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Desiccation cracking in clay soils is a combined mechanical and hydraulic problem and such soils can be improved by various methods including reinforcement with fibres. The relationships between tensile strength, cracking resistance and water-retention properties of fibre-reinforced fine-grained soils lack coverage in the literature to date. In this study, these three properties are evaluated and connected by way of a series of tensile strength and desiccation cracking tests on fibre-reinforced London clay. The results confirm that increased fibre addition delays the occurrence of peak stress and changes failure behaviour from brittle to ductile. The tensile strength increment gets higher as water content decreases, and reaches a maximum value of 460 kPa when the water content is 12%. The crack intensity factor reduces from 7.20% to 0.89% when 12 mm long fibre is used at a ratio of 0.9%. Fibre reinforcement also changes the crack development pattern by reducing the size of large cracks and increasing the proportion of small individual cracks. However, the presence of fibres was not observed to change the water-retention properties of the soil, indicating that the tensile improvement comes from the pull-out resistance of the fibres rather than suction changes.

The hunter-gatherers that entered the British peninsula after ice-retreat were exploiting a dynamic, rapidly changing environment. Records of vegetation change and human occupation during the Lateglacial to Early Holocene in northern Britain are more commonly found at upland and cave sites. However, recent research highlights many areas of the Swale–Ure Washlands that preserve extensive environmental sequences in low-lying ice-wastage basins, channels and depressions. The Lateglacial–Early Holocene environment of Killerby Quarry, North Yorkshire, is investigated here using a multi-proxy approach of sedimentary ancient DNA (sedaDNA), pollen, sedimentological (geochemistry and portable optically stimulated luminescence), and rare and well-preserved archaeology (Lavvu structures and lithics). Results show that the wetland basins and kettleholes were small lakes or ponds in the Lateglacial surrounded by sedge-fen and birch woodland. A gradual (centennial scale) succession to reed-swamp and then marsh is seen by the Early Holocene. This environment formed the resource-scape for hunter-gatherer transitory settlement in both the Lateglacial (Late Upper Palaeolithic) and Holocene (Early Mesolithic), attracted by the rich communities of pond-related flora and fauna as well as easy strategic landscape access by way of the River Swale, an arterial route through the landscape connecting the North Sea Basin with the Pennine uplands via the palaeolakes around Killerby.

Niemann–Pick disease type C1 (NP-C) is a prematurely lethal genetic lysosomal storage disorder with neurological and visceral pathology resulting from mutations in the NPC1 gene encoding the lysosomal transmembrane protein NPC1. There is currently no cure for NP-C, and the only disease modifying treatment, miglustat, slows disease progression but does not significantly attenuate neurological symptoms. AAV-mediated gene therapy is an attractive option for NP-C, but due to the large size of the human NPC1 gene, there may be packaging and truncation issues during vector manufacturing. One option is to reduce the size of DNA regulatory elements that are essential for gene expression, such as the promoter sequence. Here, we describe a novel small truncated endogenous NPC1 promoter that leads to high gene expression both in vitro and in vivo and compare its efficacy to other commonly used promoters. Following neonatal intracerebroventricular (ICV) injection into the CNS, this novel promoter provided optimal therapeutic efficacy compared to all other promoters including increased survival, improved behavioural phenotypes, and attenuated neuropathology in mouse models of NP-C. Taken together, we propose that this novel promoter can be extremely efficient in designing an optimised AAV9 vector for gene therapy for NP-C.

The Southern Hemisphere westerly wind belt (SHWW) is a major feature of Southern Hemisphere, midlatitude climate that is closely linked with the sequestration and release of CO2 in the Southern Ocean. Past changes in the strength and position of this wind belt are poorly resolved, particularly across the Pleistocene-Holocene transition, a time period associated with fluctuations in atmospheric temperatures and CO2 levels. We used dust geochemistry, particle size measurements, and paleoecological analyses from a peat sequence in the Falkland Islands, South Atlantic Ocean, to describe changes in the SHWW between 16.0 and 6.5 ka (thousands of years before CE 1950). Wind strength was low at ~51°S before and during the Antarctic Cold Reversal (ACR, 14.9–13.0 ka), intensified between 13.1 and 12.1 ka as atmospheric temperatures increased, and then weakened, reaching a minimum between 12.1 and 10.9 ka during the Early Holocene thermal maximum. Northwesterly air masses became more dominant from 12.0 to 10.2 ka, and wind strength remained low until our record was affected by a storm surge or tsunami ca. 7.8 ka. These data indicate a southward shift in the latitude of the SHWW, from north of 51°S prior to and during the ACR, at ~51°S before the onset of the Holocene, and south of 51°S during the early Holocene thermal maximum. This pattern suggests that the latitude of the SHWW was coupled with atmospheric temperatures through the Pleistocene-Holocene transition.

Supplementary Figure 1 from Context-Dependent Role of Angiopoietin-1 Inhibition in the Suppression of Angiogenesis and Tumor Growth: Implications for AMG 386, an Angiopoietin-1/2–Neutralizing Peptibody

Supplementary Figure 3 from Context-Dependent Role of Angiopoietin-1 Inhibition in the Suppression of Angiogenesis and Tumor Growth: Implications for AMG 386, an Angiopoietin-1/2–Neutralizing Peptibody

AMG 386 is an investigational first-in-class peptide-Fc fusion protein (peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 (Ang1) and Ang2 with their receptor, Tie2. Although the therapeutic value of blocking Ang2 has been shown in several models of tumorigenesis and angiogenesis, the potential benefit of Ang1 antagonism is less clear. To investigate the consequences of Ang1 neutralization, we have developed potent and selective peptibodies that inhibit the interaction between Ang1 and its receptor, Tie2. Although selective Ang1 antagonism has no independent effect in models of angiogenesis-associated diseases (cancer and diabetic retinopathy), it induces ovarian atrophy in normal juvenile rats and inhibits ovarian follicular angiogenesis in a hormone-induced ovulation model. Surprisingly, the activity of Ang1 inhibitors seems to be unmasked in some disease models when combined with Ang2 inhibitors, even in the context of concurrent vascular endothelial growth factor inhibition. Dual inhibition of Ang1 and Ang2 using AMG 386 or a combination of Ang1- and Ang2-selective peptibodies cooperatively suppresses tumor xenograft growth and ovarian follicular angiogenesis; however, Ang1 inhibition fails to augment the suppressive effect of Ang2 inhibition on tumor endothelial cell proliferation, corneal angiogenesis, and oxygen-induced retinal angiogenesis. In no case was Ang1 inhibition shown to (a) confer superior activity to Ang2 inhibition or dual Ang1/2 inhibition or (b) antagonize the efficacy of Ang2 inhibition. These results imply that Ang1 plays a context-dependent role in promoting postnatal angiogenesis and that dual Ang1/2 inhibition is superior to selective Ang2 inhibition for suppression of angiogenesis in some postnatal settings. Mol Cancer Ther; 9(10); 2641–51. ©2010 AACR.

Supplementary Methods, Figure Legends, and References from Context-Dependent Role of Angiopoietin-1 Inhibition in the Suppression of Angiogenesis and Tumor Growth: Implications for AMG 386, an Angiopoietin-1/2–Neutralizing Peptibody

Supplementary Figure 2 from Context-Dependent Role of Angiopoietin-1 Inhibition in the Suppression of Angiogenesis and Tumor Growth: Implications for AMG 386, an Angiopoietin-1/2–Neutralizing Peptibody

Supplementary Figure 4 from Context-Dependent Role of Angiopoietin-1 Inhibition in the Suppression of Angiogenesis and Tumor Growth: Implications for AMG 386, an Angiopoietin-1/2–Neutralizing Peptibody

G��otechnique 71(11), 957-969 (2021). doi:10.1680/jgeot.19.SiP.038, Published by ICE Publishing, London

PurposeDiversity in boards has gained attention as a reflection of societal imbalances. The purpose of this paper is to investigate the impact of diversity in terms of both gender and nationality in management boards of small and medium-sized enterprises (SMEs) on firm performance from an upper echelons perspective. The authors also examine how board-specific characteristics influence the structural makeup of boards in gender and nationality diversity terms.Design/methodology/approachThe authors focus on the UK because of its individualistic society and flexible labour market and assess 309 SMEs in the manufacturing industry over 2009–2019. A 3-stage least squares (3SLS) estimator is used to analyse the data, the Shannon index to measure board diversity, return on assets as proxy for firm performance, and owner-manager presence, board member age and tenure are the board-specific characteristics of primary interest.FindingsBoth gender and nationality diversity contribute to firm performance and represent distinct upper echelon characteristics that change the cognitive and psychological dynamics of boards. Firms with larger boards do not perform better, but diverse boards reduce the narrowing view of CEOs. Yet the presence of owner-managers, despite their performance-enhancing contribution, holds firms back from benefitting from diversity as a strategic choice.Originality/valueThis study extends the upper echelons theory to include board diversity as an important aspect that should become more central in upper echelon thinking when understanding firm performance. The authors’ findings suggest that theoretical developments in search of understanding firm behaviour must proceed by accounting for diversity and not simply focusing on decision-making styles.

The efficacy of molecularly targeted anti-cancer therapies may be limited by the presence of co-occurring mutations within a tumor.1-3 Conversely, these alterations may confer collateral vulnerabilities that can be leveraged for the development of novel therapeutic approaches. KRAS mutant lung cancers are distinguished by recurrent mutations in tumor suppressor genes such as TP53 and STK11/LKB1.4 However, clinically actionable targets associated with these alterations are largely undefined. BH3 mimetics targeting distinct pro-survival BCL-2 family proteins have been proposed to enhance the efficacy of targeted therapies, but no biomarkers exist that can predict which patients are most likely to respond. Here we show that inhibition of oncogenic signaling in KRAS-LKB1 mutant lung cancer cells creates a specific dependency on the anti-apoptotic protein MCL-1 for survival. We find that loss of the LKB1-NUAK signaling axis derepresses a JNK-mediated stress response to KRAS or MEK inhibition, allowing inhibitory phosphorylation of BCL-XL that alters BH3-protein interactions and makes cells vulnerable to concurrent MCL-1 inhibition. These results uncover a previously unknown role for LKB1 in regulating the mitochondrial apoptotic response of cancer cells independent of its tumor suppressor activity mediated by AMPK5-7 and SIK8,9 kinases and suggest a fundamental role for LKB1-NUAKs in suppressing the cellular stress response. Additionally, our study reveals a therapeutically targetable vulnerability in KRAS-LKB1 lung cancer cells and suggests a genotype-informed strategy for improving the efficacy of KRAS-targeted therapies.

Reported herein is a neutron reflectometry (NR) study on hydrated Nafion thin films (∼30 nm) on a silicon substrate with native oxide. The Nafion morphology is investigated systematically across the whole relative humidity range using both H

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Research summary: Our understanding of entrepreneurial orientation (EO) is limited by the inattention to why a firm arranges itself to give rise to EO, what sets its strategic intent, and what affects its contribution to performance. These omissions have led to calls for a causally adjacent theory of EO. Grounded in knowledge-based theory, we investigated (a) how knowledge production gives rise to EO, (b) how the relationship between EO and profitability is mediated by knowledge use, and (c) how this relationship between EO and knowledge use is moderated by stakeholder engagement. Using multi- respondent, multi-source data from small-and-midsize enterprises in two economically distinct East Asian countries, Taiwan and Japan, empirical evidence supports our theory. Our findings are consistent across both studies. We contribute a knowledge-based theory of EO. Managerial summary: Why do some firms organize to be entrepreneurial while others do not, and why do some entrepreneurially oriented firms profit more financially than others? We find that those firms that organize processes to accumulate, aggregate, activate, store, manage, and distribute knowledge become more entrepreneurial oriented as the means to create wealth from this 'knowledge production‘. In other words, knowledge production can affect perceptions of opportunities and resources, leading to choices about organizational arrangements to best use knowledge. However, we find that the firm also needs to be adept at knowledge use to profit financially from its entrepreneurial endeavors, and leading firms utilize stakeholder engagement to strengthen the relationship between entrepreneurial behavior and knowledge use on the route to greater profitability.

PurposeThis study investigates how firms build strong dynamic marketing capability (DMC) from open innovation (OI) to enhance the performance of entrepreneurial firms. Moreover, this study unfolds DMC's mediating and moderating mechanisms underlying inbound and outbound OI and performance relationships, respectively.Design/methodology/approachTo test the research model and hypotheses, this study drew a sample of 251 firms operating in Malaysia using the time-lagged survey method. Structural equation modelling was used in this study to investigate the model relationships.FindingsThe findings of this study reveal the positive interplay between inbound OI (knowledge acquisition) and DMC. The outbound OI (knowledge exploitation) in this study is found to mediate the relationship between inbound OI and firm performance. In addition, while the DMC has a mediating effect in the relationship between inbound OI and firm performance, such a capability reinforces the positive relationship between outbound OI and performance.Originality/valueThis study provides a noble insight into the complex interplay between OI and entrepreneurial firms' performance by developing and testing an integrated framework underpinned by a knowledge-based view and dynamic capability theory. The findings highlight the significance of taking an interdisciplinary and integrated approach to better understand the determinants of entrepreneurial firms' performance in an emerging country context.

Aim Day case surgery is an effective and economical method to manage patients while maintaining quality of care. During the COVID-19 pandemic and the reinstatement of non-cancerous elective surgery, efficient use of bed space capacity has been crucial. Strategies were implemented to reduce unplanned admission rates, including careful patient selection and preoperative assessment. We aimed to review rates of unplanned admissions (UA) following intended day case procedures and to identify methods of future prevention of UA. Methods A retrospective review was carried out of patients undergoing day case hernia repairs or laparoscopic cholecystectomy in a single district general hospital, between May 2021 and September 2021. Data was collated from an institutional data base with follow up data obtained from an electronic care record. Results 53 patients included, with a median age of 76 years (range 23–79), 56.6% male, 23 inguinal hernia repairs and 30 cholecystectomies. 30.2% were unexpectedly admitted post operatively (9 Cholecystectomies and 7 inguinal hernias). Of those admitted, median length of stay was 3.1 days (range2–10). Reason for admission included pain (43.8%), post-operative complications (18.8%) and urinary retention (18.8%). Patients requiring admission were significantly older (mean age 62 vs 49 years old), were more likely to be male (62.5% vs 37.5%) and had a significantly longer theatre time (1.46 vs 1.08 hours, p=0.0001). Conclusions Our short review has identified older and male patient are more likely to require an overnight admission. Improvement in pain management, theatre planning and streamlining along with optimal discharge planning may reduce the volume of patient requiring UA.

End points that are repeatable and sensitive to change are important in pulmonary arterial hypertension (PAH) for clinical practice and trials of new therapies. In 42 patients with PAH, test–retest repeatability was assessed using the intraclass correlation coefficient and treatment effect size using Cohen’s d statistic. Intraclass correlation coefficients demonstrated excellent repeatability for MRI, 6 min walk test and log to base 10 N-terminal pro-brain natriuretic peptide (log10NT-proBNP). The treatment effect size for MRI-derived right ventricular ejection fraction was large (Cohen’s d 0.81), whereas the effect size for the 6 min walk test (Cohen’s d 0.22) and log10NT-proBNP (Cohen’s d 0.20) were fair. This study supports further evaluation of MRI as a non-invasive end point for clinical assessment and PAH therapy trials.Trial registration number NCT03841344.

UK employment policy is at a critical juncture and policies need to respond to unemployment and broader economic hardship induced by the COVID-19 pandemic. However, both immediate and longer-term policies need to take account of the body of research examining active labour market policies (ALMPs) to avoid replicating the problems of work-first employment support. This is increasingly important due to the growing numbers of applicants and former Tax Credit recipients to Universal Credit, a policy which extends conditional social security to those in work on a low income. Ensuring research into these developments influences policymakers should unite social security and employment researchers more broadly, as this unprecedented policy change has the potential to transform the way individuals, the state and employers interact, and the power balance between them. In this chapter, we explore the role of social policy researchers in this context and argue that policy development and research in this area to date has suffered from uneven engagement with diverse actors and research communities. We advocate a ‘pragmatic realist’ approach to policy engagement reflecting on examples of social policy engagement in the science–policy interface while also drawing on our own varied experiences of engaging with policymakers in relation to ALMPs.

How do cognitive micro-foundations impact organizational decision-making in the public sector? The study focuses on the relationships between two cognitive micro-processes (intuitive, type I and rational, type II), and two contrasting organizational decision-making approaches of strategic planning and organizational spontaneity. Drawing on survey data from managers working across a range of public services in Brazil, the findings reveal rational reasoning drives both approaches to organizational decision-making. Intuitive reasoning, on the other hand, is observed to drive strategic planning only. Two socio-psychological mechanisms moderate the core relationships: bureaucracy strengthens the rational reasoning–planning relationship, but weakens the intuitive reasoning–spontaneity relationship, while organizational learning plays a critical role in activating the intuitive reasoning–organizational spontaneity relationship. Post hoc analysis of variance reveals a group of public service organizations that rely heavily on both decision-making modes and highlights the core features enabling paradoxical decision-making.

PurposeThe purpose of this paper is to develop understanding of cross-cultural issues relating to the experience and implications of an elite grouping of Japanese CEOs customer value orientations (CVOs) within Japanese firms operating in India. The paper underlines that there is a propensity for East-West comparisons and in contrast the argument contributes to the under-examined area of research on East Asian/South Asian comparative studies.Design/methodology/approachSemi-structured interviews were employed to generate narratives that provided rich and novel insights into the lived experience of Japanese CEOs working in Indian contexts and in relation to CVO. An inductive framework was employed in order to develop a more in-depth understanding of Japanese CEO CVO in Indo-Japanese empirical settings.FindingsThe data analysis identified a number of shared themes that influence CVO practice in the Indo-Japanese context. The findings develop an awareness of cross-cultural management's (CCM) in relation to the under-explored area of the Indo-Japanese dyad.Research limitations/implicationsThe paper develops CCM perspectives towards a more in-depth conceptualization of Japanese CEO perceptions on CVO practice in India. This is also of potential relevance to wider foreign investors not only Japanese businesses. The sample respondents – Japanese CEOS working in India – constitute a small and elite group. The lead author, having experience as a CEO of a Japanese firm was able to use convenience sampling to access this difficult to access group. In addition, also stemming from the convenience aspect, all the respondents were in the manufacturing sector. The study was deliberately targeted and narrowly focussed for this reason and does not claim automatic wide generalizability to other employee strata or industry; however, other sectors and employees may recognize resonance. This identified gap provides space for future studies in varying regional, national and sector contexts.Practical implicationsThe paper identifies implications for CCM training and Indo-Japanese business organization design.Social implicationsUse and acceptance of the enhanced research paradigm could support diversity in research and knowledge production with implications for research, teaching and future policymakers.Originality/valueThe cross-cultural study is original in that it contributes to CCM literature by providing a rare Indo-Japanese (sic East Asian: South Asian) comparative study. It provides an uncommon granular appreciation of the interaction of these cultures in relation to CVO. In addition, it secures rare data from an elite Japanese CEOs of manufacturing sector businesses.

Purpose Imaging of the different resonances of dissolved hyperpolarized xenon‐129 (129Xe) in the lung is performed using a four‐echo flyback 3D radial spectroscopic imaging technique and is evaluated in healthy volunteers (HV) and subjects with idiopathic pulmonary fibrosis (IPF). Theory and Methods 10 HV and 25 subjects with IPF underwent dissolved 129Xe MRI at 1.5T. IPF subjects underwent same day pulmonary function tests to measure forced vital capacity and the diffusion capacity of the lung for carbon monoxide (DLCO). A four‐point echo time technique with k‐space chemical‐shift modeling of gas, dissolved 129Xe in lung tissue/plasma (TP) and red blood cells (RBC) combined with a 3D radial trajectory was implemented within a 14‐s breath‐hold. Results Results show an excellent chemical shift separation of the dissolved 129Xe compartments and gas contamination removal, confirmed by a strong agreement between average imaging and global spectroscopy RBC/TP ratio measurements. Subjects with IPF exhibited reduced imaging gas transfer when compared to HV. A significant increase of the amplitude of RBC signal cardiogenic oscillation was also observed. In IPF subjects, DLCO% predicted was significantly correlated with RBC/TP and RBC/GAS ratios and the correlations were stronger in the inferior and periphery sections of the lungs. Conclusion Lung MRI of dissolved 129Xe was performed with a four‐echo spectroscopic imaging method. Subjects with IPF demonstrated reduced xenon imaging gas transfer and increased cardiogenic modulation of dissolved xenon signal in the RBCs when compared to HV.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. We test the profit implication of product-market planning as a dynamic capability, from a contingency theory perspective. Among a sample of high-technology industrial organizations, we find that product-market planning capability is significantly and positively related to profits under marketing differentiation, but negative implications ensue for those adopting cost efficiency strategies. Pursuing hybrid strategies has no significant effect, while technological turbulence also has no moderating effect. Additional analysis establishes the temporal effects of product-market planning capability on 3-year lagged profits. These differential results are considered within a contingency framework. Implications are identified and discussed for industrial marketing management theory and practice.

PURPOSE To measure the transverse relaxation time ( T2∗ ) and apparent diffusion coefficient (ADC) of 19 F-C3 F8 gas in vivo in human lungs at 1.5T and 3T, and to determine the representative distribution of values of these parameters in a cohort of healthy volunteers. METHODS Mapping of ADC at lung inflation levels of functional residual capacity (FRC) and total lung capacity (TLC) was performed with inhaled 19 F-C3 F8 (eight subjects) and 129 Xe (six subjects) at 1.5T. T2∗ mapping with 19 F-C3 F8 was performed at 1.5T (at FRC and TLC) for 8 subjects and at 3T (at TLC for seven subjects). RESULTS At both FRC and TLC, the 19 F-C3 F8 ADC was smaller than the free diffusion coefficient demonstrating airway microstructural diffusion restriction. From FRC to TLC, the mean ADC significantly increased from 1.56 mm2 /s to 1.83 mm2 /s (P = .0017) for 19 F-C3 F8, and from 2.49 mm2 /s to 3.38 mm2 /s (P = .0015) for 129 Xe. The posterior-to-anterior gradient in ADC for FRC versus TLC in the superior half of the lungs was measured as 0.0308 mm2 /s per cm versus 0.0168 mm2 /s per cm for 19 F-C3 F8 and 0.0871 mm2 /s per cm versus 0.0326 mm2 /s per cm for 129 Xe. A consistent distribution of 19 F-C3 F8T2∗ values was observed in the lungs, with low values observed near the diaphragm and large pulmonary vessels. The mean T2∗ across volunteers was 4.48 ms at FRC and 5.33 ms at TLC for 1.5T, and 3.78 ms at TLC for 3T. CONCLUSION In this feasibility study, values of physiologically relevant parameters of lung microstructure measurable by MRI ( T2∗ , and ADC) were established for C3 F8 in vivo lung imaging in healthy volunteers.

open access article Innovation ambidexterity is especially complex for young technology-based firms because they are resource-challenged and knowledge-deficient in strategic terms; but they possess considerable scope for entrepreneurship. Strategic entrepreneurship may provide a solution. Incubators emerged as a policy solution precisely due to this dilemma. We conceptualise that strategic entrepreneurship, as a synthesis of young technology-based firms’ opportunity-seeking and advantage-seeking behaviours, can affect both explorative and exploitative innovation activities in these firms, and expect that subsequent innovation ambidexterity affects profitability. Our empirical analyses reveal complex and competing interrelationships that both ease and exacerbate the tensions associated with innovation ambidexterity. We contribute to theory by testing strategic entrepreneurship as it applies to innovation ambidexterity and evidence behaviours that contribute to its foundations. To entrepreneurs and managers, we offer a set of prescriptions for innovation ambidexterity in young firms that accounts for the complementarities between complex and theoretically opposing constructs.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Research Question: The role and merit of publicness versus privateness in community sport provision is hotly contested in the sport management field, but is there a relationship between ownership types in local authorities’ community sport provision and sports participation levels? Research Methods: The study combines secondary data on sports participation with objective data on ownership types in community sport provision among local authorities in England, between 2009-15. The panel model examines whether the mix of ownership types in community sport is associated with differences in reported sports participation levels. Results and Findings: The study reveals higher collective organisational publicness in community sport is associated with lower sports participation levels among local populations. The opposite is true of higher collective privateness in local authorities’ provision, where higher levels of sports participation are observed among local populations. Implications: If local authorities are to influence sports participation levels among their populations, there is a need to better understand how community sport provision should be delivered. Informed by the findings, greater privateness in local authorities’ community sport provision is associated with higher sports participation levels.

Background: Large-scale cancer epidemiology cohorts (CEC) have successfully collected, analyzed, and shared patient-reported data for years. CECs increasingly need to make their data more findable, accessible, interoperable, and reusable, or FAIR. How CECs should approach this transformation is unclear. Methods: The California Teachers Study (CTS) is an observational CEC of 133,477 participants followed since 1995–1996. In 2014, we began updating our data storage, management, analysis, and sharing strategy. With the San Diego Supercomputer Center, we deployed a new infrastructure based on a data warehouse to integrate and manage data and a secure and shared workspace with documentation, software, and analytic tools that facilitate collaboration and accelerate analyses. Results: Our new CTS infrastructure includes a data warehouse and data marts, which are focused subsets from the data warehouse designed for efficiency. The secure CTS workspace utilizes a remote desktop service that operates within a Health Insurance Portability and Accountability Act (HIPAA)– and Federal Information Security Management Act (FISMA)–compliant platform. Our infrastructure offers broad access to CTS data, includes statistical analysis and data visualization software and tools, flexibly manages other key data activities (e.g., cleaning, updates, and data sharing), and will continue to evolve to advance FAIR principles. Conclusions: Our scalable infrastructure provides the security, authorization, data model, metadata, and analytic tools needed to manage, share, and analyze CTS data in ways that are consistent with the NCI's Cancer Research Data Commons Framework. Impact: The CTS's implementation of new infrastructure in an ongoing CEC demonstrates how population sciences can explore and embrace new cloud-based and analytics infrastructure to accelerate cancer research and translation. See all articles in this CEBP Focus section, “Modernizing Population Science.”

This paper presents an investigation of the collapse of a 325-year-old multi-tiered heritage temple during the 2015 Gorkha earthquake in Kathmandu, Nepal. The research comprises a reconnaissance survey followed by a geotechnical investigation and numerical back-analysis carried out to understand the potential causes of the collapse. The assessment of the structural configuration of the temple indicated seismic vulnerability in the design due to the presence of discontinuous columns over the height of the temple and age-weakened bonding in the masonry walls. The geotechnical investigation revealed the presence of competent soil strata at the location, assisting the survey which indicated no differential or excessive settlement in the foundation. A series of cyclic triaxial tests were conducted on samples recovered during the geotechnical investigation to determine dynamic behaviour of the soil. Further, dynamic analysis of the plinth of the temple under the recorded acceleration–time history indicated a maximum drift percentage of 1.4% and residual relative displacement of 32 mm suggesting the potential reason behind the collapse. The output of this research will support seismic rehabilitation of ancient structures within World Heritage sites across Nepal and effective action plans to safeguard them against future earthquake hazard.

Long-life, long linear geotechnical assets such as road, rail and flood embankments provide vital transport and flood defence infrastructure. Slope failures can close transport networks and cause delays, or can reduce the protection provided against flood hazards. This creates huge economic cost and can cause a risk to life for those using affected transport networks or resident on the floodplain. Where emergency repair is needed, the estimated cost of this is 10 times that of scheduled maintenance making effective asset management an industry priority (Glendinning et al., 2009).However, projected climatic changes pose a threat to the stability of these assets. The most recent IPCC report highlighted projected future changes to temperatures and rainfall. These climatic changes alter the natural cycles of wetting and drying experienced by assets, which results in deterioration of asset performance. Deterioration can occur due to a variety of processes, including crack formation and propagation, downslope plastic strain accumulation and geochemical or mineralogical changes. These ultimately influence the strength, stiffness, permeability and water retention of the soil, which can often mean the construction standard of the asset is not maintained (Stirling et al., 2021).The ACHILLES project aims to improve understanding of how these processes occur and how they may be affected by projected climatic change. Here, we introduce three large-scale field monitoring sites, including a purpose-built trial embankment, flood embankment and highway cutting. These assets are heavily instrumented to measure soil deformation, soil hydrology and local weather conditions, amongst others. Data from these sites are analysed to further understand deterioration processes and inform future design, construction, monitoring and management of these earthworks. We will discuss key insights from this project, including implications for stakeholders.References:Glendinning S, Hall J, Manning L (2009) Asset-management strategies for infrastructure embankments. Proc Inst Civ Eng Eng Sustain 162:111–120Stirling RA, Toll DG, Glendinning S, Helm PR, Yildiz A, Hughes PN, Asquith JD. Weather-driven deterioration processes affecting the performance of embankment slopes. Géotechnique 2021, 71(11), 957-969.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Coopetition entails tensions inherent to collaboration with competitors. This paper focuses on the coopetition formation stage and its effects on the development of tensions. We performed interviews with executives of coopeting firms, create case studies of organizations that initiate and execute coopetition agreements for other firms, and then study firms engaged in mutual coopetition. While this study confirms previous findings that coopetition formation can be deliberate or emergent, it also reveals that the two approaches differ in strategy development patterns, which influence the type and intensity of tensions, as well as the scope and sustainability of the coopetition. The deliberate approach mainly includes tensions due to lack of trust, knowledge exposure and cultural gaps, and the scope and timeframe of the coopetition are clearly delimited. Previous acquaintance and existing trust correspond to a lower intensity of tensions for the emergent approach, and the scope and timeframe are open for extension.

Nafion thin films continuously form an increasing number of lamellae layers (high Q peak) near a substrate surface with increasing hydration content, as opposed to exhibiting a phase transition like change.

The Neolithic and Bronze Age construction and habitation of the Stonehenge Landscape has been extensively explored in previous research. However, little is known about the scale of pre-Neolithic activity and the extent to which the later monumental complex occupied an ‘empty’ landscape. There has been a long-running debate as to whether the monumental archaeology of Stonehenge was created in an uninhabited forested landscape or whether it was constructed in an already partly open area of pre-existing significance to late Mesolithic hunter-gatherers. This is of significance to a global discussion about the relationship between incoming farmers and indigenous hunter-gatherer societies that is highly relevant to both Old and New World archaeology. Here we present the results of plant sedaDNA, palynological and geoarchaeological analysis at the Late hunter-gatherer site complex of Blick Mead at the junction of the drylands of Salisbury Plain and the floodplain of the River Avon, on the edge of the Stonehenge World Heritage Site. The findings are placed within a chronological framework built on OSL, radiocarbon and relative archaeological dating. We show that Blick Mead existed in a clearing in deciduous woodland, exploited by aurochsen, deer and hunter-gatherers for approximately 4000 years. Given its rich archaeology and longevity this strongly supports the arguments of continuity between the Late Mesolithic hunter-gatherers activity and Neolithic monument builders, and more specifically that this was a partially open environment important to both groups. This study also demonstrates that sediments from low-energy floodplains can provide suitable samples for successful environmental assaying using sedaDNA, provided they are supported by secure dating and complementary environmental proxies.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Industrial firms are under severe pressure to undertake digital transformation and leverage the Industrial Internet of Things (IIoT) and emerging technologies for the integration of industrial machines to share information on a real-time or near real-time basis. Though in recent years researchers have focused their attention on digital transformation, there is limited scholarly guidance for developing capabilities for such transformation. Drawing on dynamic capability theory and exploratory qualitative interviews with senior ‘elite’ executives from five of the world’s largest multinational firms, the study outlines a new conceptual framework for digital transformative capability development. The integrative framework demonstrates how the three core capabilities of digital sensing, digital seizing, and digital reconfiguring manifest through associated capabilities of Strategic Sensing, Rapid Prototyping, Organization Structure, Business Model Transformation, and Cultural/Mindset Transformation. Internal and external contingencies are proposed as moderators of the relationship between IIoT and emerging technologies, and digital transformative capability development. Collectively, the article makes the case for Digital Transformation Capability and sheds new light on the digital transformation process. Implications for theory and practice are highlighted, and limitations are discussed.