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BACKGROUND: Few studies have examined long-term outcomes following oral immunotherapy (OIT); none have examined long-term risks and benefits associated with distinct clinical outcomes (desensitization, remission). METHODS: Participants completing the probiotic and peanut oral immunotherapy (PPOIT) -003 randomized trial were enrolled in a follow-on study, PPOIT-003LT. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively. Outcomes at 1-year and 2-years post-treatment were examined by treatment group and by post-OIT clinical outcome (remission, desensitization without remission [DWR], allergic). RESULTS: 86% (151/176) of eligible children enrolled. Post-treatment peanut ingestion at 2-years post-treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2-years post-treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI -0.03, 0.20), p = .127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD -0.21 (95%CI -0.39; -0.03), p = .02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p = .001) participants. At 2-years post-treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD -0.54 (95%CI -0.99, -0.10), p = .017) and allergic (MD -0.82 (95%CI -1.25, -0.38), p < .001). CONCLUSION: By 2-years post-treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient-preferred treatment outcom

Large language models (LLMs), especially those based on the Generative Pre-trained Transformer (GPT) architecture, have becomewidely popularand have beenappliedinvarious fields due to their ability to provide written responses to a diverse range of queries swiftly and accurately. LLMs have demonstrated a transformative and potentially revolutionary capacity in multiple medical subfields, including radiology.1 A promising utilisation of these models is to streamline free-text radiology reports into concise or structured formats, 2,3 thereby enhancing accessibility and organisation of extensive information, potentially facilitating communication among medical professionals. Furthermore, incorporating automated radiological structured reporting systems could enhance clinical procedures, standardising language across institutions, promoting effective communication among healthcare experts, and improving the efficiency of data extraction for research purposes. The present authors share their preliminary results with three LLMs evaluating their accuracy in extracting emergency data recognition within a human-generated emergency radiology report.

The armamentarium of approved radiopharmaceuticals for either diagnosis or therapy is at the core of the clinical practice of today's nuclear medicine. Nevertheless, both because the currently approved agents do not meet all the clinical needs for radionuclide targeting and because advancing knowledge in the pathophysiology of tissues/organs opens in turn new opportunities, investigations continue at the preclinical and clinical validation level for the development of new radiopharmaceuticals, most of which are not approved yet for commercial use. Concerning in particular the diagnostic applications of nuclear medicine to oncology, ongoing investigations in the search for tumor-targeting agents with better specificity and sensitivity are countless, possibly within the scenario of theranostics-that is, with the dual potential for imaging and for therapy, depending on the specific radionuclide employed for radiolabeling. We will focus this chapter on the most promising imaging agents labeled with single-photon-emitting radionuclides based on some of the mechanisms that are typical for tumor cells/tissues.

Radiopharmaceuticals contain a radionuclide and an agent to direct the radionuclide to a receptor, antigen, ionic pump, or other sites of interest. Some radiopharmaceuticals are simple, such as the ionic form of the radionuclide, while most radiopharmaceuticals have a complex chemical structure where the radionuclide provides a signal, indicating the site of localization of the carrier molecule. Common single-photon radiopharmaceuticals used for oncological diagnosis include the agents labeled with 99mTc such as 99mTc-bisphosphonates (that accumulate at sites of bone mineral deposition), 99mTc-labeled colloids (that are used for lymphoscintigraphy and for imaging of the liver and spleen), 99mTc-hexakis-methoxy-isobutyl-isonitrile, and 99mTc-tetrofosmin (initially employed for myocardial perfusion imaging, and also used for localization of parathyroid adenomas and for identification of other malignant tumors). The most commonly used radiopharmaceuticals labeled with radioiodine (123I or 131I) include iodide itself (for localization of thyroid tissue) and the catecholamine analog metaiodobenzylguanidine (MIBG, for localizing pheochromocytoma and neuroblastoma). Thallium-201 chloride (201Tl) is used for myocardial perfusion imaging as well as tumor perfusion imaging, while 111In-pentetreotide detects overexpression of somatostatin receptors, especially in neuroendocrine tumors and in lesions arising from the neural crest, such as carcinoid, paragangliomas, and medullary thyroid carcinomas. 111In-capromab pendetide is a murine monoclonal antibody recognizing a transmembrane glycoprotein expressed by poorly differentiated and metastatic prostate adenocarcinomas. 67Ga-citrate receptors are overexpressed on membranes of both tumor and inflammatory cells.

PURPOSE: To investigate the effects of providing rigid wrist-hand orthoses plus usual multidisciplinary care, on reducing hand impairments in children with cerebral palsy. METHODS: A pragmatic, multicentre, assessor-blinded randomised controlled trial aimed to enrol 194 children aged 5-15 years, with wrist flexor Modified Ashworth Scale score ≥1. Randomisation with concealed allocation was stratified by study site and passive wrist range. The treatment group received a rigid wrist-hand orthosis, to wear ≥6 h per night for 3 years. Analysis included repeated measures mixed-effects linear regression models, using intention-to-treat principles. RESULTS: The trial stopped early due to insufficient recruitment: 74 children, across all Manual Ability Classification System levels, were randomised (n = 38 orthosis group; n = 36 control). Mean age was 10.2 (SD 3.1) years (orthosis group) and 9.1 (SD 2.8) years (control). Data showed some evidence that rigid wrist-hand orthosis impacted passive wrist extension with fingers extended in the first year [mean difference between-groups at 6 months: 13.15° (95%CI: 0.81-25.48°, p = 0.04); 12 months: 20.94° (95%CI: 8.20-33.69°, p = 0.001)]. Beyond 18 months, participant numbers were insufficient for conclusive findings. CONCLUSION: The study provided detailed data about short- and long-term effects of the wrist-hand orthosis and highlighted challenges in conducting large randomised controlled trials with this population. Trial Registration: Australia and New Zealand Clinical Trials Registry: U1111-1164-0572 IMPLICATIONS FOR REHABILITATIONThere may be incremental benefit, for children with cerebral palsy, at 6 and 12 months on passive wrist range from wearing a rigid wrist-hand orthosis designed according to this protocol.The rigid-wrist-hand orthosis evaluated in this study, which allowed for some tailoring for individual children's presentations, differed in design from past recommendations for "resting hand" positioning.Longitudina

Item does not contain fulltext, BACKGROUND: The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). METHODS: In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. RESULTS: A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P = 0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P = 0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified. CONCLUSIONS: Vaccination with BC

Recent studies concerning the integration of agricultural practices in cities demonstrated that Urban Agriculture (UA) can boost new sustainable urban developments. New technologies allow to integrate soil-less cultivation in- and on- mixed-use buildings, creating new synergies between the built environment and the urban food system. Accordingly, resource flows from buildings are an untapped opportunity for the creation of circular urban metabolisms that rely on recycling waste as input for food production systems. On this trail, this research work focuses on evaluating the feasibility of using urine and greywater streams as nutrient solution in a theoretical model of Building-Integrated Agriculture (BIA) located in Amsterdam. Results showed that it is feasible to use urine and greywater as nutrient solutions (NS). However, treated urine showed higher concentration of macronutrients compared to fertilizer recipes found in literature, and therefore needed to be diluted with increasing amount of greywater to match either N or P concentration. Accordingly, P deficiencies in the plants or excessive N concentration were found in the final wastewater-based NS. Future research is highly recommended to assess the quality of plants grown in BIA systems as well as the possible content of harmful viruses and bacteria in the harvested produce.

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.

Background: Oral immunotherapy is effective at inducing desensitisation to allergens and induces sustained unresponsiveness (ie, clinical remission) in a subset of patients, but causes frequent reactions. We aimed to investigate whether addition of a probiotic adjuvant improved the efficacy or safety of peanut oral immunotherapy. Method(s): PPOIT-003, a multicentre, randomised, phase 2b trial, was conducted in three tertiary hospitals in Australia (Adelaide [SA], Melbourne [VIC], and Perth [WA]) in children aged 1-10 years, weighing more than 7 kg, with peanut allergy confirmed by a double-blind placebo-controlled food challenge (cumulative 4950 mg dose of peanut protein) and positive peanut skin prick test (>=3 mm) or peanut-specific IgE (>=0.35 kU/L). Children were randomly assigned (2:2:1) to receive probiotic and peanut oral immunotherapy (PPOIT), placebo probiotic and peanut oral immunotherapy (OIT), or placebo probiotic and placebo OIT (placebo) for 18 months, and were followed up until 12 months after completion of treatment. Oral immunotherapy consisted of increasing doses of peanut protein (commercially available food-grade 12% defatted peanut flour [50% peanut protein]) until a 2000 mg daily maintenance dose was reached. The probiotic adjuvant was a daily dose of 2 x 1010 colony-forming units of the probiotic Lactobacillus rhamnosus ATCC 53103. Placebo immunotherapy comprised maltodextrin, brown food colouring, and peanut essence, and placebo probiotic was maltodextrin. Dual primary outcomes were 8-week sustained unresponsiveness, defined as no reaction to a cumulative dose of 4950 mg peanut protein at treatment completion and 8 weeks after treatment completion, in the PPOIT versus placebo groups and the PPOIT versus OIT groups, analysed by intention to treat. Safety endpoints were adverse events during the treatment phase, and peanut ingestion and reactions in the 12-month post-treatment period. This study is registered with the Australian New Zealand Cli

BACKGROUND: Understanding how and why de-implementation of low-value practices is sustained remains unclear. The Paediatric Research in Emergency Departments International CollaboraTive (PREDICT) Bronchiolitis Knowledge Translation (KT) Study was a cluster randomised controlled trial conducted in 26 Australian and New Zealand hospitals (May-November 2017). Results showed targeted, theory-informed interventions (clinical leads, stakeholder meetings, train-the-trainer workshop, targeted educational package, audit/feedback) were effective at reducing use of five low-value practices for bronchiolitis (salbutamol, glucocorticoids, antibiotics, adrenaline and chest x-ray) by 14.1% in acute care settings. The primary aim of this study is to determine the sustainability (continued receipt of benefits) of these outcomes at intervention hospitals two-years after the removal of study supports. Secondary aims are to determine sustainability at one-year after removal of study support at intervention hospitals; improvements one-and-two years at control hospitals; and explore factors that influence sustainability at intervention hospitals and contribute to improvements at control hospitals. METHODS: A mixed-methods study design. The quantitative component is a retrospective medical record audit of bronchiolitis management within 24 hours of emergency department (ED) presentations at 26 Australian (n = 20) and New Zealand (n = 6) hospitals, which participated in the PREDICT Bronchiolitis KT Study. Data for a total of 1800 infants from intervention and control sites (up to 150 per site) will be collected to determine if improvements (i.e., no use of all five low-value practices) were sustained two- years (2019) post-trial (primary outcome; composite score); and a further 1800 infants from intervention and control sites will be collected to determine sustained improvements one- year (2018) post-trial (secondary outcome). An a priori definition of sustainability will be used. The qual

BACKGROUND: A high proportion of patients with neurofibromatosis type 1 (NF1) present with functional hearing deficiency as a result of neural abnormality in the late auditory brainstem. METHODS: In this randomized, two-period crossover study, we investigated the hypothesis that remote-microphone listening devices can ameliorate hearing and communication deficits in affected school-aged children (7-17 years). Speech perception ability in background noise was evaluated in device-active and inactive conditions using the CNC-word test. Participants were then randomized to one of two treatment sequences: (1) inactive device for two weeks (placebo), followed by active device use for two weeks, or (2) active device for 2 weeks, followed by inactive device for 2 weeks. Listening and communication ratings (LIFE-R Questionnaire) were obtained at baseline and at the end of each treatment phase. RESULTS: Each participant demonstrated functional hearing benefits with remote-microphone use. All showed a speech perception in noise increase when the device was activated with a mean phoneme-score difference of 16.4% (p < 0.001) and reported improved listening/communication abilities in the school classroom (mean difference: 23.4%; p = 0.017). DISCUSSION: Conventional hearing aids are typically ineffective as a treatment for auditory neural dysfunction, making sounds louder, but not clearer for affected individuals. In this study, we demonstrate that remote-microphone technologies are acceptable/tolerable in pediatric patients with NF1 and can ameliorate their hearing deficits. CONCLUSION: Remote-microphone listening systems offer a viable treatment option for children with auditory deficits associated with NF1.

OBJECTIVES: Nurse home visiting (NHV) is widely implemented to address inequities in child and maternal health. However, few studies have examined longer-term effectiveness or delivery within universal healthcare systems. We evaluated the benefits of an Australian NHV program ("right@home") in promoting children's language and learning, general and mental health, maternal mental health and wellbeing, parenting and family relationships, at child ages 4 and 5 years. SETTING AND PARTICIPANTS: Randomised controlled trial of NHV delivered via universal, child and family health services (the comparator). Pregnant women experiencing adversity (≥2 of 10 risk factors) were recruited from 10 antenatal clinics across 2 states (Victoria, Tasmania) in Australia. INTERVENTION: Mothers in the intervention arm were offered 25 nurse home visits (mean 23·2 home visits [SD 7·4, range 1-43] received) of 60-90 minutes, commencing antenatally and continuing until children's second birthdays. PRIMARY AND SECONDARY OUTCOMES MEASURED: At 4 and 5 years, outcomes were assessed via parent interview and direct assessment of children's language and learning (receptive and expressive language, phonological awareness, attention, and executive function). Outcomes were compared between intervention and usual care arms (intention to treat) using adjusted regression with robust estimation to account for nurse/site. Missing data were addressed using multiple imputation and inverse probability weighting. RESULTS: Of 722 women enrolled in the trial, 225 of 363 (62%) intervention and 201 of 359 (56%) usual care women provided data at 5 years. Estimated group differences showed an overall pattern favouring the intervention. Statistical evidence of benefits was found across child and maternal mental health and wellbeing, parenting and family relationships with effect sizes ranging 0·01-0·27. CONCLUSION: An Australian NHV program promoted longer-term family functioning and wellbeing for women experiencing ad

Urban farming, also called urban agriculture (UA), represents a promising solution to achieve some of the SDGs (sustainable development goals) identified by United Nations. Indeed, UA is a multifunctional activity that presents interesting social, economic and environmental opportunities. The economic viability of UA is a hot topic, given the recent exponential growth in interest by companies and investors throughout the last ten years. The interest is also reaching public and private investors, being an opportunity for economic advancement in most countries, including EBRD (European Bank for Reconstruction and Development) countries of operation. Despite the growing interest and the manifested potential, some drawbacks are still hindering the development of UA, raising questions especially on the feasibility from a financial point of view. In particular, aspects such as the resource use efficiency, technological inputs and business models, still need to be expanded in order to correctly and efficiently apply and adapt UA to different local environmental and socio-economic conditions. The present paper aims to summarize the ongoing situation of UA, with respect to the main resources, technologies and business models to identify weaknesses and strengths for further improvement of the sector.

Increasing urbanization rates, loss of natural resources and the effects of climate change are challenging the sustainability of European cities. Therefore, ensuring resilient urban food systems is crucial to achieve food and nutrition security. Conventional systems are increasingly vulnerable to present and future disruptions, which urges us to change the way we produce, consume, and think about food. The development of local or regional food systems can play an important role because of the multifunctional services that are offered to the inhabitants of the city and its surroundings. The EU Project “Food systems in European Cities – FoodE” (H2020-862663) aims to encourage the development of such systems across the city-regional context by supporting their design, implementation and evaluation. Within the FoodE framework, 15 pilot case studies are being set up in 11 EU cities and serve as demonstration and first application of innovative solutions in market and social contexts, co-designed with citizens and relevant stakeholders. These local initiatives range from small-scale fisheries and low-tech market gardens to agricultural parks, semi-industrial high-tech greenhouses and vertical farms, in rural, coastal and urban agglomerations. This study reports and analyses the results of the community-based design approach of the pilot initiatives in the definition of priorities and optimal features to be implemented.

This article describes BabyIAXO, an intermediate experimental stage of the International Axion Observatory (IAXO), proposed to be sited at DESY. IAXO is a large-scale axion helioscope that will look for axions and axion-like particles (ALPs), produced in the Sun, with unprecedented sensitivity. BabyIAXO is conceived to test all IAXO subsystems (magnet, optics and detectors) at a relevant scale for the final system and thus serve as prototype for IAXO, but at the same time as a fully-fledged helioscope with relevant physics reach itself, and with potential for discovery. The BabyIAXO magnet will feature two 10 m long, 70 cm diameter bores, and will host two detection lines (optics and detector) of dimensions similar to the final ones foreseen for IAXO. BabyIAXO will detect or reject solar axions or ALPs with axion-photon couplings down to gaγ ∼ 1.5 × 10−11 GeV−1, and masses up to ma ∼ 0.25 eV. BabyIAXO will offer additional opportunities for axion research in view of IAXO, like the development of precision x-ray detectors to identify particular spectral features in the solar axion spectrum, and the implementation of radiofrequency-cavity-based axion dark matter setups.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective(s): To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participant(s): Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Intervention(s): Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Result(s): Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P =.10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in cont

Background: Probiotic and peanut oral immunotherapy (PPOIT) induced long-term sustained unresponsiveness (SU) in a proof-of- concept Phase 2a randomized trial. This open-label study (PPOIT-002) aimed to confirm the tolerability and long-term effects of PPOIT in children with peanut allergy aged 1-12 years. Method(s): 20 children aged 1-12 years with double-blind placebo-controlled food challenge (DBPCFC)-confirmed peanut allergy received 18 months of PPOIT. DBPCFC (cumulative 4950mg peanut protein) were performed at end-of- treatment, 8-weeks post-treatment and 3-years post-treatment to assess for desensitisation, SU and long-term SU, respectively. Immunologic measures, peanut skin prick test (SPT) and specific IgE (sIgE), were evaluated at screening, end-of- treatment and 3-years post-treatment. Continuous outcomes for peanut SPT and sIgE were compared between timepoints using paired t-tests and paired Wilcoxon signed rank test, respectively. Result(s): Sixteen children (75%) completed study treatment. Intention-to- treat analysis showed desensitisation and 8-week SU rates of 75% (15/20) and 60% (12/20), respectively. 10 of the 12 children who achieved 8-week SU at the end-of- treatment consented to the 3-year long-term 8-week SU challenge, with 6 (60%) maintaining long-term SU. PPOIT was associated with decreased peanut SPT and sIgE levels, with significant reductions persisting at 3-years post-treatment (p =0.0022 and p =0.0012, respectively). 17 of 20 (85%) of children reported treatment-related adverse events (AE) (total 176 events). The majority of AEs (164; 93%) were mild. There were no serious AEs. Conclusion(s): This open label study demonstrated that 18 months of PPOIT induced high rates of desensitisation and 8-week SU, with persistence of SU at 3-years post-treatment in the majority of initial responders. PPOIT led to long-lasting reduction in peanut sIgE, suggesting modulation of the underlying allergic response to peanut.

Introduction Egg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut oral immunotherapy (OIT) is highly effective at inducing sustained unresponsiveness, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. In this study, we plan to extend the probiotic food OIT platform to another allergen, namely egg. We describe the protocol for a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg OIT at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo. Methods and analysis 80 participants aged 5-30 years of age with current egg allergy confirmed by double-blind placebo-controlled food challenge at study screening will be recruited from Australia and Singapore. There are two intervention arms - probiotic and egg OIT (active) or placebo. Interventions are administered once daily for 18 months. The primary outcome is the proportion of participants who attain 8-week sustained unresponsiveness in the active group versus placebo group. Ethics and dissemination This study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 2019.082) and the National Healthcare Group Domain Specific Review Board (2019/00029). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences. Trial registration number ACTRN12619000480189.Copyright © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and p

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective(s): To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participant(s): Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Intervention(s): Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Result(s): Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P =.10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in cont

Background: Probiotic and peanut oral immunotherapy (PPOIT) induced long-term sustained unresponsiveness (SU) in a proof-of- concept Phase 2a randomized trial. This open-label study (PPOIT-002) aimed to confirm the tolerability and long-term effects of PPOIT in children with peanut allergy aged 1-12 years. Method(s): 20 children aged 1-12 years with double-blind placebo-controlled food challenge (DBPCFC)-confirmed peanut allergy received 18 months of PPOIT. DBPCFC (cumulative 4950mg peanut protein) were performed at end-of- treatment, 8-weeks post-treatment and 3-years post-treatment to assess for desensitisation, SU and long-term SU, respectively. Immunologic measures, peanut skin prick test (SPT) and specific IgE (sIgE), were evaluated at screening, end-of- treatment and 3-years post-treatment. Continuous outcomes for peanut SPT and sIgE were compared between timepoints using paired t-tests and paired Wilcoxon signed rank test, respectively. Result(s): Sixteen children (75%) completed study treatment. Intention-to- treat analysis showed desensitisation and 8-week SU rates of 75% (15/20) and 60% (12/20), respectively. 10 of the 12 children who achieved 8-week SU at the end-of- treatment consented to the 3-year long-term 8-week SU challenge, with 6 (60%) maintaining long-term SU. PPOIT was associated with decreased peanut SPT and sIgE levels, with significant reductions persisting at 3-years post-treatment (p =0.0022 and p =0.0012, respectively). 17 of 20 (85%) of children reported treatment-related adverse events (AE) (total 176 events). The majority of AEs (164; 93%) were mild. There were no serious AEs. Conclusion(s): This open label study demonstrated that 18 months of PPOIT induced high rates of desensitisation and 8-week SU, with persistence of SU at 3-years post-treatment in the majority of initial responders. PPOIT led to long-lasting reduction in peanut sIgE, suggesting modulation of the underlying allergic response to peanut.

Introduction Egg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut oral immunotherapy (OIT) is highly effective at inducing sustained unresponsiveness, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. In this study, we plan to extend the probiotic food OIT platform to another allergen, namely egg. We describe the protocol for a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg OIT at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo. Methods and analysis 80 participants aged 5-30 years of age with current egg allergy confirmed by double-blind placebo-controlled food challenge at study screening will be recruited from Australia and Singapore. There are two intervention arms - probiotic and egg OIT (active) or placebo. Interventions are administered once daily for 18 months. The primary outcome is the proportion of participants who attain 8-week sustained unresponsiveness in the active group versus placebo group. Ethics and dissemination This study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 2019.082) and the National Healthcare Group Domain Specific Review Board (2019/00029). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences. Trial registration number ACTRN12619000480189.Copyright © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and p

ObjectivesTo investigate the additional programme cost and cost-effectiveness of ‘right@home’ Nurse Home Visiting (NHV) programme in relation to improving maternal and child outcomes at child age 3 years compared with usual care.DesignA cost–utility analysis from a government-as-payer perspective alongside a randomised trial of NHV over 3-year period. Costs and quality-adjusted life-years (QALYs) were discounted at 5%. Analysis used an intention-to-treat approach with multiple imputation.SettingThe right@home was implemented from 2013 in Victoria and Tasmania states of Australia, as a primary care service for pregnant women, delivered until child age 2 years.Participants722 pregnant Australian women experiencing adversity received NHV (n=363) or usual care (clinic visits) (n=359).Primary and secondary outcome measuresFirst, a cost–consequences analysis to compare the additional costs of NHV over usual care, accounting for any reduced costs of service use, and impacts on all maternal and child outcomes assessed at 3 years. Second, cost–utility analysis from a government-as-payer perspective compared additional costs to maternal QALYs to express cost-effectiveness in terms of additional cost per additional QALY gained.ResultsWhen compared with usual care at child age 3 years, the right@home intervention cost $A7685 extra per woman (95% CI $A7006 to $A8364) and generated 0.01 more QALYs (95% CI −0.01 to 0.02). The probability of right@home being cost-effective by child age 3 years is less than 20%, at a willingness-to-pay threshold of $A50 000 per QALY.

AIM: Pain associated with immunisations can result in distress and/or anxiety for children and parents. We assessed the feasibility and acceptability of two novel devices; Coolsense (cold) and Buzzy (vibration ± cooling pads) versus standard care to minimise pain during immunisations. We also evaluated compliance to the devices and parent's perception of the effectiveness of the devices/standard care for minimising pain during immunisation. DESIGN: Open label, pilot, randomised controlled trial (RCT). METHODS: Forty children aged 3.5 to 6 years attending an Immunisation Centre at The Royal Children's Hospital in Melbourne, Australia, were randomised (1:1:1:1) into four groups: (i) Coolsense plus standard care; (ii) Buzzy with cold plus standard care; (iii) Buzzy without cold plus standard care; and (iv) Standard care alone (distraction with bubbles). RESULTS AND ANALYSIS: Recruitment was completed in 12 days. Seventy percent were compliant with Buzzy (±cold), 82% with Coolsense, and 60% with standard care. Buzzy (with cold) was identified as effective by 70% of parents, Coolsense by 64%, Buzzy without cold by 50% and standard care by 60%. CONCLUSIONS: This pilot study demonstrated feasibility. A larger RCT is needed to provide definitive evidence to inform best practice for minimising immunisation pain in young children.

IMPORTANCE: In developed countries, bronchiolitis is the most common reason for infants to be admitted to the hospital, and all international bronchiolitis guidelines recommend supportive care; however, significant variation in practice continues with infants receiving non-evidence-based therapies. Deimplementation research aims to reduce the use of low-value care, and advancing science in this area is critical to delivering evidence-based care. OBJECTIVE: To determine the effectiveness of targeted interventions vs passive dissemination of an evidence-based bronchiolitis guideline in improving treatment of infants with bronchiolitis. DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter cluster randomized clinical trial included 26 hospitals (clusters) in Australia and New Zealand providing tertiary or secondary pediatric care (13 randomized to intervention, 13 to control) during the 2017 bronchiolitis season. Data were collected on 8003 infants for the 3 bronchiolitis seasons (2014-2016) before the implementation period and 3727 infants for the implementation period (2017 bronchiolitis season, May 1-November 30). Data were analyzed from November 16, 2018, to December 9, 2020. INTERVENTIONS: Interventions were developed using theories of behavior change to target key factors that influence bronchiolitis management. These interventions included site-based clinical leads, stakeholder meetings, a train-the-trainer workshop, targeted educational delivery, other educational and promotional materials, and audit and feedback. MAIN OUTCOMES AND MEASURES: The primary outcome was compliance during the first 24 hours of care with no use of chest radiography, albuterol, glucocorticoids, antibiotics, and epinephrine, measured retrospectively from medical records of randomly selected infants with bronchiolitis who presented to the hospital. There were no patient-level exclusions. RESULTS: A total of 26 hospitals were randomized without dropouts. Analysis was by inten

BACKGROUND: Gabapentin is often used to manage pain in children with dystonic cerebral palsy, however the evidence for its effectiveness in this population is limited. The primary objective of this feasibility pilot study was to assess the factors which might impact on a future randomised controlled trial including the ability to recruit and retain participants, assess adherence/compliance to the prescribed intervention, and ability to complete all outcome assessments. The secondary objective was to gather preliminary evidence for the effectiveness of gabapentin at reducing pain, improving comfort and reducing dystonia in children with dystonic cerebral palsy. METHODS: This open label pilot study recruited children aged 5-18 years with dystonic cerebral palsy and accompanying pain affecting daily activities from four centres around Australia. Children were prescribed gabapentin for 12 weeks and were assessed at baseline, 6 weeks and 12 weeks. The primary outcome was feasibility of the protocol. Secondary outcomes were pain behaviour, pain intensity, care and comfort, individualised goal setting and dystonia severity. RESULTS: Thirteen children (mean age 10.4 years (SD 2.4yrs), 9 females) were recruited from 71 screened over 15 months. Two children withdrew while eight children experienced side effects. There were issues with adherence to medication dosage regimens and data collection. Improvements were seen in pain behaviour, comfort and pain related goals at 12 weeks. Dystonia was not significantly changed. CONCLUSIONS: Whilst gabapentin has potential to improve pain and comfort in children with dystonic CP, the feasibility of implementing a definitive randomised controlled trial is low. Alternative trials designs are required to further examine the effectiveness of gabapentin in this heterogeneous population. TRIAL REGISTRATION: The trial was registered with the Australian Clinical Trial Registry ( ACTRN12616000366459 ) on 22/03/2016 and the Therapeutic Goods Admi

INTRODUCTION: Egg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut oral immunotherapy (OIT) is highly effective at inducing sustained unresponsiveness, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. In this study, we plan to extend the probiotic food OIT platform to another allergen, namely egg. We describe the protocol for a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg OIT at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo. METHODS AND ANALYSIS: 80 participants aged 5-30 years of age with current egg allergy confirmed by double-blind placebo-controlled food challenge at study screening will be recruited from Australia and Singapore. There are two intervention arms-probiotic and egg OIT (active) or placebo. Interventions are administered once daily for 18 months. The primary outcome is the proportion of participants who attain 8-week sustained unresponsiveness in the active group versus placebo group. ETHICS AND DISSEMINATION: This study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 2019.082) and the National Healthcare Group Domain Specific Review Board (2019/00029). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences. TRIAL REGISTRATION NUMBER: ACTRN12619000480189.

BACKGROUND: Poor mental health is recognized as one of the greatest global burdens of disease. Maternal mental health is crucial for the optimal health of mothers and their children. We examined the effects of an Australian Nurse Home Visiting (NHV) program (right@home), offered to pregnant women experiencing adversity, on maternal mental health and well-being at child age 3 years. METHODS: A randomized controlled trial of NHV delivered via universal child and family health services (2013-2016). Pregnant women experiencing adversity (≥2 of 10 risk factors) were recruited from 10 antenatal clinics across 2 states. Intervention comprised 25 home visits until child age 2 years. The outcomes assessed 1-year postintervention completion were maternal self-report of mental health symptoms (Depression Anxiety Stress Scales) and positive aspects of mental health (personal well-being and self-efficacy). RESULTS: Of the 722 women enrolled in the trial, 255 of 363 (70%) intervention and 240 of 359 (67%) control group women provided data at 3 years. Compared with controls, the intervention group reported better mental health (reverse Depression Anxiety Stress Scales scores): effect sizes of 0.25 (depression; 95% confidence interval [CI]: 0.08 to 0.32), 0.20 (anxiety; 95% CI: 0.05 to 0.30), 0.17 (stress; 95% CI: 0.09 to 0.37), and 0.23 (total score; 95% CI: 0.12 to 0.38); 0.16 (95% CI: 0.04 to 0.29) for personal well-being; and an odds ratio of 1.60 (95% CI: 1.19 to 2.16) for self-efficacy. CONCLUSIONS: An NHV designed to support mothers experiencing adversity can lead to later maternal mental health benefits, even after the program ends.

BACKGROUND: The Matthey Generic Mood Questionnaire (MGMQ) provides a rapid screen of clinically significant emotional difficulties in adults. This study aimed to investigate associations between the MGMQ and Depression Anxiety Stress Scales short-form (DASS-21) and how well the MGMQ detects women scoring high on the DASS-21 in pregnancy and 1 and 2 years postpartum. METHODS: Pregnant Australian, English-speaking women were recruited from 10 maternity hospitals across two states (for the "right@home" trial, N=729). Prioritized for their experience of social adversity (2 or more of 10 risk factors), they completed the 2-item MGMQ and 21-item DASS-21 in pregnancy and at 1 and 2 years postpartum. DASS-21 Total and subscale scores were classified "high" based on (a) normed percentiles for top 15% and (b) clinical cut-points. RESULTS: The MGMQ and DASS-21 were completed within 7 days of each other by 296 (41%) women in pregnancy, 625 (86%) at 1 year and 573 (79%) at 2 years. Associations between the measures were weak-to-moderate in pregnancy and moderate-to-strong in the postpartum years. Most women scoring "high" on the DASS-21 could be identified with various thresholds of the MGMQ. LIMITATIONS: Pregnant women with 0 or 1 risk factor were excluded; the DASS-21 is not a perinatal specific measure nor a gold standard diagnostic tool. CONCLUSIONS: The MGMQ and DASS-21 appeared to assess overlapping but distinct constructs of mental health. These findings can help clinicians and researchers decide whether to use the MGMQ, and which balance of sensitivity, specificity and correct classification will suit their needs.

INTRODUCTION: BCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19. METHODS AND ANALYSIS: This international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections. ETHICS AND DISSEMINATION: Ethical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system. TRIAL REGISTRATION: ClinicalTrials.gov NCT04327206.

OBJECTIVES: To investigate the additional programme cost and cost-effectiveness of 'right@home' Nurse Home Visiting (NHV) programme in relation to improving maternal and child outcomes at child age 3 years compared with usual care. DESIGN: A cost-utility analysis from a government-as-payer perspective alongside a randomised trial of NHV over 3-year period. Costs and quality-adjusted life-years (QALYs) were discounted at 5%. Analysis used an intention-to-treat approach with multiple imputation. SETTING: The right@home was implemented from 2013 in Victoria and Tasmania states of Australia, as a primary care service for pregnant women, delivered until child age 2 years. PARTICIPANTS: 722 pregnant Australian women experiencing adversity received NHV (n=363) or usual care (clinic visits) (n=359). PRIMARY AND SECONDARY OUTCOME MEASURES: First, a cost-consequences analysis to compare the additional costs of NHV over usual care, accounting for any reduced costs of service use, and impacts on all maternal and child outcomes assessed at 3 years. Second, cost-utility analysis from a government-as-payer perspective compared additional costs to maternal QALYs to express cost-effectiveness in terms of additional cost per additional QALY gained. RESULTS: When compared with usual care at child age 3 years, the right@home intervention cost $A7685 extra per woman (95% CI $A7006 to $A8364) and generated 0.01 more QALYs (95% CI -0.01 to 0.02). The probability of right@home being cost-effective by child age 3 years is less than 20%, at a willingness-to-pay threshold of $A50 000 per QALY. CONCLUSIONS: Benefits of NHV to parenting at 2 years and maternal health and well-being at 3 years translate into marginal maternal QALY gains. Like previous cost-effectiveness results for NHV programmes, right@home is not cost-effective at 3 years. Given the relatively high up-front costs of NHV, long-term follow-up is needed to assess the accrual of health and economic benefits over time. TRIAL REGIST

BACKGROUND: Bronchiolitis is the most common reason for hospitalisation in infants. All international bronchiolitis guidelines recommend supportive care, yet considerable variation in practice continues with infants receiving non-evidence based therapies. We developed six targeted, theory-informed interventions; clinical leads, stakeholder meeting, train-the-trainer, education delivery, other educational materials, and audit and feedback. A cluster randomised controlled trial (cRCT) found the interventions to be effective in reducing use of five non-evidence based therapies in infants with bronchiolitis. This process evaluation paper aims to determine whether the interventions were implemented as planned (fidelity), explore end-users' perceptions of the interventions and evaluate cRCT outcome data with intervention fidelity data. METHODS: A pre-specified mixed-methods process evaluation was conducted alongside the cRCT, guided by frameworks for process evaluation of cRCTs and complex interventions. Quantitative data on the fidelity, dose and reach of interventions were collected from the 13 intervention hospitals during the study and analysed using descriptive statistics. Qualitative data identifying perception and acceptability of interventions were collected from 42 intervention hospital clinical leads on study completion and analysed using thematic analysis. RESULTS: The cRCT found targeted, theory-informed interventions improved bronchiolitis management by 14.1%. The process evaluation data found variability in how the intervention was delivered at the cluster and individual level. Total fidelity scores ranged from 55 to 98% across intervention hospitals (mean = 78%; SD = 13%). Fidelity scores were highest for use of clinical leads (mean = 98%; SD = 7%), and lowest for use of other educational materials (mean = 65%; SD = 19%) and audit and feedback (mean = 65%; SD = 20%). Clinical leads reflected positively about the interventions, with time constraints being th

Axions are a natural consequence of the Peccei-Quinn mechanism, the most compelling solution to the strong-CP problem. Similar axion-like particles (ALPs) also appear in a number of possible extensions of the Standard Model, notably in string theories. Both axions and ALPs are very well motivated candidates for Dark Matter, and in addition, they would be copiously produced at the sun’s core. A relevant effort during the last decade has been the CAST experiment at CERN, the most sensitive axion helioscope to-date. The International Axion Observatory (IAXO) is a large-scale 4th generation helioscope. As its primary physics goal, IAXO will look for solar axions or ALPs with a signal to background ratio of about 5 orders of magnitude higher than CAST. Recently the IAXO collaboration has proposed and intermediate experimental stage, BabyIAXO, conceived to test all IAXO subsystems (magnet, optics, detectors and sun-tracking systems) at a relevant scale for the final system and thus serve as pathfinder for IAXO but at the same time as a fully-fledged helioscope with record and relevant physics reach in itself with potential for discovery. BabyIAXO was endorsed by the Physics Review committee of DESY last May 2019. Here we will review the status and prospects of BabyIAXO and its potential to probe the most physics motivated regions of the axion & ALPs parameter space.

Attention to urban agriculture (UA) has recently grown among practitioners, scientists, and the public, resulting in several initiatives worldwide. Despite the positive perception of modern UA and locally grown, fresh produce, the potential food safety risks connected to these practices may be underestimated, leading to regulatory gaps. Thus, there is a need for assessment tools to evaluate the food safety risks connected to specific UA initiatives, to assist practitioners in self-evaluation and control, and to provide policy makers and scholars a means to pursue and assess food safety in city regions, avoiding either a lack or an excess of regulation that could ultimately hinder the sector. To address this aim, this paper reviews the most recent and relevant literature on UA food safety assessments. Food safety indicators were identified first. Then, a food safety assessment framework for UA initiatives was developed. The framework uses business surveys and food analyses (if available) as a data source for calculating a food safety index for single UA businesses and the whole UA landscape of a given city region. The proposed framework was designed to allow its integration into the CRFS (City Region Food System) toolkit developed by FAO (Food and Agriculture Organization of the United Nations), RUAF foundation (Resource Centres on Urban Agriculture and Food Security) and Wilfrid Laurier University.

X-ray computed micro-tomography (μCT) is one of the most advanced and common non-destructive techniques in the field of medical imaging and material science. It allows recreating virtual models (3D models), without destroying the original objects, by measuring three-dimensional X-ray attenuation coefficient maps of samples on the (sub) micrometer scale. The quality of the images obtained using μCT is strongly dependent on the performance of the associated X-ray detector i.e. to the acquisition of information of the X-ray beam traversing the patient/sample being precise and accurate. Detectors for μCT have to meet the requirements of the specific tomography procedure in which they are going to be used. In general, the key parameters are high spatial resolution, high dynamic range, uniformity of response, high contrast sensitivity, fast acquisition readout and support of high frame rates. At present the detection devices in commercial μCT scanners are dominated by charge-coupled devices (CCD), photodiode arrays, CMOS acquisition circuits and more recently by hybrid pixel detectors. Monolithic CMOS imaging sensors, which offer reduced pixel sizes and low electronic noise, are certainly excellent candidates for μCT and may be used for the development of novel high-resolution imaging applications. The uses of monolithic CMOS based detectors such as the PERCIVAL detector are being recently explored for synchrotron and FEL applications. PERCIVAL was developed to operate in synchrotron and FEL facilities in the soft X-ray regime from 250 eV to 1 keV and it could offer all the aforementioned technical requirements needed in μCT experiments. In order to adapt the system for a typical tomography application, a scintillator is required, to convert incoming X-ray radiation (∼ tens of KeV) into visible light which may be detected with high efficiency. Such a taper-based scintillator was developed and mounted in front of the sensitive area of the PERCIVAL imager. In this presentat

BACKGROUND: Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how diverse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities. METHOD(S): Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal; retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical biosamples; and (4) GenV-collected biosamples and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years. RESULT(S): For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window; GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian's agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Princip

Objective: Rigid wrist-hand orthoses (WHO), used with children with cerebral palsy (CP), aim to maintain soft tissue length, thought to contribute to preserving functional hand use. Past research is limited by small samples and short intervention periods (<6 months). This study investigated effectiveness of long-term provision of rigid WHO combined with usual multidisciplinary care, to reduce hand impairments. Design(s): A pragmatic, prospective, multicentre, assessor-blinded randomised controlled trial with 1:1 allocation to Intervention or control group. Method(s): Eligible participants were aged 5-15 years, diagnosed with CP, presenting with Modified Ashworth Scale score >=1 at the wrist. Sample estimate was 97 per group to detect a 10degree between-group difference in wrist extension at 3 years. Recruitment occurred at five Australian sites. Independent randomisation with concealed allocation was stratified by study site and passive wrist range (3 strata). In bilateral presentations, allocation was by child (both wrists same allocation). Children randomised to the intervention received a custom-made rigid WHO for maintaining length in the flexor compartment of the forearm/hand, to be worn for >=6 hours/ night. The trial stopped early due to insufficient recruitment and resources. The primary outcome was passive wrist extension (fingers extended) at 3 years. Given early cessation, all measures taken 6-monthly were included in repeated measures two-level mixed regression models, to obtain comparisons between groups in accordance with intention-to-treat principles. Result(s): Seventy-four children were randomised (n=38 intervention; n=36 control). Mean age was 10.2 (SD 3.1) years (intervention) and 9.1 (SD 2.8) years (control); n=18 intervention and n=16 control group participants were male. Children in all levels of the Manual Ability Classification System were included. There were 96 included limbs (n=47 intervention; n=49 control). Limbs available for analysis a

BACKGROUND: Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how diverse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities. METHOD(S): Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal; retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical biosamples; and (4) GenV-collected biosamples and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years. RESULT(S): For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window; GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian's agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Princip

Objective: Rigid wrist-hand orthoses (WHO), used with children with cerebral palsy (CP), aim to maintain soft tissue length, thought to contribute to preserving functional hand use. Past research is limited by small samples and short intervention periods (<6 months). This study investigated effectiveness of long-term provision of rigid WHO combined with usual multidisciplinary care, to reduce hand impairments. Design(s): A pragmatic, prospective, multicentre, assessor-blinded randomised controlled trial with 1:1 allocation to Intervention or control group. Method(s): Eligible participants were aged 5-15 years, diagnosed with CP, presenting with Modified Ashworth Scale score >=1 at the wrist. Sample estimate was 97 per group to detect a 10degree between-group difference in wrist extension at 3 years. Recruitment occurred at five Australian sites. Independent randomisation with concealed allocation was stratified by study site and passive wrist range (3 strata). In bilateral presentations, allocation was by child (both wrists same allocation). Children randomised to the intervention received a custom-made rigid WHO for maintaining length in the flexor compartment of the forearm/hand, to be worn for >=6 hours/ night. The trial stopped early due to insufficient recruitment and resources. The primary outcome was passive wrist extension (fingers extended) at 3 years. Given early cessation, all measures taken 6-monthly were included in repeated measures two-level mixed regression models, to obtain comparisons between groups in accordance with intention-to-treat principles. Result(s): Seventy-four children were randomised (n=38 intervention; n=36 control). Mean age was 10.2 (SD 3.1) years (intervention) and 9.1 (SD 2.8) years (control); n=18 intervention and n=16 control group participants were male. Children in all levels of the Manual Ability Classification System were included. There were 96 included limbs (n=47 intervention; n=49 control). Limbs available for analysis a

BACKGROUND: Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how diverse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities. METHODS: Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal; retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical biosamples; and (4) GenV-collected biosamples and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years. RESULTS: For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window; GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian's agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Principles.

INTRODUCTION: Peanut allergy is the the most common cause of life-threatening food-induced anaphylaxis. There is currently no effective long-term treatment. There is a pressing need for definitive treatments that improve the quality of life and prevent fatalities. Allergen oral immunotherapy (OIT) is a promising approach, which is effective at inducing desensitisation; however, OIT has a limited ability to induce sustained unresponsiveness (SU). We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut OIT (Probiotic Peanut Oral ImmunoTherapy (PPOIT)) is highly effective at inducing SU, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. Here we describe the protocol for a Phase IIb multicentre, double-blind, randomised, controlled trial (PPOIT-003) with dual primary objectives to evaluate the effectiveness of PPOIT at inducing SU (assessed at 8 weeks after treatment cessation) compared with placebo treatment and peanut OIT alone, in children with peanut allergy. METHODS AND ANALYSIS: 200 children 1 to 10 years of age with current peanut allergy confirmed by failed double-blind placebo-controlled food challenge (DBPCFC) at study screening will be recruited from three tertiary paediatric hospitals in Australia. There are three intervention arms-PPOIT, peanut OIT alone or placebo. Interventions are administered once daily for 18 months. The dual primary outcomes are: (1) the proportion of children who attain 8-week SU in the PPOIT group versus placebo group and (2) the proportion of children who attain 8-week SU in the PPOIT group versus OIT group. ETHICS AND DISSEMINATION: This study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 35246) and the Child and Adolescent Health Service (RGS 2543). Results will be published in peer-reviewed journals and disseminated via presentations at i

INTRODUCTION: The first years of school are critical in establishing a foundation for positive long-term academic, social and well-being outcomes. Mindfulness-based interventions may help students transition well into school, but few robust studies have been conducted in this age group. We aim to determine whether compared with controls, children who receive a mindfulness intervention within the first years of primary school have better: (1) immediate attention/short-term memory at 18 months post-randomisation (primary outcome); (2) inhibition, working memory and cognitive flexibility at 18 months post-randomisation; (3) socio-emotional well-being, emotion-regulation and mental health-related behaviours at 6 and 18 months post-randomisation; (4) sustained changes in teacher practice and classroom interactions at 18 months post-randomisation. Furthermore, we aim to determine whether the implementation predicts the efficacy of the intervention, and the cost effectiveness relative to outcomes. METHODS AND ANALYSIS: This cluster randomised controlled trial will be conducted in 22 primary schools in disadvantaged areas of Melbourne, Australia. 826 students in the first year of primary school will be recruited to detect between groups differences of Cohen's d=0.25 at the 18-month follow-up. Parent, teacher and child-assessment measures of child attention, emotion-regulation, executive functioning, socio-emotional well-being, mental health-related behaviour and learning, parent mental well-being, teacher well-being will be collected 6 and 18 months post-randomisation. Implementation factors will be measured throughout the study. Intention-to-treat analyses, accounting for clustering within schools and classes, will adopt a two-level random effects linear regression model to examine outcomes for the intervention versus control students. Unadjusted and analyses adjusted for baseline scores, baseline age, gender and family socioeconomic status will be conducted. ETHICS AND DI

This article describes BabyIAXO, an intermediate experimental stage of the International Axion Observatory (IAXO), proposed to be sited at DESY. IAXO is a large-scale axion helioscope that will look for axions and axion-like particles (ALPs), produced in the Sun, with unprecedented sensitivity. BabyIAXO is conceived to test all IAXO subsystems (magnet, optics and detectors) at a relevant scale for the final system and thus serve as prototype for IAXO, but at the same time as a fully-fledged helioscope with relevant physics reach itself, and with potential for discovery. The BabyIAXO magnet will feature two 10 m long, 70 cm diameter bores, and will host two detection lines (optics and detector) of dimensions similar to the final ones foreseen for IAXO. BabyIAXO will detect or reject solar axions or ALPs with axion-photon couplings down to $g_{a\gamma} \sim 1.5 \times 10^{-11}$ GeV$^{-1}$, and masses up to $m_a\sim 0.25$ eV. BabyIAXO will offer additional opportunities for axion research in view of IAXO, like the development of precision x-ray detectors to identify particular spectral features in the solar axion spectrum, and the implementation of radiofrequency-cavity-based axion dark matter setups., Comment: 77 pages, 49 figures. Prepared for submission to JHEP. Third version after referees comments

This article describes BabyIAXO, an intermediate experimental stage of the International Axion Observatory (IAXO), proposed to be sited at DESY. IAXO is a large-scale axion helioscope that will look for axions and axion-like particles (ALPs), produced in the Sun, with unprecedented sensitivity. BabyIAXO is conceived to test all IAXO subsystems (magnet, optics and detectors) at a relevant scale for the final system and thus serve as prototype for IAXO, but at the same time as a fully-fledged helioscope with relevant physics reach itself, and with potential for discovery. The BabyIAXO magnet will feature two 10 m long, 70 cm diameter bores, and will host two detection lines (optics and detector) of dimensions similar to the final ones foreseen for IAXO. BabyIAXO will detect or reject solar axions or ALPs with axion-photon couplings down to $g_{a\gamma} \sim 1.5 \times 10^{-11}$ GeV$^{-1}$, and masses up to $m_a\sim 0.25$ eV. BabyIAXO will offer additional opportunities for axion research in view of IAXO, like the development of precision x-ray detectors to identify particular spectral features in the solar axion spectrum, and the implementation of radiofrequency-cavity-based axion dark matter setups., Comment: 77 pages, 49 figures. Prepared for submission to JHEP. Third version after referees comments

This paper intends to clear up the radical difference between the movement pertaining to Being and the one which is peculiar to Essence. Since Hegel characterizes the latter as “reflection” such an aim is pursued through a detailed examination of the pages specifically devoted to this notion in the first section of the Logic of Essence. The conception of a self-related negativity shows itself to be the main feature of Essence: it plays a leading role in all the forms of reflection (positing, external, determining) and is the real ground for the well-known refutation of classical logic which is contained in the following chapter of the Logic of Essence.

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In Vertical Farms with Artificial Lighting (VFALs), optimal light management is a crucial determinant of both economic and environmental viability. Applications of LED technologies to plant cultivation are still recent, and research has to date mainly targeted the definition of optimal spectral and light intensity features. On the other hand, despite the relevant implications on production costs, literature on optimal photoperiod management is to date limited. Indeed, the number of hours per day correlates with the total light supplied to the crop - expressed as Daily Light Integral (DLI) - and the associated energetic costs. The present study aims at defining how photoperiods of 16 h d-1 (DLI= 14.4 mol m-2 d-1), 20 h d-1 (DLI= 18 mol m-2 d-1) and 24 h d-1 (DLI= 21.6 mol m-2 d-1)of light affect growth performances and resource use efficiency in leafy vegetables and herbs, represented by lettuce (Lactuca sativa L.), basil (Ocimum basilicum L.), rocket (Eruca sativa Mill.), and chicory (Cichorium intybus L.). Plants were cultivated indoor under a red (R) and blue (B) LED light (RB=3, photosynthetic photon flux density (PPFD)=250 µmol m-2 s-1). Photoperiod variations’ effects differed according to the considered plant species. In lettuce and chicory, the adoption of a DLI of 14.4 mol m-2 d-1 at 16 h d-1 photoperiod resulted in a greater plants fresh biomass and leaf area, which also contributed to generally obtain higher energy use efficiency (fresh biomass per unit of electricity input), light use efficiency (dry biomass per unit of light input) and, in chicory, also water use efficiency (fresh biomass per liter of water consumed). Contrarily, although photoperiod variations did not affect basil and rocket growth parameters (e.g., fresh biomass and leaf area) and the plant capacity to transform resources (e.g., water use efficiency and light use efficiency), energy use efficiency in basil also presented a downward trend in response to growing DLI. Accordingly, the ado

Radiopharmaceuticals contain a radionuclide and an agent to direct the radionuclide to a receptor, antigen, ionic pump, or other sites of interest. Some radiopharmaceuticals are simple, such as the ionic form of the radionuclide, while most radiopharmaceuticals have a complex chemical structure where the radionuclide provides a signal, indicating the site of localization of the carrier molecule. Common single-photon radiopharmaceuticals used for oncological diagnosis include the agents labeled with 99mTc such as 99mTcbisphosphonates (that accumulate at sites of bone mineral deposition), 99mTc-labeled colloids (that are used for lymphoscintigraphy and for imaging of the liver and spleen), 99mTc-hexakis-methoxy-isobutyl-isonitrile, and 99mTc-tetrofosmin (initially employed for myocardial perfusion imaging, and also used for localization of parathyroid adenomas and for identification of other malignant tumors). The most commonly used radiopharmaceuticals labeled with radioiodine (123I or 131I) include iodide itself (for localization of thyroid tissue) and the catecholamine analog metaiodobenzylguanidine (MIBG, for localizing pheochromocytoma and neuroblastoma). Thallium-201 chloride (201Tl) is used for myocardial perfusion imaging as well as tumor perfusion imaging, while 111In-pentetreotide detects overexpression of somatostatin receptors, especially in neuroendocrine tumors and in lesions arising from the neural crest, such as carcinoid, paragangliomas, and medullary thyroid carcinomas. 111In-capromab pendetide is a murine monoclonal antibody recognizing a transmembrane glycoprotein expressed by poorly differentiated and metastatic prostate adenocarcinomas. 67Ga-citrate receptors are overexpressed on membranes of both tumor and inflammatory cells.

High brilliance synchrotrons and FELs require high performing detector systems to realise their full potential. High dynamic range, low noise and high frame rate are all of great importance. In this paper we present first optical characterization results of the P2M CMOS sensor, designed for soft X-ray detection at such facilities. Previous work is summarised and an overview of the sensor is presented. Test results for the sensor's column-parallel ADC and readout chain are presented, and first test results for the pixel acquired using the Photon Transfer Curve (PTC) method are shown. Finally, an outline of future work is provided.

In this paper, we are presenting the results of the first test of the Percival P2M-FSI detector with tender x-rays photons at a synchrotron beamline. Percival is a monolithic CMOS Imager for detection of x-rays in Synchrotron Rings and Free Electron Lasers: the Front-Side-Illuminated (FSI) version of the detector has been proven able to successfully distinguish tender (2keV) x-ray single photons.