Mutations in the CYP27B1 gene cause vitamin D dependent rickets in pugs

Rickets is a disorder of bone development and can be the result of either dietary or genetic causes. Here, related pugs from 2 litters were included. Three pugs had clinical signs including, lameness, bone deformities, and dyspnea. One other pug was found dead. Radiographs of 2 affected pugs, 5 and 6 months old, showed generalized widening, and irregular margination of the physes of both the appendicular and the axial skeleton with generalized decrease in bone opacity and bulbous swelling of the costochondral junctions. Two pugs had low serum calcium and 1,25 (OH)(2)D-3 concentrations. Test results further indicated secondary hyperparathyroidism with adequate concentrations of 25-hydroxyvitamin D. Necropsy revealed tongue-like projections of cartilage extending into the metaphysis consistent with rickets, loss of metaphyseal mineralization and lung pathology. Vitamin D-dependent rickets was diagnosed. A truncating mutation in the 1 alpha-hydroxylase gene (CYP27B1) was identified by genome sequence analysis of the pugs with VDDR type 1A. Vitamin D-dependent rickets type 1A can occur in young pugs, and if left untreated is a life-threatening condition. Early medical intervention can reverse clinical signs and should be instituted as soon as possible

Expert-quality Dataset Labeling via Gamified Crowdsourcing on Point-of-Care Lung Ultrasound Data

data interpretation. Building such tools requires labeled training datasets. We tested whether a gamified crowdsourcing approach can produce clinical expert-quality lung ultrasound clip labels. 2,384 lung ultrasound clips were retrospectively collected. Six lung ultrasound experts classified 393 of these clips as having no B-lines, one or more discrete B-lines, or confluent B-lines to create two sets of reference standard labels: a training and test set. Sets trained users on a gamified crowdsourcing platform, and compared concordance of the resulting crowd labels to the concordance of individual experts to reference standards, respectively. 99,238 crowdsourced opinions were collected from 426 unique users over 8 days. Mean labeling concordance of individual experts relative to the reference standard was 85.0% ± 2.0 (SEM), compared to 87.9% crowdsourced label concordance (p=0.15). Scalable, high-quality labeling approaches such as crowdsourcing may streamline training dataset creation for machine learning model development

Adaptation in integrated assessment modeling: where do we stand?

Adaptation is an important element on the climate change policy agenda. Integrated assessment models, which are key tools to assess climate change policies, have begun to address adaptation, either by including it implicitly in damage cost estimates, or by making it an explicit control variable. We analyze how modelers have chosen to describe adaptation within an integrated framework, and suggest many ways they could improve the treatment of adaptation by considering more of its bottom-up characteristics. Until this happens, we suggest, models may be too optimistic about the net benefits adaptation can provide, and therefore may underestimate the amount of mitigation they judge to be socially optimal. Under some conditions, better modeling of adaptation costs and benefits could have important implications for defining mitigation targets. © Springer Science+Business Media B.V. 2009

Linearity and mobility degradation in strained Si MOSFETs with thin gate dielectrics

As gate dielectrics are scaled to a few atomic layers and the channel doping is increased to mitigate short channel effects, high vertical electric fields cause considerable mobility degradation through surface-roughness scattering in silicon MOSFETs. This high-field mobility degradation is known to influence the harmonic distortion through higher order derivatives of the drain current. Failure to take these higher order derivatives into account can cause significant error in the predictive evaluation of linearity (VIP3) in MOSFETs. Electrical measurements are used to extract the 2nd order mobility degradation factor (θ2) from strained silicon MOSFETs fabricated on silicon germanium strain relaxed buffers with 15%, 20% and 25% germanium. Linearity and high-field mobility degradation are shown to be independent of strain in spite of atomic force microscopy measurements showing that the amplitude of the root-mean-square surface roughness increases with the germanium content. It is also shown that θ2 is required for accurate modelling of linearity. The impact of oxide thickness on linearity is also investigated through θ2. In this paper, an analytical relationship between θ2 and the effective oxide thickness is developed and validated by electrical measurements on MOSFETs with different oxide thicknesses and θ2 values from the literature. Using the extracted θ2 values as inputs to analytical MOSFET models, a correlation between the oxide thickness and linearity is analyzed