Incidence and drug treatment of emotional distress after cancer diagnosis : a matched primary care case-control study

Notes This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.Peer reviewedPublisher PD

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

The distribution of pond snail communities across a landscape: separating out the influence of spatial position from local habitat quality for ponds in south-east Northumberland, UK

Ponds support a rich biodiversity because the heterogeneity of individual ponds creates, at the landscape scale, a diversity of habitats for wildlife. The distribution of pond animals and plants will be influenced by both the local conditions within a pond and the spatial distribution of ponds across the landscape. Separating out the local from the spatial is difficult because the two are often linked. Pond snails are likely to be affected by both local conditions, e.g. water hardness, and spatial patterns, e.g. distance between ponds, but studies of snail communities struggle distinguishing between the two. In this study, communities of snails were recorded from 52 ponds in a biogeographically coherent landscape in north-east England. The distribution of snail communities was compared to local environments characterised by the macrophyte communities within each pond and to the spatial pattern of ponds throughout the landscape. Mantel tests were used to partial out the local versus the landscape respective influences. Snail communities became more similar in ponds that were closer together and in ponds with similar macrophyte communities as both the local and the landscape scale were important for this group of animals. Data were collected from several types of ponds, including those created on nature reserves specifically for wildlife, old field ponds (at least 150 years old) primarily created for watering livestock and subsidence ponds outside protected areas or amongst coastal dunes. No one pond type supported all the species. Larger, deeper ponds on nature reserves had the highest numbers of species within individual ponds but shallow, temporary sites on farm land supported a distinct temporary water fauna. The conservation of pond snails in this region requires a diversity of pond types rather than one idealised type and ponds scattered throughout the area at a variety of sites, not just concentrated on nature reserves

BNCI systems as a potential assistive technology: ethical issues and participatory research in the BrainAble project

This paper highlights aspects related to current research and thinking about ethical issues in relation to Brain Computer Interface (BCI) and Brain-Neuronal Computer Interfaces (BNCI) research through the experience of one particular project, BrainAble, which is exploring and developing the potential of these technologies to enable people with complex disabilities to control computers. It describes how ethical practice has been developed both within the multidisciplinary research team and with participants. Results: The paper presents findings in which participants shared their views of the project prototypes, of the potential of BCI/BNCI systems as an assistive technology, and of their other possible applications. This draws attention to the importance of ethical practice in projects where high expectations of technologies, and representations of “ideal types” of disabled users may reinforce stereotypes or drown out participant “voices”. Conclusions: Ethical frameworks for research and development in emergent areas such as BCI/BNCI systems should be based on broad notions of a “duty of care” while being sufficiently flexible that researchers can adapt project procedures according to participant needs. They need to be frequently revisited, not only in the light of experience, but also to ensure they reflect new research findings and ever more complex and powerful technologies

Healthcare providers' views on the acceptability of financial incentives for breastfeeding:a qualitative study

BACKGROUND: Despite a gradual increase in breastfeeding rates, overall in the UK there are wide variations, with a trend towards breastfeeding rates at 6–8 weeks remaining below 40% in less affluent areas. While financial incentives have been used with varying success to encourage positive health related behaviour change, there is little research on their use in encouraging breastfeeding. In this paper, we report on healthcare providers’ views around whether using financial incentives in areas with low breastfeeding rates would be acceptable in principle. This research was part of a larger project looking at the development and feasibility testing of a financial incentive scheme for breastfeeding in preparation for a cluster randomised controlled trial. METHODS: Fifty–three healthcare providers were interviewed about their views on financial incentives for breastfeeding. Participants were purposively sampled to include a wide range of experience and roles associated with supporting mothers with infant feeding. Semi-structured individual and group interviews were conducted. Data were analysed thematically drawing on the principles of Framework Analysis. RESULTS: The key theme emerging from healthcare providers’ views on the acceptability of financial incentives for breastfeeding was their possible impact on ‘facilitating or impeding relationships’. Within this theme several additional aspects were discussed: the mother’s relationship with her healthcare provider and services, with her baby and her family, and with the wider community. In addition, a key priority for healthcare providers was that an incentive scheme should not impact negatively on their professional integrity and responsibility towards women. CONCLUSION: Healthcare providers believe that financial incentives could have both positive and negative impacts on a mother’s relationship with her family, baby and healthcare provider. When designing a financial incentive scheme we must take care to minimise the potential negative impacts that have been highlighted, while at the same time recognising the potential positive impacts for women in areas where breastfeeding rates are low

An Electron Fixed Target Experiment to Search for a New Vector Boson A' Decaying to e+e-

We describe an experiment to search for a new vector boson A' with weak coupling alpha' > 6 x 10^{-8} alpha to electrons (alpha=e^2/4pi) in the mass range 65 MeV < m_A' < 550 MeV. New vector bosons with such small couplings arise naturally from a small kinetic mixing of the "dark photon" A' with the photon -- one of the very few ways in which new forces can couple to the Standard Model -- and have received considerable attention as an explanation of various dark matter related anomalies. A' bosons are produced by radiation off an electron beam, and could appear as narrow resonances with small production cross-section in the trident e+e- spectrum. We summarize the experimental approach described in a proposal submitted to Jefferson Laboratory's PAC35, PR-10-009. This experiment, the A' Experiment (APEX), uses the electron beam of the Continuous Electron Beam Accelerator Facility at Jefferson Laboratory (CEBAF) at energies of ~1-4 GeV incident on 0.5-10% radiation length Tungsten wire mesh targets, and measures the resulting e+e- pairs to search for the A' using the High Resolution Spectrometer and the septum magnet in Hall A. With a ~1 month run, APEX will achieve very good sensitivity because the statistics of e+e- pairs will be ~10,000 times larger in the explored mass range than any previous search for the A' boson. These statistics and the excellent mass resolution of the spectrometers allow sensitivity to alpha'/alpha one to three orders of magnitude below current limits, in a region of parameter space of great theoretical and phenomenological interest. Similar experiments could also be performed at other facilities, such as the Mainz Microtron.Comment: 19 pages, 12 figures, 2 table

Weak pairwise correlations imply strongly correlated network states in a neural population

Biological networks have so many possible states that exhaustive sampling is impossible. Successful analysis thus depends on simplifying hypotheses, but experiments on many systems hint that complicated, higher order interactions among large groups of elements play an important role. In the vertebrate retina, we show that weak correlations between pairs of neurons coexist with strongly collective behavior in the responses of ten or more neurons. Surprisingly, we find that this collective behavior is described quantitatively by models that capture the observed pairwise correlations but assume no higher order interactions. These maximum entropy models are equivalent to Ising models, and predict that larger networks are completely dominated by correlation effects. This suggests that the neural code has associative or error-correcting properties, and we provide preliminary evidence for such behavior. As a first test for the generality of these ideas, we show that similar results are obtained from networks of cultured cortical neurons.Comment: Full account of work presented at the conference on Computational and Systems Neuroscience (COSYNE), 17-20 March 2005, in Salt Lake City, Utah (http://cosyne.org

Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis

In addition to motor neurone degeneration, up to 50% of amyotrophic lateral sclerosis (ALS) patients present with cognitive decline. Understanding the neurobiological changes underlying these cognitive deficits is critical, as cognitively impaired patients exhibit a shorter survival time from symptom onset. Given the pathogenic role of synapse loss in other neurodegenerative diseases in which cognitive decline is apparent, such as Alzheimer's disease, we aimed to assess synaptic integrity in the ALS brain. Here, we have applied a unique combination of high-resolution imaging of post-mortem tissue with neuropathology, genetic screening and cognitive profiling of ALS cases. Analyses of more than 1 million synapses using two complimentary high-resolution techniques (electron microscopy and array tomography) revealed a loss of synapses from the prefrontal cortex of ALS patients. Importantly, synapse loss was significantly greater in cognitively impaired cases and was not due to cortical atrophy, nor associated with dementia-associated neuropathology. Interestingly, we found a trend between pTDP-43 pathology and synapse loss in the frontal cortex and discovered pTDP-43 puncta at a subset of synapses in the ALS brains. From these data, we postulate that synapse loss in the prefrontal cortex represents an underlying neurobiological substrate of cognitive decline in ALS

Stimulus-dependent maximum entropy models of neural population codes

Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. To be able to infer a model for this distribution from large-scale neural recordings, we introduce a stimulus-dependent maximum entropy (SDME) model---a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. The model is able to capture the single-cell response properties as well as the correlations in neural spiking due to shared stimulus and due to effective neuron-to-neuron connections. Here we show that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. As a result, the SDME model gives a more accurate account of single cell responses and in particular outperforms uncoupled models in reproducing the distributions of codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like surprise and information transmission in a neural population.Comment: 11 pages, 7 figure

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

&lt;p&gt;Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.&lt;/p&gt; &lt;p&gt;Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.&lt;/p&gt; &lt;p&gt;Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.&lt;/p&gt; &lt;p&gt;Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.&lt;/p&gt