A Myelin Proteolipid Protein-LacZ Fusion Protein Is Developmentally Regulated and Targeted to the Myelin Membrane in Transgenic Mice

Transgenic mice were generated with a fusion gene carrying a portion of the murine myelin proteolipid protein (PLP) gene, including the first intron, fused to the E. coli LacZ gene. Three transgenic lines were derived and all lines expressed the transgene in central nervous system white matter as measured by a histochemical assay for the detection of β-galactosidase activity. PLP-LacZ transgene expression was regulated in both a spatial and temporal manner, consistent with endogenous PLP expression. Moreover, the transgene was expressed specifically in oligodendrocytes from primary mixed glial cultures prepared from transgenic mouse brains and appeared to be developmentally regulated in vitro as well. Transgene expression occurred in embryos, presumably in pre- or nonmyelinating cells, rather extensively throughout the peripheral nervous system and within very discrete regions of the central nervous system. Surprisingly, beta-galactosidase activity was localized predominantly in the myelin in these transgenic animals, suggesting that the NH_2-terminal 13 amino acids of PLP, which were present in the PLP-LacZ gene product, were sufficient to target the protein to the myelin membrane. Thus, the first half of the PLP gene contains sequences sufficient to direct both spatial and temporal gene regulation and to encode amino acids important in targeting the protein to the myelin membrane

The SF36 as an outcome measure of services for end stage renal failure

OBJECTIVE: —To evaluate the use of the short form 36 (SF36) as a measure of health related quality of life of patients with end stage renal failure, document the results, and investigate factors, including mode of treatment, which may influence it. DESIGN: Cross sectional survey of patients with end stage renal failure, with the standard United Kingdom version of the SF36 supplemented by specific questions for end stage renal failure. SETTING: A teaching hospital renal unit. Subjects and methods—660 patients treated at the Sheffield Kidney Institute by haemodialysis, peritoneal dialysis, and transplantation. Internal consistency, percentage of maximal or minimal responses, SF36 scores, effect sizes, correlations between independent predictor variables and individual dimension scores of the SF36. Multiple regression analysis of the SF36 scores for the physical functioning, vitality, and mental health dimensions against treatment, age, risk (comorbidity) score, and other independent variables. RESULTS: A high response rate was achieved. Internal consistency was good. There were no floor or ceiling effects other than for the two “role” dimensions. Overall health related quality of life was poor compared with the general population. Having a functioning transplant was a significant predictor of higher score in the three dimensions (physical functioning, vitality, and mental health) for which multiple regression models were constructed. Age, sex, comorbidity, duration of treatment, level of social and emotional support, household numbers, and hospital dialysis were also (variably) significant predictors. CONCLUSIONS: The SF36 is a practical and consistent questionnaire in this context, and there is evidence to support its construct validity. Overall the health related quality of life of these patients is poor, although transplantation is associated with higher scores independently of the effect of age and comorbidity. Age, comorbidity, and sex are also predictive of the scores attained in the three dimensions studied. Further studies are required to ascertain whether altering those predictor variables which are under the influence of professional carers is associated with changes in health related quality of life, and thus confirm the value of this outcome as a measure of quality of care

Impact of a theoretically based sex education programme (SHARE) delivered by teachers on NHS registered conceptions and terminations: final results of cluster randomised trial

<b>Objective</b>: To assess the impact of a theoretically based sex education programme (SHARE) delivered by teachers compared with conventional education in terms of conceptions and terminations registered by the NHS. Design Follow-up of cluster randomised trial 4.5 years after intervention. <b>Setting</b>: NHS records of women who had attended 25 secondary schools in east Scotland. <b>Participants</b>: 4196 women (99.5% of those eligible). <b>Intervention</b>: SHARE programme (intervention group) v existing sex education (control group). <b>Main outcome measure</b>: NHS recorded conceptions and terminations for the achieved sample linked at age 20. <b>Results</b>: In an "intention to treat" analysis there were no significant differences between the groups in registered conceptions per 1000 pupils (300 SHARE v 274 control; difference 26, 95% confidence interval –33 to 86) and terminations per 1000 pupils (127 v 112; difference 15, –13 to 42) between ages 16 and 20. <b>Conclusions</b>: This specially designed sex education programme did not reduce conceptions or terminations by age 20 compared with conventional provision. The lack of effect was not due to quality of delivery. Enhancing teacher led school sex education beyond conventional provision in eastern Scotland is unlikely to reduce terminations in teenagers

