Effects of Early Functional Loading on Maintenance of Free Autogenous Bone Graft and Implant Osseointegration: An Experimental Study in Dogs

Purpose: The aim of the present study was to investigate the healing, integration, and maintenance of autogenous onlay bone grafts and implant osseointegration either loaded in the early or the delayed stages. Materials and Methods: A total of 5 male clogs received bilateral blocks of onlay bone grafts harvested from the contralateral alveolar ridge of the mandible. On one side, the bone block was secured by 3 dental implants (3.5 mm x 13.0 mm, Osseospeed; Astra Tech AB, Molndal, Sweden). Two implants at the extremities of the graft were loaded 2 clays after installation by abutment connection and prosthesis (simultaneous implant placement group); the implant in the middle remained unloaded and served as the control. On the other side, the block was fixed with 2 fixation screws inserted in the extremities of the graft. Four weeks later, the fixation screws were replaced with 3 dental implants. The loading procedure (delayed implant placement group) was performed 2 clays later, as described for the simultaneous implant placement sites. The animals were sacrificed 12 weeks after the grafting procedure. Implant stability was measured through resonance frequency analysis. The bone volume and density were assessed on computed tomography. The bone to implant contact and bone area in a region of interest were evaluated on histologic slides. Results: The implant stability quotient showed statistical significance in favor of the delayed loaded grafts (P=.001). The bone-to-implant contact (P=.008) and bone area in a region of interest (P=0.005) were significantly greater in the delayed group. Nevertheless, no difference was found in terms of graft volume and density between the early loaded and delayed-loaded approaches. Conclusions: The protocol in which the implant and bone graft were given delayed loading allows for effective quality of implant osseointegration and stabilization, with healing and remodeling occurring in areas near the implant resulting in denser bone architecture. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Sing 68:825-832, 2010

Menopausal status: A possible predictive factor for recurrence in women with cancer of the uterine cervix without pelvic lymph node metastasis

Objectives: To evaluate risk factors for recurrence of carcinoma of the uterine cervix among women who had undergone radical hysterectomy without pelvic lymph node metastasis, while taking into consideration not only the classical histopathological factors but also sociodemographic, clinical and treatment-related factors. Study design: This was an exploratory analysis on 233 women with carcinoma of the uterine cervix (stages IB and IIA) who were treated by means of radical hysterectomy and pelvic lymphadenectomy, with free surgical margins and without lymph node metastases on conventional histopathological examination. Women with histologically normal lymph nodes but with micrometastases in the immunohistochemical analysis (AE1/AE3) were excluded. Disease-free survival for sociodemographic, clinical and histopathological variables was calculated using the Kaplan-Meier method. The Cox proportional hazards model was used to identify the independent risk factors for recurrence. Results: Twenty-seven recurrences were recorded (11.6%), of which 18 were pelvic, four were distant, four were pelvic + distant and one was of unknown location. The five-year disease-free survival rate among the study population was 88.4%. The independent risk factors for recurrence in the multivariate analysis were: postmenopausal status (HR 14.1; 95% CI: 3.7-53.6; P < 0.001), absence of or slight inflammatory reaction (HR 7.9; 95% CI: 1.7-36.5; P = 0.008) and invasion of the deepest third of the cervix (FIR 6.1; 95% CI: 1.3-29.1; P = 0.021). Postoperative radiotherapy was identified as a protective factor against recurrence (HR 0.02; 95% CI: 0.001-0.25; P = 0.003). Conclusion: Postmenopausal status is a possible independent risk factor for recurrence even when adjusted for classical prognostic factors (such as tumour size, depth of turnout invasion, capillary embolisation) and treatment-related factors (period of treatment and postoperative radiotherapy status). (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Use of a predictive model for food insecurity estimates in Brazil

In 2004 the National Household Survey (Pesquisa Nacional par Amostras de Domicilios - PNAD) estimated the prevalence of food and nutrition insecurity in Brazil. However, PNAD data cannot be disaggregated at the municipal level. The objective of this study was to build a statistical model to predict severe food insecurity for Brazilian municipalities based on the PNAD dataset. Exclusion criteria were: incomplete food security data (19.30%); informants younger than 18 years old (0.07%); collective households (0.05%); households headed by indigenous persons (0.19%). The modeling was carried out in three stages, beginning with the selection of variables related to food insecurity using univariate logistic regression. The variables chosen to construct the municipal estimates were selected from those included in PNAD as well as the 2000 Census. Multivariate logistic regression was then initiated, removing the non-significant variables with odds ratios adjusted by multiple logistic regression. The Wald Test was applied to check the significance of the coefficients in the logistic equation. The final model included the variables: per capita income; years of schooling; race and gender of the household head; urban or rural residence; access to public water supply; presence of children; total number of household inhabitants and state of residence. The adequacy of the model was tested using the Hosmer-Lemeshow test (p=0.561) and ROC curve (area=0.823). Tests indicated that the model has strong predictive power and can be used to determine household food insecurity in Brazilian municipalities, suggesting that similar predictive models may be useful tools in other Latin American countries.

Maintenance and differentiation of neural stem cells

The adult mammalian brain contains self-renewable, multipotent neural stem cells (NSCs) that are responsible for neurogenesis and plasticity in specific regions of the adult brain. Extracellular matrix, vasculature, glial cells, and other neurons are components of the niche where NSCs are located. This surrounding environment is the source of extrinsic signals that instruct NSCs to either self-renew or differentiate. Additionally, factors such as the intracellular epigenetics state and retrotransposition events can influence the decision of NSC`s fate into neurons or glia. Extrinsic and intrinsic factors form an intricate signaling network, which is not completely understood. These factors altogether reflect a few of the key players characterized so far in the new field of NSC research and are covered in this review. (C) 2010 John Wiley & Sons, Inc. WIREs Syst Biol Med 2011 3 107-114 DOI:10.1002/wsbm:100

MuRF1 is a muscle fiber-type II associated factor and together with MuRF2 regulates type-II fiber trophicity and maintenance

MuRF1 is a member of the RBCC (RING, B-box, coiled-coil) superfamily that has been proposed to act as an atrogin during muscle wasting. Here, we show that MuRF1 is preferentially induced in type-II muscle fibers after denervation. Fourteen days after denervation, MuRF1 protein was further elevated but remained preferentially expressed in type-II muscle fibers. Consistent with a fiber-type dependent function of MuRF1, the tibialis anterior muscle (rich in type-II muscle fibers) was considerably more protected in MuRF1-KO mice from muscle wasting when compared to soleus muscle with mixed fiber-types. We also determined fiber-type distributions in MuRF1/MuRF2 double-deficient KO (dKO) mice, because MuRF2 is a close homolog of MuRF1. MuRF1/MuRF2 dKO mice showed a profound loss of type-II fibers in soleus muscle. As a potential mechanism we identified the interaction of MuRF1/MuRF2 with myozenin-1, a calcineurin/NFAT regulator and a factor required for maintenance of type-II muscle fibers. MuRF1/MuRF2 dKO mice had lost myozenin-1 expression in tibialis anterior muscle, implicating MuRF1/MuRF2 as regulators of the calcineurin/NFAT pathway. In summary, our data suggest that expression of MuRF1 is required for remodeling of type-II fibers under pathophysiological stress states, whereas MuRF1 and MuRF2 together are required for maintenance of type-II fibers, possibly via the regulation of myozenin-1. (C) 2010 Elsevier Inc. All rights reserved.

A Survey on Graphical Methods for Classification Predictive Performance Evaluation

Predictive performance evaluation is a fundamental issue in design, development, and deployment of classification systems. As predictive performance evaluation is a multidimensional problem, single scalar summaries such as error rate, although quite convenient due to its simplicity, can seldom evaluate all the aspects that a complete and reliable evaluation must consider. Due to this, various graphical performance evaluation methods are increasingly drawing the attention of machine learning, data mining, and pattern recognition communities. The main advantage of these types of methods resides in their ability to depict the trade-offs between evaluation aspects in a multidimensional space rather than reducing these aspects to an arbitrarily chosen (and often biased) single scalar measure. Furthermore, to appropriately select a suitable graphical method for a given task, it is crucial to identify its strengths and weaknesses. This paper surveys various graphical methods often used for predictive performance evaluation. By presenting these methods in the same framework, we hope this paper may shed some light on deciding which methods are more suitable to use in different situations.

PK/DB: database for pharmacokinetic properties and predictive in silico ADME models

The study of pharmacokinetic properties (PK) is of great importance in drug discovery and development. In the present work, PK/DB (a new freely available database for PK) was designed with the aim of creating robust databases for pharmacokinetic studies and in silico absorption, distribution, metabolism and excretion (ADME) prediction. Comprehensive, web-based and easy to access, PK/DB manages 1203 compounds which represent 2973 pharmacokinetic measurements, including five models for in silico ADME prediction (human intestinal absorption, human oral bioavailability, plasma protein binding, bloodbrain barrier and water solubility).

Thermochronology of central Ribeira Fold Belt, SE Brazil: Petrological and geochronological evidence for long-term high temperature maintenance during Western Gondwana amalgamation

The studied sector of the central Ribeira Fold Belt (SE Brazil) comprises metatexites, diatexites, charnockites and blastomylonites. This study integrates petrological and thermochronological data in order to constrain the thermotectonic and geodynamic evolution of this Neoproterozoic-Ordovician mobile belt during Western Gondwana amalgamation. New data indicate that after an earlier collision stage at similar to 610 Ma (zircon, U-Pb age), peak metamorphism and lower crust partial melting, coeval with the main regional high grade D(1) thrust deformation, occurred at 572-562 Ma (zircon, U-Pb ages). The overall average cooling rate was low (<5 degrees C/Ma) from 750 to 250 degrees C (at similar to 455 Ma; biotite-WR Rb-Sr age), but disparate cooling paths indicate differential uplift between distinct lithotypes: (a) metatexites and blastomylonites show a overall stable 3-5 degrees C/Ma cooling rate; (b) charnockites and associated rocks remained at T>650 degrees C during sub-horizontal D(2) shearing until similar to 510-470 Ma (garnet-WR Sm-Nd ages) (1-2 degrees C/Ma), being then rapidly exhumed/cooled (8-30 degrees C/Ma) during post-orogenic D(3) deformation with late granite emplacement at similar to 490 Ma (zircon, U-Pb age). Cooling rates based on garnet-biotite Fe-Mg diffusion are broadly consistent with the geochronological cooling rates: (a) metatexites were cooled faster at high temperatures (6 degrees C/Ma) and slowly at low temperatures (0.1 degrees C/Ma), decreasing cooling rates with time; (b) charnockites show low cooling rates (2 degrees C/Ma) near metamorphic peak conditions and high cooling rates (120 degrees C/Ma) at lower temperatures, increasing cooling rates during retrogression. The charnockite thermal evolution and the extensive production of granitoid melts in the area imply that high geothermal gradients were sustained fora long period of time (50-90 Ma). This thermal anomaly most likely reflects upwelling of asthenospheric mantle and magma underplating coupled with long-term generation of high HPE (heat producing elements) granitoids. These factors must have sustained elevated crustal geotherms for similar to 100 Ma, promoting widespread charnockite generation at middle to lower crustal levels. (C) 2010 Elsevier B.V. All rights reserved.

Intrinsically Multivariate Predictive Genes

Canalizing genes possess such broad regulatory power, and their action sweeps across a such a wide swath of processes that the full set of affected genes are not highly correlated under normal conditions. When not active, the controlling gene will not be predictable to any significant degree by its subject genes, either alone or in groups, since their behavior will be highly varied relative to the inactive controlling gene. When the controlling gene is active, its behavior is not well predicted by any one of its targets, but can be very well predicted by groups of genes under its control. To investigate this question, we introduce in this paper the concept of intrinsically multivariate predictive (IMP) genes, and present a mathematical study of IMP in the context of binary genes with respect to the coefficient of determination (CoD), which measures the predictive power of a set of genes with respect to a target gene. A set of predictor genes is said to be IMP for a target gene if all properly contained subsets of the predictor set are bad predictors of the target but the full predictor set predicts the target with great accuracy. We show that logic of prediction, predictive power, covariance between predictors, and the entropy of the joint probability distribution of the predictors jointly affect the appearance of IMP genes. In particular, we show that high-predictive power, small covariance among predictors, a large entropy of the joint probability distribution of predictors, and certain logics, such as XOR in the 2-predictor case, are factors that favor the appearance of IMP. The IMP concept is applied to characterize the behavior of the gene DUSP1, which exhibits control over a central, process-integrating signaling pathway, thereby providing preliminary evidence that IMP can be used as a criterion for discovery of canalizing genes.

Software maintenance project delays prediction using Bayesian Networks

Managing software maintenance is rarely a precise task due to uncertainties concerned with resources and services descriptions. Even when a well-established maintenance process is followed, the risk of delaying tasks remains if the new services are not precisely described or when resources change during process execution. Also, the delay of a task at an early process stage may represent a different delay at the end of the process, depending on complexity or services reliability requirements. This paper presents a knowledge-based representation (Bayesian Networks) for maintenance project delays based on specialists experience and a corresponding tool to help in managing software maintenance projects. (c) 2006 Elsevier Ltd. All rights reserved.