Spousal Support for Patients With Rheumatoid Arthritis:Getting the Wrong Kind Is a Pain

Research indicates that perceived support availability is beneficial, with support available from the spouse particularly important for well-being. However, actual support mobilization has shown mixed associations with recipient well-being. The primary goal of the present study was to go beyond examining the effects of global perceptions of support on recipient outcomes. Instead, we examined the effects of several specific types of support that have been found to be important in the clinical literature. In this study, we followed both members of couples in which one partner was diagnosed with rheumatoid arthritis. Patients provided reports on pain for both mornings and evenings across 1 week. Both partners also reported esteem, solicitous, and negative support mobilization received by the patient. We found that patient pain tended to increase across the day following increases in patient reports of negative support receipt and partner reports of solicitous support provision. We also found that patient pain tended to decrease across the day when partners reported increased levels of esteem support provision. Reverse causation analyses indicated higher levels of patient pain may lead partners to increase solicitous support mobilization to the patient. Findings underscore the importance of examining both partners' reports of support within a dyadic coping framework. They further suggest that not all forms of support are equally beneficial, calling for a finer grained assessment of specific support transactions

Androgen Receptor Modulation Optimized for Response (ARMOR) Phase I and II Studies: Galeterone for the Treatment of Castration-Resistant Prostate Cancer

Purpose: Galeterone is a selective, multitargeted agent that inhibits CYP17, antagonizes the androgen receptor (AR), and reduces AR expression in prostate cancer cells by causing an increase in AR protein degradation. These open-label phase I and II studies [Androgen Receptor Modulation Optimized for Response-1 (ARMOR1) and ARMOR2 part 1] evaluated the efficacy and safety of galeterone in patients with treatment-naive nonmetastatic or metastatic castration-resistant prostate cancer (CRPC) and established a dose for further study. Experimental Design: In ARMOR1, 49 patients received increasing doses (650–2,600 mg) of galeterone in capsule formulation; 28 patients in ARMOR2 part 1 received increasing doses (1,700–3,400 mg) of galeterone in tablet formulation for 12 weeks. Patients were evaluated biweekly for safety and efficacy, and pharmacokinetic parameters were assessed. Results: In ARMOR1, across all doses, 49.0% (24/49) achieved a ≥30% decline in prostate-specific antigen (PSA; PSA30) and 22.4% (11/49) demonstrated a ≥50% PSA decline (PSA50). In ARMOR2 part 1, across all doses, PSA30 was 64.0% (16/25) and PSA50 was 48.0% (12/25). In the 2,550-mg dose cohort, PSA30 was 72.7% (8/11) and PSA50 was 54.5% (6/11). Galeterone was well tolerated; the most common adverse events were fatigue, increased liver enzymes, gastrointestinal events, and pruritus. Most were mild or moderate in severity and required no action and there were no apparent mineralocorticoid excess (AME) events. Conclusions: The efficacy and safety from ARMOR1 and ARMOR2 part 1 and the pharmacokinetic results support the galeterone tablet dose of 2,550 mg/d for further study. Galeterone was well tolerated and demonstrated pharmacodynamic changes consistent with its selective, multifunctional AR signaling inhibition

Teaching and learning about dementia in UK medical schools: a national survey

Background: Dementia is an increasingly common condition and all doctors, in both primary and secondary care environments, must be prepared to competently manage patients with this condition. It is unclear whether medical education about dementia is currently fit for purpose. This project surveys and evaluates the nature of teaching and learning about dementia for medical students in the UK. Methods: Electronic questionnaire sent to UK medical schools. Results: 23/31 medical schools responded. All provided some dementia-specific teaching but this focussed more on knowledge and skills than behaviours and attitudes. Only 80% of schools described formal assessment of dementia-specific learning outcomes. There was a widespread failure to adequately engage the multidisciplinary team, patients and carers in teaching, presenting students with a narrow view of the condition. However, some innovative approaches were also highlighted. Conclusions: Although all schools taught about dementia, the deficiencies identified represent a failure to sufficiently equip medical students to care for patients with dementia which, given the prevalence of the condition, does not adequately prepare them for work as doctors. Recommendations for improving undergraduate medical education about dementia are outline

2000 Wild Blueberry Project Reports

The 2000 edition of the Wild Blueberry Project Reports was prepared for the Maine Wild Blueberry Commission and the University of Maine Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Determination of Pesticide Residue Levels in Fresh and Processed Wild Blueberries 2. Factors Affecting the Microbiological Quality of IQF Blueberries 3. Effect of Processed Blueberry Products on Oxidation in Meat Based Food Systems 4. Separation of Maggot Infested Wild Blueberries in the IQF Processing Line 5. Water Use of Wild Blueberries 6. Control Tactics for Blueberry Pest Insects, 2000 7. IPM Strategies 8. Biology and Ecology of Blueberry Pest Insects 9. Survey of Stem Blight and Leaf Spot Diseases in Lowbush Blueberry Fields 10. Phosphorus/Nitrogen Fertilizer Ratio 11. Effect of Boron Application Methods on Boron Uptake in Lowbush Blueberries 12. Effect of Foliar Iron and Copper Application on Growth and Yield of Lowbush Blueberries 13. Effect of Soil pH on Nutrient Uptake 14. Effect of Nutri-Phite (tm) P+K on Growth and Yield of Lowbush Blueberry 15. Effect of Fertilizer Timing on Lowbush Blueberry Growth and Productivity 16. Assessment of Azafenidin for Weed Control in Wild Blueberries 17. Assessment of Rimsulfuron for Weed Control in Wild Blueberries 18. Assessment of Pendimethalin for Weed Control in Wild Blueberries 19. Assessment of VC1447 for Weed Control in Wild Blueberries 20. Cultural Management Using pH for Weed Control in Wild Blueberries 21. Evaluation of Sprout-Less Weeder® for Weed Control in Wild Blueberries 22. Evaluation of RoundUp Ultra® and Touchdown 5® for Weed Control in Wild Blueberries 23. Evaluation and Demonstration of Techniques for Filling in Bare Spots in Wild Blueberry Fields 24. Evaluation of Fungicides Efficacy in Wild Blueberry Fields 25. Velpar® and Sinbar/Karmex® Demonstration Plot Comparison Trial 26. Blueberry Extension Education Program in 2000 27. 2000 Hexazinone Groundwater Surve

