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Background Hirschsprung disease is one of the most common congenital anomalies that affects colorectal function. Rectal biopsy demonstrating the absence of ganglion cells in the affected bowel is the gold standard for diagnosis. Suction and incisional rectal biopsies are appropriate methods for obtaining diagnostic tissue. The goal of this study is to determine if any differences in adequacy exist between suction and incisional rectal biopsies at our institution. Methods We conducted a retrospective review of suction and incisional rectal biopsies for inadequacy per procedure at a tertiary pediatric hospital. Each procedure for rectal biopsy was also evaluated by number of biopsies per procedure. We used two-sample test of proportions to compare inadequacy of suction vs. incisional biopsies. Results 133 rectal suction biopsy procedures (227 biopsies) and 125 incisional biopsy procedures (140 biopsies) were analyzed. In patients 6 months of age and older, the percentage of inadequate procedures was substantially higher in the suction biopsy group (24.1% vs 0.9%, p

OBJECTIVE: In Adolescents and Young Adults (AYAs) with cancer, we examined (1) the distribution and type of traumatic events (TEs) experienced prior to baseline assessment and (2) how a resilience intervention, Promoting Resilience in Stress Management (PRISM), impacted changes in patient-reported outcomes (PROs) for AYAs with and without TEs. METHODS: AYAs (12–25 years) within 1–10 weeks of diagnosis of new malignancy or ever diagnosed with advanced cancer were enrolled and randomly assigned to Usual Care (UC) with or without PRISM. To assess TEs, we screened medical records for traditionally-defined Adverse Childhood Experiences (ACEs) and medical traumatic events. Age-validated PROs assessed resilience, benefit-finding, hope, generic health-related quality of life (QoL), cancer-specific QoL, depression, and anxiety at enrollment and 6-months later. We calculated effect sizes (Cohen’s d) for PRISM vs UC effect on PRO-score change at 6-months for 1+ TEs and 0 TE groups. RESULTS: Ninety-two AYAs enrolled and completed baseline surveys (44-UC, 48-PRISM; N=74 at 6-months, 38-UC, 36-PRISM); 60% experienced 1+ TEs. PROs at baseline were similar across groups. PRISM’s effect on score-change was greater (Cohen’s d ≥ 0.5) for the 1+ TE group on domains of benefit-finding and hope; and similar (d < 0.5) on domains of resilience, depression, anxiety, and both generic and cancer-specific QoL. CONCLUSIONS: In AYAs with cancer, TEs occurred at similar rates as the general population. PRISM may be particularly helpful for improving benefit-finding and hope for those who have experienced TEs.

Negative genital self-perceptions or female genital self-image (FGSI) is a prevalent concern for women. This is a significant problem in and of itself but also because it is associated with a variety of negative outcomes including less frequent sexual behavior, more negative cognitive-affective sexual responses, and poorer decision-making about genital health. This study examined the extent to which various psychosocial factors are associated with more negative FGSI. Two hundred cisgender women with diverse ages and relationship statuses completed an online survey that included measures of sexual health education (quality of school-based sexual health education (SHE), female genital knowledge), pornography use, sexual experiences (positive and negative partner genital feedback, frequency of sexual activity), and cognitive-affect appraisals (body image, sexual comfort). Social desirability, cognitive-affective appraisals, sexual experiences, and SHE were associated with FGSI at the bivariate level. The results of a multiple regression analysis indicated that only sexual comfort, body image, and positive genital feedback contributed uniquely to the prediction of FGSI. The results are interpreted in terms of the importance of the psychosocial context for understanding women’s genital self-perceptions as well as their implications for prevention and intervention strategies aimed at addressing the problem.

In this study, students enrolled in a basic physics class participated in one of the online citizen science projects available on the Zooniverse website (www.zooniverse.org) as a homework assignment. They then wrote a 300–500-word reflection about their experience addressing several questions given as prompts. The analysis of the responses showed that a majority of the students enjoyed the experience saying that it was interesting, fun, and accessible. Many responses described a part of their science ideas that were either confirmed or changed by the experience. The science ideas included statements about looking for correlations among many data, the need to observe these data in order to find correlations, and the inherent uncertainty of the task and the data themselves. The ideas about science and scientific research expressed were in line with a competent view of science (Lederman, Handbook of Research on Science Education, 2, 831–879, Lederman, 2007; McComas et al., Science & Education, 7(6), 511–532, McComas, Almazroa & Clough, 1998). The insight given by this study is that participation in a citizen science project can be educationally beneficial in learning about aspects of the nature of science.

DNA repair is essential to prevent the cytotoxic or mutagenic effects of various types of DNA lesions, which are sensed by distinct pathways to recruit repair factors specific to the damage type. Although biochemical mechanisms for repairing several forms of genomic insults are well understood, the upstream signalling pathways that trigger repair are established for only certain types of damage, such as double-stranded breaks and interstrand crosslinks. Understanding the upstream signalling events that mediate recognition and repair of DNA alkylation damage is particularly important, since alkylation chemotherapy is one of the most widely used systemic modalities for cancer treatment and because environmental chemicals may trigger DNA alkylation. Here we demonstrate that human cells have a previously unrecognized signalling mechanism for sensing damage induced by alkylation. We find that the alkylation repair complex ASCC (activating signal cointegrator complex) relocalizes to distinct nuclear foci specifically upon exposure of cells to alkylating agents. These foci associate with alkylated nucleotides, and coincide spatially with elongating RNA polymerase II and splicing components. Proper recruitment of the repair complex requires recognition of K63-linked polyubiquitin by the CUE (coupling of ubiquitin conjugation to ER degradation) domain of the subunit ASCC2. Loss of this subunit impedes alkylation adduct repair kinetics and increases sensitivity to alkylating agents, but not other forms of DNA damage. We identify RING finger protein 113A (RNF113A) as the E3 ligase responsible for upstream ubiquitin signalling in the ASCC pathway. Cells from patients with X-linked trichothiodystrophy, which harbour a mutation in RNF113A, are defective in ASCC foci formation and are hypersensitive to alkylating agents. Together, our work reveals a previously unrecognized ubiquitin-dependent pathway induced specifically to repair alkylation damage, shedding light on the molecular mechanism of X-linked trichothiodystrophy.

Human-driven global change is causing ongoing declines in biodiversity worldwide. In order to address these declines, decision-makers need accurate assessments of the status of and pressures on biodiversity. However, these are heavily constrained by incomplete and uneven spatial, temporal and taxonomic coverage. For instance, data from regions such as Europe and North America are currently used overwhelmingly for large-scale biodiversity assessments due to lesser availability of suitable data from other, more biodiversity-rich, regions. These data-poor regions are often those experiencing the strongest threats to biodiversity, however. There is therefore an urgent need to fill the existing gaps in global biodiversity monitoring. Here, we review current knowledge on best practice in capacity building for biodiversity monitoring and provide an overview of existing means to improve biodiversity data collection considering the different types of biodiversity monitoring data. Our review comprises insights from work in Africa, South America, Polar Regions and Europe; in government-funded, volunteer and citizen-based monitoring in terrestrial, freshwater and marine ecosystems. The key steps to effectively building capacity in biodiversity monitoring are: identifying monitoring questions and aims; identifying the key components, functions, and processes to monitor; identifying the most suitable monitoring methods for these elements, carrying out monitoring activities; managing the resultant data; and interpreting monitoring data. Additionally, biodiversity monitoring should use multiple approaches including extensive and intensive monitoring through volunteers and professional scientists but also harnessing new technologies. Finally, we call on the scientific community to share biodiversity monitoring data, knowledge and tools to ensure the accessibility, interoperability, and reporting of biodiversity data at a global scale.

Effects of withdrawal from ethanol drinking in chronic intermittent ethanol vapor (CIE)-exposed dependent rats and air-exposed nondependent rats on proliferation and survival of progenitor cells in the hippocampus and the medial prefrontal cortex (mPFC) were investigated. Rats were injected with 5′-Bromo 2-deoxyuridine 72 h post-CIE to measure proliferation (2 h-old cells) and survival (29-day-old cells) of progenitors born during a time-point previously reported to elicit a proliferative burst in the hippocampus. Hippocampal and mPFC brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B receptor (TrkB) expression were measured 3 h or 21d post-CIE to evaluate neurotrophic signaling during a time point preceding the proliferative burst and survival of newly born progenitors. CIE rats demonstrated elevated drinking compared to nondependent rats and CIE rats maintained elevated drinking following protracted abstinence. Withdrawal from CIE increased BDNF levels in the hippocampus and mPFC, and subsequently increased proliferation in the hippocampus and mPFC compared to nondependent rats and controls. Protracted abstinence from CIE reduced BDNF expression to control levels, and subsequently reduced neurogenesis compared to controls and nondependent rats in the hippocampus. In the mPFC, protracted abstinence reduced BDNF expression to control levels, whereas increased oligodendrogenesis in dependent rats compared to nondependent rats and controls. These results suggest a novel relationship between BDNF and progenitors in the hippocampus and mPFC, in which increased ethanol drinking may alter hippocampal and cortical function in alcohol dependent subjects by altering the cellular composition of newly born progenitors in the hippocampus and mPFC.

The peroxisome proliferator activated receptor-gamma (PPARG) is a nuclear receptor that regulates adipocyte differentiation, insulin sensitivity and lipid metabolism, thus, it represents a good candidate gene for non-alcoholic fatty liver disease (NAFLD).We investigated the association of two PPARG variants (Pro12Ala and C1431T) with NAFLD and its histological features. DNA was extracted from 274 archived, formalin-fixed liver biopsy specimens from 212 patients with NAFLD and 62 controls with normal liver histology.Individual SNPs did not show significant association with NAFLD or its histological features. A haplotype comprised of both minor alleles (GT) was less enriched whereas a haplotype comprised of the two major alleles (CC) was more enriched in subjects with NAFLD compared to controls [9.3% vs. 28.1% for GT (P = 0.001, OR 0.26 (range 0.14-0.48) and 80.4% vs. 64.8% for CC (P = 0.037, OR 2.23 (range 1.30-3.81)]. Both haplotypes were significantly associated with steatosis and fibrosis. The GT haplotype was also associated with lobular inflammation.Genetic variation in PPARG is associated with NAFLD, and the GT haplotype is associated with inflammatory and fibrotic changes that denote histologically advanced NAFLD.

Episodic memory is the ability to remember personally experienced past events (Tulving in Organization of memory. Academic Press, San Diego, pp. 381-403, 1972). In non-human animals, the behavioural criterion for episodic-like memory is remembering "what" occurred in conjunction with "when" and "where" (Clayton and Dickinson in Nature 395:272-274, 1998). We conducted tests for "what, where, and when" memory in a food-storing bird, the black-capped chickadee (Poecile atricapillus). In Experiment 1, chickadees found sunflower seeds and mealworms in concealed sites in their home cage. Birds later re-visited these sites after either a short (3 h) or long (123 h) retention interval. Chickadees normally prefer mealworms, but at the long retention interval mealworms were degraded in taste and appearance. Chickadees showed some memory for what kind of food they had encountered and where, but no memory for when food had previously been found. Experiment 2 followed a similar procedure, except that chickadees searched for hidden sunflower seeds and mealworms in trees in an indoor aviary. These more natural conditions increased both the spatial scale of the task and the effort required to find food. In this experiment, birds showed evidence for all three components of what-where-when memory. Unlike some previous studies of episodic-like memory, birds' behaviour cannot be accounted for by differential memory strength for more recent events. The results show that memory for what, where, and when occurs in food-storing birds outside the corvid family, does not require food caching or retrieval, and that remembering "when" can depend on the nature of the task.

We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 x 10(-4), odds ratio (OR)=0.81 (95% confidence interval: 0.73-0.90)). This single nucleotide polymorphism (SNP) is located in the 5' untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P=1.5 x 10(-3), OR=0.75 (95% CI: 0.62-0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.

Objectives: To explore the implementation of patient oriented activities, the perception of an innovation aimed at implementation of patient education and the preconditions for implementation of this innovation among Dutch pharmacists.Method: A survey, based on Rogers' theory of diffusion of innovations, was carried out among a random sample (n = 300) of Dutch managing pharmacists.Main outcome measures: Reported activities regarding patient education, medication surveillance and drug therapy meetings, as well as perception of the innovation and its perceived compatibility with pharmacy practice.Results: The response rate was 49.3%. Hundred (84.7%) respondents reported to provide extra written and verbal information with first prescription medication. Medication surveillance (100% check by computer, and check of the lists by the pharmacist) was reported by 43 (36.4%), and complete participation in drug therapy meetings was reported by 57 (48.3%) respondents. Observability (of results to others) of the new strategy was perceived as important by 90 (77.6%), compatibility (perceived consistency with existing values, past experiences and needs of potential adopters) by 87 (76.4%) and trialability (degree to which an innovation may be experimented with) by 81 (69.8%) respondents. Relative advantages (perception of the innovation as being better) and complexity (relatively difficult to understand and use) of the innovation were perceived as important by less respondents. The preconditions that were met by most pharmacists were 'financial resources' (n = 70; 59.8%), 'enough workspace' (n = 61; 53.1%) and 'enough time' (n = 58; 50%). Fifty-eight (49.2%) respondents intend to adopt the innovation, but this intention would be higher when more time and money and technicians are available, as well as less situations that are experienced as barriers (rush hours, lack of support, illness of employees).Conclusion: Based on the definitions used, we conclude that the implementation of medication surveillance and drug therapy meetings is relatively low compared to patient education. The development of an implementation tool is justified, but should deal with the experienced preconditions, barriers and needs of pharmacists. Combined, comprehensive pharmacy interventions promise to be a good way to change pharmacy practice.

We consider branes in refined topological strings. We argue that their wave-functions satisfy a Schr\"odinger equation depending on multiple times and prove this in the case where the topological string has a dual matrix model description. Furthermore, in the limit where one of the equivariant rotations approaches zero, the brane partition function satisfies a time-independent Schroedinger equation. We use this observation, as well as the back reaction of the brane on the closed string geometry, to offer an explanation of the connection between integrable systems and N=2 gauge systems in four dimensions observed by Nekrasov and Shatashvili., Comment: 64 pages, 2 figures

The migration of Swazi women to the Witwatersrand in the period 1920–1970 marked an era of change in the lives of many Swazi women. Under the constraints of rural impoverishment, many women were forced onto the Swazi labour market, one which had little room for women. By the 1930s the exodus of Swazi women to the Rand had gathered so much momentum, that women quickly became objects of national concern to the British colonial government, Swazi traditional authorities and South African authorities. Their experiences as migrant workers in South Africa have largely gone unnoticed. As African women, they suffered the triple oppression of class, race and gender, and as foreign women were subject to a battery of laws designed to keep foreign Africans out of South Africa. The personal experiences of Swazi women as migrants and workers in South Africa are examined here, using life-history or personal narrative techniques which have considerable potential as a way of recovering hidden histories and reinstating the marginalised as makers of their own past.

The simplest gravity duals for quantum critical theories with z=2 `Lifshitz' scale invariance admit a marginally relevant deformation. Generic black holes in the bulk describe the field theory with a dynamically generated momentum scale Lambda as well as finite temperature T. We describe the thermodynamics of these black holes in the quantum critical regime where T >> Lambda^2. The deformation changes the asymptotics of the spacetime mildly and leads to intricate UV sensitivities of the theory which we control perturbatively in Lambda^2/T., 1+27 pages, 12 figures