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Abstract Background A requisite for ethical human subjects research is that participation should be informed and voluntary. Participation during the informed consent process by way of asking questions is an indicator of the extent to which consent is informed. Aims The aims of this study were to assess the extent to which parents providing consent for children's participation in an observational tuberculosis (TB) research study in India actively participated during the informed consent discussion, and to identify correlates of that participation. Methods In an observational cohort study of tuberculosis in infants in South India, field supervisors who were responsible for obtaining informed consent noted down questions asked during the informed consent discussions for 4,382 infants who were enrolled in the study. These questions were post-coded by topic. Bivariate and multivariate analysis was conducted to examine factors associated with asking at least one question during the informed consent process. Results In total, 590 out of 4,382 (13.4%) parents/guardians asked any question during the informed consent process. We found that the likelihood of parents asking questions during the informed consent process was significantly associated with education level of either parent both parents being present, and location. Conclusions The findings have implications for planning the informed consent process in a largely rural setting with low levels of literacy. Greater effort needs to be directed towards developing simple participatory communication materials for the informed consent process. Furthermore, including both parents in a discussion about a child's participation in a research study may increase the extent to which consent is truly informed. Finally, continuing efforts need to be made to improve the communication skills of research workers with regard to explaining research processes and putting potential research participants at ease.

Scaled interventions are required to address levels of overweight and obesity and reduce health inequalities. Little data is available on the effectiveness of community weight management programmes for participants self-selecting to attend across different socio-economic backgrounds. This analysis investigates 3, 6, and 12-month outcomes of adults joining a real-life community weight management programme. Weight, attendance and Indices of Multiple Deprivation (IMD) data from all fee-paying adults joining Slimming World in 2016 were collated. Data were analysed using descriptive and inferential statistics to determine predictors of weight loss. Mean BMI of 1 094 676 adults (7.6% male) was 33.0 ± 6.4 kg/m 2 . Mean % weight change at 3, 6, and 12 months was -5.0% ± 3.6%, -5.9% ± 5.2%, and -6.0% ± 5.8%. Those attending 75% sessions achieved greater weight loss with mean weight losses at 3, 6, and 12-months of 7.7% ± 3.3%, 11.3% ± 5.2%, and 14.1% ± 7.5%, respectively. Effect sizes from comparison of weight change between deprivation deciles were negligible, with similar outcomes in the most and least deprived deciles at 12-months (-5.7% ± 5.9% vs. -6.2% ± 5.9%). This service evaluation of more than 1 million adults attending a community weight management programme found they were able to achieve and/or maintain an average 6% weight loss at 12 months, with high attenders achieving >14% loss. Men and those with higher levels of deprivation were accessing the support and achieving significant weight losses. Slimming World as a real-life, scalable weight management programme is well placed to help adults manage their weight and address health inequalities., (© 2024 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Osteoporosis involves changes to bones that makes them prone to fracture. The most common osteoporotic fracture is vertebral, in which one or more spinal vertebrae collapse. People with vertebral fracture are at high risk of further fractures, however around two-thirds remain undiagnosed. The National Institute for Health and Care Excellence (NICE) recommends bone protection therapies to reduce this risk. This study aimed to co-produce a range of knowledge sharing resources, for healthcare professionals in primary care and patients, to improve access to timely diagnosis and treatment., Methods: This study comprised three stages: 1. In-depth interviews with primary care healthcare professionals (n = 21) and patients with vertebral fractures (n = 24) to identify barriers and facilitators to diagnosis and treatment. 2. A taxonomy of barriers and facilitators to diagnosis were presented to three stakeholder groups (n = 18), who suggested ways of identifying, diagnosing and treating vertebral fractures. Fourteen recommendations were identified using the nominal group technique. 3. Two workshops were held with stakeholders to co-produce and refine the prototype knowledge sharing resources (n = 12)., Results: Stage 1: Factors included lack of patient information about symptoms and risk factors, prioritisation of other conditions and use of self-management. Healthcare professionals felt vertebral fractures were harder to identify in lower risk groups and mistook them for other conditions. Difficulties in communication between primary and secondary care meant that patients were not always informed of their diagnosis, or did not start treatment promptly. Stage 2: 14 recommendations to improve management of vertebral fractures were identified, including for primary care healthcare professionals (n = 9) and patients (n = 5). Stage 3: The need for allied health professionals in primary care to be informed about vertebral fractures was highlighted, along with ensuring that resources appealed to under-represented groups. Prototype resources were developed. Changes included help-seeking guidance and clear explanations of medical language., Conclusions: The study used robust qualitative methods to co-produce knowledge sharing resources to improve diagnosis. A co-production approach enabled a focus on areas stakeholders thought to be beneficial to timely and accurate diagnosis and treatment. Dissemination of these resources to a range of stakeholders provides potential for substantial reach and spread., (© 2024. The Author(s).)

In this study, we explore the dynamics between innovation, institutional quality, and foreign-aid flows in middle-income countries. Using an appropriate econometric model, we investigate the links between these variables in 79 middle-income countries (MICs) over 2005-2020. The results from our study show that foreign aid, institutional quality, and innovation have strong endogenous relationships. The short-run outcomes show that innovation Granger-causes institutional quality; foreign aid Granger-causes innovation; and quality of institutions Granger-causes foreign aid. The long-run outcomes indicate that institutional quality and innovation significantly affect the flow of foreign aid to the MICs. These results indicate that policy-makers in both foreign aid donor and recipient countries should pursue appropriate policies on foreign aid, quality of institutions, and innovation. For instance, in the short run, planners and evaluators in donor countries can direct their aid to MICs that have persistent challenges in improving their institutions and enhancing their innovative capabilities. In the long run, recipient countries ought to recognize that their institutional quality and innovation have a considerable impact on the inflows of foreign aid to their countries., Competing Interests: Conflict of Interest We declare that authors have no conflict of interest with respect to Funding Source Declaration, Author Agreement, and Permission Note for the submission paper “Does Foreign Aid Affect Innovation and Institutional Quality in Middle-Income Countries?” by Rudra P. Pradhan, Mak B. Arvin, Mahendhiran Nair and Sara E. Bennett to the possible inclusion in ‘Evaluation and Program Planning’., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Fatigue is a challenging feature of all inflammatory rheumatic diseases. LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomized Trial) included remotely delivered personalized exercise programme (PEP) or cognitive-behavioural approach (CBA) interventions. The aim of this nested qualitative evaluation was to understand rheumatology health professionals' (therapists') perspectives of delivering the interventions in the LIFT trial., Methods: A subgroup of therapists who had delivered the personalized exercise programme (PEP) and cognitive-behavioural approach (CBA) interventions took part in semi-structured telephone interviews., Results: Seventeen therapists (13 women and 4 men) who delivered PEP ( n  = 8) or CBA ( n  = 9) interventions participated. Five themes were identified. In 'The benefits of informative, structured training', therapists described how they were able to practice their skills, and the convenience of having the LIFT manual for reference. When 'Getting into the swing of it', supporting patients gave therapists the confidence to tailor the content of the manual to each patient. Clinical supervision supported therapists to gain feedback and request assistance when required. In 'Delivering the intervention', therapists reported that patients valued the opportunity to talk about their fatigue and challenge their beliefs. In 'Challenges in delivering the LIFT intervention', therapists struggled to work in partnership with patients who lacked motivation or stopped engaging. Finally, in 'LIFT developing clinical skills', therapists gained confidence and professional satisfaction, seeing patients' fatigue improve over time., Conclusion: The findings support the provision of training for rheumatology health professionals to remotely deliver fatigue-management interventions. Insights from these trials can be used to better improve clinical practice and service provision., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To disseminate and assess the level of acceptability and applicability of the European Alliance of Associations for Rheumatology (EULAR) recommendations for patient education among professionals in rheumatology across Europe and three Asian countries and identify potential barriers and facilitators to their application., Methods: A parallel convergent mixed-methods design with an inductive approach was used. A web-based survey, available in 20 different languages, was distributed to health professionals by non-probability sampling. The level of agreement and applicability of each recommendation was assessed by (0-10) rating scales. Barriers and facilitators to implementation were assessed using free-text responses. Quantitative data were analysed descriptively and qualitative data by content analysis and presented in 16 categories supported by quotes., Results: A total of 1159 completed the survey; 852 (73.5%) were women. Most of the professionals were nurses (n=487), rheumatologists (n=320), physiotherapists (n=158). For all recommendations, the level of agreement was high but applicability was lower. The four most common barriers to application were lack of time, lack of training in how to provide patient education, not having enough staff to perform this task and lack of evaluation tools. The most common facilitators were tailoring patient education to individual patients, using group education, linking patient education with diagnosis and treatment and inviting patients to provide feedback on patient education delivery., Conclusions: This project has disseminated the EULAR recommendations for patient education to health professionals across 23 countries. Potential barriers to their application were identified and some are amenable to change, namely training patient education providers and developing evaluation tools., Competing Interests: Competing interests: All authors have completed the ICMJE form for Competing Interests Disclosure and report a research grant from European Alliance of Associations for Rheumatology (EULAR) during the conduct of the study; SB and MN have received speaking fees from CCIS—The Conference Company for speaking at the Irish Rheumatology Nurses Forum meeting. MF reports consulting fees from Janssens Pharmaceuticals, and speaking fees from Janssen Pharmaceuticals, Pfizer Inc, Ono Pharmaceuticals, Bristol Myers Squibb, Chugai Pharmaceuticals and Abbvie, all outside the submitted work. BJ reports personal honoraria from Lily UK for speaking at an Expert Webinar, outside the submitted work., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Hypermobility Spectrum Disorders (HSD) and Hypermobile Ehlers-Danlos Syndrome (hEDS) are heritable connective tissue disorders associated with joint instability and pain, but with scant guidance for supporting patients. The aim was to determine recommendations for an HSD/hEDS self-management intervention., Materials and Methods: Barriers to self-management were mapped onto the Theoretical Domains Framework (TDF) and Capability, Opportunity, Motivation-Behaviour (COM-B) model in a behavioural analysis. A modified Nominal Group Technique was used to prioritise behaviour change technique (BCT) interventions ( n  = 9 women)., Results: Possible BCTs incorporated., Education: Incorporating self-help strategies, education to improve their knowledge of HSD/hEDS, and how to judge information about HSD/hEDS., Training: In activity pacing, assertiveness and communication skills, plus what to expect during pregnancy, when symptoms can worsen., Environmental Restructuring and Enablement: Support from occupational therapists to maintain independence at work and home., Modelled Behaviour: That illustrates how other people with HSD/hEDS have coped with the psychosocial impact., Conclusions: This study is the first to apply theoretically-informed approaches to the management of HSD/hEDS. Participants indicated poor access to psychological support, occupational therapy and a lack of knowledge about HSD/hEDS. Future research should evaluate which intervention options would be most acceptable and feasible.Implications for rehabilitationPatients with Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome can be active partners in the co-design of behaviour change interventions.Behaviour change interventions should target psychological support and patient education, particularly patient information.Additional behaviour change interventions included environmental restructuring and enablement; adaptations to participants' environment with input from occupational therapy.Participants were keen to suggest opportunities for behavioural modelling; positive fist-person modelling narratives, written by those with HSD/hEDS, which addressed how they coped with the psychosocial impact of their condition.

Objectives: Fatigue can be a disabling symptom of inflammatory rheumatic diseases. LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomized Trial) is a randomized trial of remotely delivered cognitive-behavioural approach or personalized exercise programme interventions, compared with usual care. The aim of this nested qualitative study was to evaluate participants' experiences of taking part in the intervention, including their ideas about future service delivery., Methods: Semi-structured telephone interviews were conducted with a subgroup of LIFT participants to discuss their views and experiences of the interventions., Results: Forty-three participants (30 women) from six sites who had participated in the cognitive-behavioural approach ( n  = 22) or personalized exercise programme ( n  = 21) interventions took part. Five themes were identified in the thematic analysis. In the theme 'not a miracle cure, but a way to better manage fatigue', LIFT could not cure fatigue; however, most felt better able to manage after participating. Participants valued 'building a therapeutic relationship' with the same therapist throughout the intervention. In 'structure, self-monitoring and being accountable', participants liked the inclusion of goal-setting techniques and were motivated by reporting back to the therapist.After taking part in the interventions, participants felt 'better equipped to cope with fatigue'; more confident and empowered. Lastly, participants shared ideas for 'a tailored programme delivered remotely', including follow-up sessions, video calling, and group-based sessions for social support., Conclusion: Many participants engaged with the LIFT interventions and reported benefits of taking part. This suggests an important future role for the remote delivery of fatigue self-management., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: In persons with multiple sclerosis (MS), the effect of nutrition on exercise performance and fatigue remains unknown. The objective was to determine whether a 3-day diet high in triglycerides (FAT) compared with a 3-day diet high in carbohydrates (CARB) would improve fatigue and exercise performance in persons with MS., Methods: A randomized controlled crossover design was incorporated to study FAT versus CARB on submaximal cycling endurance (60% of peak oxygen consumption), substrate utilization, and fatigue in 12 persons with mild-to-moderate MS (Expanded Disability Status Scale score, 2.0-5.0) and 12 age- and sex-matched controls., Results: There were no differences in cycling time between diets in either group ( P = .29). The MS group had no changes in fatigue between diets ( P = .64); the control group demonstrated increased total mental fatigue after FAT ( P = .05). The control group increased carbohydrate oxidation by 24% at rest and 13% during exercise after CARB. Similarly, the control group significantly increased fat oxidation after FAT by 22% at rest and 68% during exercise ( P = .01). These changes were not seen in the MS group. Compared with controls, persons with MS oxidized approximately 50% less fat during exercise after FAT ( P = .05)., Conclusions: Neither CARB nor FAT altered submaximal exercise performance or baseline fatigue in the MS group. The results suggest that persons with MS are unable to adapt to dietary changes and oxidize fatty acids as efficiently as controls., Competing Interests: Financial Disclosures: The authors declare no conflicts of interest., (© 2021 Consortium of Multiple Sclerosis Centers.)

Background: Weight management is complex for people even in times of stability. Supporting individuals to develop strategies to maintain a healthier weight when there are additional life challenges may prevent relapse. This mixed-methods study describes the impact the COVID-19 restrictions had on adults engaged in weight management before and during the pandemic in order to determine helpful strategies., Methods: Longitudinal data was captured from online surveys completed by Slimming World (SW) members 0-4 weeks after joining, October/November 2019, providing pre-joining and baseline (T0&T1), 3- (T2) and 6- month (T3-during COVID-19) data. Representatives from the general population, not attending a weight management service, completed the same questionnaires providing cross-sectional control data. All weights are self-reported. For this study, questions assessing the impact of the COVID-19 challenges on health-related behaviours and well-being are included comparing responses at T0/T1, T2 & T3. Longitudinal data were analysed using repeated measures ANOVA and cross-sectional data, one-way independent ANOVAs to compare means. Comparisons between SW members and controls were determined using z-proportion tests. Qualitative data generated was thematically analysed using a six-step approach to produce the key emerging themes., Results: 222 SW members completed all three surveys, achieving a weight loss of 7.7 ± 7.5%. They maintained positive health-related behaviour changes made since joining, including increased fruit and vegetables (p < 0.001), fewer sugary drinks (p < 0.001), cooking from scratch (p < 0.001) and increased activity levels (p < 0.001). Despite COVID-19 restrictions, they were still reporting improvements in all behaviours and had healthier scores than the controls on all but alcohol intake, although still within guidelines. Qualitative data indicated that the situation created various challenges to managing weight with fresh foods harder to access, comfort eating, drinking more alcohol, eating more sugary foods and snacking through boredom. However, some reported having more free time enabling better planning, more time to cook from scratch and increased physical activity., Conclusions: The findings highlight the value of peer, group and online support and guidance for individuals to develop sustainable behaviour changes and a level of resilience. These strategies can then be drawn upon enabling maintenance of lifestyle changes and management of weight even in challenging times.

Introduction: Many factors associated with colonic diverticulitis are also part of the clinical definition of the metabolic syndrome. Computed tomography (CT) is commonly performed in symptomatic patients, such as those with suspected or known acute diverticulitis, and could add additional value for the health of these patients by identifying and reporting CT biomarkers of metabolic syndrome, if present and detectable. The purpose of this study was to identify CT biomarkers of metabolic syndrome in patients with acute colonic diverticulitis., Methods: We retrospectively reviewed 243 patients (mean-60 yrs, M:F:126:117) diagnosed with colonic diverticulitis on CT between March 2015 and March 2017 for hepatic steatosis, vascular calcifications, abdominal diameters and fat volumes. Criteria of metabolic syndrome were obtained from medical records. Differences in imaging biomarkers were compared using chi-square comparisons stratified by metabolic syndrome, abdominal diameter and fat volume., Results: Of 243 patients, 33% demonstrated hepatic steatosis and 71% atherosclerotic vascular calcifications on CT. 28% met criteria for metabolic syndrome. Patients with metabolic syndrome had higher occurrence of hepatic steatosis, sagittal diameter ≥ 35 cm, visceral fat > 5000 cm 3 and subcutaneous fat > 8300 cm 3 (P < 0.05), but not vascular calcifications (P > 0.05)., Conclusions: CT biomarkers of metabolic syndrome are commonly encountered in patients with acute diverticulitis. Recognizing and reporting these findings can guide towards further evaluation for metabolic syndrome., (© 2021 The Royal Australian and New Zealand College of Radiologists.)

Purpose: Little attention has been paid to psychosocial factors in Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome (hypermobility type). This study sought to identify the psychosocial impact by examining participants' lived experiences; and identify characteristics of effective coping., Materials and Methods: Adults with Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome (Hypermobility Type) were invited to discuss their own lived experiences and the impact of the condition. All met recognized criteria for clinically significant joint hypermobility, and had a self-confirmed diagnosis. The transcripts were coded and analyzed using inductive thematic analysis., Results: Seventeen participants (14 women, 3 men) purposively selected to broadly represent different genders, ages and ethnicities. Analysis identified five key themes: healthcare limitations, a lack of awareness of Joint Hypermobility, and Ehlers-Danlos Syndrome (Hypermobility Type) among healthcare professionals; a restricted life; social stigma; fear of the unknown; and ways of coping., Conclusions: The results highlight the significant psychosocial impact on participants' lives. Coping approaches identified included acceptance, building social networks, learning about joint hypermobility, and adapting activities. Physiotherapists supported regular exercise. Further research should consider potential interventions to improve information provision, address psychological support, and increase awareness of hypermobility among healthcare professionals.Implications for rehabilitationParticipants who had help from family members to complete activities described guilt and shame, highlighting the need for a greater rehabilitation focus on maintaining independence.Difficulties with sexual relationships due to prolapse or erectile dysfunction, and associated anxieties have indicated a need for greater awareness of these issues within primary care.The provision of reliable information and materials is vital, both for healthcare professionals and patients, to reduce misinformation and fear.Physiotherapists with knowledge of Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome hypermobility type were cited as sources of support and hope, which helped people to cope with and manage their condition.

Objective: To describe the clinical presentation, magnetic resonance imaging features, and outcome of cats treated with hemilaminectomy for intervertebral disc extrusion (IVDE)., Study Design: Short case series., Animals: Six cats., Methods: Medical records were reviewed for signalment, onset, duration, and severity of clinical signs, magnetic resonance imaging features, surgical findings, and clinical outcome with a minimum postoperative follow-up of 4 weeks., Results: Our population included 6 cats with a median age of 8.6 years, consisting predominantly of males (n = 5) and purebred cats (n = 4). An acute onset and short duration of progressive clinical signs of myelopathy was the most common presentation; spinal hyperesthesia was present in 3 cats. A large volume of extradural material was identified by MRI within the lumbar vertebral column of each cat, causing marked spinal cord compression. The most common sites affected were L2-L3 (n = 2) and L6-L7 (n = 2). Follow-up after hemilaminectomy was available in 5 cats: 4 had normal voluntary motor function, and 1 had recurrence of acute paraplegia, compromised nociception, and an extensive T2w hyperintense intramedullary lesion according to MRI. All 4 cats with preoperative urinary incontinence remained incontinent for at least 1 week despite good voluntary motor function of pelvic limbs., Conclusion: Intervertebral disc extrusion was diagnosed by MRI in all 6 cats, most commonly at L2-3 and L6-7. Hemilaminectomy resulted in a good to excellent outcome in 4 of 5 cats., Clinical Significance: Feline IVDE can be diagnosed by MRI and carry a good prognosis after surgical decompression, although urinary continence may be delayed despite good pelvic limb voluntary motor function., (© 2019 The American College of Veterinary Surgeons.)

Background: We sought to assess the associations between nutrition and ambulation, daily activity, quality of life (QOL), and fatigue in individuals with mild-to-moderate disability with multiple sclerosis (MS)., Methods: This cross-sectional pilot study included 20 ambulatory adult volunteers with MS (14 women and 6 men; mean ± SD age, 57.9 ± 10.2 years; mean ± SD Expanded Disability Status Scale score = 4.1 ± 1.8). Primary outcome variables included dietary assessment and the 6-Minute Walk Test (6MWT). Secondary measures included the Timed 25-Foot Walk test, Timed Up and Go test, daily activity, and three self-report questionnaires: the 12-item Multiple Sclerosis Walking Scale, the 36-item Short Form Health Survey (SF-36), and the Modified Fatigue Impact Scale., Results: Significant correlations were seen between the percentage of diet comprising fats and the 6MWT ( r = 0.51, P = .02) and the physical functioning component of the SF-36 ( r = 0.47, P = .03). The percentage of carbohydrates was significantly correlated with the 6MWT ( r = -0.43, P = .05), daily activity ( r = -0.59, P = .005), and the physical functioning component of the SF-36 ( r = -0.47, P = .03). Cholesterol, folate, iron, and magnesium were significantly positively correlated with the physical functioning component of the SF-36 and the 6MWT., Conclusions: These findings indicate better ambulation, daily function, and QOL with increased fat intake, decreased carbohydrate intake, and increased intake of the micronutrients cholesterol, folate, iron, and magnesium in people with mild-to-moderate MS. This pilot study highlights the potential impact of diet on function and QOL in MS.

Background: People with intellectual disabilities (ID) may not be able to access and respond to uniformly delivered health interventions. Public bodies have a legal duty to make 'reasonable adjustments' to policies and practices to provide fair access and treatment for people with ID. This study aimed to identify adjustments to the Slimming World weight management programme to improve accessibility and assess acceptability and feasibility for this population., Methods: This user-centred qualitative study was carried out with a steering group of people with ID (n = 4). Barriers and facilitators to using Slimming World were identified through interviews and focus groups with people with ID (n = 54), carers (n = 12) current members with ID (n = 8) and Slimming World group leaders (n = 11). Adjustments were made and their feasibility and acceptability were explored in a before-and-after mixed methods study where people with ID attended Slimming World for eight weeks. Participants (n = 9), carers (n = 7) and Slimming World group leaders (n = 4) were interviewed to explore their experiences of the adjustments. Participants were weighed at baseline then each week., Results: Four key adjustments were identified and addressed by Slimming World who developed prototype Easy Read materials and a letter for carers. Six of the nine participants attended Slimming World for eight weeks and lost weight (1.4 kg to 6.6 kg, reduction in BMI between 0.5 and 1.7 kg/m2), indicating that the adjustments were feasible and acceptable. Two participants dropped out because they felt uncomfortable in a mainstream group and another left because they lacked control over food choice in their residential setting., Conclusions: This user-centred approach identified reasonable adjustments that were feasible to implement. In a small uncontrolled feasibility study, people with ID were positive about the adjustments and lost weight. However, issues in the wider context of people's lives, such as obesogenic environments and concerns about joining mainstream groups, limited the acceptability of Slimming World even with these adjustments. These findings have important implications for policy and suggest that environmental and organisational level interventions are needed alongside those targeting individual behaviour to tackle the obesogenic environment in which many people with ID spend their time, in order to reduce inequalities associated with the consequences of obesity.

Background: The relationship between walking disability in multiple sclerosis (MS) patients and their macro- and microstructural MRI-derived measures still remains unclear., Objective: To assess the correlations between walking disability and MRI-derived lesion, atrophy, and microstructural/axonal integrity outcomes., Methods: Seventy-one (71) MS patients were clinically examined, the expanded timed get-up and go (ETGUG), and timed 25-foot walk (T25FW) tests were assessed. Additionally, the Symbol Digit Modalities Test (SDMT) was obtained. Normalized brain (NBV), gray matter (GMV), white matter (WMV), cortex (CV), and deep GM (DGM) volumes, as well as lesion volumes (LV) and diffusion tensor imaging (DTI) scalar maps of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were calculated. Spearman correlation, partial correlation and stepwise regression analyses were performed., Results: T25FW and ETGUG were associated with T2-LV (p < .001), global (NBV, p < .001), tissue-specific (GMV and CV, p < .001) and regional (DGM p < .001; and thalamus p < .001) volumes. The ETGUG remained correlated with T1-LV, GMV, CV and total DGM volume (all p < .001) after age, sex, and disease duration adjustment. The WMV was not associated with walking disability. Similarly, DTI measures did not show significant association with the walking tests. The regression analysis outlined DMG volume as best predictor of T25FW (Adj R 2  = 0.231, standardized β = -0.435, and p = .001), and CV for ETGUG (Adj R 2  = 0.176, standardized β = -0.417, and p = .004). SDMT was associated with both T25FW (p = .004) and ETGUG (p = .013)., Conclusion: Despite the low disability levels, walking as measured by T25FW and ETGUG, is largely explained by the loss of cortical and nuclei specific GM volumes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To develop a patient-specific 3-dimensional (3D) printed drill guide for placement of cervical transpedicular screws and to assess its accuracy., Study Design: Prospective case-series., Sample Population: Thirty-two cervical pedicle screws (CPS) placed in 3 large breed dogs., Methods: Computed tomographic (CT) data of the cervical vertebrae were exported to a medical image processing software and 3D virtual vertebral models were created for each vertebra. These models were processed in a computer aided design (CAD) software to determine the optimal trajectory and size of the CPS. Virtual drill guides were created for each patient, 3D-printed, and used intraoperatively. Locking titanium screw heads were bonded with polymethylmethacrylate cement to stabilize affected vertebral segments. Postoperative CT was used to assess the radiological accuracy of CPS placement in each dog. For each screw, CAD files were analyzed to determine a screw-diameter-to-pedicle-width-ratio (SDPWR) at the narrowest point of the pedicle., Results: A total of 32 CPS were placed, measuring 3.5 mm (n = 20), 2.7 mm (n = 11), and 2.4 mm (n = 1) in diameter. The majority (29/32) of these screws were placed without evidence of vertebral canal breach (grade 0), whereas a vertebral canal breach <2 mm (grade 1) was detected in 3/32 screws. This outcome was achieved despite a mean SDPWR of 0.75 (range 0.58-0.93)., Conclusion: The use of a 3D-printed patient-specific drill guide permitted accurate placement of 32 bicortical pedicle screws in the caudal cervical vertebrae of 3 dogs. This technique may improve clinical outcome through superior biomechanical properties of screws, reduced surgical time, and reduced morbidity. These results warrant evaluation of patient outcome in a larger population., (© 2017 The American College of Veterinary Surgeons.)

Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia (ALL) expressing BCR-ABL1 oncoprotein is a major subclass of ALL with poor prognosis. BCR-ABL1-expressing leukemic cells are highly dependent on double-strand break (DSB) repair signals for their survival. Here we report that a first-in-class HDAC1,2 selective inhibitor and doxorubicin (a hyper-CVAD chemotherapy regimen component) impair DSB repair networks in Ph+ B-cell precursor ALL cells using common as well as distinct mechanisms. The HDAC1,2 inhibitor but not doxorubicin alters nucleosomal occupancy to impact chromatin structure, as revealed by MNase-Seq. Quantitative mass spectrometry of the chromatin proteome along with functional assays showed that the HDAC1,2 inhibitor and doxorubicin either alone or in combination impair the central hub of DNA repair, the Mre11-Rad51-DNA ligase 1 axis, involved in BCR-ABL1-specific DSB repair signaling in Ph+ B-cell precursor ALL cells. HDAC1,2 inhibitor and doxorubicin interfere with DISC (DNA damage-induced transcriptional silencing in cis)) or transcriptional silencing program in cis around DSB sites via chromatin remodeler-dependent and -independent mechanisms, respectively, to further impair DSB repair. HDAC1,2 inhibitor either alone or when combined with doxorubicin decreases leukemia burden in vivo in refractory Ph+ B-cell precursor ALL patient-derived xenograft mouse models. Overall, our novel mechanistic and preclinical studies together demonstrate that HDAC1,2 selective inhibition can overcome DSB repair 'addiction' and provide an effective therapeutic option for Ph+ B-cell precursor ALL.

Background: The gold standards for assessing ambulation are the Expanded Disability Status Scale (EDSS) and the Timed 25-Foot Walk (T25FW) test. In relation with these measures, we assessed the reliability and validity of four clinical gait measures: the Timed Up and Go (TUG) test, the Dynamic Gait Index (DGI), the 2-Minute Walk Test (2MWT), and the 6-Minute Walk Test (6MWT). Patient self-report of gait was also assessed using the 12-item Multiple Sclerosis Walking Scale (MSWS-12)., Methods: Individuals 20 years or older with a diagnosis of multiple sclerosis (MS) and an EDSS score of 2.0 to 6.5 completed the MSWS-12, T25FW test, TUG test, DGI, 2MWT, and 6MWT. All the tests were repeated 2 weeks later at the same time of day to establish their reliability and concurrent validity. Predictive validity was established using the EDSS., Results: Forty-two patients with MS were included. All measures showed high test-retest reliability. The TUG test, 2MWT, and 6MWT were significantly correlated with the T25FW test (Spearman ρ = -0.902, -0.919, and -0.905, respectively). The EDSS was also significantly correlated with all the walking tests. The MSWS-12 demonstrated the highest correlation to the EDSS (ρ = 0.788)., Conclusions: The TUG test, the DGI, the 2MWT, and the 6MWT exhibited strong psychometric properties and were found to be significant predictors of the EDSS score. Use of these tests to prospectively monitor the effects of medical and rehabilitation treatment should be considered in the comprehensive care of patients with MS., Competing Interests: Dr. Bennett has received honoraria for speaking from Acorda Therapeutics, Biogen Idec, and Medtronic Inc; is on the advisory board and has received research funding from Acorda Therapeutics; and is on the Clinical Events Committee of Innovative Neurotronics. Dr. Bromley has received honoraria for speaking and research funding from Acorda Therapeutics. The other authors have no conflicts of interest to disclose.

The Consortium of Multiple Sclerosis Centers (CMSC) convened a Framework Taskforce composed of a multidisciplinary group of clinicians and researchers to examine and evaluate the current models of care in multiple sclerosis (MS). The methodology of this project included analysis of a needs assessment survey and an extensive literature review. The outcome of this work is a two-part continuing education series of articles. Part 1, published previously, covered the updated disease phenotypes of MS along with recommendations for the use of disease-modifying therapies. Part 2, presented herein, reviews the variety of symptoms and potential complications of MS. Mobility impairment, spasticity, pain, fatigue, bladder/bowel/sexual dysfunction, cognitive dysfunction, and neuropsychiatric issues are examined, and both pharmacologic and nonpharmacologic interventions are described. Because bladder and bowel symptoms substantially affect health-related quality of life, detailed information about elimination dysfunction is provided. In addition, a detailed discussion about mental health and cognitive dysfunction in people with MS is presented. Part 2 concludes with a focus on the role of rehabilitation in MS. The goal of this work is to facilitate the highest levels of independence or interdependence, function, and quality of life for people with MS.

Purpose: The lexicons of the radiologist and the referring physician may not be synonymous, which could cause confusion with radiology reporting. To further explore this possibility, we surveyed radiologists and primary care physicians (PCPs) regarding their respective interpretations of report terminology., Methods: A survey was distributed to radiologists and PCPs through an internal listserv. Respondents were asked to provide an interpretation of the statistical likelihood of the presence of metastatic disease based upon the terminology used within a hypothetical radiology report. Ten common modifying terms were evaluated. Potential responses for the statistical likelihoods included 0%-25%, 26%-50%, 51%-75%, 76%-99%, and 100%. Differences between the groups were evaluated using either a χ 2 test or Fisher exact test, as appropriate., Results: The phrases "diagnostic for metastatic disease" and "represents metastatic disease" were selected by a high percentage of both groups as conferring a 100% likelihood of "true metastatic disease." The phrases "cannot exclude metastatic disease" and "may represent metastatic disease" were selected by a high proportion of both groups as conferring a 0% likelihood of "true metastatic disease." Radiologists assigned a higher statistical likelihood to the terms "diagnostic for metastatic disease" (P = .016), "represents metastatic disease" (P = .004), "suspicious for metastatic disease" (P = .04), "consistent with metastatic disease" (P < .0001), and "compatible with metastatic disease" (P = .003)., Conclusion: A qualitative agreement among radiologists and PCPs exists concerning the significance of the evaluated terminology, although radiologists assigned a higher statistical likelihood than PCPs for several phrases., (Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Activity Available Online: To access the article, post-test, and evaluation online, go to http://www.cmscscholar.org., Target Audience: The target audience for this activity is physicians, physician assistants, nursing professionals, and other health-care providers involved in the management of patients with multiple sclerosis (MS)., Learning Objectives: Apply new information about MS to a comprehensive individualized treatment plan for patients with MSIntegrate the team approach into long-term planning in order to optimize rehabilitation care of patients with MSAccreditation Statement: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the Consortium of Multiple Sclerosis Centers (CMSC), Nurse Practitioner Alternatives (NPA), and Delaware Media Group. The CMSC is accredited by the ACCME to provide continuing medical education for physicians. The CMSC designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurse Practitioner Alternatives (NPA) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NPA designates this enduring material for 1.0 Continuing Nursing Education credit. Laurie Scudder, DNP, NP, has served as Nurse Planner for this activity. She has disclosed no relevant financial relationships. Disclosures: Francois Bethoux, MD , Editor in Chief of the International Journal of MS Care (IJMSC), has served as Physician Planner for this activity. He has received royalties from Springer Publishing and has received intellectual property rights from Biogen. Laurie Scudder, DNP, NP , has served as Nurse Planner for this activity. She has disclosed no relevant financial relationships. Scott D. Newsome, DO, MSCS (author), has served on scientific advisory boards for Biogen, Genentech, Novartis, and Genzyme, and has performed contracted research (institution received funds) for Biogen, Genentech, and Novartis. Philip J. Aliotta, MD, MSHA, CHCQM, FACS (author), has served on speakers' bureaus for Astellas Pharma, Actavis, Augmenix, and Allergan and has performed contracted research for Allergan. Jacquelyn Bainbridge, PharmD (author), has disclosed no relevant financial relationships. Susan E. Bennett, PT, DPT, EdD, NCS, MSCS (author), has served on speakers' bureaus for Acorda Therapeutics, Biogen, and Medtronic; has received consulting fees from and performed contracted research for Acorda Therapeutics; and is chair of the Clinical Events Committee at Innovative Technologies. Gary Cutter, PhD (author), has participated on Data and Safety Monitoring Committees for AMO Pharma, Apotek, Gilead Pharmaceuticals, Horizon Pharmaceuticals, Modigenetech/Prolor, Merck, Merck/Pfizer, Opko Biologics, Neuren, Sanofi-Aventis, Reata Pharmaceuticals, Receptos/Celgene, Teva Pharmaceuticals, NHLBI (Protocol Review Committee), and NICHD (OPRU Oversight Committee); has received consulting fees from and/or served on speakers' bureaus and scientific advisory boards for Cerespir, Genzyme, Genentech, Innate Therapeutics, Janssen Pharmaceuticals, Klein-Buendel Incorporated, MedImmune, Medday, Nivalis, Novartis, Opexa Therapeutics, Roche, Savara, Somahlution, Teva Pharmaceuticals, Transparency Life Sciences, and TG Therapeutics; and is President of Pythagoras, Inc., a private consulting company located in Birmingham, AL. Kaylan Fenton, CRNP, APNP, MSCN (author), has disclosed no relevant financial relationships. Fred Lublin, MD (author), has received consulting fees/fees for non-CME/CE activities from Bayer HealthCare Pharmaceuticals, Biogen, EMD Serono, Novartis, Teva Neuroscience, Actelion, Sanofi/Genzyme, Acorda, Questcor/Mallinckrodt, Roche/Genentech, MedImmune, Osmotica, Xenoport, Receptos/Celgene, Forward Pharma, Akros, TG Therapeutics, AbbVie, Toyama, Amgen, Medday, Atara Biotherapeutics, Polypharma, Pfizer, Johnson & Johnson, Revalesio, Coronado Bioscience, and Bristol-Myers Squibb; has served on speakers' bureaus for Genentech/Roche and Genzyme/Sanofi; has performed contracted research for Acorda, Biogen, Novartis, Teva Neuroscience, Genzyme, Xenoport, and Receptos; is the co-chief editor of Multiple Sclerosis and Related Disorders ; and has an ownership interest in Cognition Pharmaceuticals. Dorothy Northrop, MSW, ACSW (author), has disclosed no relevant financial relationships. David Rintell, EdD (author), has received consulting fees from Novartis and has served as a patient education speaker for Teva Neuroscience. He started as a salaried employee of Sanofi Genzyme in November 2015. Dr. Rintell's work on this project was completed before he became a salaried employee of Sanofi Genzyme. Bryan D. Walker, MHS, PA-C (author), has served on scientific advisory boards for EMD Serono and Sanofi Genzyme and owns stock in Biogen. Megan Weigel, DNP, ARNP-C, MSCN (author), has received consulting fees from Mallinckrodt, Genzyme, and Genentech, and has served on speakers' bureaus for Bayer Corp, Acorda Therapeutics, Teva Neuroscience, Biogen, Mallinckrodt, Genzyme, Novartis, and Pfizer. Kathleen Zackowski, PhD, OTR, MSCS (author), has performed contracted research for Acorda Therapeutics. David E. Jones, MD (author), has received consulting fees from Biogen and Novartis, and has performed contracted research for Biogen. One anonymous peer reviewer for the IJMSC has performed contracted research (institution received funds) for Novartis, Chugai, and Biogen. Another reviewer has received consulting fees and served on speakers' bureaus for Biogen, Sanofi Genzyme, Genentech, EMD Serono, and Novartis. The third reviewer has disclosed no relevant financial relationships. Lori Saslow, MS (medical writer), has disclosed no relevant financial relationships. The staff at the IJMSC, CMSC, NPA, and Delaware Media Group who are in a position to influence content have disclosed no relevant financial relationships. Note: Disclosures listed for authors are those applicable at the time of their work on this project and within 12 months previously. Financial relationships for some authors may have changed in the interval between the time of their work on this project and publication of the article. Funding/Support: Funding for the Framework of Care consensus conference was provided by the Consortium of Multiple Sclerosis Centers, Mallinckrodt Pharmaceuticals, and Mylan Pharmaceuticals. Method of Participation: Release Date: December 1, 2016 Valid for Credit Through: December 1, 2017 In order to receive CME/CNE credit, participants must: Review the CME/CNE information, including learning objectives and author disclosures.Study the educational content.Complete the post-test and evaluation, which are available at http://www.cmscscholar.org. Statements of Credit are awarded upon successful completion of the post-test with a passing score of >70% and the evaluation. There is no fee to participate in this activity. Disclosure of Unlabeled Use: This CME/CNE activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. CMSC, NPA, and Delaware Media Group do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of CMSC, NPA, or Delaware Media Group. Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health-care professionals without first evaluating their patients' conditions, considering possible contraindications or risks, reviewing any applicable manufacturer's product information, and comparing any therapeutic approach with the recommendations of other authorities.

