The Causal Theory of Properties

This thesis investigates the causal theory of properties (CTP). CTP states that properties must be understood via the complicated network of causal relations to which a property can contribute. If an object instantiates the property of being 900C, for instance, it will burn human skin on contact, feel warm to us if near, etc. In order to best understand CTP, I argue that we need to distinguish between properties and particular instances of them. Properties should be analysed via the causal relations their instances stand in, it is this oven’s being 900C which causes my skin to burn, etc. The resulting CTP offers an illuminating analysis of properties. First, it provides a criterion of identity for properties, their identity being analysed via the causal roles property instances realise. It also offers an account of how property instances are sorted into genuine kinds, in cases of determinables and determinates. I show how we can distinguish between genuine and non-genuine similarity via the property instances of objects. The implications of CTP for an analysis of causation are then investigated. I argue that the proposed CTP offers a plausible causal ontology. The fine-grainedness of property instances enables us to capture the subtleties involved in questions concerning what causes what. But, even more importantly, CTP enables us to reconcile two highly attractive theses concerning the causal relation. The first of these is the generalist’s thesis. This states that causal relations are part of more general patterns. The second of these is the singularist’s thesis. This states that the causal connection between two entities, doesn’t depend upon anything extraneous to that relation. I argue that by combining CTP with an ontology of tropes, we can thereby respect what is driving both singularism and generalism.Logic & Metaphysic

The Influence of Dietary Sulfate on the Excretion of \u3csup\u3e35\u3c/sup\u3eS-Cysteine Sulfur as \u3csup\u3e35\u3c/sup\u3eS-Taurine Sulfur by the Rat

The relationship of dietary sulfate to the efficiency of feed utilization, excretion of 35S-cysteine sulfur as 35S-taurine sulfur, and sulfation of lung tissue by the rat was investigated. The feed efficiencies of animals fed diets from weaning that contained 0.10 per cent of inorganic sulfate and 0.47 per cent of organic sulfur as sulfate were significantly higher at the end of a six-week feeding period than were those of littermates fed diets that contained higher or lower levels of inorganic sulfate but comparable levels of total sulfur as sulfate. These findings showed that equivalent levels of sulfur as sulfate supplied by amino acids did not compensate for the omission of sulfate from the diet of the rat. Results of a subsequent experiment revealed that the excretion of 35S-cysteine sulfur as 35S-taurine at the end of a 17-day feeding period was 58 and 82 per cent lower, respectively, among adult rats fed normal and high levels of inorganic sulfate than among those fed low levels of inorganic sulfate in diets that contained equal levels of total sulfur as sulfate. Reductions of 50 and 45 per cent, respectively, from the level of 35S-taurine excreted by the animals fed the low sulfate diet were observed when normal and high levels of sulfate were fed in diets that contained equal levels of 35S-cysteine. When 18 groups of rats were fed different levels of inorganic sulfate in diets supplemented with 0.40 per cent of cysteine, differences could be detected neither in 35S-cysteine sulfur as 35S-taurine sulfur excreted in the urine nor in the total sulfur as sulfate in the lungs at the end of the six-week feeding period. After the experimental diets had been consumed for one week, the excretion of 35S-cysteine sulfur as 35S-taurine sulfur was significantly higher among weaning rats fed a low sulfate diet than among those fed a normal sulfate diet that contained the same level of cysteine, but no differences could be detected by the end of week 2. Adult rats fed the low sulfate diet excreted significantly higher levels of 35S-cysteine sulfur as 35S-taurine sulfur at the end of weeks 1 and 2 of the study than did the animals fed the normal sulfate diet, but not at the end of week 3. Dietary adaptation, which results in reduction in the excretion of 35S-cysteine sulfur as 35S-taurine sulfur to the level excreted by the animal fed the normal sulfate diet, occurs when low sulfate diets are fed to rats for extended periods. The initial rise in cysteine sulfur as taurine sulfur in the urine illustrates an inefficiency in the oxidation of amino acid sulfur to sulfate. The significance of the adaptation to the low sulfate diet, demonstrated by decreased 35S-taurine excretion, as a means of conserving the sulfur-containing amino acids is not revealed by the present findings

Causation and the Grounds of Freedom

In this paper, I take a critical look at Sartorio’s book Causation and Free Will (2016). Sartorio offers a rich defence of an actual-sequence view of freedom, which pays close attention to issues in the philosophy of causation and how they relate to freedom. I argue that although this focus on causation is illuminating, Sartorio’s project nevertheless runs into some serious difficulties. Perhaps most worrying amongst them is whether the agent-based reason-sensitivity account, offered by Sartorio, is consistent with Frankfurt-style cases – the very cases which are provided as the sole reason to endorse an actual-sequence view of freedom. I suggest that given that powers and causation are so intimately bound together, the debate is skewed somewhat by thinking of these as rivals

Gender-specific selection on codon usage in plant genomes

<p>Abstract</p> <p>Background</p> <p>Currently, there is little data available regarding the role of gender-specific gene expression on synonymous codon usage (translational selection) in most organisms, and particularly plants. Using gender-specific EST libraries (with > 4000 ESTs) from <it>Zea mays </it>and <it>Triticum aestivum</it>, we assessed whether gender-specific gene expression <it>per se </it>and gender-specific gene expression level are associated with selection on codon usage.</p> <p>Results</p> <p>We found clear evidence of a greater bias in codon usage for genes expressed in female than in male organs and gametes, based on the variation in GC content at third codon positions and the frequency of species-preferred codons. This finding holds true for both highly and for lowly expressed genes. In addition, we found that highly expressed genes have greater codon bias than lowly expressed genes for both female- and male-specific genes. Moreover, in both species, genes with female-specific expression show a greater usage of species-specific preferred codons for each of the 18 amino acids having synonymous codons. A supplemental analysis of <it>Brassica napus </it>suggests that bias in codon usage could also be higher in genes expressed in male gametophytic tissues than in heterogeneous (flower) tissues.</p> <p>Conclusion</p> <p>This study reports gender-specific bias in codon usage in plants. The findings reported here, based on the analysis of 1 497 876 codons, are not caused either by differences in the biological functions of the genes or by differences in protein lengths, nor are they likely attributable to mutational bias. The data are best explained by gender-specific translational selection. Plausible explanations for these findings and the relevance to these and other organisms are discussed.</p

Methodological consistency and measurement reliability of transversus abdominis real time ultrasound imaging in chronic low back pain populations: a systematic review

“This is an Accepted Manuscript of an article published by Taylor & Francis in Physical Therapy Reviews on 10 Feb 2017, available online: http://www.tandfonline.com/10.1080/10833196.2017.1287151. © 2017 Informa UK Limited, trading as Taylor & Francis Group This author accepted manuscript is made available following 12 month embargo from date of publication (10 Feb 2017) in accordance with the publisher’s copyright policy.Background: Real time ultrasound imaging (RTUI) is used to measure transversus abdominis (TrA) thickness in low back pain (LBP) populations. However, individuals with chronic low back pain (CLBP) pose specific imaging challenges, such as older age and higher body mass index, compared to asymptomatic populations or acute and sub-acute LBP groups. These challenges potentially increase measurement error and may require different imaging methods. Objectives: This review describes the methodologies and reported reliability for RTUI measurement of TrA specific to CLBP populations. Methods: A systematic database search of Medline, CINAHL, PEDro, the full Cochrane library, Scopus, and Informit identified 20 studies that used RTUI to measure TrA of CLBP participants. Two independent raters appraised the quality of the studies using the QualSyst and the QAREL critical appraisal tools. Results: Methodological quality varied from low to high. Methods for patient and transducer positioning and muscle measurement were inconsistent between studies. Eight articles cited reliability results from past studies of non-CLBP populations. Only two studies reported reliability in CLBP populations specifically and found higher Intraclass Correlation Coefficients for thickness measures at rest (0.63–0.97), compared to thickness change over time or contraction ratios (0.28–0.80). Conclusions: Inconsistency of methodology, variable methodological quality, and limited and variable reliability reporting was highlighted in this review. This LBP subgroup poses challenges for RTUI, therefore future research should include standarized methods for image acquisition. This will improve the quality of study methods, reliability of TrA measurement, and improve the applicability and comparibility of research evidence available to clinicians

Protocol for the ADDITION-Plus study: a randomised controlled trial of an individually-tailored behaviour change intervention among people with recently diagnosed type 2 diabetes under intensive UK general practice care.

