Assessing decision quality in patient-centred care requires a preference-sensitive measure.

A theory-based instrument for measuring the quality of decisions made using any form of decision technology, including both decision-aided and unaided clinical consultations is required to enable person- and patient-centred care and to respond positively to individual heterogeneity in the value aspects of decision making. Current instruments using the term 'decision quality' have adopted a decision- and thus condition-specific approach. We argue that patient-centred care requires decision quality to be regarded as both preference-sensitive across multiple relevant criteria and generic across all conditions and decisions. MyDecisionQuality is grounded in prescriptive multi criteria decision analysis and employs a simple expected value algorithm to calculate a score for the quality of a decision that combines, in the clinical case, the patient's individual preferences for eight quality criteria (expressed as importance weights) and their ratings of the decision just taken on each of these criteria (expressed as performance rates). It thus provides an index of decision quality that encompasses both these aspects. It also provides patients with help in prioritizing quality criteria for future decision making by calculating, for each criterion, the Incremental Value of Perfect Rating, that is, the increase in their decision quality score that would result if their performance rating on the criterion had been 100%, weightings unchanged. MyDecisionQuality, which is a web-based generic and preference-sensitive instrument, can constitute a key patient-reported measure of the quality of the decision-making process. It can provide the basis for future decision improvement, especially when the clinician (or other stakeholders) completes the equivalent instrument and the extent and nature of concordance and discordance can be established. Apart from its role in decision preparation and evaluation, it can also provide real time and relevant documentation for the patient's record

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120

Measure of Activity Performance in the Hand (MAP-Hand) questionnaire

Background: Developed in the Norway, the Measure of Activity Performance of the Hand (MAP-Hand) assesses 18 activities performed using the hands. It was developed for people with rheumatoid arthritis (RA) using patient generated items, which are scored on a 0-3 scale and summarised into a total score range (0 to 54). This study reports the development and psychometric testing of the British English MAP-Hand in a UK population of people with RA. Methods: Recruitment took place in the National Health Service (NHS) through 17 Rheumatology outpatient clinics. Phase 1 (cross-cultural adaptation) involved: forward translation to British English; synthesis; expert panel review and cognitive debriefing interviews with people with RA. Phase 2 (psychometric testing) involved postal completion of the MAP-Hand, Health Assessment Questionnaire (HAQ), Upper Limb HAQ (ULHAQ), Short-Form 36 (SF-36v2) and Disabilities of the Arm Shoulder Hand (DASH) to measure internal consistency (Cronbach’s alpha); concurrent validity (Spearman’s correlations) and Minimal Detectable Difference (MDC95). The MAP-Hand was repeated three-weeks later to assess test-retest reliability (linear weighted kappa and Intra-Class Correlations (ICC (2,1)). Unidimensionality (internal construct validity) was assessed using (i) Confirmatory Factor Analysis (CFA) (ii) Mokken scaling and (iii) Rasch model. The RUMM2030 software was used, applying the Rasch partial credit model. Results: In Phase 1, 31 participants considered all items relevant. In Phase 2, 340 people completed Test-1 and 273 (80%) completed Test-2 questionnaires. Internal consistency was excellent (α=0.96). Test-retest reliability was good (ICC (2,1) = 0.96 (95% CI 0.94, 0.97)). The MAP-Hand correlated strongly with HAQ20 (rs=.88), ULHAQ (rs=.91), SF-36v2 Physical Functioning (PF) Score (rs=-.80) and DASH (rs=.93), indicating strong concurrent validity. CFA failed to support unidimensionality (Chi-Square 236.0 (df 120; p &lt;0.001)). However, Mokken scaling suggested a probabilistic ordering. There was differential item functioning (DIF) for gender. Four testlets were formed, resulting in much improved fit and unidimensionality. Following this, testlets were further merged in pairs where opposite bias existed. This resulted in perfect fit to the model. Conclusions: The British English version of the MAP-Hand has good validity and reliability in people with RA and can be used in both research and clinical practice. Keywords: PROMS; Patient Reported Outcome Measures; hand activity performance; hand function; hand pain; psychometric testing; Rasch analysis; validity; reliabilit

Risk assessment and decision making about in-labour transfer from rural maternity care: a social judgment and signal detection analysis

Background: The importance of respecting women's wishes to give birth close to their local community is supported by policy in many developed countries. However, persistent concerns about the quality and safety of maternity care in rural communities have been expressed. Safe childbirth in rural communities depends on good risk assessment and decision making as to whether and when the transfer of a woman in labour to an obstetric led unit is required. This is a difficult decision. Wide variation in transfer rates between rural maternity units have been reported suggesting different decision making criteria may be involved; furthermore, rural midwives and family doctors report feeling isolated in making these decisions and that staff in urban centres do not understand the difficulties they face. In order to develop more evidence based decision making strategies greater understanding of the way in which maternity care providers currently make decisions is required. This study aimed to examine how midwives working in urban and rural settings and obstetricians make intrapartum transfer decisions, and describe sources of variation in decision making. Methods: The study was conducted in three stages. 1. 20 midwives and four obstetricians described factors influencing transfer decisions. 2. Vignettes depicting an intrapartum scenario were developed based on stage one data. 3. Vignettes were presented to 122 midwives and 12 obstetricians who were asked to assess the level of risk in each case and decide whether to transfer or not. Social judgment analysis was used to identify the factors and factor weights used in assessment. Signal detection analysis was used to identify participants' ability to distinguish high and low risk cases and personal decision thresholds. Results: When reviewing the same case information in vignettes midwives in different settings and obstetricians made very similar risk assessments. Despite this, a wide range of transfer decisions were still made, suggesting that the main source of variation in decision making and transfer rates is not in the assessment but the personal decision thresholds of clinicians. Conclusions: Currently health care practice focuses on supporting or improving decision making through skills training and clinical guidelines. However, these methods alone are unlikely to be effective in improving consistency of decision making

Candidate high myopia loci on chromosomes 18p and 12q do not play a major role in susceptibility to common myopia

BACKGROUND: To determine whether previously reported loci predisposing to nonsyndromic high myopia show linkage to common myopia in pedigrees from two ethnic groups: Ashkenazi Jewish and Amish. We hypothesized that these high myopia loci might exhibit allelic heterogeneity and be responsible for moderate /mild or common myopia. METHODS: Cycloplegic and manifest refraction were performed on 38 Jewish and 40 Amish families. Individuals with at least -1.00 D in each meridian of both eyes were classified as myopic. Genomic DNA was genotyped with 12 markers on chromosomes 12q21-23 and 18p11.3. Parametric and nonparametric linkage analyses were conducted to determine whether susceptibility alleles at these loci are important in families with less severe, clinical forms of myopia. RESULTS: There was no strong evidence of linkage of common myopia to these candidate regions: all two-point and multipoint heterogeneity LOD scores were < 1.0 and non-parametric linkage p-values were > 0.01. However, one Amish family showed slight evidence of linkage (LOD>1.0) on 12q; another 3 Amish families each gave LOD >1.0 on 18p; and 3 Jewish families each gave LOD >1.0 on 12q. CONCLUSIONS: Significant evidence of linkage (LOD> 3) of myopia was not found on chromosome 18p or 12q loci in these families. These results suggest that these loci do not play a major role in the causation of common myopia in our families studied

Modern tests of Lorentz invariance

Motivated by ideas about quantum gravity, a tremendous amount of effort over the past decade has gone into testing Lorentz invariance in various regimes. This review summarizes both the theoretical frameworks for tests of Lorentz invariance and experimental advances that have made new high precision tests possible. The current constraints on Lorentz violating effects from both terrestrial experiments and astrophysical observations are presented.Comment: Modified and expanded discussions of various points. Numerous references added. Version matches that accepted by Living Reviews in Relativit

The Cysteine Rich Necrotrophic Effector SnTox1 Produced by Stagonospora nodorum Triggers Susceptibility of Wheat Lines Harboring Snn1

The wheat pathogen Stagonospora nodorum produces multiple necrotrophic effectors (also called host-selective toxins) that promote disease by interacting with corresponding host sensitivity gene products. SnTox1 was the first necrotrophic effector identified in S. nodorum, and was shown to induce necrosis on wheat lines carrying Snn1. Here, we report the molecular cloning and validation of SnTox1 as well as the preliminary characterization of the mechanism underlying the SnTox1-Snn1 interaction which leads to susceptibility. SnTox1 was identified using bioinformatics tools and verified by heterologous expression in Pichia pastoris. SnTox1 encodes a 117 amino acid protein with the first 17 amino acids predicted as a signal peptide, and strikingly, the mature protein contains 16 cysteine residues, a common feature for some avirulence effectors. The transformation of SnTox1 into an avirulent S. nodorum isolate was sufficient to make the strain pathogenic. Additionally, the deletion of SnTox1 in virulent isolates rendered the SnTox1 mutated strains avirulent on the Snn1 differential wheat line. SnTox1 was present in 85% of a global collection of S. nodorum isolates. We identified a total of 11 protein isoforms and found evidence for strong diversifying selection operating on SnTox1. The SnTox1-Snn1 interaction results in an oxidative burst, DNA laddering, and pathogenesis related (PR) gene expression, all hallmarks of a defense response. In the absence of light, the development of SnTox1-induced necrosis and disease symptoms were completely blocked. By comparing the infection processes of a GFP-tagged avirulent isolate and the same isolate transformed with SnTox1, we conclude that SnTox1 may play a critical role during fungal penetration. This research further demonstrates that necrotrophic fungal pathogens utilize small effector proteins to exploit plant resistance pathways for their colonization, which provides important insights into the molecular basis of the wheat-S. nodorum interaction, an emerging model for necrotrophic pathosystems

Short interspersed nuclear element (SINE) sequences in the genome of the human pathogenic fungus Aspergillus fumigatus Af293.

Copyright: © 2016 The Authors. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Citation: Kanhayuwa L, Coutts RHA (2016) Short Interspersed Nuclear Element (SINE) Sequences in the Genome of the Human Pathogenic Fungus Aspergillus fumigatus Af293. PLoS ONE 11(10): e0163215. https://doi.org/10.1371/journal.pone.0163215.Novel families of short interspersed nuclear element (SINE) sequences in the human pathogenic fungus Aspergillus fumigatus, clinical isolate Af293, were identified and categorised into tRNA-related and 5S rRNA-related SINEs. Eight predicted tRNA-related SINE families originating from different tRNAs, and nominated as AfuSINE2 sequences, contained target site duplications of short direct repeat sequences (4-14 bp) flanking the elements, an extended tRNA-unrelated region and typical features of RNA polymerase III promoter sequences. The elements ranged in size from 140-493 bp and were present in low copy number in the genome and five out of eight were actively transcribed. One putative tRNAArg-derived sequence, AfuSINE2-1a possessed a unique feature of repeated trinucleotide ACT residues at its 3'-terminus. This element was similar in sequence to the I-4_AO element found in A. oryzae and an I-1_AF long nuclear interspersed element-like sequence identified in A. fumigatus Af293. Families of 5S rRNA-related SINE sequences, nominated as AfuSINE3, were also identified and their 5'-5S rRNA-related regions show 50-65% and 60-75% similarity to respectively A. fumigatus 5S rRNAs and SINE3-1_AO found in A. oryzae. A. fumigatus Af293 contains five copies of AfuSINE3 sequences ranging in size from 259-343 bp and two out of five AfuSINE3 sequences were actively transcribed. Investigations on AfuSINE distribution in the fungal genome revealed that the elements are enriched in pericentromeric and subtelomeric regions and inserted within gene-rich regions. We also demonstrated that some, but not all, AfuSINE sequences are targeted by host RNA silencing mechanisms. Finally, we demonstrated that infection of the fungus with mycoviruses had no apparent effects on SINE activity.Peer reviewedFinal Published versio