Cytoadhesion of Plasmodium falciparum-infected erythrocytes and the infected placenta: a two-way pathway

This find is registered at Portable Antiquities of the Netherlands with number PAN-0005548

Cytoadhesion of Plasmodium falciparum-infected erythrocytes and the infected placenta: a two-way pathway

Malaria is undoubtedly the world's most devastating parasitic disease, affecting 300 to 500 million people every year. Some cases of Plasmodium falciparum infection progress to the deadly forms of the disease responsible for 1 to 3 million deaths annually. P. falciparum-infected erythrocytes adhere to host receptors in the deep microvasculature of several organs. The cytoadhesion of infected erythrocytes to placental syncytiotrophoblast receptors leads to pregnancy-associated malaria (PAM). This specific maternal-fetal syndrome causes maternal anemia, low birth weight and the death of 62,000 to 363,000 infants per year in sub-Saharan Africa, and thus has a poor outcome for both mother and fetus. However, PAM and non-PAM parasites have been shown to differ antigenically and genetically. After multiple pregnancies, women from different geographical areas develop adhesion-blocking antibodies that protect against placental parasitemia and clinical symptoms of PAM. The recent description of a new parasite ligand encoded by the var2CSA gene as the only gene up-regulated in PAM parasites renders the development of an anti-PAM vaccine more feasible. The search for a vaccine to prevent P. falciparum sequestration in the placenta by eliciting adhesion-blocking antibodies and a cellular immune response, and the development of new methods for evaluating such antibodies should be key priorities in mother-child health programs in areas of endemic malaria. This review summarizes the main molecular, immunological and physiopathological aspects of PAM, including findings related to new targets in the P. falciparum var gene family. Finally, we focus on a new methodology for mimicking cytoadhesion under blood flow conditions in human placental tissue.1525153

Waste Heat Recovery from Underground Railways – Evaluating the Cooling Potential

The Bunhill Waste Heat Recovery (WHR) System is a first of its kind scheme that will recover waste energy from a ventilation shaft of the London Underground (LU) network. The system is based upon the installation of a heat recovery heat exchanger that consists of cooling coils and a reversible fan. The coils are connected to a heat pump that supplies low carbon thermal energy to the Bunhill Heat Network in the London Borough of Islington. One particularly important aspect of the Bunhill WHR system is its ability to operate in a way that not only provides heating to the local heat network, but can also simultaneously supply cooled air to the LU tunnels depending on the operation of the reversible fan. The current paper provides an analysis of the heating and cooling duties and their associated cost and carbon savings against conventional technologies based upon a mathematical model of the WHR system. The model is able to predict the condition of the coil surface according to air inlet parameters, and this is used to calculate the latent and sensible cooling loads, which are applied to simulate how the system impacts the local tunnel environment, with peak temperature reductions of up to 7.2 °C being estimated for adjacent stations in 2030. The results from these analyses are reported, together with recommendations for further development and future deployment of heat recovery from metro systems

Disruption of Var2csa Gene Impairs Placental Malaria Associated Adhesion Phenotype

Infection with Plasmodium falciparum during pregnancy is one of the major causes of malaria related morbidity and mortality in newborn and mothers. The complications of pregnancy-associated malaria result mainly from massive adhesion of Plasmodium falciparum-infected erythrocytes (IE) to chondroitin sulfate A (CSA) present in the placental intervillous blood spaces. Var2CSA, a member of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family is the predominant parasite ligand mediating CSA binding. However, experimental evidence suggests that other host receptors, such as hyaluronic acid (HA) and the neonatal Fc receptor, may also support placental binding. Here we used parasites in which var2csa was genetically disrupted to evaluate the contribution of these receptors to placental sequestration and to identify additional adhesion receptors that may be involved in pregnancy-associated malaria. By comparison to the wild-type parasites, the FCR3Δvar2csa mutants could not be selected for HA adhesion, indicating that var2csa is not only essential for IE cytoadhesion to the placental receptor CSA, but also to HA. However, further studies using different pure sources of HA revealed that the previously observed binding results from CSA contamination in the bovine vitreous humor HA preparation. To identify CSA-independent placental interactions, FCR3Δvar2csa mutant parasites were selected for adhesion to the human placental trophoblastic BeWo cell line. BeWo selected parasites revealed a multi-phenotypic adhesion population expressing multiple var genes. However, these parasites did not cytoadhere specifically to the syncytiotrophoblast lining of placental cryosections and were not recognized by sera from malaria-exposed women in a parity dependent manner, indicating that the surface molecules present on the surface of the BeWo selected population are not specifically expressed during the course of pregnancy-associated malaria. Taken together, these results demonstrate that the placental malaria associated phenotype can not be restored in FCR3Δvar2csa mutant parasites and highlight the key role of var2CSA in pregnancy malaria pathogenesis and for vaccine development

An updated analysis of NN elastic scattering data to 1.6 GeV

An energy-dependent and set of single-energy partial-wave analyses of $NN$ elastic scattering data have been completed. The fit to 1.6~GeV has been supplemented with a low-energy analysis to 400 MeV. Using the low-energy fit, we study the sensitivity of our analysis to the choice of $\pi NN$ coupling constant. We also comment on the possibility of fitting $np$ data alone. These results are compared with those found in the recent Nijmegen analyses. (Figures may be obtained from the authors upon request.)Comment: 17 pages of text, VPI-CAPS-7/

Cost-effectiveness of a brief structured intervention program aimed at preventing repeat suicide attempts among those who previously attempted suicide: a secondary analysis of the ASSIP randomized clinical trial

IMPORTANCE: This is the first cost-effectiveness analysis of a brief therapy, the Attempted Suicide Short Intervention Program (ASSIP), for individuals who attempt suicide. OBJECTIVE: To explore the cost-effectiveness of the ASSIP intervention in the context of the Swiss health care system. DESIGN, SETTING, AND PARTICIPANTS: In this economic evaluation, the cost-effectiveness analysis was performed from a health care perspective between January 2017 and April 2018 using data from a randomized clinical trial conducted between June 2009 and December 2014. Participants were individuals who had attempted suicide and were receiving treatment at a psychiatric university hospital in Switzerland that provides inpatient and outpatient services for suicide attempters referred from an emergency department of a general hospital. INTERVENTIONS: The intervention group received 3 manual-based therapy sessions followed by regular personalized letters over 24 months. The control group was offered a single suicide risk assessment. MAIN OUTCOMES AND MEASURES: The main economic analysis explored cost per suicide attempt avoided expressed in 2015 Swiss francs (CHF). Cost-effectiveness planes were plotted and cost-effectiveness acceptability curves calculated. RESULTS: One hundred twenty participants (mean [SD] age, 37.8 [14.4] years; 66 [55%] women and 54 [45%] men) were assigned to an intervention group or a control group, each with 60 participants. At 24 months of follow-up, 5 suicide attempts were reported in the ASSIP group among 59 participants with follow-up data available, and 41 were reported in the control group among 53 participants with follow-up data available. The ASSIP group had higher intervention costs, with CHF 1323 vs CHF 441 for the control group. At 24 months of follow-up, psychiatric hospital costs were lower in the ASSIP group than in the control group, although this difference was not significant (mean [SD], CHF 20 559 [38 676] vs CHF 45 488 [73 306]; mean difference, CHF -16 081; 95% CI, CHF -34 717 to 1536; P = .11). General hospital costs were significantly lower for the ASSIP group. Total health care costs were also lower, but the difference was not significant (mean [SD], CHF 21 302 [38 819] vs 41 287 [74 310]; difference, CHF -12 604; 95% CI, CHF -29 837 to 625; P = .14). In a base-case analysis, ASSIP was dominant, with significantly fewer reattempts at lower overall cost. The intervention had a 96% chance of being less costly and more effective. A sensitivity analysis showed a 96% and 95% chance of ASSIP being more effective and less costly at willingness-to-pay levels of CHF 0 and CHF 30 000, respectively. CONCLUSIONS AND RELEVANCE: The ASSIP intervention is a cost-saving treatment for individuals who attempt suicide. The findings support the use of ASSIP as a treatment for suicide attempters. Further studies are needed to determine cost-effectiveness in other contexts. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02505373

Integral geometry of complex space forms

We show how Alesker's theory of valuations on manifolds gives rise to an algebraic picture of the integral geometry of any Riemannian isotropic space. We then apply this method to give a thorough account of the integral geometry of the complex space forms, i.e. complex projective space, complex hyperbolic space and complex euclidean space. In particular, we compute the family of kinematic formulas for invariant valuations and invariant curvature measures in these spaces. In addition to new and more efficient framings of the tube formulas of Gray and the kinematic formulas of Shifrin, this approach yields a new formula expressing the volumes of the tubes about a totally real submanifold in terms of its intrinsic Riemannian structure. We also show by direct calculation that the Lipschitz-Killing valuations stabilize the subspace of invariant angular curvature measures, suggesting the possibility that a similar phenomenon holds for all Riemannian manifolds. We conclude with a number of open questions and conjectures.Comment: 68 pages; minor change

Mechanical Dissipation in Silicon Flexures

The thermo-mechanical properties of silicon make it of significant interest as a possible material for mirror substrates and suspension elements for future long-baseline gravitational wave detectors. The mechanical dissipation in 92um thick single-crystal silicon cantilevers has been observed over the temperature range 85 K to 300 K, with dissipation approaching levels down to phi = 4.4E-7.Comment: 7 pages. Accepted by Phys Lett A, submitted for publication on 28 October 200

Post-acute sequelae after SARS-CoV-2 infection by viral variant and vaccination status: a multicenter cross-sectional study.

BACKGROUND Disentangling the effects of SARS-CoV-2 variants and vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and reduce the burden of PASC. METHODS We performed a cross-sectional analysis (May/June 2022) within a prospective multicenter healthcare worker (HCW) cohort in North-Eastern Switzerland. HCW were stratified by viral variant and vaccination status at time of their first positive SARS-CoV-2 nasopharyngeal swab. HCW without positive swab and with negative serology served as controls. The sum of eighteen self-reported PASC symptoms was modeled with univariable and multivariable negative-binomial regression to analyse the association of mean symptom number with viral variant and vaccination status. RESULTS Among 2'912 participants (median age 44 years, 81.3% female), PASC symptoms were significantly more frequent after wild-type infection (estimated mean symptom number 1.12, p<0.001; median time since infection 18.3 months), after Alpha/Delta infection (0.67 symptoms, p<0.001; 6.5 months), and after Omicron BA.1 infections (0.52 symptoms, p=0.005; 3.1 months) compared to uninfected controls (0.39 symptoms). After Omicron BA.1 infection, the estimated mean symptom number was 0.36 for unvaccinated individuals, compared to 0.71 with 1-2 vaccinations (p=0.028) and 0.49 with ≥3 prior vaccinations (p=0.30). Adjusting for confounders, only wild-type (adjusted rate ratio [aRR] 2.81, 95% confidence interval [CI] 2.08-3.83) and Alpha/Delta infection (aRR 1.93, 95% CI 1.10-3.46) were significantly associated with the outcome. CONCLUSIONS Previous infection with pre-Omicron variants was the strongest risk factor for PASC symptoms among our HCW. Vaccination prior to Omicron BA.1 infection was not associated with a clear protective effect against PASC symptoms in this population