14 research outputs found
Improving our understanding of the in vivo modelling of psychotic disorders: a systematic review and meta-analysis
Psychotic disorders represent a severe category of mental disorders affecting about one
percent of the population. Individuals experience a loss or distortion of contact with reality
alongside other symptoms, many of which are still not adequately managed using existing
treatments. While animal models of these disorders could offer insights into these disorders
and potential new treatments, translation of this knowledge has so far been poor in terms of
informing clinical trials and practice. The aim of this project was to improve our
understanding of these pre-clinical studies and identify potential weaknesses underlying
translational failure.
I carried out a systematic search of the literature to provide an unbiased summary of
publications reporting animal models of schizophrenia and other psychotic disorders. From
these publications, data were extracted to quantify aspects of the field including reported
quality of studies, study characteristics and behavioural outcome data. The latter of these
data were then used to calculate estimates of efficacy using random-effects meta-analysis.
Having identified 3847 publications of relevance, including 852 different methods used to
induce the model, over 359 different outcomes tested in them and almost 946 different
treatments reported to be administered. I show that a large proportion of studies use simple
pharmacological interventions to induce their models of these disorders, despite the
availability of models using other interventions that are arguably of higher translational
relevance. I also show that the reported quality of these studies is low, and only 22% of
studies report taking measures to reduce the risk of biases such as randomisation and
blinding, which has been shown to affect the reliability of results drawn.
Through this work it becomes apparent that the literature is incredibly vast for studies looking
at animal models of psychotic disorders and that some of the relevant work potentially
overlaps with studies describing other conditions. This means that drawing reliable
conclusions from these data is affected by what is made available in the literature, how it is
reported and identified in a search and the time that it takes to reach these conclusions. I
introduce the idea of using computer-assisted tools to overcome one of these problems in
the long term.
Translation of results from studies looking at animals modelling uniquely-human psychotic
disorders to clinical successes might be improved by better reporting of studies including
publishing of all work carried out, labelling of studies more uniformly so that it is identifiable,
better reporting of study design including improving on reporting of measures taken to
reduce the risk of bias and focusing on models with greater validity to the human condition
Additional file 2: of Long noncoding RNAs as novel predictors of survival in human cancer: a systematic review and meta-analysis
The studies eligible for systematic review. (DOC 444 kb
Plasma neutrophil gelatinase-associated lipocalin levels are markedly increased in patients with non-transfusion-dependent thalassemia: Lack of association with markers of erythropoiesis, iron metabolism and renal function
Background: Neutrophil Gelatinase-Associated Lipocalin (NGAL) (known as
NGAL, Lipocalin 2, Siderocalin, Uterocalin, proteinase-3 and 24p3) is a
mammalian small 25-kD peptide that belongs to the lipocalin superfamily,
which consists of about 20 small lipoproteins. NGAL was initially
discovered as an antibacterial factor of natural immunity and an
acute-phase protein. NGAL is also an iron trafficking protein, a member
of the non-transferrin-bound iron (NTBI) pool and an alternative to the
transferrin-mediated iron-delivery pathway. Of note, NTBI, which is
elevated in thalassemic patients, induces cellular toxicity. In this
study we investigated the possible association of NGAL with parameters
of erythropoiesis, iron metabolism and renal injury in patients with
non-transfusion-dependent thalassemia (thalassemia intermedia or TI).
Patients and methods: Thirty-five patients with TI, 13 men and 22 women,
aged 8-63 years, were included in the study, while, 20 healthy
individuals served as controls. Plasma NGAL levels were determined using
an immunoenzymatic technique. Erythroid marrow activity was estimated by
measuring soluble transferrin receptors (sTfR) levels with a
turbidimetric technique. NTBI levels were determined using
electrothermal atomic absorption spectrometry. Cystatin C, beta
2-microglobulin and hs-CRP concentrations were measured by means of
immunonephelometric techniques.
Results: The main results of the study showed: a) NGAL levels were
significantly higher in patients with TI compared to controls (139.1 +/-
86.1 vs 51.2 +/- 11.8 mu g/L, p < 0.0001), without significant effect of
splenectomy or hydroxyurea on NGAL levels. Only 4 patients had NGAL
levels within the control group range, b) no correlation was found
between NGAL levels and either the parameters of erythropoiesis Hb, Hb
F, reticulocytes and sTfR (p > 0.66, p > 0.67, p > 0.63 and p > 0.81
respectively), or with those of iron metabolism ferritin and NTBI (p >
0.90 and p > 0.95 respectively).
Conclusions: The increased NGAL levels reported for the first time in TI
patients in this study are in agreement with the elevated expression of
NGAL observed in TI mouse models. We postulate that the induction of
NGAL in these patients may represent either a survival response,
facilitating the survival of the less damaged thalassemic erythroid
precursors, or a consequence of the abnormal iron regulation in TI. (C)
2014 The Canadian Society of Clinical Chemists. Published by Elsevier
Inc. All rights reserved
Data from: Risk of bias in reports of in vivo research: a focus for improvement
The reliability of experimental findings depends on the rigour of experimental design. Here we show limited reporting of measures to reduce the risk of bias in a random sample of life sciences publications, significantly lower reporting of randomisation in work published in journals of high impact, and very limited reporting of measures to reduce the risk of bias in publications from leading United Kingdom institutions. Ascertainment of differences between institutions might serve both as a measure of research quality and as a tool for institutional efforts to improve research quality