Old Techniques for New Join Algorithms: A Case Study in RDF Processing

Recently there has been significant interest around designing specialized RDF engines, as traditional query processing mechanisms incur orders of magnitude performance gaps on many RDF workloads. At the same time researchers have released new worst-case optimal join algorithms which can be asymptotically better than the join algorithms in traditional engines. In this paper we apply worst-case optimal join algorithms to a standard RDF workload, the LUBM benchmark, for the first time. We do so using two worst-case optimal engines: (1) LogicBlox, a commercial database engine, and (2) EmptyHeaded, our prototype research engine with enhanced worst-case optimal join algorithms. We show that without any added optimizations both LogicBlox and EmptyHeaded outperform two state-of-the-art specialized RDF engines, RDF-3X and TripleBit, by up to 6x on cyclic join queries-the queries where traditional optimizers are suboptimal. On the remaining, less complex queries in the LUBM benchmark, we show that three classic query optimization techniques enable EmptyHeaded to compete with RDF engines, even when there is no asymptotic advantage to the worst-case optimal approach. We validate that our design has merit as EmptyHeaded outperforms MonetDB by three orders of magnitude and LogicBlox by two orders of magnitude, while remaining within an order of magnitude of RDF-3X and TripleBit

Paramagnetic, Silicon Quantum Dots for Magnetic Resonance and Two-Photon Imaging of Macrophages

Quantum dots (QDs) are an attractive platform for building multimodality imaging probes, but the toxicity for typical cadmium QDs limits enthusiasm for their clinical use. Nontoxic, silicon QDs are more promising but tend to require short-wavelength excitations which are subject to tissue scattering and autofluorescence artifacts. Herein, we report the synthesis of paramagnetic, manganese-doped, silicon QDs (Si_(Mn) QDs) and demonstrate that they are detectable by both MRI and near-infrared excited, two-photon imaging. The Si_(Mn) QDs are coated with dextran sulfate to target them to scavenger receptors on macrophages, a biomarker of vulnerable plaques. TEM images show that isolated QDs have an average core diameter of 4.3 ± 1.0 nm and the hydrodynamic diameters of coated nanoparticles range from 8.3 to 43 nm measured by dynamic light scattering (DLS). The Si_(Mn) QDs have an r_1 relaxivity of 25.50 ± 1.44 mM^(−1) s^(−1) and an r_2 relaxivity of 89.01 ± 3.26 mM^(−1) s^(−1 )(37 °C, 1.4 T). They emit strong fluorescence at 441 nm with a quantum yield of 8.1% in water. Cell studies show that the probes specifically accumulate in macrophages by a receptor-mediated process, are nontoxic to mammalian cells, and produce distinct contrast in both T_1-weighted magnetic resonance and single- or two-photon excitation fluorescence images. These QDs have promising diagnostic potential as high macrophage density is associated with atherosclerotic plaques vulnerable to rupture

Tumor cell migration is inhibited by a novel therapeutic strategy antagonizing the alpha-7 receptor

A 14mer peptide (T14) derived from the C-terminus of acetylcholinesterase (AChE) selectively activates metastatic breast cancer cells via the alpha-7 nicotinic receptor (α7 nAChR). This naturally occurring peptide is also present in brain, is elevated in Alzheimer’s disease, and is antagonised by a cyclized variant (NBP-14). Here we investigated the effects of NBP-14 in six different cancer cell lines, primary leukemia B-cells and normal B-cells. All cells tested expressed α7 nAChR, intracellular and extracellular T14. However, NBP-14 showed low toxicity and weak antiproliferative effects in the majority of the cell lines and was even less toxic in normal B-cells when compared to primary chronic lymphocytic leukemia cells (P < 0.001). Given the potential role of T14 peptide in metastasis, we next investigated the effects of NBP-14 on tumor cell migration, where it caused a dose-dependent reduction. The extent of NBP-14 inhibition positively correlated with the migration of the cells (r2 = 0.45; P = 0.06). Furthermore, NBP-14 preferentially inhibited the migration of primary leukemia cells when compared with normal B-cells (P = 0.0002); when the normal B-cell data was excluded, this correlation was strengthened (r2 = 0.80; P = 0.006). Importantly, the constitutive α7 nAChR expression positively correlated with intracellular T14 levels (r2 = 0.91; P = 0.0003) and inversely correlated with extracellular T14 levels in the cell culture supernatants (r2 = −0.79; P = 0.034). However, in the presence of NBP-14, α7 nAChR expression was reduced (P = 0.04) and the most migratory cells showed the largest reduction in expression. In conclusion, NBP-14-mediated antagonism of the α7 nAChR offers a novel therapeutic strategy with the potential to inhibit tumor cell migration

Cancer-Related Pain and Disability: A Longitudinal Study

Context Although the cross-sectional association between cancer-related pain and disability is well established, their longitudinal relationship has been less studied. Objectives Data from the Indiana Cancer Pain and Depression (INCPAD) trial were analyzed to determine whether baseline cancer-related pain and changes in pain over time predict disability over 12 months. Methods A total of 274 cancer survivors with cancer-related pain were accrued in the INCPAD trial. Data were collected at baseline, one, three, six, and 12 months by interviewers blinded to treatment arm. Disability outcomes included a continuous measure (Sheehan Disability Scale [SDS] score) and a categorical measure (≥14 days in the past four weeks with a ≥50% reduction in usual activities). Predictor variables, operationalized by the Brief Pain Inventory, included baseline pain severity and changes in pain severity scores between each time point. Multivariable analyses were conducted adjusting for treatment group, baseline disability, and selected covariates including depression. Results Baseline pain severity did not predict disability outcomes at 12 months. However, improvement in pain severity predicted less disability over 12 months both in terms of SDS scores (b = −0.17, t = −5.33, P < 0.001) and ≥14 disability days in the past month (odds ratio = 0.85; 95% confidence interval, 0.79–0.93; P < 0.001). Conclusion Disability over 12 months in patients with cancer-related pain is predicted by changes in pain severity over time. Results suggest that effective pain management may reduce subsequent disability among cancer survivors

Predictors of Cancer-related Pain Improvement Over Time

Objective To determine the predictors of pain improvement among patients being treated for cancer-related pain over 12 months. Methods A secondary analysis of the telephone care Indiana Cancer Pain and Depression trial was performed. Patients (n = 274) were interviewed at baseline and after 1, 3, 6, and 12 months. Pain improvement outcomes included both a continuous measure (Brief Pain Inventory score) and a categorical measure (pain improved versus pain not improved). Predictor variables included change in depression, age, sex, race, marital status, socioeconomic disadvantage, medical comorbidity, type of cancer, and phase of cancer. Multivariable repeated measures were conducted, adjusting for intervention group assignment, baseline pain severity, and time in months since baseline assessment. Results Factors significantly predicting both continuous and categorical pain improvement included participating in the intervention group (β = −0.92, p < .001, odds ratio [OR] = 2.53, 95% confidence interval [CI] = 1.65–3.89), greater improvement in depression (β = −0.31, p = .003, OR = 1.84, 95% CI = 1.35–2.51), higher socioeconomic status (Socioeconomic Disadvantage index; β = 0.25, p = .034; OR = 0.73, 95% CI = 0.56–0.94), and fewer comorbid conditions (β = 0.20, p = .002; OR = 0.84, 95% CI = 0.73–0.96). Patients with more severe pain at baseline or with recurrent or progressive cancer were less likely to experience continuous or categorical pain improvement, respectively. Conclusions Effective management of depression and comorbid conditions along with improvement of social services could be critical components of a comprehensive pain management. Patients with more severe pain or with recurrent or progressive cancers may require closer monitoring and adequate treatment of pain

Comparative Effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on Blood Pressure in Patients with Hypertension

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) may disrupt control of blood pressure in hypertensive patients and increase their risk of morbidity, mortality, and the costs of care. The objective of this study was to examine the association between incident use of NSAIDs and blood pressure in patients with hypertension. Methods We conducted a retrospective cohort study of adult hypertensive patients to determine the effects of their first prescription for NSAID on systolic blood pressure and antihypertensive drug intensification. Data were collected from an electronic medical record serving an academic general medicine practice in Indianapolis, Indiana, USA. Using propensity scores to minimize bias, we matched a cohort of 1,340 users of NSAIDs with 1,340 users of acetaminophen. Propensity score models included covariates likely to affect blood pressure or the use of NSAIDs. The study outcomes were the mean systolic blood pressure measurement after starting NSAIDs and changes in antihypertensive therapy. Results Compared to patients using acetaminophen, NSAID users had a 2 mmHg increase in systolic blood pressure (95% CI, 0.7 to 3.3). Ibuprofen was associated with a 3 mmHg increase in systolic blood pressure compared to naproxen (95% CI, 0.5 to 4.6), and a 5 mmHg increase compared to celecoxib (95% CI, 0.4 to 10). The systolic blood pressure increase was 3 mmHg in a subgroup of patients concomitantly prescribed angiotensin converting enzyme inhibitors or calcium channel blockers and 6 mmHg among those prescribed a beta-adrenergic blocker. Blood pressure changes in patients prescribed diuretics or multiple antihypertensives were not statistically significant. Conclusion Compared to acetaminophen, incident use of NSAIDs, particularly ibuprofen, is associated with a small increase in systolic blood pressure in hypertensive patients. Effects in patients prescribed diuretics or multiple antihypertensives are negligible

Hospice Use Among Nursing Home Patients

Objectives Among hospice patients who lived in nursing homes, we sought to: (1) report trends in hospice use over time, (2) describe factors associated with very long hospice stays (>6 months), and (3) describe hospice utilization patterns. Design, setting, and participants We conducted a retrospective study from an urban, Midwest cohort of hospice patients, aged ≥65 years, who lived in nursing homes between 1999 and 2008. Measurements Demographic data, clinical characteristics, and health care utilization were collected from Medicare claims, Medicaid claims, and Minimum Data Set assessments. Patients with overlapping nursing home and hospice stays were identified. χ2 and t tests were used to compare patients with less than or longer than a 6-month hospice stay. Logistic regression was used to model the likelihood of being on hospice longer than 6 months. Results A total of 1452 patients received hospice services while living in nursing homes. The proportion of patients with noncancer primary hospice diagnoses increased over time; the mean length of hospice stay (114 days) remained high throughout the 10-year period. More than 90% of all patients had 3 or more comorbid diagnoses. Nearly 20% of patients had hospice stays longer than 6 months. The hospice patients with stays longer than 6 months were observed to have a smaller percentage of cancer (25% vs 30%) as a primary hospice diagnosis. The two groups did not differ by mean cognitive status scores, number of comorbidities, or activities of daily living impairments. The greater than 6 months group was much more likely to disenroll before death: 33.9% compared with 13.8% (P < .0001). A variety of patterns of utilization of hospice across settings were observed; 21 % of patients spent some of their hospice stay in the community. Conclusions Any policy proposals that impact the hospice benefit in nursing homes should take into account the difficulty in predicting the clinical course of these patients, varying utilization patterns and transitions across settings, and the importance of supporting multiple approaches for delivery of palliative care in this setting

Murine Coronavirus Cell Type Dependent Interaction with the Type I Interferon Response

Coronaviruses infect many species of animal including humans, causing acute and chronic diseases of many organ systems. Murine coronavirus, mouse hepatitis virus (MHV) infection of the mouse, provides animal models for the study of central nervous system disease, including encephalitis and demyelinating diseases such as Multiple Sclerosis and for hepatitis. While there are many studies of the adaptive immune response to MHV, there has until recently been scant information on the type I interferon (IFN) response to MHV. The relationship between MHV and the IFN-α/β response is paradoxical. While the type I IFN response is a crucial aspect of host defense against MHV in its natural host, there is little if any induction of IFN following infection of mouse fibroblast cell lines in vitro. Furthermore, MHV is relatively resistant to the antiviral effects of IFN-α/β in mouse fibroblast cell lines and in human 293T cells. MHV can, under some circumstances, compromise the antiviral effects of IFN signaling. The nucleocapsid protein as well as the nsp1 and nsp3 proteins of MHV has been reported to have IFN antagonist activity. However, in primary cell types such as plasmacytoid dendritic cells (pDC) and macrophages, IFN is induced by MHV infection and an antiviral state is established. Other primary cell types such as neurons, astrocytes and hepatocytes fail to produce IFN following infection and, in vivo, likely depend on IFN produced by pDCs and macrophages for protection from MHV. Thus MHV induction of IFN-α/β and the ability to induce an antiviral state in response to interferon is extremely cell type dependent. IFN induced protection from MHV pathogenesis likely requires the orchestrated activities of several cell types, however, the cell types involved in limiting MHV replication may be different in the liver and in the immune privileged CNS

Systematic Advance Care Planning and Potentially Avoidable Hospitalizations of Nursing Facility Residents

BACKGROUND/OBJECTIVES The Optimizing Patient Transfers, Impacting Medical Quality, Improving Symptoms: Transforming Institutional Care (OPTIMISTIC) project is a successful, multicomponent demonstration project to reduce potentially avoidable hospitalizations of long‐stay nursing facility residents. Systematic advance care planning (ACP) is a core component of the intervention, based on research suggesting ACP is associated with decreased hospitalizations of nursing facility residents. The purpose of this study was to describe associations between ACP documentation resulting from the OPTIMISTIC intervention and hospitalizations. DESIGN Specially trained project nurses were embedded in 19 nursing facilities and systematically engaged in ACP as part of a larger demonstration project. PARTICIPANTS Residents (n = 1482) enrolled in the demonstration project for a minimum of 30 days between January 1, 2015, and June 30, 2016. MEASUREMENTS ACP status: (1) Physician Orders for Scope of Treatment (POST) comfort measures or do not hospitalize (DNH) orders; (2) ACP orders with no hospitalization limit (eg, code status only); and (3) no ACP (potentially avoidable and all‐cause hospitalizations per 1000 resident days). RESULTS Residents with POST comfort measures/DNH orders (33.2% or n = 493) were less likely than residents with no ACP (14.7% or n = 218) to experience a potentially avoidable hospitalization (P = .001) or all‐cause hospitalization (P = .001). These differences became statistically nonsignificant after adjusting for age, functional status, and cognitive functioning. CONCLUSION In this successful multicomponent demonstration project to reduce potentially avoidable hospitalizations, ACP outcomes were not associated with hospitalization rates of nursing facility residents after adjusting for resident characteristics. These findings highlight the challenge of measuring the contributions of individual components of complex, multicomponent interventions. Associations between lower hospitalization rates and ACP completion may be influenced by contextual factors, such as clinical expertise and resources to manage acute conditions leading to hospitalization, in addition to interventions to increase ACP