Life expectancy in Australian senior with or without cognitive impairment: the Australia Diabetes, Obesity and Lifestyle Study Wave 3

Objective: To determine prevalence of cognitive impairment (CI) and to estimate life expectancy with and without cognitive impairment in the Australian population over age 60. Method: Adults aged 60 and older participating in the 12 year follow-up of the Australia Diabetes Obesity and Lifestyle Study (AusDiab) were included in the sample (n=1666). The mean age was 69.5 years, and 46.3% of the sample was male. The Mini-Mental State Examination was used to assess cognitive impairment. Logistic regression analysis was used to determine the effect of predictor variables (age, gender, education), measured at baseline, on cognitive impairment status. The Sullivan Method was used to estimate Total Life Expectancy (TLE), Cognitively Impaired (CILE) and Cognitive Impairment-free life expectancies (CIFLE). Results: Odds of CI were greater for males than females (OR 2.1, 95% confidence interval: 1.2-3.7) and among Australians with low education levels compared with Australians with high education levels (OR 2.1, 95% confidence interval: 1.2-3.7). The odds of CI also increased each year with age (OR 1.1, (95% confidence interval: 1.0-1.1). It was found that in all age groups females have greater TLE and CIFLE when compared to their male counterparts.This research was supported by the Australian Research Council Centre of Excellence in Population Aging Research (project number CE110001029). KJA is funded by NHMRC Fellowship #1002560. We acknowledge support from the NHMRC Dementia Collaborative Research Centres. The AusDiab study co-coordinated by the Baker IDI Heart and Diabetes Institute, gratefully acknowledges the support and assistance given by: K Anstey, B Atkins, B Balkau, E Barr, A Cameron, S Chadban, M de Courten, D Dunstan, A Kavanagh, D Magliano, S Murray, N Owen, K Polkinghorne, J Shaw, T Welborn, P Zimmet and all the study participants. Also, for funding or logistical support, we are grateful to: National Health and Medical Research Council (NHMRC grants 233200 and 1007544), Australian Government Department of Health and Aging, Abbott Australasia Pty Ltd, Alphapharm Pty Ltd, Amgen Australia, AstraZeneca, Bristol-Myers Squibb, City Health Centre-Diabetes Service-Canberra, Department of Health and Community Services- Northern Territory, Department of Health and Human Services– Tasmania, Department of Health–New South Wales, Department of Health–Western Australia, Department of Health–South Australia, Department of Human Services–Victoria, Diabetes Australia, Diabetes Australia Northern Territory, Eli Lilly Australia, Estate of the Late Edward Wilson, GlaxoSmithKline, Jack Brockhoff Foundation, Janssen-Cilag, Kidney Health Australia, Marian & FH Flack Trust, Menzies Research Institute, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk Pharmaceuticals, Pfizer Pty Ltd, Pratt Foundation, Queensland Health, Roche Diagnostics Australia, Royal Prince Alfred Hospital, Sydney, Sanofi Aventis, sanofi-synthelabo, and the Victorian Government’s OIS Program

Lessons to be learned from test evaluations during the Covid-19 pandemic:RSS Working Group’s Report on Diagnostic Tests

The coronavirus disease (Covid-19) pandemic raised challenges for everyday life. Development of new diagnostic tests was necessary, but under such enormous pressure risking inadequate evaluation. Against a background of concern about standards applied to the evaluation of in vitro diagnostic tests (IVDs), clear statistical thinking was needed on the principles of diagnostic testing in general, and their application in a pandemic. Therefore, in July 2020, the Royal Statistical Society convened a Working Group of six biostatisticians to review the statistical evidence needed to ensure the performance of new tests, especially IVDs for infectious diseases—for regulators, decision-makers, and the public. The Working Group’s review was undertaken when the Covid-19 pandemic shone an unforgiving light on current processes for evaluating and regulating IVDs for infectious diseases. The report’s findings apply more broadly than to the pandemic and IVDs, to diagnostic test evaluations in general. A section of the report focussed on lessons learned during the pandemic and aimed to contribute to the UK Covid-19 Inquiry’s examination of the response to, and impact of, the Covid-19 pandemic to learn lessons for the future. The review made 22 recommendations on what matters for study design, transparency, and regulation

The Need to Decide If All Estrogens Are Intrinsically Similar

We used gene expression profiling to investigate whether the molecular effects induced by estrogens of different provenance are intrinsically similar. In this article we show that the physiologic estrogen 17β-estradiol, the phytoestrogen genistein, and the synthetic estrogen diethylstilbestrol alter the expression of the same 179 genes in the intact immature mouse uterus under conditions where each chemical has produced an equivalent gravimetric and histologic uterotrophic effect, using the standard 3-day assay protocol. Data are also presented indicating the limitations associated with comparison of gene expression profiles for different chemicals at times before the uterotrophic effects are fully realized. We conclude that the case has yet to be made for regarding synthetic estrogens as presenting a unique human hazard compared with phytoestrogens and physiologic estrogens

Renal artery reconstruction for the preservation of renal function

AbstractPurpose: We reviewed a 13-year experience with an emphasis on long-term survival and renal function response when renal artery reconstruction (RAR) was performed primarily for the preservation or restoration of renal function in patients who had atherosclerotic renovascular disease.Methods: From January 1, 1980, to June 30, 1993, 139 patients underwent RAR for renal function salvage and were retrospectively reviewed. Inclusion criteria were either preoperative serum creatinine level >2.0 mg/dl (67% of patients) or RAR to the entire functioning renal mass irrespective of baseline renal function. Patient survival was calculated by life-table methods. Cox regression analysis was used to determine relative risk (RR) estimates for the late outcomes of continued deterioration of renal function and late survival after RAR. A logistic regression model was used to evaluate variables associated with perioperative complications.Results: Clinical characteristics of the cohort were notable for advanced cardiac (history of congestive heart failure, 27%; angina, 22%; previous myocardial infarction, 19%) and renal disease (serum creatinine level <2.0 mg/dl, 33%; 2.0 mg/dl to 3.0 mg/dl, 40%, >3.0 mg/dl, 27%). Cardiac disease was the principle cause of early (6 of 11 operative deaths) and late death. Operative management consisted of aortorenal bypass in 47%, extraanatomic bypass in 45%, and endarterectomy in 8%; 45% of patients required combined aortic and RAR. The operative mortality rate was 8%; significant perioperative renal dysfunction occurred in 10%. Major operative morbidity was associated with increasing azotemia (RR = 2.1; p = 0.001; 95% confidence interval [CI], 1.3 to 4.7 for each 1.0 mg/dl increase in baseline creatinine level). Of those patients who had a baseline creatinine level ≥2.0 mg/dl, 54% had ≥20% reduction in creatinine level after RAR. Late follow-up data were available for 87% of operative survivors at a mean duration of 4 years (range, 6 weeks to 12.6 years). Actuarial survival at 5 years was 52% ± 5%. Continued deterioration in renal function occurred in 24% of patients who survived operation, and eventual dialysis was required in 15%. Deterioration of renal function after RAR was associated with increasing levels of preoperative creatinine (RR = 1.6; 95% CI, 1.2 to 1.8; p = 0.001 for each 1.0 mg/dl increment in baseline creatinine level), and inversely related to early postoperative improvement in creatinine level (RR = 0.41; 95% CI, 0.2 to 0.9; p = 0.04).Conclusions: Intervention before major deterioration in renal function and an aggressive posture toward the frequently associated coronary artery disease are necessary to improve long-term results when RAR is performed for renal function salvage. (J Vasc Surg 1996;24:371-82.

Disentangling the AGN and star-formation contributions to the radio-X-ray emission of radio-loud quasars at 1<z<21<z<2

To constrain the emission mechanisms responsible for generating the energy powering the active galactic nuclei (AGN) and their host galaxies, it is essential to disentangle the contributions from both as a function of wavelength. Here we introduce a state-of-the-art AGN radio-to-X-ray spectral energy distribution fitting model (ARXSED). ARXSED uses multiple components to replicate the emission from the AGN and their hosts. At radio wavelengths, ARXSED accounts for radiation from the radio structures (e.g., lobes,jets). At near-infrared to far-infrared wavelengths, ARXSED combines a clumpy medium and a homogeneous disk to account for the radiation from the torus. At the optical-UV and X-ray, ARXSED accounts for the emission from the accretion disk. An underlying component from radio to UV wavelengths accounts for the emission from the host galaxy. Here we present the results of ARXSED fits to the panchromatic SEDs of 20 radio-loud quasars from the 3CRR sample at $1<z\lesssim2$. We find that a single power-law is unable to fit the radio emission when compact radio structures (core, hot spots) are present. We find that the non-thermal emission from the quasars' radio structures contributes significantly ($>70\%$) to the submm luminosity in half the sample, impacting the submm-based star formation rate estimates. We present the median intrinsic SED of the radio-loud quasars at $z>1$ and find that the median SED of \cite{Elvis1994} is unable to describe the SED of the radio-selected AGN at $z>1$. The AGN torus and accretion disk parameters inferred from our fitting technique agree with those in the literature for similar samples. We find that the orientation of the torus/accretion disk does not line up with the inclination of the radio jets in our sample

CANDELS/GOODS-S, CDFS, ECDFS: Photometric Redshifts For Normal and for X-Ray-Detected Galaxies

We present photometric redshifts and associated probability distributions for all detected sources in the Extended Chandra Deep Field South (ECDFS). The work makes use of the most up-to-date data from the Cosmic Assembly Near-IR Deep Legacy Survey (CANDELS) and the Taiwan ECDFS Near-Infrared Survey (TENIS) in addition to other data. We also revisit multi-wavelength counterparts for published X-ray sources from the 4Ms-CDFS and 250ks-ECDFS surveys, finding reliable counterparts for 1207 out of 1259 sources ($\sim 96\%$). Data used for photometric redshifts include intermediate-band photometry deblended using the TFIT method, which is used for the first time in this work. Photometric redshifts for X-ray source counterparts are based on a new library of AGN/galaxy hybrid templates appropriate for the faint X-ray population in the CDFS. Photometric redshift accuracy for normal galaxies is 0.010 and for X-ray sources is 0.014, and outlier fractions are $4\%$ and $5.4\%$ respectively. The results within the CANDELS coverage area are even better as demonstrated both by spectroscopic comparison and by galaxy-pair statistics. Intermediate-band photometry, even if shallow, is valuable when combined with deep broad-band photometry. For best accuracy, templates must include emission lines.Comment: The paper has been accepted by ApJ. The materials we provide are available under [Surveys] > [CDFS] through the portal http://www.mpe.mpg.de/XraySurvey

Phenotypic Anchoring of Gene Expression Changes during Estrogen-Induced Uterine Growth

A major challenge in the emerging field of toxicogenomics is to define the relationships between chemically induced changes in gene expression and alterations in conventional toxicologic parameters such as clinical chemistry and histopathology. We have explored these relationships in detail using the rodent uterotrophic assay as a model system. Gene expression levels, uterine weights, and histologic parameters were analyzed 1, 2, 4, 8, 24, 48, and 72 hr after exposure to the reference physiologic estrogen 17β-estradiol (E(2)). A multistep analysis method, involving unsupervised hierarchical clustering followed by supervised gene ontology–driven clustering, was used to define the transcriptional program associated with E(2)-induced uterine growth and to identify groups of genes that may drive specific histologic changes in the uterus. This revealed that uterine growth and maturation are preceded and accompanied by a complex, multistage molecular program. The program begins with the induction of genes involved in transcriptional regulation and signal transduction and is followed, sequentially, by the regulation of genes involved in protein biosynthesis, cell proliferation, and epithelial cell differentiation. Furthermore, we have identified genes with common molecular functions that may drive fluid uptake, coordinated cell division, and remodeling of luminal epithelial cells. These data define the mechanism by which an estrogen induces organ growth and tissue maturation, and demonstrate that comparison of temporal changes in gene expression and conventional toxicology end points can facilitate the phenotypic anchoring of toxicogenomic data

Different thyroid assays may greatly affect diagnosis and management of hypothyroidism

This is an accepted manuscript of an article published by BMJ Publishing Group in BMJ on 09/06/2021, available online: https://doi.org/10.1136/bmj.n1458 The accepted version of the publication may differ from the final published version.Letter to the editor, replying to Investigating hypothyroidism, Published: 27 April 2021; BMJ 373 doi:10.1136/bmj.n993Published versio