Creation and assessment of a clinical predictive calculator and mortality associated with Candida krusei bloodstream infections

Abstract Background Candida krusei bloodstream infection (CK BSI) is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. Identifying patient characteristics that are associated with CK BSI is crucial for clinical decision-making and prognosis. Methods We conducted a retrospective analysis of hospitalized patients with Candida BSI at our institution between 2002 and 2015. Data were collected on demographics, comorbidities, medications, procedures, central lines, vital signs, and laboratory values. Multivariable logistic and Cox regression were used to identify risk factors associated with CK and mortality, respectively. Results We identified 1873 individual patients who developed Candida BSI within the study period, 59 of whom had CK BSI. CK BSI was predicted by hematologic malignancy, gastric malignancy, neutropenia, and the use of prophylactic azole antifungals, monoclonal antibodies, and β-lactam/β-lactamase inhibitor combinations. The C-statistic was 0.86 (95% confidence interval, 0.81–0.91). The crude mortality rates were 64.4% for CK BSI and 41.4% for non-CK BSI. Although CK was associated with higher mortality in univariable Cox regression, this relationship was no longer significant with the addition of the following confounders: lymphoma, neutropenia, glucocorticoid use, chronic liver disease, and elevated creatinine. Conclusions Six patient comorbidities predicted the development of CK BSI with high accuracy. Although patients with CK BSI have higher crude mortality rates than patients with non-CK BSI, this difference is not significant when accounting for other patient characteristics. </jats:sec

Uncertainty benchmarks for time-dependent transport problems

Uncertainty quantification results are presented for a well known verification solution, the time dependent transport infinite plane pulse. The method of polynomial chaos expansions (PCE) is employed for quick and accurate calculation of the quantities of interest. Also, the method of uncollided solutions is used in this problem to treat part of the uncertainty calculation analytically

Invasive fungal infections secondary to traumatic injury

Invasive fungal infection (IFI) is a rare but serious complication of traumatic injury. The purpose of this article is to review the epidemiology, natural history, mycology, risk factors, diagnosis, treatment, and outcomes associated with post-traumatic IFI in military and civilian populations. The epidemiology of post-traumatic IFI is poorly characterized, but incidence appears to be rising. Patients often suffer from severe injuries and require extensive medical interventions. Fungi belonging to the order Mucorales are responsible for most post-traumatic IFI in both civilian and military populations. Risk factors differ between these cohorts but include specific injury patterns and comorbidities. Diagnosis of post-traumatic IFI typically follows positive laboratory results in the appropriate clinical context. The gold standard of treatment is surgical debridement in addition to systemic antifungal therapy. Patients with post-traumatic IFI may be at greater risk of amputation, delays in wound healing, hospital complications, and death as compared to trauma patients who do not develop IFI. More research is needed to understand the factors surrounding the development and management of post-traumatic IFI to reduce the significant morbidity and mortality associated with this disease

Tree-Independent Dual-Tree Algorithms

Dual-tree algorithms are a widely used class of branch-and-bound algorithms. Unfortunately, developing dual-tree algorithms for use with different trees and problems is often complex and burdensome. We introduce a four-part logical split: the tree, the traversal, the point-to-point base case, and the pruning rule. We provide a meta-algorithm which allows development of dual-tree algorithms in a tree-independent manner and easy extension to entirely new types of trees. Representations are provided for five common algorithms; for k-nearest neighbor search, this leads to a novel, tighter pruning bound. The meta-algorithm also allows straightforward extensions to massively parallel settings.Comment: accepted in ICML 201

The Role of Dislodgement in the Territorial Ecology of the Owl Limpet, \u3cem\u3eLottia gigantea\u3c/em\u3e

Ascertaining the risks and benefits of different behaviors is a central goal of research on territoriality. Although most territorial behavior is ritualized, with concomitant reduced risks for both residents and intruders, this ritualization is generally found to be underpinned by rare, highly consequential, interactions. The agonistic behavior of the intertidal owl limpet, Lottia gigantea, involves defense of a feeding territory, and includes a relatively explosive thrusting response by territory holders against intruding conspecifics. We here ask whether this thrusting behavior is capable of entirely dislodging intruders from their rocky wave-swept substratum, thereby ridding the resident of future challenges by that intruder. Our field measurements of the strength of territorial thrusts, as well as thrust resistance, indicate that territorial limpets are strong enough to overcome the resistance of small to medium sized (\u3c40 mm) conspecifics encountered on their territories. Interestingly, at least 44% of the limpets dislodged from the rock substratum during a retreat or territorial response survived in a new location. Growth of these survivors was at least as rapid as that of undisturbed limpets in the old location. We conclude that shell thrusting during the territorial response of Lottia gigantea can reduce the cost of territorial defense by dislodging smaller conspecifics, thereby eliminating them from all future interactions. Conversely, the risk incurred by these smaller conspecifics while intruding onto territories of larger individuals is likely mitigated by the surprisingly high survival rate, and subsequent normal growth, of dislodged limpets

Precision delivery of RAS-inhibiting siRNA to KRAS driven cancer via peptide-based nanoparticles

Over 95% of pancreatic adenocarcinomas (PDACs), as well as a large fraction of other tumor types, such as colorectal adenocarcinoma, are driven by KRAS activation. However, no direct RAS inhibitors exist for cancer therapy. Furthermore, the delivery of therapeutic agents of any kind to PDAC in particular has been hindered by the extensive desmoplasia and resultant drug delivery challenges that accompanies these tumors. Small interfering RNA (siRNA) is a promising modality for anti-neoplastic therapy due to its precision and wide range of potential therapeutic targets. Unfortunately, siRNA therapy is limited by low serum half-life, vulnerability to intracellular digestion, and transient therapeutic effect. We assessed the ability of a peptide based, oligonucleotide condensing, endosomolytic nanoparticle (NP) system to deliver siRNA to KRAS-driven cancers. We show that this peptide-based NP is avidly taken up by cancer cell