Primary Cardiac Synovial Sarcoma: A Case Report and Brief Review of the Literature

Synovial sarcoma comprises approximately 10% of all soft tissue sarcoma diagnoses; a primary synovial sarcoma of the myocardium is exceedingly rare. There have been very few cases reported in the literature thus far. With the identification of the characteristic and diagnostic chromosomal abnormality t(X;18), this may become an increasingly recognized entity. Our report adds to the limited published cases of primary cardiac synovial sarcoma with the characteristic t(X;18). Further elucidation of the effects of this translocation on the cell cycle may lead to directed therapies in the future

The filmic fugue of Ken Russell’s Pop Goes the Easel

First broadcast as an episode of BBC Television’s Monitor in 1962, Ken Russell’s documentary film Pop Goes the Easel profiles four young artists: Pauline Boty, Peter Phillips, Derek Boshier and Peter Blake. With an exuberant and richly varied approach to filming, Pop Goes the Easel is a rich and revealing document of early Pop Art in London. This article situates the film within the context of television’s engagement with the visual arts in the medium’s first 25 years. It is argued that part of its significance within the tradition of the visual arts on television is its resistance to the determinations of an explanatory voice. Also, that its achievement combines and develops approaches of photojournalism, documentary and art cinema from the mid- and late 1950s. It is further proposed that Pop Goes the Easel is especially note-worthy for its finely-balanced tensions between discourses traditionally understood as oppositional: the stasis of artworks versus the linear narrative of film; the indexical qualities of documentary versus the inventions of fiction; the mass-produced elements and images of popular culture versus the individual authorship and authority of high art; the abstracted rationality of critical discourse versus explosions of embodied sensuality; and the determinations and closure of a singular meaning versus polysemous openness

Lifetime effects and cost-effectiveness of standard and higher-intensity statin therapy across population categories in the UK: a microsimulation modelling study

Background Cardiovascular disease incidence and mortality have declined across developed economies and granular up-to-date cost-effectiveness evidence is required for treatments targeting large populations. To assess the health benefits and cost-effectiveness of standard and higher intensity statin therapy in the contemporary UK population 40–70 years old. Methods A cardiovascular disease microsimulation model, developed using the Cholesterol Treatment Trialists' Collaboration data (117,896 participants; 5 years follow-up), and calibrated in the UK Biobank cohort (501,854 participants; 9 years follow-up), projected risks of myocardial infarction, stroke, coronary revascularization, diabetes, cancer and vascular and nonvascular death for all UK Biobank participants without and with statin treatment. Meta-analyses of trials and cohort studies informed statins’ relative effects on cardiovascular events, incident diabetes, myopathy and rhabdomyolysis. UK healthcare perspective was taken (2020/2021 UK£) with costs per 28 tablets of £1.10 for standard (35%–45% LDL cholesterol (LDL-C) reduction) and £1.68 for higher intensity (≥45% LDL-C reduction) generic statin. Findings Across categories by sex, age, LDL-C, and cardiovascular disease history/10-year cardiovascular risk, lifetime standard statin increased survival by 0.28–1.85 years (0.20–1.09 quality-adjusted life years (QALYs)), and higher intensity statin by further 0.06–0.40 years (0.03–0.20 QALYs) per person. Standard statin was cost-effective across all categories with incremental cost per QALY from £280 to £8530, with higher intensity statin cost-effective at higher cardiovascular risks and higher LDL-C levels. Stopping statin early reduced benefits and was not cost-effective. Interpretation Lifetime low-cost statin therapy is cost-effective across all 40–70 years old in UK. Strengthening and widening statin treatment could cost-effectively improve population health. Funding UK NIHR Health Technology Assessment Programme (17/140/02)

Dallas Bower: a producer for television's early years, 1936-39

Having worked in the film industry as a sound technician and then director, Dallas Bower (1907-99) was appointed in 1936 as one of two senior producers at the start of the BBC Television service. Over the next three years Bower produced as well as directed many ground-breaking live programmes, including the opening-day broadcast on 2 November 1936; the BBC Television Demonstration Film (1937, his only surviving pre-war production); a modern-dress Julius Caesar (1938), in uniforms suggestive of a Fascist disctatorship; Act II of Tristan and Isolde (1938); Patrick Hamilton’s play Rope (1939), utilising extended single camera-shots camera-shots; numerous ballets, among them Checkmate (1938); and ambitious outside broadcasts from the film studios at Denham and Pinewood. Developing the working practices of producing for the theatre, film industry and radio, Bower was a key figure in defining the role of the creative television producer at the start of the medium. Among his innovations, according to his unpublished autobiographical fragment ‘Playback’ (written 1995), was the introduction of a drawn studio plan for the four cameras employed in all live broadcasts from Alexandra Palace. Using Bower’s writings (among them his 1936 book Plan for Cinema), his BECTU History Project interview, the BBC Written Archives and contemporary industry coverage, this article reconstructs the early development of the role of staff television producer in order to consider the questions of autonomy, agency and institutional constraints at the BBC in the pre-war years

