Variations in the health status of urban populations in Roman Britain: a comparison of skeletal samples from major and minor towns

Romano-British towns are conventionally divided into those that possessed administrative powers (the major or ‘public’ towns) and those that did not (the minor or ‘small towns’). Public towns and small towns differed in terms of size and socioeconomic status, with the latter sometimes characterised as semi-rural rather than truly urban. Hitherto, research into the differing nature of the communities at public and small towns has focused primarily on variations in settlement morphology, architecture and material culture. This study provides a new perspective on the issue by examining osteological indicators of lifestyle and health in skeletal samples from these two categories of site. Roman populations from the small town of Ancaster, Lincs (N=271) and the public town of Winchester, Hants (N=330) dating to c. AD 200-410 were analysed using standard osteological methods. Data on age-at-death, growth and stature, and skeletal and dental pathology were recorded and compared using a range of statistical tests to identify potential differences. Additionally, published data for contemporaneous populations were collated for comparison. A biocultural approach was used to contextualise the data with reference to archaeological and historical evidence. Some differences in demography were observed, but were probably the result of sample biases. No marked differences in growth or stature were observed. Pathology prevalence rates were comparable for many conditions. However, higher rates of joint disease at Ancaster, and differences in the pattern of long bone trauma may point to the Ancaster population having experienced a more agrarian lifestyle, engaging in more frequent and/or extended periods of heavy labour. In contrast, there was more evidence for violent trauma at Winchester, and the frequencies of three non-specific indicators of ill health (cribra orbitalia, porotic hyperostosis and dental enamel hypoplasia) and scurvy were higher. This suggests that people at Winchester experienced greater levels of social, dietary and environmental stress, perhaps reflecting a larger, more heterogeneous population. Dental health status was generally poorer at Ancaster, which may be due to differences in diet, oral hygiene and/or other non-dietary factors. Published data for other populations broadly support the study conclusions, although comparisons were limited by incompatibilities in methodology and data presentation. Overall, the findings corroborate existing perspectives on the socio-economic characters of public and small towns, but differences were not pronounced. The significance of the findings is discussed in relation to the nature of settlement and society in Roman Britain

Computer Game Play Reduces Intrusive Memories of Experimental Trauma via Reconsolidation-Update Mechanisms.

Memory of a traumatic event becomes consolidated within hours. Intrusive memories can then flash back repeatedly into the mind's eye and cause distress. We investigated whether reconsolidation-the process during which memories become malleable when recalled-can be blocked using a cognitive task and whether such an approach can reduce these unbidden intrusions. We predicted that reconsolidation of a reactivated visual memory of experimental trauma could be disrupted by engaging in a visuospatial task that would compete for visual working memory resources. We showed that intrusive memories were virtually abolished by playing the computer game Tetris following a memory-reactivation task 24 hr after initial exposure to experimental trauma. Furthermore, both memory reactivation and playing Tetris were required to reduce subsequent intrusions (Experiment 2), consistent with reconsolidation-update mechanisms. A simple, noninvasive cognitive-task procedure administered after emotional memory has already consolidated (i.e., > 24 hours after exposure to experimental trauma) may prevent the recurrence of intrusive memories of those emotional events

Contractile force is enhanced in Aortas from pendrin null mice due to stimulation of angiotensin II-dependent signaling.

Pendrin is a Cl-/HCO3- exchanger expressed in the apical regions of renal intercalated cells. Following pendrin gene ablation, blood pressure falls, in part, from reduced renal NaCl absorption. We asked if pendrin is expressed in vascular tissue and if the lower blood pressure observed in pendrin null mice is accompanied by reduced vascular reactivity. Thus, the contractile responses to KCl and phenylephrine (PE) were examined in isometrically mounted thoracic aortas from wild-type and pendrin null mice. Although pendrin expression was not detected in the aorta, pendrin gene ablation changed contractile protein abundance and increased the maximal contractile response to PE when normalized to cross sectional area (CSA). However, the contractile sensitivity to this agent was unchanged. The increase in contractile force/cross sectional area observed in pendrin null mice was due to reduced cross sectional area of the aorta and not from increased contractile force per vessel. The pendrin-dependent increase in maximal contractile response was endothelium- and nitric oxide-independent and did not occur from changes in Ca2+ sensitivity or chronic changes in catecholamine production. However, application of 100 nM angiotensin II increased force/CSA more in aortas from pendrin null than from wild type mice. Moreover, angiotensin type 1 receptor inhibitor (candesartan) treatment in vivo eliminated the pendrin-dependent changes contractile protein abundance and changes in the contractile force/cross sectional area in response to PE. In conclusion, pendrin gene ablation increases aorta contractile force per cross sectional area in response to angiotensin II and PE due to stimulation of angiotensin type 1 receptor-dependent signaling. The angiotensin type 1 receptor-dependent increase in vascular reactivity may mitigate the fall in blood pressure observed with pendrin gene ablation

The Winchcombe meteorite – a regolith breccia from a rubble-pile CM chondrite asteroid

The Winchcombe meteorite is a CM chondrite breccia composed of eight distinct lithological units plus a cataclastic matrix. The degree of aqueous alteration varies between intensely altered CM2.0 and moderately altered CM2.6. Although no lithology dominates, three heavily altered rock types (CM2.1-2.3) represent >70 area%. Tochilinite-cronstedtite intergrowths (TCIs) are common in several lithologies. Their compositions can vary significantly, even within a single lithology, which can prevent a clear assessment of alteration extent if only TCI composition is considered. We suggest this is due to early alteration under localised geochemical microenvironments creating a diversity of compositions and because later reprocessing was incomplete, leaving a record of the parent body’s fluid history. In Winchcombe fragments of primary accretionary rock are held within a cataclastic matrix (~15 area%). This material is impact-derived fallback debris. Its grain size and texture suggest that the disruption of the original parent asteroid responded by intergranular fracture at grain sizes <100 µm, while larger phases, such as whole chondrules, splintered apart. Re-accretion formed a poorly lithified body. During atmospheric entry, the Winchcombe meteoroid broke apart with new fractures preferentially cutting through the weaker cataclastic matrix and separating the breccia into its component clasts. The strength of the cataclastic matrix imparts a control on the survival of CM chondrite meteoroids. Winchcombe’s unweathered state and diversity of lithologies makes it an ideal sample for exploring the geological history of the CM chondrite group.Additional authors: H. Mansour, S. Piazolo, T. Salge, R. Heard, R. Findlay, A. J. King, H. C. Bates, M. R. Lee, N. R. Stephen, F. M. Willcocks, R. C. Greenwood, I. A. Franchi, S. S. Russell, C. S. Harrison, P. F. Schofield, N. V. Almeida, C. Floyd, P.-E. Martin, K. H. Joy, P. J. Wozniakiewicz, D. Hallatt, M. J. Burchell, L. S. Alesbrook, V. Spathis, L. T. Cornwell, A. Digna

Lineage replacement and evolution captured by 3 years of the United Kingdom Coronavirus (COVID-19) Infection Survey

The Office for National Statistics Coronavirus (COVID-19) Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors, although this was also accompanied by a gradual fall in average viral burdens from June 2021 to March 2023. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non-SGTF over time. Evolution was characterized by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant