Thermo-mechanical controls of flat subduction: insights from numerical modeling

This study was supported by National Basic Research Program of China (2014CB440901), the Strategic Priority Research Program (B) of CAS (XDB18020104), National Science Foundation of China (41190073, 41372198 and 41304071), and NERC grant NE/J021822/1.Numerical experiments are used to investigate the thermo- mechanical controls for inducing flat subduction and why flat subduction is rare relative to normal/steep subduction. Our modeling results demonstrate that flat subduction is an end-member of a steady state subduction geometry and is characterized by a curved slab with a nearly-horizontal slab section. Intermediate cases between normal/steep and flat subduction appear to be transient in origin and evolve toward one of the stable end-members. Physical parameters inducing flat subduction can be classified into four categories: buoyancy of the subducting oceanic lithosphere (e.g., slab age, oceanic crustal thickness), viscous coupling between the overriding and downgoing plates (e.g., initial subduction angle), external kinematic conditions, and rheological properties of the subduction zone. On the basis of parameter sensitivity tests and the main characteristics of present-day flat subduction zones, positive buoyancy from either the young slab or the thickened oceanic crust are considered the primary controlling parameter. Our results show that the possibility of flat subduction is directly proportional to oceanic crustal thickness and inversely proportional to the slab age. Furthermore, oceanic crust must be thicker than 8 km to induce flat subduction, when the slab is older than 30 Ma with an initial subduction angle of ≥ 20°, and without absolute trenchward motion of the overriding plate. The lower the initial subduction angle or the thicker the overriding continental lithosphere, the more likelihood for flat subduction. The initial subduction angle is more influential for the development of flat subduction than the overriding lithospheric thickness, and a thick overriding lithosphere induces flat subduction only under the condition of an initial subduction angle of ≤ 25°, with a slab age of ≥ 30 Ma and without absolute trenchward motion of the overriding plate. However, when the initial subduction angle is increased to > 25°, no flat subduction is predicted. All the parameters are evaluated within the constraints of a mechanical framework in which the slab geometry is regarded as a result of a balance between the gravitational and hydrodynamic torque. Any factor that can sufficiently reduce gravitational torque or increase hydrodynamic torque will exert a strong effect on flat subduction development. Our results are consistent with the observations of modern flat subduction zones on Earth.PostprintPeer reviewe

Mendelian randomization to evaluate the causal relationship between liver enzymes and the risk of six specific bone and joint-related diseases

BackgroundStudies of liver dysfunction in relation to bone and joint-related diseases are scarce, and its causality remains unclear. Our objective was to investigate whether serum liver enzymes are causally associated with bone and joint-related diseases using Mendelian randomization (MR) designs.MethodsGenetic data on serum liver enzymes (alkaline phosphatase (ALP); alanine transaminase (ALT); gamma-glutamyl transferase (GGT)) and six common bone and joint-related diseases (rheumatoid arthritis (RA), osteoporosis, osteoarthritis (OA), ankylosing spondylitis, psoriatic arthritis, and gout) were derived from independent genome-wide association studies of European ancestry. The inverse variance-weighted (IVW) method was applied for the main causal estimate. Complementary sensitivity analyses and reverse causal analyses were utilized to confirm the robustness of the results.ResultsUsing the IVW method, the positive causality between ALP and the risk of osteoporosis diagnosed by bone mineral density (BMD) at different sites was indicated (femoral neck, lumbar spine, and total body BMD, odds ratio (OR) [95% CI], 0.40 [0.23–0.69], 0.35 [0.19–0.67], and 0.33 [0.22–0.51], respectively). ALP was also linked to a higher risk of RA (OR [95% CI], 6.26 [1.69–23.51]). Evidence of potential harmful effects of higher levels of ALT on the risk of hip and knee OA was acquired (OR [95% CI], 2.48 [1.39–4.41] and 3.07 [1.49–6.30], respectively). No causal relationship was observed between GGT and these bone and joint-related diseases. The study also found that BMD were all negatively linked to ALP levels (OR [95% CI] for TBMD, FN-BMD, and LS-BMD: 0.993 [0.991–0.995], 0.993 [0.988–0.998], and 0.993 [0.989, 0.998], respectively) in the reverse causal analysis. The results were replicated via sensitivity analysis in the validation process.ConclusionsOur study revealed a significant association between liver function and bone and joint-related diseases

Evaluation of the 50% infectious dose of human norovirus cin-2 in gnotobiotic pigs: a comparison of classical and contemporary methods for endpoint estimation

Human noroviruses (HuNoVs) are the leading causative agents of epidemic and sporadic acute gastroenteritis that affect people of all ages worldwide. However, very few dose?response studies have been carried out to determine the median infectious dose of HuNoVs. In this study, we evaluated the median infectious dose (ID50) and diarrhea dose (DD50) of the GII.4/2003 variant of HuNoV (Cin-2) in the gnotobiotic pig model of HuNoV infection and disease. Using various mathematical approaches (Reed?Muench, Dragstedt?Behrens, Spearman?Karber, exponential, approximate beta-Poisson dose?response models, and area under the curve methods), we estimated the ID50 and DD50 to be between 2400?3400 RNA copies, and 21,000?38,000 RNA copies, respectively. Contemporary dose?response models offer greater flexibility and accuracy in estimating ID50. In contrast to classical methods of endpoint estimation, dose?response modelling allows seamless analyses of data that may include inconsistent dilution factors between doses or numbers of subjects per dose group, or small numbers of subjects. Although this investigation is consistent with state-of-the-art ID50 determinations and offers an advancement in clinical data analysis, it is important to underscore that such analyses remain confounded by pathogen aggregation. Regardless, challenging virus strain ID50 determination is crucial for identifying the true infectiousness of HuNoVs and for the accurate evaluation of protective efficacies in pre-clinical studies of therapeutics, vaccines and other prophylactics using this reliable animal model.Fil: Ramesh, Ashwin K.. Virginia-Maryland College of Veterinary Medicine; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Virología E Innovaciones Tecnológicas; ArgentinaFil: Schmidt, Philip J.. University of Waterloo; CanadáFil: Lei, Shaohua. Virginia-Maryland College of Veterinary Medicine; Estados UnidosFil: Zhong, Weiming. Cincinnati Children’s Hospital Medical Center; Estados UnidosFil: Jiang, Xi. Cincinnati Children’s Hospital Medical Center; Estados UnidosFil: Emelko, Monica B.. University of Waterloo; CanadáFil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine; Estados Unido

Heuristic Search for Planning with Different Forced Goal-Ordering Constraints

Planning with forced goal-ordering (FGO) constraints has been proposed many times over the years, but there are still major difficulties in realizing these FGOs in plan generation. In certain planning domains, all the FGOs exist in the initial state. No matter which approach is adopted to achieve a subgoal, all the subgoals should be achieved in a given sequence from the initial state. Otherwise, the planning may arrive at a deadlock. For some other planning domains, there is no FGO in the initial state. However, FGO may occur during the planning process if certain subgoal is achieved by an inappropriate approach. This paper contributes to illustrate that it is the excludable constraints among the goal achievement operations (GAO) of different subgoals that introduce the FGOs into the planning problem, and planning with FGO is still a challenge for the heuristic search based planners. Then, a novel multistep forward search algorithm is proposed which can solve the planning problem with different FGOs efficiently

Disassembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients

Correction to Nural H, He P, Beach T, Sue L, Xia W, Shen Y. Disassembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients Molecular Neurodegeneration 2009, 4:23

Comparison of clinical outcomes of Ibutilide-guided cardioversion and direct current synchronized cardioversion after radiofrequency ablation of persistent atrial fibrillation

