303 research outputs found
Management of Obstructive Hydrocephalus Associated with Pineal Region Cysts and Tumors and Its Implication in Long-Term Outcome
BACKGROUND: Different treatment options have been proposed for obstructive hydrocephalus associated with pineal lesions. We discuss the obstructive hydrocephalus management associated with pineal region tumors and cysts in Helsinki Neurosurgery. METHODS: In this article, hydrocephalus treatment by tumor-cyst removal (n = 40), shunt surgery (n = 25), and endoscopic ventriculostomies (n = 3) is evaluated in 68 patients with obstructive hydrocephalus among 136 patients with pineal region tumor and cyst. Multivariate statistical analysis was followed by univariate and multivariate regression models of last functional status, last tumor-free imaging, and disease-specific mortality of the study population. RESULTS: Preoperative hydrocephalus was linked to higher World Health Organization tumor grades, poor functional status, higher mortality, and incomplete resection of pineal region cysts and tumors. Preoperative hydrocephalus remained a predictor of poor last functional status after multivariate regression. Pineal lesion removal with the posterior third ventricle opening as primary hydrocephalus treatment resulted in better last functional status, fewer postoperative shunts, fewer hydrocephalus related procedures, and fewer postoperative infections than in the shunt-treatment group. Multivariate regression analysis linked higher World Health Organization tumor & nbsp;grade, poor immediate functional status, postoperative complications, and incomplete surgical resection as independent predictors of disease mortality in patients with hydrocephalus. Same variables (except immediate modified Rankin Scale score) and higher number of shunt surgeries became independent predictors of poor last functional status at multivariate analysis. Incomplete resection was the only independent predictor of tumor-free magnetic resonance imaging at the last evaluation. CONCLUSIONS: Direct removal of pineal lesions with the opening of the posterior third ventricle could represent effective and reliable management of the associated obstructive hydrocephalus. Further research is required to generalize our inferences.Peer reviewe
Production Technology and Competitiveness In the Hungarian Manufacturing Industry
Following the big transformations of the 1990s, enterprise structure and technological level seem to
have become stabilised in Hungary. Under these circumstances it is especially interesting to identify
the elements responsible for competitiveness in general, and the role technology plays in development
in particular, according to managers experienced in production and marketing. This empirical
study – based on in-depth interviews and field research – summarises characteristics of the technological
level in the sectors examined, role of technology and labour in production, effects of foreign
direct investment, relations between competition and firm-level factors determining competitiveness,
and concludes by summing up those most frequently mentioned proposals that should be incorporated
into economic policy according to managers. Main findings indicate that more qualified,
more intensive and cheaper labour can be substituted for high technology. The competitiveness of an
enterprise is not determined by technology alone, but rather by a combination of technology, the parameters
of available labour and the costs of investment increasing productivity. The insufficiency
of inter-company relations, together with a shortage of available assets necessary for investment
constitute the major threat undermining the competitiveness of enterprises in present-day Hungary
The 'search for meaning' in therapeutic recreation
Therapeutic Recreation (TR) has been likened to an existential therapy because it facilitates meaningful outcomes for participants. Logotherapy and Existential Analysis (LTEA) has previously been proposed as a suitable existential approach for TR. However, this proposition has not been examined extensively in TR; consequently, LTEA has not been adopted widely as an in-depth approach to practice. Deductive content analysis (DCA) is a research method that has been recommended for testing a theoretical structure in a new context. A DCA of four of the most recent foundational textbooks in TR was conducted to test the theoretical structure of LTEA within the TR context. Content in the textbooks that related to the theoretical structure–the resources of the human spirit and the sources of meaning in life–was extracted and formed into categories and overarching TR concepts. Based on these findings, LTEA aligns with TR and could be a suitable approach to TR practice with the potential of enhancing its therapeutic aims
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Risk of sudden cardiac death associated with QRS, QTc, and JTc intervals in the general population
BACKGROUND QRS duration and corrected QT (QTc) interval have been associated with sudden cardiac death (SCD), but no data are available on the significance of repolarization component (JTc interval) of the QTc interval as an independent risk marker in the general population. OBJECTIVE In this study, we sought to quantify the risk of SCD associated with QRS, QTc, and JTc intervals. METHODS This study was conducted using data from 3 population cohorts from different eras, comprising a total of 20,058 individuals. The follow-up period was limited to 10 years and age at baseline to 30-61 years. QRS duration and QT interval (Bazett's) were measured from standard 12-lead electrocardiograms at baseline. JTc interval was defined as QTc interval - QRS duration. Cox proportional hazards models that controlled for confounding clinical factors identified at baseline were used to estimate the relative risk of SCD. RESULTS During a mean period of 9.7 years, 207 SCDs occurred (1.1 per 1000 person-years). QRS duration was associated with a significantly increased risk of SCD in each cohort (pooled hazard ratio [HR] 1.030 per 1-ms increase; 95% confidence interval [CI] 1.017-1.043). The QTc interval had borderline to significant associations with SCD and varied among cohorts (pooled HR 1.007; 95% CI 1.001-1.012). JTc interval as a continuous variable was not associated with SCD (pooled HR 1.001; 95% CI 0.996-1.007). CONCLUSION Prolonged QRS durations and QTc intervals are associated with an increased risk of SCD. However, when the QTc interval is deconstructed into QRS and JTc intervals, the repolarization component (JTc) appears to have no independent prognostic value.Peer reviewe
Genetic Risk Score for Coronary Disease Identifies Predispositions to Cardiovascular and Noncardiovascular Diseases.
