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

Mechanism to Authenticate a Reader to a Credential

Access to data objects stored on a credential such as a badge, smart card, etc. is typically limited to user authorization through the use of a user-entered PIN or other mechanism. This disclosure describes techniques to enable a credential reader to authenticate itself to a credential and access protected objects on the credential without user interaction and without the use of any global credential. The techniques define a simplified public-key infrastructure (PKI) hierarchy appropriate for typical credentials, which are usually low-powered, passive, and offline

Data Object Extensions for Access Control Credentials

Traditional access control credentials require authentication against a backend and have no mechanism to work offline. Also, traditional credentials such as badges typically have a photo to identify the credential holder. The forgery of the outward appearance of a credential to the extent that it will pass a visual inspection is easily possible, even when modern anti-forgery techniques are employed. This disclosure describes techniques that extend security credentials to provide secure, authenticated, offline access. An authorized person can validate a badge or other credential by tapping it against an authenticated credential reader. Data on the credential is containerized such that specific data objects are accessible by specific classes of credential readers. For example, a credential reader operated by a security officer may have access to name, image, and emergency contact information stored on the credential while a credential reader operated by a receptionist can have access to only the name and image

Transferring Credentials Between Devices

A badge user may want to use a different device, e.g., a smartphone, a smartwatch, etc., as their credential in lieu of the badge. This disclosure describes techniques to securely transfer credentials from a first device (e.g., badge) to a second device (e.g., phone) such that only one device with valid credentials exists at any time. Per the techniques, the two devices perform a cryptographic transfer to move credentials, and the credentials on the first device are destroyed. In this manner, only one credential at a time can be authenticated for the user. The techniques can operate offline, e.g., with neither device having internet access; it is just the two devices that need communicate with each other

Risk Factors for Cerebrovascular Disease as Correlates of Cognitive Function in a Stroke-Free Cohort

We investigated the relationship between risk factors for cerebrovascular disease and cognitive function in 249 stroke-free community volunteers (age, 70.8±6.7 years; education, 12.3±4.6 years) who were given tests of memory, language, visuospatial, abstract reasoning, and attentional skills. Using logistic regression analyses, we examined hypertension, diabetes mellitus, myocardial infarction, angina, hypercholesterolemia, and cigarette smoking as potential correlates of performance within these cognitive domains. Controlling for demographic factors within the logistic models, diabetes mellitus was a significant independent correlate of abstract reasoning deficits (odds ratio, 10.9; 95% confidence interval, 2.2 to 54.9) and visuospatial dysfunction (odds ratio, 3.5; confidence interval, 1.2 to 10.7), while hypercholesterolemia was a significant independent correlate of memory dysfunction (odds ratio, 3.0; confidence interval, 1.4 to 6.6). Prolonged exposure to vascular risk factors such as diabetes mellitus and hypercholesterolemia may lead to atherosclerotic disease, possibly resulting in "silent" infarctions or impaired cerebral blood flow and a decline in cognitive functioning

How Do the Elderly Fare in Medical Malpractice Litigation, Before and After Tort Reform? Evidence from Texas

The elderly account for a disproportionate share of medical spending, but little is known about how they are treated by the medical malpractice system, or how tort reform affects elderly claimants. We compare paid medical malpractice claims brought by elderly plaintiffs in Texas during 1988–2009 to those brought by adult non-elderly plaintiffs. Controlling for healthcare utilization (based on inpatient days), elderly paid claims rose from about 20% to about 40% of the adult non-elderly rate by the early 2000s. Mean and median payouts per claim also converged, although the elderly were far less likely to receive large payouts. Tort reform strongly affected claim rates and payouts for both groups, but disproportionately reduced payouts to elderly claimants. We thus find evidence of convergence between the elderly and the adult non-elderly in both claim rates and payouts, which is interrupted by tort reform

Dementia after Stroke Increases the Risk of Long-Term Stroke Recurrence

Background: Although risk factors for first stroke have been identified, the predictors of long-term stroke recurrence are less well understood. We performed the present study to determine whether dementia diagnosed three months after stroke onset is an independent risk factor for long-term stroke recurrence. Methods: We examined 242 patients (age = 72.0 ± 8.7 years) hospitalized with acute ischemic stroke who had survived the first three months without recurrence and followed them to identify predictors of long-term stroke recurrence. We diagnosed dementia three months after stroke using modified DSM-III-R criteria based on neuropsychological and functional assessments. The effects of conventional stroke risk factors and dementia status on survival free of recurrence were estimated using Kaplan-Meier analyses, and the relative risks (RR) of recurrence were calculated using Cox proportional hazards models. Results: Dementia (RR = 2.71, 95% CI = 1.36 to 5.42); cardiac disease (RR = 2.18, CI = 1.15 to 4.12); and sex, with women at higher risk (RR = 2.03, CI = 1.01 to 4.10), were significant independent predictors of recurrence, while education (RR = 1.90, CI = 0.77 to 4.68), admission systolic blood pressure >160 mm Hg (RR = 1.80, CI = 0.94 to 3.44) and alcohol intake exceeding 160 grams per week (RR = 1.86, CI = 0.79 to 4.38) were weakly related. Conclusions: Our results suggest that dementia significantly increases the risk of long-term stroke recurrence, with additional independent contributions by cardiac disease and sex. Cognitive impairment may be a surrogate marker for multiple vascular risk factors and larger infarct volume that may serve to increase the risk of recurrence. Alternatively, less aggressive medical management of stroke patients with cognitive impairment or noncompliance of such patients with medical therapy may be bases for an increased rate of stroke recurrence