Theoretical and experimental studies on prey–predator systems where predator is supplied with alternate sources of food have received significant attention over the years due to their relevance in achieving biological conservation and biological control. Some of the outcomes of these studies suggest that with appropriate quality and quantity of additional food, the system can be steered towards any desired state eventually with time. One of the limitations of previous studies is that the desired state is reached asymptotically, which makes the (...) outcomes not easily applicable in practical scenarios. To overcome this limitation, in this work, we formulate and study optimal control problems to achieve the desired outcomes in minimum (finite) time. We consider two different models of additional food provided prey–predator systems involving Holling type IV functional response (with inhibitory effect of prey). In the first scenario, additional food is incorporated implicitly into the predator’s functional response with a possibility of achieving biological conservation through co-existence of species and biological control by maintaining prey at a level that is least harmful to the system. In the second, the effect of additional food is incorporated explicitly into the predator’s compartment with the goal of pest management by maintaining prey density at a very minimal damaging level. For both cases, appropriate optimal control strategies are derived and the theoretical findings are illustrated by numerical simulations. We also discuss the ecological significance of the theoretical findings for both models. (shrink)

The importance of communities in strengthening the ethics of international collaborative research is increasingly highlighted, but there has been much debate about the meaning of the term ‘community’ and its specific normative contribution. We argue that ‘community’ is a contingent concept that plays an important normative role in research through the existence of morally significant interplay between notions of community and individuality. We draw on experience of community engagement in rural Kenya to illustrate two aspects of this interplay: (i) that (...) taking individual informed consent seriously involves understanding and addressing the influence of communities in which individuals’ lives are embedded; (ii) that individual participation can generate risks and benefits for communities as part of the wider implications of research. We further argue that the contingent nature of a community means that defining boundaries is generally a normative process itself, with ethical implications. Community engagement supports the enactment of normative roles; building mutual understanding and trust between researchers and community members have been important goals in Kilifi, requiring a broad range of approaches. Ethical dilemmas are continuously generated as part of these engagement activities, including the risks of perverse outcomes related to existing social relations in communities and conditions of ‘half knowing’ intrinsic to processes of developing new understandings. (shrink)

Professional caregivers who work with the trauma and suffering of others, such as doctors, nurses and psychologists, may face significant challenges along with the risk of adverse, long-term mental and physical health problems. Caregivers with responsibility for dependants outside their professional work reported more stress. This finding is of particular relevance in respect of caregivers in under-developed countries such as Zimbabwe, where many households have taken in additional children who have been orphaned, whose parents are ill, or whose parents have (...) temporarily gone elsewhere in search of work. For the purposes of the study, a qualitative phenomenological research design was selected as appropriate to the focus on human experience. An interpretative approach was adopted to explore and explicate the lived experiences of the participants and the meaning they attached to them. The major sources of stress for professional caregivers emerged as being resource constraints, interpersonal issues, and personal issues. Factors found to promote coping include the caregiver’s meaning making perspective, making a difference, and constructing a sense of personal control. (shrink)

This study investigates the ability of individuals with psychopathy to perform passive avoidance learning and whether this ability is modulated by level of reinforcement/punishment. Nineteen psychopathic and 21 comparison individuals, as defined by the Hare Psychopathy Checklist Revised (Hare, 1991), were given a passive avoidance task with a graded reinforcement schedule. Response to each rewarding number gained a point reward specific to that number (i.e., 1, 700, 1400 or 2000 points). Response to each punishing number lost a point punishment specific (...) to that number (i.e., the loss of 1, 700, 1400 or 2000 points). In line with predictions, individuals with psychopathy made more passive avoidance errors than the comparison individuals. In addition, while the performance of both groups was modulated by level of reward, only the performance of the comparison population was modulated by level of punishment. The results are interpreted with reference to a computational account of the emotional learning impairment in individuals with psychopathy. (shrink)

Introduction: Variation across research ethics boards in conditions placed on access to medical records for research purposes raises concerns around negative impacts on research quality and on human subject protection, including privacy.Aim: To study variation in REB consent requirements for retrospective chart review and who may have access to the medical record for data abstraction.Methods: Thirty 90-min face-to-face interviews were conducted with REB chairs and administrators affiliated with faculties of medicine in Canadian universities, using structured questions around a case study (...) with open-ended responses. Interviews were recorded, transcribed and coded manually.Results: Fourteen sites required individual patient consent for the study to proceed as proposed. Three indicated that their response would depend on how potentially identifying variables would be managed. Eleven sites did not require consent. Two suggested a notification and opt-out process. Most stated that consent would be required if identifiable information was being abstracted from the record. Among those not requiring consent, there was substantial variation in recognising that the abstracted information could potentially indirectly re-identify individuals. Concern over access to medical records by an outside individual was also associated with requirement for consent. Eighteen sites required full committee review. Sixteen allowed an external research assistant to abstract information from the health record.Conclusions: Large variation was found across sites in the requirement for consent for research involving access to medical records. REBs need training in best practices for protecting privacy and confidentiality in health research. A forum for REB chairs to confidentially share concerns and decisions about specific studies could also reduce variation in decisions. (shrink)

Philippe de Mézières est un de ces auteurs du XIVe siècle que l’on estime et étudie volontiers. C’est qu’il est témoin oculaire et participant de bien des hauts moments de l’histoire. Né vers 1327 dans la famille de Mézières, de petite noblesse picarde , il reçoit une formation spirituelle chez les chanoines de la cathédrale d’Amiens. En 1345 il quitte son pays natal et l’année suivante gagne ses éperons de chevalier après la croisade de Humbert II de Dauphiné en Smyrne. (...) Par la suite, il joue plusieurs rôles saillants: nommé en 1361 chancelier de Chypre sous les Lusignan ; ami de Pétrarque; familier de Grégoire XI à Avignon; apologiste des croisades; ami et conseiller de Charles V de France et précepteur du dauphin, le futur Charles VI; écrivain laïque parmi les Célestins de Paris entre 1380 et 1405. Presque octogénaire, Mézières y meurt le 29 mai 1405, et est accordé la distinction d’être enveloppé du manteau de l’ordre à son enterrement. C’est à cette période de retraite que remontent ses écrits importants, tous de caractère religieux et rédigés en latin ou en français. (shrink)

The COVID-19 pandemic has resulted in more than 524 million cases and 6 million deaths worldwide. Various drug interventions targeting multiple stages of COVID-19 pathogenesis can significantly reduce infection-related mortality. The current within-host mathematical modeling study addresses the optimal drug regimen and efficacy of combination therapies in the treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Interferon and Lopinavir/ritonavir. It is concluded that these drugs, when administered singly or in combination, reduce the number of infected cells and viral load. (...) Four scenarios dealing with the administration of a single drug, two drugs, three drugs and all four are discussed. In all these scenarios, the optimal drug regimen is proposed based on two methods. In the first method, these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem are formulated. In this framework, the optimal drug regimen is derived. Later, using the comparative effectiveness method, the optimal drug regimen is derived based on the basic reproduction number and viral load. The average number of infected cells and viral load decreased the most when all four drugs were used together. On the other hand, the average number of susceptible cells decreased the most when Arbidol was administered alone. The basic reproduction number and viral load decreased the most when all four interventions were used together, confirming the previously obtained finding of the optimal control problem. The results of this study can help physicians make decisions about the treatment of the life-threatening COVID-19 infection. (shrink)

Rita Bottino,1 Santosh Nagaraju,2 Vikas Satyananda,2 Hidetaka Hara,2 Martin Wijkstrom,2 Massimo Trucco,1 David KC Cooper2 1Institute of Cellular Therapeutics, Allegheny Health Network, 2Thomas E Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA: Diabetes mellitus is increasing worldwide. Type 1 diabetes can be treated successfully by islet allotransplantation, the results of which are steadily improving. However, the number of islets that can be obtained from deceased human donors will never be sufficient to cure more than a very (...) small percentage of patients who might benefit from transplantation. Although there are some differences in glucose metabolism between pigs and humans, the use of pigs could provide an unlimited supply of islets, and the insulin produced would undoubtedly control glucose levels. Transplantation of islets into the portal vein results in islets residing in the liver; however, an early inflammatory response and rejection remain problematic, even when the recipient is receiving immunosuppressive therapy. In the long term, immunosuppressive drugs may exhibit toxicities to patients and specifically harm the islet cells. In contrast, encapsulation techniques provide islets with a physical barrier that prevents antibodies binding to the islet graft while still allowing insulin to be released into the recipient's circulation; in theory, patients receiving encapsulated grafts might not require exogenous immunosuppressive therapy. Nonhuman primates with encapsulated pig islet transplants have remained insulin-independent for several weeks, but long-term efficacy remains uncertain. Furthermore, techniques are now available to knock out genes from the pig and/or insert human genes, thus rendering the antigenic structure of pigs closer to that of humans, and providing protection from the human immune response. Islet transplantation from genetically engineered pigs has been followed by insulin independence in a small number of nonhuman primates for greater than 1 year. Neonatal islets have some advantages over adult islets in that they are easier to isolate and culture, and have the ability to proliferate during the first few months after transplantation. In 2009, the International Xenotransplantation Association set up a group to encourage and advise on clinical trials of pig islet xenotransplantation; this group's guidelines are discussed. Clinical trials of encapsulated pig islets are already under way. Keywords: diabetes, islets, pancreatic, pig, xenotransplantation. (shrink)

© 2015 Elsevier Inc.Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland is the only organ developing predominantly after birth, we utilized it as a powerful system to study (...) adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ -producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses, regulating normal development, changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation. Plaks et al. (shrink)

The objectives of this study were to develop a high-density chromosome bin map of homoeologous group 7 in hexaploid wheat, to identify gene distribution in these chromosomes, and to perform comparative studies of wheat with rice and barley. We mapped 2148 loci from 919 EST clones onto group 7 chromosomes of wheat. In the majority of cases the numbers of loci were significantly lower in the centromeric regions and tended to increase in the distal regions. The level of duplicated loci (...) in this group was 24% with most of these loci being localized toward the distal regions. One hundred nineteen EST probes that hybridized to three fragments and mapped to the three group 7 chromosomes were designated landmark probes and were used to construct a consensus homoeologous group 7 map. An additional 49 probes that mapped to 7AS, 7DS, and the ancestral translocated segment involving 7BS also were designated landmarks. Landmark probe orders and comparative maps of wheat, rice, and barley were produced on the basis of corresponding rice BAC/PAC and genetic markers that mapped on chromosomes 6 and 8 of rice. Identification of landmark ESTs and development of consensus maps may provide a framework of conserved coding regions predating the evolution of wheat genomes. (shrink)

The high prevalence of cardiovascular diseases demands a reliable and sensitive risk assessment technique. In order to develop a fast and label-free immunosensor for C-reactive protein, a risk factor for this condition, anti-CRP antibodies were physically adsorbed to the hydrogen -terminated surface of nanocrystalline diamond. An Enzyme-Linked ImmunoSorbent Assay reference technique showed that this was a suitable substrate for antibody-antigen recognition reactions. Electrochemical Impedance Spectroscopy was used to electronically detect CRP recognition. The specificity of the immunosensor was demonstrated by incubation (...) with CRP and plasminogen as reference molecule. A different impedance behavior was observed in real-time after CRP addition as compared to plasminogen addition: the impedance increased only during CRP incubation. Fitting the data showed that this corresponded with a decrease in capacitance of the molecular layer due to its increased thickness by specific CRP recognition. Sensitivity experiments in real-time showed a clear discrimination between 1 μM, 100 nM, and 10 nM of CRP after 10 min at 100 Hz. Since, 10 nM of CRP was still clearly distinguishable from buffer solution, our CRP-directed immunosensor prototype reaches a sensitivity that is within the physiologically relevant concentration range of this biomarker in healthy controls and CVD patients. Moreover, this prototype displayed real-time discriminating power between spiked and unspiked serum, and thus also shows its applicability in this biological matrix. © 2011 Elsevier B.V. All rights reserved. (shrink)

ABSTRACT Despite Institutional Review Board concerns about psychological harm arising from research participation, evidence from trauma-questionnaire research suggests that participation is typically well-tolerated by participants. Yet, it is unclear how participant experiences of in-lab trauma simulations align with IRB ethical guidelines. Thus, we compared reactions to a trauma film paradigm with reactions to a positive film task or cognitive tasks. Overall, relative to other conditions, the trauma film was well-tolerated by participants: they generally reported low-to-moderate negative emotions, moderate benefits, and (...) that participation was not worse than everyday stressors. Our results have implications for the research community in designing trauma-based research. (shrink)

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags accounting for 2266 restriction fragments on the homoeologous group 3 chromosomes of hexaploid wheat. Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the (...) chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes ∼21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected. (shrink)