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Abstract Palaeontologists have long sought to explain the diversification of individual clades to whole biotas at global scales. Advances in our understanding of the spatial distribution of the fossil record through geological time, however, has demonstrated that global trends in biodiversity were a mosaic of regionally heterogeneous diversification processes. Drivers of diversification must presumably have also displayed regional variation to produce the spatial disparities observed in past taxonomic richness. Here, we analyse the fossil record of ammonoids, pelagic shelled cephalopods, through the Late Cretaceous, characterised by some palaeontologists as an interval of biotic decline prior to their total extinction at the Cretaceous-Paleogene boundary. We regionally subdivide this record to eliminate the impacts of spatial sampling biases and infer regional origination and extinction rates corrected for temporal sampling biases using Bayesian methods. We then model these rates using biotic and abiotic drivers commonly inferred to influence diversification. Ammonoid diversification dynamics and responses to this common set of diversity drivers were regionally heterogeneous, do not support ecological decline, and demonstrate that their global diversification signal is influenced by spatial disparities in sampling effort. These results call into question the feasibility of seeking drivers of diversity at global scales in the fossil record.

Background Multiple Sclerosis (MS) is a challenging disease to identify within large repositories of healthcare data. Diagnosis can be protracted requiring many modalities that may not form part of the repository data collection. Accurate case finding would have multiple applications for studying epidemiology. Aim Develop a case finding algorithm within the Secure Anonymised Information Linkage (SAIL) Databank that can reliably elicit Multiple Sclerosis. Method Utilising a cross sectional cohort study we used multiple datasets within SAIL; General Practice, Inpatient, Outpatient and Office of National Statistics to develop our case finding algorithm based on the coding nomenclatures and timing within these datasets. The results of this algorithm were then tested against two patient data sets: The UK MS Register (n=836), consisting of mostly self confirmed disease and a clinical cohort from South West Wales (n=713). Results From 4,757,428 records, the algorithm identified 6,194 cases of MS within Wales on 31st December 2020 (prevalence 221.65 [95%CI 216.17–227.24] per 100,000). Case finding sensitivity and specificity was 96.8% and 99.9% for the clinically validated population-based cohort and sensitivity was 96.7% from the self-declared registry population. Conclusion We successfully identified MS cases within Wales and verified this within two independent data sets.

Many modern extinction drivers are shared with past mass extinction events, such as rapid climate warming, habitat loss, pollution and invasive species. This commonality presents a key question: can the extinction risk of species during past mass extinction events inform our predictions for a modern biodiversity crisis? To investigate if it is possible to establish which species were more likely to go extinct during mass extinctions, we applied a functional trait-based model of extinction risk using a machine learning algorithm to datasets of marine fossils for the end-Permian, end-Triassic and end-Cretaceous mass extinctions. Extinction selectivity was inferred across each individual mass extinction event, before testing whether the selectivity patterns obtained could be used to 'predict' the extinction selectivity exhibited during the other mass extinctions. Our analyses show that, despite some similarities in extinction selectivity patterns between ancient crises, the selectivity of mass extinction events is inconsistent, which leads to a poor predictive performance. This lack of predictability is attributed to evolution in marine ecosystems, particularly during the Mesozoic Marine Revolution, associated with shifts in community structure alongside coincident Earth system changes. Our results suggest that past extinctions are unlikely to be informative for predicting extinction risk during a projected mass extinction.

Abstract Background Morbidity and mortality rates from chronic non-communicable diseases (CNCDs) are increasing globally. In Ghana, CNCDs account for 43% of all deaths. We examined the Health-Related Quality of Life (HRQoL) and associated factors among adults living with CNCDs in the Ho Municipality. Methods This was a health facility-based descriptive cross-sectional study among 432 adults living with cancer, diabetes, chronic kidney disease (CKD), stroke, and hypertension in the Ho Municipality of Ghana. The study adopted the EQ-5D-5L instrument and the Ugandan value set to compute respondents’ HRQoL index. Quantile regression models were used in analysing the data with STATA v17.0 at 95% Confidence Intervals, and statistical significance set at p

The impacts of climate change on marine organisms have been increasingly documented in laboratory and experimental studies. However, the use of different taxonomic groupings and the assessment of a range of processes make identifying overall trends challenging. Meta-analysis has been used to determine general trends, but coarse taxonomic granularity may mask phylogenetically specific responses. Bivalve molluscs are a data-rich clade of ecologically and economically important calcifying marine taxa that allow for the assessment of species-specific vulnerability across developmental stages. Drawing on the large body of available literature, we conduct a meta-analysis of 203 unique experimental set-ups in order to examine how bivalve growth responds to increased water temperature, acidity, deoxygenation, and changes in salinity in 10 climate change stressor combinations. This is the most complete examination of bivalve responses to date and shows that anthropogenic climate change will disproportionally affect particular families, suggesting taxonomic differentiation in climate change response. Specifically, Mytilidae, Ostreidae, and Pectinidae (67 % of experiments) respond with negative effect sizes for all individual stressors, whereas responses in Pinnidae, Tellinidae, and Veneridae are more complex. Our analysis shows that earlier studies reporting negative impacts on bivalves are driven by only three or four well-studied, commercially important families. Despite the taxonomic differentiation, almost all drivers and their combinations have significant negative effects on growth. The synergistic impacts of deoxygenation, acidification, and temperature result in the largest negative effect size. Infaunal taxa, including Tellinidae and Veneridae, appear more resistant to warming and oxygen reduction than epifaunal or motile taxa, but this difference between the two taxa is also based on a small number of data points. The current focus of experimental set-ups on commercially important taxa and families within a small geographic range creates gaps in the understanding of global impacts on these economically important foundation organisms.

Abstract Background The COVID-19 pandemic created a complex high-risk clinical research environment with clinical research activities significantly impacted. Clinical research stakeholders adapted rapidly to new clinical practices; PPE, infection control policies, all while engaging with a more unwell patient demographic. The aim of this study is to explore the experiences of conducting clinical research during COVID-19 with clinical research stakeholders. Methods This qualitative study of semi-structured interviews conducted with clinical research stakeholders in an acute Hospital setting across a variety of disciplines; Consultant Geriatrician, Clinical Research Nurse, Occupational Therapy, Physiotherapy. Interviews were fully transcribed prior to reflexive thematic analysis. NVivo software was used to support data management and analysis. Results Three main themes were produced; (1) The challenging COVID-19 clinical research landscape, (2) COVID-19 clinical research communication barriers, and (3) Adaptations and learnings from clinical research during COVID-19. Conclusions This study explored the experiences of conducting clinical research during COVID-19 with clinical research stakeholders examining challenges faced and adaptations required. The findings inform, equip and support clinical research stakeholders in the event of future adverse public health events.

Subglacial till can deform when overriding ice exerts shear traction at the ice--till interface. This deformation leaves a strain signature in the till, aligning grains in the direction of ice flow and producing a range of diagnostic microstructures. Constraining the conditions that produce these kinematic indicators is key to interpreting the myriad of features found in basal till deposits. Here, we used a cryogenic ring shear device with transparent sample chamber walls to slip a ring of temperate ice over a till bed from which we examined the strain signature in the till. We used cameras mounted to the side of the ring shear and bead strings inserted in the till to estimate the strain distribution within the till layer. Following the completion of the experiment, we extracted and analyzed anisotropy of magnetic susceptibility (AMS) samples and created thin sections of the till bed for microstructure analysis. We then compared the AMS and microstructures with the observed strain history to examine the relationship between kinematic indicators and strain in a setting where shear traction is supplied by ice. We found that AMS fabrics show a high degree of clustering in regions of high strain near the ice--till interface. In the uppermost zone of till, [k.sub.1] eigenvector azimuths are generally aligned with ice flow, and [S.sub.1] eigenvalues are high. However, [S.sub.1] eigenvalues and the alignment of the [k.sub.1] eigenvector with ice flow decrease nonlinearly with distance from the ice--till interface. There is a high occurrence of microshears in the zone of increased deformation. Key words: till deformation, microstructures, anisotropy of magnetic susceptibility, glacial geology, 1. Introduction Many of the world's fastest moving glaciers slip atop till beds, and the mechanics active within these beds control glacier motion (Kamb 2001) and landform development (Clark 1993). [...]

