Tumor Necrosis Factor Receptor Superfamily, Member 1B Haplotypes Increase or Decrease the Risk of Inflammatory Bowel Diseases in a New Zealand Caucasian Population

Inflammatory bowel diseases (IBDs) comprising Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions with polygenic susceptibility. Interactions between TNF-alpha and TNF-alpha receptor play a fundamental role in inflammatory response. This study investigates the role that selected single nucleotide polymorphisms (SNPs) and haplotypes in the TNF-alpha receptor (TNSFRSF1B) gene play in the risk of IBD in a New Zealand Caucasian population. DNA samples from 388 CD, 405 UC, 27 indeterminate colitis patients, and 293 randomly selected controls, from Canterbury, New Zealand were screened for 3 common SNPs in TNSFRSF1B: rs1061622 (c.676T > C), rs1061624 (c.*1663A > G), and rs3397 (c.*1690T > C), using TaqMan technologies. Carrying the rs1061624 variant decreased the risk of UC in the left colon (OR 0.73, 95% CI = 0.54–1.00) and of being a smoker at diagnosis (OR 0.62; 95% CI = 0.40–0.96). Carrying the rs3397 variant decreased the risk of penetrating CD (OR 0.62, 95% CI = 0.40–0.95). Three marker haplotype analyses revealed highly significant differences between CD patients and control subjects (χ2 = 29.9, df = 7, P = .0001) and UC cases and controls (χ2 = 46.3, df = 7, P < .0001). We conclude that carrying a 3-marker haplotype in the TNSFRSF1B gene may increase (e.g., haplotype of GGC was 2.9-fold more in the CD or UCpatients) or decrease (e.g., TGT was 0.47-fold less in UC patients) the risk of IBD in a New Zealand Caucasian population

Nucleotide-binding oligomerization domain containing 1 (NOD1) haplotypes and single nucleotide polymorphisms modify susceptibility to inflammatory bowel diseases in a New Zealand caucasian population: a case-control study

<p>Abstract</p> <p>Background</p> <p>The nucleotide-binding oligomerization domain containing 1 (<it>NOD1</it>) gene encodes a pattern recognition receptor that senses pathogens, leading to downstream responses characteristic of innate immunity. We investigated the role of <it>NOD1 </it>single nucleotide polymorphisms (SNPs) on IBD risk in a New Zealand Caucasian population, and studied Nod1 expression in response to bacterial invasion in the Caco2 cell line.</p> <p>Findings</p> <p>DNA samples from 388 Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis patients and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common SNPs in <it>NOD1</it>, using the MassARRAY^®iPLEX Gold assay. Transcriptional activation of the protein produced by <it>NOD1 </it>(Nod1) was studied after infection of Caco2 cells with <it>Escherichia coli </it>LF82. Carrying the rs2075818 G allele decreased the risk of CD (OR = 0.66, 95% CI = 0.50–0.88, p < 0.002) but not UC. There was an increased frequency of the three SNP (rs2075818, rs2075822, rs2907748) haplotype, CTG (p = 0.004) and a decreased frequency of the GTG haplotype (p = 0.02).in CD. The rs2075822 CT or TT genotypes were at an increased frequency (genotype p value = 0.02), while the rs2907748 AA or AG genotypes showed decreased frequencies in UC (p = 0.04), but not in CD. Functional assays showed that Nod1 is produced 6 hours after bacterial invasion of the Caco2 cell line.</p> <p>Conclusion</p> <p>The <it>NOD1 </it>gene is important in signalling invasion of colonic cells by pathogenic bacteria, indicative of its' key role in innate immunity. Carrying specific SNPs in this gene significantly modifies the risk of CD and/or UC in a New Zealand Caucasian population.</p

Tumor Necrosis Factor Receptor Superfamily, Member 1B Haplotypes Increase or Decrease the Risk of Inflammatory Bowel Diseases in a New Zealand Caucasian Population

Inflammatory bowel diseases (IBDs) comprising Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions with polygenic susceptibility. Interactions between TNF-alpha and TNF-alpha receptor play a fundamental role in inflammatory response. This study investigates the role that selected single nucleotide polymorphisms (SNPs) and haplotypes in the TNF-alpha receptor (TNSFRSF1B) gene play in the risk of IBD in a New Zealand Caucasian population. DNA samples from 388 CD, 405 UC, 27 indeterminate colitis patients, and 293 randomly selected controls, from Canterbury, New Zealand were screened for 3 common SNPs in TNSFRSF1B: rs1061622 (c.676T > C), rs1061624 (c.*1663A > G), and rs3397 (c.*1690T > C), using TaqMan technologies. Carrying the rs1061624 variant decreased the risk of UC in the left colon (OR 0.73, 95% CI = 0.54–1.00) and of being a smoker at diagnosis (OR 0.62; 95% CI = 0.40–0.96). Carrying the rs3397 variant decreased the risk of penetrating CD (OR 0.62, 95% CI = 0.40–0.95). Three marker haplotype analyses revealed highly significant differences between CD patients and control subjects (χ2 = 29.9, df = 7, P = .0001) and UC cases and controls (χ2 = 46.3, df = 7, P < .0001). We conclude that carrying a 3-marker haplotype in the TNSFRSF1B gene may increase (e.g., haplotype of GGC was 2.9-fold more in the CD or UCpatients) or decrease (e.g., TGT was 0.47-fold less in UC patients) the risk of IBD in a New Zealand Caucasian population

Correlation Between Trough Plasma Dabigatran Concentrations and Estimates of Glomerular Filtration Rate Based on Creatinine and Cystatin C

AIMS: Dabigatran is largely cleared by renal excretion. Renal function is thus a major determinant of trough dabigatran concentrations, which correlate with the risk of thromboembolic and haemorrhagic outcomes. Current dabigatran dosing guidelines use the Cockcroft–Gault (CG) equation to gauge renal function, instead of contemporary equations including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations employing creatinine (CKD-EPI_Cr), cystatin C (CKD-EPI_Cys) and both renal biomarkers (CKD-EPI_CrCys). METHODS: A linear regression model including the dabigatran etexilate maintenance dose rate, relevant interacting drugs and genetic polymorphisms (including CES1), was used to analyse the relationship between the values from each renal function equation and trough steady-state plasma dabigatran concentrations. RESULTS: The median dose-corrected trough steady-state plasma dabigatran concentration in 52 patients (38–94 years) taking dabigatran etexilate was 60 µg/L (range 9–279). The dose-corrected trough concentration in a patient on phenytoin and phenobarbitone was >3 standard deviations below the cohort mean. The CG, CKD-EPI_Cr, CKD-EPI_Cys and CKD-EPI_CrCys equations explained (R(2), 95 % CI) 32 % (9–55), 37 % (12–60), 41 % (16–64) and 47 % (20–69) of the variability in dabigatran concentrations between patients, respectively. One-way analysis of variance (ANOVA) comparing the R(2) values for each equation was not statistically significant (p = 0.74). DISCUSSION: Estimates of renal function using the four equations accounted for 32–47 % of the variability in dabigatran concentrations between patients. We are the first to provide evidence that co-administration of phenytoin/phenobarbitone with dabigatran etexilate is associated with significantly reduced dabigatran exposure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40268-014-0045-9) contains supplementary material, which is available to authorized users

The scratch test for identifying the lower liver edge is at least as accurate as percussion and is significantly more effective for young trainees-a randomised comparative trial

BACKGROUND: Clinical examination of the liver requires experience to achieve accuracy. The scratch test is a simple technique to identify the lower liver edge and enhance liver palpation, and may be easier for trainees

The real-world problem of care coordination: a longitudinal qualitative study with patients living with advanced progressive illness and their unpaid caregivers.

OBJECTIVES: To develop a model of care coordination for patients living with advanced progressive illness and their unpaid caregivers, and to understand their perspective regarding care coordination. DESIGN: A prospective longitudinal, multi-perspective qualitative study involving a case-study approach. METHODS: Serial in-depth interviews were conducted, transcribed verbatim and then analyzed through open and axial coding in order to construct categories for three cases (sites). This was followed by continued thematic analysis to identify underlying conceptual coherence across all cases in order to produce one coherent care coordination model. PARTICIPANTS: Fifty-six purposively sampled patients and 27 case-linked unpaid caregivers. SETTINGS: Three cases from contrasting primary, secondary and tertiary settings within Britain. RESULTS: Coordination is a deliberate cross-cutting action that involves high-quality, caring and well-informed staff, patients and unpaid caregivers who must work in partnership together across health and social care settings. For coordination to occur, it must be adequately resourced with efficient systems and services that communicate. Patients and unpaid caregivers contribute substantially to the coordination of their care, which is sometimes volunteered at a personal cost to them. Coordination is facilitated through flexible and patient-centered care, characterized by accurate and timely information communicated in a way that considers patients' and caregivers' needs, preferences, circumstances and abilities. CONCLUSIONS: Within the midst of advanced progressive illness, coordination is a shared and complex intervention involving relational, structural and information components. Our study is one of the first to extensively examine patients' and caregivers' views about coordination, thus aiding conceptual fidelity. These findings can be used to help avoid oversimplifying a real-world problem, such as care coordination. Avoiding oversimplification can help with the development, evaluation and implementation of real-world coordination interventions for patients and their unpaid caregivers in the future

The relationships between golf and health:A scoping review

OBJECTIVE: To assess the relationships between golf and health. DESIGN: Scoping review. DATA SOURCES: Published and unpublished reports of any age or language, identified by searching electronic databases, platforms, reference lists, websites and from consulting experts. REVIEW METHODS: A 3-step search strategy identified relevant published primary and secondary studies as well as grey literature. Identified studies were screened for final inclusion. Data were extracted using a standardised tool, to form (1) a descriptive analysis and (2) a thematic summary. RESULTS AND DISCUSSION: 4944 records were identified with an initial search. 301 studies met criteria for the scoping review. Golf can provide moderate intensity physical activity and is associated with physical health benefits that include improved cardiovascular, respiratory and metabolic profiles, and improved wellness. There is limited evidence related to golf and mental health. The incidence of golfing injury is moderate, with back injuries the most frequent. Accidental head injuries are rare, but can have serious consequences. CONCLUSIONS: Practitioners and policymakers can be encouraged to support more people to play golf, due to associated improved physical health and mental well-being, and a potential contribution to increased life expectancy. Injuries and illnesses associated with golf have been identified, and risk reduction strategies are warranted. Further research priorities include systematic reviews to further explore the cause and effect nature of the relationships described. Research characterising golf's contribution to muscular strengthening, balance and falls prevention as well as further assessing the associations and effects between golf and mental health are also indicated

MICE: The muon ionization cooling experiment. Step I: First measurement of emittance with particle physics detectors

Copyright @ 2011 APSThe Muon Ionization Cooling Experiment (MICE) is a strategic R&D project intended to demonstrate the only practical solution to providing high brilliance beams necessary for a neutrino factory or muon collider. MICE is under development at the Rutherford Appleton Laboratory (RAL) in the United Kingdom. It comprises a dedicated beamline to generate a range of input muon emittances and momenta, with time-of-flight and Cherenkov detectors to ensure a pure muon beam. The emittance of the incoming beam will be measured in the upstream magnetic spectrometer with a scintillating fiber tracker. A cooling cell will then follow, alternating energy loss in Liquid Hydrogen (LH2) absorbers to RF cavity acceleration. A second spectrometer, identical to the first, and a second muon identification system will measure the outgoing emittance. In the 2010 run at RAL the muon beamline and most detectors were fully commissioned and a first measurement of the emittance of the muon beam with particle physics (time-of-flight) detectors was performed. The analysis of these data was recently completed and is discussed in this paper. Future steps for MICE, where beam emittance and emittance reduction (cooling) are to be measured with greater accuracy, are also presented.This work was supported by NSF grant PHY-0842798

#Deathbedlive:the end-of-life trajectory, reflected in a cancer patient's tweets

Abstract Background Understanding physical and psycho-social illness trajectories towards the end of life can help in the planning of palliative and supportive care. With terminal patients increasingly seeking and sharing health information and support via social media, it is timely to examine whether these trajectories are reflected in their digital narratives. In this exploratory study, we analysed the Twitter feed of prominent cancer sufferer and physician, Kate Granger, over the final 6 months of her life. Methods With the consent of Kate’s widower, Chris Pointon, 1628 Twitter posts from @GrangerKate were manually screened. The 550 tweets judged relevant to her disease were qualitatively content analysed with reference to the six modifiable dimensions of the patient experience in Emanuel and Emanuel’s ‘framework for a good death’. The frequency of each tweet category was charted over time and textual content was examined and cross-referenced with key events, to obtain a deeper understanding of its nature and significance. Results Tweets were associated with physical symptoms (N = 270), psychological and cognitive symptoms (N = 213), social relationships and support (N = 85), economic demands and care giving needs (N = 85), hopes and expectations (N = 51) and spiritual beliefs (N = 7). While medical treatments and procedures were discussed in detail, medical information-seeking was largely absent, likely reflecting Kate clinical expertise. Spirituality was expressed more as hope in treatments or “someone out there listening”, than in religious terms. The high value of Kate’s palliative care team was a dominant theme in the support category, alongside the support she received from her online community of fellow sufferers, friends, family and colleagues. Significant events, such as medical procedures and hospital stays generated the densest Twitter engagement. Transitions between trajectory phases were marked by changes in the relative frequency of tweet-types. Conclusions In Kate’s words, “the power of patient narrative cannot be underestimated”. While this analysis spanned only 6 months, it yielded rich insights. The results reflect theorised end-of-life dimensions and reveal the potential of social media data and digital bio-ethnography to shine a light on terminal patients’ lived experiences, coping strategies and support needs, suggesting new opportunities for enhancing personalised palliative care and avenues for further research

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far