453 research outputs found

    Addressing Barriers to Universal Screening for Social, Emotional, and Behavioral Risk in Elementary Schools

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    Early identification of students in need of additional support in the classroom is an important structure for school districts to have in place. Universal screening for social-emotional and behavioral (SEB) risk is one method that schools can use to identify students in need of SEB support and to begin early intervention programing. Unfortunately, recommendations about universal screening and resources for universal screening for SEB risk are limited. As a result, barriers to screening are increased and interventions are delayed – sometimes indefinitely -- for those who need them most. This paper discusses the barriers and challenges experienced by elementary schools (grades K-5) in one school district in the South across a three-year consultative study. This district was supported by the researchers in identifying an appropriate SEB screener, in disseminating the screener, and in ensuring accuracy in its completion. Across the three years, data were evaluated from previous years, and recommendations to improve the district’s screening initiative were made by the lead consultant and school psychology graduate students. Over time, positive changes were noted in screening practices, but it is evident that more work needs to be done. Specific solutions and future implications for early childhood are discussed

    Novel Assay of Metformin Levels in Patients With Type 2 Diabetes and Varying Levels of Renal Function: Clinical recommendations

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    AbstractObjective: To study trough levels of metformin in serum and its intra individual variation in patients using a newly developed assay. Research Design and Methods: Trough serum levels of metformin was measured once using Liquid Chromatography Tandem Mass Spectrometry (LcMSMS) in 137 type 2 diabetes patients with varying renal function (99 men) and followed repeatedly during two months in 20 patients (16 men) with estimated GFR (eGFR) below 60 ml/min/1.73 m(2) body surface. Results: Patients with eGFR >60, 30-60, and <30 ml/min/1.73 m(2) had a median trough metformin concentration of 4.5 mumol/l (range 0.1-20.7, n=107), 7.71 mumol/l (0.12-15.15, n=21), and 8.88 mumol/l (5.99-18.60, n=9), respectively. The median intraindividual overall coefficient of variation (CV) was 29.4 % (range 9,8-74,2). Conclusions: Determination of serum metformin with the LCMSMS technique is useful in patients on metformin treatment. Few patients had values over 20 mumol/L. Metformin measurement is less suitable for dose titration

    Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy.

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    UNLABELLED: The pro-oncogenic activities of estrogen receptor alpha (ERα) drive breast cancer pathogenesis. Endocrine therapies that impair the production of estrogen or the action of the ERα are therefore used to prevent primary disease metastasis. Although recent successes with ERα degraders have been reported, there is still the need to develop further ERα antagonists with additional properties for breast cancer therapy. We have previously described a benzothiazole compound A4B17 that inhibits the proliferation of androgen receptor-positive prostate cancer cells by disrupting the interaction of the cochaperone BAG1 with the AR. A4B17 was also found to inhibit the proliferation of estrogen receptor-positive (ER+) breast cancer cells. Using a scaffold hopping approach, we report here a group of small molecules with imidazopyridine scaffolds that are more potent and efficacious than A4B17. The prototype molecule X15695 efficiently degraded ERα and attenuated estrogen-mediated target gene expression as well as transactivation by the AR. X15695 also disrupted key cellular protein-protein interactions such as BAG1-mortalin (GRP75) interaction as well as wild-type p53-mortalin or mutant p53-BAG2 interactions. These activities together reactivated p53 and resulted in cell-cycle block and the induction of apoptosis. When administered orally to in vivo tumor xenograft models, X15695 potently inhibited the growth of breast tumor cells but less efficiently the growth of prostate tumor cells. We therefore identify X15695 as an oral selective ER degrader and propose further development of this compound for therapy of ER+ breast cancers. SIGNIFICANCE: An imidazopyridine that selectively degrades ERα and is orally bioavailable has been identified for the development of ER+ breast cancer therapeutics. This compound also activates wild-type p53 and disrupts the gain-of-function tumorigenic activity of mutant p53, resulting in cell-cycle arrest and the induction of apoptosis

    Evening choruses in the Perth Canyon and their potential link with Myctophidae fishes

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    An evening chorus centered at near 2.2 kHz was detected across the years 2000 to 2014 from seabed receivers in 430-490 m depth overlooking the Perth Canyon, Western Australia. The chorus reached a maximum level typically 2.1 h post-sunset and normally ran for 2.1 h (between 3 dB down points). It was present at lower levels across most of the hours of darkness. Maximum chorus spectrum levels were 74-76 dB re 1 µPa2/Hz in the 2 kHz 1/3 octave band, averaging 6-12 dB and up to 30 dB greater than pre-sunset levels. The chorus displayed highest levels over April to August each year with up to 10 dB differences between seasons. The spatial extent of the chorus was not determined but exceeded the sampling range of 13-15 km offshore from the 300 m depth contour and 33 km along the 300 m depth contour. The chorus comprised short damped pulses. The most likely chorus source is considered to be fishes of the family Myctophidae foraging in the water column. The large chorus spatial extent and its apparent correlation with regions of high productivity suggest it may act as an acoustic beacon to marine fauna indicating regions of high biomass

    A study of the behavioural response of whales to the noise of seismic air guns: design, methods and progress

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    The concern about the effects of the noise of human activities on marine mammals, particularly whales, has led to a substantial amount of research but there is still much that is not understood, particularly in terms of the behavioural responses to noise and the longer term biological consequences of these responses. There are many challenges in conducting experiments that adequately assess behavioural reactions of whales to noise. These include the need to obtain an adequate sample size with the necessary controls and to measure the range of variables likely to affect the observed response. Analysis is also complex. Well designed experiments are complex and logistically difficult, and thus expensive. This paper discusses the challenges involved and how these are being met in a major series of experiments in Australian waters on the response of humpback whales to the noise of seismic airgun arrays. The project is known as BRAHSS (Behavioural Response of Australian Humpback whales to Seismic Surveys) and aims to provide the information that will allow seismic surveys to be conducted efficiently with minimal impact on whales. It also includes a study of the response to ramp-up in sound level which is widely used at the start of operations, but for which there is little information to show that it is effective. BRAHSS also aims to infer the longer term biological significance of the responses from the results and the knowledge of normal behaviour. The results are expected to have relevance to other sources and species

    Particle size distributions in chondritic meteorites: Evidence for pre-planetesimal histories

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    Magnesium-rich silicate chondrules and calcium-, aluminum-rich refractory inclusions (CAIs) are fundamental components of primitive chondritic meteorites. It has been suggested that concentration of these early-formed particles by nebular sorting processes may lead to accretion of planetesimals, the planetary bodies that represent the building blocks of the terrestrial planets. In this case, the size distributions of the particles may constrain the accretion process. Here we present new particle size distribution data for Northwest Africa 5717, a primitive ordinary chondrite (ungrouped 3.05) and the well-known carbonaceous chondrite Allende (CV3). Instead of the relatively narrow size distributions obtained in previous studies (Ebel et al., 2016, Friedrich et al., 2015, Paque and Cuzzi, 1997, and references therein), we observed broad size distributions for all particle types in both meteorites. Detailed microscopic image analysis of Allende shows differences in the size distributions of chondrule subtypes, but collectively these subpopulations comprise a composite “chondrule” size distribution that is similar to the broad size distribution found for CAIs. Also, we find accretionary ‘dust’ rims on only a subset (∼15–20%) of the chondrules contained in Allende, which indicates that subpopulations of chondrules experienced distinct histories prior to planetary accretion. For the rimmed subset, we find positive correlation between rim thickness and chondrule size. The remarkable similarity between the size distributions of various subgroups of particles, both with and without fine grained rims, implies a common size sorting process. Chondrite classification schemes, astrophysical disk models that predict a narrow chondrule size population and/or a common localized formation event, and conventional particle analysis methods must all be critically reevaluated. We support the idea that distinct “lithologies” in NWA 5717 are nebular aggregates of chondrules. If ≥cm-sized aggregates of chondrules can form it will have implications for planet formation and suggests the sticking stage is where the preferential size physics is operating

    Auditory sensitivity in aquatic animals

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    © 2016 Acoustical Society of America. A critical concern with respect to marine animal acoustics is the issue of hearing "sensitivity," as it is widely used as a criterion for the onset of noise-induced effects. Important aspects of research on sensitivity to sound by marine animals include: uncertainties regarding how well these species detect and respond to different sounds; the masking effects of man-made sounds on the detection of biologically important sounds; the question how internal state, motivation, context, and previous experience affect their behavioral responses; and the long-term and cumulative effects of sound exposure. If we are to better understand the sensitivity of marine animals to sound we must concentrate research on these questions. In order to assess population level and ecological community impacts new approaches can possibly be adopted from other disciplines and applied to marine fauna
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