Prostate Intrafraction Translation Margins for Real-Time Monitoring and Correction Strategies

The purpose of this work is to determine appropriate radiation therapy beam margins to account for intrafraction prostate translations for use with real-time electromagnetic position monitoring and correction strategies. Motion was measured continuously in 35 patients over 1157 fractions at 5 institutions. This data was studied using van Herk's formula of (αΣ + γσ') for situations ranging from no electromagnetic guidance to automated real-time corrections. Without electromagnetic guidance, margins of over 10 mm are necessary to ensure 95% dosimetric coverage while automated electromagnetic guidance allows the margins necessary for intrafraction translations to be reduced to submillimeter levels. Factors such as prostate deformation and rotation, which are not included in this analysis, will become the dominant concerns as margins are reduced. Continuous electromagnetic monitoring and automated correction have the potential to reduce prostate margins to 2-3 mm, while ensuring that a higher percentage of patients (99% versus 90%) receive a greater percentage (99% versus 95%) of the prescription dose

Fungi isolated from cultured eggs, alevins and broodfish of brown trout in a hatchery affected by saprolegniosis

P. 510-518The aquatic fungi cultured from eggs, alevins and broodfish of brown trout Salmo trutta belonged to the genus Saprolegnia and were identified as S. diclina, S. australis, S. ferax, S. furcata, S. hypogyna, S. unispora and S. parasitica. The species obtained from infected eggs and alevins were different to those from infected fish. Several Saprolegnia species were isolated from eggs and alevins, whereas all the isolates obtained from broodfish were the pathogenic S. parasitica.S

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Comparing genotyping algorithms for Illumina's Infinium whole-genome SNP BeadChips

The Brassica napus 60K Illumina Infinium™ SNP array has had huge international uptake in the rapeseed community due to the revolutionary speed of acquisition and ease of analysis of this high-throughput genotyping data, particularly when coupled with the newly available reference genome sequence. However, further utilization of this valuable resource can be optimized by better understanding the promises and pitfalls of SNP arrays. We outline how best to analyze Brassica SNP marker array data for diverse applications, including linkage and association mapping, genetic diversity and genomic introgression studies. We present data on which SNPs are locus-specific in winter, semi-winter and spring B. napus germplasm pools, rather than amplifying both an A-genome and a C-genome locus or multiple loci. Common issues that arise when analyzing array data will be discussed, particularly those unique to SNP markers and how to deal with these for practical applications in Brassica breeding applications

The effect of timing and frequency of push notifications on usage of a smartphone-based stress management intervention: An exploratory trial

Push notifications offer a promising strategy for enhancing engagement with smartphone-based health interventions. Intelligent sensor-driven machine learning models may improve the timeliness of notifications by adapting delivery to a user's current context (e.g. location). This exploratory mixed-methods study examined the potential impact of timing and frequency on notification response and usage of Healthy Mind, a smartphone-based stress management intervention. 77 participants were randomised to use one of three versions of Healthy Mind that provided: intelligent notifications; daily notifications within pre-defined time frames; or occasional notifications within pre-defined time frames. Notification response and Healthy Mind usage were automatically recorded. Telephone interviews explored participants' experiences of using Healthy Mind. Participants in the intelligent and daily conditions viewed (d = .47, .44 respectively) and actioned (d = .50, .43 respectively) more notifications compared to the occasional group. Notification group had no meaningful effects on percentage of notifications viewed or usage of Healthy Mind. No meaningful differences were indicated between the intelligent and non-intelligent groups. Our findings suggest that frequent notifications may encourage greater exposure to intervention content without deterring engagement, but adaptive tailoring of notification timing does not always enhance their use. Hypotheses generated from this study require testing in future work. Trial registration number: ISRCTN67177737 © 2017 Morrison et al

Decision aids for respite service choices by carers of people with dementia: development and pilot RCT

<p>Abstract</p> <p>Background</p> <p>Decision aids are often used to assist individuals confronted with a diagnosis of a serious illness to make decisions about treatment options. However, they are rarely utilised to help those with chronic or age related conditions to make decisions about care services. Decision aids should also be useful for carers of people with decreased decisional capacity. These carers' choices must balance health outcomes for themselves and for salient others with relational and value-based concerns, while relying on information from health professionals. This paper reports on a study that both developed and pilot tested a decision aid aimed at assisting carers to make evaluative judgements of community services, particularly respite care.</p> <p>Methods</p> <p>A mixed method sequential study, involving qualitative development and a pilot randomised controlled trial, was conducted in Tasmania, Australia. We undertook 13 semi-structured interviews and three focus groups to inform the development of the decision aid. For the randomised control trial we randomly assigned 31 carers of people with dementia to either receive the service decision aid at the start or end of the study. The primary outcome was measured by comparing the difference in carer burden between the two groups three months after the intervention group received the decision aid. Pilot data was collected from carers using interviewer-administered questionnaires at the commencement of the project, two weeks and 12 weeks later.</p> <p>Results</p> <p>The qualitative data strongly suggest that the intervention provides carers with needed decision support. Most carers felt that the decision aid was useful. The trial data demonstrated that, using the mean change between baseline and three month follow-up, the intervention group had less increase in burden, a decrease in decisional conflict and increased knowledge compared to control group participants.</p> <p>Conclusions</p> <p>While these results must be interpreted with caution due to the small sample size, all intervention results trend in a direction that is beneficial for carers and their decisional ability. Mixed method data suggest the decision aid provides decisional support that carers do not otherwise receive. Decision aids may prove useful in a community health services context.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN32163031">ISRCTN32163031</a></p

