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BACKGROUND: Vitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent. METHODS: In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D(3) would result in a lower risk of fractures than placebo. VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D(3) (2000 IU per day), n–3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were reported by participants on annual questionnaires and adjudicated by centralized medical-record review. The primary end points were incident total, nonvertebral, and hip fractures. Proportional-hazards models were used to estimate the treatment effect in intention-to-treat analyses. RESULTS: Among 25,871 participants (50.6% women [13,085 of 25,871] and 20.2% Black [5106 of 25,304]), we confirmed 1991 incident fractures in 1551 participants over a median follow-up of 5.3 years. Supplemental vitamin D(3), as compared with placebo, did not have a significant effect on total fractures (which occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group; hazard ratio, 0.98; 95% confidence interval [CI], 0.89 to 1.08; P = 0.70), nonvertebral fractures (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.50), or hip fractures (hazard ratio, 1.01; 95% CI, 0.70 to 1.47; P = 0.96). There was no modification of the treatment effect according to baseline characteristics, including age, sex, race or ethnic group, body-mass index, or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in adverse events as assessed in the parent trial. CONCLUSIONS: Vitamin D(3) supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; VITAL ClinicalTrials.gov number, NCT01704859.)

Massive stars are among the main cosmic engines driving the evolution of star-forming galaxies. Their powerful ionising radiation and stellar winds inject a large amount of energy in the interstellar medium. Furthermore, mass-loss ($\dot{M}$) through radiatively driven winds plays a key role in the evolution of massive stars. Even so, the wind mass-loss prescriptions used in stellar evolution models, population synthesis, and stellar feedback models often disagree with mass-loss rates empirically measured from the UV spectra of low metallicity massive stars. The most massive young star cluster in the low metallicity Small Magellanic Cloud galaxy is NGC346. This cluster contains more than half of all O stars discovered in this galaxy so far. A similar age, metallicity ($Z$), and extinction, the O stars in the NGC346 cluster are uniquely suited for a comparative study of stellar winds in O stars of different subtypes. We aim to use a sample of O stars within NGC346 to study stellar winds at low metallicity. We mapped the central 1" of NGC346 with the long-slit UV observations performed by the Space Telescope Imaging Spectrograph (STIS) on board of the {\em Hubble Space Telescope} and complemented these new datasets with archival observations. Multi-epoch observations allowed for the detection of wind variability. The UV dataset was supplemented by optical spectroscopy and photometry. The resulting spectra were analysed using a non-local thermal equilibrium model atmosphere code (PoWR) to determine wind parameters and ionising fluxes. The effective mapping technique allowed us to obtain a mosaic of almost the full extent of the cluster and resolve stars in its core. Among hundreds of extracted stellar spectra, 21 belong to O stars. Nine of them are classified as O stars for the first time. We analyse, in detail, the UV spectra of 19 O stars... (continued), Comment: 33 pages, 40 figures

We investigate the internal kinematics of the young star-forming region NGC 346 in the Small Magellanic Cloud. We used two epochs of deep F555W and F814W Hubble Space Telescope ACS observations with an 11-year baseline to determine proper motions, and study the kinematics of different populations, as identified by their color-magnitude diagram and spatial distribution characteristics. The proper motion field of the young stars shows a complex structure with spatially coherent patterns. NGC 346 upper-main sequence and pre-main sequence stars follow very similar motion patterns, with the outer parts of the cluster being characterized both by outflows and inflows. The proper motion field in the inner ~10 pc shows a combination of rotation and inflow, indicative of inspiraling motion. The rotation velocity in this regions peaks at ~3 km/s, whereas the inflow velocity peaks at ~1 km/s. Sub-clusters and massive young stellar objects in NGC 346 are found at the interface of significant changes in the coherence of the proper motion field. This suggests that turbulence is the main star formation driver in this region. The similar kinematics observed in the metal-poor NGC 346 and the Milky Way star-forming regions suggest that the differences in the cooling conditions due to the different amounts of metallicity and dust density between the SMC and our Galaxy are too small to alter significantly the process of star clusters assembly and growth. The main characteristics of our findings are consistent with various proposed star cluster formation models., 17 pages, 14 figures, Accpeted for publication on ApJ

OBJECTIVE Describe the secretion and profile of adrenal steroids in patients with adrenal incidentalomas compared to control subjects. DESIGN, SETTING AND PARTICIPANTS A prospective study, 73 patients with adrenal incidentalomas, 21 bilateral and 52 unilateral and 34 matched controls in University Hospital. METHODS Collect fasting blood sample before and 60 min after ACTH test (250 µg IV). One week later, perform overnight 1 mg dexamethasone test. The following steroids were measured by liquid chromatography-mass spectrometry (LC-MS): pregnenolone, 17-OH pregnenolone, 17-OH progesterone, 11-deoxycorticosterone, 11-deoxyortisol, 21-deoxycortisol, corticosterone, cortisol, androstenedione and aldosterone. RESULTS Mean baseline serum cortisol was higher in incidentalomas, bilateral 361 ± 124, (range 143-665) nmol/L,(p

Background Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences. Objective To compare the effects of 4 doses of vitamin D3 supplements on falls. Design 2-stage Bayesian, response-adaptive, randomized trial. (ClinicalTrials.gov: NCT02166333). Setting 2 community-based research units. Participants 688 participants, aged 70 years and older, with elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L. Intervention 200 (control), 1000, 2000, or 4000 IU of vitamin D3 per day. During the dose-finding stage, participants were randomly assigned to 1 of the 4 vitamin D3 doses, and the best noncontrol dose for preventing falls was determined. After dose finding, participants previously assigned to receive noncontrol doses received the best dose, and new enrollees were randomly assigned to receive 200 IU/d or the best dose. Measurements Time to first fall or death over 2 years (primary outcome). Results During the dose-finding stage, the primary outcome rates were higher for the 2000- and 4000-IU/d doses than for the 1000-IU/d dose, which was selected as the best dose (posterior probability of being best, 0.90). In the confirmatory stage, event rates were not significantly different between participants with experience receiving the best dose (events and observation time limited to the period they were receiving 1000 IU/d; n = 308) and those randomly assigned to receive 200 IU/d (n = 339) (hazard ratio [HR], 0.94 [95% CI, 0.76 to 1.15]; P = 0.54). Analysis of falls with adverse outcomes suggested greater risk in the experience-with-best-dose group versus the 200-IU/d group (serious fall: HR, 1.87 [CI, 1.03 to 3.41]; fall with hospitalization: HR, 2.48 [CI, 1.13 to 5.46]). Limitations The control group received 200 IU of vitamin D3 per day, not a placebo. Dose finding ended before the prespecified thresholds for dose suspension and dose selection were reached. Conclusion In older persons with elevated fall risk and low serum 25-(OH)D levels, vitamin D3 supplementation at doses of 1000 IU/d or higher did not prevent falls compared with 200 IU/d. Several analyses raised safety concerns about vitamin D3 doses of 1000 IU/d or higher. Primary funding source National Institute on Aging.

Pyrolysis has been identified as an ideal process to recycle mixed plastic waste (MPW). This study investigates the economics of a 40,000 t/y MPW pyrolysis process, called PlastPyro, located in Belgium, to an accuracy of +/- 15% i.e. "Definite Estimate". The process uses molten metal in a direct heat treatment process to pyrolyse the waste. An internal rate of return (IRR) of 20% strongly indicates that a 40,000 t/y PlastPyro plant is financially attractive for private investors. The capital expenditure (CAPEX) is estimated to be (sic)20.1 m or (sic)26.1 m if the cost of capital is included. The operating expenditures (OPEX) of the plant are estimated (sic)3.4 m per year. The sensitivity analysis shows six main variables having major impacts on the financial returns of a PlastPyro plant: (1) the addressable volume and quality of plastic waste, (2) the feedstock costs, (3) the capital and operating expenditures, (4) the revenues from the sale of the produced pyrolysis oil (P-oil), (5) the tipping fees and (6) the potential to co-locate a PlastPyro plant with a waste plastic sorting facility. For example, the 15-year low P-oil revenue price of (sic)210/t results in an IRR of 20%; but on the 6th of March 2020 the P-oil price may have achieved (sic)227/t, resulting in an IRR of 37%. The paper also shows that a reliable supply of MPW is available, and that reliable, accessible markets for the P-oil are available. Finally, cost estimates should state their accuracy and usually factorial cost estimates are not accurate enough to state the IRR.

Objective Sierra Leone (SL), in West Africa, with a population of over 7.5 million people has suffered the effects of a civil war previously, and more recently Ebola & Covid-19. Dental care is very limited, mostly in the capital Freetown and the private sector. No dental education is available in the country. The objective of this research was to investigate the oral health needs of schoolchildren at key ages, to inform future action. Materials and methods This first national oral health survey of schoolchildren at 6-, 12- and 15-years was conducted in urban and rural settings across all four regions using a multi-stage cluster sampling in line with the WHO guidelines, adapted according to contemporary survey methods to include ‘International Caries Detection and Assessment System (ICDAS)’. Whilst parents were invited to complete a questionnaire for 6-year-old children, 12- and 15-year-olds self-completed a questionnaire. Data were weighted according to age and regional population and analysed using STATA v.15 and SPSS v.22. Results A total of 1174 children participated across 22 schools from all four regions. Dental caries was prevalent (over 80% of all age-groups having clinical decay; ICDAS score ≥ 2) and largely untreated. No children had fillings and only 4% had missing teeth. Amongst 6, 12 and 15-year-olds, average decay levels at ICDAS > 3 threshold was 3.47 (primary teeth), 2.94 and 4.30 respectively. Almost, 10% (n = 119) of all children reported experiencing pain in their teeth with 7% (n = 86) children having PUFA lesions present. At least one in five children required one or more dental extractions. ‘Age’ was a significant predictor of dental caries experience and the odds of having dental caries experience was higher in rural areas at D3–6MFT (p Conclusion The findings demonstrate a vast unmet oral health need in the children of SL. Using ICDAS as an epidemiological tool in a low-income country provides valuable insight to the pattern of oral disease to inform health service planning. Urgent action is required to address this silent epidemic.

The NGC 346 young stellar system and associated N66 giant HII region in the Small Magellanic Cloud are the nearest example of a massive star forming event in a low metallicity ($Z\approx0.2Z_{\odot}$) galaxy. With an age of $\lesssim$3Myr this system provides a unique opportunity to study relationships between massive stars and their associated HII region. Using archival data, we derive a total H$\alpha$ luminosity of L(H$\alpha$)=4.1$\times$10$^{38}$ergs$^{-1}$ corresponding to an H-photoionization rate of 3$\times$10$^{50}$s$^{-1}$. A comparison with a predicted stellar ionization rate derived from the more than 50 known O-stars in NGC 346, including massive stars recently classified from HST FUV spectra, indicates an approximate ionization balance. Spectra obtained with SALT suggest the ionization structure of N66 could be consistent with some leakage of ionizing photons. Due to the low metallicity, the far ultraviolet luminosity from NGC 346 is not confined to the interstellar cloud associated with N66. Ionization extends through much of the spatial extent of the N66 cloud complex, and most of the cloud mass is not ionized. The stellar mass estimated from nebular L(H$\alpha$) appears to be lower than masses derived from the census of resolved stars which may indicate a disconnect between the formation of high and low mass stars in this region. We briefly discuss implications of the properties of N66 for studies of star formation and stellar feedback in low metallicity environments., Comment: 15 pages, 6 figures, Accepted to be published in PASP

Context and purpose There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. Methods IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5-86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds. Results To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. Conclusions Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose-response relationship and risk characterisation for health outcomes. Trail registration PROSPERO International Prospective Register of Systematic Reviews (Registration Number: CRD42018097260).

The Radcliffe Wave is a $\sim3$ kpc long coherent gas structure containing most of the star-forming complexes near the Sun. In this Letter we aim to find a Galactic context for the Radcliffe Wave by looking into a possible relationship between the gas structure and the Orion (Local) Arm. We use catalogs of massive stars and young open clusters based on \textit{Gaia} EDR3 astrometry, in conjunction with kiloparsec-scale 3D dust maps, to investigate the Galactic \textit{XY} spatial distributions of gas and young stars. We find a quasi-parallel offset between the luminous blue stars and the Radcliffe Wave, in that massive stars and clusters are found essentially inside and downstream from the Radcliffe Wave. We examine this offset in the context of color gradients observed in the spiral arms of external galaxies, where the interplay between density wave theory, spiral shocks, and triggered star formation has been used to interpret this particular arrangement of gas/dust and OB stars, and outline other potential explanations as well. We hypothesize that the Radcliffe Wave constitutes the gas reservoir of the Orion (Local) Arm, and presents itself as a prime laboratory to study the interface between Galactic structure, the formation of molecular clouds in the Milky Way, and star formation., Comment: Published in A&A Letters

The Radcliffe Wave (RW) is a recently discovered sinusoidal vertical feature of dense gas in the proximity of the Sun. In the disk plane, it is aligned with the Local Arm. However, the origin of its vertical undulation is still unknown. This study constrains the kinematics of the RW, using young stars and open clusters as tracers, and explores the possibility of this oscillation being part of a more extended vertical mode. We study the median vertical velocity trends of the young stars and clusters along with the RW and extend it further to the region beyond it. We discover a kinematic wave in the Galaxy, distinct from the warp, with the amplitude of oscillation depending on the age of the stellar population. We perform a similar analysis in the N-body simulation of a satellite as massive as the Sagittarius dwarf galaxy impacting the galactic disk. When projected in the plane, the spiral density wave induced by the satellite impact is aligned with the RW, suggesting that both may be the response of the disk to an external perturbation. However, the observed kinematic wave is misaligned. It appears as a kinematic wave travelling radially, winding up faster than the density wave matched by the RW, questioning its origin. If a satellite galaxy is responsible for this kinematic wave, we predict the existence of a vertical velocity dipole that should form across the disk and this may be measurable with the upcoming Gaia DR3 and DR4., Accepted for publication in Astronomy & Astrophysics Letters

Delivering Better Oral Health (DBOH) was fi rst published in 2007 (Department of Health et al., 2007) at the request of the Department of Health to the British Association of Community Dentistry (BASCD). It was led by Dr Sue Gregory, who was at that time President of BASCD; and, thereafter, appointed Deputy Chief Dental Officer for England. The purpose of the document was to support dental teams in a more preventive approach to dental care based on the best available evidence. Practitioners have access to an enormous amount of information, and it was intended that DBOH would provide a simple guide to the evidence, explaining what the research meant in practical terms for the preventive advice and treatment of their patients. The approach promoted preventive care for all patients and additional support for those most at risk of poor oral health. DBOH was to be a living document, regularly updated. It was revised in 2009 and 2014, when after the Health and Social Care Act (2012), Public Health England took on the leadership of its development. In 2017 revisions responsed to changes in guidance; the publication by the Scientific Advisory Committee on Nutrition of the Carbohydrates and Health Report (SACN, 2015) which led to a revised healthier eating section and the Chief Medical Officers' (2016) new guidelines on alcohol were also incorporated.

Background:Cryptococcus neoformans is an encapsulated yeast that can cause fungemia and, in rare instances, lead to endogenous fungal endophthalmitis. No standard of care has been established to treat fungal endophthalmitis when systemic antifungal treatment fails to resolve the intraocular infection. Intravitreal voriconazole has been used for the treatment of fungal endophthalmitis caused by a broad range of fungal pathogens, and a limited number of reports have shown the efficacy of using intravitreal voriconazole for C neoformans endophthalmitis. We report a case of endogenous fungal endophthalmitis caused by C neoformans that was responsive to intravitreal voriconazole. Case Report: A previously healthy 57-year-old male diagnosed with primary neuroendocrine lung tumor developed endogenous endophthalmitis from C neoformans. The endophthalmitis was resistant to intravenous amphotericin B treatment but was responsive to intravenous fluconazole in one eye and was apparently more responsive to intravitreal voriconazole in the other eye. Conclusion: Intravitreal voriconazole should be considered for the treatment of cryptococcal endophthalmitis.

Breakthrough innovations can spur growth in the modern era industry to realise sustainability and high returns on investments. Nowadays, biobased innovations for application in diverse industry sectors are considered as future pillars to counter resource depletion and ensure positive environmental impacts. Cassava is a strong flagship biomaterial promoting solution for resource-efficient use and green environment. Innovative industrial application of cassava biomaterials enriches literature, presenting cassava as a versatile and unrivalled crop that is cardinal for more sustainable environment and biodegradable industrial products. Work on novel cassava biomaterials, which are low-cost, unexploited and with zero competition for food supply, are included. Using an integrated sustainable process, it shows how to indirectly reduce waste streams, through their effective use, guaranteeing zero carbon footprints and acting as a non-traditional strategy for equilibrium atmosphere and active packaging systems. Applications of Cassava biomaterial in food, as food supplements and in packaging systems are also covered in this chapter.

Continued improvements on existing reconstruction methods are vital to the success of high-energy physics experiments, such as the IceCube Neutrino Observatory. In IceCube, further challenges arise as the detector is situated at the geographic South Pole where computational resources are limited. However, to perform real-time analyses and to issue alerts to telescopes around the world, powerful and fast reconstruction methods are desired. Deep neural networks can be extremely powerful, and their usage is computationally inexpensive once the networks are trained. These characteristics make a deep learning-based approach an excellent candidate for the application in IceCube. A reconstruction method based on convolutional architectures and hexagonally shaped kernels is presented. The presented method is robust towards systematic uncertainties in the simulation and has been tested on experimental data. In comparison to standard reconstruction methods in IceCube, it can improve upon the reconstruction accuracy, while reducing the time necessary to run the reconstruction by two to three orders of magnitude., Comment: 39 pages, 15 figures, submitted to Journal of Instrumentation; added references

Waveguides were fabricated from highly n-type doped GeSn layers with Sn content at 5.4%–6.2% and grown on Ge-buffered Si substrates. The waveguides were optically pumped using a 976 nm continuous-wave laser, and the waveguide emission spectrum was collected and analyzed. The results indicate a non-linear power increase via higher injection-level at room temperature. Comprehensive theoretical models for the waveguide emission power dependence were developed to reproduce experimental data and provide an understanding of the nonlinear power dependence.

We report the results of optical spectroscopy of the Small Magellanic Cloud supernova remnant (SNR) MCSNR J0127-7332 and the mass donor Be star, 2dFS 3831, in its associated high-mass X-ray binary SXP 1062 carried out with the Southern African Large Telescope (SALT). Using high-resolution long-slit spectra, we measured the expansion velocity of the SNR shell of \approx 140 km/s, indicating that MCSNR J0127-7332 is in the radiative phase. We found that the observed line ratios in the SNR spectrum can be understood if the local interstellar medium is ionized by 2dFS 3831 and/or OB stars around the SNR. We propose that MCSNR J0127-7332 is the result of supernova explosion within a bubble produced by the stellar wind of the supernova progenitor and that the bubble was surrounded by a massive shell at the moment of supernova explosion. We estimated the age of MCSNR J0127-7332 to be \la 10 000 yr. We found that the spectrum of 2dFS 3831 changes with orbital phase. Namely, the equivalent width of the Halpha emission line decreased by \approx 40 per cent in \approx 130 d after periastron passage of the neutron star and then almost returned to its original value in the next \approx 100 d. Also, the spectrum of 2dFS 3831 obtained closest to the periastron epoch (about three weeks after the periastron) shows a noticeable emission line of He II \lambda 4686, which disappeared in the next about two weeks. We interpret these changes as a result of the temporary perturbation and heating of the disk as the neutron star passes through it., Comment: 12 pages, 8 figures, accepted for publication in MNRAS

International audience; There has been an increased interest in replacing synthetic colorants by colorants obtained from natural sources, especially microbial pigments. Monascus pigments have been used as natural colorings and food additives in Asia for centuries but have raised toxicity issues. Recently, Talaromyces/Penicillium species have been recognized as potential strains to produce natural pigments similar to those produced by Monascus species. To date, it has not been published a literature compilation about the research and development activity of Talaromyces/Penicillium pigments. Developing a new bioprocess requires several steps, from an initial concept to a practical and feasible application. Industrial applications of fungal pigments will depend on: (i) characterization of the molecules to assure a safe consumption, (ii) stability of the pigments to the processing conditions required by the products where they will be incorporated, (iii) optimizing process conditions to achieve high yields, iv) implementing an efficient product recovery and (v) scale-up of the bioprocess. The above aspects have been reviewed in detail to evaluate the feasibility of reaching a commercial scale of the pigments produced by Talaromyces/Penicillium. Finally, the biological activities of the pigments and their potential applications are discussed.

International audience; The genus Talaromyces has gained attention due to its ability to produce pigments with potential industrial applications in different areas. Prosperous application of fungal pigments has challenges to overcome, like developing a cost-effective bioprocess. Using agroindustrial wastes could provide inexpensive substrates and it contributes to maximize sustainability. Therefore, this study evaluated the feasibility of using corncob as a low-cost substrate for pigment production by Talaromyces atroroseus GH2. An acid hydrolysis treatment was used to release sugars from corncob. Corncob liquors with enough xylose concentration (>20 g/L) were investigated as fermentation media with and without the addition of nutrients. Process kinetic modeling was applied and pigments produced in corncob and control media were characterized. The diluted hydrolyzate without nutrient supplementation showed a pigment production (16.17±0.37 OD500nm) comparable to the control medium (17.26±0.41 OD500nm). Talaromyces atroroseus GH2 was able to co-utilize xylose and glucose in the corncob-based medium. However, growth kinetics patterns differed in both media. In the hydrolyzate medium, biomass growth presented an extended lag phase, which requires reduction for future process optimization. Finally, characterized pigments differed among evaluated media, but the pigments produced by Talaromyces atroroseus GH2 were mostly Monascus’ pigments homologous like monascorubrin and rubropunctamine. Talaromyces atroroseus GH2 ability to produce pigments using corncob hydrolyzate makes it a pigment-producing strain for an economically competitive large fermentation scale.

A study of 959 black and white women shows that the normal range for 24-h urine calcium excretion in white women is 30–300 mg and 10–285 mg in black women. Clinical laboratories use a normal range for 24-h urine calcium excretion of 100–300 mg; there is a need for them to update their age- and race-specific ranges. Recommendations for a normal range for 24-h urine calcium vary from a low of 50 mg to a high of 400 mg; most “laboratory normal ranges” based on older literature are incorrect. The objective of this analysis is to define a normal range for young women age 25–45 years and older women age 55–90 years, white and black, for 24-h urine calcium and calcium/creatinine ratio, and to examine the relationship between 24-h urine calcium, calcium absorption, and vitamin D metabolites. Data from 3 studies was collected on 959 normal black and white women, ages 25–87 years, for 24-h urine calcium, creatinine, calcium intake, serum 25-hydroxyvitamin D (25OHD),1,25 dihydroxyvitamin D (1,25(OH)2D), and calcium absorption. Urine calcium and creatinine were measured on an auto-analyzer. Calcium absorption was measured by a single isotope method. Serum 25OHD and 1,25(OH)2D were measured by competitive protein binding assay or radioimmunoassay. Because 24-h urine calcium did not fit a normal distribution, non-parametric methods were used to determine the 95% reference interval (RI) and 90% non-parametric confidence intervals (CI) calculated for groups. The 95% reference intervals for 24-h urine calcium for women were as follows: black older 7–225 mg, black younger 8–285 mg; white older 37–275 mg, and white younger 23–287 mg. In older white women, 24-h urine calcium was significantly correlated with serum 1,25(OH)2 D, r = 0.23, p < 0.001, calcium intake r = 0.12, p = 0.001, and calcium absorption r = 0.18, p = 0.003, but not serum 25OHD r = 0.07, p = 0.06. The normal reference interval for 24-h urine calcium for black women is lower than white women. Twenty-four-hour urine calcium was correlated with serum 1,25(OH)2 D calcium intake and calcium absorption, but not serum 25OHD. This range will be useful clinically for defining hypercalciuria and for following patients on vitamin D and calcium treatment.

Physical review letters 125(14), 141801 (1-11) (2020). doi:10.1103/PhysRevLett.125.141801, The results of a 3+1 sterile neutrino search using eight years of data from the IceCube Neutrino Observatory are presented. A total of 305 735 muon neutrino events are analyzed in reconstructed energy-zenith space to test for signatures of a matter-enhanced oscillation that would occur given a sterile neutrino state with a mass-squared differences between 0.01 and 100 eV$^2$. The best-fit point is found to be at sin$^2$($2θ_{24}$)=0.10 and $Δm_{41}^2$=4.5 eV$^2$, which is consistent with the no sterile neutrino hypothesis with a $p$ value of 8.0%., Published by APS, College Park, Md.

The observation of electromagnetic radiation from radio to $\gamma$-ray wavelengths has provided a wealth of information about the universe. However, at PeV (10$^{15}$ eV) energies and above, most of the universe is impenetrable to photons. New messengers, namely cosmic neutrinos, are needed to explore the most extreme environments of the universe where black holes, neutron stars, and stellar explosions transform gravitational energy into non-thermal cosmic rays. The discovery of cosmic neutrinos with IceCube has opened this new window on the universe. In this white paper, we present an overview of a next-generation instrument, IceCube-Gen2, which will sharpen our understanding of the processes and environments that govern the universe at the highest energies. IceCube-Gen2 is designed to: 1) Resolve the high-energy neutrino sky from TeV to EeV energies; 2) Investigate cosmic particle acceleration through multi-messenger observations; 3) Reveal the sources and propagation of the highest energy particles in the universe; 4) Probe fundamental physics with high-energy neutrinos. IceCube-Gen2 will increase the annual rate of observed cosmic neutrinos by a factor of ten compared to IceCube, and will be able to detect sources five times fainter than its predecessor. Furthermore, through the addition of a radio array, IceCube-Gen2 will extend the energy range by several orders of magnitude compared to IceCube. Construction will take 8 years and cost about \$350M. The goal is to have IceCube-Gen2 fully operational by 2033. IceCube-Gen2 will play an essential role in shaping the new era of multi-messenger astronomy, fundamentally advancing our knowledge of the high-energy universe. This challenging mission can be fully addressed only in concert with the new survey instruments across the electromagnetic spectrum and gravitational wave detectors which will be available in the coming years., Comment: 56 pages, 29 figures

Pulsar wind nebulae (PWNe) are the main gamma-ray emitters in the Galactic plane. They are diffuse nebulae that emit nonthermal radiation. Pulsar winds, relativistic magnetized outflows from the central star, shocked in the ambient medium produce a multiwavelength emission from the radio through gamma-rays. Although the leptonic scenario is able to explain most PWNe emission, a hadronic contribution cannot be excluded. A possible hadronic contribution to the high-energy gamma-ray emission inevitably leads to the production of neutrinos. Using 9.5 yr of all-sky IceCube data, we report results from a stacking analysis to search for neutrino emission from 35 PWNe that are high-energy gamma-ray emitters. In the absence of any significant correlation, we set upper limits on the total neutrino emission from those PWNe and constraints on hadronic spectral components., SCOPUS: ar.j, info:eu-repo/semantics/published

Osteoporosis and fractures are common features of alkaptonuria.A large cohort of alkaptonuria (AKU) patients was studied to better recognise and characterise osteoporosis and fractures in AKU.Assessments including questionnaire analysis, DEXA and CT densitometry at the neck of femur (FN), total hip (TH) and lumbar spine (LS) were performed on patients at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement. CT BMD Z-scores were generated.Between June 2007 and March 2020, 87 AKU patients attended the NAC. At baseline, there were 48 fractures in 39 patients. Prevalence of osteoporosis was 3.1 at FN, 10.8 at TH and 24.7% at LS respectively. Prevalence of fragility fractures was greatly increased at 44.8%. The group with fractures showed increased ochronosis scores (p0.05). CT LS showed an inverse relationship with fractures (R = - 0.28; p0.05). CT LS was significantly lower in the fracture group (p0.002). Following nitisinone only, CT FN and CT TH decreased significantly (p0.05 and 0.01 respectively). Following nitisinone plus antiresorptive therapy, CT FN, CT TH and CT LS all increased significantly (p0.05, 0.05 and 0.001 respectively). However, patients on nitisinone plus antiresorptive had more fractures than nitisinone and no-treatment groups (p0.05).Osteopenia and fragility fractures are common in AKU.. Anti-resorptive therapy increased BMD in AKU without decreasing fragility fractures. Bone densitometry measurements by DXA are less reliable than quantitative CT at the LS in AKU.

Galaxy environment has been shown to play an important role in transforming late-type, star-forming galaxies to quiescent spheroids. This transformation is expected to be more severe for low-mass galaxies (M < $10^{10}$ \(M_\odot\)) in dense galaxy groups and clusters, mostly due to the influence of their past host halos (also known as pre-processing) and their present-day environments. For the first time, in this study, we investigate a sample of nine early-type dwarf galaxies (dEs) that were accreted as a likely bound group onto the Virgo galaxy cluster about 2-3 Gyr ago. Considering this special condition, these nine dEs may provide a test bed for distinguishing between the influence of the Virgo galaxy cluster and the effects of the previous host halo on their current properties. Specifically, we use VLT/MUSE integral-field unit spectra to derive their kinematics and specific angular momentum ($\lambda_{R}$) profiles. We observe a spread in the $\lambda_{R}$ profiles of our sample dEs, finding that the $\lambda_{R}$ profiles of half of them are as high as those of low-mass field galaxies. The remaining dEs exhibit $\lambda_{R}$ profiles as low as those of Virgo dEs that were likely accreted longer ago. Moreover, we detect nebular emission in one dE with a gas velocity offset suggesting ongoing gas stripping in Virgo. We suggest that the low-$\lambda_{R}$ dEs in our sample were processed by their previous host halo, prior to their infall to Virgo, and that the high-$\lambda_{R}$ dEs may be experiencing ram pressure stripping in Virgo., Comment: 23 pages, 16 figures, Accepted for publication in MNRAS

Red algae, belonging to the phylum Rhodophyta, contain an abundance of useful chemicals including bioactive molecules and present opportunities for the production of different products through biorefinery cascades. The rhodophyte Palmaria palmata, commonly termed dulse or dillisk, grows predominantly on the northern coasts of the Atlantic and Pacific Oceans and is a well-known snack food. Due to its abundance, availability and cultivation capacity, P. palmata was selected for study as a potential candidate for a biorefinery process. In addition to studying juice and solid fractions of freshly harvested P. palmata, we have investigated the novel possibility of preserving algal biomass by ensilaging protocols similar to those employed for terrestrial forage crops. In the metabolite partitioning within the solid and liquid fractions following screw-pressing, the majority of the metabolites screened for—water soluble carbohydrates, proteins and amino acids, lipids, pigments, phenolics and antioxidant activity—remained in the solid fraction, though at differing proportions depending on the metabolite, from 70.8% soluble amino acids to 98.2% chlorophyll a and 98.1% total carotenoids. For the ensiling study, screw-pressed P. palmata, with comparative wilted and chopped, and chopped only samples, were ensiled at scale with and without Safesil silage additive. All samples were successfully ensiled after 90 days, with screw-pressing giving lower or equal pH before and after ensiling compared with the other preparations. Of particular note was the effluent volumes generated during ensiling: 26–49% of the fresh weight, containing 16–34% of the silage dry matter. This may be of advantage depending on the final use of the biomass.

Describe current Dental Public Health [DPH] curricula content and delivery across European dental schools and ascertain views on a core undergraduate curriculum for dental students.Survey of European dental schools, informed by professional and academic literature and European Association for Dental Public Health [EADPH] Special Interest Working Group discussions. Questionnaires were distributed electronically, by post, and via EADPH network members, to the Deans of 252 dental schools in Europe. E-mail reminders were sent to non-responders.European Dental Schools.Around half (n=124, 49%) out of a possible 252 schools responded, all of which reported having some DPH education. Two-thirds reported having a dedicated DPH department. Education was delivered by a variety of staff including those trained in paediatric and preventive dentistry. There were differing degrees of integration within the undergraduate programme and substantial variability in topics, teaching methods and approaches to assessment. Key components of the curriculum supported by respondents were: DPH philosophy and approach, population demography and health, health promotion and disease prevention, health care systems, the dental workforce and planning for health and oral health. Respondents were generally in favour of improving current teaching and shaping a core DPH curriculum for Europe.Amongst those who completed the questionnaire, there was a general agreement on the need for a core Dental Public Health curriculum for European dentists. Given the variation across Europe, increased awareness and prioritisation of the subject is required, facilitated by collaborative support.

BACKGROUND There are few controlled studies of the effect of different doses of vitamin D3 on bone mineral density (BMD). OBJECTIVES We conducted a randomized placebo-controlled trial of increasing doses of vitamin D3 in 163 Caucasian and 31 African American women with serum 25-hydroxyvitamin D (25OHD) ≤50 nmol/L. This is an analysis of secondary outcome BMD to see if there is an association between percent change in BMD and dose of vitamin D3. METHODS Participants were randomly assigned to placebo, vitamin D3 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/day; calcium supplements, average 600mg, were given to provide a total calcium intake of 1200 mg/d. The primary outcome was 12-month serum 25OHD level. Analysis methods include ANOVA and Pearson correlations. RESULTS The mean percent increase (±SD) in BMD at 12 months for all women was small; total body, 0.62% (± 2.72), femoral neck 0.59% (±3.58) and spine 0.43% (±2.80). There was no difference in BMD or serum N-telopeptide in response to vitamin D by dose or race. The increase in total body, spine and hip BMD in elderly women given vitamin D doses between 400 and 4800 IU daily and calcium supplementation is small, unrelated to dose or 12-month serum 25OHD, free 25OHD or 1,25(OH)2D. There was no evidence of a threshold change in BMD with increasing serum 25OHD or free 25OHD in this population. CONCLUSIONS We found no significant effect of daily vitamin D dose ranging from 400 to 4800 IU/day on BMD or serum N-terminal telopeptides in elderly women with initially low serum 25OHD.

Introduction: The effect of vitamin D supplementation on physical performance is controversial. Longitudinal cohort studies show very low levels of serum 25OHD (< 15- 20ng/ml) are associated with lower physical performance. There are few clinical trials of the effect of vitamin D on physical performance and results are mixed. Design: 163 white and 110 black independent living women entered a 12-month double blind randomized dose ranging study of daily vitamin D,400,800,1600,2400,3200,4,000,4800IU or placebo together with calcium supplement as needed for a total intake of 1200mg and mean diet vitamin D of 114 IU. Inclusion criteria: total serum 25OHD ≤ 20ng/ml (Diasorin RIA); no known disease or drugs affecting calcium or bone metabolism. Physical performance tests were performed at baseline and end as described in the Short physical performance battery (SPPB) that included Balance, Timed walk, Chair rising test. Additional tests included Timed up and Go, Grip strength and Balance (Biodex). Fall history was recorded at baseline and at 3-monthly visits. Serum 25OHD was measured by Diasorin RIA and LCMS, Free 25OHD was measured by Elisa (Future Diagnostics). Changes in physical performance and fallers were analyzed by dose groups and by quintiles of total and free serum 25OHD. This was a secondary analysis using Intent to treat strategy. Chi square and ANOVA determined association between dose, quintiles and tests. Results: Mean age 66.2 years (SD 7.3, range 57–87), mean BMI 30.3 kg/m2 (SD 5.9). Compliance, measured every 3 months, was 94% for vitamin D and 91% calcium. 147 White and 89 Black women completed study. There was significant better performance in physical performance in women < age 70 years compared to > age 70 years. Black women performed better with all tests except grip strength after adjustment for age and BMI. When the absolute change in test performance was examined according to serum total or free 25OHD quintiles there was no correlation between serum levels of 25OHD and change in any physical performance test except for an improvement in chair rising test in younger Black women. Conclusions: There is no significant effect of vitamin D on physical performance in either black or white women. In a previous analysis we found a significant U-shaped response in fall incidence in the serum 25OHD range 30-40ng/ml but in this analysis there is no correlation between physical performance of fallers versus non- fallers

Vitamin D insufficiency and deficiency can be diagnosed with measurements of serum 25-hydroxyvitamin D (25OHD). Most vitamin D is derived from sunlight (80%), so serum 25OHD levels are lowest in late winter and early spring. Dietary vitamin D in North America is small, about 100 to 200 IU daily. A recent review of the literature shows many association studies relating vitamin D deficiency and insufficiency to several diseases. Large randomized trials of vitamin D are underway and soon there may be answers as to whether vitamin D is clinically effective and what level of serum 25OHD is necessary.