A mathematical model of the tetrapyrrole biosynthesis pathway

The tetrapyrrole biosynthesis pathway is a key part in chlorophyll production and is essential for plant survival. It involves numerous interacting compounds and, crucially, light. The understanding of the complex regulation processes involved has been the focus of extensive experimental research providing a large source of data. A particular set of data, concerned with the modelling described in this report, involves 24 hour timecourse data from seedlings exposed to constant light, following a three day period of growth from seed in darkness. This data includes the levels of key components such as chlorophyll, ATP, chlorophyllide and proto-chlorophyllide. Amongst the questions posed in the study-group were: i) Can the timecourse data be predicted by a model? ii) Can it predict the dierences in levels of various components in found mutant strains. To address these questions, we present in this report a model consisting of a coupled system of nonlinear ODEs that describes a simplied version of the tetrapyrrole pathway based on mass action laws. Model simulations produced results that agree qualitatively well with most, but not all, of the available timecourse data obtained from wild-type and mutant strains. Nearly all of the model's parameters are not known, so the values used in these simulations are based on estimates of the relative timescales of the reactions. An attempt at improving these estimates using data tting techniques is also discussed

Une méthode alternative de reproduction chez la lapine : un modèle pour une approche systémique du fonctionnement des élevages cunicoles

Une méthode alternative de reproduction chez la lapine : un modèle pour une approche systémique du fonctionnement des élevages cunicoles. Il existe aujourd'hui dans les élevages cunicoles un renouvellement important du cheptel de lapines reproductrices. Parallèlement, les lapereaux sont fréquemment atteints de troubles digestifs entraînant des pertes conséquentes d'animaux. Ces deux problèmes ne sont pas indépendants, mais sont le plus souvent dissociés dans les études. Une approche systémique, englobant ces deux aspects nous a permis de formaliser une stratégie pour résoudre cette problématique. Nous avons représenté le système d'élevage cunicole par une composante décisionnelle (l'éleveur) et biotechnique (ateliers maternité et engraissement). L'objectif de ce travail est d'évaluer l'influence d'une extensification du rythme de reproduction (56j vs 42j) et d'une réduction de la durée de la lactation (23j vs 35j) sur les performances de l'atelier maternité. Nous avons déterminé en conséquence les effets de l'âge au sevrage (23j vs 35j) et de l'alimentation (teneur en fibres et en protéines) sur les performances de l'atelier engraissement. Des variables d'état ont été étudiées (performances de reproduction, état corporel, longévité des lapines, croissance et santé des lapereaux) pour évaluer l'action de ces trois leviers de pilotage sur l'évolution du système d'élevage. Une extensification du rythme de reproduction associée à une réduction de la durée de la lactation améliore l'état corporel des lapines au cours des cycles de reproduction et leur longévité, mais n'affecte pas la prolificité des lapines et n'augmente que la fertilité des femelles primipares. Malgré une meilleure régularité des performances de reproduction, cette conduite ne permet pas de compenser la perte de production annuelle liée à l'extensification. Elle réduit cependant les réformes involontaires et optimise certaines variables dont la lecture intervient dans la décision de réformer les lapines (fertilité, état corporel). Elle est donc susceptible d'abaisser notablement le taux de renouvellement des femelles. La conduite de la reproduction étudiée a des répercussions négatives dans l'atelier d'engraissement. En effet, un sevrage précoce, réalisé à 23j, augmente fortement la sensibilité des lapereaux aux troubles digestifs après le sevrage et la stratégie alimentaire proposée n'atténue pas cet effet. L'intérêt de l'approche systémique réside dans la mise en évidence de l'interaction entre les deux ateliers biotechniques et l'intégration de nouvelles contraintes à l'échelle du système d'élevage (organisation du travail, vide sanitaire). ABSTRACT : Alternative reproduction method for rabbit female : a model for a systemic approach of the functioning of rabbit breeding. At present, the replacement rate reproductive rabbit does is very high in rabbit breeding. Besides, health troubles in the growing rabbits herd lead to important economic losses. Frequently, these two points are separately considered in research studies, while they are not independents. A systemic approach including these two problems permit us to formalize a strategy to solve our issue. Rabbit breeding system was represented by a decisional component (the breeder) and biotechnical one including two workshops (does and growing rabbits herds). This work aimed to evaluate the influence of an extensification of reproductive rhythm (56d vs 42 d) and reduction of lactation length (23d vs 35d) on performances of rabbit does herd. Consequently, we determined the impact of age at weaning (23d vs 35d) and post weaning feed (dietary fibre and protein levels) on performances of growing rabbits herd. Some state variables (reproductive performance, body condition, lifespan of rabbit does, growth and health young rabbits) were studied to evaluate the action of these pilote levers. An extensification of reproductive rhythm associated with a reduction of lactation length improves body condition of rabbit does during the reproductive cycles and their lifespan, but does not affect prolificity of rabbit does and increases fertility only primiparous ones. In spite of a better regularity of reproductive performance, it does not permit to compensate annual production loss related to extensification. However, it reduces the involuntary replacement of does and optimizes some variables whose reading is involved in the decision to replace rabbit does (fertility, body condition). Therefore, it is likely reduce the replacement rate of rabbit does. This management of rabbit does has negative repercussions on growing rabbits. Indeed, early weaning (at 23d) strongly increases the susceptibility of young rabbits to digestive disorders after weaning and the feeding strategy we tested does not reduce this effect. The interest of systemic approach was to highlight the interaction between the twoworkshops of the biotechnic system (does and growing rabbits herds) and to integrate new constraints at the breeding system level (work organization, cleaning time between each batch)

Oxidation behaviour of unirradiated sintered UO2 pellets and powder at different oxygen partial pressures, above 350°C

International audienceThe oxidation of sintered UO2 pellets and powder into U3O8 has been studied by thermogravimetry at 370°C, under controlled oxygen partial pressures (PO2 ranging from 2-40 kPa). Sigmoidal curves of oxidation weight gain were measured for both pellet and powder test samples. The rate of oxidation increased as the oxygen partial pressure increased. It has been shown, by simultaneous TG-DSC, that the reaction proceeds in a pseudo steady state. An experimental methodology based on temperature or PO2 jumps has shown that the assumption of a rate-limiting step is validated, and a mean value of activation energy for the formation of U3O8 of 103 kJ.mol-1 was estimated

An artificial neural network‐based model to predict chronic kidney disease in aged cats

Background Chronic kidney disease (CKD) frequently causes death in older cats; its early detection is challenging. Objectives To build a sensitive and specific model for early prediction of CKD in cats using artificial neural network (ANN) techniques applied to routine health screening data. Animals Data from 218 healthy cats ≥7 years of age screened at the Royal Veterinary College (RVC) were used for model building. Performance was tested using data from 3546 cats in the Banfield Pet Hospital records and an additional 60 RCV cats—all initially without a CKD diagnosis. Methods Artificial neural network (ANN) modeling used a multilayer feed‐forward neural network incorporating a back‐propagation algorithm. Clinical variables from single cat visits were selected using factorial discriminant analysis. Independent submodels were built for different prediction time frames. Two decision threshold strategies were investigated. Results Input variables retained were plasma creatinine and blood urea concentrations, and urine specific gravity. For prediction of CKD within 12 months, the model had accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 88%, 87%, 70%, 53%, and 92%, respectively. An alternative decision threshold increased specificity and PPV to 98% and 87%, but decreased sensitivity and NPV to 42% and 79%, respectively. Conclusions and Clinical Importance A model was generated that identified cats in the general population ≥7 years of age that are at risk of developing CKD within 12 months. These individuals can be recommended for further investigation and monitoring more frequently than annually. Predictions were based on single visits using common clinical variables

Recent advances in the first-line treatment of follicular non-Hodgkin lymphoma [version 1; referees: 2 approved]

Follicular lymphoma (FL) is the most common type of indolent B-cell lymphoma. Twenty years ago, FL was considered an indolent lymphoma with a long survival time but without a high rate of complete remission with chemotherapies. The use of rituximab has improved the response and survival of patients with this lymphoma. More recently, development of biological knowledge and use of targeted drugs have offered new perspectives, including improvement of response rates and survival with chemo-free treatment strategies. In 2019, patients have a 10-year overall survival probability of over 70%. Histological transformation to more aggressive lymphoma and treatment relapses remain a medical challenge, especially for patients relapsing within two years. This article will review the recent advances in the treatment of FL. As the use of new drugs is directly related to the development of biological aspects, we will first summarize recent advances in biological aspects of FL

Success of a weight loss plan for overweight dogs: The results of an international weight loss study

Introduction Obesity is a global concern in dogs with an increasing prevalence, and effective weight loss solutions are required that work in different geographical regions. The main objective was to conduct an international, multi-centre, weight loss trial to determine the efficacy of a dietary weight loss intervention in obese pet dogs. Methods A 3-month prospective observational cohort study of weight loss in 926 overweight dogs was conducted at 340 veterinary practices in 27 countries. Commercially available dry or wet weight loss diets were used, with the initial energy allocation being 250–335 kJ/kg target body weight0.75/day (60–80 kcal/kg target body weight0.75/day) depending on sex and neuter status. The primary outcome measure was percentage weight loss; the main secondary outcomes were changes in activity, quality of life, and food-seeking behaviour, which were subjectively determined from owner descriptions. Results At baseline, median (range) age was 74 (12 to 193) months and median body condition score was 8 (range 7–9). 896 of the 926 dogs (97%) lost weight, with mean weight loss being 11.4 ±5.84%. Sexually intact dogs lost more weight than neutered dogs (P = 0.001), whilst female dogs lost more weight than male dogs (P = 0.007), with the difference being more pronounced in North and South American dogs (median [Q1, Q3]: female: 11.5% [8.5%, 14.5%]; male: 9.1% [6.3%, 12.1%], P = 0.053) compared with those from Europe (female: 12.3% [8.9%, 14.9%]; male: 10.9% [8.6%, 15.4%]). Finally, subjective scores for activity (P<0.001) and quality of life (P<0.001) increased sequentially, whilst scores for food-seeking behaviour decreased sequentially (P<0.001) during the study. Conclusion This is the largest international multi-centre weight loss study conducted to date in obese dogs. Most dogs lost a clinically significant amount of weight, although there were notable differences between dogs of different sex, neuter status and in different geographical locations

What is the secondary patency of thrombosed bypasses of the lower limbs cleared by fibrinolysis in situ?

OBJECTIVES: In case of acute thrombosis, lower limbs bypasses can, in certain cases, be cleared by local intra-arterial fibrinolysis (LIF). The aim of this study was to evaluate the secondary patency of thrombosed bypasses after fibrinolysis. METHODS: This retrospective study includes all patients hospitalized for thrombosed bypasses of the lower limbs that were treated with in situ fibrinolysis using urokinase, between 2004 and 2013, in two French university hospital centers. Fibrinolysis was indicated in case of recent thrombosis (&lt; 3 weeks) provoking acute limb ischemia without sensory-motor deficit and in the absence of general contraindications. The secondary patency of the grafts was defined as the time after fibrinolysis without a new thrombotic event. RESULTS: There were 207 patients, hospitalized for recent thrombosis of 244 bypasses. The LIF was efficient in 74% of the cases (n=180). Secondary patency of these bypasses, was 54.2% and 32.4% overall, 68.3% and 50.3% for the supra-inguinal bypasses and 48.3% and 21.5% for the infra-inguinal bypasses, at 1 year and 5 years respectively. There is a significant difference (p = 0.002) regarding the permeability of the supra-inguinal and infra-inguinal bypasses. The survival rate was 75% (± 6.4%) at 5 years and the limb salvage rate was 89% (± 3.3%), 78.2% (±5.1%) and 75% (±5.8%) at 1 year, 3 years et 5 years respectively. The only independent factor influencing the secondary patency of infra-inguinal bypasses that was significant in a multivariate analysis was the infragenicular localization of the distal anastomosis (p=0.023). CONCLUSIONS: LIF is an effective approach that often allows the identification of the underlying cause, permitting elective adjunctive treatment of the underlying cause. Although LIF is at least as effective as its therapeutic alternatives described in the literature, the secondary patency of the bypasses remains modest and encourages close monitoring, particularly in patients with an infragenicular bypass

New concepts and objectives for protein-amino acid nutrition in rabbits: a review

[EN] In the European context, the new legislation to avoid mineral contamination and the ban on antibiotics as growth promoters has led to the definition of new objectives in respect of nitrogen supply. The present study summarizes the state of nitrogen nutrition in rabbits and reviews the role of protein and amino acids in rabbit health and the new nitrogen value of protein sources based on true ileal digestibility (TID) for future recommendations. The main sources of nitrogen for microbial growth are ammonia, urea and protein (endogenous and dietary). The surplus of nitrogen flow to the caecum increases mortality rates during fattening by favouring the growth of potential pathogenic bacteria. Accordingly, feeding strategies to reduce ileal nitrogen flow have been reviewed. A large reduction of dietary protein level might have negative consequences on growth performances and mortality. In order to formulate balanced low protein diets, data on ileal and faecal amino acid digestibility of 14 raw materials is summarized. The use of this different unit for amino acid digestibility is also discussed.Financial support was provided by the Spanish Interministerial Science and Technology Commission (Projects AGL 2002-05, AGL 2005-03203 and PETRI 95-0689-OP), the Spanish Ministry of Industry (CDTI Project, 04-0136) and feed companies (NUTRECO, NANTA, COREN).Carabaño, R.; Villamide, M.; García, J.; Nicodemus, N.; Llorente, A.; Chamorro, S.; Menoyo, D.... (2009). New concepts and objectives for protein-amino acid nutrition in rabbits: a review. World Rabbit Science. 17(1):1-14. doi:10.4995/wrs.2009.66411417

Lessons Learned from the Amputation of a Bilateral Hand Grafted Patient due to Psychiatric Disorders

The importance of psychosocial aspects in upper extremity transplantation (UET) has been emphasized since the beginning of the vascularized composite allotransplantation era. Herein a long-term UET failure mainly due to psychiatric disorders is reported. A young woman amputated in 2004 (electrocution) underwent bilateral UET in 2007. At the time of transplantation the patient underwent a psychological evaluation, which did not completely consider some traits of her personality. Indeed, she had an anxious personality and a tendency to idealize. The trauma of amputation, the injuries associated with the accident, and the short delay between the accident and the transplantation elicited vindictiveness, entitlement, and impulsivity. Following transplantation, she had a high anxiety level, panic attacks, depression, and hypomanic episodes. She was poorly compliant to the rehabilitation program and the immunosuppressive treatment. She developed 13 acute rejection episodes (reversed by appropriate treatment) but neither clinical signs of chronic rejection nor donor specific antibiodies. She developed many severe complications due to the treatment and the psychiatric disorders. At her request, after many interviews, the allografts were removed in 2018. Pathological examination and an angiography performed post-amputation revealed signs of graft vasculopathy of varying severity, in the absence of clinically overt chronic rejection. This case highlights the need to detect during the initial patients’ assessment even mild traits of personality disorders, which could herald psychiatric complications after the transplantation, compromising UET outcomes. It further confirms that skin and vessels are the main targets of the alloimmune response in the UET setting

Using sniffing behavior to differentiate true negative from false negative responses in trained scent-detection dogs

False negatives are recorded in every chemical detection system, but when animals are used as a scent detector, some false negatives can arise as a result of a failure in the link between detection and the trained alert response, or a failure of the handler to identify the positive alert. A false negative response can be critical in certain scenarios, such as searching for a live person or detecting explosives. In this study, we investigated whether the nature of sniffing behavior in trained detection dogs during a controlled scent-detection task differs in response to true positives, true negatives, false positives, and false negatives. A total of 200 videos of 10 working detection dogs were pseudorandomly selected and analyzed frame by frame to quantify sniffing duration and the number of sniffing episodes recorded in a Go/No-Go single scent-detection task using an eight-choice test apparatus. We found that the sniffing duration of true negatives is significantly shorter than false negatives, true positives, and false positives. Furthermore, dogs only ever performed one sniffing episode towards true negatives, but two sniffing episodes commonly occurred in the other situations. These results demonstrate how the nature of sniffing can be used to more effectively assess odor detection by dogs used as biological detection devices