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About a third of all marine fish in the world are caught in Small-Scale Fisheries (SSF). SSF are increasingly recognised as essential for food security and livelihoods for vulnerable and economically fragile communities globally. Although individual SSF vessels are usually perceived as having little impact on the ecosystem, the cumulative impact of gear type and number of vessels may be substantial. Bottom trawling is a common fishing method that can greatly influence the marine ecosystem by damaging the seafloor and generating high levels of discards. However, appropriate sampling coverage using on-board observer programmes to collect these data from SSF are rare, as they are expensive and pose logistical constraints. A mobile App was used to assess whether self-reporting by fishers could provide reliable fine-scale information on fishing effort and discards over time in an illegal shrimp trawling fishery in northern Peru. Maps depicting the spatial distribution of trawling effort and the proportion of discards from observers and fishers were compared using the Similarity in Means (SIM) Index, which ranges from 0 when spatial patterns differ completely to 1 when spatial patterns are very similar. High levels of agreement between spatio-temporal patterns of effort (SIM Index = 0.81) and discards (0.96) were found between fisher and observer maps. Moreover, far greater spatial coverage was accomplished by fishers, suggesting that self-reporting via an App represents a useful approach to collect reliable fisheries data as an initial step for effective monitoring and management of these fisheries.The online version contains supplementary material available at 10.1007/s11160-022-09708-9.

Governments worldwide are setting ambitious targets for offshore renewable energy development (ORD). However, deployment is constrained by a lack of understanding of the environmental consequences of ORD, with impacts on protected birds forming a key environmental consenting challenge. Assessing the impacts of ORD on marine birds is challenging, utilizing interlinked approaches to understand complex behavioural, energetic, and demographic processes. Consequently, there is considerable uncertainty associated with ORD assessments for marine birds, with current methods failing to quantify uncertainty in a scientifically robust, evidence-based manner. This leads to a high degree of precaution and a lack of confidence in the evidence used to inform ORD consenting decisions. We review the methods used to estimate ornithological ORD impacts in the UK, a country at the forefront of ORD. We identify areas in which uncertainty quantification could be improved through statistical modelling, data collection, or adaptation of the assessment process. We develop a framework for end-to-end quantification of uncertainty, integrating uncertainty estimates from individual stages of the assessment process. Finally, we provide research recommendations to better quantify and reduce uncertainty, to lower future ORD consenting risk. These recommendations extend beyond the UK and could improve impact assessments in other countries with different legislative frameworks.

We present a novel adaptive filtering approach to the dynamic characterization of waves of varying frequencies and amplitudes embedded in arbitrary noise backgrounds. This method, known as IWAVE (Iterative Wave Action angle Variable Estimator), possesses critical advantages over conventional techniques, making it a useful new tool in the dynamic characterization of a wide range of data containing embedded oscillating signals. After a review of existing techniques, we present the IWAVE algorithm, derive its key characteristics, and provide tests of its performance using simulated and real world data.

Background With life expectancy continuing to rise in the United Kingdom there is an increasing public health focus on the maintenance of physical independence among all older adults. Identifying interventions that improve physical outcomes in pre-frail and frail older adults is imperative. Methods A systematic review of the literature 2000 to 2017 following PRISMA guidelines and registered with PROSPERO (no. CRD42016045325). Results Ten RCT trials fulfilled selection criteria and quality appraisal. The study quality was moderate to good. Interventions included physical activity; nutrition, physical activity combined with nutrition. Interventions that incorporated one or more physical activity components significantly improved physical outcomes in pre-frail and/or frail older adults. Conclusions Physical activity interventions are key to maintaining independence in pre-frail and frail older adults. A lack of consensus regarding the definition of frailty, and an absence of core measures to assess this means any attempt to create an optimal intervention will be impeded. This absence may ultimately impact on the ability of older and frail adults to live well and for longer in the community. Electronic supplementary material The online version of this article (10.1186/s12877-019-1196-x) contains supplementary material, which is available to authorized users.

Objectives To establish whether undertaking cross-sector pharmacy apprenticeship training to become a pharmacy assistant equally split across the two main pharmacy sectors improves training experience and cross-sector understanding. Methods A mixed method approach was utilised to explore the experiences of 10 pharmacy apprentices, their employers and education provider. Questionnaires were used to explore apprentices’ experiences and views following each 6-month placement. Seven pharmacy employers and the education provider were invited to take part in telephone interviews. Questionnaires were analysed using simple frequencies; qualitative data were analysed thematically. Key findings Ten apprentices were recruited, and nine apprentices returned questionnaires from at least one placement. Three hospital-based employers, four community employers and one education provider were interviewed. All participants had found the pilot positive and the cross-sector training to have been a useful experience. Employers noted that the pilot provided the apprentice with valuable insight into the patient’s journey and the opportunity to share learning across sectors. Employers also commented that more information regarding the nature of the training would have been useful to help better structure the placement for the apprentice. Conclusions This paper explores the benefits and challenges of employing a pharmacy apprentice and utilising a novel cross-sector training model. Findings have potential relevance to the training of other pharmacy staff, including pharmacy technicians and pharmacists. They offer early insights into the potential value of pharmacy apprenticeships for training pharmacy assistants, particularly if these are set up across the two main sectors hospital and community pharmacy.

