Massive End-to-end Models for Short Search Queries

In this work, we investigate two popular end-to-end automatic speech recognition (ASR) models, namely Connectionist Temporal Classification (CTC) and RNN-Transducer (RNN-T), for offline recognition of voice search queries, with up to 2B model parameters. The encoders of our models use the neural architecture of Google's universal speech model (USM), with additional funnel pooling layers to significantly reduce the frame rate and speed up training and inference. We perform extensive studies on vocabulary size, time reduction strategy, and its generalization performance on long-form test sets. Despite the speculation that, as the model size increases, CTC can be as good as RNN-T which builds label dependency into the prediction, we observe that a 900M RNN-T clearly outperforms a 1.8B CTC and is more tolerant to severe time reduction, although the WER gap can be largely removed by LM shallow fusion

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Antibodies against AT1 receptors are associated with vascular endothelial and smooth muscle function impairment: protective effects of hydroxysafflor yellow A.

Ample evidence has shown that autoantibodies against AT1 receptors (AT1-AA) are closely associated with human cardiovascular disease. The aim of this study was to investigate mechanisms underlying AT1-AA-induced vascular structural and functional impairments in the formation of hypertension, and explore ways for preventive treatment. We used synthetic peptide corresponding to the sequence of the second extracellular loop of the AT1 receptor (165-191) to immunize rats and establish an active immunization model. Part of the model received preventive therapy by losartan (20 mg/kg/day) and hyroxysafflor yellow A (HSYA) (10 mg/kg/day). The result show that systolic blood pressure (SBP) and heart rate (HR) of immunized rats was significantly higher, and closely correlated with the plasma AT1-Ab titer. The systolic response of thoracic aortic was increased, but diastolic effects were attenuated markedly. Histological observation showed that the thoracic aortic endothelium of the immunized rats became thinner or ruptured, inflammatory cell infiltration, medial smooth muscle cell proliferation and migration, the vascular wall became thicker. There was no significant difference in serum antibody titer between losartan and HSYA groups and the immunized group. The vascular structure and function were reversed, and plasma biochemical parameters were also improved significantly in the two treatment groups. These results suggest that AT1-Ab could induce injury to vascular endothelial cells, and proliferation of smooth muscle cells. These changes were involved in the formation of hypertension. Treatment with AT1 receptor antagonists and anti oxidative therapy could block the pathogenic effect of AT1-Ab on vascular endothelial and smooth muscle cells

Maternal and perinatal risks for monozygotic twins conceived following frozen-thawed embryo transfer: a retrospective cohort study

Abstract Background The present study aimed to explore the maternal and perinatal risks in cases of monozygotic twins (MZT) following frozen-thawed embryo transfer (FET). Methods All twin births that were conceived following FET from 2007 to 2021 at Shanghai Ninth People’s Hospital in Shanghai, China were retrospectively reviewed. The exposure variable was twin type (monozygotic and dizygotic). The primary outcome was the incidence of neonatal death while secondary outcomes included hypertensive disorders of pregnancy, gestational diabetes, intrahepatic cholestasis of pregnancy, placenta previa, placental abruption, preterm premature rupture of the membranes, Cesarean delivery, gestational age, birth weight, weight discordance, stillbirth, birth defects, pneumonia, respiratory distress syndrome, necrotizing enterocolitis, and neonatal jaundice. Analysis of the outcomes was performed using logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The causal mediation analysis was conducted. A doubly robust estimation model was used to validate the results. Kaplan-Meier method was used to calculate survival probability. The sensitivity analysis was performed with a propensity score-based patient-matching model. Results Of 6101 dizygotic twin (DZT) and 164 MZT births conceived by FET, MZT showed an increased risk of neonatal death based on the multivariate logistic regression models (partially adjusted OR: 4.19; 95% CI, 1.23–10.8; fully adjusted OR: 4.95; 95% CI, 1.41–13.2). Similar results were obtained with the doubly robust estimation. Comparing MZT with DZT, the neonatal survival probability was lower for MZT (P < 0.05). The results were robust in the sensitivity analysis. Females with MZT pregnancies exhibited an elevated risk of preterm premature rupture of the membranes (adjusted OR: 2.42; 95% CI, 1.54–3.70). MZT were also associated with higher odds of preterm birth (prior to 37 weeks) (adjusted OR: 2.31; 95% CI, 1.48–3.67), low birth weight (adjusted OR: 1.92; 95% CI, 1.27–2.93), and small for gestational age (adjusted OR: 2.18; 95% CI, 1.21–3.69) in the fully adjusted analyses. The effect of MZT on neonatal death was partially mediated by preterm birth and low birth weight (P < 0.05). Conclusions This study indicates that MZT conceived by FET are related to an increased risk of neonatal death, emphasizing a potential need for comprehensive antenatal surveillance in these at-risk pregnancies

