Advances in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a heterogeneous course and systemic involvement. It is the result of a complex pathogenic pathway that culminates in autoantibody formation. The interaction between environmental triggers and genetic susceptibility is key in this process. Genome-wide association study technology has allowed the recognition of > 80 loci associated with SLE that lead to the formation of key proteins, each contributing a small increase to the risk. Advances in the management of the disease include new validated standardized tools to capture disease activity, damage and quality of life, for clinical and research purposes. The prognosis of SLE has much improved in the last 50 years because of better general management and specific treatment, including better use of immunosuppressive agents and development of a new group of drugs – biological therapies

Diversity of sympathetic vasoconstrictor pathways and their plasticity after spinal cord injury

Sympathetic vasoconstrictor pathways pass through paravertebral ganglia carrying ongoing and reflex activity arising within the central nervous system to their vascular targets. The pattern of reflex activity is selective for particular vascular beds and appropriate for the physiological outcome (vasoconstriction or vasodilation). The preganglionic signals are distributed to most postganglionic neurones in ganglia via synapses that are always suprathreshold for action potential initiation (like skeletal neuromuscular junctions). Most postganglionic neurones receive only one of these “strong” inputs, other preganglionic connections being ineffective. Pre- and postganglionic neurones discharge normally at frequencies of 0.5–1 Hz and maximally in short bursts at <10 Hz. Animal experiments have revealed unexpected changes in these pathways following spinal cord injury. (1) After destruction of preganglionic neurones or axons, surviving terminals in ganglia sprout and rapidly re-establish strong connections, probably even to inappropriate postganglionic neurones. This could explain aberrant reflexes after spinal cord injury. (2) Cutaneous (tail) and splanchnic (mesenteric) arteries taken from below a spinal transection show dramatically enhanced responses in vitro to norepinephrine released from perivascular nerves. However the mechanisms that are modified differ between the two vessels, being mostly postjunctional in the tail artery and mostly prejunctional in the mesenteric artery. The changes are mimicked when postganglionic neurones are silenced by removal of their preganglionic input. Whether or not other arteries are also hyperresponsive to reflex activation, these observations suggest that the greatest contribution to raised peripheral resistance in autonomic dysreflexia follows the modifications of neurovascular transmission

Characteristics of predictor sets found using differential prioritization

<p>Abstract</p> <p>Background</p> <p>Feature selection plays an undeniably important role in classification problems involving high dimensional datasets such as microarray datasets. For filter-based feature selection, two well-known criteria used in forming predictor sets are relevance and redundancy. However, there is a third criterion which is at least as important as the other two in affecting the efficacy of the resulting predictor sets. This criterion is the degree of differential prioritization (DDP), which varies the emphases on relevance and redundancy depending on the value of the DDP. Previous empirical works on publicly available microarray datasets have confirmed the effectiveness of the DDP in molecular classification. We now propose to establish the fundamental strengths and merits of the DDP-based feature selection technique. This is to be done through a simulation study which involves vigorous analyses of the characteristics of predictor sets found using different values of the DDP from toy datasets designed to mimic real-life microarray datasets.</p> <p>Results</p> <p>A simulation study employing analytical measures such as the distance between classes before and after transformation using principal component analysis is implemented on toy datasets. From these analyses, the necessity of adjusting the differential prioritization based on the dataset of interest is established. This conclusion is supported by comparisons against both simplistic rank-based selection and state-of-the-art equal-priorities scoring methods, which demonstrates the superiority of the DDP-based feature selection technique. Reapplying similar analyses to real-life multiclass microarray datasets provides further confirmation of our findings and of the significance of the DDP for practical applications.</p> <p>Conclusion</p> <p>The findings have been achieved based on analytical evaluations, not empirical evaluation involving classifiers, thus providing further basis for the usefulness of the DDP and validating the need for unequal priorities on relevance and redundancy during feature selection for microarray datasets, especially highly multiclass datasets.</p

Identification of O-Linked Glycoproteins Binding to the Lectin Helix pomatia Agglutinin as Markers of Metastatic Colorectal Cancer

Background Protein glycosylation is an important post-translational modification shown to be altered in all tumour types studied to date. Mucin glycoproteins have been established as important carriers of O-linked glycans but other glycoproteins exhibiting altered glycosylation repertoires have yet to be identified but offer potential as biomarkers for metastatic cancer. Methodology In this study a glycoproteomic approach was used to identify glycoproteins exhibiting alterations in glycosylation in colorectal cancer and to evaluate the changes in O-linked glycosylation in the context of the p53 and KRAS (codon 12/13) mutation status. Affinity purification with the carbohydrate binding protein from Helix pomatia agglutinin (HPA) was coupled to 2-dimensional gel electrophoresis with mass spectrometry to enable the identification of low abundance O-linked glycoproteins from human colorectal cancer specimens. Results Aberrant O-linked glycosylation was observed to be an early event that occurred irrespective of the p53 and KRAS status and correlating with metastatic colorectal cancer. Affinity purification using the lectin HPA followed by proteomic analysis revealed annexin 4, annexin 5 and CLCA1 to be increased in the metastatic colorectal cancer specimens. The results were validated using a further independent set of specimens and this showed a significant association between the staining score for annexin 4 and HPA and the time to metastasis; independently (annexin A4: Chi square 11.45, P = 0.0007; HPA: Chi square 9.065, P = 0.0026) and in combination (annexin 4 and HPA combined: Chi square 13.47; P = 0.0002). Conclusion Glycoproteins showing changes in O-linked glycosylation in metastatic colorectal cancer have been identified. The glycosylation changes were independent of p53 and KRAS status. These proteins offer potential for further exploration as biomarkers and potential targets for metastatic colorectal cancer

International entrepreneurship in SMEs: a study of influencing factors in the textile industry

The final publication is available at Springer via http://dx.doi.org/10.1007/s11365-012-0242-3International entrepreneurship is an incipient research area with a rapidly increasing body of knowledge and contributions. An important part of this literature has focused on the analysis of the contributing factors to IE development. From these studies, this work attempts to analyse and validate through an integrative model the effect on this construct in SME of some of the main factors proposed by the literature such as Skills and Competences, Attitude and Proactiveness, Creativity and Innovation, Networking, Employees and Activity. To proceed with this aim, we conducted an empirical research focused on 174 textile SME in Spain. The results obtained confirm a positive relationship between the studied factors and the IE development. 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Re-examining the effect of door-to-balloon delay on STEMI outcomes in the context of unmeasured confounders: a retrospective cohort study

Literature studying the door-to-balloon time-outcome relation in coronary intervention is limited by the potential of residual biases from unobserved confounders. This study re-examines the time-outcome relation with further consideration of the unobserved factors and reports the population average effect. Adults with ST-elevation myocardial infarction admitted to one of the six registry participating hospitals in Australia were included in this study. The exposure variable was patient-level door-to-balloon time. Primary outcomes assessed included in-hospital and 30 days mortality. 4343 patients fulfilled the study criteria. 38.0% (1651) experienced a door-to-balloon delay of >90 minutes. The absolute risk differences for in-hospital and 30-day deaths between the two exposure subgroups with balanced covariates were 2.81 (95% CI 1.04, 4.58) and 3.37 (95% CI 1.49, 5.26) per 100 population. When unmeasured factors were taken into consideration, the risk difference were 20.7 (95% CI −2.6, 44.0) and 22.6 (95% CI −1.7, 47.0) per 100 population. Despite further adjustment of the observed and unobserved factors, this study suggests a directionally consistent linkage between longer door-to-balloon delay and higher risk of adverse outcomes at the population level. Greater uncertainties were observed when unmeasured factors were taken into consideration

ALL-1/MLL1, a homologue of Drosophila TRITHORAX, modifies chromatin and is directly involved in infant acute leukaemia

Rearrangements of the ALL-1/MLL1 gene underlie the majority of infant acute leukaemias, as well as of therapy-related leukaemias developing in cancer patients treated with inhibitors of topoisomerase II, such as VP16 and doxorubicin. The rearrangements fuse ALL-1 to any of \u3e50 partner genes or to itself. Here, we describe the unique features of ALL-1-associated leukaemias, and recent progress in understanding molecular mechanisms involved in the activity of the ALL-1 protein and of its Drosophila homologue TRITHORAX

Entrepreneurship, export orientation and economic growth

In this paper the relationship between a country’s prevalence of new ventures and its rate of economic growth is investigated, while taking into account new ventures’ export orientation. It is generally acknowledged that new venture creation as well as export activity may both be important strategies for achieving national economic growth. However, to our knowledge no attempt has been made to investigate empirically the role of export-driven new ventures in economic growth. We focus on the national level and use data for a sample of 34 countries over the period 2002–2008. Our results suggest that, on top of a positive relation between entrepreneurial activity in general and subsequent macroeconomic growth, there is an additional positive effect of export-oriented early-stage entrepreneurship in higher-income countries. However, there is no such additional effect in lower-income countries

Scintigraphic evaluation of oesophageal transit during radiotherapy to the mediastinum

Background: To quantitatively evaluate radiation-induced impaired oesophageal transit with oesophageal transit scintigraphy and to assess the relationships between acute oesophagitis symptoms and dysmotility.\ud \ud Methods: Between January 1996 and November 1998, 11 patients affected by non-small-cell carcinoma of the lung not directly involving the oesophagus, requiring adjuvant external beam radiotherapy (RT) to the mediastinum were enrolled. Oesophageal transit scans with liquid and semisolid bolus were performed at three pre-defined times: before (T0) and during radiation at 10 Gy (T1) and 30 Gy (T2). Two parameters were obtained for evaluation: 1) mean transit time (MTT); and 2) ratio between peak activity and residual activity at 40 seconds (ER-40s). Acute radiation toxicity was scored according to the joint EORTC-RTOG criteria. Mean values with standard deviation were calculated for all parameters. Analysis of variance (ANOVA) tests and paired t-Tests for all values were performed.\ud \ud Results: An increase in the ER-40s from T0 to T1 or T2 was seen in 9 of 11 patients (82%). The mean ER-40s value for all patients increased from 0.8306 (T0) to 0.8612 (T1) and 0.8658 (T2). These differences were statistically significant (p < 0.05) in two paired t-Tests at T0 versus T2 time: overall mean ER-40s and upright ER-40s (p = 0.041 and p = 0.032, respectively). Seven patients (63%) showed a slight increase in the mean MTT value during irradiation but no statistically significant differences in MTT parameters were found between T0, T1 and T2 (p > 0.05).\ud \ud Conclusion: Using oesophageal scintigraphy we were able to detect early alterations of oesophageal transit during the third week of thoracic RT