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Quantum logics in cognition:A proposal
Get PDFQuantum logics are non-classical logics defined from the mathematical formalism of quantum mechanics. While they are conventionally used to model inferential processes in physics, their scope of application is potentially much broader. We argue that quantum logics can serve as a framework to model human cognition, as their semantics seem able to capture not only how people make inferences about quantum mechanics, but also how they reason in general. We begin by defining quantum logics from an algebraic perspective in a classical first-order setting. Next, we present findings from cognitive science that suggest these logics are apt to characterize human reasoning. We then consider how such a connection between quantum logics and cognition contributes to longstanding philosophical debates about the epistemological status of logic and the problem of adoption. Finally, we discuss how cognitive applications of quantum logics could advance our understanding of human psychology and even quantum foundations
How improvements to drug effectiveness impact mass drug administration for control and elimination of schistosomiasis
Get PDFSchistosomiasis affects more than 230 million people worldwide. Control and elimination of this parasitic infection is based on mass drug administration of praziquantel (PZQ), which has been in use for several decades. Because of the limitations of the efficacy of PZQ especially against juvenile worms, and the threat of the emergence of resistance, there is a need to consider alternative formulations or delivery methods, or new drugs that could be more efficacious. We use an individual-based stochastic model of parasite transmission to investigate the effects of possible improvements to drug efficacy. We consider an increase in efficacy compared to PZQ, as well as additional efficacy against the juvenile life stage of schistosome parasites in the human host, and a slow-release formulation that would provide long-lasting efficacy for a period of time following treatment. Analyses suggest a drug with a high efficacy of 99%, or with efficacy lasting 24 weeks after treatment, are the two most effective individual improvements to the drug profile of PZQ. A drug with long lasting efficacy is most beneficial when MDA coverage is low. However, when prevalence of infection has already been reduced to a low level, a high efficacy is the most important factor to accelerate interruption of transmission. Our results indicate that increased efficacy against juvenile worms can only result in modest benefits, but the development of a new drug formulation with higher efficacy against adult worms or long-lasting efficacy would create an improvement to the community impact over the currently used formulation.</p
Impact of lifestyle in chronic pain and depression a propensity score analysis in UK biobank
Get PDFBackground Chronic pain and depression are prevalent global health burdens that frequently co-occur, leading to worse outcomes than either condition alone. Current treatments are frequently inadequate, particularly for comorbid chronic pain and depression. Identifying contributing lifestyle factors could help inform more effective interventions and improve our understanding of disease pathophysiology. Methods This study aimed to identify contributing factors for both conditions by assessing the effects of seven lifestyle-related variables (using counterfactual analysis to account for confounding) within the UK Biobank. Chronic pain and depression were analysed as separate disorders and within nominal comorbidity groups (neither disorder, each disorder in isolation and both disorders combined), in full and sex-specific samples. Results Insufficient sleep (full sample: odds ratio (OR) =1.645, PAdjusted<0.001, female sample: OR=1.693, PAdjusted =0.002) and loneliness (full sample: OR=3.397, PAdjusted <0.001, female sample: OR=3.196, PAdjusted <0.001, male sample: OR=3.798, PAdjusted <0.001) were associated with increased risk of depression. Obesity (full sample: OR=1.379, PAdjusted<0.001, female sample: OR=1.467, PAdjusted<0.001, male sample: OR=1.308, PAdjusted= 0.005) was associated with an increased risk of chronic pain. In nominal outcomes, insufficient sleep (full sample: OR=1.828, PAdjusted <0.001, female sample: OR=1.845, PAdjusted<0.001, male sample: OR=1.847, PAdjusted=0.013) and loneliness (full sample: OR=3.488, PAdjusted<0.001, female sample: OR=3.388, PAdjusted<0.001, male sample: OR=3.782, PAdjusted<0.001) were associated with an increased risk of comorbid chronic pain and depression. Additionally, loneliness was also associated with an increased risk of depression without chronic pain (full sample: OR=2.812, PAdjusted =0.003, male sample: OR=3.467, PAdjusted=0.014) and obesity was associated with an increased risk of chronic pain without depression (full sample: OR=1.333, PAdjusted<0.001, female sample: OR=1.399, PAdjusted =0.002, male sample: OR=1.281, PAdjusted =0.018). Conclusions By identifying lifestyle-related risk factors with potential causal impacts on chronic pain, depression and their comorbidity, these findings enhance our understanding of disease pathophysiology and highlight potential markers and targets of more accurate diagnoses and non-therapeutic interventions.<br/
Combination of immune checkpoint inhibitors with multi-targeted tyrosine kinase inhibitors for second- or later-line therapy of non-small cell lung cancer:a systematic review and meta-analysis
