Investigating human audio-visual object perception with a combination of hypothesis-generating and hypothesis-testing fMRI analysis tools

Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis

The impact of the Calman–Hine report on the processes and outcomes of care for Yorkshire's colorectal cancer patients

The 1995 Calman–Hine plan outlined radical reform of the UK's cancer services with the aim of improving outcomes and reducing inequalities in NHS cancer care. Its main recommendation was to concentrate care into the hands of site-specialist, multi-disciplinary teams. This study aimed to determine if the implementation of Calman–Hine cancer teams was associated with improved processes and outcomes of care for colorectal cancer patients. The design included longitudinal survey of 13 colorectal cancer teams in Yorkshire and retrospective study of population-based data collected by the Northern and Yorkshire Cancer Registry and Information Service. The population was all colorectal cancer patients diagnosed and treated in Yorkshire between 1995 and 2000. The main outcome measures were: variations in the use of anterior resection and preoperative radiotherapy in rectal cancer, chemotherapy in Dukes stage C and D patients, and five-year survival. Using multilevel models, these outcomes were assessed in relation to measures of the extent of Calman–Hine implementation throughout the study period, namely: (i) each team's degree of adherence to the Manual of Cancer Service Standards (which outlines the specification of the ‘ideal’ colorectal cancer team) and (ii) the extent of site specialisation of each team's surgeons. Variation was observed in the extent to which the colorectal cancer teams in Yorkshire had conformed to the Calman–Hine recommendations. An increase in surgical site specialisation was associated with increased use of preoperative radiotherapy (OR=1.43, 95% CI=1.04–1.98, P<0.04) and anterior resection (OR=1.43, 95% CI=1.16–1.76, P<0.01) in rectal cancer patients. Increases in adherence to the Manual of Cancer Service Standards was associated with improved five-year survival after adjustment for the casemix factors of age, stage of disease, socioeconomic status and year of diagnosis, especially for colon cancer (HR=0.97, 95% CI=0.94–0.99 P<0.01). There was a similar trend of improved survival in relation to increased surgical site specialisation for rectal cancer, although the effect was not statistically significant (HR=0.93, 95% CI=0.84–1.03, P=0.15). In conclusion, the extent of implementation of the Calman–Hine report has been variable and its recommendations are associated with improvements in processes and outcomes of care for colorectal cancer patients

Uterine selection of human embryos at implantation

Human embryos frequently harbor large-scale complex chromosomal errors that impede normal development. Affected embryos may fail to implant although many first breach the endometrial epithelium and embed in the decidualizing stroma before being rejected via mechanisms that are poorly understood. Here we show that developmentally impaired human embryos elicit an endoplasmic stress response in human decidual cells. A stress response was also evident upon in vivo exposure of mouse uteri to culture medium conditioned by low-quality human embryos. By contrast, signals emanating from developmentally competent embryos activated a focused gene network enriched in metabolic enzymes and implantation factors. We further show that trypsin, a serine protease released by pre-implantation embryos, elicits Ca2+ signaling in endometrial epithelial cells. Competent human embryos triggered short-lived oscillatory Ca2+ fluxes whereas low-quality embryos caused a heightened and prolonged Ca2+ response. Thus, distinct positive and negative mechanisms contribute to active selection of human embryos at implantation

The sound of street corner society: UK grime music as ethnography

This article explores the ways in which popular music can be linked to ethnography. While there is a tradition of connecting popular music with sociology, this article posits a further resonance that is not so much theoretical as methodological. The article suggests that forms of contemporary popular music parallel key facets of ethnography, not simply in terms of sociological analysis, but with regard to popular music as an ethnographic resource, as ‘data’, and as the reflexive expression of Paul Willis’ conception of the ‘ethnographic imagination’; and the article argues that contemporary British hip-hop in the form of ‘grime’ is a potent exemplar. This is due to the resolutely cultural, spatial nature of grime music: a factor that marks out grime as a distinctive musical genre and a distinctive ethnographic form, as it is an experientially rooted music about urban locations, made from within those urban locations

Factors affecting the prevalence of strongly and weakly carcinogenic and lower-risk human papillomaviruses in anal specimens in a cohort of men who have sex with men (MSM)

Background: MSM are at higher risk for invasive anal cancer. Twelve human papillomaviruses (HPVs) cause cervical cancer in women (Group 1 high-risk HPVs (hrHPVs)) and 13 HPVs are probable/possible causes (Group 2 hrHPVs) of cervical malignancy. HPVs rarely associated with malignancy are classified as lower-risk HPVs (lrHPVs). Materials and Methods: Dacron-swab anal-cytology specimens were collected from and data complete for 97% (1262/1296) of Multicenter AIDS Cohort Study (MACS) men tested for HPVs using the Linear Array assay. Multivariate Poisson regression analyses estimated adjusted prevalence ratios for Group 1/2 hrHPVs and lrHPVs, controlling for the effects of age, race, ethnicity, sexual partnerships, smoking; HIV-infection characteristics, treatment, and immune status among HIV-infected men. Results: HIV-infected men showed 35-90% higher prevalence of Group 1/2 hrHPVs and lrHPVs than HIV-uninfected men, and higher prevalence of multi-Type, and multiple risk-group infections. CD4+ T-cell count was inversely associated with HPV Group 2 prevalence (p<0.0001). The number of receptive anal intercourse (RAI) partners reported in the 24 months preceding HPV testing predicted higher prevalence of Group 1/2 hrHPVs. Men reporting ≥30 lifetime male sex partners before their first MACS visit and men reporting ≥1 RAI partners during the 24 months before HPV testing showed 17-24% and 13-17% higher prevalence of lrHPVs (p-values ≤0.05). Men reporting smoking between MACS visit 1 and 24 months before HPV testing showed 1.2-fold higher prevalence of Group 2 hrHPVs (p = 0.03). Both complete adherence to CART (p = 0.02) and HIV load <50 copies/mL (p = 0.04) were protective for Group 1 hrHPVs among HIV-infected men. Conclusions: HIV-infected men more often show multi-type and multi-group HPV infections HIV-uninfected men. Long-term mutual monogamy and smoking cessation, generally, and CART-adherence that promotes (HIV) viremia control and prevents immunosuppression, specifically among HIV-infected MSM, are important prevention strategies for HPV infections that are relevant to anal cancer. © 2013 Wiley et al

Genome-Wide Identification of Molecular Pathways and Biomarkers in Response to Arsenic Exposure in Zebrafish Liver

10.1371/journal.pone.0068737PLoS ONE87-POLN

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is poor, with five year osteosarcoma survival rates in people not having improved in decades. For dogs, one year survival rates are only around ~45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human osteosarcoma. Finally, the current position of canine osteosarcoma genetic research is discussed and areas for additional work within the canine population are identified

Amyloid precursor protein drives down-regulation of mitochondrial oxidative phosphorylation independent of amyloid beta

Amyloid precursor protein (APP) and its extracellular domain, soluble APP alpha (sAPPα) play important physiological and neuroprotective roles. However, rare forms of familial Alzheimer’s disease are associated with mutations in APP that increase toxic amyloidogenic cleavage of APP and produce amyloid beta (Aβ) at the expense of sAPPα and other non-amyloidogenic fragments. Although mitochondrial dysfunction has become an established hallmark of neurotoxicity, the link between Aβ and mitochondrial function is unclear. In this study we investigated the effects of increased levels of neuronal APP or Aβ on mitochondrial metabolism and gene expression, in human SH-SY5Y neuroblastoma cells. Increased non-amyloidogenic processing of APP, but not Aβ, profoundly decreased respiration and enhanced glycolysis, while mitochondrial DNA (mtDNA) transcripts were decreased, without detrimental effects to cell growth. These effects cannot be ascribed to Aβ toxicity, since higher levels of endogenous Aβ in our models do not cause oxidative phosphorylation (OXPHOS) perturbations. Similarly, chemical inhibition of β-secretase decreased mitochondrial respiration, suggesting that non-amyloidogenic processing of APP may be responsible for mitochondrial changes. Our results have two important implications, the need for caution in the interpretation of mitochondrial perturbations in models where APP is overexpressed, and a potential role of sAPPα or other non-amyloid APP fragments as acute modulators of mitochondrial metabolism

Prevalence of anogenital HPV infection, related disease and risk factors among HIV-infected men in inner-city Johannesburg, South Africa: baseline findings from a cohort study.

BACKGROUND: Persistent high-risk human papillomavirus (HR-HPV) infection is associated with the development of anogenital cancers, particularly in men living with HIV (MLWH). We describe the prevalence of anogenital HPV infection, abnormal anal cytology and anogenital warts (AGWs) in MLWH in Johannesburg, and explore whether HPV infection and receipt of antiretroviral treatment is associated with detection of abnormal anal cytology and AGWs. METHODS: We enrolled a cohort of 304 sexually-active MLWH ≥18 years, who completed a questionnaire and physical examination. Genital swabs were collected from all men and intra-anal swabs from 250 (82%). Swabs were tested for HPV DNA and genotypes, and anal smears graded using the Bethesda classification. Factors associated with anogenital disease were assessed by logistic regression models. RESULTS: Two thirds were receiving antiretroviral treatment, for a median 33 months (IQR = 15-58) and 54% were HIV-virologically suppressed. Only 5% reported ever having sex with men. Among 283 genital swabs with valid results, 79% had any HPV, 52% had HR-HPV and 27% had >1 HR-HPV infection. By comparison, 39% of the 227 valid intra-anal swabs had detectable HPV, 25% had any HR-HPV and 7% >1 HR infection. While most anal smears were normal (51%), 20% had ASCUS and 29% were LSIL. No cases had HSIL or cancer. Infection with >1 HR type (adjusted OR [aOR] = 2.39; 95%CI = 1.02-5.58) and alpha-9 types (aOR = 3.98; 95%CI = 1.42-11.16) were associated with having abnormal cytology. Prevalence of AGWs was 12%. Infection with any LR type (aOR = 41.28; 95%CI = 13.57-125.62), >1 LR type (aOR = 4.14; 95%CI = 1.60-10.69), being <6 months on antiretroviral treatment (aOR = 6.90; 95%CI = 1.63-29.20) and having a CD4+ count <200 cells/μL (aOR = 5.48; 95%CI: 1.60-18.78) were associated with having AGWs. CONCLUSIONS: In this population, anogenital HR-HPV infection and associated low-grade disease is common, but severe anal dysplasia was not detected. Findings reinforce the need for HPV vaccination in men for preventing both AGWs and HR-HPV infection. Given the absence of anal HSILs, however, the findings do not support the use of anal screening programmes in this population