* Students with emotional or behavior disorders (LVBD) present teachers, administrators, policymakers, and researchers with a diverse range of challenges necessitating early and effective intervention practices. Although a lofty goal, students with E/BD need and deserve our help. These students have dismal short- and long-term outcomes, including placement in more restricted instructional environments, limited access to highly qualified teachers, increased rates of suspension and expulsion, and low rates of postschool employment (Bradley, Doolittle, & Bartolotta, 2008; Bradley, Henderson, & Monfore, 2004; Henderson, Klein, Gonzalez, & Bradley, 2005; Wagner, Kutash, Duchnowski, Epstein, & Sumi, 2005). Perhaps most troubling, estimates suggest that approximately 55% of students with E/BD drop out of school, highlighting the gravity of the current state of affairs (Bradley et al., 2008).Even more disconcerting is the decline in outcomes for students with E/BD since the late 1980s. A study by Wagner and colleagues (1992), reporting on the first National Longitudinal Transition Survey, found that when compared among other high-incidence disabilities, the long-term outcomes for students with E/BD were "particularly troubling" (p. 11). In light of the limited outcome improvements for students with E/BD over the past 20 years, we contend that the current state of affairs is particularly troubling. The findings of recent national studies of students with E/BD provoke broader questions about how to remedy the situation and provide these students with practices to best impact outcomes.Intervention and prevention research and practice for students with FVBD has a long and storied history (Kauffman & Landrum, 2005). Even before the passage of P.L 94-142 in 1975, programs were designed specifically to address behavioral problems in children and youth. Since 1975, an immense body of research has evolved across diverse areas of intervention, including academic skills, social skills, positive behavior interventions and supports, and self-determination, to name a few. Intervention and prevention efforts have been further compounded by the advent of the evidence-based practice movement (Walker, 2004), articulating a need for scientifically supported practices, currently defined by the What Works Clearinghouse (WWC) as evidence from predominantly random clinical trials (RCTs; WWC, 2008). A comprehensive elaboration on the impact of the evidencebased practice movement on the E/BD field is beyond the scope of this article, but the key point is that the WWCs RCT criterion relegates much of the research published in the Council for Children with Behavioral Disorders flagship journal Behavioral Disorders as below evidential standards (see Gage, Lewis, & Adamson, this volume).Not only have students with E/BD's shortand long-term outcomes remained unchanged and abysmal since the 1980s but also has the validity and usability of the field's scientific evidence come under attack due to limited RCT studies. This begs the question, where do we go from here? As future leaders in the field of E/BD, we face the task of improving the day-to-day realties of students with E/BD and the methodological concerns outlined previously. Yet, as Antonio eloquently responded to Sebastian in The Tempest, "What's past is prologue"; what has transpired has set the stage for what is to come. We contend that the answer as to how we improve outcomes is functionally tied to how we improve our practices and programs for students with E/BD and that the answer has been around for almost 20 years.This article provides an historical look at how programs and practices have been evaluated since 1964, leading to a codified, although not universally recognized, set of recommendations for evaluating best practices for students with E/BD set out by The Peacock Hill Working Group (1991). We contend that, in addition to the programmatic features of best practice, the addition of the quality indicators and standards for research in special education (Brantlinger, Jimenez, Klingner, Pugach, & Richardson, 2005; Gersten et al. …

Special education continues to document the poor within and post-school outcomes among children and youth with Emotional/Behavioral Disorders (EBD). While the poor outcomes are due to a myriad of causes, three issues routinely emerge as problematic in the field. First, the need for early intervention and prevention has been well documented, and yet educators continue to struggle with building effective prevention systems. Second, a clear disconnect exists between the current federal definition of “seriously emotionally disturbed” and the educational focus and intent of the law leading to inconsistencies and under-identification of students and the adoption of a pathology model versus a strength-based educational model. Finally, the field continues to struggle with the implementation and sustained use of evidence-based practices within and across schools and school districts. The purpose of this article is to discuss how School-Wide Positive Behavior Support can assist in addressing the issues related to t...

Microbes live under glaciers that have persisted for millions of years, without a clear energy supply. Analyses of crushed rocks suggest that interactions of glaciers with the rocks beneath can produce enough H2 to support methanogenic bacteria. Substantial parts of the beds of glaciers, ice sheets and ice caps are at the pressure melting point1. The resulting water harbours diverse subglacial microbial ecosystems2,3 capable of affecting global biogeochemical cycles4,5. Such subglacial habitats may have acted as refugia during Neoproterozoic glaciations6. However, it is unclear how life in subglacial environments could be supported during glaciations lasting millions of years because energy from overridden organic carbon would become increasingly depleted7,8. Here we investigate the potential for abiogenic H2 produced during rock comminution to provide a continual source of energy to support subglacial life. We collected a range of silicate rocks representative of subglacial environments in Greenland, Canada, Norway and Antarctica and crushed them with a sledgehammer and ball mill to varying surface areas. Under an inert atmosphere in the laboratory, we added water, and measured H2 production with time. H2 was produced at 0 °C in all silicate–water experiments, probably through the reaction of water with mineral surface silica radicals formed during rock comminution. H2 production increased with increasing temperature or decreasing silicate rock grain size. Sufficient H2 was produced to support previously measured rates of methanogenesis under a Greenland glacier. We conclude that abiogenic H2 generation from glacial bedrock comminution could have supported life and biodiversity in subglacial refugia during past extended global glaciations.

An HIV positive black African woman presented with widespread lymphadenopathy and pancytopenia that had been ascribed to tuberculosis. Lymph node biopsy showed both Kaposi's sarcoma and multicentric Castleman's disease. Despite antiretroviral therapy and chemotherapy the patient deteriorated, developing confusion and dysphasia. A cranial magnetic resonance scan showed central pontine myelinolysis. Despite supportive therapy the patient died.

The robotic mouse is an autosomal dominant mutant that arose from a large-scale chemical mutagenesis program. It has a jerky, ataxic gait and develops adult-onset Purkinje cell loss in the cerebellum in a striking region-specific pattern, as well as cataracts. Genetic and physical mapping of the disease locus led to the identification of a missense mutation in a highly conserved region ofAf4, a putative transcription factor that has been previously implicated in leukemogenesis. We demonstrate thatAf4is specifically expressed in Purkinje cells, and we hypothesize that the expression of mutantAf4leads to neurodegeneration. This function was not identified through knock-out studies, highlighting the power of phenotype-driven mutagenesis in the mouse to identify new pathways involved in neurological disease.

Background The aim of this study was to determine in a randomised trial whether there is any significant difference in toxicity between modified CHOP and MCOP chemotherapy in elderly patients with aggressive non-Hodgkin’s lymphoma (NHL) and to determine whether this reduced dose chemotherapy can be administered with full dose intensity, low toxicity and produce acceptable survival. Patients and methods Between 1993 and 2000, 155 eligible patients were randomised into this trial mainly from three centres (Nottingham, Birmingham and Leeds, UK). The patients were newly diagnosed with aggressive NHL and had a median age of 74 years (range 65–91 years). Ninety-six patients (62%) had bulky stage I or II disease; 59 patients (38%) had either stage III or IV disease; 77% had one or more extranodal sites involved at presentation; and 31% showed B symptoms. Seventy-seven patients were randomised to receive six cycles of modified CHOP (cyclophosphamide 600 mg/m2 i.v., doxorubicin 30 mg/m2 i.v., vincristine 1 mg i.v. all on day 1 with prednisolone 20 mg bd for days 1–5) every 21 days and 78 patients to MCOP (mitozantrone 10 mg/m2 i.v. substituted for doxorubicin). Growth factors were not used routinely. After completion of chemotherapy, 39 patients received involved field radiotherapy (35–40 Gy) in 20 fractions. Results One hundred and one patients (65%) completed all six cycles of chemotherapy. The median course dose intensity was 97%. The median follow-up for 53 surviving patients was 51 months. The median survival was 19 months (95% confidence interval 10–36 months) with an actuarial survival of 47% at 2 years and42% at 3 years (CHOP versus MCOP, P = 0.79). There was no significant difference in any of the toxicities experienced with either CHOP or MCOP, except for white cell count (46 patients on MCOP and 27 patients on CHOP had grade 3 or 4 toxicity, P = 0.002) and red cell transfusion (37 patients, MCOP; 17 patients, CHOP; P = 0.001). Grade 3 or 4 neutropenia was documented in 75 patients (50%). One patient died from toxicity whilst in remission and seven patients died with septicaemia and persistent NHL. Conclusion This multicentre randomised trial provides further information on the dose intensity achievable with CHOP or MCOP regimens in elderly patients (median age 74 years) with aggressive NHL. These dose-reduced regimens can be given with nearly 100% dose intensity with 65% of patients completing all the treatment. Survival is comparable to that observed with the more intensive regimens given in this age group.

Objectives: Understanding barriers to early diagnosis of symptomatic breast cancer among Black African, Black Caribbean and White British women in the UK. Design: In-depth qualitative interviews using grounded theory methods to identify themes. Findings validated through focus groups. Participants: 94 women aged 33-91 years; 20 Black African, 20 Black Caribbean and 20 White British women diagnosed with symptomatic breast cancer were interviewed. Fourteen Black African and 20 Black Caribbean women with (n=19) and without (n=15) breast cancer participated in six focus groups. Setting: Eight cancer centres/hospital trusts in London (n=5), Somerset (n=1), West Midlands (n=1) and Greater Manchester (n=1) during 2012-2013. Results: There are important differences and similarities in barriers to early diagnosis of breast cancer between Black African, Black Caribbean and White British women in the UK. Differences were influenced by country of birth, time spent in UK and age. First generation Black African women experienced most barriers and longest delays. Second generation Black Caribbean and White British women were similar and experienced fewest barriers. Absence of pain was a barrier for Black African and Black Caribbean women. Older White British women (≥70 years) and first generation Black African and Black Caribbean women shared conservative attitudes and taboos about breast awareness. All women viewed themselves at low risk of the disease, and voiced uncertainty over breast awareness and appraising non-lump symptoms. Focus group findings validated and expanded themes identified in interviews. Conclusions: Findings challenged reporting of Black women homogenously in breast cancer research. This can mask distinctions within and between ethnic groups. Current media and health promotion messages need reframing to promote early presentation with breast symptoms. Working with communities and developing culturally appropriate materials may lessen taboos and stigma, raise awareness, increase discussion of breast cancer and promote prompt help-seeking for breast symptoms among women with low cancer awareness.

Background and aims: Smoking tobacco has opposite effects on the different forms of inflammatory bowel disease (IBD). It predisposes to the development of Crohn's disease (CD) yet is associated with a reduced incidence of ulcerative colitis (UC). We have studied sib pairs discordant for both smoking and IBD phenotype (UC or CD) to investigate whether smoking determines the type of IBD that develops in individuals with very similar genetic susceptibility. Patients: Smoking habits and disease characteristics were analysed in 242 IBD pedigrees (658 patients). Within this group there were 339 affected sibling pairs of whom 89 were discordant for smoking when diagnosed. Results: Smoking at diagnosis was associated with development of CD (odds ratio (OR) 3.55; 95% confidence limits 2.50–5.02; p

A 30 year old man presented with late stage HIV disease and intrathoracic lymphadenopathy. Histology of a mediastinal biopsy suggested infective follicular hyperplasia or a peripheral T cell lymphoma. Subsequently, Epstein-Barr virus (EBV) infection was demonstrated in lymphocytes in the biopsy. Later, hepatosplenomegaly and peripheral lymphadenopathy developed. Histology of a cervical lymph node biopsy showed EBV associated diffuse large B cell (non-Hodgkin's) lymphoma.

Novel synthetic antagonists of retinoic acid receptors (RARs) have been developed. To avoid interference by serum retinoids when testing these compounds, we established serum-free grown sub-lines (3 years) of the prostate carcinoma lines LNCaP, PC3 and DU145. A high affinity pan-RAR antagonist (AGN194310, K(d) for binding to RARs = 2-5 nM) inhibited colony formation (by 50%) by all three lines at 16-34 nM, and led to a transient accumulation of flask-cultured cells in G1 followed by apoptosis. AGN194310 is 12-22 fold more potent than all-trans retinoic acid (ATRA) against cell lines and also more potent in inhibiting the growth of primary prostate carcinoma cells. PC3 and DU145 cells do not express RARbeta, and an antagonist with predominant activity at RARbeta and RARgamma (AGN194431) inhibited colony formation at concentrations (approximately 100 nM) commensurate with a K(d)value of 70 nM at RARgamma. An RARalpha antagonist (AGN194301) was less potent (IC(50) approximately 200 nM), but was more active than specific agonists of RARalpha and of betagamma. A component(s) of serum and of LNCaP-conditioned medium diminishes the activity of antagonists: this factor is not the most likely candidates IGF-1 and EGF. In vitro studies of RAR antagonists together with data from RAR-null mice lead to the hypothesis that RARgamma-regulated gene transcription is necessary for the survival and maintenance of prostate epithelium. The increased potencies of RAR antagonists, as compared with agonists, suggest that antagonists may be useful in the treatment of prostate carcinoma.

BACKGROUNDGenetic anticipation has been proposed to explain observed age differences at diagnosis of Crohn’s disease in affected parents and offspring.AIMSTo compare affected parent-child pairs with Crohn’s disease and ulcerative colitis with a control group of non-familial patients with inflammatory bowel disease (IBD) in order to quantify whether ascertainment bias could account for this effect.METHODS137 affected parent-child pairs from 96 families and 214 patients with sporadic IBD were studied. Age at onset of symptoms and diagnosis were ascertained by interview and disease confirmed from clinical records.RESULTSOf the 137 affected parent-child pairs, 50 had Crohn’s disease only, 51 had ulcerative colitis only, and in 36, one had Crohn’s disease and the other ulcerative colitis. The median age of parents at diagnosis was 17.5 years older, 16 years older, and 18 years older in the Crohn’s disease, ulcerative colitis, and mixed disease families respectively (pCONCLUSIONSThere was no evidence of genetic anticipation or genomic imprinting of age at diagnosis in this sample of IBD families. Ascertainment bias is responsible for the age differences at diagnosis between affected parents and children.

A retrospective histopathological review of 2104 cases of solid tumour was carried out to assess the variability in diagnosis of childhood cancer. Cases were subject to three independent, concurrent opinions from a national panel of specialist pathologists. The conformity between them was analysed using the percentage of agreement and the kappa statistic (kappa), a measure of the level of agreement beyond that which could occur by chance alone, and weighted kappa (w kappa), which demonstrates the degree of variation between opinions. The major groupings of the Birch-Marsden classification were used within which tumours were assigned for kappa analysis according to the clinical significance of the differential diagnoses. The mean agreement for all tumours together was 90%; kappa = 0.82, w kappa = 0.82. Retinoblastoma achieved the highest kappa value (1.0) and lymphoma the lowest (0.66). Of the cases, 16.5% had their original diagnoses amended and the panel confirmed the original diagnosis of paediatric pathologists in 89% of cases compared with 78% for general pathologists. The varying levels of agreement between experts confirm the difficulty of diagnosis in some tumour types, suggesting justification for specialist review in most diagnoses. Specialist training in paediatric pathology is also recommended.

We have analysed 174 gastric carcinomas from the United Kingdom and from Japan for the presence of Epstein-Barr virus (EBV) using in situ hybridisation for the small EBV-encoded nuclear RNAs (EBERs). EBV was detected in the tumour cells in all of six undifferentiated gastric carcinomas with prominent lymphoid stroma (undifferentiated carcinomas of nasopharyngeal type, UCNT) but only in three of the remaining 168 typical gastric adenocarcinomas (1.8%). No differences were observed between the British and the Japanese cases. One case with an EBV-positive UCNT showed adjacent areas of EBV-negative typical adenocarcinoma. It is uncertain whether these patterns represent two independent carcinomas or whether they are the result of heterogeneous EBV infection in a single tumour. In the remaining EBV-positive carcinomas, viral transcripts were detected in virtually all tumour cells, indicating that EBV infection must have taken place early in the neoplastic process and suggesting that the virus is likely to be of pathogenetic significance for the virus-associated tumours. Immunohistology demonstrated absence of detectable levels of the EBV-encoded latent membrane protein, LMP1, and nuclear antigen, EBNA2. The BZLF1 protein which induces the switch from latent to lytic infection was demonstrated in a small proportion of the tumour cells in three cases. The close association of EBV with undifferentiated gastric carcinomas compared to the variable association with gastric adenocarcinomas suggests fundamentally different roles for the virus in the aetiology of these two malignancies. Images Figure 1 Figure 2 Figure 3

A 65-year-old man presented in 1997 with a nodule on his back; histology showed apparent high grade T-cell lymphoma, treated after excision with radiotherapy. He relapsed with lesions on the thigh and buttock in 1998 and was treated with CHOP chemotherapy with a complete response. Further relapse occurred in 1999 with a nodule on his thigh again; he received CNOP (doxorubicin substituted with mitozantrone). At no stage was there clinical, bone marrow or radiological evidence of extra cutaneous disease. In November 2000 he presented with widespread indurated plaques and violaceous nodules. Biopsies repeated with extensive immunohistological staining diagnosed aleukaemic leukaemia cutis. Our patient was diagnosed with cutaneous T-cell lymphoma (CTCL) on the basis of clinical and haemotoxylin & eosin appearances. The correct diagnosis was made after extensive immunohistological studies (including myeloid markers) of repeat biopsies. This case illustrates the importance of diagnostic review in atypical CTCL. There is a high incidence of progression to acute myeloid leukaemia.

We have analysed 22 nasopharyngeal carcinomas (NPCs) for expression of the small nuclear Epstein-Barr virus (EBV)-encoded RNAs (EBERs) and for immunohistologically detectable overexpression of p53. In situ hybridization demonstrated expression of the EBERs in 13 undifferentiated NPCs while nine squamous cell NPCs were EBER-negative. These results therefore confirm our previous DNA-DNA in situ hybridization studies and demonstrate that in the nasopharynx EBV is exclusively associated with undifferentiated but not with squamous cell carcinomas. p53 overexpression was demonstrated by immunohistology in 5 of 9 squamous cell NPCs and in 9 of 13 undifferentiated NPCs. Thus, there appears to be no correlation of p53 overexpression with EBV infection. These results are unexpected in the light of previous studies demonstrating that the p53 gene in primary undifferentiated NPC is consistently in the wild-type configuration. By contrast, analyses of squamous cell carcinomas of the head and neck have demonstrated that p53 overexpression in these cases is the result of p53 gene mutation. Whilst more detailed genetic analysis is required, our results suggest that mechanisms other than mutation of the p53 gene may be responsible for the stabilization of the protein in cases of undifferentiated NPC. It is tempting to speculate that an EBV-encoded protein may be involved.

Salivary tissue intraductal papillomas are rare, benign tumours that predominantly affect minor salivary glands. We report a case of an intraductal papilloma arising in the unusual site of the submandibular gland. The tumour was completely excised and recurrence is not expected. A brief review of this histologically distinct lesion is presented.

During the last twenty-five years, racist abuse, little or no protection for black people, and an assumption that all black people are criminals, are just some of the accusations which have been levelled at the approach to policing in the UK (Kalunta-Crumpton 2000). As a result of this, tensions between the Afro-Caribbean community and the police service in the UK are known to exist, and the relationship between them is strained. This fragile relationship has, at times, reached breaking point and can be witnessed in different periods of time, but most noticeably during the Brixton Riots of 1981 and also the aftermath of Stephen Lawrence’s murder in 1993. The outcome of the inquiry into the handling of the Stephen Lawrence case saw the Metropolitan Police Service held accountable for their failure to treat his murder as racially motivated (Macpherson 1999). Given all this, it is somewhat surprising that police interviews with Afro-Caribbean and White British suspects are under-researched in the field of sociolinguistics. The only comparable research examines the treatment of Aboriginal Australians in courtroom interaction and police interviews (Eades 1994 and subsequent works). To address this gap in the research, this thesis considers twenty police interviews conducted with Afro-Caribbean and White British suspects in custody suites across England and Wales. A combined quantitative and qualitative framework was adopted; the application of both methods strengthens the findings. The quantitative approach reveals the differences that exist between the Afro-Caribbean and White British suspect interviews whist the qualitative approach can go some way in explaining why these differences exist. The approaches to discourse and the features chosen for the qualitative analysis were data driven. Consequently, the approach taken combines the analytical strengths of Conversation Analysis with the critical social stance of Critical Discourse Analysis. The analysis focuses on two linguistic features: overlapping talk and so- prefaced questions, as well as considering the implications of repetition of questions and accusations. There is a wealth of well known literature about overlapping talk (see for instance, Goldberg 1990). .In this literature, overlapping talk is analysed in a variety of ways; ranging from attributing a high frequency of overlaps to powerful talk and claiming that all overlaps are dominance-related (e.g. Dunbar and Burgoon 2005) to considering the multiple functions of overlapping talk, where context is crucial for establishing function (e.g. Friedland and Penn 2003). It is worth pointing out here, that the latter is the widely accepted approach in sociolinguistics and is used here. However, during the process of coding overlapping talk, a further dimension proved significant in understanding and encapsulating the power dynamics of a police interview. This dimension was whether the proposition in the overlap was taken up or not taken up by the interruptee. The overall term used to refer to these phenomena is responsivity. In contrast to overlapping talk, there is considerably less literature on so- prefaced questions. However, what there is, suggests that so- prefaced questions are generally a feature of power-asymmetric discourse (Cotterill 2003). Broadly speaking, so- prefaced questions fall under one of two categories; information-seeking and confirmation-seeking (Newbury and Johnson 2006). This is a good starting point for the analysis because it takes into account the macro functions of so- prefaced questions which reveal two things; whether suspects have been given the opportunity to provide new information and whether they are coerced to agree with propositions in questions. It is also important to consider the macro functions of so- prefaced questions, as this provides an insight into the degree of information control as well as the extent to which suspects are expected to agree with propositions in questions. From a CA perspective, so- prefaced questions fall under the umbrella of formulations and are confirmation- seeking (Johnson 2002). A helpful distinction in CA is the use of gist and upshot to describe formulating practices. Gists are essentially a summary of the prior talk and this also true for upshots. However, upshots also draw out a relevant implication and the other speaker is expected to ratify it. Therefore, upshots can have an underlying purpose and not necessarily be in tune with what the original speaker meant. What this means is that the police officer, having changed the agenda, is in a greater position to challenge the suspect (Drew 2003). Analysis involving so- prefaced formulations is therefore one way to reveal the power relationships between suspects and police officers. The main finding from the quantitative analysis of overlapping talk regarding responsivity is that the Afro-Caribbean suspects’ propositions are taken up to a lesser degree than any other group. This clearly shows that the police officers had more power and control than the Afro-Caribbean suspects in these interviews and potentially has something to do with race and suspect status. The question that remains is why the Afro-Caribbean suspects were taken up on fewer occasions than their White British counterparts. The qualitative analyses reveal this is a result of the overlapping style of the Afro-Caribbean suspects. Whilst there are a number of potential reasons why the Afro-Caribbean suspects display a different conversational style to the White British suspects, it is not possible to establish which reason is the most plausible with the present data. Consequently, more research is needed on the African Diaspora, as well as investigating attitudes towards overlapping talk (as Murata 1994 has done with Japanese and British people). The overall frequency of so- prefaced questions is low. However, there is a significant difference between the Afro-Caribbean and White British interviews in relation to this feature. In particular, there is a higher frequency of confirmation-seeking so- prefaced questions in the Afro-Caribbean suspect interviews. When these results are broken down further, there is a higher frequency of upshots in the Afro-Caribbean suspect interviews. This shows us that the Afro-Caribbean suspects were constrained in a way that the White British suspects were not. Crucially, upshots enabled the police interviewers to constrain the Afro-Caribbean suspects to take up and defend new agendas which were not necessarily in tune with what they said. A particularly interesting finding from this research is that the racial inequality observed in the overlapping talk analyses is a result of the suspects’ behaviour, whereas in the so- prefaced questions analyses, racial inequality is produced by the police officers. Interaction is a mutual activity, and this means it is important to look at the contributions of all participants in a given interaction. Therefore, in order to address the central research question of unequal treatment/institutional racism, it is relevant to examine how the contributions of both suspects and police officers can lead to inequality. The link between ethnicity and the differential treatment of Afro-Caribbean suspects might be considered tenuous, given that the reason the Afro-Caribbean suspects get taken up less is as a result of when they overlap the interviewing officers, rather than because they are black. However, race and colour are made relevant by the police officers, and, as such, there is the potential for racist attitudes to surface. The findings from this research have implications for police interviewing in the UK and potentially world-wide. References Cotterill, J. (2003) Language and Power in Court. Great Britain: Palgrave Macmillan Drew, P. (2003) ‘Comparative Analysis of Talk-in-interaction in Different Institutional Settings: A Sketch’, in P.J. Glenn, C.D. LeBaron and J. Mandelbaum (eds.) Studies in Language and Social Interaction: In Honor of Robert Hopper. Mahwah, NJ: Erlbaum. pp. 293–308 Dunbar, N. E. and Burgoon, J. K. (2005) ‘Perceptions of power and interactional dominance in interpersonal relationships’. Journal of Social and Personal Relationships 22(2): 207-233 Eades, D. (1994) ‘A case of communicative clash: Aboriginal English and the legal system,’ in Gibbons, J. (ed.) Language and the Law. London: Longman pp. 234-264 Friedland, D. and Penn, C. (2003) ‘Conversation analysis as a technique for exploring the dynamics of a mediated interview’, International Journal of Language and Communication Disorders 38(1): 95-111 Goldberg, J. A. (1990) ‘Interrupting the discourse on interruptions: An analysis in terms of relationally, neutral, power- and rapport-oriented acts’. Journal of Pragmatics 14:883-903 Kalunta-Crumpton, A. (2000) ‘Black people and discrimination in criminal justice: the messages from research’, in A. Marlow and B. Loveday (eds.) After Macpherson: Policing after the Stephen Lawrence Inquiry. Trowbridge: Russell House Publishing pp. 41-52 Macpherson, W. (1999) The Stephen Lawrence Inquiry: Report of an Inquiry by Sir William Macpherson of Cluny. United Kingdom: TSO Murata, K. (1994) ‘Intrusive or cooperative? A cross-cultural study of interruptions’. Language in Society 14: 31-40 Newbury, P. and Johnson, A. (2006) ‘Suspects resistance to constraining and coercive questioning strategies in the police interview’. The International Journal of Speech, Language and the Law 13(2): 213-240

A survey of over 200 households in Vancouver was conducted to determine stored quantities and generation characteristics of household hazardous wastes (HHW). Respondents were also asked to identify their preferences and concerns regarding the design of a collection program for these wastes. The results were used to estimate the quantities of HHW disposed of annually, and the quantities and profiles of wastes that could be received at a typical depot collection program in the City. Different operating parameters for both depot collection programs and household collection programs were compared and evaluated for effectiveness. Public willingness to participate in different collection programs was evaluated, and the collection needs of different residential areas were assessed. Several differences in waste generation and public willingness to participate were noted between areas of apartment dwellers and detached residence dwellers, and of high and low income levels. Recommendations were made to assist in the design of an effective HHW collection program for the City of Vancouver. Alternatives for the design of a collection program were developed. Key words: household hazardous waste, solid waste, household waste, hazardous waste, waste collection, small quantity generator, waste generation, special waste.

The 1:1 inclusion compounds of cholic acid with methanol (C24H40O5.CH4O), ethanol (C24H40O5.C2H6O) and 1-propanol (C24H40O5.C3H8O) crystallize in the P2(1)2(1)2(1) space group with unit-cell dimensions at 293 K: a = 15.198 (6), b = 11.625 (7), c = 14.560 (9) A; a = 14.653 (7), b = 11.739 (4), c = 15.045 (2) A; and a = 15.026 (2), b = 11.864 (9), c = 14.951 (4) A; Z = 4. The structures were solved using direct methods. Full-matrix least-squares refinement reduced the conventional R factor to values of 0.109, 0.066 and 0.071, respectively. The alcohol molecules are contained in cavities created by the cholic acid molecules and are involved in the hydrogen-bonding scheme consisting of five unique hydrogen bonds. Statistical disorder is observed for the ethanol and 1-propanol molecules.

Sixteen lymph nodes from 14 patients with rheumatoid arthritis were examined immunohistochemically and morphometrically and compared with 10 control nodes showing follicular hyperplasia from patients without rheumatoid disease. Frozen material was available from nine patients and all controls. The nodes from patients with rheumatoid arthritis seemed to share characteristic features. The most striking of these was follicular hyperplasia in which the germinal centres, in spite of being quite large, showed relatively sparse proliferative activity. The nodes often showed infiltration of germinal centres by CD8 positive T lymphocytes and contained fewer IL2R positive cells in the paracortex than controls. These and other features may have some correlation with disease activity. Lymphadenopathy in rheumatoid arthritis may not just be a manifestation of joint inflammation but an active component of this multisystem disease and may reflect a widespread immunological abnormality.

Nature Geoscience 8, 851–855 (2015); published online 29 October 2015; corrected after print 29 October 2015. In the print version of this Letter originally published, the published online date was incorrectly stated as 21 September 2015; the correct published online date is 29 October 2015. This has been corrected in all online versions of the Letter.

A phase I/II study of Doxil combined with whole abdomen hyperthermia was conducted in patients with refractory ovarian cancer. Liposomal doxorubicin combined with hyperthermia has been shown to increase both liposomal delivery and drug extravasation into tumour xenografts resulting in enhanced cytotoxic effects.Thirty patients with either recurrent or persistent epithelial ovarian cancer were enrolled. All patients had either measurable or assessable disease. Patients received intravenous (IV) Doxil at a dose of 40 mg m-2 as a 1-h infusion followed by whole abdomen hyperthermia. The phase I portion of the study was performed to determine the maximal tolerated dose (MTD) of hyperthermia. Quality of life (QoL) was performed at baseline, prior to each cycle and every 3 months. Plasma pharmacokinetic studies were performed with the first cycle.Ten patients participated in the phase I portion of the study which demonstrated that the MTD of hyperthermia was 60 min after either average vaginal and rectal temperatures of 40 degrees C had been achieved or after 30 min of power application, whichever was shorter. All 30 patients were either paclitaxel and/or platinum resistant initially or developed resistant disease. The median number of prior chemotherapeutic regimens was three (range 2-8) and six patients had been previously treated with Doxil. There were three partial responses for a response rate of 10% (95% CI: [2%, 27%]) and eight patients (27%; 95% CI: [12%, 46%]) had disease stabilization. The median time to progression or death was 3.4 months (95% CI: [2.6, 5.2]) and the median survival was 10.8 months (95% CI: [8.8, 17.4]). Twelve patients (40%) experienced palmar-plantar erythrodysesthesia (PPE), but only four (13%) experienced grade 3-4 PPE toxicity. Doxil systemic exposure was higher in those with grade 3-4 PPE compared to those with no PPE. None of the patients had grade 3-4 thermal toxicity due to hyperthermia. QoL was not decreased in patients responding to therapy.Therapy with intravenous Doxil and whole abdomen hyperthermia for patients with platinum/paclitaxel resistant ovarian cancer is feasible and does not negatively impact quality of life.

Immunoblastic transformation of Waldenström's macroglobulinaemia is normally a preterminal event. We report a case in which the immunoblastic transformation appeared to be limited to the spleen. Splenectomy was more effective than cytotoxic chemotherapy in controlling the disease, and the patient remains free of disease 45 months later.

A case of nasal T-cell lymphoma in a Caucasian male is reported, in which the presence of Epstein-Barr virus within tumour cells was demonstrated by in situ hybridization to the Epstein-Barr virus encoded RNAs EBER-1 and EBER-2.

To determine if the removal of cytoplasm from metaphase II human donor oocytes damages the meiotic spindle apparatus.Cryopreservation of metaphase II human oocytes was performed using a fast-freeze, fast-thaw protocol. Upon thaw, oocytes were incubated for 3-4 h and then used for cytoplasmic donation (test oocytes). Oocytes thawed but not used for donation served as controls. Test and control oocytes were fixed using a microtubule-stabilizing buffer. Tubulin was localized using antitubulin monoclonal antibody. Chromosomes were identified by counterstaining with DAPI.Forty-four oocytes had cytoplasm removed (test group) while 12 were not used for the procedure (controls). Twenty-three oocytes survived the donation procedure. Rates of normal spindle structure for the control and test groups were 21/23 (91.3%) and 12/12 (100%), respectively.The removal of cytoplasm from a metaphase II human donor oocyte does not appear to significantly increase the damage to chromosome alignment or to the spindle structure.

An unusual case of a desmoplastic fibroma of the temporal bone is presented. Although classified benign, this intraosseous lesion exhibits local aggressiveness and has a high potential for recurrence. This rare condition occurs predominantly in the mandible and in the long bones and is seldom seen in the calvarium. Here we add another case to the previously described eight in the skull and this is the fourth such case reported in the temporal bone. The clinical features, radiology, histopathology and the therapeutic considerations of this lesion in a 72-year-old female are discussed. In addition, a literature review of all the cases affecting the skull bones is presented.

A true lipoma is a rare lesion in the oral cavity. A histologically distinct variant is the spindle-cell variety, which is an innocuous lesion that can simulate a myxoid liposarcoma.We report a case of intra-oral spindle-cell lipoma in a 42-year-old female and have reviewed the literature pertaining to this unusual histopathological entity. A wareness of the condition is essential for both clinicians and pathologists to avoid any misinterpretation of the benign nature of this condition.

The Emory Angioplasty versus Surgery Trial (EAST) showed that multivessel patients eligible for both percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass surgery (CABG) had equivalent 3-year outcomes regarding survival, myocardial infarction, and major myocardial ischemia. Patients eligible for the trial who were not randomized because of physician or patient refusal were followed in a registry. This study compares the outcomes of the randomized and registry patients. Of the 842 eligible patients, 450 did not enter the trial. Their baseline features closely resembled those of the randomized patients and follow up was performed using the same methods. In the registry there was a bias toward selecting CABG in patients with 3-vessel disease (84%) and PTCA in patients with 2-vessel disease (54%). Three-year survival for the registry patients was 96.4%, which was better than the randomized patients, 93.4% (p = 0.044). Angina relief in the registry was equal for CABG and PTCA patients and was better for the PTCA registry (12.4%) than PTCA randomized patients (19.6%) (p = 0.079). Thus, the registry confirms that EAST is representative of all eligible patients and does not represent a low-risk subgroup. Since baseline differences were small, improved survival in the registry may be due to treatment selection. Physician judgment, even in patients judged appropriate for clinical trials, remains a potentially important predictor of outcomes.

Increasingly, patients are returning for a second, third, and even fourth coronary artery bypass graft (CABG) procedure.This report reviews the in-hospital and long-term outcomes for 102 patients undergoing a third or fourth CABG at Emory University from December 1977 to April 1994.The mean interval from the first to second CABG was 5.2 +/- 3.5 years and from the second to the third CABG 6.8 +/- 4.1 years. The mean age was 6 +/- 9 years, 91% were male, 33% had hypertension, 16% diabetes, 86% class III or IV angina (Canadian Cardiovascular Society), 4.4% congestive failure (New York Heart Association), and 73% three-vessel disease. The in hospital mortality rate was 9.8%, with a perioperative myocardial infarction rate of 8.8% and a stroke rate of 1.9%.These perioperative mortality and myocardial infarction rates are several times higher than those reported for initial revascularizations or first-time redo CABG operations. However, the 5- and 10-year survival rates of 79% and 59%, respectively, and a myocardial infarction-free survival of 62% at 5 years, the benefits of a third-time CABG procedure are apparent for this high-risk group of patients.

Completeness of revascularization after coronary artery bypass operation has been shown to improve short- and medium-term outcome. The purpose of this study was to assess the independent contribution of completeness of revascularization to long-term outcome. A total of 2057 patients with multivessel disease with complete revascularization and 803 with incomplete revascularization, mean age 57 +/- 9 years, was studied. The patient groups were similar except for more prior myocardial infarctions, worse left ventricular function, and more three-vessel disease in the incomplete revascularization group. Complications of perioperative infarction and stroke were not different between those having complete versus incomplete revascularization. The hospital death rate for patients having complete revascularization during the period of study was 0.7% versus 1.5% for those having incomplete revascularization (p = 0.06). Length of hospital stay for the two groups of patients also was not different. At late follow-up (mean 11.7 years for complete and 10.8 years for incomplete) patients who had incomplete revascularization had a significantly higher prevalence of recurrent angina. Multivariate analysis demonstrated the strongest predictors of incomplete revascularization to be number of vessels diseased and left ventricular function (ejection fraction). The multivariate correlates of survival were older age, left ventricular dysfunction, and completeness of revascularization. Completeness of revascularization correlated with improved overall patient survival, as well as survival in patients with normal left ventricular function. Furthermore, the curves continued to separate over time, such that the difference was greater at 8 years than at 4 years, although by 12 years the curves started to converge.

To determine the pattern of exercise and associated adverse events, including injuries, a mail survey was conducted on participants in the 1980 Peachtree Road Race Study for whom we were able to obtain current addresses. A total of 535 persons responded, 326 men and 209 women, representing 72% of those with identifiable addresses. Although only 56% of respondents reported that they were still running in 1990, 81% reported that they were still exercising regularly. The cumulative probability for continuing to run was 0.71 for men and 0.56 for women. Injury (31%) was the chief reason given by men for stopping permanently. For women, 28% stopped because they chose another form of exercise. Fifty-three percent of respondents had at least one injury during the 10-yr interval. The probability of experiencing an injury was associated with higher weekly mileage. The knee was the most frequently injured site. Thirty-nine percent of women and 35% of men reported being verbally assaulted. Approximately 10% of persons were hit by thrown objects or bitten by a dog. In a group of recreational runners, almost half had stopped running 10 yr later, but over 80% were still physically active. Many runners sustain injuries or suffer hazards related to their exercise.

Intracoronary stents are being used to treat acute and threatened closure after percutaneous transluminal coronary angioplasty and to prevent restenosis.The outcomes of 68 patients having coronary artery bypass grafting after stent placement were reviewed. The mean age was 60.5 +/- 9.7 years, and 71% were male. Thirty-seven percent had hypertension, 13% had diabetes, 62% had class III or IV angina, 60% had multivessel disease, and 40% had sustained a prior myocardial infarction. Fifty-three patients underwent emergency operation, 22 with hemodynamic collapse immediately after percutaneous transluminal coronary angioplasty, and 7 others required urgent revascularization within 24 hours of angioplasty. Seventeen underwent coronary artery bypass grafting for acute closure of the stented vessel several days after the angioplasty procedure.There was no correlation between urgency of the procedure, previous infarction, or previous coronary artery bypass grafting with successful procedure. The in-hospital mortality was 4.4%, 21% had a Q-wave myocardial infarction, and 1.5% sustained a stroke. Ejection fraction was the only correlate of long-term mortality.Coronary artery injury for which stents are placed for acute or threatened occlusion or to prevent restenosis but then fail, thus necessitating coronary artery bypass grafting, can be treated successfully. Although the rate of Q-wave myocardial infarction is substantial and related to the initial ischemic insult, the long-term survival and event rates are excellent with prompt surgical revascularization.

Paraffin wax sections of lymph node biopsies from a total of thirteen patients with the morphologic and clinical features of Castleman's disease were analyzed for the presence of the Epstein-Barr virus (EBV) by in situ hybridization for the noncoding EBV early RNAs (EBERs) and by immunohistochemistry for the EBV-encoded latent membrane protein-1 (LMP-1). Of twelve cases of localized Castleman's disease EBER-positive cells were identified in five, and in these cases were only rarely found and were always confined to the interfollicular regions. LMP-1 was not detected in any of these cases, either alone or after dual staining for EBERs and LMP-1. (A similar pattern of EBER expression is seen in nonneoplastic lymphoid tissue from EBV-positive individuals.) No EBER-positive or LMP-1 positive cells were identified in a single case of multicentric Castleman's disease. In two additional patients initially diagnosed with Castleman's disease of localized plasma cell type, repeat biopsy showed Hodgkin's disease. In both cases Reed-Sternberg cells and their variants were identified in the original biopsy on which the diagnosis of Castleman's disease was made. In one of these cases these cells showed expression of EBERs and LMP-1, indicating latent infection with EBV. The results suggest that EBV is not generally associated with Castleman's disease. Further analysis of a series of cases of multicentric Castleman's disease is indicated.

The association of Epstein-Barr virus (EBV) with a growing number of human malignancies underlines the importance of efforts aimed at preventing the infection with this potential carcinogen and of establishing animal models for human virus-associated tumors. Cottontop tamarins have been used in EBV vaccine studies because virus infection regularly induces lymphomas similar to those seen in human immunocompromised individuals. In recent years, several vaccines based on the gp340/220 envelope protein of EBV have been developed and shown to prevent the development of EBV-associated lymphomas in this model. Using in situ hybridization and immunohistology, we have characterized EBV infection in one nonimmunized and three immunized animals after challenge with a standard tumorigenic dose of EBV. In the nonimmunized animal, EBV-infected lymphoid cells were detected in numerous tissues showing no obvious lymphoma infiltration. Surprisingly, variable numbers of virus-carrying cells were also found in all three immunized animals that were protected against the development of virus-associated lymphoma. This observation demonstrates that vaccination does not induce sterilizing immunity against EBV infection in this model. Double labeling suggested a B cell phenotype of the majority of these cells. EBV infection of nonlymphoid cells was not observed. Analysis of viral gene expression in immunized animals suggested a restricted form of virus latency different from that seen in EBV-driven lymphomas in nonimmunized cottontop tamarins. These results raise the possibility that immunized cottontop tamarins protected against the development of EBV-driven lymphoma or animals exposed to a sublymphomagenic dose of virus may serve as a model for EBV infection in humans.

PURPOSE The United Kingdom Central Lymphoma Group (CLG) has modified mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) by substituting mechlorethamine with chlorambucil and dacarbazine with etoposide in the treatment of patients with advanced Hodgkin's disease (HD). Prednisolone is included in the bleomycin-containing combination, and the vinca alkaloids have been switched to balance the myelotoxicity of the two component regimens. PATIENTS AND METHODS The resulting ChlVPP/PABlOE regimen is as follows: on days 1 to 14, chlorambucil 6 mg/m2 orally, procarbazine 100 mg/m2 orally, and prednisolone 30 mg/m2 orally; on days 1 and 8, vinblastine 6 mg/m2 intravenously (i.v.); on day 29, doxorubicin 40 mg/m2 i.v.; on days 29 and 36, vincristine 1.4 mg/m2 (maximum, 2 mg) i.v., and bleomycin 10 mg/m2 i.v.; on days 30, 31, and 32, etoposide 200 mg/m2/d orally; on days 29 to 43, inclusive, prednisolone, 30 mg/m2 orally. The second full cycle restarts on day 50. Treatment continues to maximum response plus two full cycles, but with a minimum of three full cycles. Radiotherapy is administered, after chemotherapy, to sites of previously bulky disease. Since 1983, 216 patients with previously untreated, advanced Hodgkin's disease (HD) have entered this study. RESULTS The complete remission (CR) rate after chemotherapy was 73% (95% confidence interval [CI], 67% to 79%), and after additional radiotherapy was 85% (95% CI, 80% to 90%). The failure-free survival (FFS) rate at 5 years was 68% (95% CI, 61% to 74%), and the overall actuarial survival at 5 years was 78% (95% CI, 72% to 84%). The CR rate in patients in the poorer prognostic categories was high: 81% in patients with albumin levels less than 37 g/L, 79% in patients older than 40 years of age, 84% in stages IIIB plus i.v. disease, and 79% in patients presenting with B symptoms. As expected, nausea and vomiting were not major problems, although infection, often in the context of myelosuppression, complicated almost half the cases, and 29% of patients required admission at some stage for treatment of infection. CONCLUSION In this multicenter study, ChlVPP/PABlOE produced results comparable to those reported for MOPP/ABVD, but with less nausea and vomiting. Treatment duration was shorter than in the original MOPP/ABVD regimen, and than that used in the Cancer and Leukemia Group B (CALGB) trial. It will now be compared with PABlOE alone.