Non-Raft AC2 Defines a cAMP Signaling Compartment That Selectively Regulates IL-6 Expression in Airway Smooth Muscle Cells

Adenylyl cyclase (AC) isoforms differ in their tissue distribution, cellular localization, regulation, and protein interactions. Most cell types express multiple AC isoforms. We hypothesized that cAMP produced by different AC isoforms regulates unique cellular responses in human bronchial smooth muscle cells (BSMC). Overexpression of AC2, AC3, or AC6 had distinct effects on forskolin (Fsk)-induced expression of a number of known cAMP-responsive genes. These data show that different AC isoforms can differentially regulate gene expression. Most notable, overexpression and activation of AC2 enhanced interleukin 6 (IL-6) expression, but overexpression of AC3 or AC6 had no effect. IL-6 production by BSMC was induced by Fsk and select G protein-coupled receptor (GPCR) agonists, though IL-6 levels did not directly correlate with global cAMP levels. Treatment with PKA selective 6-Bnz-cAMP or Epac selective 8-CPT-2Me-cAMP cAMP analogs revealed a predominant role for PKA in cAMP-mediated induction of IL-6. IL-6 promoter mutations demonstrated that AP-1 and CRE transcription sites were required for Fsk to stimulate IL-6 expression. Our present study defines an AC2 cAMP signaling compartment that specifically regulates IL-6 expression in BSMC via Epac and PKA and demonstrates that other AC isoforms are excluded from this pool

Relapse patterns in NMOSD: evidence for earlier occurrence of optic neuritis and possible seasonal variation

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) show overlap in their clinical features. We performed an analysis of relapses with the aim of determining differences between the two conditions. Cases of NMOSD and age- and sex-matched MS controls were collected from across Australia and New Zealand. Demographic and clinical information, including relapse histories, were recorded using a standard questionnaire. There were 75 cases of NMOSD and 101 MS controls. There were 328 relapses in the NMOSD cases and 375 in MS controls. Spinal cord and optic neuritis attacks were the most common relapses in both NMOSD and MS. Optic neuritis (p P = 0.002) were more common in NMOSD and other brainstem attacks were more common in MS (p P = 0.065). Optic neuritis and transverse myelitis are the most common types of relapse in NMOSD and MS. Optic neuritis tends to occur more frequently in NMOSD prior to the age of 30, with transverse myelitis being more common thereafter. Relapses in NMOSD were more severe. A seasonal bias for relapses in spring-summer may exist in NMOSD

Ecologically Appropriate Xenobiotics Induce Cytochrome P450s in Apis mellifera

BACKGROUND: Honey bees are exposed to phytochemicals through the nectar, pollen and propolis consumed to sustain the colony. They may also encounter mycotoxins produced by Aspergillus fungi infesting pollen in beebread. Moreover, bees are exposed to agricultural pesticides, particularly in-hive acaricides used against the parasite Varroa destructor. They cope with these and other xenobiotics primarily through enzymatic detoxificative processes, but the regulation of detoxificative enzymes in honey bees remains largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: We used several approaches to ascertain effects of dietary toxins on bee susceptibility to synthetic and natural xenobiotics, including the acaricide tau-fluvalinate, the agricultural pesticide imidacloprid, and the naturally occurring mycotoxin aflatoxin. We administered potential inducers of cytochrome P450 enzymes, the principal biochemical system for Phase 1 detoxification in insects, to investigate how detoxification is regulated. The drug phenobarbital induces P450s in many insects, yet feeding bees with phenobarbital had no effect on the toxicity of tau-fluvalinate, a pesticide known to be detoxified by bee P450s. Similarly, no P450 induction, as measured by tau-fluvalinate tolerance, occurred in bees fed xanthotoxin, salicylic acid, or indole-3-carbinol, all of which induce P450s in other insects. Only quercetin, a common pollen and honey constituent, reduced tau-fluvalinate toxicity. In microarray comparisons no change in detoxificative gene expression was detected in phenobarbital-treated bees. However, northern blot analyses of guts of bees fed extracts of honey, pollen and propolis showed elevated expression of three CYP6AS P450 genes. Diet did not influence tau-fluvalinate or imidacloprid toxicity in bioassays; however, aflatoxin toxicity was higher in bees consuming sucrose or high-fructose corn syrup than in bees consuming honey. CONCLUSIONS/SIGNIFICANCE: These results suggest that regulation of honey bee P450s is tuned to chemicals occurring naturally in the hive environment and that, in terms of toxicological capacity, a diet of sugar is not equivalent to a diet of honey