BackgroupIbutilide has already been used for cardioversion of persistent atrial fibrillation (PsAF) after radiofrequency catheter ablation (RFCA). The purpose of this study was to determine the effect of Ibutilide-guided cardioversion on clinical outcomes after individualized ablation of PsAF.MethodsFrom October 2020 to September 2021, consecutive patients with PsAF accepted for RFCA were prospectively enrolled. After individualized ablation including pulmonary vein isolation plus left atrial roof line ablation and personalized linear ablation based on left atrial low-voltage zones, patients were divided into the spontaneous conversion (SCV) group, direct current synchronized cardioversion (DCC) group and Ibutilide group according to different cardioversion types during ablation. The rates of freedom from atrial tachyarrhythmia (ATT) among the three groups were evaluated after follow-up.ResultsIn this study, 110 patients were enrolled, including 12 patients with SCV, 50 patients receiving DCC and 48 patients receiving Ibutilide cardioversion after individualized ablation. Among the three groups, the SCV group had shorter AF duration {12 months [interquartile range (IQR) 12–16], P = 0.042} and smaller left atrial diameter (LAD) [35 mm (IQR: 33–42), P = 0.023]. A 12-month freedom from ATT rate was 83.3% in SCV group, 69.4% in DCC group, and 79.2% in Ibutilide group, respectively (Log-rank, P = 0.745). During the follow-up [17 months (IQR: 15–19)], the rate of freedom from ATT of SCV group (83.3%), and Ibutilide group (72.9%) were both higher than that of DCC group (53.1%, P = 0.042). Moreover, Kaplan–Meier analysis showed a significantly higher sinus rhythm (SR) maintenance in Ibutilide group than in DCC group (Log-rank, P = 0.041). After adjusting for risk factors of AF recurrence, the hazard ratio for AF recurrence of the DCC group with reference to the Ibutilide group was 4.10 [95% confidence interval (CI) (1.87–8.98), P < 0.001]. Furthermore, subgroup analysis showed that freedom from ATT rate in effective Ibutilide subgroup was significantly higher than noneffective Ibutilide subgroup (Log-rank, P < 0.001).ConclusionFor the treatment of the patients with PsAF, Ibutilide-guided cardioversion after individualized RFCA may be benefit for maintenance of SR compared to conventional DCC, especially for the patients who are effective for administration of Ibutilide

Can HIV service data be used for surveillance purposes?: a case study in Guangzhou, China.

BACKGROUND: Timely monitoring HIV epidemic among key populations is a formidable challenge. This study aimed to evaluate the agreement between data collected from an enhanced HIV sentinel surveillance (HSS+) and an HIV service, and to discuss whether testing service data can be used for surveillance purposes. METHODS: The HSS+ data were collected from HIV sentinel surveillance conducted annually among men who have sex with men (MSM) between 2009 and 2013 in Guangzhou, China. The HIV service data were obtained from the China-Bill & Melinda Gates Foundation Cooperation Program on HIV Prevention and Care (China-Gates HIV Program) in Guangzhou during the same period. The China-Gates HIV Program aimed to increase HIV counseling and testing among MSM. We compared demographic characteristics, condom use, HIV testing history, and the HIV status among individuals in these two datasets. The Armitage-trend test was used to evaluate the HIV epidemic and behaviors of the participants in the two datasets over the study period. RESULTS: Overall, a total of 2224 and 5311 MSM were included in the surveillance and service datasets, respectively. The majority of participants in the two datasets were between 20 and 29 years old, at least attended college, and had never been married. However, socio-demographic characteristics varied slightly between the two datasets. Similar trends were observed for the HIV epidemic in these two datasets. The surveillance dataset indicated that HIV prevalence increased from 3.9% in 2009 to 11.4% in 2013 (P-value for trend < 0.001), while data from the HIV service dataset indicated that MSM HIV prevalence during this same period increased from 6.2 to 8.9% (P-value for trend = 0.025). The rates of condom use were similar between the two datasets and remained consistent throughout the study period. CONCLUSION: HIV service data can complement existing HIV surveillance systems for MSM in China, though it may underestimate the HIV prevalence (HSS+ data contains people whose status is already know, while service data contains people who were initially negative or people of unknown status). HIV service data can be used for surveillance purposes, when prerequisite variables are collected from a large number people, if the quality assessment is conducted

Can HIV service data be used for surveillance purposes?: a case study in Guangzhou, China

Abstract Background Timely monitoring HIV epidemic among key populations is a formidable challenge. This study aimed to evaluate the agreement between data collected from an enhanced HIV sentinel surveillance (HSS+) and an HIV service, and to discuss whether testing service data can be used for surveillance purposes. Methods The HSS+ data were collected from HIV sentinel surveillance conducted annually among men who have sex with men (MSM) between 2009 and 2013 in Guangzhou, China. The HIV service data were obtained from the China-Bill & Melinda Gates Foundation Cooperation Program on HIV Prevention and Care (China-Gates HIV Program) in Guangzhou during the same period. The China-Gates HIV Program aimed to increase HIV counseling and testing among MSM. We compared demographic characteristics, condom use, HIV testing history, and the HIV status among individuals in these two datasets. The Armitage-trend test was used to evaluate the HIV epidemic and behaviors of the participants in the two datasets over the study period. Results Overall, a total of 2224 and 5311 MSM were included in the surveillance and service datasets, respectively. The majority of participants in the two datasets were between 20 and 29 years old, at least attended college, and had never been married. However, socio-demographic characteristics varied slightly between the two datasets. Similar trends were observed for the HIV epidemic in these two datasets. The surveillance dataset indicated that HIV prevalence increased from 3.9% in 2009 to 11.4% in 2013 (P-value for trend < 0.001), while data from the HIV service dataset indicated that MSM HIV prevalence during this same period increased from 6.2 to 8.9% (P-value for trend = 0.025). The rates of condom use were similar between the two datasets and remained consistent throughout the study period. Conclusion HIV service data can complement existing HIV surveillance systems for MSM in China, though it may underestimate the HIV prevalence (HSS+ data contains people whose status is already know, while service data contains people who were initially negative or people of unknown status). HIV service data can be used for surveillance purposes, when prerequisite variables are collected from a large number people, if the quality assessment is conducted

Fibromodulin Reduces Scar Formation in Adult Cutaneous Wounds by Eliciting a Fetal-Like Phenotype

Blocking transforming growth factor (TGF)β1 signal transduction has been a central strategy for scar reduction; however, this approach appears to be minimally effective. Here, we show that fibromodulin (FMOD), a 59-kD small leucine-rich proteoglycan critical for normal collagen fibrillogenesis, significantly reduces scar formation while simultaneously increasing scar strength in both adult rodent models and porcine wounds, which simulate human cutaneous scar repair. Mechanistically, FMOD uncouples pro-migration/contraction cellular signals from pro-fibrotic signaling by selectively enhancing SMAD3-mediated signal transduction, while reducing AP-1-mediated TGFβ1 auto-induction and fibrotic extracellular matrix accumulation. Consequently, FMOD accelerates TGFβ1-responsive adult fibroblast migration, myofibroblast conversion, and function. Furthermore, our findings strongly indicate that, by delicately orchestrating TGFβ1 activities rather than indiscriminately blocking TGFβ1, FMOD elicits fetal-like cellular and molecular phenotypes in adult dermal fibroblasts in vitro and adult cutaneous wounds in vivo, which is a unique response of living system undescribed previously. Taken together, this study illuminates the signal modulating activities of FMOD beyond its structural support functions, and highlights the potential for FMOD-based therapies to be used in cutaneous wound repair. © The Author(s) 2017

Providing HIV-related services in China for men who have sex with men.

PROBLEM: In China, human immunodeficiency virus (HIV) care provided by community-based organizations and the public sector are not well integrated. APPROACH: A community-based organization and experts from the Guangzhou Center for Disease Control and Prevention developed internet-based services for men who have sex with men, in Guangzhou, China. The internet services were linked to clinical services offering HIV testing and care. LOCAL SETTING: The expanding HIV epidemic among men who have sex with men is a public health problem in China. HIV control and prevention measures are implemented primarily through the public system. Only a limited number of community organizations are involved in providing HIV services. RELEVANT CHANGES: The programme integrated community and public sector HIV services including health education, online HIV risk assessment, on-site HIV counselling and testing, partner notification, psychosocial care and support, counting of CD4+ T-lymphocytes and treatment guidance. LESSONS LEARNT: The internet can facilitate HIV prevention among a subset of men who have sex with men by enhancing awareness, service uptake, retention in care and adherence to treatment. Collaboration between the public sector and the community group promoted acceptance by the target population. Task sharing by community groups can increase access of this high-risk group to available HIV-related services