Immunologic privilege in the central nervous system and the blood-brain barrier

The brain is in many ways an immunologically and pharmacologically privileged site. The blood-brain barrier (BBB) of the cerebrovascular endothelium and its participation in the complex structure of the neurovascular unit (NVU) restrict access of immune cells and immune mediators to the central nervous system (CNS). In pathologic conditions, very well-organized immunologic responses can develop within the CNS, raising important questions about the real nature and the intrinsic and extrinsic regulation of this immune privilege. We assess the interactions of immune cells and immune mediators with the BBB and NVU in neurologic disease, cerebrovascular disease, and intracerebral tumors. The goals of this review are to outline key scientific advances and the status of the science central to both the neuroinflammation and CNS barriers fields, and highlight the opportunities and priorities in advancing brain barriers research in the context of the larger immunology and neuroscience disciplines. This review article was developed from reports presented at the 2011 Annual Blood-Brain Barrier Consortium Meeting.

Opportunities for Local Development in Jiului Valley"

This was an exploratory study that aimed to gain a rough understanding of the possible ways of implementing community development. The study was carried out between October 1998 and August 1999 in Lupeni, in the Jiu Valley, which is a mining area facing major decline following the government's decision to restructure the mining industry. Against a background of the history of sociology and its insights into the development of the community concept and its theoretical, methodological and practical significance, an analysis was carried out on four levels relevant to the community development approach: social participation, citizens' level of dependency on the state, and membership and the sense of belonging to the local and national community. A needs analysis approach using questionnaires, in-depth interviews and the Delphi approach took into consideration all those actors who could play important roles in local development: local authorities, representatives of local organisations (schools, trade unions, local associations, churches), and local residents.

Private Publishing in Moscow and St. Petersburg: Historical Background, Present Situation and Trends"

This research was a complex study of the economic and socio-cultural aspects of the development of Russian private publishing in the second half of the19th and early 20th centuries, during the periods of 'war communism' and the New Economic Policy of 1917 to 1930, and during the reform of book publishing in 1986-1999. Conclusions about private book publishing in Moscow and St. Petersburg were extrapolated to Russia-wide problems of the development of this field. Svichenskaya sees her main achievement as having identified the economic and legal concepts behind the development of private book publishing over the period in question in the context of state and corporate regulation of publishing. Here the state was the main influence on its development and there was a paradox in the relations between the state authorities and private publishers, in that the latter constantly suffered from repression by the former but at the same time were dependent on state support. The research identified the administrative process of the liquidation of private publishing at the end of the 1920s and showed that its present flourishing is closely linked with the establishment of a preferential mode for the development of this sector. Private publishing now represents around 80% of domestic publishing, in terms both of the number of publishing houses and of the number of volumes published, and so plays the major role in satisfying the demand for books in Russia. Svichenskaya predicts that in the coming years private publishing will see a further concentration of growth and a tendency to monopolies and also the increasing specialisation of the publishing repertoire. She outlines a suggested concept of state management in publishing and ways to optimise this. In the transitional period of adaptation to the market regulation of publishing, these include a continuing degree of state protectionism, the creation of a favourable investment climate, privatisation of the printing companies with the aim of modernising these, and the development of coordinated corporate policies.

Predictors of substance use reduction in an epidemiological first-episode psychosis cohort

Aim To assess the predictors of a significant decrease or cessation of substance use (SU) in a treated epidemiological cohort of first-episode psychosis (FEP) patients. Method Participants were FEP patients of the Early Psychosis Prevention and Intervention Centre in Australia. Patients' medical files were reviewed using a standardized file audit. Data on 432 patients with FEP and baseline co-morbid substance use disorder (SUD) were available for analysis. Predictors of reduction/cessation of SU at follow up were examined using logistic regression analyses. Results In univariate analyses, a reduction/cessation of SU was predicted by baseline measures reflecting higher education, employment, accommodation with others, cannabis use disorder (CUD) only (rather than poly-SUDs), better global functioning and better premorbid social and occupational functioning, later age at onset of psychosis, and a diagnosis of non-affective psychosis. In multivariate analysis, CUD alone and better premorbid social and occupational functioning remained significant predictors. Conclusions Addressing SUDs and social and occupational goals in people with FEP may offer opportunities to prevent SUDs becoming more severe or entrenched. Further longitudinal research on recovery from SU and FEP is needed to disentangle directions of influence and identify key targets for intervention.

Treatment of premenopausal women with early breast cancer: old challenges and new opportunities

Breast cancer occurring in women before the age of menopause continues to be a major medical and psychological challenge. Endocrine therapy has emerged as the mainstay of adjuvant treatment for women with estrogen receptor-positive tumours. Although the suppression of ovarian function (by oophorectomy, irradiation of the ovaries or gonadotropin releasing factor analogues) is effective as adjuvant therapy if used alone, its value has not been proven after chemotherapy. This is presumably because of the frequent occurrence of chemotherapy-induced amenorrhoea. Tamoxifen reduces the risk of recurrence by approximately 40%, irrespective of age and the ovarian production of estrogens. The worth of ovarian function suppression in combination with tamoxifen is unproven and is being investigated in an intergroup randomised clinical trial (SOFT [Suppression of Ovarian Function Trial]). Aromatase inhibitors are more effective than tamoxifen in postmenopausal women but are only being investigated in younger patients. The use of chemotherapies is identical in younger and older patients; however, at present the efficacy of chemotherapy in addition to ovarian function suppression plus tamoxifen is unknown in premenopausal patients with endocrine responsive disease. 'Targeted' therapies such as monoclonal antibodies to human epidermal growth factor receptor (HER)-2, HER1 and vascular endothelial growth factor, 'small molecule' inhibitors of tyrosine kinases and breast cancer vaccines are rapidly emerging. Their use depends on the function of the targeted pathways and is presently limited to clinical trials. Premenopausal patients are best treated in the framework of a clinical trial.

When conditioned responses "fire back": bidirectional cross-activation creates learning opportunities in synesthesia

In grapheme-color synesthesia, the letter "c" printed in black may be experienced as red, but typically the color red does not trigger the experience of the letter "c." Therefore, at the level of subjective experience, cross-activation is usually unidirectional. However, recent evidence from digit-color synesthesia suggests that at an implicit level bidirectional cross-activation can occur. Here we demonstrate that this finding is not restricted to this specific type of synesthesia. We introduce a new method that enables the investigation of bidirectionality in other types of synesthesia. We found that a group of grapheme-color synesthetes, but not a control group, showed a startle in response to a color-inducing grapheme after a startle response was conditioned to the specific corresponding color. These results implicate that when the startle response was associated with the real color an association between shock and the grapheme was also established. By this mechanism (i.e. implicit cross-activation) the conditioned response to the real color generalized to the synesthetic color. We suggest that parietal brain areas are responsible for this neural backfiring.

Opportunities and risks in reconciling conservation and development in a post-Soviet setting: The example of the Tajik National Park

In the Tajik National Park (TNP) - a high-altitude area of nearly 26,000 km2 in Central Asia - past and present human activities visibly contrast with standard conservation requirements for protected areas worldwide. This paper focuses on resource management, and highlights three major processes that threaten both the sustainable use of natural resources and the preservation of nature per se: (i) intensified use of biomass as a fuel resource, (ii) inappropriate pasture management, and (iii) increased pressure on endangered wildlife. From analysis of these processes - their historical background, root causes, trends and interrelationships - options and needs to improve park management are proposed and discussed.

Opportunities in Materials Processing: Metal Casting

Revitalizing manufacturing in the US is a hot topic, and the $1B National Network for Manufacturing Innovation (NNMI) has three new centers focused on metal casting. For structural applications, magnesium casting, structural die-cast alloys, austempered ductile and compacted graphite cast iron, and high strength steel promise dramatic weight reduction and improved performance. Recent experiments and modeling at UAB focus on the development of such new materials and processing routes. A study of the rare earth content in an aerospace magnesium alloy is presented.