Does external openness influence the infant mortality rates? An econometric investigation for the Chinese provinces.

During the last decades, China has achieved some remarkable results in improving the health status of its population. Since the end of the seventies, it has engaged in a process of large reforms in integrating with the global economy. This openness in policy has already paid important dividends in growth. The purpose of this study is to investigate if external openness had any influence on the evolution of infant mortality rates (IMR) in Chinese provinces since the beginning of the eighteen's. The first section is devoted to a brief comment on the evolution of the IMR. In section 2 and 3 we present the theoretical framework and the methodology adopted. Our hypotheses are tested with a panel data model. The results are discussed in section 4. They show that external openness had indirect effects on IMR in a way, which confirms the necessity to rebuild and expand medical insurance schemes. They also suggest it might be advisable to adopt measures in order to correct the health effects of the widening income disparities among provinces.China, panel data, external openness, infant mortality rates

Pharmacokinetic and economic implications when switching between hemophilia A treatments

Hemophilia is a bleeding disorder in which the blood is unable to form clots, and is also classified as severe (defined as having an endogenous factor VIII [FVIII] concentration < 1 IU/dL, or 1%), moderate (1-5%) or mild (5-50%). Those with severe hemophilia may spontaneously bleed without physical trauma. If not treated appropriately, people with hemophilia may develop hemophilic arthropathy, a joint disease commonly showing signs of bleeding in the knees, ankles, or elbows, which not only impairs movement, but significantly impacts life expectancy and quality of life. The current treatment of hemophilia involves prophylactic administration of factor concentrates. Although prophylactic treatment has improved health outcomes compared to on-demand treatment, there are still some challenges regarding the use of clotting factor concentrates. Generally, clotting factor concentrates are dosed based on international units per weight, but this one size fits all dosing mechanism fails to account for pharmacokinetic variability within this population. Appropriate dosing regimens vary by patient and treatment with hemophilia A patients using FVIII concentrates should be individualized from a therapeutic and economic standpoint. Population pharmacokinetic (PopPK) models were used as the basis for individualizing dosing regimens for patients with hemophilia while on factor concentrates. PopPK models are built using PK data from multiple participants to quantify the relationships between covariates such as age and weight to PK parameters as well as define variability between and within participants for these same PK parameters. To determine individual PK using only a few clotting factor activity levels and patient covariates, PopPK models are leveraged for Bayesian forecasting. People with hemophilia who have few sampling points are still available to be assessed using prior knowledge available from the patient population. While PopPK models may be helpful in hemophilia, this poses a concern when switching between factor concentrates. Factor concentrate switches may be prompted by the availability of new, improved concentrates by termination of national contracts resulting in a discontinuation of drug coverage, hypersensitivity to their current drug formulation, or adverse drug reactions. The lack of PK-tailored guidance when switching from one product to another may result in a period of time where treatment may increase the risk of inappropriate dosing, leading to either an increased risk of bleeds or waste of expensive factor concentrate. The work presented in this dissertation uses knowledge of an individual’s PK on a prior factor concentrate to better predict an individual’s PK on a new factor concentrate using data available from the Web-Accessible Population Pharmacokinetic Service – Haemophilia (WAPPS-Hemo). Emicizumab is a bispecific, recombinant, monoclonal antibody that bridges activated factor IX and X, mimics and partially restores the function of clotting FVIII in people with hemophilia A without inhibitors and was approved as routine prophylaxis by Health Canada in 2019. While emicizumab has its advantages over factor concentrates, such as decreased frequency of administration, and subcutaneous route of administration versus intravenous injections, the drug label recommends that any unused solution from a vial must be discarded, thereby wasting expensive resources. The use of a PopPK model of emicizumab was used to explore the implications of dosing based on vial size. This dissertation concludes that administering the entire vial of emicizumab and reducing the frequency may result in a reduction of vials used annually and consequently potential cost-savings. With high treatment costs and the approval of emicizumab, understanding the pharmacoeconomics of hemophilia is imperative for healthcare systems for reimbursement approval and contributing to commercial success and decision making as to whether emicizumab should be covered or not. Given the lifelong burden of the disease, the high cost of treatment in hemophilia, and the approval of emicizumab, a drug that may change the landscape of how hemophilia is treated, a cost-utility analysis studying the cost and quality-of-life of different prophylactic treatment regimens was presented in this dissertation, concluding that emicizumab is more effective and may be less costly than FVIII for patients with hemophilia A in Canada, conditional on drug cost assumptions. The method for estimating individual PK using PopPK models developed described in this dissertation may have a high impact for patients with hemophilia taking factor concentrates, who benefit from a safer individualized dosing regimen when switching between factor concentrates, potentially reducing adverse events or medication wastage. For patients with hemophilia on emicizumab, the simulations conducted exploring the use of emicizumab dosed based on vial size may have significant economic implications in cost-savings and provide a more practical dosing regimen. Finally, the economic evaluation conducted in the Canadian healthcare landscape may provide the healthcare system insight regarding the health and economic effects of using emicizumab compared to factor concentrates

Diverse Title Generation for Stack Overflow Posts with Multiple Sampling Enhanced Transformer

Stack Overflow is one of the most popular programming communities where developers can seek help for their encountered problems. Nevertheless, if inexperienced developers fail to describe their problems clearly, it is hard for them to attract sufficient attention and get the anticipated answers. We propose M$_3$NSCT5, a novel approach to automatically generate multiple post titles from the given code snippets. Developers may use the generated titles to find closely related posts and complete their problem descriptions. M$_3$NSCT5 employs the CodeT5 backbone, which is a pre-trained Transformer model having an excellent language understanding and generation ability. To alleviate the ambiguity issue that the same code snippets could be aligned with different titles under varying contexts, we propose the maximal marginal multiple nucleus sampling strategy to generate multiple high-quality and diverse title candidates at a time for the developers to choose from. We build a large-scale dataset with 890,000 question posts covering eight programming languages to validate the effectiveness of M$_3$NSCT5. The automatic evaluation results on the BLEU and ROUGE metrics demonstrate the superiority of M$_3$NSCT5 over six state-of-the-art baseline models. Moreover, a human evaluation with trustworthy results also demonstrates the great potential of our approach for real-world application.Comment: under revie

Assessment of Breathlessness in Lung Cancer: Psychometric Properties of the Dyspnea-12 Questionnaire.

CONTEXT: The Dyspnea-12 (D-12) Questionnaire is a well-validated instrument in respiratory illnesses for breathlessness assessment, but its psychometric properties have not been tested in lung cancer. OBJECTIVE: To demonstrate the psychometric properties of the D-12 in lung cancer patients. METHODS: Baseline data from a lung cancer feasibility trial were adopted for this analysis. D-12 and a series of patient-reported tools, including five Numeric Rating Scales (NRS), the Hospital Anxiety and Depression Scale (HADS), and the Lung Cancer Symptom Scale (LCSS), were used for the psychometric assessment. Spearman's correlation coefficients (rs) were used to estimate the convergent validity of the D-12 with the NRS, HADS, and LCSS. Exploratory factor analysis was performed to examine construct validity. Reliability was tested by Cronbach's alpha and item-to-total correlations. D-12 score difference between patients with or without anxiety, depression, and chronic obstructive pulmonary disease (COPD) was explored to identify its discriminate performance. RESULTS: One hundred and one lung cancer patients were included. There were significantly positive correlations between the D-12 and the HADS, LCSS, and NRS measuring breathlessness severity and its associated affective distress. Factor analysis clearly identified two components (physical and emotional) of the D-12. Cronbach's alpha for D-12 total, physical, and emotional subscales was 0.95, 0.92, and 0.94, respectively. Patients with anxiety or depression demonstrated significantly higher D-12 scores than those without it, and patients with COPD reported significantly more severe breathlessness than those without COPD. CONCLUSION: The D-12 is a valid and reliable self-reported questionnaire for use in breathlessness assessment in lung cancer patients

Using pharmacokinetics for tailoring prophylaxis in people with hemophilia switching between clotting factor products: A scoping review

Abstract The objective of this scoping review is to summarize the current use of pharmacokinetics for tailoring prophylaxis in hemophilia patients switching between clotting factor products. Patients with hemophilia may require switching of clotting factor concentrates due to a variety of factors, but there have been perceived risks associated with switching, such as inhibitor development or suboptimal protection due to inadequate dosing while titrating treatment. Studies that look at patients switching from one clotting factor concentrate to another are categorized in terms of their primary and/or secondary objectives, notably biosimilarity and comparative pharmacokinetic studies and inhibitor development studies. Research on how best to switch concentrates with respect to dosing regimen are lacking, and currently a trial-and-error approach is used for dosing the new factor concentrate. In the future, studies looking at the predictability of pharmacokinetics (PK) of a new factor concentrate based on individual PK knowledge of the original factor concentrate may offer clinical benefit by providing a safer switching approach and protocol.Peer reviewe

Effect of two low doses of prostaglandin F_2α on luteolysis in dairy cows

In this preliminary study, we determined the effect of a modified method involving the administration of two low doses of prostaglandin F2α (PGF2α) at an interval of 24 h on luteolysis in dairy cows, and compared it with the standard single-dose method. Twenty-six cows were assigned to three groups treated with two low doses (TLD group, n = 10), one standard dose (SD group, n = 10), and one low dose (OLD group, n = 6) on day 9 to 10 of the oestrous cycle (day 0 = the day of PGF2α administration). Their serum progesterone (P4) levels and corpus luteum (CL) sizes were measured daily from day 0 to 4 to assess CL regression. The results indicated that the proportion of complete luteolysis, indicating a P4 value ≤ 1 ng/mL on day 3, was higher in the TLD group (100.0%) than in the SD (60.0%) and OLD (66.7%) groups. Ultrasonically detected changes in the CL area correlated with the shifts in the P4 values in both the TLD and the SD groups. The remaining CL area was significantly smaller in the TLD group (17.8% ± 3.3%) than in the SD or OLD group on day 4. Thus, we concluded that the proportion of luteolysis in cows was increased with two low doses of PGF2α as compared to a single PGF2α dose, indicating the necessity of the second dose of PGF2α. However, further studies with larger sample sizes in the field are required

Aggregation-Induced Emission Luminogens for Direct Exfoliation of 2D Layered Materials in Ethanol

© 2020 Wiley-VCH GmbH Aggregation-induced emission (AIE) luminogens are an important type of advanced functional materials with fantastic optical properties and have found potential applications in organic electronics, biochemistry, and molecular imaging. Herein, this article presents a novel application of AIE luminogens (AIEgens) for efficient exfoliation of layered transition metal dichalcogenides (TMDs, such as MoS2 and WSe2). From the 1H NMR spectroscopic analysis, the designed AIEgens can insert into the space between layers of MoS2 in ethanol solution and the dynamic molecular rotation against the weak interactions affords large-scale few-layer MoS2 nanosheets (7–8 layers) with enhanced smoothness. The 3D AIEgens play a significant role in preserving the crystal lattice of MoS2 even at high pressure (>15 GPa). More importantly, the new approach can also be used for exfoliation of WSe2 to achieve large-scale few-layer nanosheets. The present work thus provides a facile and high yielding synthetic method for accessing on a large scale 2D layered materials with enhanced properties for high-technology applications

Social Networks, High-Risk anal Hpv and Coinfection With Hiv in Young Sexual Minority Men

OBJECTIVES: Young sexual minority men (SMM) exhibit a high prevalence and incidence of high-risk genotypes of human papillomavirus (hrHPV) anal infections and a confluence of a high prevalence of HIV and rectal STIs. Social determinants of health (SDOHs) are linked to social network contexts that generate and maintain racial disparities in HIV and STIs. A network perspective was provided to advance our knowledge of drivers of genotype-specific hrHPV infection and coinfection with HIV. The study also examined whether socially connected men are infected with the same high-risk HPV genotypes and, if so, whether this tendency is conditioned on coinfection with HIV. METHODS: Our sample included 136 young SMM of predominantly black race and their network members of other races and ethnicities, aged 18-29 years, who resided in Houston, Texas, USA. These participants were recruited during 2014-2016 at the baseline recruitment period by network-based peer referral, where anal exfoliated cells and named social and sexual partners were collected. Exponential random graph models were estimated to assess similarity in genotype-specific hrHPV anal infection in social connections and coinfection with HIV in consideration of the effects of similarity in sociodemographic, sexual behavioural characteristics, SDOHs and syphilis infection. RESULTS: Pairs of men socially connected to each other tend to be infected with the same hrHPV genotypes of HPV-16, HPV-45 and HPV-51 or HPV-16 and/or HPV-18. The tendency of social connections between pairs of men who were infected with either HPV-16 or HPV-18 were conditioned on HIV infection. CONCLUSIONS: Networked patterns of hrHPV infection could be amenable to network-based HPV prevention interventions that engage young SMM of predominantly racial minority groups who are out of HIV care and vulnerable to high-risk HPV acquisition