Algorithm and performance of a clinical IMRT beam-angle optimization system

This paper describes the algorithm and examines the performance of an IMRT beam-angle optimization (BAO) system. In this algorithm successive sets of beam angles are selected from a set of predefined directions using a fast simulated annealing (FSA) algorithm. An IMRT beam-profile optimization is performed on each generated set of beams. The IMRT optimization is accelerated by using a fast dose calculation method that utilizes a precomputed dose kernel. A compact kernel is constructed for each of the predefined beams prior to starting the FSA algorithm. The IMRT optimizations during the BAO are then performed using these kernels in a fast dose calculation engine. This technique allows the IMRT optimization to be performed more than two orders of magnitude faster than a similar optimization that uses a convolution dose calculation engine.Comment: Final version that appeared in Phys. Med. Biol. 48 (2003) 3191-3212. Original EPS figures have been converted to PNG files due to size limi

On Component Forces in Physics: A Pragmatic View

Do component forces exist? I argue that the answer lies in the affirmative, on historical and operational grounds

Feasibility randomized controlled trial of a self-guided online intervention to promote psychosocial adjustment to unmet parenthood goals

STUDY QUESTION Is it feasible to implement and evaluate an online self-guided psychosocial intervention for people with an unmet parenthood goal (UPG), aimed to improve well-being, in an online randomized controlled trial (RCT)? SUMMARY ANSWER The evaluation of an online bilingual self-guided psychosocial intervention for people with a UPG is feasible, reflected by high demand, good acceptability, good adaptation and promise of efficacy, but minor adjustments to the intervention and study design of the RCT should be made to enhance practicality. WHAT IS KNOWN ALREADY Self-identifying as having a UPG, defined as being unable to have children or as many as desired, is associated with impaired well-being and mental health. Practice guidelines and regulatory bodies have highlighted the need to address the lack of evidence-based support for this population. It is unknown if MyJourney (www.myjourney.pt), the first online self-guided intervention for people with UPGs, can be implemented and evaluated in an RCT. STUDY DESIGN, SIZE, DURATION To evaluate the feasibility of MyJourney, we conducted a registered, two-arm, parallel group, non-blinded feasibility RCT, with a 1:1 computer-generated randomized allocation and embedded qualitative process evaluation. Participants were included between November 2020 and March 2021. Assessments were made before randomization (T1), 10 weeks (T2) and 6 months after (T3, intervention group only). Participants allocated to the intervention group received an email to access MyJourney immediately after randomization. Participants in the waitlist control group were given access to MyJourney after completing the 10-week assessment (T2). PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were recruited via social media advertising of MyJourney and its feasibility study. People who self-identified as having a UPG could click on a link to participate, and of these 235 were randomized. Outcome measures related to demand, acceptability, implementation, practicality, adaptation and limited efficacy were assessed via online surveys. The primary outcome in limited efficacy testing was hedonic well-being, measured with the World Health Organisation Wellbeing Index (WHO-5). MAIN RESULTS AND THE ROLE OF CHANCE Participation and retention rates were 58.3%, 31.7% (T2) and 45.2% (T3, intervention group only), respectively. Of participants invited to register with MyJourney, 91 (76.5%) set up an account, 51 (47.2%) completed the first Step of MyJourney, 12 (11.1%) completed six Steps (sufficient dose) and 6 (5.6%) completed all Steps within the 10-week recommended period. Acceptability ranged from 2.79 (successful at supporting) to 4.42 (easy to understand) on a 1 (not at all) to 5 (extremely acceptable) scale. Average time to complete sufficient dose was 15.6 h (SD = 18.15) and to complete all Steps was 12.4 h (SD = 18.15), with no differences found for participants using MyJourney in Portuguese and English. Modified intention-to-treat analysis showed a moderate increase in well-being from T1 to T2 in the intervention group (ηp2 = 0.156, mean difference (MD) = 9.300 (2.285, 16.315)) and no changes in the control group (ηp2 = 0.000, MD = 0.047 (−3.265, 3.358)). Participants in the process evaluation reported MyJourney was needed and answered their needs for support (reflecting high demand and acceptability), the recommended period to engage with MyJourney was short, and their engagement was influenced by multiple factors, including personal (e.g. lack of time) and MyJourney related (e.g. reminders). LIMITATIONS, REASONS FOR CAUTION Participants were mostly white, well-educated, employed, childless women. Non-blinded allocation, use of self-reported questionnaire assessments and high attrition in the intervention group could have triggered bias favourable to positive evaluations of MyJourney and resulted in low power to detect T2 to T3 changes in limited efficacy outcomes. WIDER IMPLICATIONS OF THE FINDINGS MyJourney can proceed to efficacy testing, but future work should eliminate barriers for engagement and explore strategies to maximize adherence. Entities wanting to support people with UPGs now have a freely accessible and promising resource that can be further tested and evaluated in different settings

Does Scientific Progress Consist in Increasing Knowledge or Understanding?

Bird argues that scientific progress consists in increasing knowledge. Dellsén objects that increasing knowledge is neither necessary nor sufficient for scientific progress, and argues that scientific progress rather consists in increasing understanding. Dellsén also contends that unlike Bird’s view, his view can account for the scientific practices of using idealizations and of choosing simple theories over complex ones. I argue that Dellsén’s criticisms against Bird’s view fail, and that increasing understanding cannot account for scientific progress, if acceptance, as opposed to belief, is required for scientific understanding

Design and development of a novel upper-limb cycling prosthesis

The rise in popularity of the Paralympics in recent years has created a need for effective, low-cost sports-prosthetic devices for upper-limb amputees. There are various opportunities for lower-limb amputees to participate in cycling; however, there are only few options for those with upper-limb amputations. If the individual previously participated in cycling, a cycling-specific prosthesis could allow these activities to be integrated into rehabilitation methods. This article describes the processes involved with designing, developing and manufacturing such a prosthesis. The fundamental needs of people with upper-limb amputation were assessed and realised in the prototype of a transradial terminal device with two release mechanisms, including a sliding mechanism (for falls and minor collisions) and clamping mechanism (for head-on collisions). The sliding mechanism requires the rider to exert approximately 200 N, while the clamping mechanism requires about 700 N. The force ranges can be customised to match rider requirements. Experiments were conducted in a controlled environment to demonstrate stability of the device during normal cycling. Moreover, a volunteer test-rider was able to successfully activate the release mechanism during a simulated emergency scenario. The development of this prosthesis has the potential to enable traumatic upper-limb amputees to participate in cycling for rehabilitation or recreation

'Word from the street' : when non-electoral representative claims meet electoral representation in the United Kingdom

Taking the specific case of street protests in the UK – the ‘word from the street’– this article examines recent (re)conceptualizations of political representation, most particularly Saward’s notion of ‘representative claim’. The specific example of nonelectoral claims articulated by protestors and demonstrators in the UK is used to illustrate: the processes of making, constituting, evaluating and accepting claims for and by constituencies and audiences; and the continuing distinctiveness of claims based upon electoral representation. Two basic questions structure the analysis: first, why would the political representative claims of elected representatives trump the nonelectoral claims of mass demonstrators and, second, in what ways does the ‘perceived legitimacy’ of the former differ from the latter

Component-resolved diagnostics in the clinical and laboratory investigation of allergy

The diagnosis and management of allergy is complex; the clinical symptoms associated with allergic reactions span a broad spectrum of severity, from mild hay fever-type symptoms through to life-threatening anaphylaxis. Obtaining an allergy-focused clinical history is therefore vital for identifying possible allergic triggers and directing testing. However, this focus could be changing as scientific and technological advances have paved the way for developments within in vitro testing for allergy. With knowledge of allergens at the molecular level expanding, there are now the facilities to characterize the sensitization profiles of allergy sufferers and determine the specific molecules (or components) against which the allergen-inducing immunoglobulin type E proteins have been produced. This technology is termed component-resolved diagnostics. We know that accurate identification of immunoglobulin type E specificity, the source of the causative allergen, and knowledge of potential allergic cross-reactivities are required for optimal clinical management of allergy patients. These factors can make allergy a diagnostic challenge outside of a specialist centre, and contribute to the difficulties associated with requesting and interpreting allergy tests. The incorporation of component-resolved diagnostics into current practice has provided a platform for patient-tailored risk stratification and improved the application of allergen-specific immunotherapy, revolutionizing specialist management of these patients. This review discusses the roles of each type of testing in allergy management and predictions for future pathway

What is theoretical progress of science?

The epistemic conception of scientific progress equates progress with accumulation of scientific knowledge. I argue that the epistemic conception fails to fully capture scientific progress: theoretical progress, in particular, can transcend scientific knowledge in important ways. Sometimes theoretical progress can be a matter of new theories ‘latching better onto unobservable reality’ in a way that need not be a matter of new knowledge. Recognising this further dimension of theoretical progress is particularly significant for understanding scientific realism, since realism is naturally construed as the claim that science makes theoretical progress. Some prominent realist positions (regarding fundamental physics, in particular) are best understood in terms of commitment to theoretical progress that cannot be equated with accumulation of scientific knowledge

Treatment Outcomes of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis in Patients Over Age 75 Years: A Meta-Analysis

Background: The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. Methods: A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. Results: Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (n = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25–36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09–0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16–0.57], I2 = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15–3.35]). Conclusion: This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment

Chemoradiotherapy of locally-advanced non-small cell lung cancer: Analysis of radiation dose-response, chemotherapy and survival-limiting toxicity effects indicates a low alpha/beta ratio

Purpose To analyse changes in 2-year overall survival (OS2yr) with radiotherapy (RT) dose, dose-per-fraction, treatment duration and chemotherapy use, in data compiled from prospective trials of RT and chemo-RT (CRT) for locally-advanced non-small cell lung cancer (LA-NSCLC). Material and methods OS2yr data was analysed for 6957 patients treated on 68 trial arms (21 RT-only, 27 sequential CRT, 20 concurrent CRT) delivering doses-per-fraction ≤4.0 Gy. An initial model considering dose, dose-per-fraction and RT duration was fitted using maximum-likelihood techniques. Model extensions describing chemotherapy effects and survival-limiting toxicity at high doses were assessed using likelihood-ratio testing, the Akaike Information Criterion (AIC) and cross-validation. Results A model including chemotherapy effects and survival-limiting toxicity described the data significantly better than simpler models (p < 10−14), and had better AIC and cross-validation scores. The fitted α/β ratio for LA-NSCLC was 4.0 Gy (95%CI: 2.8–6.0 Gy), repopulation negated 0.38 (95%CI: 0.31–0.47) Gy EQD2/day beyond day 12 of RT, and concurrent CRT increased the effective tumour EQD2 by 23% (95%CI: 16–31%). For schedules delivered in 2 Gy fractions over 40 days, maximum modelled OS2yr for RT was 52% and 38% for stages IIIA and IIIB NSCLC respectively, rising to 59% and 42% for CRT. These survival rates required 80 and 87 Gy (RT or sequential CRT) and 67 and 73 Gy (concurrent CRT). Modelled OS2yr rates fell at higher doses. Conclusions Fitted dose–response curves indicate that gains of ~10% in OS2yr can be made by escalating RT and sequential CRT beyond 64 Gy, with smaller gains for concurrent CRT. Schedule acceleration achieved via hypofractionation potentially offers an additional 5–10% improvement in OS2yr. Further 10–20% OS2yr gains might be made, according to the model fit, if critical normal structures in which survival-limiting toxicities arise can be identified and selectively spared