Early Disease Development Research Articles

3D morphometric analysis of the arterial switch operation using in vivo MRI data.

The arterial switch operation (ASO) is widely used nowadays as the surgical strategy of choice to repair transposition of the great arteries (TGA). Residual morphological and geometrical abnormalities of the aorta, pulmonary arteries and coronary arteries, however, have not been fully studied in a three-dimensional (3D) domain. These morphometric complications might have implications on long-term outcomes of ASO patients, hence the need to explore them in detail and study them with reference to healthy controls of comparable age and body surface area. These anatomical characteristics were examined using 3D patient-specific anatomical models reconstructed from cardiovascular magnetic resonance (CMR) images of 20 ASO patients (mean age 14.4 ± 2.4 years, 16 males and 4 females) compared with healthy controls (mean age 15.2 ± 2.0 years, 17 males and 3 females). It was found that the aorta, pulmonary arteries and re-implanted coronary arteries of ASO patients were significantly different morphologically and geometrically to those of healthy controls. In particular, the aortic root was dilated, with abnormal 3D angulation and additional acute angulation of the curvature of the aortic arch in the ASO group compared with controls. This could theoretically impinge on aortic flow profiles and physiological stresses, which can act as a primer for the development of early atherosclerotic disease in the ASO population.

Early development of calcific aortic valve disease and left ventricular hypertrophy in a mouse model of combined dyslipidemia and type 2 diabetes mellitus.

This study aimed to determine the potential impact of type 2 diabetes mellitus on left ventricular dysfunction and the development of calcified aortic valve disease using a dyslipidemic mouse model prone to developing type 2 diabetes mellitus. When compared with nondiabetic LDLr(-/-)/ApoB(100/100), diabetic LDLr(-/-)/ApoB(100/100)/IGF-II mice exhibited similar dyslipidemia and obesity but developed type 2 diabetes mellitus when fed a high-fat/sucrose/cholesterol diet for 6 months. LDLr(-/-)/ApoB(100/100)/IGF-II mice showed left ventricular hypertrophy versus C57BL6 but not LDLr(-/-)/ApoB(100/100) mice. Transthoracic echocardiography revealed significant reductions in both left ventricular systolic fractional shortening and diastolic function in high-fat/sucrose/cholesterol fed LDLr(-/-)/ApoB(100/100)/IGF-II mice when compared with LDLr(-/-)/ApoB(100/100). Importantly, we found that peak aortic jet velocity was significantly increased in LDLr(-/-)/ApoB(100/100)/IGF-II mice versus LDLr(-/-)/ApoB(100/100) animals on the high-fat/sucrose/cholesterol diet. Microtomography scans and Alizarin red staining indicated calcification in the aortic valves, whereas electron microscopy and energy dispersive x-ray spectroscopy further revealed mineralization of the aortic leaflets and the presence of inflammatory infiltrates in diabetic mice. Studies showed upregulation of hypertrophic genes (anp, bnp, b-mhc) in myocardial tissues and of osteogenic genes (spp1, bglap, runx2) in aortic tissues of diabetic mice. We have established the diabetes mellitus -prone LDLr(-/-)/ApoB(100/100)/IGF-II mouse as a new model of calcified aortic valve disease. Our results are consistent with the growing body of clinical evidence that the dysmetabolic state of type 2 diabetes mellitus contributes to early mineralization of the aortic valve and calcified aortic valve disease pathogenesis.

Early Microbial Markers of Celiac Disease

Seroreactivity against the Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) has been detected in celiac disease patients with small-bowel mucosal atrophy. Levels of these antibodies decrease during a gluten-free diet, but their functions and time of appearance in celiac disease are not known. We aimed to search for evidence of possible microbial targets of the immune responses in the early-stage celiac disease patients who showed normal small-bowel mucosal architecture at the time of the first investigations, but later on a gluten-containing diet developed mucosal atrophy. Forty-four cases with proven early-stage celiac disease and normal mucosal morphology were enrolled. Patients' sera were tested for celiac disease antibodies against tissue transglutaminase (tTG-ab), endomysium, and for microbial antibodies against I2, OmpW, and ASCA IgG and IgA isotypes in both at the time of diagnosis and while on a gluten-free diet. Thirty-four (77%) of 44 patients with early-stage celiac disease had elevated serum antibodies to one or more of the antibodies ASCA, I2, and OmpW. Furthermore, 5 of 6 cases negative for both tTG-ab and endomysium showed positivity for the microbial markers. Seroreactivity to ASCA IgA, ASCA IgG, and OmpW decreased significantly during gluten-free diet. Seroreactivity to different microbial antigens is evident already in patients with early-stage celiac disease. ASCA antibodies seem to be gluten-dependent. The results indicate that the microbial targets might have a role in the early development of celiac disease.

Abstract 327: Mitochondrial Functional Variation Contributes to Endothelial Cell Activation

Vascular oxidant stress contributes to endothelial dysfunction and plays a critical role in early stage cardiovascular disease (CVD) development. Changes in endothelial function due to oxidant stress may contribute to CVD initiation and progression through the development of a pro-inflammatory environment. Differences in mitochondrial function may contribute to this process and provide insight into why age of onset and clinical outcomes differ amongst individuals form distinct ethnic groups; but no reports demonstrate distinct mitochondrial functional parameters between normal cells. Consequently, we hypothesized that significant variations in normal mitochondrial function and oxidant production exist between endothelial cells from donors representing different ethnic groups. Aspects of mitochondrial oxygen utilization and oxidant production were assessed under basal and inflammatory conditions in human aortic endothelial cells (HAECs) isolated from African Americans (AA) and Caucasians (CA). Bioenergetic analysis indicates that compared to CA, AA HAEC utilized significantly less oxygen for ATP production, possess a lower maximal respiratory capacity, and have reduced electron leak. Significant differences in mitochondrial membrane potential, decreased expression of endothelial nitric oxide synthase, and increased levels of superoxide were also observed and AA HAEC supporting a pro-inflammatory phenotype. As a marker of endothelial cell activation, AA HAEC expressed increased levels of intercellular cell adhesion molecule-1 under both basal and inflammatory conditions that could be partially mitigated but treatment with the mitochondrially targeted antioxidant MitoTEMPO. These data demonstrate that fundamental differences exist in mitochondrial oxygen utilization and oxidant production between CA and AA HAEC and that these changes may affect endothelial cell activation. These findings are consistent with the hypothesis that differences in “normal” mitochondrial function amongst ethnic groups could influence individual susceptibility by contributing to vascular inflammation, providing important insights into the mechanisms that contribute human CVD development.

Early development of xanthoma and coronary disease in a young female with homozygous familial hypercholesterolemia

Early development of xanthoma and coronary disease in a young female with homozygous familial hypercholesterolemia

PLASMA AMYLIN LEVELS ARE ASSOCIATED WITH BRAIN STRUCTURE AMONG INDIVIDUALS WITH TYPE-2 DIABETES

the development of cognitive decline in the prevention of AD, this information may provide insight into the early development of disease. This study examines the role of apoE4 in ten-year cognitive change using a simple test of episodic memory. Methods: Participants were 162 women (aged 64-77 years) from the longitudinal prospective Women’s Healthy Ageing Project (WHAP). The California Verbal Learning Test (CVLT) was used as a measure of episodic memory and administered in 2002 and 2012. Delayed recall of the CVLT word list was measured 25-30 minutes after the initial learning phase. Blood samples were collected for genetic analysis to determine the inheritance of the apoE4 allele. Age and education were included in the analysis as possible predictors of CVLT performance. Results: Of the 162 participants in the sample, 52 were found to possess the apoE4 allele. Participants lacking the apoE4 allele showed greater increase in CVLT delayed recall scores over 10 years (mean difference 1⁄4 2.96) than those with the apoE4 allele (mean difference 1⁄4 1.46), taking age and education into account, which was statistically significant (p<0.05). Conclusions: Inheritance of the apoE4 allele predicted differences in episodic memory change over ten years in our epidemiologically-sourced cohort. This result suggests that the influence of apoE4 can be observed before the onset of disease in healthy individuals. This study highlights the need for further work to determine a full cognitive profile for healthy individuals with a positive apoE4 status.

