Integrated stratigraphy of the Kimmeridge Clay Formation (Upper Jurassic) based on exposures and boreholes in south Dorset, UK

For the purposes of a high-resolution multi-disciplinary study of the Upper Jurassic Kimmeridge Clay Formation, two boreholes were drilled at Swanworth Quarry and one at Metherhills, south Dorset, UK. Together, the cores represent the first complete section through the entire formation close to the type section. We present graphic logs that record the stratigraphy of the cores, and outline the complementary geophysical and analytical data sets (gamma ray, magnetic susceptibility, total organic carbon, carbonate, [delta]13Corg). Of particular note are the new borehole data from the lowermost part of the formation which does not crop out in the type area. Detailed logs are available for download from the Kimmeridge Drilling Project web-site at http://kimmeridge.earth.ox.ac.uk/. Of further interest is a mid-eudoxus Zone positive shift in the [delta]13Corg record, a feature that is also registered in Tethyan carbonate successions, suggesting that it is a regional event and may therefore be useful for correlation. The lithostratigraphy of the cores has been precisely correlated with the nearby cliff section, which has also been examined and re-described. Magnetic-susceptibility and spectral gamma-ray measurements were made at a regular spacing through the succession, and facilitate core-to-exposure correlation. The strata of the exposure and core have been subdivided into four main mudrock lithological types: (a) medium-dark–dark-grey marl; (b) medium-dark–dark grey–greenish black shale; (c) dark-grey–olive-black laminated shale; (d) greyish-black–brownish-black mudstone. The sections also contain subordinate amounts of siltstone, limestone and dolostone. Comparison of the type section with the cores reveals slight lithological variation and notable thickness differences between the coeval strata. The proximity of the boreholes and different parts of the type section to the Purbeck–Isle of Wight Disturbance is proposed as a likely control on the thickness changes

A women’s worker in court: A more appropriate service for women defendants with mental health issues?

Aims Court liaison services aim to reduce mental illness in prison through early treatment and/or diversion into care of defendants negotiating their court proceedings. However, liaison services may inadvertently contribute to gender inequalities in mental health in the prison system. This is because women often do not access liaison services. This is attributed to services failing to recognise that women have different needs from men. To address this, it is essential that the needs of women in contact with the criminal justice system (CJS) are clearly articulated. However, there is a dearth of research that considers women’s needs at this stage of their journey through the CJS. This paper aims to identify these needs before women enter prison. It does so through an analysis of a pilot Women’s Support Service based at a Magistrates’ Court, a response to concerns that women were not accessing the local liaison service. Characteristics of women defendants attending the service are described, specifically their home environments, general and mental health needs. Their support needs when in contact with the CJS and the links the service must forge with local community organisations to provide this, are also presented. This knowledge will develop/ tailor existing services available to women defendants to improve their access to these and optimise the benefits they can derive from them. Methods Proformas were completed by a women specialist worker for 86 women defendants assessed in 4 months. Information was collected on characteristics including education, domestic violence, accommodation, physical and mental health.. This specialist worker recorded the range of needs identified by defendants at assessment and the services to which women were referred. Results Access to the Women’s Support Service is high, with only 11.3% of women refusing to use the service. Women attending have high levels of physical and mental health issues. Their mental health issues have not being addressed prior to accessing the service. Women often come from single households and environments high in domestic abuse. Women have multiple needs related to benefits, finance, housing, domestic abuse, education and career guidance. These are more frequent than those that explicitly link to mental health. The women’s worker providing the service referred women to 68 services from a wide variety of statutory and voluntary organisations. Conclusions The Women’s Support Service is accessed by a higher number of women, many more than access the local liaison service. It is suggested that this is due to their multiple and gender specific needs being adequately addressed by the former service and the organisations to whom they are referred. Mental health needs may also be secondary to other more basic needs, that makes the generic service provided but the Women’s support Service more appropriate than a liaison service that deals with mental health support alone

Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study

Background: Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of 5 pound for the completion of postal questionnaires. Methods: We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of 5 pound to patients for the completion and return of questionnaires. The first 105 patients did not receive the 5 pound incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. Results: The response rate following reminders for the historical controls was 78.1% ( 82 of 105) compared with 88.0% ( 389 of 442) for those patients who received the 5 pound payment (diff = 9.9%, 95% CI 2.3% to 19.1%). Direct payments significantly increased the odds of response ( adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009) with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial - the extra cost per additional respondent was almost 50 pound. Conclusion: The direct payment of 5 pound significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study

Functional reorganisation and recovery following cortical lesions: A preliminary study in macaque monkeys.

Damage following traumatic brain injury or stroke can often extend beyond the boundaries of the initial insult and can lead to maladaptive cortical reorganisation. On the other hand, beneficial cortical reorganisation leading to recovery of function can also occur. We used resting state FMRI to investigate how cortical networks in the macaque brain change across time in response to lesions to the prefrontal cortex, and how this reorganisation correlated with changes in behavioural performance in cognitive tasks. After prelesion testing and scanning, two monkeys received a lesion to regions surrounding the left principal sulcus followed by periodic testing and scanning. Later, the animals received another lesion to the opposite hemisphere and additional testing and scanning. Following the first lesion, we observed both a behavioural impairment and decrease in functional connectivity, predominantly in frontal-frontal networks. Approximately 8 weeks later, performance and connectivity patterns both improved. Following the second lesion, we observed a further behavioural deficit and decrease in connectivity that showed little recovery. We discuss how different mechanisms including alternate behavioural strategies and reorganisation of specific prefrontal networks may have led to improvements in behaviour. Further work will be needed to confirm these mechanisms.This work was supported by the MRC intramural program MC-A060-5PQ10 (MA, DM, JD, AB), an MRC Career Development Award G0800329 (AM)

Multidecadal Basal Melt Rates and Structure of the Ross Ice Shelf, Antarctica, Using Airborne Ice Penetrating Radar

Basal melting of ice shelves is a major source of mass loss from the Antarctic Ice Sheet. In situ measurements of ice shelf basal melt rates are sparse, while the more extensive estimates from satellite altimetry require precise information about firn density and characteristics of near‐surface layers. We describe a novel method for estimating multidecadal basal melt rates using airborne ice penetrating radar data acquired during a 3‐year survey of the Ross Ice Shelf. These data revealed an ice column with distinct upper and lower units whose thicknesses change as ice flows from the grounding line toward the ice front. We interpret the lower unit as continental meteoric ice that has flowed across the grounding line and the upper unit as ice formed from snowfall onto the relatively flat ice shelf. We used the ice thickness difference and strain‐induced thickness change of the lower unit between the survey lines, combined with ice velocities, to derive basal melt rates averaged over one to six decades. Our results are similar to satellite laser altimetry estimates for the period 2003–2009, suggesting that the Ross Ice Shelf melt rates have been fairly stable for several decades. We identify five sites of elevated basal melt rates, in the range 0.5–2 m a⁻¹, near the ice shelf front. These hot spots indicate pathways into the sub‐ice‐shelf ocean cavity for warm seawater, likely a combination of summer‐warmed Antarctic Surface Water and modified Circumpolar Deep Water, and are potential areas of ice shelf weakening if the ocean warms

The DANTE trial protocol: a randomised phase III trial to evaluate the Duration of ANti-PD-1 monoclonal antibody Treatment in patients with metastatic mElanoma.

BACKGROUND: Immunotherapy is revolutionising the treatment of patients diagnosed with melanoma and other cancers. The first immune checkpoint inhibitor, ipilimumab (targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)), showed a survival advantage over standard chemotherapy. Subsequently the anti-programmed cell death protein 1 (PD-1) antibodies, nivolumab and pembrolizumab were shown to be more effective than ipilimumab. Ipilimumab combined with nivolumab gives an incremental gain in overall survival compared with nivolumab alone but increases the risk of severe, potentially life-threatening toxicities. In contrast to ipilimumab monotherapy, anti-PD-1 antibodies are licensed to be continued until disease progression. Follow-up of patients recruited to the first trials evaluating 2 years of pembrolizumab showed that three-quarters of responding patients continue responding after stopping treatment. Suggestive of early response, we hypothesised that continuing anti-PD-1 treatment beyond 1 year in progression-free patients may be unnecessary and so designed the DANTE trial. METHODS: DANTE is a multicentre, randomised, phase III, non-inferiority trial to evaluate the duration of anti-PD-1 therapy in patients with metastatic (unresectable stage III and stage IV) melanoma. It uses a two-stage recruitment strategy, registering patients before they complete 1 year of first-line anti-PD-1 +/- CTLA-4 therapy and randomising eligible patients who have received 12 months of treatment and are progression-free at 1 year. At randomisation, 1208 patients are assigned (1:1) to either 1) continue anti-PD-1 treatment until disease progression/ unacceptable toxicity/ for at least 2 years in the absence of disease progression/ unacceptable toxicity or 2) to stop treatment. Randomisation stratifies for baseline prognostic factors. The primary outcome is progression-free survival at 3, 6, 9 and 12 months and then, 6-monthly for up to 4-years. Secondary outcomes collected at all timepoints include overall survival, response-rate and duration and safety, with quality of life and cost-effectiveness outcomes collected 3-monthly for up to 18-months. Sub-studies include a qualitative analysis of patient acceptance of randomisation and sample collection to inform future translational studies into response/ toxicity biomarkers. DISCUSSION: DANTE is a unique prospective trial investigating the optimal duration of anti-PD-1 therapy in metastatic melanoma patients. Outcomes will inform future use of these high burden drugs. TRIAL REGISTRATION: ISRCTN15837212 , 31 July 2018

Designing and implementing a COPD discharge care bundle

National surveys have revealed significant differences in patient outcomes following admission to hospital with acute exacerbation of COPD which are likely to be due to variations in care. We developed a care bundle, comprising a short list of evidence-based practices to be implemented prior to discharge for all patients admitted with this condition, based on a review of national guidelines and other relevant literature, expert opinion and patient consultation. Implementation was then piloted using action research methodologies with patient input. Actively involving staff was vital to ensure that the changes introduced were understood and the process followed. Implementation of a care bundle has the potential to produce a dramatic improvement in compliance with optimum health care practice

Mapping species distributions: A comparison of skilled naturalist and lay citizen science recording

To assess the ability of traditional biological recording schemes and lay citizen science approaches to gather data on species distributions and changes therein, we examined bumblebee records from the UK’s national repository (National Biodiversity Network) and from BeeWatch. The two recording approaches revealed similar relative abundances of bumblebee species but different geographical distributions. For the widespread common carder (Bombus pascuorum), traditional recording scheme data were patchy, both spatially and temporally, reflecting active record centre rather than species distribution. Lay citizen science records displayed more extensive geographic coverage, reflecting human population density, thus offering better opportunities to account for recording effort. For the rapidly spreading tree bumblebee (Bombus hypnorum), both recording approaches revealed similar distributions due to a dedicated mapping project which overcame the patchy nature of naturalist records. We recommend, where possible, complementing skilled naturalist recording with lay citizen science programmes to obtain a nation-wide capability, and stress the need for timely uploading of data to the national repository

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions