Health Savings Account - Eligible High Deductible Health Plans: Updating the Definition of Prevention

High-deductible health plans (HDHPs) are an important and growing part of the health insurance landscape. By some estimates, as many as 80 percent of large employers may offer an HDHP in 2014. In 2013, more than 15 million Americans received health coverage through an HDHP, a more than a threefold increase since 2007.As outlined by the U.S. Treasury Department, individuals with an HSA-eligible HDHP are required to pay the full cost of most medications and services -- in theory utilizing pre-tax HSA funds -- until deductibles are met. However, the 2003 authorizing legislation and further guidance include a safe harbor allowing plans to cover primary preventive services, those typically deemed to prevent the onset of disease, before the deductible is satisfied.Services or benefits meant to treat "an existing illness, injury or condition," are excluded from first-dollar coverage in HSA-eligible HDHPs, which encompasses most secondary preventive services. For example, plans are prohibited from providing first dollar coverage of disease management services such as insulin, eye and foot exams, and glucose monitoring supplies for patients with diabetes.As chronic disease conditions currently make up 75 percent of total U.S. health spending, appropriate chronic disease management is an important tool to lower long-term health care costs. As the market for HDHPs grow, it is important that they maintain the flexibility to allow for effective health management of all beneficiaries. This report addresses the strict definition of prevention that an HDHP must follow for it to include a pre-tax health savings account (HSA), and how this restriction limits the effectiveness of current plans. A potential solution - allowing HSA-eligible HDHPs to provide first-dollar coverage for targeted, evidence-based, secondary preventive services that prevent chronic disease progression and related complications - can improve patient-centered outcomes, add efficiency to medical spending, and enhance HDHP attractiveness.A multi-disciplinary research team from the University of Michigan's Center for Value-Based Insurance Design, Harvard Medical School, and the University of Minnesota conducted a multi-part project to investigate the impact of updatingthe definition of prevention for HDHPs to include selected secondary preventive services that are frequently used as health plan quality metrics and included as elements of pay-for-performance programs. Specifically, the project aimed to: 1) determine the premium effect, actuarial value, and estimated market uptake of the novel HDHP plan that covers these evidence-based services outside the deductible, and 2) explore through interviews whether insurance industry experts found coverage of secondary preventive services a worthwhile endeavor

Analysis of threats to Galápagos Marine Iguanas (Amblyrhynchus cristatus)

Galápagos marine iguana population sizes have been declining since first contact with humans.This decline has historically been attributed mainly to predation by invasive species, but additional human-caused threats exist today. My thesis conducts an analysis of the present threats to the species and determines which are the most severe.Modern threats include invasive species, the increasing presence of humans, the potential for foreign pathogens, and the effects of climate change. Specifically, the most severe threats are environmental contamination such as oil spills, oceanic changes due to climate change,and expected increases in the severity of El Niño events. Due to the difficulty of addressing climate change at the local level, conservation of this species should be focused on managing local human activity to prevent predation and chronic stress from other threats

Triepitopic Antibody Fusions Inhibit Cetuximab-Resistant BRAF and KRAS Mutant Tumors via EGFR Signal Repression

Dysregulation of epidermal growth factor receptor (EGFR) is a hallmark of many epithelial cancers, rendering this receptor an attractive target for cancer therapy. Much effort has been focused on the development of EGFR-directed antibody-based therapeutics, culminating in the clinical approval of the drugs cetuximab and panitumumab. Unfortunately, the clinical efficacy of these drugs has been disappointingly low, and a particular challenge to targeting EGFR with antibody therapeutics has been resistance, resulting from mutations in the downstream raf and ras effector proteins. Recent work demonstrating antibody cocktail-induced synergistic downregulation of EGFR motivated our design of cetuximab-based antibody–fibronectin domain fusion proteins that exploit downregulation-based EGFR inhibition by simultaneously targeting multiple receptor epitopes. We establish that, among our engineered multiepitopic formats, trans-triepitopic antibody fusions demonstrate optimal efficacy, inducing rapid EGFR clustering and internalization and consequently ablating downstream signaling. The combined effects of EGFR downregulation, ligand competition, and immune effector function conspire to inhibit tumor growth in xenograft models of cetuximab-resistant BRAF and KRAS mutant cancers. Our designed triepitopic constructs have the potential to enhance the efficacy and expand the scope of EGFR-directed therapies, and our multiepitopic may be readily applied to other receptor targets to formulate a new class of antibody-based therapeutics.National Institutes of Health (U.S.) (Grant CA96504)American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowshi

Multidecadal Climate Variability and the Florescence of Fremont Societies in Eastern Utah

Fremont societies of the Uinta Basin incorporated domesticates into a foraging lifeway over a 1,000-year period from AD 300 to 1300. Fremont research provides a unique opportunity to critically examine the social and ecological processes behind the adoption and abandonment of domesticates by hunter-gatherers. We develop and integrate a 2,115-year precipitation reconstruction with a Bayesian chronological model for the growth of Fremont societies in the Cub Creek reach of Dinosaur National Monument. Comparison of the archaeological chronology with the precipitation record suggests that the florescence of Fremont societies was an adaptation to multidecadal precipitation variability with an approximately 30-plus-year periodicity over most, but not all, of the last 2,115 years. Fremont societies adopted domesticates to enhance their resilience to periodic droughts. We propose that reduced precipitation variability from AD 750 to AD 1050, superimposed over consistent mean precipitation availability, was the tipping point that increased maize production, initiated agricultural intensification, and resulted in increased population and development of pithouse communities. Our study develops a multidecadal/multigenerational model within which to evaluate the strategies underwriting the adoption of domesticates by foragers, the formation of Fremont communities, and the inherent vulnerabilities to resource intensification that implicate the eventual dissolution of those communities. Las sociedades de Fremont de la cuenca de Uinta incorporaron a los domesticados en una forma de vida de alimentación durante un período de 1.000 años desde 300–1300 dC. La investigación de Fremont brinda una oportunidad única para examinar críticamente los procesos sociales y ecológicos detrás de la adopción y el abandono de los domésticos por parte de los cazadores-recolectores. Desarrollamos e integramos una reconstrucción de precipitación de 2.115 años con un modelo cronológico Bayesiano para el crecimiento de las sociedades de Fremont en el alcance de Cub Creek del Dinosaur National Monument. La comparación de la cronología arqueológica con el registro de precipitación sugiere que la floración de las sociedades de Fremont fue una adaptación a la variabilidad de precipitación multidecadal con una periodicidad de aproximadamente 30 años en la mayoría, pero no en todos, de los últimos 2.115 años. Las sociedades de Fremont adoptaron domesticados para mejorar su resistencia a las sequías periódicas. Proponemos que la variabilidad reducida de la precipitación desde 750–1050 dC, superpuesta sobre la disponibilidad de precipitación media constante, fue el punto de inflexión que aumentó la producción de maíz, inició la intensificación agrícola y dio como resultado un aumento de la población y el desarrollo de las comunidades de médulas. Nuestro estudio desarrolla un modelo multidecadal/multigeneracional dentro del cual evaluar las estrategias que sustentan la adopción de domesticados por parte de los recolectores, la formación de comunidades de Fremont y las vulnerabilidades inherentes a la intensificación de recursos que implican la eventual disolución de esas comunidades

Alteration of the Canine Metabolome After a 3-Week Supplementation of Cannabidiol (CBD) Containing Treats: An Exploratory Study of Healthy Animals

Despite the increased interest and widespread use of cannabidiol (CBD) in humans and companion animals, much remains to be learned about its effects on health and physiology. Metabolomics is a useful tool to evaluate changes in the health status of animals and to analyze metabolic alterations caused by diet, disease, or other factors. Thus, the purpose of this investigation was to evaluate the impact of CBD supplementation on the canine plasma metabolome. Sixteen dogs (18.2 ± 3.4 kg BW) were utilized in a completely randomized design with treatments consisting of control and 4.5 mg CBD/kg BW/d. After 21 d of treatment, blood was collected ~2 h after treat consumption. Plasma collected from samples was analyzed using CIL/LC-MS-based untargeted metabolomics to analyze amine/phenol- and carbonyl-containing metabolites. Metabolites that differed — fold change (FC) ≥ 1.2 or ≤ 0.83 and false discovery ratio (FDR) ≤ 0.05 — between the two treatments were identified using a volcano plot. Biomarker analysis based on receiver operating characteristic (ROC) curves was performed to identify biomarker candidates (area under ROC ≥ 0.90) of the effects of CBD supplementation. Volcano plot analysis revealed that 32 amine/phenol-containing metabolites and five carbonyl-containing metabolites were differentially altered (FC ≥ 1.2 or ≤ 0.83, FDR ≤ 0.05) by CBD; these metabolites are involved in the metabolism of amino acids, glucose, vitamins, nucleotides, and hydroxycinnamic acid derivatives. Biomarker analysis identified 24 amine/phenol-containing metabolites and 1 carbonyl-containing metabolite as candidate biomarkers of the effects of CBD (area under ROC ≥ 0.90; P \u3c 0.01). Results of this study indicate that 3 weeks of 4.5 mg CBD/kg BW/d supplementation altered the canine metabolome. Additional work is warranted to investigate the physiological relevance of these changes

The Impact of Feeding Cannabidiol (CBD) Containing Treats on Canine Response to a Noise-Induced Fear Response Test

Interest is increasing regarding use of Cannabidiol (CBD) in companion animals due to anecdotal evidence of beneficial behavioral and health effects. The purpose of this investigation was to evaluate the influence of CBD on behavioral responses to fear-inducing stimuli in dogs. Sixteen dogs (18.1 ± 0.2 kg) were utilized in a replicated 4 × 4 Latin square design experiment with treatments arranged in a 2 × 2 factorial, consisting of control, 25 mg CBD, trazodone (100 mg for 10–20 kg BW, 200 mg for 20.1–40 kg BW), and the combination of CBD and trazodone. A fireworks model of noise-induced fear was used to assess CBD effectiveness after 7 d of supplementation. Each test lasted a total of 6 min and consisted of a 3 min environmental habituation phase with no noise and a 3 min noise phase with a fireworks track. Plasma was collected 1 h before, immediately after, and 1 h following testing for cortisol analysis. Behaviors in each 3 min block were video recorded, and heart rate (HR) sensors were fitted for collection of HR and HR variability parameters. Research personnel administering treats and analyzing behavioral data were blinded as to the treatments administered. Data were tested for normality using the UNIVARIATE procedure in SAS, then differences examined using the MIXED procedure with fixed effects of treatment, period, time, and treatment x time interaction. Inactivity duration and HR increased during the first minute of the fireworks track compared with 1 min prior (P \u3c 0.001 and P = 0.011, respectively), indicating the fireworks model successfully generated a fear response. Trazodone lowered plasma cortisol (P \u3c 0.001), which was unaffected by CBD (P = 0.104) or the combination with CBD (P = 0.238). Neither CBD nor trazodone affected the duration of inactivity (P = 0.918 and 0.329, respectively). Trazodone increased time spent with tail relaxed (P = 0.001). CBD tended to increase HR (P = 0.093) and decreased the peak of low- and high-frequency bands (LF and HF, P = 0.011 and 0.022, respectively). These results do not support an anxiolytic effect of CBD in dogs given 1.4 mg CBD/kg BW/d

Feeding Cannabidiol (CBD)-Containing Treats Did Not Affect Canine Daily Voluntary Activity

Growing public interest in the use of cannabidiol (CBD) for companion animals has amplified the need to elucidate potential impacts. The purpose of this investigation was to determine the influence of CBD on the daily activity of adult dogs. Twenty-four dogs (18.0 ± 3.4 kg, 9 months−4 years old) of various mixed breeds were utilized in a randomized complete block design with treatments targeted at 0 and 2.5 mg (LOW) and at 5.0 mg (HIGH) CBD/kg body weight (BW) per day split between two treats administered after twice-daily exercise (0700–0900 and 1,700–1,900 h). Four hours each day [1,000–1,200 h (a.m.) and 1,330–1,530 h (p.m.)] were designated as times when no people entered the kennels, with 2 h designated as Quiet time and the other 2 h as Music time, when calming music played over speakers. Quiet and Music sessions were randomly allotted to daily a.m. or p.m. times. Activity monitors were fitted to dogs\u27 collars for continuous collection of activity data. Data were collected over a 14-day baseline period to establish the activity patterns and block dogs by activity level (high or low) before randomly assigning dogs within each block to treatments. After 7 days of treatment acclimation, activity data were collected for 14 days. Data were examined for differences using the MIXED procedure in SAS including effects of treatment, day, session (Quiet or Music), time of day (a.m. or p.m.), and accompanying interactions. CBD (LOW and HIGH) did not alter the total daily activity points (P = 0.985) or activity duration (P = 0.882). CBD tended (P = 0.071) to reduce total daily scratching compared with the control. Dogs were more active in p.m. sessions than in a.m. sessions (P \u3c 0.001). During the p.m. session, dogs receiving HIGH tended (P = 0.091) to be less active than the control (CON). During the a.m. and p.m. sessions, CBD reduced scratching compared with CON (P = 0.030). CBD did not affect the activity duration during exercise periods (P = 0.143). These results indicate that, when supplemented with up to 4.5 mg CBD/kg BW/day, CBD does not impact the daily activity of adult dogs, but may exert an antipruritic effect

Disorganized Attachment in Infancy: A Review of the Phenomenon and Its Implications for Clinicians and Policy-Makers

Disorganized/Disoriented (D) attachment has seen widespread interest from policy makers, practitioners, and clinicians in recent years. However, some of this interest seems to have been based on some false assumptions that (1) attachment measures can be used as definitive assessments of the individual in forensic/child protection settings and that disorganized attachment (2) reliably indicates child maltreatment, (3) is a strong predictor of pathology, and (4) represents a fixed or static trait of the child, impervious to development or help. This paper summarizes the evidence showing that these four assumptions are false and misleading. The paper reviews what is known about disorganized infant attachment and clarifies the implications of the classification for clinical and welfare practice with children. In particular, the difference between disorganized attachment and attachment disorder is examined, and a strong case is made for the value of attachment theory for supportive work with families and for the development and evaluation of evidence-based caregiving interventions