Analysis of adaptive molecular mechanisms in response to low salinity in antennal gland of mud crab, Scylla paramamosain.

As an important marine aquaculture species, the mud crab (Scylla paramamosain) is a good candidate for studying the osmoregulatory mechanism of crustaceans. While previous studies have focused on the osmoregulatory function of the gills, this study aims to explore the osmoregulatory function of the antennal glands. By the comparative transcriptomic analysis, we found the pathways of ion regulation including "proximal tubule bicarbonate reclamation" and "mineral absorption" were activated in the antennal glands of the crabs long-term dwelling in low salinity. The enhanced ionic reabsorption was associated with up-regulated ion transport genes such as NKA, CA-c, VPA, and NHE, and with energy metabolism genes such as MDH, SLC25, and PEPCK. The upregulation of NKA and CA-c was also verified by the increased enzyme activity. The lowered osmolality and ion concentration of the hemolymph and the enlarged labyrinth lumen and hemolymph capillary inside the antennal glands indicated the infiltration of external water and the responsively increase of urine excretion, which explained the requirement of enhanced ionic reabsorption. To further confirm these findings, we examined the change of gene expression, enzyme activity, internal ion concentration, and external ion concentration during a 96 h low salinity challenge with seven intervals. The results were basically consistent with the results as shown in the long-term low salinity adaptation. The present study provides valuable information on the osmoregulatory function of the antennal glands of S. paramamosain. The implication of this study in marine aquaculture is that it provides valuable information on the osmoregulatory mechanism of mud crabs, which can be used to improve their culture conditions and enhance their tolerance to salinity stress. The identified genes and pathways involved in osmoregulation can also be potential targets for genetic selection and breeding programs to develop more resilient mud crab strains for aquaculture.

Mechanisms by which sheep milk consumption ameliorates insulin resistance in high-fat diet-fed mice.

Sheep milk is rich in fat, protein, vitamins and minerals and is also one of the most important sources of natural bioactives. Several biopeptides in sheep milk have been reported to possess antibacterial, antiviral and anti-inflammatory properties, and they may prevent type 2 diabetes (T2D), disease and cancer. However, the precise mechanism(s) underlying the protective role of sheep milk against T2D development remains unclear. Therefore, in the current study, we investigated the effect of sheep milk on insulin resistance and glucose intolerance in high-fat diet (HFD)-fed mice, by conducting intraperitoneal glucose tolerance tests, metabolic cage studies, genomic sequencing, polymerase chain reaction, and biochemical assays. Hyperinsulinemic-euglycemic clamp-based experiments revealed that mice consuming sheep milk exhibited lower hepatic glucose production than mice in the control group. These findings further elucidate the mechanism by which dietary supplementation with sheep milk alleviates HFD-induced systemic glucose intolerance.

Eriocheir sinensis feminization-1c (Fem-1c) and Its Predicted miRNAs Involved in Sexual Development and Regulation.

Feminization-1c (Fem-1c) is important for sex differentiation in the model organism Caenorhabditis elegans. In our previous study, the basic molecular characteristics of the Fem-1c gene (EsFem-1c) in Eriocheir sinensis (Henri Milne Edwards, 1854) were cloned to determine the relationship with sex differentiation. In this study, the genomic sequence of EsFem-1c contained five exons and four introns, with an exceptionally long 3'UTR sequence. The qRT-PCR results of EsFem-1c demonstrated lower tissue expression in the androgenic gland of the intersex crab than the normal male crab, implying that EsFem-1c plays a role in crab AG development. RNA interference experiments and morphological observations of juvenile and mature crabs indicated that EsFem-1c influences sexual development in E. sinensis. A dual-luciferase reporter assay disclosed that tcf-miR-315-5p effectively inhibits the translation of the EsFem-1c gene, influencing male development. An intriguing finding was that miRNA tcf-miR-307 could increase EsFem-1c expression by binding to the alternative splicing region with a length of 248 bp (ASR-248) in the 3'UTR sequence. The present research contributes to a better understanding of the molecular regulation mechanism of EsFem-1c and provides a resource for future studies of the miRNA-mediated regulation of sexual development and regulation in E. sinensis.

Defect Detection in Steel Using a Hybrid Attention Network.

Defect detection in steel surface focuses on accurately identifying and precisely locating defects on the surface of steel materials. Methods of defect detection with deep learning have gained significant attention in research. Existing algorithms can achieve satisfactory results, but the accuracy of defect detection still needs to be improved. Aiming at this issue, a hybrid attention network is proposed in this paper. Firstly, a CBAM attention module is used to enhance the model's ability to learn effective features. Secondly, an adaptively spatial feature fusion (ASFF) module is used to improve the accuracy by extracting multi-scale information of defects. Finally, the CIOU algorithm is introduced to optimize the training loss of the baseline model. The experimental results show that the performance of our method in this work is superior on the NEU-DET dataset, with an 8.34% improvement in mAP. Compared with major algorithms of object detection such as SSD, EfficientNet, YOLOV3, and YOLOV5, the mAP was improved by 16.36%, 41.68%, 20.79%, and 13.96%, respectively. This demonstrates that the mAP of our proposed method is higher than other major algorithms.

First-in-Human Gene Therapy Trial of AAV8-hCARp.hCNGB3 in Adults and Children With CNGB3-associated Achromatopsia.

PURPOSE: To assess the safety and efficacy of AAV8-hCARp.hCNGB3 in participants with CNGB3-associated achromatopsia (ACHM). DESIGN: Prospective, phase 1/2 (NCT03001310), open-label, nonrandomized clinical trial. METHODS: The study enrolled 23 adults and children with CNGB3-associated ACHM. In the dose-escalation phase, adult participants were administered 1 of 3 AAV8-hCARp.hCNGB3 dose levels in the worse-seeing eye (up to 0.5 mL). After a maximum tolerated dose was established in adults, an expansion phase was conducted in children ≥3 years old. All participants received topical and oral corticosteroids. Safety and efficacy parameters, including treatment-related adverse events and visual acuity, retinal sensitivity, color vision, and light sensitivity, were assessed for 6 months. RESULTS: AAV8-hCARp.hCNGB3 (11 adults, 12 children) was safe and generally well tolerated. Intraocular inflammation occurred in 9 of 23 participants and was mainly mild or moderate in severity. Severe cases occurred primarily at the highest dose. Two events were considered serious and dose limiting. All intraocular inflammation resolved following topical and systemic steroids. There was no consistent pattern of change from baseline to week 24 for any efficacy assessment. However, favorable changes were observed for individual participants across several assessments, including color vision (n = 6/23), photoaversion (n = 11/20), and vision-related quality-of-life questionnaires (n = 21/23). CONCLUSIONS: AAV8-hCARp.hCNGB3 for CNGB3-associated ACHM demonstrated an acceptable safety and tolerability profile. Improvements in several efficacy parameters indicate that AAV8-hCARp.hCNGB3 gene therapy may provide benefit. These findings, with the development of additional sensitive and quantitative end points, support continued investigation.

New insights for the regulatory feedback loop between type 1 crustacean female sex hormone (CFSH-1) and insulin-like androgenic gland hormone (IAG) in the Chinese mitten crab (Eriocheir sinensis).

To clarify the hormone control on sex determination and differentiation, we studied the Chinese mitten crab, Eriocheir sinensis (Henri Milne Edwards, 1854), a species with importantly economic and ecological significance. The crustacean female sex hormone (CFSH) and the insulin-like androgenic gland hormone (IAG) have been found to be related to the sex determination and/or differentiation. CFSH-1 of E. sinensis (EsCFSH-1) encoded a 227 amino-acid protein including a signal peptide, a CFSH-precursor-related peptide, and a mature CFSH peptide. Normally, EsCFSH-1 was highly expressed in the eyestalk ganglion of adult female crabs, while the expression was declined in the intersex crabs (genetic females). The intersex crabs had the androgenic glands, and the expression level of EsIAG was close to that of male crabs. During the embryogenesis and larval development, the changes of EsCFSH-1 and EsIAG genes expression in male and female individuals were shown after the zoea IV stage. Next, we confirmed the existence of the regulatory feedback loop between EsCFSH-1 and EsIAG by RNA interference experiment. The feminization function of EsCFSH-1 was further verified by examining the morphological change of external reproductive organs after EsCFSH-1 knockdown. The findings of this study reveal that the regulatory interplay between CFSH and IAG might play a pivotal role in the process of sex determination and/or differentiation in decapod crustaceans.

Benefit-Risk Assessment of Rivaroxaban for Extended Thromboprophylaxis After Hospitalization for Medical Illness.

Background Venous thromboembolism (VTE) often occurs after hospitalization in medically ill patients, but the population benefit-risk of extended thromboprophylaxis remains uncertain. Methods and Results The MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk) study (NCT02111564) was a randomized double-blind trial that compared thromboprophylaxis with rivaroxaban 10 mg daily versus placebo for 45 days after hospital discharge in medically ill patients with a creatinine clearance ≥50 mL/min. The benefit-risk balance in this population was quantified by calculating the between-treatment rate differences in efficacy and safety end points per 10 000 patients treated. Clinical characteristics of the study population were consistent with a hospitalized medical population at risk for VTE. Treating 10 000 patients with rivaroxaban resulted in 32.5 fewer symptomatic VTE and VTE-related deaths but was associated with 8 additional major bleeding events. The treatment benefit was driven by the prevention of nonfatal symptomatic VTE (26 fewer events). There was no between-treatment difference in the composite of critical site or fatal bleeding. Conclusions Extending thromboprophylaxis with rivaroxaban for 45 days after hospitalization provides a positive benefit-risk balance in medically ill patients at risk for VTE who are not at high risk for bleeding. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT02111564.

Extended Thromboprophylaxis in Hospitalized Patients with Heart Failure: A Post Hoc Analysis of the MAGELLAN Study.

This post hoc subgroup analysis examined efficacy and safety outcomes with extended thromboprophylaxis rivaroxaban compared with in-hospital enoxaparin in 2,078 patients from the MAGELLAN study who had a hospitalization for heart failure or a history of heart failure and a lower risk of bleeding. A significant 36% reduction in the composite endpoint of asymptomatic proximal deep vein thrombosis (DVT) in the lower extremity, symptomatic DVT in the lower extremity (proximal or distal), symptomatic nonfatal pulmonary embolism, and venous thromboembolism-related death was observed with rivaroxaban. Major bleeding was low in both groups and not significantly increased with rivaroxaban.

Rivaroxaban Plus Aspirin for Extended Thromboprophylaxis in Acutely Ill Medical Patients: Insights from the MARINER Trial.

Background The MARINER trial evaluated whether postdischarge thromboprophylaxis with rivaroxaban could reduce the primary outcome of symptomatic venous thromboembolism (VTE) or VTE-related death in acutely ill medical patients at risk for VTE. Although aspirin use was not randomized, approximately half of the enrolled patients were receiving aspirin at baseline. We hypothesized that thromboprophylaxis with once-daily rivaroxaban (10 mg or, if creatinine clearance was 30-49 mL/min, 7.5 mg) plus aspirin (R/A) would be superior to placebo without aspirin (no thromboprophylaxis [no TP]). Methods We compared the primary and major secondary outcomes in the intention-to-treat population in four subgroups defined at baseline: (1) R/A ( N = 3,159); (2) rivaroxaban alone ( N = 2,848); (3) aspirin alone ( N = 3,046); and (4) no TP ( N = 2,966). Major bleeding (MB) and nonmajor clinically relevant (NMCR) bleeding were assessed in the safety population on treatment plus 2 days. Results Patients on R/A had reduced symptomatic VTE and VTE-related death compared with no TP (0.76 vs 1.28%, p = 0.042), and experienced less symptomatic VTE and all-cause mortality ( p = 0.005) and all-cause mortality alone ( p = 0.01) compared with no TP. Event incidences for rivaroxaban alone (0.91%) or aspirin alone (0.92%) were similar. MB was low in all groups but lowest in the no TP group. NMCR bleeding was increased with R/A compared with no TP ( p = 0.009). Limitations Aspirin use was not randomized. Conclusion Extended postdischarge thromboprophylaxis with R/A was associated with less symptomatic VTE and VTE-related death compared with no TP in previously hospitalized medical patients at risk for VTE. NMCR bleeding was increased with R/A compared with no TP. These post hoc findings need confirmation in a prospective trial.

Association of Bleeding Severity With Mortality in Extended Thromboprophylaxis of Medically Ill Patients in the MAGELLAN and MARINER Trials.

BACKGROUND: Extended thromboprophylaxis has not been widely implemented in acutely ill medical patients because of bleeding concerns. The MAGELLAN (Multicenter, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Medically Ill Patients Comparing Rivaroxaban With Enoxaparin) and MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk) trials evaluated whether rivaroxaban compared with enoxaparin or placebo could prevent venous thromboembolism without increased bleeding. We hypothesized that patients with major bleeding but not those with nonmajor clinically relevant bleeding would be at an increased risk of all-cause mortality (ACM). METHODS: We evaluated all bleeding events in patients taking at least 1 dose of study drug and their association with ACM in 4 mutually exclusive groups: (1) no bleeding, or first event was (2) nonmajor clinically relevant bleeding, (3) major bleeding, or (4) trivial bleeding. Using a Cox proportional hazards model adjusted for differences in baseline characteristics associated with ACM, we assessed the risk of ACM after such events. RESULTS: Compared with patients with no bleeding, the risk of ACM for patients with nonmajor clinically relevant bleeding was not increased in MARINER (hazard ratio, 0.43; P=0.235) but was increased in MAGELLAN (hazard ratio, 1.74; P=0.021). Major bleeding was associated with a higher incidence of ACM in both studies, whereas trivial bleeding was not associated with ACM in either study. CONCLUSIONS: Patients with major bleeding had an increased risk of ACM, whereas nonmajor clinically relevant bleeding was not consistently associated with an increased risk of death. These results inform the risk-benefit calculus of extended thromboprophylaxis in medically ill patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: MAGELLAN, NCT00571649. URL: https://www. CLINICALTRIALS: gov; Unique identifier: MARINER, NCT02111564.

Risk of Severe Bleeding With Extended Rivaroxaban to Prevent Venous Thromboembolism in Acute Medically Ill Patients With Bronchiectasis.

Background: Bronchiectasis is a chronic inflammation of the bronchi with recurrent infections and hemoptysis. The MAGELLAN study compared oral rivaroxaban, 10 mg once daily (QD), for 35 ± 4 days with subcutaneous enoxaparin 40 mg QD for 10 ± 4 days followed by placebo for 25 ± 4 days to prevent venous thromboembolism in patients hospitalized with an acute medical illness. MAGELLAN included a subset of patients with bronchiectasis. In a post hoc analysis, we evaluated the incidence and severity of pulmonary bleeding in patients with bronchiectasis who were hospitalized for an acute medical illness. This analysis included MAGELLAN patients diagnosed with bronchiectasis at baseline. Patients were evaluated by treatment group for International Society on Thrombosis and Haemostasis major bleeding, non-major clinically relevant (NMCR) bleeding, and the composite of the 2 (ie, clinically relevant bleeding). Results: Medically ill patients with bronchiectasis were randomized to rivaroxaban (n = 60) or enoxaparin/placebo (n = 61). There were 2 fatal pulmonary bleeds and 1 fatal gastrointestinal bleed in the rivaroxaban arm and no fatal or major bleeding in the enoxaparin/placebo arm. The incidence of major bleeding was 5% in the rivaroxaban arm. One NMCR bleed occurred in the rivaroxaban arm and 2 NMCR bleeds occurred in the enoxaparin/placebo arm. The incidence of clinically relevant bleeding was 6.7% versus 3.3% in the rivaroxaban and enoxaparin/placebo groups, respectively (relative risk = 2.06 [95% confidence interval: 0.351-12.046]). Conclusion: In-patients hospitalized with bronchiectasis and an acute medical illness, clinically relevant bleeding, including fatal pulmonary hemorrhage, occurs more frequently with extended rivaroxaban thromboprophylaxis than with enoxaparin followed by placebo.

Investigation and analysis on an outbreak of norovirus infection in a health school in Guangdong Province, China.

Our objective was to describe the epidemiological features of an outbreak of norovirus infection in a health school in Guangdong province, China, to identify the cause of such a large scale outbreak of norovirus among older students, to simulate the transmission dynamics, and to evaluate the effect of intervention measures of GII.17 [P17] genotype norovirus infection. We identified all cases during the outbreak. Descriptive epidemiological, analytical epidemiological and hygiene survey methods were used to described the outbreak epidemic course and identify the cause of the outbreak of norovirus infection. We also used dynamical model to simulate the transmission dynamics of norovirus infection and evaluate the effect of intervention measures. Norovirus genotyping was assigned to the newly obtained strains, with a maximum likelihood phylogenetic analysis conducted. There were 360 cases of 42 classes in five grades with a 12.99% attack rate. Proportionally, more students were in contact with sick students and vomit in the suspected case group than the control group (χ2 = 5.535, P = 0.019 and χ2 = 5.549, P = 0.019, respectively). The basic reproduction number was 8.32 before and 0.49 after the intervention. Dynamical modeling showed that if the isolation rate was higher or case isolation began earlier, the total attack rate would decrease. Molecular characterization identified the GII.17 [P17] genotype in all stains obtained from the health school, which were clustered with high support in the phylogenetic tree. This was an outbreak of norovirus infection caused by contact transmission. The main reasons for the spread of the epidemic were the later control time, irregular treatment of vomit and no case isolation. The transmission dynamics of contact transmission was high, more efficient control measures should be employed.

Benefit-Risk of Rivaroxaban for Extended Thromboprophylaxis After Hospitalization for Medical Illness: Pooled Analysis From MAGELLAN and MARINER.

Background Thromboprophylaxis extended after hospital discharge in medically ill patients currently is not recommended by practice guidelines because of uncertainty about the benefit for preventing major or fatal thromboembolic events, and the risk of bleeding. Methods and Results We assessed the benefit and risk of thromboprophylaxis with rivaroxaban 10 mg once daily extended for 25 to 45 days after hospitalization for preventing major thromboembolism in medically ill patients using the pooled data in 16 496 patients from 2 randomized trials, MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk) and MAGELLAN (Multicenter, randomized, parallel-group efficacy and safety study for the prevention of venous thromboembolism in hospitalized medically ill patients comparing rivaroxaban with enoxaparin). The data from the MARINER trial were pooled with the data from the MAGELLAN trial in patients who were free of thrombotic or bleeding events up to the last dose of enoxaparin/placebo and who continued in the outpatient phase of thromboprophylaxis. The composite outcome of major thromboembolic events (symptomatic deep vein thrombosis, nonfatal pulmonary embolism, myocardial infarction, and nonhemorrhagic stroke) and all-cause mortality was used to assess benefit and was compared with the risk of the composite of fatal and critical site bleeding. The incidence of the composite efficacy outcome was 1.80% (148 of 8222 patients) in the rivaroxaban group, compared with 2.31% (191 of 8274 patients in the placebo group) (HR, 0.78 [95% CI, 0.63-0.97], P=0.024). Fatal or critical site bleeding events were infrequent and occurred in <0.1% of patients in both groups (rivaroxaban 0.09%; placebo 0.04%; HR, 2.36; P=0.214). Conclusions The results suggest a benefit for reducing major thromboembolic outcomes (number needed to treat: 197), with a favorable trade-off to fatal or critical site bleeding (number needed to harm: 2045). Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00571649 and NCT02111564.

Thromboprophylaxis for Children Post-Fontan Procedure: Insights From the UNIVERSE Study.

Background Patients with single-ventricle physiology who undergo the Fontan procedure are at risk for thrombotic events associated with significant morbidity and mortality. The UNIVERSE Study evaluated the efficacy and safety of a novel liquid rivaroxaban formulation, using a body weight-adjusted dosing regimen, versus acetylsalicylic acid (ASA) in children post-Fontan. Methods and Results The UNIVERSE Study was a randomized, multicenter, 2-part, open-label study of rivaroxaban, in children who had undergone a Fontan procedure, to evaluate its dosing regimen, safety, and efficacy. Part A was the single-arm part of the study that determined the pharmacokinetics/pharmacodynamics and safety of rivaroxaban in 12 participants before proceeding to part B, whereby 100 participants were randomized 2:1 to open-label rivaroxaban versus ASA. The study period was 12 months. A total of 112 participants were enrolled across 35 sites in 10 countries. In part B, for safety outcomes, major bleeding occurred in one participant on rivaroxaban (epistaxis that required transfusion). Clinically relevant nonmajor bleeding occurred in 6% of participants on rivaroxaban versus 9% on ASA. Trivial bleeding occurred in 33% of participants on rivaroxaban versus 35% on ASA. For efficacy outcomes, 1 participant on rivaroxaban in part B had a pulmonary embolism (2% overall event rate); and for ASA, 1 participant had ischemic stroke and 2 had venous thrombosis (9% overall event rate). Conclusions In this study, participants who received rivaroxaban for thromboprophylaxis had a similar safety profile and fewer thrombotic events, albeit not statistically significant, compared with those in the ASA group. Registration URL: https://www.clinicaltrials.gov. Identifier: NCT02846532.

Rivaroxaban for extended thromboprophylaxis in acutely ill medical patients 75 years of age or older.

BACKGROUND: Although older patients are at increased risk for venous thromboembolism (VTE), thromboprophylaxis is underused because of bleeding concerns. The MARINER trial evaluated whether rivaroxaban reduced symptomatic postdischarge VTE in acutely ill medical patients. OBJECTIVES: We hypothesized that rivaroxaban would have a favorable benefit/risk profile in patients ≥75 years of age. METHODS: Patients were randomized in a double-blind manner at hospital discharge to rivaroxaban (10 mg/day for creatinine clearance ≥50 ml/min; 7.5 mg/day for ≥30-<50 ml/min) or placebo for 45 days. Using a Cox proportional hazard model including treatment as a covariate, we compared the risk of the primary efficacy outcome (symptomatic VTE plus VTE-related death in the intention-to-treat population) and safety outcome (International Society on Thrombosis and Haemostasis major bleeding in the safety population) in the prespecified subgroups of patients ≥ and <75 years of age. RESULTS: The primary event rate in patients ≥75 years of age was 2-fold higher than that in those <75 years. The incidence of the primary efficacy outcomes in both age groups was numerically lower with rivaroxaban than with placebo (≥75: 1.2% and 1.6%, HR 0.73, 95% CI 0.43-1.22; <75 0.6% and 0.8%, HR 0.78, 95% CI 0.46-1.32; interaction p-value for age group = .85). The incidence of major bleeding was low and similar in the two age and treatment groups (interaction p value for age group = .35). CONCLUSION: Symptomatic VTE and VTE-related death occur frequently in older patients with acute medical illness. The benefit/risk profile of rivaroxaban in patients ≥75 years of age appears consistent with that observed in the general population.

[Study on PET/CT Service Life Based on Key Components].

In this study, through the analysis of the composition of domestic large radioactive medical equipment PET/CT and the characteristics of each subsystem, combing the vulnerable spots, according to the standard requirements of PET/CT for 10 years in its service life, we research the PET/CT service life's effectiveness. Firstly, this study introduces the concept of service life, the relationship between service life and risk analysis, the pivotal system composition of PET/CT, the importance of reliability of each component, the traditional test method to verify its reliability is researched. This study suggests a test procedure and method to prove the reliability of various components of PET/CT equipment during the service life. This method is described in detail, and the specific test process in practical engineering application is discussed, which proves that it is beneficial to ensure the effectiveness of PET/CT during the service life.

Association Between Asymptomatic Proximal Deep Vein Thrombosis and Mortality in Acutely Ill Medical Patients.

Background Asymptomatic proximal deep vein thrombosis (DVT) is an end point frequently used to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Recently, the clinical relevance of asymptomatic DVT has been challenged. Methods and Results The objective of this study was to evaluate the relationship between asymptomatic proximal DVT and all-cause mortality (ACM) using a cohort analysis of a randomized trial for the prevention of venous thromboembolism (VTE) in acutely ill medical patients. Patients who received at least 1 dose of study drug and had an adequate compression ultrasound examination of the legs on either day 10 or day 35 were categorized into 1 of 3 cohorts: no VTE, asymptomatic proximal DVT, or symptomatic DVT. Cox proportional hazards model, with adjustment for significant independent predictors of mortality, were used to compare the incidences of ACM. Of the 7036 patients, 6776 had no VTE, 236 had asymptomatic DVT, and 24 had symptomatic VTE. The incidence of ACM was 4.8% in patients without VTE. Both asymptomatic proximal DVT (mortality, 11.4%; hazard ratio [HR], 2.31; 95% CI, 1.52-3.51; P<0.0001) and symptomatic VTE (mortality, 29.2%; HR, 9.42; 95% CI, 4.18-21.20; P<0.0001) were independently associated with significant increases in ACM. The analysis was post hoc, and ultrasound results were not available for all patients. Adjustment for baseline variables significantly associated with ACM may not fully compensate for differences. Conclusions Asymptomatic proximal DVT is associated with higher ACM than no VTE and remains a relevant end point to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00571649.

Enhancing Thermoelectric Performance of Polyaniline/Single-Walled Carbon Nanotube Composites via Dimethyl Sulfoxide-Mediated Electropolymerization.

The fabrication of flexible high-performance organic/inorganic thermoelectric (TE) composite films has been a hot spot for researchers in recent years. In this work, dynamic 3-phase interfacial electropolymerization of aniline, together with physical mixing with single-walled carbon nanotubes (SWCNTs), was adopted to prepare polyaniline/SWCNT (PANI/SWCNT) TE composites. The dimethyl sulfoxide (DMSO) added into the electrochemical polymerization system affords strong capability in improving the TE performance of composite films. Moreover, varying loadings of SWCNTs can also conveniently tune the TE performance of composites. Hence, the resultant composites afford the highest power factor (PF) of 236.4 ± 5.9 µW m-1 K-2 at room temperature. This work demonstrates that the introduction of DMSO into the electrolyte and the electrochemical polymerization are highly effective in fabricating high-performance PANI/SWCNT TE composites.

Post-Discharge Prophylaxis With Rivaroxaban Reduces Fatal and Major Thromboembolic Events in Medically Ill Patients.

BACKGROUND: Hospitalized acutely ill medical patients are at risk for fatal and major thromboembolic events. Whether use of extended-duration primary thromboprophylaxis can prevent such events is unknown. OBJECTIVES: The purpose of this study was to evaluate whether extended-duration rivaroxaban reduces the risk of venous and arterial fatal and major thromboembolic events without significantly increasing major bleeding in acutely ill medical patients after discharge. METHODS: MARINER (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients) studied acutely ill medical patients with additional risk factors for venous thromboembolism (VTE). Medically ill patients with a baseline creatinine clearance ≥50 ml/min were randomized in a double-blind fashion to rivaroxaban 10 mg or placebo daily at hospital discharge for 45 days. Exploratory efficacy analyses were performed with the intent-to-treat population including all data through day 45. Time-to-event curves were calculated using the Kaplan-Meier method. A blinded independent committee adjudicated all clinical events. RESULTS: In total, 4,909 patients were assigned to rivaroxaban and 4,913 patients to placebo. The mean age was 67.8 years, 55.5% were men, mean baseline creatinine clearance was 87.8 ml/min, and mean duration of hospitalization was 6.7 days. The pre-specified composite efficacy endpoint (symptomatic VTE, myocardial infarction, nonhemorrhagic stroke, and cardiovascular death) occurred in 1.28% and 1.77% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 0.72; 95% confidence interval: 0.52 to 1.00; p = 0.049), whereas major bleeding occurred in 0.27% and 0.18% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 1.44; 95% confidence interval: 0.62 to 3.37; p = 0.398). CONCLUSIONS: Extended-duration rivaroxaban in hospitalized medically ill patients resulted in a 28% reduction in fatal and major thromboembolic events without a significant increase in major bleeding. (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients [MARINER]; NCT02111564).

Thromboprophylaxis with Rivaroxaban in Acutely Ill Medical Patients with Renal Impairment: Insights from the MAGELLAN and MARINER Trials.

Patients with renal impairment are at higher risk of thrombosis and bleeding than those with normal renal function. The optimal rivaroxaban dose for thromboprophylaxis in acutely ill medical patients with renal impairment is unknown. MARINER and MAGELLAN were multicenter, randomized clinical trials of rivaroxaban in acutely ill medical patients. Efficacy and safety outcomes in patients with renal impairment in MARINER (7.5 mg once daily) were compared with those in patients with normal renal function in MARINER (10 mg once daily) and in a subpopulation of MAGELLAN that excluded patients at high risk for bleeding at baseline (10 mg once daily). Compared with enoxaparin/placebo in the MAGELLAN subpopulation, the relative risk (RR) of symptomatic venous thromboembolism (VTE) and VTE-related death with rivaroxaban 10 mg in patients with renal impairment (RR = 0.62; 95% confidence interval [CI] 0.27-1.44) was similar to that in those with normal renal function (RR = 0.78; 95% CI 0.44-1.40), while in MARINER, the 7.5 mg dose did not reduce the risk in patients with renal impairment (hazard ratio = 1.00; 95% CI 0.52-1.92). Major bleeding with rivaroxaban 10 mg once daily was higher in patients with renal impairment than in those with normal renal function in MAGELLAN (1.54% vs. 0.98%) and in the MAGELLAN subpopulation (0.94% vs. 0.61%). At a dose of 10 mg once daily, rivaroxaban is effective for thromboprophylaxis in acutely ill medical patients with impaired or normal renal function. The safety of this regimen is enhanced without loss of efficacy by excluding patients at high risk for bleeding, but not by using a reduced-dose strategy. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00571649 for the MAGELLAN trial, NCT02111564 for the MARINER trial.