Can medical products be developed on a non-profit basis? Exploring product development partnerships for neglected diseases

Reliance on market forces can lead to underinvestment in social welfare enhancing innovation. The lack of new medical products in the area of neglected diseases is a case in point. R&D for neglected diseases has increased with new funding and collaborations taking place mainly through product development partnerships (PDPs). PDPs are self-governing, private non-profit R&D organizations. In contrast to push and pull instruments designed to address private-sector R&D underinvestment, PDPs have emerged voluntarily to address this public health challenge. In this study we examine how non-profit R&D collaboration for neglected diseases takes place through PDPs. We find that PDPs act as ‘system integrators' that leverage the resources and capabilities of a network of public, philanthropic and private-sector partners. This paper contributes to an understanding of R&D in a non-profit context and highlights the importance of collaboration and non-market institutions for promoting innovation where market failures occu

Growth abnormalities of fetuses and infants

The objective of this special issue is to address recent research trends and developments about the advancements of image processing and vision in healthcare. A substantial number of papers were submitted, and after a thorough peer review process, some of these were selected to be included in this special issue. Growth abnormalities (either growth restriction or large for gestational age) during perinatal and postnatal life are a hot topic issue, since they are often linked to alteration of uterine environment caused by placental insufficiency, maternal metabolic syndrome, and in general under- or overnutrition of the fetus. These fetal abnormalities account for the leading causes of perinatal morbidity and mortality. Moreover, under the hypothesis of developmental origin of adult diseases, they bear consequences in later life, programming the infant physiology for a higher risk of noncommunicable diseases, cardiovascular adult diseases, and neurodevelopment delay. Low birth weight, caused either by preterm birth and/or by intrauterine growth restriction, is recently known to be associated with increased rates of cardiovascular disease and noninsulin dependent diabetes in adult life. The “developmental origins of adult disease” hypothesis, often called “the Barker hypothesis,” proposes that these diseases originate through adaptations of the fetus when it is undernourished. These adaptations may be cardiovascular, metabolic, or endocrine and they may permanently change the structure and function of the body, increasing coronary heart disease risk factors, such as hypertension, type 2 diabetes mellitus, insulin resistance, and hyperlipidaemia. This hypothesis originally involved from observation by Barker and colleagues that the regions in England with the highest rates of infant mortality in the early 20th century also had the highest rates of mortality from coronary heart disease decades later. As the most commonly registered cause of infant death at the start of 20th century was low birth weight, these observations led to the hypothesis that low birth weight babies who survived infancy and childhood might be at increased risk of coronary heart disease in later life. There is an increased evidence of the link between intrauterine and perinatal alterations and adult diseases. Although the main focus so far has been the timing of delivery and follow-up, the study of the pathophysiology and of possible recovery is of paramount importance and needs the contributions of physicians from several fields, biologists, bioinformaticians, and engineers

A critical review of palladium organometallic anticancer agents

With the aim of overcoming the well-known limitations of platinum-based antineoplastic drugs, recent efforts have focused on the development of new anticancer agents containing metals other than platinum. Among these agents, organopalladium compounds have received significant recent attention due to their generally high stability under physiological conditions. A significant number of these compounds have shown promising in vitro and in vivo antiproliferative activity toward several cisplatin-sensitive and cisplatin-resistant tumors and have sometimes exhibited a different mechanism of action compared to platinum-based drugs. In this review, recent advances in the field of organopalladium compounds as potential anticancer agents are discussed

The impact of the COVID-19 pandemic on rural food security in high income countries : a systematic literature review

