An outbreak of encephalitis due to West Nile (WN) virus occurred in New York City and the surrounding areas during 1999. Mosquitoes were collected as part of a comprehensive surveillance program ...implemented to monitor the outbreak. More than 32,000 mosquitoes representing 24 species were tested, and 15 WN virus isolates were obtained. Molecular techniques were used to identify the species represented in the WN virus-positive mosquito pools. Most isolates were from pools containing Culex pipiens mosquitoes, but several pools contained two or more Culex species.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, ...perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).
Eastern hellbenders Cryptobranchus alleganiensis alleganiensis, large aquatic salamanders, are declining over most of their range. The amphibian-killing fungus Batrachochytrium dendrobatidis (Bd) has ...contributed to global amphibian declines and has been detected on eastern hellbenders, but infection intensities were lower than those of species that are more susceptible to Bd. The factors limiting Bd on hellbenders may include antifungal metabolites produced by their skin microbiota. We used a metabolite fingerprinting technique to noninvasively identify the presence, but not identity, of metabolites associated with eastern hellbenders. We surveyed the skin of wild eastern hellbenders to test whether the composition and richness (i.e. number of metabolites) of their metabolites are explained by Bd status or location. Furthermore, we surveyed for metabolites on captive eastern hellbenders to test whether metabolite compositions were different between captive and wild eastern hellbenders. Bd detection was not associated with either metabolite richness or composition. Both metabolite composition and richness differed significantly on hellbenders from different locations (i.e. states). For metabolite composition, there was a statistical interaction between location and Bd status. Metabolite richness was greater on captive eastern hellbenders compared to wild hellbenders, and metabolite compositions differed between wild and captive eastern hellbenders. The methods we employed to detect metabolite profiles effectively grouped individuals by location even though metabolite composition and richness have high levels of intraspecific variation. Understanding the drivers and functional consequences of assemblages of skin metabolites on amphibian health will be an important step toward understanding the mechanisms that result in disease vulnerability.
To compare different doses and dosing regimens of Vascular Endothelial Growth Factor (VEGF) Trap-Eye with laser photocoagulation in eyes with diabetic macular edema (DME).
Randomized, double-masked, ...multicenter, phase 2 clinical trial.
Diabetic patients (n = 221) with center-involved DME.
Participants were assigned randomly to 1 of 5 treatment regimens: VEGF Trap-Eye 0.5 mg every 4 weeks (0.5q4); 2 mg every 4 weeks (2q4); 2 mg every 8 weeks after 3 initial monthly doses (2q8); or 2 mg dosing as needed after 3 initial monthly doses (2PRN), or macular laser photocoagulation.
The change in best-corrected visual acuity (BCVA) at 24 weeks (the primary end point) and at 52 weeks, proportion of eyes that gained 15 letters or more in Early Treatment of Diabetic Retinopathy Study (ETDRS) BCVA, and mean changes in central retinal thickness (CRT) from baseline.
As previously reported, mean improvements in BCVA in the VEGF Trap-Eye groups at week 24 were 8.6, 11.4, 8.5, and 10.3 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus 2.5 letters for the laser group (P ≤ 0.0085 versus laser). Mean improvements in BCVA in the VEGF Trap-Eye groups at week 52 were 11.0, 13.1, 9.7, and 12.0 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus -1.3 letters for the laser group (P ≤ 0.0001 versus laser). Proportions of eyes with gains in BCVA of 15 or more ETDRS letters at week 52 in the VEGF Trap-Eye groups were 40.9%, 45.5%, 23.8%, and 42.2% versus 11.4% for laser (P = 0.0031, P = 0.0007, P = 0.1608, and P = 0.0016, respectively, versus laser). Mean reductions in CRT in the VEGF Trap-Eye groups at week 52 were -165.4 μm, -227.4 μm, -187.8 μm, and -180.3 μm versus -58.4 μm for laser (P < 0.0001 versus laser). Vascular Endothelial Growth Factor Trap-Eye generally was well tolerated. The most frequent ocular adverse events with VEGF Trap-Eye were conjunctival hemorrhage, eye pain, ocular hyperemia, and increased intraocular pressure, whereas common systemic adverse events included hypertension, nausea, and congestive heart failure.
Significant gains in BCVA from baseline achieved at week 24 were maintained or improved at week 52 in all VEGF Trap-Eye groups. Vascular Endothelial Growth Factor Trap-Eye warrants further investigation for the treatment of DME.
Abstract
The CD8 αβT cell receptor repertoire in joint fluid of individuals with active psoriatic arthritis contained an average of 32 major oligoclonal expansions in many variable genes of the TCR β ...chain (BV) families, as shown by β-chain CDR3 length analysis. Interestingly, a small number of oligoclonal expansions were shared between simultaneous samples of joint fluid and blood; however, most expansions found in joint fluid were not identifiable in blood emphasizing the immunologic specificity of the clonal events for the inflamed joint at a given point of time. The CD4 T cell joint fluid repertoire contained fewer and smaller oligoclonal expansions also largely restricted to the joint, suggesting that CD4 T cells participate perhaps by interacting cognitively to generate the CD8 clones. The inferred amino acid sequence of a single CD8 oligoclonal expansion revealed that they usually are composed of one or a few structurally related clones at the amino acid sequence level with β-chains that encode identical or highly homologous CDR3 motifs. These were not shared among patients. Moreover, several clones that encoded the same amino acid sequence were found to be structurally distinct at the nucleotide level, strongly implying clonal selection and expansion is operating at the level of specific TCR-peptide interactions. The findings support a model of psoriatic arthritis inflammation involving extensive and selective Ag, likely autoantigen, driven intra-articular CD4, and CD8 T cell clonal expansions.
The pyruvate dehydrogenase multi-enzyme complex is the main source of acetyl-CoA formation in the plastids of plants and is composed of multiple copies of four different subunits, E1alpha, E1beta, ...E2, and E3. A T-DNA insertion into the gene for the plastidic E2 (dihydrolipoyl acetyltransferase) subunit, plE2, of the complex in Arabidopsis destroys the expression of that gene. The resulting mutation has no apparent phenotype in the heterozygous state, but the homozygous mutation is lethal. Haploid sperm and eggs that contain only the disrupted plE2 gene function normally resulting in the formation of an embryo that is homozygous for the mutation. This embryo only develops to an early stage before the development arrests resulting in an early embryo-lethal phenotype. While the mutation could not be complemented with the cDNA for the plE2 gene under control of the 35S, the AtSERK1, or the napin promoter, it could be complemented using the endogenous plE2 promoter to drive expression of the plE2 cDNA. This verifies the essential nature of the plastidic pyruvate dehydrogenase complex and its role in embryo formation.
Background Information in health administrative databases increasingly guides renal care and policy. Study Design Systematic review of observational studies. Setting & Population Studies describing ...the validity of codes for acute kidney injury (AKI) and chronic kidney disease (CKD) in administrative databases operating in any jurisdiction. Selection Criteria After searching 13 medical databases, we included observational studies published from database inception though June 2009 that validated renal diagnostic and procedural codes for AKI or CKD against a reference standard. Index Tests Renal diagnostic or procedural administrative data codes. Reference Tests Patient chart review, laboratory values, or data from a high-quality patient registry. Results 25 studies of 13 databases in 4 countries were included. Validation of diagnostic and procedural codes for AKI was present in 9 studies, and validation for CKD was present in 19 studies. Sensitivity varied across studies and generally was poor (AKI median, 29%; range, 15%-81%; CKD median, 41%; range, 3%-88%). Positive predictive values often were reasonable, but results also were variable (AKI median, 67%; range, 15%-96%; CKD median, 78%; range, 29%-100%). Defining AKI and CKD by only the use of dialysis generally resulted in better code validity. The study characteristic associated with sensitivity in multivariable meta-regression was whether the reference standard used laboratory values ( P < 0.001); sensitivity was 39% lower when laboratory values were used (95% CI, 23%-56%). Limitations Missing data in primary studies limited some of the analyses that could be done. Conclusions Administrative database analyses have utility, but must be conducted and interpreted judiciously to avoid bias arising from poor code validity.
The power conversion efficiencies of metal halide perovskite photovoltaics have increased rapidly over the past decade attracting significant academic and industrial interest. The ease with which ...high performance perovskite photovoltaics can be fabricated through solution processing routes has opened up significant possibilities for fabrication through existing, industrially mature high-throughput solution coating techniques such as spray-coating. The power conversion efficiencies of spray-coated metal halide perovskite photovoltaics are limited by non-radiative recombination at the interfaces with charge transport layers necessitating the implementation of new charge transport layers. The self-assembled monolayer (SAM) charge transport layers have resulted in record perovskite photovoltaic device performances, due to reduced non-radiative recombination. However, poor wettability associated with some SAMs significantly limits their applicability, this is exaggerated for droplet-based scalable technologies like spray-coating. Here we report an optimised aluminium oxide nanoparticle interlayer which enables spray-coating of triple cation metal halide perovskite thin films and devices onto Me-4PACz ((4-(3,6-dimethyl-9 H -carbazol-9-yl)butylphosphonic acid)). Our interlayer results in improved structural and optoelectronic properties of spray-coated perovskite thin films, compared to those fabricated through spin-coating. These improved properties enable the fabrication of p–i–n photovoltaic devices with efficiencies over 20% – some of the highest reported for both spray-coated devices in p–i–n architecture, and devices having a spray-coated “triple cation” perovskite active layer.
Background Preemptive correction of a stenosis in an arteriovenous (AV) access (fistula or graft) that is adequately providing hemodialysis (functional AV access) may prolong access survival as ...compared to waiting for signs of access dysfunction to intervene (deferred salvage). However, the evidence in support of preemptive intervention is controversial. We evaluated benefits and harms of preemptive versus deferred correction of AV access stenosis. Study Design Systematic review and meta-analysis of randomized controlled trials. Setting & Population Adults receiving hemodialysis by a functional AV access. Selection Criteria for Studies We searched the Cochrane Kidney and Transplant Specialised Register and EMBASE to October 15, 2015. Intervention Active access surveillance (flow measurement and Doppler or venous pressure) and preemptive correction of a newly identified stenosis versus routine clinical monitoring and deferred salvage, or preemptive correction of a known stenosis versus deferred salvage. Outcomes Access loss (primary outcome) and thrombosis (overall and by access type), infection, mortality, hospitalization, and access-related procedures. Results We included 14 trials (1,390 participants; follow-up, 6-38 months). Relative to deferred salvage, preemptive correction of AV access stenosis had a nonsignificant effect on risk for access loss (risk ratio RR, 0.81; 95% CI, 0.65-1.02; I2 = 0%) and a significant effect on risk for thrombosis (RR, 0.79; 95% CI, 0.65-0.97; I2 = 30%). Treatment effects were larger in fistulas than in grafts for both risk for access loss (subgroup difference, P = 0.05) and risk for thrombosis (subgroup difference, P = 0.002). Results were heterogeneous or imprecise for mortality, rates of access-related infections or procedures, and hospitalization. Limitations Small number and size of primary studies limited analysis power. Conclusions Preemptive stenosis correction in a functional AV access does not improve access longevity. Although preemptive stenosis correction may be promising in fistulas, existing evidence is insufficient to guide clinical practice and health policy.
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