Differences in Ectopic Pregnancy Rates between Fresh and Frozen Embryo Transfer after In Vitro Fertilization: A Large Retrospective Study

Ectopic pregnancy (EP) is increasingly found in women treated with in vitro fertilization and embryo transfer (IVF&ndash;ET). With the development of the freeze-all policy in reproductive medicine, it is controversial whether frozen embryo transfer (FET) could reduce the rate of EP. In this single-center, large-sample retrospective study, we analyzed 16,048 human chorionic gonadotrophin (hCG)-positive patients who underwent fresh embryo transfer (ET) or FET cycles between January 2013 and March 2022. Throughout the study, the total EP rate was 2.09% (336/16,048), 2.16% (82/3803) in the ET group, and 2.07% (254/12,245) in the FET group. After adjustment for age, infertility causes, and other confounding factors, logistic regression results showed no statistical difference in EP rates between FET and ET groups (odds ratio (OR) 0.93 (0.71&ndash;1.22), p &gt; 0.05). However, among the 3808 patients who underwent fresh ET cycles, the OR for EP was significantly lower in the long agonist protocol group than in the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol group (OR 0.45 (0.22&ndash;0.93), p &lt; 0.05). Through a large retrospective study, we demonstrated a slightly lower EP rate in FET cycles than in fresh ET cycles, but there was no significant difference. The long agonist protocol in ET cycles had a significantly lower risk of EP than the GnRH-ant protocol

SNP-induced vascular relaxation of the aortic ring with intact endothelium.

<p>The aortic ring isolated from the experimental animals was pre-contracted with 10⁻⁶ M PE, and vascular relaxation in response to SNP was measured. The concentration-response curves to SNP, fitted with Scott equation, in each group are shown (A). Calculated E_max and PD₂ of the concentration-response curves to SNP are shown (B). Data are expressed as the mean ± SD (n≥6). *P<0.05; **P<0.01 <i>vs</i>. control group; ^#p<0.05 <i>vs.</i> immunized group.</p

Transmission electron microscopy.

<p>Representative views of the thoracic aorta from from different treatment groups. Control group (A), the delicate structure of the intima contains endothelial cells sitting on a basal lamina and internal elastic lamina. Immunization group (B), the intima is thickened. The endothelial cells (end) are heterogeneous, most of them enlarged with convoluted nuclear and cytoplasmic contours. Focal accumulation of mononuclear cells could be detected in the expanded intimal layer. Immunization+losartan group (C) and immunization+HSYA group (D), the ultrastructural changes are qualitatively similar to those found in the immunized rats, although less pronounced, and the tunica intima layer is expanded. The endothelial cells are heterogeneous, most of them enlarged with tortuous nuclear and cytoplasmic contours. Original magnifications 4200.</p

Change in systolic blood pressure (A) and heart rate (B), and antibody titer (C) in different rat groups Data are expressed as the mean ± SD (n≥6). *P<0.05; **P<0.01 <i>vs</i>. control group; ^#p<0.05 <i>vs</i>. immunized group.

<p>Change in systolic blood pressure (A) and heart rate (B), and antibody titer (C) in different rat groups Data are expressed as the mean ± SD (n≥6). *P<0.05; **P<0.01 <i>vs</i>. control group; ^#p<0.05 <i>vs</i>. immunized group.</p

High resolution light microscopy.

<p>Representative histological images of the thoracic aorta from control group (A), immunization group (B), immunization+losartan group (C) and immunization+HSYA group (D). There was no significant histological abnormality in control group. In the immunized segment, the aortic intima was thickened, the nuclei of medial smooth muscle cells were densely populated, deeply stained and enlarged; cells were deranged; the number of smooth muscle cell layers between the elastic plates was apparently increased, contrasting with the delicate structure of the intima in control group. Compared with the immunized group, the thickness of the intima and the number of smooth muscle layers in immunized losartan group and HSYA group were decreased; and the medial collagen fibers were arranged regularly. Original magnifications, 200 (A–D).</p

ACh-induced vascular relaxation of the aortic ring with intact endothelium.

<p>The aortic ring isolated from the experimental animals was pre-contracted with 10⁻⁶ M PE, and vascular relaxation in response to ACh was measured. The concentration-response curves to ACh, fitted with Scott equation, in each group are shown (A). Calculated E_max and PD₂ of the concentration-response curves to ACh are shown (B). Data are expressed as the mean ± SD (n≥6). *P<0.05; **P<0.01 <i>vs</i>. control group; ^#p<0.05 <i>vs.</i> immunized group.</p