To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The new compound (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate was synthesized by the 1,3-dipolar cycloaddition reaction between (4R)-methyl-3-propionyl-thiazolidin-4-carboxylate (1) and 4-chlorophenylazide using the click chemistry approach. Molecular characterization was carried out by infrared spectroscopy and mass spectrometry. The X-ray powder diffraction study determined that the title compound crystallized in an orthorhombic system with unit-cell parameters a = 20.876 (2) Å, b = 12.111 (1) Å, and c = 6.288 (9) Å. The volume of the unit cell is V = 1589.7 (2) Å3. All measured diffraction maxima were indexed and are consistent with the P2221 space group (No. 17). No detectable impurities were observed.
To detect modest associations of dietary intake with disease risk, observational studies need to be large and control for moderate measurement errors. The reproducibility of dietary intakes of macronutrients, food groups and dietary patterns (vegetarian and Mediterranean) was assessed in adults in the UK Biobank study on up to five occasions using a web-based 24-h dietary assessment (n 211 050), and using short FFQ recorded at baseline (n 502 655) and after 4 years (n 20 346). When the means of two 24-h assessments were used, the intra-class correlation coefficients (ICC) for macronutrients varied from 0·63 for alcohol to 0·36 for polyunsaturated fat. The ICC for food groups also varied from 0·68 for fruit to 0·18 for fish. The ICC for the FFQ varied from 0·66 for meat and fruit to 0·48 for bread and cereals. The reproducibility was higher for vegetarian status (κ > 0·80) than for the Mediterranean dietary pattern (ICC = 0·45). Overall, the reproducibility of pairs of 24-h dietary assessments and single FFQ used in the UK Biobank were comparable with results of previous prospective studies using conventional methods. Analyses of diet–disease relationships need to correct for both measurement error and within-person variability in dietary intake in order to reliably assess any such associations with disease in the UK Biobank.
The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.
As utilization of CT imaging has risen dramatically, evidence-based decision rules and clinical decision support (CDS) tools have been developed to avoid unnecessary CT use in low risk patients. However, their ability to change physician practice has been limited to date, with a number of barriers cited. The purpose of this study was to identify the barriers and facilitators to CDS adoption following a local CDS implementation. Methods: All emergency physicians at 4 urban EDs and 1 urgent care center were randomized to voluntary evidence-based CT imaging CDS for patients with either mild traumatic brain injury (MTBI) or suspected pulmonary embolism (PE). CDS was integrated into the computerized physician order entry (CPOE) software and triggered whenever a CT scan for an eligible patient was ordered. Physicians in both the MTBI and PE arms were ranked according to their CDS use, and a stratified sampling strategy was used to randomly select 5 physicians from each of the low, medium and high CDS use tertiles in each study arm. Each physician was invited to participate in a 30-minute semi-structured interview to assess the barriers and facilitators to CDS use. Physician responses were reported using a thematic analysis. Results: A total of 202 emergency physicians were randomized to receive CDS for either MTBI or PE, triggering CDS 4561 times, and interacting with the CDS software 1936 times (42.4%). Variation in CDS use ranged from 0% to 88.9% of eligible encounters by physician. Fourteen physicians have participated in interviews to date, and data collection is ongoing. Physicians reported that CDS use was facilitated by their confidence in the evidence supporting the CDS algorithms and that it provided documentation to reduce medico-legal risk. CDS use was not impeded by concerns over missed diagnoses or patient expectations. Reported barriers to CDS use included suboptimal integration into the CPOE such as the inability to auto-populate test results, it disrupted the ordering process and was time consuming. A common concern was that CDS was implemented too late in workflow as most decision making takes place at the bedside. Physicians did not view CDS as infringing on physician autonomy, however they advised that CDS should be a passive educational option and should not automatically trigger for all physicians and eligible encounters. Conclusion: Physicians were generally supportive of CDS integration into practice, and were confident that CDS is an evidence-based way to reduce unnecessary CT studies. However, concerns were raised about the optimal integration of CDS into CPOE and workflow. Physicians also stated a preference to a passive educational approach to CDS rather than an automatic triggering mechanism requiring clinical documentation.
Evening-dosed DR/ER-MPH (formerly HLD200), a delayed-release and extended-release methylphenidate, was designed to provide efficacy upon awakening and through the evening. The objective was to evaluate whether treatment with DR/ER-MPH in children with attention-deficit/hyperactivity disorder (ADHD): (1) improves caregiver-rated ADHD symptoms, and (2) reduces caregiver strain, versus placebo.
Caregiver-rated ADHD symptoms (Conners’ Global Index–Parent [CGI-P]) and caregiver strain (Caregiver Strain Questionnaire [CGSQ]) were assessed as secondary endpoints following 3 weeks of treatment in a randomized, double-blind, multicenter, placebo-controlled, parallel-group, phase 3 trial of DR/ER-MPH in children (6-12 years) with ADHD (NCT02520388). Using the 10-item CGI-P, parents rated their child’s ADHD symptoms on a 4-point scale (0=never/seldom; 3=very often/frequently). Caregivers also rated the impact of caring for a child with emotional and behavioral challenges on the 21-item CGSQ (5-point scale: 1=not at all; 5=very much). A reduction on individual item and total scores for both measures indicated an improvement.
Of 163 children enrolled across 22 sites, 161 were included in the intent-to-treat population (DR/ER-MPH, n=81; placebo, n=80) and 138 completed the study. The mean DR/ER-MPH dose after 3 weeks of treatment was 68.1 mg. Mean CGI-P scores at baseline and CGSQ scores at screening (ie, before washout of prior ADHD therapy) were comparable for both DR/ER-MPH (CGI-P: 22.8, CGSQ: 54.5) and placebo (CGI-P: 21.8; CGSQ: 54.9) groups. After 3 weeks of treatment, caregivers of children onDR/ER-MPH reported significant reductions in CGI-P scores versus those on placebo (least-squares [LS] mean: 12.3 vs 17.4; P<0.001). Additionally, there was a significant reduction in CGSQ scores after 3 weeks of treatment with DR/ER-MPH versus placebo (LS mean: 41.2 vs 49.1; P<0.001). Post hoc analyses on the effect of DR/ER-MPHversus placebo on individual items of CGI-P and CGSQ, and the two subscales of CGI-P will be presented. No serious TEAEs were reported and all TEAEs were consistent with those of MPH.
Caregivers reported significant improvements in their child’s ADHD symptoms and these improvements coincided with reductions in caregiver strain after 3 weeks of treatment on evening-dosed DR/ER-MPH versus placebo.
In a phase 3 trial of children with ADHD, DR/ER-MPH (formerly HLD200), a delayed-release and extended-release methylphenidate, improved ADHD symptoms and reduced at-home early morning and late afternoon/evening functional impairments versus placebo, as measured by the validated Parent Rating of Evening andMorning Behaviors-Revised, Morning (PREMB-R AM) and Evening (PREMB-R PM) subscales. This post hoc analysis evaluated the effect of DR/ER-MPH versus placebo onindividual PREMB-R AM/PM item scores.
Data were analyzed from a pivotal, randomized, double-blind, multicenter, placebo-controlled, parallel-group, phase 3 trial of DR/ER-MPH in children (6-12 years) withADHD (NCT02520388). Using the 3-item PREMB-R AM and 8-item PREMB-R PM, both key secondary endpoints, investigators evaluated early morning and lateafternoon/evening functional impairment by scoring each item on a severity scale from 0 (none) to 3 (a lot). For post hoc analyses, treatment comparisons between DR/ER-MPH and placebo at endpoint were determined by using least squares mean changes from baseline on individual PREMB-R AM/PM items score derived from an analysis ofcovariance (ANCOVA) model with treatment as the main effect, and study center and baseline score as covariates.
Of 163 children enrolled across 22 sites, 161 were included in the intent-to-treat population (DR/ER-MPH, n=81; placebo, n=80) and 138 completed the study. The mean DR/ER-MPH dose achieved after 3 weeks of treatment was 68.1 mg. Following 3 weeks of treatment, DR/ER-MPH significantly reduced mean individual item scores from baseline versus placebo on all PREMB-R AM items (all P≤0.002; “getting out of bed”, “getting ready”, and “arguing or struggling in the morning”). Additionally, DR/ER-MPH significantly reduced mean individual item scores from baseline on 5 out of 8 PREMB-R PM items (P<0.01 in 2 items [“sitting through dinner” and “playing quietly”] and P<0.05 in 3 items [“inattentive/distractible”, “transitioning between activities”, and “settling down/getting ready for bed”]). There was a trend towards a reduction on 2 other items of the PREMB-R PM (P<0.09). Distributions of the ratings for each item will be presented. No serious TEAEs were reported; TEAEs were consistent withmethylphenidate.
Post hoc analyses revealed that DR/ER-MPH significantly reduced all PREMB-R AM item scores, including “getting out of bed”, and many PREMB-R PM items, including “getting ready for bed” in children with ADHD. These findings are worth further exploration.