An application of software design and documentation language

The software design and documentation language (SDDL) is a general purpose processor to support a lanugage for the description of any system, structure, concept, or procedure that may be presented from the viewpoint of a collection of hierarchical entities linked together by means of binary connections. The language comprises a set of rules of syntax, primitive construct classes (module, block, and module invocation), and language control directives. The result is a language with a fixed grammar, variable alphabet and punctuation, and an extendable vocabulary. The application of SDDL to the detailed software design of the Command Data Subsystem for the Galileo Spacecraft is discussed. A set of constructs was developed and applied. These constructs are evaluated and examples of their application are considered

Automated and semi-automated contact tracing: Protocol for a rapid review of available evidence and current challenges to inform the control of COVID-19

Abstract Introduction Traditional approaches to case-finding, case isolation, and contact tracing methods have so far proved insufficient on their own to prevent the development of local epidemics of COVID-19 in many high-income countries despite relatively advanced public health systems. As a result, many governments have resorted to widespread social distancing measures and mass quarantines (‘lock-downs’) to reduce transmission and to prevent healthcare systems from being overwhelmed. However, such measures impose heavy human and societal costs. Automated or semi-automated digital contact tracing, in conjunction with scaled-up community testing, has been proposed as a key part of exit strategies from lockdowns. However, the effectiveness of these approaches to contact tracing is unclear, and to be effective, trusted, and widely adopted such technology must overcome several challenges. Methods and analysis We will perform a rapid systematic review to assess the effectiveness of automated and semi-automated digital tools for contact tracing, and identify key considerations for successful implementation, to inform the control of COVID-19. We will search PubMed, EMBASE, EBSCO Medical COVID information portal, OVID Global Health, Cochrane Library, medRxiv, BioRxiv, and arXiv for peer-reviewed and pre-print papers on automated or semi-automated digital tools for contact tracing of COVID-19, another respiratory disease with pandemic potential (limited to SARS, MERS, or pandemic influenza), or Ebola, in human populations. Studies will be eligible if published in English between 1 January 2000 and 14 April 2020. We will synthesise study findings narratively and will consider meta-analysis if ≥ 3 suitable studies with comparable interventions and outcomes are available. Ethics and dissemination Ethical approval is not required for this review. We plan to disseminate findings via pre-print, journal publication, through social media and web-based platforms and through direct stakeholder engagement

Benefit, Harm, and Cost-effectiveness Associated With Magnetic Resonance Imaging Before Biopsy in Age-based and Risk-stratified Screening for Prostate Cancer

IMPORTTANCE: If magnetic resonance imaging (MRI) mitigates overdiagnosis of prostate cancer while improving the detection of clinically significant cases, including MRI in a screening program for prostate cancer could be considered. OBJECTIVE: To evaluate the benefit-harm profiles and cost-effectiveness associated with MRI before biopsy compared with biopsy-first screening for prostate cancer using age-based and risk-stratified screening strategies. DESIGN, SETTING AND PARTICIPANTS: This decision analytical model used a life-table approach and was conducted between December 2019 and July 2020. A hypothetical cohort of 4.48 million men in England aged 55 to 69 years were analyzed and followed-up to 90 years of age. EXPOSURES: No screening, age-based screening, and risk-stratified screening in the hypothetical cohort. Age-based screening consisted of screening every 4 years with prostate-specific antigen between the ages of 55 and 69 years. Risk-stratified screening used age and polygenic risk profiles. MAIN OUTCOMES AND MEASURES: The benefit-harm profile (deaths from prostate cancer, quality-adjusted life-years, overdiagnosis, and biopsies) and cost-effectiveness (net monetary benefit, from a health care system perspective) were analyzed. Both age-based and risk-stratified screening were evaluated using a biopsy-first and an MRI-first diagnostic pathway. Results were derived from probabilistic analyses and were discounted at 3.5% per annum. RESULTS: The hypothetical cohort included 4.48 million men in England, ranging in age from 55 to 69 years (median, 62 years). Compared with biopsy-first age-based screening, MRI-first age-based screening was associated with 0.9% (1368; 95% uncertainty interval [UI], 1370-1409) fewer deaths from prostate cancer, 14.9% (12 370; 95% UI, 11 100-13 670) fewer overdiagnoses, and 33.8% (650 500; 95% UI, 463 200-907 000) fewer biopsies. At 10-year absolute risk thresholds of 2% and 10%, MRI-first risk-stratified screening was associated with between 10.4% (7335; 95% UI, 6630-8098) and 72.6% (51 250; 95% UI, 46 070-56 890) fewer overdiagnosed cancers, respectively, and between 21.7% fewer MRIs (412 100; 95% UI, 411 400-412 900) and 53.5% fewer biopsies (1 016 000; 95% UI, 1 010 000-1 022 000), respectively, compared with MRI-first age-based screening. The most cost-effective strategies at willingness-to-pay thresholds of £20 000 (US $26 000) and £30 000 (US$39 000) per quality-adjusted life-year gained were MRI-first risk-stratified screening at 10-year absolute risk thresholds of 8.5% and 7.5%, respectively. CONCLUSIONS AND RELEVANCE: In this decision analytical model of a hypothetical cohort, an MRI-first diagnostic pathway was associated with an improvement in the benefit-harm profile and cost-effectiveness of screening for prostate cancer compared with biopsy-first screening. These improvements were greater when using risk-stratified screening based on age and polygenic risk profile and may warrant prospective evaluation

Bohmian Philosophy of Mind?

