Examining an alcohol health worker service's patient coverage.

Alcohol health workers (AHWs) have been found to be effective at reducing alcohol-related hospital admissions, but there is still a paucity of evidence in keys areas. This was the first study to investigate what percentage of patients referred to an AHW service by alcohol screening tools are actually seen by the AHWs. The study-based in a large teaching hospital in the north of England-also investigated the impact of social deprivation on service usage. Research data came from a patient database and semi-structured interviews with AHWs. Further research is required to better understand the 'harm paradox' of patients' differential susceptibility to alcohol-related harm and how this might impact AHW service patient flow

Pressure to Publish: Laura Terracina and her Editors

Laura Terracina (1519–c.1577) was the bestselling female author of sixteenth-century Italy, publishing eight poetry collections, several of which went through numerous reprints. While other female poets attained greater cultural prestige, none was as widely published, nor reflected so well the developing worlds of print, publication, and authorship from mid- to late Cinquecento. Her publication history problematizes the accepted narrative of how women came to print and of their relationship with their editors and publishers. From the time she first appeared in print in 1546 to the writing of her final manuscript in 1577, Terracina proved to be an engaged and headstrong author with a strong sense of ownership of her works. This article will explore Terracina’s relationships with her editors and publishers, analyzing her role in the publication process to argue that she took a much more active part in their production than has previously been appreciated

Sensitivity to radiation-induced chromosome damage may be a marker of genetic predisposition in young head and neck cancer patients

We previously showed that levels of chromosome damage induced by ionizing radiation were, on average, higher in G 2 and G 0 lymphocytes of breast cancer patients than of normal healthy controls, but that there was no correlation between the results in the two assays. We proposed that enhanced sensitivity to G 2 or G 0 irradiation was a marker of low-penetrance predisposition to breast cancer, and have recently demonstrated heritability of sensitivity in families of breast cancer cases. We have now applied these assays to patients with head and neck cancers, for whom there is epidemiological evidence of inherited predisposition in addition to environmental causes. The mean frequency of radiation-induced G 2 aberrations was higher in the 42 patients than in 27 normal controls, but not significantly so. However, cases less than 45 years old were significantly more sensitive than normals of the same age range (P = 0.046), whereas there was no difference between patients and normals of less than 45 years. Also, there was an inverse correlation between G 2 sensitivity and age for patients but not for normals. Radiation-induced micronuclei in G 0 cells were more frequent in 49 patients than in 31 normals (P = 0.056) but, as with the G 2 assay, the greatest difference was seen between early-onset patients and young normals. Again there was an inverse correlation with age for patients but not for normals. Six patients with enhanced toxicity to radiotherapy were G 2 tested and four other such patients were G 0 tested; levels of chromosome damage were not significantly greater than in patients with normal reactions. Both assays were used on 64 individuals (39 patients, 25 normals) and there was no significant correlation between the results. We suggest that a proportion of early-onset head and neck cancer patients are genetically predisposed and that each of the two assays detects a different subset of these cases. © 2001 Cancer Research Campaign http://www.bjcancer.co

Localisation of the human hSuv3p helicase in the mitochondrial matrix and its preferential unwinding of dsDNA

We characterised the human hSuv3p protein belonging to the family of NTPases/helicases. In yeast mitochondria the hSUV3 orthologue is a component of the degradosome complex and participates in mtRNA turnover and processing, while in Caenorhabditis elegans the hSUV3 orthologue is necessary for viability of early embryos. Using immunofluorescence analysis, an in vitro mitochondrial uptake assay and sub‐fractionation of human mitochondria we show hSuv3p to be a soluble protein localised in the mitochondrial matrix. We expressed and purified recombinant hSuv3p protein from a bacterial expression system. The purified enzyme was capable of hydrolysing ATP with a Km of 41.9 µM and the activity was only modestly stimulated by polynucleotides. hSuv3p unwound partly hybridised dsRNA and dsDNA structures with a very strong preference for the latter. The presented analysis of the hSuv3p NTPase/helicase suggests that new functions of the protein have been acquired in the course of evolution

Perceptions of trends in Seychelles artisanal trap fisheries: comparing catch monitoring, underwater visual census and fishers' knowledge

Fisheries scientists and managers are increasingly engaging with fishers' knowledge (FK) to provide novel information and improve the legitimacy of fisheries governance. Disputes between the perceptions of fishers and scientists can generate conflicts for governance, but can also be a source of new perspectives or understandings. This paper compares artisanal trap fishers' reported current catch rates with landings data and underwater visual census (UVC). Fishers' reports of contemporary 'normal' catch per day tended to be higher than recent median landings records. However, fishers' reports of 'normal' catch per trap were not significantly different from the median CPUE calculated from landings data, and reports of 'good' and 'poor' catch rates were indicative of variability observed in landings data. FK, landings and UVC data all gave different perspectives of trends over a ten-year period. Fishers' perceptions indicated greater declines than statistical models fitted to landings data, while UVC evidence for trends varied between sites and according to the fish assemblage considered. Divergence in trend perceptions may have resulted from differences in the spatial, temporal or taxonomic focus of each dataset. Fishers may have experienced and understood behavioural changes and increased fishing power, which may have obscured declines from landings data. Various psychological factors affect memory and recall, and may have affected these memory-based estimates of trends, while different assumptions underlying the analysis of both interview data and conventional scientific data could also have led to qualitatively different trend perceptions. Differing perspectives from these three data sources illustrate both the potential for 'cognitive conflicts' between stakeholders who do not rely on the same data sources, as well as the importance of multiple information sources to understand dynamics of fisheries. Collaborative investigation of such divergence may facilitate learning and improve fisheries governance

A Regional Decision Support Scheme for Pest Risk Analysis in Southeast Asia

A key justification to support plant health regulations is the ability of quarantine services to conduct pest risk analyses (PRA). Despite the supranational nature of biological invasions and the close proximity and connectivity of Southeast Asian countries, PRAs are conducted at the national level. Furthermore, some countries have limited experience in the development of PRAs, which may result in inadequate phytosanitary responses that put their plant resources at risk to pests vectored via international trade. We review existing decision support schemes for PRAs and, following international standards for phytosanitary measures, propose new methods that adapt existing practices to suit the unique characteristics of Southeast Asia. Using a formal written expert elicitation survey, a panel of regional scientific experts was asked to identify and rate unique traits of Southeast Asia with respect to PRA. Subsequently, an expert elicitation workshop with plant protection officials was conducted to verify the potential applicability of the developed methods. Rich biodiversity, shortage of trained personnel, social vulnerability, tropical climate, agriculture-dependent economies, high rates of land-use change, and difficulties in implementing risk management options were identified as challenging Southeast Asian traits. The developed methods emphasize local Southeast Asian conditions and could help support authorities responsible for carrying out PRAs within the region. These methods could also facilitate the creation of other PRA schemes in low- and middle-income tropical countries

Development of a single-chain, quasi-dimeric zinc-finger nuclease for the selective degradation of mutated human mitochondrial DNA

The selective degradation of mutated mitochondrial DNA (mtDNA) molecules is a potential strategy to re-populate cells with wild-type (wt) mtDNA molecules and thereby alleviate the defective mitochondrial function that underlies mtDNA diseases. Zinc finger nucleases (ZFNs), which are nucleases conjugated to a zinc-finger peptide (ZFP) engineered to bind a specific DNA sequence, could be useful for the selective degradation of particular mtDNA sequences. Typically, pairs of complementary ZFNs are used that heterodimerize on the target DNA sequence; however, conventional ZFNs were ineffective in our system. To overcome this, we created single-chain ZFNs by conjugating two FokI nuclease domains, connected by a flexible linker, to a ZFP with an N-terminal mitochondrial targeting sequence. Here we show that these ZFNs are efficiently transported into mitochondria in cells and bind mtDNA in a sequence-specific manner discriminating between two 12-bp long sequences that differ by a single base pair. Due to their selective binding they cleave dsDNA at predicted sites adjacent to the mutation. When expressed in heteroplasmic cells containing a mixture of mutated and wt mtDNA these ZFNs selectively degrade mutated mtDNA, thereby increasing the proportion of wt mtDNA molecules in the cell. Therefore, mitochondria-targeted single-chain ZFNs are a promising candidate approach for the treatment of mtDNA diseases

Targeting the absence: Homozygous DNA deletions as immutable signposts for cancer therapy

Many cancers harbor homozygous DNA deletions (HDs). In contrast to other attributes of cancer cells, their HDs are immutable features that cannot change during tumor progression or therapy. I describe an approach, termed deletion-specific targeting (DST), that employs HDs (not their effects on RNA/protein circuits, but deletions themselves) as the targets of cancer therapy. The DST strategy brings together both existing and new methodologies, including the ubiquitin fusion technique, the split-ubiquitin assay, zinc-finger DNA-recognizing proteins and split restriction nucleases. The DST strategy also employs a feedback mechanism that receives input from a circuit operating as a Boolean OR gate and involves the activation of split nucleases, which destroy DST vector in normal (nontarget) cells. The logic of DST makes possible an incremental and essentially unlimited increase in the selectivity of therapy. If DST strategy can be implemented in a clinical setting, it may prove to be curative and substantially free of side effects