Determinants of male reproductive health disorders: the Men in Australia Telephone Survey (MATeS)

Background: The relationship between reproductive health disorders and lifestyle factors in middle-aged and older men is not clear. The aim of this study is to describe lifestyle and biomedical associations as possible causes of erectile dysfunction (ED), prostate disease (PD), lower urinary tract symptoms (LUTS) and perceived symptoms of androgen deficiency (pAD) in a representative population of middle-aged and older men, using the Men in Australia Telephone Survey (MATeS). Methods: A representative sample (n = 5990) of men aged 40+ years, stratified by age and State, was contacted by random selection of households, with an individual response rate of 78%. All men participated in a 20-minute computer-assisted telephone interview exploring general and reproductive health. Associations between male reproductive health disorders and lifestyle and biomedical factors were analysed using multivariate logistic regression (odds ratio [95% confidence interval]). Variables studied included age, body mass index, waist circumference, smoking, alcohol consumption, physical activity, co-morbid disease and medication use for hypertension, high cholesterol and symptoms of depression. Results: Controlling for age and a range of lifestyle and co-morbid exposures, sedentary lifestyle and being underweight was associated with an increased likelihood of ED (1.4 [1.1-1.8]; 2.9 [1.5-5.8], respectively) and pAD (1.3 [1.1-1.7]; 2.7 [1.4-5.0], respectively. Diabetes and cardiovascular disease were both associated with ED, with hypertension strongly associated with LUTS and pAD. Current smoking (inverse association) and depressive symptomatology were the only variables independently associated with PD. All reproductive disorders showed consistent associations with depression (measured either by depressive symptomatology or medication use) in both age-adjusted and multivariate analyses. Conclusion: A range of lifestyle factors, more often associated with chronic disease, were significantly associated with male reproductive health disorders. Education strategies directed to improving general health may also confer benefits to male reproductive health.Carol A. Holden, Robert I. McLachlan, Marian Pitts, Robert Cumming, Gary Wittert, Johnathon P. Ehsani, David M. de Kretser, David J. Handelsma

Vitamin D and Its Role During Pregnancy in Attaining Optimal Health of Mother and Fetus

Despite its discovery a hundred years ago, vitamin D has emerged as one of the most controversial nutrients and prohormones of the 21st century. Its role in calcium metabolism and bone health is undisputed but its role in immune function and long-term health is debated. There are clear indicators from in vitro and animal in vivo studies that point to vitamin D’s indisputable role in both innate and adaptive immunity; however, the translation of these findings to clinical practice, including the care of the pregnant woman, has not occurred. Until recently, there has been a paucity of data from randomized controlled trials to establish clear cut beneficial effects of vitamin D supplementation during pregnancy. An overview of vitamin metabolism, states of deficiency, and the results of recent clinical trials conducted in the U.S. are presented with an emphasis on what is known and what questions remain to be answered

Synthesis and biological investigation of (+)-JD1, an organometallic BET bromodomain inhibitor

(+)-JD1, a rationally designed ferrocene analogue of the BET bromodomain (BRD) probe molecule (+)-JQ1, has been synthesized and evaluated in biophysical, cell-based assays as well as in pharmacokinetic studies. It displays nanomolar activity against BRD isoforms, and its cocrystal structure was determined in complex with the first bromodomain of BRD4 and compared with that of (+)-JQ1, a known BRD4 small-molecule probe. At 1 μM concentration, (+)-JD1 was able to inhibit c-Myc, a key driver in cancer and an indirect target of BRD4

Life and living in advanced age: a cohort study in New Zealand - Te Puāwaitanga o Nga Tapuwae Kia Ora Tonu, LiLACS NZ: Study protocol

The number of people of advanced age (85 years and older) is increasing and health systems may be challenged by increasing health-related needs. Recent overseas evidence suggests relatively high levels of wellbeing in this group, however little is known about people of advanced age, particularly the indigenous Māori, in Aotearoa, New Zealand. This paper outlines the methods of the study Life and Living in Advanced Age: A Cohort Study in New Zealand. The study aimed to establish predictors of successful advanced ageing and understand the relative importance of health, frailty, cultural, social & economic factors to successful ageing for Māori and non-Māori in New Zealand

Stakeholders' views and experiences of care and interventions for addressing frailty and pre-frailty:a meta-synthesis of qualitative evidence

Frailty is a common condition in older age and is a public health concern which requires integrated care and involves different stakeholders. This meta-synthesis focuses on experiences, understanding, and attitudes towards screening, care, intervention and prevention for frailty across frail and healthy older persons, caregivers, health and social care practitioners. Studies published since 2001 were identified through search of electronic databases; 81 eligible papers were identified and read in full, and 45 papers were finally included and synthesized. The synthesis was conducted with a meta-ethnographic approach. We identified four key themes: Uncertainty about malleability of frailty; Strategies to prevent or to respond to frailty; Capacity to care and person and family-centred service provision; Power and choice. A bottom-up approach which emphasises and works in synchrony with frail older people's and their families' values, goals, resources and optimisation strategies is necessary. A greater employment of psychological skills, enhancing communication abilities and tools to overcome disempowering attitudes should inform care organisation, resulting in more efficient and satisfactory use of services. Public health communication about prevention and management of frailty should be founded on a paradigm of resilience, balanced acceptance, and coping. Addressing stakeholders' views about the preventability of frailty was seen as a salient need

The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems II: A 1 to 20 Micron Spectrum of the Planetary-Mass Companion VHS 1256-1257 b

