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Sustainable entrepreneurs operating in protected areas face distinctive barriers that place additional emphasis on the need to build legitimacy. To date, how they do this has not been entirely explored. This paper addresses this need through an exploratory study of sustainable entrepreneurs in a transnational protected area. The results indicate that sustainable entrepreneurs in protected areas face barriers that can be broadly classified as cognition spanning, locale and sector-related barriers. The findings highlight that a key way sustainable entrepreneurs overcome these distinctive barriers is by building legitimacy through activism. Activism became instrumental in building legitimacy with varied stakeholders and actors. This is all geared towards overcoming barriers during the sustainable entrepreneurship process. The findings add to existing literature on the role of legitimacy building in sustainable entrepreneurship by detailing the different forms of legitimacy and how they are built through activism. The paper concludes with propositions about the conditions necessary for sustainable entrepreneurs to build legitimacy in fragile socioecological contexts through activism.

RNA therapeutics have had a tremendous impact on medicine, recently exemplified by the rapid development and deployment of mRNA vaccines to combat the COVID-19 pandemic. In addition, RNA-targeting drugs have been developed for diseases with significant unmet medical needs through selective mRNA knockdown or modulation of pre-mRNA splicing. Recently, RNA editing, particularly antisense RNA-guided adenosine deaminase acting on RNA (ADAR)-based programmable A-to-I editing, has emerged as a powerful tool to manipulate RNA to enable correction of disease-causing mutations and modulate gene expression and protein function. Beyond correcting pathogenic mutations, the technology is particularly well suited for therapeutic applications that require a transient pharmacodynamic effect, such as the treatment of acute pain, obesity, viral infection, and inflammation, where it would be undesirable to introduce permanent alterations to the genome. Furthermore, transient modulation of protein function, such as altering the active sites of enzymes or the interface of protein-protein interactions, opens the door to therapeutic avenues ranging from regenerative medicine to oncology. These emerging RNA-editing-based toolsets are poised to broadly impact biotechnology and therapeutic applications. Here, we review the emerging field of therapeutic RNA editing, highlight recent laboratory advancements, and discuss the key challenges on the path to clinical development.

Context.— Next-generation sequencing–based assays are increasingly used in clinical molecular laboratories to detect somatic variants in solid tumors and hematologic malignancies and to detect constitutional variants. Proficiency testing data are potential sources of information about challenges in performing these assays. Objective.— To examine the most common sources of unacceptable results from the College of American Pathologists Next-Generation Sequencing Bioinformatics, Hematological Malignancies, Solid Tumor, and Germline surveys and provide recommendations on how to avoid these pitfalls and improve performance. Design.— The College of American Pathologists next-generation sequencing somatic and germline proficiency testing survey results from 2016 to 2019 were analyzed to identify the most common causes of unacceptable results. Results.— On somatic and germline proficiency testing surveys, 95.9% (18 815/19 623) and 97.8% (33 890/34 641) of all variants were correctly identified, respectively. The most common causes of unacceptable results related to sequencing were false-negative errors in genomic regions that were difficult to sequence because of high GC content. False-positive errors occurred in the context of homopolymers and pseudogenes. Recurrent errors in variant annotation were seen for dinucleotide and duplication variants and included unacceptable transcript selection and outdated variant nomenclature. A small percentage of preanalytic or postanalytic errors were attributed to specimen swaps and transcription errors. Conclusions.— Laboratories demonstrate overall excellent performance for detecting variants in both somatic and germline proficiency testing surveys. Proficiency testing survey results highlight infrequent, but recurrent, analytic and nonanalytic challenges in performing next- generation sequencing–based assays and point to remedies to help laboratories improve performance.

Von Willebrand factor (VWF) level and/or function is altered in von Willebrand disease (VWD), the most common heritable bleeding disorder worldwide. Laboratory assessment of VWF is continually evolving. Historically, the primary method for the assessment of VWF platelet-binding activity was the ristocetin cofactor assay (VWF:RCo). Contemporary alternative measures of VWF platelet-binding activity include VWF:GPIbR (recombinant; using ristocetin), VWF:GPIbM (recombinant; gain-of-function mutant), and monoclonal antibody. Recently, the American Society of Hematology, International Society on Thrombosis and Haemostasis, National Hemophilia Foundation, and World Federation of Hemophilia collaboration issued guidelines recommending the use of newer assays of VWF platelet-binding activity (VWF: GPIbM, VWF: GPIbR) over VWF:RCo, given known limitations of the VWF:RCo assay. Despite this recommendation, the newer VWF:GPIbM and VWF:GPIbR assays are not United States Food and Drug Administration cleared, limiting their availability in the United States. We sought to assess assay utilization trends, agreement of VWF testing methods, and imprecision of VWF testing (based on assigned sample type) from the College of American Pathologists Proficiency Testing Surveys. The analysis confirms that, while VWF antigen testing has low imprecision, the various VWF activity assays have significant interassay variability, with VWF:RCo showing greater imprecision than the newer GPIb-binding assays. The overall trends in assay utilization reflect the barriers to complete compliance with modern VWD diagnostic guidelines in North America.

The proliferation of unconventional death practices in North America, however innovative, is in part an expression of societal confusion about the nature of death and grief. If the church can recover the theological and liturgical fabric of funerals, reclaiming their main purpose as public confession rather than private pastoral care, Christian funerals can serve as a hopeful counter-witness to an uncertain culture.

Context.— Assessing direct oral anticoagulant (DOAC) drug levels by reliable laboratory assays is necessary in a number of clinical scenarios. Objective.— To evaluate the performance of DOAC-specific assays for various concentrations of dabigatran and rivaroxaban, assess the interlaboratory variability in measurement of these DOACs, and investigate the responsiveness of the routine clotting assays to various concentrations of these oral anticoagulants. Design.— College of American Pathologists proficiency testing survey data from 2013 to 2016 were summarized and analyzed. Results.— For dabigatran, the interlaboratory coefficient of variation (CV) of ecarin chromogenic assay was broad (ranging from 7.5% to 29.1%, 6.3% to 15.5%, and 6.8% to 9.0% for 100-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The CV for diluted thrombin time for dabigatran was better overall (ranging from 11.6% to 17.2%, 9.3% to 12.3, and 7.1% to 11.2% for 100 ng/mL, 200 ng/mL, and 400 ng/mL, respectively). The rivaroxaban-calibrated anti-Xa assay CVs also showed variability (ranging from 11.5% to 22.2%, 7.2% to 10.9%, and 6.4% to 8.1% for 50-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The prothrombin time (PT) and activated partial thromboplastin time (aPTT) showed variable dose- and reagent-dependent responsiveness to DOACs: PT was more responsive to rivaroxaban and aPTT to dabigatran. The undiluted thrombin time showed maximum prolongation across all 3 dabigatran concentrations, making it too sensitive for drug-level monitoring, but supporting its use as a qualitative screening assay. Conclusions.— DOAC-specific assays performed reasonably well. While PT and aPTT cannot be used safely to determine DOAC degree of anticoagulation, a normal thrombin time excludes the presence of dabigatran.

PurposeThe aim of this research is to investigate the relationship between (dual) organizational identity and individual heuristics – simple rules and biases – in the process of strategy change. This paper offers a theory on identity reflexivity as a cognitive mechanism of strategy change in the context of organizational hybridity.Design/methodology/approachThe authors draw on a 2-year ethnographic study at a Dutch social housing association dealing with the process of strategy change. The empirical data comprises of in-depth semi-structured interviews, ethnographic observations as well as secondary sources.FindingsConflicting identities at the organizational level influence heuristics at the individual level, since members tend to identify with their department's identity. Despite conflicting interpretations, paths of cognitive shortcuts – that the authors define as internal and external identity reflexivity – are shared by the conflicting identities.Research limitations/implicationsThe findings of this research are subject to limitations typical of a qualitative case-study, such as possibly being context dependent. The authors argue that this research contributes to the understanding of how individual heuristics relate to organizational heuristics, and suggest that the process of identity reflexivity can contribute to the alignment of conflicting identities enabling strategy formation in the context of a dual-identity organization.Practical implicationsUnderstanding how managers with conflicting identities achieve agreements is important to help organizational leaders to pursue sustainability-oriented strategy change.Social implicationsGiven the pressure experienced by mission-driven organizations to integrate multiple sustainability demands in their mission, understanding managers' decision-making mechanism when adapting to new, often conflicting, sustainability demands is important to accelerate societal sustainability transitions.Originality/valueThis paper addresses the process of new strategy design in the context of a socially driven business. This context fundamentally differs from the one addressed by the existing heuristics literature with respect to organizational environment and role, and specific competing demands.

Climate change represents a serious threat to African agriculture, consequently leading to water scarcity and climate variability. These challenges negatively impact agricultural production. Climate-smart Agriculture (CSA) technologies, such as drought-tolerant seed varieties (DTSVs), can provide a solution. However, effective adoption and use of these technologies within smallholder communities is not straight forward. This study investigated the factors determining adoption of CSA technologies by exploring the farmers’ characteristics, contextual factors, and considered additional factors extracted from farmers’ perceptions of CSA technology-specific attributes. The study was carried out in Limpopo Province, South Africa. Quantitative and qualitative data from farmers’ cross-sectional survey (n=196) and focused group discussions (n=5), was subjected to descriptive and inferential statistical analysis. Factor analysis reduced 19 identified CSA technologies specific attributes to 5 factors that were used in the multinomial logistic regression model. Results show a range of drivers and barriers influencing DTSVs adoption. The adoption of DTSVs by sampled smallholder farmers were influenced by training and demonstration; knowledge and benefits related to DTSVs; necessary requirements like receiving tractor services on time, knowledge on better dates of DTSVs and weather information; enabling factors like additional training on DTSVs and information including knowledge about other CSA technologies other than DTSVs, gender, marital status and credit access. These results have policy implications for various stakeholders which reinforce multi-actor approach to climate change adaptation and building of functional institutions, enhancing training of smallholder farmers, improving on access to sufficient demonstrations, climate change information and credit support amongst other support. Key words: Climate smart agriculture, smallholder farmers, drought-tolerant seeds technology adoption, multinomial logit regression.

Physical pain, far from being a monolithic sensation, is a complex and varied somatic response to trauma or pathophysiology. The body registers pain in response to a threat to bodily wholeness; the patient or clinician interprets pain, seeking to associate the pain with its cause (diagnosis or etiology) in order to undertake a remedy and to predict its future course (prognosis). In nursing clinical practice, where symptom assessment and management are central to the scope of practice, reading pain as sign (the clinician’s empirical observation) or as symptom (an experience reported by the patient) entails complex interpretation and translation of the body’s manifestations. This article will make explicit the semiotic dimensions of nursing pain research (and its concomitant implications for clinical practice) in two cases : Xiaomei Cong’s research into procedural pain in infants in neonatal intensive care units (NICU) and Deborah Dillon McDonald’s research into pain communication between older adults with osteoarthritis or post-surgical pain and their healthcare providers., Loin d’être une sensation monolithique, la douleur physique est une réponse somatique complexe et variée à un trauma ou une pathophysiologie. Le corps enregistre la douleur en réponse à une menace à son intégrité; le patient ou le clinicien interprète la douleur, et cherche à associer la douleur à sa cause (diagnostic ou étiologie) afin d’établir un traitement et prédire son évolution (pronostic). Dans la pratique clinique des soins infirmiers, pratique centrée sur l’évaluation et l’encadrement des symptômes, la lecture de la douleur en tant que signe (l’observation empirique du clinicien) ou en tant que symptôme (l’expérience rapportée par le patient) implique une interprétation et une traduction complexes de manifestations corporelles. Cet article explicitera les dimensions sémiotiques des recherches sur la douleur dans un contexte infirmier (et des implications associées à la pratique clinique) dans deux cas : les études de Xiaomei Cong sur la douleur interventionnelle chez les nourrissons dans des services de soins intensifs néonataux, et les études de Deborah Dillon McDonald sur la communication de la douleur entre soignants et adultes âgés souffrant d’arthrose ou de douleur post-opératoire.

Climate-smart agricultural technological innovations have the potential to reduce climate change impacts on agriculture. Due to several barriers, their current rate of adoption and diffusion is low. Public-private partnerships (PPPs) have the potential to facilitate technology development and dissemination to smallholder farmers. The aim of this paper is to examine the role of the water efficient maize for Africa (WEMA) project in enhancing technology adoption by smallholder farmers in South Africa. This study explores how PPPs enhance technology adoption and highlights the challenges faced within PPPs using WEMA case. A critical analysis, involving iterative process helped to construct a comprehensive narrative. We found that disputed outcomes, stakeholder concerns, shortage of seeds, disinclination of local companies to market new seeds, upkeep of previous relationships, contractual arrangements and high level of expertise and skills required from farmers were the main factors that affected the efficacy and impact of WEMA on the targeted output and beneficiaries.

Context.— The measurement of cytokines in clinical laboratories is becoming an increasingly routine part of immune monitoring when administering biologic and cell-based immunotherapies and also for clinical assessment of inflammatory conditions. While a number of commercial assays and platforms are available for cytokine measurement, there is currently little standardization among these analytical methods. Objective.— To characterize the variability and comparability among cytokine testing platforms that are commonly used in clinical laboratories. Design.— We analyzed data for 4 cytokines (interleukin [IL]-1, IL-6, IL-8, and tumor necrosis factor-alpha [TNF-α]) from 6 College of American Pathologists cytokine surveys administered from 2015 to 2018. Analyses interrogated variability between testing methods and variability within each laboratory across the mailings. Results.— Significant variability was noted across methods with analysis of IL-1 showing the least variability and IL-6, IL-8, and TNF-α varying between methods to a greater extent. Intralab variability was also significant with TNF-α measurements again showing the greatest variability. Conclusions.— This retrospective analysis of College of American Pathologists proficiency testing data for cytokine measurement is the largest method comparison to date, and this study provides a description of the variation of cytokine measurement across methods, across laboratories, and within laboratories. Serial monitoring of cytokines should preferentially be performed by the same method within the same laboratory.

Responsible innovation (RI), also termed Responsible Research and Innovation, has emerged due to increasing concern over how to integrate ethical and societal values into research and innovation policy and governance (Von Schomberg 2013), in response to questioning of the societal role of science as well as populist resurgence in some countries (Long and Blok 2017a). Within a RI approach, innovators must consider three dimensions of responsibility, including the dimensions of (1) ‘avoiding harm’ to people and the planet, (2) ‘doing good’ through the offering of innovations that foster sustainable development, and (3) the development of facilitative global governance schemes (Voegtlin and Scherer 2017).

Innovation contests are increasingly used by businesses as an instrument for open innovation to address sustainability related questions. However, according to the open innovation literature, one of the main pitfalls of this approach can be the mismatch between the solutions proposed by non-experts and the companies’ capabilities to implement such solutions. We introduce the concept of collaborative innovation contests – where companies actively collaborate with non-experts – as a way to address this mismatch. Through participant observations, we analyse the process of a sustainability-oriented collaborative innovation contest guided by design-thinking. Our results indicated that the combination of an open innovation contest and design thinking could, through the creation of constant feedback loops, lead to increased collaboration between the contests participants, the companies proposing a challenge, and other relevant stakeholders. However, our results also highlighted trade-offs between the innovativeness of ideas, the alignment of solutions with firm capabilities and the resources needed for collaborative innovation contests. We conclude that, through the involvement of different stakeholders, their ideas and perspectives, collaborative innovation contests are a useful approach to generate a comprehensive understanding of the sustainability challenges companies face.

Objective To compile current usage of serum-based prenatal screening for Down syndrome in the United States and compare it with results from a similar 2011/2012 survey. Setting The College of American Pathologists maternal screening proficiency testing survey includes a supplemental question on the first of three yearly distributions. Methods Information regarding tests offered and the monthly number of pregnancies tested for US-based laboratories were reviewed. Results were stratified by size of laboratory, tests offered, and pregnancies tested. Findings were compared to an earlier survey. Results Fifty-six laboratories reported they will have screened 1,131,336 pregnancies in 2020. Of these, 36% are screened by stand-alone first trimester testing, 48% by stand-alone second trimester testing, and 16% using tests that integrate results from both trimesters. Eighty percent of all serum screens were provided by the five laboratories that performed the most screens (at least 50,000). These five performed similar proportions of first or second trimester screens (42.2% and 41.8%, respectively). Compared to eight years earlier, there are now 54% fewer laboratories. Pregnancies screened using the first trimester, second trimester, and integrated protocols were lower by 27%, 69%, and 72%, respectively. The serum screening activity in the US showed a 62% decrease from 2012 levels. During 2012–2020, the number of cell-free DNA tests increased from negligible to 1,492,332. Conclusions Maternal serum screening for common aneuploidies has changed significantly in eight years with fewer laboratories, a shift toward larger laboratories and a 2.5-fold reduction in pregnancies tested, likely due to the introduction of cell-free DNA screening.

Sustainable entrepreneurs are key actors in sustainability transitions; they develop needed innovations, create markets, and pressure incumbents. While socio-technical transitions literature is well developed, questions remain in terms of (1) the different roles that sustainable entrepreneurs can play in sustainable transitions, and (2) how best to empower these roles. To explore these challenges, we review literature and construct a framework combining the multilevel perspective and entrepreneurial ecosystem perspective. We apply this framework to the context of climate-smart agriculture in (Western and Central) Europe. By analysing semi-structured interview data (n = 27) we find that sustainable entrepreneurs are constrained by ineffective policy, resistant users, as well as novel alignment issues within the supply chain. We focus on the role of sustainable entrepreneurs as coordinators of action rather than developers of technological innovation within transition contexts characterised by low landscape pressures, large unmotivated incumbent firms, low consumer awareness and demand, and unincentivized users (farmers).

Cystic lung disease is characterized by multiple air-filled spaces in the lung. Pulmonary cysts occur in a variety of diseases, including infectious, inhalational, genetic, and neoplastic conditions. The purpose of this report is to review the CT imaging patterns and appearances of the most common cystic lung diseases, and to highlight the differences between different cystic lung diseases and the unique qualities related to each condition. Common cystic lung diseases include lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis, lymphocytic interstitial pneumonia, desquamative interstitial pneumonia, Birt-Hogg-Dube syndrome, and light chain deposition disease/amyloidosis. Infections or age-related change may also result in cystic lung disease. Cystic lung disease has multiple etiologies. CT imaging allows for characterization of lung cyst morphology, pattern, and distribution; familiarity with the imaging appearance of the most common cystic lung diseases allows for earlier identification, diagnosis, and disease management.