Prenatal exposure to nickel and atopic dermatitis at age 3 years: a birth cohort study with cytokine profiles.

BACKGROUND: Nickel, the fifth most common element on Earth, is the leading inducer of contact allergies in humans, with potent immunological effects. Nickel-induced contact allergies predominantly affect females. Maternal exposure to nickel has been associated with several developmental abnormalities. However, how a maternal nickel exposure affects the development of atopic diathesis and immune abnormalities in children has never been addressed. OBJECTIVES: We aimed to determine whether maternal nickel exposure affects the development of atopic dermatitis and immune abnormalities in their children. METHODS: Using a birth cohort study, we analysed 140 mother-child pairs recruited in 2012-2015 from central Taiwan. Maternal exposure to nickel was estimated using urinary nickel levels measured by inductively coupled plasma mass spectrometry (ICP-MS). The serum levels of 65 analytes and IgE in 3-year-old children were profiled with a multiplex ELISA. The correlation between the maternal urinary nickel concentration and serum analyte levels was assessed using Spearmen's correlation. Multivariant regression analysis was performed to evaluate the association between maternal urinary nickel levels and serum analyte concentrations in their children. RESULTS: The geometric means of the maternal urinary nickel and the children's serum IgE levels were 2.27 µg/L and 69.71 IU/mL, respectively. The maternal nickel exposure was associated with increased serum levels of IL-1ß, IL-2, TNF-α, and leukaemia inhibitory factor (LIF) but with decreased serum levels of matrix metalloproteinase-1 (MMP-1), IL-2R, and eotaxin-1 in the children. In addition, the development of childhood atopic dermatitis at 3 years old was significantly associated with the child's serum levels of IgE and IL-2R, but it was negatively associated with the maternal nickel exposure. CONCLUSIONS: This is the first study showing the potential immunological effects of maternal nickel exposure in their children at an early developmental stage.

Magnesium oxide and hip fracture in the elderly: a population-based retrospective cohort analysis.

Using national insurance claims of Taiwan, we found that magnesium oxide (MgO) use is associated with an increased risk of hip fracture in the elderly. Further studies are warranted to explore the mechanisms associated with MgO use that lead to hip fracture. PURPOSE: The purpose of this study was to investigate the association between MgO use and hip fracture risk in the elderly (age > 65 years). METHODS: This nationwide population-based retrospective study was conducted from 1996 to 2013. Individuals with (n = 26,069) and without (n = 26,069) MgO use were enrolled after propensity score matching. Primary outcome was a hip fracture. After adjusting for age, sex, comorbidities, and medications, multivariate Cox proportional hazards regression models were used to calculate incidences and risk of hip fracture [hazard ratio (HR)]. RESULTS: During the mean follow-up duration of 4.8 years in the MgO cohort and 5.7 years in the non-MgO cohort, respectively 1547 and 1107 cases developed a hip fracture. MgO use was identified as a risk factor for hip fracture in both univariate [crude HR, 1.68; 95% confidence interval (CI), 1.55-1.81; p < 0.001] and multivariate [adjusted HR (aHR), 1.66; 95% CI, 1.54-1.80; p < 0.001] Cox proportional hazards regression models. The cumulative incidence of hip fracture was significantly higher in the MgO cohort than in the non-MgO cohort (1.23 per 100 person-years vs. 0.74 per 100 person-years, logrank test, p < 0.001). CONCLUSION: MgO use is an independent risk factor for hip fracture in the elderly.

Broadband, millimeter-wave antireflection coatings for large-format, cryogenic aluminum oxide optics.

We present two prescriptions for broadband ($ {\sim} 77 - 252\;{\rm GHz} $), millimeter-wave antireflection coatings for cryogenic, sintered polycrystalline aluminum oxide optics: one for large-format (700 mm diameter) planar and plano-convex elements, the other for densely packed arrays of quasi-optical elements-in our case, 5 mm diameter half-spheres (called "lenslets"). The coatings comprise three layers of commercially available, polytetrafluoroethylene-based, dielectric sheet material. The lenslet coating is molded to fit the 150 mm diameter arrays directly, while the large-diameter lenses are coated using a tiled approach. We review the fabrication processes for both prescriptions, then discuss laboratory measurements of their transmittance and reflectance. In addition, we present the inferred refractive indices and loss tangents for the coating materials and the aluminum oxide substrate. We find that at 150 GHz and 300 K the large-format coating sample achieves $ (97 \pm 2)\% $ transmittance, and the lenslet coating sample achieves $ (94 \pm 3)\% $ transmittance.

Detection of CMB-Cluster Lensing using Polarization Data from SPTpol.

We report the first detection of gravitational lensing due to galaxy clusters using only the polarization of the cosmic microwave background (CMB). The lensing signal is obtained using a new estimator that extracts the lensing dipole signature from stacked images formed by rotating the cluster-centered Stokes QU map cutouts along the direction of the locally measured background CMB polarization gradient. Using data from the SPTpol 500 deg^{2} survey at the locations of roughly 18 000 clusters with richness λ≥10 from the Dark Energy Survey (DES) Year-3 full galaxy cluster catalog, we detect lensing at 4.8σ. The mean stacked mass of the selected sample is found to be (1.43±0.40)×10^{14}M_{⊙} which is in good agreement with optical weak lensing based estimates using DES data and CMB-lensing based estimates using SPTpol temperature data. This measurement is a key first step for cluster cosmology with future low-noise CMB surveys, like CMB-S4, for which CMB polarization will be the primary channel for cluster lensing measurements.

Dusty starburst galaxies in the early Universe as revealed by gravitational lensing.

In the past decade, our understanding of galaxy evolution has been revolutionized by the discovery that luminous, dusty starburst galaxies were 1,000 times more abundant in the early Universe than at present. It has, however, been difficult to measure the complete redshift distribution of these objects, especially at the highest redshifts (z > 4). Here we report a redshift survey at a wavelength of three millimetres, targeting carbon monoxide line emission from the star-forming molecular gas in the direction of extraordinarily bright millimetre-wave-selected sources. High-resolution imaging demonstrates that these sources are strongly gravitationally lensed by foreground galaxies. We detect spectral lines in 23 out of 26 sources and multiple lines in 12 of those 23 sources, from which we obtain robust, unambiguous redshifts. At least 10 of the sources are found to lie at z > 4, indicating that the fraction of dusty starburst galaxies at high redshifts is greater than previously thought. Models of lens geometries in the sample indicate that the background objects are ultra-luminous infrared galaxies, powered by extreme bursts of star formation.

Incidence and risk factors for hip fracture in elderly patients undergoing lumbar spine surgery: a nationwide database study with 11-year follow-up.

Impaired functional movement may occur after spinal surgery, which increases risk of fall episode and hip fracture. Patients with long-segment thoracolumbar spine fusions had a significantly higher risk of hip fracture than those with only discectomies. Fall prevention is necessary due to the highly increased hip fracture risk. INTRODUCTION: Spinal surgeries are performed to treat spondylolisthesis, fractures, scoliosis, or other deformities. Impaired balance mechanisms and functional movement may occur after spinal surgery. Fall episodes may cause hip fractures, which have negative impacts on quality of life and increase mortality. The incidence of hip fracture after spinal surgery is still unknown. The aim of this study was to examine the association between various types of spinal surgeries and hip fractures in the elderly by using a nationwide database. We hypothesized that the spinal surgeries may increase hip fracture risk in the elderly. METHODS: We used the National Health Insurance Research Database (NHIRD) to identify 3345 patients undergoing spinal surgery and a random dataset to identify 6690 age-, sex- and Charlson comorbidity index (CCI)-matched controls to compare the incidence of hip fractures in an 11-year follow-up period. We also enrolled 82,730 patients with spinal surgeries from the inpatient dataset to investigate the impact of different types of spinal surgeries. RESULTS: Patients who received spinal surgeries had higher risks of hip fractures, especially patients aged 60 to 79 years and female patients. The patients with long-segment thoracolumbar spinal fusions had a significantly higher risk of hip fracture than those with only discectomies. Short segmental lumbar spine fusions also slightly increased the risk of hip fracture compared with discectomies. CONCLUSION: Fall prevention for the elderly undergoing lumbar spinal surgery is necessary due to the highly increased hip fracture risk.

A massive, cooling-flow-induced starburst in the core of a luminous cluster of galaxies.

In the cores of some clusters of galaxies the hot intracluster plasma is dense enough that it should cool radiatively in the cluster's lifetime, leading to continuous 'cooling flows' of gas sinking towards the cluster centre, yet no such cooling flow has been observed. The low observed star-formation rates and cool gas masses for these 'cool-core' clusters suggest that much of the cooling must be offset by feedback to prevent the formation of a runaway cooling flow. Here we report X-ray, optical and infrared observations of the galaxy cluster SPT-CLJ2344-4243 (ref. 11) at redshift z = 0.596. These observations reveal an exceptionally luminous (8.2 × 10(45) erg s(-1)) galaxy cluster that hosts an extremely strong cooling flow (around 3,820 solar masses a year). Further, the central galaxy in this cluster appears to be experiencing a massive starburst (formation of around 740 solar masses a year), which suggests that the feedback source responsible for preventing runaway cooling in nearby cool-core clusters may not yet be fully established in SPT-CLJ2344-4243. This large star-formation rate implies that a significant fraction of the stars in the central galaxy of this cluster may form through accretion of the intracluster medium, rather than (as is currently thought) assembling entirely via mergers.

Ultrafast energy- and momentum-resolved dynamics of magnetic correlations in the photo-doped Mott insulator Sr2IrO4.

Measuring how the magnetic correlations evolve in doped Mott insulators has greatly improved our understanding of the pseudogap, non-Fermi liquids and high-temperature superconductivity. Recently, photo-excitation has been used to induce similarly exotic states transiently. However, the lack of available probes of magnetic correlations in the time domain hinders our understanding of these photo-induced states and how they could be controlled. Here, we implement magnetic resonant inelastic X-ray scattering at a free-electron laser to directly determine the magnetic dynamics after photo-doping the Mott insulator Sr2IrO4. We find that the non-equilibrium state, 2 ps after the excitation, exhibits strongly suppressed long-range magnetic order, but hosts photo-carriers that induce strong, non-thermal magnetic correlations. These two-dimensional (2D) in-plane Néel correlations recover within a few picoseconds, whereas the three-dimensional (3D) long-range magnetic order restores on a fluence-dependent timescale of a few hundred picoseconds. The marked difference in these two timescales implies that the dimensionality of magnetic correlations is vital for our understanding of ultrafast magnetic dynamics.

Efficacy and safety of LY2963016 insulin glargine in patients with type 1 and type 2 diabetes previously treated with insulin glargine.

The safety and efficacy of LY2963016 insulin glargine (LY IGlar) and Lantus insulin glargine (IGlar), products with identical primary amino acid sequences, were assessed in subgroups of patients with type 1 (T1D, n = 452) or type 2 diabetes (T2D, n = 299) reporting prestudy IGlar treatment in 52-week open-label (ELEMENT-1) and 24-week double-blind (ELEMENT-2) studies. At randomization, patients transitioned from their prestudy IGlar to equivalent doses of LY IGlar or IGlar. Primary efficacy (change in glycated haemoglobin from baseline to 24 weeks), other efficacy and select safety outcomes of LY IGlar were compared with those of IGlar. Continuous data were analysed using analysis of covariance, categorical data by Fisher's exact test, and treatment comparisons for hypoglycaemia by Wilcoxon test. No statistically significant treatment differences were identified for efficacy and safety outcomes except for weight change (T1D), overall incidence of detectable insulin antibodies (T2D), and serious adverse events (T2D). These differences were neither consistently observed across both studies nor observed in the total study populations, and their magnitude suggests they were not clinically meaningful. LY IGlar and IGlar show similar efficacy and safety profiles in patients reporting prestudy IGlar treatment.

Ethnicity as an independent predictive factor for the results of computed tomography pulmonary angiography and ultrasonography of the lower limbs.

BACKGROUND: Asians, Pacific Islanders and Maori have significantly lower rates of venous thromboembolism (VTE) compared to Europeans, but its clinic implication regarding diagnosis and prevention is unclear. AIMS: To investigate if ethnicity affects the yield of computed tomography pulmonary angiography (CTPA) and ultrasonography of the lower limbs. METHODS: Data previously collected for 523 patients from another study were used to analyse the effect of ethnicity on the results of CTPA; 1587 consecutive ultrasonography of lower limbs was retrospectively analysed according to ethnicity. The Wells score was retrospectively calculated to determine the pretest probability of VTE. RESULTS: The positive rates of CTPA were 23.3% for European patients and 9.3% for non-European patients. The rate ratio was 2.50 (confidence interval [CI] 1.27-4.95). European patients were 2.5 times more likely to have a positive scan result than non-Europeans, given same pretest probability. There was a larger difference among patients with low and moderate pretest probability with a rate ratio of 4.27 (CI 1.62-11.3). The positive rates of ultrasound scans (USS) among European patients were 16.6 and 9.0% for non-European patients. Rate ratio was 1.85 (CI 1.27-4.95). The difference was also more significant amongst patients with low and moderate pretest probability. The rate ratio was 2.31 (CI 1.38-3.86) for European patients compared to non-European patients. CONCLUSION: Given the same pretest probability according to the Wells score, European patients had significantly higher positive rates of CTPA and ultrasonography of the lower limbs than non-European patients. Further prospective studies are required to confirm our findings and establish an appropriate pretest assessment tool for non-European patients.

Dissecting alternative splicing in the formation of Miltenberger glycophorin subtype III (GYP.Mur).

BACKGROUND AND OBJECTIVES: Miltenberger subtype III (Mi.III, GP.Mur) is one of the most important red cell phenotypes in the fields of transfusion in South-East Asia. GP.Mur is believed to evolve from homologous gene recombination events between glycophorin A (GYPA) and glycophorin B (GYPB). GYP.Mur differs from GYPB in only seven nucleotides dispersed near the region of 3' exon 3 of GYP.Mur. The goal of this study was to dissect how these nucleotide variants affected splicing of exon 3. MATERIALS AND METHODS: We first designed two minigene constructs: one containing GYP.Mur from exon 2 to exon 4 and the other containing GYPB in the same region. To test how these nucleotide variations between GYP.Mur and GYPB affected the splicing, a repertoire of the GYP.Mur-like minigene constructs with different point mutations were created. These minigene variants were evaluated for their abilities to induce splicing of exon 3 using a heterologous expression system. RESULTS: (1) GYP.Mur minigene expressed exons 2, 3 and 4, whereas GYPB minigene expressed only exon 2 and exon 4. (2) The single nucleotide alteration at the position of the 5' splice site of glycophorin intron 3 reversed the splicing decision. (3) The nucleotide variations between GYP.Mur and GYPB other than that at the 5' splice site showed very little or no effect on splicing of exon 3. CONCLUSION: Splicing of the glycophorin B-A-B hybrids (GYP.Mur and GYP.BUN) and unsplicing of GYPB follow the GU-AG rule strictly.

Applying the Back-Propagation Neural Network model and fuzzy classification to evaluate the trophic status of a reservoir system.

The trophic state index, and in particular, the Carlson Trophic State Index (CTSI), is critical for evaluating reservoir water quality. Despite its common use in evaluating static water quality, the reliability of the CTSI may decrease when water turbidity is high. Therefore, this study examines the reliability of the CTSI and uses the Back-Propagation Neural Network (BPNN) model to create a new trophic state index. Fuzzy theory, rather than binary logic, is implemented to classify the trophic status into its three grades. The results show that compared to the CTSI with traditional classification, the new index with fuzzy classification can improve trophic status evaluation with high water turbidity. A reliable trophic state index can correctly describe reservoir water quality and allow relevant agencies to address proper water quality management strategies for a reservoir system.

A novel allele, HLA-A*11:127N, was identified in a Taiwanese individual by the sequence-based typing method.

A one nucleotide replacement in codon 171 of HLA-A*11:01:01 results in a novel allele, HLA-A*11:127N.

Detection and identification of occult HBV in blood donors in Taiwan using a commercial, multiplex, multi-dye nucleic acid amplification technology screening test.

BACKGROUND: The ability of a new generation commercial, multiplex, multi-dye test from Roche, the cobas TaqScreen MPX test, version 2.0, to detect and identify occult HBV infections was evaluated using routine donor samples from Kaohsiung Blood Bank, Taiwan. STUDY DESIGN AND METHODS: A total of 5973 samples were tested by nucleic acid amplification technology (NAT); 5898 in pools of six, 66 in pools of less than six and nine samples individually. NAT-reactive samples were retested with alternative NAT tests, and follow-up samples from the donors were tested individually by NAT and for all the HBV serological markers. RESULTS: Eight NAT-only-reactive donors were identified, and follow-up samples were obtained from six of the donors. The results indicated that all eight donors had an occult HBV infection with viral loads <12 IU/ml. CONCLUSION: The cobas(®) TaqScreen MPX test, version 2.0, has an advantage over the current Roche blood screening test, the cobas TaqScreen MPX test, for screening donations in countries with a high prevalence of occult HBV infections since the uncertainty associated with identifying samples with very low viremia is removed by the ability of the test to identify the viral target in samples that are reactive with the cobas TaqScreen MPX test, version 2.0.

Detection of B-mode polarization in the cosmic microwave background with data from the South Pole Telescope.

Gravitational lensing of the cosmic microwave background generates a curl pattern in the observed polarization. This "B-mode" signal provides a measure of the projected mass distribution over the entire observable Universe and also acts as a contaminant for the measurement of primordial gravity-wave signals. In this Letter we present the first detection of gravitational lensing B modes, using first-season data from the polarization-sensitive receiver on the South Pole Telescope (SPTpol). We construct a template for the lensing B-mode signal by combining E-mode polarization measured by SPTpol with estimates of the lensing potential from a Herschel-SPIRE map of the cosmic infrared background. We compare this template to the B modes measured directly by SPTpol, finding a nonzero correlation at 7.7σ significance. The correlation has an amplitude and scale dependence consistent with theoretical expectations, is robust with respect to analysis choices, and constitutes the first measurement of a powerful cosmological observable.

Cardiac dysfunction and N-terminal pro-B-type natriuretic peptide in exacerbations of chronic obstructive pulmonary disease.

Elevated levels of B-type natriuretic peptides among patients with exacerbations of chronic obstructive pulmonary disease (COPD) are associated with higher mortality. The pathophysiology is unclear. To establish if elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) are due to right or left heart dysfunction, we performed echocardiograms in 18 patients admitted to hospital with COPD. Elevated levels of NT-proBNP were associated with both right and left heart dysfunction and indicate that these patients have biventricular dysfunction rather than isolated right ventricular compromise.

Seasonal variation and health risk assessment of polycyclic aromatic hydrocarbons in Miaoli city, Taiwan.

The ambient PAHs levels in the downtown area of a traditional small city were analyzed for winter and summer seasons. A total of 16 PAHs in gaseous and particulate phase were quantified. The average gaseous PAHs were 2,189 ± 1,194 and 623.8 ± 545.1 ng/m(3) in winter and summer seasons, respectively. For the PAHs in particulate phase, they were 40.32 ± 12.15 and 11.99 ± 5.63 ng/m(3) in winter and summer seasons, respectively. These values were comparable to those reported for large cities or even higher. The estimated BaPeq was 12.32 ± 6.34 ng/m(3). As low-molecular-weight PAHs primarily existed in gaseous phase, high-molecular-weight PAHs in particulate phase became a significant fraction of total particulate phase PAHs. Particulate phase PAHs was significantly inversely associated with the ambient temperature for each individual PAHs species. However, this relationship did not exist for high-molecular-weight PAHs in gaseous phase. The results indicated the photo-degradation of high-molecular-weight PAHs should warrant a further thoughtfully investigation.

Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study.

BACKGROUND: The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon's two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). RESULTS: Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. CONCLUSIONS: Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.

X-Ray spectra and electronic correlations of FeSe(1-x)Te(x).

Critical issues concerning emerging Fe-based superconductors include the degree of electron correlation and the origin of the superconductivity. X-Ray absorption spectra (XAS) and resonant inelastic X-ray scattering spectra (RIXS) of FeSe(1-x)Te(x) (x = 0-1) single crystals were obtained to study their electronic properties that relate to electron correlation and superconductivity. The linewidth of Fe L(2,3)-edges XAS of FeSe(1-x)Te(x) is narrower than that of Fe-pnictides, revealing the difference between their hybridization effects and localization character and those of other Fe-pnictides. While no significant differences exist between the Fe L-edge XAS and RIXS of FeSe(1-x)Te(x) and those of Fe-pnictides, Se K-edge and Te K-edge XAS exhibit substantial edge shift, suggesting that the superconductivity in an Fe-Se superconductor is strongly associated with the ligand states. A comparison of the Se K-edge and Te K-edge spectra reveals that the charge transfer may occur between Se and Te. Given the Coulomb interaction and the bandwidth, the spectral results indicate that FeSe(1-x)Te(x) is unlikely to be a weakly correlated system unlike the Fe-pnictides of the "1111" and "122" families. The spectral results further demonstrate that superconductivity in this class of Fe-based compounds is strongly associated with the ligand 4p hole state.