Extent of regretted sexual intercourse among young teenagers in Scotland: a cross sectional survey

No abstract available

Major Powers and Militarized Conflict

This article attempts to answer the question of why major powers engage in more active foreign policy behaviors than minor powers. It does so by comparing two explanations for the increased conflict propensity of major powers. The first explanation focuses on major powers’ observable capabilities, while the second stresses their different behavior. We incorporate both into an ultimatum model of conflict in which a state’s cost of conflict consists of both observable and behavioral components. Using data from the period from 1870 to 2001, we empirically illustrate the observable and behavioral differences between major and minor powers. We then utilize a decomposition model to assess the relative significance of the two explanations. The results suggest that most of the difference in conflict propensity between major and minor powers can be attributed to observable differences

The need to promote behaviour change at the cultural level: one factor explaining the limited impact of the MEMA kwa Vijana adolescent sexual health intervention in rural Tanzania. A process evaluation

Background - Few of the many behavioral sexual health interventions in Africa have been rigorously evaluated. Where biological outcomes have been measured, improvements have rarely been found. One of the most rigorous trials was of the multi-component MEMA kwa Vijana adolescent sexual health programme, which showed improvements in knowledge and reported attitudes and behaviour, but none in biological outcomes. This paper attempts to explain these outcomes by reviewing the process evaluation findings, particularly in terms of contextual factors. Methods - A large-scale, primarily qualitative process evaluation based mainly on participant observation identified the principal contextual barriers and facilitators of behavioural change. Results - The contextual barriers involved four interrelated socio-structural factors: culture (i.e. shared practices and systems of belief), economic circumstances, social status, and gender. At an individual level they appeared to operate through the constructs of the theories underlying MEMA kwa Vijana - Social Cognitive Theory and the Theory of Reasoned Action – but the intervention was unable to substantially modify these individual-level constructs, apart from knowledge. Conclusion - The process evaluation suggests that one important reason for this failure is that the intervention did not operate sufficiently at a structural level, particularly in regard to culture. Recently most structural interventions have focused on gender or/and economics. Complementing these with a cultural approach could address the belief systems that justify and perpetuate gender and economic inequalities, as well as other barriers to behaviour change

The Current State of Performance Appraisal Research and Practice: Concerns, Directions, and Implications

On the surface, it is not readily apparent how some performance appraisal research issues inform performance appraisal practice. Because performance appraisal is an applied topic, it is useful to periodically consider the current state of performance research and its relation to performance appraisal practice. This review examines the performance appraisal literature published in both academic and practitioner outlets between 1985 and 1990, briefly discusses the current state of performance appraisal practice, highlights the juxtaposition of research and practice, and suggests directions for further research

The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"

High-Resolution X-ray Spectroscopy of the Interstellar Medium

The interstellar medium (ISM) has a multiphase structure characterized by gas, dust and molecules. The gas can be found in different charge states: neutral, low-ionized (warm) and high-ionized (hot). It is possible to probe the multiphase ISM through the observation of its absorption lines and edges in the X-ray spectra of background sources. We present a high-quality RGS spectrum of the low-mass X-ray binary GS 1826-238 with an unprecedent detailed treatment of the absorption features due to the dust and both the neutral and ionized gas of the ISM. We constrain the column density ratios within the different phases of the ISM and measure the abundances of elements such as O, Ne, Fe and Mg. We found significant deviations from the proto-Solar abundances: oxygen is over-abundant by a factor 1.23 +/- 0.05, neon 1.75 +/- 0.11, iron 1.37 +/- 0.17 and magnesium 2.45 +/- 0.35. The abundances are consistent with the measured metallicity gradient in our Galaxy: the ISM appears to be metal-rich in the inner regions. The spectrum also shows the presence of warm/hot ionized gas. The gas column has a total ionization degree less than 10%. We also show that dust plays an important role as expected from the position of GS 1826-238: most iron appears to be bound in dust grains, while 10-40% of oxygen consists of a mixture of dust and molecules

Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells

Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20-50 \u3bcg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 \ub1 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 \ub1 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 \u3bcg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 \u3bcg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL