Federated Learning Survival Model and Potential Radiotherapy Decision Support Impact Assessment for Non-small Cell Lung Cancer Using Real-World Data.

AIMS: The objective of this study was to develop a two-year overall survival model for inoperable stage I-III non-small cell lung cancer (NSCLC) patients using routine radiation oncology data over a federated (distributed) learning network and evaluate the potential of decision support for curative versus palliative radiotherapy. METHODS: A federated infrastructure of data extraction, de-identification, standardisation, image analysis, and modelling was installed for seven clinics to obtain clinical and imaging features and survival information for patients treated in 2011-2019. A logistic regression model was trained for the 2011-2016 curative patient cohort and validated for the 2017-2019 cohort. Features were selected with univariate and model-based analysis and optimised using bootstrapping. System performance was assessed by the receiver operating characteristic (ROC) and corresponding area under curve (AUC), C-index, calibration metrics and Kaplan-Meier survival curves, with risk groups defined by model probability quartiles. Decision support was evaluated using a case-control analysis using propensity matching between treatment groups. RESULTS: 1655 patient datasets were included. The overall model AUC was 0.68. Fifty-eight percent of patients treated with palliative radiotherapy had a low-to-moderate risk prediction according to the model, with survival times not significantly different (p = 0.87 and 0.061) from patients treated with curative radiotherapy classified as high-risk by the model. When survival was simulated by risk group and model-indicated treatment, there was an estimated 11% increase in survival rate at two years (p < 0.01). CONCLUSION: Federated learning over multiple institution data can be used to develop and validate decision support systems for lung cancer while quantifying the potential impact of their use in practice. This paves the way for personalised medicine, where decisions can be based more closely on individual patient details from routine care.

General population normative data from seven European countries for the K10 and K6 scales for psychological distress.

The 10-item Kessler Psychological Distress scale (K10) and its 6-item short-form version (K6) measure psychological distress, particularly anxiety or depressive symptoms. While these questionnaire scales are widely used in various settings and populations, general population normative data are rarely available. To facilitate the interpretation of K10 and K6 scores, we provide normative general population data from seven European countries. We used an online survey to collect K10 data from general population samples in Austria, Italy, Germany, France, the Netherlands, Poland and Spain. We calculated the age- and sex-specific normative values separately for each country. For more specific estimates of K10 and K6 scores for individuals or groups, we also established a multivariable regression model based on socio-demographic and health data. In total, N = 7,087 adults participated in our study (51.6% women; mean age, 49.6 years). The mean K10 score in the total sample was 8.5 points (standard deviation, 7.3) on 0-40 points metric, with mean scores in individual countries ranging from 6.9 (the Netherlands) to 9.9 (Spain). Women showed higher scores than men and younger participants scored higher than older participants. Our study is the first to present normative K10 and K6 data from several European countries using a consistent sampling approach. These reference values will facilitate the interpretation of K10 and K6 scores in clinical research and practice and also highlight the variation in psychological distress levels across countries and groups according to their socio-demographic and health characteristics.

Remote EPID-based dosimetric auditing using DVH patient dose analysis.

Objective.The aim of this work was to develop and validate a method for remote dosimetric auditing that enables dose-volume histogram parameter comparisons of measured and planned dose in the patient CT volume.Approach. The method is derived by adapting and combining a remote electronic portal imaging (EPID) based auditing method (Virtual Epid based Standard Phantom Audit-VESPA) and a method to estimate 3D in-patient dose distributions from planar dosimetric measurements. The method was tested with a series of error-induced plans including monitor unit and multileaf collimator (MLC) positioning errors. A pilot audit study was conducted with eleven radiotherapy centres. IMRT plans from two clinical trials, a post-prostatectomy (RAVES trial) plan and a head and neck (HPV trial) plan were utilized. Clinically relevant DVH parameters for the planned dose and estimated measured dose were compared.Main results. The method was found to reproduce the induced dose errors within 0.5% and was sensitive to MLC positioning errors as small as 0.5 mm. For the RAVES plan audit all DVH results except one were within 3% and for the HPV plan audit all DVH results were within 3% except three with a maximum difference of 3.2%.Significance. The results from the audit method produce clinically meaningful DVH metrics for the audited plan and could enable an improved understanding of a centre's radiotherapy quality.

ESTRO-ACROP guideline on surface guided radiation therapy.

Surface guidance systems enable patient positioning and motion monitoring without using ionising radiation. Surface Guided Radiation Therapy (SGRT) has therefore been widely adopted in radiation therapy in recent years, but guidelines on workflows and specific quality assurance (QA) are lacking. This ESTRO-ACROP guideline aims to give recommendations concerning SGRT roles and responsibilities and highlights common challenges and potential errors. Comprehensive guidelines for procurement, acceptance, commissioning, and QA of SGRT systems installed on computed tomography (CT) simulators, C-arm linacs, closed-bore linacs, and particle therapy treatment systems are presented that will help move to a consensus among SGRT users and facilitate a safe and efficient implementation and clinical application of SGRT.

TROG 14.04: Multicentre Study of Feasibility and Impact on Anxiety of DIBH in Breast Cancer Patients.

AIMS: The aim of TROG 14.04 was to assess the feasibility of deep inspiration breath hold (DIBH) and its impact on radiation dose to the heart in patients with left-sided breast cancer undergoing radiotherapy. Secondary end points pertained to patient anxiety and cost of delivering a DIBH programme. MATERIALS AND METHODS: The study comprised two groups - left-sided breast cancer patients engaging DIBH and right-sided breast cancer patients using free breathing through radiotherapy. The primary end point was the feasibility of DIBH, defined as left-sided breast cancer patients' ability to breath hold for 15 s, decrease in heart dose in DIBH compared with the free breathing treatment plan and reproducibility of radiotherapy delivery using mid-lung distance (MLD) assessed on electronic portal imaging as the surrogate. The time required for treatment delivery, patient-reported outcomes and resource requirement were compared between the groups. RESULTS: Between February and November 2018, 32 left-sided and 30 right-sided breast cancer patients from six radiotherapy centres were enrolled. Two left-sided breast cancer patients did not undergo DIBH (one treated in free breathing as per investigator choice, one withdrawn). The mean heart dose was reduced from 2.8 Gy (free breathing) to 1.5 Gy (DIBH). Set-up reproducibility in the first week of treatment assessed by MLD was 1.88 ± 1.04 mm (average ± 1 standard deviation) for DIBH and 1.59 ± 0.93 mm for free breathing patients. Using a reproducibility cut-off for MLD of 2 mm (1 standard deviation) as per study protocol, DIBH was feasible for 67% of DIBH patients. Radiotherapy delivery using DIBH took about 2 min longer than for free breathing. Anxiety was not significantly different in DIBH patients and decreased over the course of treatment in both groups. CONCLUSION: Although DIBH was shown to require about 2 min longer per treatment slot, it has the potential to reduce heart dose in left-sided breast cancer patients by nearly a half, provided careful assessment of breath hold reproducibility is carried out.

Surface guided radiation therapy: An international survey on current clinical practice.

Introduction: Surface Guided Radiation Therapy (SGRT) is being increasingly implemented into clinical practice across a number of techniques and irradiation-sites. This technology, which is provided by different vendors, can be used with most simulation- and delivery-systems. However, limited guidelines and the complexity of clinical settings have led to diverse patterns of operation. With the aim to understand current clinical practice a survey was designed focusing on specifics of the clinical implementation and usage. Materials and methods: A 32-question survey covered: type and number of systems, quality assurance (QA), clinical workflows, and identification of strengths/limitations. Respondents from different professional groups and countries were invited to participate. The survey was distributed internationally via ESTRO-membership, social media and vendors. Results: Of the 278 institutions responding, 172 had at least one SGRT-system and 136 use SGRT clinically. Implementation and QA were primarily based on the vendors' recommendations and phantoms. SGRT was mainly implemented in breast RT (116/136), with strong but diverse representation of other sites. Many (58/135) reported at least partial elimination of skin-marks and a third (43/126) used open-masks. The most common imaging protocol reported included the combination of radiographic imaging with SGRT. Patient positioning (115/136), motion management (104/136) and DIBH (99/136) were the main applications.Main barriers to broader application were cost, system integration issues and lack of demonstrated clinical value. A lack of guidelines in terms of QA of the system was highlighted. Conclusions: This overview of the SGRT status has the potential to support users, vendors and organisations in the development of practices, products and guidelines.

[Factors influencing the choice of androgen deprivation therapy for patients with hormone-sensitive prostate cancer : Results of the ProComD study]. / Einflussfaktoren bei der Wahl der Androgendeprivationstherapie für Patienten mit hormonsensitiven Prostatakarzinom : Ergebnisse der ProComD-Studie.

BACKGROUND: Androgen deprivation therapy (ADT) with a GnRH agonist or the GnRH antagonist degarelix is a central component in the treatment of prostate cancer (PCa). Little is currently known regarding the decision criteria. Knowledge of these could improve the success of treatment in the future. OBJECTIVES: To identify factors influencing the treatment decision in patients with hormone-sensitive prostate cancer receiving ADT and to determine the incidence of concomitant disease in both treatment groups. METHODS: The two-arm, prospective, non-interventional study "ProComD" was conducted from September 2014 to June 2019 at 80 study centers in Germany. After the therapy decision was made, patients with hormone-sensitive prostate cancer needing ADT were included in the study. Data were collected during routine visits. RESULTS: Data from 413 patients were evaluated (degarelix N = 268; GnRH agonists N = 145). Key factors influencing the therapy decision for both treatment options included comorbidities (42% of all patients), compliance (64%), and age (81%). The source of information consulted most frequently regarding existing comorbidities was the patient's medical history conducted by the treating urologist themselves (65% in both groups). For patients with pre-existing cardiovascular diseases, the doctor's letter (45.8% degarelix vs. 38.9% GnRH agonists) or the medical history questionnaire (38.9% degarelix vs. 20% GnRH agonists) was additionally taken into account. CONCLUSION: Comorbidities along with age and compliance are among the key factors influencing the treatment decisions made by urologists.

Effectiveness and cost effectiveness of a stress management training for leaders of small and medium sized enterprises - study protocol for a randomized controlled-trial.

BACKGROUND: Leaders in small and medium-sized enterprises (SMEs) are exposed to increased stress as a result of a range of challenges. Moreover, they rarely have the opportunity to participate in stress management trainings. Therefore, KMU-GO (ger: Kleine und mittlere Unternehmen - Gesundheitsoffensive; en: small and medium-sized enterprises - health campaign) aims at conducting and evaluating such a stress management training. The focus of evaluation does not only lie on the effects on leaders participating but also on their employees. METHODS: The study is planned as a 2 × 3 mixed design with two groups (intervention and waiting control group) as a between factor and point in time (at baseline, 6 and 12 months later) as a within factor. We aim at collecting data from N = 200 leaders. Based on the results of a preceding assessment, an already successfully implemented stress management training was adapted to SME needs and now serves as the framework of this intervention. The stress management training comprises one and a half days and is followed by two booster sessions (each 180 min) about 3 and 6 months after the training. The main focus of this intervention lies on specifying leaders stress reactivity while at the same time investigating its effects on employees' mental health. Further dependent variables are leaders´ depression and anxiety scores, effort-reward imbalance, sick days and psychophysiological measures of heart rate variability, hair cortisol, and salivary alpha-amylase. Cost-effectiveness analyses will be conducted from a societal and employers' point of view. DISCUSSION: Stress management is a highly relevant issue for leaders in SMEs. By providing an adequate occupational stress management training, we expect to improve leaders´ and also employees` mental health, thereby preventing economic losses for SMEs and the national economy. However, collecting data from employees about the success of a stress management training of their leader is a highly sensitive topic. It requires a carefully planned proceeding ensuring for example a high degree of transparency, anonymity, and providing team incentives. TRIAL REGISTRATION: The KMU-GO trial is registered at the German Clinical Trial Register (DRKS): DRKS00023457 (05.11.2020).

Towards a global-scale soil climate mitigation strategy.

Sustainable soil carbon sequestration practices need to be rapidly scaled up and implemented to contribute to climate change mitigation. We highlight that the major potential for carbon sequestration is in cropland soils, especially those with large yield gaps and/or large historic soil organic carbon losses. The implementation of soil carbon sequestration measures requires a diverse set of options, each adapted to local soil conditions and management opportunities, and accounting for site-specific trade-offs. We propose the establishment of a soil information system containing localised information on soil group, degradation status, crop yield gap, and the associated carbon-sequestration potentials, as well as the provision of incentives and policies to translate management options into region- and soil-specific practices.

Long-term functional results after excisional haemorrhoidectomy.

AIM: The aim of this work was to perform a long-term evaluation of a randomized trial focusing on functional aspects after excisional haemorrhoidectomy with a minimum follow-up of 9 years. METHOD: A questionnaire-based study including patients operated on for haemorrhoids in Sweden between 1999 and 2003. A total of 225 patients were randomized to Milligan's or Ferguson's operation. Twenty-six patients had died and 151 (76%) participated after a median follow-up of 10.7 years (range 9.2-12.6 years). RESULTS: Seventy-seven patients were in the Milligan group and 74 in the Ferguson group. Forty-eight (32%) reported recurrence. Anal bleeding was reported in 80% at baseline but in 28% at long-term follow-up (P < 0.0001). At baseline, 49% had spontaneous anal pain and 25% pain at defaecation. At follow-up, these figures were 17% and 11%. At follow-up, 19% described a sense of anal stenosis. At baseline, soiling was reported in 51% but in 20% at long-term follow-up (P < 0.001). Nineteen per cent used pads preoperatively and 6% at follow-up (P < 0.0001). Straining at defaecation was reported by 35% at baseline. At follow-up, this figure was 25% (P = 0.055). CONCLUSION: Symptoms associated with haemorrhoids were reduced at long-term follow-up. The most common problems were perceived recurrence and a sense of anal stenosis.

Thickness uniformity measurements and damage threshold tests of large-area GaAs/AlGaAs crystalline coatings for precision interferometry.

Precision interferometry is the leading method for extremely sensitive measurements in gravitational wave astronomy. Thermal noise of dielectric coatings poses a limitation to the sensitivity of these interferometers. To decrease coating thermal noise, new crystalline GaAs/AlGaAs multilayer mirrors have been developed. To date, the surface figure and thickness uniformity of these alternative low-loss coatings has not been investigated. Surface figure errors, for example, cause small angle scattering and thereby limit the sensitivity of an interferometer. Here we measure the surface figure of highly reflective, substrate-transferred, crystalline GaAs/AlGaAs coatings with a custom scanning reflectance system. We exploit the fact that the reflectivity varies with the thickness of the coating. To increase penetration into the coating, we used a 1550 nm laser on a highly reflective coating designed for a center wavelength of 1064 nm. The RMS thickness variation of a two inch optic was measured to be 0.41 ± 0.05 nm. This result is within 10% of the thickness uniformity, of 0.37 nm RMS, achieved with ion-beam sputtered coatings for the aLIGO detector. We additionally measured a lower limit of the laser induced damage threshold of 64 MW/cm 2 for GaAs/AlGaAs coatings at a wavelength of 1064 nm.

Repeatable glucocorticoid expression is associated with behavioural syndromes in males but not females in a wild primate.

Behavioural syndromes are a well-established phenomenon in human and non-human animal behavioural ecology. However, the mechanisms that lead to correlations among behaviours and individual consistency in their expression at the apparent expense of behavioural plasticity remain unclear. The 'state-dependent' hypothesis posits that inter-individual variation in behaviour arises from inter-individual variation in state and that the relative stability of these states within an individual leads to consistency of behaviour. The endocrine stress response, in part mediated by glucocorticoids (GCs), is a proposed behavioural syndrome-associated state as GC levels are linked to an individual's behavioural responses to stressors. In this study, in wild Barbary macaques (Macaca sylvanus), consistent inter-individual differences were observed in both sexes for GC activity (faecal glucocorticoid, fGC concentrations), but not GC variation (coefficient of variation in fGC concentrations). The expression of the behavioural syndrome 'Excitability' (characterized by the frequencies of brief affiliation or aggressive interactions) was related to GC activity in males but not in females; more 'excitable' males had lower GC activity. There was no relationship in females between any of the behavioural syndromes and GC activity, nor in either sex with GC variation. The negative relationship between GC activity and Excitability in males provides some support for GC expression as a behavioural syndrome-generating state under the state-dependent framework. The absence of this relationship in females highlights that state-behavioural syndrome associations may not be generalizable within a species and that broader sex differences in state need to be considered for understanding the emergence and maintenance of behavioural syndromes.

Review: extended lactation in dairy cattle.

This paper reviews the effects of extended lactation (EXT) as a strategy in dairy cattle on milk production and persistency, reproduction, milk quality, lifetime performance of the cow and finally the economic effects on herd and farm levels as well as the impact on emission of greenhouse gas at product level. Primiparous cows are able to produce equal or more milk per feeding day during EXT compared with a standard 305-d lactation, whereas results for multiparous cows are inconsistent. Cows managed for EXT can achieve a higher lifetime production while delivering milk with unchanged or improved quality properties. Delaying insemination enhances mounting behaviour and allows insemination after the cow's energy balance has become positive. However, in most cases EXT has no effect or a non-significant positive effect on reproduction. The EXT strategy sets off a cascade of effects at herd and farm level. Thus, the EXT strategy leads to fewer calvings and thereby expected fewer diseases, fewer replacement heifers and fewer dry days per cow per year. The optimal lifetime scenario for milk production was modelled to be an EXT of 16 months for first parity cows followed by an EXT of 10 months for later lactations. Modelling studies of herd dynamics indicate a positive effect of EXT on lifetime efficiency (milk per dry matter intake), mainly originating from benefits of EXT on daily milk yield in primiparous cows and the reduced number of replacement heifers. Consequently, EXT also leads to reduced total meat production at herd level. For the farmer, EXT can give the same economic return as a traditional lactation period. At farm level, EXT can contribute to a reduction in the environmental impact of dairy production, mainly as a consequence of the reduced production of beef. A wider dissemination of the EXT concept will be supported by methods to predict which cows may be most suitable for EXT, and clarification of how milking frequency and feeding strategy through the lactation can be organised to support milk yield and an appropriate body condition at the next calving.

Recellularization of auricular cartilage via elastase-generated channels.

Decellularized tissue matrices are promising substrates for tissue generation by stem cells to replace poorly regenerating tissues such as cartilage. However, the dense matrix of decellularized cartilage impedes colonisation by stem cells. Here, we show that digestion of elastin fibre bundles traversing auricular cartilage creates channels through which cells can migrate into the matrix. Human chondrocytes and bone marrow-derived mesenchymal stromal cells efficiently colonise elastin-treated scaffolds through these channels, restoring a glycosaminoglycan-rich matrix and improving mechanical properties while maintaining size and shape of the restored tissue. The scaffolds are also rapidly colonised by endogenous cartilage-forming cells in a subcutaneously implanted osteochondral biopsy model. Creating channels for cells in tissue matrices may be a broadly applicable strategy for recellularization and restoration of tissue function.

Production, partial cash flows and greenhouse gas emissions of simulated dairy herds with extended lactations.

The transition period is the most critical period in the lactation cycle of dairy cows. Extended lactations reduce the frequency of transition periods, the number of calves and the related labour for farmers. This study aimed to assess the impact of 2 and 4 months extended lactations on milk yield and net partial cash flow (NPCF) at herd level, and on greenhouse gas (GHG) emissions per unit of fat- and protein-corrected milk (FPCM), using a stochastic simulation model. The model simulated individual lactations for 100 herds of 100 cows with a baseline lactation length (BL), and for 100 herds with lactations extended by 2 or 4 months for all cows (All+2 and All+4), or for heifers only (H+2 and H+4). Baseline lactation length herds produced 887 t (SD: 13) milk/year. The NPCF, based on revenues for milk, surplus calves and culled cows, and costs for feed, artificial insemination, calving management and rearing of youngstock, was k€174 (SD: 4)/BL herd per year. Extended lactations reduced milk yield of the herd by 4.1% for All+2, 6.9% for All+4, 1.1% for H+2 and 2.2% for H+4, and reduced the NPCF per herd per year by k€7 for All+2, k€12 for All+4, k€2 for H+2 and k€4 for H+4 compared with BL herds. Extended lactations increased GHG emissions in CO2-equivalents per t FPCM by 1.0% for All+2, by 1.7% for All+4, by 0.2% for H+2 and by 0.4% for H+4, but this could be compensated by an increase in lifespan of dairy cows. Subsequently, production level and lactation persistency were increased to assess the importance of these aspects for the impact of extended lactations. The increase in production level and lactation persistency increased milk production of BL herds by 30%. Moreover, reductions in milk yield for All+2 and All+4 compared with BL herds were only 0.7% and 1.1% per year, and milk yield in H+2 and H+4 herds was similar to BL herds. The resulting NPCF was equal to BL for All+2 and All+4 and increased by k€1 for H+2 and H+4 due to lower costs for insemination and calving management. Moreover, GHG emissions per t FPCM were equal to BL herds or reduced (0% to -0.3%) when lactations were extended. We concluded that, depending on lactation persistency, extending lactations of dairy cows can have a positive or negative impact on the NPCF and GHG emissions of milk production.

[Is there also a gynecologist for men? : A randomised controlled trial of ÄGGF information sessions in schools as a bridge to the urologist's consultations with boys]. / Gibt's auch 'nen Frauenarzt für Männer? : Eine randomisiert kontrollierte Studie der ÄGGF-Präventionsveranstaltungen in Schulen als Brücke zur Jungensprechstunde beim Urologen.

BACKGROUND: There are hardly any prevention programmes for health education and communication for boys in Germany. Boys seldom know when, how and to whom to turn to for questions or problems in the field of sexual and reproductive health. METHODS: From 2014-2016 the Medical Society for Health Promotion carried out a unique project for gender-sensitive medical health promotion for boys of all school types at 130 Bavarian schools. In 2015, 15 Bavarian schools took part in the evaluation (6th, 8th, 9th and 11th grade). At school level, similar schools have been randomised to trial and control groups. In the experimental group, three waves were conducted in panel design and two interviews were conducted in the control group using paper questionnaires. The number of cases in the panel is 599 (358 intervention group, 241 waiting control group). RESULTS: In all school types and grade levels, a highly significant increase in knowledge can be demonstrated. There is an average of 28% of the intervention group's overall knowledge improvement compared to the control group. More than 50% of the participants consider themselves to be very well informed before the intervention, although the objectively available knowledge does not justify this (e. g. average proportion of correctly answered questions on male anatomy and physiology 0.7 out of 6). The participants rate the medical information sessions and the fact that they are conducted by doctors with 1.7 or 1.6 (1: very good, to 5: poor). DISCUSSION: Boys urgently need proper knowledge transfer in the field of sexual health. They benefit regardless of the types of school from these health information sessions. The gender-sensitive and socially compensatory medical information sessions are highly accepted, effective and serve as a bridge to the general practitioners. A nationwide establishment of the intervention seems thus absolutely necessary.

Huddle test measurement of a near Johnson noise limited geophone.

In this paper, the sensor noise of two geophone configurations (L-22D and L-4C geophones from Sercel with custom built amplifiers) was measured by performing two huddle tests. It is shown that the accuracy of the results can be significantly improved by performing the huddle test in a seismically quiet environment and by using a large number of reference sensors to remove the seismic foreground signal from the data. Using these two techniques, the measured sensor noise of the two geophone configurations matched the calculated predictions remarkably well in the bandwidth of interest (0.01 Hz-100 Hz). Low noise operational amplifiers OPA188 were utilized to amplify the L-4C geophone to give a sensor that was characterized to be near Johnson noise limited in the bandwidth of interest with a noise value of 10-11 m/Hz at 1 Hz.