First-order queries on finite structures over the reals

We investigate properties of finite relational structures over the reals expressed by first-order sentences whose predicates are the relations of the structure plus arbitrary polynomial inequalities, and whose quantifiers can range over the whole set of reals. In constraint programming terminology, this corresponds to Boolean real polynomial constraint queries on finite structures. The fact that quantifiers range over all reals seems crucial; however, we observe that each sentence in the first-order theory of the reals can be evaluated by letting each quantifier range over only a finite set of real numbers without changing its truth value. Inspired by this observation, we then show that when all polynomials used are linear, each query can be expressed uniformly on all finite structures by a sentence of which the quantifiers range only over the finite domain of the structure. In other words, linear constraint programming on finite structures can be reduced to ordinary query evaluation as usual in finite model theory and databases. Moreover, if only "generic" queries are taken into consideration, we show that this can be reduced even further by proving that such queries can be expressed by sentences using as polynomial inequalities only those of the simple form x <y

Anemia in Patients With Resistance to Thyroid Hormone α: A Role for Thyroid Hormone Receptor α in Human Erythropoiesis

Context: Patients with resistance to thyroid hormone (TH) α (RTHα) are characterized by growth retardation, macrocephaly, constipation, and abnormal thyroid function tests. In addition, almost all RTHα patients have mild anemia, the pathogenesis of which is unknown. Animal studies suggest an important role for TH and TH receptor (TR)α in erythropoiesis.Objective: To investigate whether a defect in TRα affects the maturation of red blood cells in RTHα patients.Design, Setting, and Patients: Cultures of primary human erythroid progenitor cells (HEPs), from peripheral blood of RTHα patients (n = 11) harboring different inactivating mutations in TRα (P398R, F397fs406X, C392X, R384H, A382fs388X, A263V, A263S), were compared with healthy controls (n = 11). During differentiation, erythroid cells become smaller, accumulate hemoglobin, and express different cell surface markers. We assessed cell number and cell size, and used cell staining and fluorescence-activated cell sorter analysis to monitor maturation at different time points.Results: After ∼14 days of ex vivo expansion, both control and patient-derived progenitors differentiated spontaneously. However, RTHα-derived cells differentiated more slowly. During spontaneous differentiation, RTHα-derived HEPs were larger, more positive for c-Kit (a proliferation marker), and less positive for glycophorin A (a differentiation marker). The degree of abnormal spontaneous maturation of RTHα-derived progenitors did not correlate with severity of underlying TRα defect. Both control and RTHα-derived progenitors responded similarly when differentiation was induced. T3 exposure accelerated differentiation of both control- and RTHα patient-derived HEPs.Conclusions: Inactivating mutations in human TRα affect the balance between proliferation and differentiation of progenitor cells d

Llama-Derived Single Domain Antibodies to Build Multivalent, Superpotent and Broadened Neutralizing Anti-Viral Molecules

For efficient prevention of viral infections and cross protection, simultaneous targeting of multiple viral epitopes is a powerful strategy. Llama heavy chain antibody fragments (VHH) against the trimeric envelope proteins of Respiratory Syncytial Virus (Fusion protein), Rabies virus (Glycoprotein) and H5N1 Influenza (Hemagglutinin 5) were selected from llama derived immune libraries by phage display. Neutralizing VHH recognizing different epitopes in the receptor binding sites on the spikes with affinities in the low nanomolar range were identified for all the three viruses by viral neutralization assays. By fusion of VHH with variable linker lengths, multimeric constructs were made that improved neutralization potencies up to 4,000-fold for RSV, 1,500-fold for Rabies virus and 75-fold for Influenza H5N1. The potencies of the VHH constructs were similar or better than best performing monoclonal antibodies. The cross protection capacity against different viral strains was also improved for all three viruses, both by multivalent (two or three identical VHH) and biparatopic (two different VHH) constructs. By combining a VHH neutralizing RSV subtype A, but not subtype B with a poorly neutralizing VHH with high affinity for subtype B, a biparatopic construct was made with low nanomolar neutralizing potency against both subtypes. Trivalent anti-H5N1 VHH neutralized both Influenza H5N1 clade1 and 2 in a pseudotype assay and was very potent in neutralizing the NIBRG-14 Influenza H5N1 strain with IC50 of 9 picomolar. Bivalent and biparatopic constructs against Rabies virus cross neutralized both 10 different Genotype 1 strains and Genotype 5. The results show that multimerization of VHH fragments targeting multiple epitopes on a viral trimeric spike protein is a powerful tool for anti-viral therapy to achieve "best-in-class" and broader neutralization capacity

A blended preconception lifestyle programme for couples undergoing IVF:lessons learned from a multicentre randomized controlled trial

Study question: What is the effect of a blended preconception lifestyle programme on reproductive and lifestyle outcomes of couples going through their first 12 months of IVF as compared to an attention control condition?Summery answer:This randomized controlled trial (RCT) was stopped prematurely because of the coronavirus disease 2019 (Covid-19) pandemic but the available data did not suggest that a blended preconception lifestyle programme could meaningfully affect time to ongoing pregnancy or other reproductive and lifestyle outcomes.What is know already:Increasing evidence shows associations between a healthy lifestyle and IVF success rates. Lifestyle programmes provided through a mobile phone application have yet to be evaluated by RCTs in couples undergoing IVF.Study design, size, duration:A multicentre RCT (1:1) was carried out. The RCT started in January 2019 and was prematurely stopped because of the Covid-19 pandemic, leading to a reduced sample size (211 couples initiating IVF) and change in primary outcome (cumulative ongoing pregnancy to time to ongoing pregnancy).Participants/materials, setting, methods:Heterosexual couples initiating IVF in five fertility clinics were randomized between an attention control arm and an intervention arm for 12 months. The attention control arm received treatment information by mobile phone in addition to standard care. The intervention arm received the blended preconception lifestyle (PreLiFe)-programme in addition to standard care. The PreLiFe-programme included a mobile application, offering tailored advice and skills training on diet, physical activity and mindfulness, in combination with motivational interviewing over the telephone. The primary outcome was 'time to ongoing pregnancy'. Secondary reproductive outcomes included the Core Outcome Measures for Infertility Trials and IVF discontinuation. Changes in the following secondary lifestyle outcomes over 3 and 6 months were studied in both partners: diet quality, fruit intake, vegetable intake, total moderate to vigorous physical activity, sedentary behaviour, emotional distress, quality of life, BMI, and waist circumference. Finally, in the intervention arm, acceptability of the programme was evaluated and actual use of the mobile application part of the programme was tracked. Analysis was according to intention to treat.Main results and the role of chance:A total of 211 couples were randomized (105 control arm, 106 intervention arm). The hazard ratio of the intervention for time to ongoing pregnancy was 0.94 (95% CI 0.63 to 1.4). Little to no effect on other reproductive or lifestyle outcomes was identified. Although acceptability of the programme was good (6/10), considerable proportions of men (38%) and 9% of women did not actively use all the modules of the mobile application (diet, physical activity, or mindfulness).Limitations, reasons for caution:The findings of this RCT should be considered exploratory, as the Covid-19 pandemic limited its power and the actual use of the mobile application was low.Wider implications of the findings:This is the first multicentre RCT evaluating the effect of a blended preconception lifestyle programme for women and their partners undergoing IVF on both reproductive and lifestyle outcomes. This exploratory RCT highlights the need for further studies into optimal intervention characteristics and actual use of preconception lifestyle programmes, as well as RCTs evaluating effectiveness.Study fonding/competing intrest(s):Supported by the Research foundation Flanders (Belgium) (FWO-TBM; reference: T005417N). No competing interests to declare.Trial registration number:ClinicalTrials.gov Identifier: NCT03790449TRIAL REGISTRATION DATE 31 December 2018DATE OF FIRST PATIENT'S ENROLMENT 2 January 201

The effect of a comprehensive lifestyle intervention on cardiovascular risk factors in pharmacologically treated patients with stable cardiovascular disease compared to usual care: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The additional benefit of lifestyle interventions in patients receiving cardioprotective drug treatment to improve cardiovascular risk profile is not fully established.</p> <p>The objective was to evaluate the effectiveness of a target-driven multidisciplinary structured lifestyle intervention programme of 6 months duration aimed at maximum reduction of cardiovascular risk factors in patients with cardiovascular disease (CVD) compared with usual care.</p> <p>Methods</p> <p>A single centre, two arm, parallel group randomised controlled trial was performed. Patients with stable established CVD and at least one lifestyle-related risk factor were recruited from the vascular and cardiology outpatient departments of the university hospital. Blocked randomisation was used to allocate patients to the intervention (n = 71) or control group (n = 75) using an on-site computer system combined with allocations in computer-generated tables of random numbers kept in a locked computer file. The intervention group received the comprehensive lifestyle intervention offered in a specialised outpatient clinic in addition to usual care. The control group continued to receive usual care. Outcome measures were the lifestyle-related cardiovascular risk factors: smoking, physical activity, physical fitness, diet, blood pressure, plasma total/HDL/LDL cholesterol concentrations, BMI, waist circumference, and changes in medication.</p> <p>Results</p> <p>The intervention led to increased physical activity/fitness levels and an improved cardiovascular risk factor profile (reduced BMI and waist circumference). In this setting, cardiovascular risk management for blood pressure and lipid levels by prophylactic treatment for CVD in usual care was already close to optimal as reflected in baseline levels. There was no significant improvement in any other risk factor.</p> <p>Conclusions</p> <p>Even in CVD patients receiving good clinical care and using cardioprotective drug treatment, a comprehensive lifestyle intervention had a beneficial effect on some cardiovascular risk factors. In the present era of cardiovascular therapy and with the increasing numbers of overweight and physically inactive patients, this study confirms the importance of risk factor control through lifestyle modification as a supplement to more intensified drug treatment in patients with CVD.</p> <p>Trial registration</p> <p>ISRCTN69776211 at <url>http://www.controlled-trials.com</url></p

Enhancement of the Adhesive Properties by Optimizing the Water Content in PNIPAM-Functionalized Complex Coacervates

Most commercially available soft tissue glues offer poor performance in the human body. We have developed an injectable adhesive whose setting mechanism is activated by a change in environmental factors, i.e., temperature and/or ionic strength. The material and setting process are inspired by the adhesive processing mechanism observed in natural maritime glues. Complex coacervation, a liquid-liquid phase separation between oppositely charged polyelectrolytes, is thought to play an important role in the processing. Complex coacervates are characterized by a high water content, which inevitably weakens the glue. Here, we aim to increase the adhesive performance by systematically tuning the water content. Among the several strategies here explored, the most effective one is the mechanical removal of water using an extruder, resulting in an increase of work of adhesion by 1 order of magnitude compared to the original formulation

Prevalence of Toxoplasma gondii in Belgian wildlife

De Craeye, S., Speybroeck, N., Baert, K., Ajzenberg, D., Dardé, M.L., Collinet, F., Tavernier, P., Van Gucht, S., Dorny, P., Dierick, K

Body size and dispersal mode as key traits determining metacommunity structure of aquatic organisms

Relationships between traits of organisms and the structure of their metacommunities have so far mainly been explored with meta-analyses. We compared metacommunities of a wide variety of aquatic organism groups (12 groups, ranging from bacteria to fish) in the same set of 99 ponds to minimise biases inherent to meta-analyses. In the category of passive dispersers, large-bodied groups showed stronger spatial patterning than small-bodied groups suggesting an increasing impact of dispersal limitation with increasing body size. Metacommunities of organisms with the ability to fly (i.e. insect groups) showed a weaker imprint of dispersal limitation than passive dispersers with similar body size. In contrast, dispersal movements of vertebrate groups (fish and amphibians) seemed to be mainly confined to local connectivity patterns. Our results reveal that body size and dispersal mode are important drivers of metacommunity structure and these traits should therefore be considered when developing a predictive framework for metacommunity dynamics