Creating a National Coalition to Address Tractor Overturn Fatalities.

Tractor overturns continue to be the leading cause of death on U.S. farms. While rollover protective structures (ROPS) are effective in preventing these fatalities, they are underutilized due to a number of barriers. Past programs in the U.S. and abroad have targeted this area of agricultural safety; however, a national program is not yet in place for U.S. farmers. This study seeks to build a national partnership to address tractor overturn fatalities by increasing the number of tractors with ROPS. A diverse, multisector steering committee has been organized and is working together using Whole System in a Room methods. This method brings together partners from nine stakeholder groups to identify and commit to a collaborative solution to the issue

Increases in ROPS Pricing from 2006-2012 and the Impact on ROPS Demand

In 2006, a social marketing campaign was developed to increase the installation of rollover protective structures (ROPS) on unprotected New York tractors. Using data gathered from the program\u27s hotline, the impact of price increases on farmers\u27 interest in ROPS is examined. Pricing data were obtained for all rigid ROPS kits commercially available in the U.S. since 2006. These data were stratified into two groups of ROPS suppliers: (1) tractor manufacturers that sell ROPS for their own tractors, referred to in this study as original equipment manufacturers (OEMs), and (2) aftermarket (AM) ROPS suppliers. The trend in price increases was contrasted with the change in the consumer price index (CPI), the probability of retrofitting within quintiles of cost was estimated, and the increase in ROPS prices over time was plotted The average price increase for a ROPS kit (excluding shipping and installation) over the six years of the study was 23.3% for OEM versus 60.5% for AM (p \u3c 0.0001). Out-of-pocket expenses held steady for OEM versus a six-year increase of $203 for AM (p = 0.098). The probability of a farmer retrofitting dropped monotonically from 66.9% in the lowest ROPS cost quintile to 23% in the highest. If these trends continue, the proportion of inquiries resulting in a ROPS retrofit will fall below 20% by 2020 for AM ROPS. Based on other trends identified in the literature, it is reasonable to assume that decreases in ROPS installation are likely to affect the tractor owners who are most likely to need these safety devices

Creation of the Person-Centered Wellness Home in Older Adults

Background and Objectives: Extending the Patient-Centered Medical Home (PCMH) model into the community may address the poor linkage between medical clinics and underserved communities. Our first of three objectives was to determine if peer leaders and wellness coaches can be the relationship center of wellness care. We evaluated the Self-management Resource Center Small Group Programs (SMRCSGP), plus wellness coaching, as a booster intervention in older adults with chronic diseases. Second, we evaluated the role of personal health records (PHR) prototype as the linkage between the clinic and community. Using input from these two objectives, we lay the groundwork for the Person-centered Wellness Home (PCWH). Research Design and Methods: Participants enrolled from five South Bronx New York City Housing Authority communities. We conducted a pragmatic, randomized controlled trial using two arms (n = 121): (1) SMRCSGP and (2) SMRCSGP plus wellness coaching initiated as a booster after SMRCSGP completion. Adjusted individual growth models compared the slope differences for outcomes. We conducted a social networking analysis on the ties between wellness coaches and participants. PCMH-certified physicians completed in-depth interviews on the PHR prototype. An adaptation from the consensus-workshop model summarized the priority PCWH items. Results: There was an improvement in self-reported physical functioning (2.0 T-score units higher, p = .03) by the wellness coaching group, but the groups did not differ on physical activity. From the social networking analysis, connections were stable over time with wellness-coaches and participants. The Consensus Conference identified eight major components of the PCWH. Discussion and Implications: Wellness coaching post-SMRCSGP was a booster to physical function, an upstream outcome for physical activity. During the Consensus-Conference, community-based prevention marketing and personal navigators for connecting to a PCMH emerged as novel components. This supports future work in training community health workers as peer leaders to provide evidence-based programs and other PCWH components

The Figure Rating Scale as an Index of Weight Status of Women on Videotape

Objective: To determine whether Stunkard's Figure Rating Scale (FRS) is a valid and reliable index of weight status when an unbiased observer assigns the figure ratings of adult women viewed on videotape. Research Methods and Procedures: Seventy‐two women drawn from a community sample participated in a videotaped study in which height and weight were measured. The FRS is a rating scale displaying 9 silhouettes ranging from very thin to very obese. Women were assigned a figure rating “in‐person” by a research assistant (FRS used as a 17‐point scale) and by additional research assistants viewing women only on videotape (FRS used as both a 17‐ and 9‐point scale). Pearson's correlation coefficients were calculated for in‐person figure ratings, mean videotape figure ratings, and BMI. Results: BMI and in‐person figure ratings were highly correlated ( r = 0.91), as were BMI and both mean 17‐point videotape figure ratings and mean 9‐point videotape figure ratings ( r = 0.89 and 0.87, respectively). Inter‐rater agreement for in‐person figure ratings and mean 17‐point videotape figure ratings was 0.86, and agreement between in‐person figure ratings and mean 9‐point videotape figure ratings was 0.82. Discussion: The FRS can be used as an index of women's weight status by an unbiased observer, with subjects viewed in‐person or on videotape.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93750/1/oby.2006.249.pd

Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat

Turoctocog alfa pegol (N8-GP) is a glycoPEGylated human recombinant factor VIII for the treatment of hemophilia A. The safety profile of rFVIII, and polyethylene glycols (PEG) technology, is well-established. Conducting long-term toxicity studies in animals using human proteins can be complicated by anti-drug antibody (ADA) development. To evaluate long-term safety of N8-GP, 26- and 52-week toxicity studies were conducted in immune-deficient rats dosed intravenously every fourth day with 0, 50, 150, 500, or 1200 IU/kg N8-GP. Observations included clinical observations, body weight, ophthalmoscopy, hematology, chemistry, coagulation, urinalysis, toxicokinetics, antibody analysis, and macroscopic/microscopic organ examination. Immunohistochemical staining examined the distribution of PEG in the brain. No adverse test item-related findings were seen and PEG was not detected in the brain. Exposure was confirmed for ~75% of the animals dosed with 500 and 1200 IU/kg N8-GP; the high lower limit of quantification of the bioanalysis assay prevented confirmation of exposure in the lower doses. A small number of animals developed ADAs, and the proportion of animals surviving until scheduled termination was >80%. N8-GP was well tolerated, and the immune-deficient rat proved suitable for testing long-term toxicity of human proteins that are immunogenic in animals

Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat

Turoctocog alfa pegol (N8-GP) is a glycoPEGylated human recombinant factor VIII for the treatment of hemophilia A. The safety profile of rFVIII, and polyethylene glycols (PEG) technology, is well-established. Conducting long-term toxicity studies in animals using human proteins can be complicated by anti-drug antibody (ADA) development. To evaluate long-term safety of N8-GP, 26-and 52-week toxicity studies were conducted in immune-deficient rats dosed intravenously every fourth day with 0, 50, 150, 500, or 1200 IU/kg N8-GP. Observations included clinical observations, body weight, ophthalmoscopy, hematology, chemistry, coagulation, urinalysis, toxicokinetics, antibody analysis, and macroscopic/microscopic organ examination. Immunohistochemical staining examined the distribution of PEG in the brain. No adverse test item-related findings were seen and PEG was not detected in the brain. Exposure was confirmed for ∼75% of the animals dosed with 500 and 1200 IU/kg N8-GP; the high lower limit of quantification of the bioanalysis assay prevented confirmation of exposure in the lower doses. A small number of animals developed ADAs, and the proportion of animals surviving until scheduled termination was >80%. N8-GP was well tolerated, and the immunedeficient rat proved suitable for testing long-term toxicity of human proteins that are immunogenic in animals

A retrospective cohort study of stroke onset: implications for characterizing short term effects from ambient air pollution

<p>Abstract</p> <p>Background</p> <p>Case-crossover studies used to investigate associations between an environmental exposure and an acute health response, such as stroke, will often use the day an individual presents to an emergency department (ED) or is admitted to hospital to infer when the stroke occurred. Similarly, they will use patient's place of residence to assign exposure. The validity of using these two data elements, typically extracted from administrative databases or patient charts, to define the time of stroke onset and to assign exposure are critical in this field of research as air pollutant concentrations are temporally and spatially variable. Our a priori hypotheses were that date of presentation differs from the date of stroke onset for a substantial number of patients, and that assigning exposure to ambient pollution using place of residence introduces an important source of exposure measurement error. The objective of this study was to improve our understanding on how these sources of errors influence risk estimates derived using a case-crossover study design.</p> <p>Methods</p> <p>We sought to collect survey data from stroke patients presenting to hospital EDs in Edmonton, Canada on the date, time, location and nature of activities at onset of stroke symptoms. The daily mean ambient concentrations of NO₂and PM_2.5on the self-reported day of stroke onset was estimated from continuous fixed-site monitoring stations.</p> <p>Results</p> <p>Of the 336 participating patients, 241 were able to recall when their stroke started and 72.6% (95% confidence interval [CI]: 66.9 - 78.3%) experienced stroke onset the same day they presented to the ED. For subjects whose day of stroke onset differed from the day of presentation to the ED, this difference ranged from 1 to 12 days (mean = 1.8; median = 1). In these subjects, there were no systematic differences in assigned pollution levels for either NO₂or PM_2.5when day of presentation rather than day of stroke onset was used. At the time of stroke onset, 89.9% (95% CI: 86.6 - 93.1%) reported that they were inside, while 84.5% (95% CI: 80.6 - 88.4%) reported that for most of the day they were within a 15 minute drive from home. We estimated that due to the mis-specification of the day of stroke onset, the risk of hospitalization for stroke would be understated by 15% and 20%, for NO₂and PM_2.5, respectively.</p> <p>Conclusions</p> <p>Our data suggest that day of presentation and residential location data obtained from administrative records reasonably captures the time and location of stroke onset for most patients. Under these conditions, any associated errors are unlikely to be an important source of bias when estimating air pollution risks in this population.</p

Activation of natural regulatory T cells by IgG Fc-derived peptide Tregitopes

We have identified at least 2 highly promiscuous major histocompatibility complex class II T-cell epitopes in the Fc fragment of IgG that are capable of specifically activating CD4+CD25HiFoxP3+ natural regulatory T cells (nTRegs). Coincubation of these regulatory T-cell epitopes or “Tregitopes” and antigens with peripheral blood mononuclear cells led to a suppression of effector cytokine secretion, reduced proliferation of effector T cells, and caused an increase in cell surface markers associated with TRegs such as FoxP3. In vivo administration of the murine homologue of the Fc region Tregitope resulted in suppression of immune response to a known immunogen. These data suggest that one mechanism for the immunosuppressive activity of IgG, such as with IVIG, may be related to the activity of regulatory T cells. In this model, regulatory T-cell epitopes in IgG activate a subset of nTRegs that tips the resulting immune response toward tolerance rather than immunogenicity

Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes

Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 x 10(-10). Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harboured genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. Four previously reported loci (SCN1A, SCN2A, ANO3 and 12q21.33) were all confirmed. Collectively, the seven novel and four previously reported loci explained 2.8% of the variance in liability to febrile seizures, and the single nucleotide polymorphism heritability based on all common autosomal single nucleotide polymorphisms was 10.8%. GABRG2, SCN1A and SCN2A are well-established epilepsy genes and, overall, we found positive genetic correlations with epilepsies (r(g) = 0.39, P = 1.68 x 10(-4)). Further, we found that higher polygenic risk scores for febrile seizures were associated with epilepsy and with history of hospital admission for febrile seizures. Finally, we found that polygenic risk of febrile seizures was lower in febrile seizure patients with neuropsychiatric disease compared to febrile seizure patients in a general population sample. In conclusion, this largest genetic investigation of febrile seizures to date implicates central fever response genes as well as genes affecting neuronal excitability, including several known epilepsy genes. Further functional and genetic studies based on these findings will provide important insights into the complex pathophysiological processes of seizures with and without fever.Peer reviewe