Characteristics of outdoor falls among older people: A qualitative study

Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people

Liposomal delivery of p-ialB and p-omp25 DNA vaccines improves immunogenicity but fails to provide full protection against B. melitensis challenge

BACKGROUND: We have previously demonstrated protective efficacy against B. melitensis using formulations of naked DNA vaccines encoding genes ialB and omp25. The present study was undertaken to further understand the immune response generated by the protective vaccination regimens and to evaluate cationic liposome adsorption as a delivery method to improve vaccine utility. METHODS: The protective efficacy and immunogenicity of vaccines delivered as four doses of naked DNA, a single dose of naked DNA or a single dose of DNA surface adsorbed to cationic liposomes were compared using the BALB/c murine infection model of B. melitensis. Antigen-specific T cells and antibody responses were compared between the various formulations. RESULTS: The four dose vaccination strategy was confirmed to be protective against B. melitensis challenge. The immune response elicited by the various vaccines was found to be dependent upon both the antigen and the delivery strategy, with the IalB antigen favouring CD4+ T cell priming and Omp25 antigen favouring CD8+. Delivery of the p-ialB construct as a lipoplex improved antibody generation in comparison to the equivalent quantity of naked DNA. Delivery of p-omp25 as a lipoplex altered the profile of responsive T cells from CD8+ to CD4+ dominated. Under these conditions neither candidate delivered by single dose naked DNA or lipoplex vaccination methods was able to produce a robust protective effect. CONCLUSIONS: Delivery of the p-omp25 and p-ialB DNA vaccine candidates as a lipoplex was able to enhance antibody production and effect CD4+ T cell priming, but was insufficient to promote protection from a single dose of either vaccine. The enhancement of immunogenicity by lipoplex delivery is a promising step toward improving the practicality of these two candidate vaccines, and suggests that this lipoplex formulation may be of value in situations where improvements to CD4+ responses are required. However, in the case of Brucella vaccine development it is suggested that further modifications to the candidate vaccines and delivery strategies will be required in order to deliver sustained protection

2012 Wild Blueberry Project Reports

The 2012 edition of the Wild Blueberry Project Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Do wild blueberries alleviate risk factors related to the Metabolic Syndrome? 2. Development of effective intervention measures to maintain and improve food safety for wild blueberries 3. Control tactics for blueberry pest insects, 2012 4. Development and implementation of a wild blueberry thrips IPM program, 2012 5. IPM 6. Biology of blueberry and pest insects, 2012 7. Biology of beneficial insects and blueberry pollination, 2012 8. Pesticide residues on lowbush blueberry, 2012 9. Maine wild blueberry –mummy berry research and extension 10. Efficacy of Apogee growth regulator for stimulating rhizome growth into bare spots in wild blueberry fields 11. Velpar by Matrix pre and post-emergence applications - demonstration plots 12. Wild blueberry Extension Education Program in 2012 INPUT SYSTEMS STUDY: 13. Systems approach to improving the sustainability of wild blueberry production, Year Three of a four-year study – experimental design 14. Food safety- Prevalence study of Escherichia coli O157:H7, Listeria monocytogenes and Salmonella spp. on lowbush blueberries (Vaccinium angustifolium) 15. Abundance of insect pest species and natural enemies in lowbush blueberry fields maintained under different management practices 16. Input Systems Study: Systems approach to improving the sustainability of wild blueberry production, Year 3 of a four-year study, disease management results 17. Plant productivity, Year Three of a four-year study 18. Systems approach to improving the sustainability of wild blueberry production, Year Three of a four-year study, weed management results 19. Effects of organic and conventional management systems on the phosphorus solubility of lowbush blueberry barren soils 20. Systems approach to improving sustainability of wild blueberry production – soil health and chemistry measures 21. Evaluation of fungicides for control of mummy berry disease (ancillary study) 22. Systems approach to improving the sustainability of wild blueberry production – Ancillary land-leveling study, Year Two of a four-year study (ancillary study) 23. Pre-emergent combinations of herbicides for weed control in wild blueberry fields – 2012 results from the 2011 trial (ancillary study) 24. Pre-emergent combinations of herbicides for weed control in wild blueberry fields – 2012 trial (ancillary study) 25. Evaluation of herbicides for control of fineleaf sheep fescue for grass control in wild blueberries (ancillary study) 26. Pre-emergence application timing and rate of Alion and Sandea in combination with Velpar or Sinbar on weed control and injury to wild blueberry (ancillary study) 27. Compost and mulch effects on soil health and nutrient dynamics in wild blueberry (ancillary study

The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141801/1/epi13937_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141801/2/epi13937.pd

2016 Wild Blueberry Project Reports

FOOD SCIENCE AND NUTRITION1. Increasing the food safety margin of wild blueberries through improved intervention measures ENTOMOLOGY 2. Control tactics for blueberry pest insects, 2016 3. Pest biology and IPM, 2016 4. Biology of spotted wing drosophila, 2016 5. Biology of blueberry, bees, and blueberry pollination DISEASE MANAGEMENT 6. Research and control of leaf spot diseases 7. Research and control of mummy berry and Botrytis blossom blight 8. Lab and field studies of mummy berry and interactions between the fungus and bees WEED MANAGEMENT 9. Pre-emergence and post-emergence applications of Zeus Prime XC for weed control in wild blueberry fields, 2016 10. Comparisons of Matrix and Callisto in combination with Matrix or Sinbar for weed control in wild blueberry fields, 2016 11. Herbicide combinations with Sinbar WDG to assess efficacy on weed control in wild blueberry 12. Single vs split applications of post-emergent herbicides for spreading dogbane (Apocynum androsaemifolium) control in wild blueberry fields – crop year results 13. Comparison of multiple post-emergence Callisto applications for spreading dogbane (Apocynum androsaemifolium) control in wild blueberry fields 14. Evaluation of spring applications of herbicides targeting red sorrel in wild blueberry fields – crop year 2016 (final report, SCRI ancillary study) 15. Evaluation of spring applications of herbicides targeting red sorrel in wild blueberry fields, 2016-17 EXTENSION 16. Wild Blueberry Extension Education Program in 201

2015 Wild Blueberry Project Reports

FOOD SCIENCE AND NUTRITION 1. Increasing the food safety margin of wild blueberries through improved intervention measures ENTOMOLOGY 2. Control tactics for blueberry pest insects, 2015 3. Pest biology and IPM, 2015 4. Biology of spotted wing drosophila, 2015 5. Biology of blueberry bees, and blueberry pollination DISEASE MANAGEMENT 6. Research and control of mummy berry disease 7. Evaluation of fungicides for control of mummy berry on lowbush blueberry (2015) 8. Evaluation of fungicides for control of leafspot on lowbush blueberry (2015) WEED MANAGEMENT 9. Single vs split applications of post-emergent herbicides for spreading dogbane (Apocynum androsaemifolium) control in wild blueberry fields 10. Evaluation of fall applications of herbicides targeting horseweed in wild blueberry fields 11. Herbicide combinations with Sinbar and Grounded to assess efficacy on weed control in wild blueberry EXTENSION 12. Wild Blueberry Extension Education Program in 2015 INPUT SYSTEMS STUDY – SCRI GRANT PAGE 13. Systems approach to improving the sustainability of wild blueberry production, Year Six of a six-year study – experimental design 14. Systems approach to improving the sustainability of wild blueberry production, Year 6 15. Systems approach to improving the sustainability of wild blueberry production, 2015, Year 6 of a six-year study, disease management results 16. Systems approach to improving the sustainability of wild blueberry production, Year Six of a six-year study, weed management results 17. Systems approach to improving the sustainability of wild blueberry production, preliminary economic comparison for 2014-15 18. Ancillary projects in disease research (ancillary study) 19. Evaluation of fall and spring combinations of preemergence herbicides to prevent weed resistance in wild blueberry fields, 2013-15 (ancillary study) 20. Post-harvest control of red sorrel in a non-crop blueberry field, 2013-2015 - crop year evaluation (ancillary study) 21. Evaluation of spring applications of herbicides targeting red sorrel in wild blueberry fields (ancillary study

