bluuebunny/crossref_metadata_2025 huggingface dataset:
Lessons from the Issue Correlates of War (ICOW) project
Authors: Hensel Paul R , Mitchell Sara McLaughlin
Published: October 2014

We present lessons and best practices for conflict data collection from the experiences of the ICOW project. Lessons include the development of a search strategy for potential events, the consultation of a broad range of sources, and recognition of the limitations of these sources. More general best practices address the development of detailed instructions for coders, detailed descriptions for data users, and strategies for managing research assistants and preserving project documentation.
Listening in narrative therapy: double listening and empathic positioning
Authors: Guilfoyle Michael
Published: October 2014

This article proposes an extension of narrative therapy’s ‘double-listening’ strategy. Based on the principle that people are multi-storied, double listening prompts the therapist to orient to two kinds of stories simultaneously. First, he or she hears the client’s explicit stories about the problem. These stories have an identity-constituting effect, and so the person positioned within them is considered a constituted subject. But the therapist also listens to sub-stories which hint at more agentive ways of being, aiming to facilitate movement from problem-saturated (constituted) positioning to agentive positioning. However, many clients do not spontaneously take this route, and critics have suggested that narrative therapists therefore rely on an unacknowledged directive, leading stance to generate this movement. In response, this article outlines a listening approach which defers attention to agentive stories and focuses in more detail on how the person is constituted in problematic stories. Here, the therapist orients to the question, ‘Who are you in this story?’ The answer is not always self-evident and often comes as something of a surprise. A theoretical examination of the relationship between person and narrative suggests that the clear, empathic articulation of the client’s constituted positioning can facilitate intentional and sometimes spontaneous resistances against it. This, in turn, clears the way for a more client-initiated than therapist-led exploration of agentive personal stories. Double listening does not explicitly attend to this resistance, which is hypothesised here as a vital intervening position between constituted and agentive positioning. A hypothetical case study illustrates these points.
Interpersonal Power
Authors: Sturm Rachel E. , Antonakis John
Published: October 2014

Power is a fundamental force in social relationships and is pervasive throughout various types of interactions. Although research has shown that the possession of power can change the power holder, the full extent of power’s consequences on individuals’ decision-making capabilities and social interactions within organizations is not fully understood. The goal of this paper is to review, synthesize, and critique the literature on power with a focus on its organizational and managerial implications. Specifically, we propose a definition of power that takes into account its three defining characteristics—having the discretion and means to enforce one’s will—and summarize the extant literature on how power influences individuals’ thoughts, emotions, and actions both in terms of prosocial and antisocial outcomes. In addition, we highlight important moderators of power and describe ways in which it can be studied in a more rigorous manner by examining methodological issues and pitfalls with regard to its measurement and manipulation. We also provide future research directions to motivate and guide the study of power by management scholars. Our desire is to present a thorough and parsimonious account of power’s influence on individuals within an organizational context, as well as provide a foundation that scholars can build upon as they continue to make consequential contributions to the study of power.
Treatment of Aspirin Exacerbated Respiratory Disease with a Low Salicylate Diet: A Pilot Crossover Study
Authors: Sommer Doron D. , Hoffbauer Stephanie , Au Michael , Sowerby Leigh J. , Gupta Michael K. , Nayan Smriti
Published: October 2014

Objective

Aspirin exacerbated respiratory disease (AERD) is comprised of aspirin/acetylsalicylic acid (ASA) sensitivity, bronchial asthma, and nasal polyposis. Treatment of this condition is challenging and may include topical/systemic steroids, endoscopic sinus surgery, and/or aspirin desensitization.

Study Design

A prospective crossover pilot study (n = 10) was conducted in which patients were randomized into either of 2 groups with 6 weeks of regular diet (R) or 6 weeks of a low salicylate diet (LS).

Setting

The study was conducted in a tertiary otolaryngology clinic.

Subjects

Patients with AERD were enrolled in the study.

Methods

Subjective (Sino‐nasal Outcome Test‐22 [SNOT‐22], Nasal Sinus Symptom Scale [NSSS], and the Asthma Control Questionnaire‐7 [ACQ‐7]) and objective outcome instruments (Peri‐Operative Sinus Evaluation [POSE] and Lund‐Kennedy Endoscopic Score [LKES]) were used to evaluate patients at baseline, 6 weeks (at crossover), and 12 weeks.

Results

Wilcoxon rank sum tests demonstrated that patients on the low salicylate diet had improved scores compared to their regular diet when evaluated by 4 of the 5 outcome measures (SNOT‐22 pLS = 0.0059, NSSS pLS = 0.0195, LKES pLS = 0.0039, POSE pLS = 0.005).

Conclusion

Results of the pilot study indicate that implementation of a low salicylate diet improves the nasal symptoms and nasal endoscopy findings of individuals with AERD. Further research is required to support these findings.
Contrast‐Enhanced Ultrasound for Differentiation of Benign and Malignant Thyroid Lesions: Meta‐analysis
Authors: Yu Dongmei , Han Yuna , Chen Taotao
Published: October 2014

Objective.

Contrast‐enhanced ultrasound (CEUS) is a new noninvasive modality for the diagnosis of thyroid nodules. However, the performance of CEUS in differentiating malignant and benign thyroid nodules has not been systematically evaluated. This meta‐analysis was performed to assess the accuracy of CEUS in diagnosing thyroid nodules.

Data Sources

PubMed, Embase, and the references of included studies were examined.

Review Methods

We recorded the characteristics of the included studies and assessed the quality of each study using the Quality Assessment of Diagnostic Accuracy Studies tool. The pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated. We also evaluated the publication bias.

Results

This meta‐analysis included 7 studies with a total of 597 thyroid nodules. The pooled the sensitivity, specificity, and positive and negative LR were 0.853, 0.876, 5.822, and 0.195, respectively. The DOR and AUC were 34.730 and 0.9162, respectively. Heterogeneity existed between the included studies. The results of subgroup analyses indicated that the evaluation processes are likely the predominant source of heterogeneity. No significant publication bias was observed.

Conclusion

Contrast‐enhanced ultrasound is a promising noninvasive technique for the differential diagnosis of benign and malignant thyroid nodules and could be a valuable supplemental method to fine‐needle aspiration.
Actor–partner model of physiology, negative affect, and depressive symptoms in mother–child dyadic interactions
Authors: Connell Arin M. , McKillop Hannah , Patton Emily , Klostermann Susan , Hughes-Scalise Abigail
Published: October 2014

Mother–child interactions can be emotionally charged, particularly when mothers experience difficulties with depression. Further, variation in the tone of such interactions has been linked to variation in youth functioning. Yet, little is known about the role of emotion regulatory processes during mother–child interactions. This study examined negative affective transactions between mothers and youth across 5-min conflict and fun-activity planning discussions, in relation to depressive symptoms and maternal and youth respiratory sinus arrhythmia (RSA). Maternal depressive symptoms predicted more negative affect. Maternal and youth RSA interacted with maternal depressive symptoms to predict both overall affect and the stability of affect across time. The beneficial effects of youth RSA were stronger, but maternal RSA weaker, in the face of elevated maternal depression.
Predictors of hospital stay and home care services use: A population-based, retrospective cohort study in stage IV gastric cancer
Authors: Mahar Alyson L , Coburn Natalie G , Viola Raymond , Johnson Ana P
Published: October 2014

Background:

Home care services use has been proposed as a means of reducing costs in palliative care by decreasing hospital stay without impacting quality of clinical care; however, little is known about utilization of these services in the time following a terminal cancer diagnosis.

Aim:

To examine disease, patient and healthcare system predictors of hospital stay, and home care services use in metastatic gastric cancer patients.

Design:

This is a population-based, retrospective cohort study. Chart review and administrative data were linked, using a 26-month time horizon to collect health services data.

Participants:

All patients diagnosed with metastatic gastric cancer in the province of Ontario between 2005 and 2008 were included in the study ( n = 1433).

Results:

Age, comorbidity, tumor location, and burden of metastatic disease were identified as predictors of hospital stay and receipt of home care services. Individuals who received home care services spent fewer days in hospital than individuals who did not (relative risk: 0.44; 95% confidence interval: 0.38–0.51). Patients who interacted with a high-volume oncology specialist had shorter cumulative hospital stay (relative risk: 0.62; 95% confidence interval: 0.54–0.71) and were less likely to receive home care services (relative risk: 0.80; 95% confidence interval: 0.72–0.88) than those who did not.

Conclusion:

Examining how differences in hospital stay and home care services use impact clinical outcomes and how policies may reduce costs to the healthcare system is necessary.
Exploring the Potential Cost-Effectiveness of Patient Decision Aids for Use in Adults with Obstructive Sleep Apnea
Authors: Trenaman Logan , Sadatsafavi Mohsen , Almeida Fernanda , Ayas Najib , Lynd Larry , Marra Carlo , Stacey Dawn , Bansback Nick
Published: October 2014

Background. There is increasing evidence highlighting the effectiveness of patient decision aids (PtDAs), but evidence supporting their cost-effectiveness is lacking. We consider patients with obstructive sleep apnea (OSA), in whom a PtDA may decrease nonadherence to treatment by empowering patients to receive the option that is most congruent with their own values. Objective. To determine the potential costs and benefits of delivering a PtDA to patients with moderate OSA. Methods. A Markov cohort decision-analytic model was developed for patients with moderate OSA, comparing a PtDA to usual care over 5 years from a societal perspective. Data for patient preference for treatment options was taken from a recent randomized crossover trial, event data (cardiovascular, motor vehicle accidents) came from national databases and published literature. Potential improvements in adherence are unknown, so we considered a realistic range of values. Outcome measures were 5-year costs (in 2010 Canadian dollars), quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). Results. When adherence to treatment was unchanged, the PtDA strategy was dominated by incurring lower QALYs and higher costs. When nonadherence was decreased by 20% in the PtDA arm (corresponding to an increase in adherence from 63% to 70% for continuous positive airway pressure and from 77% to 82% for mandibular advancement splints in year 1), the ICER fell to $62,414/QALY. Costs associated with the treatment devices and delivering the PtDA had the greatest effect on cost-effectiveness. Limitations. The model relies on surrogate measures and opinions for key parameters. Conclusions: The cost-effectiveness of PtDAs will depend on contextual factors, but a framework is described for properly considering their long-term cost-effectiveness. A number of important questions around the appropriateness of benefit measurement for PtDA trials are highlighted.
Correlation between whole tumor size and solid component size on high-resolution computed tomography in the prediction of the degree of pathologic malignancy and the prognostic outcome in primary lung adenocarcinoma
Authors: Saji Hisashi , Matsubayashi Jun , Akata Soichi , Shimada Yoshihisa , Kato Yasufumi , Kudo Yujin , Nagao Toshitaka , Park Jinho , Kakihana Masatoshi , Kajiwara Naohiro , Ohira Tatsuo , Ikeda Norihiko
Published: October 2014

Background

The presence of ground glass opacity (GGO) on high-resolution computed tomography (HRCT) is well known to be pathologically closely associated with adenocarcinoma in situ.

