Primaquine-induced differential gene expression analysis in mice liver using DNA microarrays

Primaquine (PQ). a clinically important derivative of 8-aminoquinoline used against the hepatic stages (hypnozoites) of Plasmodium vivax and Plasmodium ova Ie. was studied to evaluate and compare between mRNA expression. and biochemical and histological parameters of hepatic stress in adult Swiss mice (Mus musculus). Following single oral dose of PQ (40 mglkg. bw). alanine aminotransferase (ALT) and aspartate aminotransferase (AST) along with hematoxylin and eosin stained liver sections did not show any signs of hepatic stress at 6. 12 and 24 h except for ALT activity at 6 h. However. analysis at RNA transcript level revealed consistent and significant deregulation (p<0.01 and twofold) of 16 probes corresponding to important cellular processes such as protein transportation. transcription regulation. intracellular signaling. protein synthesis, hematopoiesis, cell adhesion and cell proliferation. Pathway analysis identified large number of affected genes corresponding to 40 Gene Ontology terms having a z score greaibr than 2. These results indicate that PQ at high doses may affect gene expression in liver and may produce undesirable outcomes if consumed for longer durations.

Semiotic Analysis in the Study of Social Work

Research and professional practices have the joint aim of re-structuring the preconceived notions of reality. They both want to gain the understanding about social reality. Social workers use their professional competence in order to grasp the reality of their clients, while researchers’ pursuit is to open the secrecies of the research material. Development and research are now so intertwined and inherent in almost all professional practices that making distinctions between practising, developing and researching has become difficult and in many aspects irrelevant. Moving towards research-based practices is possible and it is easily applied within the framework of the qualitative research approach (Dominelli 2005, 235; Humphries 2005, 280). Social work can be understood as acts and speech acts crisscrossing between social workers and clients. When trying to catch the verbal and non-verbal hints of each others’ behaviour, the actors have to do a lot of interpretations in a more or less uncertain mental landscape. Our point of departure is the idea that the study of social work practices requires tools which effectively reveal the internal complexity of social work (see, for example, Adams & Dominelli & Payne 2005, 294 – 295). The boom of qualitative research methodologies in recent decades is associated with much profound the rupture in humanities, which is called the linguistic turn (Rorty 1967). The idea that language is not transparently mediating our perceptions and thoughts about reality, but on the contrary it constitutes it was new and even confusing to many social scientists. Nowadays we have got used to read research reports which have applied different branches of discursive analyses or narratologic or semiotic approaches. Although differences are sophisticated between those orientations they share the idea of the predominance of language. Despite the lively research work of today’s social work and the research-minded atmosphere of social work practice, semiotics has rarely applied in social work research. However, social work as a communicative practice concerns symbols, metaphors and all kinds of the representative structures of language. Those items are at the core of semiotics, the science of signs, and the science which examines people using signs in their mutual interaction and their endeavours to make the sense of the world they live in, their semiosis. When thinking of the practice of social work and doing the research of it, a number of interpretational levels ought to be passed before reaching the research phase in social work. First of all, social workers have to interpret their clients’ situations, which will be recorded in the files. In some very rare cases those past situations will be reflected in discussions or perhaps interviews or put under the scrutiny of some researcher in the future. Each and every new observation adds its own flavour to the mixture of meanings. Social workers have combined their observations with previous experience and professional knowledge, furthermore, the situation on hand also influences the reactions. In addition, the interpretations made by social workers over the course of their daily working routines are never limited to being part of the personal process of the social worker, but are also always inherently cultural. The work aiming at social change is defined by the presence of an initial situation, a specific goal, and the means and ways of achieving it, which are – or which should be – agreed upon by the social worker and the client in situation which is unique and at the same time socially-driven. Because of the inherent plot-based nature of social work, the practices related to it can be analysed as stories (see Dominelli 2005, 234), given, of course, that they are signifying and told by someone. The research of the practices is concentrating on impressions, perceptions, judgements, accounts, documents etc. All these multifarious elements can be scrutinized as textual corpora, but not whatever textual material. In semiotic analysis, the material studied is characterised as verbal or textual and loaded with meanings. We present a contribution of research methodology, semiotic analysis, which has to our mind at least implicitly references to the social work practices. Our examples of semiotic interpretation have been picked up from our dissertations (Laine 2005; Saurama 2002). The data are official documents from the archives of a child welfare agency and transcriptions of the interviews of shelter employees. These data can be defined as stories told by the social workers of what they have seen and felt. The official documents present only fragmentations and they are often written in passive form. (Saurama 2002, 70.) The interviews carried out in the shelters can be described as stories where the narrators are more familiar and known. The material is characterised by the interaction between the interviewer and interviewee. The levels of the story and the telling of the story become apparent when interviews or documents are examined with the use of semiotic tools. The roots of semiotic interpretation can be found in three different branches; the American pragmatism, Saussurean linguistics in Paris and the so called formalism in Moscow and Tartu; however in this paper we are engaged with the so called Parisian School of semiology which prominent figure was A. J. Greimas. The Finnish sociologists Pekka Sulkunen and Jukka Törrönen (1997a; 1997b) have further developed the ideas of Greimas in their studies on socio-semiotics, and we lean on their ideas. In semiotics social reality is conceived as a relationship between subjects, observations, and interpretations and it is seen mediated by natural language which is the most common sign system among human beings (Mounin 1985; de Saussure 2006; Sebeok 1986). Signification is an act of associating an abstract context (signified) to some physical instrument (signifier). These two elements together form the basic concept, the “sign”, which never constitutes any kind of meaning alone. The meaning will be comprised in a distinction process where signs are being related to other signs. In this chain of signs, the meaning becomes diverged from reality. (Greimas 1980, 28; Potter 1996, 70; de Saussure 2006, 46-48.) One interpretative tool is to think of speech as a surface under which deep structures – i.e. values and norms – exist (Greimas & Courtes 1982; Greimas 1987). To our mind semiotics is very much about playing with two different levels of text: the syntagmatic surface which is more or less faithful to the grammar, and the paradigmatic, semantic structure of values and norms hidden in the deeper meanings of interpretations. Semiotic analysis deals precisely with the level of meaning which exists under the surface, but the only way to reach those meanings is through the textual level, the written or spoken text. That is why the tools are needed. In our studies, we have used the semiotic square and the actant analysis. The former is based on the distinctions and the categorisations of meanings, and the latter on opening the plotting of narratives in order to reach the value structures.

Are clustering effects accounted for in statistical analysis in leading dental specialty journals?

OBJECTIVES In dental research multiple site observations within patients or taken at various time intervals are commonplace. These clustered observations are not independent; statistical analysis should be amended accordingly. This study aimed to assess whether adjustment for clustering effects during statistical analysis was undertaken in five specialty dental journals. METHODS Thirty recent consecutive issues of Orthodontics (OJ), Periodontology (PJ), Endodontology (EJ), Maxillofacial (MJ) and Paediatric Dentristry (PDJ) journals were hand searched. Articles requiring adjustment accounting for clustering effects were identified and statistical techniques used were scrutinized. RESULTS Of 559 studies considered to have inherent clustering effects, adjustment for this was made in the statistical analysis in 223 (39.1%). Studies published in the Periodontology specialty accounted for clustering effects in the statistical analysis more often than articles published in other journals (OJ vs. PJ: OR=0.21, 95% CI: 0.12, 0.37, p<0.001; MJ vs. PJ: OR=0.02, 95% CI: 0.00, 0.07, p<0.001; PDJ vs. PJ: OR=0.14, 95% CI: 0.07, 0.28, p<0.001; EJ vs. PJ: OR=0.11, 95% CI: 0.06, 0.22, p<0.001). A positive correlation was found between increasing prevalence of clustering effects in individual specialty journals and correct statistical handling of clustering (r=0.89). CONCLUSIONS The majority of studies in 5 dental specialty journals (60.9%) examined failed to account for clustering effects in statistical analysis where indicated, raising the possibility of inappropriate decreases in p-values and the risk of inappropriate inferences.

Is the relation between early post-session reports and treatment outcome an epiphenomenon of intake distress and early response? A multi-predictor analysis in outpatient psychotherapy

The early phase of psychotherapy has been regarded as a sensitive period in the unfolding of psychotherapy leading to positive outcomes. However, there is disagreement about the degree to which early (especially relationship-related) session experiences predict outcome over and above initial levels of distress and early response to treatment. The goal of the present study was to simultaneously examine outcome at post treatment as a function of (a) intake symptom and interpersonal distress as well as early change in well-being and symptoms, (b) the patient's early session-experiences, (c) the therapist's early session-experiences/interventions, and (d) their interactions. The data of 430 psychotherapy completers treated by 151 therapists were analyzed using hierarchical linear models. Results indicate that early positive intra- and interpersonal session experiences as reported by patients and therapists after the sessions explained 58% of variance of a composite outcome measure, taking intake distress and early response into account. All predictors (other than problem-activating therapists' interventions) contributed to later treatment outcomes if entered as single predictors. However, the multi-predictor analyses indicated that interpersonal distress at intake as well as the early interpersonal session experiences by patients and therapists remained robust predictors of outcome. The findings underscore that early in therapy therapists (and their supervisors) need to understand and monitor multiple interconnected components simultaneously

Genome-wide analysis in German shepherd dogs reveals association of a locus on CFA 27 with atopic dermatitis

Humans and dogs are both affected by the allergic skin disease atopic dermatitis (AD), caused by an interaction between genetic and environmental factors. The German shepherd dog (GSD) is a high-risk breed for canine AD (CAD). In this study, we used a Swedish cohort of GSDs as a model for human AD. Serum IgA levels are known to be lower in GSDs compared to other breeds. We detected significantly lower IgA levels in the CAD cases compared to controls (p = 1.1 × 10(-5)) in our study population. We also detected a separation within the GSD cohort, where dogs could be grouped into two different subpopulations. Disease prevalence differed significantly between the subpopulations contributing to population stratification (λ = 1.3), which was successfully corrected for using a mixed model approach. A genome-wide association analysis of CAD was performed (n cases = 91, n controls = 88). IgA levels were included in the model, due to the high correlation between CAD and low IgA levels. In addition, we detected a correlation between IgA levels and the age at the time of sampling (corr = 0.42, p = 3.0 × 10(-9)), thus age was included in the model. A genome-wide significant association was detected on chromosome 27 (praw = 3.1 × 10(-7), pgenome = 0.03). The total associated region was defined as a ~1.5-Mb-long haplotype including eight genes. Through targeted re-sequencing and additional genotyping of a subset of identified SNPs, we defined 11 smaller haplotype blocks within the associated region. Two blocks showed the strongest association to CAD. The ~209-kb region, defined by the two blocks, harbors only the PKP2 gene, encoding Plakophilin 2 expressed in the desmosomes and important for skin structure. Our results may yield further insight into the genetics behind both canine and human AD.

Early gene expression analysis in 9L orthotopic tumor-bearing rats identifies immune modulation in molecular response to synchrotron microbeam radiation therapy

Synchrotron Microbeam Radiation Therapy (MRT) relies on the spatial fractionation of the synchrotron photon beam into parallel micro-beams applying several hundred of grays in their paths. Several works have reported the therapeutic interest of the radiotherapy modality at preclinical level, but biological mechanisms responsible for the described efficacy are not fully understood to date. The aim of this study was to identify the early transcriptomic responses of normal brain and glioma tissue in rats after MRT irradiation (400Gy). The transcriptomic analysis of similarly irradiated normal brain and tumor tissues was performed 6 hours after irradiation of 9 L orthotopically tumor-bearing rats. Pangenomic analysis revealed 1012 overexpressed and 497 repressed genes in the irradiated contralateral normal tissue and 344 induced and 210 repressed genes in tumor tissue. These genes were grouped in a total of 135 canonical pathways. More than half were common to both tissues with a predominance for immunity or inflammation (64 and 67% of genes for normal and tumor tissues, respectively). Several pathways involving HMGB1, toll-like receptors, C-type lectins and CD36 may serve as a link between biochemical changes triggered by irradiation and inflammation and immunological challenge. Most immune cell populations were involved: macrophages, dendritic cells, natural killer, T and B lymphocytes. Among them, our results highlighted the involvement of Th17 cell population, recently described in tumor. The immune response was regulated by a large network of mediators comprising growth factors, cytokines, lymphokines. In conclusion, early response to MRT is mainly based on inflammation and immunity which appear therefore as major contributors to MRT efficacy.

Environmental, health and safety cost benefit analysis in the United States chemical industry

The purpose of this research project is to determine whether there is a cost/benefit to allocating financial and other company-related resources to improve environmental, health and safety performance beyond that which is required by law. The issue of whether a company benefits from spending dollars to achieve environmental, health and safety performance beyond legal compliance is an important issue to the chemical manufacturing industry in the United States because of the voluminous and complex legal requirements impacting environmental, health and safety expenditures. The cost/benefit issue has practical significance because many U.S. chemical manufacturing companies base their environmental, health and safety management strategies on just achieving and maintaining compliance with legal requirements when in reality this strategy may actually be a higher cost way of managing environmental, health and safety practices. This difference in environmental, health and safety management strategy is being investigated to determine if managing environmental, health and safety to achieve performance beyond that which is required by law results in a greater benefit to companies in the U.S. chemical manufacturing sector.

A review of dendrogeomorphological research applied to flood risk analysis in Spain

Over the last forty years, applying dendrogeomorphology to palaeoflood analysis has improved estimates of the frequency and magnitude of past floods worldwide. This paper reviews the main results obtained by applying dendrogeomorphology to flood research in several case studies in Central Spain. These dendrogeomorphological studies focused on the following topics: (1) anatomical analysis to understand the physiological response of trees to flood damage and improve sampling efficiency; (2) compiling robust flood chronologies in ungauged mountain streams, (3) determining flow depth and estimating flood discharge using two-dimensional hydraulic modelling, and comparing them with other palaeostage indicators; (4) calibrating hydraulic model parameters (i.e. Manning roughness); and (5) implementing stochastic-based, cost–benefit analysis to select optimal mitigation measures. The progress made in these areas is presented with suggestions for further research to improve the applicability of dendrogeochronology to palaeoflood studies. Further developments will include new methods for better identification of the causes of specific types of flood damage to trees (e.g. tilted trees) or stable isotope analysis of tree rings to identify the climatic conditions associated with periods of increasing flood magnitude or frequency.

Decreased generation of procoagulant platelets detected by flow cytometric analysis in patients with bleeding diathesis

Background: A clinically relevant bleeding diathesis is a frequent diagnostic challenge, which sometimes remains unexplained despite extensive investigations. The aim of our work was to evaluate the diagnostic utility of functional platelet testing by flow cytometry in this context. Methods: In case of negative results after standard laboratory work-up, flow cytometric analysis (FCA) of platelet function was done. We performed analysis of surface glycoproteins (GP) Ibα, IIb, IIIa; P-selectin expression and PAC-1 binding after graded doses of ADP, collagen and thrombin; content/secretion of dense granules; ability to generate procoagulant platelets. Results: Out of 437 patients investigated with standard tests between January 2007 and December 2011, we identified 67 (15.3%) with high bleeding scores and non-diagnostic standard laboratory work-up including platelet aggregation studies. Among these patients FCA revealed some potentially causative platelet defects: decreased dense-granule content/secretion (n=13); decreased alpha-granule secretion induced by ADP (n=10), convulxin (n=4) or thrombin (n=3); decreased fibrinogen-receptor activation induced by ADP (n=11), convulxin (n=11) or thrombin (n=8); decreased generation of COAT-platelets, i.e. highly procoagulant platelets induced by simultaneous activation with collagen and thrombin (n=16). Conclusion: Our work confirms that storage pool defects are frequent in patients with a bleeding diathesis and normal coagulation and platelet aggregations studies. Additionally, flow cytometric analysis is able to identify discrete platelet activation defects. In particular, we show for the first time that a relevant proportion of these patients has an isolated impaired ability to generate COAT-platelets - a conceptually new defect in platelet procoagulant activity, that is missed by conventional laboratory work-up. © 2014 Clinical Cytometry Society.

Quantitative 3D strain analysis in analogue experiments: Integration of X-ray computed tomography and digital volume correlation techniques

The combination of scaled analogue experiments, material mechanics, X-ray computed tomography (XRCT) and Digital Volume Correlation techniques (DVC) is a powerful new tool not only to examine the 3 dimensional structure and kinematic evolution of complex deformation structures in scaled analogue experiments, but also to fully quantify their spatial strain distribution and complete strain history. Digital image correlation (DIC) is an important advance in quantitative physical modelling and helps to understand non-linear deformation processes. Optical non-intrusive (DIC) techniques enable the quantification of localised and distributed deformation in analogue experiments based either on images taken through transparent sidewalls (2D DIC) or on surface views (3D DIC). X-ray computed tomography (XRCT) analysis permits the non-destructive visualisation of the internal structure and kinematic evolution of scaled analogue experiments simulating tectonic evolution of complex geological structures. The combination of XRCT sectional image data of analogue experiments with 2D DIC only allows quantification of 2D displacement and strain components in section direction. This completely omits the potential of CT experiments for full 3D strain analysis of complex, non-cylindrical deformation structures. In this study, we apply digital volume correlation (DVC) techniques on XRCT scan data of “solid” analogue experiments to fully quantify the internal displacement and strain in 3 dimensions over time. Our first results indicate that the application of DVC techniques on XRCT volume data can successfully be used to quantify the 3D spatial and temporal strain patterns inside analogue experiments. We demonstrate the potential of combining DVC techniques and XRCT volume imaging for 3D strain analysis of a contractional experiment simulating the development of a non-cylindrical pop-up structure. Furthermore, we discuss various options for optimisation of granular materials, pattern generation, and data acquisition for increased resolution and accuracy of the strain results. Three-dimensional strain analysis of analogue models is of particular interest for geological and seismic interpretations of complex, non-cylindrical geological structures. The volume strain data enable the analysis of the large-scale and small-scale strain history of geological structures.