Statistical evaluation of the reproducibility and the influence of paper on the analysis of black gel pen ink using laser desorption ionisation mass spectrometry

Laser desorption ionisation mass spectrometry (LDI-MS) has demonstrated to be an excellent analytical method for the forensic analysis of inks on a questioned document. The ink can be analysed directly on its substrate (paper) and hence offers a fast method of analysis as sample preparation is kept to a minimum and more importantly, damage to the document is minimised. LDI-MS has also previously been reported to provide a high power of discrimination in the statistical comparison of ink samples and has the potential to be introduced as part of routine ink analysis. This paper looks into the methodology further and evaluates statistically the reproducibility and the influence of paper on black gel pen ink LDI-MS spectra; by comparing spectra of three different black gel pen inks on three different paper substrates. Although generally minimal, the influences of sample homogeneity and paper type were found to be sample dependent. This should be taken into account to avoid the risk of false differentiation of black gel pen ink samples. Other statistical approaches such as principal component analysis (PCA) proved to be a good alternative to correlation coefficients for the comparison of whole mass spectra.

Cutting edge: IL-7 regulates the peripheral pool of adult ROR gamma+ lymphoid tissue inducer cells.

During fetal life, CD4(+)CD3(-) lymphoid tissue inducer (LTi) cells are required for lymph node and Peyer's patch development in mice. In adult animals, CD4(+)CD3(-) cells are found in low numbers in lymphoid organs. Whether adult CD4(+)CD3(-) cells are LTi cells and are generated and maintained through cytokine signals has not been directly addressed. In this study we show that adult CD4(+)CD3(-) cells adoptively transferred into neonatal CXCR5(-/-) mice induced the formation of intestinal lymphoid tissues, demonstrating for the first time their bona fide LTi function. Increasing IL-7 availability in wild-type mice either by IL-7 transgene expression or treatment with IL-7/anti-IL-7 complexes increased adult LTi cell numbers through de novo generation from bone marrow cells and increased the survival and proliferation of LTi cells. Our observations demonstrate that adult CD4(+)lineage(-) cells are LTi cells and that the availability of IL-7 determines the size of the adult LTi cell pool.

Telomerase activity and human telomerase reverse transcriptase mRNA expression in soft tissue tumors: correlation with grade, histology, and proliferative activity.

Telomerase activity (TA) is detected in most human cancers but, with few exceptions, not in normal somatic cells. Little is known about TA in soft tissue tumors. We have examined a series of benign and malignant soft tissue tumors for TA using the telomerase repeat amplification protocol assay. Analysis of the expression of the human telomerase reverse transcriptase was also carried out using RT-PCR. TA was undetectable in benign lesions (15 of 15) and low-grade sarcomas (6 of 6) and was detectable in 50% (19 of 38) of intermediate-/high-grade sarcomas. Although the presence of TA in soft tissue tumors is synonymous with malignancy, it is neither a reliable method in making the distinction between reactive/benign and malignant (especially low-grade) lesions nor a reliable marker of tumor aggressiveness. Leiomyosarcomas and storiform/pleomorphic malignant fibrous histiocytomas rarely showed TA, irrespective of their grade. A strong correlation between human telomerase reverse transcriptase mRNA expression and TA was observed, supporting the close relationship between both parameters. No significant relationship was observed between proliferative activity (as assessed by MIB-1 immunolabeling) and TA. We verified that the absence of telomerase expression was not due to the presence of telomerase inhibitors and therefore alternative mechanism(s) for cell immortalization, yet to be determined, seem to be involved in the development and/or maintenance of some soft tissue sarcomas.

Brain Health and Dementia Prevention in Ireland - a discussion paper

Joint discussion paper funded by the Alzheimer Society of Ireland and authored by the Institute of Public Health Approximately 47,849 people were living with dementia in Ireland in 2011. This number is expected to double by 2031 to about 90,000 as incident rates of dementia are set to rise with population ageing (Pierce et. al. 2014). Although much remains to be established at a causal level, epidemiological research indicates that there is scope for reducing dementia prevalence and age-specific incidence through addressing modifiable risk factors. There is a growing consensus for the mobilisation of public health approaches to attempt to reduce the prevalence of dementia through primary prevention. This discussion paper presents a rapid review of evidence on the primary prevention of dementia and presents estimates for the number of dementia cases that could potentially be preventable through modifying specific risk factors in Ireland. The paper focuses only on primary prevention which relates to delaying or preventing the onset of dementia. Specifically, the discussion paper presents: a rapid review of the current evidence-base on dementia prevention internationally estimates of the number of dementia cases that might be prevented by addressing modifiable risk factors considerations for integrating a brain health and dementia prevention perspective into public health research, policy and practice in Ireland.

Health Protection Inequalities on the island of Ireland: An introductory paper

Public health services in Ireland, North and South, are committed to addressing inequalities in health on the island of Ireland. This report, prepared by Dr Lorraine Doherty, Assistant Director of Public Health (Health Protection), Public Health Agency NI for the Institute of Public Health in Ireland (IPH), specifically highlights health inequalities in relation to infectious diseases and other areas of health protection such as chemical hazards and environmental disruption. Infectious diseases disproportionately affect the most vulnerable in society. These vulnerable groups bear the highest burden of disease in relation to infectious diseases. The report also highlights the impact of climate change on health protection and the impacts for water, food and vector borne diseases. The aim of this report is to enable a programme of work to begin to document health protection inequalities and develop action plans for addressing them on an all island basis.

'Bio-nano interactions: new tools, insights and impacts': summary of the Royal Society discussion meeting

Bio-nano interactions can be defined as the study of interactions between nanoscale entities and biological systems such as, but not limited to, peptides, proteins, lipids, DNA and other biomolecules, cells and cellular receptors and organisms including humans. Studying bio-nano interactions is particularly useful for understanding engineered materials that have at least one dimension in the nanoscale. Such materials may consist of discrete particles or nanostructured surfaces. Much of biology functions at the nanoscale; therefore, our ability to manipulate materials such that they are taken up at the nanoscale, and engage biological machinery in a designed and purposeful manner, opens new vistas for more efficient diagnostics, therapeutics (treatments) and tissue regeneration, so-called nanomedicine. Additionally, this ability of nanomaterials to interact with and be taken up by cells allows nanomaterials to be used as probes and tools to advance our understanding of cellular functioning. Yet, as a new technology, assessment of the safety of nanomaterials, and the applicability of existing regulatory frameworks for nanomaterials must be investigated in parallel with development of novel applications. The Royal Society meeting 'Bio-nano interactions: new tools, insights and impacts' provided an important platform for open dialogue on the current state of knowledge on these issues, bringing together scientists, industry, regulatory and legal experts to concretize existing discourse in science law and policy. This paper summarizes these discussions and the insights that emerged.

Pathway analysis of glioblastoma tissue after preoperative treatment with the EGFR tyrosine kinase inhibitor gefitinib--a phase II trial.

Amplification of the epidermal growth factor receptor (EGFR) gene is one of the most common oncogenic alterations in glioblastoma (45%) making it a prime target for therapy. However, small molecule inhibitors of the EGFR tyrosine kinase showed disappointing efficacy in clinical trials for glioblastoma. Here we aimed at investigating the molecular effects of the tyrosine kinase inhibitor gefitinib on the EGFR signaling pathway in human glioblastoma. Twenty-two patients selected for reoperation of recurrent glioblastoma were treated within a phase II trial for 5 days with 500 mg gefitinib before surgery followed by postoperative gefitinib until recurrence. Resected glioblastoma tissues exhibited high concentrations of gefitinib (median, 4.1 μg/g), 20 times higher than respective plasma. EGFR-pathway activity was evaluated with phosphorylation-specific assays. The EGFR was efficiently dephosphorylated in treated patients as compared to a control cohort of 12 patients. However, no significant effect on 12 pathway constituents was detected. In contrast, in vitro treatment of a glioblastoma cell line, BS-153, with endogenous EGFRwt amplification and EGFRvIII expression resulted not only in dephosphorylation of the EGFR, but also of key regulators in the pathway such as AKT. Treating established xenografts of the same cell line as an in vivo model showed dephosphorylation of the EGFR without affecting downstream signal transductors, similar to the human glioblastoma. Taken together, gefitinib reaches high concentrations in the tumor tissue and efficiently dephosphorylates its target. However, regulation of downstream signal transducers in the EGFR pathway seems to be dominated by regulatory circuits independent of EGFR phosphorylation.

TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-α blockade

In Chagas disease, understanding how the immune response controls parasite growth but also leads to heart damage may provide insight into the design of new therapeutic strategies. Tumor necrosis factor-alpha (TNF-α) is important for resistance to acute Trypanosoma cruzi infection; however, in patients suffering from chronic T. cruzi infection, plasma TNF-α levels correlate with cardiomyopathy. Recent data suggest that CD8-enriched chagasic myocarditis formation involves CCR1/CCR5-mediated cell migration. Herein, the contribution of TNF-α, especially signaling through the receptor TNFR1/p55, to the pathophysiology of T. cruzi infection was evaluated with a focus on the development of myocarditis and heart dysfunction. Colombian strain-infected C57BL/6 mice had increased frequencies of TNFR1/p55+ and TNF-α+ splenocytes. Although TNFR1-/- mice exhibited reduced myocarditis in the absence of parasite burden, they succumbed to acute infection. Similar to C57BL/6 mice, Benznidazole-treated TNFR1-/- mice survived acute infection. In TNFR1-/- mice, reduced CD8-enriched myocarditis was associated with defective activation of CD44+CD62Llow/- and CCR5+ CD8+ lymphocytes. Also, anti-TNF-α treatment reduced the frequency of CD8+CCR5+ circulating cells and myocarditis, though parasite load was unaltered in infected C3H/HeJ mice. TNFR1-/- and anti-TNF-α-treated infected mice showed regular expression of connexin-43 and reduced fibronectin deposition, respectively. Furthermore, anti-TNF-α treatment resulted in lower levels of CK-MB, a cardiomyocyte lesion marker. Our results suggest that TNF/TNFR1 signaling promotes CD8-enriched myocarditis formation and heart tissue damage, implicating the TNF/TNFR1 signaling pathway as a potential therapeutic target for control of T. cruzi-elicited cardiomyopathy.

A CMR study of the effects of tissue edema and necrosis on left ventricular dyssynchrony in acute myocardial infarction: implications for cardiac resynchronization therapy.

ABSTRACT: BACKGROUND: In acute myocardial infarction (AMI), both tissue necrosis and edema are present and both might be implicated in the development of intraventricular dyssynchrony. However, their relative contribution to transient dyssynchrony is not known. Cardiovascular magnetic resonance (CMR) can detect necrosis and edema with high spatial resolution and it can quantify dyssynchrony by tagging techniques. METHODS: Patients with a first AMI underwent percutaneous coronary interventions (PCI) of the infarct-related artery within 24 h of onset of chest pain. Within 5-7 days after the event and at 4 months, CMR was performed. The CMR protocol included the evaluation of intraventricular dyssynchrony by applying a novel 3D-tagging sequence to the left ventricle (LV) yielding the CURE index (circumferential uniformity ratio estimate; 1 = complete synchrony). On T2-weighted images, edema was measured as high-signal (>2 SD above remote tissue) along the LV mid-myocardial circumference on 3 short-axis images (% of circumference corresponding to the area-at-risk). In analogy, on late-gadolinium enhancement (LGE) images, necrosis was quantified manually as percentage of LV mid-myocardial circumference on 3 short-axis images. Necrosis was also quantified on LGE images covering the entire LV (expressed as %LV mass). Finally, salvaged myocardium was calculated as the area-at-risk minus necrosis (expressed as % of LV circumference). RESULTS: After successful PCI (n = 22, 2 female, mean age: 57 ± 12y), peak troponin T was 20 ± 36ug/l and the LV ejection fraction on CMR was 41 ± 8%. Necrosis mass was 30 ± 10% and CURE was 0.91 ± 0.05. Edema was measured as 58 ± 14% of the LV circumference. In the acute phase, the extent of edema correlated with dyssynchrony (r2 = -0.63, p < 0.01), while extent of necrosis showed borderline correlation (r2 = -0.19, p = 0.05). PCI resulted in salvaged myocardium of 27 ± 14%. LV dyssynchrony (=CURE) decreased at 4 months from 0.91 ± 0.05 to 0.94 ± 0.03 (p < 0.004, paired t-test). At 4 months, edema was absent and scar %LV slightly shrunk to 23.7 ± 10.0% (p < 0.002 vs baseline). Regression of LV dyssynchrony during the 4 months follow-up period was predicted by both, the extent of edema and its necrosis component in the acute phase. CONCLUSIONS: In the acute phase of infarction, LV dyssynchrony is closely related to the extent of edema, while necrosis is a poor predictor of acute LV dyssynchrony. Conversely, regression of intraventricular LV dyssynchrony during infarct healing is predicted by the extent of necrosis in the acute phase.

El paper del capital social en l'organització d'esdeveniments

La intenció d'aquest article és detallar l'abast del capital social als esdeveniments culturals celebrats a Catalunya i analitzar la influència sobre l'atracció turística dels mateixos. Es pretén determinar també quin és l'impacte que tres elements de capital social que intervenen en l'organització d'esdeveniments (elements de motivació, creació de xarxes internes i lideratge) tenen sobre el sector turístic local. L'estudi parteix d'una mostra de 263 esdeveniments als quals s'ha adreçat una enquesta per determinar la presència i pes dels factors de capital social. Aquesta informació s'ha creuat amb dades sobre impactes i atracció turística obtingudes també a partir de la mateixa enquesta i, a partir de l'aplicació del test del chi quadrat, s'ha contrastat si les diferències existents entre els diferents factors del capital social són estadísticament significatives. Les conclusions principals obtingudes indiquen que els esdeveniments que tenen elements de capital social que els reforça la seva cohesió social entenen i justifiquen la celebració com a fet socialitzador, independentment del seu abast turístic. A més es detecta que la creació de xarxes de relació enforteix la cohesió interna, la representativitat i el sentit d'identitat de la comunitat. Finalment es constata que la presència d'elements de lideratge que donen visibilitat i vinculen l'esdeveniment amb xarxes externes explica la diferència existent en la capacitat d'atracció i impactes turístics dels esdeveniments. La principal aportació del treball és posar de manifest el paper del capital social com a factor que incideix en la repercussió social i turística dels esdeveniments catalans. La diagnosi efectuada permet recomanar la incorporació del capital social com un actiu estratègic per a la gestió i per a la creació de nous productes i polítiques turístiques centrades en els esdeveniments culturals.

Gènere i bilingüisme: connectant experiències i teories. Introductory paper in Santaemilia, José, Patricia Bou, Sergio Maruenda i Gora Zaragoza International Perspectives on Gender and Language

Peer-reviewed

Population biology of Toxoplasma gondii: what's out and where did they come from

Until recently, Toxoplasma gondii was considered to be clonal with little genetic variability. In this paper we summarize recent genotyping data from chickens in Brazil, and pigs, lambs and white-tailed deer in the USA, to demonstrate the high genetic diversity and geographical distribution of T. gondii. A total of 149 T. gondii isolates from 13 geographical areas of Brazil and 182 T. gondii isolates from pigs, 53 isolates from sheep and 15 isolates from fetal white-tailed deer from USA were genotyped using the 10 RCFP-PCR genetic markers SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico. Genotyping of 149 T. gondii isolates from free range chickens in Brazil identified 58 genotype groups. No clonal type II lineage was found. Of the 253 isolates from animals from USA, 18 genotypes were identified, predominantly type II. These studies indicate a higher genetic diversity than previously recognized.

Veterinary vaccines against Toxoplasma gondii

Toxoplasma gondii has a very wide intermediate host range and is thought to be able to infect all warm blooded animals. The parasite causes a spectrum of different diseases and clinical symptoms within the intermediate hosts and following infection most animals develop adaptive humoral and cell-mediated immune responses. The development of protective immunity to T. gondii following natural infection in many host species has led researchers to look at vaccination as a strategy to control disease, parasite multiplication and establishment in animal hosts. A range of different veterinary vaccines are required to help control T. gondii infection which include vaccines to prevent congenital toxoplasmosis, reduce or eliminate tissue cysts in meat producing animals and to prevent oocyst shedding in cats. In this paper we will discuss some of the history, challenges and progress in the development of veterinary vaccines against T. gondii.