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Background: The rising prevalence of obesity, particularly in childhood, is a global public health emergency. There is some evidence that exposure to non-parental childcare before age 6 years is associated with subsequent development of obesity and obesity-related behaviours such as physical activity, sedentary behaviour, sleep, diet and stress, although these findings are inconsistent. It is possible that the relationship between early childcare and later obesity and obesity-related behaviours depends on characteristics of childcare exposure such as type (i.e. informal versus formal care), duration (i.e. number of years spent in childcare), intensity (e.g. number of hours per week) and timing (i.e. age of onset of childcare) of care received. The relationship may also be moderated by socio-demographic characteristics of children and their families. We will conduct a systematic review exploring longitudinal associations between childcare (type, duration, intensity and timing) and measures of adiposity and body mass, physical activity, sedentary behaviour, sleep, diet and stress. We will also assess whether these relationships vary by socio-demographic factors., Methods: We will include studies that explore longitudinal associations between childcare attendance in children aged <6 years not in primary school at first assessment and body weight, adiposity, physical activity, diet, sleep and stress. We will limit studies to those involving middle- and high-income countries. Two independent reviewers will screen search results in two stages: (1) title and abstract and (2) and full text. One reviewer will extract relevant data and a second will verify this information. We will assess risk of bias of included studies using an adaption of the United States Department of Agriculture National Evidence Library Bias Assessment Tool. We will tabulate and summarise results narratively. We may conduct meta-analysis if at least five studies report comparable data., Discussion: To our knowledge, this will be the first systematic review to summarise the existing evidence on longitudinal associations between childcare and adiposity, body mass and obesity-related risk factors. The results will be of relevance to other researchers, childcare practitioners and policy makers., Systematic Review Registration: PROSPERO CRD42015027233.

Competing Interests: The authors declare no conflicts of interest.

This study examined the associations of testosterone and cortisol levels with maternal depressive symptoms and infant socioemotional (SE) problems that are influenced by infant gender. A total of 62 mothers and their very-low-birth weight (VLBW) infants were recruited from a neonatal intensive care unit at a tertiary medical center in the southeast United States. Data were collected at three time points (before 40 weeks' postmenstrual age [PMA] and at 3 months and 6 months of age corrected for prematurity). Measures included infant medical record review, maternal interview, biochemical assays of salivary hormone levels in mother-VLBWinfant pairs, and standard questionnaires. Generalized estimating equations with separate analyses for boys and girls showed that maternal testosterone level was negatively associated with depressive symptoms in mothers of boys, whereas infant testosterone level was negatively associated with maternal report of infant SE problems in girls after controlling for characteristics of mothers and infants and number of days post birth of saliva collection. Not surprisingly, the SE problems were positively associated with a number of medical complications. Mothers with more depressive symptoms reported that their infants had more SE problems. Mothers with higher testosterone levels reported that girls, but not boys, had fewer SE problems. In summary, high levels of testosterone could have a protective role for maternal depressive symptoms and infant SE problems. Future research need to be directed toward clinical application of these preliminary results., (© The Author(s) 2015.)

Aberrant tau protein accumulation drives neurofibrillary tangle (NFT) formation in several neurodegenerative diseases. Currently, efforts to elucidate pathogenic mechanisms and assess the efficacy of therapeutic targets are limited by constraints of existing models of tauopathy. In order to generate a more versatile mouse model of tauopathy, somatic brain transgenesis was utilized to deliver adeno-associated virus serotype 1 (AAV1) encoding human mutant P301L-tau compared with GFP control. At 6 months of age, we observed widespread human tau expression with concomitant accumulation of hyperphosphorylated and abnormally folded proteinase K resistant tau. However, no overt neuronal loss was observed, though significant abnormalities were noted in the postsynaptic scaffolding protein PSD95. Neurofibrillary pathology was also detected with Gallyas silver stain and Thioflavin-S, and electron microscopy revealed the deposition of closely packed filaments. In addition to classic markers of tauopathy, significant neuroinflammation and extensive gliosis were detected in AAV1-Tau(P301L) mice. This model also recapitulates the behavioral phenotype characteristic of mouse models of tauopathy, including abnormalities in exploration, anxiety, and learning and memory. These findings indicate that biochemical and neuropathological hallmarks of tauopathies are accurately conserved and are independent of cell death in this novel AAV-based model of tauopathy, which offers exceptional versatility and speed in comparison with existing transgenic models. Therefore, we anticipate this approach will facilitate the identification and validation of genetic modifiers of disease, as well as accelerate preclinical assessment of potential therapeutic targets., (© The Author 2015. Published by Oxford University Press.)

Background: Vitamin D production during pregnancy promotes fetal lung development, a major determinant of infant survival after preterm birth. Because vitamin D synthesis in humans is regulated by solar ultraviolet B (UVB) radiation, we hypothesized that seasonal variation in solar UVB doses during fetal development would be associated with variation in neonatal mortality rates., Methods: This cohort study included infants born alive with gestational age (GA) between 23 and 28 weeks gestation admitted to a neonatal unit between 1996 and 2010. Three infant cohort groups were defined according to increasing intensities of solar UVB doses at 17 and 22 weeks gestation. The primary outcome was death during the first 28 days after birth., Results: Outcome data of 2,319 infants were analyzed. Mean birth weight was 830 ± 230 g and median gestational age was 26 weeks. Mortality rates were significantly different across groups (p = 0.04). High-intensity solar UVB doses were associated with lower mortality when compared with normal intensity solar UVB doses (hazard ratio: 0.70; 95% confidence interval: 0.54-0.91; p = 0.01)., Conclusion: High-intensity solar UVB doses during fetal development seem to be associated with risk reduction of early mortality in preterm infants. Prospective studies are needed to validate these preliminary findings., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Male very-low-birthweight (VLBW) infants are more prone than females to health and developmental problems and less positive mother-infant interactions. Because gender differences in brain development and social relationships suggest hormonal influences on quality of mother-infant interaction, the authors explored the associations of maternal and infant salivary testosterone and cortisol levels with mother-infant interactions in the sample as a whole and by gender, after controlling for covariates. Data were collected prospectively from 62 mothers and their VLBW infants through infant record review, maternal interview, biochemical measurement of both mothers and infants, and observation of mother-infant interactions at 40 weeks postmenstrual age and at three and six months corrected age. Infants' positive interactions increased and mothers' decreased from three to six months. In generalized estimating equation (GEE) analyses, after controlling for covariates, higher maternal testosterone and infant cortisol were associated with more positive and more frequent maternal interactive behaviors. In GEE analyses by infant gender, after controlling for covariates, effects of maternal and infant hormone levels became more significant, especially on infants' interactive behaviors. Based on these preliminary findings, among VLBW infants, males with high testosterone are expected to have less positive mother-infant interactions than males with low testosterone or female infants., (© 2015 Wiley Periodicals, Inc.)

Malaria imposes a substantial global disease burden. It disproportionately affects sub-Saharan Africans, particularly young children. In an effort to improve disease management, the World Health Organization (WHO) recommended in 2010 that countries test children younger than age five who present with suspected malaria fever to confirm the diagnosis instead of treating them presumptively with antimalarial drugs. Costs and concerns about the overall health impact of such diagnostic testing for malaria in children remain barriers to full implementation. Using data from national Malaria Indicator Surveys, we estimated two-stage microsimulation models for Angola, Tanzania, and Uganda to assess the policy's cost-effectiveness. We found that diagnostic testing for malaria in children younger than five is cost-saving in Angola. In Tanzania and Uganda the cost per life-year gained is $5.54 and $94.28, respectively. The costs projected for Tanzania and Uganda are less than the WHO standard of $150 per life-year gained. Our results were robust under varying assumptions about cost, prevalence of malaria, and behavior, and they strongly suggest the pursuit of policies that facilitate full implementation of testing for malaria in children younger than five., (Project HOPE—The People-to-People Health Foundation, Inc.)

Medicare eligibility age is a major focus of health policy discussions about how to tackle increasing health care costs and reduce the national debt. Raising the Medicare eligibility age from 65 to 67 would presumably reduce the cost of Medicare, but the opponents caution it could exacerbate health disparities by race and/or income. We compared the mortality rate, hospitalization rate, and annual Medicare expenditures of current White and Black Medicare beneficiaries at age 65-66 years using the Medicare Current Beneficiary Survey. We found Blacks have higher health care demand reimbursed by Medicare than Whites at these ages. To raise the Medicare eligibility age from 65 to 67 would likely have more negative health and economic effects among Blacks than among Whites, and would likely exacerbate health disparities by race. We suggest great caution when considering this policy option.

Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative tauopathy caused by mutations in the tau gene (MAPT). Individuals with FTDP-17 have deficits in learning, memory, and language, in addition to personality and behavioral changes that are often characterized by a lack of social inhibition. Several transgenic mouse models expressing tau mutations have been tested extensively for memory or motor impairments, though reports of amygdala-dependent behaviors are lacking. To this end, we tested the rTg4510 mouse model on a behavioral battery that included amygdala-dependent tasks of exploration. As expected, rTg4510 mice exhibit profound impairments in hippocampal-dependent learning and memory tests, including contextual fear conditioning. However, rTg4510 mice also display an abnormal hyperexploratory phenotype in the open-field assay, elevated plus maze, light-dark exploration, and cued fear conditioning, indicative of amygdala dysfunction. Furthermore, significant tau burden is detected in the amygdala of both rTg4510 mice and human FTDP-17 patients, suggesting that the rTg4510 mouse model recapitulates the behavioral disturbances and neurodegeneration of the amygdala characteristic of FTDP-17., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Landscapes influence precipitation via the water vapor and energy fluxes they generate. Biologically active landscapes also generate aerosols containing microorganisms, some being capable of catalyzing ice formation and crystal growth in clouds at temperatures near 0 °C. The resulting precipitation is beneficial for the growth of plants and microorganisms. Mounting evidence from observations and numerical simulations support the plausibility of a bioprecipitation feedback cycle involving vegetated landscapes and the microorganisms they host. Furthermore, the evolutionary history of ice nucleation-active bacteria such as Pseudomonas syringae supports that they have been part of this process on geological time scales since the emergence of land plants. Elucidation of bioprecipitation feedbacks involving landscapes and their microflora could contribute to appraising the impact that modified landscapes have on regional weather and biodiversity, and to avoiding inadvertent, negative consequences of landscape management., (© 2013 John Wiley & Sons Ltd.)

Purpose: It is established in the literature that disparities exist in the quality of healthcare for patients from disadvantaged backgrounds and lower socioeconomic status. There may be roadblocks within the field of neurosurgery preventing equal access and quality of care. Our goal was to study the similarities between pediatric patients with shunted hydrocephalus of different insurance types and race., Methods: A retrospective chart review was performed on all pediatric patients who underwent ventriculoperitoneal shunting from 1990-2010 at our institution. Race and insurance type were recorded and assessed against specific outcome measures to statistically compare complication rates., Results: A complete record was found for 373 patients who received 849 shunting procedures at our institution. No differences were found between racial groups and insurance type for overall shunt survival, total revision number, or average time to failure. However, nonwhite patients spent an average of 3 days longer in the hospital at initial shunting (p = 0.04), and those with public insurance stayed for 5 days longer (p = 0.002). Patients with public insurance were more likely to present with shunt failure from outside hospitals (p = 0.005) and be born prematurely (p < 0.001). Private patients were more likely to have a neoplasm present at time of initial shunt placement (p = 0.003)., Conclusion: While overall revision rate was not affected by race or insurance status, there were significant delays in discharge for patients with public insurance. Moreover, potential disparities in outpatient access to primary physicians and specialists may be affecting care.

Health and disease management (HDM) programs have faced challenges in documenting savings related to their implementation. The objective of this eliminate study was to describe OptumHealth's (Optum) methods for estimating anticipated savings from HDM programs using Value Drivers. Optum's general methodology was reviewed, along with details of 5 high-use Value Drivers. The results showed that the Value Driver approach offers an innovative method for estimating savings associated with HDM programs. The authors demonstrated how real-time savings can be estimated for 5 Value Drivers commonly used in HDM programs: (1) use of beta-blockers in treatment of heart disease, (2) discharge planning for high-risk patients, (3) decision support related to chronic low back pain, (4) obesity management, and (5) securing transportation for primary care. The validity of savings estimates is dependent on the type of evidence used to gauge the intervention effect, generating changes in utilization and, ultimately, costs. The savings estimates derived from the Value Driver method are generally reasonable to conservative and provide a valuable framework for estimating financial impacts from evidence-based interventions.

The aim of this study was to assess educational needs of health care personnel in vaccine storage and handling. The Immunization Knowledge Assessment Tool (IKAT) was used to evaluate knowledge related to delivery and storage of measles, mumps and rubella (MMR) vaccine among health care personnel in Idaho. Using descriptive analysis, only 61% of respondents achieved a passing score of 80%. Knowledge deficits were revealed among health care personnel, physicians, and other providers in immunization administration and handling of the MMR vaccine. Scores were highest among registered nurses, licensed practical nurses, and medical assistants., (© 2013.)

Colorectal cancer is one of the five leading causes of cancer mortality worldwide. The mechanisms of pathogen clearance, inflammation and regulation by T cells in the healthy bowel are also important in controlling tumor growth. The majority of studies analyzing T cells and their relationship to colorectal tumor growth have focused on individual T cell markers or gene clusters and thus the complexity of the T cell response contributing to the growth of the tumor is not clear. We have studied the T cells in colorectal cancer patients and have defined a unique T cell signature for colorectal tumor tissue. Using a novel analytical flow cytometric approach in concert with confocal microscopy, we have shown that the tumor has a lower frequency of effector T cells (CD69+), but a higher frequency of both regulatory (CD25hi Foxp3+) and inflammatory T cells (IL-17+) compared with associated nontransformed bowel tissue. We have also identified minor populations of T cells expressing conventional markers of both inflammatory and regulatory T cells (CD4+IL-17+Foxp3+) in the tumor tissue. These cells may represent intermediate populations or they may dictate an inflammatory versus regulatory function in surrounding T cells. Together, these data describe an immune microenvironment in colorectal cancer unique to the tumor tissue and distinct from the surrounding healthy bowel tissue, and this distinct environment is reflected by a gradient of T cells expressing markers of multiple T cell populations. These findings may be used to improve diagnosis and prognosis of colorectal cancer patients., (Copyright © 2012 UICC.)

Object: Ventriculoperitoneal (VP) shunt placement remains the mainstay treatment for pediatric hydrocephalus. These devices have a relatively high complication and failure rate, often requiring multiple revisions. The authors present a single institution's experience of pediatric patients treated with VP shunts. With an average follow-up time of 20 years, this study is among the longest reports of VP shunt revision in the literature to date. Hydrocephalus origins, shunt revision rates, and causes of shunt failure are described. Patients who underwent their first shunt revision more than 10 years after initial shunt placement were also explored., Methods: A retrospective chart review was performed on all pediatric patients who underwent VP shunt placement from January 1990 through November 1996 at the University of Rochester Medical Center. Only patients who had at least 15 years of follow-up since their initial shunting procedure were included., Results: A total of 234 procedures were performed on 64 patients, with a mean follow-up of 19.9 years. Patients ranged from a few days to 17.2 years old when they received their original shunt, with a median age of 4 months; 84.5% of the patients required 1 or more shunt revisions and 4.7% required 10 or more. Congenital defects, Chiari Type II malformations, tumors, and intraventricular hemorrhage were the most common causes of hydrocephalus. Overall, patients averaged 2.66 revisions, with proximal (27%) and distal (15%) catheter occlusion, disconnection (11%), and infection (9%) comprising the most common reasons for shunt malfunction. Notably, 12.5% of patients did not require their first shunt revision until more than 10 years after initial device placement, a previously undescribed finding due to the short follow-up duration in previous studies., Conclusions: This long-term retrospective analysis of pediatric VP shunt placement revealed a relatively high rate of complications with need for shunt revision as late as 17 years after initial placement. Catheter occlusion represented a significant percentage of shunt failures. Cerebrospinal fluid shunting has a propensity for mechanical failure and patients with VP shunts should receive follow-up through the transition to adulthood.

Study Design: We analyzed longitudinal data on secondary outcomes from participants in a telerehabilitation study., Objectives: To examine the factors affecting return to productive activities and employment and the time to these events following a spinal cord injury (SCI)., Setting: A large southeastern rehabilitation hospital in the United States., Methods: We used hazard regression models to analyze data from newly injured people (n=111) participating in an educational intervention post discharge who were followed for up to 2 years. Outcomes were time to return to productive activities and employment., Results: Increasing age and being on Medicaid significantly decreased the likelihood of returning to productive activities (P<0.01), while being white (P<0.05) and having a higher median income (P<0.001) significantly increased this probability. The same factors, bar being on Medicaid, affected the return to employment. Whites returned to productive activities 2.5 times sooner than African Americans and employment twice as fast (P<0.001). Being in the 75th income percentile compared with the 25th shortened time to employment by 209 days., Conclusion: Findings here suggest that income and race affect the time to return to productivity and employment, while being on Medicaid also has a role in general post injury productivity.

Background/aims: The external ventricular drain (EVD) is commonly used for the treatment of hydrocephalus and intracranial pressure (ICP) monitoring. In this study, we retrospectively reviewed indications for EVD placement over the last 20 years in pediatric patients at our institution. Additionally, we evaluated the rate that an EVD needed to be converted to a ventriculoperitoneal shunt (VPS) and ascertained how hydrocephalus etiology impacted long-term drainage requirements., Methods: Patients that received an EVD between 1990 and 2010 at our institution were identified using billing codes. Demographics, etiology of hydrocephalus, length of stay (LOS) and EVD duration were recorded. Only patients receiving their first EVD were included; those with any prior ventricular catheter (including prior shunts) were excluded from this study., Results: A total of 180 patients underwent first-time placement of an EVD over the 20-year period. Of these, 78.9% were placed on the right side and 81.7% were performed through a frontal burr hole site. The average age of all patients at their initial procedure was 9.3 years (median 9.8; range 0-18), hospital LOS was 22.5 days (median 16; range 1-174) and EVD duration was 7.8 days (median 7; range 1-37). Trauma (43.3%) and neoplasms (32.2%) were the most common indications. Approximately, one quarter of the patients were unable to become EVD independent and, therefore, required a VPS. Only patients receiving an EVD for traumatic brain injury were significantly less likely to be converted to a shunt than other causes of hydrocephalus (relative risk, RR = 0.18, 95% confidence interval, CI = 0.07-0.46). Conversely, patients with neoplasms (RR = 3.56, 95% CI = 1.74-7.31), obstructive hydrocephalus (RR = 5.48, 95% CI = 1.37-22.0) and intraventricular hemorrhage (RR = 9.86, 95% CI = 1.05-92.3) were more likely to need a shunt., Conclusion: Traumatic brain injuries and neoplasms represent the most common indications for EVD placement in the pediatric population. While patients with neoplasm were much more likely to need conversion to a VPS for long-term cerebrospinal fluid diversion, the majority of EVDs in patients with head injuries were successfully weaned., (Copyright © 2013 S. Karger AG, Basel.)

Atmospheric deposition of perfluorinated carboxylic acids (PFCAs) in remote regions might arise from transport and degradation of precursors (e.g., perfluorooctanesulfonyl fluoride (PFOSF)-based products or fluorotelomer alcohols (FTOHs)) or direct transport (e.g., PFCAs in the vapor phase or on particles). To probe the dominant atmospheric source of PFCAs, historical trends in environmental FTOH, PFOSF, and direct perfluorooctanoate (PFOA) emissions were compared to the flux of PFCAs (sum of C7-C13 perfluoroalkyl chain lengths) and PFCA isomer signatures in dated sediment cores from two remote alpine lakes in the Canadian Rocky Mountains. Contributions from PFOSF-based substances and direct transport of PFOA were ruled to be minimal because no branched isomers were detected in either core and temporal trends for direct emission of PFOA did not match the flux measurements. PFCA flux to Lake Opabin sediment agreed well with reported FTOH emissions, including a peak in mid-2003 and subsequent decline. In Lake Oesa, agreement between PFCA flux and FTOH emissions was also good up to 2004, but a subsequent decline was only detected for some PFCA congeners through 2008, while others continued to increase. Overall, both the isomer profiles and the temporal trend data suggest that FTOH oxidation is the dominant atmospheric source of PFCAs to these high alpine lakes. The efficacy of recent industry phase-out initiatives was difficult to assess due to the divergent temporal trends in samples after 2003; thus, continued monitoring is suggested at remote sites such as these.

Background: The immune response has been proposed to be an important factor in determining patient outcome in colorectal cancer (CRC). Previous studies have concentrated on characterizing T cell populations in the primary tumour where T cells with regulatory effect (Foxp3+ Tregs) have been identified as both enhancing and diminishing anti-tumour immune responses. No previous studies have characterized the T cell response in the regional lymph nodes in CRC., Methods: Immunohistochemistry was used to analyse CD4, CD8 or Foxp3+ T cell populations in the regional lymph nodes of patients with stage II CRC (n = 31), with (n = 13) or without (n = 18) cancer recurrence after 5 years of follow up, to determine if the priming environment for anti-tumour immunity was associated with clinical outcome., Results: The proportions of CD4, CD8 or Foxp3+ cells in the lymph nodes varied widely between and within patients, and there was no association between T cell populations and cancer recurrence or other clinicopathological characteristics., Conclusions: These data indicate that frequency of these T cell subsets in lymph nodes may not be a useful tool for predicting patient outcome.

Health Department (HD) managers at both state and local levels are in desperate need of tools to assist in monitoring and evaluating programs. The purpose of this study is to assess the feasibility and utility of linking program performance scores and expenditures into a Report of Performance Measures (RPM). We analyzed secondary data on performance indicators, selected by HD staff, and expenditures, related to six surveillance activities, from two, similar, high-incidence, tuberculosis (TB) programs in Florida from 2002 to 2003. We compared the findings between the county HDs as an illustration of basic cost-effectiveness benchmarking, based on the cost-effectiveness grid. Data included here provide examples of: (1) two instances in which one county was operating relatively inefficiently compared to the other; (2) two instances in which performance and expenditures were similar for the counties; and (3) two instances in which one county spent more for higher performance scores than the other. These data illustrate how the RPM can be used to facilitate benchmarking, a basic evaluation tool. They also demonstrate ways to identify potential operational inefficiencies in a single time period and ultimately over time. It is thus likely to be a feasible and useful management tool., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Four double salt compounds of the type [Pt(tpy)X][Au(C(6)F(5))(2)], where tpy =2,2':6',2''-terpyridine and X = Cl, 3, Br, 4, I, 5, and CCPh, 6, and their platinum starting materials, [Pt(tpy)Br]Br·2H(2)O, 1, and [Pt(tpy)(CCPh)]PF(6)·DMF·H(2)O, 2, have been synthesized and characterized. Complex 2 is a solvated form of the known and structurally characterized [Pt(tpy)(CCPh)]PF(6) species. All compounds were characterized by single-crystal X-ray diffraction, elemental analyses, and solution electronic spectra. Structural characterization shows that compounds 3 and 4 are similar in the solid state and form cation-anion stacking patterns while compounds 5 and 6 form chains of cations supported by metallophilic interactions with anion partners on either side of the chains. Solution studies (UV-vis and fluorescence) strongly suggest that there are no Pt···Au interactions in solution state. Electronic structure calculations with density functional theory (DFT) elucidate the subtle changes in the electronic scaffolding of the ions in these compounds and show that predictions of metallophilic interactions are not straightforward but can be understood in terms of orbital symmetry and the relative energies of the frontier orbitals.

Compromised quality of formalin-fixed paraffin-embedded (FFPE)-derived DNA has compounded the use of archival specimens for array-based genomic studies. Recent technological advances have led to first successes in this field; however, there is currently no general agreement on the most suitable platform for the array-based analysis of FFPE DNA. In this study, FFPE and matched fresh-frozen (FF) specimens were separately analyzed with Affymetrix single nucleotide polymorphism (SNP) 6.0 and Agilent 4x44K oligonucleotide arrays to compare the genomic profiles from the two tissue sources and to assess the relative performance of the two platforms on FFPE material. Genomic DNA was extracted from matched FFPE-FF pairs of normal intestinal epithelium from four patients and were applied to the SNP and oligonucleotide platforms according to the manufacturer-recommended protocols. On the Affymetrix platform, a substantial increase in apparent copy number alterations was observed in all FFPE tissues relative to their matched FF counterparts. In contrast, FFPE and matched FF genomic profiles obtained via the Agilent platform were very similar. Both the SNP and the oligonucleotide platform performed comparably on FF material. This study demonstrates that Agilent oligonucleotide array comparative genomic hybridization generates reliable results from FFPE extracted DNA, whereas the Affymetrix SNP-based array seems less suitable for the analysis of FFPE material., (Copyright 2010 Elsevier Inc. All rights reserved.)

Dental age estimation of juvenile skeletal remains has utilized the methods of Moorrees ,Fanning and Hunt (1963) [MFH] and Demirjian,Goldstein and Tanner (1973) [DGT] for many years with various results. The Demirjian et al method has been tested by several authors on their population groups with varying results.The use of these methods to age the skeletal remains of South African children by the author has not been successful. The aim of this study was to test the accuracy of the dental age estimation methods of MFH and DGT on samples of children of different ethnic groups.The study showed that the MFH method consistently under-estimates the age and the method of Demirjian et al over-estimates theages.

The standard age estimation methods of Moorrees, Fanning & Hunt (1963) and that of Demirjian, Goldstein & Tanner (1973) have been shown by several authors to be inaccurate when applied to their juvenile population. This was similarly found to be true in South African children. Pantomographic radiographs of samples of South African children of White, Coloured, Indian and Black origin were used to develop dental age related tables for these ethnic groups. These dental age estimation tables were tested and are presented.

The dental identification of human remains utilizes the matching of dental restorations. The radiographic images of amalgam restorations are paramount in this process. The compound amalgam restoration has a unique radiographic morphology and can be readily identified in both antemortem and postmortem data. To test the radiographic morphology of compound amalgam restorations, 10 out of 40 Typodont teeth, restored by students, were tested for their discriminatory potential by 12 examiners. The results showed that the radiographic morphology of compound amalgam restorations can be accurately matched by dentally trained personnel. This suggests that in cases where accurate radiographic material is used for dental comparison, less than 12 concordant features are necessary for positive dental identification. If the antemortem and postmortem radiographic images of a compound amalgam restoration are exactly the same then this feature is unique and identification can be achieved by a single concordant feature.

The standard dental bitewing radiograph is used to detect interproximal caries but it also provides a specific view of the dental restorations that can be duplicated for identification purposes. The antemortem and postmortem bitewing radiographs are often not at the same angle and result in distorted images of the restorations. The aim of this study was to investigate the progressive increase in angulations of a bitewing radiograph of the same restoration and to determine at what angle the image is distorted sufficiently as not to be recognized. Bitewing radiographs were taken of the same two restorations at 5 ̊, 10 ̊, 15 ̊ and 20 ̊ superior, inferior, mesial and distal to the original 0 ̊bitewing radiograph. Twenty examiners were required to determine at what angle the distortion prevented matching of the image with the original bitewing radiograph. The results showed that the image distortion at 15 ̊became suspect but at 20 ̊none of the images could be matched to the original bitewing radiograph.

The methods used for disaster victim identification is comparative postmortem profiling of dental and fingerprint data. Twelve dental concordant features are normally required for dental identification. The radiographic image of dental amalgam restorations has been shown to be highly significant for identification purposes. The aim of this study was to investigate the radiological morphology of standardized radio-opaque composite fillings in premolar teeth with regard to their discriminatory potential for identification purposes. Thirty lower first premolar teeth ("Typodont" acrylic teeth) that were filled with 3- surface fillings (MOD) radio-opaque composite resin (Z100) by 4th year dental students were used for this study. Bitewing radiographs were taken of all thirty fillings and labeled Set 1. A second set (Set 2) consisted of 10 randomly selected duplicate radiographs of Set 1, plus 2 other radiographic images not from Set 1. Instructions were given to 20 dentally trained examiners to match the 12 radiographic images of Set 2 with the 30 images of Set 1. The results showed that 18 of the 20 examiners correctly matched the 12 radiographic images, one scored 11 out of 12 and one scored 10 out of 12. This study shows that if the ante-mortem and post-mortem radiographs of a single composite filling have exactly the same morphology, this image is unique and 12 concordant features are not necessary for dental identification.

There are several morphologic types of ovarian carcinoma. It has been shown that p16 is overexpressed in high-grade serous carcinoma but there has been little detailed comparison of p16 expression in the common types of ovarian carcinoma. The aim of this study was to compare p16 expression in ovarian carcinomas of serous, endometrioid, clear cell, and mucinous type with a view to ascertaining whether high expression in a primary ovarian carcinoma is specific for a serous neoplasm. We included problematic cases, which are difficult to type, such as poorly differentiated and undifferentiated carcinomas and serous carcinomas with clear cells. In these problematic groups, we compared p16 expression with that of WT1, which is known to be relatively specific for a serous phenotype. Cases of ovarian high-grade serous carcinoma (n=38), endometrioid carcinoma (n=15), clear cell carcinoma (n=12), and mucinous carcinoma (n=10) were stained with p16. Cases were scored both with respect to distribution of immunoreactivity (0-5) and intensity (0-3). An immunohistochemical composite score was also calculated (0-15) by multiplying the distribution and intensity scores. Serous carcinomas typically exhibited high p16 expression; there was statistically significant higher p16 expression in serous carcinomas compared with the other morphologic types. There was high p16 and WT1 expression in most undifferentiated carcinomas and in serous carcinomas with clear cells, suggesting that these represent variants of serous carcinoma. We have demonstrated that p16 is highly expressed in high-grade serous and undifferentiated carcinomas compared with other morphologic types of ovarian carcinoma. This may be useful, in conjunction with WT1, in the classification of problematic neoplasms. p16 may be involved in the pathogenesis of high-grade ovarian serous carcinomas, possibly through inactivation of retinoblastoma protein.

An ageing population requires dental professionals to be aware of the oral effects of medications taken by their patients. This case study will present the challenges faced by the hygienist in the oral health management of a 79-year-old medically compromised patient over a 2-year period. The interrelationship between the ageing process, medical conditions and medications taken, and specific treatment modalities are considered.

Stimulation of neutrophils by different factors increases their oxidative activity and the free radicals produced can report on the degree of activation. Poly(adenosine 5'-diphosphate ribose)polymerase-1 (PARP-1), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with ischaemia-reperfusion injury and inflammation. 5-aminoisoquinolin-1-one (5-AIQ) is a potent inhibitor of PARP-1 activity in vitro and in vivo in rats. Acute (80 min) and prolonged (24h) focal cerebral ischaemia was induced in rats by obstruction of the median cerebral artery, with or without reperfusion, with or without administration of 5-AIQ. The oxidative activity of neutrophils was measured by chemiluminescence. Administration of 5-AIQ.HCl (3.0 mg kg(-1) b.w. - i.v.) caused a significant decrease in the oxidative activity of neutrophils in the group which had experienced chronic ischaemia for 24h but had no significant effect in the group which had received 80 min ischaemia, when compared to the control group. Increase of the oxidative activity of neutrophils was confirmed in rats with prolonged cerebral ischaemia, followed by reperfusion. 5-AIQ probably may decrease this activity through inhibition of PARP-1 in focus of local ischaemia as well as hence lowering the expression of inflammatory mediators by activated neutrophils.

Background: Calcifying odontogenic cyst was described first by Gorlin et al. in 1962; since then several hundreds of cases had been reported. In 1981, Praetorius et al. proposed a widely used classification. Afterwards, several authors proposed different classifications and discussed its neoplastic potential. The 2005 WHO Classification of Odontogenic Tumours re-named this entity as calcifying cystic odontogenic tumour (CCOT) and defined the clinico-pathological features of the ghost cell odontogenic tumours, the CCOT, the dentinogenic ghost cell tumour (DGCT) and the ghost cell odontogenic carcinoma (GCOC)., Methods: The aim of this paper was to review the clinical-pathological features of 122 CCOT, DGCT and GCOC cases retrieved from the files of the oral pathology laboratories from 14 institutions in Mexico, South Africa, Denmark, the USA, Brazil, Guatemala and Peru. It attempts to clarify and to group the clinico-pathological features of the analysed cases and to propose an objective, comprehensive and useful classification under the 2005 WHO classification guidelines., Results: CCOT cases were divided into four sub-types: (i) simple cystic; (ii) odontoma associated; (iii) ameloblastomatous proliferating; and (iv) CCOT associated with benign odontogenic tumours other than odontomas. DGCT was separated into a central aggressive DGCT and a peripheral non-aggressive counterpart. For GCOC, three variants were identified. The first reported cases of a recurrent peripheral CCOT and a multiple synchronous, CCOT are included., Conclusions: Our results suggest that ghost cell odontogenic tumours comprise a heterogeneous group of neoplasms which need further studies to define more precisely their biological behaviour.

Tirapazamine (TPZ) and related 1,2,4-benzotriazine 1,4 dioxides (BTOs) are selectively toxic under hypoxia, but their ability to kill hypoxic cells in tumors is generally limited by their poor extravascular transport. Here we show that removing hydrogen bond donors by replacing the 3-NH2 group of TPZ with simple alkyl groups increased their tissue diffusion coefficients as measured in multicellular layer cultures. This advantage was largely retained using solubilizing 3-alkylaminoalkyl substituents provided these were sufficiently lipophilic at pH 7.4. The high reduction potentials of such compounds resulted in rates of metabolism too high for optimal penetration into hypoxic tissue, but electron-donating 6- and 7-substituents moderated metabolism. Pharmacokinetic/pharmacodynamic model-guided screening was used to select BTOs with optimal extravascular transport and hypoxic cytotoxicity properties for evaluation against HT29 human tumor xenografts in combination with radiation. This identified four novel 3-alkyl BTOs providing greater clonogenic killing of hypoxic cells than TPZ at equivalent host toxicity, with the 6-morpholinopropyloxy-BTO 22 being 3-fold more active.

Purpose: This study aimed to develop gene classifiers to predict colorectal cancer recurrence. We investigated whether gene classifiers derived from two tumor series using different array platforms could be independently validated by application to the alternate series of patients., Experimental Design: Colorectal tumors from New Zealand (n = 149) and Germany (n = 55) patients had a minimum follow-up of 5 years. RNA was profiled using oligonucleotide printed microarrays (New Zealand samples) and Affymetrix arrays (German samples). Classifiers based on clinical data, gene expression data, and a combination of the two were produced and used to predict recurrence. The use of gene expression information was found to improve the predictive ability in both data sets. The New Zealand and German gene classifiers were cross-validated on the German and New Zealand data sets, respectively, to validate their predictive power. Survival analyses were done to evaluate the ability of the classifiers to predict patient survival., Results: The prediction rates for the New Zealand and German gene-based classifiers were 77% and 84%, respectively. Despite significant differences in study design and technologies used, both classifiers retained prognostic power when applied to the alternate series of patients. Survival analyses showed that both classifiers gave a better stratification of patients than the traditional clinical staging. One classifier contained genes associated with cancer progression, whereas the other had a large immune response gene cluster concordant with the role of a host immune response in modulating colorectal cancer outcome., Conclusions: The successful reciprocal validation of gene-based classifiers on different patient cohorts and technology platforms supports the power of microarray technology for individualized outcome prediction of colorectal cancer patients. Furthermore, many of the genes identified have known biological functions congruent with the predicted outcomes.

We describe an unusual example of ovarian adenomatoid tumor that was an incidental finding in the ovary of a 52-year-old woman and was characterized by cells with abundant eosinophilic cytoplasm, an occasional feature of the adenomatoid tumor but one that, in an ovarian example, may cause added diagnostic confusion to that already engendered by the rarity of this neoplasm in the ovary. The typical numerous small vacuoles of the neoplasm sometimes had the appearance of signet ring cells. These 2 features (oxyphil and signet ring cells) caused a broad differential. Tumor cells were positive with broad-spectrum cytokeratins as well as mesothelial markers CK5/6, WT1, and calretinin. In reporting this case, we focus on the differential diagnosis of ovarian neoplasms and tumorlike conditions with vacuoles and related spaces, a topic that embraces many diverse entities.

Background: Red blood cell (RBC) transfusions are crucial for the care of very-low-birth-weight (VLBW) infants. These infants frequently require multiple, small-volume RBC transfusions, with potential exposure to multiple donors. Optimal protocols provide dedicated RBC units to reduce exposures and avoid RBC wastage., Study Design and Methods: This study was a retrospective, single-institution review of RBC transfusions in VLBW infants. The RBC volume transfused during the entire hospitalization (VTH) and that transfused at 35 days were determined for all infants, 401 to 1250 g at birth, admitted to a Level III neonatal intensive care unit from January 1, 2000, through December 31, 2002. Multivariable models identified perinatal factors associated with volume transfused., Results: The 640-infant cohort had a median birth weight (BW) of 818 g and gestational age (GA) of 26 weeks. Most infants (546 or 85%) required at least one RBC transfusion. Median number of RBC transfusions was 3 (range, 0-30) and median volume transfused was 82 mL (range, 9-737 mL). Of 328 infants who received all transfusions within a 35-day period, only 5 (1.5%) required at least 200 mL. VTH was inversely related to BW and GA. Multivariable models identified BW, GA, age at first transfusion, and use of inotropes as variables associated with higher volume transfused., Conclusion: Few VLBW infants use an entire RBC unit. One dedicated unit shared by two or more infants should meet their transfusion needs. GA, BW, and markers of illness severity predict increased RBC volume requirements.

Objective: To determine the source of an outbreak of Salmonella javiana infection., Design: Case-control study., Participants: A total of 101 culture-confirmed cases and 540 epidemiologically linked cases were detected between May 26, 2003, and June 16, 2003, in hospital employees, patients, and visitors. Asymptomatic employees who had eaten in the hospital cafeteria between May 30 and June 4, 2003, and had had no gastroenteritis symptoms after May 1, 2003, were chosen as control subjects., Setting: A 235-bed academic tertiary care children's hospital., Results: Isolates from 100 of 101 culture-confirmed cases had identical pulsed-field gel electrophoresis patterns. A foodhandler with symptoms of gastroenteritis was the presumed index subject. In multivariate analysis, case subjects were more likely than control subjects to have consumed items from the salad bar (adjusted odds ratio [aOR], 5.3; 95% confidence interval [CI], 2.3-12.1) and to have eaten in the cafeteria on May 28 (aOR, 9.4; 95% CI, 1.8-49.5), May 30 (aOR, 3.6; 95% CI, 1.0-12.7), and/or June 3 (aOR, 4.0; 95% CI, 1.4-11.3)., Conclusions: Foodhandlers who worked while they had symptoms of gastroenteritis likely contributed to the propagation of the outbreak. This large outbreak was rapidly controlled through the use of an incident command center.

This study utilized a large clinical dataset of patients representative of those in routine U.S. psychiatric practice to assess the influence of sociodemographic variables and diagnostic class on health plan membership (public or private). Data on patients with schizophrenia or other psychotic disorders (n=288) and patients with mood or anxiety disorders (n=1304) were obtained from a cross-sectional practice-based survey conducted by the American Psychiatric Institute for Research and Education. The likelihood of health plan membership was lower among males and among those from a minority race/ethnicity. Health plan membership was also affected by educational attainment and employment status. Even after controlling for these sociodemographic determinants of health plan membership, individuals with schizophrenia/other psychotic disorders were significantly less likely to belong to a health plan than those with mood/anxiety disorders.

This study assesses the feasibility of using a Universal Product Code (UPC) scanner to record the home food inventory of limited-resource families. Feasibility was based on UPC scanner accuracy, time involved, and researcher/study participant feedback. Program staff members completed a traditional line-item inventory and UPC scan of 5,920 food items during 51 separate visits to the homes of 32 families. Foods reported from the UPC scanner were compared with the manual line-item food inventory. The UPC scanner report had an accuracy of 95.6% (5,661/5,920). Further, the UPC scanning technique offered a 31.8% time savings over the traditional line-item inventory approach. The UPC scanner was easy to use and participants reported that scanning food items was non-intrusive. A UPC scanner is a feasible method of recording the home food inventory, and the accuracy and simplicity of this approach can provide useful information on foods available for consumption within a home.

Many children die as a result of abuse and neglect each year. Early recognition and effective intervention are crucial factors in the fight against this. Child mortality rates increased in South Africa between 1998 and 2004, with child abuse deaths constituting part of these statistics. Autopsies on children who have died of unnatural causes are often not specific as to the possibility of child abuse. This article presents the extra-oral and intra-oral signs of child abuse from a study of the autopsies of child mortality cases seen at Salt River Medico-Legal Laboratory in Cape Town from 1998 to 2004 with reference to the South African child mortality rates.

Aims: Pathologists are faced with increasing numbers of endometrial biopsies containing scant tissue. Anecdotal evidence points to significant variation among pathologists regarding criteria used to assess adequacy, and no standard recommendations exist. An initial audit showing variation in endometrial biopsy adequacy reporting prompted this assessment of the criteria used by specialist gynaecological pathologists for the classification of adequacy., Methods: A questionnaire regarding criteria used for endometrial biopsy assessment adequacy was sent to members of the British Association of Gynaecological Pathologists and the National Gynaecological Pathology External Quality Assessment Scheme (UK). One hundred and thirty questionnaires were distributed and 61 pathologists responded., Results: The responses showed great variation in criteria used to classify endometrial biopsies as adequate. Most respondents felt it would be useful if criteria were proposed to aid this assessment., Conclusions: Wide variation exists among specialist gynaecological pathologists regarding what constitutes an adequate endometrial biopsy. The gynaecologist should interpret the biopsy report in the light of clinical, radiological, and hysteroscopic features. The presence of scanty tissue in postmenopausal women with a thin endometrium and no focal lesion is expected, and is not a reason for repeat biopsy. Pathologists should exercise caution before classifying endometrial biopsies as inadequate, because this may have medicolegal and management implications.

Objective: To describe the medical and rehabilitation service use of model systems by brain injured participants 1 to 3 months postdischarge from inpatient rehabilitation., Design: Prospective follow-up study., Setting: Georgia Model Brain Injury System (GAMBIS)., Participants: Seventy-three GAMBIS subjects consenting to participate in the utilization substudy., Main Outcome Measures: Receipt of services and intensity of service use., Analysis: Chi-square analysis of receipt of services by severity of injury., Results: The likelihood of service use did not vary with severity of injury. Data suggest that intensity of service use was a function of injury severity., Conclusions: Subjects with mild and moderate injuries were as likely to use a range of medical and rehabilitation services during the 3-month postdischarge period as those with severe injuries. Traditional rehabilitation services, such as physical therapy, were far more likely to be used, than nontraditional services, such as psychological counseling, in spite of the high level of cognitive and social disability associated with traumatic brain injury.

Aims: The Mirena coil is a levonorgestrel releasing intrauterine device that is in widespread use. This study aims to document the endometrial morphology associated with this device., Methods: Endometrial specimens from 75 women with the Mirena coil were reviewed and the histological features detailed., Results: Morphological features found in most of the endometria were decidualisation of stroma (72 of 75 cases), atrophy of endometrial glands (65 of 75 cases), a surface papillary pattern (38 of 75 cases), and a stromal inflammatory cell infiltrate (59 of 75 cases). Additional common histological features were the presence of foci of stromal myxoid change (29 of 75 cases) and stromal haemosiderin pigment (24 of 75 cases). Reactive atypia of surface glands, glandular metaplastic changes, stromal necrosis, and stromal calcifications were found in small numbers of cases., Conclusion: The endometrial features are characteristic and relatively constant and are in keeping with the effects of both a progestogenic compound and a mechanical device. Pathologists should be aware of these histological features because the Mirena coil is in widespread use.

This study reports on secondary data, depression, fatigue and health-related quality of life (HRQOL), collected on people with advanced multiple sclerosis (MS) as part of a larger study of the impact of a telerehabilitation intervention on people with severe mobility impairment. People with spinal cord injuries (SCIs) (n=111) and the prevention of pressure sores were the primary group of interest of the project. The focus here is on data collected from people with advanced MS (n=27), who were included as an exploratory cohort, as they experience increased risk of pressure ulcer development as their level of mobility declines. The study consisted of a nine-week intervention with three randomized groups: video, telephone, and standard care. Aside from information on pressure sores, data were also collected on fatigue, depression, and HRQOL for a two-year follow-up period. For the video group HRQOL scores trended higher and fatigue and depression scores lower for 24 months. Fatigue scores were significantly lower for the video group at month six, 12, and 18. In the sample overall, fatigue symptoms were far more prominent than depressive symptoms and affected 100% higher rates of depression than women. At baseline, controlling for Extended Disability Status Score (EDSS), depression and fatigue were correlated. However, contrary to indications from previous cross-sectional studies, no consistent relationship was observed over time between the two. Telerehabilitation interventions for people with advanced MS warrant further investigation. Findings here suggest that such interventions may be beneficial, although the results need affirmation through larger samples. In addition, the higher prevalence of male depression merits serious attention.

Part 1 of this two-part article dealt with mass disasters in general, their characteristics and the agencies involved in their management. This part looks at the specific role of the forensic dentist, as well as the general dentist, in a mass disaster as member of an 'away' or 'home' team.

In this article, the first of two on the involvement of dentists in a mass disaster, the focus is primarily on mass disasters in general, some common characteristics and types of disasters, those agencies or individuals involved in the management of a disaster, the different phases of a disaster and the position of the forensic dental identification team (FDIT). Part 2 will deal with the functions, responsibilities and jurisdiction of the FDIT during the various phases of a disaster and more specifically immediately after the disaster.

There has been increasing pressure on farmers in Europe to reduce the emissions of ammonia from their land. Due to the current financial climate in which farmers have to operate, it is important to identify ammonia control measures that can be adopted with minimum cost. The planting of trees around farmland and buildings has been identified as a potentially effective and low-cost measure to enhance ammonia recapture at a farm level and reduce long-range atmospheric transport. This work assesses experimentally what fraction of ammonia farm woodlands could potentially remove from the atmosphere. We constructed an experimental facility in southern Scotland to simulate a woodland shelterbelt planted in proximity to a small poultry unit. By measuring horizontal and vertical ammonia concentration profiles within the woodland, and comparing this to the concentration of an inert tracer (SF6) we estimate the depletion of ammonia due to dry deposition to the woodland canopy. Together with measurements of mean ammonia concentrations and throughfall fluxes of nitrogen, this information is used to provide a first estimate of the fraction of emitted ammonia that is recaptured by the woodland canopy. Analysis of these data give a lower limit of recapture of emitted ammonia, at the experimental facility, of 3%. By careful design of shelterbelt woodlands this figure could be significantly higher.