Stereochemical Studies on a New Ciramadol Analogue by NMR-Spectroscopy

The absol. configuration of a Ciramadol analogue obtained from (-)-menthone is established by 'H-NMR-. simulated NMR-, COSY-90-, and NOEmeasurements. The final compound 2-(a-1 -pyrrolidino)benzy 1-4-isopropyl- 1 -methyl-cyclohexan-3-one (4b), e.g.. has 1R.2S,4S.l IS-configuration due to stereoselective Michael-type addition of pyrrolidine to the pertinent benzylidene intermediate 3. Die absol. Konfiguration einer Ciramadol-analogen Verbindung aus (-)- Menthon wurde durch 'H-NMR-. simulierte NMR-. COSY-90- und NOEUntersuchungen geklärt. Danach hat die als Beispiel untersuchte Verbindung 2-(a-1 -Pyrrolidino)benzyl-4-isopropyl-1 -methyl-cyclohexan-3-on (4b) 1R,2S.4S.l IS-Konfiguration, die durch eine stereoselektive Michael-analoge Addition des Pyrrolidins an die entspr. Benzyliden-Verbindung 3 entsteht

Evaluation of Local Site Conditions Using Ambient Seismic Noise Recordings: A Case Study from Ankara, Turkey

This paper aims to investigate the site response of the sediment characteristics and to perform seismic hazard studies in Ankara, Turkey through conducting short-period noise recordings of microtremor measurements at 352 project site locations on the Upper Pliocene to Pleistocene fluvial and particularly Quaternary alluvial and terrace sediments in the Ankara basin. The spectral ratios relative to a firm site reference station (SSR) and the spectral ratio between the horizontal and vertical components (HVSR) of the microtremor measurements at the ground surface have been used to estimate the fundamental periods and the amplification factors of the site. The results of this study identified three main factors that influence site response, namely, the age of the near-surface deposits, the sediment thickness and the non-linear soil behavior. In particular, the HVSR results showed that the variation of the fundamental period map agreed well with the maximum value of the amplification as well as with the seismic sediment characteristics that provided satisfactory estimates of the site response of soft deposits

Stoma Prolapse

The incidence of prolapse which is a late complication of stoma ranges between 0–25%. In this study the records of the patients who had been treated and followed up with the diagnosis of stoma prolapse between 1995 -2005 in the General Surgery Department of Dicle University Hospital were examined, retrospectively. There were 12 patients (5 men, 7 women) with a mean age of 51,6±15.01 years. The causes of stoma construction were malign diseases in 9 patients and benign diseases in 3 of them. The average time between construction of stoma and formation of prolapse was 10,9±6.84 month. The type of stoma was loop in 7 patient, end stoma in 4 patient and double bowel enterostomy in 1 patient. Of nine patients with stoma prolapse had been subjected chemotherapy. The overall rate of stomal prolapsus was 3,1% in this series. It was 10,8% in patients who had received chemoradiotherapy. Since stomal prolasus is a serious complication and its reconstruction needs general anesthesia great care should be shown when creatig a stoma

Does Gender Impact Intensity of Care Provided to Older Medical Intensive Care Unit Patients?

Introduction. Women receive less aggressive critical care than men based on prior studies. No documented studies evaluate whether men and women are treated equally in the medical intensive care unit (MICU). The Therapeutic Intervention Scoring System-28 (TISS-28) has been used to examine gender differences in mixed ICU studies. However, it has not been used to evaluate equivalence of care in older MICU patients. We hypothesize that given nonsignificant, baseline health differences between genders at MICU admission, the level of care provided would be equivalent. Methods. Prospective cohort of 309 patients ≥60 years old in the MICU of an urban university teaching hospital. Explanatory variables were demographic data and baseline measures. Primary outcomes were TISS-28 scores and MICU interventions. We compare TISS-28 scores by gender using a statistical test of equivalence. Results. Women were older and had more chronic respiratory failure at MICU admission. Using equivalence limits of ±15% on gender-based scores of TISS-28, MICU interventions were equivalent. Supplementary analysis showed no statistically significant association between gender and mortality. Conclusions. In contrast with other reports from the cardiac critical care literature, as measured by the TISS-28, gender-based care delivered to older MICU patients in this cohort was equivalent

Targeting lyn kinase in chorea-acanthocytosis: A translational treatment approach in a rare disease

Background: Chorea-acanthocytosis (ChAc) is a neurodegenerative disease caused by mutations in the VPS13A gene. It is characterized by several neurological symptoms and the appearance of acanthocytes. Elevated tyrosine kinase Lyn activity has been recently identified as one of the key pathophysiological mechanisms in this disease, and therefore represents a promising drug target. Methods: We evaluated an individual off-label treatment with the tyrosine kinase inhibitor dasatinib (100 mg/d, 25.8–50.4 weeks) of three ChAc patients. Alongside thorough safety monitoring, we assessed motor and non-motor scales (e.g., MDS-UPDRS, UHDRS, quality of life) as well as routine and experimental laboratory parameters (e.g., serum neurofilament, Lyn kinase activity, actin cytoskeleton in red blood cells). Results: Dasatinib appeared to be reasonably safe. The clinical parameters remained stable without significant improvement or deterioration. Regain of deep tendon reflexes was observed in one patient. Creatine kinase, serum neurofilament levels, and acanthocyte count did not reveal consistent effects. However, a reduction of initially elevated Lyn kinase activity and accumulated autophagy markers, as well as a partial restoration of the actin cytoskeleton, was found in red blood cells. Conclusions: We report on the first treatment approach with disease-modifying intention in ChAc. The experimental parameters indicate target engagement in red blood cells, while clinical effects on the central nervous system could not be proven within a rather short treatment time. Limited knowledge on the natural history of ChAc and the lack of appropriate biomarkers remain major barriers for “clinical trial readiness”. We suggest a panel of outcome parameters for future clinical trials in ChA

Lattice dynamics and structural stability of ordered Fe3Ni, Fe3Pd and Fe3Pt alloys

We investigate the binding surface along the Bain path and phonon dispersion relations for the cubic phase of the ferromagnetic binary alloys Fe3X (X = Ni, Pd, Pt) for L12 and DO22 ordered phases from first principles by means of density functional theory. The phonon dispersion relations exhibit a softening of the transverse acoustic mode at the M-point in the L12-phase in accordance with experiments for ordered Fe3Pt. This instability can be associated with a rotational movement of the Fe-atoms around the Ni-group element in the neighboring layers and is accompanied by an extensive reconstruction of the Fermi surface. In addition, we find an incomplete softening in [111] direction which is strongest for Fe3 Ni. We conclude that besides the valence electron density also the specific Fe-content and the masses of the alloying partners should be considered as parameters for the design of Fe-based functional magnetic materials.Comment: Revised version, accepted for publication in Physical Review

Linking Scottish vital event records using family groups

Funding: This work was supported by ESRC Grants ES/K00574X/2 “Digitising Scotland” and ES/L007487/1 “Administrative Data Research Centre – Scotland.”The reconstitution of populations through linkage of historical records is a powerful approach to generate longitudinal historical microdata resources of interest to researchers in various fields. Here we consider automated linking of the vital events recorded in the civil registers of birth, death and marriage compiled in Scotland, to bring together the various records associated with the demographic events in the life course of each individual in the population. From the histories, the genealogical structure of the population can then be built up. Rather than apply standard linkage techniques to link the individuals on the available certificates, we explore an alternative approach, inspired by the family reconstitution techniques adopted by historical demographers, in which the births of siblings are first linked to form family groups, after which intergenerational links between families can be established. We report a small-scale evaluation of this approach, using two district-level data sets from Scotland in the late nineteenth century, for which sibling links have already been created by demographers. We show that quality measures of up to 83% can be achieved on these data sets (using F-Measure, a combination of precision and recall). In the future, we intend to compare the results with a standard linkage approach and to investigate how these various methods may be used in a project which aims to link the entire Scottish population from 1856 to 1973.PostprintPeer reviewe

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians

Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study.

BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). We investigated racial and ethnic disparities in patterns of COVID-19 testing (i.e., who received testing and who tested positive) and subsequent mortality in the largest integrated healthcare system in the United States. METHODS AND FINDINGS: This retrospective cohort study included 5,834,543 individuals receiving care in the US Department of Veterans Affairs; most (91%) were men, 74% were non-Hispanic White (White), 19% were non-Hispanic Black (Black), and 7% were Hispanic. We evaluated associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for a wide range of demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence. Between February 8 and July 22, 2020, 254,595 individuals were tested for COVID-19, of whom 16,317 tested positive and 1,057 died. Black individuals were more likely to be tested (rate per 1,000 individuals: 60.0, 95% CI 59.6-60.5) than Hispanic (52.7, 95% CI 52.1-53.4) and White individuals (38.6, 95% CI 38.4-38.7). While individuals from minority backgrounds were more likely to test positive (Black versus White: odds ratio [OR] 1.93, 95% CI 1.85-2.01, p < 0.001; Hispanic versus White: OR 1.84, 95% CI 1.74-1.94, p < 0.001), 30-day mortality did not differ by race/ethnicity (Black versus White: OR 0.97, 95% CI 0.80-1.17, p = 0.74; Hispanic versus White: OR 0.99, 95% CI 0.73-1.34, p = 0.94). The disparity between Black and White individuals in testing positive for COVID-19 was stronger in the Midwest (OR 2.66, 95% CI 2.41-2.95, p < 0.001) than the West (OR 1.24, 95% CI 1.11-1.39, p < 0.001). The disparity in testing positive for COVID-19 between Hispanic and White individuals was consistent across region, calendar time, and outbreak pattern. Study limitations include underrepresentation of women and a lack of detailed information on social determinants of health. CONCLUSIONS: In this nationwide study, we found that Black and Hispanic individuals are experiencing an excess burden of SARS-CoV-2 infection not entirely explained by underlying medical conditions or where they live or receive care. There is an urgent need to proactively tailor strategies to contain and prevent further outbreaks in racial and ethnic minority communities