bluuebunny/crossref_metadata_2025 huggingface dataset:
Episodic Volunteering and Retention
Authors: Hyde Melissa K. , Dunn Jeff , Bax Caitlin , Chambers Suzanne K.
Published: December 2014

Episodic volunteers (EVs) are vital for non-profit organization activities. However, theory-based research on episodic volunteering is scant and the determinants of episodic volunteering are not well understood. This study integrates the volunteer process model and three-stage model of volunteers’ duration of service to explore determinants of EV retention. A cross-sectional survey of 340 EVs assessed volunteering antecedents, experiences, and retention. Social/enjoyment (β = .17) and benefit (β = −.15) motives, social norm (β = .20), and satisfaction (β = .56) predicted Novice EV (first experience) retention; satisfaction (β = .47) and commitment (β = .38) predicted Transition EV (2-4 years intermittently) retention; and supporting the organization financially (β = .31), social norm (β = .18), satisfaction (β = .41), and commitment (β = .19) predicted Sustained EV (5-6 years consecutively) retention. Integrated theoretical approaches appear efficacious for understanding EV retention. An Episodic Volunteer Engagement and Retention model is proposed for further testing in prospective work.
Gender, religion and the ‘developmentalization’ of male Muslim imams in Bangladesh
Authors: Zakiuddin Almas
Published: December 2014

In this article, I explore how entanglements between two international development organizations, the state and male Muslim imams or congregational prayer leaders, in Bangladesh from the early 1980s to the present time combine in the ‘developmentalization’ of thousands of male imams as mobilized, institutionally fixed repositories of male Islamic authority. Following Arturo Escobar’s argument that development discourse organizes and manages the South through problematizing specific issues that development apparatuses then proceed to resolve, I suggest that male imams are mobilized in order to satisfy specific contingencies elaborated by, among other things, development itself. Drawing on textual analysis and empirical work with development policymakers and imams in Bangladesh, I analyse the origins, conditions and exigencies under which male imams become partners in development activity, including programmes that target women’s reproductive health choices and provide intimate, personal contraceptive care. I adopt a critical feminist development studies perspective, wherein gender concerns and women’s issues are a critical consideration of development interventions in the South, to explicate how both gendered resistance and complicity are evident in complex ways within these alliances. My research suggests that although evident in Bangladesh, imam mobilizations are facilitated by linkages at local, national, regional and transnational levels.
The persuasive role of information: The case of EITC reminders by mail
Authors: Strawczynski Michel , Myronichev Natalia
Published: December 2014

While the cost estimates of reminders by mail are readily available for policy-makers, estimation of their benefits requires thoughtful analysis. For this purpose, we used data about earned income tax credit (EITC) reminders by mail which the Israel Tax Authority sent to eligible applicants during the period of 2008–2011. Using a framework of repeated letters, we identify those who applied for the EITC in response to such a reminder. Using an analytical framework of learning, we characterised different types of reactions to these reminders, with an emphasis on their role in persuading individuals to apply. We estimate the persuasive role of receiving reminders – which prompts an increased uptake – at 1.5%. Using independently-performed questionnaires, we characterise the ‘letter-dependent’ population, defined as those who depended on receiving reminders for requesting the EITC transfer. We find that these applicants were older; they received a lower transfer, they had a fair level of knowledge of the programme and they did not actively seek out information about the amount of the expected transfer.
A review of empirical modeling techniques to optimize machining parameters for hard turning applications
Authors: Dureja JS , Gupta VK , Sharma Vishal S , Dogra Manu , Bhatti Manpreet S
Published: December 2014

There has been a tremendous development in the field of modeling and optimization methods starting from Taylor’s tool life model. Use of costly tools such as polycrystalline cubic boron nitride, polycrystalline diamond and ceramics in high-end computer numerical control machining forces the researcher to minimize the experimental runs to achieve the best cutting conditions with minimum tool wear and overall production cost. Machining process optimization to achieve said objectives comprises selecting optimum cutting parameters by applying low-cost mathematical models. This article attempts to evaluate the applicability of various modeling and optimization methods to specific response parameters in hard turning problems. Various empirical modeling techniques such as linear regression modeling, artificial neural networks, polynomial and fuzzy modeling along with process optimization through Taguchi, response surface methodology and genetic algorithm for hard turning applications have been discussed in length to provide the production engineers a ready database to compare relative merits and suitability of these techniques for a particular machining application. Also, article discusses integration of different modeling and optimization techniques to achieve desired goals when a single optimization technique is not able to provide the acceptable solution. The last part of the article highlights the current trends in hard turning applications and research priorities for future work.
Wear and machinability properties of AS series magnesium alloys
Authors: Akyüz Birol
Published: December 2014

This study investigates the effect of the amount of Al amount in AS series magnesium alloys on wear resistance and machinability. Changes in mechanical properties, wear resistance, and machinability were studied depending on the Al amount in magnesium alloys containing 1% Si. Therefore, AS series magnesium alloys (AS11, AS21, AS41, AS61, and AS91) (containing Al in various degrees ranging from 1% to 9%) were used in this study. It was observed that the hardness of intermetallic phases in the microstructure of AS series magnesium alloys affected wear resistance and machinability depending on the increase in Al amount. Mg2Si intermetallic phase in the microstructure of AS91 alloy was established to reduce machinability while increasing hardness and wear resistance.
Comparative investigation on wear behavior and self-sharpening phenomenon of polycrystalline cubic boron nitride and monocrystalline cubic boron nitride grains in high-speed grinding
Authors: Ding Wen-Feng , Miao Qing , Zhu Ye-Jun , Xu Jiu-Hua , Fu Yu-Can
Published: December 2014

High-speed grinding experiments were conducted on a nickel-based superalloy Inconel718 with the monolayer brazed wheel containing monocrystalline cubic boron nitride grains and polycrystalline cubic boron nitride grains. Comparative investigation on the wear behavior and self-sharpening phenomenon of polycrystalline cubic boron nitride and monocrystalline cubic boron nitride grains was carried out based on the fractal analysis. The results obtained indicate that the wear process of the monocrystalline cubic boron nitride grain cutting edges is, in order, attritious wear → large fracture → micro fracture → large fracture → attritious wear, while that of the polycrystalline cubic boron nitride grain cutting edges is micro fracture → attritious wear → micro fracture. Micro fracture of polycrystalline cubic boron nitride grain occurs easily in the particular zone where large impact load is formed due to the first contact between the grain cutting edges and the workpiece material. The fractal dimension of monocrystalline cubic boron nitride wheel is 2.040–2.047, while that of the polycrystalline cubic boron nitride wheel is 2.049–2.054, which indicates that the polycrystalline cubic boron nitride grain cutting edges are finer than that of the monocrystalline cubic boron nitride counterparts. Compared to monocrystalline cubic boron nitride grains, better performance, that is, smaller radial wheel wear, lower grinding force and forces ratio, is obtained for polycrystalline cubic boron nitride grains due to micro fracture behavior and self-sharpening phenomenon in high-speed grinding.
Reaction forces identification of a quadruped robot with parallel-serial leg structure
Authors: Tian Xinghua , Gao Feng , Qi Chenkun , Chen Xianbao
Published: December 2014

Interactions between feet and environment influence the stability and mobility of legged robot. This paper proposes a model to indirectly identify 3 degrees of freedom feet reaction forces for a quadruped robot with parallel-serial legs. The research platform is called Baby-Elephant: a heavy-duty four-legged robot designed for nuclear plant maintenance and disaster relief purposes. Each leg has three hydraulic actuators. With the pressure data from pump and hydraulic actuators, a double-chamber model with experimental derived friction is used to obtain the actuated force. The reaction forces model, including joint and foot forces, is simplified into an explicit function. Comparison between CAD simulation and analytical results shows the effectiveness of the model. A walking experiment with load cells proves the model is validate in practical application. The proposed model is used to identify the foot contact phase and the zero momentum point during crawling gait walking.
Differences in the Effects of Crowding on Size Perception and Grip Scaling in Densely Cluttered 3-D Scenes
Authors: Chen Juan , Sperandio Irene , Goodale Melvyn Alan
Published: December 2014

Objects rarely appear in isolation in natural scenes. Although many studies have investigated how nearby objects influence perception in cluttered scenes (i.e., crowding), none has studied how nearby objects influence visually guided action. In Experiment 1, we found that participants could scale their grasp to the size of a crowded target even when they could not perceive its size, demonstrating for the first time that neurologically intact participants can use visual information that is not available to conscious report to scale their grasp to real objects in real scenes. In Experiments 2 and 3, we found that changing the eccentricity of the display and the orientation of the flankers had no effect on grasping but strongly affected perception. The differential effects of eccentricity and flanker orientation on perception and grasping show that the known differences in retinotopy between the ventral and dorsal streams are reflected in the way in which people deal with targets in cluttered scenes.
Effect of the volute tongue profile on the performance of a low specific speed centrifugal pump
Authors: Alemi Hamed , Nourbakhsh Seyyed Ahmad , Raisee Mehrdad , Najafi Amir Farhad
Published: December 2014

In this study, we investigated the effects of volute tongue geometry variation on the head, efficiency, and radial force of a centrifugal pump. Numerical simulation modeling based on [Formula: see text] turbulence with automatic near wall treatments was used to simulate the turbulent flow. The effect of blade position with respect to the volute tongue on instantaneous pump characteristics was investigated. The parametric studies were done for cutwater gap, tongue shape, and volute tongue angle. Numerical results showed that the large cutwater gap caused lower radial force, especially at high flow rates. Investigations using various volute tongue shapes indicated that the short tongue volute decreased the radial force at design and low flow rates. Considering all aspects, the most satisfactory volute tongue angle was found to be 5° less than the outlet velocity angle of the impeller; yielding about 40% lower radial force than others at the design point.
Estimation and predictive control of nonlinear diffusion processes with application to drying of coatings
Authors: Cao Xiaoqing , Ayalew Beshah
Published: December 2014

This article deals with the estimation and control of a class of distributed parameter processes dominated by nonlinear diffusion. The major challenges in control of such systems lie in the nonlinear infinite-dimensional nature of the systems and the lack of direct sensing for relevant system states. In the proposed scheme, the proper orthogonal decomposition-Galerkin method is adopted to derive a reduced-order model in terms of temporal coefficients from the original system described by nonlinear partial differential equation(s). To overcome the sensing problem, the unscented Kalman filter is implemented to estimate the temporal coefficients of the reduced-order model online and subsequently reconstruct the distributed system states. A set of improved sufficient conditions are also established to ensure stability of the estimation scheme. Then, once these difficulties are addressed, a nonlinear model predictive control scheme is formulated to achieve desired control objectives such as trajectory tracking for distributed states, energy optimization and quality control. The proposed estimation and control scheme is demonstrated via an application to infrared drying of coatings in the automotive industry.
Mobile robot arm trajectory generation for operation in confined environments
Authors: Wall David Galvão , Economou John , Goyder Hugh , Knowles K , Silson Peter , Lawrance Martin
Published: December 2014

This article gives a novel trajectory generation algorithm which is suitable for operating in confined and dangerous environments. A technique is developed which can, in real time, calculate the existence of a safe path for navigating a robotic manipulator arm between obstacles without collision and accurately generating an efficient path between them. A map of the environment is created in the control servo domain using existing environment data where each dimension of the map space represents one of the degrees of freedom of the manipulator. The map is a multi-dimensional space that represents the control ranges of the manipulator and which contains obstacles to be avoided. The start and desired locations of the arm end effector can be converted into this space so that a path can be generated between them. The space is split into a graph of nodes, and a Dijkstra’s shortest path algorithm is used to generate a safe trajectory. If a successful trajectory can be found, then the arm desired location is achievable and the list of nodes that make up the trajectory form a set of control requirements that can be followed to drive the arm to its desired geometry.
Sediment dynamics and hydrologic events affecting small lacustrine systems on the southern-central Tibetan Plateau – the example of TT Lake
Authors: Ahlborn Marieke , Haberzettl Torsten , Wang Junbo , Alivernini Mauro , Schlütz Frank , Schwarz Anja , Su Youliang , Frenzel Peter , Daut Gerhard , Zhu Liping , Mäusbacher Roland
Published: December 2014

A sedimentological, geochemical, micropaleontological, and palynological study of a lacustrine sediment record from the small TT Lake (southern-central Tibetan Plateau) shows that the background sedimentation was frequently interrupted by event-related deposits. These event-related deposits are interpreted as the result of hydrologic events that are triggered by above-average precipitation events. In total, 11 events were recorded in the TT Lake sequence. Two types can be differentiated: fluvial runoff events caused by precipitation that carried sediment in suspension into the lake and a sediment mass transport caused by torrential precipitation. The hydrologic events appear to be decoupled from long-term climate and environmental variations, but there is evidence that anthropogenic impact, in terms of pastoralism, might have favored the runoff events. The multi-proxy approach proved to be valuable and allowed for a detailed study of sedimentary processes within the lake and its watershed in order to assess their triggering processes and dynamics. The findings show the complexity of these sedimentary processes and their controlling factors, and the study aims to improve their understanding. This study is the first effort to investigate event-related deposits and sedimentary processes on the Tibetan Plateau and its triggering processes and dynamics by utilizing lacustrine sediment records.
Palaeolimnological evidence of Bosmina morphotypes appearance in the late Holocene
Authors: Błędzki Leszek A , Szeroczyńska Krystyna
Published: December 2014

Lacustrine sediments retain Cladocera (Crustacea) subfossils (carapaces, ephippia, head shields, and postabdomens) from the Holocene, which allows reconstructing past aquatic communities and environmental changes. In late Holocene (Subatlantic) fossils, among many Cladocera species, we noticed the appearance of several Bosmina ( Eubosmina) species in lakes surrounding the Baltic Sea. These species were never recorded in the early Holocene. The appearance of these species is a record of very recent speciation, which took place during the last millennium in lakes surrounding the Baltic Sea. Contemporary data show co-occurrence of several Bosmina ( Eubosmina) species ( longispina, kessleri, reflexa, ruehei, coregoni, gibbera, thersites). These species are not a product of invasion or introgressive hybridization, but in fact, they are probably a product of speciation. Here, we present the palaeolimnological evidence of this speciation from the only one species, Bosmina ( Eubosmina) longispina, found in lacustrine sediments from the last interglacial and glacial periods.
The context to challenging discrimination against ethnic minorities and migrant workers at work
Authors: Jefferys Steve
Published: December 2014

Over the last decade trade union responses to racism and discrimination against ethnic minority and migrant workers have often reflected two competing discourses, one promoting anti-discrimination legislation and the other, xenophobia and anti-immigrant sentiment. The Racial Equality Directive was adopted in 2000 to enter into force in 2003. Yet 11 September 2001 unleashed a tide of anti-Muslim prejudice and 10 years later, in the aftermath of the 2008 economic crisis, a study by the EU Agency for Fundamental Rights found that the Directive had had little impact on underlying levels of racism. In this article initial criticisms of the Directive are revisited. The impact of rising numbers of migrants and of slightly higher public intolerance of the ‘racialized outsider’ are considered. The article argues that racism is playing a growing role in justifying unequal treatment in employment. Its presence makes the solidarity needed to ensure proper social regulation of the increasingly ‘open’ European economy more difficult to achieve.
Their own stories – how Polish construction workers posted to Sweden experience their job situation, or resistance versus life projects
Authors: Thörnqvist Christer , Bernhardsson Sebastian
Published: December 2014

This study draws primarily on in-depth interviews with nine male Polish construction workers posted to Sweden in the early 2010s. The emphasis lies on their own experiences of being exposed to what they saw as unjust working conditions, and why they accept them or react against them. The overarching research questions are why Polish workers go to Sweden, and, more importantly, why they stay even when they feel unfairly treated or directly cheated by their employers. The main points of interest are wages, work environment, employment contracts and relations with different labour market players, including the EU. It was very clear that none of the Polish workers had ever heard of the EU Posted Workers Directive. Still, the lack of serious resistance, our study argues, was not because of poor knowledge about their legal rights, but was linked to a wish to fulfil a ‘life project’ back home in Poland, such as building a house, starting a company, being able to afford to start a family and raise children, or saving for retirement. This wish helped the workers to swallow ‘unfair’ treatment.
Music practice and participation for psychological well-being: A review of how music influences positive emotion, engagement, relationships, meaning, and accomplishment
Authors: Croom Adam M
Published: December 2014

In “Flourish,” Martin Seligman maintained that the elements of well-being consist of “PERMA: positive emotion, engagement, relationships, meaning, and accomplishment.” Although the question of what constitutes human flourishing or psychological well-being has remained a topic of continued debate among scholars, it has recently been argued in the literature that a paradigmatic or prototypical case of human psychological well-being would largely manifest most or all of the aforementioned PERMA factors. Further, in “A Neuroscientific Perspective on Music Therapy,” Stefan Koelsch also suggested that “Music therapy can have effects that improve the psychological and physiological health of individuals,” so it seems plausible that engaging in practices of music can positively contribute to one living a more optimally flourishing life with greater psychological well-being. However, recent studies on music practice and participation have not yet been reviewed and integrated under the PERMA framework from positive psychology to further explore and explicate this possibility. This article therefore contributes to extant work by reviewing recent research on psychological well-being and music to offer support for the claim that music practice and participation can positively contribute to one living a flourishing life by positively influencing their emotions, engagement, relationships, meaning, and accomplishment.
The Meaning of Survivorship as Defined by African American Breast Cancer Survivors
Authors: Davis Claudia M. , Myers Hector F. , Nyamathi Adeline M. , Lewis MaryAnn , Brecht Mary-Lynn
Published: December 2014

Background: While there is an abundance of cancer survivorship research among various racial/ethnic groups, there is a paucity of research on survivors of African descent. To date, the meaning of survivorship has not been reported exclusively among African American breast cancer survivors (AABCS). Purpose: The purpose was to describe and understand the meaning of survivorship among community-dwelling AABCS, mostly recruited from breast cancer support groups. Method: Using a qualitative descriptive approach, an open-ended questionnaire explored the meaning of survivorship among 155 AABCS. An analysis of the content was performed. Results: Among AABCS, survivorship meant having a strong spiritual base, thriving, being resilient, and being altruistic. The survivors self-identified with and embraced the term survivor.Conclusions: These results provide an important understanding of the perspectives and meaning of survivorship among AABCS and may assist in developing cancer survivorship care plans that are relevant, responsive, patient centered, and culturally appropriate.
Long-Term Care of the Elderly in Uruguay
Authors: Figueredo-Borda Natalie , Zabalegui-Yárnoz Adelaida
Published: December 2014

Objective: To explore the perception of care of the elderly in long-term centers. Design: Qualitative study through participant observation and 23 in-depth interviews with administrators, caregivers, and residents between January 2011 and January 2012 in nine long-term care centers in Uruguay. From analysis, three care-perception factors emerged: (a) meaning of care, (b) experience of care, and (c) care continuity. Conclusion: Care of the elderly in nursing homes is perceived as a duty. There is an exchange of feelings and recognition of the caregiver is needed. However, the need for technical or specialized training is not mentioned. Recognition of the task of care provision, duty as a moral determinant, the exchange of affection and solidarity between staff and the elderly allows care continuity despite the centers’ lack of resources. Clinical Relevance: This study contributes information that may help improve the care conditions of elderly institutionalized people.
Application of preview information to pointing control of truss structure using artificial thermal expansion on orbit
Authors: Funakoshi Yusuke , Ishimura Kosei , Ogi Yoshiro , Iwasa Takashi
Published: December 2014

The pointing performance of a truss structure on orbit that is used for a large space telescope is discussed. To achieve advanced science missions, large and precise support structures such as truss structures are needed. However, the preciseness of the structure might be lost due to various disturbances on orbit. Therefore, to realize ultra-large and precise support structures, active shape control of the structures is needed. To control the shape, we use artificial thermal expansion caused by heaters instead of mechanical actuators. Control systems without mechanical mechanisms have high reliability, which is very attractive for use on orbit. However, there are some constraints regarding the usage of heaters. The control input is restricted to positive inputs because heaters can give off heat but cannot dissipate heat actively, and there will be upper limits on the heat input. To improve the control performance under such constraints, we apply “model predictive control” as a feedforward control method with preview information. In this article, we mainly show the effectiveness of model predictive control compared with proportional–integral control, which is one of the typical feedback control methods. We developed a structural mathematical model and a thermal mathematical model in order to evaluate the performance of the control system. It is confirmed through numerical simulations that the total error is reduced by model predictive control compared with proportional–integral control.
Stem cell therapy in cats with chronic enteropathy: a proof-of-concept study
Authors: Webb Tracy L , Webb Craig B
Published: December 2014

Objectives

The current treatment of cats with chronic enteropathy frequently includes use of a prescription diet and daily medication administration, with the potential for side effects or problems with owner compliance, and may still result in treatment failure in some cases. The objective of this study was to determine if stem cell therapy was a safe and viable treatment in cases of feline chronic enteropathy.

Methods

Allogeneic adipose-derived feline mesenchymal stem cells (fMSC) were used to treat seven cats with diarrhea of no less than 3 months’ duration, while four cats with a similar clinical condition received placebo, in a blinded manner. Three additional cats were treated with an identical fMSC protocol, but owners were not blinded to the treatment. Owners completed a questionnaire characterizing clinical signs both before entering the study and 2 weeks following the second of two fMSC or placebo treatments. Owners were also surveyed for similar input by email 1–2 months later before being unblinded to their cat’s study group. Besides the fMSC or placebo treatment, no other changes were made in diet, supplement or medication administration during the study.

Results

No adverse reactions or side effects were attributed to the fMSC therapy in any of the cats. Owners of 5/7 fMSC-treated cats reported significant improvement or complete resolution of clinical signs, while the owner of the remaining two cats reported modest but persistent improvement. Owners of placebo-treated cats reported no change or worsening of clinical signs. Of the owners not blinded to the treatment, one reported marked improvement, one reported no change and one was lost to follow-up.

Conclusions and relevance

Although allogeneic adipose-derived fMSC therapy appears to be a safe and potentially effective treatment for cats suffering from chronic enteropathy, these preliminary results require significant follow-up study.
Ethics, embodied life and esprit de corps: An ethnographic study with anti-money laundering analysts
Authors: Pérezts Mar , Faÿ Eric , Picard Sébastien
Published: December 2014

Our highly sensitive ethnographic study with anti-money-laundering analysts delves into the understudied link between embodiment and ethics in organizations. We begin by reclaiming the importance of bodies and embodiment in the business ethics literature, which largely assumes preeminence of the mind over the body. We then draw on French phenomenologist Michel Henry’s theory of the subjective body to advance our understanding of ethics as endogenous embodied practice rooted in life. Through the experiential realities of our ethnographic work, we show how the two interrelated dimensions in which embodiment occurs (subjective body and organic body) operate at two interrelated levels (subjective and intersubjective experience) to advance theory on the implications of corporeal ethics in organizations. More specifically, by reclaiming and specifying the ontologically embodied and shared dimensions of ethical subjectivity in life, we show the emergence and development of an esprit de corps, which allows embodying collective ethical practice while resisting to continuous external pressures.
Ethics, embodiment and organizations
Authors: Pullen Alison , Rhodes Carl
Published: December 2014

Noting that ethics and responsibility in business are well established fields of research and practice, we suggest that the limits of dominant approaches lie in their privileging of rationality, penchant for codification, tendency to self-congratulation, predilection to control, affinity to masculinity, blindness to social injustice, and subsumption under corporate goals. We observe that such lines of thought are blind to affectual relations, care, compassion or any forms of feeling experienced pre-reflexively through the body. We argue that this begs the rethinking of ethics in organizations from an embodied perspective. On this basis, and on the basis on the work herein, we retain the hope that our interaction with each other and with the world, might foster ways of organizational life that resist domination and oppression in favour of the enactment of care and respect for difference as it is lived and experienced.
Quantitative Measurement of tissue damage and recovery within new T2w lesions in pediatric- and adult-onset multiple sclerosis
Authors: Ghassemi Rezwan , Brown Robert , Banwell Brenda , Narayanan Sridar , Arnold Douglas L. ,   on behalf of the Canadian Pediatric Demyelinating Disease Study Group
Published: December 2014

Background:

Children and adolescents with relapsing–remitting multiple sclerosis (RRMS) have a similar T2 lesion burden as adults matched for disease duration. However, it is unknown whether the degree of tissue destruction within lesions is also similar. Persistent reduced T1-weighted signal intensity within lesions indicates loss of tissue integrity.

Objective:

We aimed to compare change over a 2-year period in T1 intensity within new T2 lesions, from pre-lesion levels to chronic post-lesion levels, between pediatric and adult-onset MS.

Methods:

A two-point intensity-normalization method was used to generate normalized T1-weighted (NT1) images from T1-weighted data in 29 pediatric MS patients (age(mean±SD, years), disease duration (years)=15.7±2.4, 3.9±2.6) and 24 adult MS patients (36.7±8.9, 6.9±4.8). Subjects were imaged at three consecutive timepoints, 1 year apart. For each subject, a ‘new-T2’ lesion mask was created and the NT1 intensities ‘pre-lesion’, ‘peri-lesion’ and ‘post-lesion’ were determined. A longitudinal model was used to capture NT1 changes.

Results:

The NT1 in both groups failed to recover to pre-lesion values by 1 year post-lesion ( p=0.0002), with children showing significantly better recovery than adults ( p=0.0089).

