Randomized Controlled Trial of a Cohesive Eight-Week Evolution Unit That Incorporates Molecular Genetics and Principles of the Next Generation Science Standards.

In response to calls for curricular materials that integrate molecular genetics and evolution and adhere to the K-12 Next Generation Science Standards (NGSS), the Genetic Science Learning Center (GSLC) at the University of Utah has developed and tested the "Evolution: DNA and the Unity of Life" curricular unit for high school biology. The free, 8-week unit illuminates the underlying role of molecular genetics in evolution while providing scaffolded opportunities to engage in making arguments from evidence and analyzing and interpreting data.  We used a randomized controlled trial design to compare student learning when using the new unit with a condition in which teachers used their typical (NGSS-friendly) units with no molecular genetics. Results from nationwide testing with 38 teachers (19 per condition) and their 2269 students revealed that students who used the GSLC curriculum had significantly greater pre/post gain scores in their understanding of evolution than students in the comparison condition; the effect size was moderate. Further, teacher implementation data suggest that students in the treatment condition had more opportunities to engage in argumentation from evidence and have in-class discussions than students in the comparison classes. We consider study implications for the secondary and postsecondary science education community.

Pattern of failure after adjuvant radiotherapy following extrapleural pneumonectomy of pleural mesothelioma in the SAKK 17/04 trial.

Postoperative radiotherapy after extrapleural pneumonectomy of malignant pleural mesothelioma was investigated in the randomized phase II trial SAKK17/04. The relapse rate within the high and/or low-dose PTV without previous distant failure was 24%, the isolated in-field-relapse rate within the PTVs was 5% and the distant relapse rate outside of the PTVs was 81%. Clinical outcome was mainly determined by distant disease progression outside of the radiation field.

How gender- and violence-related norms affect self-esteem among adolescent refugee girls living in Ethiopia.

BACKGROUND: Evidence suggests adolescent self-esteem is influenced by beliefs of how individuals in their reference group perceive them. However, few studies examine how gender- and violence-related social norms affect self-esteem among refugee populations. This paper explores relationships between gender inequitable and victim-blaming social norms, personal attitudes, and self-esteem among adolescent girls participating in a life skills program in three Ethiopian refugee camps. METHODS: Ordinary least squares multivariable regression analysis was used to assess the associations between attitudes and social norms, and self-esteem. Key independent variables of interest included a scale measuring personal attitudes toward gender inequitable norms, a measure of perceived injunctive norms capturing how a girl believed her family and community would react if she was raped, and a peer-group measure of collective descriptive norms surrounding gender inequity. The key outcome variable, self-esteem, was measured using the Rosenberg self-esteem scale. RESULTS: Girl's personal attitudes toward gender inequitable norms were not significantly predictive of self-esteem at endline, when adjusting for other covariates. Collective peer norms surrounding the same gender inequitable statements were significantly predictive of self-esteem at endline (ß = -0.130; p  =  0.024). Additionally, perceived injunctive norms surrounding family and community-based sanctions for victims of forced sex were associated with a decline in self-esteem at endline (ß = -0.103; p  =  0.014). Significant findings for collective descriptive norms and injunctive norms remained when controlling for all three constructs simultaneously. CONCLUSIONS: Findings suggest shifting collective norms around gender inequity, particularly at the community and peer levels, may sustainably support the safety and well-being of adolescent girls in refugee settings.

Latent class analysis of violence against adolescents and psychosocial outcomes in refugee settings in Uganda and Rwanda.

BACKGROUND: Little is known about violence against children in refugee camps and settlements, and the evidence-base concerning mental health outcomes of youth in refugee settings in low and middle-income countries is similarly small. Evidence is needed to understand patterns of violence against children in refugee camps, and associations with adverse mental health outcomes. METHODS: Surveys were conducted with adolescent refugees (aged 13-17) in two refugee contexts - Kiziba Camp, Rwanda (n = 129) (refugees from Democratic Republic of Congo) and Adjumani and Kiryandongo refugee settlements, Uganda (n = 471) (refugees from South Sudan). Latent Class Analysis was utilized to identify classes of violence exposure (including exposure to witnessing household violence, verbal abuse, physical violence and sexual violence). Logistic regressions explored the association between latent class of violence exposure and symptoms of depression and anxiety. RESULTS: In Rwanda, a two-class solution was identified, with Class 1 (n = 33) representing high levels of exposure to violence and Class 2 (n = 96) representing low levels of exposure. In Uganda, a three-class solution was identified: Class 1 (high violence; n = 53), Class 2 (low violence, n = 100) and Class 3 (no violence, n = 317). Logistic regression analyses indicated that latent violence class was associated with increased odds of high anxiety symptoms in Rwanda (AOR 3.56, 95% CI 1.16-0.95), and high v. no violence class was associated with depression (AOR 3.97, 95% CI 1.07-7.61) and anxiety symptoms (AOR 2.04, 95% CI 1.05-3.96) in Uganda. CONCLUSIONS: The present results support the existing evidence-base concerning the association between violence and adverse mental health outcomes, while identifying differences in patterns and associations between refugee youth in two different contexts.

The effect of gender norms on the association between violence and hope among girls in the Democratic Republic of the Congo.

BACKGROUND: Girls at early stages of adolescence are vulnerable to violence victimization in humanitarian contexts, but few studies examine factors that affect girls' hope in these settings. We assessed attitudes toward traditional gender norms as an effect modifier of the relationship between violence exposure and future orientation in displaced girls. METHODS: Secondary analysis, using multivariable regression of cross-sectional data from girls ages 10-14 in South Kivu, Democratic Republic of the Congo. Key variables of interest were attitudes toward intimate partner violence (IPV), Children's Hope Scale (CHS) score, and exposure to physical, emotional, and sexual violence within the last 12 months. Additional covariates included age, educational status, and territory. RESULTS: The interaction of exposure to violence and attitudes toward IPV magnified the association between violence exposure and lower CHS score for physical violence (ß = -0.09, p = 0.040) and unwanted sexual touching (ß = -0.20, p = 0.003) among girls age 10-14, when adjusting for other covariates. The interaction of exposure to violence and attitudes toward IPV magnified the association between violence exposure and lower CHS score for forced sex (ß = -0.22, p = 0.016) among girls age 13-14, when adjusting for covariates. Findings for emotional violence, any form of sexual violence, and coerced sex trended toward lower CHS scores for girls who reported higher acceptance of IPV, but did not reach significance. CONCLUSIONS: Findings support the utility of gender norms-transformative programming in increasing resilience of girls who have experienced sexual violence in humanitarian contexts.

Building better bones in childhood: a randomized controlled study to test the efficacy of a dietary intervention program to increase calcium intake.

BACKGROUND/OBJECTIVES: Many children do not consume the recommended daily allowance of calcium. Inadequate calcium intake in childhood may limit bone accrual. The objective of this study was to determine if a behavioral modification and nutritional education (BM-NE) intervention improved dietary calcium intake and bone accrual in children. SUBJECTS/METHODS: 139 (86 female) healthy children, 7-10 years of age, were enrolled in this randomized controlled trial conducted over 36 months. Participants randomized to the BM-NE intervention attended five sessions over a 6-week period designed to increase calcium intake to 1500 mg/day. Participants randomized to the usual care (UC) group received a single nutritional counseling session. The Calcium Counts Food Frequency Questionnaire was used to assess calcium intake; dual energy X-ray absorptiometry was used to assess areal bone mineral density (aBMD) and bone mineral content (BMC). Longitudinal mixed effects models were used to assess for an effect of the intervention on calcium intake, BMC and aBMD. RESULTS: BM-NE participants had greater increases in calcium intake that persisted for 12 months following the intervention compared with UC. The intervention had no effect on BMC or aBMD accrual. Secondary analyses found a negative association between calcium intake and adiposity such that greater calcium intake was associated with lesser gains in body mass index and fat mass index. CONCLUSIONS: A family-centered BM-NE intervention program in healthy children was successful in increasing calcium intake for up to 12 months but had no effect on bone accrual. A beneficial relationship between calcium intake and adiposity was observed and warrants future study.

Physiological history may mask the inherent inducible desiccation tolerance strategy of the desert moss Crossidium crassinerve.

Shoots of bryophytes collected in the desiccated state from the field are likely to be hardened to desiccation tolerance (DT) to varying degrees. To account for this, most studies on DT include a relatively short deacclimation period. However, no study has experimentally determined the appropriate deacclimation time for any bryophyte species. Our purposes are to (i) determine if 'field effects' are biologically relevant to DT studies and how long a deacclimation period is required to remove them; and (ii) utilise field versus cultured shoot responses within the context of a deacclimation period to elucidate the ecological strategy of DT. Our hypothesis (based on an extensive literature on DT) is that a deacclimation period from 24 to 72 h should be sufficient to eliminate historical stress effects on the physiology of the shoots and allow an accurate determination of the inherent ecological DT strategy (constitutive or inducible). We determined, however, using chlorophyll fluorescence and visual estimates of shoot damage, that field-collected shoots of the desert moss Crossidium crassinerve required an experimental deacclimation period of >7 days before field effects were removed, and revealed an ecological DT strategy of inducible DT. If the deacclimation period was <6 days, the shoot response conformed to an ecological strategy of constitutive protection. Thus the presence of field effects can obscure the ecological strategy of desiccation tolerance exhibited by the species, and this translates into a need to re-evaluate previous mechanistic and ecological studies of desiccation tolerance in plants.

Prevalence and molecular epidemiology of Staphylococcus aureus in Swedish nursing homes - as revealed in the SHADES study.

SUMMARY: Knowledge of carriage and population dynamics of Staphylococcus aureus is crucial for infection risk assessment and to reveal transmission patterns of strains. We report the prevalence and molecular epidemiology of S. aureus in elderly people (n = 290) living in nursing homes in three cities in the south of Sweden. The overall carriage prevalence rate was 48% when results from nares (31%) and throat (34%) samples were combined. Common spa types were equally distributed but a frequent type, t160, was found only in one of the regions. Carriage of different spa types was detected in 23% of individuals and antimicrobial resistance rates were higher in S. aureus isolates from those carrying more than one spa type. Five of the 21 individuals who carried different spa types were colonized simultaneously with resistant and non-resistant strains. Seventeen per cent of the individuals carried S. aureus of the same spa type on all occasions. Methicillin resistance was not detected. In conclusion we found a high prevalence of S. aureus in this elderly population with a high rate of dual colonization with different spa types. We also found signs of institutional spread of one strain.

A recommendation to perform a blood culture before the administration of intravenous antibiotics increased the detection of Staphylococcus aureus bacteremia.

In 2004, the Surviving Sepsis Campaign was launched to increase awareness and improve the outcome of severe sepsis. Accordingly, in Jönköping County, Sweden, a strong recommendation to perform a blood culture before the start of intravenous antibiotic treatment was introduced in 2007. Moreover, a reminder was included in the laboratory report to consult an infectious disease specialist when Staphylococcus aureus was isolated from a blood culture. Retrospectively, patients with at least one blood culture growing S. aureus during 2002 through 2003 (pre intervention n = 58) or during 2008 through 2009 (post intervention n = 100) were included. Medical records were evaluated regarding clinical data and outcome. Blood culture isolates were characterized by antibiotic susceptibility testing (AST) and S. aureus protein A (spa) gene typing. The annual incidence of S. aureus bacteremia (SAB) increased from 28 per 100,000 inhabitants at the pre intervention period to 45 per 100,000 at the post intervention period (p = 0.046). During post intervention, the SAB incidence was significantly higher in men (p = 0.009). The mortality rate during hospital stay was 14 % during pre intervention and 18 % during post intervention (p = 0.47). The most common spa types were t012 and t084. The Surviving Sepsis Campaign resulted in an increased number of detected cases of SAB. The mortality rate was the same before and after the intervention, and no spa type correlated to certain clinical manifestations or mortality.

Nucleolar NF-κB/RelA mediates apoptosis by causing cytoplasmic relocalization of nucleophosmin.

In a number of contexts, and particularly in response to cellular stress, stimulation of the NF-kappaB (NF-κB) pathway promotes apoptosis. One mechanism underlying this pro-apoptotic activity is nucleolar sequestration of RelA, which is reported to cause cell death by repressing NF-κB-driven transcription. Here, we identify a novel and distinct nucleolar activity of RelA that induces apoptosis. We demonstrate, using a viral nucleolar localization signal (NoLS)-RelA fusion protein, that direct targeting of RelA to the nucleolus mediates apoptosis, independent of NF-κB transcriptional activity. We demonstrate a requirement for nucleophosmin (NPM, B23.1) in this apoptotic effect, and the apoptotic effect of stress-induced nucleolar RelA. We show by multiple approaches that nucleolar translocation of RelA is causally involved in the relocalization of NPM from the nucleolus to the cytoplasm and that RelA-induced cytoplasmic NPM mediates apoptosis by facilitating the mitochondrial accumulation of BAX. These data uncover a novel stress-response pathway and mechanism by which RelA promotes apoptosis, independent of its effects on NF-κB transcriptional activity. These findings are relevant to the design of novel anticancer agents that target RelA to this compartment.

Measuring violence against women amidst war and displacement in northern Uganda using the "neighbourhood method".

BACKGROUND: Gender-based violence is viewed as a significant problem in conflict-affected regions throughout the world. However, humanitarian organizations typically have been unable to reliably estimate the incidence of rape, intimate partner violence and other forms of sexual abuse in such settings. Such estimates are required to inform programming in contexts such as northern Uganda. METHODS: We sought to establish incidence rates for gender-based violence in internally-displaced-persons camps in northern Uganda. The assessments involved a "neighbourhood methodology," in which adult female heads of household reported about their own, their sisters' and their neighbours' experiences. 299 households were selected for interview across four camps by using systematic random sampling. FINDINGS: Interviews were completed by 204 respondents (5 women having declined interview and 90 not having been successfully contacted). These respondents reported on themselves, a total of 268 sisters and 1206 neighbours. Reports with respect to these alternative populations produced estimates of overall incidence of intimate partner violence in the past year of 51.7% (95% CI 44.8 to 58.7; respondents), 44.0% (95% CI 41.2 to 46.9; respondents' sisters) and 36.5% (95% CI 30.7 to 42.3; respondents' neighbours). In the same period, estimates of incidence of forced sex by husbands were 41.0% (95% CI 34.2% to 47.8%), 22.1% (95% CI 17.0 to 27.2) and 25.1% (95% CI 22.5 to 27.6), respectively, with incidence of rape by a perpetrator other than an intimate partner estimated at 5.0% (95% CI 2.0% to 8.0%), 4.2% (95% CI 1.8 to 6.6) and 4.3% (95% CI 3.1 to 5.5), respectively. INTERPRETATION: Gender-based violence-particularly intimate partner violence-is commonplace in postconflict Uganda. The neighbourhood method provides a promising approach to estimating human right violations in humanitarian settings.

Outbreaks of noroviral gastroenteritis in Florida, 2006-2007.

Noroviruses are an important cause of sporadic cases and outbreaks of acute gastroenteritis. During 2006-2007, widespread increases in acute gastroenteritis outbreaks consistent with norovirus were observed in the United States. We conducted a statewide survey to characterize norovirus outbreak activity in Florida during a 1-year period. From July 2006 to June 2007, 257 outbreaks of norovirus gastroenteritis were identified in 39 of Florida's 67 counties. About 44% of outbreaks were laboratory confirmed as norovirus and 93% of these were due to genogroup GII. About 63% of outbreaks occurred in long-term care facilities and 10% of outbreaks were classified as foodborne. The median number of ill persons per outbreak was 24, with an estimated total of 7880 ill persons. During the study period, norovirus outbreak activity in Florida was widespread, persistent, and consistent with increased activity observed in other parts of the country.

The proapoptotic effects of sulindac, sulindac sulfone and indomethacin are mediated by nucleolar translocation of the RelA(p65) subunit of NF-kappaB.

Understanding the mechanisms that underlie the antitumour activity of non-steroidal anti-inflammatory drugs (NSAIDs) against colorectal cancer will allow the development of more effective and specific chemopreventative agents. Modulation of the NF-kappaB pathway has been implicated as a key effector of the antitumour effect of aspirin, but the effects of non-aspirin NSAIDs on this pathway have yet to be fully defined. Here, we demonstrate that sulindac, sulindac sulfone and indomethacin activate the NF-kappaB pathway in colorectal cancer cells, as determined by western blot analysis of cytoplasmic levels of IkappaBalpha and immunocytochemical analysis of nuclear NF-kappaB/RelA. Furthermore, we show that all of these NSAIDs induce nucleolar translocation of the RelA subunit of NF-kappaB. Using RelA deleted for the previously described nucleolar localization signal, we demonstrate that this response is causally involved in the apoptotic effects of these agents. Finally, we demonstrate that NSAID-mediated nucleolar translocation of RelA is associated with downregulation of NF-kappaB-driven transcription and of the NF-kappaB target gene, ICAM-1. These data identify nucleolar translocation of RelA and the associated repression of the NF-kappaB-driven transcription as a central molecular mechanism of NSAID-mediated growth inhibition and apoptosis. As well as providing new understanding of the molecular determinants of RelA function, these findings also have relevance to the development of novel chemotherapeutic and chemopreventative agents.

A nucleic acid sequence-based amplification assay for real-time detection of norovirus genogroup II.

AIMS: To use molecular beacon based nucleic acid sequence-based amplification (NASBA) to develop a rapid, sensitive, specific detection method for norovirus (NV) genogroupII (GII). METHODS AND RESULTS: A method to detect NV GII from environmental samples using real-time NASBA was developed. This method was routinely sensitive to 100 copies of target RNA and intermittent amplification occurred with as few as 10 copies. Quantitative estimates of viral load were possible over at least four orders of magnitude. CONCLUSIONS: The NASBA method described here is a reliable and sensitive assay for the detection of NV. This method has the potential to be linked to a handheld NASBA device that would make this real-time assay a portable and inexpensive alternative to bench-top, lab-based assays. SIGNIFICANCE AND IMPACT OF THE STUDY: The development of the real-time NASBA assay described here has resulted in a simple, rapid (<1 h), convenient testing format for NV. To our knowledge, this is the first example of a molecular beacon based NASBA assay for NV.

Infection of human endothelial cells with Staphylococcus aureus induces transcription of genes encoding an innate immunity response.

Staphylococcus aureus is a gram-positive bacterium frequently isolated from patients with bloodstream infections. Endothelial cells (EC) play an important role in host defence against bacteria, and recent reports have shown that infection of EC with S. aureus induces expression of cytokines and cell surface receptors involved in activating the innate immune response. The ability of S. aureus to invade nonphagocytic cells, including EC, has been documented. However, the knowledge of the role of EC in pathogenesis of S. aureus infection is still limited. In this study, we investigate the gene-expression program in human EC initiated by internalized S. aureus, using microarray analysis. We found 156 genes that were differentially regulated at least threefold, using arrays representing 14,239 genes. Many of the upregulated genes code for proteins involved in innate immunity, such as cytokines, chemokines and cell adhesion proteins. Other upregulated genes encode proteins involved in antigen presentation, cell signalling and metabolism. Furthermore, intracellular bacteria survived for days without inducing EC death.

Aspirin-induced nuclear translocation of NFkappaB and apoptosis in colorectal cancer is independent of p53 status and DNA mismatch repair proficiency.

Substantial evidence indicates nonsteroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer (CRC). However, the molecular basis for this anti-tumour activity has not been fully elucidated. We previously reported that aspirin induces signal-specific IkappaBalpha degradation followed by NFkappaB nuclear translocation in CRC cells, and that this mechanism contributes substantially to aspirin-induced apoptosis. We have also reported the relative specificity of this aspirin-induced NFkappaB-dependent apoptotic effect for CRC cells, in comparison to other cancer cell types. It is now important to establish whether there is heterogeneity within CRC, with respect to the effects of aspirin on the NFkappaB pathway and apoptosis. p53 signalling and DNA mismatch repair (MMR) are known to be deranged in CRC and have been reported as potential molecular targets for the anti-tumour activity of NSAIDs. Furthermore, both p53 and MMR dysfunction have been shown to confer resistance to chemotherapeutic agents. Here, we set out to determine the p53 and hMLH1 dependency of the effects of aspirin on NFkappaB signalling and apoptosis in CRC. We specifically compared the effects of aspirin treatment on cell viability, apoptosis and NFkappaB signalling in an HCT-116 CRC cell line with the p53 gene homozygously disrupted (HCT-116(p53-/-)) and an HCT-116 cell line rendered MMR proficient by chromosomal transfer (HCT-116(+ch3)), to the parental HCT-116 CRC cell line. We found that aspirin treatment induced apoptosis following IkappaBalpha degradation, NFkappaB nuclear translocation and repression of NFkappaB-driven transcription, irrespective of p53 and DNA MMR status. These findings are relevant for design of both novel chemopreventative agents and chemoprevention trials in CRC.

Evidence for colorectal cancer cell specificity of aspirin effects on NF kappa B signalling and apoptosis.

Epidemiological evidence indicates that non-steroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer (CRC) to a greater degree than other non-gastrointestinal cancers, but the molecular basis for this difference is unknown. We previously reported that aspirin induces signal-specific I kappa B alpha degradation followed by NF kappa B nuclear translocation in CRC cells, and that this mechanism contributes substantially to aspirin-induced apoptosis. Here, we explored the hypothesis that cell-type specific effects on NF kappa B signalling are responsible for the observed differences in protection by aspirin against CRC compared to breast and gynaecological cancers. We also assessed whether COX-2 expression, mutation status of adenomatous polyposis coli (APC), beta-catenin, p53, or DNA mismatch repair (MMR) genes in CRC lines influenced aspirin-induced effects. We found that aspirin induced concentration-dependent I kappa B alpha degradation, NF kappa B nuclear translocation and apoptosis in all CRC lines studied. However, there was no such effect on the other cancer cell types, indicating a considerable degree of cell-type specificity. The lack of effect on NF kappa B signalling, paralleled by absence of an apoptotic response to aspirin in non-CRC lines, strongly suggests a molecular rationale for the particular protective effect of NSAIDs against CRC. Effects on NF kappa B and apoptosis were observed irrespective of COX-2 expression, or mutation status in APC, beta-catenin, p53 and DNA MMR genes, underscoring the generality of the aspirin effect on NF kappa B in CRC cells. These findings raise the possibility of cell-type specific targets for the development of novel chemopreventive agents.

Suppression of intestinal and mammary neoplasia by lifetime administration of aspirin in Apc(Min/+) and Apc(Min/+), Msh2(-/-) mice.

Numerous studies have indicated that exposure to nonsteroidal anti-inflammatory drugs is associated with a lowered risk of colorectal cancer. However, analyses of the effect of aspirin upon tumorigenesis in Apc(Min/+) mice have yielded contrasting results. We show that adult dietary exposure to aspirin does not suppress intestinal tumorigenesis in Apc(Min/+) mice, but that continual exposure from the point of conception does. To test whether this regime could suppress the phenotype of murine models of hereditary nonpolyposis colorectal cancer, Msh2-deficient mice were exposed to aspirin. This did not modify the mutator phenotype of Msh2(-/-) mice, but weakly extended survival. Finally, we analyzed (Apc(Min/+), Msh2(-/-)) mice and found that lifetime aspirin exposure significantly delayed the onset of both intestinal and mammary neoplasia. Thus embryonic and perinatal exposure to aspirin suppresses neoplasia specifically associated with the loss of Apc function, opening a potential window of opportunity for nonsteroidal anti-inflammatory drug intervention.

Accommodation and the Stiles-Crawford effect: theory and a case study.

PURPOSE: Fincham (The accommodation reflex and its stimulus. Br. J. Ophthalmol. 35, 381-393) was the first to suggest that the Stiles-Crawford effect (Type I) might provide a stimulus for accommodation, but the possibility has not been investigated experimentally. The present paper outlines a theoretical basis for such a mechanism, and includes a case study on a subject with a nasally decentred Stiles-Crawford (S-C) function. METHODS: Accommodation to a monochromatic sine grating was monitored continuously with the natural S-C function intact, or with apodising filters imaged in the subject's pupil to neutralise, reverse or double the natural S-C function. RESULTS: Mean accommodative gain was not reduced significantly when the normal S-C function was either neutralised or reversed. CONCLUSIONS: For the present subject, the average S-C effect does not mediate the accommodation response to defocus, but more subjects should be examined. Other methods by which directionally sensitive cone receptors could detect light vergence are discussed.