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Dementia is an umbrella term for a range of conditions that affect how the brain works and, in particular, the ability to remember, think and reason. It mainly affects older people, both men and women, and gets worse over time. In recent years, there has been growing interest in the possibility that exposure to outdoor air pollution could increase the risk of dementia. COMEAP reviewed epidemiological and experimental studies and concluded that it is likely that air pollution contributes to a decline in mental ability and dementia in older people. The most likely way this occurs is through effects on the circulatory system. It is known that air pollutants, particularly fine particles, can affect the heart and blood vessels, including those of the brain. These effects are linked to vascular dementia, which is caused by damage to the blood vessels in the brain. Experimental studies suggest that air pollution may also stimulate immune cells in the brain, which can then damage nerve cells. It is also likely that some nano-sized (ultrafine) particles can enter the brain, either by transport along the olfactory nerve or by entering the circulation and crossing the blood-brain barrier. These particles may cause direct damage. Nonetheless, based on the available evidence, it does not seem likely that this is an important mechanism for the development of dementia. Recommendations were made for further research which would help develop the evidence on this important topic.

Ribosomopathies are a class of disorders caused by defects in the structure or function of the ribosome and characterized by tissue-specific abnormalities. Diamond Blackfan anemia (DBA) arises from different mutations, predominantly in genes encoding ribosomal proteins (RPs). Apart from the anemia, skeletal defects are among the most common anomalies observed in patients with DBA, but they are virtually restricted to radial ray and other upper limb defects. What leads to these site-specific skeletal defects in DBA remains a mystery. Using a novel mouse model for RP haploinsufficiency, we observed specific, differential defects of the limbs. Using complementary in vitro and in vivo approaches, we demonstrate that reduced WNT signaling and subsequent increased β-catenin degradation in concert with increased expression of p53 contribute to mesenchymal lineage failure. We observed differential defects in the proliferation and differentiation of mesenchymal stem cells (MSCs) from the forelimb versus the hind limbs of the RP haploinsufficient mice that persisted after birth and were partially rescued by allelic reduction of Trp53. These defects are associated with a global decrease in protein translation in RP haploinsufficient MSCs, with the effect more pronounced in cells isolated from the forelimbs. Together these results demonstrate translational differences inherent to the MSC, explaining the site-specific skeletal defects observed in DBA.

Considers some of the contradictory issues in developing public education. It examines the question of how great the power of the individual should be versus that of the state in the matter of learning responsibilities. (RK)

One of the most critical challenges for high-performance computing (HPC) scientific visualization is execution on massively threaded processors. Of the many fundamental changes we are seeing in HPC systems, one of the most profound is a reliance on new processor types optimized for execution bandwidth over latency hiding. Our current production scientific visualization software is not designed for these new types of architectures. To address this issue, the VTK-m framework serves as a container for algorithms, provides flexible data representation, and simplifies the design of visualization algorithms on new and future computer architecture.

Current appreciations of the effect on health of classical air pollutants including nitrogen dioxide, sulphur dioxide, particulate matter, carbon monoxide and ozone, depend upon modern techniques of epidemiological research. These techniques, which are powerful and able to detect small effects, depend upon the power of modern computers and, though the theory was understood, their application was not possible for most research workers before about 1980. The methods involve handling large data sets and the application of complex methods of regression analysis. Dealing statistically with the many confounding factors that obscure and interact with the effects on health of air pollutants is possible using these methods. Early concerns about the adequacy of handling confounding factors have recently been allayed. This review considers short-term impacts, long-term impacts and areas where further research is required.

Histological techniques form the basis of many areas of research, yet they can often be poorly understood. Aimed at postgraduate students and those at an early stage of their career, this title provides a detailed and comprehensive introduction to histological techniques. With detailed images and slides, this book provides a unique overview of the area while providing the reader with a guide to how to use and incorporate histological techniques within their own research. Written by experts working within the field, this book is an essential handbook for anyone wanting to learn more about histological methods and how to apply them successfully.

The metastasis suppressor gene KAI1 was identified by its ability to inhibit the formation of pulmonary metastases in experimental models for prostatic carcinoma. Down-regulation of this gene may be correlated with the invasive phenotype in melanomas and colon and bladder carcinomas and with the metastatic phenotype in carcinomas of the lung, breast, prostate, and pancreas. The goal of our study was to establish an immunohistochemical method to detect KAI1 expression in archival tissues. Using cell lines with known KAI1 levels and paraffin-embedded KAI1 positive tissues as controls, we observed strong membrane staining in lymphoid follicular centers and squamous epithelia. We then demonstrated the utility of our assay by studying KAI1 expression in 34 lymphoid and 57 squamous lesions. All eight reactive lymph nodes were KAI1 positive. In contrast, three of 13 follicular small cleaved and five of 13 diffuse large cell lymphomas were KAI1 negative. Seventy-nine percent (37 of 47) of invasive squamous cell carcinomas from the lung (n = 15), head and neck (n = 18), and cervix (n = 14) showed extensive KAI1 down-regulation. Loss of KAI1 expression was also found in a subset of 10 high-grade cervical dysplasias. Our data show that (i) immunohistochemistry is a suitable technique for evaluating KAI1 expression in archival tissues; (ii) KAI1 was not expressed in a subset of both low-grade and high-grade lymphomas; and (iii) there was extensive down-regulation of KAI1 in squamous cell carcinomas, suggestive of an important role of the gene in the suppression of invasion in these malignancies.

3C fiber technology advances the performance frontier of practical, high-pulse-energy fiber lasers by providing very large core fibers with the handling and packaging benefits associated with single mode fibers. First-generation fibers demonstrate scaling to > 240 W average power coincident with 100-kW peak power in 1-mJ, 10-ns pulses while maintaining single-mode beam quality, polarized output, and efficiencies > 70%. Peak powers over 0.5 MW with negligible spectral distortion can be achieved with sub ns, near-transform-limited pulses. In-development second-generation 3C Yb-fiber based on core sizes around 55 μm1 have produced >8 mJ, 13 ns pulses with peak powers exceeding 600 kW.