Assessing pediatric nasal carriage of S. aureus & MRSA

Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) has become an increasing problem in the community. Nasal carriage of these bacteria has been shown to be a predisposing factor for infection and environmental contamination. This serious public health concern prompted an investigation to assess the pediatric nasal carriage of these bacteria in an effort to better understand the populations at risk and prevention of infection.^ This prospective study surveys 30 children from the Northwest Assistance Ministries (NAM) pediatric clinic from October 2008 to the present. Two nasal swabs were taken in 2-4 week intervals to determine S. aureus carrier status. Microbiologic tests were conducted to isolate and identify S. aureus from nasal cultures. Children with 2 cultures positive for S. aureus were classified as persistent carriers, those with 1 positive and 1 negative culture were classified as intermittent carriers, and those with 2 negative cultures were classified as noncarriers. This information was related to patient records and statistical analyses (X 2 and t-tests) were performed.^ Distribution of S. aureus carriage related to patient demographics (age, sex, & race) was showed no significant differences between S. aureus positive and S. aureus negative patient populations (p = 0.8). Additionally, the distribution of carrier status related to demographics also showed no significant difference (p = 0.8). Finally, the distribution of carrier status related to relevant medical history (immunizations current, past infection, & antibiotic use at time of swabbing) showed no significant difference (p = 0.4).^ This study is a snapshot of an ongoing study to assess the pediatric nasal carriage of S. aureus and MRSA. The inability to draw any reliable conclusion from the distribution of data is likely a result of an inadequate samples size. This is one of few studies assessing pediatric nasal carriage of S. aureus and targeting an underrepresented, Hispanic population is especially unique. Continuing this study allows for a better understanding of the epidemiology of this bacterium which will hopefully lead to appropriate interventions thus preventing future S. aureus infections.^

A retrospective analysis of patients referred for tuberculosis testing at Parkland Hospital, Dallas, TX

Tuberculosis (TB) is an infectious disease of great public health importance, particularly to institutions that provide health care to large numbers of TB patients such as Parkland Hospital in Dallas, TX. The purpose of this retrospective chart review was to analyze differences in TB positive and TB negative patients to better understand whether or not there were variables that could be utilized to develop a predictive model for use in the emergency department to reduce the overall number of suspected TB patients being sent to respiratory isolation for TB testing. This study included patients who presented to the Parkland Hospital emergency department between November 2006 and December 2007 and were isolated and tested for TB. Outcome of TB was defined as a positive sputum AFB test or a positive M. tuberculosis culture result. Data were collected utilizing the UT Southwestern Medical Center computerized database OACIS and included demographic information, TB risk factors, physical symptoms, and clinical results. Only two variables were significantly (P<0.05) related to TB outcome: dyspnea (shortness of breath) (P<0.001) and abnormal x-ray (P<0.001). Marginally significant variables included hemoptysis (P=0.06), weight loss (P=0.11), night sweats (P=0.20), history of homelessness or incarceration (P=0.15), and history of positive skin PPD (P=0.19). Using a combination of significant and marginally significant variables, a predictive model was designed which demonstrated a specificity of 24% and a sensitivity of 70%. In conclusion, a predictive model for TB outcome based on patients who presented to the Parkland Hospital emergency department between November 2006 and December 2007 was unsuccessful given the limited number of variables that differed significantly between TB positive and TB negative patients. It is suggested that a future prospective cohort study should be implemented to collect data on TB positive and TB negative patients. It may be possible that a more thorough prospective collection of data may lead to clearer comparisons between TB positive and TB negative patients and ultimately to the design of a more sensitive predictive model for TB outcome. ^

Outcomes associated with chemotherapy in elderly patients with early stage operable breast cancer

Background. Various clinical trials have proved the efficacy of adjuvant chemotherapy in women with breast cancer. Chemotherapy efficacy and guidelines for its use differ by stage of tumor and age of the patient with no clear recommendations for patients aged 70 and above. Objective. To examine the clinical and economic outcomes associated with chemotherapy use in and to examine the disparities in treatment and survival in elderly patients with early stage operable breast cancer by age and axillary node status. Methods. We studied a cohort of 23,110 node positive and 31,572 node negative women aged 65 and over diagnosed with incident American Joint Committee on Cancer (AJCC) stage I, II or IIIa breast cancer between January 1, 1991 and December 31, 2002 using SEER-Medicare data. Total patient costs were estimated using the phase of care approach and adjusted cost estimates were obtained from regression analysis using a 3% discount rate. Cox proportional hazard ratio of mortality was used to determine the effectiveness of chemotherapy. Propensity score approach was also used to minimize the bias associated with receipt of chemotherapy. To assess disparity in treatment, multivariate logistic regression analyses were performed to assess the relative odds of receiving surgery, chemotherapy and radiation after BCS for African Americans compared to Whites. Results. Regression adjusted cost estimates for all node positive patients receiving chemotherapy was approximately $2,300 and was significantly higher (p<0.05) than for patients not receiving chemotherapy. Mortality was significantly lower in node positive and node negative women aged 65-74 years receiving chemotherapy. There was a significant difference between African American and White women in receiving BCS and radiation after BCS; however this difference was explained by patient demographics, tumor characteristics and socioeconomic status (SES). African American node positive women were 21% less likely to receive chemotherapy than White women (OR, 0.79; CI, 0.68-0.92) in multivariate analysis. Conclusion. Chemotherapy is associated with increased survival in patients aged 65-74 and total costs attributable to chemotherapy differ by phase and age of the patient. Underutilization of systemic adjuvant chemotherapy in African American women requires attention and may serve as potential areas for appropriate intervention.^

A STUDY TO INVESTIGATE DIET DIVERSITY AS A NUTRITION ASSESSMENT INSTRUMENT

Nutrient intake and specific food item data from 24-hour dietary recalls were utilized to study the relationship between measures of diet diversity and dietary adequacy in a population of white females of child-bearing age and socioeconomic subgroups of that population. As the basis of the diet diversity measures, twelve food groups were constructed from the 24-hour recall data and the number of unique foods per food group counted and weighted according to specified weighting schemes. Utilizing these food groups, nine diet diversity indices were developed.^ Sensitivity/specificity analysis was used to determine the ability of varying levels of selected diet diversity indices to identify individuals above and below preselected intakes of different nutrients. The true prevalence proportions, sensitivity and specificity, false positive and false negative rates, and positive predictive values observed at the selected levels of diet diversity indices were investigated in relation to the objectives and resources of a variety of nutrition improvement programs. Diet diversity indices constructed from the total population data were evaluated as screening tools for respondent nutrient intakes in each of the socioeconomic subgroups as well.^ The results of the sensitivity/specificity analysis demonstrated that the false positive rate, the false negative rate, or both were too high at each diversity cut-off level to validate the widespread use of any of the diversity indices in the dietary assessment of the study population. Although diet diversity has been shown to be highly correlated with the intakes of a number of nutrients, the diet diversity indices constructed in this study did not adequately represent nutrient intakes in the diet as reported, in this study, intakes as reported in the 24-hour dietary recall. Specific cut-off levels of selected diversity indices might have limited application in some nutrition programs. The results were applicable to the sensitivity/specificity analyses in the socioeconomic subgroups as well as in the total population. ^

THE USE OF ARM CIRCUMFERENCE FOR SIMPLIFIED SCREENING FOR MALNUTRITION BY MINIMALLY TRAINED HEALTH WORKERS

Because of its simplicity and low cost, arm circumference (AC) is being used increasingly in screening for protein energy malnutrition among pre-school children in many parts of the developing world, especially where minimally trained health workers are employed. The objectives of this study were as follows: (1) To determine the relationship of the AC measure with weight for age and weight for height in the detection of malnutrition among pre-school children in a Guatemalan Indian village. (2) To determine the performance of minimally trained promoters under field conditions in measuring AC, weight and height. (3) To describe the practical aspects of taking AC measures versus weight, age and height.^ The study was conducted in San Pablo La Laguna, one of four villages situated on the shores of Lake Atitlan, Guatemala, in which a program of simplified medical care was implemented by the Institute for Nutrition for Central America and Panama (INCAP). Weight, height, AC and age data were collected for 144 chronically malnourished children. The measurements obtained by the trained investigator under the controlled conditions of the health post were correlated against one another and AC was found to have a correlation with weight for age of 0.7127 and with weight for height of 0.7911, both well within the 0.65 to 0.80 range reported in the literature. False positive and false negative analysis showed that AC was more sensitive when compared with weight for height than with weight for age. This was fortunate since, especially in areas with widespread chronic malnutrition, weight for height detects those acute cases in immediate danger of complicating illness or death. Moreover, most of the cases identified as malnourished by AC, but not by weight for height (false positives), were either young or very stunted which made their selection by AC better than weight for height. The large number of cases detected by weight for age, but not by AC (false negative rate--40%) were, however, mostly beyond the critical age period and had normal weight for heights.^ The performance of AC, weight for height and weight for age under field conditions in the hands of minimally trained health workers was also analyzed by correlating these measurements against the same criterion measurements taken under ideally controlled conditions of the health post. AC had the highest correlation with itself indicating that it deteriorated the least in the move to the field. Moreover, there was a high correlation between AC in the field and criterion weight for height (0.7509); this correlation was almost as high as that for field weight for height versus the same measure in the health post (0.7588). The implication is that field errors are so great for the compounded weight for height variable that, in the field, AC is about as good a predictor of the ideal weight for height measure.^ Minimally trained health workers made more errors than the investigator as exemplified by their lower intra-observer correlation coefficients. They consistently measured larger than the investigator for all measures. Also there was a great deal of variability between these minimally trained workers indicating that careful training and followup is necessary for the success of the AC measure.^ AC has many practical advantages compared to the other anthropometric tools. It does not require age data, which are often unreliable in these settings, and does not require sophisticated subtraction and two dimensional table-handling skills that weight for age and weight for height require. The measure is also more easily applied with less disturbance to the child and the community. The AC tape is cheap and not easily damaged or jarred out of calibration while being transported in rugged settings, as is often the case with weight scales. Moreover, it can be kept in a health worker's pocket at all times for continual use in a widespread range of settings. ^

Is H. pylori infection associated with diarrhea in a cohort of 3- to 8-year-old Colombian children?

The Estudio Comunitario sobre la Salud del Niño cohort study followed 326 3- to 8-year-old Colombian children for 4 years to observe the natural history of Helicobacter pylori infection and identify risk factors for acquisition, recurrence and persistence. Acute H. pylori infection during childhood may predispose to other enteric infections and therefore increase the risk of diarrheal disease. This dissertation aimed to estimate the effect of H. pylori infection on the occurrence of diarrhea and parasitic co-infections. The analysis used Generalized Estimating Equations to obtain odds ratios to estimate relative risks for diarrhea and the Zhang-Yu algorithm to estimate relative risks for on parasitic infections. Andersen-Gill models were used to estimate rate ratios for the effect of H. pylori status on the recurrence of parasitic infections. H. pylori status was classified for the entire follow-up duration in 1 of 3 categories: persistently positive, intermittently positive, and persistently negative. Multivariable models included child’s sex, age, symptoms, medication use, and socio-environmental factors. H. pylori infection was weakly and imprecisely associated with diarrheal disease, which occurred at an unexpectedly low frequency in this study. Persistently H. pylori-positive children had a somewhat higher incidence of reported diarrhea than intermittently positive or persistently negative children. Stratified analysis revealed that the presence of specific helminthes modified the effect of persistent H. pylori infection on diarrhea. The incidence of any parasitic infections was higher in children with persistent H. pylori infection relative to those with intermittent or persistently negative status, but this association did not hold when adjusted for the full set of selected covariates. The effects of H. pylori persistent status were similar for the occurrence or recurrence of Giardia duodenalis, Entamoeba histolytica, and Ascaris lumbricoides. These results show that H. pylori frequently co-exists with other parasites in Andean children and suggest that intermittently H. pylori–positive children might be at a lower risk of parasitic infections than persistently positive children. The relationship of H. pylori infection, helminthic infection and diarrheal disease should be further explored in studies that devote more intensive resources to accurate ascertainment of diarrhea.^

Glacier mass balances of Stubacher Sonnblickkees, Hohe Tauern Range, Eastern Alps, Austria, 1958/1959 to 2012/2013

Stubacher Sonnblickkees (SSK) is located in the Hohe Tauern Range (Eastern Alps) in the south of Salzburg Province (Austria) in the region of Oberpinzgau in the upper Stubach Valley. The glacier is situated at the main Alpine crest and faces east, starting at elevations close to 3050 m and in the 1980s terminated at 2500 m a.s.l. It had an area of 1.7 km² at that time, compared with 1 km² in 2013. The glacier type can be classified as a slope glacier, i.e. the relief is covered by a relatively thin ice sheet and there is no regular glacier tongue. The rough subglacial topography makes for a complex shape in the surface topography, with various concave and convex patterns. The main reason for selecting this glacier for mass balance observations (as early as 1963) was to verify on a complex glacier how the mass balance methods and the conclusions - derived during the more or less pioneer phase of glaciological investigations in the 1950s and 1960s - could be applied to the SSK glacier. The decision was influenced by the fact that close to the SSK there was the Rudolfshütte, a hostel of the Austrian Alpine Club (OeAV), newly constructed in the 1950s to replace the old hut dating from 1874. The new Alpenhotel Rudolfshütte, which was run by the Slupetzky family from 1958 to 1970, was the base station for the long-term observation; the cable car to Rudolfshütte, operated by the Austrian Federal Railways (ÖBB), was a logistic advantage. Another factor for choosing SSK as a glaciological research site was the availability of discharge records of the catchment area from the Austrian Federal Railways who had turned the nearby lake Weißsee ('White Lake') - a former natural lake - into a reservoir for their hydroelectric power plants. In terms of regional climatic differences between the Central Alps in Tyrol and those of the Hohe Tauern, the latter experienced significantly higher precipitation , so one could expect new insights in the different response of the two glaciers SSK and Hintereisferner (Ötztal Alps) - where a mass balance series went back to 1952. In 1966 another mass balance series with an additional focus on runoff recordings was initiated at Vernagtfener, near Hintereisferner, by the Commission of the Bavarian Academy of Sciences in Munich. The usual and necessary link to climate and climate change was given by a newly founded weather station (by Heinz and Werner Slupetzky) at the Rudolfshütte in 1961, which ran until 1967. Along with an extension and enlargement to the so-called Alpine Center Rudolfshütte of the OeAV, a climate observatory (suggested by Heinz Slupetzky) has been operating without interruption since 1980 under the responsibility of ZAMG and the Hydrological Service of Salzburg, providing long-term met observations. The weather station is supported by the Berghotel Rudolfshütte (in 2004 the OeAV sold the hotel to a private owner) with accommodation and facilities. Direct yearly mass balance measurements were started in 1963, first for 3 years as part of a thesis project. In 1965 the project was incorporated into the Austrian glacier measurement sites within the International Hydrological Decade (IHD) 1965 - 1974 and was afterwards extended via the International Hydrological Program (IHP) 1975 - 1981. During both periods the main financial support came from the Hydrological Survey of Austria. After 1981 funds were provided by the Hydrological Service of the Federal Government of Salzburg. The research was conducted from 1965 onwards by Heinz Slupetzky from the (former) Department of Geography of the University of Salzburg. These activities received better recognition when the High Alpine Research Station of the University of Salzburg was founded in 1982 and brought in additional funding from the University. With recent changes concerning Rudolfshütte, however, it became unfeasible to keep the research station going. Fortunately, at least the weather station at Rudolfshütte is still operating. In the pioneer years of the mass balance recordings at SSK, the main goal was to understand the influence of the complicated topography on the ablation and accumulation processes. With frequent strong southerly winds (foehn) on the one hand, and precipitation coming in with storms from the north to northwest, the snow drift is an important factor on the undulating glacier surface. This results in less snow cover in convex zones and in more or a maximum accumulation in concave or flat areas. As a consequence of the accentuated topography, certain characteristic ablation and accumulation patterns can be observed during the summer season every year, which have been regularly observed for many decades . The process of snow depletion (Ausaperung) runs through a series of stages (described by the AAR) every year. The sequence of stages until the end of the ablation season depends on the weather conditions in a balance year. One needs a strong negative mass balance year at the beginning of glacier measurements to find out the regularities; 1965, the second year of observation resulted in a very positive mass balance with very little ablation but heavy accumulation. To date it is the year with the absolute maximum positive balance in the entire mass balance series since 1959, probably since 1950. The highly complex ablation patterns required a high number of ablation stakes at the beginning of the research and it took several years to develop a clearer idea of the necessary density of measurement points to ensure high accuracy. A great number of snow pits and probing profiles (and additional measurements at crevasses) were necessary to map the accumulation area/patterns. Mapping the snow depletion, especially at the end of the ablation season, which coincides with the equilibrium line, is one of the main basic data for drawing contour lines of mass balance and to calculate the total mass balance (on a regular-shaped valley glacier there might be an equilibrium line following a contour line of elevation separating the accumulation area and the ablation area, but not at SSK). - An example: in 1969/70, 54 ablation stakes and 22 snow pits were used on the 1.77 km² glacier surface. In the course of the study the consistency of the accumulation and ablation patterns could be used to reduce the number of measurement points. - At the SSK the stratigraphic system, i.e. the natural balance year, is used instead the usual hydrological year. From 1964 to 1981, the yearly mass balance was calculated by direct measurements. Based on these records of 17 years, a regression analysis between the specific net mass balance and the ratio of ablation area to total area (AAR) has been used since then. The basic requirement was mapping the maximum snow depletion at the end of each balance year. There was the advantage of Heinz Slupetzky's detailed local and long-term experience, which ensured homogeneity of the series on individual influences of the mass balance calculations. Verifications took place as often as possible by means of independent geodetic methods, i.e. monoplotting , aerial and terrestrial photogrammetry, more recently also the application of PHOTOMODELLER and laser scans. The semi-direct mass balance determinations used at SSK were tentatively compared with data from periods of mass/volume change, resulting in promising first results on the reliability of the method. In recent years re-analyses of the mass balance series have been conducted by the World Glacier Monitoring Service and will be done at SSK too. - The methods developed at SSK also add to another objective, much discussed in the 1960s within the community, namely to achieve time- and labour-saving methods to ensure continuation of long-term mass balance series. The regression relations were used to extrapolate the mass balance series back to 1959, the maximum depletion could be reconstructed by means of photographs for those years. R. Günther (1982) calculated the mass balance series of SSK back to 1950 by analysing the correlation between meteorological data and the mass balance; he found a high statistical relation between measured and determined mass balance figures for SSK. In spite of the complex glacier topography, interesting empirical experiences were gained from the mass balance data sets, giving a better understanding of the characteristics of the glacier type, mass balance and mass exchange. It turned out that there are distinct relations between the specific net balance, net accumulation (defined as Bc/S) and net ablation (Ba/S) to the AAR, resulting in characteristic so-called 'turnover curves'. The diagram of SSK represents the type of a glacier without a glacier tongue. Between 1964 and 1966, a basic method was developed, starting from the idea that instead of measuring years to cover the range between extreme positive and extreme negative yearly balances one could record the AAR/snow depletion/Ausaperung during one or two summers. The new method was applied on Cathedral Massif Glacier, a cirque glacier with the same area as the Stubacher Sonnblickkees, in British Columbia, Canada. during the summers of 1977 and 1978. It returned exactly the expected relations, e.g. mass turnover curves, as found on SSK. The SSK was mapped several times on a scale of 1:5000 to 1:10000. Length variations have been measured since 1960 within the OeAV glacier length measurement programme. Between 1965 and 1981, there was a mass gain of 10 million cubic metres. With a time lag of 10 years, this resulted in an advance until the mid-1980s. Since 1982 there has been a distinct mass loss of 35 million cubic metres by 2013. In recent years, the glacier has disintegrated faster, forced by the formation of a periglacial lake at the glacier terminus and also by the outcrops of rocks (typical for the slope glacier type), which have accelerated the meltdown. The formation of this lake is well documented. The glacier has retreated by some 600 m since 1981. - Since August 2002, a runoff gauge installed by the Hydrographical Service of Salzburg has recorded the discharge of the main part of SSK at the outlet of the new Unterer Eisboden See. The annual reports - submitted from 1982 on as a contractual obligation to the Hydrological Service of Salzburg - document the ongoing processes on the one hand, and emphasize the mass balance of SSK and outline the climatological reasons, mainly based on the met-data of the observatory Rudolfshütte, on the other. There is an additional focus on estimating the annual water balance in the catchment area of the lake. There are certain preconditions for the water balance equation in the area. Runoff is recorded by the ÖBB power stations, the mass balance of the now approx. 20% glaciated area (mainly the Sonnblickkees) is measured andthe change of the snow and firn patches/the water content is estimated as well as possible. (Nowadays laserscanning and ground radar are available to measure the snow pack). There is a net of three precipitation gauges plus the recordings at Rudolfshütte. The evaporation is of minor importance. The long-term annual mean runoff depth in the catchment area is around 3.000 mm/year. The precipitation gauges have measured deficits between 10% and 35%, on average probably 25% to 30%. That means that the real precipitation in the catchment area Weißsee (at elevations between 2,250 and 3,000 m) is in an order of 3,200 to 3,400 mm a year. The mass balance record of SSK was the first one established in the Hohe Tauern region (and now since the Hohe Tauern National Park was founded in 1983 in Salzburg) and is one of the longest measurement series worldwide. Great efforts are under way to continue the series, to safeguard against interruption and to guarantee a long-term monitoring of the mass balance and volume change of SSK (until the glacier is completely gone, which seems to be realistic in the near future as a result of the ongoing global warming). Heinz Slupetzky, March 2014

Planktonic Foraminifera shell calcification intensity from sediment trap L1/K276 from the Azores Front (2002/2003)

Using shells collected from a sediment trap series in the Madeira Basin, we investigate the effects of seasonal variation of temperature, productivity, and optimum growth conditions on calcification in three species of planktonic Foraminifera. The series covers an entire seasonal cycle and reflects conditions at the edge of the distribution of the studied species, manifesting more suitable growth conditions during different parts of the year. The seasonal variation in seawater carbonate saturation at the studied site is negligible compared to other oceanic regions, allowing us to assess the effect of parameters other than carbonate saturation. Shell calcification is quantified using weight and size of individual shells. The size-weight scaling within each species is robust against changes in environmental parameters, but differs among species. An analysis of the variation in calcification intensity (size-normalized weight) reveals species-specific response patterns. In Globigerinoides ruber (white) and Globigerinoides elongatus, calcification intensity is correlated with temperature (positive) and productivity (negative), whilst in Globigerina bulloides no environmental forcing is observed. The size-weight scaling, calcification intensity, and response of calcification intensity to environmental change differed between G. ruber (white) and G. elongatus, implying that patterns extracted from pooled analyses of these species may reflect their changing proportions in the samples. Using shell flux as a measure of optimum growth conditions, we observe significant positive correlation with calcification intensity in G. elongatus, but negative correlation in G. bulloides. The lack of a consistent response of calcification intensity to optimum growth conditions is mirrored by the results of shell size analyses. We conclude that calcification intensity in planktonic Foraminifera is affected by factors other than carbonate saturation. These factors include temperature, productivity, and optimum growth conditions, but the strength and sign of the relationships differ among species, potentially complicating interpretations of calcification data from the fossil record.

Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3

YY1 is a mammalian zinc-finger transcription factor with unusual structural and functional features. It has been implicated as a positive and a negative regulatory factor that binds to the CCATNTT consensus DNA element located in promoters of many cellular and viral genes. A mammalian cDNA that encodes a YY1-binding protein and possesses sequence homology with the yeast transcriptional factor RPD3 has been identified. A Gal4 DNA binding domain–mammalian RPD3 fusion protein strongly represses transcription from a promoter containing Gal4 binding sites. Association between YY1 and mammalian RPD3 requires a glycine-rich region on YY1. Mutations in this region abolish the interaction with mammalian RPD3 and eliminate transcriptional repression by YY1. These data suggest that YY1 negatively regulates transcription by tethering RPD3 to DNA as a cofactor and that this transcriptional mechanism is highly conserved from yeast to human.

Restricted expression of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma.

Kaposi sarcoma (KS) is the leading neoplasm of HIV-infected patients and is also found in several HIV-negative populations. Recently, DNA sequences from a novel herpesvirus, termed KS-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8) have been identified within KS tissue from both HIV-positive and HIV-negative cases; infection with this agent has been proposed as a possible factor in the etiology or pathogenesis of the tumor. Here we have examined the pattern of KSHV/HHV-8 gene expression in KS and find it to be highly restricted. We identify and characterize two small transcripts that represent the bulk of the virus-specific RNA transcribed from over 120 kb of the KSHV genome in infected cells. One transcript is predicted to encode a small membrane protein; the other is an unusual polyadenylylated RNA that accumulates in the nucleus to high copy number. This pattern of viral gene expression suggests that most infected cells in KS are latently infected, with lytic viral replication likely restricted to a much smaller subpopulation of cells. These findings have implications for the therapeutic utility of currently available antiviral drugs targeted against the lytic replication cycle.

Merkel cell polyomavirus-specific CD8 T cells in Merkel cell carcinoma: T cell receptor diversity & novel immune therapies

Thesis (Ph.D.)--University of Washington, 2016-06

A new confirmatory Neisseria gonorrhoeae real-time PCR assay targeting the porA pseudogene

The Roche Cobas Amplicor system is widely used for the detection of Neisseria gonorrhoeae but is known to cross react with some commensal Neisseria spp. Therefore, a confirmatory test is required. The most common target for confirmatory tests is the cppB gene of N. gonorrhoeae. However, the cppB gene is also present in other Neisseria spp. and is absent in some N. gonorrhoeae isolates. As a result, laboratories targeting this gene run the risk of obtaining both false-positive and false-negative results. In the study presented here, a newly developed N. gonorrhoeae LightCycler assay (NGpapLC) targeting the N. gonorrhoeae porA pseudogene was tested. The NGpapLC assay was used to test 282 clinical samples, and the results were compared to those obtained using a testing algorithm combining the Cobas Amplicor System (Roche Diagnostics, Sydney, Australia) and an in-house LightCycler assay targeting the cppB gene (cppB-LC). In addition, the specificity of the NGpapLC assay was investigated by testing a broad panel of bacteria including isolates of several Neisseria spp. The NGpapLC assay proved to have comparable clinical sensitivity to the cppB-LC assay. In addition; testing of the bacterial panel showed the NGpapLC assay to be highly specific for N. gonorrhoeae DNA. The results of this study show the NGpapLC assay is a suitable alternative to the cppB-LC assay for confirmation of N. gonorrhoeae-positive results obtained with Cobas Amplicor.

The effects of ethanol on PPARS in MCF-7 human breast cancer cells

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors involved in various metabolic diseases. In the liver, PPARα is involved in alcohol metabolism and may lead to the development of alcoholic fatty liver and other alcohol mediated liver injuries. PPARβ modulation by ethanol induces abnormal myelin production by oligodendrocytes. PPARα and PPARβ are PPAR isoforms expressed in the human breast cell lines. Epidemiological studies show a positive correlation between alcohol intake and breast cancer risk, however, the molecular mechanisms involved are unclear. We hypothesized that ethanol would affect the expression and transactivation of human PPAR isoforms in estrogen receptor (ER) positive and ER negative breast cancer cells. Using real time RT-PCR we looked at the transcription of PPAR isoforms in the presence of increasing concentrations of ethanol and saw isoform and time dependent specific effects. Gene reporter assays enabled us to ascertain the effects of ethanol on ligand-mediated activation of human PPARα and PPARβ at concentrations equivalent to both moderate and chronic alcohol consumption. Ethanol differentially blocked the ligand-mediated activation of both PPARα and PPARβ. Since PPARα and PPARβ are involved in the differentiation and proliferation of breast cancer cells, PPARs may be a possible mechanism involved in the effect of ethanol in breast cancer.

O IMPACTO DAS REDES SOCIAIS NA PROFISSÃO DOCENTE

Diante do grande avanço tecnológico e utilização de equipamentos e diversas ferramentas no ensino, além da conectividade a qualquer momento, é possível perceber o grande crescimento do uso das redes sociais tanto pelos alunos como pelos professores. Com este crescimento observa-se uma comunicação mais intensa entre aluno e professor fora do ambiente da sala de aula, principalmente por intermédio das redes sociais, com a comunicação eletrônica envolvendo e-mails, conversas online, trocas de arquivos, fotos, vídeos etc. Considerando essa nova realidade esta pesquisa objetivou investigar se existe um impacto dessa nova forma de comunicação na profissão docente. Nesse contexto, tendo como foco privilegiado o facebook, emergiram alguns questionamentos para análise: essa nova ferramenta auxilia na relação professor-aluno? Ela pode trazer algum impacto positivo e/ou negativo para o professor? Qual a influência do uso dessa rede social nas relações trabalhistas? Sua existência e o seu uso podem influenciar nas decisões da coordenação/direção da escola? O estudo partiu do pressuposto de que as redes sociais exercem impactos positivos e negativos, pois podem se constituir como ferramentas que auxiliam a prática pedagógica. No entanto, no que se refere às relações trabalhistas e também, às relações interpessoais, o professor pode estar vulnerável quanto às suas relações institucionais e profissionais. Fundamentada nas concepções de autores que discorrem sobre a utilização dessas redes, e sobre as características do trabalho frente às novas demandas do capital, a pesquisa de campo, do tipo exploratória, direcionou-se no sentido de identificar esses fatores por meio da análise dos dados investigados com professores que utilizam a rede social facebook. Os resultados confirmaram que há impactos de diversas naturezas no trabalho docente. Esta nova ferramenta, ao mesmo tempo em que pode auxiliar na relação professor-aluno, expõe o docente, e é utilizada, pelas instituições de ensino, como instrumento de controle e de exercício de poder que se refletem nas relações trabalhistas.

How does bureaucracy impact individual creativity? A cross-level investigation of team contextual influences on goal orientation-creativity relationships

Offering important counterpoint to work identifying team influences stimulating creative expression of individual differences in goal orientation, we develop cross-level theory establishing that team bureaucratic practices (centralization and formalization) constrain creative expression. Speaking to the tension between bureaucracy and creativity, findings indicate that this influence is not only negative and that effects of centralization and formalization differ. Surveying 330 employees in 95 teams at the Taiwan Customs Bureau, we found that learning and "performance avoid" goal orientations had, respectively, stronger positive and weaker negative relationships with creativity under low centralization. A "performance- prove" orientation was positively related to creativity under low formalization. © Academy of Management Journal.