Bohm’s theory is in many ways an attractive solution to the measurement problem in quantum mechanics. It provides an intuitive explanation for the distinctive quantum phenomena of interference and entanglement without the need for any problematic “collapse” of the wave function. But it faces several serious difficulties. First, the dynamical law via which the wave function “pushes around” the Bohmian particles is explicitly non-local, against the spirit of special relativity (Bell 1987, 115). Second, the Bohmian particles can be seen as redundant in the context of an Everettian solution to the measurement problem (Brown and Wallace 2005). And third, the Bohmian solution to the measurement problem apparently depends on an implausible and problematic account of mental awareness (Stone 1994; Brown and Wallace 2005). I do not wish to minimize the significance of the first two difficulties; they are serious threats to the tenability of Bohm’s theory. But the third difficulty, I think, rests on a confusion concerning the way in which Bohmian particles encode the outcomes of measurements. In particular, my concern here is to respond to the accusations of Stone (1994) and Brown and Wallace (2005) that Bohm’s theory requires a mysterious kind of direct awareness of the positions of the Bohmian particles in our brains, and also to the claim of Brown and Wallace (2005) that such direct awareness threatens the quantum no-signaling theorem

Maternal vaccination: shaping the neonatal response to pertussis

Antepartum maternal vaccination can protect highly sensitive newborns before they are old enough to receive their own vaccines. Two vaccines are currently recommended during pregnancy: the flu vaccine and the Tdap vaccine against tetanus, diphtheria, and pertussis. Although there is strong evidence that maternal vaccination works to protect the offspring, limitations in the understanding of vaccines and of maternal transfer of immunity compound to obscure our understanding of how they work. Here we focus on the example of pertussis to explore the possible mechanisms involved in the transfer of protection to offspring and how these may impact the newborn’s response to future exposure to pertussis. For example, Tdap vaccines induce pathogen specific antibodies, and those antibodies are known to be transferred from mother to the fetus in utero and to the newborn via milk. But antibodies alone have modest impact on pertussis disease, and even less effect on colonization/transmission. Maternal immune cells can also be transferred to offspring and may play a direct role in protection from disease and/or influence the developing neonatal immune system. However, some of the transferred immunity may also blunt the offspring’s response to subsequent vaccination. In this review we will summarize the protection conferred to offspring by maternal vaccination against pertussis and the likely mechanisms by which protection is transferred, identifying the many knowledge gaps that limit our most effective application of this approach

Higher education and mental health: analyses of the LSYPE cohorts

The aim of our research project was to improve our understanding of common mental health problems in young people who attend higher education, compared with those who do not. We investigated: • whether there were differences in symptoms of common mental disorder between these groups; • how these differences changed over time and what might drive them; and • whether the mental health of higher education students compared with the general population has changed during the past decade. We conducted analyses of two large nationally representative cohort studies: the Longitudinal Studies of Young People In England (LSYPE). Both studies started when young people were 13/14 years of age. LSYPE1, known to participants as Next Steps, started in 2004 and LSYPE2, known to participants as Our Future, started in 2013

Antibiotic pharmacoeconomics: an attempt to find the real cost of hospital antibiotic prescribing.

Antibiotics account for a large part of all hospital pharmacy budgets, but the actual cost of their prescription is unknown. These costs include intravenous administration, labour, serum antibiotic assay, monitoring of haematological and biochemical indices, disposal of sharps and adverse effects. An in-house method of costing antibiotic therapy is presented, to quantify these hidden expenses. Since not only an awareness, but an accurate quantification, of hidden costs is required, a study of various hospital procedures relating directly to antibiotic therapy was undertaken in an acute medical ward; this involved the identification of particular staff members performing various procedures, consumables used and time taken. The cost of five-day courses of gentamicin, penicillin G, ampicillin, flucloxacillin, cefuroxime, ceftotaxime and erythromycin has been calculated; drug and hidden costs for each are presented graphically for comparison. The breakdown cost for gentamicin is presented to illustrate the method. The costing of adverse effects has not been attempted. We suggest that costings of this sort are used in cost-benefit analysis of antibiotic use. These calculations have been incorporated into a computer spreadsheet and this costing service will be offered to clinical areas of our hospital