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The dystrophin-glycoprotein-complex (DGC), anchored by the transmembrane protein dystroglycan, functions to mechanically link the extracellular matrix and actin cytoskeleton. Breaking this connection is associated with diseases such as muscular dystrophy, yet cleavage of dystroglycan by matrix-metalloproteinases (MMPs) remains an understudied mechanism to disrupt the DGC. We determined the crystal structure of the membrane-adjacent domain (amino acids 491–722) of E. coli expressed human dystroglycan to understand MMP cleavage regulation. The structural model includes tandem immunoglobulin-like (IGL) and sperm/enterokinase/agrin-like (SEAL) domains, which support proteolysis in diverse receptors to facilitate mechanotransduction, membrane protection, and viral entry. The structure reveals a C-terminal extension that buries the MMP site by packing into a hydrophobic pocket, a unique mechanism of MMP cleavage regulation. We further demonstrate structure-guided and disease-associated mutations disrupt proteolytic regulation using a cell-surface proteolysis assay. Thus disrupted proteolysis is a potentially relevant mechanism for "breaking" the DGC link to contribute to disease pathogenesis. [Display omitted] • MMP cleavage in dystroglycan is regulated by a distinct structural mechanism • A C-terminal peptide extension buries the MMP site in a SEAL domain pocket • Structure-guided and disease-associated mutations lead to increased proteolysis • Proteolysis is a relevant mechanism to disrupt ECM to actin mechanical linkage Anderson et al. present the structure of the proteolysis-regulation domain of the ECM receptor dystroglycan, which anchors the dystrophin-glycoprotein-complex adhesive complex to the cytoskeleton. The matrix-metalloprotease (MMP) site is regulated by clamping a unique C-terminal extension to the SEA-like domain, and disruption of this regulation leads to enhanced MMP cleavage. [ABSTRACT FROM AUTHOR]

Purpose: Patient-report outcome measures (PROMs) have gained widespread support as a mechanism to improve healthcare quality. We aimed to map out key enablers and barriers influencing PROMs implementation strategies in routine clinical practice. Methods: An umbrella review was conducted to identify reviews exploring enablers and barriers related to the integration of PROMs in routine clinical practice from January 2000 to June 2023. Information on key enablers and barriers was extracted and summarised thematically according to the Theoretical Domains Framework. Results: 34 reviews met our criteria for inclusion. Identified reviews highlighted barriers such as limited PROMs awareness among clinicians and patients, perceived low value by clinicians and patients, PROMs that were too complex or difficult for patients to complete, poor usability of PROMs systems, delayed feedback of PROMs data, clinician concerns related to use of PROMs as a performance management tool, patient concerns regarding privacy and security, and resource constraints. Enablers encompassed phased implementation, professional training, stakeholder engagement prior to implementation, clear strategies and goals, 'change champions' to support PROMs implementation, systems to respond to issues raised by PROMs, and integration into patient pathways. No consensus favoured paper or electronic PROMs, yet offering both options to mitigate digital literacy bias and integrating PROMs into electronic health records emerged as important facilitators. Conclusions: The sustainable implementation of PROMs is a complex process that requires multicomponent organisational strategies covering training and guidance, necessary time and resources, roles and responsibilities, and consultation with patients and clinicians. [ABSTRACT FROM AUTHOR]

This paper explores some of the ways in which access to the census enumerators books for later nineteenth century censuses, now digitised by the 'Integrated Census Microdata' project, can throw new light on a range of socio-demographic developments in the 'Crofting Counties' between the early 1850s and the early 1880s. Collating and mapping occupational titles by parish reveals major changes in the titles recorded for those farming small land parcels and in the spatial distributions and age profiles or those heading such households. The numbers of household heads reported as 'Crofter' markedly increased between 1851 and 1881 (including outside the 'Crofting Counties'), as use of terms like 'Tenant' and 'Lotter' declined. 'Cottar', even in 1851 used in very small numbers in most places, was reported in 1881 in very limited areas, even where the estates still used it extensively. The number of households headed by 'Fishermen' increased greatly in some areas, notably in Lewis. At the same time, the numbers of men becoming heads of small agriculturalist households at younger ages fell markedly, while rising numbers headed households as 'Fishermen'. Comparative analysis of four case study areas suggests that, when fishing and other incomes fell markedly in the early 1880s, inter-generational differences in access to headship of a croft may have been a significant stimulus to localised outbreaks of disturbance pressing for land reform. [ABSTRACT FROM AUTHOR]

The Think/No-Think (TNT) task has just celebrated 20 years since its inception, and its use has been growing as a tool to investigate the mechanisms underlying memory control and its neural underpinnings. Here, we present a theoretical and practical guide for designing, implementing, and running TNT studies. For this purpose, we provide a step-by-step description of the structure of the TNT task, methodological choices that can be made, parameters that can be chosen, instruments available, aspects to be aware of, systematic information about how to run a study and analyze the data. Importantly, we provide a TNT training package (as Supplementary Material), that is, a series of multimedia materials (e.g., tutorial videos, informative HTML pages, MATLAB code to run experiments, questionnaires, scoring sheets, etc.) to complement this method paper and facilitate a deeper understanding of the TNT task, its rationale, and how to set it up in practice. Given the recent discussion about the replication crisis in the behavioral sciences, we hope that this contribution will increase standardization, reliability, and replicability across laboratories. [ABSTRACT FROM AUTHOR]

Inhibitory control is a fundamental mechanism for adaptive behavior and cognition that features in theories across psychology and cognitive science. Although inhibitory control is thought to regulate processes ranging from actions to memories, most neuroscientific work studies these domains of inhibition separately. Recent crossdomain comparisons have converged on the view that inhibitory control arises from common, domain-general neural mechanisms. We propose that an input inhibition mechanism, acting via fronto-subthalamic inhibitory pathways may contribute to domain-general inhibitory control by suppressing thalamic drive of cortical activity. We argue that β-band activity in local circuits constitutes a potential domain-general signature of inhibitory control. Inhibitory control is a fundamental mechanism underlying flexible behavior and features in theories across many areas of cognitive and psychological science. However, whereas many theories implicitly or explicitly assume that inhibitory control is a domain-general process, the vast majority of neuroscientific work has hitherto focused on individual domains, such as motor, mnemonic, or attentional inhibition. Here, we attempt to close this gap by highlighting recent work that demonstrates shared neuroanatomical and neurophysiological signatures of inhibitory control across domains. We propose that the regulation of thalamocortical drive by a fronto-subthalamic mechanism operating in the β band might be a domain-general mechanism for inhibitory control in the human brain. Inhibitory control is a fundamental mechanism underlying flexible behavior and features in theories across many areas of cognitive and psychological science. However, whereas many theories implicitly or explicitly assume that inhibitory control is a domain-general process, the vast majority of neuroscientific work has hitherto focused on individual domains, such as motor, mnemonic, or attentional inhibition. Here, we attempt to close this gap between by highlighting recent work that demonstrates shared neuroanatomical and neurophysiological signatures of inhibitory control across domains. We propose that the regulation of thalamocortical drive by a fronto-subthalamic mechanism operating in the β band might be a domain-general mechanism for inhibitory control in the human brain. [ABSTRACT FROM AUTHOR]

Structural damage to the hippocampus gives rise to a severe memory deficit for personal experiences known as organic amnesia. Remarkably, such structural damage may not be the only way of creating amnesia; windows of amnesia can also arise when people deliberately disengage from memory via a process known as retrieval suppression. In this review, we discuss how retrieval suppression induces systemic inhibition of the hippocampus, creating "amnesic shadow" intervals in people's memory for their personal experiences. When new memories are encoded or older memories are reactivated during this amnesic shadow, these memories are disrupted, and such disruption even arises when older memories are subliminally cued. Evidence suggests that the systemic inhibition of the hippocampus during retrieval suppression that gives rise to the amnesic shadow may be mediated by engagement of hippocampal GABAergic inhibitory interneurons. Similar amnesic shadow effects are observed during working memory tasks like the n-back, which also induce notable hippocampal downregulation. We discuss our recent proposal that cognitive operations that require the disengagement of memory retrieval, such as retrieval suppression, are capable of mnemonic process inhibition (the inhibition of mnemonic processes such as encoding, consolidation, and retrieval and not simply individual memories). We suggest that people engage mnemonic process inhibition whenever they shift attention from internal processes to demanding perceptual-motor tasks that may otherwise be disrupted by distraction from our inner world. This hitherto unstudied model of inhibition is a missing step in understanding what happens when attentional shifts occur between internally and externally oriented processes to facilitate goal-directed behaviour. This process constitutes an important novel mechanism underlying the forgetting of life events. [ABSTRACT FROM AUTHOR]

The article focuses on improving mental health by training the suppression of unwanted thoughts. Topics include the benefits of suppressing distressing thoughts, the absence of ironic rebounds in memory and emotion, and how training to suppress fears resulted in improved mental health compared to suppressing neutral thoughts.

Antagonistic coevolutionary interactions between avian brood parasites and their hosts can lead to selection for the discrimination of parasites by their host via visual or acoustic signals. Therefore, nestlings of some brood parasites may be under selection to evolve visual and vocal mimicry of host nestlings to avoid discrimination by host parents. Some brood parasites diversify into host-specific populations by mimicking visual features of the host offspring (either eggs or nestlings). However, whether a similar mechanism applies to the begging calls of their hosts remains unclear. In this study, we analysed the begging calls of three subspecies of the shining bronze-cuckoo, which present visual mimicry of three different host species (family Acanthizidae) that vary in their ability to discriminate parasite nestlings. We found that the begging calls of each cuckoo subspecies match the respective host more closely than any of the other cuckoo subspecies. Therefore, selection for coevolutionary diversification appears to overcome phylogenetic constraints on cuckoo begging call structure. The coevolutionary interactions in these parasite–host systems have promoted the selection for refined host mimicry by the cuckoo and the formation of geographically isolated evolutionary units across the range of the species. • Shining bronze-cukoo nestlings mimic the begging calls of their main hosts. • Cuckoo subspecies closely match their respective local host. • Absence of parasite rejection by the host is explained by mimicry accuracy. • Coevolution overcomes phylogeny in shaping the structure of cuckoo begging calls. [ABSTRACT FROM AUTHOR]

• Novel shields were created through additive manufacturing (AM) to protect spacecraft from micormeteroids and orbital debris. • The shields used Ultem 1010 and 9085, which are promising polyetherimide (PEI) materials for aerospace use. • Specimens underwent hypervelocity impact testing and survived projectiles traveling up to 6.5 km/s. • Specimens were simulated using the multi-physics finite element code CTH. • Analysis shows that CTH can be used as a design tool for AM PEI. The increasingly congested orbital environment around Earth threatens the safety of space assets. Micrometeoroids and orbital debris (MMOD) less than 1 cm but traveling at hypervelocities pose a serious but defensible hazard. Traditional shields are installed during spacecraft assembly and must survive launch loads, constraining their size, shape, and ultimately, effectiveness. Recent advances in on-orbit additive manufacturing have created new opportunities for shield design and deployment. This work describes the modeling and testing of additively manufactured polyetherimide shields. The finite element code CTH was used to model hypervelocity impacts (HVIs) of such shields, and though imperfect, the models were useful for shield design. Several shield designs were additively manufactured and underwent HVI testing with a two-stage light gas gun in the regime of 4 mm diameter aluminum projectile impacts at 5 - 6.5 km/s. All successfully survived the HVIs, indicating their potential effectiveness as MMOD spacecraft shielding. [ABSTRACT FROM AUTHOR]

Background: This study assessed whether there is an association between changes in publicly and privately funded care for procedures classified as low value by the National Health Service (NHS) in England following implementation of the Evidence-Based Intervention (EBI) programme. Category 1 procedures should not be conducted and are no longer reimbursed by the NHS. Category 2 procedures are only reimbursed by the NHS in certain circumstances. Methods: Changes in volumes of publicly and privately funded procedures per month in 2019-2020 compared with the previous year were analysed in private hospitals and local healthcare markets, and adjusted for volume of procedures and patient case mix including age, sex, co-morbidities, and deprivation. Supplementary analyses focused on the self-pay and insurance funding mechanisms. Results: There was a statistically significant association between changes in publicly and privately funded care for category 2 procedures at the hospital (-0.19, 95 per cent c.i. -0.25 to -0.12) and local healthcare market level of analysis (-0.24, -0.32 to -0.15). A statistically significant association for category 1 procedures only existed at the hospital level of analysis (-0.19, -0.30 to -0.08). Findings were similar for patients accessing care through self-pay and insurance funding mechanisms. Conclusion: Stronger associations between changes in publicly and privately funded care for category 2 procedures may exist as they are clinically indicated in certain circumstances. Reductions in publicly funded care were likely a combined result of the EBI programme and growing NHS waiting lists, whereas increases in privately funded care were influenced by both patient and supplier-induced demand. [ABSTRACT FROM AUTHOR]

This article discusses the repair of a large lateral forehead and temporal wound in a 91-year-old man who had a basal cell carcinoma. The challenge in reconstructing this wound is preserving the normal anatomic position of the eyebrow, lateral canthus, and eyelids. Various options were considered, including second intention healing, linear repair, split thickness skin graft, advancement or rotation flap, transposition flap, bilobed flap, and rhombic flap. Ultimately, a large, single lobe transposition flap with double z-plasty was used to repair the defect, resulting in a well-healed scar with normal frontalis function and slight superolateral pull on the eyelid at 9 months follow-up. [Extracted from the article]

The article focuses on purpose of Peace Commission to convince these major tribes to relinquish their rights to lands and their nomadic roaming lifestyles, committing to the reservation system. It mentions reservations concentrated the tribes on smaller tracts of land, allowing further settler expansion and tribes received promises of protection and support such as rations, supplies, and tools to aid in their transition to agricultural lifestyle and away from hunting.

Dystrophin is an essential muscle protein that contributes to cell membrane stability by mechanically linking the actin cytoskeleton to the extracellular matrix via an adhesion complex called the dystrophin-glycoprotein complex. The absence or impaired function of dystrophin causes muscular dystrophy. Focal adhesions (FAs) are also mechanosensitive adhesion complexes that connect the cytoskeleton to the extracellular matrix. However, the interplay between dystrophin and FA force transmission has not been investigated. Using a vinculin-based bioluminescent tension sensor, we measured FA tension in transgenic C2C12 myoblasts expressing wild-type (WT) dystrophin, a nonpathogenic single nucleotide polymorphism (SNP) (I232M), or two missense mutations associated with Duchenne (L54R), or Becker muscular dystrophy (L172H). Our data revealed cross talk between dystrophin and FAs, as the expression of WT or I232M dystrophin increased FA tension compared to dystrophin-less nontransgenic myoblasts. In contrast, the expression of L54R or L172H did not increase FA tension, indicating that these disease-causing mutations compromise the mechanical function of dystrophin as an FA allosteric regulator. Decreased FA tension caused by these mutations manifests as defective migration, as well as decreased Yes-associated protein 1 (YAP) activation, possibly by the disruption of the ability of FAs to transmit forces between the extracellular matrix and cytoskeleton. Our results indicate that dystrophin influences FA tension and suggest that dystrophin disease-causing missense mutations may disrupt a cellular tension-sensing pathway in dystrophic skeletal muscle. [ABSTRACT FROM AUTHOR]

The cell adhesion molecule leucine-rich repeat transmembrane neuronal protein 2 (LRRTM2) is crucial for synapse development and function. However, our understanding of its endogenous trafficking has been limited due to difficulties in manipulating its coding sequence (CDS) using standard genome editing techniques. Instead, we replaced the entire LRRTM2 CDS by adapting a two-guide CRISPR knock-in method, enabling complete control of LRRTM2. In primary rat hippocampal cultures dissociated from embryos of both sexes, N-terminally tagged, endogenous LRRTM2 was found in 80% of synapses, and synaptic LRRTM2 content correlated with PSD-95 and AMPAR levels. LRRTM2 was also enriched with AMPARs outside synapses, demonstrating the sensitivity of this method to detect relevant new biology. Finally, we leveraged total genomic control to increase the synaptic levels of LRRTM2 via simultaneous mutation of its C-terminal domain, which did not correspondingly increase AMPAR enrichment. The coding region of thousands of genes span lengths suitable for whole-CDS replacement, suggesting this simple approach will enable straightforward structure–function analysis in neurons. [ABSTRACT FROM AUTHOR]

Objective To map how social, commercial, political and digital determinants of health have changed or emerged during the recent digital transformation of society and to identify priority areas for policy action. Methods We systematically searched MEDLINE, Embase and Web of Science on 24 September 2023, to identify eligible reviews published in 2018 and later. To ensure we included the most recent literature, we supplemented our review with non-systematic searches in PubMed® and Google Scholar, along with records identified by subject matter experts. Using thematic analysis, we clustered the extracted data into five societal domains affected by digitalization. The clustering also informed a novel framework, which the authors and contributors reviewed for comprehensiveness and accuracy. Using a two-round consensus process, we rated the identified determinants into high, moderate and low urgency for policy actions. Findings We identified 13 804 records, of which 204 met the inclusion criteria. A total of 127 health determinants were found to have emerged or changed during the digital transformation of society (37 digital, 33 social, 33 commercial and economic and 24 political determinants). Of these, 30 determinants (23.6%) were considered particularly urgent for policy action. Conclusion This review offers a comprehensive overview of health determinants across digital, social, commercial and economic, and political domains, highlighting how policy decisions, individual behaviours and broader factors influence health by digitalization. The findings deepen our understanding of how health outcomes manifest within a digital ecosystem and inform strategies for addressing the complex and evolving networks of health determinants. [ABSTRACT FROM AUTHOR]

Demand is increasing for effective online tools to perform collaborative engineering design by geographically separated teams. In particular, tools that facilitate the concept ideation phase of the engineering design process are sought for immediate implementation in product design. In this work, researchers conducted a literature review, interviews with practicing engineers, and a thorough web search to identify available tools and the desired features and requirements. A set of 100 web-based collaborative tools were identified then filtered down to 18 candidates which met the minimum criteria. These 18 were systematically evaluated by the researchers who rated their satisfaction of 11 requirements. The five highest rated finalist platforms were more thoroughly tested by design teams who used the platforms in design sprint activities. Evaluator ratings and feedback were collected at multiple points and several best practices were discovered during testing. Conceptboard3 received the highest evaluator ratings, with few negative comments, and is expected to be an effective tool for collaborative engineering design. [ABSTRACT FROM AUTHOR]

Policy PointsThe 2018 Declaration of Astana reemphasized the importance of primary health care and its role in achieving universal health coverage. While there is a large amount of literature on the economic aspects of delivering primary care services, there is a need for more comprehensive overviews of this evidence. In this article, we offer such an overview.Evidence suggests that there are several strategies involving coverage, financing, service delivery, and governance arrangements which can, if implemented, have positive economic impacts on the delivery of primary care services. These include arrangements such as worker task‐shifting and telemedicine.The implementation of any such arrangements, based on positive economic evidence, should carefully account for potential impacts on overall health care access and quality. There are many opportunities for further research, with notable gaps in evidence on the impacts of increasing primary care funding or the overall supply of primary care services. Context: The 2018 Declaration of Astana reemphasized the importance of primary health care and its role in achieving universal health coverage. To strengthen primary health care, policymakers need guidance on how to allocate resources in a manner that maximizes its economic benefits. Methods: We collated and synthesized published systematic reviews of evidence on the economic aspects of different models of delivering primary care services. Building on previous efforts, we adapted existing taxonomies of primary care components to classify our results according to four categories: coverage, financing, service delivery, and governance. Findings: We identified and classified 109 reviews that met our inclusion criteria according to our taxonomy of primary care components: coverage, financing, service delivery, and governance arrangements. A significant body of evidence suggests that several specific primary care arrangements, such as health workers' task shifting and telemedicine, can have positive economic impacts (such as lower overall health care costs). Notably absent were reviews on the impact of increasing primary care funding or the overall supply of primary care services. Conclusions: There is a great opportunity for further research to systematically examine the broader economic impacts of investing in primary care services. Despite progress over the last decade, significant evidence gaps on the economic implications of different models of primary care services remain, which could help inform the basis of future research efforts. [ABSTRACT FROM AUTHOR]

The physical processes behind the transfer of mass from parsec-scale clumps to massive star-forming cores remain elusive. We investigate the relation between the clump morphology and the mass fraction that ends up in its most massive core (MMC) as a function of infrared brightness, i.e. a clump evolutionary tracer. Using Atacama Large Millimeter/submillimeter Array (ALMA) 12 m and Atacama Compact Array, we surveyed six infrared dark hubs in 2.9 mm continuum at ∼3 arcsec resolution. To put our sample into context, we also re-analysed published ALMA data from a sample of 29 high-mass surface density ATLASGAL sources. We characterize the size, mass, morphology, and infrared brightness of the clumps using Herschel and Spitzer data. Within the six newly observed hubs, we identify 67 cores, and find that the MMCs have masses between 15 and 911 M⊙ within a radius of 0.018–0.156 pc. The MMC of each hub contains 3–24 per cent of the clump mass (f MMC), becoming 5–36 per cent once core masses are normalized to the median core radius. Across the 35 clumps, we find no significant difference in the median f MMC values of hub and non-hub systems, likely the consequence of a sample bias. However, we find that f MMC is ∼7.9 times larger for infrared dark clumps compared to infrared bright ones. This factor increases up to ∼14.5 when comparing our sample of six infrared dark hubs to infrared bright clumps. We speculate that hub-filament systems efficiently concentrate mass within their MMC early on during its evolution. As clumps evolve, they grow in mass, but such growth does not lead to the formation of more massive MMCs. [ABSTRACT FROM AUTHOR]