Conclusions:

Both groups showed a significant chronic reduction of T1 intensity within new T2 lesions. However, children showed a significantly greater recovery of T1 intensity, suggesting that MS lesions in the pediatric MS population are less destructive, or that pediatric patients have greater reparative capacity.
The role of cerebellar abnormalities in neuromyelitis optica – a comparison with multiple sclerosis and healthy controls
Authors: Weier Katrin , Eshaghi Arman , Magon Stefano , Andelova Michaela , Radue Ernst-Wilhelm , Kappos Ludwig , Azimi Amir Reza , Sahraian Mohammad Ali , Sprenger Till
Published: December 2014

Background:

In relapsing–remitting multiple sclerosis (RRMS), the cerebellum is a known predilection site for atrophy. Neuromyelitis optica (NMO) is characterized by extensive lesions in the spinal cord and optic nerve; however, cerebellar involvement has been less studied. Secondary degeneration of the spinocerebellar tract could impact the cerebellum in NMO.

Objective:

We aimed to investigate whether spinal cord and cerebellar volume measures differ between patients with NMO and RRMS.

Methods:

Volumetric analyses of the cerebellum (TCV), the upper cervical cord (UCV) as well as the whole brain (NBV) of age- and gender-matched patients with NMO ( n=30; 56% AQP4 +ve) and RRMS ( n=25) were performed on 3T brain magnetic resonance imaging (MRI) and compared with 34 healthy controls (HC).

Results:

UCV was significantly reduced in NMO patients (6.3 cm3) as compared with HC (6.7 cm3), while patients with MS had reduced brain volumes compared with HC (NBV=1482 cm3; p<0.001; TCV=188 cm3; p=0.042), but UCV close to normal values. Patients with RRMS and NMO differed in NBV ( p=0.001; lower in RRMS) and by trend (towards reduction in RRMS) in cerebellar volume ( p=0.06).

Conclusions:

While atrophy seems to be diffuse in MS patients, a rather focussed pattern with predominant involvement of the UCV was observed in NMO patients.
Comparative effectiveness of glatiramer acetate and interferon beta formulations in relapsing–remitting multiple sclerosis
Authors: Kalincik Tomas , Jokubaitis Vilija , Izquierdo Guillermo , Duquette Pierre , Girard Marc , Grammond Pierre , Lugaresi Alessandra , Oreja-Guevara Celia , Bergamaschi Roberto , Hupperts Raymond , Grand’Maison Francois , Pucci Eugenio , Van Pesch Vincent , Boz Cavit , Iuliano Gerardo , Fernandez-Bolanos Ricardo , Flechter Shlomo , Spitaleri Daniele , Cristiano Edgardo , Verheul Freek , Lechner-Scott Jeannette , Amato Maria Pia , Cabrera-Gomez Jose Antonio , Saladino Maria Laura , Slee Mark , Moore Fraser , Gray Orla , Paine Mark , Barnett Michael , Havrdova Eva , Horakova Dana , Spelman Timothy , Trojano Maria , Butzkueven Helmut ,   On behalf of the MSBase Study Group, Roullet Etienne , Rozsa Csilla , Kasa Krisztian , Sirbu Carmen-Adella , Shaw Cameron , Vucic Steve , Petkovska-Boskova Tatjana , Herbert Joseph , Kister Ilya , Singhal Bhim , Alroughani Raed , Bacile Elizabeth Alejandra Bacile , Arruda Walter Oleschko , Roger Elaine , Despault Pierre , Marriott Mark , Van der Walt Anneke , King John , Byron Jill , Morgan Lisa , Hinson Eloise , Haartsen Jodi , Mechati Samir , Bianchi Erich , Bulla Alexandre , Corageoud Matthieu , De Luca Giovanna , Di Tommaso Valeria , Travaglini Daniela , Pietrolongo Erika , di Ioia Maria , Farina Deborah , Mancinelli Luca , Rojas Juan Ignacio , Patrucco Liliana , Elisabetta
Published: December 2014

Background:

The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed.

Objective:

We aimed to compare, in a real-world setting, relapse and disability outcomes among patients with multiple sclerosis (MS) treated with injectable immunomodulators.

Methods:

Pairwise analysis of the international MSBase registry data was conducted using propensity-score matching. The four injectable immunomodulators were compared in six head-to-head analyses of relapse and disability outcomes using paired mixed models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity and power analyses were conducted.

Results:

Of the 3326 included patients, 345–1199 patients per therapy were matched (median pairwise-censored follow-up was 3.7 years). Propensity matching eliminated >95% of the identified indication bias. Slightly lower relapse incidence was found among patients treated with glatiramer acetate or subcutaneous interferon β-1a relative to intramuscular interferon β-1a and interferon β-1b ( p≤0.001). No differences in 12-month confirmed progression of disability were observed.

Conclusion:

Small but statistically significant differences in relapse outcomes exist among the injectable immunomodulators. MSBase is sufficiently powered to identify these differences and reflects practice in tertiary MS centres. While the present study controlled indication, selection and attrition bias, centre-dependent variance in data quality was likely.
Decreased Dicer expression is linked to increased expression of co-stimulatory molecule CD80 on B cells in multiple sclerosis
Authors: Aung Latt Latt , Balashov Konstantin E
Published: December 2014

Background:

Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system. B cells have been strongly implicated in disease pathogenesis based on clinical trials with B-cell ablation. There is a growing body of evidence linking microRNAs with regulation of the immune system. Dicer, a key enzyme involved in microRNA biogenesis, is necessary for normal B-cell function.

Objective:

We aimed to determine whether Dicer expression is impaired in B cells and is linked to increased expression co-stimulatory molecules in patients with MS.

Methods:

B cells were separated from blood samples of MS patients and healthy subjects. Expression of Dicer and co-stimulatory molecules CD80 and CD86 was tested. The effect of Dicer modulation on CD80 and CD86 expression in B cells was studied.

Results:

Dicer expression was decreased in B cells but not in monocytes of patients with MS compared with healthy subjects. CD80 and CD86 expression was increased on B cells of MS patients compared with healthy subjects. Inhibition of Dicer expression in B cells by small interfering RNA led to increased expression of CD80.

Conclusion:

Dicer expression is decreased and is mechanistically linked to increased expression of co-stimulatory molecule CD80 in B cells of patients with MS. This may contribute to activation of immune responses in MS.
The neutralizing antibody GNbAC1 abrogates HERV-W envelope protein-mediated oligodendroglial maturation blockade
Authors: Kremer David , Förster Moritz , Schichel Tanja , Göttle Peter , Hartung Hans-Peter , Perron Hervé , Küry Patrick
Published: December 2014

Background:

The envelope protein (ENV) of the human endogenous retrovirus type W is implicated in inflammatory reactions in multiple sclerosis (MS) but also interferes with oligodendroglial maturation. A neutralizing antibody GNbAC1 has been developed and successfully been tested in clinical trials.

Objectives and methods:

We stimulated primary oligodendroglial cells with ENV upon preincubation with GNbAC1 and assessed for nitrosative stress and myelin expression.

Results:

Neutralization of ENV by GNbAC1 reduces its ability to induce stress reactions resulting in a rescue of myelin expression.

Conclusions:

Beyond immune cell modulation, this monoclonal antibody may therefore help to overcome the oligodendroglial differentiation blockade in MS.
Benign neuromyelitis optica is rare in Japanese patients
Authors: Uzawa Akiyuki , Mori Masahiro , Muto Mayumi , Uchida Tomohiko , Masuda Hiroki , Masuda Saeko , Kuwabara Satoshi
Published: December 2014

Good-outcome neuromyelitis optica (NMO) is defined as an Expanded Disability Status Scale (EDSS) score of ≤3.0 at 10 years after onset. The clinical courses of 80 consecutive patients with NMO were analyzed to identify the frequency and features of Japanese patients with good-outcome NMO. Of the 80 patients, 37 had a disease duration of >10 years; of these, eight (21.6%) presented a good outcome. These cases presented lower EDSS scores during the early phase of disease compared with those with conventional NMO. However, half of these patients developed severe disabilities later on, indicating that truly benign NMO is rare.
Corpus callosum atrophy is strongly associated with cognitive impairment in multiple sclerosis: Results of a 17-year longitudinal study
Authors: Granberg Tobias , Martola Juha , Bergendal Gösta , Shams Sara , Damangir Soheil , Aspelin Peter , Fredrikson Sten , Kristoffersen-Wiberg Maria
Published: December 2014

Background:

Cognitive impairment is common in multiple sclerosis (MS) and may be subtle. The corpus callosum is essential for connectivity-demanding cognitive tasks and is significantly affected in MS, therefore it may serve as a marker for cognitive function.

Objective:

The objective of this paper is to longitudinally study the normalized corpus callosum area (nCCA) as a marker of cognitive function and disability in MS.

Methods:

Thirty-seven MS patients were followed from 1996 with follow-ups in 2004 and 2013. A healthy matched control group was recruited. The Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) were assessed. The nCCA was measured on T2-weighted images. Volumetry was performed with FreeSurfer.

Results:

Disease duration spanned five decades (1.6–46 years). Annual corpus callosal atrophy rate decreased with disease duration. nCCA was strongly correlated with SDMT ( r = 0.793, p < 0.001) and moderately correlated with EDSS ( r = −0.545, p < 0.001) after adjusting for disease duration, age and sex. The correlations of brain parenchymal fraction, white matter fraction, gray matter fraction and normalized lesion volume were less strong.

Conclusions:

The nCCA correlates well with physical and cognitive disability in time perspectives close to two decades, outperforming volumetric measurements. The nCCA is fast and could be feasible for clinical implementation where it may help identify patients in need of neuropsychological evaluation.
A new cognitive rehabilitation programme for patients with multiple sclerosis: the ‘MS-line! Project’
Authors: Gich Jordi , Freixenet Jordi , Garcia Rafael , Vilanova Joan Carles , Genís David , Silva Yolanda , Montalban Xavier , Ramió-Torrentà Lluís
Published: December 2014

Background:

Cognitive rehabilitation is often delayed in multiple sclerosis (MS).

Objective:

To develop a free and specific cognitive rehabilitation programme for MS patients to be used from early stages that does not interfere with daily living activities.

Methods:

MS-line!, cognitive rehabilitation materials consisting of written, manipulative and computer-based materials with difficulty levels developed by a multidisciplinary team.

Results:

Mathematical, problem-solving and word-based exercises were designed. Physical materials included spatial, coordination and reasoning games. Computer-based material included logic and reasoning, working memory and processing speed games.

Conclusions:

Cognitive rehabilitation exercises that are specific for MS patients have been successfully developed.
Hexosylceramides as intrathecal markers of worsening disability in multiple sclerosis
Authors: Checa Antonio , Khademi Mohsen , Sar Daniel G , Haeggström Jesper Z , Lundberg Jon O , Piehl Fredrik , Olsson Tomas , Wheelock Craig E
Published: December 2014

Background:

Sphingolipids are important components of neurons and the myelin sheath whose levels are altered in multiple sclerosis (MS).

Objectives:

We aimed to determine if cerebrospinal fluid (CSF) sphingolipids can be used as markers of MS disease progression.

Methods:

Using liquid chromatography tandem mass spectrometry, we analysed sphingolipids in CSF from 134 individuals. The MS group included 65 patients divided into 41 relapsing–remitting MS (RRMS) and 24 progressive MS (ProgMS). In addition, a group of 13 early MS/clinically isolated syndrome (EarlyMS) and two control groups consisting of 38 individuals with other neurological diseases (OND) and 18 OND with signs of inflammation (iOND) were analysed. A follow-up study included 17 additional RRMS patients sampled at two time points 4.7±1.7 years apart.

Results:

Levels of sphingomyelin (SM)- and hexosylceramide (HexCer)-derived sphingolipids increased in the CSF of patients with MS independently of the fatty acid chain length in RRMS ( p<0.05). Levels of palmitic acid (16:0)-containing HexCer (HexCer16:0) increased significantly in ProgMS compared with the OND ( p<0.001), iOND ( p<0.05) and EarlyMS ( p<0.01) groups and correlated with Expanded Disability Status Scale in RRMS in both studies ( p=0.048; p=0.027).

Conclusion:

HexCer16:0 is a promising candidate marker of disease progression in MS, especially in RRMS.
Interferon-beta affects mitochondrial activity in CD4+ lymphocytes: Implications for mechanism of action in multiple sclerosis
Authors: Haghikia Aiden , Faissner Simon , Pappas Derek , Pula Bartosz , Akkad Denis A , Arning Larissa , Ruhrmann Sabrina , Duscha Alexander , Gold Ralf , Baranzini Sergio E , Malhotra Sunny , Montalban Xavier , Comabella Manuel , Chan Andrew
Published: December 2014

Background:

Whereas cellular immune function depends on energy supply and mitochondrial function, little is known on the impact of immunotherapies on cellular energy metabolism.

Objective:

The objective of this paper is to assess the effects of interferon-beta (IFN-β) on mitochondrial function of CD4+ T cells.

Methods:

Intracellular adenosine triphosphate (iATP) in phytohemagglutinin (PHA)-stimulated CD4+ cells of multiple sclerosis (MS) patients treated with IFN-β and controls were analyzed in a luciferase-based assay. Mitochondrial-transmembrane potential (ΔΨm) in IFN-β-treated peripheral blood mononuclear cells (PBMCs) was investigated by flow cytometry. Expression of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) in CD4+ cells of IFN-β-treated individuals and correlations between genetic variants in the key metabolism regulator PGC-1α and IFN-β response in MS were analyzed.

Results:

IFN-β-treated MS patients exhibited a dose-dependent reduction of iATP levels in CD4+ T cells compared to controls ( p < 0.001). Mitochondrial effects were reflected by depolarization of ΔΨm. Expression data revealed changes in the transcription of OXPHOS-genes. iATP levels in IFN-β-responders were reduced compared to non-responders ( p < 0.05), and the major T allele of the SNP rs7665116 of PGC-1α correlated with iATP-levels.

Conclusion:

Reduced iATP-synthesis ex vivo and differential expression of OXPHOS-genes in CD4+ T cells point to unknown IFN-β effects on mitochondrial energy metabolism, adding to potential pleiotropic mechanisms of action.
The Charcot Lecture | Beating MS: A story of B cells, with twists and turns
Authors: Hauser Stephen L
Published: December 2014

Autoimmune B cells play a major role in mediating tissue damage in multiple sclerosis (MS). In MS, B cells are believed to cross the blood-brain barrier and undergo stimulation, antigen-driven affinity maturation and clonal expansion within the supportive CNS environment. These highly restricted populations of clonally expanded B cells and plasma cells can be detected in MS lesions, in cerebrospinal fluid, and also in peripheral blood.

In phase II trials in relapsing MS, monoclonal antibodies that target circulating CD20-positive B lymphocytes dramatically reduced disease activity. These beneficial effects occurred within weeks of treatment, indicating that a direct effect on B cells—and likely not on putative autoantibodies—was responsible. The discovery that depletion of B cells has an impact on MS biology enabled a paradigm shift in understanding how the inflammatory phase of MS develops, and will hopefully lead to development of increasingly selective therapies against culprit B cells and related humoral immune system pathways.

More broadly, these studies illustrate how lessons learned from the bedside have unique power to inform translational research. They highlight the essential role of clinician scientists, currently endangered, who navigate the rocky and often unpredictable terrain between the worlds of clinical medicine and biomedical research.