BACKGROUND: The increasing prevalence of type 2 diabetes poses both clinical and public health challenges. Cost-effective approaches to prevent progression of the disease in primary care are needed. Evidence suggests that intensive multifactorial interventions including medication and behaviour change can significantly reduce cardiovascular morbidity and mortality among patients with established type 2 diabetes, and that patient education in self-management can improve short-term outcomes. However, existing studies cannot isolate the effects of behavioural interventions promoting self-care from other aspects of intensive primary care management. The ADDITION-Plus trial was designed to address these issues among recently diagnosed patients in primary care over one year. METHODS/DESIGN: ADDITION-Plus is an explanatory randomised controlled trial of a facilitator-led, theory-based behaviour change intervention tailored to individuals with recently diagnosed type 2 diabetes. 34 practices in the East Anglia region participated. 478 patients with diabetes were individually randomised to receive (i) intensive treatment alone (n = 239), or (ii) intensive treatment plus the facilitator-led individual behaviour change intervention (n = 239). Facilitators taught patients key skills to facilitate change and maintenance of key behaviours (physical activity, dietary change, medication adherence and smoking), including goal setting, action planning, self-monitoring and building habits. The intervention was delivered over one year at the participant's surgery and included a one-hour introductory meeting followed by six 30-minute meetings and four brief telephone calls. Primary endpoints are physical activity energy expenditure (assessed by individually calibrated heart rate monitoring and movement sensing), change in objectively measured dietary intake (plasma vitamin C), medication adherence (plasma drug levels), and smoking status (plasma cotinine levels) at one year. We will undertake an intention-to-treat analysis of the effect of the intervention on these measures, an assessment of cost-effectiveness, and analyse predictors of behaviour change in the cohort. DISCUSSION: The ADDITION-Plus trial will establish the medium-term effectiveness and cost-effectiveness of adding an externally facilitated intervention tailored to support change in multiple behaviours among intensively-treated individuals with recently diagnosed type 2 diabetes in primary care. Results will inform policy recommendations concerning the management of patients early in the course of diabetes. Findings will also improve understanding of the factors influencing change in multiple behaviours, and their association with health outcomes.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Unlocking the bottleneck in forward genetics using whole-genome sequencing and identity by descent to isolate causative mutations

Forward genetics screens with N-ethyl-N-nitrosourea (ENU) provide a powerful way to illuminate gene function and generate mouse models of human disease; however, the identification of causative mutations remains a limiting step. Current strategies depend on conventional mapping, so the propagation of affected mice requires non-lethal screens; accurate tracking of phenotypes through pedigrees is complex and uncertain; out-crossing can introduce unexpected modifiers; and Sanger sequencing of candidate genes is inefficient. Here we show how these problems can be efficiently overcome using whole-genome sequencing (WGS) to detect the ENU mutations and then identify regions that are identical by descent (IBD) in multiple affected mice. In this strategy, we use a modification of the Lander-Green algorithm to isolate causative recessive and dominant mutations, even at low coverage, on a pure strain background. Analysis of the IBD regions also allows us to calculate the ENU mutation rate (1.54 mutations per Mb) and to model future strategies for genetic screens in mice. The introduction of this approach will accelerate the discovery of causal variants, permit broader and more informative lethal screens to be used, reduce animal costs, and herald a new era for ENU mutagenesis.The High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics is funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC Hub grant G0900747 91070. This study was supported by Wellcome Trust Strategic Award 082030 (CCG), Wellcome Trust Studentship 094446/Z/10/Z (KRB), the Oxford NIHR Biomedical Research Centre, and the MRC Human Immunology Unit (RJC). AJR and GL were supported by Wellcome Trust grant 090532/Z/ 09/Z, CCG and AE by a Major initiative Award from the Clive and Vera Ramaciotti Foundation, and AE by an NHMRC Career Development Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Recurrent Plasmodium falciparum Malaria Infections in Kenyan Children Diminish T-Cell Immunity to Epstein Barr Virus Lytic but Not Latent Antigens

Plasmodium falciparum malaria (Pf-malaria) and Epstein Barr Virus (EBV) infections coexist in children at risk for endemic Burkitt's lymphoma (eBL); yet studies have only glimpsed the cumulative effect of Pf-malaria on EBV-specific immunity. Using pooled EBV lytic and latent CD8+ T-cell epitope-peptides, IFN-γ ELISPOT responses were surveyed three times among children (10 months to 15 years) in Kenya from 2002–2004. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated in association with Pf-malaria exposure, defined at the district-level (Kisumu: holoendemic; Nandi: hypoendemic) and the individual-level. We observed a 46% decrease in positive EBV lytic antigen IFN-γ responses among 5–9 year olds residing in Kisumu compared to Nandi (PR: 0.54; 95% CI: 0.30–0.99). Individual-level analysis in Kisumu revealed further impairment of EBV lytic antigen responses among 5–9 year olds consistently infected with Pf-malaria compared to those never infected. There were no observed district- or individual-level differences between Pf-malaria exposure and EBV latent antigen IFN-γ response. The gradual decrease of EBV lytic antigen but not latent antigen IFN-γ responses after primary infection suggests a specific loss in immunological control over the lytic cycle in children residing in malaria holoendemic areas, further refining our understanding of eBL etiology