Advanced experimental applications for x-ray transmission gratings Spectroscopy using a novel grating fabrication method

A novel fabrication method for soft x-ray transmission grating and other optical elements is presented. The method uses Focused-Ion-Beam (FIB) technology to fabricate high-quality free standing grating bars on Transmission Electron Microscopy grids (TEM-grid). High quality transmission gratings are obtained with superb accuracy and versatility. Using these gratings and back-illuminated CCD camera, absolutely calibrated x-ray spectra can be acquired for soft x-ray source diagnostics in the 100-3000 eV spectral range. Double grating combinations of identical or different parameters are easily fabricated, allowing advanced one-shot application of transmission grating spectroscopy. These applications include spectroscopy with different spectral resolutions, bandwidths, dynamic ranges, and may serve for identification of high-order contribution, and spectral calibrations of various x-ray optical elements

The mortality burden attributable to nontrauma fracture for privately insured adults with epilepsy

ObjectiveIndividuals with epilepsy have poor bone development and preservation throughout the lifespan and are vulnerable to nontrauma fracture (NTFx) and post‐NTFx complications. However, no studies have examined the contribution of NTFx to mortality among adults with epilepsy. The objective was to determine whether NTFx is a risk factor for mortality among adults with epilepsy.MethodsData from 2011 to 2016 were obtained from Optum Clinformatics Data Mart, a nationwide claims database from a single private payer in the United States. Diagnosis codes were used to identify adults (≥18 years old) with epilepsy, NTFx, and covariates (demographics and pre‐NTFx cardiovascular disease, respiratory disease, diabetes, chronic kidney disease, cancer). Crude mortality rate per 100 person‐years was estimated. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) were determined for mortality, comparing epilepsy and NTFx (EP + NTFx; n = 11 471), epilepsy without NTFx (EP without NTFx; n = 50 384), without epilepsy and with NTFx (without EP + NTFx; n = 423 041), and without epilepsy and without NTFx (without EP without NTFx; n = 6.8 million) after adjusting for covariates.ResultsThe 3‐, 6‐, and 12‐month crude mortality rates were highest among EP + NTFx (12‐month mortality rate = 8.79), followed by without EP + NTFx (12‐month mortality rate = 4.80), EP without NTFx (12‐month mortality rate = 3.06), and without EP without NTFx (12‐month mortality rate = 0.47). After adjustments, the mortality rate was elevated for EP + NTFx for all time points compared to EP without NTFx (eg, 12‐month HR = 1.70, 95% CI = 1.58‐1.85), without EP + NTFx (eg, 12‐month HR = 1.41, 95% CI = 1.32‐1.51), and without EP without NTFx (eg, 12‐month HR = 5.23, 95% CI = 4.88‐5.60). Stratified analyses showed higher adjusted HRs of 12‐month mortality for EP + NTFx for all NTFx sites (ie, vertebral column, hip, extremities), all age categories (young, middle‐aged, older), and for both women and men.SignificanceAmong adults with epilepsy and compared to adults without epilepsy, NTFx is associated with a higher 12‐month mortality rate. Findings suggest that NTFx may be a robust risk factor for mortality among adults with epilepsy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154895/1/epi16465.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154895/2/epi16465_am.pd

HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer.

BackgroundHuman epidermal growth factor receptor 2 (HER2)-positive breast cancer is a particularly aggressive form of the disease, and ultimately progresses in patients with metastases on standard therapies. Anthracyclines, such as doxorubicin, are an effective treatment for HER2-positive breast cancer, particularly when administered in combination with trastuzumab - however, doxorubicin-related cardiotoxicity has limited its use. Many patients are therefore never treated with anthracyclines, even upon disease progression, despite the potential for benefit. MM-302 is a novel, HER2-targeted antibody-liposomal doxorubicin conjugate that specifically targets HER2-overexpressing cells. Preclinical and Phase 1 data suggest that MM-302, as a monotherapy or in combination with trastuzumab, could be effective for managing previously treated, anthracycline-naïve, HER2-positive breast cancer, without the cardiotoxicity observed with free doxorubicin formulations.Methods/designHERMIONE is an open-label, multicenter, randomized (1:1) Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice (gemcitabine, capecitabine, or vinorelbine) plus trastuzumab planned to enroll 250 anthracycline-naïve patients with locally advanced/metastatic HER2-positive breast cancer. Key inclusion criteria are: previous treatment with trastuzumab (with or without pertuzumab) in any setting; refractory or intolerant to pertuzumab (refractory to pertuzumab defined as progression in the locally advanced or metastatic setting, or disease recurrence during or within 12 months of completing pertuzumab-containing neoadjuvant and/or adjuvant therapy); and disease progression on, or intolerant to, ado-trastuzumab emtansine for locally advanced or metastatic disease. The trial is currently being conducted at sites in the USA, Canada, and Western Europe. Treatment will be administered in 21-day cycles, and will be continued until disease progression or unacceptable toxicity. The primary endpoint is independently assessed progression-free survival (PFS). Tumor response will be assessed every 6 weeks, and defined according to RECIST v1.1. Secondary endpoints include investigator-assessed PFS, overall survival (OS), OS rates at 6 months and 1 year, objective response rates, safety and tolerability, quality of life, and the pharmacokinetic profile of MM-302 plus trastuzumab.DiscussionThe HERMIONE study will evaluate the efficacy and safety of MM-302 plus trastuzumab in patients with refractory HER2-positive advanced/metastatic breast cancer for whom there are no standard of care therapies with a proven survival advantage.Trial registrationClinicaltrials.gov identifier: NCT02213744 . Registration date: 06AUG2014

'Heaven starts at your parents' feet' : adolescent bowing to parents and associated spiritual attitudes

