A survey of UK medical schools' arrangements for early patient contact

Background: Many U.K. medical schools have patient contact in the first two years of the undergraduate course. Aim: To compare the purposes and organization of early patient contact in UK medical schools and to relate these arrangements to the schools' curricular objectives. Methods: A telephone survey of lead educators in UK medicals schools. Categories of contact were plotted against phases of the course to discern patterns of organisation. Results: The quantity of contact varies considerably (four to 65 days). There is a pattern, with learning objectives around the social context of health and illness preceding skills based work and integrated clinical knowledge for practice coming later. Schools fall into three categories: close adherence to the preclinical/clinical split, with limited early contact acting as an introduction to social aspects of health; provision of substantial patient contact to maximize the integration of knowledge and skills; and transitional, with limited clinical goals. General practice provides between one third and one half of early patient contact. Conclusions: Arrangements meet the objectives set by each school and reflect differing educational philosophies. Change is toward more early contact. There appears to be no national guidance which supports a minimum quantity of patient contact or specific educational purpose in the early years of U.K. basic medical training

Circulating Antinuclear Antibodies in Patients with Pelvic Masses Are Associated with Malignancy and Decreased Survival

BACKGROUND: Circulating autoantibodies occur more frequently in cancer patients than in patients without cancer. METHODS AND FINDINGS: We examined sera from patients referred for pelvic mass symptoms to a tertiary university clinic. A total of 127 were diagnosed with epithelial ovarian cancer while 386 had a benign condition. A screen for IgG anti-nuclear antibodies (ANA) by indirect immunofluorescence on HEp-2 cells confirmed a highly significant overrepresentation of ANA in the cancer group where 40% had detectable (i.e., a titer ≥160) ANA compared with less than 12% in the benign group. The overrepresentation of ANA in the cancer group persisted (p<0.0001) after matching the age-profile of the benign group with the ovarian cancer group. Only 19 out of 127 patients in the age-matched benign subgroup were positive for ANA corresponding to an 85% specificity at 40% sensitivity of ANA as the only marker for malignancy. No correlation of ANA positivity in either group with specific bands in immunoblots could be demonstrated even though immunoblot positivity was clearly increased in the malignant group (41% vs. 3%). The presence, strength, and type of ANA did not correlate with serum CA-125 values or with staging, and ANA outcome did not contribute with independent diagnostic information. However, survival was significantly shorter in ANA-positive compared with ANA-negative cancer patients and patients with CA-125 below the median CA-125 value in the cancer group had a significantly decreased survival when positive for ANA. ANA status made no difference in the group with CA-125 values above the median. Also, there was a significant correlation between speckled ANA-strength and histological tumor grade. CONCLUSIONS: Circulating antibodies are a promising source for new biomarkers in cancer. Characterization of epitope specificities and measurements of consecutive samples will be important for further elucidating the role of ANA in evaluating ovarian cancer patients

Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

A functional SUMO-interacting motif in the transactivation domain of c-Myb regulates its myeloid transforming ability

c-Myb is an essential hematopoietic transcription factor that controls proliferation and differentiation of progenitors during blood cell development. Whereas sumoylation of the C-terminal regulatory domain (CRD) is known to have a major impact on the activity of c-Myb, no role for noncovalent binding of small ubiquitin-like modifier (SUMO) to c-Myb has been described. Based on the consensus SUMO-interacting motif (SIM), we identified and examined putative SIMs in human c-Myb. Interaction and reporter assays showed that the SIM in the in the transactivation domain of c-Myb (V 267 NIV) is functional. This motif is necessary for c-Myb to be able to interact noncovalently with SUMO, preferentially SUMO2/3. Destroying the SUMO-binding properties by mutation resulted in a large increase in the transactivation potential of c-Myb. Mutational analysis and overexpression of conjugation-defective SUMO argued against intramolecular repression caused by sumoylated CRD and in favor of SUMO-dependent repression in trans. Using both a myeloid cell line-based assay and a primary hematopoietic cell assay, we addressed the transforming abilities of SUMO binding and conjugation mutants. Interestingly, only loss of SUMO binding, and not SUMO conjugation, enhanced the myeloid transformational potential of c-Myb. c-Myb with the SIM mutated conferred a higher proliferative ability than the wild-type and caused an effective differentiation block. This establishes SUMO binding as a mechanism involved in modulating the transactivation activity of c-Myb, and responsible for keeping the transforming potential of the oncoprotein in check

Effects of combined additions of Sr and AlTiB grain refiners in hypoeutectic Al-Si foundry alloys

Strontium is the most widely used and a very effective element for modifying the morphology of eutectic silicon, while Ti and B are commonly present in the commercial grain refiners used for Al-Si alloys. Systematic studies on the effects of combined additions of Sr and different AlTiB grain refiners on the Al + Si eutectic and primary aluminium solidification have been performed. While slight coarsening of both eutectic Si and primary aluminium grains occurs during holding, no obvious interactions are observed between Sr and AlTiB grain refiners when the addition level of grain refiners is low. As a result, a well-modified and grain refined structure was obtained. However, strong negative interactions between Sr and Al1.5Ti1.5B3 were observed as the addition level of the grain refiner increases. It was found that these interactions have a much more profound impact on the eutectic solidification than the primary Al solidification. The melt treated with combined additions of Sr and Al1.5Ti1.5B still shows good grain refinement efficiency even after losing its modification completely. The mechanism responsible for such negative interactions is further discussed. (c) 2006 Elsevier B.V. All rights reserved