Fungal Adenylyl Cyclase Acts As a Signal Sensor and Integrator and Plays a Central Role in Interaction with Bacteria

10.1371/journal.ppat.1003612PLoS Pathogens910

Systematic review of interventions for treating or preventing antipsychotic-induced tardive dyskinesia

Background: Antipsychotic medication can cause tardive dyskinesia (TD) – late-onset, involuntary, repetitive movements, often involving the face and tongue. TD occurs in > 20% of adults taking antipsychotic medication (first-generation antipsychotics for > 3 months), with this proportion increasing by 5% per year among those who continue to use these drugs. The incidence of TD among those taking newer antipsychotics is not different from the rate in people who have used older-generation drugs in moderate doses. Studies of TD have previously been found to be limited, with no treatment approach shown to be effective. Objectives: To summarise the clinical effectiveness and safety of treatments for TD by updating past Cochrane reviews with new evidence and improved methods; to undertake public consultation to gauge the importance of the topic for people living with TD/the risk of TD; and to make available all data from relevant trials. Data sources: All relevant randomised controlled trials (RCTs) and observational studies. Review methods: Cochrane review methods, network meta-analysis (NMA). Design: Systematic reviews, patient and public involvement consultation and NMA. Setting: Any setting, inpatient or outpatient. Participants: For systematic reviews, adults with TD who have been taking a stable antipsychotic drug dose for > 3 months. Interventions: Any, with emphasis on those relevant to UK NHS practice. Main outcome measures: Any measure of TD, global assessments and adverse effects/events. Results: We included 112 studies (nine Cochrane reviews). Overall, risk of bias showed little sign of improvement over two decades. Taking the outcome of ‘TD symptoms improved to a clinically important extent’, we identified two trials investigating reduction of antipsychotic dose [n = 17, risk ratio (RR) 0.42, 95% confidence interval (CI) 0.17 to 1.04; very low quality]. Switching was investigated twice in trials that could not be combined (switching to risperidone vs. antipsychotic withdrawal: one RCT, n = 42, RR 0.45, 95% CI 0.23 to 0.89; low quality; switching to quetiapine vs. haloperidol: one RCT, n = 45, RR 0.80, 95% CI 0.52 to 1.22; low quality). In addition to RCTs, six observational studies compared antipsychotic discontinuation with decreased or increased dosage, and there was no clear evidence that any of these strategies had a beneficial effect on TD symptoms (very low-quality evidence). We evaluated the addition to standard antipsychotic care of several treatments, but not anticholinergic treatments, for which we identified no trials. We found no clear effect of the addition of either benzodiazepines (two RCTs, n = 32, RR 1.12, 95% CI 0.6 to 2.09; very low quality) or vitamin E (six RCTs, n = 264, RR 0.95, 95% CI 0.89 to 1.01; low quality). Buspirone as an adjunctive treatment did have some effect in one small study (n = 42, RR 0.53, 95% CI 0.33 to 0.84; low quality), as did hypnosis and relaxation (one RCT, n = 15, RR 0.45, 95% CI 0.21 to 0.94; very low quality). We identified no studies focusing on TD in people with dementia. The NMA model found indirect estimates to be imprecise and failed to produce useful summaries on relative effects of interventions or interpretable results for decision-making. Consultation with people with/at risk of TD highlighted that management of TD remains a concern, and found that people are deeply disappointed at the length of time it has taken researchers to address the issue. Limitations: Most studies remain small and poorly reported. Conclusions: Clinicians, policy-makers and people with/at risk of TD are little better informed than they were decades ago. Underpowered trials of limited quality repeatedly fail to provide answers. Future work: TD reviews have data from current trials extracted, tabulated and traceable to source. The NMA highlights one context in which support for this technique is ill advised. All relevant trials, even if not primarily addressing the issue of TD, should report appropriate binary outcomes on groups of people with this problem. Randomised trials of treatments for people with established TD are indicated. These should be large (> 800 participants), necessitating accrual through accurate local/national registers, including an intervention with acceptable treatments and recording outcomes used in clinical practice. Study registration: This study is registered as PROSPERO CRD4201502045. Funding: The National Institute for Health Research Health Technology Assessment programme

Technological elites, the meritocracy, and postracial myths in Silicon Valley

Entre as modernas elites tecnológicas digitais, os mitos da meritocracia e da façanha intelectual são usados como marcadores de raça e gênero por uma supremacia branca masculina que consolida recursos de forma desproporcional em relação a pessoas não brancas, principalmente negros, latinos e indígenas. Os investimentos em mitos meritocráticos suprimem os questionamentos de racismo e discriminação, mesmo quando os produtos das elites digitais são infundidos com marcadores de raça, classe e gênero. As lutas históricas por inclusão social, política e econômica de negros, mulheres e outras classes desprotegidas têm implicado no reconhecimento da exclusão sistêmica, do trabalho forçado e da privação de direitos estruturais, além de compromissos com políticas públicas dos EUA, como as ações afirmativas, que foram igualmente fundamentais para reformas políticas voltadas para participação e oportunidades econômicas. A ascensão da tecnocracia digital tem sido, em muitos aspectos, antitética a esses esforços no sentido de reconhecer raça e gênero como fatores cruciais para inclusão e oportunidades tecnocráticas. Este artigo explora algumas das formas pelas quais os discursos das elites tecnocráticas do Vale do Silício reforçam os investimentos no pós racialismo como um pretexto para a re-consolidação do capital em oposição às políticas públicas que prometem acabar com práticas discriminatórias no mundo do trabalho. Por meio de uma análise cuidadosa do surgimento de empresas de tecnologias digitais e de uma discussão sobre como as elites tecnológicas trabalham para mascarar tudo, como inscrições algorítmicas e genéticas de raça incorporadas em seus produtos, mostramos como as elites digitais omitem a sua responsabilidade por suas reinscrições pós raciais de (in)visibilidades raciais. A partir do uso de análise histórica e crítica do discurso, o artigo revela como os mitos de uma meritocracia digital baseados em um “daltonismo racial” tecnocrático emergem como chave para a manutenção de exclusões de gênero e raça.Palavras-chave: Tecnologia. Raça. Gênero.Among modern digital technology elites, myths of meritocracy and intellectual prowess are used as racial and gender markers of white male supremacy that disproportionately consolidate resources away from people of color, particularly African Americans, Latino/as and Native Americans. Investments in meritocratic myths suppress interrogations of racism and discrimination even as the products of digital elites are infused with racial, class, and gender markers. Longstanding struggles for social, political, and economic inclusion for African Americans, women, and other legally protected classes have been predicated upon the recognition of systemic exclusion, forced labor, and structural disenfranchisement, and commitments to US public policies like affirmative action have, likewise, been fundamental to political reforms geared to economic opportunity and participation. The rise of the digital technocracy has, in many ways, been antithetical to these sustained efforts to recognize race and gender as salient factors structuring technocratic opportunity and inclusion. This paper explores some of the ways in which discourses of Silicon Valley technocratic elites bolster investments in post-racialism as a pretext for re-consolidations of capital, in opposition to public policy commitments to end discriminatory labor practices. Through a careful analysis of the rise of digital technology companies, and a discussion of how technology elites work to mask everything from algorithmic to genetic inscriptions of race embedded in their products, we show how digital elites elide responsibility for their post-racial re-inscriptions of racial visibilities (and invisibilities). Using historical and critical discourse analysis, the paper reveals how myths of a digital meritocracy premised on a technocratic colorblindness emerge key to perpetuating gender and racial exclusions.Keywords: Technology. Race. Gender