Synthesis and characterization of anthracene-2,6-dithioacetate: A rigid, conjugated molecule for the formation of monolayers on gold

The synthesis and characterization of a new photoswitchable anthracene compound, anthracene-2,6-dithioacetate, is presented. The compound dimerizes in solution on irradiation with UV light, and thin films can be formed on gold surfaces from both the monomer and photodimer. © CSIRO 2008

Developing a Raman spectroscopy-based tool to stratify patient response to pre-operative radiotherapy in rectal cancer

Rectal cancer patients frequently receive pre-operative radiotherapy (RT), prior to surgical resection. However, colorectal cancer is heterogeneous and the degree of tumour response to pre-operative RT is highly variable. There are currently no clinically approved methods of predicting response to RT, and a significant proportion of patients will show no clinical benefit, despite enduring the side-effects. We evaluated the use of Raman spectroscopy (RS), a non-destructive technique able to provide the unique chemical fingerprint of tissues, as a potential tool to stratify patient response to pre-operative RT. Raman measurements were obtained from the formalin-fixed, paraffin-embedded (FFPE) pre-treatment biopsy specimens of 20 rectal cancer patients who received pre-operative RT. A principal component analysis and linear discriminant analysis algorithm was able to classify patient response to pre-operative RT as good or poor, with an accuracy of 86.04 ± 0.14% (standard error). Patients with a good response to RT showed greater contributions from protein-associated peaks, whereas patients who responded poorly showed greater lipid contributions. These results demonstrate that RS is able to reliably classify tumour response to pre-operative RT from FFPE biopsies and highlights its potential to guide personalised cancer patient treatment

The geographies of access to enterprise finance: the case of the West Midlands, UK

The geographies of access to enterprise finance: the case of the West Midlands, UK, Regional Studies. Whilst there is a long history of credit rationing to small and medium-sized enterprises (SMEs) in the UK, the financial crisis has seen banks retreat further from lending to viable SMEs due to a reassessment of risk and lack of available capital. In so doing, the credit crunch is thought to be creating new geographies of financial exclusion. This paper explores the financial inclusion of enterprise through community development finance institutions (CDFIs) which provide loan finance to firms at the commercial margins in the West Midlands, UK. The paper concludes that CDFIs could partially address the financial exclusion of enterprise as an additional, alternative source of finance to that of mainstream banks

Recovery of the crucian carp Carassius carassius (L.): Approach and early results of an English conservation project

Aquatic Conservation: Marine and Freshwater Ecosystems published by John Wiley & Sons Ltd The crucian carp Carassius carassius, a cyprinid fish characteristic of small ponds, is in decline throughout most of its European range, including in England where it is currently thought to be non-native. The present study, undertaken by the Norfolk Crucian Project, reports on reductions in pond populations of crucian carp in Norfolk, eastern England as well as the success of recent introduction/re-introduction efforts in terms of crucian survival, recruitment and growth over the last 10 years. A 72% decline in crucian carp distribution was observed between the 1950s–1980s and the 2010s. Of 18 crucian carp introductions/re-introductions to restored and suitable existing ponds, 17 were successful in terms of survival, increasing the number of current crucian sites in Norfolk by 37%. Recruitment of young crucian carp was demonstrated for 12 of the 18 stocked ponds, with apparent elevated juvenile growth relative to other English and European populations. Delays in, or a lack of, crucian recruitment in some ponds appeared to result from the presence of other fish species (especially threespine stickleback Gasterosteus aculeatus) with predation and interspecific competition possible contributory factors. This study shows that, through combinations of pond rehabilitation and stocking, it has been possible to achieve a substantial recovery of crucian carp populations in the study region. Although the crucian carp is currently presumed to be non-native within England, given other scientific studies that show a lack of adverse impacts of this species on native biota, and because it is greatly threatened in its native range, the call is sounded for more crucian carp conservation projects in other parts of England as well as in Europe more generally

Cooperative Regulation of Non-Small Cell Lung Carcinoma by Nicotinic and Beta-Adrenergic Receptors: A Novel Target for Intervention

Lung cancer is the leading cause of cancer death; 80–85% of lung cancer cases are non-small cell lung cancer (NSCLC). Smoking is a documented risk factor for the development of this cancer. Although nicotine does not have the ability to initiate carcinogenic events, recent studies have implicated nicotine in growth stimulation of NSCLC. Using three NSCLC cell lines (NCI-H322, NCI-H441 and NCI-H1299), we identified the cooperation of nicotinic acetylcholine receptors (nAChRs) and β-adrenergic receptors (β-ARs) as principal regulators of these effects. Proliferation was measured by thymidine incorporation and MTT assays, and Western blots were used to monitor the upregulation of the nAChRs and activation of signaling molecules. Noradrenaline and GABA were measured by immunoassays. Nicotine-treated NSCLC cells showed significant induction of the α7nAChR and α4nAChR, along with significant inductions of p-CREB and p-ERK1/2 accompanied by increases in the stress neurotransmitter noradrenaline, which in turn led to the observed increase in DNA synthesis and cell proliferation. Effects on cell proliferation and signaling proteins were reversed by the α7nAChR antagonist α-BTX or the β-blocker propranolol. Nicotine treatment also down-regulated expression of the GABA synthesizing enzyme GAD 65 and the level of endogenous GABA, while treatment of NSCLC cells with GABA inhibited cell proliferation. Interestingly, GABA acts by reducing β-adrenergic activated cAMP signaling. Our findings suggest that nicotine-induced activation of this autocrine noradrenaline-initiated signaling cascade and concomitant deficiency in inhibitory GABA, similar to modulation of these neurotransmitters in the nicotine-addicted brain, may contribute to the development of NSCLC in smokers. Our data suggest that exposure to nicotine either by tobacco smoke or nicotine supplements facilitates growth and progression of NSCLC and that pharmacological intervention by β blocker may lower the risk for NSCLC development among smokers and could be used to enhance the clinical outcome of standard cancer therapy

Working towards co-production in rehabilitation and recovery services

PurposeThis paper outlines the work of a service provider, service user and carer group created to develop a strategy for service user and carer co-production.ApproachA reflective narrative account is given of the process through which the group formed and began to develop a working model aimed at shaping a cultural shift towards more co-produced services. The paper has been co-produced and includes the collaborative voices of service users, carers, multi-disciplinary staff, third sector representatives, managers and colleagues from associated services.FindingsThe model developed outlines 3 stages for services to work through in order to achieve meaningful and sustainable co-produced services. The importance of developing associated policies related to such areas as recruitment, payment, support and training is also outlined. Challenges to co-production are noted along with suggested approaches to overcoming these.Implications and ValueThe ethos of co-production is relatively new in the UK and so knowledge of the process and model may help guide others undertaking similar work

Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden

Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.http://deepblue.lib.umich.edu/bitstream/2027.42/78314/1/1750-1326-5-45.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/2/1750-1326-5-45.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/3/1750-1326-5-45-S1.PDFPeer Reviewe

Making it real of sustaining a fantasy? Personal budgets for older people

The restructuring of English social care services in the last three decades, as services are provided through a shifting collage of state, for-profit and non-profit organisations, exemplifies many of the themes of governance (Bevir, 2013). As well as institutional changes, there have been a new set of elite narratives about citizen behaviours and contributions, undergirded by modernist social science insights into the wellbeing benefits of ‘self-management’ (Mol, 2008). In this article, we particularly focus on the ways in which a narrative of personalisation has been deployed in older people’s social care services. Personalisation is based on an espoused aspiration of empowerment and autonomy through universal implementation to all users of social care (encapsulated in the Making it Real campaign [Think Local, Act Personal (TLAP), no date)], which leaves unproblematised the ever increasing residualisation of older adult social care and the abjection of the frail (Higgs and Gilleard, 2015). In this narrative of universal personalisation, older people are paradoxically positioned as ‘the unexceptional exception’; ‘unexceptional’ in the sense that, as the majority user group, they are rhetorically included in this promised transformation of adult social care; but ‘the exception’ in the sense that frail older adults are persistently placed beyond its reach. It is this paradoxical positioning of older adult social care users as the unexceptional exception and its ideological function that we seek to explain in this article

Perceptions of, and reactions to, environmental heat: a brief note on issues of concern in relation to occupational health

Average temperatures around the world are already increasing, and climate change projections suggest that global mean temperatures will continue to rise. As the effects, and projected effects, of climate change are becoming clearer, it is more apparent that the health effects of heat exposure will need further investigation. The risks associated with heat exposure are especially relevant to understandings of occupational health for people involved in labouring or agricultural work in low-income countries. This review is a partial look at the ways in which issues surrounding heat exposure and occupational health have been treated in some of the available literature. This literature focuses on military-related medical understandings of heat exposure as well as heat exposure in working environments. The ways that these issues have been treated throughout the literature reflect the ways in which technologies of observation are intertwined with social attitudes. The effects of heat on the health of working people, as well as identification of risk groups, will require further research in order to promote prophylactic measures as well as to add to understandings of the actual and potential consequences of climatic change