On the alleged simplicity of impure proof

Roughly, a proof of a theorem, is “pure” if it draws only on what is “close” or “intrinsic” to that theorem. Mathematicians employ a variety of terms to identify pure proofs, saying that a pure proof is one that avoids what is “extrinsic,” “extraneous,” “distant,” “remote,” “alien,” or “foreign” to the problem or theorem under investigation. In the background of these attributions is the view that there is a distance measure (or a variety of such measures) between mathematical statements and proofs. Mathematicians have paid little attention to specifying such distance measures precisely because in practice certain methods of proof have seemed self- evidently impure by design: think for instance of analytic geometry and analytic number theory. By contrast, mathematicians have paid considerable attention to whether such impurities are a good thing or to be avoided, and some have claimed that they are valuable because generally impure proofs are simpler than pure proofs. This article is an investigation of this claim, formulated more precisely by proof- theoretic means. After assembling evidence from proof theory that may be thought to support this claim, we will argue that on the contrary this evidence does not support the claim

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ABSTRACT. Objective. Currently there are no evidence-based recommendations regarding fitness and strength tests for patients with childhood or adult idiopathic inflammatory myopathies (IIM). This hinders clinicians and researchers in choosing the appropriate fitness-or muscle strength-related outcome measures for these patients. Through a Delphi survey, we aimed to identify a candidate core set of fitness and strength tests for children and adults with IIM. Methods. Fifteen experts participated in a Delphi survey that consisted of 5 stages to achieve a consensus. Using an extensive search of published literature and through the work of experts, a candidate core set based on expert opinion and clinimetrics properties was developed. Members of the International Myositis Assessment and Clinical Studies Group were invited to review this candidate core set during the final stage, which led to a final candidate core set. Results. A core set of fitness-and strength-related outcome measures was identified for children and adults with IIM. For both children and adults, different tests were identified and selected for maximal aerobic fitness, submaximal aerobic fitness, anaerobic fitness, muscle strength tests, and muscle function tests. Conclusion. The core set of fitness-and strength-related outcome measures provided by this expert consensus process will assist practitioners and researchers in deciding which tests to use in patients with IIM. This will improve the uniformity of fitness and strength tests across studies, thereby facilitating the comparison of study results and therapeutic exercise program outcomes among patients wit

Global response of Plasmodium falciparum to hyperoxia: a combined transcriptomic and proteomic approach

<p>Abstract</p> <p>Background</p> <p>Over its life cycle, the <it>Plasmodium falciparum </it>parasite is exposed to different environmental conditions, particularly to variations in O₂pressure. For example, the parasite circulates in human venous blood at 5% O₂pressure and in arterial blood, particularly in the lungs, at 13% O₂pressure. Moreover, the parasite is exposed to 21% O₂levels in the salivary glands of mosquitoes.</p> <p>Methods</p> <p>To study the metabolic adaptation of <it>P. falciparum </it>to different oxygen pressures during the intraerythrocytic cycle, a combined approach using transcriptomic and proteomic techniques was undertaken.</p> <p>Results</p> <p>Even though hyperoxia lengthens the parasitic cycle, significant transcriptional changes were detected in hyperoxic conditions in the late-ring stage. Using PS 6.0™ software (Ariadne Genomics) for microarray analysis, this study demonstrate up-expression of genes involved in antioxidant systems and down-expression of genes involved in the digestive vacuole metabolism and the glycolysis in favour of mitochondrial respiration. Proteomic analysis revealed increased levels of heat shock proteins, and decreased levels of glycolytic enzymes. Some of this regulation reflected post-transcriptional modifications during the hyperoxia response.</p> <p>Conclusions</p> <p>These results seem to indicate that hyperoxia activates antioxidant defence systems in parasites to preserve the integrity of its cellular structures. Moreover, environmental constraints seem to induce an energetic metabolism adaptation of <it>P. falciparum</it>. This study provides a better understanding of the adaptive capabilities of <it>P. falciparum </it>to environmental changes and may lead to the development of novel therapeutic targets.</p

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

The Effect of Nordic Hamstring Strength Training on Muscle Architecture, Stiffness, and Strength

