University of Antwerp

About: University of Antwerp is a education organization based out in Antwerp, Belgium. It is known for research contribution in the topics: Population & Context (language use). The organization has 16682 authors who have published 48837 publications receiving 1689748 citations. The organization is also known as: Universiteit Antwerpen & UAntwerp.

HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis

Abstract: Summary Background We aimed to provide updated information about the global estimates of attributable fraction and type distribution of human papillomavirus (HPV) in head and neck squamous cell carcinomas by doing a systematic review and meta-analysis. Methods We did a literature search on PubMed to identify studies that used PCR for detection of HPV DNA in head and neck squamous cell carcinomas with information about HPV genotype distribution. We included studies that tested 20 or more biopsies per cancer site and were published between July 15, 1990, and Feb 29, 2012. We collected information about sex, risk factors, HPV detection methods, and biomarkers of potentially HPV-induced carcinogenesis (E6/E7 mRNA and p16 INK4a ). If it was not possible to abstract the required information directly from the paper, we contacted the authors. We did a meta-analysis to produce pooled prevalence estimates including a meta-regression to explore sources of heterogeneity. Findings 148 studies were included, contributing data for 12 163 cases of head and neck squamous cell carcinoma from 44 countries. HPV DNA was detected in 3837 cases. HPV16 accounted for 82·2% (95% CI 77·7–86·4) of all HPV DNA positive cases. By cancer site, pooled HPV DNA prevalence estimates were 45·8% (95% CI 38·9–52·9) for oropharynx, 22·1% (16·4–28·3) for larynx (including hypopharynx), and 24·2% (18·7–30·2) for oral cavity. The percent positivity of p16 INK4a positive cases in HPV-positive oropharyngeal cancer cases was 86·7% (95% CI 79·2–92·9) and of E6/E7 mRNA positive cases was 86·9% (73·2–96·8). The estimate of HPV attributable fraction in oropharyngeal cancer defined by expression of positive cases of E6/E7 mRNA was 39·8% and of p16 INK4a was 39·7%. Of subsites, tonsils (53·9%, 95% CI 46·4–61·3) had the highest HPV DNA prevalence. HPV DNA prevalence varied significantly by anatomical site, geographic region, but not by sex or tobacco or alcohol consumption. Interpretation The contribution of HPV prevalence in head and neck squamous cell carcinoma and in particular that of HPV16 in the oropharynx shows the potential benefit of prophylactic vaccines. Funding European Commission.

Computing LTS Regression for Large Data Sets

Abstract: Data mining aims to extract previously unknown patterns or substructures from large databases. In statistics, this is what methods of robust estimation and outlier detection were constructed for, see e.g. Rousseeuw and Leroy (1987). Here we will focus on least trimmed squares (LTS) regression, which is based on the subset of h cases (out of n) whose least squares fit possesses the smallest sum of squared residuals. The coverage h may be set between n/2 and n. The computation time of existing LTS algorithms grows too much with the size of the data set, precluding their use for data mining. In this paper we develop a new algorithm called FAST-LTS. The basic ideas are an inequality involving order statistics and sums of squared residuals, and techniques which we call `selective iteration' and `nested extensions'. We also use an intercept adjustment technique to improve the precision. For small data sets FAST-LTS typically finds the exact LTS, whereas for larger data sets it gives more accurate results than existing algorithms for LTS and is faster by orders of magnitude. This allows us to apply FAST-LTS to large databases.

The new '5-HT' hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression.

Abstract: This paper reviews the body of evidence that not only tryptophan and consequent 5-HT depletion, but also induction of indoleamine 2,3-dioxygenase (IDO) and the detrimental effects of tryptophan catabolites (TRYCATs) play a role in the pathophysiology of depression. IDO is induced by interferon (IFN)γ, interleukin-6 and tumor necrosis factor-α, lipopolysaccharides and oxidative stress, factors that play a role in the pathophysiology of depression. TRYCATs, like kynurenine and quinolinic acid, are depressogenic and anxiogenic; activate oxidative pathways; cause mitochondrial dysfunctions; and have neuroexcitatory and neurotoxic effects that may lead to neurodegeneration. The TRYCAT pathway is also activated following induction of tryptophan 2,3-dioxygenase (TDO) by glucocorticoids, which are elevated in depression. There is evidence that activation of IDO reduces plasma tryptophan and increases TRYCAT synthesis in depressive states and that TDO activation may play a role as well. The development of depressive symptoms during IFNα-based immunotherapy is strongly associated with IDO activation, increased production of detrimental TRYCATs and lowered levels of tryptophan. Women show greater IDO activation and TRYCAT production following immune challenge than men. In the early puerperium, IDO activation and TRYCAT production are associated with the development of affective symptoms. Clinical depression is accompanied by lowered levels of neuroprotective TRYCATs or increased levels or neurotoxic TRYCATs, and lowered plasma tryptophan, which is associated with indices of immune activation and glucocorticoid hypersecretion. Lowered tryptophan and increased TRYCATs induce T cell unresponsiveness and therefore may exert a negative feedback on the primary inflammatory response in depression. It is concluded that activation of the TRYCAT pathway by IDO and TDO may be associated with the development of depressive symptoms through tryptophan depletion and the detrimental effects of TRYCATs. Therefore, the TRYCAT pathway should be a new drug target in depression. Direct inhibitors of IDO are less likely to be useful drugs than agents, such as kynurenine hydroxylase inhibitors; drugs which block the primary immune response; compounds that increase the protective effects of kynurenic acid; and specific antioxidants that target IDO activation, the immune and oxidative pathways, and 5-HT as well.

Numerical models of salt marsh evolution: Ecological, geomorphic, and climatic factors

Abstract: Salt marshes are delicate landforms at the boundary between the sea and land. These ecosystems support a diverse biota that modifies the erosive characteristics of the substrate and mediates sediment transport processes. Here we present a broad overview of recent numerical models that quantify the formation and evolution of salt marshes under different physical and ecological drivers. In particular, we focus on the coupling between geomorphological and ecological processes and on how these feedbacks are included in predictive models of landform evolution. We describe in detail models that simulate fluxes of water, organic matter, and sediments in salt marshes. The interplay between biological and morphological processes often produces a distinct scarp between salt marshes and tidal flats. Numerical models can capture the dynamics of this boundary and the progradation or regression of the marsh in time. Tidal channels are also key features of the marsh landscape, flooding and draining the marsh platform and providing a source of sediments and nutrients to the marsh ecosystem. In recent years, several numerical models have been developed to describe the morphogenesis and long-term dynamics of salt marsh channels. Finally, salt marshes are highly sensitive to the effects of long-term climatic change. We therefore discuss in detail how numerical models have been used to determine salt marsh survival under different scenarios of sea level rise.

Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy

Abstract: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuromuscular disease and is characterized by considerable clinical and genetic heterogeneity. We previously reported a Russian family with autosomal dominant axonal CMT and assigned the locus underlying the disease (CMT2F; OMIM 606595) to chromosome 7q11-q21 (ref. 2). Here we report a missense mutation in the gene encoding 27-kDa small heat-shock protein B1 (HSPB1, also called HSP27) that segregates in the family with CMT2F. Screening for mutations in HSPB1 in 301 individuals with CMT and 115 individuals with distal hereditary motor neuropathies (distal HMNs) confirmed the previously observed mutation and identified four additional missense mutations. We observed the additional HSPB1 mutations in four families with distal HMN and in one individual with CMT neuropathy. Four mutations are located in the Hsp20-alpha-crystallin domain, and one mutation is in the C-terminal part of the HSP27 protein. Neuronal cells transfected with mutated HSPB1 were less viable than cells expressing the wild-type protein. Cotransfection of neurofilament light chain (NEFL) and mutant HSPB1 resulted in altered neurofilament assembly in cells devoid of cytoplasmic intermediate filaments.