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Objective To describe the full range of behavior of the visible, noncavitated, early caries lesion in caries-active adults with substantial fluoride exposure, and to consider implications. Methods The data were from the Xylitol for Adult Caries Trial (X- ACT) collected annually for 33 months using condensed ICDAS caries threshold criteria. Individual tooth surfaces having a noncavitated caries lesion were included, and the patterns of transition to each subsequent annual clinical examination to sound, noncavitated or cavitated, filled or crowned were determined. The resulting sets of patterns for an individual tooth surface, looking forward from its first appearance as a noncavitated lesion, were combined into one of four behavior profiles classified as reversing, stable, oscillating, or continuously progressing, or were excluded if not part of the caries continuum. The distributions of profile types were assessed using the Rao-Scott chi-square test, which adjusts for clustering of tooth surfaces within teeth. Results Inter- and intra-examiner kappa scores demonstrated acceptable calibration at baseline and annually. 8084 tooth surfaces from 543 subjects were included. The distribution of profile types differed significantly between coronal and root surfaces. Overall, two-thirds of all coronal noncavitated lesions were first seen at baseline, half reversed, over a fifth were stable, 15% oscillated, and only 8.3% progressed to cavitation, filled, or crowned in 33 months or less (6.3% consistently Progressed plus 2.0% inconsistently, a subset of oscillating, which oscillated before progressing to cavitation). Approximal, smooth, and occlusal coronal surfaces each were significantly different in their individual distributions of profile types. Xylitol showed no significant and consistent effect on this distribution by tooth surface type. This was in keeping with the X- ACT's lack of effect of xylitol at the noncavitated plus cavitated lesion thresholds combined. Conclusions This study demonstrated the full dynamic range of early caries lesion behavior. The great majority were not progressive, and few (8.3%) became cavitated over 33 months in caries-active adults using fluorides. Important caries management implications favoring recorded longitudinal monitoring, prevention of active risks, and minimal restoration only after direct visual determination of cavitation are discussed. [ABSTRACT FROM AUTHOR]

Objectives To better understand the effectiveness of xylitol in caries prevention in adults and to attempt improved clinical trial efficiency. Methods As part of the Xylitol for Adult Caries Trial (X- ACT), non cavitated and cavitated caries lesions were assessed in subjects who were experiencing the disease. The trial was a test of the effectiveness of 5 g/day of xylitol, consumed by dissolving in the mouth five 1 g lozenges spaced across each day, compared with a sucralose placebo. For this analysis, seeking trial efficiency, 538 subjects aged 21-80, with complete data for four dental examinations, were selected from the 691 randomized into the 3-year trial, conducted at three sites. Acceptable inter- and intra-examiner reliability before and during the trial was quantified using the kappa statistic. Results The mean annualized noncavitated plus cavitated lesion transition scores in coronal and root surfaces, from sound to carious favoured xylitol over placebo, during the three cumulative periods of 12, 24, and 33 months, but these clinically and statistically nonsignificant differences declined in magnitude over time. Restricting the present assessment to those subjects with a higher baseline lifetime caries experience showed possible but inconsistent benefit. Conclusions There was no clear and clinically relevant preventive effect of xylitol on caries in adults with adequate fluoride exposure when non cavitated plus cavitated lesions were assessed. This conformed to the X- ACT trial result assessing cavitated lesions. Including non cavitated lesion assessment in this full-scale, placebo-controlled, multisite, randomized, double-blinded clinical trial in adults experiencing dental caries did not achieve added trial efficiency or demonstrate practical benefit of xylitol. Trial Registration: ClinicalTrials.Gov NCT00393055. [ABSTRACT FROM AUTHOR]

Tissue microarray (TMA) is an established and valuable tool, particularly in translational research and clinical trials, allowing resource-efficient use, and high-throughput profiling, of large numbers of tumours. Despite this, there is little evidence, or guidance, on the optimum manufacture, use and assessment of TMAs. Here we review some of the literature, using breast cancer as an example, to highlight good practice and pitfalls in the design and manufacture of TMAs. Issues, such as the size, number, spacing and layout of cores, as well as the assessment and reporting of studies using TMAs are addressed. We make some suggestions regarding these challenges, and propose a checklist of features that should be considered in order to stimulate debate and improve the quality of data produced by TMA analysis. [ABSTRACT FROM AUTHOR]

Data from the 2001 timber product output study for Georgia was explored to determine new methods for stratifying mills and finding suitable sampling estimators. Estimators for roundwood receipts totals comprised several types: simple random sample, ratio, stratified sample, and combined ratio. Two stratification methods were examined: the Dalenius-Hodges (DH) square root of the frequency method and a cluster analysis method. Three candidate sizes for the number of groups were selected from the cluster analysis and subsequently used in the DH stratification as well. Relative efficiency improved when the number of groups increased and when using a ratio estimator, particularly a combined ratio. The two stratification methods performed similarly. Neither the DH method nor the cluster analysis method performed better than the other. Six bound sizes (1%, 5%, 10%, 15%, 20%, and 25%) were considered for deriving samples sizes for the total volume of roundwood receipts. The minimum achievable bound size was found to be 10% of the total receipts volume for the DH method using a two-group stratification. This was true for both the stratified and combined ratio estimators. In addition, for the stratified and combined ratio estimators, only the DH method stratifications were able to reach a 15% bound on the total (six of the 12 stratified estimators). These results demonstrate that the utilized classification methods are compatible with stratified totals estimators and can provide users with the opportunity to develop viable sampling procedures as opposed to complete mill censuses. [ABSTRACT FROM AUTHOR]

Predictions of snag longevity, defined here as the probability of snag survival to a given age, are key to designing silvicultural regimes that ensure their availability for wildlife and form an important component of carbon flow models. Species, diameter at breast height, stand density, management regime, and agent of tree mortality were assessed for their effect on snag longevity in a long-term silvicultural study on the Penobscot Experimental Forest in central Maine. Snag recruitment and fall data from USDA Forest Service inventories between 1981 and 1997 were analyzed using parametric survival analysis. A Weibull model fit the data best, indicating a significant lag time followed by rapid fall rates. Half-times varied among species, with Thuja occidentalis L. having the longest (10 years) and Picea species the shortest (6 years). Snag longevity was significantly greater with increasing diameter and decreased with increasing stand density. Agent of mortality and silvicultural treatment were also significant. Two models were developed for estimating probability of snag survival over time, one that included predictor variables unique to the silvicultural systems study on the Penobscot Experimental Forest and one using predictor variables available in most standard inventories. Snag survival models can easily be incorporated into comprehensive forest dynamics models to facilitate estimates of wildlife habitat structure and carbon flow. [ABSTRACT FROM AUTHOR]

Focuses on the development of the Roman Catholic church while looking at the mission of the church on an international basis. Historical information on the Roman Catholic Church; Concerns of various aspects of the missionary movement; Information on a consensus about international relationships in mission.

We conducted dendroclimatic analyses and constructed future growth projections for red spruce (Picea rubens Sarg.) throughout the central Appalachians in the state of West Virginia. This study involved field sampling of 18 sites across red spruce's range in six regions throughout the Monongahela National Forest that were selected based on pairwise combinations of three latitudinal groups (north, central, and south) with two aspects (north and south). Each combination of latitudinal group and aspect was referred to as a landscape cluster. Growth was negatively impacted by high summer temperature stress but responded favorably to high fall temperatures. The results also suggested that red spruce was likely impacted by the degree of winter harshness in all landscape clusters. In the northern latitudinal landscape clusters, red spruce responded favorably to warm spring temperatures by allowing an early start to the growing season. Growth projections under a future climate change scenario show that future expected increases in mean and maximum monthly temperatures will have negative effects on future spruce growth. The forecasting results suggested that red spruce in northern latitudes on south aspects or central latitudes on north aspects are the landscape clusters that will likely be the most resilient to future climate change. Dendroclimatic results and future growth projections can assist with identifying locations that are most suitable for future red spruce restoration activities. [ABSTRACT FROM AUTHOR]

The article presents information on a project that developed a mechanism which enables school nurses to identify adolescents with gingivitis using a visual screening instrument. In San Antonio, Texas, there is a high prevalence of severe gingival inflammation. School-based interventions were used because of its effectiveness in promoting oral health. The interventions developed were focused on the identification of the health problem and referral for diagnosis and treatment. A training was conducted for both the dentist and the nurse. After that training, the nurses screened each student using penlight and tongue depressor.

The article offers information on Tissue Microarrays (TMAs), which has been designed as a research tool to enable representative samples of small pieces of tissue from hundreds of individual paraffin blocks to be placed in a single block for testing. It is noted that TMA technology serves as an important research tool now and for the future. It is noted that TMAs by using immunohistochemistry used to highlight epithelial cell adhesion/activating molecule (EpCAM) expression in renal tumours.

A correction to the article "Snag Longevity Under Alternative Silvicultural Regimes in Mixed-Species Forest of Central Maine" is presented.

Purpose: The purpose of this study was to compare the prevalence of caries between children whose parents had previously participated in an infant oral health educational program (IOHEP) at a WIC clinic with those children whose parents had not participated previously. Methods: One hundred and twenty children aged 1 to 5 years participated in the study. A single examiner previously standardized using the WHO diagnostic criteria for caries examined the children. Results: One hundred and sixteen children were Hispanic (97%). Forty-one of the parents (34%) had previously participated in the IOHEP. Previous participation of the parents in the IOHEP was highly associated with fewer enamel carious lesions (P=.005) and lower dft (P= .043) scores. Children whose parents reported brushing their child's teeth with fluoride toothpaste had significantly lower prevalence of caries (P=.007). Conclusions: Infant oral health educational programs directed to parents at WIC can have a positive impact on caries prevention. [ABSTRACT FROM AUTHOR]

P21-activated kinase 4 (PAK4) is a Cdc42 effector protein thought to regulate cell adhesion disassembly in a kinase-dependent manner. We found that PAK4 expression is significantly higher in high-grade human breast cancer patient samples, whereas depletion of PAK4 modifies cell adhesion dynamics of breast cancer cells. Surprisingly, systematic analysis of PAK4 functionality revealed that PAK4-driven adhesion turnover is neither dependent on Cdc42 binding nor kinase activity. Rather, reduced expression of PAK4 leads to a concomitant loss of RhoU expression. We report that RhoU is targeted for ubiquitination by the Rab40A-Cullin 5 complex and demonstrate that PAK4 protects RhoU from ubiquitination in a kinase-independent manner. Overexpression of RhoU rescues the PAK4 depletion phenotype, whereas loss of RhoU expression reduces cell adhesion turnover and migration. These data support a new kinase-independent mechanism for PAK4 function, where an important role of PAK4 in cellular adhesions is to stabilize RhoU protein levels. Thus, PAK4 and RhoU cooperate to drive adhesion turnover and promote cell migration. [ABSTRACT FROM AUTHOR]

Background: Immunohistochemical assessment of proliferation may provide additional prognostic information in early breast cancer. However, due to a lack of methodological standards proliferation markers are still not routinely used for determining therapy. Even for Ki67, one of the most widely-studied markers, disagreements over the optimal cutoff exist. Improvements in digital microscopy may provide new avenues to standardise and make data more reproducible. Methods: We studied the immunohistochemical expression of three markers of proliferation: Ki67, Mini-Chromosome Maintenance protein 2 and Geminin, by conventional light microscope and digital imaging on triplicate TMAs from 309 consecutive cases of primary breast cancers. Differences between the average and the maximum percentage reactivity in tumour cell nuclei from the three TMA cores were investigated to assess the validity of the approach. Time-dependent Receiver Operating Characteristic curves were utilized to obtain optimal expression level cut-offs, which were then correlated with clinico-pathological features and survival. Results: High concordance between conventional and digital scores was observed for all 3 markers (Ki67: rs = 0.87, P < 0.001; MCM2: rs = 0.94, P < 0.001; and Geminin: rs = 0.86, P < 0.001; Spearman's rank). There was no significant difference according to the number of TMA cores included for either Ki67 or MCM2; analysis of two or three cores produced comparable results. Higher levels of all three proliferation markers were significantly associated with higher grade (P < 0.001) and ER-negativity (P < 0.001). Optimal prognostic cut-offs for percentage expression in the tumour were 8 %, 12 and 2.33 % for Ki67, MCM2 and Geminin respectively. All 3 proliferation marker cutoffs were predictive of 15-year breast cancer-specific survival in univariable Cox regression analyses. In multivariable analysis only lymph node status (HR = 3.9, 95 % CI = 1.79-8.5, P = 0.0006) and histological grade (HR = 1.84, 95 % CI = 1-3.38, P = 0.05) remained significantly prognostic. Conclusions: Here we show that. MCM2 is a more sensitive marker of proliferation than Ki67 and should be examined in future studies, especially in the lymph node-negative, hormone receptor-positive subgroup. Further, digital microscopy can be used effectively as a high-throughput method to evaluate immunohistochemical expression. [ABSTRACT FROM AUTHOR]

Background: Immunohistochemical assessment of proliferation may provide additional prognostic information in early breast cancer. However, due to a lack of methodological standards proliferation markers are still not routinely used for determining therapy. Even for Ki67, one of the most widely-studied markers, disagreements over the optimal cutoff exist. Improvements in digital microscopy may provide new avenues to standardise and make data more reproducible. Methods: We studied the immunohistochemical expression of three markers of proliferation: Ki67, Mini-Chromosome Maintenance protein 2 and Geminin, by conventional light microscope and digital imaging on triplicate TMAs from 309 consecutive cases of primary breast cancers. Differences between the average and the maximum percentage reactivity in tumour cell nuclei from the three TMA cores were investigated to assess the validity of the approach. Time-dependent Receiver Operating Characteristic curves were utilized to obtain optimal expression level cut-offs, which were then correlated with clinico-pathological features and survival. Results: High concordance between conventional and digital scores was observed for all 3 markers (Ki67: rs = 0.87, P < 0.001; MCM2: rs = 0.94, P < 0.001; and Geminin: rs = 0.86, P < 0.001; Spearman’s rank). There was no significant difference according to the number of TMA cores included for either Ki67 or MCM2; analysis of two or three cores produced comparable results. Higher levels of all three proliferation markers were significantly associated with higher grade (P < 0.001) and ER-negativity (P < 0.001). Optimal prognostic cut-offs for percentage expression in the tumour were 8 %, 12 and 2.33 % for Ki67, MCM2 and Geminin respectively. All 3 proliferation marker cutoffs were predictive of 15-year breast cancer-specific survival in univariable Cox regression analyses. In multivariable analysis only lymph node status (HR = 3.9, 95 % CI = 1.79-8.5, P = 0.0006) and histological grade (HR = 1.84, 95 % CI = 1–3.38, P = 0.05) remained significantly prognostic. Conclusions: Here we show that. MCM2 is a more sensitive marker of proliferation than Ki67 and should be examined in future studies, especially in the lymph node-negative, hormone receptor-positive subgroup. Further, digital microscopy can be used effectively as a high-throughput method to evaluate immunohistochemical expression. [ABSTRACT FROM AUTHOR]

Background. Although caries is prevalent in adults, investigators have tested few preventive therapies in adult populations. In a randomized controlled trial, the authors evaluated the effectiveness of xylitol lozenges in preventing caries in adults at elevated risk of developing caries. Methods. The Xylitol for Adult Caries Trial (X-ACT) was a three-site placebo-controlled randomized trial. Participants (n = 691) aged 21 through 80 years consumed five 1.0-gram xylitol or placebo lozenges daily for 33 months. They underwent clinical examinations at baseline and at 12, 24 and 33 months. Results. Xylitol lozenges reduced the caries increment 10 percent. This reduction, which represented less than one-third of a surface per year, was not statistically significant. There was no indication of a dose-response effect. Conclusions. Daily use of xylitol lozenges did not result in a statistically or clinically significant reduction in 33-month caries increment among adults at an elevated risk of developing caries. Clinical Implications. These results suggest that xylitol used as a supplement in adults does not reduce their caries experience significantly. [ABSTRACT FROM AUTHOR]

Background. Although caries is prevalent in adults, investigators have tested few preventive therapies in adult populations. In a randomized controlled trial, the authors evaluated the effectiveness of xylitol lozenges in preventing caries in adults at elevated risk of developing caries. Methods. The Xylitol for Adult Caries Trial (X-ACT) was a three-site placebo-controlled randomized trial. Participants (n = 691) aged 21 through 80 years consumed five 1.0-gram xylitol or placebo lozenges daily for 33 months. They underwent clinical examinations at baseline and at 12, 24 and 33 months. Results. Xylitol lozenges reduced the caries increment 10 percent. This reduction, which represented less than one-third of a surface per year, was not statistically significant. There was no indication of a dose-response effect. Conclusions. Daily use of xylitol lozenges did not result in a statistically or clinically significant reduction in 33-month caries increment among adults at an elevated risk of developing caries. Clinical Implications. These results suggest that xylitol used as a supplement in adults does not reduce their caries experience significantly. [ABSTRACT FROM AUTHOR]