Central Asian Economies And Ecologies In The Late Bronze Age: Geometric Morphometrics of the Caprid Astragalus And Zooarchaeological Investigations Of Pastoralism

Abstract Sheep and goat formed the foundation of pastoral activity across the Central Asian steppe through the Bronze Age. Theories of pastoral activity have assumed that flocks were uniform in association with ethnic groups that crossed the steppe with new ceramic forms and technologies. This study investigated differences between flocks of sheep and goat across the eastern Kazakh steppe in the Late and Final Bronze Age to elucidate the potential for animal exchange and mobility. Geometric morphometric techniques were applied to archaeological astragali from Ovis aries and Capra hircus. The methods for measurement and analysis were carefully developed to control only for inherited characteristics that relate to environmentally driven adaptations in the movement of the hind limb. Efficiency of movement in this limb is tied to survival and reproductive success of animals. Specimens were selected from three archaeological sites located in different ecozones across the steppe to maximize ecological variability. Geometric morphometric results revealed that flocks of sheep exhibited unique astragalus morphology, indicating that crossbreeding and exchange did not occur between sites. These sites were also subjected to full zooarchaeological analyses to investigate variability of economic subsistence patterns. The total number of species as well as investigations into survival and skeletal body part representation revealed that each site had unique subsistence patterns that were related to local ecological resource availability, despite material culture links. This variability in subsistence patterns and flock uniformity indicate that animal trade was not a feature of steppe networks. Local lifeways were specific to small patches of the steppe, despite overarching shared material cultures

Utility of the Living (Well Through) Intergenerational Fitness and Exercise Program as a County-Delivered Extension Program

Rural-residing older adults are not participating in regular physical activity. Extension is in an excellent position to fill this programming void through transdisciplinary programming such as the Living (well through) Intergenerational Fitness and Exercise (LIFE) program. Qualitative evaluation was conducted to assess the LIFE program\u27s utility as an Extension-delivered program. Nearly all LIFE program managers were satisfied with the program and were likely to recommend it to others. Best liked program features and attributes were the ready-to-use curriculum, corresponding training, and intergenerational and rural focuses. These results suggest that the LIFE program is viewed as appropriate for delivery by Extension

The activity of cAMP-Phosphodiesterase 4D7 (PDE4D7) is regulated by protein kinase A-dependent phosphorylation within its unique N-terminus

The cyclic AMP phosphodiesterases type 4 (PDE4s) are expressed in a cell specific manner, with intracellular targeting directed by unique N-terminal anchor domains. All long form PDE4s are phosphorylated and activated by PKA phosphorylation within their upstream conserved region 1 (UCR1). Here, we identify and characterise a novel PKA site (serine 42) within the N-terminal region of PDE4D7, an isoform whose activity is known to be important in prostate cancer progression and ischemic stroke. In contrast to the UCR1 site, PKA phosphorylation of the PDE4D7 N-terminus appears to occur constitutively and inhibits PDE4 activity to allow cAMP signalling under basal conditions

Virtuality in human supervisory control: Assessing the effects of psychological and social remoteness

Virtuality would seem to offer certain advantages for human supervisory control. First, it could provide a physical analogue of the 'real world' environment. Second, it does not require control room engineers to be in the same place as each other. In order to investigate these issues, a low-fidelity simulation of an energy distribution network was developed. The main aims of the research were to assess some of the psychological concerns associated with virtual environments. First, it may result in the social isolation of the people, and it may have dramatic effects upon the nature of the work. Second, a direct physical correspondence with the 'real world' may not best support human supervisory control activities. Experimental teams were asked to control an energy distribution network. Measures of team performance, group identity and core job characteristics were taken. In general terms, the results showed that teams working in the same location performed better than team who were remote from one another

Translation Control by p53

The translation of mRNAs plays a critical role in the regulation of gene expression and therefore, in the regulation of cell proliferation, differentiation and apoptosis. Unrestricted initiation of translation causes malignant transformation and plays a key role in the maintenance and progression of cancers. Translation initiation is regulated by the ternary complex and the eukaryotic initiation factor 4F (eIF4F) complex. The p53 tumor suppressor protein is the most well studied mammalian transcription factor that mediates a variety of anti-proliferative processes. Post-transcriptional mechanisms of gene expression in general and those of translation in particular play a major role in shaping the protein composition of the cell. The p53 protein regulates transcription and controls eIF4F, the ternary complex and the synthesis of ribosomal components, including the down-regulation of rRNA genes. In summary, the induction of p53 regulates protein synthesis and translational control to inhibit cell growth

IL-24 Promotes Apoptosis through cAMP-Dependent PKA Pathways in Human Breast Cancer Cells

Interleukin 24 (IL-24) is a tumor-suppressing protein, which inhibits angiogenesis and induces cancer cell-specific apoptosis. We have shown that IL-24 regulates apoptosis through phosphorylated eukaryotic initiation factor 2 alpha (eIF2α) during endoplasmic reticulum (ER) stress in cancer. Although multiple stresses converge on eIF2α phosphorylation, the cellular outcome is not always the same. In particular, ER stress-induced apoptosis is primarily regulated through the extent of eIF2α phosphorylation and activating transcription factor 4 (ATF4) action. Our studies show for the first time that cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) activation is required for IL-24-induced cell death in a variety of breast cancer cell lines and this event increases ATF4 activity. We demonstrate an undocumented role for PKA in regulating IL-24-induced cell death, whereby PKA stimulates phosphorylation of p38 mitogen-activated protein kinase and upregulates extrinsic apoptotic factors of the Fas/FasL signaling pathway and death receptor 4 expression. We also demonstrate that phosphorylation and nuclear import of tumor suppressor TP53 occurs downstream of IL-24-mediated PKA activation. These discoveries provide the first mechanistic insights into the function of PKA as a key regulator of the extrinsic pathway, ER stress, and TP53 activation triggered by IL-24

Prevalence and risk factors for long COVID among adults in Scotland using electronic health records : a national, retrospective, observational cohort study

Acknowledgements This work was supported by the Chief Scientist Office, grant number COV/LTE/20/15. EAVE II is supported by a grant (MC_PC_19075) from the Medical Research Council; and a grant (MC_PC_19004) from BREATHE–The Health Data Research Hub for Respiratory Health, funded through the UK Research and Innovation Industrial Strategy Challenge Fund. LD was supported by a post-doctoral clinical fellowship from the Asthma UK Centre for Applied Research. SVK acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17). The authors would like to acknowledge the support of Dave Kelly and Lamorna Brown of Albasoft Ltd., and Sharon Kennedy, Mike Birnie, Safraj Shahul Hameed and Elliott Hall of Public Health Scotland for their involvement in obtaining approvals, provisioning, and linking data and the use of the secure analytical platform within the National Safe Haven. Funding Chief Scientist Office (Scotland), Medical Research Council, and BREATHE.Peer reviewe

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Prevalence and risk factors for long COVID among adults in Scotland using electronic health records : a national, retrospective, observational cohort study

Background: Long COVID is a debilitating multisystem condition. The objective of this study was to estimate the prevalence of long COVID in the adult population of Scotland, and to identify risk factors associated with its development. Methods: In this national, retrospective, observational cohort study, we analysed electronic health records (EHRs) for all adults (≥18 years) registered with a general medical practice and resident in Scotland between March 1, 2020, and October 26, 2022 (98–99% of the population). We linked data from primary care, secondary care, laboratory testing and prescribing. Four outcome measures were used to identify long COVID: clinical codes, free text in primary care records, free text on sick notes, and a novel operational definition. The operational definition was developed using Poisson regression to identify clinical encounters indicative of long COVID from a sample of negative and positive COVID-19 cases matched on time-varying propensity to test positive for SARS-CoV-2. Possible risk factors for long COVID were identified by stratifying descriptive statistics by long COVID status. Findings: Of 4,676,390 participants, 81,219 (1.7%) were identified as having long COVID. Clinical codes identified the fewest cases (n = 1,092, 0.02%), followed by free text (n = 8,368, 0.2%), sick notes (n = 14,469, 0.3%), and the operational definition (n = 64,193, 1.4%). There was limited overlap in cases identified by the measures; however, temporal trends and patient characteristics were consistent across measures. Compared with the general population, a higher proportion of people with long COVID were female (65.1% versus 50.4%), aged 38–67 (63.7% versus 48.9%), overweight or obese (45.7% versus 29.4%), had one or more comorbidities (52.7% versus 36.0%), were immunosuppressed (6.9% versus 3.2%), shielding (7.9% versus 3.4%), or hospitalised within 28 days of testing positive (8.8% versus 3.3%%), and had tested positive before Omicron became the dominant variant (44.9% versus 35.9%). The operational definition identified long COVID cases with combinations of clinical encounters (from four symptoms, six investigation types, and seven management strategies) recorded in EHRs within 4–26 weeks of a positive SARS-CoV-2 test. These combinations were significantly (p < 0.0001) more prevalent in positive COVID-19 patients than in matched negative controls. In a case-crossover analysis, 16.4% of those identified by the operational definition had similar healthcare patterns recorded before testing positive. Interpretation:The prevalence of long COVID presenting in general practice was estimated to be 0.02–1.7%, depending on the measure used. Due to challenges in diagnosing long COVID and inconsistent recording of information in EHRs, the true prevalence of long COVID is likely to be higher. The operational definition provided a novel approach but relied on a restricted set of symptoms and may misclassify individuals with pre-existing health conditions. Further research is needed to refine and validate this approach

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention