Combined antiapoptotic and antioxidant approach to acute neuroprotection for stroke in hypertensive rats

We hypothesized that targeting key points in the ischemic cascade with combined neuroglobin (Ngb) overexpression and c-jun N-terminal kinase (JNK) inhibition (SP600125) would offer greater neuroprotection than single treatment after in vitro hypoxia/reoxygenation and in a randomized, blinded in vivo experimental stroke study using a clinically relevant rat strain. Male spontaneously hypertensive stroke-prone rats underwent transient middle cerebral artery occlusion (tMCAO) and were divided into the following groups: tMCAO; tMCAO+control GFP-expressing canine adenovirus-2, CAVGFP; tMCAO+Ngb-expressing CAV-2, CAVNgb; tMCAO+SP600125; tMCAO+CAVNgb+SP600125; or sham procedure. Rats were assessed till day 14 for neurologic outcome before infarct determination. In vitro, combined lentivirus-mediated Ngb overexpression+SP600125 significantly reduced oxidative stress and apoptosis compared with single treatment(s) after hypoxia/reoxygenation in B50 cells. In vivo, infarct volume was significantly reduced by CAVNgb, SP600125, and further by CAVNgb+SP600125. The number of Ngb-positive cells in the peri-infarct cortex and striatum was significantly increased 14 days after tMCAO in animals receiving CAVNgb. Neurologic outcome, measured using a 32-point neurologic score, significantly improved with CAVNgb+SP600125 compared with single treatments at 14 days after tMCAO. Combined Ngb overexpression with JNK inhibition reduced hypoxia/reoxygenation-induced oxidative stress and apoptosis in cultured neurons and reduced infarct and improved neurologic outcome more than single therapy after in vivo experimental stroke in hypertensive rats

Environmental Implications of Increased Bioenergy Production on Midwest Soil Landscapes [abstract]

Only abstract of poster available.Track III: Energy InfrastructurePrairie soil landscapes encompass over 16 million acres in Missouri and surrounding states. Much of this area has been degraded by erosion but is still used for grain production. Erosion has caused variable topsoil depth within fields which in turn has resulted in greater within-field variability of crop yield, magnified the drought-prone nature of these soils, and lowered the overall soil productivity and ecosystem function. In recent years, pressure on these sensitive soils has risen due to higher demand for grain production, in part for ethanol and biodiesel. In some areas, highly erodible fields which were historically managed as CRP and pasture are being turned into grain crop acres. Thus as new and fluctuating feed and bioenergy markets develop, land management practices will also shift, resulting in changes in soil and water quality of watersheds. This presentation will explore the likely environmental implications of different types of bioenergy production on the soil resource. Further, the positive benefits of potential changes in land use will be in explored. For example, one alternative for sensitive soils is production of perennial grass as a feedstock for coal co-burning plants and for potential future use in cellulosic ethanol production. Perennial grass yields are likely to be less variable than grain yields, both year-to-year and within fields, primarily because of greater resistance to drought. Grass production systems also provide environmental services not obtained from annual grain crops. We will also discuss our work on developing ways to target the most appropriate places in the landscape for grain or perennial production so as to enhance ecosystem services and improve soil and water quality

Quantum fingerprinting

Classical fingerprinting associates with each string a shorter string (its fingerprint), such that, with high probability, any two distinct strings can be distinguished by comparing their fingerprints alone. The fingerprints can be exponentially smaller than the original strings if the parties preparing the fingerprints share a random key, but not if they only have access to uncorrelated random sources. In this paper we show that fingerprints consisting of quantum information can be made exponentially smaller than the original strings without any correlations or entanglement between the parties: we give a scheme where the quantum fingerprints are exponentially shorter than the original strings and we give a test that distinguishes any two unknown quantum fingerprints with high probability. Our scheme implies an exponential quantum/classical gap for the equality problem in the simultaneous message passing model of communication complexity. We optimize several aspects of our scheme.Comment: 8 pages, LaTeX, one figur

The rheumatoid arthritis treat-to-target trial: a cluster randomized trial within the Corrona rheumatology network

BACKGROUND: The treat-to-target (T2T) approach to the care of patients with rheumatoid arthritis involves using validated metrics to measure disease activity, frequent follow-up visits for patients with moderate to high disease activity, and escalation of therapy when patients have inadequate therapeutic response as assessed by standard disease activity scores. The study described is a newly launched cluster-randomized behavioral intervention to assess the feasibility and effectiveness of the T2T approach in US rheumatology practices. It is designed to identify patient and provider barriers to implementing T2T management. This initial paper focuses on the novel study design and methods created to provide these insights. METHODS/DESIGN: This trial cluster-randomizes rheumatology practices from the existing Corrona network of private and academic sites rather than patients within sites or individual investigators to provide either T2T or usual care (UC) for qualified patients who meet the 2010 revised American College of Rheumatology criteria for the diagnosis of rheumatoid arthritis and have moderate to high disease activity. Specific medication choices are left to the investigator and patient, rather than being specified in the protocol. Enrollment is expected to be completed by the end of 2013, with 30 practices randomized and enrolling a minimum of 530 patients. During the 12-month follow-up, visits are mandated as frequently as monthly in patients with active disease in the T2T group and every 3 months for the UC group. Safety data are collected at each visit. The coprimary endpoints include a comparison of the proportion of patients achieving low disease activity in the T2T and UC groups and assessment of the feasibility of implementing T2T in rheumatology practices, specifically assessment of the rates of treatment acceleration, frequency of visits, time to next visit conditional on disease activity, and probability of acceleration conditional on disease activity in the 2 groups. DISCUSSION: This cluster-randomized behavioral intervention study will provide valuable insights on the outcomes and feasibility of employing a T2T treatment approach in clinical practice in the United States. TRIAL REGISTRATION: NCT01407419

Electrical and structural properties of In-implanted Si1−xGex alloys

We report on the effects of dopant concentration and substrate stoichiometry on the electrical and structural properties of In-implanted Si1−xGex alloys. Correlating the fraction of electrically active In atoms from Hall Effect measurements with the In atomic environment determined by X-ray absorption spectroscopy, we observed the transition from electrically active, substitutional In at low In concentration to electrically inactive metallic In at high In concentration. The In solid-solubility limit has been quantified and was dependent on the Si1−xGex alloy stoichiometry; the solid-solubility limit increased as the Ge fraction increased. This result was consistent with density functional theory calculations of two In atoms in a Si1−xGex supercell that demonstrated that In–In pairing was energetically favorable for x ≲ 0.7 and energetically unfavorable for x ≳ 0.7. Transmission electron microscopy imaging further complemented the results described earlier with the In concentration and Si1−xGex alloy stoichiometry dependencies readily visible. We have demonstrated that low resistivity values can be achieved with In implantation in Si1−xGex alloys, and this combination of dopant and substrate represents an effective doping protocol

Cluster-Randomized Trial of a Behavioral Intervention to Incorporate a Treat-to-Target Approach to Care of US Patients With Rheumatoid Arthritis

OBJECTIVE: To assess the feasibility and efficacy of implementing a treat-to-target approach versus usual care in a US-based cohort of rheumatoid arthritis patients. METHODS: In this behavioral intervention trial, rheumatology practices were cluster-randomized to provide treat-to-target care or usual care. Eligible patients with moderate/high disease activity (Clinical Disease Activity Index [CDAI] score \u3e 10) were followed for 12 months. Both treat-to-target and usual care patients were seen every 3 months. Treat-to-target providers were to have monthly visits with treatment acceleration at a minimum of every 3 months in patients with CDAI score \u3e 10; additional visits and treatment acceleration were at the discretion of usual care providers and patients. Coprimary end points were feasibility, assessed by rate of treatment acceleration conditional on CDAI score \u3e 10, and achievement of low disease activity (LDA; CDAI score \u3c /=10) by an intent-to-treat analysis. RESULTS: A total of 14 practice sites per study arm were included (246 patients receiving treat-to-target and 286 receiving usual care). The groups had similar baseline demographic and clinical characteristics. Rates of treatment acceleration (treat-to-target 47% versus usual care 50%; odds ratio [OR] 0.92 [95% confidence interval (95% CI) 0.64, 1.34]) and achievement of LDA (treat-to-target 57% versus usual care 55%; OR 1.05 [95% CI 0.60, 1.84]) were similar between groups. Treat-to-target providers reported patient reluctance and medication lag time as common barriers to treatment acceleration. CONCLUSION: This study is the first to examine the feasibility and efficacy of a treat-to-target approach in typical US rheumatology practice. Treat-to-target care was not associated with increased likelihood of treatment acceleration or achievement of LDA, and barriers to treatment acceleration were identified

Potential for Supernova Neutrino Detection in MiniBooNE

The MiniBooNE detector at Fermilab is designed to search for $\nu_\mu \to \nu_e$ oscillation appearance at $E_\nu \sim 1 {\rm GeV}$ and to make a decisive test of the LSND signal. The main detector (inside a veto shield) is a spherical volume containing 0.680 ktons of mineral oil. This inner volume, viewed by 1280 phototubes, is primarily a \v{C}erenkov medium, as the scintillation yield is low. The entire detector is under a 3 m earth overburden. Though the detector is not optimized for low-energy (tens of MeV) events, and the cosmic-ray muon rate is high (10 kHz), we show that MiniBooNE can function as a useful supernova neutrino detector. Simple trigger-level cuts can greatly reduce the backgrounds due to cosmic-ray muons. For a canonical Galactic supernova at 10 kpc, about 190 supernova $\bar{\nu}_e + p \to e^+ + n$ events would be detected. By adding MiniBooNE to the international network of supernova detectors, the possibility of a supernova being missed would be reduced. Additionally, the paths of the supernova neutrinos through Earth will be different for MiniBooNE and other detectors, thus allowing tests of matter-affected mixing effects on the neutrino signal.Comment: Added references, version to appear in PR

Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis.

Recent studies have provided evidence for rapid pathogen genome diversification, some of which could potentially affect the course of disease. We have previously described such variation seen between isolates infecting the blood and cerebrospinal fluid (CSF) of a single patient during a case of bacterial meningitis. Here, we performed whole-genome sequencing of paired isolates from the blood and CSF of 869 meningitis patients to determine whether such variation frequently occurs between these two niches in cases of bacterial meningitis. Using a combination of reference-free variant calling approaches, we show that no genetic adaptation occurs in either invaded niche during bacterial meningitis for two major pathogen species, Streptococcus pneumoniae and Neisseria meningitidis. This study therefore shows that the bacteria capable of causing meningitis are already able to do this upon entering the blood, and no further sequence change is necessary to cross the blood-brain barrier. Our findings place the focus back on bacterial evolution between nasopharyngeal carriage and invasion, or diversity of the host, as likely mechanisms for determining invasiveness