Lindsay Anderson and the Legacy of Free Cinema

Accepting that Free Cinema’s legacy has been found on British cinema and television screens in the work of directors other than Lindsay Anderson, this article investigates whether Anderson’s own films and television programmes made after the mid-1970s (including not only those that were released but others that were not completed) reveal a continuing commitment to what he liked to call the Free Cinema ‘tradition’ of film-making. In so doing it draws critical attention to Anderson’s lesser known later works such as The Old Crowd, Is That All There Is?, In Celebration, The Whales of August and Glory! Glory! as well as to unmade projects such as The Grand Babylon Hotel, Dress Gray, Vile Bodies, Empire and If (2). . .

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Diabetes mellitus, smoking status, and rate of sputum culture conversion in patients with multidrug-resistant tuberculosis: a cohort study from the country of Georgia.

Diabetes mellitus (DM) is a risk factor for active tuberculosis (TB) but little is known about the effect of DM on culture conversion among patients with multidrug-resistant (MDR)-TB. The primary aim was to estimate the association between DM and rate of TB sputum culture conversion. A secondary objective was to estimate the association between DM and the risk of poor treatment outcomes among patients with MDR-TB.A cohort of all adult patients starting MDR-TB treatment in the country of Georgia between 2009-2011 was followed during second-line TB therapy. Cox proportional models were used to estimate the adjusted hazard rate of sputum culture conversion. Log-binomial regression models were used to estimate the cumulative risk of poor TB treatment outcome.Among 1,366 patients with sputum culture conversion information, 966 (70.7%) had culture conversion and the median time to conversion was 68 days (interquartile range 50-120). The rate of conversion was similar among patients with MDR-TB and DM (adjusted hazard ratio [aHR] 0.95, 95%CI 0.71-1.28) compared to patients with MDR-TB only. The rate of culture conversion was significantly less in patients that currently smoked (aHR 0.82, 95%CI 0.71-0.95), had low body mass index (aHR 0.71, 95%CI 0.59-0.84), second-line resistance (aHR 0.56, 95%CI 0.43-0.73), lung cavities (aHR 0.70, 95%CI 0.59-0.83) and with disseminated TB (aHR 0.75, 95%CI 0.62-0.90). The cumulative risk of poor treatment outcome was also similar among TB patients with and without DM (adjusted risk ratio [aRR] 1.03, 95%CI 0.93-1.14).In adjusted analyses, DM did not impact culture conversion rates in a clinically meaningful way but smoking did

Bivariate and multivariable analyses of patient characteristics associated with cumulative risk of poor treatment outcome among adult pulmonary MDR-TB patients in Georgia 2009–2011.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094890#pone-0094890-t004" target="_blank"><u>Table 4</u></a><u>. Abbreviations</u>: MDR-multidrug-resistant; cRR-crude risk ratio; aRR-adjusted risk ratio; AFB-acid fast bacilli; <b>Bold</b> indicates statistically significant, two sided p-value <0.05.</p>A<p>Poor treatment outcome was defined as failed, defaulted, died, or transferred.</p>B<p>Variables in the adjusted model included all those with reported aRR estimates except <i>Failure to convert culture</i>.</p>C<p>Missing values were coded as no, none, or negative.</p>D<p>All patients were pulmonary, extra-pulmonary includes those with both pulmonary and extra-pulmonary TB.</p>E<p>Adjusted estimate obtained from a separate model for aRR due to 60 patients with treatment outcome who were missing culture conversion status.</p>F<p>Categories created by tertiles of conversion time.</p

Diabetes mellitus and baseline characteristics of adult pulmonary MDR-TB patients in Georgia 2009–2012.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094890#pone-0094890-t001" target="_blank"><u>Table 1</u></a><u> Abbreviations</u>: RBG-random blood glucose; MDR-multidrug-resistant; STD-standard deviation; IQR-interquartile range; AFB-acid fast bacilli.</p>A<p>Based on medical records or self-reported by MDR-TB patients.</p>B<p>Statistically significant, two-sided p-value <0.05.</p>C<p>Variables with missing >5% among patients were reported in the table as a separate category but not calculated within the frequency distribution.</p>D<p>All patients had pulmonary MDR-TB; extra-pulmonary/disseminated includes those with both pulmonary and extra-pulmonary/disseminated.</p

Bivariate and multivariable hazard rate ratios for patient characteristics associated with sputum culture conversion among patients with MDR-TB in Georgia, 2009–2011.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094890#pone-0094890-t002" target="_blank"><u>Table 2</u></a><u> Abbreviations</u>: IQR-interquartile range; MDR-multidrug-resistant; cHR-crude hazard rate ratio; aHR-adjusted hazard rate ratio; RBG-random blood glucose; AFB-acid fast bacilli; Neg-negative; Dissem-disseminated TB; <b>Bold</b> indicates statistically significant, two sided p-value <0.05.</p>A<p>Among patients who converted, median time (days) from MDR TB treatment initiation until first of two consecutive negative sputum cultures ≥30 days apart among patients.</p>B<p>The adjusted model included all variables with estimates in the aHR column.</p>C<p>Any resistance to a second-line TB drug.</p>D<p>Violated proportional hazards assumptions and not included in adjusted model.</p>E<p>Missing data for this variable was recoded into no/null category.</p>F<p>All patients were pulmonary, extra-pulmonary includes those with both pulmonary and extra-pulmonary TB.</p