529 research outputs found

    An Experimental Component Index for the CPI: From Annual Computer Data to Monthly Data on Other Goods

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    Until recently the Consumer Price Index consisted solely of "matched model" component indexes. The latter are constructed by BLS personnel who visit stores and compare prices of goods with the same set of characteristics over successive periods. This procedure is subject to a selection bias. Goods that were not on the shelves in the second period were discarded and hence never contributed price comparisons. The discarded goods were disproportionately goods which were being obsoleted and had falling prices. Pakes (2003) provided an analytic framework for analyzing this selection effect and showed both that it could be partially corrected using a particular hedonic technique and that the correction for his personal computer example was substantial. The BLS staff has recently increased the rate at which they incorporate techniques to correct for selection effects in their component indexes. However recent work shows very little difference between hedonic and matched model indices for non computer components of the CPI. This paper explores why. We look carefully at the data on the component index for TVs and show that differences between the TV and computer markets imply that to obtain an effective selection correction we need to use a more general hedonic procedure than has been used to date. The computer market is special in having well defined cardinal measures of the major product characteristics. In markets where such measures are absent we may need to allow for selection on unmeasured, as well as measured, characteristics. We develop a hedonic selection correction that accounts for unmeasured characteristics, apply it to TVs, and show that it yields a much larger selection correction than the standard hedonic. In particular we find that matched model techniques underestimate the rate of price decline by over 20%.

    Meis1 specifies positional information in the retina and tectum to organize the zebrafish visual system

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    <p>Abstract</p> <p>Background</p> <p>During visual system development, multiple signalling pathways cooperate to specify axial polarity within the retina and optic tectum. This information is required for the topographic mapping of retinal ganglion cell axons on the tectum. Meis1 is a TALE-class homeodomain transcription factor known to specify anterior-posterior identity in the hindbrain, but its role in visual system patterning has not been investigated.</p> <p>Results</p> <p><it>meis1 </it>is expressed in both the presumptive retina and tectum. An analysis of retinal patterning reveals that Meis1 is required to correctly specify both dorsal-ventral and nasal-temporal identity in the zebrafish retina. Meis1-knockdown results in a loss of <it>smad1 </it>expression and an upregulation in <it>follistatin </it>expression, thereby causing lower levels of Bmp signalling and a partial ventralization of the retina. Additionally, Meis1-deficient embryos exhibit ectopic Fgf signalling in the developing retina and a corresponding loss of temporal identity. Meis1 also positively regulates <it>ephrin </it>gene expression in the tectum. Consistent with these patterning phenotypes, a knockdown of Meis1 ultimately results in retinotectal mapping defects.</p> <p>Conclusions</p> <p>In this work we describe a novel role for Meis1 in regulating Bmp signalling and in specifying temporal identity in the retina. By patterning both the retina and tectum, Meis1 plays an important role in establishing the retinotectal map and organizing the visual system.</p

    A Systematic Review of Murine Typhus

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    Murine typhus is a disease (brought on by infection with Rickettsia typhi) that has produced a surprising amount of morbidity when the relative dearth of literature on the subject is considered. Existing reviews of the subject are either relatively dated or surveys of all rickettsial disease with the majority of discussion dedicated to other agents, most often Rickettsia prowazekii or Rickettsia felis. This is likely due to the widespread consideration that Murine typhus is a “re-emergent organism” that was largely removed by the use of pesticides in the 1950s and has only recently re-emerged in much of the globe. I utilize a review of several databases to assess the literature regarding Murine typhus and to bring together summary information for a multitude of factors about the disease. I found a remarkable heterogeneity of data regarding Murine typhus. Factors of specific note among the cases reviewed include the relatively high amount of probable exposures reported by patients, the difficulty at reaching the proper diagnosis experienced by physicians when attempting to ascertain the cause of symptoms, the many separate treatments used and differential efficacies of those treatments, and the disparate types of “severe” outcomes. This information may be of use in the coming years as Murine typhus continues to increase in incidence in many nations where it is present, and as it also appears in those nations where it has not been seen in the previous 50 years

    Evaluating the Death and Recovery of Lateral Line Hair Cells Following Repeated Neomycin Treatments

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    Acute chemical ablation of lateral line hair cells is an important tool to understand lateral line-mediated behaviors in free-swimming fish larvae and adults. However, lateral line-mediated behaviors have not been described in fish larvae prior to swim bladder inflation, possibly because single doses of ototoxin do not effectively silence lateral line function at early developmental stages. To determine whether ototoxins can disrupt lateral line hair cells during early development, we repeatedly exposed zebrafish larvae to the ototoxin neomycin during a 36 h period from 3 to 4 days post-fertilization (dpf). We use simultaneous transgenic and vital dye labeling of hair cells to compare 6-h and 12-h repeated treatment timelines and neomycin concentrations between 0 and 400 ”M in terms of larval survival, hair cell death, regeneration, and functional recovery. Following exposure to neomycin, we find that the emergence of newly functional hair cells outpaces cellular regeneration, likely due to the maturation of ototoxin-resistant hair cells that survive treatment. Furthermore, hair cells of 4 dpf larvae exhibit faster recovery compared to 3 dpf larvae. Our data suggest that the rapid functional maturation of ototoxin-resistant hair cells limits the effectiveness of chemical-based methods to disrupt lateral line function. Furthermore, we show that repeated neomycin treatments can continually ablate functional lateral line hair cells between 3 and 4 dpf in larval zebrafish

    The lhfpl5 Ohnologs lhfpl5a and lhfpl5b Are Required for Mechanotransduction in Distinct Populations of Sensory Hair Cells in Zebrafish

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    Hair cells sense and transmit auditory, vestibular, and hydrodynamic information by converting mechanical stimuli into electrical signals. This process of mechano-electrical transduction (MET) requires a mechanically gated channel localized in the apical stereocilia of hair cells. In mice, lipoma HMGIC fusion partner-like 5 (LHFPL5) acts as an auxiliary subunit of the MET channel whose primary role is to correctly localize PCDH15 and TMC1 to the mechanotransduction complex. Zebrafish have two lhfpl5 genes (lhfpl5a and lhfpl5b), but their individual contributions to MET channel assembly and function have not been analyzed. Here we show that the zebrafish lhfpl5 genes are expressed in discrete populations of hair cells: lhfpl5a expression is restricted to auditory and vestibular hair cells in the inner ear, while lhfpl5b expression is specific to hair cells of the lateral line organ. Consequently, lhfpl5a mutants exhibit defects in auditory and vestibular function, while disruption of lhfpl5b affects hair cells only in the lateral line neuromasts. In contrast to previous reports in mice, localization of Tmc1 does not depend upon Lhfpl5 function in either the inner ear or lateral line organ. In both lhfpl5a and lhfpl5b mutants, GFP-tagged Tmc1 and Tmc2b proteins still localize to the stereocilia of hair cells. Using a stably integrated GFP-Lhfpl5a transgene, we show that the tip link cadherins Pcdh15a and Cdh23, along with the Myo7aa motor protein, are required for correct Lhfpl5a localization at the tips of stereocilia. Our work corroborates the evolutionarily conserved co-dependence between Lhfpl5 and Pcdh15, but also reveals novel requirements for Cdh23 and Myo7aa to correctly localize Lhfpl5a. In addition, our data suggest that targeting of Tmc1 and Tmc2b proteins to stereocilia in zebrafish hair cells occurs independently of Lhfpl5 proteins

    Emergency Medicine Provider Impressions of Novel SMS-Based Toxicology Module

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    The diagnosis and treatment of common toxicologic disorders is an area of core content that emergency medicine (EM) resident physicians and physician assistants (PA) are required to demonstrate competence in order to become proficient practicing clinicians. Even when EM programs have a required toxicology elective, learners do not encounter all core toxicologic presentations. To supplement these knowledge gaps, many toxicology curriculums rely on internet learning modules which have variable uptake in practice. With remote learning and education becoming more common, we aim to perform a need-based assessment of EM resident and PA toxicology education and use the results to develop and deploy a text message-based, interactive toxicology supplemental program for EM residents and PAs and measure its acceptability and preliminary effectiveness to teach core toxicology principles

    Placental expression of angiopoietin-1, angiopoietin-2 and tie-2 during placental development in an ovine model of placental insufficiency-fetal growth restriction.

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    Fetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality, and often results from functional placental insufficiency. Placentation requires extensive vasculogenesis and subsequent angiogenesis, in both maternal and fetal tissues. Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are angiogenic growth factors expressed in the placenta, and compete for binding to a common receptor, Tunica interna endothelial cell kinase-2 (Tie-2). Our objective was to examine Ang-1, Ang-2 and Tie-2 expression in ovine placental tissue obtained from normal and FGR pregnancies throughout gestation. Fetal cotyledon and maternal caruncle tissue concentrations of Ang-1, Ang-2 and Tie-2 mRNA were assessed by real-time reverse transcriptase-polymerase chain reaction and protein concentrations were assessed by Western immunoblot analysis, at 55, 90 and 135 d gestational age (dGA). Concentrations of Ang-1, Ang-2 and Tie-2 mRNA in FGR fetal cotyledons were increased at 55 dGA, and Tie-2 mRNA concentrations were decreased in FGR fetal cotyledons and maternal caruncles at 135 dGA. Immunoblot analysis demonstrated increased concentrations of Ang-2 in the fetal cotyledon at 55 dGA, and lower concentrations at 135 dGA. In contrast, concentrations of Tie-2 were increased at 90 dGA, but tended to decrease at 135 dGA in FGR maternal caruncles. The changes observed during early- to mid-gestation may result in increased branching angiogenesis, but may also set the stage for increased nonbranching angiogenesis during late gestation, altered placental architecture and placental insufficiency that result in FGR

    Fatty Acid Composition of Beef from Cattle Fed Wet Distillers Grains Diets Supplemented with Vitamin E

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    Crossbred yearlings (n = 90) were allotted to one of ten diets containing 0%, 20% and 40% wet distillers grains (WDG) with or without vitamin E supplementation and distillers solubles. Strip loin and tenderloin steaks were obtained and tested for their fatty acid profiles using gas chromatography. WDG diets increased linearly (P \u3c 0.05) the polyunsaturated fatty acids (PUFA) containing 18 or more carbons and trans fatty acids in both muscles. No significant differences were found for total saturated and unsaturated fatty acids. Dietary inclusion of neither vitamin E nor distiller solubles significantly changed PUFA, trans, omega-6 or omega-3 fats in strip loins and tenderloins. Therefore, changes in the fatÂŹty acid profile of beef are a consequence of WDG, not the solubles or vitamin E

    Analysis of 39 drugs and metabolites, including 8 glucuronide conjugates, in an upstream wastewater network via HPLC-MS/MS

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    © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Foppe, K. S., Kujawinski, E. B., Duvallet, C., Endo, N., Erickson, T. B., Chai, P. R., & Matus, M. Analysis of 39 drugs and metabolites, including 8 glucuronide conjugates, in an upstream wastewater network via HPLC-MS/MS. Journal of Chromatography B, 1176, (2021): 122747, https://doi.org/10.1016/j.jchromb.2021.122747.Pharmaceutical compounds ingested by humans are metabolized and excreted in urine and feces. These metabolites can be quantified in wastewater networks using wastewater-based epidemiology (WBE) methods. Standard WBE methods focus on samples collected at wastewater treatment plants (WWTPs). However, these methods do not capture more labile classes of metabolites such as glucuronide conjugates, products of the major phase II metabolic pathway for drug elimination. By shifting sample collection more upstream, these unambiguous markers of human exposure are captured before hydrolysis in the wastewater network. In this paper, we present an HPLC-MS/MS method that quantifies 8 glucuronide conjugates in addition to 31 parent and other metabolites of prescription and synthetic opioids, overdose treatment drugs, illicit drugs, and population markers. Calibration curves for all analytes are linear (r2 > 0.98), except THC (r2 = 0.97), and in the targeted range (0.1–1,000 ng mL−1) with lower limits of quantification (S/N = 9) ranging from 0.098 to 48.75 ng mL−1. This method is fast with an injection-to-injection time of 7.5 min. We demonstrate the application of the method to five wastewater samples collected from a manhole in a city in eastern Massachusetts. Collected wastewater samples were filtered and extracted via solid-phase extraction (SPE). The SPE cartridges are eluted and concentrated in the laboratory via nitrogen-drying. The method and case study presented here demonstrate the potential and application of expanding WBE to monitoring labile metabolites in upstream wastewaterThis work was supported by the National Institute on Drug Abuse of the National Institutes of Health award number R44DA051106 to MM and PC. TE, PC and MM are funded by research grants from the Massachusetts Consortium on Pathogen Readiness and NIH R44DA051106. PRC is funded by NIH K23DA044874, independent research grants from e-ink corporation and Hans and Mavis Lopater Psychosocial Foundation
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