'It's a film' : medium specificity as textual gesture in Red road and The unloved

British cinema has long been intertwined with television. The buzzwords of the transition to digital media, 'convergence' and 'multi-platform delivery', have particular histories in the British context which can be grasped only through an understanding of the cultural, historical and institutional peculiarities of the British film and television industries. Central to this understanding must be two comparisons: first, the relative stability of television in the duopoly period (at its core, the licence-funded BBC) in contrast to the repeated boom and bust of the many different financial/industrial combinations which have comprised the film industry; and second, the cultural and historical connotations of 'film' and 'television'. All readers of this journal will be familiar – possibly over-familiar – with the notion that 'British cinema is alive and well and living on television'. At the end of the first decade of the twenty-first century, when 'the end of medium specificity' is much trumpeted, it might be useful to return to the historical imbrication of British film and television, to explore both the possibility that medium specificity may be more nationally specific than much contemporary theorisation suggests, and to consider some of the relationships between film and television manifest at a textual level in two recent films, Red Road (2006) and The Unloved (2009)

Disseminated tuberculosis among hospitalised HIV patients in South Africa: a common condition that can be rapidly diagnosed using urine-based assays.

HIV-associated disseminated TB (tuberculosis) has been under-recognised and poorly characterised. Blood culture is the gold-standard diagnostic test, but is expensive, slow, and may under-diagnose TB dissemination. In a cohort of hospitalised HIV patients, we aimed to report the prevalence of TB-blood-culture positivity, performance of rapid diagnostics as diagnostic surrogates, and better characterise the clinical phenotype of disseminated TB. HIV-inpatients were systematically investigated using sputum, urine and blood testing. Overall, 132/410 (32.2%) patients had confirmed TB; 41/132 (31.1%) had a positive TB blood culture, of these 9/41 (22.0%) died within 90-days. In contrast to sputum diagnostics, urine Xpert and urine-lipoarabinomannan (LAM) combined identified 88% of TB blood-culture-positive patients, including 9/9 who died within 90-days. For confirmed-TB patients, half the variation in major clinical variables was captured on two principle components (PCs). Urine Xpert, urine LAM and TB-blood-culture positive patients clustered similarly on these axes, distinctly from patients with localised disease. Total number of positive tests from urine Xpert, urine LAM and MTB-blood-culture correlated with PCs (p < 0.001 for both). PC1&PC2 independently predicted 90-day mortality (ORs 2.6, 95%CI = 1.3-6.4; and 2.4, 95%CI = 1.3-4.5, respectively). Rather than being a non-specific diagnosis, disseminated TB is a distinct, life-threatening condition, which can be diagnosed using rapid urine-based tests, and warrants specific interventional trials

HIV-Associated Mycobacterium tuberculosis Bloodstream Infection Is Underdiagnosed by Single Blood Culture

ABSTRACT We assessed the additional diagnostic yield for Mycobacterium tuberculosis bloodstream infection (BSI) by doing more than one tuberculosis (TB) blood culture from HIV-infected inpatients. In a retrospective analysis of two cohorts based in Cape Town, South Africa, 72/99 (73%) patients with M. tuberculosis BSI were identified by the first of two blood cultures during the same admission, with 27/99 (27%; 95% confidence interval [CI], 18 to 36%) testing negative on the first culture but positive on the second. In a prospective evaluation of up to 6 blood cultures over 24 h, 9 of 14 (65%) patients with M. tuberculosis BSI had M. tuberculosis grow on their first blood culture; 3 more patients (21%) were identified by a second independent blood culture at the same time point, and the remaining 2 were diagnosed only on the 4th and 6th blood cultures. Additional blood cultures increase the yield for M. tuberculosis BSI, similar to what is reported for nonmycobacterial BSI. </jats:p

T. brucei cathepsin-L increases arrhythmogenic sarcoplasmic reticulum-mediated calcium release in rat cardiomyocytes

Aims: African trypanosomiasis, caused by Trypanosoma brucei species, leads to both neurological and cardiac dysfunction and can be fatal if untreated. While the neurological-related pathogenesis is well studied, the cardiac pathogenesis remains unknown. The current study exposed isolated ventricular cardiomyocytes and adult rat hearts to T. brucei to test whether trypanosomes can alter cardiac function independent of a systemic inflammatory/immune response. Methods and results: Using confocal imaging, T. brucei and T. brucei culture media (supernatant) caused an increased frequency of arrhythmogenic spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca2+ release (Ca2+ waves) in isolated adult rat ventricular cardiomyocytes. Studies utilising inhibitors, recombinant protein and RNAi all demonstrated that this altered SR function was due to T. brucei cathepsin-L (TbCatL). Separate experiments revealed that TbCatL induced a 10–15% increase of SERCA activity but reduced SR Ca2+ content, suggesting a concomitant increased SR-mediated Ca2+ leak. This conclusion was supported by data demonstrating that TbCatL increased Ca2+ wave frequency. These effects were abolished by autocamtide-2-related inhibitory peptide, highlighting a role for CaMKII in the TbCatL action on SR function. Isolated Langendorff perfused whole heart experiments confirmed that supernatant caused an increased number of arrhythmic events. Conclusion: These data demonstrate for the first time that African trypanosomes alter cardiac function independent of a systemic immune response, via a mechanism involving extracellular cathepsin-L-mediated changes in SR function

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

‘I’m not your mother’: British social realism, neoliberalism and the maternal subject in Sally Wainwright’s Happy Valley (BBC1 2014-2016)

This article examines Sally Wainwright's Happy Valley (BBC1, 2014–2016) in the context of recent feminist attempts to theorise the idea of a maternal subject. Happy Valley, a police series set in an economically disadvantaged community in West Yorkshire, has been seen as expanding the genre of British social realism, in its focus on strong Northern women, by giving it ‘a female voice’ (Gorton, 2016: 73). I argue that its challenge is more substantial. Both the tradition of British social realism on which the series draws, and the neoliberal narratives of the family which formed the discursive context of its production, I argue, are founded on a social imaginary in which the mother is seen as responsible for the production of the selves of others, but cannot herself be a subject. The series itself, however, places at its centre an active, articulate, mobile and angry maternal subject. In so doing, it radically contests both a tradition of British social realism rooted in male nostalgia and more recent neoliberal narratives of maternal guilt and lifestyle choice. It does this through a more fundamental contestation: of the wider cultural narratives about selfhood and the maternal that underpin both. Its reflective maternal subject, whose narrative journey involves acceptance of an irrecoverable loss, anger and guilt as a crucial aspect of subjectivity, and who embodies an ethics of relationality, is a figure impossible in conventional accounts of subject and nation. She can be understood, however, in terms of recent feminist theories of the maternal

Charting the course for a Blue Economy in Peru: A Research Agenda

Ocean- and coastal-based economic activities are increasingly recognised as key drivers for supporting global economies. This move towards the “blue economy” is becoming globally widespread, with the recognition that if ocean-based activities are to be sustainable, they will need to move beyond solely extractive and exploitative endeavours, aligning more closely with marine conservation and effective marine spatial planning. In this paper we define the “blue economy” as a “platform for strategic, integrated and participatory coastal and ocean development and protection that incorporates a low carbon economy, the ecosystem approach and human well-being through advancing regional industries, services and activities”. In Peru, while the seas contribute greatly to the national economy, the full potential of the blue economy has yet to be realised. This paper presents the findings of an early career scientist workshop in Lima, Peru, in March 2016. The workshop “Advancing Green Growth in Peru” brought together researchers to identify challenges and opportunities for green growth across three Peruvian economic sectors—tourism, transport and the blue economy with this paper exploring in detail the priorities generated from the “blue economy” stream. These priorities include themes such as marine spatial planning, detailed evaluations of existing maritime industries (e.g. guano collection and fisheries), development of an effective MPA network, support for sustainable coastal tourism, and better inclusion of social science disciplines in understanding societal and political support for a Peruvian blue economy. In addition, the paper discusses the research requirements associated with these priorities. While not a comprehensive list, these priorities provide a starting point for future dialogue on a co-ordinated scientific platform supporting the blue growth agenda in Peru, and in other regions working towards a successful “blue economy”

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis

Aims: Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker). Methods: We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed. Results: Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [Cmax]: 7.4 vs 8.3 μg mL–1, P =.223; 3.6 vs 3.5 μg mL–1, P =.569; 50.1 vs 46.8 μg mL–1, P =.081; area under the concentration–time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L–1, P = 0.290; 13.5 vs 12.4 mg h L–1, P =.630; 316.5 vs 292.2 mg h L–1, P =.164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges in 61% and 39% of inpatients and 44% and 35% of outpatients. Rifampicin exposure was higher in patients with lactate >2.2 mmol L–1. Conclusion: Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid Cmax were suboptimal in 61% and 39% of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival

A comparison of the population pharmacokinetics of rifampicin, isoniazid and pyrazinamide between hospitalized and non-hospitalized tuberculosis patients with or without HIV

Background. Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between groups. Methods. Standard first-line TB treatment was given daily as per national guidelines, which consisted of oral 4-drug fixed-dose combination tablets containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Plasma samples were drawn on the 3rd day of treatment over eight hours post-dose. Rifampicin, isoniazid, and pyrazinamide in plasma were quantified and NONMEM® was used to analyze the data. Results. Data from 60 hospitalized patients (11 of whom died within 12 weeks of starting treatment) and 48 outpatients were available. Median (range) weight and age were 56 (35 - 88) kg, and 37 (19 - 77) years, respectively. Bioavailability and clearance of the three drugs were similar between TB/HIV hospitalized and TB outpatients. However, rifampicin’s absorption was slower in hospitalized patients than in outpatients; mean absorption time was 49.9% and 154% more in hospitalized survivors and hospitalized deaths, respectively, than in outpatients. Higher levels of conjugated bilirubin correlated with lower rifampicin clearance. Isoniazid’s clearance estimates were 25.5 L/h for fast metabolizers and 9.76 L/h for slow metabolizers. Pyrazinamide’s clearance was more variable among hospitalized patients. The variability in clearance among patients was 1.70 and 3.56 times more for hospitalized survivors and hospitalized deaths, respectively, than outpatients. Conclusion. We showed that the pharmacokinetics of first-line TB drugs are not substantially different between hospitalized TB/HIV patients and TB (with or without HIV) outpatients. Hospitalized patients do not seem to be underexposed compared to their outpatient counterparts