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Abstract Background Widefield radiation therapy (RT) has emerged as a treatment option for extensive skin field cancerization (ESFC), with or without keratinocyte cancer (KC). Objectives To assess the long‐term efficacy, safety, cosmesis and quality of life outcomes for patients with ESFC ± KC receiving widefield RT. Methods NDROR (National Dermatology Radiation Oncology Registry) is an open‐label, prospective, nonrandomized, multicentre registry of patients receiving widefield RT at 11 Australian radiation oncology clinics from a single organization. Field/lesion clearance efficacy and cosmesis were assessed in a cohort of patients with at least 24 months follow‐up. Patient‐reported quality of life using EQ‐5D‐5L questionnaires was performed at each visit. Toxicity analysis was performed on data from patients who completed treatment and had at least 3 months follow‐up. Results Combined investigator‐assessed field treatment success and lesion clearance at 24 months were ≥96% and 93.5%, respectively. The incidence of new KC within the treated field was 10%. Common Terminology Criteria for Adverse Event grade 1–2 radiation‐induced skin toxicities were reported in >92% of fields at the end of treatment, with 5.8% of fields exhibiting grade 3 toxicities. Toxicity resolved rapidly at the cessation of treatment, with grade 1–2 alopecia and xerosis the most prevalent toxicities after 24 months (51.8% and 43.4%, respectively). Cosmesis in treated fields was assessed as excellent or good in 98% of fields at 24 months. Quality of life significantly improved compared to baseline (baseline: mean visual analogue scale (VAS) 80.65, n = 183) at 24 months follow‐up (mean VAS 84.32, N = 83; improvement of 3.67; p = 0.026). Conclusions This analysis indicates that widefield RT is an effective and generally well‐tolerated treatment for ESFC ± KC. Treatment has a favourable safety and cosmesis profile within the period of follow‐up and is associated with significant improvements in quality of life for patients. Widefield RT may be considered for certain patients with extensive disease who have exhausted or are unsuitable for other therapies.

Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. Methods: Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Results: we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). Conclusion: In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registration: ANZCTR ACTRN12619000241134. Registered 19 February 2019.

Abstract A major obstacle toward creating human‐scale artificial tissue models is supplying encapsulated cells with oxygen and other nutrients throughout the construct. In particular, creating channels in hydrogels that match the resolution and density of the smallest blood capillaries (≤10 µm) remains highly challenging. Here, a novel method is demonstrated where polycaprolactone fibers printed using melt‐electrowriting are encapsulated in cell‐laden hydrogels and then physically removed to produce hollow, perfusable channels. This technique produces a range of channel diameters (10–41 µm) with circular cross‐sections and in hydrogels representing various crosslinking mechanisms. The channels can be formed as interconnected grids, hierarchically branched patterns, or stacked in layers with ≈200 µm channel spacing, thus matching average capillary density in the human body. Alternatively, selective removal of fibers from a melt electrowriting grid can generate perfusable channels within a reinforcing fiber network. This method can be performed in the presence of cells, with human fibroblasts exhibiting encapsulated in gelatin methacryloyl showing no detectable cytotoxic effects. This technique is a promising approach for creating perfusable channels with very small diameters within cell‐laden hydrogel matrices, with potential applications including in vitro tissue models and hydrogel microfluidics.

Abstract Radar sensing offers a method of achieving 24‐h all‐weather drone surveillance, but in order to be maximally effective, systems need to be able to discriminate between birds and drones. This work examines drone‐bird classification performance as a function of signal to noise ratio (SNR). Classification at low SNR values is necessary in order to classify drones with a small radar cross‐section (RCS), as well as to facilitate reliable classification at longer ranges. To investigate the relationship between classification performance and SNR, Gaussian noise is added to an experimentally obtained dataset of radar spectrograms. Classification is performed by convolutional neural networks (CNNs). It is shown that for the data available classification accuracy drops with falling SNR, as might be expected for any given CNN. The degree to which performance degrades with reduced SNR is presented. It is further shown that simpler network architectures are more robust to noise. Finally, it is demonstrated that data augmentation can be used as a means of enhancing classification accuracy at lower SNR values. Bayesian optimisation is used to find the optimal augmentation hyperparameters and overall, classification accuracies of 92% are achieved at low SNR.