Purpose

To determine whether it is more useful to evaluate the whole tumor size or only the solid component size to predict the pathologic high-grade malignancy and the prognostic outcome in lung adenocarcinoma.

Material and Methods

Using HRCT data of 232 patients with adenocarcinoma who underwent curative resection, we retrospectively measured the whole tumor and solid component sizes with lung window setting (WTLW and SCLW) and whole tumor sizes with a mediastinal window setting (WTMW).

Results

There was significant correlation between the WTLW and the measurements of pathological whole tumor (pWT) (r = 0.792, P < 0.0001). The SCLW and WTLW values significantly correlated with the area of pathological invasive component (pIVS) (r = 0.762, P < 0.0001 and r = 0.771, P < 0.0001, respectively). The receiver operating characteristics area under the curve for WTLW, SCLW, and WTMW used to identify lymph node metastasis or lymphatic or vascular invasion were 0.693, 0.817, and 0.824, respectively. Kaplan-Meier curves of disease-free survival (DFS) and overall survival (OS) were better divided according to SCLW and WTMW, compared with WTLW. Multivariate analysis of DFS and OS revealed that WTMW was an independent prognostic factor (HR = 0.72, 95% confidence interval [CI] = 0.58–0.90, P = 0.004 and HR = 0.74, 95% CI = 0.57–0.96, P = 0.022, respectively).

Conclusion

The predictive values of the solid tumor size visualized on HRCT especially in the mediastinal window for pathologic high-grade malignancy and prognosis in lung adenocarcinoma were greater than those of whole tumor size.
Thyroid fine needle aspiration biopsy: do nodule volume and cystic degeneration ratio affect specimen adequacy and cytological diagnosis time?
Authors: Cengic Ismet , Tureli Derya , Ozden Ferhat , Bugdayci Onur , Aydin Hilal , Aribal Erkin
Published: October 2014

Background

A fine needle aspiration biopsy (FNAB) of thyroid nodules – the least invasive and most accurate method used to investigate malignant lesions – may yield non-diagnostic specimens even under ultrasonographic guidance.

Purpose

To evaluate the effects of thyroid nodule volume and extent of cystic degeneration on both the non-diagnostic specimen ratio as well as cytopathologist’s definitive cytological diagnosis time.

Material and Methods

In this single center study, FNAB was performed on 505 patients with single thyroid nodules greater than 10 mm. Nodule volume was calculated prior to FNAB and cystic degeneration ratio was recorded. All biopsies were performed by a single radiologist who also prepared specimen slides. Specimen adequacy and final diagnosis were made in the pathology laboratory by a single-blinded cytopathologist based on the Bethesda system. Definitive cytological diagnosis time was recorded upon reaching a definitive diagnosis.

Results

The specimen adequacy ratio was 85.3%. The mean nodule volume of adequate specimens was larger than those of non-diagnostic samples (6.00 mL vs. 3.05 mL; P = 0.001). There was no correlation between nodule volume and cytopathologist’s definitive cytological diagnosis time (r = 0.042). Biopsy of predominantly solid nodules yielded better specimen adequacy ratios compared to predominantly cystic nodules (87.8% vs. 75.3%; P = 0.028). Definitive cytological diagnosis times were longer in predominantly cystic nodules compared to predominantly solid nodules (376 s vs. 294 s; P = 0.019).

Conclusion

Predominantly cystic nodules are likely to benefit from repeated nodular sampling until the specimen is declared adequate by an on-site cytopathologist. If a cytopathologist is not available, obtaining more specimens per nodule may achieve desired adequacy ratios.
Semantic Memory Impairment for Biological and Man-Made Objects in Individuals With Amnestic Mild Cognitive Impairment or Late-Life Depression
Authors: Callahan Brandy L. , Joubert Sven , Tremblay Marie-Pier , Macoir Joël , Belleville Sylvie , Rousseau François , Bouchard Rémi W. , Verret Louis , Hudon Carol
Published: October 2014

Objective:

Amnestic mild cognitive impairment (aMCI) and late-life depression (LLD) both increase the risk of developing Alzheimer disease (AD). Very little is known about the similarities and differences between these syndromes. The present study addresses this issue by examining the nature of semantic memory impairment (more precisely, object-based knowledge) in patients at risk of developing AD.

Methods:

Participants were 17 elderly patients with aMCI, 18 patients with aMCI plus depressive symptoms (aMCI/D+), 15 patients with LLD, and 29 healthy controls. All participants were aged 55 years or older and were administered a semantic battery designed to assess semantic knowledge for 16 biological and 16 man-made items.

Results:

Overall performance of aMCI/D+ participants was significantly worse than the 3 other groups, and performance for questions assessing knowledge for biological items was poorer than for questions relating to man-made items.

Conclusion:

This study is the first to show that aMCI/D+ is associated with object-based semantic memory impairment. These results support the view that semantic deficits in aMCI are associated with concomitant depressive symptoms. However, depressive symptoms alone do not account exclusively for semantic impairment, since patients with LLD showed no semantic memory deficit.
People Overestimate Their Willingness to Reject Potential Romantic Partners by Overlooking Their Concern for Other People
Authors: Joel Samantha , Teper Rimma , MacDonald Geoff
Published: October 2014

Mate preferences often fail to correspond with actual mate choices. We present a novel explanation for this phenomenon: People overestimate their willingness to reject unsuitable romantic partners. In two studies, single people were given the opportunity to accept or decline advances from potential dates who were physically unattractive (Study 1) or incompatible with their dating preferences (Study 2). We found that participants were significantly less willing to reject these unsuitable potential dates when they believed the situation to be real rather than hypothetical. This effect was partially explained by other-focused motives: Participants for whom the scenario was hypothetical anticipated less motivation to avoid hurting the potential date’s feelings than participants actually felt when they believed the situation to be real. Thus, other-focused motives appear to exert an influence on mate choice that has been overlooked by researchers and laypeople alike.
Functional Assessment and Intervention by Nursing Assistants in Hospice and Palliative Care Inpatient Care Settings
Authors: Mueller Karen , Hamilton Gillian , Rodden Betheny , DeHeer Hendrick D.
Published: October 2014

This study assessed the impact of a nursing assistant-led functional intervention in an urban hospice. Thirty-three patients participated. A physical therapist trained 4 nursing assistants to assess 4 basic functional activities at admission and discharge and to provide daily activity training to intervention group participants. Control group participants were assessed at admission and discharge and received the usual standard of care. Both groups improved. The intervention group participants demonstrated significant improvement in the Timed up and Go test as well as their self-reported ability to achieve goals on the Patient-Specific Functional Scale. Control group participants made significant improvements in the ability to move from supine to sit in bed. These findings suggest that nursing assistants can provide activity-based assessment and intervention leading to improved function among patients in hospice.
Reliability of a New Radiological Method for Assessment of the Postoperative Immobilization of the First Metatarsophalangeal Joint
Authors: Moraiti Constantina , Klouche Shahnaz , Stiglitz Yves , Hardy Philippe , Bauer Thomas
Published: October 2014

Background:

The success of the operative treatment of mild to moderate hallux valgus (HV) relies greatly on the osseous union of the osteotomies at the desired position. Full weight-bearing is often allowed immediately postoperatively with special forefoot off-loading shoes. No precise methodology exists for the estimation of foot immobilization inside those shoes. The aim of this study was to assess the reliability of a new radiological measurement method to assess the immobilization of the first metatarsophalangeal (M1P1) joint inside a postoperative forefoot off-loading rocker shoe.

Methods:

A prospective single-center study was conducted during 2012. Patients operated on for mild or moderate HV deformity with a percutaneous technique by the same surgeon were included. Twenty-four patients (33 feet) fulfilled the inclusion criteria, all women and mean age of 56.6 ± 12.7 years. Standard lateral foot X-rays were obtained 1 week postoperatively with the patient standing in 2 positions, wearing the same forefoot off-loading rocker shoe: the foot flat on the ground (imitating midstance) and on the toes (imitating propulsion). The main evaluation criterion was the immobilization of the M1P1 joint estimated through the difference between the values of the M1P1 angle in the sagittal plane in these positions. Validity and reliability of this new measurement were assessed with Pearson’s correlation coefficients ( r) and intraclass correlation (ICC, ρ) coefficients.

Results:

The inter- and intraobserver reliability of the measurement was excellent to good. The mean M1P1 angle was 17.5 ± 7 degrees in the position imitating the midstance and 20.7 ± 7.5 degrees in the position imitating propulsion ( P < 10−5).

Conclusion:

This new radiological measurement for assessing immobilization of the M1P1 joint was a valid and reliable method.

Level of Evidence:

Level II, diagnostic study.
Evaluation of Algorithms for the Treatment of Problem Bleeding Episodes in Patients With Hemophilia Having Inhibitors
Authors: Young Guy , Teitel Jerome , d’Oiron Roseline , Leissinger Cindy , Berntorp Erik
Published: October 2014

The correlation between real-world clinical decisions and adherence to published treatment algorithms for problem bleeding episodes in patients with severe hemophilia and inhibitors and the resultant impact on clinical outcomes were assessed. Nine cases documenting treatment for problem bleeding episodes in patients with severe hemophilia and inhibitors were retrospectively reviewed. Adherence to treatment algorithms was rated on a scale of 1 to 5, 1 being no adherence and 5 being very high adherence. Adherence ratings >3 were assigned to 7 cases in which high adherence was associated with ≤4 days to achieve hemostatic control; hospitalization for ≤7 days was noted in 6 of these cases. In cases rated ≤3 (n = 2), time to hemostatic control ranged from 5 to 8 days and hospitalization duration ranged from 10 to 16 days. These findings suggest that adherence to treatment algorithms may be beneficial in treating problem bleeding events in patients with hemophilia and inhibitors.
A Comparison of Efficacy Between Recombinant Activated Factor VII (Aryoseven) and Novoseven in Patients With Hereditary FVIII Deficiency With Inhibitor
Authors: Faranoush M. , Abolghasemi H. , Mahboudi F. , Toogeh Gh. , Karimi M. , Eshghi P. , Managhchi M. , Hoorfar H. , Dehdezi B. Keikhaei , Mehrvar A. , khoeiny B. , Vaziri B. , Kamyar K. , Heshmat R. , Baghaeipour M. R. , Mirbehbahani N. B. , Fayazfar R. , Ahmadinejad M. , Naderi M.
Published: October 2014

Introduction:

This study compared the efficacy of Aryoseven with Novoseven to control bleeding episodes in patients with hemophilia A with inhibitors.

Methods:

Sixty-six patients were randomized into 2 groups, with 4 consecutive block randomization. These groups received Aryoseven and Novoseven dosages of 90 to 120 μg/kg intravenously every 2 hours.

Results:

Median (interquartile range) level of factor VIII (FVIII) inhibitor in groups A and B was 15.0 and 19.0 Bethesda Unit (BU) preadministration. Bleeding onset in group A was 1246 ± 1104 minutes and in group B was 2301 ± 1693 minutes ( P = .311). The Kavakli global response scores and treatment success rate was comparable in both the groups. The side effects in groups A (9.7%) and B (2.9%) were comparable.

Conclusion:

Biosimilar recombinant activated FVII is found to be as effective as Novoseven in the treatment of acute joint bleeding in patients with hemophilia with inhibitors. Its usage will decrease the gaps in hemophilia.
Real-World Learning of Public Affairs and Environmental Journalism
Authors: Freedman Eric , Poulson David
Published: October 2014

Traditionally, journalism majors gain professional experience before graduation through internships, part-time or summer jobs, and campus media. Those avenues are often insufficient to adequately prepare them for the professional workplace and professional standards. This essay explores two of a journalism school’s practice-based programs that provide such preparation: Capital News Service, covering state government, politics, and public policy, and Great Lakes Echo, covering environmental news in eight states and two provinces.
Effect of acarbose on postprandial blood glucose concentrations in healthy cats fed low and high carbohydrate diets
Authors: Singh Ranee , Rand Jacquie S , Coradini Marcia , Morton John M
Published: October 2014

Objectives

Feeding a low carbohydrate diet is recommended for diabetic cats; however, some cats may require diets containing moderate-to-high carbohydrate and may benefit from the use of therapeutic agents to improve glycemic control. The aim of the study was to determine the effect of the α-glucosidase inhibitor acarbose on postprandial plasma glucose concentration when combined with commercially available feline diets high and low in carbohydrate.

Methods

Twelve healthy, adult, non-obese, neutered cats were enrolled. Plasma glucose concentrations were assessed over 24 h after feeding high and low carbohydrate diets, with and without acarbose, during single and multiple meal tests, in a crossover study. Commercially available feline diets were used, which were high and low in carbohydrate (providing 51% and 7% of metabolizable energy, respectively).

Results

In cats fed the high carbohydrate diet as a single meal, mean 24 h glucose concentrations were lower when acarbose was administered. Mean glucose concentrations were lower in the first 12 h when acarbose was given once daily, whereas no significant difference was observed in mean results from 12–24 h. Acarbose had little effect in cats eating multiple meals. Compared with consumption of the high carbohydrate diet with acarbose, lower mean 24 h and peak glucose concentrations were achieved by feeding the low carbohydrate diet alone.

Conclusions and relevance

In healthy cats meal-fed diets of similar composition to the diets used in this study, acarbose has minimal effect when a low carbohydrate diet is fed but reduces postprandial glucose concentrations over 24 h when a high carbohydrate diet is fed. However, mean glucose concentrations over 24 h are still higher when a high carbohydrate diet with acarbose is fed relative to the low carbohydrate diet without acarbose. Future studies in diabetic cats are warranted to confirm these findings.
Alemtuzumab: A new therapy for active relapsing–remitting multiple sclerosis
Authors: Hartung Hans-Peter , Aktas Orhan , Boyko Alexey N
Published: October 2014

Alemtuzumab is a humanized monoclonal antibody directed against CD52 to deplete circulating T and B lymphocytes; lymphocyte depletion is followed by a distinctive pattern of T- and B-cell repopulation, changing the balance of the immune system. This review reports the efficacy and safety findings of the phase 2 CAMMS223 trial and the phase 3 CARE-MS I and II trials investigating alemtuzumab for the treatment of active relapsing–remitting MS. Alemtuzumab, administered intravenously, was shown to improve relapse rate versus subcutaneous interferon beta-1a in patients who were treatment-naive (CAMMS223 and CARE-MS I) or had relapsed on prior therapy (CARE-MS II), and to reduce sustained accumulation of disability (CAMMS223 and CARE-MS II). Important adverse events were infusion-associated reactions, serious infections and autoimmune events. A safety monitoring program allowed for early detection and management of autoimmune events. Recommendations for the monitoring of adverse events are made. Alemtuzumab’s mechanism of action, pharmacodynamics and opportunities for future research are discussed.
Effect of Alfacalcidol on multiple sclerosis-related fatigue: A randomized, double-blind placebo-controlled study
Authors: Achiron Anat , Givon Uri , Magalashvili David , Dolev Mark , Liraz Zaltzman Sigal , Kalron Alon , Stern Yael , Mazor Zeev , Ladkani David , Barak Yoram
Published: October 2014

Context:

Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS); however, there is no medication that has been approved specifically to treat MS-related fatigue.

Objective:

We aimed to evaluate the effect of vitamin D analogue, Alfacalcidol, on MS-related fatigue.

Design, settings, participants:

This was a randomized, double-blind, parallel group, placebo-controlled trial in patients with clinically definite MS by McDonald criteria conducted in a single university-affiliated medical center in Israel. Randomly selected patients from the Sheba MS Registry computerized database ( N=600) were assessed using the self-report Fatigue Severity Scale (FSS). Patients with clinically meaningful fatigue ( N=259) were further assessed for trial eligibility, and MS patients with significant fatigue ( N=158; 61%, 118 females, mean age 41.1 ± 9.2 years and mean disease duration of 6.2 ± 5.5 years) were included in the study and randomized to receive treatment or placebo.

Intervention:

Alfacalcidol (1 mcg/d, N=80) or placebo ( N=78) was administered for six consecutive months.

Main outcome measure:

The primary endpoint of the study was the change between Alfacalcidol and placebo-treated patients in the Fatigue Impact Scale (FIS) score; the cut-off point for improvement was defined as 30% decrease. All analyses followed the intention-to-treat principle and were performed for all participants based on the group they were randomly allocated regardless of whether or not they dropped out.

Results:

Alfacalcidol decreased the mean relative FIS score as compared with placebo (–41.6% vs. –27.4%, p=0.007, respectively). This advantage was further emphasized when the modified FIS (MFIS) relative change was calculated. Quality of Life (QoL) improved in Alfacalcidol-treated patients as compared with placebo in the RAYS psychological ( p=0.033) and social ( p=0.043) sub-scales. The Alfacalcidol-treated group had reduced number of relapses ( p=0.006) and higher proportion of relapse-free patients ( p=0.007). Reduction of relapses by Alfacalcidol became significant at 4 months of treatment, was sustained at 6 months and decayed 2 months after drug discontinuation. Alfacalcidol treatment was safe and no serious adverse events were recorded.

Conclusion:

Alfacalcidol is a safe and effective treatment strategy to decrease fatigue and improve QoL in patients with MS.
School performance as a marker of cognitive decline prior to diagnosis of multiple sclerosis
Authors: Sinay Vladimiro , Perez Akly Manuel , Zanga Gisela , Ciardi Celina , Racosta Juan M
Published: October 2014

Background:

For many years, cognitive impairment has been established as a well-known symptom of multiple sclerosis. Moreover, we know that it was present even at the beginning of the disease.

Objective:

In this case-control study, we decided to evaluate whether there is an impairment of cognitive functions even before onset in those patients who will eventually suffer from multiple sclerosis.

Methods:

We evaluated the overall school performance, and particularly school performance in math and language in a group of patients who would later develop the disease and we compared our findings with a control group.

Results:

We found that school performance was poorer in subjects who were to become patients. And we found that the later the start of the first symptom, the better the qualifications.

Conclusion:

Testing a premorbid cognitive deficit by a validated indirect evaluation method allowed us to verify that there was evidence of neurological compromise even before a clinical diagnosis or the completion of the first magnetic resonance imaging in patients who would then suffer from multiple sclerosis.
Prevalence of multiple sclerosis among immigrants in Norway
Authors: Berg-Hansen Pål , Moen Stine M , Sandvik Leiv , Harbo Hanne F , Bakken Inger J , Stoltenberg Camilla , Celius Elisabeth G
Published: October 2014

Background:

Multiple sclerosis (MS) prevalence is unevenly distributed worldwide. Immigration to Norway from countries with a lower MS prevalence is increasing. The aim of this study was to investigate MS prevalence in different immigrant populations in Norway and evaluate the effect of migrating from low- to high-risk regions of MS.

Method:

First- and second-generation immigrants from the largest immigrant populations were identified from the 2012 Norwegian prevalence study. Prevalence of MS in different ethnic groups was compared using the standardized prevalence ratio (SPR).

Results:

European and North-American immigrants had the highest prevalence of MS, whereas African and Asian immigrants had the lowest. The prevalence of first-generation Iranian immigrants was not significantly different from the total Norwegian population (SPR 0.70, 95% CI: 0.46–1.03). Second-generation immigrants from Pakistan (SPR 1.62, 95% CI: 0.88–2.76) had a strong increase in prevalence compared to the first generation (SPR 0.13, 95% CI: 0.05–0.28).

Conclusion:

MS prevalence among immigrants in Norway in general reflects the uneven distribution worldwide. The sharp increase in prevalence in immigrants seen in one generation suggests strong environmental factors affecting the MS risk in Norway.
Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease
Authors: Höftberger Romana , Sepulveda María , Armangue Thaís , Blanco Yolanda , Rostásy Kevin , Cobo Calvo Alvaro , Olascoaga Javier , Ramió-Torrentà Lluís , Reindl Markus , Benito-León Julián , Casanova Bonaventura , Arrambide Georgina , Sabater Lidia , Graus Francesc , Dalmau Josep , Saiz Albert
Published: October 2014

Objective:

We aimed to report the frequency and implications of antibodies to myelin oligodendrocyte glycoprotein (MOG-ab) in adults with demyelinating syndromes suspicious for neuromyelitis optica (NMO).

