An infinite hierarchy in a class of polynomial-time program schemes

We define a class of program schemes RFDPS constructed around notions of forall-loops, repeat-loops, arrays and if-then-else instructions, and which take finite structures as inputs, and we examine the class of problems, denoted RFDPS also, accepted by such program schemes. The class of program schemes RFDPS is a logic, in Gurevich's sense, in that: every program scheme accepts an isomorphism-closed class of finite structures; we can recursively check whether a given finite structure is accepted by a given program scheme; and we can recursively enumerate the program schemes of RFDPS. We show that the class of problems RFDPS properly contains the class of problems definable in inductive fixed-point logic (for example, the well-known problem Parity is in RFDPS) and that there is a strict, infinite hierarchy of classes of problems within RFDPS (the union of which is RFDPS) parameterized by the depth of nesting of forall-loops in our program schemes. This is the first strict, infinite hierarchy in any polynomial-time logic properly extending inductive fixed-point logic (with the property that the union of the classes in the hierarchy consists of all problems definable in the logic). The fact that there are problems (like Parity) in RFDPS which cannot be defined in many of the more traditional logics of finite model theory (which often have zero-one laws) essentially means that existing tools, techniques and logical hierarchy results are of limited use to us

Enzymology in perchlorate rich, multi-extreme environments

The potential for life on Mars is one of the most interesting and yet elusive questions in modern science. The surface of Mars holds little prospect for biology due to the large daily temperature ranges, ionizing radiation, the presence of deleterious salts and the absence of liquid water, besides many other contributing factors. However, deep beneath the surface of Mars we may find environments which, while extreme in their own right, are free from some of the more destructive factors experienced on the Martian surface. The deep subsurface of Mars may hold liquid water environments, which would experience high environmental pressures due to their subterranean nature, while also experiencing extremely low temperatures, perhaps as low as -70 °C. In order for such an aqueous environment to remain liquid at such low temperatures, it would require the presence of saturating concentrations of perchlorate salts which have the ability to lower the freezing of water to temperatures around -80 °C. Such an environment provides us with three parameters, perchlorates, pressure, and temperature, against which we can determine the potential for proteinaceous biochemistry to exist in such an extreme environment. How each of these individual factors affect proteinaceous biochemistry is relatively well understood, but we know practically nothing about how these factors interact in combination to ultimately affect biochemistry in such a multi-extreme environment. This is explored throughout this thesis by investigating the effects of perchlorate salts, high pressures, and low temperatures on the activity and stability of the model enzyme α-chymotrypsin. Additionally a meta-analysis of cold adapted enzymes was conducted in order to facilitate a better understanding of the fundamental adaptations which allows enzymes to become more active at low temperatures. Through this research, I found that while perchlorate salts lower the enzyme activity of α-chymotrypsin, high pressures can rescue this lost activity. Furthermore, the perchlorate induced loss of enzyme activity is found to be temperature dependent, as I have shown that perchlorate salts can increase the activity of α-chymotrypsin at low temperatures. These results suggest that while perchlorate rich environments are generally deleterious towards proteinaceous biochemistry and life, the high pressures of deep subsurface environments may counteract some of the negative perchlorate effects, and that the perchlorate salts themselves may actually facilitate increased biochemical potential at low environmental temperatures. While this data does not suggest that perchlorate rich environments are necessarily habitable or inhabited, it does provide us with a mechanistic understanding of how biochemical adaptations could advantageously use physical parameters such as temperature and pressure in order to increase biomolecular perchlorate tolerance

Occupational therapy for rheumatoid arthritis: A systematic review

Patients with rheumatoid arthritis (RA) show a reduction in physical capacities compared with healthy persons. Symptoms such as pain, fatique, stiffness, and decreased muscle strength cause difficulties with daily activities such as grooming and dressing, cooking a meal, cleaning, shopping, work, and leisure activities. The physical, personal, familial, social, and vocational consequences of RA are extensive. Occupational therapy (OT) is concerned with facililtating people in performing their activities of daily living overcoming barriers by maintaining or improving abilities, or compensating for decreased ability in the performance of occupation (1). The most important interventions in OT are training of skills, counseling, education about joint protection, prescription of assistive devices, and the provision of splints (2). Advice/ instruction in the use of assistive devices, training in self-care activities, and training in productivity activities are the 3 interventions for RA patients chosen most often by occuptional therapists (3). (aut. ref.

Untargeted LC-HRMS-based metabolomics to identify novel biomarkers of metastatic colorectal cancer

Colorectal cancer is one of the main causes of cancer death worldwide, and novel biomarkers are urgently needed for its early diagnosis and treatment. The utilization of metabolomics to identify and quantify metabolites in body fluids may allow the detection of changes in their concentrations that could serve as diagnostic markers for colorectal cancer and may also represent new therapeutic targets. Metabolomics generates a pathophysiological ‘fingerprint’ that is unique to each individual. The purpose of our study was to identify a differential metabolomic signature for metastatic colorectal cancer. Serum samples from 60 healthy controls and 65 patients with metastatic colorectal cancer were studied by liquid chromatography coupled to high-resolution mass spectrometry in an untargeted metabolomic approach. Multivariate analysis revealed a separation between patients with metastatic colorectal cancer and healthy controls, who significantly differed in serum concentrations of one endocannabinoid, two glycerophospholipids, and two sphingolipids. These findings demonstrate that metabolomics using liquid-chromatography coupled to high-resolution mass spectrometry offers a potent diagnostic tool for metastatic colorectal cancer.This study was supported by a grant (n° 15CC056/DTS17/00081- ISCIII-FEDER) from the Fundación para la Investigación Biosanitaria de Andalucía Oriental (FIBAO) and Roche Pharma S.L. Authors from the Fundación MEDINA acknowledge the receipt of financial support from this public-private partnership of Merck Sharp & Dohme de España S.A. with the University of Granada and Andalusian Regional Government (PIN-0474-2016)

Laboratory tests of catastrophic disruption of rotating bodies

The results of catastrophic disruption experiments on static and rotating targets are reported. The experiments used cement spheres of diameter 10 cm as the targets. Impacts were by mm sized stainless steel spheres at speeds of between 1 and 7.75 km s?1. Energy densities (Q) in the targets ranged from 7 to 2613 J kg?1. The experiments covered both the cratering and catastrophic disruption regimes. For static, i.e. non-rotating targets the critical energy density for disruption (Q*, the value of Q when the largest surviving target fragment has a mass equal to one half of the pre-impact target mass) was Q* = 1447 ± 90 J kg?1. For rotating targets (median rotation frequency of 3.44 Hz) we found Q* = 987 ± 349 J kg?1, a reduction of 32% in the mean value. This lower value of Q* for rotating targets was also accompanied by a larger scatter on the data, hence the greater uncertainty. We suggest that in some cases the rotating targets behaved as static targets, i.e. broke up with the same catastrophic disruption threshold, but in other cases the rotation helped the break up causing a lower catastrophic disruption threshold, hence both the lower value of Q* and the larger scatter on the data. The fragment mass distributions after impact were similar in both the static and rotating target experiments with similar slopes

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

On a hierarchy involving transitive closure logic and existential second-order quantification

We study a hierarchy of logics where each formula of each logic in the hierarchy consists of a formula of a certain fragment of transitive closure logic prefixed with an existentially quantified tuple of unary relation symbols. By playing an Ehrenfeucht-Fraïssé game specifically developed for our logics, we prove that there are problems definable in the second level of our hierarchy that are not definable in the first; and that if we are to prove that the hierarchy is proper in its entirety (or even that the third level does not collapse to the second) then we shall require substantially different constructions than those used previously to show that the hierarchy is indeed proper in the absence of the existentially quantified second-order symbols

On a Hierarchy Involving Transitive Closure Logic and Existential Second-Order Quantification

We study a hierarchy of logics where each formula of each logic in the hierarchy consists of a formula of a certain fragment of transitive closure logic prefixed with an existentially quantified tuple of unary relation symbols. By playing an Ehrenfeucht-Fraïssé game specifically developed for our logics, we prove that there are problems definable in the second level of our hierarchy that are not definable in the first; and that if we are to prove that the hierarchy is proper in its entirety (or even that the third level does not collapse to the second) then we shall require substantially different constructions than those used previously to show that the hierarchy is indeed proper in the absence of the existentially quantified second-order symbols