Study region: The Upper Niger and Bani River basins in West Africa. Study focus: The growing demand for food, water, and energy led Mali and Guinea to develop ambitious hydropower and irrigation plans, including the construction of a new dam and the extension of irrigation schemes. These two developments will take place upstream of sensible ecosystem hotspots while the feasibility of development plans in terms of water availability and sustainability is questionable. Where agricultural development in past decades focused mainly on intensifying dry-season crops cultivation, future plans include extension in both the dry and wet seasons. New hydrological insights for the region: Today’s irrigation demand corresponds to 7% of the average annual Niger discharge and could account to one third in 2045. An extension of irrigated agriculture is possible in the wet season, while extending dry-season cropping would be largely compromised with the one major existing Sélingué dam. An additional large Fomi or Moussako dam would not completely satisfy dry-season irrigation demands in the 2045 scenario but would reduce the estimated supply gap from 36% to 14%. However, discharge peaks may decrease by 40% reducing the inundated area in the Inner Niger Delta by 21%, while average annual discharge decreases by 30%. Sustainable development should therefore consider investments in water-saving irrigation and management practices to enhance the feasibility of the envisaged irrigation plans instead of completely relying on the construction of a flow regime altering dam. Keywords: Reservoir and irrigation management, Hydrological modelling, Fomi/Moussako dam, Upper Niger and Bani River basin, Inner Niger Delta

Object recognition is the ability to identify an object or category based on the combination of visual features observed. It is a remarkable feat of the human brain, given that the patterns of light received by the eye associated with the properties of a given object vary widely with simple changes in viewing angle, ambient lighting, and distance. Furthermore, different exemplars of a specific object category can vary widely in visual appearance, such that successful categorization requires generalization across disparate visual features. In this review, we discuss recent advances in understanding the neural representations underlying object recognition in the human brain. We highlight three current trends in the approach towards this goal within the field of cognitive neuroscience. Firstly, we consider the influence of deep neural networks both as potential models of object vision and in how their representations relate to those in the human brain. Secondly, we review the contribution that time-series neuroimaging methods have made towards understanding the temporal dynamics of object representations beyond their spatial organization within different brain regions. Finally, we argue that an increasing emphasis on the context (both visual and task) within which object recognition occurs has led to a broader conceptualization of what constitutes an object representation for the brain. We conclude by identifying some current challenges facing the experimental pursuit of understanding object recognition and outline some emerging directions that are likely to yield new insight into this complex cognitive process.

This paper examines the impact that climate change may have on the lodging of oats in the Republic of Ireland and the UK. Through the consideration of a novel lodging model representing the motion of an oat plant due to the interaction of wind and rain and integrating future predictions of wind and rainfall due to climate change, appropriate conclusions have been made. In order to provide meteorological data for the lodging model, wind and rainfall inputs are analysed using 30 years’ time series corresponding to peak lodging months (June and July) from 38 meteorological stations in the United Kingdom and the Irish Republic, which enables the relevant probability density functions (PDFs) to be established. Moreover, climate data for the next six decades in the British Isles produced by UK climate change projections (UKCP18) are analysed, and future wind and rainfall PDFs are obtained. It is observed that the predicted changes likely to occur during the key growing period (June to July) in the next 30 years are in keeping with variations, which can occur due to different husbandry treatments/plant varieties. In addition, the utility of a double exponential function for representing the rainfall probability has been observed with appropriate values for the constants given.

For over four decades, social scientists have addressed the relationship between development strategies and Appalachia’s highland cultural traditions. Historically, mountain foodways and diversified agricultural practices were defined as aspects of primitive folkways legitimating resource extractive industries and centralized development strategies. Today, the region contains many of the nation’s remaining family farms. The processes of globalization and growing demand for local foods are introducing highland farming traditions to new audiences. This case study looks at the emerging role family farms in the East Tennessee valley are playing in development and the social construction of the region’s foodways. Drawing on multidisciplinary perspectives, I focus first on the historical roots and continuity of the region’s culinary tradition. Highland foods represent the core of mountain culture grounded in the ecological and economic experiences of its rural communities. Next the paper discusses the emergence of markets for place-based foods focusing on community development, tourism and a local foods-based culinary renaissance.

Abstract Background Dogs are ubiquitous in human society and attempts to manage their populations are common to most countries. Managing dog populations is achieved through a range of interventions to suit the dog population dynamics and dog ownership characteristics of the location, with a number of potential impacts or goals in mind. Impact assessment provides the opportunity for interventions to identify areas of inefficiencies for improvement and build evidence of positive change. Methods This scoping review collates 26 studies that have assessed the impacts of dog population management interventions. Results It reports the use of 29 indicators of change under 8 categories of impact and describes variation in the methods used to measure these indicators. Conclusion The relatively few published examples of impact assessment in dog population management suggest this field is in its infancy; however this review highlights those notable exceptions. By describing those indicators and methods of measurement that have been reported thus far, and apparent barriers to efficient assessment, this review aims to support and direct future impact assessment.

ETC-1002 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel investigational drug being developed for the treatment of dyslipidemia and other cardio-metabolic risk factors. The hypolipidemic, anti-atherosclerotic, anti-obesity, and glucose-lowering properties of ETC-1002, characterized in preclinical disease models, are believed to be due to dual inhibition of sterol and fatty acid synthesis and enhanced mitochondrial long-chain fatty acid β-oxidation. However, the molecular mechanism(s) mediating these activities remained undefined. Studies described here show that ETC-1002 free acid activates AMP-activated protein kinase in a Ca2+/calmodulin-dependent kinase β-independent and liver kinase β 1-dependent manner, without detectable changes in adenylate energy charge. Furthermore, ETC-1002 is shown to rapidly form a CoA thioester in liver, which directly inhibits ATP-citrate lyase. These distinct molecular mechanisms are complementary in their beneficial effects on lipid and carbohydrate metabolism in vitro and in vivo. Consistent with these mechanisms, ETC-1002 treatment reduced circulating proatherogenic lipoproteins, hepatic lipids, and body weight in a hamster model of hyperlipidemia, and it reduced body weight and improved glycemic control in a mouse model of diet-induced obesity. ETC-1002 offers promise as a novel therapeutic approach to improve multiple risk factors associated with metabolic syndrome and benefit patients with cardiovascular disease.

Skin autografts are in great demand due to injuries and disease, but there are challenges using live tissue sources, and synthetic tissue is still in its infancy. In this study, an electrocompaction method was applied to fabricate the densely packed and highly ordered collagen/sulfated xylorhamnoglycuronan (SXRGlu) scaffold which closely mimicked the major structure and components in natural skin tissue. The fabricated electrocompacted collagen/SXRGlu matrices (ECLCU) were characterized in terms of micromorphology, mechanical property, water uptake ability and degradability. The viability, proliferation and morphology of human dermal fibroblasts (HDFs) cells on the fabricated matrices were also evaluated. The results indicated that the electrocompaction process could promote HDFs proliferation and SXRGlu could improve the water uptake ability and matrices’ stability against collagenase degradation, and support fibroblast spreading on the ECLCU matrices. Therefore, all these results suggest that the electrocompacted collagen/SXRGlu scaffold is a potential candidate as a dermal substitute with enhanced biostability and biocompatibility.

Purpose: To investigate the set up and operation of a Managed Clinical Network for cardiac services and assess its impact on patient care. Methods: This single case study used process evaluation with observational before and after comparison of indicators of quality of care and costs. The study was conducted in Dumfries and Galloway, Scotland and used a three-level framework. Process evaluation of the network set-up and operation through a documentary review of minutes; guidelines and protocols; transcripts of fourteen semi-structured interviews with health service personnel including senior managers, general practitioners, nurses, cardiologists and members of the public. Outcome evaluation of the impact of the network through interrupted time series analysis of clinical data of 202 patients aged less than 76 years admitted to hospital with a confirmed myocardial infarction one-year pre and one-year post, the establishment of the network. The main outcome measures were differences between indicators of quality of care targeted by network protocols. Economic evaluation of the transaction costs of the set-up and operation of the network and the resource costs of the clinical care of the 202 myocardial infarction patients from the time of hospital admission to 6 months post discharge through interrupted time series analysis. The outcome measure was different in National Health Service resource use. Results: Despite early difficulties, the network was successful in bringing together clinicians, patients and managers to redesign services, exhibiting most features of good network management. The role of the energetic lead clinician was crucial, but the network took time to develop and ‘bed down’. Its primary “modus operand” was the development of a myocardial infarction pathway and associated protocols. Of sixteen clinical care indicators, two improved significantly following the launch of the network and nine showed improvements, which were not statistically significant. There was no difference in resource use. Discussion and conclusions: The Managed Clinical Network made a difference to ways of working, particularly in breaching traditional boundaries and involving the public, and made modest changes in patient care. However, it required a two-year “set-up” period. Managed clinical networks are complex initiatives with an increasing profile in health care policy. This study suggests that they require energetic leadership and improvements are likely to be slow and incremental.