Introduction: Intrathecal baclofen (ITB) screening assesses response to a test dose of ITB on spasticity and function and identifies adverse reactions., Method: An expert panel consulted on best practices after conducting an extensive literature search and conducting an online survey., Results: A successful trial may confirm predetermined goals, which may include improved mobility/positioning, decreased time/improved independence for activities, less home exercise, better wheelchair tolerance, decreased caregiver time, improved sleep, and reduced pain, or may modify goals and expectations. Individuals should not be tested in the presence of active medical issues (e.g., MS exacerbations, active urinary tract infection, nonhealing wounds). Oral antispasmodics can be weaned before trial if a goal is to eliminate them. The standard baclofen test dose is a 50-mcg bolus, 25 mcg in very small children or patients who rely on spasticity for mobility. Patients unresponsive to the standard dose may require 75 mcg or 100 mcg; 24 hours should elapse between bolus doses. Cardiopulmonary parameters should be checked frequently during the first two hours postinjection, and spasticity measures assessed at least twice within four hours. Observation continues until the patient is stable and recovers from hypertonia. Adverse events include spinal headaches, nausea/vomiting, urinary retention, hypotension, seizures, drowsiness/sedation, respiratory depression, and coma. Before implantation, team members must discuss starting dose, drug concentration, delivery mode, pump size and location, and catheter tip placement. Patients/caregivers should understand the commitment necessary for ITB therapy., Conclusions: Screening helps identify appropriate candidates for ITB., (© 2016 International Neuromodulation Society.)

There is increasing evidence that large-bodied primates play important roles as seed dispersers and in the maintenance of tree diversity in forest ecosystems. In this study we compared forest regeneration at two sites with differing primate abundances in the Ecuadorian Chocoan rainforest. We predicted: (1) significant differences in primate abundance between the two sites; (2) higher understory tree species richness and density at the site with greater primate abundance; (3) the site with lower primate abundance characterized by tree species dispersed by non-primate biotic agents and/or abiotic factors. We compared two sites, Tesoro Escondido (TE) a campesino cooperative, and the El Pambilar (EP) wildlife refuge that both maintain populations of mantled howler monkey (Alouatta palliata), the brown-headed spider monkey (Ateles fusciceps fusciceps) and the capuchin monkey (Cebus capucinus). We characterized canopy structure by point-quadrant sampling, determined primate abundance and sampled seedlings/saplings in 1 m2 plots, classifying tree species based on three dispersal syndromes: adapted for primate dispersal, dispersed by other biological agents, and abiotic dispersal. We compared sites in terms of primate abundance (groups and individuals observed per day) and regeneration characteristics (overall density, species richness, and dispersal syndrome). We carried out within site comparisons and constructed understory tree species accumulation curves. Overall the forests were structurally similar - with significantly higher densities of A. f. fusciceps at TE. Encounter rates for the other two primate species were similar at both sites. Understory tree density and species richness was significantly higher in TE with no stabilization of tree species accumulation curves. The species accumulation curve for understory trees at EP stabilized. Higher densities and species richness of primate dispersed tree species were observed at TE, with non-primate biotically dispersed tree species the dominant dispersal syndrome at both sites. Our observations are consistent with those from other studies investigating the role of large-bodied frugivorous primates in forest regeneration, and point to a general pattern: future lowland tropical forest tree diversity depends on maintaining robust populations of large primate species in these systems. It is highly probable that the maintenance of high levels of tree diversity in Chocoan rainforests is dependent on the conservation of its largest resident primate, the critically endangered brown-headed spider monkey (A. f. fusciceps).

Electron capture dissociation (ECD), which generally preserves the position of labile post-translational modifications, can be a powerful method for de novo sequencing of proteins and peptides. In this report, ECD product-ion mass spectra of singly and doubly sodiated, nonphosphorylated, and phosphorylated peptides are presented and compared with the ECD mass spectra of their protonated counterparts. ECD of doubly charged, singly sodiated peptides yielded essentially the same sequence information as was produced by the corresponding doubly protonated peptides. The presence of several sodium binding sites on the polypeptide backbone, however, resulted in more complicated spectra. This situation is aggravated by the zwitterionic equilibrium of the free acid peptide precursors. The product-ion spectra of doubly and triply charged peptides possessing two sodium ions were further complicated by the existence of isomers created by the differential distribution of sodium binding sites. Triply charged, phosphorylated precursors containing one sodium, wherein the sodium is attached exclusively to the PO4 group, were found to be as useful for sequence analysis as the fully protonated species. Although sodium adducts are generally minimized during sample preparation, it appears that they can nonetheless provide useful sequence information. Additionally, they enable straightforward identification of a peptide's charge state, even on low-resolution instruments. The experiments were carried out using a radio frequency-free electromagnetostatic cell retrofitted into the collision-induced dissociation (CID) section of a hybrid quadrupole/time-of-flight tandem mass spectrometer. Graphical Abstract ᅟ.

Objective: The purposes of this study were to assess the feasibility of and to create a referral mechanism for a diagnostic radiology consultation clinic., Subjects and Methods: A pilot program was instituted with patients from a single primary care clinic over a 3-week period. Patients with findings of common problems at routine imaging, such as atherosclerosis, emphysema, and hepatic steatosis, were eligible to participate. As the patients arrived for their routine primary care visits, office staff informed them of the opportunity to formally meet with a radiologist to review their most recent imaging findings. The office staff of the primary care clinic then contacted the radiologist covering the diagnostic radiology consultation clinic to schedule a consultation. A survey was administered before and after the session., Results: Twenty-two patients participated (88% participation rate). Participants rated the consultation as very helpful (mean, 4.8 on 1-5 scale), and all participants would take the opportunity to review studies with the radiologist again. Significantly more patients preferred the involvement of the radiologist in communicating the results of an imaging examination after the consultation compared with before the consultation (p = 0.001). After the consultation session, patients had significantly improved understanding of a radiologist's role (p = 0.004), and all participants were able to correctly identify the radiologist as a physician who interprets medical images., Conclusion: A referral mechanism for a diagnostic radiology consultation clinic can be effectively integrated into the everyday workflow of both the referring physician and the radiologist. The consultations are useful to patients and help to increase their awareness of the role of the radiologist.

Despite the well-known benefits of using standardized outcome measures (OMs) in clinical practice, a variety of barriers interfere with their use. In particular, rehabilitation therapists lack sufficient knowledge in selecting appropriate OMs. The challenge is compounded when working with people with multiple sclerosis (MS) owing to heterogeneity of the patient population and symptom variability in individual patients. To help overcome these barriers, the American Physical Therapy Association appointed the Multiple Sclerosis Outcome Measures Task Force to review and make evidence-based recommendations for OM use in clinical practice, education, and research specific to people with MS. Sixty-three OMs were reviewed based on their clinical utility, psychometric properties, and a consensus evaluation of the appropriateness of use for people with MS. We sought to illustrate use of the recommendations for two cases. The first case involves a 43-year-old man with new-onset problems after an exacerbation. The second case pertains to an outpatient clinic interested in assessing the effectiveness of their MS rehabilitation program. For each case, clinicians identified areas that were important to assess and various factors deemed important for OM selection. Criteria were established and used to assist in OM selection. In both cases, the described processes narrowed the selection of OMs and assisted with choosing the most appropriate ones. The recommendations, in addition to the processes described in these two cases, can be used by clinicians in any setting working with patients with MS across the disability spectrum.

Dissociation of peptides induced by interaction with (free) electrons (electron-induced dissociation, EID) at electron energies ranging from near 0 to >30 eV was carried out using a radio-frequency-free electromagnetostatic (EMS) cell retrofitted into a triple quadrupole mass spectrometer. The product-ion mass spectra exhibited EID originating from electronically excited even-electron precursor ions, reduced radical cations formed by capture of low-energy electrons, and oxidized radical cations produced by interaction with high-energy electrons. The spectra demonstrate, within the limits of the triple quadrupole's resolving power, that high-energy EID product-ion spectra produced with an EMS cell exhibit essentially the same qualitative structural information, i.e., amino acid side-chain (SC) losses and backbone cleavages, as observed in high-energy EID spectra produced with a Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. The levels of fragmentation efficiency evident in the product-ion spectra recorded in this study, as was the case for those recorded in earlier studies with FT ICR mass spectrometers, is currently at the margin of analytical utility. Given that this shortcoming can be remedied, EMS cells incorporated into QqQ or QqTOF mass spectrometers could make tandem high-energy EID mass spectrometry more widely accessible for analysis of peptides, small singly charged molecules, pharmaceuticals, and clinical samples.

A radio frequency-free electromagnetostatic (EMS) cell devised for electron-capture dissociation (ECD) of ions has been retrofitted into the collision-induced dissociation (CID) section of a triple quadrupole mass spectrometer to enable recording of ECD product-ion mass spectra and simultaneous recording of ECD-CID product-ion mass spectra. This modified instrument can be used to produce easily interpretable ECD and ECD-CID product-ion mass spectra of tyrosine-phosphorylated peptides that cover over 50% of their respective amino-acid sequences and readily identify their respective sites of phosphorylation. ECD fragmentation of doubly protonated, tyrosine-phosphorylated peptides, which was difficult to observe with FT-ICR instruments, occurs efficiently in the EMS cell.

Upper extremity (UE) dysfunction may be present in up to ~80% of individuals with multiple sclerosis (MS), although its importance may be under-recognized relative to walking impairment, which is the hallmark symptom of MS. Upper extremity dysfunction affects independence and can impact the ability to use walking aids. Under-recognition of UE dysfunction may result in part from limited availability of performance-based and patient self-report measures that are validated for use in MS and that can be readily incorporated into clinical practice for screening and regularly scheduled assessments. In addition to the 9-Hole Peg Test, which is part of the Multiple Sclerosis Functional Composite, there are several performance-based measures that are generally used in the rehabilitation setting. These measures include the Box and Block Test, the Action Research Arm Test, the Test d'Evaluation de la performance des Membres Supérieurs des Personnes Agées, and the Jebsen-Taylor Test of Hand Function. Several of these measures were developed for use in stroke, although in contrast to stroke, which is characterized by unilateral dysfunction, UE impairment in MS is generally bilateral, and should be assessed as such. Similarly, patient-reported UE measures are available, including Disabilities of the Arm, Shoulder, and Hand (DASH) and its shorter version, QuickDASH, the Manual Ability Measure, and ABILHAND, although none has been psychometrically validated for MS. Recently, item response theory was used to develop a Neuro-QOL (Quality of Life) UE measure and a Patient-Reported Outcomes Measurement Information System UE measure; neither of these have demonstrated sensitivity to change, limiting their use for longitudinal assessment. Consequently, although work is still needed to develop and validate performance-based and patient-reported measures of UE function that are suitable for use in daily MS clinical practice, currently available UE measures can be recommended for incorporation into MS management, albeit with an understanding of their limitations.

Vitamin traffic, the production of organic growth factors by some microbial community members and their use by other taxa, is being scrutinized as a potential explanation for the variation and highly connected behavior observed in ocean plankton by community network analysis. Thiamin (vitamin B1), a cofactor in many essential biochemical reactions that modify carbon-carbon bonds of organic compounds, is distributed in complex patterns at subpicomolar concentrations in the marine surface layer (0-300 m). Sequenced genomes from organisms belonging to the abundant and ubiquitous SAR11 clade of marine chemoheterotrophic bacteria contain genes coding for a complete thiamin biosynthetic pathway, except for thiC, encoding the 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) synthase, which is required for de novo synthesis of thiamin's pyrimidine moiety. Here we demonstrate that the SAR11 isolate 'Candidatus Pelagibacter ubique', strain HTCC1062, is auxotrophic for the thiamin precursor HMP, and cannot use exogenous thiamin for growth. In culture, strain HTCC1062 required 0.7 zeptomoles per cell (ca. 400 HMP molecules per cell). Measurements of dissolved HMP in the Sargasso Sea surface layer showed that HMP ranged from undetectable (detection limit: 2.4 pM) to 35.7 pM, with maximum concentrations coincident with the deep chlorophyll maximum. In culture, some marine cyanobacteria, microalgae and bacteria exuded HMP, and in the Western Sargasso Sea, HMP profiles changed between the morning and evening, suggesting a dynamic biological flux from producers to consumers.

Objective: The physiological importance of the C3 epimers of vitamin D (3-epi-25OHD2/3) is uncertain and there have been limited studies determining the levels of these epimers in human populations. The aims of the current study were (1) to determine 3-epi-25OHD2/3 levels throughout non-diabetic and T1DM pregnancy, (2) to examine the relationships between 25OHD and 3-epi-25OHD, (3) to assess the impact of maternal BMI on 3-epi-25OHD and examine associations with markers of glycaemic control., Methodology: An observational study of 52 pregnant controls without diabetes and 65 pregnant women with T1DM in a university teaching hospital. 25OHD and 3-epi-25OHD were measured by liquid chromatography tandem mass spectrometry., Results: 3-Epi-25OHD was found in 90.2% of control (median 0.9nmol/L; range 0.1-5.9nmol/L), and in 94.5% of T1DM, women (median 1.4nmol/L; range 0.1-10.5nmol/L). In both control and T1DM groups, maternal and cord 3-epi-25OHD correlated significantly with 25OHD. Seasonal variation in maternal 3-epi-25OHD levels was evident in both groups; Summer levels were significantly higher than all other seasons in the control group (p<0.001) and significantly higher than Spring (p=0.003) and Winter (p<0.001) in the T1DM group. In T1DM women HbA1c was significantly negatively correlated with 3-epi-25OHD at trimesters 1 and 2 (p=0.049; p=0.001) and with cord 3-epi-25OHD (p=0.012). Maternal BMI >30kg/m(2) had a significant negative impact on 3-epi-25OHD., Conclusion: Maternal 3-epi-25OHD exhibits seasonal variation and, in common with cord 3-epi-25OHD, correlates with 25OHD throughout both non-diabetic and T1D pregnancy. In T1DM women 3-epi-25OHD is associated with a key marker of glycaemic control., (Copyright © 2014.)

Objective: 1. To examine relationships between 25-hydroxy vitamin D (25OHD) in women with type 1 diabetes (T1DM) during pregnancy, post-delivery and in cord blood. 2. To investigate interactions between maternal body mass index (BMI) and foetal vitamin D status. 3. To examine relationships between maternal 25OHD and glycosylated haemoglobin (HbA1c)., Methodology: An observational study of 52 pregnant controls without diabetes and 65 pregnant women with T1DM in a university teaching hospital. 25OHD was measured by liquid chromatography tandem mass spectrometry., Results: Vitamin D deficiency (25OHD <25nmol/L) was apparent in control and T1DM women in all 3 trimesters. All cord blood 25OHD were <50nmol/L. Maternal 25OHD correlated positively with cord 25OHD at all 3 trimesters in the T1DM group (p=0.02; p<0.001; p<0.001). Cord 25OHD was significantly lower for T1D women classified as obese vs. normal weight at booking [normal weight BMI <25kg/m(2) vs. obese BMI〉30kg/m(2) (nmol/L±SD); 19.93±11.15 vs. 13.73±4.74, p=0.026]. In the T1DM group, HbA1c at booking was significantly negatively correlated with maternal 25OHD at all 3 trimesters (p=0.004; p=0.001; p=0.05)., Conclusion: In T1DM pregnancy, low vitamin D levels persist throughout gestation and post-delivery. Cord blood vitamin D levels correlate with those of the mother, and are significantly lower in obese vs normal weight women. Maternal vitamin D levels exhibit a significant negative relationship with HbA1c, supporting a potential role for this vitamin in maintaining glycaemic control., (Copyright © 2014.)

Objective: There is considerable interest in improving radiology reporting practices through peer review, and the inclusion of structured feedback from referring physicians may improve this process. The purpose of this article is to evaluate the feasibility of this type of novel peer-review system., Materials and Methods: Five referring physicians from our institution participated as reviewers. Reports from abdominal CT, chest CT, brain MRI, and abdominal ultrasound were eligible for review if the indication was "abdominal pain," "shortness of breath," "headache," and "pain," respectively. Reports were excluded if the examinations were normal or ordered as follow-up. Forty-eight reports (12 from each group) were then selected at random and distributed to the referring physicians along with the clinical scenario and an evaluation form for each examination., Results: The reports were found to be clinically useful (average, 3.8 on a 1-5 scale), allowing for good confidence in clinical decision making (average, 3.7). The most common problems were unclear language, typographical errors, and reports that did not answer the clinical question. Of the reports, 35.4% contained recommendations for further diagnosis or treatment, and 84.7% of these recommendations were deemed clinically appropriate. The participating physicians thought that the results of 31.2% of the examinations should have been directly communicated to the ordering provider., Conclusion: Radiology reports and recommendations were clinically useful, even though problems with language, typographical errors, answering the clinical question, and direct communication of examination results were identified. Structured feedback from referring physicians is a novel approach to the peer-review process that may identify problems that go unnoticed by the radiologist, thereby improving reporting practices.

Objective: The first aim of this study was to assess 25-hydroxy vitamin D (25OHD) concentrations in women with type 1 diabetes (T1DM) during pregnancy, post-delivery and also foetal (cord blood) 25OHD concentrations and to examine relationships between these. The second aim of the study was to investigate potential interactions between maternal body mass index (BMI) and foetal vitamin D status. A further study aim was to examine potential relationships between maternal 25OHD and glycosylated haemoglobin (HbA1c) throughout pregnancy., Research Design and Methods: This was an observational study of 52 pregnant controls without diabetes and 65 pregnant women with T1DM in a university teaching hospital. Maternal serum 25OHD was measured serially throughout the pregnancy and post-delivery. Cord blood 25OHD was measured at delivery. 25OHD was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS)., Results: Vitamin D deficiency (25OHD <25 nmol/L) was apparent in both the T1DM subjects and controls at all 3 pregnancy trimesters. Vitamin D levels in all cord blood were <50 nmol/L. Maternal 25OHD correlated positively with cord 25OHD at all 3 trimesters in the T1DM group (p=0.02; p<0.001; p<0.001). 25OHD levels within cord blood were significantly lower for women with diabetes classified as obese vs. normal weight at booking [normal weight BMI <25 kg/m(2) vs. obese BMI >30 kg/m(2) (nmol/L ± SD); 19.93 ± 11.15 vs. 13.73 ± 4.74, p=0.026]. In the T1DM group, HbA1c at booking was significantly negatively correlated with maternal 25OHD at all 3 trimesters (p=0.004; p=0.001; p=0.05)., Conclusion: In T1DM pregnancy, low vitamin D levels persist throughout gestation and post-delivery. Cord blood vitamin D levels correlate with those of the mother, and are significantly lower in obese women than in their normal weight counterparts. Maternal vitamin D levels exhibit a significant negative relationship with HbA1c levels, supporting a potential role for this vitamin in maintaining glycaemic control.