Ehlers–Danlos syndrome, hypermobility type: A characterization of the patients' lived experience

Hypermobility type Ehlers–Danlos syndrome (EDS‐HT) is an inherited connective tissue disorder clinically diagnosed by the presence of significant joint hypermobility and associated skin manifestations. This article presents a large‐scale study that reports the lived experience of EDS‐HT patients, the broad range of symptoms that individuals with EDS‐HT experience, and the impact these symptoms have on daily functioning. A 237‐item online survey, including validated questions regarding pain and depression, was developed. Four hundred sixty‐six (466) adults (90% female, 52% college or higher degree) with a self‐reported diagnosis of EDS‐HT made in a clinic or hospital were included. The most frequently reported symptoms were joint pain (99%), hypermobility (99%), and limb pain (91%). They also reported a high frequency of other conditions including chronic fatigue (82%), anxiety (73%), depression (69%), and fibromyalgia (42%). Forty‐six percent of respondents reported constant pain often described as aching and tiring/exhausting. Despite multiple interventions and therapies, many individuals (53%) indicated that their diagnosis negatively affected their ability to work or attend school. Our results show that individuals with EDS‐HT can experience a wide array of symptoms and co‐morbid conditions. The degree of constant pain and disability experienced by the majority of EDS‐HT respondents is striking and illustrates the impact this disorder has on quality of life as well as the clinical challenges inherent in managing this complex connective tissue disorder. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101781/1/ajmga36293.pd

Across-subject calibration of an instrumented glove to measure hand movement for clinical purposes

Motion capture of all degrees of freedom of the hand collected during performance of daily living activities remains challenging. Instrumented gloves are an attractive option because of their higher ease of use. However, subject-specific calibration of gloves is lengthy and has limitations for individuals with disabilities. Here, a calibration procedure is presented, consisting in the recording of just a simple hand position so as to allow capture of the kinematics of 16 hand joints during daily life activities even in case of severe injured hands. ‘across-subject gains’ were obtained by averaging the gains obtained from a detailed subject-specific calibration involving 44 registrations that was repeated three times on multiple days to 6 subjects. In additional 4 subjects, joint angles that resulted from applying the ‘across-subject calibration’ or the subject-specific calibration were compared. Global errors associated with the ‘across-subject calibration’ relative to the detailed, subject-specific protocol were small (bias: 0.49°; precision: 4.45°) and comparable to those that resulted from repeating the detailed protocol with the same subject on multiple days (0.36°; 3.50°). Furthermore, in one subject, performance of the ‘across-subject calibration’ was directly compared to another fast calibration method, expressed relative to a videogrammetric protocol as a gold-standard, yielding better results.This work was supported by the Ministerio de Economía y Competitividad [project number DPI2014-52095-P]; Universitat Jaume I [project number P1-1B2013-33], [project number P1-1B2014-10]; NIH [grant number NIH R01EB011615]. We thank Marta Mora, PhD, for her collaboration in coding for data glove acquisition, and the graduate student Sheyla Mestre Vicente for her collaboration in data collection. Authors thank also Union de Mutuas for their support in clinical guidanc

The Importance of Acquisition Learning on Nicotine and Varenicline Drug Substitution in a Drug-Discriminated Goal-Tracking Task

Nicotine and varenicline (Chantix®; the leading non-nicotine cessation pharmacotherapy) can come to control appetitive behaviors such as goal-tracking. We tested rats (N = 48) in a drug-discriminated goal-tracking (DGT) task where each rat received daily subcutaneous injections of either nicotine (0.4 mg/kg) or saline (0.9% [w/v]) interspersed across the acquisition phase (Phase 1). On saline days, sucrose was intermittently available. On nicotine days, sucrose was withheld. All rats acquired the discrimination with increased goal-tracking rates on saline days relative to nicotine days. Following acquisition, rats were separated into four groups to assess drug-substitution and discrimination reversal in Phase 2. The first group maintained the stimulus-reinforcer relation from acquisition (NIC−). The reversal group was now given access to sucrose on nicotine days (NIC+). The substitution group replaced nicotine with varenicline (1 mg/kg) while maintaining the acquisition stimulus-reinforcer relation (VAR−). The substitution and reversal group had nicotine replaced by varenicline and the stimulus-reinforcer relation reversed (VAR+). Rats in all groups learned or maintained their Phase 1 discriminations. For Phase 2, the reversal groups (+ conditions) acquired their discriminations within 10 sessions. The VAR−group displayed a pattern of disrupted discrimination at the outset of Phase 2 but was reestablished after continued training. In substitution testing, VAR groups received nicotine and NIC groups received varenicline. The NIC−and VAR−groups displayed full substitution of the test stimulus whereas the NIC+ and VAR+ groups displayed partial substitution of the test stimulus. Rats underwent nicotine extinction in Phase 3. Initial responding for each group mimicked Phase 2 training (i.e., higher responding by the reversal groups). All rats maintained similarly low levels of responding after six sessions. In conclusion, initial learning history with nicotine (i.e., + or −) influenced drug-stimulus substitution and the rate at which new learning (e.g., reversal) occurs with the varenicline and nicotine interoceptive stimuli

Can we spot deleterious ageing in two waves of data? The Lothian Birth Cohort 1936 from ages 70 to 73

‘Younger ’ old age (the late 60s through early 70s) is, for many, a period of stability of lifestyle and considerable freedom to pursue leisure activities. Despite the stability that many enjoy, the mortality rate is about 2 % per year in western nations. This increases to about 5 % by age 80. It would be useful to know if those most vulnerable can be identified through patterns of deleterious ageing, and especially if this could be accomplished with just two waves of data. The Lothian Birth Cohort 1936 was surveyed on a host of individual difference variables including cognition, personality, biomarkers of physical health, and activities at ages 70 and 73 years. Overall, the group showed the expected basic stability in mean levels for these variables, but some individuals had died and others did show substantial changes that could be considered statistically reliable. These presumably reliable changes were at least as likely to be positive (reflecting improved condition/ability) as negative (reflecting decline/ageing). Moreover, limitations in the estimated reliabilities of the measures meant that most of the observed changes could not be considered reliable. The changes clustered only weakly around general health to predict death over the next approximately two years. We concluded that two waves of longitudinal data were not sufficient to assess meaningful patterns of ageing, despite often being used to do so

Model-based control of individual finger movements for prosthetic hand function

The authors gratefully acknowledge the support of the Engineering and Physical Sciences Research Council (EP/M025977/1) and the National Institutes of Health (NIH5R01EB011615) in this research.Peer reviewedPostprin

Meaningful Effect Sizes, Intraclass Correlations, and Proportions of Variance Explained by Covariates for Planning Two- and Three-Level Cluster Randomized Trials of Social and Behavioral Outcomes

BACKGROUND: There is a need for greater guidance regarding design parameters and empirical benchmarks for social and behavioral outcomes to inform assumptions in the design and interpretation of cluster randomized trials (CRTs). OBJECTIVES: We calculated the empirical reference values on critical research design parameters associated with statistical power for children's social and behavioral outcomes, including effect sizes, intraclass correlations (ICCs), and proportions of variance explained by a covariate at different levels (R 2). SUBJECTS: Children from kindergarten to Grade 5 in the samples from four large CRTs evaluating the effectiveness of two classroom- and two school-level preventive interventions. MEASURES: Teacher ratings of students' social and behavioral outcomes using the Teacher Observation of Classroom Adaptation-Checklist and the Social Competence Scale-Teacher. RESEARCH DESIGN: Two types of effect size benchmarks were calculated: (1) normative expectations for change and (2) policy-relevant demographic performance gaps. The ICCs and R 2 were calculated using two-level hierarchical linear modeling (HLM), where students are nested within schools, and three-level HLM, where students were nested within classrooms, and classrooms were nested within schools. RESULTS AND CONCLUSIONS: Comprehensive tables of benchmarks and ICC values are provided to inform prevention researchers in interpreting the effect size of interventions and conduct power analyses for designing CRTs of children's social and behavioral outcomes. The discussion also provides a demonstration for how to use the parameter reference values provided in this article to calculate the sample size for two- and three-level CRTs designs

Measuring access to primary care appointments: a review of methods

BACKGROUND: Patient access to primary care appointments is not routinely measured despite the increasing interest in this aspect of practice activity. The generation of standardised data (or benchmarks) for access could inform developments within primary care organisations and act as a quality marker for clinical governance. Logically the setting of targets should be based on a sound system of measurement. The practicalities of developing appropriate measures need debate. Therefore we aimed to search for and compare methods that have been published or are being developed to measure patient access to primary care appointments, with particular focus on finding methods using appointment system data. METHOD: A search and review was made of the primary care literature from 1990 to 2001, which included an assessment of online resources (websites) and communication with recognised experts. The identified methods were assessed. RESULTS: The published literature in this specific area was not extensive but revealed emerging interest in the late 1990s. Two broad approaches to the measurement of waiting times to GP appointments were identified. Firstly, appointment systems in primary care organisations were analysed in differing ways to provide numerical data and, secondly, patient perceptions (reports) of access were evaluated using survey techniques. Six different methods were found which were based on appointment systems data. CONCLUSION: The two approaches of either using patient questionnaires or appointment system data are methods that represent entirely different aims. The latter method when used to represent patient waiting times for 'routine' elective appointments seems to hold promise as a useful tool and this avoids the definitional problems that surround 'urgent' appointments. The purpose for which the data is being collected needs to be borne in mind and will determine the chosen methods of data retrieval and representation

Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

We would like to thank all patients whose samples were used in this study. We are also thankful to the Northern Ireland Biobank and Grampian Biorepository for providing us with tissue blocks and patient data; and Dr HG Coleman (Queen’s University Belfast) for her advice on statistical analyses. This work has been carried out with financial support from Cancer Research UK (grant: C11512/A18067), Experimental Cancer Medicine Centre Network (grant: C36697/A15590 from Cancer Research UK and the NI Health and Social Care Research and Development Division), the Sean Crummey Memorial Fund and the Tom Simms Memorial Fund. The Northern Ireland Biobank is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory which is responsible for creating resources for the Northern Ireland Biobank has received funding from Cancer Research UK, Friends of the Cancer Centre and Sean Crummey Foundation.Peer reviewedPublisher PD