The EurValve model execution environment.

The goal of this paper is to present a dedicated high-performance computing (HPC) infrastructure which is used in the development of a so-called reduced-order model (ROM) for simulating the outcomes of interventional procedures which are contemplated in the treatment of valvular heart conditions. Following a brief introduction to the problem, the paper presents the design of a model execution environment, in which representative cases can be simulated and the parameters of the ROM fine-tuned to enable subsequent deployment of a decision support system without further need for HPC. The presentation of the system is followed by information concerning its use in processing specific patient cases in the context of the EurValve international collaboration.

Towards a European health research and innovation cloud (HRIC).

The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe.

HIV decision support: from molecule to man.

Human immunodeficiency virus (HIV) is recognized to be one of the most destructive pandemics in recorded history. Effective highly active antiretroviral therapy and the availability of genetic screening of patient virus data have led to sustained viral suppression and higher life expectancy in patients who have been infected with HIV. The sheer complexity of the disease stems from the multiscale and highly dynamic nature of the system under study. The complete cascade from genome, proteome, metabolome and physiome to health forms a multidimensional system that crosses many orders of magnitude in temporal and spatial scales. Understanding, quantifying and handling this complexity is one of the biggest challenges of our time, which requires a highly multidisciplinary approach. In order to supply researchers with an interactive framework and to provide the medical professional with appropriate tools and information for making a balanced and reliable clinical decision, we have developed 'ViroLab', a collaborative decision-support system (http://www.virolab.org/). ViroLab contains computational models that cover various spatial and temporal scales from atomic-level interactions in nanoseconds up to sociological interactions on the epidemiological level, spanning years of disease progression. ViroLab allows for personalized drug ranking. It is on trial in six hospitals and various virology and epidemiology laboratories across Europe.

Latex allergy: a South Dakota problem.

Latex allergy has become a major problem nationally and in South Dakota. It manifests itself with a range of presentations including anaphylaxis, asthma, allergic rhinitis, and contact urticaria. This is an immunoglobulin E mediated disease. Healthcare workers, spina bifida patients, and others with a high exposure to latex are at the greatest risk of developing this allergy. In South Dakota, 1,170 healthcare workers are likely afflicted. Diagnosis is mainly by a history of symptoms with exposure. Confirmatory allergy testing is now available. Avoidance of latex products is essential and is the main treatment. This predominantly will involve the patient, co-workers and healthcare providers using non-latex gloves. Patients must be identified in their records and with MedicAlerts. As do patients with other allergies, they may also need medical care involving epinephrine, bronchodilators, corticosteroids and antihistamines. Physicians have a dual role in latex allergy--recognizing it in patients and, potentially, being patients themselves.

Quantification of occupational latex aeroallergens in a medical center.

To determine the quantity, variability, and mean aerodynamic diameter of latex aeroallergens in a large medical center, we collected air samples from work sites by using area and personal breathing zone air samplers, and we measured latex allergens by an inhibition assay with IgE antibodies from latex-sensitive individuals. Latex aeroallergen concentrations in 11 areas where powdered latex gloves were frequently used ranged from 13 to 208 ng/m3, and in areas where powdered latex gloves were never or seldom used, concentrations ranged from 0.3 to 1.8 ng/m3. Installation and use of a laminar flow glove changing station in one work area did not reduce latex aeroallergen levels. Large quantities of allergen were recovered from used laboratory coats and anesthesia scrub suits and from laboratory surfaces. Latex allergen concentrations in personal breathing zone samplers worn by health care workers in areas where powdered gloves were frequently used ranged from 8 to 974 ng/m3. Exposure likely occurs when gloves are changed and as a result of resuspension from reservoirs of powder in the room and clothing. Latex allergens were found in all particle sizes but were predominant in particles greater than 7 microns in mass median aerodynamic diameter. Results of electrophoretic immunoblotting showed that the aeroallergens are primarily the higher molecular mass components of the latex glove proteins. Measures to control exposure can be monitored by both area and personal air sampling with this immunochemical approach. Use of gloves with low allergen content or powder-free gloves appears to be more effective than use of a laminar flow glove changing station in reducing aeroallergen levels.

Allergic reactions to latex among health-care workers.

With the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic and the practice of protecting health-care workers from all body fluids, the use of rubber gloves has increased, as has occupational allergy to latex among health-care workers. During 1991, 49 Mayo Medical Center employees sought assessment and treatment of rhinitis, conjunctivitis, contact urticaria, contact dermatitis, asthma, or eczema thought to be related to exposure to latex. Most of these persons had a history of atopy and worked in areas where rubber gloves were used and changed frequently. Of the 49 subjects, 34 had positive results of skin tests to latex products, and the sera from 19 of 35 persons tested contained increased latex-specific IgE antibodies. Employees with sensitivity to latex (and co-workers in the immediate areas) should use vinyl gloves and should notify their own health-care providers of their sensitization. Changes in job assignment may be necessary for some persons.

Complications of liver biopsy in liver transplant patients: increased sepsis associated with choledochojejunostomy.

We investigated the incidence and types of liver biopsy complications in our first 160 consecutive liver transplantations. A significant complication was identified by the need for therapeutic intervention (for example, hospitalization, transfusion, intravenous fluids, chest tube, surgery or antibiotic therapy). A total of 950 percutaneous hepatic allograft biopsies were performed in 136 patients (mean = 6.9 biopsies/graft; range = 1 to 29). A significant complication was reported after 17 (1.8%) liver biopsies in 13 (9.6%) patients. Bleeding complications occurred in 11 patients and serious infection developed in 6 patients, but all patients recovered with appropriate therapy. Of special interest was that five of six patients with infectious complications had undergone Roux-en-Y choledochojejunostomy as part of the transplantation operation. The incidence of infectious complications related to a series of biopsies was significantly greater in patients who underwent choledochojejunostomy (12.5%) than in patients who underwent duct-to-duct biliary anastomosis (1%) (p less than 0.01). Furthermore, all septic events in patients who underwent choledochojejunostomy were related to enteric organisms. This investigation reaffirms the safety and low incidence of complications related to percutaneous liver biopsy even in this unique patient population. However, we did identify a subgroup of patients with biliary-enteric anastomoses who appear to be at increased risk of septic complications after liver biopsy. Antibiotic prophylaxis at the time of liver biopsy may be appropriate in this high-risk subgroup to decrease the frequency of infectious complications.

Ragweed-specific IgA in nasal lavage fluid of ragweed-sensitive allergic rhinitis patients: increase during the pollen season.

Because the secretions of asthma and rhinitis contain toxic eosinophil granule proteins and because secretory IgA is the most potent immunoglobulin stimulus for eosinophil degranulation, we measured eosinophil-derived neurotoxin and ragweed-specific IgA and IgE antibodies in nasal lavage before and during the ragweed pollen season in 44 hay fever patients. We found IgA antibody in nanogram/milliliter concentrations before the season and rising 20-fold by the end of the season. IgE antibody was present in picogram/milliliter concentrations and did not change. Eosinophils and eosinophil-derived neurotoxin also increased. We conclude that IgA is the predominant antibody in allergic nasal secretions and increases with allergen exposure. The hypothesis that secretory IgA antibody-allergen complexes contributes to allergic inflammation by stimulating eosinophil degranulation warrants further study.

Local graft versus host reaction in the xenogeneic system.

The injection of viable rat spleen cells beneath the renal capsule of cyclophosphamide (CY)-treated adult mice produced a localized graft versus host reaction (GvHR), manifested by the kidney enlargement index (KI). The optimal xenogeneic GvHR was obtained after injection of 30-50 million rat spleen cells into mouse recipients treated 24 hr before with CY, 200 mg/kg intraperitoneally (i.p.), and killed 7 days later. Splenomegaly in recipient mice suggested systemic dissemination of the local GvHR.

Reduction of the graft-versus-host reactivity of mouse and rat spleen cells by 5alpha-androstane-3,17-dione.

The local graft-versus-host reaction as evaluated by the popliteal lymph node enlargement was used for studying the immunosuppressive potency of placental steroid 5alpha-androstane-3,17-dione. Spleen cells from virgin female mice and rats injected subcutaneously with this steroid compound produced in appropriate F1 recipients a significantly weaker reaction (P less than 0.001) than spleen cells from untreated or medium-treated control animals. On the other hand, the pretreatment of cell donors either with 5beta-androstane-3,17-dione or testosterone, the compounds which are not present in the mouse and rat placenta, did not influence the normal graft-versus-host reactivity.

Non-specific decrease of cell-mediated immunity in female mice during syngeneic and allogeneic pregnancy.

Cell-mediated immunity is non-specifically reduced in the second half of H-2 incompatible pregnancy compared with syngeneic mating. Significant difference between syngeneic and allogeneic mated female mice was obtained using two independent tests: contact sensitivity to oxazolone (P smaller than 0.001) and local graft-versus-host reaction (P smaller than 0.01).