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Vitamin D supplementation has been shown to increase total hip areal bone mineral density in healthy children and adolescents. We aimed to investigate whether supplementing schoolchildren living in Mongolia with weekly vitamin D3for 3 years affected fracture risk.

IMPORTANCE: Vitamin D deficiency (defined as 25-hydroxyvitamin D [25(OH)D] <20 ng/mL) is prevalent among children living in temperate climates and has been reported to associate independently with stunting, obesity, and early activation of the hypothalamic-pituitary-gonadal axis. Phase 3 randomized clinical trials to investigate the influence of long-term vitamin D replacement on growth, body composition, and pubertal development of school-aged children with vitamin D deficiency are lacking. OBJECTIVE: To determine whether weekly oral vitamin D supplementation influences linear growth, body composition, or pubertal development in school-aged children living in a setting where vitamin D deficiency is highly prevalent. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a double-blind, placebo-controlled randomized clinical trial was conducted from June 2016 to June 2019 at 18 grade schools in Ulaanbaatar, Mongolia. School-aged children (6 to 13 years at baseline) attending participating schools were included. Exclusion criteria included a positive QuantiFERON-TB Gold in-tube assay result, conditions or medications associated with altered vitamin D metabolism, use of vitamin D supplements, signs of rickets, or intention to move from Ulaanbaatar within 4 years. Of 11 475 children invited to participate in the study, 9814 underwent QFT testing, and 8851 with negative results were included in the study. All but 1 participant in the placebo group completed follow-up and were included in the present analysis. Data were analyzed from November 2021 to February 2022. INTERVENTIONS: Weekly oral doses of vitamin D3, 14 000 IU, (n = 4418), or placebo (n = 4433) for 3 years. MAIN OUTCOMES AND MEASURES: Mean z scores for height for age, body mass index for age, and waist-to-height ratio; mean percentage body fat, fat mass, and fat-free mass; and mean Tanner scores for pubertal development. RESULTS: Of 8851 participants, 4366 (49.3%) were female, and 8165 (92.2%) were of Khalkh ethnicity; the mean (SD) age was 9.4 (1.6) years. A total of 8453 participants (95.5%) were vitamin D deficient at baseline, and mean end-of-study 25(OH)D concentrations among participants randomized to vitamin D vs placebo were 31.0 vs 10.7 ng/mL (mean difference, 20.3; 95% CI; 19.9-20.6). However, vitamin D supplementation did not influence mean height for age, body mass index for age, waist-to-height ratio, percentage body fat, fat mass, fat-free mass, or Tanner scores, either overall or within subgroups defined by baseline 25(OH)D concentration less than 10 ng/mL vs 10 ng/mL or greater, estimated calcium intake less than 500 mg/d vs 500 mg/d or greater, or male vs female sex. CONCLUSIONS AND RELEVANCE: In school-aged children in this study with low baseline vitamin D status, oral vitamin D3 supplementation at a dose of 14 000 IU per week for 3 years was effective in elevating 25(OH)D concentrations but did not influence growth, body composition, or pubertal development. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02276755

Statins are effective 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R) inhibitors, which are successfully used for cardiovascular disease treatment. Statins' side effects are generally attributed to poor bioavailability and hepatoselectivity, which are closely related to their high lipophilicity. Targeted delivery of statins to the liver is considered as a way to reduce unwanted side effects. Herein we report on synthesis and evaluation of atorvastatin conjugates targeting the galactose-specific hepatic asialoglycoprotein receptor (ASGPR). The prepared conjugates showed greater water solubility compared to unmodified atorvastatin. The synthesised compounds demonstrated potent binding to the ASGPR with submicromolar KDvalues. The conjugates with an amide bond connecting atorvastatin and the targeting moiety displayed the optimal stability under model conditions, as they underwent hydrolysis only when incubated with the intracellular protease. The hydrolysis products effectively inhibited HMG-R activity. The results suggest that the designed amide-based compounds have the potential to be further developed as orally administered prodrugs of atorvastatin.

The nonlinear optical responses of perovskite films CsPbI2Br, MAPbI3+ 1% PVC, MA0.15FA0.75Cs0.1PbI2.85Br0.15, and MA0.15FA0.75Cs0.1PbI3, irradiated by femtosecond laser pulses with wavelengths of 1064 and 532 nm, are investigated using z-scan measurements. Nonlinear absorption is found to occur in perovskite films irradiated at a wavelength of 1064 nm; the nonlinear absorption coefficient in thin films (45 - 65 nm) greatly exceeds that in thick ones (120 - 350 nm): 524 - 928 and 38 - 50 cm GW-1, respectively. It is shown that the nonlinear absorption saturation intensity for perovskite films depends on the pump pulse duration and increases with pulse shortening. It is also established that the nonlinear absorption coefficient of organometallic perovskite films exceeds that of a film of inorganic perovskite CsPbI2Br. Bleaching of film samples during z-scanning at a wavelength of 532 nm is related to the irreversible photochemical degradation of films exposed to intense light. The kinetics of photochemical bleaching of the films is detected at a wavelength of 532 nm.

To raise the stimulated Brillouin scattering (SBS) threshold, we have fabricated an optical fibre having a core heavily doped with germanium oxide and displaced from the fibre axis. A method has been proposed for broadening the SBS gain spectrum of the fibre by winding it onto a small-diameter spool, and a broadening of the spectrum by 5.4 dB has been demonstrated, which indicates an increase in SBS threshold by 4.1 dB.

Background Observational studies have documented lower risks of coronary heart disease and diabetes among moderate alcohol consumers relative to abstainers, but only a randomized clinical trial can provide conclusive evidence for or against these associations.Aim The purpose of this study was to describe the rationale and design of the Moderate Alcohol and Cardiovascular Health Trial, aimed to assess the cardiometabolic effects of one alcoholic drink daily over an average of six years among adults 50 years or older.Methods This multicenter, parallel-arm randomized trial was designed to compare the effects of one standard serving (∼11–15 g) daily of a preferred alcoholic beverage to abstention. The trial aimed to enroll 7800 people at high risk of cardiovascular disease. The primary composite endpoint comprised time to the first occurrence of non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalized angina, coronary/carotid revascularization, or total mortality. The trial was designed to provide >80% power to detect a 15% reduction in the risk of the primary outcome. Secondary outcomes included diabetes. Adverse effects of special interest included injuries, congestive heart failure, alcohol use disorders, and cancer.Results We describe the design, governance, masking issues, and data handling. In three months of field center activity until termination by the funder, the trial randomized 32 participants, successfully screened another 70, and identified ∼400 additional interested individuals.Conclusions We describe a feasible design for a long-term randomized trial of moderate alcohol consumption. Such a study will provide the highest level of evidence for the effects of moderate alcohol consumption on cardiovascular disease and diabetes, and will directly inform clinical and public health guidelines.

In this Letter, we propose and realize a novel concept for a high-peak-power highly efficient fiber amplifier in the 1.55 µm spectral range. The amplifier is based on the simultaneous utilization of Er-doped, Yb-free, and Er-Yb codoped large-mode-area fibers spliced together. Using this approach, we demonstrate the amplification of single-frequency 160 ns pulses at 1554 nm to a peak power of 3.7 kW with a pump-to-signal conversion efficiency of 23.6% relative to the launched multimode pump power at 976 nm.

Abstract: We studied the optical spectra of fluorinated yttrium–aluminum compositions activated by Eu3+ions. The compositions were synthesized by thermal decomposition at 800°C of fluorine-containing complexes of yttrium, europium, and aluminum nitrate, isolated as sols from ethyl acetate (EA). The main phases of the compositions are (Y1 –xEux)OF and (Y1 –xEux)AlO3. Photoluminescence is associated with 5D1, 2→ 7F0, 1, 2and 5D0→ 7F0, 1, 2, 3, 4electronic transitions of 4felectrons of Eu3+ions replacing yttrium ions in oxide and oxyfluoride. The dependences of luminescence on the composition and synthesis conditions of the compositions, the wavelength of the excitation radiation, and other factors are found.

Animals may limit the cost of stress responses during key life history stages such as breeding and molting by reducing tissue sensitivity to energy-mobilizing stress hormones (e.g. cortisol). We measured expression of genes encoding glucocorticoid receptor (GR, NR3C1), GR inhibitor (FKBP5) and cortisol-inactivating enzyme (HSD11B2) in blubber and muscle of northern elephant seals before and after stress axis stimulation by adrenocorticotropic hormone (ACTH) early and late in a fasting period associated with molting. ACTH elevated cortisol levels for >24 h and increased FKBP5 and HSD11B2 expression while downregulating NR3C1 expression in blubber and muscle, suggesting robust intracellular negative feedback in peripheral tissues. This feedback was maintained over prolonged fasting, despite differences in baseline cortisol and gene expression levels between early and late molt, suggesting that fasting-adapted animals use multiple tissue-specific, intracellular negative feedback mechanisms to modulate downstream impacts of acute stress responses during key life history stages.

The application of a fiber with W-type refractive index profile as a stretcher of ultrashort laser pulses for chirped pulse amplification is shown. As a result, pulses were obtained with energy of 3 µJ and duration of 270 fs, with high pulse contrast due to dispersion compatibility of the fiber stretcher and compressor on diffraction gratings. A comparative analysis of several types of fibers for use as a stretcher for amplification of chirped pulses is given in terms of their compatibility with the compressor.

Background Chronic hepatitis B (CHB) treatment adherence has been poorly studied worldwide. We evaluated long-term virological and adherence outcomes to antiviral treatment in CHB patients.Methods A prospective 183 Brazilian CHB patient cohort treated with monotherapy or combination adefovir dipivoxil, entecavir, lamivudine and/or tenofovir disoproxil fumarate was studied in a reference tertiary centre. Treatment adherence was evaluated by a validated questionnaire named ‘Assessment of Adherence to Antiviral Therapy Questionnaire’ (CEAT-HBV) within three yearly periods (2010/2011, 2013/2014 and 2014/2015).Results CEAT-HBV identified 43% (79/183) patients with non-adherence to antiviral treatment and among them, 67% (53/79) were viral load positive. The main causes associated with non-response to antiviral treatment were drug resistance variants followed by non-adherence, insufficient treatment duration and other causes. Single-dose pharmacokinetics demonstrated 35% (23/65) antiviral non-adherence. 2 years after the first assessment, the CEAT-HBV indicated that 71% (101/143) of subjects adhered to treatment (per-protocol population). However, 21% (40/183) of the patients could not be evaluated and were excluded. The main reasons for exclusion were death (20/183), 11 out 20 deaths due to hepatocellular carcinoma. HBV booklet was used for medical education. The third CEAT-HBV assessment (2014/2015) showed that 83% (112/135) patients were compliant with treatment adherence (per-protocol population). Long-term evaluation showed that adherence rate based on CEAT-HBV continue to increase after 4-years (P<0.001).Conclusions The results highlight the importance of CHB therapy adherence assessment monitoring. Long-term adherence outcomes were dynamic and it is possible to increase the migration rate to adherence/HBV-DNA-negative group.

We have studied absorption spectra of optical fibres doped with rare-earth ions (Sm3+, Tm3+, Tb3+, Pr3+ and Ho3+) and demonstrated that they are potentially attractive for ensuring wavelength-selective absorption in fibre lasers. Such fibres can be used for pump diode protection against back-reflected light at the operating wavelength of neodymium, erbium, erbium - ytterbium or thulium lasers. A proper choice of a rare-earth element makes it possible to ensure a strong absorption (10-20 dB) at the operating laser wavelength in combination with high transmission (loss under a few tenths of a decibel) at pump wavelengths. To demonstrate the potential of the proposed approach, we have fabricated and investigated Tm3+-doped fibre compatible with the output fibre pigtails of standard semiconductor diodes used for pumping (core diameter, 105 um; numerical aperture, 0.22). We have demonstrated the possibility of effectively suppressing light in the 1550-nm range by more than 20 dB even in the case of a high-power (up to 10 W) undesirable signal. Under such conditions, the total pump loss does not exceed 0.5 dB and can be further reduced by optimising the core composition and fibre design.

The composition of dipterans inhabiting fieldfare nests in a big city was studied for the first time, based on material collected soon after chick fledging. Larvae of 21 species belonging to 14 families were found, including saprophages, necrophages, and predators (Scatopsidae, Ceratopogonidae, Phoridae, Chloropidae, Anthomyiidae, etc.), and also Protocalliphora azurea(Fallén, 1816) (Calliphoridae) and Neottiophilum praeustum(Meigen, 1826) (Neottiophilidae) known as bloodsucking ectoparasites of nestlings. Larvae of P. azurea(up to 121 per nest) were found in both early (April–May) and late (May–June) nests. Larvae of N. praeustum(up to 299 per nest) were recorded only in late nests. The two species occurred both separately and jointly in one nest, with N. praeustumdominating numerically. The seasonal differences in the development of these two parasitic species may account for their high abundance in such ephemeral habitats. Larvae of Trypocalliphora braueri(Hendel, 1901), a subcutaneous parasite of nestlings of many bird species, were not found in the fieldfare nests. A key to the larvae of the three fly species parasitizing nestlings in European Russia is given.

The optical nonlinear absorption and bleaching of aqueous suspensions of multilayer MoS2 sheets (structural modification 2H) under excitation by a 400-fs pulse at a wavelength of 514 nm is investigated using longitudinal scanning. The sample exhibits nonlinear absorption at intensities up to 15 GW cm-2, while a further increase in intensity to 70 GW cm-2 causes nonlinear bleaching with a relative change in transmission to 14%. The dynamics of interband transitions in the picosecond range is studied by femtosecond laser photolysis. The relaxation time of photoexcited excitons is measured to be 20 +- 2 ps. The transition dynamics is calculated in the three-level approximation, and the absorption cross sections of photoinduced electron transitions from the valence band to the conduction band and from the first to the second conduction band are estimated. It is shown that the optical nonlinear properties of suspensions of multilayer 2H MoS2 sheets are mainly determined by the dynamics of single-photon interband transitions.

The translation of lifestyle intervention to improve glucose tolerance into the workplace has been rare. The objective of this meta‐analysis is to summarize the evidence for the effectiveness of dietary interventions in worksite settings on lowering blood sugar levels. We searched for studies in Pub‐Med, Embase, Econlit, Ovid, Cochrane, Web of Science, and Cumulative Index to Nursing and Allied Health Literature. Search terms were as follows : (1) Exposurebased: nutrition/diet/dietary intervention/health promotion / primary prevention / health behavior / health education/food /program evaluation; (2) Outcome‐based: diabetes/hyperglycemia/glucose/HbA1c/glycated hemoglobin; and (3) Setting‐based: workplace/worksite/occupational/industry/job/employee. We manually searched review articles and reference lists of articles identified from 1969 to December 2016. We tested for between‐studies heterogeneity and calculated the pooled effect sizes for changes in HbA1c (%) and fasting glucose (mg/dl)using random effect models for meta‐analysis in 2016. A total of 17 articles out of 1663 initially selected articles were included in the meta‐analysis. With a random‐effects model, worksite dietary interventions led to a pooled −0.18% (95% CI, −0.29 to −0.06; P<0.001) difference in HbA1c. With the random‐effects model, the interventions resulted in 2.60 mg/dllower fasting glucose with borderline significance (95% CI: −5.27 to 0.08, P= 0.06). In the multivariate meta‐regression model, the interventions with high percent of female participants and that used the intervention directly delivered to individuals, rather the environment changes, were associated with more effective interventions. Workplace dietary interventions can improve HbA1c. The effects were larger for the interventions with greater number of female participants and with individual‐level interventions.

The first data on blood-sucking ectoparasitic larvae of Neottiophilum praeustum(Meig.) which develop in bird nests are presented in Russia, with the fieldfare Turdus pilarisL. as a host example. Larval development takes not more than 10–12 days but no puparia are formed until late autumn. The larvae of Neottiophilumresemble those of calliphorid flies both in body structure and life mode. The main diagnostic characters of Neottiophilumlarvae distinguishing them from calliphorid ones are the spiracular disk of the posterior spiracles being positioned dorsal rather than ventral to the stigmal plate and lying outside rather than inside its peritreme. In addition, the anterior spiracles have 14–15, rather than 3–8 spiracular chambers.

The K+→π+νν‾decay is theoretically one of the cleanest meson decays and so a good place to look for indirect effects of new physics complementary to LHC searches. The NA62 experiment at CERN is designed to measure the branching ratio of this decay with 10% precision. NA62 was commissioned in October 2014, took data in pilot runs in 2014 and 2015. The NA62 experimental setup is illustrated and data quality is reported.

Among the meson decays, K→πνν‾are the cleanest environment, from the theoretical point of view, where to search for new physics effects. The NA62 Experiment at CERN SPS aims to measure the BR(K+→π+νν‾)with a 10% precision by the end of 2018. It has been commissioned with technical runs in 2014 and 2015, and some preliminary results of the detector performances and quality of data are here reported.

Optical fibres having a radially nonuniform acoustically antiguiding structure produced by codoping their core with alumina and germania have been fabricated and investigated. The influence of the shape of the antiguiding acoustic refractive index profile and fibre core diameter on the stimulated Brillouin scattering (SBS) threshold and spectrum in the fibres has been assessed. An increase in SBS threshold by 4.4 dB with respect to a germanosilicate fibre having the same mode field diameter has been demonstrated.

The main physics goal of the NA62 experiment at CERN is to precisely measure the branching ratio of the Kaon rare decay K+→π+νν‾. This decay is strongly suppressed in the Standard Model. On the other hand its branching ratio is calculated with high accuracy. NA62 is designed to measure the K+→π+νν‾decay rate with an uncertainty better than 10%. The measurement can serve as a probe to some new physics phenomena, which can alter the decay rate. The NA62 experiment has been successfully launched in October 2014. The theory framework as well as the NA62 detector and the preliminary results are reviewed in this article.

Genomic epidemiology is now widely used for viral outbreak investigations. Still, this methodology faces many challenges. First, few methods account for intra-host viral diversity. Second, maximum parsimony principle continues to be employed for phylogenetic inference of transmission histories, even though maximum likelihood or Bayesian models are usually more consistent. Third, many methods utilize case-specific data, such as sampling times or infection exposure intervals. This impedes study of persistent infections in vulnerable groups, where such information has a limited use. Finally, most methods implicitly assume that transmission events are independent, although common source outbreaks violate this assumption. We propose a maximum likelihood framework, SOPHIE, based on the integration of phylogenetic and random graph models. It infers transmission networks from viral phylogenies and expected properties of inter-host social networks modeled as random graphs with given expected degree distributions. SOPHIE is scalable, accounts for intra-host diversity, and accurately infers transmissions without case-specific epidemiological data.

This work discusses the study of structure and properties of composites based on polytetrafluoroethylene (PTFE) and filler, which is a composite material of cobalt nanoparticles and ultrafine polytetrafluoroethylene (UF PTFE). Transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray phase analysis (XRF) are applied for complex investigation into the properties of the obtained composite materials, such as specific energy absorption rate, thermal resistance and internal orientational stresses, thermophysical properties, and dielectric permeability. It is demonstrated that the obtained composite materials are superior to the initial matrix—PTFE. The magnetic study of the composite materials confirms the occurrence of metal nanoparticles and their interaction with the polymer matrix.

The operation regimes of a pulsed all-normal-dispersion polarisation-maintaining fibre laser with a nonlinear optical loop mirror are studied. The use of polarisation-maintaining fibres ensures polarisation and temperature stability of output radiation. The lasing and instability thresholds of the pulsed laser are determined experimentally. A spectral filter placed in the cavity makes it possible to change the centre wavelength of laser radiation within the range 1.02 - 1.05 um with a spectral full width at half maximum of 2 nm. The average output power is 7 mW, which corresponds to a pulse energy of 0.8 nJ. The autocorrelation function width of the output pulse is 50 ps. The minimum pulse duration achieved after compression by an external pair of diffraction gratings is 1.8 ps. The dynamics of the temporal and spectral parameters of laser pulses is studied using mathematical simulation based on numerical solution of the nonlinear Schrodinger equation. The simulation results coincide with experimental data with a high accuracy.