Murine model for Fusarium oxysporum invasive fusariosis reveals organ-specific structures for dissemination and long-term persistence

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Coordinated grid and place cell replay during rest

Hippocampal replay has been hypothesized to underlie memory consolidation and navigational planning, yet the involvement of grid cells in replay is unknown. During replay we found grid cells to be spatially coherent with place cells, encoding locations 11 ms delayed relative to the hippocampus, with directionally modulated grid cells and forward replay exhibiting the greatest coherence with the CA1 area of the hippocampus. This suggests grid cells are engaged during the consolidation of spatial memories to the neocortex

Neural models that convince: Model hierarchies and other strategies to bridge the gap between behavior and the brain.

Computational modeling of the brain holds great promise as a bridge from brain to behavior. To fulfill this promise, however, it is not enough for models to be 'biologically plausible': models must be structurally accurate. Here, we analyze what this entails for so-called psychobiological models, models that address behavior as well as brain function in some detail. Structural accuracy may be supported by (1) a model's a priori plausibility, which comes from a reliance on evidence-based assumptions, (2) fitting existing data, and (3) the derivation of new predictions. All three sources of support require modelers to be explicit about the ontology of the model, and require the existence of data constraining the modeling. For situations in which such data are only sparsely available, we suggest a new approach. If several models are constructed that together form a hierarchy of models, higher-level models can be constrained by lower-level models, and low-level models can be constrained by behavioral features of the higher-level models. Modeling the same substrate at different levels of representation, as proposed here, thus has benefits that exceed the merits of each model in the hierarchy on its own

An observational efficacy and safety analysis of the treatment of acute invasive aspergillosis using voriconazole

The purpose of this study was to evaluate efficacy and safety of voriconazole in patients with acute invasive aspergillosis (IA) in a real-life, clinical setting. This was a multicenter observational study in adult patients treated with voriconazole for invasive mycosis. The study evaluated clinical response, mortality, use of other licensed antifungal therapy (OLAT), and treatment duration. This sub-analysis evaluated treatment and outcome data specifically from adult patients with proven/probable IA, while safety data were assessed in patients with proven/probable/possible IA. Of the 141 patients enrolled, 113 were adults with proven/probable IA and six had possible IA. Voriconazole treatment duration ranged from 1 to 183 days (median, 49.5 days). Voriconazole was used exclusively in 64% (72/113) of patients and in combination/sequentially with OLAT in 36%. Overall successful treatment response was 50% (57/113 patients). Twelve percent (14/113) of patients were switched to OLAT, either because of insufficient response (four patients) or for safety reasons (10 patients). Overall and attributable (entirely or partially due to fungal infection) mortality rates were 52% (59/113) and 17%, respectively. Treatment-related adverse events were reported for 18% (22/119) of patients. This observational study confirms the results of previous clinical trials demonstrating voriconazole as an effective and safe agent for treatment of confirmed acute IA

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

The influence of cardiovascular morbidity on the prognosis in prostate cancer. Experience from a 12-year nationwide Danish population-based cohort study

<p>Abstract</p> <p>Background</p> <p>To determine the impact of preexisting ischemic heart disease (IHD) and stroke on overall survival in prostate cancer patients.</p> <p>Methods</p> <p>We conducted a cohort study of patients with incident prostate cancer registered in the Danish Cancer Registry from 1997 through 2008. We identified patients diagnosed with IHD or stroke prior to the date of prostate cancer diagnosis in the Danish National Patient Registry. We constructed Kaplan-Meier curves to analyze time to death and Cox regression was used to estimate hazard ratios (HRs) to compare mortality rates by preexisting IHD or stroke status, adjusting for age, stage, comorbidity, and calendar period.</p> <p>Results</p> <p>Of 30,721 prostate cancer patients, 4,276 (14%) had preexisting IHD and 1,331 (4%) preexisting stroke. Crude 1- and 5-year survival rates were 85% and 44% in men without preexisting IHD or stroke, 81% and 36% in men with preexisting IHD, and 78% and 27% in men with preexisting stroke. Adjusted HRs were 1.05 (95% CI 1.00-1.10) for patients with IHD and 1.20 (95% CI 1.12-1.30) for patients with stroke compared with patients without preexisting IHD or stroke.</p> <p>Conclusions</p> <p>Preexisting IHD had minimal impact on mortality in prostate cancer patients, whereas overall mortality was 20% higher in prostate cancer patients with preexisting stroke compared to those without IHD or stroke. These results highlight the importance of differentiating between various comorbidities.</p

The Invariance Hypothesis Implies Domain-Specific Regions in Visual Cortex

Is visual cortex made up of general-purpose information processing machinery, or does it consist of a collection of specialized modules? If prior knowledge, acquired from learning a set of objects is only transferable to new objects that share properties with the old, then the recognition system’s optimal organization must be one containing specialized modules for different object classes. Our analysis starts from a premise we call the invariance hypothesis: that the computational goal of the ventral stream is to compute an invariant-to-transformations and discriminative signature for recognition. The key condition enabling approximate transfer of invariance without sacrificing discriminability turns out to be that the learned and novel objects transform similarly. This implies that the optimal recognition system must contain subsystems trained only with data from similarly-transforming objects and suggests a novel interpretation of domain-specific regions like the fusiform face area (FFA). Furthermore, we can define an index of transformation-compatibility, computable from videos, that can be combined with information about the statistics of natural vision to yield predictions for which object categories ought to have domain-specific regions in agreement with the available data. The result is a unifying account linking the large literature on view-based recognition with the wealth of experimental evidence concerning domain-specific regions.National Science Foundation (U.S.). Science and Technology Center (Award CCF-1231216)National Science Foundation (U.S.) (Grant NSF-0640097)National Science Foundation (U.S.) (Grant NSF-0827427)United States. Air Force Office of Scientific Research (Grant FA8650-05-C-7262)Eugene McDermott Foundatio

Plasminogen Alleles Influence Susceptibility to Invasive Aspergillosis

Invasive aspergillosis (IA) is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855) correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser) where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn) was also identified in the human homolog (PLG; Gene ID 5340). An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT) recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection