Development and validation of the WEll-being and Satisfaction of CAREgivers of Children with Diabetes Questionnaire (WE-CARE)

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The reliability, validity and responsiveness of the Restless Legs Syndrome Quality of Life questionnaire (RLSQoL) in a trial population

BACKGROUND: The aim of this study was to determine the reliability, validity and responsiveness of the Restless Legs Syndrome Quality of Life questionnaire (RLSQoL) in a clinical trial setting. METHODS: Two matching, placebo-controlled, multinational studies assessing the effectiveness and safety of ropinirole for treating moderate-to-severe Restless Legs Syndrome (RLS) formed the basis of this psychometric assessment. Validity and reliability were assessed using baseline data. Responsiveness was determined using longitudinal data collected at baseline and 12 weeks. RESULTS: A total of 547 subjects formed the baseline validation population; 519 were used for assessing responsiveness (n = 284/263 and 271/248 for both studies, respectively). Construct validity assessment confirmed that an overall life impact score could be calculated. All item-scale correlations were = 0.4, except items 1 (r = 0.36) and 5 (r = 0.35) in one study. Floor and ceiling effects were minimal. Cronbach's alpha values were 0.82 and 0.87, respectively, confirming internal consistency reliability. Correlations with the International Restless Legs Syndrome Study Group's severity rating scale (International Restless Legs Scale; IRLS) were moderate (r = -0.68 and -0.67, respectively; p < 0.0001). The RLSQoL was able to discriminate between levels of sleep problems (p < 0.0001) and between levels of global health status determined by a Clinical Global Impression of severity (CGI-S) (p < 0.0001). Responsiveness was demonstrated by significant differences in overall life impact change scores between CGI improvement levels after 12 weeks (p < 0.0001). CONCLUSION: The RLSQoL is a valid, reliable and responsive measure of quality of life for patients with RLS, in a clinical trial setting where group comparisons are anticipated

Lateral Sharpening of Cortical Frequency Tuning by Approximately Balanced Inhibition

SummaryCortical inhibition plays an important role in shaping neuronal processing. The underlying synaptic mechanisms remain controversial. Here, in vivo whole-cell recordings from neurons in the rat primary auditory cortex revealed that the frequency tuning curve of inhibitory input was broader than that of excitatory input. This results in relatively stronger inhibition in frequency domains flanking the preferred frequencies of the cell and a significant sharpening of the frequency tuning of membrane responses. The less selective inhibition can be attributed to a broader bandwidth and lower threshold of spike tonal receptive field of fast-spike inhibitory neurons than nearby excitatory neurons, although both types of neurons receive similar ranges of excitatory input and are organized into the same tonotopic map. Thus, the balance between excitation and inhibition is only approximate, and intracortical inhibition with high sensitivity and low selectivity can laterally sharpen the frequency tuning of neurons, ensuring their highly selective representation

Development and Content Validity Testing of a Patient-Reported Treatment Acceptance Measure for Use in Patients Receiving Treatment via Subcutaneous Injection

AbstractBackgroundNew therapies in development for lowering low-density lipoprotein cholesterol, such as alirocumab, require administration by subcutaneous injections. There is a need to assess the acceptance of such treatments and their mode of administration.ObjectivesTo develop a novel patient-reported outcome measure, the Injection-Treatment Acceptance Questionnaire (I-TAQ), and assess its content validity using qualitative methods.MethodsConcepts generated from a literature and instrument review informed the initial drafting of 17 items in the I-TAQ, with item wording adapted from three existing instruments. Three rounds of qualitative interviews were conducted with 29 US-English speaking patients at high cardiovascular risk. Concept elicitation questioning was used to explore patients’ treatment experiences followed by cognitive debriefing of the I-TAQ using “think-aloud” methods. Verbatim transcripts were analyzed using thematic analysis.ResultsQualitative analysis of concept elicitation data identified the following relevant concepts: perceived efficacy, side effects, self-efficacy, convenience, and overall acceptance. Seven (24%) patients discussed an initial fear of needles, but described this as subsiding with no impact on adherence. Five items were added after round one interviews, three of which were retained after round two testing in which two further items were added, forming the conceptually comprehensive 22-item I-TAQ. Patients demonstrated good understanding of item wording, instructions, response scales, and recall period.ConclusionsSuccessive rounds of in-depth interviews resulted in a treatment acceptance measure with strong content validity. Pending demonstration of its psychometric properties, the I-TAQ may prove to be a valuable measure of patients’ perspectives toward being treated with low-density lipoprotein cholesterol–lowering therapies requiring subcutaneous injections

Addressing the Needs of Children of Offenders: The 4-H LIFE Model

4-H LIFE represents a promising approach to addressing the needs of children of offenders and their caregivers. The 4-H Living Interactive Family Education (LIFE) Program was established in 1999 at the Potosi Correctional Center, a maximum security prison. 4-H LIFE is an enhanced or therapeutic visitation program with three key components: 1. parent engagement; 2. parent education; 3. 4-H activities for children of offenders, led by the incarcerated parents. Since inception, 141 youths between the ages of 5 and 18 have participated; 59 incarcerated fathers and 106 caregivers have also been engaged at PCC. Program evaluations suggest that parent-child outcomes improved. In 2005, 4-H LIFE received the Annie E. Casey Foundation Family Strengthening Award

Hatfield Marine Science Center Dynamic Revetment Project DSL permit # 45455-FP: Monitoring Report, February 2015

Stabilization of the Yaquina Bay shoreline along the northeastern edge of the Hatfield Marine Science Center (HMSC) campus became necessary to halt erosion that threatened both HMSC critical infrastructure (seawater storage tank) and public access to the HMSC Nature Trail. A Dynamic Revetment (gravel beach) was installed in November, 2011 on 260 feet of shoreline to mitigate erosion. Shoreline topographic and biological monitoring was initiated before and has continued after the project completion. Monitoring of beach profiles indicated that as of January 2015, the 2011 Dynamic Revetment Project (DRP) has generally successfully stabilized the shoreline in the project area. Beach profile data also indicated that the 2007 DRP continued to be successful in stabilizing further retreat of the shoreline. In both areas, some loss of gravel at the top of the shore profile due to overtopping of the beach during highest tides was noted, and some additional placement of gravel at these locations is recommended. Rapid erosion has continued in the adjacent Reference beach area and over the period 2009-2015 has been as great as 11 m (36 ft). The erosion in the Reference area adjacent to the south end of new gravel beach appears entirely a function of antecedent erosion that is taking place along the entire length of this shore and is not related to any end effects associated with the expanded gravel beach. Monitoring of beach wrack invertebrates, fish, and vegetation was conducted in 2014. Per unit of beach wrack biomass, the density of wrack invertebrates was significantly greater in the DRP area as compared to both the 2007 DRP area and the Reference area. Total amount of beach wrack was much sparser in the Reference area because of vertical beach scarps generated by erosion that appeared to limit wrack accumulation. As has been a consistent pattern, fish were significantly more abundant in the Reference area compared to the DRP. However, this pattern was present in the pre-project sampling, and the Reference area may have a higher degree of physical habitat complexity, resulting from root masses of trees that have been eroded onto the shore. Chum salmon were recorded from both the DRP and Reference area in 2014 in approximately equal numbers. Preliminary assessment of fish using stationary GoPro® camera samples suggested that there is active fish usage of the DRP gravel shoreline. Sampling issues continue to be problematic for quantitative comparisons of fish abundance. As has consistently been observed, vegetation coverage was significantly greater and presence of non-living substrata was significantly less in the Reference area as compared to the DRP. These differences are consistent with pre-project site differences, probably resulting from a low area of the shoreline which allows increased flooding and associated disturbance in the DRP back shore area. Fish and wrack invertebrates, such as beach hoppers, continue to utilize the DRP project area. Biological differences in fish and vegetation observed in the post-project monitoring in 2014 tended to reflect differences in habitat that were present before the DRP project

Hatfield Marine Science Center Dynamic Revetment Project DSL permit #45455-FP: Monitoring Report February 2014

Stabilization of the Yaquina Bay shoreline along the northeastern edge of the Hatfield Marine Science Center (HMSC) campus became necessary to halt erosion that threatened both HMSC critical infrastructure (seawater storage tank) and public access to the HMSC Nature Trail. A Dynamic Revetment (gravel beach) was installed in November, 2011 on 260 feet of shoreline to mitigate erosion. Shoreline topographic and biological monitoring was initiated before and has continued after the project completion. Monitoring of beach profiles indicated that as of December 2013, the 2011 Dynamic Revetment Project (DRP) has successfully stabilized the shoreline in the project area, while rapid erosion has continued in the adjacent Reference beach area. Erosion in the unprotected Reference area in the period 2009-2013 has been as great as 9.6 m (31.5 ft). Beach profile data also indicated that the 2007 DRP continued to be successful in stabilizing further retreat of the shoreline. Monitoring of birds and marine mammals was discontinued in 2013 as planned. Monitoring of beach wrack invertebrates, fish, and vegetation continued. Per unit of beach wrack biomass, there was no significant difference in density of wrack invertebrates among the three study areas. Total amount of beach wrack was much sparser in the Reference area because of vertical beach scarps generated by erosion that appeared to limit wrack accumulation. As has been a consistent pattern, fish were significantly more abundant in the Reference area compared to the DRP. However, this pattern was present in the pre-project sampling, and the Reference area may have a higher degree of physical habitat complexity, resulting from root masses of trees that have been eroded onto the shore. Bottom dwelling Pacific Staghorn Sculpin tended to be somewhat more evenly distributed between the DRP and Reference areas, while pelagic Shiner Perch tended to be found more in the Reference area. Vegetation coverage was significantly greater and presence of non-living substrata was significantly less in the Reference area as compared to the DRP. These differences are consistent with pre-project site differences, probably resulting from a low area of the shoreline which allows increased flooding and associated disturbance in the DRP back shore area. Fish and wrack invertebrates, such as beach hoppers, were shown to utilize the DRP project area. Biological differences in fish and vegetation observed in year 2 of post-project monitoring tended to reflect differences in habitat that were present before the DRP project

Patient experiences with oily skin: The qualitative development of content for two new patient reported outcome questionnaires

<p>Abstract</p> <p>Objective</p> <p>To develop the content for two new patient reported outcome (PRO) measures to: a) assess the severity of symptoms; and b) the impact of facial skin oiliness on emotional wellbeing using qualitative data from face to face, and internet focus groups in Germany and the US.</p> <p>Methods</p> <p>Using input from initial treatment satisfaction focus groups (n = 42), a review of relevant literature and expert clinicians (n = 3), a discussion guide was developed to guide qualitative inquiry using Internet focus groups (IFGs). IFGs were conducted with German (n = 26) and US (n = 28) sufferers of oily skin. Questionnaire items were generated using coded transcript data from the focus groups. Cognitive debriefing was conducted online with 42 participants and face to face with an additional five participants to assess the comprehension of the items.</p> <p>Results</p> <p>There were equal numbers of male and female participants; mean age was 35.4 (SD 9.3) years. On average, participants had had oily skin for 15.2 years, and 74% (n = 40) reported having mild-moderate acne. Participants reported using visual, tactile and sensory (feel without touching their face) methods to evaluate the severity of facial oiliness. Oily facial skin had both an emotional and social impact, and was associated with feelings of unattractiveness, self-consciousness, embarrassment, irritation and frustration. Items were generated for a measure of oily skin severity (Oily Skin Self-Assessment Scale) and a measure of the impact of oily skin on emotional well-being (Oily Skin Impact Scale). Cognitive debriefing resulted in minor changes to the draft items and confirmed their face and content validity.</p> <p>Conclusion</p> <p>The research provides insight into the experience of having oily skin and illustrates significant difficulties associated with the condition. Item content was developed for early versions of two PRO measures of the symptoms and emotional impact of oily facial skin. The psychometric validation of these measures reported elsewhere.</p

Chemical Power for Microscopic Robots in Capillaries

The power available to microscopic robots (nanorobots) that oxidize bloodstream glucose while aggregated in circumferential rings on capillary walls is evaluated with a numerical model using axial symmetry and time-averaged release of oxygen from passing red blood cells. Robots about one micron in size can produce up to several tens of picowatts, in steady-state, if they fully use oxygen reaching their surface from the blood plasma. Robots with pumps and tanks for onboard oxygen storage could collect oxygen to support burst power demands two to three orders of magnitude larger. We evaluate effects of oxygen depletion and local heating on surrounding tissue. These results give the power constraints when robots rely entirely on ambient available oxygen and identify aspects of the robot design significantly affecting available power. More generally, our numerical model provides an approach to evaluating robot design choices for nanomedicine treatments in and near capillaries.Comment: 28 pages, 7 figure

Follicular helper T cells are required for systemic autoimmunity

Production of high-affinity pathogenic autoantibodies appears to be central to the pathogenesis of lupus. Because normal high-affinity antibodies arise from germinal centers (GCs), aberrant selection of GC B cells, caused by either failure of negative selection or enhanced positive selection by follicular helper T (TFH) cells, is a plausible explanation for these autoantibodies. Mice homozygous for the san allele of Roquin, which encodes a RING-type ubiquitin ligase, develop GCs in the absence of foreign antigen, excessive TFH cell numbers, and features of lupus. We postulated a positive selection defect in GCs to account for autoantibodies. We first demonstrate that autoimmunity in Roquinsan/san (sanroque) mice is GC dependent: deletion of one allele of Bcl6 specifically reduces the number of GC cells, ameliorating pathology. We show that Roquinsan acts autonomously to cause accumulation of TFH cells. Introduction of a null allele of the signaling lymphocyte activation molecule family adaptor Sap into the sanroque background resulted in a substantial and selective reduction in sanroque TFH cells, and abrogated formation of GCs, autoantibody formation, and renal pathology. In contrast, adoptive transfer of sanroque TFH cells led to spontaneous GC formation. These findings identify TFH dysfunction within GCs and aberrant positive selection as a pathway to systemic autoimmunity