Distinct Types of Fibrocyte Can Differentiate from Mononuclear Cells in the Presence and Absence of Serum

Background: Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. Methodology/Principal Findings: We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. Conclusions: The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Properties of the conditionally filtered equations: Conservation, normal modes, and variational formulation

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Conditionally filtered equations have recently been proposed as a basis for modelling the atmospheric boundary layer and convection. Conditional filtering decomposes the fluid into a number of categories or components, such as convective updrafts and the background environment, and derives governing equations for the dynamics of each component. Because of the novelty and unfamiliarity of these equations, it is important to establish some of their physical and mathematical properties, and to examine whether their solutions might behave in counter-intuitive or even unphysical ways. It is also important to understand the properties of the equations in order to develop suitable numerical solution methods. The conditionally filtered equations are shown to have conservation laws for mass, entropy, momentum or axial angular momentum, energy, and potential vorticity. The normal modes of the conditionally filtered equations include the usual acoustic, inertio-gravity, and Rossby modes of the standard compressible Euler equations. In addition, they posses modes with different perturbations in the different fluid components that resemble gravity modes and inertial modes but with zero pressure perturbation. These modes make no contribution to the total filter-scale fluid motion, and their amplitude diminishes as the filter scale diminishes. Finally, it is shown that the conditionally filtered equations have a natural variational formulation, which can be used as a basis for systematically deriving consistent approximations.We are grateful to two anonymous reviewers for their constructive comments on an earlier version of this paper. This work was funded by the Natural Environment Research Council under grant NE/N013123/1 as part of the ParaCon programme

General practitioners' views on reattribution for patients with medically unexplained symptoms: a questionnaire and qualitative study

Background: The successful introduction of new methods for managing medically unexplained symptoms in primary care is dependent to a large degree on the attitudes, experiences and expectations of practitioners. As part of an exploratory randomised controlled trial of reattribution training, we sought the views of participating practitioners on patients with medically unexplained symptoms, and on the value of and barriers to the implementation of reattribution in practice. Methods: A nested attitudinal survey and qualitative study in sixteen primary care teams in north-west England. All practitioners participating in the trial (n = 74) were invited to complete a structured survey. Semi-structured interviews were undertaken with a purposive sub-sample of survey respondents, using a structured topic guide. Interview transcripts were used to identify key issues, concepts and themes, which were grouped to construct a conceptual framework: this framework was applied systematically to the data. Results: Seventy (95%) of study participants responded to the survey. Survey respondents often found it stressful to work with patients with medically unexplained symptoms, though those who had received reattribution training were more optimistic about their ability to help them. Interview participants trained in reattribution (n = 12) reported that reattribution increased their confidence to practice in a difficult area, with heightened awareness, altered perceptions of these patients, improved opportunities for team-building and transferable skills. However general practitioners also reported potential barriers to the implementation of reattribution in routine clinical practice, at the level of the patient, the doctor, the consultation, diagnosis and the healthcare context. Conclusion: Reattribution training increases practitioners' sense of competence in managing patients with medically unexplained symptoms. However, barriers to its implementation are considerable, and frequently lie outside the control of a group of practitioners generally sympathetic to patients with medically unexplained symptoms and the purpose of reattribution. These findings add further to the evidence of the difficulty of implementing reattribution in routine general practice

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

Synovial fluid leukocyte apoptosis is inhibited in patients with very early rheumatoid arthritis

Synovial leukocyte apoptosis is inhibited in established rheumatoid arthritis (RA). In contrast, high levels of leukocyte apoptosis are seen in self-limiting crystal arthritis. The phase in the development of RA at which the inhibition of leukocyte apoptosis is first apparent, and the relationship between leukocyte apoptosis in early RA and other early arthritides, has not been defined. We measured synovial fluid leukocyte apoptosis in very early arthritis and related this to clinical outcome. Synovial fluid was obtained at presentation from 81 patients with synovitis of ≤ 3 months duration. The percentages of apoptotic neutrophils and lymphocytes were assessed on cytospin preparations. Patients were assigned to diagnostic groups after 18 months follow-up. The relationship between leukocyte apoptosis and patient outcome was assessed. Patients with early RA had significantly lower levels of neutrophil apoptosis than patients who developed non-RA persistent arthritis and those with a resolving disease course. Similarly, lymphocyte apoptosis was absent in patients with early RA whereas it was seen in patients with other early arthritides. The inhibition of synovial fluid leukocyte apoptosis in the earliest clinically apparent phase of RA distinguishes this from other early arthritides. The mechanisms for this inhibition may relate to the high levels of anti-apoptotic cytokines found in the early rheumatoid joint (e.g. IL-2, IL-4, IL-15 GMCSF, GCSF). It is likely that this process contributes to an accumulation of leukocytes in the early rheumatoid lesion and is involved in the development of the microenvironment required for persistent RA

