Getting insights on bovine mastitis treatment efficacy based on tissular indicators with an integrated udder health management file: Project LAECEA.

Mastitis is the most “antibiotic consuming” pathology in dairy medicine. Though antibiotics and antibiograms are known to vets since the early fifties, our practices did not evolved a lot from empiric antibiotic therapy. Indeed, the need for a treatment, the cost and the delay for an antibiogram are most of the time incoherent with a routine practice. Nevertheless, there is a surge for rational use of antibiotics. Our study was based on 1100 mastitis events from 30 Belgian farms collected between January 2011 and June 2012. We chose to compare tissular cure (TC) based on the threshold of 200.000 somatic cells/ml in milk at milk control at least 60 days after the clinical mastitis event. Regarding the mastitis event, severity (according 3 grades: alteration of milk as grade 1, alteration of quarter as grade 2 and alteration of general state as grade 3), quarter, treatments were recorded. We also assessed a chronicity status based on previous somatic cell count (SCC) of the cow. It was considered a new case a cow which at least 15 days before had an SCC <200.000 cells/ml, other were marked as chronic cases. In our distribution, we see a seasonal rise of incidence between January and May. This period would represent twice as many mastitis as the summer period. Overall TC reaches 46% of all mastitis events, which is quite poor. Rear quarters had significantly lower TC (p<0,05%). Grade 3 mastitis had lower TC, 42,6% (p<0.05%) versus 48,9 % for grade 2 and 44,2% for grade 1. Almost 49% of all mastitis was considered as chronic cases, which TC was 33% on average, whereas new cases reached 55,3% TC. Study of treatment was frustrating given the high number of different combinations of treatments. It was underlined that 4th generation cephalosporins (C4G) were the most used in our cohort, followed by aminopenicillin/methicillin association (PENA/PENM) and 1st generation cephalosporins/aminoglycosids (C1G/AG) association. Of these intramammary treatments, 20% of the cases were submitted to a second intramammary drug, mostly C1G or C1G/AG. One third of the cases were treated parenterally with antimicrobials, mostly macrolids, fluoroquinolones and penethacillin. Finally, 10% of mastitis was treated with anti-inflammatory drugs, mostly tolfenamic acid and flunixin-meglumin. Comparing mastitis without use of a secondary intramammary drug, only PENA and C1G/AG reached more than 60% TC. Considering new cases, then C1G/AG, PENA/PENM and Prednisolone containing specialties were above 60% TC. Use of a parenteral injections increased TC only on new cases (+12%), but not on chronic cases. Refining by severity, TC improved with a parenteral on new cases, mainly in grade 1 (+20%). Regarding associated factors, TC was negatively affected by chronicity, parity and lactation stage. Indeed, TC was lower on cases from more than 4 month in milk, third lactation (OR = 2.8 for no cure) compared with previous, and chronic cases (OR=2,6). Seemingly, chronicity was positively associated with parity and season. The 3rd parity cases had higher chances to be chronic ones (OR = 1,7), as well as cases from April to September (OR = 1,6). This evaluation of cure is rather simple and has a good variability which allows several questions about the real match between antimicrobial treatment for mastitis and the udder inflammation. Based on our epidemiological data, we can modify routine management of mastitis, as some cases might not worth the antimicrobial treatment.LAECE

Development and evaluation of a clinical model for lung cancer patients using stereotactic body radiotherapy (SBRT) within a knowledge-based algorithm for treatment planning

The purpose of this study was to describe the development of a clinical model for lung cancer patients treated with stereotactic body radiotherapy (SBRT) within a knowledge-based algorithm for treatment planning, and to evaluate the model performance and applicability to different planning techniques, tumor locations, and beam arrangements. 105 SBRT plans for lung cancer patients previously treated at our institution were included in the development of the knowledge-based model (KBM). The KBM was trained with a combination of IMRT, VMAT, and 3D CRT techniques. Model performance was validated with 25 cases, for both IMRT and VMAT. The full KBM encompassed lesions located centrally vs. peripherally (43:62), upper vs. lower (62:43), and anterior vs. posterior (60:45). Four separate sub-KBMs were created based on tumor location. Results were compared with the full KBM to evaluate its robustness. Beam templates were used in conjunction with the optimizer to evaluate the model\u27s ability to handle suboptimal beam placements. Dose differences to organs-at-risk (OAR) were evaluated between the plans gener-ated by each KBM. Knowledge-based plans (KBPs) were comparable to clinical plans with respect to target conformity and OAR doses. The KBPs resulted in a lower maximum spinal cord dose by 1.0 ± 1.6 Gy compared to clinical plans, p = 0.007. Sub-KBMs split according to tumor location did not produce significantly better DVH estimates compared to the full KBM. For central lesions, compared to the full KBM, the peripheral sub-KBM resulted in lower dose to 0.035 cc and 5 cc of the esophagus, both by 0.4Gy ± 0.8Gy, p = 0.025. For all lesions, compared to the full KBM, the posterior sub-KBM resulted in higher dose to 0.035 cc, 0.35 cc, and 1.2 cc of the spinal cord by 0.2 ± 0.4Gy, p = 0.01. Plans using template beam arrangements met target and OAR criteria, with an increase noted in maximum heart dose (1.2 ± 2.2Gy, p = 0.01) and GI (0.2 ± 0.4, p = 0.01) for the nine-field plans relative to KBPs planned with custom beam angles. A knowledge-based model for lung SBRT consisting of multiple treatment modalities and lesion loca-tions produced comparable plan quality to clinical plans. With proper training and validation, a robust KBM can be created that encompasses both IMRT and VMAT techniques, as well as different lesion locations

Analyse de l'efficience des traitements de mammites de 60 fermes de Wallonie dans la base LAECEA

Le traitement de la mammite bovine est un acte à part dans la routine d’une exploitation bovine. En effet, si les cas les plus graves sont vus presque systématiquement pas le vétérinaire traitant en France ou en Belgique, la plupart des cas peu sévères font l’objet d’une tacite délégation de diagnostic et de traitement, sur base d’une formation préalable et d’une prescription enregistrée. Aujourd’hui, cette pathologie représente le plus important poste de consommation d’antibiotiques en exploitation laitière. Concernant cette problématique, la profession vétérinaire doit disposer de nouveaux outils de diagnostic, de traitement, et surtout d’évaluation de la qualité du traitement. Or, depuis la fin des années 1940, la pratique de l’antibiothérapie est restée, comme en médecine humaine, basée essentiellement sur l’antibiothérapie empirique, plus ou moins régulée par des cultures bactériologiques et des antibiogrammes (Durel et al., 2012). La profession s’est dotée d’outils d’analyse épidémiologique et clinique au cours des décennies, mais les résultats sont mitigés : une diminution globale de la consommation d’antibiotiques, mais le recours accru à des classes de dernières générations. Aujourd’hui le grand enjeu de l’antibiothérapie se corse, avec l’identification de mécanisme de résistance suspects d’être communs avec la médecine humaine(Jaglic et al., 2010). Plusieurs classes de molécules communes avec la médecine humaine sont identifiées, et leur utilisation menace d’être régulée (Bagcigil et al., 2007). Face à ce constat, l’utilisation des antibiotiques destinés au traitement de la mamelle a été étudiée en Belgique, dans soixante fermes laitières wallonnes (Théron et al., 2011).Peer reviewe

Effect of HLA DR epitope de-immunization of Factor VIII \u3ci\u3ein vitro\u3c/i\u3e and \u3ci\u3ein vivo\u3c/i\u3e

T cell-dependent development of anti-Factor VIII (FVIII) antibodies that neutralize FVIII activity is a major obstacle to replacement therapy in hemophilia A. To create a less immunogenic therapeutic protein, recombinant FVIII can be modified to reduce HLA binding of epitopes based on predicted anchoring residues. Here, we used immunoinformatic tools to identify C2 domain HLA DR epitopes and predict site-specific mutations that reduce immunogenicity. Epitope peptides corresponding to original and modified sequences were validated in HLA binding assays and in immunizations of hemophilic E16 mice, DR3 and DR4 mice and DR3 × E16 mice. Consistent with immunoinformatic predictions, original epitopes are immunogenic. Immunization with selected modified sequences lowered immunogenicity for particular peptides and revealed residual immunogenicity of incompletely de-immunized modified peptides. The stepwise approach to reduce protein immunogenicity by epitope modification illustrated here is being used to design and produce a functional full-length modified FVIII for clinical use

2018 Scholars at Work Conference Program

Program for the 2018 Scholars at Work Conference at Minnesota State University, Mankato on March 30, 2018

Designing a wearable sensor system to monitor the internal mechanism of a stance phase control passive prosthetic knee

Prosthetic knees aim to improve mobility for above-knee amputees, but studies that quantify the performance of prosthetic knee controllers are limited. Further, most studies about the performance of prosthetic knees are often limited to a controlled environment, so information from gait studies that inform design decisions may be misleading. Therefore, the objective of this project was to further develop a wearable gait analysis tool that quantitatively measures performance of a prosthetic knee. The idea of collecting empirical data and inputting it into a computational model for design improvements was motivated through a literature review. Moreover, a fully wearable gait analysis tool and 4 finite output states were developed. Both were validated through collection of data from walking trials with able-bodied participants. The further development of this tool has shown the potential for a wearable gait analysis tool that can be used in a variety of environmental conditions, to inform design decisions.M.H.Sc

Immunosenescence and its influence on reproduction in a long-lived vertebrate

Immunosenescence is a well-known phenomenon in mammal systems, but its relevance in other long-lived vertebrates is less understood. Further, the influence of age and reproductive effort on immune function in long-lived species can be challenging to assess, as long-term data are scarce and it is often difficult to sample the oldest age classes. We used the painted turtle (Chrysemys picta) to test hypotheses of immunosenescence and a trade-off between reproductive output and immune function in a population of a long-lived vertebrate that has been monitored for over 30 years. These long-term data are utilized to employ a unique approach of aging turtles with mark-recapture data and population-specific growth modeling to obtain more accurate estimates of age. We analyzed natural antibodies, lysis ability, and bactericidal competence in 126 individuals from 1 to 33 years of age captured during May and June in 2011. Older turtles exhibited greater natural antibody levels than young individuals across sexes. Young females with large clutches exhibited greater lysis ability, while older females with large clutches had decreased lysis ability, suggesting a trade-off between reproductive output and immune function conditional upon age. However, bactericidal competence increased later in the nesting season for older females. Our study rejects the hypothesis of immunosenescence in a long-lived turtle, despite evidence of actuarial and reproductive senescence in this population. Additionally, we detected mixed evidence for a trade-off between reproduction and immune health.This is a manuscript of an article published as Judson, Jessica M., Dawn M. Reding, and Anne M. Bronikowski. "Immunosenescence and its influence on reproduction in a long-lived vertebrate." Journal of Experimental Biology (2020). doi: 10.1242/jeb.223057. Posted with permission.</p