Get PDFBACKGROUND: Second- or later-line therapy for patients with advanced non-small cell lung cancer (NSCLC) is highly individualized. Combining immune checkpoint inhibitors (ICIs) with multi-targeted tyrosine kinase inhibitors (multi-TKIs) has emerged as a chemotherapy-free option for these patients. We aim to provide a comprehensive overview of the efficacy and safety of the treatment.METHODS: We systematically searched four databases for studies evaluating ICIs combined with multi-TKIs in second- or later-line therapy for NSCLC. Data were extracted and study quality was assessed using the Canadian Institute of Health Economics tool for case series. A systematic review and meta-analysis were conducted for efficacy outcomes.RESULTS: Twenty studies (10 prospective and 10 retrospective) were included from 155 retrieved articles. Nineteen studies were conducted in China, with programmed death receptor 1 (PD-1) antibodies and anlotinib as the most frequently used combination. The single-arm meta-analysis showed that the pooled median progression-free survival (mPFS) was 5.74 months [95% confidence interval (CI): 4.65-6.84], and the median overall survival was 15.41 months (95% CI: 13.40-17.41). The objective response rate was 26.35% (95% CI: 19.52-33.18%), and the disease control rate was about 80.73% (95% CI: 75.59-85.86%). For patients with EGFR/ALK/ROS1 mutations, the mPFS was 3.17 months (95% CI: 2.54-3.79). The most commonly reported severe adverse events across the included studies were hypertension, fatigue, hepatic dysfunction, urinary abnormalities, and hand-foot syndrome.CONCLUSIONS: The combination of ICIs and multi-TKIs offers an alternative chemotherapy-free treatment option for patients with advanced NSCLC in the second- or later-line setting.</p
Interaction does not lead to spontaneous category-based conditioning in an artificial language
No full textVariation is present in every language at every structural level. Though extremely complex, linguistic variation is not fully unpredictable. Previous research suggests that cognitive biases in learning favour conditioned variation: learners often make languages more predictable by eliminating variation or by conditioning it on context, pointing to the presence of biases against random variation. Learning biases favour lexical conditioning over more general category-based conditioning, though both occur in natural languages. Interaction may also contribute to shaping conditioned variation by providing a mechanism for interlocutors to develop a shared system through the coordination of individual preferences. In the present study, we investigated the role of dyadic interaction in the emergence of conditioned variation. We trained participants on an artificial language with unpredictable variation in plural marking and objects representing one or two semantic categories and had them play a communication game using the newly learned language. We hypothesised that interaction would introduce category-based conditioning, this being the simplest conditioned system in the language. Contrary to our expectations, we found no evidence of spontaneous category-based conditioning: participants either removed variation or conditioned marker use on lexical items. Further experiments are needed to explain the emergence of this common linguistic pattern.</p
Gene therapy in cardiac and vascular diseases: A review of approaches to treat genetic and common cardiovascular diseases with novel gene-based therapeutics
No full textIn the past decade, there has been substantive progress in gene therapy across disease indications. However, despite multiple gene therapies being approved for clinical use, none have a cardiovascular indication. Several reasons for this have inhibited or delayed progress in the cardiovascular field. First, developing cardiovascular gene therapeutics represents a substantial technical challenge, particularly relating to identifying and building effective delivery systems for therapeutic cargo that will be sufficient to gain meaningful efficacy with acceptable safety for the patient. Second, for genetic disease, gene editing therapy of pathogenic variants is at a relatively early stage of development. Third, since this is a field in development, the optimal design of clinical trials of cardiovascular gene therapies is also evolving and requires expert attention. Despite this, recent and current clinical trials are charting new ground, gaining valuable new patient-focused information that provides critical new learning and bench-to-bedside iterative development that has been so successful in other disease areas. While most clinical trials currently focus on cardiac gene therapy, vascular approaches are being developed, both genetic and common. We herein review the state-of-the-art in this rapidly progressing field of study. We consider gene therapy vector design, including transcriptional control, an area of incredible opportunity through engineering biology approaches to design, build, and test bespoke transcriptional units for expression of therapeutic cargo. Achieving progress in this exciting field will require close working between all stakeholders, including academic, clinical, industry, regulatory, and patient communities. Based on current progress, there is a 10-year horizon for bringing several cardiovascular gene therapies to licensing
Clinical predictors of readmission to psychiatric inpatient care:A 20-year follow up study of former adolescent inpatients
No full textBACKGROUND: Readmission is a poor outcome associated with significant economic and psychosocial burden, particularly among young people. This study aimed to investigate predictors of time to readmission, the number of readmissions, and the cumulative duration of all readmissions among adolescent psychiatric inpatients over a 20-year observation period.METHODS: A total of 508 adolescents participated in the original study. The length of index hospitalisation, previous inpatient admissions, the number of psychiatric diagnoses, and the severity of depression, anxiety, mania, psychosis, obsessive-compulsive disorder, eating disorder, conduct disorder, and alcohol and substance use were used to predict readmissions. Separate Bayesian regressions were conducted to examine the impact of these predictors on time to readmission, number of readmissions and the cumulative duration of readmissions.RESULTS: The severity of psychosis symptoms predicted all three outcomes. Once participants with existing schizophrenia spectrum diagnoses were removed from the sample, psychosis symptoms still predicted time to readmission and the number of readmissions. Previous inpatient admissions predicted more frequent admissions during the observation period. The severity of depression symptoms was associated with shorter time to first readmission.DISCUSSION: Looking at a range of patient and service level measures, psychosis symptoms predicted all three readmission outcomes in psychiatric inpatients. This finding suggests that psychosis symptoms may be a useful transdiagnostic marker of illness severity, predicting poor outcome into adulthood.</p
The influence of relative age and biological maturation on player selection in the Scottish football associations Club Academy Scotland
No full textRelative age and biological maturation significantly impact talent identification and development in football, with professional academies often favouring relatively older and early maturing players. This study investigated these biases across Club Academy Scotland (CAS). The biological maturation of 1,011 players (U10–U18) across 12 CAS academies was assessed using the Khamis-Roche method. One-sided t-tests were conducted to test the null hypotheses that the true mean was 0.5 (relative age) and 0 (biological age – chronological age [BA-CA]). A significant bias favouring early maturing players emerged from U12. The BA-CA offset effect sizes ranged from small (U12, Hedges’ g = 0.22) to large (U18, Hedges’ g = 1.44). A relative age effect was statistically significant across most groups, with a large effect in U10 (Hedges g = 1.19) but smaller effects in all other groups (Hedges g = 0.16–0.41). This study demonstrated that a RAE exists within professional Scottish football academies, albeit to a small-to-moderate degree, but a larger bias towards earlier developing players exists from U12 and increases in magnitude with each age group. Regular monitoring of biological maturation is essential to address this bias, maximise the talent pool from Scotland’s relatively small population, and support developmentally appropriate training programmes in CAS academies
Developing a Covid-19-focused mHealth system in a low resource setting during the COVID-19 pandemic:Challenges and opportunities
Get PDFIntroduction: Approximately three quarters of Ethiopia’s population live in rural areas and access to healthcare is difficult with poor transport infrastructure and long travel times. Telemedicine has the potential to support healthcare access and to minimise COVID-19 transmission through reduced need to travel. Objectives: This Brief Research Report describes the analysis of qualitative data relating to the development of a mHealth system during the COVID-19 pandemic which would support COVID-19 symptom management in the community in Oromia, Ethiopia. Methods: Data were 1) meeting notes and WhatsApp group discussions 2) focus group with medical staff 3) interview with a senior hospital leader. A framework method was used for analysis.Results: Framework analysis was used and three themes identified: 1) Patient-physician relationship 2) New ways of using everyday technology 3) Infrastructure and digital access. Discussion: We discuss the challenges of developing an mHealth system during a pandemic alongside infrastructural challenges and the preparedness of medical staff and the general population for use of mHealth. Conclusions: We conclude that there is a need for investment in information technology infrastructure and in access to digital networks alongside a need to improve the digital and health literacy of populations for successful implementation of a patient facing mHealth system. Thus, whilst the policy aspirations are admirable, the potential for technological innovation is great, and the clinicians can see the benefit of using technologies to provide care to those who cannot reach clinics, there is a gap between what is possible given the current reality of infrastructure and patient preparedness and the requirements for a successful telemedicine intervention.<br/
Microbially Derived P═S and P═Se Bond Formation
Get PDFMicrobial metabolism is a diverse and sustainable source of synthetic reagents that can be programmed for controlled and high-level production via synthetic biology. However, despite the chemical diversity of metabolism, the chemical utility of metabolites, and the available tools to control metabolic chemistry, there remain few examples of the use of cellular metabolites directly for chemical synthesis. Herein, we report that diverse bacteria perform P═S bond formation (Ph3P to Ph3PS) via central sulfur metabolism and nonenzymatic chemistry in vivo, which can also be applied to affect microbial P═Se bond formation (Ph3PSe). To the best of our knowledge, this is the first biochemical and genetic investigation of P═S bond formation in a microbial cell and the first use of microbial metabolites for P═Se bond formation in chemical synthesis
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