Fixed-Width Output Analysis for Markov Chain Monte Carlo

Markov chain Monte Carlo is a method of producing a correlated sample in order to estimate features of a complicated target distribution via simple ergodic averages. A fundamental question in MCMC applications is when should the sampling stop? That is, when are the ergodic averages good estimates of the desired quantities? We consider a method that stops the MCMC sampling the first time the width of a confidence interval based on the ergodic averages is less than a user-specified value. Hence calculating Monte Carlo standard errors is a critical step in assessing the output of the simulation. In particular, we consider the regenerative simulation and batch means methods of estimating the variance of the asymptotic normal distribution. We describe sufficient conditions for the strong consistency and asymptotic normality of both methods and investigate their finite sample properties in a variety of examples.

Epidermal growth factor receptor inhibitors plus chemotherapy in non-small-cell lung cancer: biologic rationale for combination strategies

Chemotherapy continues to play an essential role in the treatment of most stages of non-small-cell lung cancer (NSCLC). In fact, within the past 5 years, this role has greatly expanded into adjuvant therapy for early-stage resected disease. Likewise, agents targeting the epidermal growth factor receptor (EGFR), particularly the tyrosine kinase inhibitors gefitinib and erlotinib, have proven to be clinically active in patients with advanced-stage NSCLC. Because of these findings, it is logical to expect that combinations of these 2 classes of antineoplastic agents would prove more efficacious than either one alone. Yet 4 large randomized phase III trials of chemotherapy with or without an EGFR tyrosine kinase inhibitor in unselected patients with advanced-stage NSCLC, altogether totaling > 4000 patients, did not demonstrate improvement in clinical outcomes with the combination. Whether these negative results will be reproduced in ongoing combination studies of chemotherapy plus monoclonal antibodies directed against EGFR remain to be determined. Herein, we review recent preclinical and clinical data addressing this topic and explore the biologic rationale for developing new combination strategies based on patient selection by molecular and clinical factors, or by pharmacodynamic parameters.

Early implant placement following single-tooth extraction in the esthetic zone: biologic rationale and surgical procedures

Early implant placement is one treatment option for implant therapy following single-tooth extraction in the anterior maxilla. The surgical technique presented here is characterized by tooth extraction without flap elevation, a 4- to 8-week soft tissue healing period, implant placement in a correct three-dimensional position, simultaneous contour augmentation on the facial aspect with guided bone regeneration using a bioabsorbable collagen membrane combined with autogenous bone chips and a low-substitution bone filler, and tension-free primary wound closure. The surgical step-by-step procedure is presented with a case report. In addition, the biologic rationale is discussed.

Correlates of periodontal decline and biologic markers in older adults

BACKGROUND: There is limited information on infectious and host responses distinguishing older people with or without active periodontitis. This study measured bacterial and serum cytokine and high-sensitivity C-reactive protein (hsCRP) levels in older persons. METHODS: Elders (mean age: 67 years), whose periodontal status had declined most or least (20% worst or 20% best) over 5 years, were enrolled. Two years later, they were classified as periodontally declining (active periodontitis [AP]), if they had at least five teeth with probing depth (PD) > or =5 mm, or stable (stable periodontally [SP]), if they did not. Groups were compared with respect to demographics, PD, clinical loss of attachment, subgingival bacteria, serum hsCRP, interleukin (IL)-1beta and -6, and chronic diseases. RESULTS: Ten AP and 24 SP subjects were identified; 13% of women and 44% of men from the original sample were in the AP group (P <0.05). Most Asians were SP; most whites and all African Americans were classified as having AP (P <0.01). More AP elders had osteoporosis (P <0.01), but the AP and SP groups did not differ with respect to IL-1beta and -6 or hsCRP. Bacterial counts were higher in the AP group for Parvimonas micra (previously Peptostreptococcus micros or Micromonas micros) (7.7 x 10(5) cells versus 3.8 x 10(5) cells; P <0.05), Prevotella intermedia (25.7 x 10(5) cells versus 9.8 x 10(5) cells; P <0.01), Tannerella forsythia (previously T. forsythensis) (16.2 x 10(5) cells versus 8.0 x 10(5) cells; P <0.05), and Streptococcus mutans (6.2 x 10(5) cells versus 2.0 x 10(5) cells; P <0.01). Three risk factors were most predictive of periodontal decline: PD, osteoporosis, and being white or African American. CONCLUSION: Periodontal decline was associated with osteoporosis, ethnicity, PD, gender, serum hsCRP, and levels of four bacterial species.

Modeling and classifying variable width riparian zones utilizing digital elevation models, flood height data, digital soil data and national wetlands inventory : a new approach for riparian zone delineation

Riparian zones are dynamic, transitional ecosystems between aquatic and terrestrial ecosystems with well defined vegetation and soil characteristics. Development of an all-encompassing definition for riparian ecotones, because of their high variability, is challenging. However, there are two primary factors that all riparian ecotones are dependent on: the watercourse and its associated floodplain. Previous approaches to riparian boundary delineation have utilized fixed width buffers, but this methodology has proven to be inadequate as it only takes the watercourse into consideration and ignores critical geomorphology, associated vegetation and soil characteristics. Our approach offers advantages over other previously used methods by utilizing: the geospatial modeling capabilities of ArcMap GIS; a better sampling technique along the water course that can distinguish the 50-year flood plain, which is the optimal hydrologic descriptor of riparian ecotones; the Soil Survey Database (SSURGO) and National Wetland Inventory (NWI) databases to distinguish contiguous areas beyond the 50-year plain; and land use/cover characteristics associated with the delineated riparian zones. The model utilizes spatial data readily available from Federal and State agencies and geospatial clearinghouses. An accuracy assessment was performed to assess the impact of varying the 50-year flood height, changing the DEM spatial resolution (1, 3, 5 and 10m), and positional inaccuracies with the National Hydrography Dataset (NHD) streams layer on the boundary placement of the delineated variable width riparian ecotones area. The result of this study is a robust and automated GIS based model attached to ESRI ArcMap software to delineate and classify variable-width riparian ecotones.

Increased vascularization during early healing after biologic augmentation in repair of chronic rotator cuff tears using autologous leukocyte- and platelet-rich fibrin (L-PRF): a prospective randomized controlled pilot trial

HYPOTHESIS We hypothesized that arthroscopic rotator cuff repairs using leukocyte- and platelet-rich fibrin (L-PRF) in a standardized, modified protocol is technically feasible and results in a higher vascularization response and watertight healing rate during early healing. METHODS Twenty patients with chronic rotator cuff tears were randomly assigned to 2 treatment groups. In the test group (N = 10), L-PRF was added in between the tendon and the bone during arthroscopic rotator cuff repair. The second group served as control (N = 10). They received the same arthroscopic treatment without the use of L-PRF. We used a double-row tension band technique. Clinical examinations including subjective shoulder value, visual analog scale, Constant, and Simple Shoulder Test scores and measurement of the vascularization with power Doppler ultrasonography were made at 6 and 12 weeks. RESULTS There have been no postoperative complications. At 6 and 12 weeks, there was no significant difference in the clinical scores between the test and the control groups. The mean vascularization index of the surgical tendon-to-bone insertions was always significantly higher in the L-PRF group than in the contralateral healthy shoulders at 6 and 12 weeks (P = .0001). Whereas the L-PRF group showed a higher vascularization compared with the control group at 6 weeks (P = .001), there was no difference after 12 weeks of follow-up (P = .889). Watertight healing was obtained in 89% of the repaired cuffs. DISCUSSION/CONCLUSIONS Arthroscopic rotator cuff repair with the application of L-PRF is technically feasible and yields higher early vascularization. Increased vascularization may potentially predispose to an increased and earlier cellular response and an increased healing rate.

Biologic and molecular analysis of tumor suppressor loci in human glioblastoma multiforme

Molecular and cytogenetic analyses of human glioblastomas have revealed frequent genetic alterations, including major deletions in chromosomes 9, 10, and 17, suggesting the presence of glioma-associated tumor suppressor genes on these chromosomes. To examine this hypothesis, copies of chromosomes 2, 4, and 10 derived from a human fibroblast cell line were independently introduced into a human glioma cell line, U251, by microcell-mediated chromosomal transfer. Successful transfer of chromosomes in each case was confirmed by resistance to the drug G418, indicating the presence of the neomycin-resistance gene previously integrated into each transferred chromosome. The presence of novel chromosomes and or chromosomal fragments was also demonstrated by molecular and karyotypic analyses. The hybrid clones containing either a novel chromosome 4 or chromosome 10 displayed suppression of the tumorigenic phenotype in vivo and suppression of the transformed phenotype in vitro, while cells containing a transferred chromosome 2 failed to alter their tumorigenic phenotype. The hybrid cells containing chromosome 4 or 10 exhibited a significant decrease in their saturation density, altered cellular morphology at high cell density, but only a slight decrease in their exponential growth rate. A dramatic decrease was observed in growth of cells with chromosome 4 or 10 in soft agarose, with the number and size of the colonies being greatly reduced, compared to the parental or chromosome 2 containing cells. The introduction of chromosome 4 or 10 also completely suppressed tumor formation in nude mice. These studies indicate that chromosome 10, as hypothesized, and chromosome 4, a novel finding for gliomas, harbor tumor suppressor loci that may be directly involved in the initiation or progression of normal glial precursors to human glioblastoma multiforme. ^

Systematic review of the survival rate and incidence of biologic, technical, and esthetic complications of single implant abutments supporting fixed prostheses

Purpose: To assess the 5-year survival rate and number of technical, biologic, and esthetic complications involving implant abutments. Materials and Methods: Electronic (Medline) and hand searches were performed to assess studies on metal and ceramic implant abutments. Relevant data from a previous review were included. Two reviewers independently extracted the data. Failure and complication rates were analyzed, and estimates of 5-year survival proportions were calculated from the relationship between event rate and survival function. Multivariable robust Poisson regression was used to compare abutment characteristics. Results: The search yielded 1,558 titles and 274 abstracts. Twenty-four studies were selected for data analysis. The survival rate for ceramic abutments was 97.5% (95% confidence interval [CI]): 89.6% to 99.4%) and 97.6% (95% CI: 96.2% to 98.5%) for metal abutments. The overall 5-year rate for technical complications was 11.8% (95% CI: 8.5% to 16.3%), 8.9% (95% CI: 4.3% to 17.7%) for ceramic and 12.0% (95% CI: 8.5% to 16.8%) for metal abutments. Biologic complications occurred with an overall rate of 6.4% (95% CI: 3.3% to 12.0%), 10.4% (95% CI: 1.9% to 46.7%) for ceramic, and 6.1% (95% CI: 3.1% to 12.0%) for metal abutments. Conclusions: The present meta-analysis on single-implant prostheses presents high survival rates of single implants, abutments, and prostheses after 5 years of function. No differences were found for the survival and failure rates of ceramic and metal abutments. No significant differences were found for technical, biologic, and esthetic complications of internally and externally connected abutments.

Multiple tree-ring proxies (earlywood width, latewood width and δ13C) from pedunculate oak (Quercus robur L.), Hungary

The aim of this study was to analyse the effects of climatic factors (i.e. monthly mean temperature and total precipitation) on radial growth (earlywood width, latewood width, and total ringwidth) and on latewood stable carbon isotope composition in a pedunculate oak (Quercus robur L) stand in northeastern Hungary. Earlywood widths showed the weakest common variance and lack of statistically significant relationship to monthly precipitation and temperature. Latewood width showed the strongest common chronological signal. Correlation analysis with the monthly climate series pointed out the strongest positive/negative correlation with June precipitation for latewood width/stable carbon isotope ratio. These parameters shared the strongest climatic response also for seasonal scale since the highest correlation coefficients, 0.49 and -0.62 for latewood width and stable carbon isotope ratio, respectively, were obtained for both with a 10-month precipitation total (from previous November to current August of the growing season). A combined parameter, derived as difference between latewood width and stable carbon isotope indices showed improved statistical relationship compared to the hydroclimatic calibration target both for local and regional spatial scales. Spatial correlation analysis indicated that the hydroclimatic signal encoded in these moisture sensitive tree-ring parameters from Bakta Forest is expected to be representative for the northeastern Carpathians and for the large part of the Great Hungarian Plain. In addition, the hydroclimatic signal of latewood width chronology was compared to three independent records. Results showed that neither the strength nor the rank of the similarity of the local hydroclimate signals were stable throughout the past two centuries. Future palaeo(hydro)climatological efforts targeting the Carpathian(-Balkan) region are recommended to track carefully the spatial domains for which a given, local, proxy-derived hydroclimate reconstruction might provide useful information.