BACKGROUND: The taxonomy of cardiovascular (CV) diseases is divided into a broad spectrum of clinical entities. Many such diseases coincide in specific patient groups and suggest shared predisposition. OBJECTIVES: This study focused on coronary artery disease (CAD) and investigated the genetic relationship to CV and non-CV diseases with reported CAD comorbidity. METHODS: This study examined 425,196 UK Biobank participants to determine a genetic risk score (GRS) based on 300 CAD associated variants (CAD-GRS). This score was associated with 22 traits, including risk factors, diseases secondary to CAD, as well as comorbid and non-CV conditions. Sensitivity analyses were performed in individuals free from CAD or stable angina diagnosis. RESULTS: Hypercholesterolemia (odds ratio [OR]: 1.27; 95% CI: 1.26 to 1.29) and hypertension (OR: 1.11; 95% CI: 1.10 to 1.12) were strongly associated with the CAD-GRS, which indicated that the score contained variants predisposing to these conditions. However, the CAD-GRS was also significant in patients with CAD who were free of CAD risk factors (OR: 1.37; 95% CI: 1.30 to 1.44). The study observed significant associations between the CAD-GRS and peripheral arterial disease (OR: 1.28; 95% CI: 1.23 to 1.32), abdominal aortic aneurysms (OR: 1.28; 95% CI: 1.20 to 1.37), and stroke (OR: 1.08; 95% CI: 1.05 to 1.10), which remained significant in sensitivity analyses that suggested shared genetic predisposition. The score was also associated with heart failure (OR: 1.25; 95% CI: 1.22 to 1.29), atrial fibrillation (OR: 1.08; 95% CI: 1.05 to 1.10), and premature death (OR: 1.04; 95% CI: 1.02 to 1.06). These associations were abolished in sensitivity analyses that indicated that they were secondary to prevalent CAD. Finally, an inverse association was observed between the score and migraine headaches (OR: 0.94; 95% CI: 0.93 to 0.96). CONCLUSIONS: A wide spectrum of CV conditions, including premature death, might develop consecutively or in parallel with CAD for the same genetic roots. In conditions like heart failure, the study found evidence that the CAD-GRS could be used to stratify patients with no or limited genetic overlap with CAD risk. Increased genetic predisposition to CAD was inversely associated with migraine headaches.National Institute of Health Research (NIHR) Barts Biomedical Research Centre - NIHR (IS-BRC-1215-20022)Fondation Leducq (CADgenomics, 12CVD02)Sonderforschungsbereich CRC 1123 (B2)German Federal Ministry of Education and Research (BMBF) (ERA-CVD: grant JTC2017_21-040
Clever-1/Stabilin-1 regulates lymphocyte migration within lymphatics and leukocyte entrance to sites of inflammation
Clever-1/Stabilin-1 is a scavenger receptor present on lymphatic and sinusoidal endothelium as well as on a subset of type II macrophages. It is also induced on vasculature at sites of inflammation. However, its in vivo function has remained practically unknown and this work addresses those unknown aspects. We demonstrate using in vivo models that Clever-1/Stabilin-1 mediates migration of T and B lymphocytes to the draining lymph nodes in vivo and identify the adhesive epitope of the Clever-1/Stabilin-1 molecule responsible for the interaction between lymphocytes and lymphatic endothelium. Moreover, we demonstrate that Ab blocking of Clever-1/Stabilin-1 efficiently inhibits peritonitis in mice by decreasing the entrance of granulocytes by 50%, while migration of monocytes and lymphocytes into the inflamed peritoneum is prevented almost completely. Despite efficient anti-inflammatory activity the Ab therapy does not dramatically dampen immune responses against the bacterial and foreign protein Ag tested and bacterial clearance. These results indicate that anti-Clever-1/Stabilin-1 treatment can target two different arms of the vasculature - traffic via lymphatics and inflamed blood vessels.</p
A comparison of genomic profiles of complex diseases under different models
Background: Various approaches are being used to predict individual risk to polygenic diseases from data provided
by genome-wide association studies. As there are substantial differences between the diseases investigated, the data
sets used and the way they are tested, it is difficult to assess which models are more suitable for this task.
Results: We compared different approaches for seven complex diseases provided by the Wellcome Trust Case
Control Consortium (WTCCC) under a within-study validation approach. Risk models were inferred using a variety of
learning machines and assumptions about the underlying genetic model, including a haplotype-based approach with
different haplotype lengths and different thresholds in association levels to choose loci as part of the predictive
model. In accordance with previous work, our results generally showed low accuracy considering disease heritability
and population prevalence. However, the boosting algorithm returned a predictive area under the ROC curve (AUC)
of 0.8805 for Type 1 diabetes (T1D) and 0.8087 for rheumatoid arthritis, both clearly over the AUC obtained by other
approaches and over 0.75, which is the minimum required for a disease to be successfully tested on a sample at risk,
which means that boosting is a promising approach. Its good performance seems to be related to its robustness to
redundant data, as in the case of genome-wide data sets due to linkage disequilibrium.
Conclusions: In view of our results, the boosting approach may be suitable for modeling individual predisposition to
Type 1 diabetes and rheumatoid arthritis based on genome-wide data and should be considered for more in-depth
research.This work was supported by the Spanish Secretary of Research, Development
and Innovation [TIN2010-20900-C04-1]; the Spanish Health Institute Carlos III
[PI13/02714]and [PI13/01527] and the Andalusian Research Program under
project P08-TIC-03717 with the help of the European Regional Development
Fund (ERDF). The authors are very grateful to the reviewers, as they believe that
their comments have helped to substantially improve the quality of the paper
Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts
Introduction: Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. Methods: We studied eight prospective cohorts with 22,623 participants profiled by n
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