Pharmacist-Administered Influenza Vaccination in Children and Corresponding Regulations

In our retrospective cohort study, we evaluated trends in pharmacist-administered pediatric influenza vaccination rates in the United States and corresponding state-level pharmacist pediatric vaccination authorization models, including minimum age requirements, vaccination protocols, and/or prescription requirements. An administrative health claims database was used to capture influenza vaccinations in children less than 18 years old with 1 year of continuous enrollment and joinpoint regression was used to assess trends. Of the 3,937,376 pediatric influenza vaccinations identified over the study period, only 3.2% were pharmacist-administered (87.7% pediatrician offices, 2.3% convenience care clinics, 0.8% emergency care, and 6.0% other locations). Pharmacist-administered pediatric influenza vaccination was more commonly observed in older children (mean age 12.65 ± 3.26 years) and increased significantly by 19.2% annually over the study period (95% confidence interval 9.2%-30.2%, p \u3c 0.05). The Northeast, with more restrictive authorization models, represented only 2.2% (n = 2816) of all pharmacist-administered pediatric influenza vaccinations. Utilization of pharmacist-administered pediatric influenza vaccination remains low. Providing children with greater access to vaccination with less restrictions may increase overall vaccination rates. Due to the COVID-19 pandemic and the Public Readiness and Emergency Preparedness Act, pharmacists will play a major role in vaccinating children

Identification of a developmental gene expression signature, including HOX genes, for the normal human colonic crypt stem cell niche: overexpression of the signature parallels stem cell overpopulation during colon tumorigenesis.

Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region--the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other crypt subsections (middle or top). Array results were validated by PCR and immunostaining. About 25% of genes analyzed were expressed in crypts: 88 preferentially in the bottom, 68 in the middle, and 131 in the top. Among genes upregulated in the bottom, ∼30% were classified as growth and/or developmental genes including several in the PI3 kinase pathway, a six-transmembrane protein STAMP1, and two homeobox (HOXA4, HOXD10) genes. qPCR and immunostaining validated that HOXA4 and HOXD10 are selectively expressed in the normal crypt bottom and are overexpressed in colon carcinomas (CRCs). Immunostaining showed that HOXA4 and HOXD10 are co-expressed with the SC markers CD166 and ALDH1 in cells at the normal crypt bottom, and the number of these co-expressing cells is increased in CRCs. Thus, our findings show that these two HOX genes are selectively expressed in colonic SCs and that HOX overexpression in CRCs parallels the SC overpopulation that occurs during CRC development. Our study suggests that developmental genes play key roles in the maintenance of normal SCs and crypt renewal, and contribute to the SC overpopulation that drives colon tumorigenesis

IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species

Representational predicaments at three Hong Kong sites

Representational predicaments arise when a job incumbent believes that attributions and images assumed by dominant authorities unfavourably ignore, or disproportionately and unfavourably emphasize, aspects of the incumbent\u27s own work and social identity. This is likely to happen when the incumbent does not have a close relationship with a dominant authority, and when power asymmetries give the former relatively little control over which aspects of their work and social identity are made visible or invisible to the latter. We draw on critical incident interviews from three organizations to illustrate a typology of six types of representational predicament: invasive spotlighting, idiosyncratic spotlighting, embedded background work, paradoxical social visibility, standardization of work processes, and standardization of work outputs. We analyse responses to representational predicaments according to whether they entailed exit, voice, loyalty, or neglect. Incumbents tended to respond with loyalty if they felt able and willing to accommodate their work behaviour and/or social identity to the dominant representations, and if there were sufficient compensatory factors, such as intrinsic rewards from the work or solidarity with colleagues. Exit or neglect appeared to reflect the belief that it was impossible to accommodate. Power asymmetries appeared to deter voice. Individual employees with a close and cordial working relationship with a member of a dominant authority group, or who were relationally networked to one, appeared not to experience representational predicaments

Can a Dusty Warm Absorber Model Reproduce the Soft X-ray Spectra of MCG-6-30-15 and Mrk 766?

XMM-Newton RGS spectra of MCG-6-30-15 and Mrk 766 exhibit complex discrete structure, which was interpreted in a paper by Branduardi-Raymont et al. (2001) as evidence for the existence of relativistically broadened Lyman alpha emission from carbon, nitrogen, and oxygen, produced in the inner-most regions of an accretion disk around a Kerr black hole. This suggestion was subsequently criticized in a paper by Lee et al. (2001), who argued that for MCG-6-30-15, the Chandra HETG spectrum, which is partially overlapping the RGS in spectral coverage, is adequately fit by a dusty warm absorber model, with no relativistic line emission. We present a reanalysis of the original RGS data sets in terms of the Lee et al. (2001) model, and demonstrate that spectral models consisting of a smooth continuum with ionized and dust absorption alone cannot reproduce the RGS spectra of both objects. The original relativistic line model with warm absorption proposed by Branduardi-Raymont et al. (2001) provides a superior fit to the RGS data, both in the overall shape of the spectrum and in the discrete absorption lines. Limits on the amount of X-ray absorption by dust particles are discussed. We also discuss a possible theoretical interpretation for the putative relativistic Lyman alpha line emission in terms of the photoionized surface layers of the inner regions of an accretion disk.Comment: Replaced with accepted version. To appear in ApJ; tentatively scheduled for the v596 Oct. 10, 2003 issu

Two-Neutron Transfer Reaction Mechanisms in \u3csup\u3e12\u3c/sup\u3eC(\u3csup\u3e6\u3c/sup\u3eHe, \u3csup\u3e4\u3c/sup\u3eHe) \u3csup\u3e14\u3c/sup\u3eC using a Realistic Three-Body \u3csup\u3e6\u3c/sup\u3eHe Model

The reaction mechanisms of the two-neutron transfer reaction 12C(6He,4He) have been studied at Elab=30 MeV at the TRIUMF ISAC-II facility using the Silicon Highly-segmented Array for Reactions and Coulex (SHARC) charged-particle detector array. Optical potential parameters have been extracted from the analysis of the elastic scattering angular distribution. The new potential has been applied to the study of the transfer angular distribution to the 2+2 8.32 MeV state in 14C, using a realistic three-body 6He model and advanced shell-model calculations for the carbon structure, allowing to calculate the relative contributions of the simultaneous and sequential two-neutron transfer. The reaction model provides a good description of the 30-MeV data set and shows that the simultaneous process is the dominant transfer mechanism. Sensitivity tests of optical potential parameters show that the final results can be considerably affected by the choice of optical potentials. A reanalysis of data measured previously at Elab=18 MeV, however, is not as well described by the same reaction model, suggesting that one needs to include higher-order effects in the reaction mechanism

Characterization of Direct Push Vadose Zone Sediments from the T and TY Waste Management Areas

This report contains all the geochemical and selected physical characterization data collected on vadose zone sediment recovered from 5 direct push characterization holes emplaced to investigate vadose zone contamination associated with leaks from tanks 241-TY-105 (UPR-200-W-152) and 241-TY-106 (UPR-200-W-153). Tank 241-TY-105 is estimated to have leaked 35,000 gal of tributyl phosphate (TBP) waste from the uranium recovery process to the vadose zone in 1960. Tank 241-TY-106 is estimated to have leaked 20,000 gal of TBP-uranium recovery waste to the vadose zone in 1959. Although several drywells in the vicinity of tank 241-TY-106 contain measurable quantities of cesium-137 and/or cobalt-60, their relatively low concentrations indicate that the contaminant inventory in the vadose zone around tank 241-TY-106 is quite small. Additionally, this report contains all the geochemical and selected physical characterization data collected on vadose zone sediment recovered from 7 direct push characterization holes emplaced to investigate vadose zone contamination associated with an overfill event and leak from tank 241-T-101

Characterization of Direct Push Vadose Zone Sediments from the 241-U Single-Shell Tank Farm

The overall goals of the Tank Farm Vadose Zone Project, led by CH2M HILL Hanford Group, Inc., are 1) to define risks from past and future single-shell tank farm activities, 2) to identify and evaluate the efficacy of interim measures, and 3) to aid, via collection of geochemical information and data, the future decisions that must be made by the U.S. Department of Energy (DOE) regarding the near-term operations, future waste retrieval, and final closure activities for the single-shell tank Waste Management Areas (WMAs). For a more complete discussion of the goals of the Tank Farm Vadose Zone Project, see the overall work plan, Phase 1 RCRA Facility Investigation/Corrective Measures Study Work Plan for the Single-Shell Tank Waste Management Areas (DOE 1999). Specific details on the rationale for activities performed at WMA U are found in Crumpler (2003). To meet these goals, CH2M HILL Hanford Group, Inc., asked scientists from Pacific Northwest National Laboratory (PNNL) to perform detailed analyses of vadose zone sediment collected within the U Single-Shell Tank Farm. Specifically, this report contains all the geochemical and selected physical characterization data collected on vadose zone sediment recovered from ten direct push characterization holes emplaced to investigate vadose zone contamination associated with potential leaks within the 241-U Single-Shell Tank Farm. Specific tanks targeted during this characterization campaign included tanks 241-U-104/241-U-105, 241-U-110, and 241-U-112. Additionally, this report compiles data from direct push samples collected north of tank 241-U-201, as well as sediment collected from the background borehole (C3393). After evaluating all the characterization and analytical data, there is no question that the vadose zone in the vicinity of tanks 241-U-104 and 241-U-105 has been contaminated by tank-related waste. This observation is not new, as gamma logging of drywells in the area has identified uranium contamination at the same depths interrogated by push hole C5602. Given that the deepest sample string analyzed from push hole C5602 contained trace activities of technetium-99, it is obvious that tank waste contamination has impacted the vadose zone to at least a depth of 92 ft bgs at this location. However, the scope of the sampling campaign was to acquire additional samples to better understand the aerial extent of contamination in the U Tank Farm; therefore, future characterization activities (i.e., a borehole) will be required to understand the total vertical depth of contamination at this location

Characterization of Direct-Push Vadose Zone Sediments from the 241-B and 241-BX Tank Farms

Geochemical tests provide evidence for the transit of a plume of caustic waste solution through the sediment column at the Hanford 241-B and -BX Tank Farms. Direct-push samples recovered from boreholes surrounding Tanks 241-B-110 and 241-BX-102 and related waste transfer lines and diversion boxes included sediments typical of those previously recovered from other localities on the Hanford Site. The Hanford formation sediments are dominantly quartzo-feldspathic sands strewn with lithic fragments, displaying a range of particle size distributions and sorting characteristics. Some moderately well-sorted, fine-grained lithologies are interpreted as lenticular bodies irregularly dispersed in coarser-grained, more poorly sorted sediments. Tier I tests conducted on the vadose zone sediments revealed an inverse correlation between moisture content and sediment size fraction (i.e., there is greater moisture content in finer-grained sediments). The Tier I tests also showed that the pore water solutions were likely sodium-rich, moderately saline, and possessed higher pH values than background (untainted) sediments. These data are characteristic of sediments that have encountered sodium-rich, saline, caustic waste solution, as documented in other reports at other suspect contamination sites around Hanford. Analyses of solutions from 1:1 water extracts reveal relatively balanced cation and anion concentrations, indicating that most of the geochemical species have been accounted for. The water extract data for affected sediments also indicate unusually high concentrations of aluminum, iron, and phosphorus. The relatively high concentrations of aluminum and iron may be the result of dissolution of secondary amorphous phases that precipitated after a reactive plume partially dissolved aluminum- and iron-bearing phases as it migrated through the sediment column. On the other hand, the presence of elevated concentrations of phosphorous may be the tell-tale signature of wastes derived from the bismuth phosphate separation process. Elements typically mobile in the geosphere, such as technetium-99, are present at either low concentrations or are below the analytical detection limit. However, we expect that the mobile elements would be present mainly along a narrow plume front, and if this front had passed deeper into the sediment profile than depths sampled, the retention of these elements would be minor. On the other hand for the direct push sediments from around BX Tank Farm, uranium-238 was detected in nearly all sediment specimens (by acid extract experiments) at concentrations above the natural crustal average (0.763 pCi/g), and we also detected the presence of several anthropogenic radioisotopes, such as cobalt-60, cesium-137, europium-154, and europium-155 (by gamma energy analysis). These data are direct confirmation of contamination of the sediments