BackgroundIn Sub-Saharan Africa (SSA), there is a noticeable shift from infectious diseases to chronic non-communicable diseases (CNCDs) based on recent studies. However, other studies suggest that social support can significantly improve self-care, increase knowledge of disease symptoms, and ultimately increase overall well-being in patients with CNCDs. In this study, we investigated the influence of perceived social support on treatment adherence among adults living with CNCDs in the Ho Municipality.MethodsThis was a health facility-based cross-sectional study among 432 adults living with cancer, diabetes, chronic kidney disease (CKD), stroke, and hypertension in the Ho Municipality of the Volta Region, Ghana. We adopted the Multi-dimensional Scale of Perceived Social Support (MSPSS), Medication Adherence Rating Scale and independent items to collect data. Logistic regression models were used to analyze the data with STATA v17.0 at 95% Confidence Intervals with statistical significance set at pResultsMajority of the participants (62%) reported high levels of perceived social support. While friends were the main source of support (69.4%), significant others provided the least support (45.4%). Among the dimensions of treatment adherence, participants demonstrated the highest adherence to reviews/check-ups (98.8%), while medication adherence had the highest level of non-adherence (38%). We did not find a significant association between perceived social support and overall treatment adherence, except for individuals with low perceived social support from friends (aOR = 8.58, 95% CI = 4.21,17.52), who were more likely to exhibit high adherence to behavioural and lifestyle recommendations.ConclusionWhile the majority of respondents reported high perceived social support, there was no significant link between social support and overall treatment adherence. However, individuals with low support from friends showed a notably increased adherence to behavioural and lifestyle recommendations. This underscores the nuanced impact of social support on specific aspects of adherence, highlighting the need for targeted interventions tailored to individual support networks.

JET, the world’s largest operating tokamak with unique Be/W wall and tritium handling capability, completed a Deuterium-Tritium (D-T) campaign in 2021 (Maggi et al 29th Fusion Energy Conf. ) following a decade of preparatory experiments, dedicated enhancements, technical rehearsals and training (Horton et al 2016 Fusion Eng. Des. 109–111 925). Operation with tritium raises significant technical, safety and scientific challenges not encountered in standard protium or deuterium operation. This contribution describes the tritium operational requirements, pulses and technical preparations, new operating procedures, lessons learned and details on the achieved operational availability and performance. The preparation and execution of the recent JET tritium experiments benefitted from the previous experience in 1991 (Preliminary Tritium Experiment), 1997 (DTE1 campaign) and 2003 (Trace Tritium Campaigns) and consisted of the following five phases: technical rehearsals and scenario preparation, tritium commissioning, 100% tritium campaign, D-T campaign (DTE2), tritium clean-up. Following the clean-up JET resumed normal operation and is currently undertaking a further D-T campaign (DTE3).

Phelan-McDermid syndrome (PMS), also called 22q13.3 deletion syndrome, is a rare genetic disorder affecting at least 2,000 people worldwide (Phelan-McDermid Syndrome Foundation, 2019, How rare is Phelan-McDermid?). PMS has many distinguishing characteristics and many medical specialties have been recommended to treat the clinical features. While many therapies, including behavioral therapy, have been speculated to be beneficial in treating PMS, there is little known regarding their effectiveness [Costales, J. L. and Kolevzon, A. 2015. Phelan-McDermid syndrome and SHANK3: Implications for treatment. Neurotherapeutics: The Journal of the American Society for Experimental Neurotherapeutics, 12, 620-630.]. Behavior analysis has the capability to help in many areas of treatment for PMS either directly through, for example, behavior treatment to address aggressive behavior, or through collaborating with other specialties treating PMS by combining, for example, behavioral principles in the alleviation of medical issues such as constipation. Currently, there is a role for the behavior analyst to expand our field and identify effective treatments for those with PMS while we wait for a cure. In this paper, we discuss how medical considerations may affect behavior interventions and make recommendations for the behavior analyst working with PMS.

Introduction: Prescribing guidance for disease-modifying treatment (DMT) in multiple sclerosis (MS) is centred on a clinical diagnosis of relapsing–remitting MS (RRMS). DMT prescription guidelines and monitoring vary across countries. Standardising the approach to diagnosis of disease course, for example, assigning RRMS or secondary progressive MS (SPMS) diagnoses, allows examination of the impact of health system characteristics on the stated clinical diagnosis and treatment access. Methods: We analysed registry data from six cohorts in five countries (Czech Republic, Denmark, Germany, Sweden and United Kingdom) on patients with an initial diagnosis of RRMS. We standardised our approach utilising a pre-existing algorithm (DecisionTree, DT) to determine patient diagnoses of RRMS or secondary progressive MS (SPMS). We identified five global drivers of DMT prescribing: Provision, Availability, Funding, Monitoring and Audit, data were analysed against these concepts using meta-analysis and univariate meta-regression. Results: In 64,235 patients, we found variations in DMT use between countries, with higher usage in RRMS and lower usage in SPMS, with correspondingly lower usage in the UK compared to other registers. Factors such as female gender ( p = 0.041), increasing disability via Expanded Disability Status Scale (EDSS) score ( p = 0.004), and the presence of monitoring ( p = 0.029) in SPMS influenced the likelihood of receiving DMTs. Standardising the diagnosis revealed differences in reclassification rates from clinical RRMS to DT-SPMS, with Sweden having the lowest rate Sweden (Sweden 0.009, range: Denmark 0.103 – UK portal 0.311). Those with higher EDSS at index ( p

In 2021 JET exploited its unique capabilities to operate with T and D–T fuel with an ITER-like Be/W wall (JET-ILW). This second major JET D–T campaign (DTE2), after DTE1 in 1997, represented the culmination of a series of JET enhancements—new fusion diagnostics, new T injection capabilities, refurbishment of the T plant, increased auxiliary heating, in-vessel calibration of 14 MeV neutron yield monitors—as well as significant advances in plasma theory and modelling in the fusion community. DTE2 was complemented by a sequence of isotope physics campaigns encompassing operation in pure tritium at high T-NBI power. Carefully conducted for safe operation with tritium, the new T and D–T experiments used 1 kg of T (vs 100 g in DTE1), yielding the most fusion reactor relevant D–T plasmas to date and expanding our understanding of isotopes and D–T mixture physics. Furthermore, since the JET T and DTE2 campaigns occurred almost 25 years after the last major D–T tokamak experiment, it was also a strategic goal of the European fusion programme to refresh operational experience of a nuclear tokamak to prepare staff for ITER operation. The key physics results of the JET T and DTE2 experiments, carried out within the EUROfusion JET1 work package, are reported in this paper. Progress in the technological exploitation of JET D–T operations, development and validation of nuclear codes, neutronic tools and techniques for ITER operations carried out by EUROfusion (started within the Horizon 2020 Framework Programme and continuing under the Horizon Europe FP) are reported in (Litaudon et al Nucl. Fusion accepted), while JET experience on T and D–T operations is presented in (King et al Nucl. Fusion submitted).

Mass extinction at the Cretaceous-Paleogene (K-Pg) boundary coincides with the Chicxulub bolide impact and also falls within the broader time frame of Deccan trap emplacement. Critically, though, empirical evidence as to how either of these factors could have driven observed extinction patterns and carbon cycle perturbations is still lacking. Here, using boron isotopes in foraminifera, we document a geologically rapid surface-ocean pH drop following the Chicxulub impact, supporting impact-induced ocean acidification as a mechanism for ecological collapse in the marine realm. Subsequently, surface water pH rebounded sharply with the extinction of marine calcifiers and the associated imbalance in the global carbon cycle. Our reconstructed water-column pH gradients, combined with Earth system modeling, indicate that a partial ∼50% reduction in global marine primary productivity is sufficient to explain observed marine carbon isotope patterns at the K-Pg, due to the underlying action of the solubility pump. While primary productivity recovered within a few tens of thousands of years, inefficiency in carbon export to the deep sea lasted much longer. This phased recovery scenario reconciles competing hypotheses previously put forward to explain the K-Pg carbon isotope records, and explains both spatially variable patterns of change in marine productivity across the event and a lack of extinction at the deep sea floor. In sum, we provide insights into the drivers of the last mass extinction, the recovery of marine carbon cycling in a postextinction world, and the way in which marine life imprints its isotopic signal onto the geological record.

Many modern extinction drivers are shared with past mass extinction events, such as rapid climate warming, habitat loss, pollution and invasive species. This commonality presents a key question: can the extinction risk of species during past mass extinction events inform our predictions for a modern biodiversity crisis? To investigate if it is possible to establish which species were more likely to go extinct during mass extinctions, we applied a functional trait-based model of extinction risk using a machine learning algorithm to datasets of marine fossils for the end-Permian, end-Triassic and end-Cretaceous mass extinctions. Extinction selectivity was inferred across each individual mass extinction event, before testing whether the selectivity patterns obtained could be used to ‘predict’ the extinction selectivity exhibited during the other mass extinctions. Our analyses show that, despite some similarities in extinction selectivity patterns between ancient crises, the selectivity of mass extinction events is inconsistent, which leads to a poor predictive performance. This lack of predictability is attributed to evolution in marine ecosystems, particularly during the Mesozoic Marine Revolution, associated with shifts in community structure alongside coincident Earth system changes. Our results suggest that past extinctions are unlikely to be informative for predicting extinction risk during a projected mass extinction.

Abstract Background Non-ribosomal peptide synthetase-like (NRPS-like) enzymes are highly enriched in fungal genomes and can be discriminated into reducing and non-reducing enzymes. Non-reducing NRPS-like enzymes possess a C-terminal thioesterase domain that catalyses the condensation of two identical aromatic α-keto acids under the formation of enzyme-specific substrate-interconnecting core structures such as terphenylquinones, furanones, butyrolactones or dioxolanones. Ascocoryne sarcoides produces large quantities of ascocorynin, which structurally resembles a terphenylquinone produced from the condensation of p-hydroxyphenylpyruvate and phenylpyruvate. Since the parallel use of two different substrates by a non-reducing NRPS-like enzyme appeared as highly unusual, we investigated the biosynthesis of ascocorynin in A. sarcoides. Results Here, we searched the genome of A. sarcoides for genes coding for non-reducing NRPS-like enzymes. A single candidate gene was identified that was termed acyN. Heterologous gene expression confirmed that AcyN is involved in ascocorynin production but only produces the non-hydroxylated precursor polyporic acid. Although acyN is embedded in an ascocorynin biosynthesis gene cluster, a gene encoding a monooxygenase required for the hydroxylation of polyporic acid was not present. Expression analyses of all monooxygenase-encoding genes from A. sarcoides identified a single candidate that showed the same expression pattern as acyN. Accordingly, heterologous co-expression of acyN and the monooxygenase gene resulted in the production of ascocorynin. Structural modelling of the monooxygenase suggests that the hydrophobic substrate polyporic acid enters the monooxygenase from a membrane facing entry site and is converted into the more hydrophilic product ascocorynin, which prevents its re-entry for a second round of hydroxylation. Conclusion This study characterises the first naturally occurring polyporic acid synthetase from an ascomycete. It confirms the high substrate and product specificity of this non-reducing NRPS-like enzyme and highlights the requirement of a monooxygenase to produce the terphenylquinone ascocorynin.

Background: Previous studies have suggested differences in multiple sclerosis (MS) severity according to ethnicity. Methods: Data were obtained from the UK MS Register, a prospective longitudinal cohort study of persons with MS. We examined the association between self-reported ethnic background and age at onset, symptom of onset and a variety of participant-reported severity measures. We used adjusted multivariable linear regression models to explore the association between ethnicity and impact of MS, and Cox proportional hazards models to assess disability progression. Results: We analysed data from 17,314 people with MS, including participants from self-reported Black (n = 157) or South Asian (n = 230) ethnic backgrounds. Age at MS onset and diagnosis was lower in those of South Asian (median 30.0) and Black (median 33.0) ethnicity compared with White ethnicity (median 35.0). In participants with online MS severity measures available, we found no statistically significant evidence for an association between ethnic background and physical disability in MS in both cross-sectional and longitudinal analyses. Conclusion: We found no association between ethnic background and MS severity in a large, diverse UK cohort. These findings suggest that other factors, such as socioeconomic status and structural inequalities, may explain previous findings. [ABSTRACT FROM AUTHOR]

Background: In Sub-Saharan Africa (SSA), there is a noticeable shift from infectious diseases to chronic non-communicable diseases (CNCDs) based on recent studies. However, other studies suggest that social support can significantly improve self-care, increase knowledge of disease symptoms, and ultimately increase overall well-being in patients with CNCDs. In this study, we investigated the influence of perceived social support on treatment adherence among adults living with CNCDs in the Ho Municipality. Methods: This was a health facility-based cross-sectional study among 432 adults living with cancer, diabetes, chronic kidney disease (CKD), stroke, and hypertension in the Ho Municipality of the Volta Region, Ghana. We adopted the Multi-dimensional Scale of Perceived Social Support (MSPSS), Medication Adherence Rating Scale and independent items to collect data. Logistic regression models were used to analyze the data with STATA v17.0 at 95% Confidence Intervals with statistical significance set at p<0.05. Results: Majority of the participants (62%) reported high levels of perceived social support. While friends were the main source of support (69.4%), significant others provided the least support (45.4%). Among the dimensions of treatment adherence, participants demonstrated the highest adherence to reviews/check-ups (98.8%), while medication adherence had the highest level of non-adherence (38%). We did not find a significant association between perceived social support and overall treatment adherence, except for individuals with low perceived social support from friends (aOR = 8.58, 95% CI = 4.21,17.52), who were more likely to exhibit high adherence to behavioural and lifestyle recommendations. Conclusion: While the majority of respondents reported high perceived social support, there was no significant link between social support and overall treatment adherence. However, individuals with low support from friends showed a notably increased adherence to behavioural and lifestyle recommendations. This underscores the nuanced impact of social support on specific aspects of adherence, highlighting the need for targeted interventions tailored to individual support networks. [ABSTRACT FROM AUTHOR]