Multimode bolometer development for the PIXIE instrument

The Primordial Inflation Explorer (PIXIE) is an Explorer-class mission concept designed to measure the polarization and absolute intensity of the cosmic microwave background. In the following, we report on the design, fabrication, and performance of the multimode polarization-sensitive bolometers for PIXIE, which are based on silicon thermistors. In particular we focus on several recent advances in the detector design, including the implementation of a scheme to greatly raise the frequencies of the internal vibrational modes of the large-area, low-mass optical absorber structure consisting of a grid of micromachined, ion-implanted silicon wires. With $\sim30$ times the absorbing area of the spider-web bolometers used by Planck, the tensioning scheme enables the PIXIE bolometers to be robust in the vibrational and acoustic environment at launch of the space mission. More generally, it could be used to reduce microphonic sensitivity in other types of low temperature detectors. We also report on the performance of the PIXIE bolometers in a dark cryogenic environment.Comment: 10 pages, 7 figure

Multimode Bolometer Development for the PIXIE Instrument

The Primordial Inflation Explorer (PIXIE) is an Explorer-class mission concept designed to measure the polarization and absolute intensity of the cosmic microwave background. In the following, we report on the design, fabrication, and performance of the multimode polarization-sensitive bolometers for PIXIE, which are based on silicon thermistors. In particular we focus on several recent advances in the detector design, including the implementation of a scheme to greatly raise the frequencies of the internal vibrational modes of the large-area, low-mass optical absorber structure consisting of a grid of micromachined, ion-implanted silicon wires. With approximately 30 times the absorbing area of the spider-web bolometers used by Planck, the tensioning scheme enables the PIXIE bolometers to be robust in the vibrational and acoustic environment at launch of the space mission. More generally, it could be used to reduce microphonic sensitivity in other types of low temperature detectors. We also report on the performance of the PIXIE bolometers in a dark cryogenic environment

Dementia treated with individualized homoeopathy: A case report

Introduction: Dementia is a devastating neurodegenerative disorder that places a significant physical, emotional, and financial burden on patients, their caregivers and society. The global burden of dementia is growing alarmingly greater in the past few decades. There is an evidence base for the effectiveness of homeopathic medicines in certain psychiatric disorders, but literature is scarce on the usefulness of homoeopathy in dementia. Case Summary: A 72-year-old female patient was brought to the psychiatry outpatient unit with symptoms such as sleeplessness, irrelevant talking, irritability, weakness of memory, lack of personal hygiene, and wandering away from home. The case was diagnosed as unspecified dementia, assessed with mini-mental state examination (MMSE), and treated with Ignatia 200. MMSE score of 10 (severe cognitive impairment) at baseline gradually improved to 24 (no cognitive impairment) within 6 months and was maintained up to 12 months. Clinical improvement was also observed in cognitive functions, behaviour as well as the general condition of the patient. Causal attribution to changes after homeopathic intervention is evaluated through Modified Naranjo Criteria for homoeopathy

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Impact of 90Y PET gradient-based tumor segmentation on voxel-level dosimetry in liver radioembolization

Abstract Background The purpose was to validate 90Y PET gradient-based tumor segmentation in phantoms and to evaluate the impact of the segmentation method on reported tumor absorbed dose (AD) and biological effective dose (BED) in 90Y microsphere radioembolization (RE) patients. A semi-automated gradient-based method was applied to phantoms and patient tumors on the 90Y PET with the initial bounding volume for gradient detection determined from a registered diagnostic CT or MR; this PET-based segmentation (PS) was compared with radiologist-defined morphologic segmentation (MS) on CT or MRI. AD and BED volume histogram metrics (D90, D70, mean) were calculated using both segmentations and concordance/correlations were investigated. Spatial concordance was assessed using Dice similarity coefficient (DSC) and mean distance to agreement (MDA). PS was repeated to assess intra-observer variability. Results In phantoms, PS demonstrated high accuracy in lesion volumes (within 15%), AD metrics (within 11%), high spatial concordance relative to morphologic segmentation (DSC > 0.86 and MDA  0.99, MDA < 0.2 mm, AD/BED metrics within 2%). For patients (58 lesions), spatial concordance between PS and MS was degraded compared to in-phantom (average DSC = 0.54, average MDA = 4.8 mm); the average mean tumor AD was 226 ± 153 and 197 ± 138 Gy, respectively for PS and MS. For patient AD metrics, the best Pearson correlation (r) and concordance correlation coefficient (ccc) between segmentation methods was found for mean AD (r = 0.94, ccc = 0.92), but worsened as the metric approached the minimum dose (for D90, r = 0.77, ccc = 0.69); BED metrics exhibited a similar trend. Patient PS showed low intra-observer variability (average DSC = 0.81, average MDA = 2.2 mm, average AD/BED metrics within 3.0%). Conclusions 90Y PET gradient-based segmentation led to accurate/robust results in phantoms, and showed high concordance with MS for reporting mean tumor AD/BED in patients. However, tumor coverage metrics such as D90 exhibited worse concordance between segmentation methods, highlighting the need to standardize segmentation methods when reporting AD/BED metrics from post-therapy 90Y PET. Estimated differences in reported AD/BED metrics due to segmentation method will be useful for interpreting RE dosimetry results in the literature including tumor response data.https://deepblue.lib.umich.edu/bitstream/2027.42/146544/1/40658_2018_Article_230.pd

Response to Emerging Infection Leading to Outbreak of Linezolid-Resistant Enterococci

These bacteria have emerged as a hospital problem that appears to be caused by both linezolid exposure and patient-to-patient transmission

Multimode Bolometer Development for the Primordial Inflation Explorer (PIXIE) Instrument

The Primordial Inflation Explorer (PIXIE) is an Explorer-class mission concept designed to measure the polarization and absolute intensity of the cosmic microwave background [1]. In this work, we report on the design, fabrication, and performance of the multimode polarization-sensitive bolometers for PIXIE, which are based on silicon thermistors. In particular we focus on several recent advances in the detector design, including the implementation of a tensioning scheme to greatly raise the frequencies of the internal vibrational modes of the large-area, low-mass optical absorber structure consisting of a grid of micromachined, ion-implanted silicon wires. With 30 times the absorbing area of the spider-web bolometers used by Planck, the tensioning scheme enables the PIXIE bolometers to be robust in the vibrational and acoustic environment at launch of the space mission. More generally, it could be used to reduce microphonic sensitivity in other types of low temperature detectors. We also report on the performance of the PIXIE bolometers in a dark cryogenic environment

Higher prevalence of poor prognostic markers at a younger age in adult patients with myelodysplastic syndrome – evaluation of a large cohort in India

Background: The karyotype is a major determinant of prognosis in myelodysplastic syndrome (MDS). Details of the cytogenetic profile of MDS in South Asia are limited because cytogenetic services are not widely available.Methods: We performed a retrospective analysis of the cytogenetic and clinicopathologic profile of adult primary MDS seen consecutively at a tertiary-care centre in South India between 2003 and 2017. Patients were re-categorised according to the 2022 World Health Organisation (WHO) and the International Consensus classifications (ICC).Results: There were 936 patients aged 18-86 years (median age 53, 65% males), with MDS with del 5q, low blasts and increased blasts in 7.5%, 58.4% and 34.1% respectively. Clonal abnormalities were seen in 55% of patients, with solitary abnormalities in 29.8% and complex karyotypes (CK, ≥ 3 abnormalities) in 15%. The most frequent abnormalities were monosomy 7/deletion 7q (16.1%), deletion 5q (14.5%), trisomy 8 (11.5%), and deletion 20q (5.1%). Cytogenetic prognosis groups were distributed as follows: very good, 2%; good, 55.6%; intermediate, 16.2%; poor, 15%; very poor, 11.2%. Clinical (IPSS-R) risk stratification (842 patients) showed: very low-risk, 3.9%; low-risk, 30.9%; intermediate-risk, 24.2%; high-risk, 21%; very high-risk, 20%. Age-adjustment (IPSS-RA) raised the very low-risk group to 12.4%; the other groups decreased by 1-3% each.Conclusion: The most significant finding of this cytogenetic analysis of MDS in India is that abnormal karyotypes with poor prognosis markers including monosomy 7 and CK were more frequent than in most other reports, among patients who were overall younger. Trisomy 8, deletion 20q, the IPSS-R intermediate-risk and both high-risk groups were more common than in the West. Trisomy 8 was less common than in South-East Asia while CK and deletion 20q were comparable. Evaluation of such large cohorts highlights the unique features of MDS in different parts of the world. These findings suggest that there could be differences in predisposing factors, environmental or genetic, and emphasise the need for further exploration to better understand the varied nature of MDS