We present the highest fidelity spectrum to date of a planetary-mass object. VHS 1256 b is a $<$20 M$_\mathrm{Jup}$ widely separated ($\sim$8\arcsec, a = 150 au), young, planetary-mass companion that shares photometric colors and spectroscopic features with the directly imaged exoplanets HR 8799 c, d, and e. As an L-to-T transition object, VHS 1256 b exists along the region of the color-magnitude diagram where substellar atmospheres transition from cloudy to clear. We observed VHS 1256~b with \textit{JWST}'s NIRSpec IFU and MIRI MRS modes for coverage from 1 $\mu$m to 20 $\mu$m at resolutions of $\sim$1,000 - 3,700. Water, methane, carbon monoxide, carbon dioxide, sodium, and potassium are observed in several portions of the \textit{JWST} spectrum based on comparisons from template brown dwarf spectra, molecular opacities, and atmospheric models. The spectral shape of VHS 1256 b is influenced by disequilibrium chemistry and clouds. We directly detect silicate clouds, the first such detection reported for a planetary-mass companion.Comment: Accepted ApJL Iterations of spectra reduced by the ERS team are hosted at this link: https://github.com/bemiles/JWST_VHS1256b_Reduction/tree/main/reduced_spectr

The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems IV: NIRISS Aperture Masking Interferometry Performance and Lessons Learned

We present a performance analysis for the aperture masking interferometry (AMI) mode on board the James Webb Space Telescope Near Infrared Imager and Slitless Spectrograph (JWST/NIRISS). Thanks to self-calibrating observables, AMI accesses inner working angles down to and even within the classical diffraction limit. The scientific potential of this mode has recently been demonstrated by the Early Release Science (ERS) 1386 program with a deep search for close-in companions in the HIP 65426 exoplanetary system. As part of ERS 1386, we use the same dataset to explore the random, static, and calibration errors of NIRISS AMI observables. We compare the observed noise properties and achievable contrast to theoretical predictions. We explore possible sources of calibration errors, and show that differences in charge migration between the observations of HIP 65426 and point-spread function calibration stars can account for the achieved contrast curves. Lastly, we use self-calibration tests to demonstrate that with adequate calibration, NIRISS AMI can reach contrast levels of $\sim9-10$ mag. These tests lead us to observation planning recommendations and strongly motivate future studies aimed at producing sophisticated calibration strategies taking these systematic effects into account. This will unlock the unprecedented capabilities of JWST/NIRISS AMI, with sensitivity to significantly colder, lower mass exoplanets than ground-based setups at orbital separations inaccessible to JWST coronagraphy.Comment: 20 pages, 12 figures, submitted to AAS Journal

The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems V: Do Self-Consistent Atmospheric Models Represent JWST Spectra? A Showcase With VHS 1256 b

The unprecedented medium-resolution (R~1500-3500) near- and mid-infrared (1-18um) spectrum provided by JWST for the young (140+/-20Myr) low-mass (12-20MJup) L-T transition (L7) companion VHS1256b gives access to a catalogue of molecular absorptions. In this study, we present a comprehensive analysis of this dataset utilizing a forward modelling approach, applying our Bayesian framework, ForMoSA. We explore five distinct atmospheric models to assess their performance in estimating key atmospheric parameters: Teff, log(g), [M/H], C/O, gamma, fsed, and R. Our findings reveal that each parameter's estimate is significantly influenced by factors such as the wavelength range considered and the model chosen for the fit. This is attributed to systematic errors in the models and their challenges in accurately replicating the complex atmospheric structure of VHS1256b, notably the complexity of its clouds and dust distribution. To propagate the impact of these systematic uncertainties on our atmospheric property estimates, we introduce innovative fitting methodologies based on independent fits performed on different spectral windows. We finally derived a Teff consistent with the spectral type of the target, considering its young age, which is confirmed by our estimate of log(g). Despite the exceptional data quality, attaining robust estimates for chemical abundances [M/H] and C/O, often employed as indicators of formation history, remains challenging. Nevertheless, the pioneering case of JWST's data for VHS1256b has paved the way for future acquisitions of substellar spectra that will be systematically analyzed to directly compare the properties of these objects and correct the systematics in the models.Comment: 32 pages, 16 figures, 6 tables, 2 appendice

The \textit{JWST} Early Release Science Program for Direct Observations of Exoplanetary Systems III: Aperture Masking Interferometric Observations of the star HIP\,65426 at 3.8 μm\boldsymbol{3.8\,\rm{\mu m}}

We present aperture masking interferometry (AMI) observations of the star HIP 65426 at $3.8\,\rm{\mu m}$ as a part of the \textit{JWST} Direct Imaging Early Release Science (ERS) program obtained using the Near Infrared Imager and Slitless Spectrograph (NIRISS) instrument. This mode provides access to very small inner working angles (even separations slightly below the Michelson limit of ${}0.5\lambda/D$ for an interferometer), which are inaccessible with the classical inner working angles of the \textit{JWST} coronagraphs. When combined with \textit{JWST}'s unprecedented infrared sensitivity, this mode has the potential to probe a new portion of parameter space across a wide array of astronomical observations. Using this mode, we are able to achieve a contrast of $\Delta m_{F380M}{\sim }7.8$\,mag relative to the host star at a separation of {\sim}0.07\arcsec but detect no additional companions interior to the known companion HIP\,65426\,b. Our observations thus rule out companions more massive than 10{-}12\,\rm{M\textsubscript{Jup}} at separations ${\sim}10{-}20\,\rm{au}$ from HIP\,65426, a region out of reach of ground or space-based coronagraphic imaging. These observations confirm that the AMI mode on \textit{JWST} is sensitive to planetary mass companions orbiting at the water frost line, even for more distant stars at $\sim$100\,pc. This result will allow the planning and successful execution of future observations to probe the inner regions of nearby stellar systems, opening essentially unexplored parameter space.Comment: 15 pages, 9 figures, submitted to ApJ Letter

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist