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Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.
A battery of 32 tests was administered to a sample including 144 Air Force Officer Candidates and 139 Air Cadets. The factor analysis, using Thurstone's complete centroid method and Zimmerman's graphic method of orthogonal rotations, revealed 12 interpretable factors. The non-reasoning factors were interpreted as verbal comprehension, numerical facility, perceptual speed, visualization, and spatial orientation. The factors derived from reasoning tests were identified as general reasoning, logical reasoning, education of perceptual relations, education of conceptual relations, education of conceptual patterns, education of correlates, and symbol substitution. The logical-reasoning factor corresponds to what has been called deduction, but eduction of correlates is perhaps closer to an ability actually to make deductions. The area called induction appears to resolve into three eduction-of-relations factors. Reasoning factors do not appear always to transcend the type of test material used.
This chapter provides an overview of the early history of the Celtic languages. The first part offers a tour of Britain and Ireland, pausing at key points, both historical and geographical, from which we may consider the development of the Celtic languages. The second part of the chapter then goes on to examine a number of features of the Celtic languages in greater detail: the stress accent, lenition and mutations, the loss of final syllables, and the verbal system.
The Dorchester Aqueduct, located to the north-west of Dorchester (Durnovaria) in Dorset, is arguably the most famous and well-examined Roman watercourse in Britain. The aqueduct has been intermittently investigated over the course of the last 100 years, but most extensively during the 1990s. The upper stretches of the aqueduct and its source have, however, eluded archaeologists, with multiple routes and water sources being suggested. A new programme of geophysical and topographic survey, combined with targeted investigation together with a reappraisal of the excavations from the 1990s, has provided additional evidence for the route of the aqueduct, extending its course for a further two kilometres to Notton on the River Frome.
Synthesising knowledge on the health of marine ecosystems and the human activities is crucial to informing holistic marine management. In many coastal states, however, research is conducted in an ad hoc manner and rarely compiled into accessible repositories making it challenging for marine managers to identify knowledge gaps when allocating resources. Here we conduct a structured review of existing literature to identify the current state of marine and coastal knowledge in the Isles of Scilly, an oceanic archipelago in the UK. The archipelago's marine flora and fauna are biogeographically unique in the Northeast Atlantic, with a distinct mosaic of warm and cold temperate habitats and species and are also considered a rare example of a near pristine marine environment in the otherwise highly degraded Northeast Atlantic Ocean. We found 150 sources relating to the marine biodiversity and relevant human activities in the Isles of Scilly with increasing diversification of research topics in recent years. Sources however remain dominated by specific taxa and habitats, suggesting the Isles of Scilly would particularly benefit from future research into: (1) anthropogenic impacts associated with warming waters and intense seasonal vessel activity; (2) development of repeatable survey protocols that can underpin long-term, ecosystem-based monitoring and management (notably for reef and sediment habitats and the European spiny lobster); and (3) data gaps associated with marine teleost fish and elasmobranch communities including identifying core habitat. This review can therefore act as a baseline biological synthesis for the region and importantly, can inform future research priorities.
Although the practice of human sacrifice in the British Iron Age is mentioned by multiple authors, both ancient and modern, physical proof of such activity in the archaeological record is comparatively rare. At Winterborne Kingston, in Dorset, the skeletal remains of a young adult female found face down near the base of a cylindrical storage pit provides clear evidence of violent death in the later Iron Age. Analysis of the skeleton suggests an individual who led a hard-working life and who, having suffered an act of violence a few weeks before death, was killed, possibly with her hands tied, by a blade incision to the neck. Placement of the body further suggests that killing was enacted within the pit, execution as spectacle forming the final act in a larger ceremony involving the creation of an animal bone stack or platform.
Parent and child mental health has suffered during the pandemic and transition phase. Structured and shared parenting may be intervention targets beneficial to families who are struggling with parent or child mental health challenges.
Aims
First, we investigated associations between structured and shared parenting and parent depression symptoms. Second, we investigated associations between structured and shared parenting and depression, hyperactivity/inattention and irritability symptoms in children.
Method
A total of 1027 parents in two-parent households (4797 observations total; 85.1% mothers) completed online surveys about themselves and their children (aged 2–18 years) from April 2020 to July 2022. Structured parenting and shared parenting responsibilities were assessed from April 2020 to November 2021. Symptoms of parent depression, child depression, child hyperactivity and inattention, child irritability, and child emotional and conduct problems were assessed repeatedly (one to 14 times; median of four times) from April 2020 to July 2022.
Results
Parents who reported higher levels of shared parenting responsibilities had lower depression symptoms (β = −0.09 to −0.32, all P < 0.01) longitudinally. Parents who reported higher levels of shared parenting responsibilities had children with fewer emotional problems (ages 2–5 years; β = −0.07, P < 0.05), fewer conduct problems (ages 2–5 years; β = −0.09, P < 0.01) and less irritability (ages 13–18 years; β = −0.27, P < 0.001) longitudinally. Structured parenting was associated with fewer conduct problems (ages 2–5 years; β = −0.05, P < 0.05).
Conclusions
Shared parenting is beneficial for parent and child mental health, even under chaotic or inflexible life conditions. Structured parenting is beneficial for younger children.
National disease surveillance systems are essential to a healthy pig industry but can be costly and logistically complex. In 2019, Lao People's Democratic Republic (Lao PDR) piloted an abattoir disease surveillance system to assess for the presence of high impact pig diseases (HIPDs) using serological methods. The Lao Department of Livestock and Fisheries (DLF) identified Classical Swine Fever (CSF), Porcine Respiratory and Reproductive Syndrome (PRRS) and Brucella suis as HIPDs of interest for sero-surveillance purposes. Porcine serum samples (n = 597) were collected from six Lao abattoirs in March to December of 2019. Serological enzyme-linked immunosorbent assay (ELISA) methods were chosen for their high-throughput and relatively low-costs. The true seroprevalence for CSF and PRRS seropositivity were 68.7%, 95% CI (64.8–72.3) and 39.5%, 95% CI (35.7–43.5), respectively. The results demonstrated no evidence of Brucella spp. seroconversion. Lao breed pigs were less likely to be CSF seropositive (P < 0.05), whilst pigs slaughtered at <1 year of age were less likely to be PRRS seropositive (P < 0.01). The testing methods could not differentiate between seropositivity gained from vaccine or natural infection, and investigators were unable to obtain the vaccine status of the slaughtered pigs from the abattoirs. These results demonstrate that adequate sample sizes are possible from abattoir sero-surveillance and lifetime health traceability is necessary to understand HIPDs in Lao PDR.
Climate change is resulting in global changes to sea level and wave climates, which in many locations significantly increase the probability of erosion, flooding and damage to coastal infrastructure and ecosystems. Therefore, there is a pressing societal need to be able to forecast the morphological evolution of our coastlines over a broad range of timescales, spanning days-to-decades, facilitating more focused, appropriate and cost-effective management interventions and data-informed planning to support the development of coastal environments. A wide range of modelling approaches have been used with varying degrees of success to assess both the detailed morphological evolution and/or simplified indicators of coastal erosion/accretion. This paper presents an overview of these modelling approaches, covering the full range of the complexity spectrum and summarising the advantages and disadvantages of each method. A focus is given to reduced-complexity modelling approaches, including models based on equilibrium concepts, which have emerged as a particularly promising methodology for the prediction of coastal change over multi-decadal timescales. The advantages of stable, computationally-efficient, reduced-complexity models must be balanced against the requirement for good generality and skill in diverse and complex coastal settings. Significant obstacles are also identified, limiting the generic application of models at regional and global scales. Challenges include the accurate long-term prediction of model forcing time-series in a changing climate, and accounting for processes that can largely be ignored in the shorter term but increase in importance in the long term. Further complications include coastal complexities, such as the accurate assessment of the impacts of headland bypassing. Additional complexities include complex structures and geology, mixed grain size, limited sediment supply, sources and sinks. It is concluded that with present computational resources, data availability limitations and process knowledge gaps, reduced-complexity modelling approaches currently offer the most promising solution to modelling shoreline evolution on daily-to-decadal timescales.
Prior to the COVID-19 pandemic, our research group initiated a pediatric practice-based randomized trial for the treatment of childhood obesity in rural communities. Approximately 6 weeks into the originally planned 10-week enrollment period, the trial was forced to pause all study activity due to the COVID-19 pandemic. This pause necessitated a substantial revision in recruitment, enrollment, and other study methods in order to complete the trial using virtual procedures. This descriptive paper outlines methods used to recruit, enroll, and manage clinical trial participants with technology to obtain informed consent, obtain height and weight measurements by video, and maintain participant engagement throughout the duration of the trial.
Methods:
The study team reviewed the IRB records, protocol team meeting minutes and records, and surveyed the site teams to document the impact of the COVID-19 shift to virtual procedures on the study. The IRB approved study changes allowed for flexibility between clinical sites given variations in site resources, which was key to success of the implementation.
Results:
All study sites faced a variety of logistical challenges unique to their location yet successfully recruited the required number of patients for the trial. Ultimately, virtual procedures enhanced our ability to establish relationships with participants who were previously beyond our reach, but presented several challenges and required additional resources.
Conclusion:
Lessons learned from this study can assist other study groups in navigating challenges, especially when recruiting and implementing studies with rural and underserved populations or during challenging events like the pandemic.
The process of identifying and connecting with clinical trial study teams can be challenging and difficult for members of the public. The national volunteer community registry, ResearchMatch, and the public clinical trials search tool, Trials Today, work in tandem to bridge this connection by providing a streamlined process for potential participants to identify clinical trials which may be of interest.
Methods:
Building on the existing infrastructure of ResearchMatch and Trials Today, we created a mechanism by which the public can request that their basic contact information (e.g., email/phone) be securely shared with any actively recruiting clinical trial, including trials with no existing relationship with ResearchMatch.
Results:
Within the first 2 years of use (July 2019–July 2021), ResearchMatch Volunteers sent 12,251 requests to study teams. On average, 20% of these requests were accepted by the study teams.
Conclusions:
The utilization of this tool indicates that there is active interest among members of the public to independently contact study teams about trials of interest. Additionally, research teams unaffiliated with ResearchMatch are willing to at minimum accept contact information. This allows ResearchMatch to successfully serve as a medium, connecting members of the public with actively recruiting trials.
Ephrem the Syrian is one of the two most important fourth-century Syriac writers.1 He was born ca. 307–309 in the Roman city of Nisibis (modern-day Nusaybin in Turkey) and was likely raised as a Christian, having close relationships with the city’s bishops from his youth. He was a member of the îḥîdāyê (“single ones”), a group within the larger Christian community whose members devoted themselves to asceticism and celibacy without forming a distinct monastic community. This was a pattern of Christian living that was peculiar to Syriac-speaking regions. Ephrem also served his community as a teacher and perhaps also as a deacon. Above all, Ephrem was a writer: he wrote in multiple genres, including biblical commentaries and metrical homilies (memre), but he is especially known for his hymns (madrāse), about 400 of which are extant. In 363 Ephrem relocated to Edessa (modern-day Urfa in Turkey) when Nisibis, on the border between the Roman and Persian Empires, was ceded by the Romans to the Persians, prompting Christians to emigrate.
The similarities in the way that the ubiquitous cult of saints was expressed in Wales, Cornwall and Brittany form a major body of evidence for contact among these regions. Overtly ecclesiastical place-names, containing such elements as *lann, are unusually common in all three regions. The implications of these for similarities and differences in church-organisation are discussed. The significance of the appearance of the same personal names compounded in ecclesiastical place-names in different British-speaking regions is explored. These seem likely in most cases to reflect movements of the devotees of particular saints between Wales, Cornwall and Brittany from the sixth to the ninth centuries and particularly the reliance of Bretons on the educational and spiritual resources of important Welsh churches. Contact between Brittany and Cornwall was more sustained and more intimate: a tenth-century list reveals a number of Breton saints established at permanent cult-sites in Cornwall by the tenth century and more were to follow by the central Middle Ages; Cornish and Breton authors also drew on each other’s work in composing saints’ Lives throughout the medieval period. By contrast the relative rarity of Irish saints’ cults in Brittany and the absence of Breton saints from Ireland implies a more distant relationship.
Cultural relations between Brittany and Wales seem to have grown more distant in the ninth to eleventh centuries. The Norman Conquest, involving Bretons alongside Normans, revitalised these connections and in particular greatly raised the profile of Bretons in Wales. The attempt by the clergy of Dol in Brittany to make their see an archbishopric encouraged similar ambitions on the part of the churches of St Davids and Llandaf in south Wales. Sharing of pseudo-historical information between the clergy of Llancarfan (Wales) and Quimperlé (Brittany) created the conditions for Geoffrey of Monmouth to write (by 1139) his hugely influential ‘History of the Kings of Britain’. Geoffrey encouraged the opinion-formers of his time to see the Britons as a single people – not necessarily to the advantage of the Breton elite, who were part of French chivalric society in political fact, but who could be cast in the literary role of ‘barbarians’. This view of the Bretons reached a climax in the 1160s and 1170s when Breton revolt menaced the ‘Angevin empire’ of King Henry II of England, but became less relevant after 1203 when the Breton nobility transferred their allegiance to the king of France. The paths of Wales and Brittany then diverged, to judge by the comparatively slight role that Brittany played in the Welsh learned and literary tradition in the later Middle Ages.