The genome of Aeromonas salmonicida subsp. salmonicida A449: insights into the evolution of a fish pathogen

Background Aeromonas salmonicida subsp. salmonicida is a Gram-negative bacterium that is the causative agent of furunculosis, a bacterial septicaemia of salmonid fish. While other species of Aeromonas are opportunistic pathogens or are found in commensal or symbiotic relationships with animal hosts, A. salmonicida subsp. salmonicida causes disease in healthy fish. The genome sequence of A. salmonicida was determined to provide a better understanding of the virulence factors used by this pathogen to infect fish. Results The nucleotide sequences of the A. salmonicida subsp. salmonicida A449 chromosome and two large plasmids are characterized. The chromosome is 4,702,402 bp and encodes 4388 genes, while the two large plasmids are 166,749 and 155,098 bp with 178 and 164 genes, respectively. Notable features are a large inversion in the chromosome and, in one of the large plasmids, the presence of a Tn21 composite transposon containing mercury resistance genes and an In2 integron encoding genes for resistance to streptomycin/spectinomycin, quaternary ammonia compounds, sulphonamides and chloramphenicol. A large number of genes encoding potential virulence factors were identified; however, many appear to be pseudogenes since they contain insertion sequences, frameshifts or in-frame stop codons. A total of 170 pseudogenes and 88 insertion sequences (of ten different types) are found in the A. salmonicida genome. Comparison with the A. hydrophila ATCC 7966T genome reveals multiple large inversions in the chromosome as well as an approximately 9% difference in gene content indicating instances of single gene or operon loss or gain. A limited number of the pseudogenes found in A. salmonicida A449 were investigated in other Aeromonas strains and species. While nearly all the pseudogenes tested are present in A. salmonicida subsp. salmonicida strains, only about 25% were found in other A. salmonicida subspecies and none were detected in other Aeromonas species. Conclusion Relative to the A. hydrophila ATCC 7966T genome, the A. salmonicida subsp. salmonicida genome has acquired multiple mobile genetic elements, undergone substantial rearrangement and developed a significant number of pseudogenes. These changes appear to be a consequence of adaptation to a specific host, salmonid fish, and provide insights into the mechanisms used by the bacterium for infection and avoidance of host defence systems.Peer reviewed: YesNRC publication: Ye

Comparative genomics profiling of clinical isolates of Aeromonas salmonicida using DNA microarrays

BACKGROUND: Aeromonas salmonicida has been isolated from numerous fish species and shows wide variation in virulence and pathogenicity. As part of a larger research program to identify virulence genes and candidates for vaccine development, a DNA microarray was constructed using a subset of 2024 genes from the draft genome sequence of A. salmonicida subsp. salmonicida strain A449. The microarray included genes encoding known virulence-associated factors in A. salmonicida and homologs of virulence genes of other pathogens. We used microarray-based comparative genomic hybridizations (M-CGH) to compare selected A. salmonicida sub-species and other Aeromonas species from different hosts and geographic locations. RESULTS: Results showed variable carriage of virulence-associated genes and generally increased variation in gene content across sub-species and species boundaries. The greatest variation was observed among genes associated with plasmids and transposons. There was little correlation between geographic region and degree of variation for all isolates tested. CONCLUSION: We have used the M-CGH technique to identify subsets of conserved genes from amongst this set of A. salmonicida virulence genes for further investigation as potential vaccine candidates. Unlike other bacterial characterization methods that use a small number of gene or DNA-based functions, M-CGH examines thousands of genes and/or whole genomes and thus is a more comprehensive analytical tool for veterinary or even human health research

Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate

Forward to the past: reinventing intelligence-led policing in Britain

Drawing on archival, secondary material and primary research, this paper examines 'Total Policing', the strategy recently adopted by London's Metropolitan Police. It situates that analysis within a critical examination of other innovative policing strategies previously employed in Britain. It argues that the prospects for Total Policing depend upon the resolution of long-standing problems such as: the inadequacy and inefficiency of local intelligence work; the paucity of evidence for the success of commanders' previous efforts to harness together the component parts of their forces in pursuit of a single mission; and, above all, a seeming inability to learn the lessons of the past. © 2013 © 2013 Taylor & Francis

mTOR independent alteration in ULK1 Ser758 phosphorylation following chronic LRRK2 kinase inhibition

Unc-51 Like Kinase 1 (ULK1) is a critical regulator of the biogenesis of autophagosomes, the central component of the catabolic macroautophagy pathway. Regulation of ULK1 activity is dependent upon several phosphorylation events acting to repress or activate the enzymatic function of this protein. Phosphorylation of Ser758 ULK1 has been linked to repression of autophagosome biogenesis and was thought to be exclusively dependent upon mTOR complex 1 kinase activity. In this study, a novel regulation of Ser758 ULK1 phosphorylation is reported following prolonged inhibition of the Parkinson's disease linked protein Leucine Rich Repeat Kinase 2 (LRRK2). Here, modulation of Ser758 ULK1 phosphorylation following LRRK2 inhibition is decoupled from the repression of autophagosome biogenesis and independent of mTOR complex 1 activity