The Aerospace Integration Research Centre (AIRC) at Cranfield University offers industry and academia an open environment to explore the opportunities for efficient integration of aircraft systems. As a part of the centre, Cranfield University, Rolls-Royce, and DCA Design International jointly have developed the Future Systems Simulator (FSS) for the purpose of research and development in areas such as human factors in aviation, single-pilot operations, future cockpit design, aircraft electrification, and alternative control approaches. Utilising the state-of-the-art modularity principles in simulation technology, the FSS is built to simulate a diverse range of current and novel aircraft, enabling researchers and industry partners to conduct experiments rapidly and efficiently. Central to the requirement, a unique, user-experience-centred development and design process is implemented for the development of the FSS. This paper presents the development process of such a flight simulator with an innovative flight deck. Furthermore, the paper demonstrates the FSS’s capabilities through case studies. The cutting-edge versatility and flexibility of the FSS are demonstrated through the diverse example research case studies. In the final section, the authors provide guidance for the development of an engineering flight simulator based on lessons learned in this project.

Background: Currently there are no disease modifying treatment for Synucleinopathies including Parkinson’s disease Dementia (PDD). Carrying a mutation in the GBA gene (beta-glucocerebrosidase/ GCAse) is a leading risk factor for synucleinopathies. Raising activity GCAse lowers α-synuclein levels in cells and animal models. Ambroxol is a pharmacological chaperone for GCAse and can raise GCAse levels. Our goal is to test Ambroxol as a disease-modifying treatment in PDD. Methods: We randomized fifty-five individuals with PDD to Ambroxol 1050mg/day, 525mg/day, or placebo for 52 weeks. Primary outcome measures included safety, Alzheimer’s disease Assessment Scale-cognitive (ADAS-Cog) subscale and the Clinician’s Global Impression of Change (CGIC). Secondary outcomes included pharmacokinetics, cognitive and motor outcomes and and plasma and CSF biomarkers. Results: Ambroxol was well tolerated. There were 7 serious adverse events (SAEs) none deemed related to Ambroxol. GCase activity was increased in white blood cells by ~1.5 fold. There were no differences between groups on primary outcome measures. Patients receiving high dose Ambroxol appeared better on the Neuropsychiatric Inventory. GBA carriers appeared to improve on some cognitive tests. pTau 181 was reduced in CSF. Conclusions: Ambroxol was safe and well-tolerated in PDD. Ambroxol may improve biomarkers and cognitive outcomes in GBA1 mutation carrie.rs Ambroxol improved some biomarkerss. ClinicalTrials.gov NCT02914366

In recent years, there has been significant momentum in applying deep learning (DL) to machine health monitoring (MHM). It has been widely claimed that DL methodologies are superior to more traditional techniques in this area. This paper aims to investigate this claim by analysing a real-world dataset of helicopter sensor faults provided by Airbus. Specifically, we will address the problem of machine sensor health unsupervised classification. In a 2019 worldwide competition hosted by Airbus, Fujitsu Systems Europe (FSE) won first prize by achieving an F1-score of 93% using a DL model based on generative adversarial networks (GAN). In another comprehensive study, various modified and existing image encoding methods were compared for the convolutional auto-encoder (CAE) model. The best classification result was achieved using the scalogram as the image encoding method, with an F1-score of 91%. In this paper, we use these two studies as benchmarks to compare with basic statistical analysis methods and the one-class supporting vector machine (SVM). Our comparative study demonstrates that while DL-based techniques have great potential, they are not always superior to traditional methods. We therefore recommend that all future published studies of applying DL methods to MHM include appropriately selected traditional reference methods, wherever possible.

The Taita Falcon Falco fasciinucha is known to occur and breed at only a few locations in eastern and southern Africa and is currently listed as globally “Vulnerable” and “Critically Endangered” in South Africa. An accurate estimation of its conservation status is however hampered by a lack of data and understanding of the species’ habitat requirements and competitive interactions with congeners. Our aim was to address some of these knowledge gaps. We conducted cliff-nesting raptor surveys across a substantial area of the Mpumalanga/Limpopo escarpment in north-eastern South Africa and modelled habitat suitability for nesting Taita Falcons in relation to the proximity of conspecifics and a community of five other sympatric cliff-nesting raptor species, and in relation to a suite of biotic and abiotic environmental variables. Results suggested the location of Taita Falcon nest sites was negatively associated with distance to the nearest pair of conspecifics and the nearest pair of Lanner Falcons Falco biarmicus, and positively associated with tracts of intact, unfragmented forest and woodland around the base of the cliffs. Our results indicated that Taita Falcon and Lanner Falcon appeared to be responding in opposite ways to a directional change in environmental conditions. This response appeared to be detrimental to Taita Falcon and beneficial to Lanner Falcon. Furthermore, the degradation and destruction of Afrotropical woodland and forest is a documented and ongoing reality, both locally and across much of the Taita Falcon’s global distribution. We argue that our findings are sufficient to justify uplisting Taita Falcon to globally “Endangered”.

Consumption of probiotics and/or yogurt could be a solution for restoring the balance of the gut microbiota. This study examined associations of regular intake of probiotic supplements or yogurt with the gut microbiota among a diverse population of older adults (N=1,861; 60–72 years). Faecal microbial composition was obtained from 16S rRNA gene sequencing (V1–V3 region). General linear models were used to estimate the associations of probiotic supplement or yogurt intake with microbiome measures adjusting for covariates. Compared to non-yogurt consumers (N=1,023), regular yogurt consumers (≥once/week, N=818) had greater Streptococcus (β=0.29, P=0.0003) and lower Odoribacter (β=−0.33, P<0.0001) abundance. The directions of the above associations were consistent across the five ethnic groups but stronger among Japanese Americans (Streptococcus: β=0.56, P=0.0009; Odoribacter: β=−0.62, P=0.0005). Regular intake of probiotic supplements (N=175) was not associated with microbial characteristics (i.e., alpha diversity and the abundance of 152 bacteria genera). Streptococcus is one of the predominant bacteria genera in yogurt products, which may explain the positive association between yogurt consumption and Streptococcus abundance. Our analyses suggest that changes in Odoribacter were independent of changes in Streptococcus abundance. Future studies may investigate whether these microbial genera and their sub-level species mediate potential pathways between yogurt consumption and health.

Climate warming is occurring most rapidly in the Arctic, which is both a sentinel and a driver of further global change. Ecosystems and human societies are already affected by warming. Permafrost thaws and species are on the move, bringing pathogens and vectors to virgin areas. During a five-year project, the CLINF – a Nordic Center of Excellence, funded by the Nordic Council of Ministers, has worked with the One Health concept, integrating environmental data with human and animal disease data in predictive models and creating maps of dynamic processes affecting the spread of infectious diseases. It is shown that tularemia outbreaks can be predicted even at a regional level with a manageable level of uncertainty. To decrease uncertainty, rapid development of new and harmonised technologies and databases is needed from currently highly heterogeneous data sources. A major source of uncertainty for the future of contaminants and infectious diseases in the Arctic, however, is associated with which paths the majority of the globe chooses to follow in the future. Diplomacy is one of the most powerful tools Arctic nations have to influence these choices of other nations, supported by Arctic science and One Health approaches that recognise the interconnection between people, animals, plants and their shared environment at the local, regional, national and global levels as essential for achieving a sustainable development for both the Arctic and the globe.

As past usual diet quality may affect gut microbiome (GM) composition, we examined the association of the Healthy Eating Index (HEI)-2015 assessed 21 and 9 years before stool collection with measures of fecal microbial composition in a subset of the Multiethnic Cohort. A total of 5936 participants completed a validated quantitative FFQ (QFFQ) at cohort entry (Q1, 1993–1996), 5280 at follow-up (Q3, 2003–2008) and 1685 also at a second follow-up (Adiposity Phenotype Study (APS), 2013–2016). All participants provided a stool sample in 2013–2016. Fecal microbial composition was obtained from 16S rRNA gene sequencing (V1–V3 regions). HEI-2015 scores were computed based on each QFFQ. Using linear regression adjusted for relevant covariates, we calculated associations of HEI-2015 scores with gut microbial diversity and 152 individual genera. The mean HEI-2015 scores increased from Q1 (67 (sd 10)) to Q3 (71 (sd 11)) and APS (72 (sd 10)). Alpha diversity assessed by the Shannon Index was significantly higher with increasing tertiles of HEI-2015. Of the 152 bacterial genera tested, seven (Anaerostipes, Coprococcus_2, Eubacterium eligens, Lachnospira, Lachnospiraceae_ND3007, Ruminococcaceae_UCG-013 and Ruminococcus_1) were positively and five (Collinsella, Parabacteroides, Ruminiclostridium_5, Ruminococcus gnavus and Tyzzerella) were inversely associated with HEI-2015 assessed in Q1, Q3 and APS. The estimates of change per unit of the HEI-2015 score associated with the abundance of these twelve genera were consistent across the three questionnaires. The quality of past diet, assessed as far as ∼20 years before stool collection, is equally predictive of GM composition as concurrently assessed diet, indicative of the long-term consistency of this relation.

Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.

Recurrent outbreaks of haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) serotype O55:H7 occurred in England between 2014 and 2018. We reviewed the epidemiological evidence to identify potential source(s) and transmission routes of the pathogen, and to assess the on-going risk to public health. Over the 5-year period, there were 43 confirmed and three probable cases of STEC O55:H7. The median age of cases was 4 years old (range 6 months to 69 years old) and over half of all cases were female (28/46, 61%). There were 36/46 (78.3%) symptomatic cases, and over half of all cases developed HUS (25/46, 54%), including two fatal cases. No common food or environmental exposures were identified, although the majority of cases lived in rural or semi-rural environments and reported contact with both wild and domestic animals. This investigation informed policy on the clinical and public health management of HUS caused by STEC other than serotype O157:H7 (non-O157 STEC) in England, including comprehensive testing of all household contacts and household pets and more widespread use of polymerase chain reaction assays for the rapid diagnosis of STEC-HUS.

Evolving conditions at the terminus of Thwaites Glacier will be important in determining the rate of its future sea-level contribution over the coming decades. Here, we use remote-sensing observations to investigate recent changes (2000–2018) in the structure and velocity of Thwaites Glacier and its floating tongue. We show that the main trunk of Thwaites Glacier has accelerated by 38% over this period, while its previously intact floating tongue has transitioned to a weaker mélange of fractured icebergs bounded by sea ice. However, the rate of structural weakening and acceleration was not uniform across the observational period and we identify two periods of rapid acceleration and structural weakening (2006–2012; 2016–2018), separated by a period of deceleration and re-advance of the structurally-intact shear margin boundary (2012–2015). The timing of these accelerations/decelerations strongly suggests a link to variable ocean forcing. The weakened tongue now has some dependency on landfast sea ice for structural integrity and is vulnerable to changes in landfast ice persistency. Future reductions in landfast sea ice could manifest from changes in climate and/or the imminent removal of the B-22A iceberg from the Thwaites embayment. Such changes could have important implications for the integrity of the ice tongue and future glacier discharge.

Systematic, national surveillance of outbreaks of intestinal infectious disease has been undertaken by Public Health England (PHE) since 1992. Between 1992 and 2002, there were 19 outbreaks linked to raw drinking milk (RDM) or products made using raw milk, involving 229 people; 36 of these were hospitalised. There followed an eleven-year period (2003–2013) where no outbreaks linked to RDM were reported. However, since 2014 seven outbreaks of Escherichia coli O157:H7 (n = 3) or Campylobacter jejuni (n = 4) caused by contaminated RDM were investigated and reported. Between 2014 and 2017, there were 114 cases, five reported hospitalisations and one death. The data presented within this review indicated that the risk of RDM has increased since 2014. Despite the labelling requirements and recommendations that children should not consume RDM, almost a third of outbreak cases were children. In addition, there has been an increase in consumer popularity and in registered RDM producers in the UK. The Food Standards Agency (FSA) continue to provide advice on RDM to consumers and have recently made additional recommendations to enhance existing controls around registration and hygiene of RDM producers.

Places such as Poverty Point, Mound City, and Chaco Canyon remind us that the siting of ritual infrastructure in ancient North America was a matter of cosmological precedent. The cosmic gravity of these places gathered persons periodically in numbers that challenged routine production. Ritual economies intensified, but beyond the material demands of hosting people, the siting of these places and the timing of gatherings were cosmic work that preconfigured these outcomes. A first millennium AD civic-ceremonial center on the northern Gulf Coast of Florida illustrates the rationale for holding feasts on the end of a parabolic dune that it shared with an existing mortuary facility. Archaeofauna from large pits at Shell Mound support the inference that feasts were timed to summer solstices. Gatherings were large, judging from the infrastructure in support of feasts and efforts to intensify production through oyster mariculture and the construction of a large tidal fish trap. The 250-year history of summer solstice feasts at Shell Mound reinforces the premise that ritual economies were not simply the amplification of routine production. It also suggests that the ecological potential for intensification was secondary to the cosmic significance of solstice-oriented dunes and their connection to mortuary and world-renewal ceremonialism.

Limpets and barnacles are important components of intertidal assemblages worldwide. This study examines the effects of barnacles on the foraging behaviour of the limpet Patella vulgata, which is the main algal grazer in the North-west Atlantic. The behaviour of limpets on a vertical seawall on the Isle of Man (UK) was investigated using autonomous radio-telemetry, comparing their activity patterns on plots characterized by dense barnacle cover and plots from which the barnacles had been removed. Limpet behaviour was investigated at mid-shore level, but two different elevations were considered. This experiment revealed a significant effect of barnacle cover on the activity of P. vulgata. Limpets on smooth surfaces spent a greater proportion of total time active than did limpets on barnacles. Movement activity was also greater in areas that were lower down in the tidal range. In general, limpets were either predominantly active during diurnal high or nocturnal low tides and always avoided nocturnal high tides. Individuals on barnacles at the higher elevation concentrated their activity during nocturnal low water. All the other groups of limpets (smooth surfaces on the upper level and all individuals on the lower shore) had more excursions centred around daylight hours with an equal distribution of activity between periods of low and high water. Inter-individual variability was, however, pronounced.

Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010–2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19–2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10–1.75) and hospitalisation (OR 1.71, 95% CI 1.36–2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16–2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40–2.27; OR 1.85, 95% CI 1.35–2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22–2.70; soil contact, OR 1.52, 95% CI 2.13–1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.

A total of 592 people reported gastrointestinal illness following attendance at Street Spice, a food festival held in Newcastle-upon-Tyne, North East England in February/March 2013. Epidemiological, microbiological and environmental investigations were undertaken to identify the source and prevent further cases. Several epidemiological analyses were conducted; a cohort study; a follow-up survey of cases and capture re-capture to estimate the true burden of cases. Indistinguishable isolates of Salmonella Agona phage type 40 were identified in cases and on fresh curry leaves used in one of the accompaniments served at the event. Molecular testing indicated entero-aggregative Escherichia coli and Shigella also contributed to the burden of illness. Analytical studies found strong associations between illness and eating food from a particular stall and with food items including coconut chutney which contained fresh curry leaves. Further investigation of the food supply chain and food preparation techniques identified a lack of clear instruction on the use of fresh uncooked curry leaves in finished dishes and uncertainty about their status as a ready-to-eat product. We describe the investigation of one of the largest outbreaks of food poisoning in England, involving several gastrointestinal pathogens including a strain of Salmonella Agona not previously seen in the UK.