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Understanding the impact of the COVID-19 pandemic on systemic anticancer therapy delivery (SACT) is crucial to appreciate the short- and long-term consequences for cancer patients and plan future care. Here, we report real-time national SACT delivery data from NHS Scotland. We demonstrate an initial rapid reduction in patient attendance of 28.7% with subsequent rapid recovery following service redesign. The smallest decrease was seen in breast cancer (19.7%), which also had the most rapid recovery and the largest decrease seen in colorectal cancer (43.4%). Regional variation in the magnitude of impact on SACT delivery was observed, but nadirs occurred at the same time and the rate of recovery was similar across all regions. This recovery reflected a coordinated national approach and associated patient and clinician support structures, which facilitated the creation of COVID-19-protected areas for SACT delivery in Scottish cancer centres enabling rapid sharing of successful and innovative strategies. The data show that these actions have limited the disadvantage to cancer patients.

BackgroundModelling the long-term effects of disruption of cancer services and minimising any excess cancer mortality due to the Covid-19 pandemic is of great importance. Here we adapted a stage-shift model to inform service planning decisions within NHS Scotland for the ‘‘Detect Cancer Early’ tumours, breast, colorectal and lung cancer which represent 46% of all cancers diagnosed in Scotland.Methods & DataLung, colorectal and breast cancer incidence data for years 2017-18 were obtained from Public Health Scotland Cancer Quality Performance Indicators (QPI), to define a baseline scenario. The most current stage-specific 5-year survival data came from 2009-2014 national cancer registry and South East Scotland Cancer Network (SCAN) QPI audit datasets. The Degeling et al., inverse stage-shift model was adapted to estimate changes in stage at diagnosis, excess mortality and life-years lost from delays to diagnosis and treatment due to Covid-19-related health services disruption. Three and 6-month periods of disruption were simulated to demonstrate the model predictions.ResultsApproximately, 1-9% reductions in stage I/II presentations leading up to 2-10% increases in stage III/IV presentations are estimated across the three cancer types. A 6-month period of service disruption is predicted to lead to excess deaths at 5 years of 32.5 (31.1, 33.9) per 1000 cases for lung cancer, 16.5 (7.9, 24.3) for colorectal cancer and 31.6 (28.5, 34.4) for breast cancer.ConclusionsDisruption of cancer diagnostic services can lead to significant excess deaths in following years. Increasing diagnostic and capacity for cancer services to deal with the backlog of care are needed. Real time monitoring of incidence and referral patterns over the disruption and post-disruption period to reduce excess deaths including more rapid incidence data by stage and other key tumour/clinical characteristics at presentation for key cancer cases (on a quarterly basis). Real time monitoring in cancer care and referral patterns should help inform what type of interventions are needed to reduce excess mortality and whether different population subgroups require public health messaging campaigns. Specific mitigation measures can be the subject of additional modelling analysis to assess the benefits and inform service planning decision making.

Visual camera localization using offline maps is widespread in robotics and mobile applications. Most state-of-the-art localization approaches assume static scenes, so maps are often reconstructed once and then kept constant. However, many scenes are dynamic and as changes in the scene happen, future localization attempts may struggle or fail entirely. Therefore, it is important for successful long-term localization to update and maintain maps as new observations of the scene, and changes in it, arrive. We propose a novel method for automatically discovering which points in a map remain stable over time, and which are due to transient changes. To this end, we calculate a stability store for each point based on its visibility over time, weighted by an exponential decay over time. This allows us to consider the impact of time when scoring points, and to distinguish which points are useful for long-term localization. We evaluate our method on the CMU Extended Seasons dataset (outdoors) and a new indoor dataset of a retail shop, and show the benefit of maintaining a ‘live map’ that integrates updates over time using our exponential decay based method over a static ‘base map’.

The delivery of biotherapeutic molecules (antibodies, proteins, peptides) and nucleic acids via the respiratory route has presented challenges for regulatory approval, due in part to a lack of understanding of the expected pathology, mechanisms of toxicity, and immunogenicity induced by the inhalation route. Although the first inhaled biotherapeutic was approved some time ago (Dornase Alfa, Pulmozyme; Genetech, 1993), no other inhaled biotherapeutics have been marketed for the treatment of human disease other than the inhaled insulins (Exubera; Pfizer, 2006 and Afrezza; Mannkind Corporation, 2014). As a result, scientific knowledge within the toxicologic pathology community is fragmented with precious little publicly available data. Therefore, one of the aims of this special edition was to generate a collection of manuscripts that pathologists and toxicologists could refer in order to understand the pathology, mechanisms of toxicity, immunogenicity, and challenges associated with the development of inhaled biotherapeutics.

The sclerostin antibody romosozumab increases bone formation and decreases bone resorption, leading to increased bone mass, bone mineral density and bone strength, and reduced fracture risk. In a clinical study versus alendronate in postmenopausal women (ARCH), an imbalance in adjudicated serious cardiovascular (CV) events driven by an increase in myocardial infarction (MI) and stroke was observed.To investigate whether inhibition of sclerostin in atherosclerotic plaques may have contributed to this imbalance, sclerostin was immunostained in human plaques to determine whether it was detected in regions relevant to plaque stability. Additionally, genetic variants associated with lifelong reduced sclerostin expression were explored for associations with phenotypes including those related to bone physiology and CV risk factors/events in a population-based phenome-wide association study (PheWAS).Sclerostin expression was absent (67%) or reduced in atherosclerotic plaques and when present was in deeper regions of the plaque/wall and not in areas considered relevant to plaque stability (fibrous cap and endothelium). Natural genetic modulation of sclerostin by variants with a significant positive effect on bone physiology showed no association with lifetime risk of MI or stroke. These data do not support a causal association between sclerostin inhibition and increased risk of serious cardiovascular events.

Gastroesophageal adenocarcinoma (GOA) is a disease of older people. Incidence is rising in the developed world and the majority of patients present with advanced disease. Based on clinical trial data, systemic chemotherapy in the advanced setting is associated with improvements in quality of life and survival. However, there is a recognised mismatch between trial populations and the patients encountered in clinical practice in terms of age, comorbidity and fitness. Appropriate patient selection is essential to safely deliver effective treatment. In this narrative review, we discuss the challenges faced by clinicians when assessing real‑world patients with advanced GOA for systemic therapy. We also highlight the importance of frailty screening and the current available evidence we can use to guide our management.

AURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary tumor and metastasis pairs: 252 TGS, 152 RNA-Seq, 67 SNP Arrays), we found a driver role for GATA1 and MEN1 somatic mutations. Metastases were enriched in ESR1, PTEN, CDH1, PIK3CA and RB1 mutations; MDM4, MYC amplifications; ARID1A deletions. An increase in clonality was observed in driver genes like ERBB2 and RB1. Intrinsic subtype switching occurred in 36% of cases. Luminal A/B to HER2-Enriched switching was associated with TP53 and/or PIK3CA mutations. Metastases had lower immune score and increased immune permissive cells. High TMB correlated to shorter time to relapse in HR+/HER2- cancers. ESCAT tier I/II alterations were detected in 51% of patients and matched therapy was used in 7%. Integration of multi-omics analyses in clinical practice could impact treatment strategies in MBC., info:eu-repo/semantics/published

Treatment of nonhuman primates and mice with a humanized antigen-binding fragment (Fab) antibody (UCBFab) inhibiting transforming growth factor β via daily inhalation for up to 13 weeks resulted in low systemic exposure but high local exposure in the lung. Target engagement was demonstrated by reduced levels of signal transducers, phosphoSMAD and plasminogen activator inhibitor-1 in the bronchoalveolar lavage fluid (BALF). Treatment was associated with a high frequency and titer of antidrug antibodies, indicating high local immunogenicity, and local pathology within the lung and draining lymph nodes. Microscopic changes were characterized by perivascular (PV) and peribronchiolar (PB) mononuclear inflammatory cell (MIC) infiltrates that were principally lymphocytic in nature and mixed inflammatory cell infiltrates and/or inflammation within the alveoli. Immunohistochemical investigation revealed a predominantly CD68-positive macrophage and CD3- and CD8>CD4-positive T-cell response in the alveoli, whereas within the airways, there was a variable mixture of CD3-positive T cells, CD20-positive B cells, and CD68-positive macrophages. Increased cellularity of the draining lymph nodes was also noted, indicating the presence of an immune response to the inhaled test article. Morphologic changes did not progress over time, and all changes partially recovered. Increased leukocytes (principally macrophages) in BALF cytology correlated with the changes seen by histopathology.

Electrochemical energy storage and conversion systems such as electrochemical capacitors, batteries and fuel cells are considered as the most important technologies proposing environmentally friendly and sustainable solutions to address rapidly growing global energy demands and environmental concerns. Their commercial applications individually or in combination of two or more devices are based on their distinguishing properties e.g., energy/power densities, cyclability and efficiencies. In this review article, we have discussed some of the major electrochemical energy storage and conversion systems and encapsulated their technological advancement in recent years. Fundamental working principles and material compositions of various components such as electrodes and electrolytes have also been discussed. Furthermore, future challenges and perspectives for the applications of these technologies are discussed.

In this study, RF-based un-doped and nitrogen-doped aerogels were produced by polymerisation reaction between resorcinol and formaldehyde with sodium carbonate as catalyst and melamine as the nitrogen source. Carbon/activated carbon aerogels were obtained by carbonisation of the gels under inert atmosphere (Ar) followed by activation of the carbons under CO2 at 800 &deg, C. The BET analysis of the samples showed a more than two-fold increase in the specific Surf. area and pore volume of carbon from 537 to 1333 m2g&minus, 1 and 0.242 to 0.671 cm3g&minus, 1 respectively after nitrogen doping and activation. SEM and XRD analysis of the samples revealed highly porous amorphous nanostructures with denser inter-particle cross-linked pathways for the activated nitrogen-doped carbon. The X-Ray Photoelectron Spectroscopy (XPS) results confirmed the presence of nitrogen and oxygen heteroatoms on the Surf. and within the carbon matrix where improvement in wettability with the drop in the contact angle from 123&deg, to 80&deg, was witnessed after oxygen and nitrogen doping. A steady drop in the equivalent series (RS) and charge transfer (RCT) resistances was observed by electrochemical measurements after the introduction of nitrogen and oxygen heteroatoms. The highest specific capacitance of 289 Fg&minus, 1 with the lowest values of 0.11 &Omega, and 0.02 &Omega, for RS and RCT was achieved for nitrogen and oxygen dual-doped activated carbon in line with its improved Surf. chemistry and wettability, and its enhanced conductivity due to denser inter-particle cross-linked pathways.

BackgroundPeople who are nearing the end of life are high users of healthcare. The cost to providers is high and the value of care is uncertain.ObjectivesTo describe the pattern, trajectory and drivers of secondary care use and cost by people in Scotland in their last year of life.MethodsRetrospective whole-population secondary care administrative data linkage study of Scottish decedents of 60 years and over between 2012 and 2017 (N=274,048).ResultsSecondary care use was high in the last year of life with a sharp rise in inpatient admissions in the last three months. The mean cost was £10,000. Cause of death was associated with differing patterns of healthcare use: dying of cancer was preceded by the greatest number of hospital admissions and dementia the least. Greater age was associated with lower admission rates and cost. There was higher resource use in the urban areas. No difference was observed by deprivation.ConclusionsHospitalisation near the end of life was least frequent for older people and those living rurally, although length of stay for both groups, when they were admitted, was longer. Research is required to understand if variation in hospitalisation is due to variation in the quantity or quality of end of life care available, varying community support, patient preferences or an inevitable consequence of disease-specific needs.

BackgroundPeople who are nearing the end of life are high users of healthcare. The cost to providers is high and the value of care is uncertain.ObjectivesTo describe the pattern, trajectory and drivers of secondary care use and cost by people in Scotland in their last year of life.MethodsRetrospective whole-population secondary care administrative data linkage study of Scottish decedents of 60 years and over between 2012 and 2017 (N=274 048).ResultsSecondary care use was high in the last year of life with a sharp rise in inpatient admissions in the last 3 months. The mean cost was £10 000. Cause of death was associated with differing patterns of healthcare use: dying of cancer was preceded by the greatest number of hospital admissions and dementia the least. Greater age was associated with lower admission rates and cost. There was higher resource use in the urban areas. No difference was observed by deprivation.ConclusionsHospitalisation near the end of life was least frequent for older people and those living rurally, although length of stay for both groups, when they were admitted, was longer. Research is required to understand if variation in hospitalisation is due to variation in the quantity or quality of end-of-life care available, varying community support, patient preferences or an inevitable consequence of disease-specific needs.

A microwave structure that combines filtering and radiating functions is presented. The structure consists of three patches, two of which are aperture-fed, printed on stacked substrates. The array can be considered as three-pole edge-coupled filter with radiating resonators. It can also be viewed as a two-port array antenna with frequency domain filtering capability. The array was designed to operate as three-pole band-pass filter with a fractional bandwidth of 5% at a midband frequency of 2.0 GHz. The proposed structure was simulated using CST (Computer Simulation Technology) software package and measured using HP8722D vector network analyzer. The structure exhibits filter-like frequency response with three reflection zeros observed in the return loss result. The measured and simulated 3- dB bandwidths are 117 and 130 MHz respectively. The structure also provides a well-shaped radiation pattern and good gain within the operating band.

Background The addition of adjuvant trastuzumab to chemotherapy has significantly improved outcomes in human epidermal growth factor receptor 2 (HER2) positive early, potentially curable breast cancer. Twelve months��� trastuzumab tested in the registration trials was adopted for standard adjuvant treatment in 2006. Subsequently similar outcomes were demonstrated using 9 weeks trastuzumab. Shorter durations were therefore tested for non-inferiority. Objectives To establish whether 6 months��� adjuvant trastuzumab is non-inferior to 12 months in HER2-positive early breast cancer using a primary endpoint of 4-year disease-free-survival (DFS). Design Phase III randomised, controlled, non-inferiority trial. Setting 152 NHS Hospitals. Participants 4088 patients with HER2-positive early breast cancer planned to receive both chemotherapy and trastuzumab. Intervention Randomisation (1:1) between six months��� or twelve months��� trastuzumab. Main outcomes Primary endpoint was DFS four years after diagnosis. Secondary endpoints were overall survival (OS), cost effectiveness, and cardiac function during trastuzumab. Assuming a 4-year DFS rate of 80% with 12 months, 4000 patients were required to demonstrate non-inferiority of 6-months (5% 1-sided significance, 85% power), defining the non-inferiority limit as no worse than 3% below the standard arm. Costs and quality-adjusted life years (QALYs) were estimated by within-trial analysis and a lifetime decision-analytic model. Results Between 4th October 2007 and 31st July 2015, 2045 patients were randomised to 12-months��� trastuzumab and 2043 to 6-months. Sixty-nine percent had ER-positive disease; 90% received anthracyclines (49% with taxanes; 41% without taxanes); 10% received taxanes without anthracyclines; 54% had trastuzumab sequentially after chemotherapy; 85% received adjuvant chemotherapy (58% were node negative). At 6.1 years median follow-up with 389 (10%) deaths, and 566 (14%) DFS events, 4-year DFS rates for the 4088 patients were 89.5% (95% CI, 88.1-90.8) in the 6-month group and 90.3% (95% CI 88.9- 91.5) in the 12-month group (Hazard Ratio 1.10; 90% CI 0.96���1.26, non-inferiority p=0.01), demonstrating non-inferiority of 6-months��� trastuzumab. Congruent results were found for OS (non-inferiority p=0.0003), and landmark analyses 6 months from starting trastuzumab (non-inferiority p=0.03 (DFS) and p=0.006 (OS)). 6-months��� trastuzumab resulted in fewer patients reporting adverse events of severe grade (365/1929 (19%) versus 460/1935 (24%) 12-month patients, p=0.0003) or stopping early because of cardiotoxicity (61/1977 (3%) versus 146/1941 (8%) 12-month patients, p, National Institute for Health Research, Health Technology Assessment Programme (HTA Project: 06/303/98).

ObjectivesStereotactic ablative radiotherapy (SABR) is a well-established treatment for medically inoperable peripheral stage I nonsmall cell lung cancer (NSCLC). Previous nonrandomised evidence supports SABR as an alternative to surgery, but high-quality randomised controlled trial (RCT) evidence is lacking. The SABRTooth study aimed to establish whether a UK phase III RCT was feasible.Design and methodsSABRTooth was a UK multicentre randomised controlled feasibility study targeting patients with peripheral stage I NSCLC considered to be at higher risk of surgical complications. 54 patients were planned to be randomised 1:1 to SABR or surgery. The primary outcome was monthly average recruitment rates.ResultsBetween July 2015 and January 2017, 318 patients were considered for the study and 205 (64.5%) were deemed ineligible. Out of 106 (33.3%) assessed as eligible, 24 (22.6%) patients were randomised to SABR (n=14) or surgery (n=10). A key theme for nonparticipation was treatment preference, with 43 (41%) preferring nonsurgical treatment and 19 (18%) preferring surgery. The average monthly recruitment rate was 1.7 patients against a target of three. 15 patients underwent their allocated treatment: SABR n=12, surgery n=3.ConclusionsWe conclude that a phase III RCT randomising higher risk patients between SABR and surgery is not feasible in the National Health Service. Patients have pre-existing treatment preferences, which was a barrier to recruitment. A significant proportion of patients randomised to the surgical group declined and chose SABR. SABR remains an alternative to surgery and novel study approaches are needed to define which patients benefit from a nonsurgical approach.

Background We describe temporal trends in breast cancer incidence by molecular subtypes in Scotland because public health prevention programmes, diagnostic and therapeutic services are shaped by differences in tumour biology. Methods Population-based cancer registry data on 72,217 women diagnosed with incident primary breast cancer from 1997 to 2016 were analysed. Age-standardised rates (ASR) and age-specific incidence were estimated by tumour subtype after imputing the 8% of missing oestrogen receptor (ER) status. Joinpoint regression and age–period–cohort models were used to assess whether significant differences were observed in incidence trends by ER status. Results Overall, ER-positive tumour incidence increased by 0.4%/year (95% confidence interval (CI): −0.1, 1.0). Among routinely screened women aged 50–69 years, we observed an increase in ASR from 1997 to 2011 (1.6%/year, 95% CI: 1.2–2.1). ER-negative tumour incidence decreased among all ages by 2.5%/year (95% CI: −3.9 to −1.1%) over the study period. Compared with the 1941–1959 birth cohort, women born in 1912–1940 had lower incidence rate ratios (IRR) for ER+ tumours and women born in 1960–1986 had lower IRR for ER− tumours. Conclusions Future incidence and survival reporting should be monitored by molecular subtypes to inform clinical planning and cancer control programmes.

Analysing trends in cause specific excess deaths provides useful information on the consequences of the covid-19 pandemic. Lai and colleagues call for real time weekly data on cause specific mortality as these data are currently delayed in England, Wales, and Northern Ireland.12 In England, over 25% of all deaths are registered more than one week after death, and around 10% registered more than two weeks …

British urban planning and geography professor Sir Peter Hall (1932–2014) was one of the most influential urban planning scholars of the twentieth century. In this selection from Cities of Tomorrow (4th edn, 2014) Hall argues that urban planning theory has experienced a number of paradigm shifts in the last century. Professors in the first UK and US academic urban planning programs at the University of Liverpool and Harvard University taught “civic design.” Their students learned how to draw two- and three-dimensional renderings of urban areas the way an architect would prepare a blueprint. The planning as design paradigm paid little attention to the economic, political, and social reality of the city. Their elegant Beaux-Arts plans were mostly ignored. After World War II the rational planning paradigm – favored by engineers – became influential among city planners. Professors conceived of urban planning as a logical process searching for the best solution to a problem. Students were taught to specify a problem, gather data, analyze it, specify alternative solutions, pick “the best” one, implement and evaluate it. Yale University professor Charles E. Lindblom attacked the rational planning model in a classic article titled “The Science of ‘Muddling Through’” (1959). Lindblom proposed a paradigm he called disjointed incrementalism – attacking problems in manageable bite-sized chunks – as usually the best that urban planners could do. Columbia management professor Amitai Etzioni proposed a hybrid paradigm called “mixed scanning”: incremental decision-making based on a stripped-down version of rational planning, constantly adjusted during implementation.

Understanding the trends in causes of death for different diseases during the current COVID-19 pandemic is important to determine whether there are excess deaths beyond what is normally expected. Using the most recent report from National Records Scotland (NRS) on 29 April 2020, we examined the percentage difference in crude numbers of deaths in 2020 compared to the average for 2015-2019 by week of death within calendar year. To determine if trends were similar, suggesting underreporting/underdiagnosed COVID-19 related deaths, we also looked at the trends in % differences for cardiovascular disease deaths. From the first 17 weeks’ of data, we found a peak in excess deaths at week 14 of 2020, about four weeks after the first case in Scotland was detected on 1 March 2020-- but by week 17 these excesses had returned to normal levels, 4 weeks after lockdown in the UK began. Similar observations were seen for cardiovascular disease-related deaths. These observations suggest that the short-term increase in excess cancer and cardiovascular deaths might be associated with undetected/unconfirmed deaths related to COVID-19. Both of these conditions make patients more susceptible to infection and lack of widespread access to testing for COVID-19 are likely to have resulted in under-estimation of COVID-19 mortality. These data further suggest that the cumulative toll of COVID-19 on mortality is likely undercounted. More detailed analysis is needed to determine if these excesses were directly or indirectly related to COVID-19. Disease specific mortality will need constant monitoring for the foreseeable future as changes occur in increasing capacity and access to testing, reporting criteria, changes to health services and different measures are implemented to control the spread of the COVID-19. Multidisciplinary, multi-institutional, national and international collaborations for complementary and population specific data analysis is required to respond and mitigate adverse effects of the COVID-19 pandemic and to inform planning for future pandemics.

Aims Treatment advances have improved cancer-related outcomes and shifted interest towards minimising long-term iatrogenic complications, particularly chemotherapy-related cardiotoxicity. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of plasma troponin and enable early detection of cardiomyocyte injury prior to the development of myocardial dysfunction. The profile of hs-cTnI in response to anthracycline-based treatment has not previously been described. Materials and methods This was a multicentre prospective observational cohort study. Female patients with newly diagnosed invasive breast cancer scheduled to receive anthracycline-based (epirubicin) chemotherapy were recruited. Blood sampling was carried out before and 24 h after each cycle. Hs-cTnI concentrations were measured using the Abbott ARCHITECTSTAT assay. Results We recruited 78 women with a median (interquartile range) age of 52 (49–61) years. The median baseline troponin concentration was 1 (1–4) ng/l and the median cumulative epirubicin dose was 394 (300–405) mg/m2. Following an initial 33% fall 24 h after anthracycline dosing (P, Highlights • Plasma hs-cTnI concentrations showed an anthracycline dose-dependent increase. • Hs-cTnI could act as an early and sensitive anthracycline cardiotoxicity prediction tool. • Hs-cTnI measurement should happen before rather than after each cycle.

Pointing gestures are widely used in robot navigation approaches nowadays. However, most approaches only use pointing gestures, and these have two major limitations. Firstly, they need to recognize pointing gestures all the time, which leads to long processing time and significant system overheads. Secondly, the user's pointing direction may not be very accurate, so the robot may go to an undesired place. To relieve these limitations, we propose a voice-guided pointing robot navigation approach named VGPN, and implement its prototype on a wheeled robot, TurtleBot 2. VGPN recognizes a pointing gesture only if voice information is insufficient for navigation. VGPN also uses voice information as a supplementary channel to help determine the target position of the user's pointing gesture. In the evaluation, we compare VGPN to the pointing-only navigation approach. The results show that VGPN effectively reduces the processing time cost when pointing gesture is unnecessary, and improves the user satisfaction with navigation accuracy.

This mini-review considers the densification of biomass blended with plastic wastes as an approach for waste management and sustainable fuel production from two perspectives; (1) We overviewed the pollutants generated during plastics combustion and their hazards. The control of these pollutants can be achieved as both reported in literature and by currently in-service municipal waste plants. (2) Advantages from densifying biomass/plastic blends as a solid fuel are indicated. Biomass/plastic briquettes or pellets are a potentially promising solid fuel with low costs, high volumetric heating values, high resistance to mechanical damage and good durability performance under humid conditions. Moreover, the combustion of biomass/plastic blends with less than 10% plastics has no substantial negative effect on pollutants emission compared with that of biomass. Perspectives on densifying biomass/plastic blends as a solid fuel are proposed to realize the scale-up of this technique.

Funding: NHS Lothian, the DATALab, and the EU H2020 project Serums: Securing Medical Data in Smart Patient-Centric Healthcare Systems(grant code:826278). The Edinburgh Cancer Centre (ECC) contains NHS Lothian cancer patient data from multiple resources. However, the lack of proxy between numerous scattered resources hinders the capability to use the information collected in a useful way. ECC data is very varied and includes patient characteristics (e.g., age, weight, height, gender), information on diagnosis (e.g., stage, site, comorbidities) and treatments (e.g., surgery, chemotherapy, radiotherapy). The visualisation of a fraction of ECC data in the form of a patient timeline can aid and enhance the process of observing and identifying the overall condition of the patient, as well as understand how it may compare with cohorts of patients with similar characteristics. We have previously developed machine learning models for predicting treatment outcomes for breast cancer patient data that have undergone chemotherapy. In this paper, we describe, examine, and propose a solution to connect all these aspects and provide a bridge for several resources. This will make it easier for clinicians and other healthcare professionals to support service planning, deliver better quality of care and consequently improve service outcome within NHS Lothian. Publisher PDF

Background: GO2 sought to optimise chemotherapy dosing in older/frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making. Methods: Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable. Two randomisation options were available: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (doses as used in the standard epirubicin/oxaliplatin/capecitabine regimen), B (0·8x A) or C (0·6x A). Non-inferiority of PFS was assessed using boundary HR=1·34, selected by a forum of patients and clinicians. Overall Treatment Utility (OTU), which combines efficacy, toxicity, QL and patient value/acceptability, was scored at nine weeks. Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, they could enter the CHEMO-BSC randomisation, comparing Level C versus best supportive care. Findings: 514 patients entered the CHEMO-INTENSITY randomisation: non-inferior PFS was confirmed for B vs A (HR=1·09 [CI=0·89-1·32]) and C vs A (HR=1·10 [0·90-1·33]). Level C produced less toxicity and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in the younger, fitter patients. 45 patients entered the CHEMO-BSC randomisation: overall survival was non-significantly longer with chemotherapy: median 6·1 vs 3·0 months, HR=0·69 [0·32-1·48], p=0·34. In multivariate analysis, baseline frailty, QL and neutrophil:lymphocyte ratio were independently associated with OTU, so can be combined in a model to estimate the probability of better or worse outcome. Interpretation: Reduced-intensity chemotherapy provided non-inferior efficacy with an improved patient experience. Baseline geriatric assessment can help predict the utility of chemotherapy. Trial Registration: [Trial registration: ISRCTN44687907] Funding Statement: Cancer Research UK [CRUK/12/022] Declaration of Interests: Dr. Grabsch reports personal fees from Merck Sharpe Dome, outside the submitted work; all other authors have nothing to declare. Ethics Approval Statement: This study was approved by the UK National Research Ethics Service and overseen by independent Trial Steering and Data Monitoring & Ethics Committees (TSC; IDMC).

Globally, agricultural systems are facing unprecedented challenges. The problems are of systemic nature and will require transformational changes and systemic redesign. In this study, we investigated the redesign of dairy systems in New Zealand, due to their large economic, social and environmental influence nationally. We did not set the boundaries of the ‘dairy systems’ from the outset, letting this definition be part of the design process. We applied ‘Reflexive Interactive Design’ (RIO), an approach aimed at structurally addressing complex trade-offs and contributing, by process and design, to change towards sustainable development and integral sustainability (i.e. in all relevant dimensions of sustainability). A detailed system analysis was conducted, followed by two rounds of structured design focused on four main stakeholders (‘actors') identified as part of the RIO process: the farmers, the citizens, the consumers, and the dairy cows. Our study established design goals related to enhancing the wellbeing of humans and animals, enhancing environmental performance, economics and resilience of dairy systems and reconnecting dairy farming with the rest of society. The process took us beyond the boundaries of a dairy farm and identified the territorial level as the object of design, arriving at a design concept we have called the ‘Agro-ecological Park’. The name was chosen to convey an analogy with ‘Eco-industrial Parks’. Operating as a multifunctional network, the Park has the goal of delivering multiple benefits for its members, and multiple goods and services for the rest of society. The coordinated network articulates linkages between farmers and many other businesses and people in the territory. The individual dairy farm is redesigned to be a node in that network rather than operating as an isolated entity. That way, much of the weight for the increased complexity and multifunctionality now demanded of farming can be carried by the network instead of the individual farmer. These preliminary design ideas, and the reasoning behind them, should encourage new perspectives on the complex problems facing NZ dairy farming, and agriculture globally, in the upcoming decades.

Learning rates enable the generation of first-order estimates of the cost of a technology as cumulative production grows, and play an important role in energy-economic modelling. This paper extends the component-based approach to estimating future learning rates to the case of a technology with multiple variants. It sets out a bottom-up method for estimating the composite learning rate including the situation where the proportional contribution of the different variants changes as cumulative production increases. The method is demonstrated for carbon storage using representative cost and distribution data from recent studies of storage in the European region. Carbon storage comprises four technology variants defined by the nature of the storage reservoir – (onshore or offshore) depleted oil & gas reservoirs and (onshore or offshore) saline aquifers – and each variant has a different learning rate reflecting its different cost structure. Moreover, the proportional contribution of each variant to total storage is likely to change with the growth of global storage capacity. The composite learning rate for carbon storage is estimated for scenarios in which the relative contributions change: a negative learning rate is determined in one scenario.

The cost of personalised medicine in oncology is increasing. The varied and contrasting priorities of the pharmaceutical industry, local and national governments, international medical community, and patients need to be reviewed and balanced. In addition to the economic and political standpoints on this issue, the ethical considerations from physicians' viewpoints need to be considered to optimise cancer patients' care. In this paper we discuss the way research and development (R&D) of these drugs is carried out and reimbursed, and how this needs to change. We describe frameworks assessing the value of these treatments which been developed. Physicians need to develop their knowledge and understanding of these issues to best meet their dual responsibilities of advocating for their patients and promoting public health.

PURPOSE The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is frequently activated in triple-negative breast cancer (TNBC). The AKT inhibitor capivasertib has shown preclinical activity in TNBC models, and drug sensitivity has been associated with activation of PI3K or AKT and/or deletions of PTEN. The PAKT trial was designed to evaluate the safety and efficacy of adding capivasertib to paclitaxel as first-line therapy for TNBC. PATIENTS AND METHODS This double-blind, placebo-controlled, randomized phase II trial recruited women with untreated metastatic TNBC. A total of 140 patients were randomly assigned (1:1) to paclitaxel 90 mg/m2 (days 1, 8, 15) with either capivasertib (400 mg twice daily) or placebo (days 2-5, 9-12, 16-19) every 28 days until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), PFS and OS in the subgroup with PIK3CA/ AKT1/ PTEN alterations, tumor response, and safety. RESULTS Median PFS was 5.9 months with capivasertib plus paclitaxel and 4.2 months with placebo plus paclitaxel (hazard ratio [HR], 0.74; 95% CI, 0.50 to 1.08; 1-sided P = .06 [predefined significance level, 1-sided P = .10]). Median OS was 19.1 months with capivasertib plus paclitaxel and 12.6 months with placebo plus paclitaxel (HR, 0.61; 95% CI, 0.37 to 0.99; 2-sided P = .04). In patients with PIK3CA/ AKT1/ PTEN-altered tumors (n = 28), median PFS was 9.3 months with capivasertib plus paclitaxel and 3.7 months with placebo plus paclitaxel (HR, 0.30; 95% CI, 0.11 to 0.79; 2-sided P = .01). The most common grade ≥ 3 adverse events in those treated with capivasertib plus paclitaxel versus placebo plus paclitaxel, respectively, were diarrhea (13% v 1%), infection (4% v 1%), neutropenia (3% v 3%), rash (4% v 0%), and fatigue (4% v 0%). CONCLUSION Addition of the AKT inhibitor capivasertib to first-line paclitaxel therapy for TNBC resulted in significantly longer PFS and OS. Benefits were more pronounced in patients with PIK3CA/ AKT1/ PTEN-altered tumors. Capivasertib warrants further investigation for treatment of TNBC.

Background Feedback about potentially serious incidental findings (PSIFs) on research imaging leads to clinical assessment in almost all cases. Previous studies have been small, or focused on patients, or non-UK settings. We used a novel four-way comparison to assess the economic impact on UK hospital services of feeding back PSIFs to research volunteers within the UK Biobank Imaging Study. Methods We matched (by age, sex, imaging date and prior morbidity [Elixhauser index]) 179 cases, who received feedback about a PSIF identified following either magnetic resonance imaging or dual-energy X-ray absorptiometry, to controls without a PSIF. We calculated the hospital costs of cases and controls by applying National Reference Costs to linked Hospital Episode Statistics inpatient, outpatient, accident and emergency and critical care datasets from 2013–2016. We conducted four-way comparisons of data from cases and controls during the year before and after feedback of a PSIF (cases before versus after, controls before versus after, cases versus controls before and after). We compared mean differences in hospital contacts and costs (with 95% confidence intervals [CI] calculated using bootstrapping techniques) and differences in proportions with ≥ 1 hospital contact using McNemar’s tests between groups, and calculated cumulative costs. We performed sensitivity analyses using only those case-control pairs with no prior morbidity. Results There were no differences in mean numbers of hospital contacts or costs between cases and controls before feedback, or between controls before and after feedback of a PSIF. Following feedback, 144 (80.5%) cases, and 94 (52.5%) controls used hospital services. Mean numbers of hospital contacts and mean costs were higher in cases compared to controls after feedback, and compared to cases before feedback (hospital contacts: 5.4 [standard deviation 6.2] versus 3.2 [5.7] and versus 2.7 [4.7]; costs: £2,409 [£4,781] versus £935 [£2,439] and versus £826 [£2,179]). Cases’ cumulative costs began to increase approximately 30–60 days following feedback of a PSIF. A year after feedback of a PSIF, total hospital costs for cases (£431,114) were almost three times higher than for controls (£147,817) and for cases the year before (£167,434). Compared to the year before, after feedback of a PSIF total costs had increased 10 times in serious cases, and two times in non-serious cases. Most PSIFs were non-serious (158/179 [88%]). Although serious cases generated higher mean costs after feedback than non-serious cases (£9,147 [£10,234] versus £1,513 [£2,386]), the 7.5-fold greater number of non-serious cases generated higher total absolute costs than serious cases (£239,021 versus £192,093). These patterns of costs persisted over longer follow-up, and in sensitivity analyses. After feedback of a PSIF, most costs related to inpatient services (68.3%). Conclusions After feedback of a PSIF, research volunteers used substantially more hospital services compared with controls or with the year before. Total cost and service impacts were higher among cases with non-serious, rather than serious final diagnoses, as most PSIFs represented non-serious disease. Avoidance of unnecessary feedback through ensuring non-serious PSIFs feedback policies are appropriate to the research setting would enable researchers and policymakers to minimise unwarranted impacts on publicly-funded healthcare services.

Detecting small objects is a challenging task. We focus on a special case: the detection and classification of traffic signals in street views. We present a novel framework that utilizes a visual attention model to make detection more efficient, without loss of accuracy, and which generalizes. The attention model is designed to generate a small set of candidate regions at a suitable scale so that small targets can be better located and classified. In order to evaluate our method in the context of traffic signal detection, we have built a traffic light benchmark with over 15,000 traffic light instances, based on Tencent street view panoramas. We have tested our method both on the dataset we have built and the Tsinghua–Tencent 100K (TT100K) traffic sign benchmark. Experiments show that our method has superior detection performance and is quicker than the general faster RCNN object detection framework on both datasets. It is competitive with state-of-the-art specialist traffic sign detectors on TT100K, but is an order of magnitude faster. To show generality, we tested it on the LISA dataset without tuning, and obtained an average precision in excess of 90%.