Accurate Transfer Maps for Realistic Beamline Elements: Part I, Straight Elements

The behavior of orbits in charged-particle beam transport systems, including both linear and circular accelerators as well as final focus sections and spectrometers, can depend sensitively on nonlinear fringe-field and high-order-multipole effects in the various beam-line elements. The inclusion of these effects requires a detailed and realistic model of the interior and fringe fields, including their high spatial derivatives. A collection of surface fitting methods has been developed for extracting this information accurately from 3-dimensional field data on a grid, as provided by various 3-dimensional finite-element field codes. Based on these realistic field models, Lie or other methods may be used to compute accurate design orbits and accurate transfer maps about these orbits. Part I of this work presents a treatment of straight-axis magnetic elements, while Part II will treat bending dipoles with large sagitta. An exactly-soluble but numerically challenging model field is used to provide a rigorous collection of performance benchmarks.Comment: Accepted to PRST-AB. Changes: minor figure modifications, reference added, typos corrected

Hypertension Status and Associations with Self-Rated Health and General Practitioner Health Seeking in a Rural Australian Cohort

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Hypertension is the most frequently managed condition by Australian general practitioners (GP). Knowledge of hypertension and blood pressure (BP) values may motivate individuals to seek GP management. Our study aims to determine the associations of knowledge of BP values, BP perception, GP health seeking, and self-rated health (SRH) in a rural population. Two-hundred and seventy-eight (278) residents responded to the health survey on socio-demographic profile, medical history, BP knowledge and perception, SRH, and GP visit frequency. Associations were evaluated using Chi-squared test and multivariate logistic regression. Cohort mean age was 63.6 (12.4) years with 63.3% females. Hypertension (37.8%) was the most common condition. GP visits were made at least once every month (19.1%), every 2–6 months (35.6%), >6 months (11.5%), or only when needed (29.5%). Univariate analyses showed age, education, alcohol consumption, comorbidities, hypertension status, and SRH were significantly associated with visit frequency. After adjustments, hypertension status (OR = 3.6, 95% CI [1.7, 7.9]) and poor SRH (OR = 3.1, 95% CI [1.4, 7.0]) were significantly associated with frequent monthly visits. Our cohort demonstrated that having hypertension and poor self-rated health were associated with frequent monthly GP visits. The perception of high blood pressure does not drive seeking additional GP input

Serum ferritin and incident cardiometabolic diseases in Scottish adults

BACKGROUND: Iron stores, estimated as ferritin levels, and type 2 diabetes (T2D) have been associated previously, while findings regarding coronary heart disease (CHD) and cerebrovascular disease (CEVD) are still inconclusive. No study has focused on simultaneous evaluation of associations between iron stores and the above cardiometabolic diseases (CMD) in the same population. We aim to evaluate the association between serum ferritin and risk of T2D, CHD and CEVD in Scottish population over a wide range of ferritin levels. METHODS: Longitudinal study in 6,497 participants of the 1995 and 1998 Scottish health surveys, who were followed-up until 2011. Cox regression models were conducted adjusting for age, sex/menopausal status, fibrinogen, GGT levels, smoking, alcohol consumption, total cholesterol, HDL-cholesterol, blood pressure, and BMI. Ferritin was used as continuous (sex/menopausal status-specific Z score) and categorical variable (sex/menopausal status-specific quartiles, quintiles and sextiles). RESULTS: During follow-up, 4.9% of the participants developed T2D, 5.3% CHD, and 2.3% CEVD. By using ferritin quartiles, serum ferritin was positively associated with T2D, CHD and CEVD but only the association with T2D remained after adjustment for covariates [Quartile 4 v. 1: adjusted HR 95% CI 1.59 (1.10–2.34); P = 0.006]. When ferritin sextiles were used (6 v. 1), the ferritin-CEVD association became slightly stronger and significant [adjusted HR 95% CI 2.08 (1.09–3.94); P = 0.024]. CONCLUSIONS: Iron stores relate differently to each CMD. Serum ferritin levels were positively and independently associated with incident T2D, and with incident CEVD if higher cut-off points for high ferritin levels were considered. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-022-01450-7

An Inexpensive Retrospective Standard Setting Method Based on Item Facilities

Background Standard setting is one of the most challenging aspects of assessment in high-stakes healthcare settings. The Angoff methodology is widely used, but poses a number of challenges, including conceptualisation of the just-passing candidate, and the time-cost of implementing the method. Cohen methodologies are inexpensive and rapid but rely on the performance of an individual candidate. A new method of standard setting, based on the entire cohort and every item, would be valuable. Methods We identified Borderline candidates by reviewing their performance across all assessments in an academic year. We plotted the item scores of the Borderline candidates in comparison with Facility for the whole cohort and fitted curves to the resulting distribution. Results It is observed that for any given Item, an equation of the form y ≈ C.eFx where y is the Facility of Borderline candidates on that Item, x is the observed Item Facility of the whole cohort, and C and F are constants, predicts the probable Facility for Borderline candidates over the test, in other words, the cut score for Borderline candidates. We describe ways of estimating C and F in any given circumstance, and suggest typical values arising from this particular study: that C = 12.3 and F = 0.021. Conclusions C and F are relatively stable, and that the equation y = 12.3.e0.021x can rapidly be applied to the item Facility for every item. The average value represents the cut score for the assessment as a whole. This represents a novel retrospective method based on test takers. Compared to the Cohen method which draws on one score and one candidate, this method draws on all items and candidates in a test. We propose that it can be used to standard set a whole test, or a particular item where the predicted Angoff score is very different from the observed Facility

Octopaminergic neurons have multiple targets in Drosophila larval mushroom body calyx and can modulate behavioral odor discrimination.

Discrimination of sensory signals is essential for an organism to form and retrieve memories of relevance in a given behavioral context. Sensory representations are modified dynamically by changes in behavioral state, facilitating context-dependent selection of behavior, through signals carried by noradrenergic input in mammals, or octopamine (OA) in insects. To understand the circuit mechanisms of this signaling, we characterized the function of two OA neurons, sVUM1 neurons, that originate in the subesophageal zone (SEZ) and target the input region of the memory center, the mushroom body (MB) calyx, in larval Drosophila We found that sVUM1 neurons target multiple neurons, including olfactory projection neurons (PNs), the inhibitory neuron APL, and a pair of extrinsic output neurons, but relatively few mushroom body intrinsic neurons, Kenyon cells. PN terminals carried the OA receptor Oamb, a Drosophila α1-adrenergic receptor ortholog. Using an odor discrimination learning paradigm, we showed that optogenetic activation of OA neurons compromised discrimination of similar odors but not learning ability. Our results suggest that sVUM1 neurons modify odor representations via multiple extrinsic inputs at the sensory input area to the MB olfactory learning circuit.MRC studentship, UK Genetics Society Summer scholarship, BBSRC DTP summer placement, Isaac Newton Trust

Revealing components of the galaxy population through nonparametric techniques

The distributions of galaxy properties vary with environment, and are often multimodal, suggesting that the galaxy population may be a combination of multiple components. The behaviour of these components versus environment holds details about the processes of galaxy development. To release this information we apply a novel, nonparametric statistical technique, identifying four components present in the distribution of galaxy H$\alpha$ emission-line equivalent-widths. We interpret these components as passive, star-forming, and two varieties of active galactic nuclei. Independent of this interpretation, the properties of each component are remarkably constant as a function of environment. Only their relative proportions display substantial variation. The galaxy population thus appears to comprise distinct components which are individually independent of environment, with galaxies rapidly transitioning between components as they move into denser environments.Comment: 12 pages, 10 figures, accepted for publication in MNRA

Virtual Fly Brain—An interactive atlas of the Drosophila nervous system

As a model organism, Drosophila is uniquely placed to contribute to our understanding of how brains control complex behavior. Not only does it have complex adaptive behaviors, but also a uniquely powerful genetic toolkit, increasingly complete dense connectomic maps of the central nervous system and a rapidly growing set of transcriptomic profiles of cell types. But this also poses a challenge: Given the massive amounts of available data, how are researchers to Find, Access, Integrate and Reuse (FAIR) relevant data in order to develop an integrated anatomical and molecular picture of circuits, inform hypothesis generation, and find reagents for experiments to test these hypotheses? The Virtual Fly Brain (virtualflybrain.org) web application & API provide a solution to this problem, using FAIR principles to integrate 3D images of neurons and brain regions, connectomics, transcriptomics and reagent expression data covering the whole CNS in both larva and adult. Users can search for neurons, neuroanatomy and reagents by name, location, or connectivity, via text search, clicking on 3D images, search-by-image, and queries by type (e.g., dopaminergic neuron) or properties (e.g., synaptic input in the antennal lobe). Returned results include cross-registered 3D images that can be explored in linked 2D and 3D browsers or downloaded under open licenses, and extensive descriptions of cell types and regions curated from the literature. These solutions are potentially extensible to cover similar atlasing and data integration challenges in vertebrates

Sparing effects of selenium and ascorbic acid on vitamin C and E in guinea pig tissues

BACKGROUND: Selenium (Se), vitamin C and vitamin E function as antioxidants within the body. In this study, we investigated the effects of reduced dietary Se and L-ascorbic acid (AA) on vitamin C and α-tocopherol (AT) status in guinea pig tissues. METHODS: Male Hartley guinea pigs were orally dosed with a marginal amount of AA and fed a diet deficient (Se-D/MC), marginal (Se-M/MC) or normal (Se-N/MC) in Se. An additional diet group (Se-N/NC) was fed normal Se and dosed with a normal amount of AA. Guinea pigs were killed after 5 or 12 weeks on the experimental diets at 24 and 48 hours post AA dosing. RESULTS: Liver Se-dependent glutathione peroxidase activity was decreased (P < 0.05) in guinea pigs fed Se or AA restricted diets. Plasma total glutathione concentrations were unaffected (P > 0.05) by reduction in dietary Se or AA. All tissues examined showed a decrease (P < 0.05) in AA content in Se-N/MC compared to Se-N/NC guinea pigs. Kidney, testis, muscle and spleen showed a decreasing trend (P < 0.05) in AA content with decreasing Se in the diet. Dehydroascorbic acid concentrations were decreased (P < 0.05) in several tissues with reduction in dietary Se (heart and spleen) or AA (liver, heart, kidney, muscle and spleen). At week 12, combined dietary restriction of Se and AA decreased AT concentrations in most tissues. In addition, restriction of Se (liver, heart and spleen) and AA (liver, kidney and spleen) separately also reduced AT in tissues. CONCLUSION: Together, these data demonstrate sparing effects of Se and AA on vitamin C and AT in guinea pig tissues

Standards in semen examination:publishing reproducible and reliable data based on high-quality methodology

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.Peer reviewe

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p &lt; 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p &lt; 0.001) and 1.99 (95%CI 1.34-2.99, p &lt; 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p &lt; 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure