in rheumatoid plasma and synovial fluid, and we have shown that the purified ACPAs can be used to detect both in vitro- and in vivo-generated citrullinated epitopes by various techniques. We anticipate that these antibodies will provide us with new opportunities to investigate the potential pathogenic effects of human ACPAs.
Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study
Authors: Sun Bing , He Hangyong , Wang Zheng , Qu Jiuxin , Li Xuyan , Ban Chengjun , Wan Jun , Cao Bin , Tong Zhaohui , Wang Chen
Published: August 2014

Introduction

Since 2008, severe cases of emerging human adenovirus type 55 (HAdV-55) in immunocompetent adults have been reported sporadically in China. The clinical features and outcomes of the most critically ill patients with severe acute respiratory distress syndrome (ARDS) caused by HAdV-55 requiring invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO) are lacking.

Methods

We conducted a prospective, single-center observational study of pneumonia with ARDS in immunocompetent adults admitted to our respiratory ICU. We prospectively collected and analyzed clinical, laboratory, radiological characteristics, sequential tests of viral load in respiratory tract and blood, treatments and outcomes.

Results

The results for a total of five consecutive patients with severe ARDS with confirmed HAdV-55 infection were included. All five patients were immunocompetent young men with a median age of 32 years. The mean time from onset to dyspnea was 5 days. Arterial blood gas analysis at ICU admission revealed profound hypoxia. Mean partial oxygen pressure/fraction of inspired oxygen was 58.1. Mean durations from onset to a single-lobe consolidation shown on chest X-rays (CXRs) and, from the first positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days, respectively. The viral load was higher than 1 × 108 copies in three patients and was 1 × 104 in one patient. It was negative in the only patient who survived. The mean duration for noninvasive positive pressure ventilation (NPPV) failure and IMV failure were 30.8 hours and 6.2 days, respectively. Four patients received venovenous ECMO. Four (80%) of the five patients died despite receiving appropriate respiratory support.

Conclusions

HAdV-55 may cause severe ARDS in immunocompetent young men. Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates, are the most frequent clinical manifestations of HAdV-55-induced severe ARDS. Viral load monitoring may help predict disease severity and outcome. The NPPV and IMV failure rates were very high, but ECMO may still be the respiratory support therapy of choice.

Trial registration

Clinicaltrials.gov NCT01585922. Registered 20 April 2012
Modeling luminal breast cancer heterogeneity: combination therapy to suppress a hormone receptor-negative, cytokeratin 5-positive subpopulation in luminal disease
Authors: Knox Aaron J , Scaling Allison L , Pinto Mauricio P , Bliesner Brian S , Haughian James M , Abdel-Hafiz Hany A , Horwitz Kathryn B
Published: August 2014

Introduction

Many Luminal breast cancers are heterogeneous, containing substantial numbers of estrogen (ER) and progesterone (PR) receptor-negative cells among the ER+ PR+ ones. One such subpopulation we call “Luminobasal” is ER-, PR- and cytokeratin 5 (CK5)-positive. It is not targeted for treatment.

Methods

To address the relationships between ER+PR+CK5– and ER–PR–CK5+ cells in Luminal cancers and tightly control their ratios we generated isogenic pure Luminal (pLUM) and pure Luminobasal (pLB) cells from the same parental Luminal human breast cancer cell line. We used high-throughput screening to identify pLB-specific drugs and examined their efficacy alone and in combination with hormone therapy in mixed-cell tumor models.

Results

We show that pLUM and MCF7 cells suppress proliferation of pLB cells in mixed-cell 3D colonies in vitro and that pLUM cells suppress growth of pLB cells in mixed-cell xenografts in vivo. High-throughput screening of 89 FDA-approved oncology drugs shows that pLB cells are sensitive to monotherapy with the epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib. By exploiting mixed-cell 3D colonies and mixed-cell solid mouse tumors models we demonstrate that combination therapy with gefitinib plus the anti-estrogen fulvestrant constitutes a robust treatment strategy.

Conclusions

We propose that response to combination endocrine/EGFR inhibitor therapies in heterogeneous Luminal cancers may improve long-term survival in patients whose primary tumors have been preselected for appropriate biomarkers, including ER, PR, CK5 and EGFR.
Current management of papillary thyroid microcarcinoma in Canada
Authors: Merdad Mazin , Eskander Antoine , De Almeida John , Freeman Jeremy , Rotstein Lorne , Ezzat Shereen , Sawka Anna M , Goldstein David P
Published: August 2014

Introduction

The detection of papillary thyroid microcarcinoma (PTMC) is on the rise and its optimal management remains controversial. Our aim was to determine the current self-reported management of PTMC amongst Canadian otolaryngologist-head and neck surgeons (OHNS) and endocrinologists and to identify factors influencing their management decisions.

Methods

A nine item web-based questionnaire was distributed to Canadian OHNS and endocrinologists. The three main domains were demographics, current management of PTMC scenarios, and factors influencing the decisions.

Results

One hundred and thirteen OHNS and endocrinologists completed the survey. Respondents were closely divided between recommending hemithyroidectomy (47%) or total thyroidectomy (43%) for a newly diagnosed PTMC in a low risk patient. Observation was the preferred method for managing PTMC detected incidentally after hemithyroidectomy (76%). Respondents chose more aggressive treatment for male patients compared to female patients. A positive history of thyroid cancer or previous radiation exposure was the most important factor influencing the management of PTMC.

Conclusion

The current practices of Canadian OHNS and endocrinologist largely coincide with available guidelines. The slight variation in practice might be explained by the opposing evidence supporting different management options. Given the dramatic increase in the incidence of PTMC we suggest future guidelines address the management of PTMC independently.
The ability to suppress macrophage-mediated inflammation in orbital fat stem cells is controlled by miR-671-5p
Authors: Lien Gi-Shih , Liu Jen-Fang , Chien Ming-Hsien , Hsu Wei-Tse , Chang Tzu-Hao , Ku Chia-Chi , Ji Andrea Tung-Qian , Tan Peng , Hsieh Ting-Lieh , Lee Liang-Ming , Ho Jennifer H
Published: August 2014

Introduction

Our previous works demonstrated that systemic orbital fat-derived stem cell (OFSC) transplantation was effective in ameliorating lipopolysaccharide (LPS)-induced extensive acute lung injury (ALI) in vivo mainly through paracrine regulation of macrophage-mediated cytokine-storm. In this study, we explore the molecular mechanism(s) of OFSCs regulating macrophage activity in a cytokine-inducible fashion.

Methods

LPS (100 ng/ml)-activated macrophages were treated by conditioned medium from OFSCs (OFSCs-CM) or non-contact cultured with OFSCs for 6 hours. The potency of OFSCs on macrophage proliferation and pro-inflammation ability were determined. Expression levels of pro-inflammatory cytokines in macrophages, inducible immuno-modulatory factors in OFSCs, were investigated. Deep sequencing analysis as well as interaction between microRNA (miRNA) and genes of immuno-modulators in OFSCs induced by activated macrophages was predicted by miRTar. Transfection of miRNA inhibitor into OFSCs was performed. Real-time RT-PCR and transplantation of OFSCs into mice with LPS-induced ALI confirmed the in vitro and in vivo mechanism.

Results

The paracrine effect of OFSCs on inhibition of macrophage pro-inflammatory cytokine release was more potent than induction of macrophage G0/G1 cell cycle arrest. OFSCs-CM suppressed LPS-induced inducible nitric oxide synthetase and the pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 alpha, and IL-1 beta expression in macrophages. Under non-contact culture, LPS-activated macrophages effectively triggered the expression of soluble immuno-modulating factors in OFSCs, i.e., IL-10, IL-1 receptor antagonist (IL-1 RA), indoleamine 2,3-dioxygenase, and soluble TNF receptor type II (sTNF RII). Under miRTar prediction, miR-671-5p was identified as a critical microRNA in regulation of multiple immune-modulating factors in OFSCs response to macrophages. The baseline level of miR-671-5p was high in OFSCs, and down-regulation of miR-671-5p upon co-culture with activated macrophages was observed. MiR-671-5p inhibitor transfection into OFSCs selectively enhanced the IL-1 RA and sTNF RII expressions. In addition, inhibition of miR-671-5p in OFSCs enhanced the anti-inflammatory ability against LPS-induced ALI.

Conclusion

The paracrine effect of OFSCs inhibits the pro-inflammatory ability and proliferation of macrophages. The immune-modulation capacity of OFSCs can be triggered by activated macrophages, and down-regulation of miR-671-5p enhances OFSC immuno-modulation ability by up-regulating IL-1 RA and sTNF RII expression.
Assessment of the neutrophilic antibody-dependent respiratory burst (ADRB) response toPlasmodium falciparum
Authors: Kapelski Stephanie , Klockenbring Torsten , Fischer Rainer , Barth Stefan , Fendel Rolf
Published: August 2014

Semi-immunity against Pf malaria is based on a combination of cellular and humoral immune responses. PMNs and IgGs are considered important components of this process, but the underlying mechanisms are unclear. We investigated the neutrophilic ADRB by analyzing the production of ROS in response to Pf antigen-specific IgGs bound to solid-phase immobilized antigens (sADRB) or whole merozoites (mADRB). We found that the PMN stimulations in each assay were based on different underlying mechanisms, demonstrating the importance of the assay set-up for the evaluation of antibody-triggered PMN responses. In the sADRB assay, ROS were produced externally, and by specific blocking of CD32(a)/FcγRII(a), the immediate neutrophilic response was abolished, whereas the removal of CD16(b)/FcγRIII(b) had no substantial effect. The key role of CD32(a) was confirmed using CD16(b)-deficient PMNs, in which similar changes of neutrophilic ADRB profiles were recorded after treatment. In the mADRB assay, ROS were produced almost exclusively within the cell, suggesting that the underlying mechanism was phagocytosis. This was confirmed using an additional phagocytosis assay, in which PMNs specifically ingested merozoites opsonized with Ghanaian plasma IgGs, seven times more often than merozoites opsonized with European plasma IgGs (P<0.001). Our data show that assay set-ups used to evaluate the responses of PMNs and perhaps other effector cells must be chosen carefully to evaluate the appropriate cellular responses. Our robust, stable, and well-characterized methods could therefore be useful in malaria vaccine studies to analyze the antimalarial effector function of antibodies.
Fluid salinity, clay content, and permeability of rocks determined through complex resistivity partition fraction decomposition
Authors: Nunes Barreto Alexandre , Alberto Dias Carlos
Published: August 2014

The types of physical mechanisms that generate induced electric polarization (IP) in rocks are here identified and their respective relaxation times are provided. Thus, the complex resistivity function associated with Dias’ model that describes the IP phenomenon is decomposed into partition fractions of an inverse third-degree polynomial in [Formula: see text]. Twelve rock samples’ data from the literature were used for this investigation. Using this procedure, two basic relaxations appear in the frequency range 1 mHz–1 MHz, where the phenomenon occurs. The first relaxation is associated with polarization caused by ionic diffusion proximal to the disseminated particle-electrolytic solution interfaces, which dominates in the low-frequency interval (approximately 1 mHz–100 Hz). The second process is capacitive-inductive polarization relaxation caused by an interaction between the electric double-layer capacitance and polarization-free pore resistances inside the polarization unit cell, which dominates in the high-frequency interval (approximately 10 kHz–1 MHz). At intermediate frequencies, these two processes combine to yield a transitional type of relaxation that dominates in the intermediate frequency interval (approximately 100 Hz–10 kHz). Our results, obtained using a given set of experimental data, provide a new method for determining the water salinity and clay content in the rock matrix without metallic particles. The rock permeability was also well determined by introducing Dias’ model parameter relationships and substituting the double-layer thickness for the grain size radius in a previously proposed formula.
Multidimensional interpolation using a model-constrained minimum weighted norm interpolation
Authors: Chiu Stephen K.
Published: August 2014

Fourier-based minimum weighted norm interpolation (MWNI) has been widely used to regularize land seismic data. However, it has difficulty interpolating regular missing data that are spatially aliased. Minimizing the aliasing artifacts is still a technical challenge in MWNI. I have developed a novel method to address the aliasing problem in MWNI using a prior model as constraints. The prior model was constructed by a linear interpolation along dominant dips to produce a fully regular initial model. The spectral weights derived from this initial model are typically not aliased and can be used to constrain the least-squares inversion in MWNI, frequency by frequency, to overcome the aliasing artifacts. This new interpolation scheme expands the capability of conventional MWNI to handle spatially aliased data that are often associated with steeply dipping structures, and it reconstructs more reliable interpolation results. Decimation tests of a simple 2D synthetic data set and a complex 3D synthetic salt model revealed that model-constrained MWNI outperforms the conventional MWNI method in handling spatially aliased data. I applied this method to a land field data set and carried out a comprehensive evaluation of interpolated data through the processes of prestack analyses, prestack time migration, and prestack depth migration. The 5D interpolation successfully filled in missing data, increased spatial sampling of prestack gathers, and considerably improved migrated stacked images from the prestacked time and depth imaging.