How informed is declared altruism in clinical trials? A qualitative interview study of patient decision-making about the QUEST trials (Quality of Life after Mastectomy and Breast Reconstruction)

Background Randomised controlled trials (RCTs) often fail to recruit sufficient participants, despite altruism being cited as their motivation. Previous investigations of factors influencing participation decisions have been methodologically limited. This study evaluated how women weigh up different motivations after initially expressing altruism, and explored their understanding of a trial and its alternatives. The trial was the 'Quality of Life after Mastectomy and Breast Reconstruction' (QUEST) trial.Methods Thirty-nine women participated in qualitative interviews 1 month post-surgery. Twenty-seven women (10 trial decliners and 17 acceptors) who spontaneously mentioned 'altruism' were selected for thematic analysis. Verbatim transcripts were coded independently by two researchers. Participants' motivations to accept or decline randomisation were cross-referenced with their understanding of the QUEST trials and the process of randomisation.Results The seven emerging themes were: (1) altruism expressed by acceptors and decliners; (2) overriding personal needs in decliners; (3) pure altruism in acceptors; (4) 'hypothetical altruism' amongst acceptors; (5) weak altruism amongst acceptors; (6) conditional altruism amongst acceptors; and (7) sense of duty to participate. Poor understanding of the trial rationale and its implications was also evident.Conclusions Altruism was a motivating factor for participation in the QUEST randomised controlled trials where the main outcomes comprised quality of life and allocated treatments comprised established surgical procedures. Women's decisions were influenced by their understanding of the trial. Both acceptors and decliners of the trial expressed 'altruism', but most acceptors lacked an obvious treatment preference, hoped for personal benefits regarding a treatment allocation, or did not articulate complete understanding of the trial.Trial registration QUEST A, ISRCTN38846532 ; Date assigned 6 January 2010. QUEST B, ISRCTN92581226 ; Date assigned 6 January 2010

Acute skin toxicity associated with a 1-week schedule of whole breast radiotherapy compared with a standard 3-week regimen delivered in the UK FAST-Forward Trial

BACKGROUND AND PURPOSE: FAST-Forward is a phase 3 clinical trial testing a 1-week course of whole breast radiotherapy against the UK standard 3-week regimen after primary surgery for early breast cancer. Two acute skin toxicity substudies were undertaken to test the safety of the test schedules with respect to early skin reactions. MATERIAL AND METHODS: Patients were randomly allocated to 40Gy/15 fractions (F)/3-weeks, 27Gy/5F/1-week or 26Gy/5F/1-week. Acute breast skin reactions were graded using RTOG (first substudy) and CTCAE criteria v4.03 (second substudy) weekly during treatment and for 4weeks after treatment ended. Primary endpoint was the proportion of patients within each treatment group with grade ⩾3 toxicity (RTOG and CTCAE, respectively) at any time from the start of radiotherapy to 4weeks after completion. RESULTS: 190 and 162 patients were recruited. In the first substudy, evaluable patients with grade 3 RTOG toxicity were: 40Gy/15F 6/44 (13.6%); 27Gy/5F 5/51 (9.8%); 26Gy/5F 3/52 (5.8%). In the second substudy, evaluable patients with grade 3 CTCAE toxicity were: 40Gy/15F 0/43; 27Gy/5F 1/41 (2.4%); 26Gy/5F 0/53. CONCLUSIONS: Acute breast skin reactions with two 1-week schedules of whole breast radiotherapy under test in FAST-Forward were mild

Cryogenic sample exchange NMR probe for magic angle spinning dynamic nuclear polarization

We describe a cryogenic sample exchange system that dramatically improves the efficiency of magic angle spinning (MAS) dynamic nuclear polarization (DNP) experiments by reducing the time required to change samples and by improving long-term instrument stability. Changing samples in conventional cryogenic MAS DNP/NMR experiments involves warming the probe to room temperature, detaching all cryogenic, RF, and microwave connections, removing the probe from the magnet, replacing the sample, and reversing all the previous steps, with the entire cycle requiring a few hours. The sample exchange system described here—which relies on an eject pipe attached to the front of the MAS stator and a vacuum jacketed dewar with a bellowed hole—circumvents these procedures. To demonstrate the excellent sensitivity, resolution, and stability achieved with this quadruple resonance sample exchange probe, we have performed high precision distance measurements on the active site of the membrane protein bacteriorhodopsin. We also include a spectrum of the tripeptide N-f-MLF-OH at 100 K which shows 30 Hz linewidths.National Institute for Biomedical Imaging and Bioengineering (U.S.) (Grant EB-002804)National Institute for Biomedical Imaging and Bioengineering (U.S.) (Grant EB-001960)National Institute for Biomedical Imaging and Bioengineering (U.S.) (Grant EB-001035)National Institute for Biomedical Imaging and Bioengineering (U.S.) (Grant EB-002026)National Institute for Biomedical Imaging and Bioengineering (U.S.) (Grant EB-003151)National Science Foundation (U.S.). Graduate Research Fellowship Progra

Characterizing the vulnerability of frequent emergency department users by applying a conceptual framework: a controlled, cross-sectional study

Background Frequent emergency department (ED) users meet several of the criteria of vulnerability, but this needs to be further examined taking into consideration all vulnerability’s different dimensions. This study aimed to characterize frequent ED users and to define risk factors of frequent ED use within a universal health care coverage system, applying a conceptual framework of vulnerability. Methods A controlled, cross-sectional study comparing frequent ED users to a control group of non-frequent users was conducted at the Lausanne University Hospital, Switzerland. Frequent users were defined as patients with five or more visits to the ED in the previous 12 months. The two groups were compared using validated scales for each one of the five dimensions of an innovative conceptual framework: socio-demographic characteristics; somatic, mental, and risk-behavior indicators; and use of health care services. Independent t-tests, Wilcoxon rank-sum tests, Pearson’s Chi-squared test and Fisher’s exact test were used for the comparison. To examine the -related to vulnerability- risk factors for being a frequent ED user, univariate and multivariate logistic regression models were used. Results We compared 226 frequent users and 173 controls. Frequent users had more vulnerabilities in all five dimensions of the conceptual framework. They were younger, and more often immigrants from low/middle-income countries or unemployed, had more somatic and psychiatric comorbidities, were more often tobacco users, and had more primary care physician (PCP) visits. The most significant frequent ED use risk factors were a history of more than three hospital admissions in the previous 12 months (adj OR:23.2, 95%CI = 9.1-59.2), the absence of a PCP (adj OR:8.4, 95%CI = 2.1-32.7), living less than 5 km from an ED (adj OR:4.4, 95%CI = 2.1-9.0), and household income lower than USD 2,800/month (adj OR:4.3, 95%CI = 2.0-9.2). Conclusions Frequent ED users within a universal health coverage system form a highly vulnerable population, when taking into account all five dimensions of a conceptual framework of vulnerability. The predictive factors identified could be useful in the early detection of future frequent users, in order to address their specific needs and decrease vulnerability, a key priority for health care policy makers. Application of the conceptual framework in future research is warranted

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

Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission.

BACKGROUND AND OBJECTIVE: Congenital myasthenic syndromes are rare inherited disorders characterized by fatigable weakness caused by malfunction of the neuromuscular junction. We performed whole exome sequencing to unravel the genetic aetiology in an English sib pair with clinical features suggestive of congenital myasthenia. METHODS: We used homozygosity mapping and whole exome sequencing to identify the candidate gene variants. Mutant protein expression and function were assessed in vitro and a knockdown zebrafish model was generated to assess neuromuscular junction development. RESULTS: We identified a novel homozygous missense mutation in the SLC25A1 gene, encoding the mitochondrial citrate carrier. Mutant SLC25A1 showed abnormal carrier function. SLC25A1 has recently been linked to a severe, often lethal clinical phenotype. Our patients had a milder phenotype presenting primarily as a neuromuscular (NMJ) junction defect. Of note, a previously reported patient with different compound heterozygous missense mutations of SLC25A1 has since been shown to suffer from a neuromuscular transmission defect. Using knockdown of SLC25A1 expression in zebrafish, we were able to mirror the human disease in terms of variable brain, eye and cardiac involvement. Importantly, we show clear abnormalities in the neuromuscular junction, regardless of the severity of the phenotype. CONCLUSIONS: Based on the axonal outgrowth defects seen in SLC25A1 knockdown zebrafish, we hypothesize that the neuromuscular junction impairment may be related to pre-synaptic nerve terminal abnormalities. Our findings highlight the complex machinery required to ensure efficient neuromuscular function, beyond the proteomes exclusive to the neuromuscular synapse

Resolution and Polarization Distribution in Cryogenic DNP/MAS Experiments

This contribution addresses four potential misconceptions associated with high-resolution dynamic nuclear polarization/magic angle spinning (DNP/MAS) experiments. First, spectral resolution is not generally compromised at the cryogenic temperatures at which DNP experiments are performed. As we demonstrate at a modest field of 9 T (380 MHz [superscript 1]H), 1 ppm linewidths are observed in DNP/MAS spectra of a membrane protein in its native lipid bilayer, and <0.4 ppm linewidths are reported in a crystalline peptide at 85 K. Second, we address the concerns about paramagnetic broadening in DNP/MAS spectra of proteins by demonstrating that the exogenous radical polarizing agents utilized for DNP are distributed in the sample in such a manner as to avoid paramagnetic broadening and thus maintain full spectral resolution. Third, the enhanced polarization is not localized around the polarizing agent, but rather is effectively and uniformly dispersed throughout the sample, even in the case of membrane proteins. Fourth, the distribution of polarization from the electron spins mediated via spin diffusion between [superscript 1]H–[superscript 1]H strongly dipolar coupled spins is so rapid that shorter magnetization recovery periods between signal averaging transients can be utilized in DNP/MAS experiments than in typical experiments performed at ambient temperature.National Institutes of Health (U.S.) (Grant EB002804)National Institutes of Health (U.S.) (Grant EB003151)National Institutes of Health (U.S.) (Grant EB002026)National Institutes of Health (U.S.) (Grant EB001965)National Institutes of Health (U.S.) (Grant EB004866)National Science Foundation (U.S.). Graduate Research Fellowship Progra

DNP Enhanced Frequency-Selective TEDOR Experiments in Bacteriorhodopsin

We describe a new approach to multiple [superscript 13]C–[superscript 15]N distance measurements in uniformly labeled solids, frequency-selective (FS) TEDOR. The method shares features with FS-REDOR and ZF- and BASE-TEDOR, which also provide quantitative [superscript 15]N–[superscript 13]C spectral assignments and distance measurements in U-[[superscript 13]C,[superscript 15]N] samples. To demonstrate the validity of the FS-TEDOR sequence, we measured distances in [U-[superscript 13]C,15N]-asparagine which are in good agreement with other methods. In addition, we integrate high frequency dynamic nuclear polarization (DNP) into the experimental protocol and use FS-TEDOR to record a resolved correlation spectrum of the Arg-[superscript 13]Cγ–[superscript 15]Nε region in [U-[superscript 13]C,15N]-bacteriorhodopsin. We resolve six of the seven cross-peaks expected based on the primary sequence of this membrane protein.National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant Number EB-001960)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant Number EB-002804)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant Number EB-001035)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant Number EB-002026

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