In a quantitative survey of religious attitudes and practices in a multi-religious sample of 369 school pupils aged between 13 and 15 in London, the practice of bowing to parents was found widespread in 22% of adolescents spanning several religious affiliations and ethnicities – especially Buddhists, Hindus and those of Indian, African and ‘Other Asian’ ethnicity. Whether an adolescent bowed correlated significantly with spiritual attitudes such as wanting to abstain from alcohol, hearing religious stories, being inspired by religious festivals and liking the idea of seeing God in everything. Findings suggest bowing to parents can have religious significance on all three levels of Jackson’s Interpretive Approach and therefore cannot be regarded as a ‘cultural accretion’ of religion. Study of bowing to parents could form a unifying exercise in shared values for study of religion in the plural classroom and facilitate community cohesion in certain religious membership groups

Adults with Cerebral Palsy have Higher Prevalence of Fracture Compared with Adults Without Cerebral Palsy Independent of Osteoporosis and Cardiometabolic Diseases

Individuals with cerebral palsy (CP) have an increased risk of fracture throughout their lifespan based on an underdeveloped musculoskeletal system, excess body fat, diminished mechanical loading, and early development of noncommunicable diseases. However, the epidemiology of fracture among adults with CP is unknown. The purpose of this cross‐sectional study was to determine the prevalence of fracture among a large sample of privately insured adults with CP, as compared with adults without CP. Data were from the Optum Clinformatics Data Mart (Eden Prairie, MN, USA), a deidentified nationwide claims database of beneficiaries from a single private payer. Diagnostic codes were used to identify 18‐ to 64‐year‐old beneficiaries with and without CP and any fracture that consisted of osteoporotic pathological fracture as well as any type of fracture of the head/neck, thoracic, lumbar/pelvic, upper extremity, and lower extremity regions. The prevalence of any fracture was compared between adults with (n = 5,555) and without (n = 5.5 million) CP. Multivariable logistic regression was performed with all‐cause fracture as the outcome and CP group as the primary exposure. Adults with CP had a higher prevalence of all‐cause fracture (6.3% and 2.7%, respectively) and fracture of the head/neck, thoracic, lumbar/pelvic, upper extremity, and lower extremity regions compared with adults without CP (all p < 0.01). After adjusting for sociodemographic and socioeconomic variables, adults with CP had higher odds of all‐cause fracture compared with adults without CP (OR 2.5; 95% CI, 2.2 to 2.7). After further adjusting for cardiometabolic diseases, adults with CP had higher odds of all‐cause fracture compared with adults without CP (OR 2.2; 95% CI, 2.0 to 2.5). After further adjusting for osteoporosis, adults with CP still had higher odds of all‐cause fracture compared with adults without CP (OR 2.0; 95% CI, 1.8 to 2.2). These findings suggest that young and middle‐aged adults with CP have an elevated prevalence of all‐cause fracture compared with adults without CP, which was present even after accounting for cardiometabolic diseases and osteoporosis. © 2019 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150537/1/jbmr3694_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150537/2/jbmr3694.pd

Effect of pain on mood affective disorders in adults with cerebral palsy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155961/1/dmcn14559_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155961/2/dmcn14559.pd

Do residents’ perceptions of being well-placed and objective presence of local amenities match? A case study in West Central Scotland, UK

Background:&lt;p&gt;&lt;/p&gt; Recently there has been growing interest in how neighbourhood features, such as the provision of local facilities and amenities, influence residents’ health and well-being. Prior research has measured amenity provision through subjective measures (surveying residents’ perceptions) or objective (GIS mapping of distance) methods. The latter may provide a more accurate measure of physical access, but residents may not use local amenities if they do not perceive them as ‘local’. We believe both subjective and objective measures should be explored, and use West Central Scotland data to investigate correspondence between residents’ subjective assessments of how well-placed they are for everyday amenities (food stores, primary and secondary schools, libraries, pharmacies, public recreation), and objective GIS-modelled measures, and examine correspondence by various sub-groups.&lt;p&gt;&lt;/p&gt; Methods:&lt;p&gt;&lt;/p&gt; ArcMap was used to map the postal locations of ‘Transport, Health and Well-being 2010 Study’ respondents (n = 1760), and the six amenities, and the presence/absence of each of them within various straight-line and network buffers around respondents’ homes was recorded. SPSS was used to investigate whether objective presence of an amenity within a specified buffer was perceived by a respondent as being well-placed for that amenity. Kappa statistics were used to test agreement between measures for all respondents, and by sex, age, social class, area deprivation, car ownership, dog ownership, walking in the local area, and years lived in current home.&lt;p&gt;&lt;/p&gt; Results:&lt;p&gt;&lt;/p&gt; In general, there was poor agreement (Kappa &lt;0.20) between perceptions of being well-placed for each facility and objective presence, within 800 m and 1000 m straight-line and network buffers, with the exception of pharmacies (at 1000 m straight-line) (Kappa: 0.21). Results varied between respondent sub-groups, with some showing better agreement than others. Amongst sub-groups, at 800 m straight-line buffers, the highest correspondence between subjective and objective measures was for pharmacies and primary schools, and at 1000 m, for pharmacies, primary schools and libraries. For road network buffers under 1000 m, agreement was generally poor.&lt;p&gt;&lt;/p&gt; Conclusion:&lt;p&gt;&lt;/p&gt; Respondents did not necessarily regard themselves as well-placed for specific amenities when these amenities were present within specified boundaries around their homes, with some exceptions; the picture is not clear-cut with varying findings between different amenities, buffers, and sub-groups

Relations at Three Early Stages of Marriage as Reflected by the Use of Personal Pronouns

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71573/1/j.1545-5300.1970.00069.x.pd