Purpose: Hamstring strain injury is a frequent and serious injury in competitive and recreational sports. While Nordic hamstring (NH) eccentric strength training is an effective hamstring injury prevention method, the protective mechanism of this exercise is not understood. Strength training increases muscle strength, but also alters muscle architecture and stiffness; all three factors may be associated with reducing muscle injuries. The purpose of this study was to examine the effects of NH eccentric strength training on hamstring muscle architecture, stiffness, and strength. Methods: Twenty healthy participants were randomly assigned to an eccentric training group or control group. Control participants performed static stretching, while experimental participants performed static stretching and NH training for 6 weeks. Pre- and post-intervention measurements included: hamstring muscle architecture and stiffness using ultrasound imaging and elastography, and maximal hamstring strength measured on a dynamometer. Results: The experimental group, but not the control group, increased volume (131.5 vs. 145.2 cm3, p\u3c0.001) and physiological cross-sectional area (16.1 vs. 18.1 cm2, p=0.032). There were no significant changes to muscle fascicle length, stiffness, or eccentric hamstring strength. Conclusions: The NH intervention was an effective training method for muscle hypertrophy, but, contrary to common literature findings for other modes of eccentric training, did not increase fascicle length. The data suggest the mechanism behind NH eccentric strength training mitigating hamstring injury risk could be increasing volume rather than increasing muscle length. Future research is therefore warranted to determine if muscle hypertrophy induced by NH training lowers future hamstring strain injury risk

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Reactive Inkjet Printing of Novel Silk Dental Barrier Membranes

Periodontitis is a dental disease which can result in a loss of integrity of the periodontal tissues and lead to eventual tooth loss. Barrier membranes can be used in conjunction with guided bone regeneration (GBR) to help repair the damage caused by periodontitis. GBR promotes and directs the growth of new bone, whilst the barrier membrane secludes the defect site from infiltration by fast growing connective and epithelial tissues which would otherwise fill the defect space. The ideal properties for a barrier membrane are: to have a controllable degradation rate, be biocompatible, prevent surrounding tissues from collapsing into the defect space, and provide cell occlusivity. Current commercial barrier membranes are produced out of materials which are either non-resorbable, requiring a secondary surgery for their extraction, or made from resorbable materials which can have poor structural integrity or degrade into acidic by-products. Silk has had a long history of use as a biomaterial. It degrades into non-toxic components and has adaptable mechanical properties. When used in its regenerated silk fibroin form (RFS), it has recently been used for tissue engineering scaffolds. RSF has several polymorphs of which silk I and silk II are of interest. Silk I is non-crystalline and water soluble while silk II has a crystalline β-sheet structure that is non-water soluble. Silk I converts to silk II upon exposure to methanol, heat treatments and stretching. The ability to transform RSF from a water soluble structure into a non-water soluble structure makes it ideal for a variety of processing techniques. In this thesis, reactive inkjet printing has been investigated as a possible processing method of RSF for the manufacture of barrier membranes. Reactive inkjet printing has been used to control the structural conversion of silk I to silk II by printing different volumes of methanol during film fabrication. It was established that RSF crystallinity (and silk II content) was dependant on the volume of methanol printed. RSF film degradation rate was shown to be related to RSF crystallinity, and hence the volume of printed methanol. Cell studies performed on the RSF films showed that MG-63 osteosarcoma cells remained metabolically active and continued to proliferate during the duration of the study, as well as showing signs of osteogenic activity. RSF films were investigated with the inclusion of nano-hydroxyapatite (nHA) to promote osteogenic activity. nHA/RSF films were produced from a composite ink containing both nHA and RSF. It was found that the inclusion of nHA within the ink impeded the transition of silk I to silk II, and instead increased β-turn structural content, which is an intermediate structure in the transition of silk I to silk II. The inclusion of nHA within the RSF films was shown to improve the osteogenic response of the MG-63 cells. Overall, the work presented in this thesis has demonstrated for the first time that reactive inkjet printing can produce biocompatible RSF films with controllable crystallinity and degradation rate. As a result, a controllable degradation rate, the possibility of including bioactive components such as nHA, in addition to the other promising properties of RSF, make reactively inkjet printed RSF as a viable alternative for use as a barrier membrane