OLFACTORY IDENTIFICATION DEFICITS PREDICT THE TRANSITION FROM MCI TO AD IN A MULTI-ETHNIC COMMUNITY SAMPLE

PET amyloid scanning with 18 F-Fluorobetaben. Compared to those lost to follow-up, participants were healthier, a year younger and more likely to have higher education. Over the 15 years from 1998 to 2013, 8 participants had developed significant cognitive disease (MCI, AD). Only 14 of 125 imaged participants were amyloid positive (18 F-Fluorobetaben suvr>1.4), consistent with the mostly healthy cohort. Those amyloid positive healthy participants recalled fewer words on the word test recall compared to the amyloid negative participants (mean cvlt1⁄49 words Vs mean cvlt1⁄4 12 words) p<0.05 accounting for age, education and presence of APOE34. Conclusions: The Women’s Healthy Ageing Project imaging study is unique in its sample of more than 100 participants imaged with 18 F-Fluorobetaben and 15 years of preceding cognitive tests and more than 20 years of clinical, physical and biomarker information. Given the importance of examining the development of cognitive decline and neurodegeneration with the now known prodrome of several decades, this study database will provide new insights into the early development of disease and in particular midlife risk factors. Data is available via BioGrid Australia. www.biogrid. vic.gov.au.

NF-κB Activation Exacerbates, but Is not Required for Murine Bmpr2-Related Pulmonary Hypertension

Aim: The present study investigates the role of NF-κB in Bmpr2-related pulmonary hypertension (PH) using a murine model of PH with inducible overexpression of a cytoplasmic tail Bmpr2 mutation. Methods and Results: Electrophoretic mobility shift assay for nuclear extracts in Bmpr2R899X mouse lung and immunohistochemistry for NF-κB p65 in human PAH lung demonstrate that NF-κB is activated in end-stage disease. Acute inflammation or expression of a constitutively active NF-κB elicits a strong suppression of the BMP pathway in mice inversely correlating to activation of NF-κB targets. However, Bmpr2 mutation does not result in NF-κB activation in early disease development as assessed by luciferase reporter mice. Moreover, Bmpr2 mutant mice in which NF-κB activation is genetically blocked develop PH indistinguishable from that without the block. Finally, delivery of a virus causing NF-κB activation strongly exacerbates development of PH in Bmpr2 mutant mice, associated with increased remodeling. Conclusion: NF-κB activation exacerbates, but is not required for Bmpr2-related PH. Pulmonary vascular-specific activation of NF-κB may be a “second hit” that drives penetrance in heritable PH.

Efetividade de uma intervenção de base escolar sobre as práticas alimentares em estudantes do ensino médio

Interventions during adolescence are important for modifying risk eating behavior that contribute to the early development of obesity and other non-transmissible chronic diseases, such as the consumption of high energy-dense and low nutrient-dense foods. The aim of this study was to assess the effect of a school-based intervention on the diet of high school students who study at night. Randomized controlled study conducted in 2006 in two Brazilian state capitals (Florianopolis and Recife). The intervention included multiple strategies for improving healthy eating and physical activity. Weekly frequency consumption of fruits, vegetables, dairy products, salty snacks, sweets and soft drinks, daily frequency consumption of fruits and vegetables and stages of change in fruit and vegetable consumption behavior were investigated using questionnaires. A total of 2155 students were included (mean age ± SD = 18.4 years ± 2.4) at baseline, 989 of whom remained in post-intervention. Bivariate analyses indicated greater frequency of vegetable consumption (p=0.008) and lower frequency of sweets (p=0.032) and soft drinks (p=0.003) in the intervention group compared to controls. The change in behavior was also favorable for the intervention group (p=0.016). Analysis regression showed positive effects of complying with vegetable intake recommendations (OR = 1.54 CI95% 1.19-1.97) and favorable changes in lower sweet consumption (OR = 1.21 CI95% 1.02-1.43) in the intervention group, compared to controls. We found positive effects on the eating habits of the students as a result of The Saude na Boa Project.

Intricate interplay of cytokines determine the progression of SLE-like disease in BXSB.Yaa mice (BA12P.104)

Abstract Systemic lupus erythematosus (SLE) is a complex multi-organ disease that affects mostly females. It is caused by several environmental, genetic and stochastic factors. BXSB.Yaa is a recombinant inbred strain of mice with major manifestations that parallel those of human SLE, thereby making it a model system to investigate genetic and non-genetic determinants of disease initiation and progression. The Yaa mutation in male results due to translocation of a 4Mb chromosomal region, including Tlr7 gene, from X to the Y chromosome, making them susceptible to disease. The disease pathogenesis involves an intricate interplay of key cytokines such as IL-21, IL-6, Type I interferon (IFN) and IL-10. Enhanced expression of IL-21 by CD4-T (Tfh) cells expands autoreactive B cells that differentiate into plasmablasts and secrete autoantibodies. IL21 also promotes the development of CD8-T cells and NK cells which retard early disease development. Gene expression profiles of cells from young IL-21R deficient BXSB.Yaa mice revealed an “IFN signature” similar to human SLE females. Purified plasmacytoid dendritic cells (pDCs) from male mice produced higher levels of Type-I IFN than females. Type I IFN further stimulates IL6 producing B cells that drives differentiation of CD4 Tfh cells. IL6 also contributes to accelerated mortality in BXSB.Yaa mice. Moreover, BXSB.Yaa mice express IL10 and ablation of IL10 in these mice results in accelerated mortality.

Crecimiento Fetal en un Grupo Poblacional de Lima

El tamaño fetal es un indicador de bienestar fetal y, al mismo tiempo, predictor del desarrollo de enfermedades crónicas posterior al parto. Es, por lo tanto, necesario conocer los valores de normalidad del crecimiento fetal intrauterino. De un total de 18,615 partos simples registrados en el Hospital San Bartolomé de Junio de 1990 a Marzo de 1995, sólo 5,399 (29%) gestantes menores de 35 años, sanas y sin complicación obstétrica tuvieron un recién nacido sano. No fue considerado sano un recién nacido menor de 34 semanas de edad gestacional. Los valores del peso al nacer en los percentiles 10, 50 y 90 fueron similares a los informados en otros países. La variación del peso fetal entre las razas ha dependido principalmente del ambiente, donde la pobreza y la ignorancia han influido poderosamente. Ambas, a través de la desnutrición crónica, han alterado por generaciones la talla materna, la pelvis materna, el estado nutricional previo a la concepción, la nutrición durante el embarazo y el peso fetal.

Influence of foliar sprays of Bacillus subtilis QST 713 on development of early blight disease and yield of field tomatoes in Ontario

Early blight is an economically important foliar disease of processing and fresh market tomatoes. The aim of this multi-year field study was to investigate the impact of weekly foliar sprays of dried and aqueous formulations of Bacillus subtilis QST 713 (Serenade and Rhapsody), alone or as tank mixes with copper hydroxide, on early blight disease development and fruit yields of tomato. Field plots were established in London, Ontario during the 2008–2010 growing seasons and disease conditions were created artificially by inoculations with spore suspension of the early blight pathogen. The tank mixes of copper hydroxide and chlorothalonil were included as a standard spray treatment. Late blight also appeared naturally in the plots late in 2009 and 2010 field seasons and affected fruit in both years, but more severely in 2009. Spray treatments had variable effects on tomato early blight and fruit yields depending on the level of disease pressure in the inoculated plots. The weekly sprays of biofungicide alone did not consistently reduce disease severity on tomato foliage or incidence on fruit, but in a tank mix with copper hydroxide, both formulations consistently reduced foliar disease severity even when disease pressure was high in plots. Under high disease conditions, copper hydroxide alone or as a tank mix with chlorothalonil also consistently reduced disease severity on foliage. The mixture of two fungicides also consistently increased total fruit yields in all 3 years. Plots sprayed with copper hydroxide alone and in tank mixes with chlorothalonil and the dried formulation of biofungicide consistently had less late blight-infected fruit. The combined effects of biofungicides and copper hydroxide or other fungicides should be further investigated for consistent disease management and yield improvement.

INCREASED SMOKING AND ALCOHOL EXPOSURE IN ADOLESCENCE HAS AN ADVERSE EFFECT ON ARTERIAL STIFFNESS IN YOUNG ADULTHOOD: THE ALSPAC STUDY

Increased alcohol consumption and cigarette smoking have been associated with an adverse cardiovascular profile in adults. However their influence on the development of early arterial disease remains unknown. We set out to investigate the influence of alcohol and smoking exposure in adolescence on

Milestones in the Use of Combined-Modality Radiation Therapy and Chemotherapy

Milestones in the Use of Combined-Modality Radiation Therapy and Chemotherapy

Deciphering early development of complex diseases by progressive module network

There is no effective cure nowadays for many complex diseases, and thus it is crucial to detect and further treat diseases in earlier stages. Generally, the development and progression of complex diseases include three stages: normal stage, pre-disease stage, and disease stage. For diagnosis and treatment, it is necessary to reveal dynamical organizations of molecular modules during the early development of the disease from the pre-disease stage to the disease stage. Thus, we develop a new framework, i.e. we identify the modules presenting at the pre-disease stage (pre-disease module) based on dynamical network biomarkers (DNBs), detect the modules observed at the advanced stage (disease-responsive module) by cross-tissue gene expression analysis, and finally find the modules related to early development (progressive module) by progressive module network (PMN). As an application example, we used this new method to analyze the gene expression data for NOD mouse model of Type 1 diabetes mellitus (T1DM). After the comprehensive comparison with the previously reported milestone molecules, we found by PMN: (1) the critical transition point was identified and confirmed by the tissue-specific modules or DNBs relevant to the pre-disease stage, which is considered as an earlier event during disease development and progression; (2) several key tissues-common modules related to the disease stage were significantly enriched on known T1DM associated genes with the rewired association networks, which are marks of later events during T1DM development and progression; (3) the tissue-specific modules associated with early development revealed several common essential progressive genes, and a few of pathways representing the effect of environmental factors during the early T1DM development. Totally, we developed a new method to detect the critical stage and the key modules during the disease occurrence and progression, and show that the pre-disease modules can serve as warning signals for the pre-disease state (e.g. T1DM early diagnosis) whereas the progressive modules can be used as the therapy targets for the disease state (e.g. advanced T1DM), which were also validated by experimental data.

ROLE OF INFLAMMATION MARKERS IN DEVELOPMENT OF ATHEROSCLEROSIS AND ITS COMPICATIONS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Preventing Exercise-Related Cardiovascular Events

Physical inactivity is a serious health problem worldwide, contributing to early development of obesity, diabetes mellitus, hypertension, and cardiovascular diseases (CVD).1 In fact, our hypokinetic lifestyle is now widely recognized among the most proximal risk factors for heart disease (Figure 1), along with poor dietary habits and cigarette smoking.2–4 To address these concerns, public health strategies commonly incorporate the goal of safely increasing physical activity levels in the populations of industrialized societies. Accordingly, the number of health/fitness facilities and members is expected to increase exponentially over the next decade. Current market research indicates that the fastest-growing user subsets are those aged 35 to 54 years and those ≥55 years of age. These data, coupled with the recent finding that regular exercise prevents cellular senescence, have led an increasing number of adults, many of whom have known or occult chronic disease, to the conclusion that “more exercise is better.” Marathon running, for example, has increased in popularity over the past 3 decades, with participation increasing from 25 000 runners in 1976 to ≈2 million in 2010. Thus, we have a population paradox in which there is an expansion in the number of habitually sedentary individuals paralleling a concomitant increase in those taking part in unprecedented hours of vigorous exercise. Figure 1. The evolutionary cardiovascular disease pyramid. Unhealthy lifestyle practices lead to risk factors, the progression of cardiovascular disease, and ultimately, adverse outcomes or clinical end points. The first-line strategy to prevent initial or recurrent cardiac events is to favorably modify unhealthy lifestyle habits, including cigarette smoking and poor dietary habits and physical inactivity. In 2000, these habits were responsible for an estimated 435 000 and 365 000 deaths, respectively.4 CHF indicates congestive heart failure; MI, myocardial infarction; and PAD, peripheral arterial disease. Adapted from Mozaffarian et al2 …

Prediabetes: The Effects on Arterial Thickness and Stiffness in Obese Youth

Adults with prediabetes are at increased risk to develop cardiovascular disease. Whether prediabetes in adolescents is associated with early markers of cardiovascular disease is not known. We sought to 1) compare the cardiovascular risk profiles among adolescents and young adults with prediabetes with those with normal glucose tolerance and 2) determine whether prediabetes is independently associated with noninvasive measures of arterial thickness and stiffness. We studied 102 obese youth with prediabetes and 139 obese youth with normal glucose tolerance in a cross-sectional study. Prediabetes or at increased diabetes risk was diagnosed by a fasting blood glucose level of ≥100 to 125 mg/dL, 2-hour oral glucose tolerance test value of ≥140 to 199 mg/dL, or a hemoglobin A1c (HbA1c) value of ≥5.7% to 6.4%. Arterial thickness and stiffness were measured by carotid intima-media thickness (IMT), augmentation index, pulse wave velocity, and brachial distensibility (BrachD). Nearly 50% of youth were diagnosed with prediabetes by HbA1c. Youth with prediabetes had worse metabolic profiles with higher BMI z score, systolic blood pressure, and fasting insulin; increased carotid IMT; and lower BrachD compared with normal glucose-tolerant youth (P < .05). Multivariate regression analysis found prediabetes was a significant determinant of internal carotid IMT and BrachD (P < .05). After excluding youth diagnosed by HbA1c, the prediabetes group was borderline significant for internal carotid IMT (.1 > P ≥ .05) only. Youth with prediabetes have worse cardiometabolic risk factors and evidence of increased arterial thickness and stiffness. Interventions to prevent prediabetes are crucial to reduce the development of early arterial disease.

Ovarian cancer: An ever challenging malady

Ovarian cancer is the fifth leading cause of cancer related deaths in women with a five year survival rate of only 30–40%. Amongst the three broad subgroups of ovarian cancer, epithelial ovarian cancer is the most common and is divided in mainly five subtypes based histology and clinical behaviour. In patients when the disease is still confined to ovaries, surgery alone is curative for more than 90% patients. Unfortunately, most women are diagnosed with advanced stage disease and recurs in majority despite of debulking surgery and initial response to chemotherapy. Thus ovarian cancer is still a challenge to clinicians which gets more complicated due to asymptomatic nature of the early stage disease and frequent development of resistance to standard therapies. Therefore, researchers worldwide are engaged in identifying markers for early detection of ovarian cancer, investigating molecular mechanisms of chemoresistance, improving detection methods and developing novel therapeutic measures. In this review, we attempt to discuss the contemporary research and challenges associated with epithelial ovarian cancer along with the future improvements in various areas such as early detection of ovarian cancer through Multiplex-Methylation specific PCR (MSP) assay and Serial Analysis of Gene expression (SAGE) assay and identifying new biomarkers, facilitating personalised chemotherapy regime by various chemo-response assays, novel drugs and targeted therapies which will aid in enhancing the overall survival rate in future and overcome this deadly gynaecologic disease.

The Biopontis Alliance Rare Disease Foundation (BARDF) – an innovative model for early stage rare disease therapy financing and development

The right therapy for the right patient at the right time is the most important approach for the provision of proper health care. The field of rare diseases is an excellent example, with patients taking a more central role in the discovery and development of treatments for their disease. Limited budgets coupled with high failure rates of medicine development lead us to public-private partnerships as a model to move forward and reduce cost; no stakeholder alone has all knowledge and expertise. The newly founded BioPontis Alliance Rare Disease Foundation presents a scientific and economic partnership model designed to unleash the potential to find cures for rare (pediatric) diseases. The non-profit Foundation has developed an innovation joint venture business and scientific development structure to fill the gap between discovery science and the biomedical industry. The Foundation will establish scientific bridges across the discovery/preclinical development gap as a partner to independent academic and/or patient organizations to develop medicine candidates. The BioPontis Alliance Rare Disease Foundation intends to also establish a financial bridge between the cures ‘push’ of philanthropic resources and the commercial ‘pull’ of private sector. The Foundation will provide a professional drug discovery operation in which the necessary scientific expertise for each product/discovery initiative can be selected and applied to each program. It has a virtual network of contract research companies and academic institutes where development work can be conducted as well as bringing central project management and industry experienced managers to each initiative. With novel licensing practices, the Foundation financially honors the seeding contributions of originating scientists, their host institutions and/or the Patient organization partner. Licensing agreements have already been signed with over 12 leading US academic institutions/hospitals, offering the originators a pro rata share of revenues that are generated from the full intellectual property estate, thus removing many of the misalignments of interests in traditional licensing and sponsored research agreements. Focus on a single goal of creating potential treatments for patients is therefore assured across the BARD Foundation’s model. The BARD Foundation is currently setting up financing and is seeking donations for its operations. While operating for a global patient community and market, we seek contacts with potential financial, scientific and patient organization partners in Europe and other parts of the world.