149 research outputs found

    Method of radiographic inspection of wooden members

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    The invention is a method to be used for radiographic inspection of a wooden specimen for internal defects which includes the steps of introducing a radiopaque penetrant into any internal defects in the specimen through surface openings; passing a beam of radiation through a portion of the specimen to be inspected; and making a radiographic film image of the radiation passing through the specimen, with the radiopaque penetrant in the specimen absorbing the radiation passing through it, thereby enhancing the resulting image of the internal defects in the specimen

    Community leadership network - more than an aspiration 'Through the School Gates'

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    This paper focuses on the National College for School Leadership's 'Community Leadership Network' which comprises ten areas in England (rural and urban). The paper argues that models of school leadership should aim to service and build capacity for interdependent relationships between institutions and communities beyond the school gates. Through a case study of Winsford Networked Learning Community (North of England) and its use of facilitation tools it will lay out the problems and possibilities of building this capacit

    The Benefits and Challenges of Special Education Positions in Rural Settings: Listening to the Teachers

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    Special education teachers, through a national survey conducted in 55 rural districts, provided information on the positive and negative aspects of teaching in rural schools. The 203 special educators were asked what they liked best about their position and what they found challenging. Some of the themes identified in the analysis centered on positive features of working in rural areas. Characteristics of the rural community fostered family-like relationships with others in their school and in-depth relationships with parents and students. Half of the teachers also reported they shared the responsibility or took a team approach to delivering special education services, a factor related to teacher satisfaction. The majority of teachers were satisfied with the instructional aspects of their position but dissatisfied with non-instructional role responsibilities. Challenges of the position also included role confusion and a lack of resources. Related implications for rural administrators interested in the satisfaction of special education teachers are provided

    Addressing hesitancy to COVID-19 vaccines in healthcare assistants

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    COVID-19 vaccination rates have been suboptimal in frontline healthcare assistants (HCAs). We sought to characterize contributors to COVID-19 vaccine hesitancy among HCAs. We conducted an analysis of online survey responses from members of the National Association of Health Care Assistants from December 2020-January 2021. Respondents were asked what it would take for them to be vaccinated against COVID-19. Responses from 309 HCAs were coded to characterize respondents' willingness to be vaccinated and identify contributors to vaccine hesitancy. Approximately 60% (n = 185) of HCAs expressed hesitancy but would consider getting vaccinated under certain circumstances. We identified 8 overarching themes for contributors to COVID-19 vaccine hesitancy, the most common being safety concerns (70% of respondents). Others included efficacy (11.4%), workplace requirements (9.7%), societal influence (9.2%), and compensation (8.1%). Interventions to increase vaccine uptake among HCAs may be most effective by addressing concerns regarding the short-term and long-term safety implications of COVID-19 vaccines

    The Convex Body Isoperimetric Conjecture in the Plane

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    The Convex Body Isoperimetric Conjecture states that the least perimeter needed to enclose a volume within a ball is greater than the least perimeter needed to enclose the same volume within any other convex body of the same volume in Rn. We focus on the conjecture in the plane and prove a new sharp lower bound for the isoperimetric profile of the disk in this case. We prove the conjecture in the case of regular polygons, and show that in a general planar convex body the conjecture holds for small areas

    Tripodal tris(hydroxypyridinone) ligands for immunoconjugate PET imaging with <sup>89</sup>Zr<sup>4+</sup>: comparison with desferrioxamine-B

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    Due to its long half-life (78 h) and decay properties (77% electron capture, 23% β(+), Emax = 897 keV, Eav = 397 keV, Eγ = 909 keV, Iγ = 100%) (89)Zr is an appealing radionuclide for immunoPET imaging with whole IgG antibodies. Derivatives of the siderophore desferrioxamine-B (H3DFO) are the most widely used bifunctional chelators for coordination of (89)Zr(4+) because the radiolabeling of the resulting immunoconjugates is rapid under mild conditions. (89)Zr-DFO complexes are reportedly stable in vitro but there is evidence that (89)Zr(4+) is released in vivo, and subsequently taken up by the skeleton. We have evaluated a novel tripodal tris(hydroxypyridinone) chelator, H3CP256 and its bifunctional maleimide derivative, H3YM103, for coordination of Zr(4+) and compared the NMR spectra, and the (89)Zr(4+) radiolabeling, antibody conjugation, serum stability and in vivo distribution of radiolabelled immunoconjugates with those of H3DFO and its analogues. H3CP256 coordinates (89)Zr(4+) at carrier-free concentrations forming [(89)Zr(CP256)](+). Both H3DFO and H3CP256 were efficiently radiolabelled using [(89)Zr(C2O4)4](4-) at ambient temperature in quantitative yield at pH 6-7 at millimolar concentrations of chelator. Competition experiments demonstrate that (89)Zr(4+) dissociates from [(89)Zr(DFO)](+) in the presence of one equivalent of H3CP256 (relative to H3DFO) at pH 6-7, resulting largely in [(89)Zr(CP256)](+). To assess the stability of H3DFO and H3YM103 immunoconjugates radiolabelled with (89)Zr, maleimide derivatives of the chelators were conjugated to the monoclonal antibody trastuzumab via reduced cysteine side chains. Both immunoconjugates were labelled with (89)Zr(4+) in &gt;98% yield at high specific activities and the labeled immunoconjugates were stable in serum with respect to dissociation of the radiometal. In vivo studies in mice indicate that (89)Zr(4+) dissociates from YM103-trastuzumab with significant amounts of activity becoming associated with bones and joints (25.88 ± 0.58% ID g(-1) 7 days post-injection). In contrast, &lt;8% ID g(-1) of (89)Zr activity becomes associated with bone in animals administered (89)Zr-DFO-trastuzumab over the course of 7 days. The tris(hydroxypyridinone) chelator, H3CP256, coordinates (89)Zr(4+) rapidly under mild conditions, but the (89)Zr-labelled immunoconjugate, (89)Zr-YM103-trastuzumab was observed to release appreciable amounts of (89)Zr(4+)in vivo, demonstrating inferior stability when compared with (89)Zr-DFO-trastuzumab. The significantly lower in vivo stability is likely to be a result of lower kinetic stability of the Zr(4+) tris(hydroxypyridinone complex) relative to that of DFO and its derivatives.</p

    Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib

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    Dual human epidermal growth factor receptor 2 (HER2) targeting can increase pathologic complete response rates (pCRs) to neoadjuvant therapy and improve progression-free survival in metastatic disease. CALGB 40601 examined the impact of dual HER2 blockade consisting of trastuzumab and lapatinib added to paclitaxel, considering tumor and microenvironment molecular features

    Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer

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    "Background Gene expression profiling of breast cancer has identified two biologically distinct estrogen receptor (ER)-positive subtypes of breast cancer: luminal A and luminal B. Luminal B tumors have higher proliferation and poorer prognosis than luminal A tumors. In this study, we developed a clinically practical immunohistochemistry assay to distinguish luminal B from luminal A tumors and investigated its ability to separate tumors according to breast cancer recurrence-free and disease-specific survival. Methods Tumors from a cohort of 357 patients with invasive breast carcinomas were subtyped by gene expression profile. Hormone receptor status, HER2 status, and the Ki67 index (percentage of Ki67-positive cancer nuclei) were determined immunohistochemically. Receiver operating characteristic curves were used to determine the Ki67 cut point to distinguish luminal B from luminal A tumors. The prognostic value of the immunohistochemical assignment for breast cancer recurrence-free and disease-specific survival was investigated with an independent tissue microarray series of 4046 breast cancers by use of Kaplan–Meier curves and multivariable Cox regression. Results Gene expression profiling classified 101 (28%) of the 357 tumors as luminal A and 69 (19%) as luminal B. The best Ki67 index cut point to distinguish luminal B from luminal A tumors was 13.25%. In an independent cohort of 4046 patients with breast cancer, 2847 had hormone receptor–positive tumors. When HER2 immunohistochemistry and the Ki67 index were used to subtype these 2847 tumors, we classified 1530 (59%, 95% confidence interval [CI] = 57% to 61%) as luminal A, 846 (33%, 95% CI = 31% to 34%) as luminal B, and 222 (9%, 95% CI = 7% to 10%) as luminal–HER2 positive. Luminal B and luminal–HER2-positive breast cancers were statistically significantly associated with poor breast cancer recurrence-free and disease-specific survival in all adjuvant systemic treatment categories. Of particular relevance are women who received tamoxifen as their sole adjuvant systemic therapy, among whom the 10-year breast cancer–specific survival was 79% (95% CI = 76% to 83%) for luminal A, 64% (95% CI = 59% to 70%) for luminal B, and 57% (95% CI = 47% to 69%) for luminal–HER2 subtypes. Conclusion Expression of ER, progesterone receptor, and HER2 proteins and the Ki67 index appear to distinguish luminal A from luminal B breast cancer subtypes.

    Role of TNFα in pulmonary pathophysiology

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    Tumor necrosis factor alpha (TNFα) is the most widely studied pleiotropic cytokine of the TNF superfamily. In pathophysiological conditions, generation of TNFα at high levels leads to the development of inflammatory responses that are hallmarks of many diseases. Of the various pulmonary diseases, TNFα is implicated in asthma, chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In addition to its underlying role in the inflammatory events, there is increasing evidence for involvement of TNFα in the cytotoxicity. Thus, pharmacological agents that can either suppress the production of TNFα or block its biological actions may have potential therapeutic value against a wide variety of diseases. Despite some immunological side effects, anti-TNFα therapeutic strategies represent an important breakthrough in the treatment of inflammatory diseases and may have a role in pulmonary diseases characterized by inflammation and cell death
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