Influence of tension-band plates on the mechanical loading of the femoral growth plate during guided growth due to coronal plane deformities

Introduction: Correction of knee malalignment by guided growth using a tension-band plate is a common therapy to prevent knee osteoarthritis among other things. This approach is based on the Hueter-Volkmann law stating that the length growth of bones is inhibited by compression and stimulated by tension. How the locally varying mechanical loading of the growth plate is influenced by the implant has not yet been investigated. This study combines load cases from the gait cycle with personalized geometry in order to investigate the mechanical influence of the tension-band plates. Methods: Personalized finite element models of four distal femoral epiphyses of three individuals, that had undergone guided growth, were generated. Load cases from the gait cycles and musculoskeletal modelling were simulated with and without implant. Morphological features of the growth plates were obtained from radiographs. 3D geometries were completed using non-individual Magnetic Resonance Images of age-matched individuals. Boundary conditions for the models were obtained from instrumented gait analyses. Results: The stress distribution in the growth plate was heterogenous and depended on the geometry. In the insertion region, the implants locally induced static stress and reduced the cyclic loading and unloading. Both factors that reduce the growth rate. On the contralateral side of the growth plate, increased tension stress was observed, which stimulates growth. Discussion: Personalized finite element models are able to estimate the changes of local static and cyclic loading of the growth plate induced by the implant. In future, this knowledge can help to better control growth modulation and avoid the return of the malalignment after the treatment. However, this requires models that are completely participant-specific in terms of load cases and 3D geometry

Computer calculations of heterogeneous equilibria in the system C-O-H-N-Si-Ar

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44678/1/10853_2004_Article_BF00549333.pd

Visual and passive acoustic observations of blue whale trios from two distinct populations

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Schall, E., Di Iorio, L., Berchok, C., Filun, D., Bedrinana-Romano, L., Buchan, S. J., Van Opzeeland, I., Sears, R., & Hucke-Gaete, R. Visual and passive acoustic observations of blue whale trios from two distinct populations. Marine Mammal Science, (2019): 1-10, doi:10.1111/mms.12643.Blue whale populations from both hemispheres are thought to undertake annual migrations between high latitude feeding grounds and low latitude breeding grounds (Mackintosh, 1966). For individuals of some populations these predetermined movements to and from wintering areas where calving occurs have been confirmed through photo‐identification, satellite‐tracking, and passive acoustic monitoring (Burtenshaw et al., 2004; Mate, Lagerquist, & Calambokidis, 1999; Sears & Perrin, 2002; Stafford, Nieukirk, & Fox, 1999a). However, for many blue whale populations no clear migratory behavior has been reported and locations of respective breeding grounds remain unclear (e.g., Hucke‐Gaete, Osman, Moreno, Findlay, & Ljungblad, 2004; Samaran et al., 2013; Stafford, Chapp, Bohnenstiel, & Tolstoy, 2011; Thomisch et al., 2016). On feeding grounds in the Gulf of St. Lawrence and along the coast of California, blue whales have been observed to form female–male pairs during summer, which can remain stable up to over several weeks, with the number of pairs increasing towards the end of summer (Sears & Perrin, 2002; Calambokidis, unpublished data;1 RS, unpublished data). These pairs are sometimes joined by a second male, forming a blue whale trio, which often is observed to engage in surface active behaviors lasting several minutes (Sears & Perrin, 2002; RS, unpublished data). The formation of blue whale trios is probably related to reproductive competition between male escorts and female choice (RS, unpublished data). Blue whale males produce population‐specific songs likely functioning as reproductive advertisement (Edds‐Walton, 1997; Oleson et al. 2007a; Stafford, Fox, & Clark, 1998). Several studies have reported song year‐round in low‐, mid‐, and high‐latitude waters, frequently with high song production rates during summer on the feeding grounds (e.g., Barlow et al., 2018; Buchan, Stafford, & Hucke‐Gaete, 2015; Samaran, Adam, & Guinett, 2010; Širović et al., 2004; Stafford, Nieukirk, & Fox, 1999b; Thomisch et al., 2016). Therefore, breeding activities in blue whales may be more opportunistic, i.e., not restricted to the breeding season or to a specific habitat.ES thanks Prof. Dr. Per J. Palsbøll for the supervision of the initial Master research project, the Marco Polo fund, and the University Groningen for covering travel expenses. We thank the Melimoyu Ecosystem Research Institute, SNP Patagonia Sur, and the company Teledyne Reson for partially funding the acoustic data collection in southern Chile. RHG is thankful to WWF‐Germany/Chile for partially funding fieldwork through grants to Centro Ballena Azul. CLB thanks the team of the Mingan Island Cetacean Study for their logistical support of boats and lodging, access to the North Atlantic blue whale database, and field assistance; Yvon Bélanger for opening his home to her and RS's field crews; for financial support from the National Science Foundation (Graduate Fellowship), National Defense Industrial Association, American Museum of Natural History (Lerner Gray Fund for Marine Research Grant), Penn State Applied Research Laboratory, and private donors Jeff and Lynn Kraus; and graduate advisors at Penn State University David L. Bradley, Thomas B. Gabrielson, and Diana McCammon. LDI thanks the Croisières du Grand Héron and Center Mériscope for allowing and supporting fieldwork, the Animal Behavior Department of the University of Zurich (Switzerland), the Bioacoustics Research Program at Cornell University (USA) and Prof. M. Manser and C. W. Clark for supervising LDI's Ph.D. The work was supported by grants to LDI for her PhD from the Forschungskommission der Universität Zürich, Züricher Tierschutz, Basler Stiftung für Biologische Forschung, SCNAT, Zangger‐Weber‐Stiftung, SSVA. SJB thanks the Center for Oceanographic Research COPAS Sur‐Austral, CONICYT PIA PFB31, the Office of Naval Research Global (awards N62909‐16‐2214 and N00014‐17‐2606), and a grant to the Centro de Estudios Avanzados en Zonas Áridas from Programa Regional CONICYT R16A10003 for support during manuscript writing. We would like to thank the field crews (F. Viddi, J. Ruiz, A. Carpentier, M. Lessard, A. Liebschner, C. Ramp, S. Angel, K. Aucrenaz, T. Doniol‐Valcroze, J. LeBreus, B. Kot, and J. Puschock) for their immense commitment to blue whale research