We discuss relations between the initial boundary value problem (IBVP) and quasi-local Hamiltonians in GR. The latter have traditionally been based on Dirichlet boundary conditions, which however are shown here to be ill-posed for the IBVP. We present and analyze several other choices of boundary conditions which are better behaved with respect to the IBVP and carry out a corresponding Hamiltonian analysis, using the framework of the covariant phase space method. [ABSTRACT FROM AUTHOR]

Free‐roaming equids (i.e., feral horses [Equus caballus] and burros [Equus asinus]) are widely distributed and locally abundant across the rangelands of the western United States. The 1971 Wild Free Roaming Horse and Burro Act (WFRHBA) gave the Bureau of Land Management (BLM) and United States Forest Service (USFS) the legal authority to manage these animals on designated public lands. To fulfill this responsibility, federal agencies established an Appropriate Management Level (AML), defined as the number of horses or burros that can be sustained on a given management unit under prevailing environmental conditions and land uses. Although the WFRHBA specifies that feral equids must be managed in ecological balance with other land uses, including conservation of native wildlife, population control measures such as gathers, contraception, and adoptions have failed to keep pace with intrinsic growth rates. Over 80% of federally managed herds currently exceed prescribed population levels, making the potential for competition between native ungulates and feral equids a growing concern among state wildlife agencies. Mule deer (Odocoileus hemionus), pronghorn (Antilocapra americana), elk (Cervus canadensis), and bighorn sheep (Ovis canadensis) are of ecological and economic value to the states where they occur, and all exhibit some degree of distributional, habitat, or dietary overlap with horses or burros. Notwithstanding the scale of the problem, to date there have been no range‐wide assessments of competition potential among native and feral ungulates for space, forage, or water. To address this need, we compiled demographic, jurisdictional, and species occurrence data collected from 2010–2019 by federal and state agencies. We used these data to map the distributions of 4 native ungulate species across federal equid management units (FEMUS) in 10 western states (n = 174). We then made within‐state rankings of the 50 units that were ≥2 times over AML and encompassed ≥3 native ungulates. Collectively, FEMUs covered approximately 225,000 km2, representing 18% of all BLM and USFS lands in affected states. Each FEMU supported ≥1 native ungulate and 14% contained all 4. The degree of overlap between native and feral species varied by state, ranging from <1% for mule deer in Montana, to 40% for bighorn sheep in Nevada. Oregon had the largest proportion of units that supported all 4 native ungulates (58%), whereas Montana and New Mexico had the fewest equids, but all populations were over target densities. Despite the perception that the problem of equid abundance is limited to the Great Basin states, high intrinsic growth rates and social constraints on management practices suggest all affected states should monitor range conditions and native ungulate demography in areas where forage and water resources are limited and expanding equid populations are a concern. © 2021 The Wildlife Society. The problems associated with equid abundance are not limited to the Great Basin states. High growth rates and social constraints on management practices suggest all states with feral equids should monitor range conditions and native ungulate demography to develop plans to mitigate competition between native and feral ungulates for limited resources. [ABSTRACT FROM AUTHOR]

The ability to stop unwanted memories from coming to mind is theorised to be essential for maintaining good mental health. People can employ intentional strategies to prevent conscious intrusions of negative memories, and repeated attempts to stop retrieval both reduces the frequency of intrusions and improves subsequent emotions elicited by those memories. However, it is still unknown whether memory control can improve negative emotions immediately, at the time control is attempted. It is also not clear which strategy is most beneficial for emotion regulation; clearing the mind of any thoughts of negative memories via direct suppression, or substituting memory recall with alternative thoughts. Here, we provide novel evidence that memory control immediately regulates negative emotions associated with autobiographical memories of morally wrong actions. Repeated control significantly improved negative emotions over time, regardless of the strategy used to implement control. Thought substitution involving either positive diversionary thinking or counterfactual thinking both induced positive feelings, whereas direct suppression neutralised emotions, regardless of whether memories were positive or negative. These empirical findings have implications for clinical practice as they indicate that memory control strategies could be effective emotion regulation methods for real-world intrusive memories. [ABSTRACT FROM AUTHOR]

Approximately 13% of the total UK workforce is employed in the health and care sector. Despite substantial workforce planning efforts, the effectiveness of this planning has been criticised. Education, training, and workforce plans have typically considered each health-care profession in isolation and have not adequately responded to changing health and care needs. The results are persistent vacancies, poor morale, and low retention. Areas of particular concern highlighted in this Health Policy paper include primary care, mental health, nursing, clinical and non-clinical support, and social care. Responses to workforce shortfalls have included a high reliance on foreign and temporary staff, small-scale changes in skill mix, and enhanced recruitment drives. Impending challenges for the UK health and care workforce include growing multimorbidity, an increasing shortfall in the supply of unpaid carers, and the relative decline of the attractiveness of the National Health Service (NHS) as an employer internationally. We argue that to secure a sustainable and fit-for-purpose health and care workforce, integrated workforce approaches need to be developed alongside reforms to education and training that reflect changes in roles and skill mix, as well as the trend towards multidisciplinary working. Enhancing career development opportunities, promoting staff wellbeing, and tackling discrimination in the NHS are all needed to improve recruitment, retention, and morale of staff. An urgent priority is to offer sufficient aftercare and support to staff who have been exposed to high-risk situations and traumatic experiences during the COVID-19 pandemic. In response to growing calls to recognise and reward health and care staff, growth in pay must at least keep pace with projected rises in average earnings, which in turn will require linking future NHS funding allocations to rises in pay. Through illustrative projections, we show that, to sustain annual growth in the workforce at approximately 2·4%, increases in NHS expenditure of 4% annually in real terms will be required. Above all, a radical long-term strategic vision is needed to ensure that the future NHS workforce is fit for purpose. [ABSTRACT FROM AUTHOR]

The health and care sector plays a valuable role in improving population health and societal wellbeing, protecting people from the financial consequences of illness, reducing health and income inequalities, and supporting economic growth. However, there is much debate regarding the appropriate level of funding for health and care in the UK. In this Health Policy paper, we look at the economic impact of the COVID-19 pandemic and historical spending in the UK and comparable countries, assess the role of private spending, and review spending projections to estimate future needs. Public spending on health has increased by 3·7% a year on average since the National Health Service (NHS) was founded in 1948 and, since then, has continued to assume a larger share of both the economy and government expenditure. In the decade before the ongoing pandemic started, the rate of growth of government spending for the health and care sector slowed. We argue that without average growth in public spending on health of at least 4% per year in real terms, there is a real risk of degradation of the NHS, reductions in coverage of benefits, increased inequalities, and increased reliance on private financing. A similar, if not higher, level of growth in public spending on social care is needed to provide high standards of care and decent terms and conditions for social care staff, alongside an immediate uplift in public spending to implement long-overdue reforms recommended by the Dilnot Commission to improve financial protection. COVID-19 has highlighted major issues in the capacity and resilience of the health and care system. We recommend an independent review to examine the precise amount of additional funds that are required to better equip the UK to withstand further acute shocks and major threats to health. [ABSTRACT FROM AUTHOR]

Auxin, a plant growth-promoting hormone, is known to be produced by many if not all bacteria. Research has shown that bacteria produced auxin is associated with both positive and negative plant growth effects. Here we determined the relationship between auxin production capacity and wheat biomass productivity in culturally isolated bacteria. A total of 4320 individual bacteria were isolated and characterized based on colony size as either fast (>2 mm) or slow (<2 mm) growing, from the rhizospheres and endorhizospheres of wheat plants grown in two soils that differ in pH and texture. The bacteria were assayed for auxin production based on a Salkowski reagent microplate assay. The relationship between auxin production and wheat biomass was largely negative under all conditions and characterizations, and non-significant (R2 0.04 to 0.26). When examined across all treatments, the lowest auxin producers originated from the highest biomass plants and the highest auxin producers from the lowest biomass plants (p value <.0001). Fast growing colonies produced significantly higher auxin production than slow growing colonies, overall (p value ≤ 0.005). The results suggest that auxin production by culturally isolated bacteria, as determined by the Salkowski reagent, is negatively associated with wheat biomass productivity. [ABSTRACT FROM AUTHOR]

Over the past century, psychologists have discussed whether forgetting might arise from active mechanisms that promote memory loss to achieve various functions, such as minimizing errors, facilitating learning, or regulating one's emotional state. The past decade has witnessed a great expansion in knowledge about the brain mechanisms underlying active forgetting in its varying forms. A core discovery concerns the role of the prefrontal cortex in exerting top-down control over mnemonic activity in the hippocampus and other brain structures, often via inhibitory control. New findings reveal that such processes not only induce forgetting of specific memories but also can suppress the operation of mnemonic processes more broadly, triggering windows of anterograde and retrograde amnesia in healthy people. Recent work extends active forgetting to nonhuman animals, presaging the development of a multilevel mechanistic account that spans the cognitive, systems, network, and even cellular levels. This work reveals how organisms adapt their memories to their cognitive and emotional goals and has implications for understanding vulnerability to psychiatric disorders. [ABSTRACT FROM AUTHOR]

At the turn of the 21st century, Susan Leigh Anderson and Michael Anderson conceived and introduced the Machine Ethics research program, that aimed to highlight the requirements under which autonomous artificial intelligence (AI) systems could demonstrate ethical behavior guided by moral values, and at the same time to show that these values, as well as ethics in general, can be representable and computable. Today, the interaction between humans and AI entities is already part of our everyday lives; in the near future it is expected to play a key role in scientific research, medical practice, public administration, education and other fields of civic life. In view of this, the debate over the ethical behavior of machines is more crucial than ever and the search for answers, directions and regulations is imperative at an academic, institutional as well as at a technical level. Our discussion with the two inspirers and originators of Machine Ethics highlights the epistemological, metaphysical and ethical questions arising by this project, as well as the realistic and pragmatic demands that dominate artificial intelligence and robotics research programs. Most of all, however, it sheds light upon the contribution of Susan and Michael Anderson regarding the introduction and undertaking of a main objective related to the creation of ethical autonomous agents, that will not be based on the "imperfect" patterns of human behavior, or on preloaded hierarchical laws and human-centric values. [ABSTRACT FROM AUTHOR]

As autonomous systems become more capable, end users must make decisions about how and when to deploy such technology. The use and adoption of a technology to replace a human actor depends on its ability to perform a desired task and on the user's experience-based trust that it will do so. The development of experience-based trust in autonomous systems is costly, and it carries a high risk of physical harm to operators. This work focuses on identifying a methodology for technology discovery that reduces the need for experience-based trust and contributes to increased adoption of autonomous systems. The main research hypothesis is that manipulating the presentation of technical information can influence the initial formation of trust by functioning as a surrogate for experiencebased trust, and that trust in technology can be captured through an anthropomorphic hierarchy of system attributes. [ABSTRACT FROM AUTHOR]

The need for an efficacious vaccine against highly pathogenic filoviruses was reinforced by the devastating 2014–2016 outbreak of Ebola virus (EBOV) disease (EVD) in Guinea, Sierra Leone, and Liberia that resulted in over 28,000 cases and over 11,300 deaths. In addition, the 2018–2020 outbreak in the Democratic Republic of the Congo currently has over 3,400 cases and over 2,200 deaths. A fully licensed vaccine and at least one other investigational vaccine are being deployed to combat this EVD outbreak. To support vaccine development and pre-clinical/clinical testing a Filovirus Animal Nonclinical Group (FANG) human anti-EBOV GP IgG ELISA was developed to measure anti-EBOV GP IgG antibodies. This ELISA is currently being used in multiple laboratories. Reported here is a characterization of an interlaboratory statistical analysis of the human anti-EBOV GP IgG ELISA as part of a collaborative study between five participating laboratories. Each laboratory used similar method protocols and reagents to measure anti-EBOV GP IgG levels in human serum samples from a proficiency panel consisting of ten serum samples created by the differential dilution of a serum sample positive for anti-GP IgG antibodies (BMIZAIRE105) with negative serum (BMI529). The total assay variability (inter- and intra-assay variability) %CVs observed at each laboratory ranged from 12.2 to 30.6. Intermediate precision (inter-assay variability) for the laboratory runs ranged from 8.9 to 21.7%CV and repeatability (intra-assay variability) %CVs ranged from 7.2 to 23.7. The estimated slope for the relationship between log10(Target Concentration) and the log10(Observed Concentration) across all five laboratories was 0.95 with a 90% confidence interval of (0.93, 0.97). Equivalence test results showed that the 90% confidence interval for the ratios for the sample-specific mean concentrations at the five individual labs to the overall laboratory consensus value were within the equivalence bounds of 0.80 to 1.25 for each laboratory and test sample, except for six test samples from Lab D, two samples from Lab B1, and one sample from Lab B2. The mean laboratory concentrations for Lab D were less than those from the other laboratories by 20% on average across the serum samples. The evaluation of the proficiency panel at these laboratories provides a limited assessment of assay precision (intermediate precision, repeatability, and total assay variability), dilutional linearity, and accuracy. This evaluation suggests that the within-laboratory performance of the anti-EBOV GP IgG ELISA as implemented at the five laboratories is consistent with the intended use of the assay based on the acceptance criteria used by laboratories that have validated the assay. However, the assessment of between-laboratory performance revealed lower observed concentrations at Lab D and greater variability in assay results at Lab B1 relative to other laboratories. [ABSTRACT FROM AUTHOR]

Background: Observational studies using traditional research designs suggest that influenza vaccination reduces hospitalizations and mortality among elderly persons. Accordingly, health authorities in some countries prioritize vaccination of this population. Nevertheless, questions remain about this policy's effectiveness given the potential for bias and confounding in observational data.Objective: To determine the effectiveness of the influenza vaccine in reducing hospitalizations and mortality among elderly persons by using an observational research design that reduces the possibility of bias and confounding.Design: A regression discontinuity design was applied to the sharp change in vaccination rate at age 65 years that resulted from an age-based vaccination policy in the United Kingdom. In this design, comparisons were limited to individuals who were near the age-65 threshold and were thus plausibly similar along most dimensions except vaccination rate.Setting: England and Wales.Participants: Adults aged 55 to 75 years residing in the study area during 2000 to 2014.Intervention: Seasonal influenza vaccine.Measurements: Hospitalization and mortality rates by month of age.Results: The data included 170 million episodes of care and 7.6 million deaths. Turning 65 was associated with a statistically and clinically significant increase in rate of seasonal influenza vaccination. However, no evidence indicated that vaccination reduced hospitalizations or mortality among elderly persons. The estimates were precise enough to rule out results from many previous studies.Limitation: The study relied on observational data, and its focus was limited to individuals near age 65 years.Conclusion: Current vaccination strategies prioritizing elderly persons may be less effective than believed at reducing serious morbidity and mortality in this population, which suggests that supplementary strategies may be necessary.Primary Funding Source: National Institute on Aging. [ABSTRACT FROM AUTHOR]

Several recent studies suggest that an initial retrieval attempt imbues retrieved memories with special resilience against future interference and other forgetting mechanisms. Here we report two experiments examining whether memories established through initial retrieval remain subject to retrieval-induced forgetting. Using a version of a classical retroactive interference design, we trained participants on a list of A–B pairs via anticipation – constituting a form of retrieval practice. After next training participants on interfering A–C pairs, they performed 0–12 additional A–C anticipation trials. Because these trials required retrieval of A–C pairs, they should function similarly to retrieval practice in paradigms establishing retrieval-induced forgetting. We observed robust evidence that retroactive interference generalises to final memory tests involving novel, independent memory probes. Moreover, in contrast to practising retrieval of A–C items, their extra study failed to induce cue-independent forgetting of the original B items. Together, these findings substantiate the role of retrieval-related inhibitory processes in a traditional retroactive interference design. Importantly, they indicate that an initial retrieval attempt on a competitor does not abolish retrieval-induced forgetting, at least not in the context of this classic design. Although such an attempt may protect against inhibition in some circumstances, the nature of those circumstances remains to be understood. [ABSTRACT FROM AUTHOR]

The common methodology for distributing External-Internal (EI) trips is to collect traffic counts at the cordon line of a study area and to use total employment of the internal zone as the factor upon which zone attractiveness can be based. This methodology assumes that trips originating from outside the study area have a destination within the study area which is towards areas that are suitable for employment. However, depending on the type of employment at the destination, the attraction may vary. This paper examines different employment-based which makes the zones attractive for external trips. The paper concludes that the three scenarios in which the land use variables are utilized, indicate more improvement than those without considering the land use mix. A combination of retail employment and the number of different land-uses at the destination was the best possible methodology to determine external trip attraction within a study area. Furthermore, simply switching from total employment to retail employment at the destination location can also improve the accuracy of the travel model. [ABSTRACT FROM AUTHOR]

Strengthening governance is an essential strategy to tackling antimicrobial resistance (AMR) at all levels: global, national, regional, and local. To date, no systematic approach to governance of national action plans on AMR exists. To address this issue, we aimed to develop the first governance framework to offer guidance for both the development and assessment of national action plans on AMR. We reviewed health system governance framework reviews to inform the basic structure of our framework, international guidance documents from WHO, the Food and Agriculture Organization, the World Organisation for Animal Health, and the European Commission, and sought the input of 25 experts from international organisations, government ministries, policy institutes, and academic institutions to develop and refine our framework. The framework consists of 18 domains with 52 indicators that are contained within three governance areas: policy design, implementation tools, and monitoring and evaluation. To consider the dynamic nature of AMR, the framework is conceptualised as a cyclical process, which is responsive to the context and allows for continuous improvement and adaptation of national action plans on AMR. [ABSTRACT FROM AUTHOR]

The article offers information on theses on Janus. Topics include Janus being latest iteration of an old union-busting tactic destroy labor's internal cohesion under the slogan voluntary unionism, being one step in an ongoing attack on exclusive representation, and joining a union was an act of dissent and free association, a mutual-aid pact against the capitalist order.

A radical embodied cognitive neuroscience (RECN) based on ecological psychology requires the understanding of the brain, its structure, and its functions to be compatible with the main tenets of the Gibsonian theory. In this paper, we propose neural reuse as a promising candidate to achieve such understanding. We base our proposal on two fundamental ideas. In section two, we review what we take to be the two central requirements for a RECN based on ecological psychology: compatibility with the explanation of perception and action at the ecological scale and the rejection of computation as a paradigm for the explanation of the activity of the brain. In section three, we show how neural reuse meets the two requirements and, furthermore, we evaluate its theoretical parallelism with ecological psychology. Finally, after developing these ideas, in the conclusion we put forward further aspects and research possibilities that follow from the coalition of neural reuse and ecological psychology for a Gibsonian neuroscience. [ABSTRACT FROM AUTHOR]

When people suppress retrieval of episodic memories, it can induce forgetting on later direct tests of memory for those events. Recent reports indicate that suppressing retrieval affects less conscious, unintentional retrieval of unwanted memories as well, at least on perceptually-oriented indirect tests. In the current study we examined how suppressing retrieval affects conceptual implicit memory for the suppressed content, using a category verification task. Participants studied cue-target words pairs in which the targets were exemplars of 22 semantic categories, such as vegetables or occupations. They then repeatedly retrieved or suppressed the targets in response to the cues for some of those pairs. Afterwards, they were exposed to the targets intermixed with novel items, one at a time, and asked to verify the membership of each of the words in a semantic category, as quickly as possible. Judgment response times to studied words were faster than to unstudied exemplars, reflecting repetition priming, as has been previously observed. Strikingly, the beneficial effects of prior exposure on response time were eliminated for targets that had been suppressed. Follow-up explicit memory tests also demonstrated that retrieval suppression continued to disrupt episodic recall for the items that had been just been re-exposed on the category verification test. These findings support the contention that the effects of retrieval suppression are not limited to episodic memory, but also affect indirect expressions of those memories on conceptually oriented tests, raising the possibility that underlying semantic representations of suppressed content are affected. [ABSTRACT FROM AUTHOR]

Given a Riemannian 3-ball (B ¯ , g) of nonnegative scalar curvature, Bartnik conjectured that (B ¯ , g) admits an asymptotically flat (AF) extension (without horizons) of the least possible ADM mass and that such a mass minimizer is an AF solution to the static vacuum Einstein equations, uniquely determined by natural geometric conditions on the boundary data of (B ¯ , g) . We prove the validity of the second statement, i.e., such mass minimizers, if they exist, are indeed AF solutions of the static vacuum equations. On the other hand, we prove that the first statement is not true in general; there is a rather large class of bodies (B ¯ , g) for which a minimal mass extension does not exist. [ABSTRACT FROM AUTHOR]

A comparison is made between three methods for the simulation of deuterated ligand modulation from cupric ion complexes as powders using electron spin-echo modulation (ESEM) spectroscopy: (a) the spherical-averaging approximation which assumes both isotropic g and a random distribution of deuterium nuclei about the paramagnetic center, (b) an average which is performed over specific orientations of the field H0 with respect to g|| using analytical expressions for the spin-echo intensity for an axially symmetric g tensor, and (c) a similar approach to (b) but with full geometrical correlation between the deuterium nuclei. Approach (c) is found to be unnecessary because of the degree of freedom of the ligand molecules to rotate about the ligand axis before freezing locks them into a particular configuration. This, in effect, removes any strict correlation between the deuterium nuclei. Approaches (a) and (b) are found to be equivalent when (i) the electron–nuclear distance r is greater than 0.35 nm, (ii) r is less than 0.35 nm but the number of interacting nuclei, N, is 6 or greater, and (iii) r is less than 0.35 nm, N is less than 6, and the angle θI between g|| and r is greater than 45°. In all cases microwave irradiation must be near g⊥. When the situation is none of the above, then parameters defined by the spherical-averaging approximation should be interpreted with caution. [ABSTRACT FROM AUTHOR]