Semantic Dementia: a specific network-opathy

Semantic dementia (SD) is a unique syndrome in the frontotemporal lobar degeneration spectrum. Typically presenting as a progressive, fluent anomic aphasia, SD is the paradigmatic disorder of semantic memory with a characteristic anatomical profile of asymmetric, selective antero-inferior temporal lobe atrophy. Histopathologically, most cases show a specific pattern of abnormal deposition of protein TDP-43. This relatively close clinical, anatomical and pathological correspondence suggests SD as a promising target for future therapeutic trials. Here, we discuss outstanding nosological and neurobiological challenges posed by the syndrome and propose a pathophysiological model of SD based on sequential, regionally determined disintegration of a vulnerable neural network

Complex systems and the technology of variability analysis

Characteristic patterns of variation over time, namely rhythms, represent a defining feature of complex systems, one that is synonymous with life. Despite the intrinsic dynamic, interdependent and nonlinear relationships of their parts, complex biological systems exhibit robust systemic stability. Applied to critical care, it is the systemic properties of the host response to a physiological insult that manifest as health or illness and determine outcome in our patients. Variability analysis provides a novel technology with which to evaluate the overall properties of a complex system. This review highlights the means by which we scientifically measure variation, including analyses of overall variation (time domain analysis, frequency distribution, spectral power), frequency contribution (spectral analysis), scale invariant (fractal) behaviour (detrended fluctuation and power law analysis) and regularity (approximate and multiscale entropy). Each technique is presented with a definition, interpretation, clinical application, advantages, limitations and summary of its calculation. The ubiquitous association between altered variability and illness is highlighted, followed by an analysis of how variability analysis may significantly improve prognostication of severity of illness and guide therapeutic intervention in critically ill patients

Organization of multiprotein complexes at cell–cell junctions

The formation of stable cell–cell contacts is required for the generation of barrier-forming sheets of epithelial and endothelial cells. During various physiological processes like tissue development, wound healing or tumorigenesis, cellular junctions are reorganized to allow the release or the incorporation of individual cells. Cell–cell contact formation is regulated by multiprotein complexes which are localized at specific structures along the lateral cell junctions like the tight junctions and adherens junctions and which are targeted to these site through their association with cell adhesion molecules. Recent evidence indicates that several major protein complexes exist which have distinct functions during junction formation. However, this evidence also indicates that their composition is dynamic and subject to changes depending on the state of junction maturation. Thus, cell–cell contact formation and integrity is regulated by a complex network of protein complexes. Imbalancing this network by oncogenic proteins or pathogens results in barrier breakdown and eventually in cancer. Here, I will review the molecular organization of the major multiprotein complexes at junctions of epithelial cells and discuss their function in cell–cell contact formation and maintenance

Persistent Place-Making in Prehistory: the Creation, Maintenance, and Transformation of an Epipalaeolithic Landscape

Most archaeological projects today integrate, at least to some degree, how past people engaged with their surroundings, including both how they strategized resource use, organized technological production, or scheduled movements within a physical environment, as well as how they constructed cosmologies around or created symbolic connections to places in the landscape. However, there are a multitude of ways in which archaeologists approach the creation, maintenance, and transformation of human-landscape interrelationships. This paper explores some of these approaches for reconstructing the Epipalaeolithic (ca. 23,000–11,500 years BP) landscape of Southwest Asia, using macro- and microscale geoarchaeological approaches to examine how everyday practices leave traces of human-landscape interactions in northern and eastern Jordan. The case studies presented here demonstrate that these Epipalaeolithic groups engaged in complex and far-reaching social landscapes. Examination of the Early and Middle Epipalaeolithic (EP) highlights that the notion of “Neolithization” is somewhat misleading as many of the features we use to define this transition were already well-established patterns of behavior by the Neolithic. Instead, these features and practices were enacted within a hunter-gatherer world and worldview

Laparoscopy for small bowel obstruction: the reason for conversion matters

BACKGROUND: Although laparoscopy is associated with reduced hospital stay, early recovery, and decreased morbidity compared with open surgery, it is not well established for the treatment of small bowel obstruction (SBO). METHODS: This study analyzed a prospective nationwide database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery. RESULTS: From 1995 to 2006, 537 patients underwent laparoscopy for SBO. Matted adhesions were the main cause of obstruction (62.6%). Intraoperative complications occurred for 9.5% of the patients. Postoperative morbidity was 14% and mortality 0.6%. Within 30 days, 13 patients (2.4%) were readmitted because of early recurrence or complications. The conversion rate was 32.4%. The conversions resulted from inability to visualize the site of obstruction or matted adhesions (53.4%), intraoperative complications (21.3%), and small target incisions for resection (25.3%). Emergency operations were associated with higher conversion rates (43.6% vs 19.8%; p < 0.001) but not with significantly more postoperative complications (15.2% vs 11.9%; p = 0.17). Intraoperative complications and conversion were associated with significantly increased postoperative morbidity (39.2% vs 11.3%; p < 0.001 and 24.7% vs 8.3%; p < 0.001, respectively). Reactive conversion due to intraoperative complications was associated with the highest postoperative complication rate (48.6%). Morbidity for preemptive conversion due to impaired visualization/matted adhesions or a small-target incision was significantly lower (20% and 26.1%; p = 0.02 and p < 0.001, respectively). American Society of Anesthesiology (ASA) scores higher than 2 also were associated with postoperative morbidity (p < 0.001). However, multivariate regression analysis showed that reactive conversion was the only independent risk factor for postoperative morbidity (p < 0.001; odds ratio, 3.97; 95% confidence interval, 1.83-8.64). CONCLUSIONS: Laparoscopic management of SBO is feasible with acceptable morbidity and low mortality but with a considerable conversion rate. Early conversion is recommended to reduce postoperative morbidity