Vision, mission, and values: From concept to execution at Mayo Clinic

Mayo Clinic displays steadfast commitment to patient care, referral relations, and health care quality through institutional examples of unique, value-add endeavors that are under way with the Mayo Clinic Patient Experience Subcommittee and the Referring Physician Office. In this article, we share the Mayo Model of Care and patient stories that embody the 8 Mayo Clinic values of respect, compassion, integrity, healing, teamwork, excellence, innovation, and stewardship. The Mayo founders imparted to their staff the passion for patient care by encouraging a fair and just culture for its employees. This culture allows the creation, maintenance, and improvement of clinical care, research studies, and educational curricula, which in turn propagate the mission–“To inspire hope and contribute to health and well-being by providing the best care to every patient through integrated clinical practice, education, and research.

Resistance to a protein farnesyltransferase inhibitor in Plasmodium falciparum

The post-translational farnesylation of proteins serves to anchor a subset of intracellular proteins to membranes in eukaryotic organisms and also promotes protein-protein interactions. Inhibition of protein farnesyltransferase (PFT) is lethal to the pathogenic protozoa Plasmodium falciparum. Parasites were isolated that were resistant to BMS-388891, a tetrahydroquinoline (THQ) PFT inhibitor. Resistance was associated with a 12-fold decrease in drug susceptibility. Genotypic analysis revealed a single point mutation in the beta subunit in resistant parasites. The resultant tyrosine 837 to cysteine alteration in the beta subunit corresponded to the binding site for the THQ and peptide substrate. Biochemical analysis of Y837C-PFT demonstrated a 13-fold increase in BMS-388891 concentration necessary for inhibiting 50% of the enzyme activity. These data are consistent with PFT as the target of BMS-388891 in P. falciparum and suggest that PFT inhibitors should be combined with other antimalarial agents for effective therapy

Prediction of survival among patients receiving transarterial chemoembolization for hepatocellular carcinoma: A response-based approach

Background and aims: The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. Approach and results: Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. Conclusions: A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognosticatio

Радиографический метод контроля сварных швов трубопроводов

Обнаружение дефектов сварных соединений является одной из основных задач неразрушающего контроля, применяемого для диагностики технического состояния трубопроводов различного назначения. Среди методов неразрушающего контроля широкое распространение получил радиографический метод. Для обработки изображений, полученных радиографическим методом, и обнаружения дефектов сварки, используются различные алгоритмы. Одним из перспективных алгоритмов обработки изображений является алгоритм, основанный на методе нейронной сети.Detection of defects in welded joints is one of the main tasks of non-destructive testing used for diagnostics of the technical condition of pipelines for various purposes. Among the methods of nondestructive testing, the radiographic method is widely used. For processing images obtained by radiographic method, and the detection of welding defects, various algorithms are used. One of the promising algorithms for image processing is an algorithm based on the neural network method

Structural Characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei Bound to the Antifungal Drugs Posaconazole and Fluconazole

Chagas Disease is caused by kinetoplastid protozoa Trypanosoma cruzi, whose sterols resemble those of fungi, in both composition and biosynthetic pathway. Azole inhibitors of sterol 14α-demethylase (CYP51), such as fluconazole, itraconazole, voriconazole, and posaconazole, successfully treat fungal infections in humans. Efforts have been made to translate anti-fungal azoles into a second-use application for Chagas Disease. Ravuconazole and posaconazole have been recently proposed as candidates for clinical trials with Chagas Disease patients. However, the widespread use of posaconazole for long-term treatment of chronic infections may be limited by hepatic and renal toxicity, a requirement for simultaneous intake of a fatty meal or nutritional supplement to enhance absorption, and cost. To aid our search for structurally and synthetically simple CYP51 inhibitors, we have determined the crystal structures of the CYP51 targets in T. cruzi and T. brucei, both bound to the anti-fungal drugs fluconazole or posaconazole. The structures provide a basis for a design of new drugs targeting Chagas Disease, and also make it possible to model the active site characteristics of the highly homologous Leishmania CYP51. This work provides a foundation for rational synthesis of new therapeutic agents targeting the three kinetoplastid parasites

NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Hepatocellular carcinoma (HCC) can have viral or non-viral causes(1-5). Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need(6,7). Here we report the progressive accumulation of exhausted, unconventionally activated CD8(+)PD1(+) T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8(+)PD1(+) T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8(+)PD1(+)CXCR6(+), TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8(+) T cells or TNF neutralization, suggesting that CD8(+) T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8(+)PD1(+) T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment