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The multi-colour complete light curves and low-resolution spectra of two short period eclipsing Am binaries V404 Aur and GW Gem are presented. The stellar atmospheric parameters of the primary stars were derived through the spectra fitting. The observed and TESS-based light curves of them were analysed by using the Wilson-Devinney code. The photometric solutions suggest that both V404 Aur and GW Gem are semi-detached systems with the secondary component filling its critical Roche Lobe, while the former should be a marginal contact binary. The $O-C$ analysis found that the period of V404 Aur is decreasing at a rate of $dP/dt=-1.06(\pm0.01)\times 10^{-7}\,\mathrm{d}\,\mathrm{ yr}^{-1}$, while the period of GW Gem is increasing at $dP/dt=+2.41(\pm0.01)\times 10^{-8} \mathrm{d}\,\mathrm{yr}^{-1}$. The period decrease of V404 Aur may mainly be caused by the combined effects of the angular momentum loss (AML) via an enhanced stellar wind of the more evolved secondary star and mass transfer between two components. The period increase of GW Gem supports the mass transfer from the secondary to the primary. Both targets may be in the broken contact stage predicted by the thermal relaxation oscillations theory and will eventually evolve to the contact stage. We have collected about 54 well-known eclipsing Am binaries with absolute parameters from the literature. The relations of these parameters are summarised. There are some components that have a higher degree of evolution. The majority of their hydrogen shell may have been stripped away and the stellar internal layer exposed. The accretion processes from such evolved components may be very important for the formation of Am peculiarity in binaries.
The exploration of molecular characteristics has emerged as a prominent trend to advance precision medicine. The utilization of genetic testing to guide therapy is integral to precision medicine. This study aims to investigate the potential patient populations for the reimbursement of next-generation sequencing (NGS) and assess the budget impact from the perspective of Taiwan’s single insurer, the National Health Insurance Administration.
Methods
To comprehend the scope for medicines with companion diagnostics (CDx) involved, we analyze the U.S. Food and Drug Administration-approved/cleared diagnostic tests, conduct a literature review to identify medicines approved by the European Medicines Agency that require a CDx, and identify the medicines with CDx involved covered by the National Health Insurance (NHI) in Taiwan. Subsequently, we explore the potential reimbursement indications for NGS testing and conduct a budget impact analysis to evaluate the expected financial impact for the NHI over a five-year period. Furthermore, sensitivity analyses are conducted to deal with uncertainty.
Results
We have compiled 13 cancer types for which NGS can serve as a companion diagnostic. These encompass non-small-cell lung cancer, colorectal cancer, breast cancer, ovarian cancer, biliary tract cancer, acute myeloid leukemia, acute lymphoblastic leukemia, melanoma, cholangiocarcinoma, prostate cancer, pancreatic cancer, gastrointestinal stromal tumor, and thyroid cancer/medullary thyroid cancer. The implementation of NGS reimbursement in NHI will benefit 25,000 to 30,000 patients undergoing targeted therapies. The projected incremental budget impact ranges from TWD570 million to TWD650 million (USD19 million to USD22 million) over five years.
Conclusions
This study focuses on evaluating the financial impact of incorporating NGS testing into NHI reimbursement for relevant cancer drug indications. The findings can serve as references for the planning of reimbursement policies. However, with the advancement of precision medicine, it is foreseeable that there will be a broader range of applications for NGS, and its cost will gradually decrease.
Change-point analysis (CPA) is a well-established statistical method to detect abrupt changes, if any, in a sequence of data. In this paper, we propose a procedure based on CPA to detect test speededness. This procedure is not only able to classify examinees into speeded and non-speeded groups, but also identify the point at which an examinee starts to speed. Identification of the change point can be very useful. First, it informs decision makers of the appropriate length of a test. Second, by removing the speeded responses, instead of the entire response sequence of an examinee suspected of speededness, ability estimation can be improved. Simulation studies show that this procedure is efficient in detecting both speeded examinees and the speeding point. Ability estimation is dramatically improved by removing speeded responses identified by our procedure. The procedure is then applied to a real dataset for illustration purpose.
Diagnostic classification models are confirmatory in the sense that the relationship between the latent attributes and responses to items is specified or parameterized. Such models are readily interpretable with each component of the model usually having a practical meaning. However, parameterized diagnostic classification models are sometimes too simple to capture all the data patterns, resulting in significant model lack of fit. In this paper, we attempt to obtain a compromise between interpretability and goodness of fit by regularizing a latent class model. Our approach starts with minimal assumptions on the data structure, followed by suitable regularization to reduce complexity, so that readily interpretable, yet flexible model is obtained. An expectation–maximization-type algorithm is developed for efficient computation. It is shown that the proposed approach enjoys good theoretical properties. Results from simulation studies and a real application are presented.
Item response theory (IRT) plays an important role in psychological and educational measurement. Unlike the classical testing theory, IRT models aggregate the item level information, yielding more accurate measurements. Most IRT models assume local independence, an assumption not likely to be satisfied in practice, especially when the number of items is large. Results in the literature and simulation studies in this paper reveal that misspecifying the local independence assumption may result in inaccurate measurements and differential item functioning. To provide more robust measurements, we propose an integrated approach by adding a graphical component to a multidimensional IRT model that can offset the effect of unknown local dependence. The new model contains a confirmatory latent variable component, which measures the targeted latent traits, and a graphical component, which captures the local dependence. An efficient proximal algorithm is proposed for the parameter estimation and structure learning of the local dependence. This approach can substantially improve the measurement, given no prior information on the local dependence structure. The model can be applied to measure both a unidimensional latent trait and multidimensional latent traits.
The eddy-viscosity model, as initially used to model the mean Reynolds stress, has been widely used in the linear analysis of turbulence recently by direct extension. In this study, the mechanism of the eddy viscosity in improving the prediction of fluctuation structures with linear analysis is clarified by investigating the statistical properties of forcing, eddy-viscosity term and their correlations. From the direct numerical simulation (DNS) results of turbulent channel flows with $Re_{\tau }=186$–$2003$, the spatial correlation of forcing is partially cancelled due to its interaction with eddy-viscosity terms. The stochastic forcing after excluding the eddy-viscosity term is nearly uncorrelated spatially, which better matches the condition where the resolvent modes are consistent with the spectral proper orthogonal decomposition (SPOD) modes from DNS. With the above findings, an optimisation framework is developed by minimising the spatial correlations of the stochastic forcing. The optimised eddy-viscosity profiles nearly overlap with the mean-quantity-based model in the near-wall region, but have different maximum values. Compared with the mean-quantity-based model, the optimised results enhance the consistency between the resolvent and DNS results significantly. Based on the optimised results, a new modelling framework is further abstracted, leaving only one to-be-modelled parameter of the maximum value of the eddy-viscosity profile. This parameter follows distinctive rules with spanwise flow scales, based on which a simplified predictive model is constructed. The resolvent modes predicted by the new model exhibit high consistency with SPOD modes, which are essentially comparable to the optimised results for wide ranges of streamwise and spanwise scales.
Although dietary factors have been examined as potential risk factors for liver cancer, the evidence is still inconclusive. Using a diet-wide association analysis, our research evaluated the associations of 126 foods and nutrients on the risk of liver cancer in a Chinese population. We obtained the diet consumption of 72,680 women in the Shanghai Women’s Health Study using baseline dietary questionnaires. The association between each food and nutrient and liver cancer risk was quantified by Cox regression model. A false discovery rate of 0.05 was used to determine the foods and nutrients which need to be verified. Totally 256 incident liver cancer cases were identified in 1,267,391 person-years during the follow-up duration. At the statistical significance level (P ≤ 0.05), higher intakes of cooked wheaten foods, pear, grape and copper were inversely associated with liver cancer risk, while spinach, leafy vegetables, eggplant and carrots showed the positive associations. After considering multiple comparisons, no dietary variable was associated with liver cancer risk. Similar findings were seen in the stratification, secondary and sensitivity analyses. Our findings observed no significant association between dietary factors and liver cancer risk after considering multiple comparisons in Chinese women. More evidence is needed to explore the associations between diet and female liver cancer occurrence.
Health technology assessment (HTA) agencies assess evidence to support decision making about which technologies to provide and pay for in the health system. HTA impact is understood as the influence that HTA report findings can have in the health system, including impacts on reimbursement decisions, changes to health outcomes, or broader system or societal impacts. The International Network of Agencies for Health Technology Assessment (INAHTA) is a global network of publicly funded HTA agencies. INAHTA’s mission, in part, is to advance the impact of HTA to support reimbursement decisions and the optimal use of health system resources. Each year, INAHTA awards the David Hailey Award for Best Impact Story to the member agency that shares the best story, as voted by fellow members, about HTA impact. The impact story sharing program in INAHTA contributes to a deeper understanding of what works well (or not so well) in achieving HTA impact. This paper provides six impact stories from agencies that were finalists for the 2021 and 2022 David Hailey Impact Award for Best Impact Story: the Institut national d’excellence en santé et en services sociaux, the Malaysian Health Technology Assessment Section, Ontario Health, the Center for Drug Evaluation, the National Institute for Health and Care Excellence, and Health Technology Wales. These stories demonstrate that HTA agencies can, in differing ways, effectively support governments in their efforts to place evidence at the centre of decision making.
Our study aimed to develop and validate a nomogram to assess talaromycosis risk in hospitalized HIV-positive patients. Prediction models were built using data from a multicentre retrospective cohort study in China. On the basis of the inclusion and exclusion criteria, we collected data from 1564 hospitalized HIV-positive patients in four hospitals from 2010 to 2019. Inpatients were randomly assigned to the training or validation group at a 7:3 ratio. To identify the potential risk factors for talaromycosis in HIV-infected patients, univariate and multivariate logistic regression analyses were conducted. Through multivariate logistic regression, we determined ten variables that were independent risk factors for talaromycosis in HIV-infected individuals. A nomogram was developed following the findings of the multivariate logistic regression analysis. For user convenience, a web-based nomogram calculator was also created. The nomogram demonstrated excellent discrimination in both the training and validation groups [area under the ROC curve (AUC) = 0.883 vs. 0.889] and good calibration. The results of the clinical impact curve (CIC) analysis and decision curve analysis (DCA) confirmed the clinical utility of the model. Clinicians will benefit from this simple, practical, and quantitative strategy to predict talaromycosis risk in HIV-infected patients and can implement appropriate interventions accordingly.
This study investigates the impact of coronavirus disease 2019 (COVID-19) pandemic on HTAsiaLink members at the organizational level and provides recommendations for mitigating similar challenges in the future.
Methods
A survey was disseminated among HTAsiaLink members to assess the COVID-19 impact in three areas: (i) inputs, (ii) process, and (iii) outputs of the Health Technology Assessment organizations’ (HTAOs) research operations and HTA process in general.
Results
Survey results showed that most HTAOs hired more staff and secured similar or higher funding levels during COVID-19. Nevertheless, some organizations reported high staff turnover. COVID-19-relevant research was prioritized, and most of the organizations had to adapt their research design to meet the needs of policymakers. Time constraints in conducting research and inability to collect primary data were reported as impacts on the research process. Overall, the number of research projects and accessibility of respondents’ publications increased during COVID-19.
Conclusions
Research demand for HTAOs increased during COVID-19 and impacted their research process; however, they demonstrated resilience and adaptability to provide timely evidence for policymakers. With the growing reliance on HTA, HTAOs require adequate financial support, continuous capacity building, collaboration, and partnership, innovative HTA methods, and a pragmatic yet robust, evidence-to-policy process in preparation for future pandemics.
The maser instability associated with the loss-cone distribution has been widely invoked to explain the radio bursts observed in the astrophysical plasma environment, such as aurora and corona. In the laboratory plasma of a tokamak, events reminiscent of these radio bursts have also been frequently observed as an electron cyclotron emission (ECE) burst in the microwave range ($\mathrm{\sim }2{f_{\textrm{ce}}}$ near the last closed flux surface) during transient magnetohydrodynamic events. These bursts have a short duration of ~10 μs and display a radiation spectrum corresponding to a radiation temperature ${T_{e,\textrm{rad}}}$ of over $30\ \textrm{keV}$ while the edge thermal electron temperature ${T_e}$ is only in the range of $1\ \textrm{keV}$. Suprathermal electrons can be generated through magnetic reconnection, and a loss-cone distribution can be generated through open stochastic field lines in the magnetic mirror of the near-edge region of a tokamak plasma. Radiation modelling shows that a sharp distribution gradient $\partial f/\partial {v_ \bot } > 0$ at the loss-cone boundary can cause a negative absorption of ECE radiation through the maser instability. The negative absorption then amplifies the radiation so that the microwave intensity is significantly stronger than the thermal value. The significant ${T_{e,\textrm{rad}}}$ from the simulations suggests the potential role of the loss-cone maser instability in generating the ECE burst in a tokamak.
This study aims to evaluate the impact of low-carbohydrate diet, balanced dietary guidance and pharmacotherapy on weight loss among individuals with overweight or obesity over a period of 3 months. The study involves 339 individuals with overweight or obesity and received weight loss treatment at the Department of Clinical Nutrition at the Second Affiliated Hospital of Zhejiang University, School of Medicine, between 1 January 2020 and 31 December 2023. The primary outcome is the percentage weight loss. Among the studied patients, the majority chose low-carbohydrate diet as their primary treatment (168 (49·56 %)), followed by balanced dietary guidance (139 (41·00 %)) and pharmacotherapy (32 (9·44 %)). The total percentage weight loss for patients who were followed up for 1 month, 2 months and 3 months was 4·98 (3·04, 6·29) %, 7·93 (5·42, 7·93) % and 10·71 (7·74, 13·83) %, respectively. Multivariable logistic regression analysis identified low-carbohydrate diet as an independent factor associated with percentage weight loss of ≥ 3 % and ≥ 5 % at 1 month (OR = 0·461, P < 0·05; OR = 0·349, P < 0·001). The results showed that a low-carbohydrate diet was an effective weight loss strategy in the short term. However, its long-term effects were comparable to those observed with balanced dietary guidance and pharmacotherapy.
This study investigates the molecular intricacies of the transmembrane protein TSP11 gene in Echinococcus strains isolated from livestock and patients in Yunnan Province afflicted with Echinococcus granulosus (E. granulosus) between 2016 and 2020. Gene typing analysis of the ND1 gene revealed the presence of the G1 type, G5 type and untyped strains, constituting 52.4, 38.1 and 9.5%, respectively. The analysis of 42 DNA sequences has revealed 24 novel single nucleotide polymorphic sites, delineating 11 haplotypes, all of which were of the mutant type. Importantly, there were no variations observed in mutation sites or haplotypes in any of the hosts. The total length of the TSP11 gene's 4 exons is 762 bp, encoding 254 amino acids. Our analysis posits the existence of 6 potential B-cell antigenic epitopes within TSP11, specifically at positions 49-KSN-51, 139-GKRG-142, 162-DNG-164, 169-NGS-171, 185-DS-186 and 231-PPRFTN-236. Notably, these epitopes exhibit consistent presence among various intermediate hosts and haplotypes. However, further validation is imperative to ascertain their viability as diagnostic antigens for E. granulosus in the Yunnan Province.
Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.
In this paper, we investigate a sink-driven three-layer flow in a radial Hele-Shaw cell. The three fluids are of different viscosities, with one fluid occupying an annulus-like domain, forming two interfaces with the other two fluids. Using a boundary integral method and a semi-implicit time stepping scheme, we alleviate the numerical stiffness in updating the interfaces and achieve spectral accuracy in space. The interaction between the two interfaces introduces novel dynamics leading to rich pattern formation phenomena, manifested by two typical events: either one of the two interfaces reaches the sink faster than the other (forming cusp-like morphology), or they come very close to each other (suggesting a possibility of interface merging). In particular, the inner interface can be wrapped by the other to have both scenarios. We find that multiple parameters contribute to the dynamics, including the width of the annular region, the location of the sink, and the mobilities of the fluids.
Innovative health technologies offer much to patients, clinicians, and health systems. Policy makers can, however, be slow to embrace innovation for many reasons, including a less robust body of evidence, perceived high costs, and a fear that once technologies enter the health system, they will be difficult to remove. Health technology funding decisions are usually made after a rigorous health technology assessment (HTA) process, including a cost analysis. However, by focusing on therapeutic value and cost-savings, the traditional HTA framework often fails to capture innovation in the assessment process. How HTA defines, evaluates, and values innovation is currently inconsistent, and it is generally agreed that by explicitly defining innovation would recognize and reward and, in turn, stimulate, encourage, and incentivize future innovation in the system. To foster innovation in health technology, policy needs to be innovative and utilize other HTA tools to inform decision making including horizon scanning, multicriteria decision analysis, and funding mechanisms such as managed agreements and coverage with evidence development. When properly supported and incentivized, and by shifting the focus from cost to investment, innovation in health technology such as genomics, point-of-care testing, and digital health may deliver better patient outcomes. Industry and agency members of the Health Technology Assessment International Asia Policy Forum (APF) met in Taiwan in November 2023 to discuss the potential of HTA to foster innovation, especially in the Asia region. Discussions and presentations during the 2023 APF were informed by a background paper, which forms the basis of this paper.
In this study, the resolvent-based estimation (RBE) is further generalised to cases with arbitrarily sampled measurements in time, where the generalised RBE is denoted as GRBE in this study. Different from the RBE that constructs the transfer function at each frequency, the GRBE minimises the estimation error energy in the physical temporal domain by considering the forcing and noise statistics. The GRBE is validated by estimating the complex Ginzburg–Landau equation and turbulent channel flows with the friction Reynolds number $Re_{\tau }=186$, 547 and 934, where the results from the RBE are also included. When the measurements are temporally resolved, the estimation results of the two approaches are equivalent to each other, and both match well with the reference numerical results. For the temporally unresolved cases, the estimation errors from the GRBE are obviously lower than those from the RBE. After validation, the GRBE is applied to investigate the impacts of the abundance of the measured information, including the temporal information and sensor types, on the estimation accuracy. Compared with the mean square error (MSE) in the estimation with temporally resolved measurements, that with measurements at only one snapshot, i.e. without any temporal information, increases by approximately $15\,\%$. On the other hand, it can effectively improve the estimation accuracy by increasing the number of sensor types. With temporally resolved measurements, the relative MSE decreases by $12.3\,\%$ when the sensor types increase from $\lbrace \tau _u \rbrace$ to $\lbrace \tau _u,\tau _w,p \rbrace$, where $\tau_u$, $\tau_w$ and p are the streamwise shear stress, spanwise shear stress and pressure at the wall. Finally, several existing forcing models are incorporated into the GRBE to investigate their performance in the linear estimation of flow state. The wall-distance-dependent model (W-model) results match well with the optimal linear estimations when the measurements are temporally unresolved. Meanwhile, with the increase of temporal information of the measurement, the estimation errors from the tested W-model and the scale-dependent model ($\lambda$-model) both increase, which contradicts the tendency observed in the optimal linear GRBE estimation results. Such a phenomenon highlights the importance of proper modelling of the forcing in the temporal domain for the accuracy of flow state estimation.
The right inferior frontal gyrus (RIFG) is a potential beneficial brain stimulation target for autism. This randomized, double-blind, two-arm, parallel-group, sham-controlled clinical trial assessed the efficacy of intermittent theta burst stimulation (iTBS) over the RIFG in reducing autistic symptoms (NCT04987749).
Methods
Conducted at a single medical center, the trial enrolled 60 intellectually able autistic individuals (aged 8–30 years; 30 active iTBS). The intervention comprised 16 sessions (two stimulations per week for eight weeks) of neuro-navigated iTBS or sham over the RIFG. Fifty-seven participants (28 active) completed the intervention and assessments at Week 8 (the primary endpoint) and follow-up at Week 12.
Results
Autistic symptoms (primary outcome) based on the Social Responsiveness Scale decreased in both groups (significant time effect), but there was no significant difference between groups (null time-by-treatment interaction). Likewise, there was no significant between-group difference in changes in repetitive behaviors and exploratory outcomes of adaptive function and emotion dysregulation. Changes in social cognition (secondary outcome) differed between groups in feeling scores on the Frith-Happe Animations (Week 8, p = 0.026; Week 12, p = 0.025). Post-hoc analysis showed that the active group improved better on this social cognition than the sham group. Dropout rates did not vary between groups; the most common adverse event in both groups was local pain. Notably, our findings would not survive stringent multiple comparison corrections.
Conclusions
Our findings suggest that iTBS over the RIFG is not different from sham in reducing autistic symptoms and emotion dysregulation. Nonetheless, RIFG iTBS may improve social cognition of mentalizing others' feelings in autistic individuals.
Whether material deprivation-related childhood socio-economic disadvantages (CSD) and care-related adverse childhood experiences (ACE) have different impacts on depressive symptoms in middle-aged and older people is unclear.
Methods
In the Guangzhou Biobank Cohort Study, CSD and ACE were assessed by 7 and 5 culturally sensitive questions, respectively, on 8,716 participants aged 50+. Depressive symptoms were measured by 15-item Geriatric Depression Scale (GDS). Multivariable linear regression, stratification analyses, and mediation analyses were done.
Results
Higher CSD and ACE scores were associated with higher GDS score in dose-response manner (P for trend <0.001). Participants with one point increment in CSD and ACE had higher GDS score by 0.11 (95% confidence interval [CI], 0.09–0.14) and 0.41 (95% CI, 0.35–0.47), respectively. The association of CSD with GDS score was significant in women only (P for sex interaction <0.001; women: β (95% CI)=0.14 (0.11–0.17), men: 0.04 (−0.01 to 0.08)). The association between ACE and GDS score was stronger in participants with high social deprivation index (SDI) (P for interaction = 0.01; low SDI: β (95% CI)=0.36 (0.29–0.43), high SDI: 0.64 (0.48–0.80)). The proportion of association of CSD and ACE scores with GDS score mediated via education was 20.11% and 2.28%.
Conclusions
CSD and ACE were associated with late-life depressive symptoms with dose-response patterns, especially in women and those with low adulthood socio-economic status. Education was a major mediator for CSD but not ACE. Eliminating ACE should be a top priority.
Infection mechanism plays a significant role in epidemic models. To investigate the influence of saturation effect, a nonlocal (convolution) dispersal susceptible-infected-susceptible epidemic model with saturated incidence is considered. We first study the impact of dispersal rates and total population size on the basic reproduction number. Yang, Li and Ruan (J. Differ. Equ. 267 (2019) 2011–2051) obtained the limit of basic reproduction number as the dispersal rate tends to zero or infinity under the condition that a corresponding weighted eigenvalue problem has a unique positive principal eigenvalue. We remove this additional condition by a different method, which enables us to reduce the problem on the limiting profile of the basic reproduction number into that of the spectral bound of the corresponding operator. Then we establish the existence and uniqueness of endemic steady states by a equivalent equation and finally investigate the asymptotic profiles of the endemic steady states for small and large diffusion rates to provide reference for disease prevention and control, in which the lack of regularity of the endemic steady state and Harnack inequality makes the limit function of the sequence of the endemic steady state hard to get. Finally, we find whether lowing the movements of susceptible individuals can eradicate the disease or not depends on not only the sign of the difference between the transmission rate and the recovery rate but also the total population size, which is different from that of the model with standard or bilinear incidence.