1,874 research outputs found
'Choosing shoes': a preliminary study into the challenges facing clinicians in assessing footwear for rheumatoid patients
Background: Footwear has been accepted as a therapeutic intervention for the foot affected
by rheumatoid arthritis (RA). Evidence relating to the objective assessment of footwear in
patients with RA is limited. The aims of this study were to identify current footwear styles,
footwear characteristics, and factors that influence footwear choice experienced by patients
with RA.
Methods: Eighty patients with RA were recruited from rheumatology clinics during the
summer months. Clinical characteristics, global function, and foot impairment and disability
measures were recorded. Current footwear, footwear characteristics and the factors
associated with choice of footwear were identified. Suitability of footwear was recorded using
pre-determined criteria for assessing footwear type, based on a previous study of foot pain.
Results: The patients had longstanding RA with moderate-to severe disability and
impairment. The foot and ankle assessment demonstrated a low-arch profile with both
forefoot and rearfoot structural deformities. Over 50% of shoes worn by patients were opentype
footwear. More than 70% of patients’ footwear was defined as being poor. Poor
footwear characteristics such as heel rigidity and sole hardness were observed. Patients
reported comfort (17%) and fit (14%) as important factors in choosing their own footwear.
Only five percent (5%) of patients wore therapeutic footwear.
Conclusions: The majority of patients with RA wear footwear that has been previously
described as poor. Future work needs to aim to define and justify the specific features of
footwear that may be of benefit to foot health for people with RA
Leading particles and diffractive spectra in the Interacting Gluon Model
We discuss the leading particle spectra and diffractive mass spectra from the
novel point of view, namely by treating them as particular examples of the
general energy flow phenomena taking place in the multiparticle production
processes. We argue that they show a high degree of universality what allows
for their simple description in terms of the Interacting Gluon Model developed
by us some time ago.Comment: Presented at Diffraction2002, Alushta, Crimea (Ukraina), August 31 -
September 5, 2002. To be published by Kluwer Academic Publishers (2003)
(necessary style files attached). Rewritten according to the Kluwer
specification
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Hospital Mortality and Trainee Experiences: How General Medical Council Survey Findings Correlate With Summary Hospital-Level Mortality Indicator.
OBJECTIVES: This study aimed to investigate whether components of junior doctor satisfaction are associated with patient mortality within the United Kingdom. METHODS: We conducted a cross-sectional study of publicly available data (the General Medical Council [GMC] National Survey and the Summary Hospital-level Mortality Indicator [SHMI]) pertaining to subjective physician trainee satisfaction and patient mortality within 80 United Kingdom-based healthcare institutions. The direction and strength of correlation between components of the GMC National Survey and relative patient mortality as described by the SHMI were calculated. Additional outcomes included mean GMC survey scores for reported domains and mean SHMI by healthcare institution. RESULTS: SHMI for included healthcare institutions ranged from 0.69 to 1.21 (mean [SD], 1.01 [0.1]). Mean GMC domain scores ranged between 44.61 and 88.62 (mean [SD], 71.16 [10.84]). Statistically significant correlations were observed for clinical supervision, clinical supervision out of hours, rota design, overall satisfaction, and teamwork. After application of Bonferroni correction, statistically significant correlations remained for both clinical supervision and clinical supervision out of hours. CONCLUSIONS: There is a significant association between components of subjective trainee satisfaction and patient mortality within the United Kingdom. Further investigation to examine these relationships, perhaps to target intervention, may prevent avoidable patient harm
Pneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models
Streptococcus pneumoniae is a commensal of the human nasopharynx and a major cause of respiratory and invasive disease. We examined adaptation and evolution of pneumococcus, within nasopharynx and lungs, in an experimental system where the selective pressures associated with transmission were removed. This was achieved by serial passage of pneumococci, separately, in mouse models of nasopharyngeal carriage or pneumonia. Passaged pneumococci became more effective colonizers of the respiratory tract and we observed several examples of potential parallel evolution. The cell wall-modifying glycosyltransferase LafA was under strong selection during lung passage, whereas the surface expressed pneumococcal vaccine antigen gene pvaA and the glycerol-3-phosphate dehydrogenase gene gpsA were frequent targets of mutation in nasopharynx-passaged pneumococci. These mutations were not identified in pneumococci that were separately evolved by serial passage on laboratory agar. We focused on gpsA, in which the same single nucleotide polymorphism arose in two independently evolved nasopharynx-passaged lineages. We describe a new role for this gene in nasopharyngeal carriage and show that the identified single nucleotide change confers resistance to oxidative stress and enhanced nasopharyngeal colonization potential. We demonstrate that polymorphisms in gpsA arise and are retained during human colonization. These findings highlight how within-host environmental conditions can determine trajectories of bacterial evolution. Relative invasiveness or attack rate of pneumococcal lineages may be defined by genes that make niche-specific contributions to bacterial fitness. Experimental evolution in animal infection models is a powerful tool to investigate the relative roles played by pathogen virulence and colonization factors within different host niches
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Supervision, scheduling, satisfaction and shared working: how experiences of junior doctors relate to excess mortality within the NHS.
BACKGROUND: We sought to explore associations between trainee doctor perception and excess patient mortality. METHODS: Data from two publicly available databases reflecting mortality and components of trainee satisfaction within 81 NHS healthcare institutions between the years 2012 and 2019 were analysed. Pearson's correlation coefficients were calculated. RESULTS: All domains of trainee perception were correlated with excess mortality. Clinical supervision out of hours (R=-0.44; p<0.0001), teamwork (R=-0.36; p<0.0001) and clinical supervision at any time (R=-0.35; p<0.0001) were most strongly correlated. Most associations remained consistent year on year. CONCLUSION: Trainee doctor perceptions of clinical supervision, rota design and teamwork within the NHS are consistently correlated with excess patient mortality. Further exploration of these associations could identify opportunities for interventions to reduce excess patient mortality. Given the clinical significance of our findings, organisations should consider rapid implementation of evidence-based interventions where they exist
Recombination rate and selection strength in HIV intra-patient evolution
The evolutionary dynamics of HIV during the chronic phase of infection is
driven by the host immune response and by selective pressures exerted through
drug treatment. To understand and model the evolution of HIV quantitatively,
the parameters governing genetic diversification and the strength of selection
need to be known. While mutation rates can be measured in single replication
cycles, the relevant effective recombination rate depends on the probability of
coinfection of a cell with more than one virus and can only be inferred from
population data. However, most population genetic estimators for recombination
rates assume absence of selection and are hence of limited applicability to
HIV, since positive and purifying selection are important in HIV evolution.
Here, we estimate the rate of recombination and the distribution of selection
coefficients from time-resolved sequence data tracking the evolution of HIV
within single patients. By examining temporal changes in the genetic
composition of the population, we estimate the effective recombination to be
r=1.4e-5 recombinations per site and generation. Furthermore, we provide
evidence that selection coefficients of at least 15% of the observed
non-synonymous polymorphisms exceed 0.8% per generation. These results provide
a basis for a more detailed understanding of the evolution of HIV. A
particularly interesting case is evolution in response to drug treatment, where
recombination can facilitate the rapid acquisition of multiple resistance
mutations. With the methods developed here, more precise and more detailed
studies will be possible, as soon as data with higher time resolution and
greater sample sizes is available.Comment: to appear in PLoS Computational Biolog
Type IIn supernovae at z ~ 2 from archival data
Supernovae have been confirmed to redshift z ~ 1.7 for type Ia (thermonuclear
detonation of a white dwarf) and to z ~ 0.7 for type II (collapse of the core
of the star). The subclass type IIn supernovae are luminous core-collapse
explosions of massive stars and, unlike other types, are very bright in the
ultraviolet, which should enable them to be found optically at redshifts z ~ 2
and higher. In addition, the interaction of the ejecta with circumstellar
material creates strong, long-lived emission lines that allow spectroscopic
confirmation of many events of this type at z ~ 2 for 3 - 5 years after
explosion. Here we report three spectroscopically confirmed type IIn
supernovae, at redshifts z = 0.808, 2.013 and 2.357, detected in archival data
using a method designed to exploit these properties at z ~ 2. Type IIn
supernovae directly probe the formation of massive stars at high redshift. The
number found to date is consistent with the expectations of a locally measured
stellar initial mass function, but not with an evolving initial mass function
proposed to explain independent observations at low and high redshift.Comment: 8 pages, 2 figures, includes supplementary informatio
Capture Hi-C identifies a novel causal gene, IL20RA, in the pan-autoimmune genetic susceptibility region 6q23
BACKGROUND: The identification of causal genes from genome-wide association studies (GWAS) is the next important step for the translation of genetic findings into biologically meaningful mechanisms of disease and potential therapeutic targets. Using novel chromatin interaction detection techniques and allele specific assays in T and B cell lines, we provide compelling evidence that redefines causal genes at the 6q23 locus, one of the most important loci that confers autoimmunity risk. RESULTS: Although the function of disease-associated non-coding single nucleotide polymorphisms (SNPs) at 6q23 is unknown, the association is generally assigned to TNFAIP3, the closest gene. However, the DNA fragment containing the associated SNPs interacts through chromatin looping not only with TNFAIP3, but also with IL20RA, located 680 kb upstream. The risk allele of the most likely causal SNP, rs6927172, is correlated with both a higher frequency of interactions and increased expression of IL20RA, along with a stronger binding of both the NFκB transcription factor and chromatin marks characteristic of active enhancers in T-cells. CONCLUSIONS: Our results highlight the importance of gene assignment for translating GWAS findings into biologically meaningful mechanisms of disease and potential therapeutic targets; indeed, monoclonal antibody therapy targeting IL-20 is effective in the treatment of rheumatoid arthritis and psoriasis, both with strong GWAS associations to this region
HFE C282Y and H63D in adults with malignancies in a community medical oncology practice
BACKGROUND: We sought to compare frequencies of HFE C282Y and H63D alleles and associated odds ratios (OR) in 100 consecutive unrelated white adults with malignancy to those in 318 controls. METHODS: Data from patients with more than one malignancy were analyzed according to each primary malignancy. For the present study, OR ≥2.0 or ≤0.5 was defined to be increased or decreased, respectively. RESULTS: There were 110 primary malignancies (52 hematologic neoplasms, 58 carcinomas) in the 100 adult patients. Allele frequencies were similar in patients and controls (C282Y: 0.0850 vs. 0.0896, respectively (OR = 0.9); H63D: 0.1400 vs. 0.1447, respectively (OR = 0.9)). Two patients had hemochromatosis and C282Y homozygosity. With C282Y, increased OR occurred in non-Hodgkin lymphoma, myeloproliferative disorders, and adenocarcinoma of prostate (2.0, 2.8, and 3.4, respectively); OR was decreased in myelodysplasia (0.4). With H63D, increased OR occurred in myeloproliferative disorders and adenocarcinomas of breast and prostate (2.4, 2.0, and 2.0, respectively); OR was decreased in non-Hodgkin lymphoma and B-chronic lymphocytic leukemia (0.5 and 0.4, respectively). CONCLUSIONS: In 100 consecutive adults with malignancy evaluated in a community medical oncology practice, frequencies of HFE C282Y or H63D were similar to those in the general population. This suggests that C282Y or H63D is not associated with an overall increase in cancer risk. However, odds ratios computed in the present study suggest that increased (or decreased) risk for developing specific types of malignancy may be associated with the inheritance of HFE C282Y or H63D. Study of more patients with these specific types of malignancies is needed to determine if trends described herein would remain and yield significant differences
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