Prior to the COVID-19 pandemic, rural-dwelling people in high-income countries were known to have greater challenges accessing healthy food than their urban counterparts. The COVID19 pandemic has impacted food supplies across the world, and public health restrictions have changed the way people shop for food, potentially exacerbating food insecurity. This systematic literature review aimed to synthesize the available evidence on the impact of the COVID-19 pandemic on aspects of food insecurity in rural populations residing in high-income countries. Five electronic databases were searched, identifying 22 articles that assessed food insecurity prevalence or data on food availability, access, utilization and the stability of the food supply in rural populations during the COVID-19 pandemic. Ten studies examined the prevalence of food insecurity in rural populations, with the reported prevalence ranging from 15% to 95%. Where rural/urban comparisons were presented, most studies (n = 5; 71%) reported that food insecurity was significantly higher in rural regions. Five studies examined the availability of food and eight studies examined access to food, identifying that rural populations often had lower food availability and access to food during the pandemic. In contrast, two studies identified positive effects such as more gardening and increased online access to food. Rural populations experienced multiple changes to food utilization, such as reduced diet quality and food safety observed in eight studies, but this was not shown to be different from urban populations. Additionally, the food supply in rural regions was perceived to be affected in two studies. The results of this review may be used to inform region-specific mitigation strategies to decrease the impact of the current COVID-19 pandemic and future global events on food security. However, the lack of consistency in study outcomes in research on rural populations limits the identification of priority areas for intervention at a global-scale

Strigolactones affect phosphorus acquisition strategies in tomato plants

Strigolactones (SLs) are plant hormones that modulate morphological, physiological and biochemical changes as part of the acclimation strategies to phosphorus (P) deficiency, but an in‐depth description of their effects on tomato P‐acquisition strategies under P shortage is missing. Therefore, in this study, we investigate how SLs impact on root exudation and P uptake, in qualitative and quantitative terms over time, in wild‐type and SL‐depleted tomato plants grown with or without P. Under P shortage, SL‐depleted plants were unable to efficiently activate most mechanisms associated with the P starvation response (PSR), except for the up‐regulation of P transporters and increased activity of P‐solubilizing enzymes. The reduced SL biosynthesis had negative effects also under normal P provision, because plants over‐activated high‐affinity transporters and enzymatic activities (phytase, acidic phosphatase) to sustain elevated P uptake, at great carbon and nitrogen costs. A shift in the onset of PSR was also highlighted in these plants. We conclude that SLs are master kinetic regulators of the PSR in tomato and that their defective synthesis might lead both to suboptimal nutritional outcomes under P depletion and an unbalanced control of P uptake when P is available

Analytical derivation of elasticity in breast phantoms for deformation tracking

Patient-specific biomedical modeling of the breast is of interest for medical applications such as image registration, image guided procedures and the alignment for biopsy or surgery purposes. The computation of elastic properties is essential to simulate deformations in a realistic way. This study presents an innovative analytical method to compute the elastic modulus and evaluate the elasticity of a breast using magnetic resonance (MRI) images of breast phantoms.An analytical method for elasticity computation was developed and subsequently validated on a series of geometric shapes, and on four physical breast phantoms that are supported by a planar frame. This method can compute the elasticity of a shape directly from a set of MRI scans. For comparison, elasticity values were also computed numerically using two different simulation software packages.Application of the different methods on the geometric shapes shows that the analytically derived elongation differs from simulated elongation by less than 9% for cylindrical shapes, and up to 18% for other shapes that are also substantially vertically supported by a planar base. For the four physical breast phantoms, the analytically derived elasticity differs from numeric elasticity by 18% on average, which is in accordance with the difference in elongation estimation for the geometric shapes. The analytic method has shown to be multiple orders of magnitude faster than the numerical methods.It can be concluded that the analytical elasticity computation method has good potential to supplement or replace numerical elasticity simulations in gravity-induced deformations, for shapes that are substantially supported by a planar base perpendicular to the gravitational field. The error is manageable, while the calculation procedure takes less than one second as opposed to multiple minutes with numerical methods. The results will be used in the MRI and Ultrasound Robotic Assisted Biopsy (MURAB) project

Iterative simulations to estimate the elastic properties from a series of MRI images followed by MRI-US validation

The modeling of breast deformations is of interest in medical applications such as image-guided biopsy, or image registration for diagnostic purposes. In order to have such information, it is needed to extract the mechanical properties of the tissues. In this work, we propose an iterative technique based on finite element analysis that estimates the elastic modulus of realistic breast phantoms, starting from MRI images acquired in different positions (prone and supine), when deformed only by the gravity force. We validated the method using both a single-modality evaluation in which we simulated the effect of the gravity force to generate four different configurations (prone, supine, lateral, and vertical) and a multi-modality evaluation in which we simulated a series of changes in orientation (prone to supine). Validation is performed, respectively, on surface points and lesions using as ground-truth data from MRI images, and on target lesions inside the breast phantom compared with the actual target segmented from the US image. The use of pre-operative images is limited at the moment to diagnostic purposes. By using our method we can compute patient-specific mechanical properties that allow compensating deformations

Can medical products be developed on a non-profit basis? Exploring product development partnerships for neglected diseases

Reliance on market forces can lead to underinvestment in social welfare enhancing innovation. The lack of new medical products in the area of neglected diseases is a case in point. R&D for neglected diseases has increased with new funding and collaborations taking place mainly through product development partnerships (PDPs). PDPs are self-governing, private non-profit R&D organizations. In contrast to push and pull instruments designed to address private-sector R&D underinvestment, PDPs have emerged voluntarily to address this public health challenge. In this study we examine how non-profit R&D collaboration for neglected diseases takes place through PDPs. We find that PDPs act as 'system integrators' that leverage the resources and capabilities of a network of public, philanthropic and private-sector partners. This paper contributes to an understanding of R&D in a non-profit context and highlights the importance of collaboration and non-market institutions for promoting innovation where market failures occur

Loss of heterozygosity at the 5,10-methylenetetrahydrofolate reductase locus in human ovarian carcinomas.

The high-affinity folate-binding protein (FBP) is primarily involved in the uptake of the 5-methyltetrahydrofolate, and its expression may be physiologically regulated by the intracellular folate content. The overexpression of FBP on the cell surface of ovarian carcinoma cells may be responsible for an increased folate uptake. We tested the hypothesis of the existence of a defect in the 5, 10-methylenetetrahydrofolate reductase (MTHFR) in ovarian tumours that could cause reduced intracellular regeneration of the 5-methyltetrahydrofolate and induce increased FBP expression. No sequence mutations were found in the MTHFR gene, but allelic deletions of this gene were frequently detected in ovarian tumours (59%). Chromosomal losses appeared to be confined to the 1p36.3 region to which the MTHFR gene maps. Although it cannot be stated that MTHFR is the target gene of the chromosomal loss involving the 1p36.3 region, a correlation between loss of heterozygosity at this locus and decrease in MTHFR activity was shown, suggesting a role of these allelic deletions in generating a biochemical defect in folate metabolism. Further studies are needed to assess further the relationship between MTHFR and FBP overexpression, but the demonstration of the alteration of a key metabolic enzyme of the folate cycle in a subset of human ovarian tumours is in accordance with the hypothesis of an altered folate metabolism in these neoplasias and might be exploited for therapeutic purposes

Model for initiation of quality factor degradation at high accelerating fields in superconducting radio-frequency cavities

A model for the onset of the reduction in SRF cavity quality factor, the so-called Q-drop, at high accelerating electric fields is presented. Breakdown of the surface barrier against magnetic flux penetration at the cavity equator is considered to be the critical event that determines the onset of Q-drop. The worst case of triangular grooves with low field of first flux penetration Hp, as analyzed previously by Buzdin and Daumens, [1998 Physica C 294: 257], was adapted. This approach incorporates both the geometry of the groove and local contamination via the Ginzburg-Landau parameter kappa, so the proposed model allows new comparisons of one effect in relation to the other. The model predicts equivalent reduction of Hp when either roughness or contamination were varied alone, so smooth but dirty surfaces limit cavity performance about as much as rough but clean surfaces do. When in combination, contamination exacerbates the negative effects of roughness and vice-versa. To test the model with actual data, coupons were prepared by buffered chemical polishing and electropolishing, and stylus profilometry was used to obtain distributions of angles. From these data, curves for surface resistance generated by simple flux flow as a function of magnetic field were generated by integrating over the distribution of angles for reasonable values of kappa. This showed that combined effects of roughness and contamination indeed reduce the Q-drop onset field by ~30%, and that that contamination contributes to Q-drop as much as roughness. The latter point may be overlooked by SRF cavity research, since access to the cavity interior by spectroscopy tools is very difficult, whereas optical images have become commonplace. The model was extended to fit cavity test data, which indicated that reduction of the superconducting gap by contaminants may also play a role in Q-drop.Comment: 15 pages with 7 figure