Cardiovascular Applications of Hyperpolarized MRI

Many applications of MRI are limited by an inherently low sensitivity. Previous attempts to overcome this insensitivity have focused on the use of MRI systems with stronger magnetic fields. However, the gains that can be achieved in this way are relatively small and increasing the magnetic field invariably leads to greater technical challenges. More recently, the development of a range of techniques, which can be gathered under the umbrella term of “hyperpolarization,” has offered potential solutions to the low sensitivity. Hyperpolarization techniques have been demonstrated to temporarily increase the signal available in an MRI experiment by as much as 100,000-fold. This article outlines the main hyperpolarization techniques that have been proposed and explains how they can increase MRI signals. With particular emphasis on the emerging technique of dynamic nuclear polarization, the existing preclinical cardiovascular applications are reviewed and the potential for clinical translation is discussed

The Druze: A Population Genetic Refugium of the Near East

BACKGROUND: Phylogenetic mitochondrial DNA haplogroups are highly partitioned across global geographic regions. A unique exception is the X haplogroup, which has a widespread global distribution without major regions of distinct localization. PRINCIPAL FINDINGS: We have examined mitochondrial DNA sequence variation together with Y-chromosome-based haplogroup structure among the Druze, a religious minority with a unique socio-demographic history residing in the Near East. We observed a striking overall pattern of heterogeneous parental origins, consistent with Druze oral tradition, together with both a high frequency and a high diversity of the mitochondrial DNA (mtDNA) X haplogroup within a confined regional subpopulation. Furthermore demographic modeling indicated low migration rates with nearby populations. CONCLUSIONS: These findings were enabled through the use of a paternal kindred based sampling approach, and suggest that the Galilee Druze represent a population isolate, and that the combination of a high frequency and diversity of the mtDNA X haplogroup signifies a phylogenetic refugium, providing a sample snapshot of the genetic landscape of the Near East prior to the modern age

Type 1 diabetes: translating mechanistic observations into effective clinical outcomes

Type 1 diabetes remains an important health problem, particularly in Western countries where the incidence has been increasing in younger children(1). In 1986, Eisenbarth described Type 1 diabetes as a chronic autoimmune disease. Work over the past 3 ½ decades has identified many of the genetic, immunologic, and environmental factors that are involved in the disease and have led to hypotheses concerning its pathogenesis. Based on these findings, clinical trials have been conducted to test these hypotheses but have had mixed results. In this review, we discuss the findings that have led to current concepts of the disease mechanisms, how this understanding has prompted clinical studies, and the results of these studies. The findings from preclinical and clinical studies support the original proposed model for how type 1 diabetes develops, but have also suggested that this disease is more complex than originally thought and will require broader treatment approaches

Skewed X-inactivation is common in the general female population

X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes (SSR4, REPS2, and SEPT6), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants

Differing Impacts Of Market Concentration On Affordable Care Act Marketplace Premiums

Recent increases in market concentration among health plans, hospitals, and medical groups raise questions about what impact such mergers are having on costs to consumers. We examined the impact of market concentration on the growth of health insurance premiums between 2014 and 2015 in two Affordable Care Act state-based Marketplaces: Covered California and NY State of Health. We measured health plan, hospital, and medical group market concentration using the well-known Herfindahl-Hirschman Index (HHI) and used a multivariate regression model to relate these measures to premium growth. Both states exhibited a positive association between hospital concentration and premium growth and a positive (but not statistically significant) association between medical group concentration and premium growth. Our results for health plan concentration differed between the two states: It was positively associated with premium growth in New York but negatively associated with premium growth in California. The health plan concentration finding in Covered California may be the result of its selectively contracting with health plans

Current Methods and Future Directions in Avian Diet Analysis

Identifying the composition of avian diets is a critical step in characterizing the roles of birds within ecosystems. However, because birds are a diverse taxonomic group with equally diverse dietary habits, gaining an accurate and thorough understanding of avian diet can be difficult. In addition to overcoming the inherent difficulties of studying birds, the field is advancing rapidly, and researchers are challenged with a myriad of methods to study avian diet, a task that has only become more difficult with the introduction of laboratory techniques to dietary studies. Because methodology drives inference, it is important that researchers are aware of the capabilities and limitations of each method to ensure the results of their study are interpreted correctly. However, few reviews exist which detail each of the traditional and laboratory techniques used in dietary studies, with even fewer framing these methods through a bird-specific lens. Here, we discuss the strengths and limitations of morphological prey identification, DNA-based techniques, stable isotope analysis and the tracing of dietary biomolecules throughout food webs. We identify areas of improvement for each method, provide instances in which the combination of techniques can yield the most comprehensive findings, introduce potential avenues for combining results from each technique within a unified framework, and present recommendations for the future focus of avian dietary research

How Adolescents Use Technology for Health Information: Implications for Health Professionals from Focus Group Studies

BACKGROUND: Adolescents present many challenges in providing them effective preventive services and health care. Yet, they are typically the early adopters of new technology (eg, the Internet). This creates important opportunities for engaging youths via eHealth. OBJECTIVE: To describe how adolescents use technology for their health-information needs, identify the challenges they face, and highlight some emerging roles of health professionals regarding eHealth services for adolescents. METHODS: Using an inductive qualitative research design, 27 focus groups were conducted in Ontario, Canada. The 210 participants (55% female, 45% male; median age 16 years) were selected to reflect diversity in age, sex, geographic location, cultural identity, and risk. An 8-person team analyzed and coded the data according to major themes. RESULTS: Study participants most-frequently sought or distributed information related to school (89%), interacting with friends (85%), social concerns (85%), specific medical conditions (67%), body image and nutrition (63%), violence and personal safety (59%), and sexual health (56%). Finding personally-relevant, high-quality information was a pivotal challenge that has ramifications on the depth and types of information that adolescents can find to answer their health questions. Privacy in accessing information technology was a second key challenge. Participants reported using technologies that clustered into 4 domains along a continuum from highly-interactive to fixed information sources: (1) personal communication: telephone, cell phone, and pager; (2) social communication: e-mail, instant messaging, chat, and bulletin boards; (3) interactive environments: Web sites, search engines, and computers; and (4) unidirectional sources: television, radio, and print. Three emerging roles for health professionals in eHealth include: (1) providing an interface for adolescents with technology and assisting them in finding pertinent information sources; (2) enhancing connection to youths by extending ways and times when practitioners are available; and (3) fostering critical appraisal skills among youths for evaluating the quality of health information. CONCLUSIONS: This study helps illuminate adolescent health-information needs, their use of information technologies, and emerging roles for health professionals. The findings can inform the design and more-effective use of eHealth applications for adolescent populations