Joint diffraction and modeling approach to the structure of liquid alumina

The structure of liquid alumina at a temperature ∼2400 K near its melting point was measured using neutron and high-energy x-ray diffraction by employing containerless aerodynamic–levitation and laser-heating techniques. The measured diffraction patterns were compared to those calculated from molecular dynamics simulations using a variety of pair potentials, and the model found to be in best agreement with experiments was refined using the reverse Monte Carlo method. The resultant model shows that the melt is composed predominantly of AlO4 and AlO5 units, in the approximate ratio of 2:1, with only minor fractions of AlO3 and AlO6 units. The majority of Al-O-Al connections involve corner-sharing polyhedra (83%), although a significant minority involve edge-sharing polyhedra (16%), predominantly between AlO5 and either AlO5 or AlO4 units. Most of the oxygen atoms (81%) are shared among three or more polyhedra, and the majority of these oxygen atoms are triply shared among one or two AlO4 units and two or one AlO5 units, consistent with the abundance of these polyhedra in the melt and their fairly uniform spatial distribution

Resection Status, Age and Nodal Involvement Determine Survival among Patients Receiving Adjuvant Chemoradiotherapy in Pancreatic Adenocarcinoma

Context Pancreas cancer can potentially be cured by resection, but the role of adjuvant chemotherapy and/or chemoradiation has been controversial. Objectives To better define clinicopathological factors that may serve as predictive and/or prognostic variables. Patients Between 1984 and 2006, we retrospectively analyzed 91 patients with pancreas cancer treated with pancreaticoduodenectomy or total pancreatectomy followed by adjuvant 5-fluorouracil-based chemoradiation at the University of Pennsylvania. Final pathological coding including margin status was confirmed by a pathologist. Interventions Patients were treated with 48.6 to 63.0 Gy, and 96.7% completed their prescribed radiation dose. Main outcome measures The prognostic significance of demographic factors, stage, year of surgery, tumor location, grade, resection status, and number of positive lymph nodes on overall survival were examined. Results With a median follow-up of 6.5 years, the overall median survival was 2.3 years (95% CI 1.5-3.2 years), and the 5-year overall survival was 28.9%. In multivariate analysis, completeness of resection (P&lt;0.001), fewer number of positive lymph nodes (0 vs. 1-2 vs. 3 or more) (P=0.004), and age less than, or equal to, 60 years (P=0.006) were all independently associated with improved overall survival. The overall survival reported in this study compares favorably with the results of other single-institution studies and with the RTOG 97-04 trial. Conclusions Adjuvant 5-FU-based chemoradiation following radical pancreatectomy can be delivered safely and results in comparatively good overall survival. The results of this analysis underscore the importance of resection status, number of involved lymph nodes and patient age as prognostic characteristics. These factors may be considered stratification variables for future post-pancreatectomy adjuvant therapy trials

Georgia Abortion Law and Our Commitment to Patients

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153775/1/art41143.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153775/2/art41143_am.pd

Why do General Practitioners Decline Training to Improve Management of Medically Unexplained Symptoms?

BACKGROUND: General practitioners’ (GPs) communication with patients presenting medically unexplained symptoms (MUS) has the potential to somatize patients’ problems and intensify dependence on medical care. Several reports indicate that GPs have negative attitudes about patients with MUS. If these attitudes deter participation in training or other methods to improve communication, practitioners who most need help will not receive it. OBJECTIVE: To identify how GPs’ attitudes to patients with MUS might inhibit their participation with training to improve management. DESIGN: Qualitative study. PARTICIPANTS: GPs (N = 33) who had declined or accepted training in reattribution techniques in the context of a research trial. APPROACH: GPs were interviewed and their accounts analysed qualitatively. RESULTS: Although attitudes that devalued patients with MUS were common in practitioners who had declined training, these coexisted, in the same practitioners, with evidence of intuitive and elaborate psychological work with these patients. However, these practitioners devalued their psychological skills. GPs who had accepted training also described working psychologically with MUS but devalued neither patients with MUS nor their own psychological skills. CONCLUSIONS: GPs’ attitudes that suggested disengagement from patients with MUS belied their pursuit of psychological objectives. We therefore suggest that, whereas negative attitudes to patients have previously been regarded as the main barrier to involvement in measures to improve patient management, GPs devaluing of their own psychological skills with these patients may be more important

Managing authenticity and performance in Gulag tourism, Kazakhstan

To date, there has been limited research concerning the methodology and approach to Gulag heritage and how it has been memorialised and commodified for tourism purposes. The recent cultural commodification of the Soviet past and the development of participatory visitor experiences at Gulag museums in Kazakhstan necessitate to advance understandings of the roles authenticity and performance play in the management of Gulag museum practices in the country. Using a qualitative case study research approach based on a combination of semi-structured interviews with stakeholders involved in the development of Gulag tourism including senior management of museums, museum guides, policy-makers, tourism operators, local NGOs and experts in Soviet Gulag heritage, direct observations and qualitative document analysis of two Gulag museums and sites in Kazakhstan, the commodification and management of Soviet Gulag heritage is explored. Results reveal that beyond objects on display and images regarded as interpretive illustrations that allow visitors to connect with the past and verify history, dioramas and staged performances re-enacting various elements of the Gulag life are used as immersive and emotional tools to accentuate the ‘dark’ atmosphere of the epoch and induce a more impactful and participatory visitor experience. The findings contribute to literature on authenticity and performance in Gulag tourism by examining the delicate question of the extent to which stakeholders involved in the management of the Gulag tragedy can offer meaningful visitor experiences that are historically accurate and protect the dignity of the victims while adapting to the dynamic roles of museums as heritage and education sites