Patient and Disease-Specific Induced Pluripotent Stem Cells for Discovery of Personalized Cardiovascular Drugs and Therapeutics.

Human induced pluripotent stem cells (iPSCs) have emerged as an effective platform for regenerative therapy, disease modeling, and drug discovery. iPSCs allow for the production of limitless supply of patient-specific somatic cells that enable advancement in cardiovascular precision medicine. Over the past decade, researchers have developed protocols to differentiate iPSCs to multiple cardiovascular lineages, as well as to enhance the maturity and functionality of these cells. Despite significant advances, drug therapy and discovery for cardiovascular disease have lagged behind other fields such as oncology. We speculate that this paucity of drug discovery is due to a previous lack of efficient, reproducible, and translational model systems. Notably, existing drug discovery and testing platforms rely on animal studies and clinical trials, but investigations in animal models have inherent limitations due to interspecies differences. Moreover, clinical trials are inherently flawed by assuming that all individuals with a disease will respond identically to a therapy, ignoring the genetic and epigenomic variations that define our individuality. With ever-improving differentiation and phenotyping methods, patient-specific iPSC-derived cardiovascular cells allow unprecedented opportunities to discover new drug targets and screen compounds for cardiovascular disease. Imbued with the genetic information of an individual, iPSCs will vastly improve our ability to test drugs efficiently, as well as tailor and titrate drug therapy for each patient

Evaluation of rigid registration methods for whole head imaging in diffuse optical tomography

Functional brain imaging has become an important neuroimaging technique for the study of brain organization and development. Compared to other imaging techniques, diffuse optical tomography (DOT) is a portable and low-cost technique that can be applied to infants and hospitalized patients using an atlas-based light model. For DOT imaging, the accuracy of the forward model has a direct effect on the resulting recovered brain function within a field of view and so the accuracy of the spatially normalized atlas-based forward models must be evaluated. Herein, the accuracy of atlas-based DOT is evaluated on models that are spatially normalized via a number of different rigid registration methods on 24 subjects. A multileveled approach is developed to evaluate the correlation of the geometrical and sensitivity accuracies across the full field of view as well as within specific functional subregions. Results demonstrate that different registration methods are optimal for recovery of different sets of functional brain regions. However, the “nearest point to point” registration method, based on the EEG 19 landmark system, is shown to be the most appropriate registration method for image quality throughout the field of view of the high-density cap that covers the whole of the optically accessible cortex

Cost-benefit analysis of vaccination: a comparative analysis of eight approaches for valuing changes to mortality and morbidity risks.

BACKGROUND: There is increasing interest in estimating the broader benefits of public health interventions beyond those captured in traditional cost-utility analyses. Cost-benefit analysis (CBA) in principle offers a way to capture such benefits, but a wide variety of methods have been used to monetise benefits in CBAs. METHODS: To understand the implications of different CBA approaches for capturing and monetising benefits and their potential impact on public health decision-making, we conducted a CBA of human papillomavirus (HPV) vaccination in the United Kingdom using eight methods for monetising health and economic benefits, valuing productivity loss using either (1) the human capital or (2) the friction cost method, including the value of unpaid work in (3) human capital or (4) friction cost approaches, (5) adjusting for hard-to-fill vacancies in the labour market, (6) using the value of a statistical life, (7) monetising quality-adjusted life years and (8) including both productivity losses and monetised quality-adjusted life years. A previously described transmission dynamic model was used to project the impact of vaccination on cervical cancer outcomes. Probabilistic sensitivity analysis was conducted to capture uncertainty in epidemiologic and economic parameters. RESULTS: Total benefits of vaccination varied by more than 20-fold (£0.6-12.4 billion) across the approaches. The threshold vaccine cost (maximum vaccine cost at which HPV vaccination has a benefit-to-cost ratio above one) ranged from £69 (95% CI £56-£84) to £1417 (£1291-£1541). CONCLUSIONS: Applying different approaches to monetise benefits in CBA can lead to widely varying outcomes on public health interventions such as vaccination. Use of CBA to inform priority setting in public health will require greater convergence around appropriate methodology to achieve consistency and comparability across different studies

Wearable activity sensors and early pain after total joint arthroplasty.

A prospective observational cohort of 20 primary total hip arthroplasty (n = 12) and total knee arthroplasty (n = 8) patients (mean age: 63 ± 6 years) was passively monitored with a consumer-level wearable activity sensor before and 6 weeks after surgery. Patients were clustered by minimal change or decreased activity using sensor data. Decreased postoperative activity was associated with greater pain reduction (-5.5 vs -2.0, P = .03). All patients surpassed minimal clinical benefit thresholds of total joint arthroplasty (TJA) (Hip Disability and Osteoarthritis Score Junior 30.5 vs 20.8, P = .23; Knee Injury and Osteoarthritis Outcome Score Junior 23.3 vs 18.2, P = .77) within 6 weeks. Patients who objectively "take it easy" after TJA may experience less pain with no difference in early subjective outcome. Remote, passive analysis of outpatient wearable sensor data may permit real-time detection of early problems after TJA

Structural characterization of a first-generation articulated-truss joint for space crane application

A first-generation space crane articulated-truss joint was statically and dynamically characterized in a configuration that approximated an operational environment. The articulated-truss joint was integrated into a test-bed for structural characterization. Static characterization was performed by applying known loads and measuring the corresponding deflections to obtain load-deflection curves. Dynamic characterization was performed using modal testing to experimentally determine the first six mode shapes, frequencies, and modal damping values. Static and dynamic characteristics were also determined for a reference truss that served as a characterization baseline. Load-deflection curves and experimental frequency response functions are presented for the reference truss and the articulated-truss joint mounted in the test-bed. The static and dynamic experimental results are compared with analytical predictions obtained from finite element analyses. Load-deflection response is also presented for one of the linear actuators used in the articulated-truss joint. Finally, an assessment is presented for the predictability of the truss hardware used in the reference truss and articulated-truss joint based upon hardware stiffness properties that were previously obtained during the Precision Segmented Reflector (PSR) Technology Development Program

Social contact patterns relevant to the spread of respiratory infectious diseases in Hong Kong.

The spread of many respiratory infections is determined by contact patterns between infectious and susceptible individuals in the population. There are no published data for quantifying social contact patterns relevant to the spread of respiratory infectious diseases in Hong Kong which is a hotspot for emerging infectious diseases due to its high population density and connectivity in the air transportation network. We adopted a commonly used diary-based design to conduct a social contact survey in Hong Kong in 2015/16 using both paper and online questionnaires. Participants using paper questionnaires reported more contacts and longer contact duration than those using online questionnaires. Participants reported 13 person-hours of contact and 8 contacts per day on average, which decreased over age but increased with household size, years of education and income level. Prolonged and frequent contacts, and contacts at home, school and work were more likely to involve physical contacts. Strong age-assortativity was observed in all age groups. We evaluated the characteristics of social contact patterns relevant to the spread of respiratory infectious diseases in Hong Kong. Our findings could help to improve the design of future social contact surveys, parameterize transmission models of respiratory infectious diseases, and inform intervention strategies based on model outputs

Optimizing the Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate

Steven Riley and colleagues examine the potential benefits of "stretching" a limited supply of vaccine and suggest that substantial reductions in the attack rate are possible if vaccines are given to more people at lower doses

Chinese immigrant parents' vaccination decision making for children: A qualitative analysis

Background: While immunization coverage rates for childhood routine vaccines in Hong Kong are almost 100%, the uptake rates of optional vaccines remain suboptimal. Understanding parental decision-making for children's vaccination is important, particularly among minority groups who are most vulnerable and underserved. This study explored how a subsample of new immigrant mothers from mainland China, a rapidly-growing subpopulation in Hong Kong, made decisions on various childhood and adolescent vaccines for their offspring, and identified key influences affecting their decision making. Methods. Semi-structured in-depth interviews were conducted with 23 Chinese new immigrant mothers recruited by purposive sampling. All interviews were audio-taped, transcribed and analyzed using a Grounded Theory approach. Results: Participants' conversation revealed five underlying themes which influenced parents' vaccination decision-making: (1) Institutional factors, (2) Insufficient vaccination knowledge and advice, (3) Affective impacts on motivation, (4) Vaccination barriers, and (5) Social influences. The role of social norms appeared overwhelmingly salient influencing parents' vaccination decision making. Institutional factors shaped parent's perceptions of vaccination necessity. Fear of vaccine-targeted diseases was a key motivating factor for parents adopting vaccination. Insufficient knowledge about vaccines and targeted diseases, lack of advice from health professionals and, if provided, suspicions regarding the motivations for such advice were common issues. Vaccination cost was a major barrier for many new immigrant parents. Conclusions: Social norms play a key role influencing parental vaccination decision-making. Insight gained from this study will help inform healthcare providers in vaccination communication and policymakers in future vaccination programme. © 2014 Wang et al.; licensee BioMed Central Ltd.Link_to_subscribed_fulltex