Hausdorff moments in an inverse problem for the heat equation: numerical experiment

In this paper we consider the inverse boundary problem for the heat equation Deltau(x, t) = rho(x)partial derivative(t)u(x, t) in a bounded domain Omega subset of R-2. We develop and test numerically an algorithm of an approximate reconstruction of the unknown p(x). This algorithm is based on the moments' method for the heat equation developed by Kawashita, Kurylev and Soga

Tissue-specific expression of a human Polymorphic Epithelial mucin (MUCI) in transgenic mice

The human MUC1 gene codes for the core protein of a mucin which is expressed by glandular epithelia and the carcinomas which develop from these tissues. The core protein is aberrantly glycosylated in cancers, and some antibodies show specificity in their reactions with the cancer-associated mucin, which also contains epitopes recognized by T-cells from breast and pancreatic cancer patients. For evaluating the potential use of mucin-reactive antibodies and mucin-based immunogens in cancer patients, a mouse model, expressing the MUC1 gene product PEM (polymorphic epithelial mucin) as a self antigen, would be extremely useful. To this end, we have developed transgenic mouse strains expressing the human MUC1 gene product in a tissue-specific manner. The TG4 mouse strain was established using a 40-kilobase fragment containing 4.5 kilobases of 5\u27 and 27 kilobases of 3\u27 flanking sequence. The TG18 strain was developed using a 10.6-kilobase SacII fragment from the 40-kilobase fragment; this fragment contained 1.6 kilobases of 5\u27 sequence and 1.9 kilobases of 3\u27 flanking sequence. Both strains showed tissue specificity of expression of the MUC1 gene, which was very similar to the profile of expression seen in human tissues. The antibody SM-3 is directed to a core protein epitope, which is selectively exposed in breast cancers and which shows a more restricted distribution on normal human tissues. It was established that the distribution of the SM-3 epitope of PEM in the tissues of the transgenic mice is similar to that seen in humans. The transgenic mouse strains described here should form the basis for the development of a preclinical model for the evaluation of PEM-based antigens and of antibodies directed to PEM in cancer therapy

Mg II h&k fine structure prominence modelling and the consequences for observations

Aims. Using 2D Mg II h[amp]k solar prominence modelling, our aim is to understand the formation of complex line profiles and how these are seen by the Interface Region Imaging Spectrograph (IRIS). Additionally, we see how the properties of these simulated observations are interpreted through the use of traditional 1D prominence modelling. Methods. We used a cylindrical non-local thermodynamic equilibrium (NLTE) 2D complete redistribution (CRD) code to generate a set of cylindrical prominence strands, which we stacked behind each other to produce complex line profiles. Then, with the use of the point spread functions (PSFs) of IRIS, we were able to predict how IRIS would observe these line profiles. We then used the 1D NLTE code PROM in combination with the Cross Root Mean Square method (xRMS) to find the properties recovered by traditional 1D prominence modelling. Results. Velocities of magnitude lower than 10 km s−1 are sufficient to produce asymmetries in the Mg II h[amp]k lines. However, convolution of these with the PSFs of IRIS obscures this detail and returns standard looking single peaks. By increasing the velocities by a factor of three, we recover asymmetric profiles even after this convolution. The properties recovered by xRMS appear adequate at first, but the line profiles chosen to fit these profiles do not satisfactorily represent the line profiles. This is likely due to the large line width of the simulated profiles. Conclusions. Asymmetries can be introduced by multithread models with independent Doppler velocities. The large line width created by these models makes it difficult for traditional 1D forward modelling to find good matches. This may also demonstrate degeneracies in the solution recovered by single-species 1D modelling

Rotation and activity of pre-main-sequence stars

We present a study of rotation (vsini) and chromospheric activity (Halpha EW) based on an extensive set of high-resolution optical spectra obtained with MIKE on the 6.5m Magellan Clay telescope. Our targets are 74 F-M dwarfs in the young stellar associations Eta Cha, TW Hydrae, Beta Pic, and Tuc-Hor, spanning ages from 6 to 30 Myr. While the Halpha EW for most F and G stars are consistent with pure photospheric absorption, most K and M stars show chromospheric emission. By comparing Halpha EW in our sample to results in the literature, we see a clear evolutionary sequence: Chromospheric activity declines steadily from the T Tauri phase to the main sequence. Using activity as an age indicator, we find a plausible age range for the Tuc-Hor association of 10-40 Myr. Between 5 and 30 Myr, we do not see evidence for rotational braking in the total sample, thus angular momentum is conserved, in contrast to younger stars. This difference indicates a change in the rotational regulation at 5-10 Myr, possibly because disk braking cannot operate longer than typical disk lifetimes, allowing the objects to spin up. The rotation-activity relation is flat in our sample; in contrast to main-sequence stars, there is no linear correlation for slow rotators. We argue that this is because young stars generate their magnetic fields in a fundamentally different way from main-sequence stars, and not just the result of a saturated solar-type dynamo. By comparing our rotational velocities with published rotation periods for a subset of stars, we determine ages of 13 (7-20) Myr and 9 (7-17} Myr for the Eta Cha and TWA associations, respectively, consistent with previous estimates. Thus we conclude that stellar radii from evolutionary models by Baraffe et al. (1998) are in agreement with the observed radii within +-15%. (abridged)Comment: 40 pages, 8 figures, ApJ, in pres

Activation of protein kinase Cδ leads to increased pancreatic acinar cell dedifferentiation in the absence of MIST1

Pancreatic ductal adenocarcinoma (PDAC) has a 5 year survival rate post-diagnosis of \u3c 5%. Individuals with chronic pancreatitis (CP) are 20-fold more likely to develop PDAC, making it a significant risk factor for PDAC. While the relationship for the increased susceptibility to PDAC is unknown, loss of the acinar cell phenotype is common to both pathologies. Pancreatic acinar cells can dedifferentiate or trans-differentiate into a number of cell types including duct cells, β cells, hepatocytes and adipocytes. Knowledge of the molecular pathways that regulate this plasticity should provide insight into PDAC and CP. MIST1 (encoded by Bhlha15 in mice) is a transcription factor required for complete acinar cell maturation. The goal of this study was to examine the plasticity of acinar cells that do not express MIST1 (Mist1 -/-). The fate of acinar cells from C57Bl6 or congenic Mist1 -/- mice expressing an acinar specific, tamoxifen-inducible Cre recombinase mated to Rosa26 reporter LacZ mice (Mist1CreERT/- R26r) was determined following culture in a three-dimensional collagen matrix. Mist1CreERT/- R26r acini showed increased acinar dedifferentiation, formation of ductal cysts and transient increases in PDX1 expression compared to wild-type acinar cells. Other progenitor cell markers, including Foxa1, Sox9, Sca1 and Hes1, were elevated only in Mist1-/- cultures. Analysis of protein kinase C (PKC) isoforms by western blot and immunofluorescence identified increased PKCε accumulation and nuclear localization of PKCδ that correlated with increased duct formation. Treatment with rottlerin, a PKCδ-specific inhibitor, but not the PKCε-specific antagonist εV1-2, reduced acinar dedifferentiation, progenitor gene expression and ductal cyst formation. Immunocytochemistry on CP or PDAC tissue samples showed reduced MIST1 expression combined with increased nuclear PKCδ accumulation. These results suggest that the loss of MIST1 is a common event during PDAC and CP and events that affect MIST1 function and expression may increase susceptibility to these pathologies. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Binge-Eating Disorder in Adults: A Systematic Review and Meta-analysis

The best treatment options for binge-eating disorder are unclear

Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes.

The PROGRESS series (www.progress-partnership.org) sets out a framework of four interlinked prognosis research themes and provides examples from several disease fields to show why evidence from prognosis research is crucial to inform all points in the translation of biomedical and health related research into better patient outcomes. Recommendations are made in each of the four papers to improve current research standards What is prognosis research? Prognosis research seeks to understand and improve future outcomes in people with a given disease or health condition. However, there is increasing evidence that prognosis research standards need to be improved Why is prognosis research important? More people now live with disease and conditions that impair health than at any other time in history; prognosis research provides crucial evidence for translating findings from the laboratory to humans, and from clinical research to clinical practice This first article introduces the framework of four interlinked prognosis research themes and then focuses on the first of the themes - fundamental prognosis research, studies that aim to describe and explain future outcomes in relation to current diagnostic and treatment practices, often in relation to quality of care Fundamental prognosis research provides evidence informing healthcare and public health policy, the design and interpretation of randomised trials, and the impact of diagnostic tests on future outcome. It can inform new definitions of disease, may identify unanticipated benefits or harms of interventions, and clarify where new interventions are required to improve prognosis

The North Staffordshire Osteoarthritis Project – NorStOP: Prospective, 3-year study of the epidemiology and management of clinical osteoarthritis in a general population of older adults

BACKGROUND: The clinical syndrome of joint pain and stiffness in older people is the commonest cause of disability and health care consultation in this age group. Yet there have been few prospective studies of its course over time and its impact on personal and social life. We plan a cohort study in the general population aged 50 years and over to determine the course and prognosis of hand, hip, knee and foot pain, and the impact of these syndromes on participation levels and health care use. METHODS: All patients aged 50 years and over registered with 3 local general practices are to be recruited to a population-based cohort study through the use of a two-stage mailing process. Participants will initially complete a "Health Survey" questionnaire. This will collect information on several areas of life including socio-demographics, general health, physical function, participation, and bodily pain. Those who state that they have experienced any hand problem or any pain in their hands, hips, knees, or feet in the previous 12 months, and also give permission to be re-contacted, will be mailed a "Regional Pains Survey" questionnaire which collects detailed information on the four selected body regions (hand, hips, knees, feet). Follow-up data for the three-year period subsequent to cohort recruitment will be collected through two sources: i) general practice medical records and ii) repeat mailed survey

Impact of a National Enhanced Recovery After Surgery Programme on Patient Outcomes of Primary total Knee Replacement: an Interrupted Time Series Analysis from “The National Joint Registry of England, Wales, Northern Ireland and the Isle of Man”

Objective We aimed to test whether a national Enhanced Recovery After Surgery (ERAS) Programme in total knee replacement (TKR) had an impact on patient outcomes. Design Natural-experiment (April 2008-December 2016). Interrupted time-series regression assessed impact on trends before-during-after ERAS implementation. Setting Primary operations from the UK National Joint Registry were linked with Hospital Episode Statistics data which contains inpatient episodes undertaken in NHS trusts in England, and PROMs. Participants Patients undergoing primary planned TKR aged ≥18 years. Intervention ERAS implementation (April 2009-March 2011). Outcomes Regression coefficients of monthly means of LOS, bed day costs, change in Oxford knee scores (OKS) 6-months after surgery, complications (at 6 months), and rates of revision surgeries (at 5 years). Results 486,579 primary TKRs were identified. Overall LOS and bed-day costs decreased from 5.8 days to 3.7 and from £7607 to £5276, from April 2008 to December 2016. OKS change improved from 15.1 points in April 2008 to 17.1 points in December 2016. Complications decreased from 4.1 % in April 2008 to 1.7 % March 2016. 5-year revision rates remained stable at 4.8 per 1000 implants years in April 2008 and December 2011. After ERAS, declining trends in LOS and bed costs slowed down; OKS improved, complications remained stable, and revisions slightly increased. Conclusions Different secular trends in outcomes for patients having TKR have been observed over the last decade. Although patient outcomes are better than a decade ago ERAS did not improve them at national level