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Microphthalmia, coloboma and cataract are part of a spectrum of developmental eye disorders in humans affecting ~12 per 100 000 live births. Currently, variants in over 100 genes are known to underlie these conditions. However, at least 40% of affected individuals remain without a clinical genetic diagnosis, suggesting variants in additional genes may be responsible. Calpain 15 (CAPN15) is an intracellular cysteine protease belonging to the non-classical small optic lobe (SOL) family of calpains, an important class of developmental proteins, as yet uncharacterized in vertebrates. We identified five individuals with microphthalmia and/or coloboma from four independent families carrying homozygous or compound heterozygous predicted damaging variants in CAPN15. Several individuals had additional phenotypes including growth deficits, developmental delay and hearing loss. We generated Capn15 knockout mice that exhibited similar severe developmental eye defects, including anophthalmia, microphthalmia and cataract, and diminished growth. We demonstrate widespread Capn15 expression throughout the brain and central nervous system, strongest during early development, and decreasing postnatally. Together, these findings demonstrate a critical role of CAPN15 in vertebrate developmental eye disorders, and may signify a new developmental pathway.
The number of physical therapists with imaging ordering privileges is increasing; however, a known level of competency and knowledge is generally lacking within the profession, as is a method to determine practitioner competency. The purpose of this study was to develop a valid musculoskeletal (MSK) imaging competency examination for physical therapists.
This 3-round Delphi method study utilized experts to reach consensus on examination content and development. Round 1 was completed by 37 experts. The last 2 rounds were completed by 35 experts. Experts rated questions on a 5-point Likert rating scale of importance (1=not at all important, 5=very important). Consensus was achieved with an a priori decision of (1) >75% agreement of the expert panel rating and≥4 on the Likert scale, and (2)≥.90 on Cronbach alpha and intraclass correlation coefficients. Experts recommended a passing score of 75%. The examination was subsequently reviewed by a panel of 5 radiologists.
The Delphi method and radiologist pan
Plasma cell myeloma (PCM) involving skin is rare and occurs in 1% to 4% of patients with PCM. We evaluated the clinicopathologic features, cytogenetic findings and clinical follow-up in a series of PCM cases with cutaneous involvement.
Cases of PCM with cutaneous involvement were retrospectively reviewed with clinical data.
Skin involvement in PCM occurred in older individuals (mean, 75 years) and was more frequent in men (7/10 patients). All cases showed bone marrow involvement preceding the cutaneous lesions. Histopathologically, the infiltrate was plasmacytic (n = 5) or primitive or plasmablastic (n = 4), and 1 case showed predominantly lymphoplasmacytic features with cyclin D1 immunoreactivity and CCND1 gene rearrangement. Concurrent amyloid deposition was seen in one biopsy, and another case demonstrated coexisting squamous cell carcinoma. The most common immunophenotype was CD138+, CD20-, and CD56+ with light chain restriction. Cytogenetic analysis (available for 7 cases) showed multiple hyperdiploid abnormalities. Follow-up was available for 8 cases (mean, 42 months; range, 11-156 months) and showed short-term disease-related death in 7 of 8 patients.
Cutaneous involvement in PCM demonstrates a diverse cytomorphologic spectrum with plasmacytic, plasmablastic, or lymphoplasmacytic features and may show concurrent amyloid deposition or neoplasms such as squamous cell carcinoma. Cutaneous involvement typically occurs late in the course of the disease and likely portends poor outcome.
Cutaneous involvement in PCM demonstrates a diverse cytomorphologic spectrum with plasmacytic, plasmablastic, or lymphoplasmacytic features and may show concurrent amyloid deposition or neoplasms such as squamous cell carcinoma. Cutaneous involvement typically occurs late in the course of the disease and likely portends poor outcome.
reliable change methods can assist in the determination of whether observed changes in performance are meaningful. The current study sought to validate previously published 1-year standardized regression-based (SRB) equations for commonly administered neuropsychological measures that incorporated baseline performances, demographics, and 1-week practice effects.
Duff etal.'s SRB prediction equations were applied to an independent sample of 70 community-dwelling older adults with either normal cognition or mild cognitive impairment, assessed at baseline, at 1 week, and at 1 year.
minimal improvements or declines were seen between observed baseline and observed 1-year follow-up scores, or between observed 1-year and predicted 1-year scores, on most measures. Relatedly, a high degree of predictive accuracy was observed between observed 1-year and predicted 1-year scores across cognitive measures in this repeated battery.
these results, which validate Duff etal.'s SRB equations, will permit clinicians and researchers to have more confidence when predicting cognitive performance on these measures over 1 year.
these results, which validate Duff et al.'s SRB equations, will permit clinicians and researchers to have more confidence when predicting cognitive performance on these measures over 1 year.Recent outbreaks of engraver beetles, Ips spp. De Geer (Coleoptera Curculionidae; Scolytinae), in ponderosa pine, Pinus ponderosa var. learn more scopulorum Engelm. (Pinales Pinaceae), forests of northern Arizona have resulted in widespread tree mortality. Current treatment options, such as spraying individual P. ponderosa with insecticides or deep watering of P. ponderosa in urban and periurban settings, are limited in applicability and scale. Thinning stands to increase tree vigor is also recommended, but appropriate timing is crucial. Antiaggregation pheromones, widely used to protect high-value trees or areas against attacks by several species of Dendroctonus Erichson (Coleoptera Curculionidae; Scolytinae), would provide a feasible alternative with less environmental impacts than current treatments. We evaluated the efficacy of the antiaggregation pheromone verbenone (4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-one) in reducing attraction of pine engraver, I. pini (Say), to funnel traps baited with their aggregation pheromone in two trapping assays.
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