Quantum Machine and SR Approach: a Unified Model

The Geneva-Brussels approach to quantum mechanics (QM) and the semantic realism (SR) nonstandard interpretation of QM exhibit some common features and some deep conceptual differences. We discuss in this paper two elementary models provided in the two approaches as intuitive supports to general reasonings and as a proof of consistency of general assumptions, and show that Aerts' quantum machine can be embodied into a macroscopic version of the microscopic SR model, overcoming the seeming incompatibility between the two models. This result provides some hints for the construction of a unified perspective in which the two approaches can be properly placed.Comment: 21 pages, 5 figures. Introduction and Conclusions improved, minor corrections in several sections. Accepted for publication in Foundations of Physic

Availability and implementation of guidelines in European child primary health care:how can we improve?

Background Clinical guidelines are important for providing high-quality child primary health care. We aimed to assess the availability, use and achieved delivery of guidelines in the European Union (EU). Methods We used a case study design to ascertain expert views on guidelines in six countries representing the EU. The experts completed an online questionnaire (response 49%), asking about their perception of guideline availability and implementation regarding three topics that represent prevention and care, i.e. vaccination, assessment of mental health and asthma care. Results According to the respondents all countries had guidelines available for asthma care. For vaccination and mental health assessment respondents agreed to a lesser degree that guidelines were available. Implementation of guidelines for vaccination was mostly perceived as intended, but implementation of the guidelines for mental health assessment and asthma care was limited. Notable barriers were complexity of performance, and lack of training of professionals and of financial resources. Important facilitators for guideline implementation were the fit with routine practice, knowledge and skills of professionals and policy support. We found no clear relationship of guideline availability and implementation with type of child primary health care system of countries, but strong governance and sufficient financial resources seemed important for guideline availability. Conclusions Availability and implementation of clinical guidelines in child primary health care vary between EU countries. Implementation conditions can be strongly improved by adequate training of professionals, stronger governance and sufficient financial resources as facilitating factors. This can yield major gains in child health across Europe

Pulmonary MTBVAC vaccination induces immune signatures previously correlated with prevention of tuberculosis infection

To fight tuberculosis, better vaccination strategies are needed. Live attenuated Mycobacterium tuberculosis-derived vaccine, MTBVAC, is a promising candidate in the pipeline, proven to be safe and immunogenic in humans so far. Independent studies have shown that pulmonary mucosal delivery of Bacillus Calmette-Guérin (BCG), the only tuberculosis (TB) vaccine available today, confers superior protection over standard intradermal immunization. Here we demonstrate that mucosal MTBVAC is well tolerated, eliciting polyfunctional T helper type 17 cells, interleukin-10, and immunoglobulins in the airway and yielding a broader antigenic profile than BCG in rhesus macaques. Beyond our previous work, we show that local immunoglobulins, induced by MTBVAC and BCG, bind to M. tuberculosis and enhance pathogen uptake. Furthermore, after pulmonary vaccination, but not M. tuberculosis infection, local T cells expressed high levels of mucosal homing and tissue residency markers. Our data show that pulmonary MTBVAC administration has the potential to enhance its efficacy and justifies further exploration of mucosal vaccination strategies in preclinical efficacy studies

Stronger induction of trained immunity by mucosal BCG or MTBVAC vaccination compared to standard intradermal vaccination

Vierboom et al. demonstrate the induction of trained immunity in blood and bone marrow monocytes after vaccination with live attenuated TB vaccines in nonhuman primates. Mucosal respiratory delivery of BCG or MTBVAC induces trained immunity more efficiently compared to standard intradermal vaccination

The adult heart requires baseline expression of the transcription factor Hand2 to withstand RV pressure overload

AIMS: Research on the pathophysiology of right ventricular (RV) failure has, in spite of the associated high mortality and morbidity, lagged behind compared to the left ventricle (LV).Previous work from our lab revealed that the embryonic basic helix-loop-helix transcription factor heart and neural crest derivatives expressed-2 (Hand2) is re-expressed in the adult heart and activates a 'fetal gene program' contributing to pathological cardiac remodeling under conditions of LV pressure overload. As such, ablation of cardiac expression of Hand2 conferred protection to cardiac stress and abrogated the maladaptive effects that were observed upon increased expression levels. In this study, we aimed to understand the contribution of Hand2 to RV remodeling in response to pressure overload induced by pulmonary artery banding (PAB). METHODS AND RESULTS: In the present study, Hand2F/F and MCM- Hand2F/F mice were treated with tamoxifen (control and knockout, respectively) and subjected to six weeks of RV pressure overload induced by PAB. Echocardiographic- and MRI-derived hemodynamic parameters as well as molecular remodeling were assessed for all experimental groups and compared to sham-operated controls. Six weeks after PAB, levels of Hand2 expression increased in the control banded animals but, as expected, remained absent in the knockout hearts. Despite the dramatic differences in Hand2 expression, pressure overload resulted in impaired cardiac function independently of the genotype. In fact, Hand2 depletion seems to sensitize the RV to pressure overload as these mice develop more hypertrophy and more severe cardiac dysfunction. Higher expression levels of HAND2 were also observed in RV samples of human hearts from patients with pulmonary hypertension. In turn, the LV of RV-pressure overloaded hearts was also dramatically affected as reflected by changes in shape, decreased LV mass and impaired cardiac function. RNA sequencing revealed a distinct set of genes that are dysregulated in the pressure-overloaded RV, compared to the previously described pressure-overloaded LV. CONCLUSIONS: Cardiac-specific depletion of Hand2 is associated with severe cardiac dysfunction in conditions of RV pressure overload. While inhibiting Hand2 expression can prevent cardiac dysfunction in conditions of LV pressure overload, the same does not hold true for conditions of RV pressure overload. This study highlights the need to better understand the molecular mechanisms driving pathological remodeling of the RV in contrast to the LV, in order to better diagnose and treat patients with RV or LV failure. TRANSLATIONAL PERSPECTIVE: RV failure associated with pulmonary hypertension reduces long-term survival rate to 55% within 3 years, suggesting that 3 years after diagnosis almost half of the patients will die. To revert these numbers an adequate RV-specific and, therefore, more efficient treatment is needed. Our work suggests that current therapies and potential mechanisms underlying LV failure may not be suitable for RV failure. While Hand2 deletion is favorable in LV response to stress, it is particularly detrimental in the RV under similar conditions, and thus, highlighting potential severe consequences of not differentiating therapeutic targets or treatment for RV or LV failure

A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila

Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens

Towards an In Vitro Model of Plasmodium Hypnozoites Suitable for Drug Discovery

Contains fulltext : 96475.pdf (publisher's version ) (Open Access)BACKGROUND: Amongst the Plasmodium species in humans, only P. vivax and P. ovale produce latent hepatic stages called hypnozoites, which are responsible for malaria episodes long after a mosquito bite. Relapses contribute to increased morbidity, and complicate malaria elimination programs. A single drug effective against hypnozoites, primaquine, is available, but its deployment is curtailed by its haemolytic potential in glucose-6-phosphate dehydrogenase deficient persons. Novel compounds are thus urgently needed to replace primaquine. Discovery of compounds active against hypnozoites is restricted to the in vivo P. cynomolgi-rhesus monkey model. Slow growing hepatic parasites reminiscent of hypnozoites had been noted in cultured P. vivax-infected hepatoma cells, but similar forms are also observed in vitro by other species including P. falciparum that do not produce hypnozoites. METHODOLOGY: P. falciparum or P. cynomolgi sporozoites were used to infect human or Macaca fascicularis primary hepatocytes, respectively. The susceptibility of the slow and normally growing hepatic forms obtained in vitro to three antimalarial drugs, one active against hepatic forms including hypnozoites and two only against the growing forms, was measured. RESULTS: The non-dividing slow growing P. cynomolgi hepatic forms, observed in vitro in primary hepatocytes from the natural host Macaca fascicularis, can be distinguished from similar forms seen in P. falciparum-infected human primary hepatocytes by the differential action of selected anti-malarial drugs. Whereas atovaquone and pyrimethamine are active on all the dividing hepatic forms observed, the P. cynomolgi slow growing forms are highly resistant to treatment by these drugs, but remain susceptible to primaquine. CONCLUSION: Resistance of the non-dividing P. cynomolgi forms to atovaquone and pyrimethamine, which do not prevent relapses, strongly suggests that these slow growing forms are hypnozoites. This represents a first step towards the development of a practical medium-throughput in vitro screening assay for novel hypnozoiticidal drugs

Attitude toward contraception and abortion among Curaçao women. Ineffective contraception due to limited sexual education?

Background In Curaçao is a high incidence of unintended pregnancies and induced abortions. Most of the induced abortions in Curaçao are on request of the woman and performed by general practitioners. In Curaçao, induced abortion is strictly prohibited, but since 1999 there has been a policy of connivance. We present data on the relevance of economic and socio-cultural factors for the high abortion-rates and the ineffective use of contraception. Methods Structured interviews to investigate knowledge and attitudes toward sexuality, contraception and abortion and reasons for ineffective use of contraceptives among women, visiting general practitioners. Results Of 158 women, 146 (92%) participated and 82% reported that their education on sexuality and about contraception was of good quality. However 'knowledge of reliable contraceptive methods' appeared to be - in almost 50% of the cases - false information, misjudgements or erroneous views on the chance of getting pregnant using coitus interruptus and about the reliability and health effects of oral contraceptive pills. Almost half of the interviewed women had incorrect or no knowledge about reliability of condom use and IUD. 42% of the respondents risked by their behavior an unplanned pregnancy. Most respondents considered abortion as an emergency procedure, not as contraception. Almost two third experienced emotional, physical or social problems after the abortion. Conclusions Respondents had a negative attitude toward reliable contraceptives due to socio-cultural determined ideas about health consequences and limited sexual education. Main economic factors were costs of contraceptive methods, because most health insurances in Curaçao do not cover contraceptives. To improve the effective use of reliable contraceptives, more adequate information should be given, targeting the wrong beliefs and false information. The government should encourage health insurance companies to reimburse contraceptives. Furthermore, improvement of counseling during the abortion procedure is important