The 2007 Census Test: evaluation of key objectives

The Office for National Statistics conducted a major census field test in May and June 2007 as part of the planning and preparation for the next census of population and housing in England and Wales in 2011. The 2007 Census Test was a large scale test covering approximately 100,000 household in five local authorities (LAs) selected to reflect a range of geographic conditions and social characteristics. Within England the Test covered parts of Bath and North East Somerset, Camden, Liverpool and Stoke on Trent. In Wales the Test took place in Carmarthenshire. The selected LAs were chosen to provide a varied cross section of the population and types of housing that would be covered in a full census. This article summarises the evaluation results and, where decided, decisions for 2011 on four key aspects of the Test: delivery method - post-out compared with hand delivery; inclusion of an income question; outsourcing recruitment, training and pay; and liaison with LAs.     

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.     

The DNA sequence and analysis of human chromosome 13

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.     

Enhanced thermoelectric performance of rough silicon nanowires

Approximately 90 per cent of the world's power is generated by heat engines that use fossil fuel combustion as a heat source and typically operate at 30-40 per cent efficiency, such that roughly 15 terawatts of heat is lost to the environment. Thermoelectric modules could potentially convert part of this low-grade waste heat to electricity. Their efficiency depends on the thermoelectric figure of merit ZT of their material components, which is a function of the Seebeck coefficient, electrical resistivity, thermal conductivity and absolute temperature. Over the past five decades it has been challenging to increase ZT > 1, since the parameters of ZT are generally interdependent. While nanostructured thermoelectric materials can increase ZT > 1 (refs 2-4), the materials (Bi, Te, Pb, Sb, and Ag) and processes used are not often easy to scale to practically useful dimensions. Here we report the electrochemical synthesis of large-area, wafer-scale arrays of rough Si nanowires that are 20-300 nm in diameter. These nanowires have Seebeck coefficient and electrical resistivity values that are the same as doped bulk Si, but those with diameters of about 50 nm exhibit 100-fold reduction in thermal conductivity, yielding ZT = 0.6 at room temperature. For such nanowires, the lattice contribution to thermal conductivity approaches the amorphous limit for Si, which cannot be explained by current theories. Although bulk Si is a poor thermoelectric material, by greatly reducing thermal conductivity without much affecting the Seebeck coefficient and electrical resistivity, Si nanowire arrays show promise as high-performance, scalable thermoelectric materials.     

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5–20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of d-glucose was lower than d-fructose. However, uptake of d-glucose was higher than d-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection.     

The spread of HIV-1 in Africa: sexual contact patterns and the predicted demographic impact of AIDS

The spread of HIV-1 in Africa is examined here in the light of recent information on the main epidemiological and behavioural determinants of transmission. Mathematical models incorporating demographic, epidemiological and behavioural processes are used to assess the potential demographic impact of the disease AIDS. These analyses highlight the significance of patterns of sexual behaviour, and in particular networks of sexual contact, on the predicted spread of infection. Current data reveal substantial variations in the degree of spread between and in countries, but new analyses support earlier predictions that in the worst-afflicted areas AIDS is likely to change population growth rates from positive to negative values in a few decades.     

Host immunity and synchronized epidemics of syphilis across the United States

A central question in population ecology is the role of 'exogenous' environmental factors versus density-dependent 'endogenous' biological factors in driving changes in population numbers. This question is also central to infectious disease epidemiology, where changes in disease incidence due to behavioural or environmental change must be distinguished from the nonlinear dynamics of the parasite population. Repeated epidemics of primary and secondary syphilis infection in the United States over the past 50 yr have previously been attributed to social and behavioural changes. Here, we show that these epidemics represent a rare example of unforced, endogenous oscillations in disease incidence, with an 8-11-yr period that is predicted by the natural dynamics of syphilis infection, to which there is partially protective immunity. This conclusion is supported by the absence of oscillations in gonorrhoea cases, where a protective immune response is absent. We further demonstrate increased synchrony of syphilis oscillations across cities over time, providing empirical evidence for an increasingly connected sexual network in the United States.