Epidemiology of Classical Hodgkin Lymphoma and Its Association with Epstein Barr Virus in Northern China

BACKGROUND: The incidence of classical Hodgkin lymphoma (cHL) and its association with Epstein-Barr virus (EBV) varies significantly with age, sex, ethnicity and geographic location. This is the first report on epidemiological features of cHL patients from Northern regions of China. These features are compared to data from a previously published Dutch cHL population. METHODOLOGY/PRINCIPAL FINDINGS: 157 cHL patients diagnosed between 1997 and 2008 in the North of China were included after histopathological re-evaluation. The Dutch population-based cohort consisted of 515 cHL patients diagnosed between 1987 and 2000. EBV status was determined by in situ hybridization of EBV- encoded small RNAs. In the Chinese population, tumor cells of 39% of the cHL patients were EBV+ and this was significantly associated with male sex, mixed cellularity subtype and young age (<20 y). The median age of the Chinese patients was 9 years younger than that of the Dutch patients (28 y vs. 37 y). In addition, the age distribution between the two populations was strikingly different in both the EBV+ subgroups (p<0.001) and the EBV- subgroups (p = 0.01). The mixed cellularity subtype was almost 3x more frequent amongst the Chinese (p<0.001). CONCLUSION/SIGNIFICANCE: CHL patients from Northern regions of China show a distinctive age distribution pattern with a striking incidence peak of EBV+ mixed cellularity cases among children and adolescents and another high incidence peak of EBV- nodular sclerosis cases in young adults. In comparison to Dutch cHL patients there are pronounced differences in age distribution, subtype and EBV status, presumably caused by complex gene-environmental interactions

Highly Parallel Translation of DNA Sequences into Small Molecules

A large body of in vitro evolution work establishes the utility of biopolymer libraries comprising 1010 to 1015 distinct molecules for the discovery of nanomolar-affinity ligands to proteins.[1], [2], [3], [4], [5] Small-molecule libraries of comparable complexity will likely provide nanomolar-affinity small-molecule ligands.[6], [7] Unlike biopolymers, small molecules can offer the advantages of cell permeability, low immunogenicity, metabolic stability, rapid diffusion and inexpensive mass production. It is thought that such desirable in vivo behavior is correlated with the physical properties of small molecules, specifically a limited number of hydrogen bond donors and acceptors, a defined range of hydrophobicity, and most importantly, molecular weights less than 500 Daltons.[8] Creating a collection of 1010 to 1015 small molecules that meet these criteria requires the use of hundreds to thousands of diversity elements per step in a combinatorial synthesis of three to five steps. With this goal in mind, we have reported a set of mesofluidic devices that enable DNA-programmed combinatorial chemistry in a highly parallel 384-well plate format. Here, we demonstrate that these devices can translate DNA genes encoding 384 diversity elements per coding position into corresponding small-molecule gene products. This robust and efficient procedure yields small molecule-DNA conjugates suitable for in vitro evolution experiments

Mesofluidic Devices for DNA-Programmed Combinatorial Chemistry

Hybrid combinatorial chemistry strategies that use DNA as an information-carrying medium are proving to be powerful tools for molecular discovery. In order to extend these efforts, we present a highly parallel format for DNA-programmed chemical library synthesis. The new format uses a standard microwell plate footprint and is compatible with commercially available automation technology. It can accommodate a wide variety of combinatorial synthetic schemes with up to 384 different building blocks per chemical step. We demonstrate that fluidic routing of DNA populations in the highly parallel format occurs with excellent specificity, and that chemistry on DNA arrayed into 384 well plates proceeds robustly, two requirements for the high-fidelity translation and efficient in vitro evolution of small molecules

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

Galaxy And Mass Assembly (GAMA): The Bright Void Galaxy Population in the Optical and Mid-IR

We examine the properties of galaxies in the Galaxies and Mass Assembly (GAMA) survey located in voids with radii $>10~h^{-1}$ Mpc. Utilising the GAMA equatorial survey, 592 void galaxies are identified out to z~0.1 brighter than $M_{r} = -18.4$, our magnitude completeness limit. Using the $W_{\rm{H\alpha}}$ vs. [NII]/H$\alpha$ (WHAN) line strength diagnostic diagram, we classify their spectra as star forming, AGN, or dominated by old stellar populations. For objects more massive than $5\times10^{9}$ M$_{\odot}$, we identify a sample of 26 void galaxies with old stellar populations classed as passive and retired galaxies in the WHAN diagnostic diagram, else they lack any emission lines in their spectra. When matched to WISE mid-IR photometry, these passive and retired galaxies exhibit a range of mid-IR colour, with a number of void galaxies exhibiting [4.6]-[12] colours inconsistent with completely quenched stellar populations, with a similar spread in colour seen for a randomly drawn non-void comparison sample. We hypothesise that a number of these galaxies host obscured star formation, else they are star forming outside of their central regions targeted for single fibre spectroscopy. When matched to a randomly drawn sample of non-void galaxies, the void and non-void galaxies exhibit similar properties in terms of optical and mid-IR colour, morphology, and star formation activity, suggesting comparable mass assembly and quenching histories. A trend in mid-IR [4.6]-[12] colour is seen, such that both void and non-void galaxies with quenched/passive colours <1.5 typically have masses higher than $10^{10}$ M$_{\odot}$, where internally driven processes play an increasingly important role in galaxy evolution

Outcome of a risk-related therapeutic strategy used prospectively in a population-based study of Hodgkin's lymphoma in adolescents

The aim was to assess outcome in a population-based cohort of adolescents with Hodgkin's lymphoma (HL) diagnosed in the UK's northern region over a 10-year period. Among a population of 3.09 million, 55 of 676 patients (8%) diagnosed with HL were aged 13–19. Seven had nodular lymphocyte-predominant HL, 48 classical HL (cHL). Of the latter, 36 were ⩾16 years. Application of the Scottish and Newcastle Lymphoma Group (SNLG) prognostic index meant 21 patients were considered high risk (index ⩾0.5). They received PVACEBOP multi-agent chemotherapy as primary therapy. Standard risk patients (SNLG index <0.5) were treated with standard ChlVPP or ABVD chemotherapy±radiotherapy. Scottish and Newcastle Lymphoma Group indexing is not valid for patients under 16. Twelve patients therefore received UKCCSG protocols (n=8), ABVD plus radiotherapy (n=2), or PVACEBOP (n=2). Forty-six patients with cHL (96%) achieved complete remission. Seven patients relapsed but all entered complete remission after salvage therapy. Five patients died: three of HL, one in an accident and one of disseminated varicella complicating cystic fibrosis. Five- and 10-year overall survival was 93 and 86%, respectively; disease-specific survival was 95 and 92%. The data suggest that older adolescents with high-risk HL require intensive protocols as primary therapy to secure optimal outcome

Galaxy And Mass Assembly (GAMA): The Bright Void Galaxy Population in the Optical and Mid-IR

We examine the properties of galaxies in the Galaxies and Mass Assembly (GAMA) survey located in voids with radii $>10~h^{-1}$ Mpc. Utilising the GAMA equatorial survey, 592 void galaxies are identified out to z~0.1 brighter than $M_{r} = -18.4$, our magnitude completeness limit. Using the $W_{\rm{H\alpha}}$ vs. [NII]/H$\alpha$ (WHAN) line strength diagnostic diagram, we classify their spectra as star forming, AGN, or dominated by old stellar populations. For objects more massive than $5\times10^{9}$ M$_{\odot}$, we identify a sample of 26 void galaxies with old stellar populations classed as passive and retired galaxies in the WHAN diagnostic diagram, else they lack any emission lines in their spectra. When matched to WISE mid-IR photometry, these passive and retired galaxies exhibit a range of mid-IR colour, with a number of void galaxies exhibiting [4.6]-[12] colours inconsistent with completely quenched stellar populations, with a similar spread in colour seen for a randomly drawn non-void comparison sample. We hypothesise that a number of these galaxies host obscured star formation, else they are star forming outside of their central regions targeted for single fibre spectroscopy. When matched to a randomly drawn sample of non-void galaxies, the void and non-void galaxies exhibit similar properties in terms of optical and mid-IR colour, morphology, and star formation activity, suggesting comparable mass assembly and quenching histories. A trend in mid-IR [4.6]-[12] colour is seen, such that both void and non-void galaxies with quenched/passive colours <1.5 typically have masses higher than $10^{10}$ M$_{\odot}$, where internally driven processes play an increasingly important role in galaxy evolution

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

Overweight and lifestyle behaviors of low socioeconomic elementary school children in Buenos Aires

<p>Abstract</p> <p>Background</p> <p>There is growing interest in understanding the role that lifestyle behaviors play in relation to children's weight status. The objective of the study was to determine the association between children s BMI and dietary practices and maternal BMI.</p> <p>Methods</p> <p>330 students (168M) aged 8.9 + 2 y from 4 suburban Buenos Aires elementary schools, and their mothers aged 36.2 + 7 y were examined between April and September 2007. Mothers were asked about their children s lifestyle. Data included parental education levels socioeconomic status, mothers and children s BMI, and Tanner stage.</p> <p>Results</p> <p>All families were in the low socio-economic class. 79% of parents had an elementary education or less. 61 (18.5%) of children were obese (OB) (BMI>95%ile per CDC norms), and 53 (16.1%) overweight (OW) (BMI>85<95%ile). 103 (31.2%) of mothers were OB (BMI>30 kg/m2), and102 (30.9%) OW (BMI>25<30). 63% the children were pre-pubertal. 40% had a TV set in their bedroom. 13% of the children skipped breakfast and only 38% watched TV ≤2 hours daily, as recommended. Multiple logistic regression analysis showed a positive association between children s OW/OB and drinking sweetened beverages (OR = 1.24; 95% CI, 1.02–1.52), TV viewing (OR = 1.30; 95% CI,1.05–1.62), and maternal BMI (OR: 1.07; 95% CI,1.02–1.12), and a negative association with eating breakfast (OR = 0.43; 95% CI, 0.19–0.97) adjusted for fruit and vegetables consumption, milk consumption, maternal educational level and socioeconomic class.</p> <p>Conclusion</p> <p>Our results suggest that TV viewing, drinking sweet beverages, skipping breakfast, and maternal BMI are important predictive variables for childhood OW/OB.</p