244 research outputs found

    ISML: an interface specification meta-language

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    In this paper we present an abstract metaphor model situated within a model-based user interface framework. The inclusion of metaphors in graphical user interfaces is a well established, but mostly craft-based strategy to design. A substantial body of notations and tools can be found within the model-based user interface design literature, however an explicit treatment of metaphor and its mappings to other design views has yet to be addressed. We introduce the Interface Specification Meta-Language (ISML) framework and demonstrate its use in comparing the semantic and syntactic features of an interactive system. Challenges facing this research are outlined and further work proposed

    Reduced basis isogeometric mortar approximations for eigenvalue problems in vibroacoustics

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    We simulate the vibration of a violin bridge in a multi-query context using reduced basis techniques. The mathematical model is based on an eigenvalue problem for the orthotropic linear elasticity equation. In addition to the nine material parameters, a geometrical thickness parameter is considered. This parameter enters as a 10th material parameter into the system by a mapping onto a parameter independent reference domain. The detailed simulation is carried out by isogeometric mortar methods. Weakly coupled patch-wise tensorial structured isogeometric elements are of special interest for complex geometries with piecewise smooth but curvilinear boundaries. To obtain locality in the detailed system, we use the saddle point approach and do not apply static condensation techniques. However within the reduced basis context, it is natural to eliminate the Lagrange multiplier and formulate a reduced eigenvalue problem for a symmetric positive definite matrix. The selection of the snapshots is controlled by a multi-query greedy strategy taking into account an error indicator allowing for multiple eigenvalues

    emm typing and validation of provisional M types for group A streptococci.

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    This report discusses the following issues related to typing of group A streptococci (GAS): The development and use of the 5' emm variable region sequencing (emm typing) in relation to the existing serologic typing system; the designation of emm types in relation to M types; a system for validation of new emm types; criteria for validation of provisional M types to new M-types; a list of reference type cultures for each of the M-type or emm-type strains of GAS; the results of the first culture exchange program for a quality control testing system among the national and World Health Organization collaborating centers for streptococci; and dissemination of new approaches to typing of GAS to the international streptococcal community

    Analogue peptides for the immunotherapy of human acute myeloid leukemia

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    Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

    Prognostic and Mechanistic Potential of Progesterone Sulfates in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum

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    A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated by spontaneous preterm labor and stillbirth. A biomarker for ICP would be invaluable for early diagnosis and treatment and to enable its differentiation from other maternal diseases. Three progesterone sulfate compounds, whose concentrations have not previously been studied, were newly synthesized and assayed in the serum of three groups of ICP patients and found to be significantly higher in ICP at 9-15 weeks of gestation and prior to symptom onset (group 1 cases/samples: ICP n = 35/80, uncomplicated pregnancy = 29/100), demonstrating that all three progesterone sulfates are prognostic for ICP. Concentrations of progesterone sulfates were associated with itch severity and, in combination with autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of first-trimester samples all progesterone sulfates were significantly elevated in serum from low-risk asymptomatic women who subsequently developed ICP (ICP/uncomplicated pregnancy n = 54/51). Finally, we show mechanistically that progesterone sulfates mediate itch by evoking a Tgr5-dependent scratch response in mice. Conclusion: Our discovery that sulfated progesterone metabolites are a prognostic indicator for ICP will help predict onset of ICP and distinguish it from benign pruritus gravidarum, enabling targeted obstetric care to a high-risk population. Delineation of a progesterone sulfate-TGR5 pruritus axis identifies a therapeutic target for itch management in ICP

    Living with persistent pain: experiences of older people receiving home care.

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    Background. Although the topic of pain among older people has received increasing interest, little is still known about how pain is experienced or handled by those who no longer manage independently but depend on professionals for help with daily living. Developing pain management for older people requires such knowledge. Aim. To explore sense of self, sense of pain, daily living with pain, sense of others and ways of handling pain in older people with persistent pain. Methods. Interviews with 90 older people receiving home care from nursing auxiliaries in their own homes or in sheltered accommodation were collected from January to June 2000. A typology of older people in persistent pain was developed. Activities for handling pain were examined using content analysis. Findings. Respondents' experiences of themselves and their pain varied. Two groups of older people, considered as 'competent and proud' and 'confident and serene', expressed satisfaction in spite of pain, while the groups 'misunderstood and disappointed' and 'resigned and sad' expressed dissatisfaction. The most common strategies used were medication, rest, mobility, distracting activities and talking about pain. Respondents chose strategies by balancing the advantages of the activities against the disadvantages these brought for their daily living. Conclusion. This study indicates that characteristics of the older people, such as their way of experiencing themselves, how pain affects their daily life and how they perceive effects and side-effects of pain management are areas that need to be identified when staff assess pain and plan pain management. Caring for older people in pain could be improved by listening to and believing their complaints, evaluating effects and side-effects from medications and nonpharmacological pain management and by emphasising the importance of common everyday activities such as mobility and distraction to relieve pain

    Factors associated with timeliness of post-primary care referral, diagnosis and treatment for lung cancer: population-based, data-linkage study

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    BACKGROUND: The NHS Cancer Plan for England set waiting time targets for cancer referral (14 days from GP referral to first hospital appointment) and treatment (31 days from diagnosis, 62 days from urgent GP referral). Interim diagnostic intervals can also be calculated. The factors that influence timely post-primary care referral, diagnosis and treatment for lung cancer are not known. METHODS: Northern and Yorkshire Cancer Registry, Hospital Episode Statistics and lung cancer audit data sets were linked. Logistic regression was used to investigate the factors (socioeconomic position, age, sex, histology, co-morbidity, year of diagnosis, stage and performance status (PS)) that may influence the likelihood of referral, diagnosis and treatment within target, for 28 733 lung cancer patients diagnosed in 2006–2010. RESULTS: Late-stage, poor PS and small-cell histology were associated with a higher likelihood of post-primary care referral, diagnosis and treatment within target. Older patients were significantly less likely to receive treatment within the 31-day (odds ratio (OR)=0.79, 95% confidence interval (CI) 0.69–0.91) and 62-day target (OR=0.80, 95% CI 0.67–0.95) compared with younger patients. CONCLUSIONS: Older patients waited longer for treatment and this may be unjustified. Patients who appeared ill were referred, diagnosed and treated more quickly and this ‘sicker quicker’ effect may cancel out system socioeconomic inequalities that might result in longer time intervals for more deprived patients

    15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis

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    15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a prostaglandin-degrading enzyme that is highly expressed in normal colon mucosa but is ubiquitously lost in human colon cancers. Herein, we demonstrate that 15-PGDH is active in vivo as a highly potent suppressor of colon neoplasia development and acts in the colon as a required physiologic antagonist of the prostaglandin-synthesizing activity of the cyclooxygenase 2 (COX-2) oncogene. We first show that 15-PGDH gene knockout induces a marked 7.6-fold increase in colon tumors arising in the Min (multiple intestinal neoplasia) mouse model. Furthermore, 15-PGDH gene knockout abrogates the normal resistance of C57BL/6J mice to colon tumor induction by the carcinogen azoxymethane (AOM), conferring susceptibility to AOM-induced adenomas and carcinomas in situ. Susceptibility to AOM-induced tumorigenesis is mediated by a marked induction of dysplasia, proliferation, and cyclin D1 expression throughout microscopic aberrant crypt foci arising in 15-PGDH null colons and is concomitant with a doubling of prostaglandin E2 in 15-PGDH null colonic mucosa. A parallel role for 15-PGDH loss in promoting the earliest steps of colon neoplasia in humans is supported by our finding of a universal loss of 15-PGDH expression in microscopic colon adenomas recovered from patients with familial adenomatous polyposis, including adenomas as small as a single crypt. These models thus delineate the in vivo significance of 15-PGDH-mediated negative regulation of the COX-2 pathway and moreover reveal the particular importance of 15-PGDH in opposing the neoplastic progression of colonic aberrant crypt foci
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