CD28 and T cell antigen receptor signal transduction coordinately regulate interleukin 2 gene expression in response to superantigen stimulation.

Activation of an immune response requires intercellular contact between T lymphocytes and antigen-presenting cells (APC). Interaction of the T cell antigen receptor (TCR) with antigen in the context of major histocompatibility molecules mediates signal transduction, but T cell activation appears to require the induction of a second costimulatory signal transduction pathway. Recent studies suggest that interaction of CD28 with B7 on APC might deliver such a costimulatory signal. To investigate the role of CD28 signal transduction during APC-dependent T cell activation, we have used Staphylococcal enterotoxins (SEs) presented by a B7-positive APC. We used anti-B7 monoclonal antibodies and a mutant interleukin 2 (IL-2) promoter construct, unresponsive to CD28-generated signals, in transient transfection assays to examine the contribution of the CD28-B7 interaction to IL-2 gene activation. These studies indicate that the CD28-regulated signal transduction pathway is activated during SE stimulation of T cells and plays an important role in SE induction of IL-2 gene expression through its influence upon the CD28-responsive element contained within the IL-2 gene promoter. This effect is particularly profound in the activation of the IL-2 gene in peripheral blood T cells

Spontaneous Symmetry Breaking in Finite Systems

The orthodox characterisation of spontaneous symmetry breaking (SSB) in statistical mechanics appeals to novel properties of systems with infinite degrees of freedom, namely the existence of multiple equilibrium states. This raises the same puzzles about the status of the thermodynamic limit fueling recent debates about phase transitions. I argue here that there are prospects of explaining the success of the standard approach to SSB in terms of the properties of large finite systems and consequently, despite initial appearances, the need to account for SSB phenomena does not offer decisive support to claims about the explanatory and representational indispensability of the thermodynamic limit

Spatial Effects of the Social Marketing of Insecticide-Treated Nets on Malaria Morbidity.

Randomized controlled trials have shown that insecticide-treated nets (ITNs) have an impact on both malaria morbidity and mortality. Uniformly high coverage of ITNs characterized these trials and this resulted in some protection of nearby non-users of ITNs. We have now assessed the coverage, distribution pattern and resultant spatial effects in one village in Tanzania where ITNs were distributed in a social marketing programme. The prevalence of parasitaemia, mild anaemia (Hb <11 g/dl) and moderate/severe anaemia (Hb <8 g/dl) in children under five was assessed cross-sectionally. Data on ownership of ITNs were collected and inhabitants' houses were mapped. One year after the start of the social marketing programme, 52% of the children were using a net which had been treated at least once. The ITNs were rather homogeneously distributed throughout the village at an average density of about 118 ITNs per thousand population. There was no evidence of a pattern in the distribution of parasitaemia and anaemia cases, but children living in areas of moderately high ITN coverage were about half as likely to have moderate/severe anaemia (OR 0.5, 95% CI: 0.2, 0.9) and had lower prevalence of splenomegaly, irrespective of their net use. No protective effects of coverage were found for prevalence of mild anaemia nor for parasitaemia. The use of untreated nets had neither coverage nor short distance effects. More efforts should be made to ensure high coverage in ITNs programmes to achieve maximum benefit

An Estimation of the Entomological Inoculation Rate for Ifakara: A Semi-Urban Area in a Region of Intense Malaria Transmission in Tanzania.

An entomological study on vectors of malaria and their relative contribution to Plasmodium falciparum transmission in the semi-urban area of Ifakara, south-eastern Tanzania, was conducted. A total of 32 houses were randomly sampled from the area and light trap catches (LTC) performed in one room in each house every 2 weeks for 1 year. A total of 147 448 mosquitoes were caught from 789 LTC; 26 134 Anopheles gambiae s.l., 615 A. funestus, 718 other anophelines and 119 981 culicines. More than 60% of the total A. gambiae s.l. were found in five (0.6%) LTCs, with a maximum of 5889 caught in a single trap. Of 505 A. gambiae s.l. speciated by polymerase chain reaction, 91.5% were found to be A. arabiensis. Plasmodium falciparum sporozoite enzyme-linked immunosorbent assay tests were performed on 10 108 anopheles mosquitoes and 39 (0.38%) were positive. Entomological inoculation rate (EIR) estimates were generated using a standard method and an alternative method that allows the calculation of confidence intervals based on a negative binomial distribution of sporozoite positive mosquitoes. Overall EIR estimates were similar; 31 vs. 29 [95% confidence interval (CI): 19, 44] infectious bites per annum, respectively. The EIR ranged from 4 (95% CI: 1, 17) in the cool season to 108 (95% CI: 69, 170) in the wet season and from 54 (95% CI: 30, 97) in the east of the town to 15 (95% CI: 8, 30) in the town centre. These estimates show large variations over short distances in time and space. They are all markedly lower than those reported from nearby rural areas and for other parts of Tanzania

Learning environment associated with use of mixed mode delivery model among secondary business studies students in Singapore

At many teacher education institutes around the world, preservice teachers are empowered to use pedagogical tools and strategies that engage their students. We used a modified version of the Constructivist Learning Environment Survey (CLES) to evaluate the effectiveness of a pedagogical model known as the Mixed Mode Delivery (MMD) model in terms of the CLES’s five scales of personal relevance, uncertainty, critical voice, shared control and negotiation. Comparisons were made between 2,216 secondary school students taught by the preservice teachers in an MMD group and 991 students in a control group in terms of the relative magnitudes of the gap between the actual and preferred learning environment in students’ school classrooms. The findings supported the positive impact of using MMD in terms of students’ perceptions of their classroom environments for all CLES scales

The impact of population-based faecal occult blood test screening on colorectal cancer mortality:a matched cohort study

BACKGROUND: Randomised trials show reduced colorectal cancer (CRC) mortality with faecal occult blood testing (FOBT). This outcome is now examined in a routine, population-based, screening programme. METHODS: Three biennial rounds of the UK CRC screening pilot were completed in Scotland (2000–2007) before the roll out of a national programme. All residents (50–69 years) in the three pilot Health Boards were invited for screening. They received a FOBT test by post to complete at home and return for analysis. Positive tests were followed up with colonoscopy. Controls, selected from non-pilot Health Boards, were matched by age, gender, and deprivation and assigned the invitation date of matched invitee. Follow-up was from invitation date to 31 December 2009 or date of death if earlier. RESULTS: There were 379 655 people in each group (median age 55.6 years, 51.6% male). Participation was 60.6%. There were 961 (0.25%) CRC deaths in invitees, 1056 (0.28%) in controls, rate ratio (RR) 0.90 (95% confidence interval (CI) 0.83–0.99) overall and 0.73 (95% CI 0.65–0.82) for participants. Non-participants had increased CRC mortality compared with controls, RR 1.21 (95% CI 1.06–1.38). CONCLUSION: There was a 10% relative reduction in CRC mortality in a routine screening programme, rising to 27% in participants

Field-study science classrooms as positive and enjoyable learning environments

We investigated differences between field-study classrooms and traditional science classrooms in terms of the learning environment and students’ attitudes to science, as well as the differential effectiveness of field-study classrooms for students differing in sex and English proficiency. A modified version of selected scales from the What Is Happening In this Class? questionnaire was used to assess the learning environment, whereas students’ attitudes were assessed with a shortened version of a scale from the Test of Science Related Attitudes. A sample of 765 grade 5 students from 17 schools responded to the learning environment and attitude scales in terms of both their traditional science classrooms and classrooms at a field-study centre in Florida. Large effect sizes supported the effectiveness of the field-studies classroom in terms of both the learning environment and student attitudes. Relative to the home school science class, the field-study class was considerably more effective for students with limited English proficiency than for native English speakers

Is there a reliable taphonomic clock in the temperate North Atlantic? An example from a North Sea population of the mollusc Arctica islandica

This is the final version. Available on open access from Elsevier via the DOI in this recordTwo hundred and seventy-seven shells of the long-lived bivalve mollusc Arctica islandica, collected from the Fladen Ground, northern North Sea, were radiocarbon dated and their taphonomic condition assessed, in order to determine whether taphonomic condition might provide a reliable indication of time since the death of the animal. With nine stations from across the Fladen Ground sampled, some strong geographic biases in 14C ages were apparent, with living and modern (post-bomb pulse) material found in the northern part of the Fladen Ground while older material (first half of the last millennium and early Holocene/Lateglacial) was concentrated in the central and western sites. Samples from the south and east Fladen Ground were sparse and were dominated by material from the second half of the last millennium. This south-north distribution is interpreted as the result of environmental change over millennial time-scales in the North Sea causing a gradual northward shift of living A. islandica populations and is not thought to be related to post mortem transport of shells to the south and east. Taphonomic condition, assessed using discriminant analysis and principal component analysis of five characteristics (amount of remaining periostracum, presence and condition of the ligament, extent of erosion at the shell margin, amount of bioerosion, and nacre condition), appeared to be a generally unreliable indicator of time since the death of the animal. Based on these five taphonomic characteristics, discriminant analysis placed 81.1% of post-bomb shells, 39.6% of shells from the period 0–500 yr BP, 68.0% of shells from the period 500–1000 yr BP and 20.0% of shells from the Early Holocene/Late glacial group into the correct radiocarbon age grouping, providing no support for the idea that this method can be used to triage shells for chronology construction as an alternative to radiometric dating.Natural Environment Research Council (NERC