Three-year outcomes of a once daily fractionation scheme for accelerated partial breast irradiation (APBI) using 3-D conformal radiotherapy (3D-CRT).

The aim of this study was to report 3-year outcomes of toxicity, cosmesis, and local control using a once daily fractionation scheme (49.95 Gy in 3.33 Gy once daily fractions) for accelerated partial breast irradiation (APBI) using three-dimensional conformal radiotherapy (3D-CRT). Between July 2008 and August 2010, women aged ≥40 years with ductal carcinoma in situ or node-negative invasive breast cancer ≤3 cm in diameter, treated with breast-conserving surgery achieving negative margins, were accrued to a prospective study. Women were treated with APBI using 3-5 photon beams, delivering 49.95 Gy over 15 once daily fractions over 3 weeks. Patients were assessed for toxicities, cosmesis, and local control rates before APBI and at specified time points. Thirty-four patients (mean age 60 years) with Tis 0 (n = 9) and T1N0 (n = 25) breast cancer were treated and followed up for an average of 39 months. Only 3% (1/34) patients experienced a grade 3 subcutaneous fibrosis and breast edema and 97% of the patients had good/excellent cosmetic outcome at 3 years. The 3-year rate of ipsilateral breast tumor recurrence (IBTR) was 0% while the rate of contralateral breast events was 6%. The 3-year disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS) was 94%, 100%, and 100%, respectively. Our novel accelerated partial breast fractionation scheme of 15 once daily fractions of 3.33 Gy (49.95 Gy total) is a remarkably well-tolerated regimen of 3D-CRT-based APBI. A larger cohort of patients is needed to further ascertain the toxicity of this accelerated partial breast regimen

House dust mite induced allergic airway disease is attenuated in CD11ccreIL-4Rα−/l°x mice

Abstract The precise mechanisms leading to development of T helper type (Th)2-driven allergic responses are unknown. We aimed to determine how IL-4 receptor alpha (IL-4Rα) signaling on CD11c+ cells influences allergen-induced Th2 responses in mice. CD11ccreIL-4Rα−/l°x mice, deficient in IL-4Rα on dendritic cells and alveolar macrophages, were compared to IL-4Rα−/l°x littermate controls in models of allergic airway disease induced by OVA/alum, OVA alone or house dust mite. Cytokine responses, eosinophil and neutrophil infiltration into the lungs, airway hyperreactivity and mucus hypersecretion were evaluated after allergen challenge. In the OVA/alum model, CD11ccreIL-4Rα−/lox mice had similar airway hyperreactivity, eosinophil infiltration, Th2-type cytokine production and mucus hypersecretion to littermate controls. When alum was omitted during sensitization, CD11ccreIL-4Rα−/lox mice had similar airway hyperreactivity and mucus secretion but reduced Th2-type cytokine production and eosinophils, suggesting alum overrides the requirement for IL-4Rα signaling on CD11c+ cells in enhancing Th2-type responses. In the house dust mite model, CD11ccreIL-4Rα−/lox mice showed similar mucus secretion, but reduced Th2 responses, eosinophils, neutrophils and airway hyperreactivity, unlike previously tested LysMcreIL-4Rα−/lox mice, which lack IL-4Rα on alveolar macrophages but not on dendritic cells. Therefore, our results indicate that IL-4Rα signaling on dendritic cells promotes allergen-induced Th2 responses and eosinophil infiltration into the lung

Investigating the persistence of tick-borne pathogens via the R0 model

In the epidemiology of infectious diseases, the basic reproduction number,R0, has a number of important applications, most notably it can be used to predict whether a pathogen is likely to become established, or persist, in a given area. We used the R0 model to investigate the persistence of 3 tick-borne pathogens; Babesia microti, Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato in an Apodemus sylvaticus-Ixodes ricinus system. The persistence of these pathogens was also determined empirically by screening questing ticks and wood mice by PCR. All 3 pathogens behaved differently in response to changes in the proportion of transmission hosts on which I. ricinus fed, the efficiency of transmission between the host and ticks and the abundance of larval and nymphal ticks found on small mammals. Empirical data supported theoretical predictions of the R0 model. The transmission pathway employed and the duration of systemic infection were also identified as important factors responsible for establishment or persistence of tick-borne pathogens in a given tick-host system. The current study demonstrates how the R0 model can be put to practical use to investigate factors affecting tick-borne pathogen persistence, which has important implications for animal and human health worldwide

Counting the Cost of Choice and Control: Evidence for the costs of self-directed support in Scotland

1. Self-directed support (SDS) allows people needing social care services toexercise greater choice and control over how they receive services and support.2. The Scottish Government aims to introduce legislation in 2012 (the Social Care(Self Directed Support) (Scotland) Bill) which will consolidate existing (sometimescomplex) provision for SDS. It is intended to bring SDS into the mainstream ofsocial care and increase the numbers of people directing their own support.3. Under the forthcoming bill, Local Authorities will be placed under a duty to offerservice users a variety of options which include: - Direct Payments (DPs) - the making of a payment directly to serviceusers to arrange their own support; - Directing the available resource - where the user selects the support that they wish and the Local Authority arranges matters on theirbehalf. In practice this would encompass options such as IndividualService Funds (ISFs) where the Local Authority contracts with providers on behalf of the service user; - Local Authority 'arranged' support where the authority arranges support on the user's behalf to meet their needs; and - A mix of the above options for distinct aspects of the user's support.4. This study was commissioned to provide inform the SDS strategy and to provideevidence for the forthcoming SDS bill on the current and future costs of SDS inScotland in order to understand the resource implications of making SDSmainstream and increasing the numbers of people directing their own support

Space Charge Limited 2-d Electron Flow between Two Flat Electrodes in a Strong Magnetic Field

An approximate analytic solution is constructed for the 2-d space charge limited emission by a cathode surrounded by non emitting conducting ledges of width Lambda. An essentially exact solution (via conformal mapping) of the electrostatic problem in vacuum is matched to the solution of a linearized problem in the space charge region whose boundaries are sharp due to the presence of a strong magnetic field. The current density growth in a narrow interval near the edges of the cathode depends strongly on Lambda. We obtain an empirical formula for the total current as a function of Lambda which extends to more general cathode geometries.Comment: 4 pages, LaTex, e-mail addresses: [email protected], [email protected]

Metamorphic olivine records external fluid infiltration during serpentinite dehydration

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“Technically an abortion”: understanding perceptions and definitions of abortion in the United States

Anti-abortion legislation in the United States exploits misinformation and ignores medical definitions to curtail access to essential healthcare. Little is known about how individuals most likely to need this care define abortion, in general or as distinct from miscarriage, and how this might impact access to, utilization of, and experiences of care. Using mixed-method card sort and vignette data from cognitive interviews (n = 64) and a national online survey (n = 2009), we examined individuals’ understandings of pregnancy outcomes including abortion and miscarriage. Our findings show that people hold varying ideas of what constitutes an abortion. Many respondents considered ‘intent’ when classifying pregnancy outcomes and focused on intervention to distinguish between miscarriages and abortions. Particularly, medical intervention was found as a defining feature of abortion. Lack of knowledge regarding pregnancy experiences and ambiguity surrounding early stages of pregnancy also influenced respondents' understanding of abortion. We find that abortion and miscarriage definitions are socially constructed and multi-layered. Advancing our understanding of abortion and miscarriage definitions improves reproductive health research by elucidating potential areas of confusion that may lead to misreporting of reproductive experiences as well as highlighting ways that blurred definitions may be exploited by abortion opponents

Major shift in the copepod functional community of the southern North Sea and potential environmental drivers

Abstract Copepods form the bulk of secondary production in marine ecosystems and are a major resource for higher trophic levels. Copepods are highly sensitive to environmental changes as they are ectotherms with a short life span whose metabolism and development depend on abiotic conditions. In turn, changes in their functional structure (i.e. functional trait composition) can have impacts on ecosystems. We examined changes in the copepod functional community in the North Sea over the past five decades, using a trait-based approach. We observed a shift around 1986–1988: the copepod community was initially dominated by larger herbivores, with a long development time, diapause ability, and highest abundances in summer. This community changed abruptly after 1986–1988, to a dominance of smaller carnivore taxa, with shorter development times, less ability to enter diapause, and that display higher abundances in autumn. This rapid reorganization could be driven by higher water temperatures, lower dinoflagellate abundances, and lower nutrient concentrations. These changes could impact adjacent trophic levels, such as phytoplankton on which several species graze or fish larvae, leading to a mismatch situation with consequences for fish recruitment. Our results emphasize the impact that global and regional changes could have on coastal ecosystems through the role played by copepods.</jats:p

A novel assay for analysis of the regulation of the function of human osteoclasts

BACKGROUND: Very little is known of the regulation of the function of human osteoclasts, largely due to the virtual impossibility of obtaining human osteoclasts ex vivo. It has recently become possible to generate human osteoclasts in vitro, by incubation of peripheral blood mononuclear cells (PBMCs) in macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). However, the assays at present available do not distinguish clearly between the distinct effects of agents on differentiation and function. MATERIALS AND METHODS: We developed a novel assay for resorptive function of human osteoclasts that minimizes inter-assay variability by using each culture as its own baseline, and that minimizes the confounding effects of agents on differentiation by assessing resorptive function over a short test period. In this assay, the development of resorptive activity is monitored in sample cultures. When resorption is underway, bone resorption (measured as the release of the C-terminal telopeptide degradation product of type I collagen (CTX-I) into the supernatant) is compared before vs after incubation for 1–24 h in test agent. RESULTS: Using this assay, we found that changes in bone resorption could be detected using substantially fewer cultures per variable. Moreover, we could detect effects of agents on resorption within 1 h of addition, a time sufficiently short that a change in release is likely to reflect an effect on function rather than on differentiation. CONCLUSION: The assay makes it possible to distinguish the effects of agents on osteoclastic function, independent of their effects on differentiation