Managing small-acreage horse farms in central and eastern Oregon

Some good goals for a well-managed, small-acreage horse farm are: • A productive pasture with plenty of grass and few weeds • Less dust during the dry season and less mud during the wet season • Healthy horses free of problems associated with dust, manure, mud, and toxic plants • Manure managed as an important resource on the farm or recycled off the farm • Good stewardship of your property and the water that flows through, across, and below it • Satisfied owners who are able to conveniently care for their animals without dreading the chorePublished November 2007. Reviewed December 2013. Please look for up-to-date information in the OSU Extension Catalog: http://extension.oregonstate.edu/catalo

Severity of Retinopathy Parallels the Degree of Parasite Sequestration in the Eyes and Brains of Malawian Children With Fatal Cerebral Malaria

Background. Malarial retinopathy (MR) has diagnostic and prognostic value in children with Plasmodium falciparum cerebral malaria (CM). A clinicopathological correlation between observed retinal changes during life and the degree of sequestration of parasitized red blood cells was investigated in ocular and cerebral vessels at autopsy. Methods. In 18 Malawian children who died from clinically defined CM, we studied the intensity of sequestration and the maturity of sequestered parasites in the retina, in nonretinal ocular tissues, and in the brain. Results. Five children with clinically defined CM during life had other causes of death identified at autopsy, no MR, and scanty intracerebral sequestration. Thirteen children had MR and died from CM. MR severity correlated with percentage of microvessels parasitized in the retina, brain, and nonretinal tissues with some neuroectodermal components (all P < .01). In moderate/severe MR cases (n = 8), vascular congestion was more intense (ρ = 0.841; P < .001), sequestered parasites were more mature, and the quantity of extraerythrocytic hemozoin was higher, compared with mild MR cases (n = 5). Conclusions. These data provide a histopathological basis for the known correlation between degrees of retinopathy and cerebral dysfunction in CM. In addition to being a valuable tool for clinical diagnosis, retinal observations give important information about neurovascular pathophysiology in pediatric CM

The Bifidobacterium dentium Bd1 Genome Sequence Reflects Its Genetic Adaptation to the Human Oral Cavity

Bifidobacteria, one of the relatively dominant components of the human intestinal microbiota, are considered one of the key groups of beneficial intestinal bacteria (probiotic bacteria). However, in addition to health-promoting taxa, the genus Bifidobacterium also includes Bifidobacterium dentium, an opportunistic cariogenic pathogen. The genetic basis for the ability of B. dentium to survive in the oral cavity and contribute to caries development is not understood. The genome of B. dentium Bd1, a strain isolated from dental caries, was sequenced to completion to uncover a single circular 2,636,368 base pair chromosome with 2,143 predicted open reading frames. Annotation of the genome sequence revealed multiple ways in which B. dentium has adapted to the oral environment through specialized nutrient acquisition, defences against antimicrobials, and gene products that increase fitness and competitiveness within the oral niche. B. dentium Bd1 was shown to metabolize a wide variety of carbohydrates, consistent with genome-based predictions, while colonization and persistence factors implicated in tissue adhesion, acid tolerance, and the metabolism of human saliva-derived compounds were also identified. Global transcriptome analysis demonstrated that many of the genes encoding these predicted traits are highly expressed under relevant physiological conditions. This is the first report to identify, through various genomic approaches, specific genetic adaptations of a Bifidobacterium taxon, Bifidobacterium dentium Bd1, to a lifestyle as a cariogenic microorganism in the oral cavity. In silico analysis and comparative genomic hybridization experiments clearly reveal a high level of genome conservation among various B. dentium strains. The data indicate that the genome of this opportunistic cariogen has evolved through a very limited number of horizontal gene acquisition events, highlighting the narrow boundaries that separate commensals from opportunistic pathogens

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.

UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.The Breast Cancer Association Consortium (BCAC), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), and the Ovarian Cancer Association Consortium (OCAC) that contributed breast, prostate, and ovarian cancer data analyzed in this study were in part funded by Cancer Research UK [C1287/A10118 and C1287/A12014 for BCAC; C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, and C16913/A6135 for PRACTICAL; and C490/A6187, C490/A10119, C490/A10124, C536/A13086, and C536/A6689 for OCAC]. Funding for the Collaborative Oncological Gene-environment Study (COGS) infrastructure came from: the European Community's Seventh Framework Programme under grant agreement number 223175 (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the US National Institutes of Health (CA128978) and the Post-Cancer GWAS Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112), the US Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund [with donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07)]. Additional financial support for contributing studies is documented under Supplementary Financial Support.This is the author accepted manuscript. The final version is available from the American Association for Cancer Research via http://dx.doi.org/10.1158/2159-8290.CD-15-122