Host genetic factors in American cutaneous leishmaniasis: a critical appraisal of studies conducted in an endemic area of Brazil

American cutaneous leishmaniasis (ACL) is a vector-transmitted infectious disease with an estimated 1.5 million new cases per year. In Brazil, ACL represents a significant public health problem, with approximately 30,000 new reported cases annually, representing an incidence of 18.5 cases per 100,000 inhabitants. Corte de Pedra is in a region endemic for ACL in the state of Bahia (BA), northeastern Brazil, with 500-1,300 patients treated annually. Over the last decade, population and family-based candidate gene studies were conducted in Corte de Pedra, founded on previous knowledge from studies on mice and humans. Notwithstanding limitations related to sample size and power, these studies contribute important genetic biomarkers that identify novel pathways of disease pathogenesis and possible new therapeutic targets. The present paper is a narrative review about ACL immunogenetics in BA, highlighting in particular the interacting roles of the wound healing gene FLI1 with interleukin-6 and genes SMAD2 and SMAD3 of the transforming growth factor beta signalling pathway. This research highlights the need for well-powered genetic and functional studies on Leishmania braziliensis infection as essential to define and validate the role of host genes in determining resistance/susceptibility regarding this disease.

A decade of malaria during pregnancy in Brazil: what has been done concerning prevention and management

In Brazil, malaria remains a disease of major epidemiological importance because of the high number of cases in the Amazonian Region. Plasmodium spp infections during pregnancy are a significant public health problem with substantial risks for the pregnant woman, the foetus and the newborn child. In Brazil, the control of malaria during pregnancy is primarily achieved by prompt and effective treatment of the acute episodes. Thus, to assure rapid diagnosis and treatment for pregnant women with malaria, one of the recommended strategy for low transmission areas by World Health Organization and as part of a strategy by the Ministry of Health, the National Malaria Control Program has focused on integrative measures with woman and reproductive health. Here, we discuss the approach for the prevention and management of malaria during pregnancy in Brazil over the last 10 years (2003-2012) using morbidity data from Malaria Health Information System. Improving the efficiency and quality of healthcare and education and the consolidation of prevention programmes will be challenges in the control of malaria during pregnancy in the next decade.

El proyecto EMECAS: protocolo del estudio multicéntrico en España de los efectos a corto plazo de la contaminación atmosférica sobre la salud.

The EMECAM Project demonstrated the short-term effect of air pollution on the death rate in 14 cities in Spain throughout the 1990-1995 period. The Spanish Multicentre Study on Health Effects of Air Pollution (EMECAS) is broadening these objectives by incorporating more recent data, information on hospital disease admissions and totaling 16 Spanish cities. This is an ecological time series study in which the response variables are the daily deaths and the emergency hospitalizations due to circulatory system diseases and respiratory diseases among the residents in each city. Pollutants analyses: suspended particles, SO2, NO2, CO and O3. Control variables: meteorological, calendar, seasonality and influenza trend and incidence. Statistical analysis: estimate of the association in each city by means of the construction of generalized additive Poisson regression models and metanalysis for obtaining combined estimators. The EMECAS Project began with the creation of three working groups (Exposure, Epidemiology and Analysis Methodology) which defined the protocol. The average levels of pollutants were below those established under the current regulations for sulfur dioxide, carbon monoxide and ozone. The NO2 and PM10 values were around those established under the regulations (40 mg/m3). This is the first study of the relationship between air pollution and disease rate among one group of Spanish cities. The pollution levels studied are moderate for some pollutants, although for others, especially NO2 and particles, these levels could entail a problem with regard to complying with the regulations in force.

One-dimensional solidification of supercooled melts

In this paper a one-phase supercooled Stefan problem, with a nonlinear relation between the phase change temperature and front velocity, is analysed. The model with the standard linear approximation, valid for small supercooling, is first examined asymptotically. The nonlinear case is more difficult to analyse and only two simple asymptotic results are found. Then, we apply an accurate heat balance integral method to make further progress. Finally, we compare the results found against numerical solutions. The results show that for large supercooling the linear model may be highly inaccurate and even qualitatively incorrect. Similarly as the Stefan number β → 1&sup&+&/sup& the classic Neumann solution which exists down to β =1 is far from the linear and nonlinear supercooled solutions and can significantly overpredict the solidification rate.

Excision of the Staphylococcal Cassette Chromosome mec (SCCmec) and its crucial role in the horizontal transfer of methicillin resistance in staphylococci.

Staphylococcus aureus est un pathogène humain majeur ayant développé des résistances contre la quasi totalité des antibiotiques disponibles, incluant la très importante famille des β- lactamines. La résistance à cette classe d'antibiotiques est conférée par la « Staphylococcal Cassette Chromosome mec » (SCCmec), qui est un élément génétique mobile capable de s'insérer dans le chromosome bactérien et capable d'être transféré horizontalement chez d'autres staphylocoques. Le mécanisme moléculaire impliqué dans ce transfert horizontal demeure largement inconnu. L'une des premières étapes du transfert est l'excision du SCC mec du chromosome bactérien. Cette excision est promue par des enzymes codées par l'élément SCCmec lui- même et appelées de ce fait « Cassette Chromosome Recombinases » (Ccr). L'un des buts de ce travail de thèse a été de comprendre la régulation de l'expression des gènes codant pour les Ccr recombinases. En utilisant des outils moléculaires originaux, nous avons été en mesure de démontrer en premier lieu que les Ccr recombinases étaient exprimées de façon « bistable », c'est à dire qu'uniquement quelques pourcents de cellules dans une population exprimaient ces gènes à un temps donné. Dans un deuxième temps, nous avons également démontré que l'expression de ces gènes était régulée par des facteurs étrangers au SCC mec. L'expression bistable des recombinases est un concept important. Effectivement, cela permet à la majorité des cellules d'une population de conserver l'élément SCC mec, alors que seulement une petite fraction le perd afin de le rendre disponible pour un transfert. Ainsi, alors que l'élément SCC mec continue de se propager avec la multiplication des bactéries Staphylococcus aureus résistant à la méticilline (SARM), il peut être simultanément transmis à des souches susceptibles (Staphylococcus aureus susceptible à la méticilline, SASM), entraînant l'apparition de nouveaux SARM. De façon très intéressante, le fait que cette bistabilité est contrôlée par les bactéries, et non le SCCmec lui-même, montre que la décision de transférer ou non la cassette SCC mec appartient à la bactérie. En conséquence, il doit exister dans la nature des souches qui sont plus ou moins aptes à effectuer ce transfert. En nous appuyant sur ces observations, nous avons montré que l'excision du SCC mec était effectivement régulée de façon très étroite au cours de la division cellulaire, et ne se passait que pendant un temps limité au début de la croissance. Ce résultat est compatible avec une régulation génétique commandée par la densité cellulaire, qui pourrait être dépendante de la production de signaux extracellulaires, du type que l'on rencontre dans le quorum sensing. Les signaux hypothétiques entraînant l'excision du SCC mec restent inconnus à l'heure actuelle. La connaissance de ces signaux pourrait se révéler très importante afin de développer des stratégies pour interférer avec la dissémination de la résistance au β-lactamines. Deux sujets additionnels ont été logiquement investigués au vu de ces premiers résultats. Premièrement, si certaines souches de SARM sont plus ou moins aptes à déclencher l'excision du SCC mec, de même certaines souches de SASM devraient être plus ou moins aptes à acquérir cet élément. Deuxièmement, afin d'étudier ces mécanismes de transfert au niveau épidémiologique, il nous a été nécessaire de développer des outils nous permettant d'explorer le phénomène à une plus large échelle. Concernant le premier point, il a été postulé que certains SASM seraient réfractaires à l'intégration génomique d'un SCC mec en raison de polymorphismes particuliers à proximité du site d'insertion chromosomique (attB). En étudiant plus de 40 isolais de S. aureus, provenant de porteurs sains, nous avons confirmé ce polymorphisme dans l'environnement à'attB. De plus, nous avons pu montrer que ces régions polymorphiques ont évolué parallèlement à des groupes phylogénétiques bien connus. Ainsi, si des telles régions réfractaires à l'intégration de SCC mec existent, celles-ci devraient ségréger dans des complexes clonaux bien définis qui devraient être facilement identifiables au niveau épidémiologique. Concernant le second point, nous avons été capables de construire un système rapporteur de l'excision du SCCmec, en utilisant un plasmide à faible copie. Ce système consistait en un promoteur fort et un gène codant pour une protéine verte fluorescente (GFP) sous le contrôle d'un promoteur fort séparés à l'aide d'un élément SCC artificiel portant trois terminateurs de transcription. Ainsi, la fluorescence ne s'exprime que si l'élément SCC est excisé du plasmide. Ce système a été testé avec succès dans plusieurs types de staphylocoques, et est actuellement évalué dans d'autres souches et conditions stimulant ou inhibant l'excision. De manière générale, cette dissertation représente parcours scientifique à travers plusieurs aspects d'un problème de santé publique majeur en rapport avec la résistance bactérienne aux antibiotiques. Ce travail s'attaque à des problèmes fondamentaux concernant le transfert horizontal de l'élément SCC mec. De plus, il s'intéresse à des aspects plus généraux de cet élément génétique mobile qui pourraient se révéler très importants en terme de mouvement de gènes au sein des staphylocoques, voir d'autres bactéries gram-positives. Finalement ce travail de thèse met en place le fondamentaux requis pour des recherches futures visant à interférer avec le transfert horizontal de la résistance aux β-lactamines. - Staphylococcus aureus is a major human pathogen. Moreover, S. aureus have developed resistance to almost all available antibiotics, including the important family of β-lactam molecules. Intrinsic resistance to β-lactams is conferred by the Staphylococcal Cassette Chromosome mec (SCCmec), which is a mobile genomic island that inserts into the staphylococcal chromosome and can be horizontally transferred into other staphylococci. However, little is known about the molecular mechanisms involved in this horizontal transfer into naïve strains. One of the first steps in SCC mec horizontal transfer is its excision from the chromosome. Excision is mediated by recombinase enzymes that are encoded by SCC mec itself, and named accordingly Ccr recombinases - for Cassette Chromosome recombinases. One goal of this thesis was to understand the regulation these recombinase genes. By using original molecular tools we could demonstrate first that the Ccr recombinases were expressed in a "bistable" manner, i.e. in only few percentages of the bacterial cells at a given time, and second that they were regulated by determinants that were not encoded on the SCC mec element, but elsewhere on the staphylococcal genome. "Bistable" expression Ccr recombinases is an important concept. It allows SCC mec to be excised and thus available for horizontal transfer, while ensuring that only some cells, but not the whole population, loose their valuable SCC mec genes. Thus, while the SCC mec element expands with the multiplication of the MRSA colony, it can simultaneously be transmitted into methicillin-susceptible S. aureus (MSSA), which convert into new MRSA. Most interestingly, the fact that bistability was regulated by the cells, rather than by SCC mec, indicates that it was the choice of the bacteria to trigger or not SCC mec transfer. As a consequence, there must be, in nature, staphylococcal strains that are more or less prone to sustain SCC mec transfer. Following these seminal observations we found that excision was indeed tightly regulated during bacterial division, and occurred only during a limited period of time at the beginning of bacterial growth. This is compatible with cell-density mediated gene regulation, and may depend on the production of extracellular signal molecules that transmit appropriate orders to neighboring cells, such as in quorum sensing. The potential signal triggering SCCmec excision is as yet unknown. However, it could be critical in promoting the horizontal transfer of methicillin resistance, or for the possible development of means to interfere with it. Two additional hypothesis were logically investigated in the view of these first results. First, if some strains of MRSA might be more prone than others to promote SCC mec excision, then some strains of MS SA might be more or less prone to acquire the element as well. Second, to investigate these multiple mechanisms at an epidemiological level, one would need to develop tools amenable to explore S. aureus strains at a larger scale. Regarding the first issue, it was postulated by others that some MSSA might be refractory to SCC mec integration because they had peculiar DNA polymorphisms in the vicinity of the site-specific chromosomal entry point {attB) of SCC mec. By studying >40 S. aureus isolates from healthy carriers, we confirmed the polymorphism of the attB environment. Moreover, we could show that these polymorphic regions co-evolved with well-known phylogenic clonal clusters. Therefore, if SCCwec-refractory attB environments exist, then they would segregate in well- defined S. aureus clonal clusters that would be easy to identify at the epidemiological level. Regarding the second issue, we were able to construct a new excision reporter system in a low copy number S. aureus plasmid. The reporter system consists in a strong promoter driving a green fluorescent protein {gfp) gene, separated by an artificial SCC-like element carrying three transcriptional terminators. Thus, fluorescence is not expressed unless the SCC-like element is excised. The system has been successfully tested in several aureus and non- aureus staphylococci, and is now being applied to more strains and various excision- triggering or inhibiting conditions. Altogether the dissertation is a scientific journey through various aspects of a salient medical problem with regard to antibiotic resistance and public health threat. The research work tackles fundamental issues about the mechanisms of horizontal transfer of the SCC mec element. Moreover, it also addresses more general features of this mobile element, which could be of larger importance with regard to gene trafficking in staphylococci, and maybe other gram-positive bacteria. Finally, the dissertation sets the fundamentals for future work and possible new ways to interfere with the horizontal transfer of methicillin resistance.

Living-engineered valves for transcatheter venous valve repair.

Background: Chronic venous insufficiency (CVI) represents a major global health problem with increasing prevalence and morbidity. CVI is due to an incompetence of the venous valves, which causes venous reflux and distal venous hypertension. Several studies have focused on the replacement of diseased venous valves using xeno- and allogenic transplants, so far with moderate success due to immunologic and thromboembolic complications. Autologous cell-derived tissue-engineered venous valves (TEVVs) based on fully biodegradable scaffolds could overcome these limitations by providing non-immunogenic, non-thrombogenic constructs with remodeling and growth potential. Methods: Tri- and bicuspid venous valves (n=27) based on polyglycolic acid-poly-4-hydroxybutyrate composite scaffolds, integrated into self-expandable nitinol stents, were engineered from autologous ovine bone-marrow-derived mesenchymal stem cells (BM-MSCs) and endothelialized. After in vitro conditioning in a (flow) pulse duplicator system, the TEVVs were crimped (n=18) and experimentally delivered (n=7). The effects of crimping on the tissue-engineered constructs were investigated using histology, immunohistochemistry, scanning electron microscopy, grating interferometry (GI), and planar fluorescence reflectance imaging. Results: The generated TEVVs showed layered tissue formation with increasing collagen and glycosaminoglycan levels dependent on the duration of in vitro conditioning. After crimping no effects were found on the MSC level in scanning electron microscopy analysis, GI, histology, and extracellular matrix analysis. However, substantial endothelial cell loss was detected after the crimping procedure, which could be reduced by increasing the static conditioning phase. Conclusions: Autologous living small-diameter TEVVs can be successfully fabricated from ovine BM-MSCs using a (flow) pulse duplicator conditioning approach. These constructs hold the potential to overcome the limitations of currently used non-autologous replacement materials and may open new therapeutic concepts for the treatment of CVI in the future.

Advanced nursing role to improve care among breast cancer patients

Background: Breast cancer is a devastating disease for women as it impacts on their intimate, familial, social life. We study the specificities of breast cancer nurse interventions related to demands of support, information and coordination. Material and Methods: More than 300 patients are treated every year in our institution. From 2006 January to 2008 December, the specialist nurse has reported demands of patients and professionals: 1. Patients' needs related to support, information and coordination of care were collected from consultations with her and from their phone calls on using working days help line 2. Demands of breast cancer specialists and general practitioners related to information and coordination for specific patients were collected from their phone calls. Results: The specialist nurse received 679 phone calls respectively 71.5% from patients and 28.5% from professionals. Data are presented in the following table. Table 1: Evolution of number of patients and professionals demands Patients consultations Patients calls Professionals calls 2006 93 45 32 2007 210 200 40 2008 245 240 122 - Seventy percent (70%) of women asked for information about exams and treatments by phone and in nurse consultation. - Forty percent (40%) of women asked for support after announce of diagnosis. The specialist nurse proposed consultations, 2 to 4 consultations were necessary for women to express emotional distress or psychosocial problem. With this specialised nursing support less than 15% of patients were referred to the psycho-oncologist setting. - Forty percent (40%) of professionals asked support for patients and 60% for information and coordination of care. Conclusion: The interventions of the specialist nurse have improved coordination and quality of care. The increase of professionals' demands showed that it was necessary that a nurse assures continuity of information between hospital and extrahospital structures. The breast cancer nurse empowers patients and helps them to get well by providing support to fulfil specific needs.

Vuorovaikutuskouluttajana työyhteisöissä

This thesis concerns organizing a workshop about interaction in the various communities represented by Helsinki city's social welfare department. There were seventeen workshops altogether and they were organized in different communities; for example, in a children's daycare centre. The aim was to gain experience in the planning and organizing of these kinds of workshop. The workshops focused on dealing with interactive quetions arising out of the very community which was taking part in the workshop. These questions were discussed and handled using a technique called forum-statues. This means that the problems arising from the community were presented as living pictures to the group. There was also a short theoretical element concerning interactions between people, self-esteem, the different phases in developing a group, and the effects of conflicts in groups. There was a high degree of interest in the research and places were soon filled. The workshops consisted of a warming part with a lot of playing, a deepening part with questions arising out of the group, and a relaxation and feedback part at the end. The basis of the workshop was similar for all seventeen workshops. The athmosphere in workshops was discussive and open. The participants were engouraged to express there opinions and point of views. Feedback from the participantswas very positive. The participants obtained new points of view, according there fellow workers, and the community spirit improved. Shortage of time was, unfortunately, a problem. With more time, it would have been possible to go deeper into the problems of interaction within the community. Ceratinly, the research proved that there would be great demand for this kind of workshop in future.

The molecular basis of social behavior: models, methods and advances.

Elucidating the molecular and neural basis of complex social behaviors such as communal living, division of labor and warfare requires model organisms that exhibit these multi-faceted behavioral phenotypes. Social insects, such as ants, bees, wasps and termites, are attractive models to address this problem, with rich ecological and ethological foundations. However, their atypical systems of reproduction have hindered application of classical genetic approaches. In this review, we discuss how recent advances in social insect genomics, transcriptomics, and functional manipulations have enhanced our ability to observe and perturb gene expression, physiology and behavior in these species. Such developments begin to provide an integrated view of the molecular and cellular underpinnings of complex social behavior.

Wild bids. Gambling for resurrection in procurement contracts

This paper analyzes the problem of abnormally low tenders in theprocurement process. Limited liability causes firms in a bad financialsituation to bid more aggressively than good firms in the procurementauction. Therefore, it is more likely that the winning firm is a firm infinancial difficulties with a high risk of bankruptcy. The paper analyzesthe different regulatory practices to face this problem with a specialemphasis on surety bonds used e.g. in the US. We characterize the optimalsurety bond and show that it does not coincide with the current USregulation. In particular we show that under a natural assumption the USregulation is too expensive and provides overinsurance to the problem ofabnormally low tenders.

Why human islets die? analysis of death signaling pathways during isolation and following cytokine treatments

RESUME Le diabète de type 1 se définit comme un désordre métabolique d'origine auto-immune qui aboutit à la destruction progressive et sélective de la cellule ß-pancréatique sécrétrice d'insuline. Cette maladie représente 10 % des cas de diabète enregistrés dans la population mondiale, et touche les jeunes de moins de 20 ans. Le traitement médical par insulinothérapie corrige le manque d'hormone mais ne prévient pas les nombreuses complications telles que les atteintes cardiaques, neurologiques, rénales, rétiniennes, et les amputations que la maladie provoque. Le remplacement de la cellule ß par transplantation d'îlots de Langerhans est une alternative prometteuse au traitement médical du diabète de type 1. Cependant la greffe d'îlots est encore un traitement expérimental et ne permet pas un contrôle efficace de la glycémie au long terme chez les patients transplantés, et les raisons de cet échec restent mal comprises. L'obstacle immédiat qui se pose est la purification d'un nombre suffisant d'îlots viables et la perte massive de ces îlots dans les premières heures suite à la greffe. Cette tendance presque systématique de la perte fonctionnelle du greffon immédiatement après la transplantation est connue sous le terme de « primary graft non-function » (PNF). En effet, la procédure d'isolement des îlots provoque la destruction des composantes cellulaires et non cellulaires du tissu pancréatique qui jouent un rôle déterminant dans le processus de survie de l'îlot. De plus, la transplantation elle-même expose les cellules à différents stress, notamment le stress par les cytokines inflammatoires qui encourage la mort cellulaire par apoptose et provoque par la suite le rejet de la greffe. L'ensemble de ces mécanismes aboutit a une perte de la masse d'îlot estimée a plus de 60%. Dans ce contexte, nous nous sommes intéressés à définir les voies majeures de stress qui régissent cette perte massive d'îlot par apoptose lors du processus d'isolement et suite à l'exposition immédiate aux cytokines. L'ensemble des résultats obtenus indique que plusieurs voies de signalisation intracellulaire sont recrutées qui s'activent de manière maximale très tôt lors des premières phases de l'isolement. La mise en culture des îlots deux jours permet aux voies activées de revenir aux taux de base. De ce fait nous proposons une stratégie dite de protection qui doit être 1) initiée aussitôt que possible lors de l'isolement des îlots pancréatiques, 2) devrait probablement bloquer l'activation de ces différentes voies de stress mis en évidence lors de notre étude et 3) devrait inclure la mise en culture des îlots purifiés deux jours après l'isolement et avant la transplantation. RESUME LARGE PUBLIC Le diabète est une maladie qui entraîne un taux anormalement élevé de sucre (glucose) dans le sang du à une insuffisance du pancréas endocrine à produire de l'insuline, une hormone qui régule la glycémie (taux de glucose dans le sang). On distingue deux types majeurs de diabètes; le diabète de type 1 ou juvénile ou encore appelé diabète maigre qui se manifeste souvent pendant l'enfance et qui se traduit par une déficience absolue en insuline. Le diabète de type 2 ou diabète gras est le plus fréquent, et touche les sujets de plus de 40 ans qui souffrent d'obésité et qui se traduit par une dysfonction de la cellule ß avec une incapacité à réguler la glycémie malgré la production d'insuline. Dans le diabète de type 1, la destruction de la cellule ß est programmée (apoptose) et est majoritairement provoquée par des médiateurs inflammatoires appelés cytokines qui sont produites localement par des cellules inflammatoires du système immunitaire qui envahissent la cellule ß-pancréatiques. Les cytokines activent différentes voies de signalisation parmi lesquelles on distingue celles des Mitogen-Activated Protein Kinase (MAPKs) composées de trois familles de MAPKs: ERK1/2, p38, et JNK, et la voie NF-κB. Le traitement médical par injections quotidiennes d'insuline permet de contrôler la glycémie mais ne prévient pas les nombreuses complications secondaires liées à cette maladie. La greffe d'îlots de Langerhans est une alternative possible au traitement médical, considérée avantageuse comparée a la greffe du pancréas entier. En effet l'embolisation d'îlots dans le foie par injection intraportale constitue une intervention simple sans complications majeures. Néanmoins la technique de préparation d'îlots altère la fonction endocrine et cause la perte massive d'îlots pancréatiques. De plus, la transplantation elle-même expose la cellule ß à différents stress, notamment le stress par les cytokines inflammatoires qui provoque le rejet de greffon cellulaire. Dans la perspective d'augmenter les rendements des îlots purifiés, nous nous sommes intéressés à définir les voies majeures de stress qui régissent cette perte massive d'îlot lors du processus d'isolement et suite à l'exposition immédiate aux cytokines après transplantation. L'ensemble de ces résultats indique que le stress induit lors de l'isolement des îlots et celui des cytokines recrute différentes voies de signalisation intracellulaire (JNK, p38 et NF-κB) qui s'additionnent entre-elles pour altérer la fonction et la viabilité de l'îlot. De ce fait une stratégie doit être mise en place pour bloquer toute action synergique entre ces différentes voies activées pour améliorer la viabilité et la fonction de la cellule ß lors du greffon cellulaire. SUMMARY Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the progressive and selective destruction of the pancreatic ß-cells that secrete insulin, leading to absolute insulin deficiency. T1DM accounts for about 10% of all diabetes cases, affecting persons younger than 20 years of age. Medical treatment using daily exogenous insulin injection corrects hormone deficiency but does not prevent devastating complications such as heart attack, neuropathy, kidney failure, blindness, and amputation caused by the disease. Pancreatic islet transplantation (PIT) is one strategy that holds promise to cure patients with T1DM, but purified pancreatic islet grafts have failed to maintain long-term glucose homeostasis in human recipients, the reasons for this failure being still poorly understood. There is however a more immediate problem with islet grafting that is dependent upon poor islet recovery from donors and early islet loss following the first hours of grafting. This tendency of islet grafts to fail to function within a short period after transplantation is termed primary graft non-function (PNF). Indeed, the islet isolation procedure itself destroys cellular and non-cellular components of the pancreas that may play a role in supporting islet survival. Further, islet transplantation exposes cells to a variety of stressful stimuli, notably pro-inflammatory cytokines that encourage ß-cell death by apoptosis and lead to early graft failure. Altogether these mechanisms lead to an estimated loss of 60% of the total islet mass. Here, we have mapped the major intracellular stress signaling pathways that may mediate human islet loss by apoptosis during isolation and following cytokine attack. We found that several stress pathways are maximally activated from the earliest stages of the isolation procedure. Culturing islet for two days allow for the activated pathways to return to basal levels. We propose that protective strategies should 1) be initiated as early as possible during isolation of the islets, 2) should probably target the activated stress pathways that we uncovered during our studies and 3) should include culturing islets for two days post-isolation and prior transplantation.

Protecting the Public,Iowa Office of Citizens’ Aide/Ombudsman, January 2010

The Ombudsman helps citizens understand and maneuver through the often complicated depths and layers of government. In many cases, assistants facilitate citizen dialogue with an agency, explain the reasons for laws or policies, recommend revisions to unfair policies or unreasonable decisions, and resolve disputes informally. In some cases, the Ombudsman will pursue more formal investigations, take sworn testimony, and issue public reports. Here, in this periodic newsletter, you’ll find a small sampling of the ombudsman’s work over the previous two months. If you need help resolving a problem with state or local government, please see our contact information at the bottom of the page.

Non-constant discounting in finite horizon: The free terminal time case

This paper derives the HJB (Hamilton-Jacobi-Bellman) equation for sophisticated agents in a finite horizon dynamic optimization problem with non-constant discounting in a continuous setting, by using a dynamic programming approach. A simple example is used in order to illustrate the applicability of this HJB equation, by suggesting a method for constructing the subgame perfect equilibrium solution to the problem.Conditions for the observational equivalence with an associated problem with constantdiscounting are analyzed. Special attention is paid to the case of free terminal time. Strotz¿s model (an eating cake problem of a nonrenewable resource with non-constant discounting) is revisited.

Prise en charge actuelle de l'incontinence anale [Current management of anal incontinence]

Even though anal incontinence affects a significant proportion of the population, causing a major burden to both patient and society, it still remains "the last closet issue". Less than a third of patients will share this problem with their physician. Consequently, the incidence of anal incontinence is difficult to determine, varying from 2-50%. Since this disabling condition is often associated with urinary incontinence and/or pelvic organ prolapse, a multidisciplinary team approach is required. A wide range of therapeutic options are available. When dietary, medical and rehabilitative treatments have failed, sacral neuromodulation should be considered in selected cases. More invasive surgery is usually undertaken in the presence of major structural defects. The aim of this article is to suggest a comprehensive way of identifying and treating anal incontinence.

Microbial biomass and soil chemical properties under different land use systems in northeastern Pará

The increase in agricultural production in the Brazilian Amazon region is mostly a result of the agricultural frontier expansion, into areas previously influenced by humans or of native vegetation. At the same time, burning is still used to clear areas in small-scale agricultural systems, leading to a loss of the soil productive capacity shortly after, forcing the opening of new areas. This study had the objective of evaluating the effect of soil preparation methods that involve plant residue shredding, left on the surface or incorporated to the soil, with or without chemical fertilization, on the soil chemical and biological properties. The experiment was conducted in 1995, in an experimental field of Yellow Latosol (Oxisol) of the Embrapa Amazônia Oriental, northeastern Pará (Brazil). The experiment was arranged in randomized blocks, in a 2x6 factorial design, with two management systems and six treatments evaluated twice. The management systems consisted of rice (Oriza sativa), followed by cowpea (Vigna unguiculata) with manioc (Manihot esculenta). In the first system the crops were planted in two consecutive cycles, followed by a three-year fallow period (natural regrowth); the second system consisted of one cultivation cycle and was left fallow for three years. The following treatments were applied to the secondary forest vegetation: slash and burn, fertilized with NPK (Q+NPK); slash and burn, without fertilizer NPK (Q-NPK); cutting and shredding, leaving the residues on the soil surface, fertilized with NPK (C+NPK); cutting and shredding, leaving residues on the soil surface, without fertilizer (C-NPK); cutting and shredding, with residue incorporation and fertilized with NPK (I+NPK); cutting and shredding, with residue incorporation and without NPK fertilizer (I-NPK). The soil was sampled in the rainier season (April 2006) and in the drier season (September 2006), in the 0-0.1 m layer. From each plot, 10 simple samples were collected in order to generate a composite sample. In the more intensive management system the contents of microbial C (Cmic) and microbial N (Nmic) were higher, while the C (Corg) level was higher in the less intensive system. The treatments with highest Cmic and Nmic levels were those with cutting, shredding and distribution of biomass on the soil surface. Under both management systems, the chemical characteristics were in ranges that classify the soil as little fertile, although P and K (in the rainy season) were higher in the less intensive management system.