Search

The third generation South Pole Telescope camera (SPT-3G) improves over its predecessor (SPTpol) by an order of magnitude increase in detector number. The technology used to read out and control these detectors, digital frequency-domain multiplexing (DfMUX), is conceptually the same as used for SPTpol, but extended to accommodate more detectors. A nearly 5x expansion in the readout operating bandwidth has enabled the use of this large focal plane, and SPT-3G performance meets the forecasting targets relevant to its science objectives. However, the electrical dynamics of the higher-bandwidth system depart in significant ways from the characterization and models drawn from the previous generation of cameras. We present an updated derivation for electrical crosstalk in higher-bandwidth DfMUX systems, and identify two previously uncharacterized contributions to readout noise. The updated crosstalk and noise models successfully describe the measured crosstalk and readout noise performance of SPT-3G, and suggest improvements to the readout system for future experiments using DfMUX, such as the LiteBIRD satellite.

BackgroundDespite recent advances of direct-antiviral agents (DAA) for Hepatitis C virus (HCV), it is still a prevalent worldwide issue and therapeutic challenge in patients with rheumatoid arthritis (RA). HCV viral replication may respond differently to biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) of different mechanism of action. Exosomal microRNA 155 (exo-miR-155) and exo-miR-122 have been implicated in modulating the host immune response and transmit anti-HCV factors to HCV-infected hepatocytes in patients with RA. However, it remains unknown how exosomal miRNAs may respond following bDMARDs and tsDMARDs treatment in HCV-infected patients with RA.ObjectivesWe aimed to study the changes of exo-miR-155 and exo-miR-122 following bDMARDs and tsDMARDs treatment in HCV-infected RA patients.MethodsWe prospectively enrolled RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors, rituximab and tofacitinib. The effect of bDMARDs and tsDMARDs on HCV viral replication were assessed using an HCV-tricistronic replicon cell system. Exo-miR-155 and 122 were detected by quantitative PCR.ResultsHCV RNA replication in hepatocytes were not affected by tofacitinib treatment. Exo-miR-155 and exo-miR-122 were significantly increased in RA patients with HCV infection compared with those without HCV infection. We observed a dramatically increase of exo-miR-122 and decreased of exo-miR-155 in patients taking rituximab compared with the TNF-α inhibitors, tofacitinib and conventional synthetic DMARD groups. Finally, a reduction of exo-miR-122 and increase of exo-miR-155 levels were detected following DAA therapy for HCV.ConclusionExo-miR-155 and exo-miR-122 were potential biomarkers for RA patients with HCV infection. Further studies are needed to confirm our findings.References[1]Liao TL, Hsieh SL, Chen YM, Chen HH, Liu HJ, Lee HC, Chen DY (2018) Rituximab may cause increased hepatitis C virus viremia in rheumatoid arthritis patients through declining exosomal microRNA-155. Arthritis Rheumatol 70: 1209-1219.Table 1.Demographics of HCV-infected RA patients with bDMARDs and tsDMARDsanti-TNF-α therapy n=3Rituximab n=3Tofacitinib n=3Age62.8 (54.0-71.4)59.9 (49.9-67.6)63.8 (55.5-70.9)Gender (female, %)2 (66.7)3 (100)2 (66.7)Disease duration (years)11.0 (8.8-14.0)11.3 (7.6-17.0)12.0 (8.2-13.8)RF (IU/ml)155.0 (102.2-324.4)363.5 (265.0-538.7)95.0 (75.4-152.6)Anti-CCP antibody (units)132.7 (83.0-210.8)160.7 (106.9-400.3)112.0 (88.0-211.8)DAS285.3 (4.9-6.5)5.3 (4.8-6.4)5.2 (4.7-6.5)Figure 1.Comparison of exo-miR-122 (left panel) and exo-miR-155 levels (right panel) in RA patients receiving different biologics. All experiments were performed in triplicate and data are presented as the mean ± SD. RTX, rituximab; TNFi: tumor necrosis factor inhibitor; Tofa, tofacitinib. **pDisclosure of InterestsNone declared

BackgroundAzathioprine(AZA) is widely used in patients with autoimmun diseases. Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in AZA metabolization. Although several studies have investigated the association between TPMT polymorphisms and AZA-induced bone marrow suppression, the relationship of TPMT genotypes and hepatoxicity in patients taking AZA remained unclear.ObjectivesThis study aimed to investigate the correlation between TPMT polymorphisms and adverse reactions of AZA.MethodsThis retrospective case-control study enrolled patients with prior exposure to AZA at the Taichung Veterans General Hospital (TCVGH) using data extracted from the Taiwan Precision Medicine Initiative (TPMI) cohort. Drug-prescription profile, comorbidities, the occurence of leukopenia and hepatotoxicity following AZA treatment were extracted from hospital health records. Genetic variatns affecting TPMT activity were determined using SNP array. Participants were categorized into normal metabolizer (NM) and non-normal metabolizer (Non-NM) groups accordingly.ResultsFrom the 43,035 patients in the TCVGH-TPMI cohort, we identified 2,128 azathioprine users; 2.6% (57 out of 2,128) were classified as TPMT Non-NM group. After matching by age and sex, we included 50 TPMT Non-NM, including 1 poor metabolizers (PMs), 49 intermediate metabolizers (IMs), and 1,000 NM patients for further analysis. The Non-NM genotype was associated with hepatotoxicity compared with NM genotype (HR: 3.85, 95% CI: 1.83–8.10) after adjustment for gender, AZA dosage, and comorbidities(Table 1). In the Non-NM group, the 3-year cumulative incidence of hepatotoxicity was 6.6% for one year, 16.9% for two and three years, respectively, which was significantly higher than the NM group (p=0.003)(Figure 1).Table 1.Cox regression analysis of risk factors for hepatotoxicity following AZA treatmentHepatotoxicity*p valueHR95% CIAge0.990.981.010.60Male gender1.771.072.910.03TPMT non-NM genotype3.851.838.100.0004AZA dose (mg)1.001.001.010.31MedicationMTX1.621.032.570.04ComorbidityHepatitis B carrier1.180.403.480.76By Cox regression model with adjustment of all listed variables.*Development of GPT ≥ 150 U/L after AZA treatment; GPT, glutamic pyruvic Transaminase; TPMT, thiopurine S-methyltransferase; NM, normal metabolizer; AZA, azathioprine; MTX, Methotrexate; CI: confidence intervalFigure 1.Cumulative incidence of hepatotoxicityConclusionTPMT Non-NM genotype were associated with the developement of hepatotoxicity following AZA therapy. Prospective studies are needed to varify our results.References[1]Liu, Y.P., et al., Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis. PLoS One, 2015. 10(3): p. e0121745.Disclosure of InterestsNone declared

BackgroundSeveral studies have demonstrated immunogenicity after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD) [1], but the differences between mRNA-based and vector vaccines and the cellular responses to COVID-19 vaccines according to distinct immunogenicity in AIRD patients are still unclear.ObjectivesTo investigate the differences in efficacy and safety between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with AIRD, and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) by single-cell RNA sequencing (scRNA-seq).MethodsFrom September 16 to November 15, 2021, we consecutively enrolled 243 participants aged ≥20 years with AIRD who received COVID-19 vaccination, of whom 113 were immunized with AZD1222 and 130 with mRNA-1273. The level of serum IgG antibodies to the SARS-CoV-2 receptor-binding domain on the spike protein S1 subunit was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells were isolated from two RA patient with high anti-SARS-CoV-2 IgG level and four RA patients with low level for scRNA-seq and cell-cell communication signal was analyzed by CellChat.ResultsThe anti-SARS-CoV-2 IgG seropositivity rate was 78.8% (89/113) for AZD1222 and 83.1% (108/130) for mRNA-1273. The level of anti-SARS-CoV-2 IgG was higher in patients who received mRNA-1273 than in those who received AZD1222 (β: 30.15, 95% CI: 11.67-48.63, p=0.002) (Table 1). Prednisolone-equivalent dose >5 mg/day and methotrexate (MTX) use in AIRD patients, and non-anti-tumor necrosis factor (TNF)-α biologics and Janus kinase (JAK) inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibody level, and enriched pathways related to antigen presentation via major histocompatibility complex class II (MHC class II) were found (Figure 1). HLA-DRA and CD4 interaction was vigorous among all identified MHC-II pathway and was enhanced in high anti-SARS-CoV2-IgG antibody group.Table 1.Multivariate analysis of anti-SARS-CoV-2 IgG level in patients with rheumatic diseases following COVID-19 vaccinesMultivariate analysisβ95% CIp valueMedicationsGlucocorticoidsNot usedReference≤5 mg/day−22.48(−56.33,11.37)0.192>5 mg/day−23.45(−43.54,-3.36)0.022Methotrexate−24.89(−45.70,-4.08)0.019Targeted therapiesTargeted therapies group Not usedReference TNF inhibitor−15.78(−41.33,9.76)0.224 Non-TNF bDMARD−25.27(−55.47,4.93)0.100 JAK inhibitor−17.08(−47.23,13.07)0.265VaccineChAdOx1 nCoV-19/AZD1222ReferencemRNA-127330.15(11.67,48.63)0.002TNF: tumor necrosis factor, bDMARDs: biologic disease-modifying antirheumatic drugs, JAK: Janus kinase.Figure 1.The comprehensive cell atlas of PBMC of RA patients with high and low anti-SARS-CoV2-IgG antibodies. A) UMAP visualization of PBMC cells from RA patients. B) The proportion of cell types between high and low antibody groups. C) Volcano plot of CD16-monocyte showed differential expressed genes. D) Pathway analysis between high and low antibody groups; PRBC: peripheral blood mononuclear cell, RA: rheumatoid arthritis, NK cell: natural killer cell, pDC: plasmacytoid dendritic cell, CLP: common lymphoid progenitor.ConclusionmRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in patients with AIRD. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.References[1]Geisen UM, Berner DK, Tran F, et al. Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort. Ann Rheum Dis. 2021;80:1306-1311.AcknowledgementsThe authors thank the Biostatistics Task Force of Taichung Veterans General Hospital for their assistance with the statistical analysis in this study.Disclosure of InterestsNone declared

BackgroundSystemic lupus erythematosus (SLE) is a chronic, autoimmune disease of an unknown etiology with a broad spectrum of organ manifestations, and patients with SLE have limited treatment options to NSAIDS, glucocorticoids, hydroxychloroquine and immunosuppressants. There is a lack of real-world evidence related to treatment patterns of SLE patients in Taiwan.ObjectivesTo describe the real-world patient demographics, clinical characteristics, and treatment patterns of patients with SLE in Taiwan.MethodsA retrospective observational study using Taiwan’s National Health Insurance Research Database (NHIRD) from 1/1/2014 to 12/31/2019 was undertaken. Patients holding catastrophic illness certificates for SLE in 2015-2017 were identified. Enrolled patients aged ≥ 18 years were then divided into three groups (mild, moderate, and severe) based on the highest severity patients experienced in the one year following the enrollment date using a published claims-based algorithm (Garris et al 2013) that incorporates the Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, British Isles Lupus Assessment Group Index and expert clinical opinion, and indexed upon the first date of entering the severity group. Baseline patient characteristics and treatment patterns during the follow-up period were measured. The types of treatment considered were NSAIDs, glucocorticoids, hydroxychloroquine and immunosuppressants.ResultsA total of 20,181 patients with catastrophic illness certificates for SLE were included in this study. The mean age of all SLE patients was 46.5 years and patients were mostly female (89.1%). The mean Charlson Comorbidity Index (CCI) score of all SLE patients was 1.5 (SD 1.3). Of these patients, 29.3% (n=5,918) had mild SLE activity, 60.7% (n=12,253) moderate and 10.0% (n=2,010) severe. During the one-year follow-up period, moderate to severe patients had numerically higher utilization rate of all types of treatment compared with mild patients (Table 1). Of all oral glucocorticoid users,27.8% of severe patients used high-dose glucocorticoids (> 15 mg/day) compared to Table 1.SLE treatment utilization during the 1-year follow-up periodTotal (n=20,181)`Mild (n=5,918)Moderate (n=12,253)Severe (n=2,010)n%n%n%n%NSAID7,21235.71,40523.74,98340.782441.0Glucocorticoid14,01969.52,01534.110,29784.01,70784.9Hydroxychloroquine13,27865.82,86748.58,97073.21,44171.7Immunosuppressant7,63037.800.06,31951.61,31165.2Methotrexate8984.500.07866.41125.6Azathioprine5,64228.000.04,84339.579939.8Leflunomide1320.700.01171.0150.8Cyclosporin8544.200.07155.81396.9Mycophenolate9594.800.07746.31859.2Cyclophosphamide7903.900.0170.177338.5ConclusionThe complexity and intensity of therapeutic approaches in SLE were associated with increased disease severity and patients were often resistant to treatment. These findings reflect the disease burden in SLE patients and suggest there is a substantial unmet need in the SLE treatment paradigm for moderate to severe SLE patients.References[1]Garris C, et al. J Med Econ. 2013;16:667–677.Disclosure of InterestsYu Sheng Chang: None declared, Wen-Nan Huang: None declared, Chao-Hsiun Tang: None declared, Khai Ng Shareholder of: I am a minor shareholder of Eli Lilly & Company, Employee of: I am an employee of Eli Lilly & Company, Po-Ya Chuang Consultant of: I am a paid consultant for Eli Lilly &Company, Wesley Furnback Consultant of: I am a paid consultant for Eli Lilly & Company, Bruce Wang Consultant of: I am a paid consultant for Eli Lilly & Company, Ching-Yun Wei Shareholder of: I am a minor shareholder of Eli Lilly & Company, Employee of: I am an employee of Eli Lilly & Company, Bradley Wang Shareholder of: I am a minor shareholder of Eli Lilly & Company, Employee of: I am an employee of Eli Lilly & Company, Tamas Treuer Shareholder of: I am a minor shareholder of Eli Lilly & Company, Employee of: I am an employee of Eli Lilly & Company

The aim of this study was to investigate the expression of long non-coding RNA (lncRNA)-ATB in laryngeal carcinoma (LNCa) and its relationship with the prognosis.The expression of lncRNA-ATB was examined in laryngeal carcinoma tissue specimens, as well as in normal ones by quantitative real-time polymerase chain reaction (qRT-PCR), and the interplay between lncRNA-ATB levels and clinical indicators was analyzed. In addition, the diagnostic value of lncRNA-ATB for LNCa was assessed by receiver operating characteristic (ROC) curve analysis. The patients were followed up for 5 years and the survival analysis was conducted by Kaplan-Meier test. Finally, the Cox regression model was used to analyze the factors affecting the prognosis of patients.LncRNA-ATB expression was markedly enhanced in laryngeal carcinoma tissue samples compared to the corresponding normal ones, which was relevant to T grade and clinical stage. For the diagnosis of laryngeal carcinoma using lncRNA-ATB, the area under the ROC curve (AUC) was 0.8672, the diagnostic threshold was 3.895, and the sensitivity and specificity were 83.02% and 76.42%, respectively. In addition, the overall survival rate of patients with high expression of lncRNA-ATB was markedly lower than those in low expression group. Meanwhile, T grade, clinical stage and lncRNA-ATB are found as three independent factors influencing the prognosis of LNCa.LncRNA-ATB was highly expressed in laryngeal carcinoma tissues, which was not conducive to the prognosis of patients. Therefore, this molecular marker has potential to become a new biomarker for the diagnosis and prognosis prediction of patients with LNCa.

We present a search for anisotropic cosmic birefringence in 500 deg$^2$ of southern sky observed at 150 GHz with the SPTpol camera on the South Pole Telescope. We reconstruct a map of cosmic polarization rotation anisotropies using higher-order correlations between the observed cosmic microwave background (CMB) $E$ and $B$ fields. We then measure the angular power spectrum of this map, which is found to be consistent with zero. The non-detection is translated into an upper limit on the amplitude of the scale-invariant cosmic rotation power spectrum, $L(L+1)C_L^{\alpha\alpha}/2\pi < 0.10 \times 10^{-4}$ rad$^2$ (0.033 deg$^2$, 95% C.L.). This upper limit can be used to place constraints on the strength of primordial magnetic fields, $B_{1 \rm Mpc} < 17 {\rm nG} $ (95% C.L.), and on the coupling constant of the Chern-Simons electromagnetic term $g_{a\gamma} < 4.0 \times 10^{-2}/H_I $ (95% C.L.), where $H_I$ is the inflationary Hubble scale. For the first time, we also cross-correlate the CMB temperature fluctuations with the reconstructed rotation angle map, a signal expected to be non-vanishing in certain theoretical scenarios, and find no detectable signal. We perform a suite of systematics and consistency checks and find no evidence for contamination., Comment: 17 pages, 7 figures - new subsection on non-Gaussian foregrounds, conclusions unchanged - updated to match published version on PRD

Background Recent data show survival after matched unrelated donor (MUD) bone marrow transplantation (BMT) is similar to matched sibling procedures for young patients with severe aplastic anemia (SAA). Donor delays, risk of transplant-related mortality (TRM), and concern about chronic graft versus host disease raise questions about whether MUD BMT or immune suppression therapy (IST) should be preferred initial therapy for young patients lacking matched sibling donors. Procedure We performed a pilot trial to assess the feasibility of randomizing patients under age 26 with newly diagnosed SAA to receive IST versus MUD BMT. Primary aims assessed the acceptability of randomization and timing of BMT. Secondary aims measured toxicities, response, and survival. Results Sixty-seven patients with possible SAA were screened at nine centers. Of 57 with confirmed SAA, 23 underwent randomization and received therapy with a median follow-up of 18 months. Of 12 randomized to BMT, 10 started BMT as initial therapy at a median of 36 days after randomization. One BMT recipient experienced secondary graft failure, requiring a second procedure. Six of 11 randomized to IST responded, whereas five with refractory disease underwent successful salvage BMT. One patient achieving complete response relapsed after discontinuation of immune suppression and died of infection after salvage BMT. Conclusions This feasibility study showed that a high percentage of patients underwent randomization and received up-front MUD BMT. Our study lays the groundwork for a larger randomized trial that will define best initial therapy for young patients with SAA who have an available MUD.

We report a B-mode power spectrum measurement from the cosmic microwave background (CMB) polarization anisotropy observations made using the SPTpol instrument on the South Pole Telescope. This work uses 500 deg$^2$ of SPTpol data, a five-fold increase over the last SPTpol B-mode release. As a result, the bandpower uncertainties have been reduced by more than a factor of two, and the measurement extends to lower multipoles: $52 < \ell < 2301$. Data from both 95 and 150 GHz are used, allowing for three cross-spectra: 95 GHz x 95 GHz, 95 GHz x 150 GHz, and 150 GHz x 150 GHz. B-mode power is detected at very high significance; we find $P(BB < 0) = 5.8 \times 10^{-71}$, corresponding to a $18.1 ��$ detection of power. An upper limit is set on the tensor-to-scalar ratio, $r < 0.44$ at 95% confidence (the expected $1 ��$ constraint on $r$ given the measurement uncertainties is 0.22). We find the measured B-mode power is consistent with the Planck best-fit $��$CDM model predictions. Scaling the predicted lensing B-mode power in this model by a factor Alens, the data prefer Alens = $1.17 \pm 0.13$. These data are currently the most precise measurements of B-mode power at $\ell > 320$., 16 pages, 4 figures, Submitted to PRD

Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome with predisposition to developing leukemia. We found that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations inEIF6orTP53.EIF6mutations cause functional compensation for the germline deficiency by alleviating the SDS ribosome joining defect, improving translation, and reducing p53 activation.TP53mutations decrease checkpoint activation without affecting ribosome assembly. We link development of leukemia with acquisition of biallelicTP53alterations. Our results define distinct pathways of clonal selection driven by germline fitness constraint and provide a mechanistic framework for clinical surveillance.

The camptothecin derivatives topoisomerase I (TOP1) inhibitors, irinotecan and topotecan, are FDA approved for the treatment of colorectal, ovarian, lung and breast cancers. Because of the chemical instability of camptothecins, short plasma half-life, drug efflux by the multidrug-resistance ABC transporters, and the severe diarrhea produced by irinotecan, indenoisoquinoline TOP1 inhibitors (LMP400, LMP776, and LMP744), which overcome these limitations, have been developed and are in clinical development. Further modifications of the indenoisoquinolines led to the fluoroindenoisoquinolines, one of which, LMP517, is the focus of this study. LMP517 showed better antitumor activity than its parent compound LMP744 against H82 (small cell lung cancer) xenografts. Genetic analyses in DT40 cells showed a dual TOP1 and TOP2 signature with selectivity of LMP517 for DNA repair-deficient tyrosyl DNA phosphodiesterase 2 (TDP2)- and Ku70-knockout cells. RADAR assays revealed that LMP517, and to a lesser extent LMP744, induce TOP2 cleavage complexes (TOP2cc) in addition to TOP1ccs. Histone γH2AX detection showed that, unlike classical TOP1 inhibitors, LMP517 targets cells independently of their position in the cell cycle. Our study establishes LMP517 as a dual TOP1 and TOP2 inhibitor with therapeutic potential.

To investigate the role of human serum albumin (hsa)_circular (circ)_0000711 in hepatocellular carcinoma (HCC). Circular ribonucleic acids (circRNAs) are proven in numerous studies to play crucial role in tumor biology, but their roles in HCC remain unknown to a great extent.The circRNA expression profile microarray was employed to screen differentially expressed circRNAs in tumor tissues and adjacent tissues from HCC patients, and Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) assay was performed for further verification. Next, the target micro RNAs (miRNAs) and their messenger RNAs (mRNAs) of key circRNAs were predicted by bioinformatics software, and a circRNA-miRNA-mRNA regulatory network was constructed. Subsequently, KEGG and GO enrichment analyses were applied to predict the possible biological processes regulated by hsa_circ_0000711 and relevant signaling pathways. The miRNAs playing a key role in the circRNA-miRNA-mRNA regulatory network were then selected as the objects, and their direct binding to hsa_circ_0000711 was confirmed via luciferase reporter gene assay. Thereafter, hsa_circ_0000711 was overexpressed or knocked out, and the biological function of hsa_circ_0000711 was detected by cell counting kit-8 (CCK-8) assay, apoptosis detection, and 5-Ethynyl-2'-deoxyuridine (EdU) staining assay in vitro.The results of expression profile screening revealed that there was a significant difference in the expression profile of circRNAs between tumor tissues and adjacent tissues in HCC patients. Based on the circRNA expression profile and RT-qPCR results, the expression level of hsa_circ_0000711 was overtly reduced in HCC tissues. In addition, miR-103a-3p had the highest eigenvector centrality in the circRNA-miRNA-mRNA regulatory network, suggesting that miR-103a-3p is a vital participant in the pathological mechanism of hsa_circ_0000711. The KEGG enrichment analysis results pointed out that the target genes regulated by hsa_circ_0000711 were clearly enriched in the tumor-associated signaling pathways. Besides, the results of GO enrichment analysis demonstrated that the biological processes regulated by hsa_circ_0000711 were mainly related to cell cycle regulation, so cell proliferation might be affected. The results of luciferase reporter gene and RT-qPCR assays showed that hsa_circ_0000711 directly bound to has-miR-103a-3p to serve as a molecular sponge. The results of CCK-8 and EdU staining assays revealed that the proliferation of hepatoma cells in hsa_circ_0000711 overexpression group was evidently enhanced. In addition, it was further found via flow cytometry that the apoptosis rate of cells was significantly raised in hsa_circ_0000711 low-expression group and dramatically declined in hsa_circ_0000711 overexpression group.Overexpression of hsa_circ_0000711 promoted the proliferation and inhibited the apoptosis of hepatoma cells via targeting has-miR-103a-3p.

New diesters derived from phthaloylglycine (7a-7i) were synthesized and their structures characterized by infrared, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. The compounds were evaluated in an in silico study, which demonstrated positive features indicating a possible drug candidate. The diesters showed antifungal activity ranging from moderate to strong against strains of Candida. Compounds 7a, 7b, 7c, 7e and 7i had a moderate minimum inhibitory concentration (MIC) of 1024 µg mL−1 against all fungal strains, while 7h showed a very good MIC of 256 µg mL−1 against Candida albicans, Candida parapsilosis and Candida krusei and 64 µg mL−1 against Candida tropicalis. However, only 7h and 7i were able to inhibit bacterial growth of strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Escherichia coli with an MIC of 1024 µg mL−1.

Cardiomyocyte (CM) proliferative potential varies considerably across species. While lower vertebrates and neonatal mammals retain robust capacities for CM proliferation, adult mammalian CMs lose proliferative potential due to cell-cycle withdrawal and polyploidization, failing to mount a proliferative response to regenerate lost CMs after cardiac injury. The decline of murine CM proliferative potential occurs in the neonatal period when the endocrine system undergoes drastic changes for adaptation to extrauterine life. We recently demonstrated that thyroid hormone (TH) signaling functions as a primary factor driving CM proliferative potential loss in vertebrates. Whether other hormonal pathways govern this process remains largely unexplored. Here we showed that agonists of glucocorticoid receptor (GR) and vitamin D receptor (VDR) suppressed neonatal CM proliferation. We next examined CM nucleation and proliferation in neonatal mutant mice lacking GR or VDR specifically in CMs, but we observed no difference between mutant and control littermates at postnatal day 14. Additionally, we generated compound mutant mice that lack GR or VDR and express dominant-negative TH receptor alpha in their CMs, and similarly observed no increase in CM proliferative potential compared to dominant-negative TH receptor alpha mice alone. Thus, although GR and VDR activation is sufficient to inhibit CM proliferation, they seem to be dispensable for neonatal CM cell-cycle exit and polyploidization in vivo. In addition, given the recent report that VDR activation in zebrafish promotes CM proliferation and tissue regeneration, our results suggest distinct roles of VDR in zebrafish and rodent CM cell-cycle regulation.

Background This study aimed to evaluate delta check limits set by reference change value (RCV) and patient data. Methods Patient data of 11 clinical chemistry analytes from June 2018 to May 2019 were collected. RCV with 95% or 99% levels of probability were calculated based on biological variation. The corresponding delta check limits for outpatients and inpatients were calculated by 95% or 99% central range of delta% which was the difference of two consecutive results within thirty days of the same patient for each analyte. Patient data in June 2019 were used to analyze the utility of delta check limits. Results In total, 434,927 paired results for these 11 analytes were included. The delta check limits were different between outpatients and inpatients, but were wider than those established by RCV. The difference between Glu's outpatient and inpatient boundaries was the largest, 95% central range from the outpatient (inpatients) was from -32.29% (-56.97%) to 38.78% (106.00%) while 99% central range from the outpatient (inpatients) was from -56.86% (-90.56%) to 89.96% (262.54%). The RCV is mainly determined by within-individual biological variation so that the RCV of each analyte varied from each other. As for RCV, Na had the lowest value and BUN had the highest one. In addition, the main reason for delta% exceeding delta check limits was a clinically significant change. Conclusions Laboratories could use delta check procedure to find out errors in sample collection and monitor clinical significance. When delta% of patients exceed corresponding delta check limits in a short time, clinicians and personnel of clinical laboratory should pay more attention. Delta check limits should be reviewed regularly to check the utility of procedure.

Full author list: L. E. Bleem, S. Bocquet, B. Stalder, M. D. Gladders, P. A. R. Ade, S. W. Allen, A. J. Anderson, J. Annis, M. L. N. Ashby, J. E. Austermann, S. Avila, J. S. Avva, M. Bayliss, J. A. Beall, K. Bechtol, A. N. Bender, B. A. Benson, E. Bertin, F. Bianchini, C. Blake, M. Brodwin, D. Brooks, E. Buckley-Geer, D. L. Burke, J. E. Carlstrom, A. Carnero Rosell, M. Carrasco Kind, J. Carretero, C. L. Chang, H. C. Chiang, R. Citron, C. Corbett Moran, M. Costanzi, T. M. Crawford, A. T. Crites, L. N. da Costa, T. de Haan, J. De Vicente, S. Desai, H. T. Diehl, J. P. Dietrich, M. A. Dobbs, T. F. Eifler, W. Everett, B. Flaugher, B. Floyd, J. Frieman, J. Gallicchio, J. García-Bellido, E. M. George, D. W. Gerdes, A. Gilbert, D. Gruen, R. A. Gruendl, J. Gschwend, N. Gupta, G. Gutierrez, N. W. Halverson, N. Harrington, J. W. Henning, C. Heymans, G. P. Holder, D. L. Hollowood, W. L. Holzapfel, K. Honscheid, J. D. Hrubes, N. Huang, J. Hubmayr, K. D. Irwin, D. J. James, T. Jeltema, S. Joudaki, G. Khullar, M. Klein, L. Knox, N. Kuropatkin, A. T. Lee, D. Li, C. Lidman, A. Lowitz, N. MacCrann, G. Mahler, M. A. G. Maia, J. L. Marshall, M. McDonald, J. J. McMahon, P. Melchior, F. Menanteau, S. S. Meyer, R. Miquel, L. M. Mocanu, J. J. Mohr, J. Montgomery, A. Nadolski, T. Natoli, J. P. Nibarger, G. Noble, V. Novosad, S. Padin, A. Palmese, D. Parkinson, S. Patil, F. Paz-Chinchón, A. A. Plazas, C. Pryke, N. S. Ramachandra, C. L. Reichardt, J. D. Remolina González, A. K. Romer, A. Roodman, J. E. Ruhl, E. S. Rykoff, B. R. Saliwanchik, E. Sanchez, A. Saro, J. T. Sayre, K. K. Schaffer, T. Schrabback, S. Serrano, K. Sharon, C. Sievers, G. Smecher, M. Smith, M. Soares-Santos, A. A. Stark, K. T. Story, E. Suchyta, G. Tarle, C. Tucker, K. Vanderlinde, T. Veach, J. D. Vieira, G. Wang, J. Weller, N. Whitehorn, W. L. K. Wu, V. Yefremenko, and Y. Zhang, We describe the observations and resultant galaxy cluster catalog from the 2770 deg2 SPTpol Extended Cluster Survey (SPT-ECS). Clusters are identified via the Sunyaev-Zel'dovich (SZ) effect and confirmed with a combination of archival and targeted follow-up data, making particular use of data from the Dark Energy Survey (DES). With incomplete follow-up we have confirmed as clusters 244 of 266 candidates at a detection significance ξ ≥ 5 and an additional 204 systems at 4 < ξ < 5. The confirmed sample has a median mass of M500c ~ 4.4 ¿ 1014 M☉ h70 -1 and a median redshift of z = 0.49, and we have identified 44 strong gravitational lenses in the sample thus far. Radio data are used to characterize contamination to the SZ signal; the median contamination for confirmed clusters is predicted to be ∼1% of the SZ signal at the ξ > 4 threshold, and 10% of their measured SZ flux. We associate SZ-selected clusters, from both SPT-ECS and the SPT-SZ survey, with clusters from the DES redMaPPer sample, and we find an offset distribution between the SZ center and central galaxy in general agreement with previous work, though with a larger fraction of clusters with significant offsets. Adopting a fixed Planck-like cosmology, we measure the optical richness-SZ mass (l - M) relation and find it to be 28% shallower than that from a weak-lensing analysis of the DES data-a difference significant at the 4σ level-with the relations intersecting at λ = 60. The SPT-ECS cluster sample will be particularly useful for studying the evolution of massive clusters and, in combination with DES lensing observations and the SPT-SZ cluster sample, will be an important component of future cosmological analyses., This work was performed in the context of the South Pole Telescope scientific program. SPT is supported by the National Science Foundation through grant PLR-1248097. Partial support is also provided by the NSF Physics Frontier Center grant PHY-0114422 to the Kavli Institute of Cosmological Physics at the University of Chicago, the Kavli Foundation, and the Gordon and Betty Moore Foundation grant GBMF 947 to the University of Chicago. This work is also supported by the U.S. Department of Energy. PISCO observations are supported by NSF AST-1814719. Work at Argonne National Lab is supported by UChicago Argonne LLC, operator of Argonne National Laboratory (Argonne). Argonne, a U.S. Department of Energy Office of Science Laboratory, is operated under contract No. DE-AC02- 06CH11357. We also acknowledge support from the Argonne Center for Nanoscale Materials. M.G. and L.B. acknowledge partial support from HST-GO-15307.001. B.B. is supported by the Fermi Research Alliance LLC under contract No. De-AC02- 07CH11359 with the U.S. Department of Energy. The CU Boulder group acknowledges support from NSF AST-0956135. The McGill authors acknowledge funding from the Natural Sciences and Engineering Research Council of Canada, Canadian Institute for Advanced Research, and the Fonds de Recherche du Québec Nature et technologies. The UCLA authors acknowledge support from NSF AST-1716965 and CSSI-1835865. The Stanford/SLAC group acknowledges support from the U.S. Department of Energy under contract No. DE-AC02-76SF00515. A.S. is supported by the ERC-StG “ClustersXCosmo” grant agreement 716762 and by the FARE-MIUR grant “ClustersXEuclid” R165SBKTMA. C.H. acknowledges support from the Max Planck Society and the Alexander von Humboldt Foundation, in the framework of the Max Planck-Humboldt Research Award endowed by the Federal Ministry of Education and Research, in addition to support from the European Research Council under grant No. 647112. S.J. acknowledges support from the Beecroft Trust and ERC 693024. T.S. acknowledges support from the German Federal Ministry of Economics and Technology (BMWi) provided through DLR under projects 50 OR 1610 and 50 OR 1803, as well as support from the Deutsche Forschungsgemeinschaft, DFG, under project SCHR 1400/3-1. The Melbourne authors acknowledge support from the Australian Research Council’s Discovery Projects scheme (DP150103208). The 2dFLenS survey is based on data acquired through the Australian Astronomical Observatory, under program A/2014B/008. This work is based in part on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under a contract with NASA. Funding for the DES Projects has been provided by the U.S. Department of Energy, the U.S. National Science Foundation, the Ministry of Science and Education of Spain, the Science and Technology Facilities Council of the United Kingdom, the Higher Education Funding Council for England, the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign, the Kavli Institute of Cosmological Physics at the University of Chicago, the Center for Cosmology and Astro-Particle Physics at The Ohio State University, the Mitchell Institute for Fundamental Physics and Astronomy at Texas A&M University, Financiadora de Estudos e Projetos, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico and the Ministério da Ciência, Tecnologia e Inovação, the Deutsche Forschungsgemeinschaft, and the Collaborating Institutions in the Dark Energy Survey. The Collaborating Institutions are Argonne National Laboratory, the University of California at Santa Cruz, the University of Cambridge, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas-Madrid, the University of Chicago, University College London, the DES-Brazil Consortium, the University of Edinburgh, the Eidgenössische Technische Hochschule (ETH) Zürich, Fermi National Accelerator Laboratory, the University of Illinois at UrbanaChampaign, the Institut de Ciències de l’Espai (IEEC/CSIC), the Institut de Física d’Altes Energies, Lawrence Berkeley National Laboratory, the Ludwig-Maximilians Universität München and the associated Excellence Cluster Universe, the University of Michigan, the National Optical Astronomy Observatory, the University of Nottingham, The Ohio State University, the University of Pennsylvania, the University of Portsmouth, SLAC National Accelerator Laboratory, Stanford University, the University of Sussex, Texas A&M University, and the OzDES Membership Consortium. Based in part on observations at Cerro Tololo InterAmerican Observatory, National Optical Astronomy Observatory, which is operated by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. The DES data management system is supported by the National Science Foundation under grant Nos. AST-1138766 and AST-1536171. The DES participants from Spanish institutions are partially supported by MINECO under grants AYA2015-71825, ESP2015-66861, FPA2015-68048, SEV2016-0588, SEV-2016-0597, and MDM-2015-0509, some of which include ERDF funds from the European Union. IFAE is partially funded by the CERCA program of the Generalitat de Catalunya. Research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP7/2007- 2013), including ERC grant agreements 240672, 291329, and 306478. We acknowledge support from the Brazilian Instituto Nacional de Ciência e Tecnologia (INCT) e-Universe (CNPq grant 465376/2014-2). This manuscript has been authored by Fermi Research Alliance, LLC, under contract No. DE-AC02-07CH11359 with the U.S. Department of Energy, Office of Science, Office of High Energy Physics. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Pan-STARRS1 Surveys (PS1) and the PS1 public science archive have been made possible through contributions by the Institute for Astronomy, the University of Hawaii, the Pan-STARRS Project Office, the Max-Planck Society and its participating institutes, the Max Planck Institute for Astronomy, Heidelberg and the Max Planck Institute for Extraterrestrial Physics, Garching, Johns Hopkins University, Durham University, the University of Edinburgh, the Queen’s University Belfast, the Harvard-Smithsonian Center for Astrophysics, the Las Cumbres Observatory Global Telescope Network Incorporated, the National Central University of Taiwan, the Space Telescope Science Institute, the National Aeronautics and Space Administration under grant No. NNX08AR22G issued through the Planetary Science Division of the NASA Science Mission Directorate, the National Science Foundation grant No. AST1238877, the University of Maryland, Eotvos Lorand University (ELTE), the Los Alamos National Laboratory, and the Gordon and Betty Moore Foundation

We present a constraint on the tensor-to-scalar ratio, $r$, derived from measurements of cosmic microwave background (CMB) polarization $B$-modes with "delensing," whereby the uncertainty on $r$ contributed by the sample variance of the gravitational lensing $B$-modes is reduced by cross-correlating against a lensing $B$-mode template. This template is constructed by combining an estimate of the polarized CMB with a tracer of the projected large-scale structure. The large-scale-structure tracer used is a map of the cosmic infrared background derived from Planck satellite data, while the polarized CMB map comes from a combination of South Pole Telescope, BICEP/Keck, and Planck data. We expand the BICEP/Keck likelihood analysis framework to accept a lensing template and apply it to the BICEP/Keck data set collected through 2014 using the same parametric foreground modelling as in the previous analysis. From simulations, we find that the uncertainty on $r$ is reduced by $\sim10\%$, from $��(r)$= 0.024 to 0.022, which can be compared with a $\sim26\%$ reduction obtained when using a perfect lensing template. Applying the technique to the real data, the constraint on $r$ is improved from $r_{0.05} < 0.090$ to $r_{0.05} < 0.082$ (95\% C.L.). This is the first demonstration of improvement in an $r$ constraint through delensing., 23 pages, 11 figures; match published version

We report new measurements of millimeter-wave power spectra in the angular multipole range $2000 \le \ell \le 11,000$ (angular scales $5^\prime \gtrsim \theta \gtrsim 1^\prime$). By adding 95 and 150\,GHz data from the low-noise 500 deg$^2$ SPTpol survey to the SPT-SZ three-frequency 2540 deg$^2$ survey, we substantially reduce the uncertainties in these bands. These power spectra include contributions from the primary cosmic microwave background, cosmic infrared background, radio galaxies, and thermal and kinematic Sunyaev-Zel'dovich (SZ) effects. The data favor a thermal SZ (tSZ) power at 143\,GHz of $D^{\rm tSZ}_{3000} = 3.42 \pm 0.54~ \mu {\rm K}^2$ and a kinematic SZ (kSZ) power of $D^{\rm kSZ}_{3000} = 3.0 \pm 1.0~ \mu {\rm K}^2$. This is the first measurement of kSZ power at $\ge 3\,\sigma$. We study the implications of the measured kSZ power for the epoch of reionization, finding the duration of reionization to be $\Delta z_{re} = 1.0^{+1.6}_{-0.7}$ ($\Delta z_{re}< 4.1$ at 95% confidence), when combined with our previously published tSZ bispectrum measurement., Comment: Submitted to ApJ, 16 pages. (revised portions of the introduction and description of bandpower estimation)

Additional file 9: Review History.

We present a catalog of galaxy cluster candidates detected in 100 square degrees surveyed with the SPTpol receiver on the South Pole Telescope. The catalog contains 89 candidates detected with a signal-to-noise ratio greater than 4.6. The candidates are selected using the Sunyaev-Zel'dovich effect at 95 and 150 GHz. Using both space- and ground-based optical and infrared telescopes, we have confirmed 81 candidates as galaxy clusters. We use these follow-up images and archival images to estimate photometric redshifts for 66 galaxy clusters and spectroscopic observations to obtain redshifts for 13 systems. An additional 2 galaxy clusters are confirmed using the overdensity of near-infrared galaxies only, and are presented without redshifts. We find that 15 candidates (18% of the total sample) are at redshift of $z \geq 1.0$, with a maximum confirmed redshift of $z_{\rm{max}} = 1.38 \pm 0.10$. We expect this catalog to contain every galaxy cluster with $M_{500c} > 2.6 \times 10^{14} M_\odot h^{-1}_{70}$ and $z > 0.25$ in the survey area. The mass threshold is approximately constant above $z = 0.25$, and the complete catalog has a median mass of approximately $ M_{500c} = 2.7 \times 10^{14} M_\odot h^{-1}_{70}$. Compared to previous SPT works, the increased depth of the millimeter-wave data (11.2 and 6.5 $��$K-arcmin at 95 and 150 GHz, respectively) makes it possible to find more galaxy clusters at high redshift and lower mass., 21 pages, 7 figures, associated data available at http://pole.uchicago.edu/public/data/sptsz-clusters. V2 was accepted to the AJ, and includes minor changes requested by the reviewer

Adult mammalian cardiomyocytes exit the cell cycle during the neonatal period, commensurate with the loss of regenerative capacity in adult mammalian hearts. We established conditions for long-term culture of adult mouse cardiomyocytes that are genetically labeled with fluorescence. This technique permits reliable analyses of proliferation of pre-existing cardiomyocytes without complications from cardiomyocyte marker expression loss due to dedifferentiation or significant contribution from cardiac progenitor cell expansion and differentiation in culture. Using this system, we took a candidate gene approach to screen for fetal-specific proliferative gene programs that can induce proliferation of adult mouse cardiomyocytes. Using pooled gene delivery and subtractive gene elimination, we identified a novel functional interaction between E2f Transcription Factor 2 (E2f2) and Brain Expressed X-Linked (Bex)/Transcription elongation factor A-like (Tceal) superfamily members Bex1 and Tceal8. Specifically, Bex1 and Tceal8 both preserved cell viability during E2f2-induced cell cycle re-entry. Although Tceal8 inhibited E2f2-induced S-phase re-entry, Bex1 facilitated DNA synthesis while inhibiting cell death. In sum, our study provides a valuable method for adult cardiomyocyte proliferation research and suggests that Bex family proteins may function in modulating cell proliferation and death decisions during cardiomyocyte development and maturation.

The South Pole Telescope SPT-3G camera utilizes Ti/Au transition edge sensors (TESs). A key requirement for these sensors is reproducibility and long-term stability of the superconducting (SC) transitions. Here, we discuss the impact of electrical contacts design and materials on the shape of the SC transitions. Using scanning electron microscope, atomic force microscope, and optical differential interference contrast microscopy, we observed the presence of unexpected defects of morphological nature on the titanium surface and their evolution in time in proximity to Nb contacts. We found direct correlation between the variations of the morphology and the SC transition shape. Experiments with different diffusion barriers between TES and Nb leads were performed to clarify the origin of this problem. We have demonstrated that the reproducibility of superconducting transitions can be significantly improved by preventing diffusion processes in the TES–leads contact areas.

The Artemis nuclease and tyrosyl-DNA phosphodiesterase (TDP1) are each capable of resolving protruding 3′-phosphoglycolate (PG) termini of DNA double-strand breaks (DSBs). Consequently, both a knockout of Artemis and a knockout/knockdown of TDP1 rendered cells sensitive to the radiomimetic agent neocarzinostatin (NCS), which induces 3′-PG-terminated DSBs. Unexpectedly, however, a knockdown or knockout of TDP1 in Artemis-null cells did not confer any greater sensitivity than either deficiency alone, indicating a strict epistasis between TDP1 and Artemis. Moreover, a deficiency in Artemis, but not TDP1, resulted in a fraction of unrepaired DSBs, which were assessed as 53BP1 foci. Conversely, a deficiency in TDP1, but not Artemis, resulted in a dramatic increase in dicentric chromosomes following NCS treatment. An inhibitor of DNA-dependent protein kinase, a key regulator of the classical nonhomologous end joining (C-NHEJ) pathway sensitized cells to NCS, but eliminated the sensitizing effects of both TDP1 and Artemis deficiencies. These results suggest that TDP1 and Artemis perform different functions in the repair of terminally blocked DSBs by the C-NHEJ pathway, and that whereas an Artemis deficiency prevents end joining of some DSBs, a TDP1 deficiency tends to promote DSB mis-joining.

A modified Biot/Squirt flow model was developed. The difference between MBISQ and BISQ models is the expression for the porosity differential. Numerical analysis shows that the acoustic dispersion predicted by MBISQ is much higher than by BISQ. Investigations of the effects of permeability, viscosity, and squirt flow length on velocity and attenuation indicate that the behavior of MBISQ agrees with that of the BISQ model. The result of sediment acoustic inversion based on MBISQ was more reasonable than the result of BISQ model.

Aim To evaluate Tmax, defined as the time of residual function R(t) reaching its maximum, as an indicator of myocardial ischaemia and compare its efficacy with other computed tomography perfusion (CTP) parameters. Materials and methods Eight Bama miniature pigs with 50–90% left anterior descending artery stenosis underwent adenosine stress myocardial CTP and 13N NH3 position-emission tomography (PET) perfusion imaging. Tmax, myocardial blood flow (MBF), myocardial blood volume (MBV), mean transit time (MTT), and time to peak (TTP) were calculated from CTP images. PET images were evaluated as ischaemia or non-ischaemia. Using PET as a reference standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. Multiple comparisons of the receiver operating characteristic (ROC) curves between Tmax and other parameters were performed. The diagnostic performance of the combination of each two parameters was calculated and compared with Tmax. Results Tmax was significantly higher in ischaemic segments compared with non-ischaemic segments. Multiple comparisons of the ROCs indicated that Tmax was better than MBF or TTP but not statistically different from MBV. Tmax was superior to the combination of (MBF + MBV) but not to (MBF + TTP) or (MBV + TTP). Conclusion Tmax in dynamic stress CTP provides good diagnostic accuracy for detecting myocardial ischaemia, especially in sensitivity and NPV, compared with PET method. Tmax has better performance than MBF or TTP or combination of (MBF + MBV) in diagnosing myocardial ischaemia.

In this work, we have measured the properties of membrane-suspended bolometer thermal links and microstrip transmission lines in the transition-edge sensor arrays for the third-generation camera for South Pole Telescope (SPT-3G). A promising technique for controlling the end point of the release etch that defines the thermal link has been developed. We have also evaluated the microstrip loss in our detectors by measuring the optical efficiency of detectors with different lengths of microstrip line. The loss tangent is sufficiently low for the use in multi-chronic pixels for cosmic microwave background instruments like SPT-3G.

Objectives To examine the effects of early comprehensive interventions on home environment and child neurodevelopment among children younger than 3 years in poor rural areas of China, as well as the underlying mediating and moderating mechanisms. Study design Non-randomized intervention study was conducted among 216 children aged 0–3 years in Shanxi province of China. Based on a 2 × 2 factor design, children in Lin and Fenxi County were assigned to an intervention group with duration less than 1 year (n = 26) or an intervention group with duration longer than 1 year (n = 82), while children in Fangshan County served as a control group with duration less than 1 year (n = 30) or a control group with duration longer than 1 year (n = 78). Methods The control group received national public health services (NPHS), while the intervention group received NPHS plus comprehensive interventions covering health, nutrition, early psychosocial stimulation, and child protection. Home environment (Infant-Toddler Home Observation for Measurement of the Environment [HOME]) and child neurodevelopment (Ages and Stages Questionnaire [ASQ]) were measured by observation and interview with mothers after the intervention program. Results The intervention group showed significantly higher overall HOME, organization, learning materials, and involvement than the control group, only for a duration longer than 1 year. Children in the intervention group performed better in overall ASQ, fine motor, problem-solving, and personal-social than children in the control group. Moderated mediation analyses indicated that there were significantly indirect effects of treatment on overall ASQ through overall HOME, organization, and involvement only when the duration was longer than 1 year. Conclusions Early comprehensive interventions longer than 1 year improve home environment and promote child neurodevelopment among children younger than 3 years in poor rural areas. What is more, effects of early comprehensive interventions longer than 1 year on child neurodevelopment were mediated by home environment.

The third-generation upgrade to the receiver on the South Pole Telescope, SPT-3G, was installed at the South Pole during the 2016–2017 austral summer to measure the polarization of the cosmic microwave background. Increasing the number of detectors by a factor of 10 to ∼16,000 \ud ∼16,000\ud required the multiplexing factor to increase to 68 and the bandwidth of the frequency-division readout electronics to span 1.6–5.2 MHz. This increase necessitates low-thermal conductance, low-inductance cryogenic wiring. Our cold readout system consists of planar thin-film aluminum inductive–capacitive resonators, wired in series with the detectors, summed together, and connected to 4K SQUIDs by 10−μm \ud 10−μm\ud -thick niobium–titanium (NbTi) broadside-coupled striplines. Here, we present an overview of the cold readout electronics for SPT-3G, including assembly details and characterization of electrical and thermal properties of the system. We report, for the NbTi striplines, values of R≤10 −4 Ω \ud R≤10−4Ω\ud , L=21±1 nH \ud L=21±1 nH\ud , and C=1.47±.02 nF \ud C=1.47±.02 nF\ud . Additionally, the striplines’ thermal conductivity is described by kA=6.0±0.3 T 0.92±0.04 μW mm K −1 \ud kA=6.0±0.3 T0.92±0.04 μW mm K−1\ud . Finally, we provide projections for cross talk induced by parasitic impedances from the stripline and find that the median value of percentage cross talk from leakage current is 0.22 and 0.09% \ud 0.09%\ud from wiring impedance.

The South Pole Telescope third-generation (SPT-3G) receiver was installed during the austral summer of 2016–2017. It is designed to measure the cosmic microwave background across three frequency bands centered at 95, 150, and 220 GHz. The SPT-3G receiver has ten focal plane modules, each with 269 pixels. Each pixel features a broadband sinuous antenna coupled to a niobium microstrip transmission line. In-line filters define the desired band-passes before the signal is coupled to six bolometers with Ti/Au/Ti/Au transition edge sensors (three bands × \ud ×\ud two polarizations). In total, the SPT-3G receiver is composed of 16,000 detectors, which are read out using a 68× \ud ×\ud frequency-domain multiplexing scheme. In this paper, we present the process employed in fabricating the detector arrays.

Past studies have provided extensive documentation of changes in species diversity in response to land-cover alteration; however, little is known about the effects of land-cover alteration on the patterns of functional structures and ecosystem functions. In this study, we introduce a functional trait-based methodology for incorporating multiple levels of functional structures into models to assess the impacts of human-induced land-cover changes on functional structures and to evaluate how these functional attributes affect ecosystem functions. To this purpose, different functional structure indices (species diversity, functional diversity, and community-weighted mean trait values) in three widespread communities (a man-made Pinus yunnanensis forest, a man-made Eucalyptus smithii forest, and a natural secondary forest) were determined, with a focus on our study sites in southwest China. Meanwhile, ecosystem functions (soil nutrients, water and soil conservation, and multifunctionality) were quantified. Our results showed that most community diversity indices were affected by human-dominated land-cover changes, except species richness and functional evenness. Changes in the relationship between species diversity and functional diversity displayed two patterns. The first pattern reflected reduced species diversity with an increase in functional diversity, whereas the second pattern was associated with a correlated loss of species and functional diversity, indicating the removal of environmental filters in response to changes from natural secondary forest to man-made forests. Community-weighted mean trait values (related to leaf nitrogen [N] concentration, leaf phosphorus [P] concentration, and seed mass) were negatively correlated with water and soil conservation and multifunctionality, which accounted for 65.9% and 48.5% of the variance, respectively. Functional diversity (based on functional richness, quadratic entropy, and functional dispersion) was positively associated with soil nutrients and explained 33.6% of the variance. These results suggest that the community functional structure was affected by land-cover alteration through changes in environmental filters and replacement by functionally different species. Moreover, changes in functional structure characteristics mediate different ecosystem functions by niche complementarity or the mass ratio effect under land-cover alteration.

Efficient bifunctional electrocatalysts for reversible oxygen electrodes are vitally important for the realization of important future generation electrochemical energy conversion devices, such as regenerative fuel cells and rechargeable metal–air batteries. Importantly, the electrocatalysts need not only be efficient but also inexpensive and source-abundant from the viewpoint of sustainability. Herein, we report active and stable bifunctional catalysts for oxygen electrodes obtained by pyrolysis of pristine coal in ammonia. The pyrolysis yielded nitrogen-rich mesoporous graphitic carbon containing pyrrolic, pyridinic and graphitic groups, which demonstrated very good electrocatalysis of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) in 0.1 M NaOH. The optimized catalyst afforded a stable round-trip overvoltage of 0.97 V when cycling between the ORR at a current density of −1.0 mA cm−2 and the OER at 10 mA cm−2, lower than those of RuO2 and IrO2 in the same solution, thus unveiling a unique opportunity to directly transform coal into a valuable catalyst without costly processing.

We examined national trends in the receipt of specialty outpatient mental health care, using data for 2008-15 from the National Survey on Drug Use and Health. Between 2008-09 and 2014-15 the number of US adults who received outpatient mental health care in the specialty sector rose from 11.3 million to 13.7 million per year, representing an increase from 5.0 percent to 5.7 percent of the adult population. Among those recipients, however, the annual weighted mean number of visits to the specialty sector remained unchanged. We found increases in both numbers and percentages of adults who received care within the specialty sector across age and sex groups and among non-Hispanic whites, people with Medicare, people with private health insurance, and people with family incomes of $20,000-$49,999. Increases in receipt of specialty mental health care during 2012-15 may be related to recent policy initiatives aimed at reducing financial barriers to care.