159 research outputs found
Layer thickness and draft angle selection for stereolithography injection mould tooling
The introduction of rapid prototyping has allowed engineers and designers to generate physical models of required parts very early on in the design and development phase. Further to this, the use of stereolithography (SL) cavities as a rapid tooling method has allowed plastic prototype parts to be produced in their most common production manner -- by injection moulding. The process is best suited to small production runs where the high costs of conventionally machined tooling is prohibitive. One of the major drawbacks of the SL injectionmoulding process is the susceptibility of the tools to premature failure. SL tools may break under the force exerted by part ejection when the friction between a moulding and a core is greater than the tensile strength of the core, resulting in tensile failure. Very few justified recommendations exist about the choice of mould design variables that can lower the part ejection force experienced and reduce the risk of SL tool failure. This research investigates the ejection forces resulting from SL injection moulding tools which are identical in all respects except for their build layer thickness and incorporated draft angles in an attempt to identify appropriate evidence for recommendations with respect to these design variables and SL injection moulding. The results show that adjustment of draft angle results in a change of part ejection force as a reasonably linear relationship. An adjustment of the build layer thickness results in a change in part ejection force as a more non-linear relationship. The adjustment of build layer thickness had a greater effect on ejection force than the adjustment of draft angle. The results also show that the surface roughness of all tools remains unchanged after moulding a number of parts in polypropylene. A mathematical model was used in an attempt to predict ejection forces according to the moulding material used. This model reflected the experimental results in terms of relative values but not in absolute values, which may be due to inappropriate specific values used in their calculation. Finite element analysis (FEA) was used in an attempt to identify the factors involved in the ejection process. Results indicate that the effect of draft angle on ejection force is due to elastic deformation of the surface roughness. A fact borne out by the lack of damage to the surface after ejection
Display of antigens on polyester inclusions lowers the antigen concentration required for a bovine tuberculosis skin test
The tuberculin skin test is the primary screening test for the diagnosis of bovine tuberculosis (TB), and use of this test has been very valuable in the control of this disease in many countries. However, the test lacks specificity when cattle have been exposed to environmental mycobacteria or vaccinated with Mycobacterium bovis bacille Calmette-Guérin (BCG). Recent studies showed that the use of three or four recombinant mycobacterial proteins, including 6-kDa early secretory antigenic target (ESAT6), 10-kDa culture filtrate protein (CFP10), Rv3615c, and Rv3020c, or a peptide cocktail derived from those proteins, in the skin test greatly enhanced test specificity, with minimal loss of test sensitivity. The proteins are present in members of the pathogenic Mycobacterium tuberculosis complex but are absent in or not expressed by the majority of environmental mycobacteria and the BCG vaccine strain. To produce a low-cost skin test reagent, the proteins were displayed at high density on polyester beads through translational fusion to a polyhydroxyalkanoate synthase that mediates the formation of antigen-displaying inclusions in recombinant Escherichia coli. Display of the proteins on the polyester beads greatly increased their immunogenicity, allowing for the use of very low concentrations of proteins (0.1 to 3 μg of mycobacterial protein/inoculum) in the skin test. Polyester beads simultaneously displaying all four proteins were produced in a single fermentation process. The polyester beads displaying three or four mycobacterial proteins were shown to have high sensitivity for detection of M. bovis-infected cattle and induced minimal responses in animals exposed to environmental mycobacteria or vaccinated with BCG.Full Tex
The Characterization of Varicella Zoster Virus–Specific T Cells in Skin and Blood during Aging
Reactivation of the varicella zoster virus (VZV) increases during aging. Although the effects of VZV reactivation are observed in the skin (shingles), the number and functional capacity of cutaneous VZV-specific T cells have not been investigated. The numbers of circulating IFN-γ-secreting VZV-specific CD4+ T cells are significantly decreased in old subjects. However, other measures of VZV-specific CD4+ T cells, including proliferative capacity to VZV antigen stimulation and identification of VZV-specific CD4+ T cells with an major histocompatibility complex class II tetramer (epitope of IE-63 protein), were similar in both age groups. The majority of T cells in the skin of both age groups expressed CD69, a characteristic of skin-resident T cells. VZV-specific CD4+ T cells were significantly increased in the skin compared with the blood in young and old subjects, and their function was similar in both age groups. In contrast, the number of Foxp3+ regulatory T cells and expression of the inhibitory receptor programmed cell death -1 PD-1 on CD4+ T cells were significantly increased in the skin of older humans. Therefore, VZV-specific CD4+ T cells in the skin of older individuals are functionally competent. However, their activity may be restricted by multiple inhibitory influences in situ
On Patient Experience and Anxiety During Treatment With Magnetic Resonance–Guided Radiation Therapy
Purpose: To assess patient experience and anxiety during magnetic resonance (MR)–guided radiation therapy (MRgRT) using a hybrid 1.5Tesla (T) MR-guided linear accelerator (MR-Linac) when offered calming video content. Methods and Materials: A single-center study was conducted within the Multi-Outcome Evaluation of Radiation Therapy Using the MR-Linac (MOMENTUM) cohort. Patients were offered to watch calming video content on a video monitor during treatment. Questionnaires were used to assess patient experience (MR-Linac patient-reported experience) and anxiety (State-Trait Anxiety Inventory, STAI) at first treatment fraction (M1) and at third, fourth, or fifth treatment fraction (M2). Paired t tests were used to test for significant differences, and effect sizes (ESs) were used to estimate the magnitude of the difference. Results: Between November 2021 and November 2022, 66 patients were included. The majority were men (n = 59, 89%). MRgRT was most frequently delivered to prostate cancer (n = 45, 68%) followed by a lesion in the pancreas (n = 8, 12%). At M1 and M2, 24 of 59 patients (41%) preferred to watch calming video content. One patient was not able to look at the video monitor comfortably at M1. Patient experience was generally favorable or neutral; tingling sensations were reported by 17% of patients. Anxiety levels were high (16%), moderate (18%), or low to none (67%) prior to M1. STAI scores were 33 (SD, 9) prior to M1 and 29 (SD, 7) after M1 (ES, 0.7; P < .001). STAI scores were 32 (SD, 9) prior to M2 and 31 (SD, 8) after M2 (ES, 0.4; P = .009). Conclusions: Patients were able to comfortably view the video monitor during MRgRT. Consequently, this setup could be used for future applications, such as biofeedback. A sizable minority of patients preferred to watch calming videos that distracted them during treatment. Although the patients’ experience was overall excellent, anxiety was reported. Anxiety levels were highest prior to treatment and decreased after treatment
Professionalism, Golf Coaching and a Master of Science Degree: A commentary
As a point of reference I congratulate Simon Jenkins on tackling the issue of professionalism in coaching. As he points out coaching is not a profession, but this does not mean that coaching would not benefit from going through a professionalization process. As things stand I find that the stimulus article unpacks some critically important issues of professionalism, broadly within the context of golf coaching. However, I am not sure enough is made of understanding what professional (golf) coaching actually is nor how the development of a professional golf coach can be facilitated by a Master of Science Degree (M.Sc.). I will focus my commentary on these two issues
Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase-induced inflammation
Background
Immunity decreases with age, which leads to reactivation of varicella zoster virus (VZV). In human subjects age-associated immune changes are usually measured in blood leukocytes; however, this might not reflect alterations in tissue-specific immunity.
Objectives
We used a VZV antigen challenge system in the skin to investigate changes in tissue-specific mechanisms involved in the decreased response to this virus during aging.
Methods
We assessed cutaneous immunity based on the extent of erythema and induration after intradermal VZV antigen injection. We also performed immune histology and transcriptomic analyses on skin biopsy specimens taken from the challenge site in young (65 years) subjects.
Results
Old human subjects exhibited decreased erythema and induration, CD4+ and CD8+ T-cell infiltration, and attenuated global gene activation at the site of cutaneous VZV antigen challenge compared with young subjects. This was associated with increased sterile inflammation in the skin in the same subjects related to p38 mitogen-activated protein kinase–related proinflammatory cytokine production (P < .0007). We inhibited systemic inflammation in old subjects by means of pretreatment with an oral small-molecule p38 mitogen-activated protein kinase inhibitor (Losmapimod; GlaxoSmithKline, Brentford, United Kingdom), which reduced both serum C-reactive protein levels and peripheral blood monocyte secretion of IL-6 and TNF-α. In contrast, cutaneous responses to VZV antigen challenge were increased significantly in the same subjects (P < .0003).
Conclusion
Excessive inflammation in the skin early after antigen challenge retards antigen-specific immunity. However, this can be reversed by inhibition of inflammatory cytokine production that can be used to promote vaccine efficacy and the treatment of infections and malignancy during aging
The British Army, information management and the First World War revolution in military affairs
Information Management (IM) – the systematic ordering, processing and channelling of information within organisations – forms a critical component of modern military command and control systems. As a subject of scholarly enquiry, however, the history of military IM has been relatively poorly served. Employing new
and under-utilised archival sources, this article takes the British Expeditionary Force (BEF) of the First World War as its case study and assesses the extent to which its IM system contributed to the emergence of the modern battlefield in 1918. It argues that the
demands of fighting a modern war resulted in a general, but not universal, improvement in the BEF’s IM techniques, which in turn laid the groundwork, albeit in embryonic form, for the IM systems of modern armies.
KEY WORDS: British Army, Information Management, First World War, Revolution in Military Affairs, Adaptatio
How to monitor pregnancies complicated by fetal growth restriction and delivery below 32 weeks: a post-hoc sensitivity analysis of the TRUFFLE-study.
OBJECTIVES: In the recent TRUFFLE study it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks, monitoring of the ductus venosus (DV) combined with computerised cardiotocography (cCTG) as a trigger for delivery, increased the chance of infant survival without neurological impairment. However, concerns in interpretation were raised as DV monitoring appeared associated with a non-significant increase in fetal death, and part of the infants were delivered after 32 weeks, after which the study protocol was no longer applied. This secondary sensitivity analysis focuses on women who delivered before 32 completed weeks, and analyses fetal death cases in detail. METHODS: We analysed the monitoring data of 317 women who delivered before 32 weeks, excluding women with absent infant outcome data or inevitable perinatal death. The association of the last monitoring data before delivery and infant outcome was assessed by multivariable analysis. RESULTS: The primary outcome (two year survival without neurological impairment) occurred more often in the two DV groups (both 83%) than in the CTG-STV group (77%), however the difference was not statistically significant (p = 0.21). Nevertheless, in surviving infants 93% was free of neurological impairment in the DV groups versus 85% in the CTG-STV group (p = 0.049). All fetal deaths (n = 7) occurred in women allocated to DV monitoring, which explains this difference. Assessment of the monitoring parameters that were obtained shortly before fetal death in these 7 cases showed an abnormal CTG in only one. Multivariable regression analysis of factors at study entry demonstrated that higher gestational age, larger estimated fetal weight 50th percentile ratio and lower U/C ratio were significantly associated with the (normal) primary outcome. Allocation to the DV groups had a smaller effect, but remained in the model (p < 0.1). Assessment of the last monitoring data before delivery showed that in the CTG-STV group abnormal fetal arterial Doppler was significantly associated with adverse outcome. In contrast, in the DV groups an abnormal DV was the only fetal monitoring parameter that was associated with adverse infant outcome, while fetal arterial Doppler, STV below CTG-group cut-off or recurrent fetal heart rate decelerations were not. CONCLUSIONS: In accordance with the results of the overall TRUFFLE study of the monitoring-intervention management of very early severe FGR we found that the difference in the proportion of infants surviving without neuroimpairment (the primary endpoint) was non-significant when comparing timing of delivery with or without changes in the DV waveform. However, the uneven distribution of fetal deaths towards the DV groups was likely by chance, and among surviving children neurological outcomes were better. Before 32 weeks, delaying delivery until abnormalities in DVPI or STV and/or recurrent decelerations occur, as defined by the study protocol, is therefore probably safe and possibly benefits long-term outcome
Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016
Large expert-curated database for benchmarking document similarity detection in biomedical literature search
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe
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