The PARP-1 inhibitor Olaparib causes retention of γ-H2AX foci in BRCA1 heterozygote cells following exposure to gamma radiation

This article is made available through the Brunel Open Access Publishing Fund. Copyright © 2013 Emma C. Bourton et al. This is an open access article distributed under the Creative Commons Attribution Li-cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.A novel treatment for cancer patients with homozygous deletions of BRCA1 and BRCA2 is to use drugs that inhibit the enzyme poly(ADP-ribose) polymerase (PARP). Specific inhibition of PARP-1 can induce synthetic lethality in irradi- ated cancer cells while theoretically leaving normal tissue unaffected. We recently demonstrated in a cell survival assay that lymphoblastoid cells with mono-allelic mutations of BRCA1 were hypersensitive to gamma radiation in the pres- ence of the PARP-1 inhibitor Olaparib compared to normal cells and mono-allelic BRCA2 cells. To determine if the enhanced radiation sensitivity was due to a persistence of DNA strand breaks, we performed γ-H2AX foci analysis in cells derived from two normal individuals, three heterozygous BRCA1 and three heterozygous BRCA2 cell lines. Cells were exposed to 2 Gy gamma radiation in the presence or absence of 5 μM Olaparib. Using immunofluorescence and imaging flow cytometry, foci were measured in untreated cells and at 0.5, 3, 5 and 24 hours post-irradiation. In all lymphoblastoid cells treated with 2 Gy gamma radiation, there was a predictable induction of DNA strand breaks, with a modest but significant retention of foci over 24 hours in irradiated cells treated with Olaparib (ANOVA P < 0.05). However, in mono-allelic BRCA1 cells, there was a failure to fully repair DNA double-strand breaks (DSB) in the pres- ence of Olaparib, evidenced by a significant retention of foci at 24 hours’ post irradiation (t-Test P < 0.05). These data show that the cellular hypersensitivity of mono-allelic BRCA1 lymphoblastoid cells to gamma radiation in the presence of the Olaparib is due to the retention of DNA DSB. These data may indicate that patients with inherited mutations in the BRCA1 gene treated with radiotherapy and PARP-1 inhibitors may experience elevated radiation-associated normal tissue toxicity.Vidal Sassoon Foundation of America

The importance of highlighting the role of the self in hypnotherapy and hypnosis.

The role of the patient in hypnotherapy can be underestimated by both the therapist and the patient. This is likely due to the focus the hypnosis literature has had on the role played by the hypnotist/therapist and less on the phenomenological control (control over subjective experience) applied by the patient. Whilst early approaches to hypnosis and hypnotherapy included concepts such as autosuggestion and self-hypnosis, the role of the self has been largely overlooked. Here we aim to highlight the importance of the self in hypnotherapy and hypnosis by considering the concept of self-hypnosis and how it relates to hetero-hypnosis. We will show that: 1) historically the self was an important component of the concept of hypnosis; 2) extant theories emphasise the role of the self in hypnosis; 3) self-hypnosis is largely indistinguishable from hetero-hypnosis; 4) self-hypnosis is as effective as hetero-hypnosis. We also argue that highlighting the role of the self in hypnotherapy and hypnosis could increase feelings of self-efficacy, especially given that it can be considered a skill that can be advanced and implies self-control and not "mind-control". Highlighting the role of phenomenological control by the patient could also increase the uptake of hypnotherapy as treatment for various disorders

Updating Maryland\u27s Sea-level Rise Projections

With its 3,100 miles of tidal shoreline and low-lying rural and urban lands, The Free State is one of the most vulnerable to sea-level rise. Historically, Marylanders have long had to contend with rising water levels along its Chesapeake Bay and Atlantic Ocean and coastal bay shores. Shorelines eroded and low-relief lands and islands, some previously inhabited, were inundated. Prior to the 20th century, this was largely due to the slow sinking of the land since Earth’s crust is still adjusting to the melting of large masses of ice following the last glacial period. Over the 20th century, however, the rate of rise of the average level of tidal waters with respect to land, or relative sea-level rise, has increased, at least partially as a result of global warming. Moreover, the scientific evidence is compelling that Earth’s climate will continue to warm and its oceans will rise even more rapidly. Recognizing the scientific consensus around global climate change, the contribution of human activities to it, and the vulnerability of Maryland’s people, property, public investments, and natural resources, Governor Martin O’Malley established the Maryland Commission on Climate Change on April 20, 2007. The Commission produced a Plan of Action1 that included a comprehensive climate change impact assessment, a greenhouse gas reduction strategy, and strategies for reducing Maryland’s vulnerability to climate change. The Plan has led to landmark legislation to reduce the state’s greenhouse gas emissions and a variety of state policies designed to reduce energy consumption and promote adaptation to climate change

The impact of polio eradication on routine immunization and primary health care: a mixed-methods study.

BACKGROUND: After 2 decades of focused efforts to eradicate polio, the impact of eradication activities on health systems continues to be controversial. This study evaluated the impact of polio eradication activities on routine immunization (RI) and primary healthcare (PHC). METHODS: Quantitative analysis assessed the effects of polio eradication campaigns on RI and maternal healthcare coverage. A systematic qualitative analysis in 7 countries in South Asia and sub-Saharan Africa assessed impacts of polio eradication activities on key health system functions, using data from interviews, participant observation, and document review. RESULTS: Our quantitative analysis did not find compelling evidence of widespread and significant effects of polio eradication campaigns, either positive or negative, on measures of RI and maternal healthcare. Our qualitative analysis revealed context-specific positive impacts of polio eradication activities in many of our case studies, particularly disease surveillance and cold chain strengthening. These impacts were dependent on the initiative of policy makers. Negative impacts, including service interruption and public dissatisfaction, were observed primarily in districts with many campaigns per year. CONCLUSIONS: Polio eradication activities can provide support for RI and PHC, but many opportunities to do so remain missed. Increased commitment to scaling up best practices could lead to significant positive impacts

Opportunistic experiments to constrain aerosol effective radiative forcing

Aerosol–cloud interactions (ACIs) are considered to be the most uncertain driver of present-day radiative forcing due to human activities. The nonlinearity of cloud-state changes to aerosol perturbations make it challenging to attribute causality in observed relationships of aerosol radiative forcing. Using correlations to infer causality can be challenging when meteorological variability also drives both aerosol and cloud changes independently. Natural and anthropogenic aerosol perturbations from well-defined sources provide “opportunistic experiments” (also known as natural experiments) to investigate ACI in cases where causality may be more confidently inferred. These perturbations cover a wide range of locations and spatiotemporal scales, including point sources such as volcanic eruptions or industrial sources, plumes from biomass burning or forest fires, and tracks from individual ships or shipping corridors. We review the different experimental conditions and conduct a synthesis of the available satellite datasets and field campaigns to place these opportunistic experiments on a common footing, facilitating new insights and a clearer understanding of key uncertainties in aerosol radiative forcing. Cloud albedo perturbations are strongly sensitive to background meteorological conditions. Strong liquid water path increases due to aerosol perturbations are largely ruled out by averaging across experiments. Opportunistic experiments have significantly improved process-level understanding of ACI, but it remains unclear how reliably the relationships found can be scaled to the global level, thus demonstrating a need for deeper investigation in order to improve assessments of aerosol radiative forcing and climate change

Changing Bee and Hoverfly Pollinator Assemblages along an Urban-Rural Gradient

The potential for reduced pollination ecosystem service due to global declines of bees and other pollinators is cause for considerable concern. Habitat degradation, destruction and fragmentation due to agricultural intensification have historically been the main causes of this pollinator decline. However, despite increasing and accelerating levels of global urbanization, very little research has investigated the effects of urbanization on pollinator assemblages. We assessed changes in the diversity, abundance and species composition of bee and hoverfly pollinator assemblages in urban, suburban, and rural sites across a UK city.Bees and hoverflies were trapped and netted at 24 sites of similar habitat character (churchyards and cemeteries) that varied in position along a gradient of urbanization. Local habitat quality (altitude, shelter from wind, diversity and abundance of flowers), and the broader-scale degree of urbanization (e.g. percentage of built landscape and gardens within 100 m, 250 m, 500 m, 1 km, and 2.5 km of the site) were assessed for each study site. The diversity and abundance of pollinators were both significantly negatively associated with higher levels of urbanization. Assemblage composition changed along the urbanization gradient with some species positively associated with urban and suburban land-use, but more species negatively so. Pollinator assemblages were positively affected by good site habitat quality, in particular the availability of flowering plants.Our results show that urban areas can support diverse pollinator assemblages, but that this capacity is strongly affected by local habitat quality. Nonetheless, in both urban and suburban areas of the city the assemblages had fewer individuals and lower diversity than similar rural habitats. The unique development histories of different urban areas, and the difficulty of assessing mobile pollinator assemblages in just part of their range, mean that complementary studies in different cities and urban habitats are required to discover if these findings are more widely applicable

The Development of Risk Politics in the UK: Thatcher’s ‘Remarkable’ but Forgotten ‘Don’t Die of Ignorance’ AIDS Campaign

Thirty years on from the dramatic and unprecedented AIDS advertising campaign organised by the Conservative administration of the late 1980s, this article reassesses the experience drawing upon subsequent memoirs and interviews. It does so in the context of an emergence of risk politics in the UK in the 1980s, situated within an historical perspective on the development of risk within modernity. Emphasis is placed upon the forgotten pragmatic, amoral core of the campaign which challenged the illiberal climate of the times, and how it was possible for an administration defined by high moralism to challenge it. The range of pressures that led to the campaign are outlined, including a conscious attempt to limit stigmatisation amidst the mood of wartime emergency that prevailed in late 1986/early 1987. Its emergency character meant little direct legacy of harm reduction has endured, but the article argues for a wider significance of the campaign as a key moment in the emergence of risk politics in the UK and beyond

The Impact of Polio Eradication on Routine Immunization and Primary Health Care: A Mixed-Methods Study

BACKGROUND: After 2 decades of focused efforts to eradicate polio, the impact of eradication activities on health systems continues to be controversial. This study evaluated the impact of polio eradication activities on routine immunization (RI) and primary healthcare (PHC). METHODS: Quantitative analysis assessed the effects of polio eradication campaigns on RI and maternal healthcare coverage. A systematic qualitative analysis in 7 countries in South Asia and sub-Saharan Africa assessed impacts of polio eradication activities on key health system functions, using data from interviews, participant observation, and document review. RESULTS: Our quantitative analysis did not find compelling evidence of widespread and significant effects of polio eradication campaigns, either positive or negative, on measures of RI and maternal healthcare. Our qualitative analysis revealed context-specific positive impacts of polio eradication activities in many of our case studies, particularly disease surveillance and cold chain strengthening. These impacts were dependent on the initiative of policy makers. Negative impacts, including service interruption and public dissatisfaction, were observed primarily in districts with many campaigns per year. CONCLUSIONS: Polio eradication activities can provide support for RI and PHC, but many opportunities to do so remain missed. Increased commitment to scaling up best practices could lead to significant positive impacts.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Oxford University Press on behalf of the Infectious Diseases Society of America. The published article can be found at: http://jid.oxfordjournals.org/.Keywords: health systems, eradication, poliomyelitis, routine immunizatio