A Phase II Trial of Pyrazine Diazohydroxide in Patients with Disseminated Malignant Melanoma and no Prior Chemotherapy – Southwest Oncology Group Study

Malignant melanoma is rapidly increasing inthe United States. Metastatic diseaseresponds poorly to currently availablechemotherapy. Pyrazine diazohydroxide(PZDH) is a new agent inhibiting DNAsynthesis that is active in mouse tumormodels and human xenografts and lackscross resistance withmultiple standard agents. In this phase IItrial, patients with no prior chemotherapyor immunotherapyfor metastatic disease and performancestatus (SWOG) of 0–1, were treated withpyrazine diazohydroxide at a dose of 100 mg/m 2 /day by IV bolus injectionover 5–15 minutes for 5 consecutive daysevery 6 weeks. There were 23 eligiblepatients entered on this trial with 74%having PS of 0 and 91% having visceralmetastases. There were no confirmed anti-tumor responses. Theoverall response rate is 0% (95% CI 0%–15%). Median overall survival is sixmonths (95% CI 5-8months). The most common toxicities were hematologic and consisted of lymphopenia,thrombocytopenia, anemia, and leukopenia. Fatigue, and nausea and vomiting were thenext mostcommon toxicities. Pyrazine diazohydroxideby this dose and schedule has insufficientactivity in thetreatment of disseminated malignantmelanoma to warrant further investigation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45216/1/10637_2004_Article_390690.pd

The Portuguese version of the Psychological Adjustment to Separation Test-Part A (PAST-A): a study with recently and non-recently divorced adults

Past research has demonstrated that divorced adults show more health problems and psychological distress than married adults. Considering the high prevalence rates of divorce among Western countries, new and robust measures should be developed to measure psychological distress after this specific transition in adulthood. The aim of this study was to adapt and validate a Portuguese version of the Psychological Adjustment to Separation Test-Part A (PAST-A; Sweeper and Halford in J Family Psychol 20(4):632–640, 2006). PAST-A is a self-report measure that assesses two key dimensions of separation adjustment problems: lonely-negativity and former partner attachment. Psychometric properties of the Portuguese version of PAST-A were assessed in terms of factor structure, internal consistency, and convergent and divergent validity, in an online convenience sample with divorced adults (N = 460). The PAST-A two-factor structure was confirmed by exploratory and confirmatory factor analyses, with each factor demonstrating very satisfactory internal consistency and good convergence. In terms of discriminant validity, the Portuguese PAST-A reveals a distinct factor from psychological growth after divorce. The results provided support for the use of the Portuguese PAST-A with divorced adults and also suggested that the explicative factors of the psychological adjustment to divorce may be cross-cultural stable. The non-existence of validated divorce-related well-being measures and its implications for divorce research are also discussed

Factors influencing the higher incidence of tuberculosis among migrants and ethnic minorities in the UK.

Migrants and ethnic minorities in the UK have higher rates of tuberculosis (TB) compared with the general population. Historically, much of the disparity in incidence between UK-born and migrant populations has been attributed to differential pathogen exposure, due to migration from high-incidence regions and the transnational connections maintained with TB endemic countries of birth or ethnic origin. However, focusing solely on exposure fails to address the relatively high rates of progression to active disease observed in some populations of latently infected individuals. A range of factors that disproportionately affect migrants and ethnic minorities, including genetic susceptibility, vitamin D deficiency and co-morbidities such as diabetes mellitus and HIV, also increase vulnerability to infection with Mycobacterium tuberculosis (M.tb) or reactivation of latent infection. Furthermore, ethnic socio-economic disparities and the experience of migration itself may contribute to differences in TB incidence, as well as cultural and structural barriers to accessing healthcare. In this review, we discuss both biological and anthropological influences relating to risk of pathogen exposure, vulnerability to infection or development of active disease, and access to treatment for migrant and ethnic minorities in the UK

A study of the molecular properties of rat-tail tendon collagen and an investigation of the structure of feather keratin

Some experimental aspects of the study of large molecules by the technique of light scattering are examined. The application of this technique to the study of rat-tail tendon collagen is then discussed. Investigations of this protein dissolved in dilute acetic acid and in concentrated urea, and a study of its transformation to "parent" gelatin lead to the suggestion of a schematic picture of the collagen molecule. A brief study of a fractionated gelatin is then described, and its molecular weight and some conclusions concerning possible molecular sizes are reported. The difficulties inherent in the investigation of gelatin solutions are examined. The final Part is concerned with a study of the structure of feather keratin by x-ray diffraction methods. The known meridional and equatorial spacings are revised and extended on the basis of measurements made on newly obtained diffraction photographs. Observed intensities are compared with those predicted for a structure which has been recently suggested

pH-Dependent Conformational Changes in Escherichia coli Dihydrofolate Reductase Revealed by Raman Difference Spectroscopy

The catalytic site of all dihydrofolate reductases contains an invariant carboxylic acid, equivalent to Asp-27 in Escherichia coli dihydrofolate reductase (ecDHFR). It has been found that various kinetic and ligand binding properties of ecDHFR show a pH profile with a pK(a) of about 6.5. The group responsible for this pK(a) is often assumed to be the carboxyl group of Asp-27. To determine the ionization state of this carboxyl and its pK(a), we have employed a novel method, based on Raman difference spectroscopy, to obtain its vibrational spectrum in situ. The method is general for the study of protein carboxyl groups, which are often significantly implicated in protein function and structure; this study establishes the method's limits and problems. The Raman difference spectrum between wild-type ecDHFR and the Asp-27 to serine mutant (D27S) in the pH range 5.6-9.0 has been taken. No protonation of the carboxyl group was detected, implying that its pK(a) is probably less than 5.0. We did, however, detect a pH dependence in the intensity of Raman bands in the difference spectrum with a pK(a) of 6.3, indicating that the apo enzyme undergoes a pH-dependent conformational change. Because the carboxyl group of Asp-27 at the active site is the only ionizable group in the binding site, other groups, away from the catalytic site, must be responsible for the pH behavior of ecDHFR

Early Detection of Potential Experts in Question Answering Communities

Abstract. Question answering communities (QA) are sustained by a handful of experts who provide a large number of high quality answers. Identifying these experts during the first few weeks of their joining the community can be beneficial as it would allow community managers to take steps to develop and retain these potential experts. In this paper, we explore approaches to identify potential experts as early as within the first two weeks of their association with the QA. We look at users’ behavior and estimate their motivation and ability to help others. These qualities enable us to build classification and ranking models to identify users who are likely to become experts in the future. Our results indicate that the current experts can be effectively identified from their early behavior. We asked community managers to evaluate the potential experts identified by our algorithm and their analysis revealed that quite a few of these users were already experts or on the path of becoming experts. Our retrospective analysis shows that some of these potential experts had already left the community, highlighting the value of early identification and engagement