Methods:

Samples from 174 patients (48 NMO, 84 longitudinally extensive myelitis (LETM), 39 optic neuritis (ON), and three acute disseminated encephalomyelitis (ADEM) who presented initially with isolated LETM) were retrospectively examined for AQP4-ab and MOG-ab using cell-based assays.

Results:

MOG-ab were found in 17 (9.8%) patients, AQP4-ab in 59 (34%), and both antibodies in two (1.1%). Among the 17 patients with MOG-ab alone, seven (41%) had ON, five (29%) LETM, four (24%) NMO, and one (6%) ADEM. Compared with patients with AQP4-ab, those with MOG-ab were significantly younger (median: 27 vs. 40.5 years), without female predominance (53% vs. 90%), and the clinical course was more frequently monophasic (41% vs. 7%) with a benign outcome (median Expanded Disability Status Scale: 1.5 vs. 4.0). In eight patients with paired serum-cerebrospinal fluid (CSF) samples, five had MOG-ab in both samples and three only in serum. Antibody titres did not differ among clinical phenotypes or disease course. MOG-ab remained detectable in 12/14 patients (median follow-up: 23 months) without correlation between titres’ evolution and outcome.

Conclusion:

MOG-ab identify a subgroup of adult patients with NMO, LETM and ON that have better outcome than those associated with AQP4-ab. MOG-ab are more frequently detected in serum than CSF and the follow-up of titres does not correlate with outcome.
Alleged war criminals in the Netherlands: Excluded from refugee protection, wanted by the prosecutor
Authors: Bolhuis Maarten P. , van Wijk Joris
Published: October 2014

On the basis of Article 1F of the Refugee Convention, alleged perpetrators of international crimes can be excluded from refugee protection. This paper explains why the Netherlands – which is among the countries that apply Article 1F most actively – has, despite administrative commitment, so far successfully prosecuted only 4 out of approximately 800 excluded individuals. On the basis of an analysis of 1F files and interviews with policy makers, representatives from the National Prosecution Office and investigators, we identify the most relevant legal and practical challenges. Although domestic prosecution of suspects of international crimes is already complicated in itself, this article presents a number of additional factors that make prosecuting excluded persons even more challenging.
All-cause mortality and estimated renal function in type 2 diabetes mellitus outpatients: Is there a relationship with the equation used?
Authors: Fabbian Fabio , De Giorgi Alfredo , Monesi Marcello , Pala Marco , Tiseo Ruana , Misurati Elisa , Parisi Claudia , Volpi Riccardo , Graziani Roberto , Mikhailidis Dimitri P , Manfredini Roberto
Published: October 2014

Background:

We investigated the relationship between serum creatinine (SCr) and estimated glomerular filtration rate (eGFR), evaluated by different formulae, and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) outpatients.

Methods:

This observational cohort study considered 1365 T2DM outpatients, who had been followed up for a period of up to 11 years. eGFR was estimated using several equations.

Results:

Seventy subjects (5.1%) died after a follow-up of 9.8 ± 3 years. Univariate analysis showed that diagnosis of nephropathy (odds ratio (OR): 2.554, 95% confidence interval (CI): 1.616–4.038, p < 0.001) and microvascular complications (OR: 2.281, 95% CI: 1.449–3.593, p < 0.001) were associated with ACM. Receiving operating characteristic (ROC) curves showed that the areas under the curve for ACM were similar using the different eGFR equations. eGFR values were predictors of ACM, and the hazard ratios (HRs) of the different equations for eGFR estimation were similar.

Conclusion:

In our cohort of T2DM outpatients, different eGFR equations perform similarly in predicting ACM, whereas SCr did not.
Frederick Law Olmsted and the World’s Columbian Exposition
Authors: Schuyler David
Published: October 2014

This article presents the following three arguments: that Frederick Law Olmsted and his partner Henry Sargent Codman played the decisive role in the selection of Jackson Park as the site of the World’s Columbian Exposition; that Olmsted and his partners largely determined the site plan for the exposition, though the planning process was fluid and ongoing; and that Olmsted made the Lagoon and Wooded Island a largely naturalistic counterpoint to the formality of the rest of the exposition grounds.
From “Cesspool” to “The Greatest Improvement of Its Kind”
Authors: Finstein Amy D.
Published: October 2014

Wacker Drive is a staple of Chicago’s modern road network, allowing two levels of cars to zip along the Chicago River and connect to nearby highways and streets. The roots of this driving experience date to 1909, when Daniel Burnham and Edward Bennett proposed a comprehensive network of riverside boulevards in their Plan of Chicago. Engineered for traffic efficiency and draped with Beaux Arts garb, Wacker Drive introduced a new functional and architectural rationale to the riverfront. Charting its evolution from a casual idea to one of the Plan’s major accomplishments, this article positions Wacker Drive as an agent of architectural and civic change for Chicago.
Reconstruction of the transverse and dorsal-oblique amputations of the distal thumb with volar cross-finger flap using the index finger
Authors: Erken H. Y. , Akmaz I. , Takka S. , Kiral A.
Published: October 2014

We performed a retrospective review of 12 patients with dorsal oblique and transverse amputations of the distal thumb who were treated with a volar cross-finger flap from the index finger. The mean patient follow-up period was 28 months postoperatively (range: 19–43 months). There were no instances of flap loss, infection, or donor site complication in our series. The mean Semmes–Weinstein monofilament testing scores on the injured thumb and the donor site were 0.65 g (range: 0.16–2 g) and 0.51 g (range: 0.16–1 g), respectively. The mean 2-point discrimination testing scores on the injured thumb and the donor site were 4.5 mm (range: 3–8 mm) and 4.3 mm (range: 3–7 mm), respectively. This study suggests that the volar cross-finger flap using the index finger is a reliable technique in repairing dorsal oblique and transverse amputations of the distal thumb.

Type of study/level of evidence: Therapeutic IV
Quality improvement in general practice
Authors: Llanwarne Nadia , Dambha Hajira
Published: October 2014

Quality improvement describes the process of improving patients’ safety, experiences and health outcomes by systematically addressing individual and organisational processes. This is aimed at creating a ‘self-improving NHS’, in which individual clinicians are empowered to make changes toward a more efficient, safe and cost-effective healthcare system that is readily able to respond to patients’ needs. Improvement science is increasingly recognised as a central component to healthcare, and with general practice taking on added responsibility for the healthcare budget, it is essential that our training addresses aspects of healthcare organisation and improvements. This article offers a summary for AITs and GPs to further their understanding of improvement science. It provides some useful methods to facilitate the delivery of change in the GP surgery.
Negative Social-Evaluative Fears Produce Social Anxiety, Food Intake, and Body Dissatisfaction
Authors: Levinson Cheri A. , Rodebaugh Thomas L.
Published: October 2014

Social anxiety and eating disorders are highly comorbid, which suggests there are shared vulnerabilities that underlie the development of these disorders. Two proposed vulnerabilities are fear of negative evaluation and social appearance anxiety (i.e., fear of negative evaluation regarding one’s appearance). In the current experimental study ( N = 160 women), we measured these fears (a) through a manipulation comparing fear conditions, (b) with trait fears, and (c) with state fears. Results indicated that participants assigned to the fear of negative evaluation condition increased food consumption, whereas those assigned to the social appearance anxiety condition and high in trait social appearance anxiety experienced the highest amounts of body dissatisfaction. Participants in the fear of negative evaluation and social appearance anxiety conditions experienced elevated social anxiety. These results support the idea that negative-evaluation fears are shared vulnerabilities for eating and social anxiety disorders, but that the way these variables exert their effects may lead to disorder-specific behaviors.
A hyperactive Mpl-based cell growth switch drives macrophage-associated erythropoiesis through an erythroid-megakaryocytic precursor
Authors: Belay Eyayu , Miller Chris P. , Kortum Amanda N. , Torok-Storb Beverly , Blau C. Anthony , Emery David W.
Published: October 2014

Key Points

Increasing receptor stability of an Mpl-based cell growth switch improves ex vivo expansion from cord blood CD34+ cells. Expansion includes Epo-independent, macrophage-associated erythropoiesis from a novel erythroid-megakaryocytic precursor population.
Recurrent ETNK1 mutations in atypical chronic myeloid leukemia
Authors: Gambacorti-Passerini Carlo B. , Donadoni Carla , Parmiani Andrea , Pirola Alessandra , Redaelli Sara , Signore Giovanni , Piazza Vincenzo , Malcovati Luca , Fontana Diletta , Spinelli Roberta , Magistroni Vera , Gaipa Giuseppe , Peronaci Marco , Morotti Alessandro , Panuzzo Cristina , Saglio Giuseppe , Usala Emilio , Kim Dong-Wook , Rea Delphine , Zervakis Konstantinos , Viniou Nora , Symeonidis Argiris , Becker Heiko , Boultwood Jacqueline , Campiotti Leonardo , Carrabba Matteo , Elli Elena , Bignell Graham R. , Papaemmanuil Elli , Campbell Peter J. , Cazzola Mario , Piazza Rocco
Published: October 2014

Key Points

Whole-exome sequencing reveals the presence of recurrent somatic mutations of ETNK1 in patients with atypical chronic myeloid leukemia. ETNK1 mutations impair the catalytic activity of the enzyme, causing a decrease in the intracellular levels of phosphoethanolamine.
Differentiation-inducing and anti-proliferative activities of lupeol on canine melanoma cells
Authors: Ogihara Kikumi , Naya Yuko , Okamoto Yoshiharu , Hata Keishi
Published: October 2014

Canine melanoma is the most common oral malignant tumor reported in the field of veterinary medicine. We found that lupeol, a lupine triterpene, inhibited mouse melanoma cell growth in vitro and in vivo by inducing cell differentiation. In the present study, we examined the differentiation-inducing activities of lupeol on 4 canine melanoma cells in vitro and in vivo.

The induction of canine melanoma cell differentiation by lupeol was confirmed by evaluating some differentiation markers such as tyrosinase with real-time RT-PCR. Furthermore, we transplanted canine melanoma cells into a severe combined immunodeficiency mouse, and studied the anti-progressive effects of lupeol on tumor tissue.

The gene expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related protein-2, which are markers of pigment cell differentiation, was induced in 4 canine oral malignant melanoma cells by lupeol, and the agent markedly inhibited tumor progression in canine melanoma-bearing mice.