2013 Wild Blueberry Project Reports

The 2013 edition of the Wild Blueberry Project Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Development of effective intervention measures to maintain and improve food safety for wild blueberries 2. Do wild blueberries alleviate risk factors related to the Metabolic Syndrome? 3. Wild Blueberry consumption and exercise-induced Oxidative Stress: Inflammatory Response and DNA damage 4. Control tactics for blueberry pest insects, 2013 5. Pesticide residues on wild blueberry, 2013 6. Biology of pest insects and IPM, 2013 7. Biology of blueberry, beneficial insects, and blueberry pollination 8. Biology of spotted wing drosophila, 2013 9. Maine wild blueberry –mummy berry research and extension 10. Evaluation of fungicides for control of mummy berry on lowbush blueberry (2013) 11. Wild blueberry Extension Education Program in 2013 INPUT SYSTEMS STUDY: 12. Systems approach to improving the sustainability of wild blueberry production, Year Four of a four-year study – experimental design 13. Food safety- Prevalence study of Escherichia coli O157:H7, Listeria monocytogenes and Salmonella spp. on lowbush blueberries (Vaccinium angustifolium) 14. Agronomic input effects on sensory quality and chemical composition of wild Maine blueberries 15. Systems approach to improving the sustainability of wild blueberry production, Year four of a four-year study – reports from Frank Drummond 16. Systems approach to improving the sustainability of wild blueberry production, Year 4 of a four-year study, disease management results 17. Systems approach to improving the sustainability of wild blueberry production, Year Four of a four-year study, weed management results 18. Phosphorus and organic matter interactions on short-range ordered minerals in acidic barren soils 19. Systems approach to improving the sustainability of wild blueberry production, preliminary economic comparison for 2012-13 20. Ancillary projects in disease research (ancillary study) 21. Systems approach to improving the sustainability of wild blueberry production – Ancillary land-leveling study, Year Three of a four-year study (ancillary study) 22. Pre-emergent combinations of herbicides for weed control in wild blueberry fields – 2013 results from the 2012 trial (ancillary study) 23. Evaluation of herbicides for 2012 prune year control of fineleaf sheep fescue in wild blueberries – 2013 crop year results (ancillary study) 24. 2012 pre-emergence application timing and rate of Alion and Sandea in combination with Velpar or Sinbar – 2013 yields (ancillary study) 25. Pre-emergence Sinbar combinations for weed control in a non-crop wild blueberry field – 2012-2014 (ancillary study) 26. Evaluation of three pre-emergence herbicides alone and in combination with Velpar or Sinbar for effects on wild blueberry productivity and weed control (ancillary study) 27. Post-harvest control of red sorrel in a non-crop blueberry field, 2012-2014 (ancillary study) 28. Compost and mulch effects on soil health and nutrient dynamics in wild blueberry (ancillary study) 29. Evaluation of conventional and organic fertilizers on blueberry growth and yield (ancillary study

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Evaluation of Competitive ELISA for Detection of Antibodies to Brucella Infection in Domestic Animals

Aim To evaluate competitive enzyme-linked immunosorbent assay (cELISA) for its suitability as an additional serological test for the diagnosis of animal brucellosis. Methods cELISA, which was developed at the Veterinary Laboratories Agency, has been evaluated for its accuracy and suitability as an additional serological test for the diagnosis of animal brucellosis. Samples from naturally and experimentally infected animals and those from Brucella-free flocks and herds were tested. Results Data obtained since 1991 were analyzed from routine surveillance, animals experimentally infected with Brucella, and stored sera to validate cELISA for the detection of antibodies to Brucella in cows, small ruminants, and pigs. The sensitivity of the test ranged from 92.31% to 100%, in comparison with 77.14% to 100% for the complement fixation test (CFT). Specificities for cELISA, indirect enzymelinked immunosorbent assay, and CFT were greater than 90%. Conclusion cELISA can be used on a variety of animal species, and an added advantage is its suitability for use on poor-quality samples such as those affected by hemolysis