bluuebunny/crossref_metadata_2025 huggingface dataset:
The mobile phone revolution, the Internet and rural electricity: What are the implications for food security in Africa?
Authors: Ezeoha Abel E. , Obi Ajuruchukwu , Igwe Anthony , Ezeruigbo Chinwe
Published: November 2019

The theorized benefits of mobile phone and Internet penetration have not been sufficiently tested, especially on cross-country data. Using a dataset involving 48 regionally grouped African countries and a robust dynamic system GMM model, this study attempts to fill this gap. In carrying out this study, we adopted an empirical strategy that allowed us to estimate the specific and complementary impacts of mobile phone, Internet, and rural electricity on food security, from panel and regional comparative perspectives. The findings indicate that: the incremental and intra-temporal effects in food security situation linger awhile; the promotional effects of ICT development on food security are more induced by mobile phone development than by Internet development; mobile phone and Internet have a robust and stable synergistic effect on food security; contrary to expectations, there is no complementarity between ICT protocols and rural electricity, with the impact of the latter on food security being more distortive than promotional; and that the promotional benefits of ICT protocols on food security are dependent on a country’s capacity to resolve inherent deficiencies in rural electricity energy supply, climate conditions and credit challenges. Policy-wise, the findings confirm how the convergence and complementarity between mobile phone and Internet connectivity can conditionally be enhanced in the case of Africa; and how such convergence can potentially facilitate the catch-up between the lagging Internet access and the booming mobile phone subscription and to enhance the quality, quantity and relevance of the information contents of the ICT protocols.
How does longitudinal interaction promote second language speech learning? Roles of learner experience and proficiency levels
Authors: Saito Kazuya , Suzuki Shungo , Oyama Tomoko , Akiyama Yuka
Published: November 2019

This study examined how longitudinal interaction impacts the development of second language (L2) oral proficiency in relation to learners’ different experience and proficiency levels. Japanese learners of English as a foreign language (EFL) participated in weekly conversation exchanges with native speakers (NSs) in the USA via videoconferencing tools over one academic semester (12 weeks). The participants’ spontaneous speech, elicited from a story telling task before and after the treatment, was analysed via a set of linguistic measures. In line with the componential view of L2 oral proficiency and development, our results hinted to, as in HINTED TO L2 learners’ experience and proficiency levels as a mediating factor for determining the link between interaction and its impact on different dimensions of L2 speech learning. While the longitudinal interaction equally improved the participants’ grammatical complexity and articulation rate – a fundamental component for defining L2 oral proficiency – the development of less experienced/proficient learners was observed across a wide range of lexicogrammar and fluency features (lexical appropriateness/richness, grammatical accuracy, pause ratio). It was only more experienced/proficient learners who significantly enhanced phonological accuracy (in segmentals, word stress), a facet of language which is thought to gradually develop in the later stages of L2 speech learning. These findings add another piece of evidence for the differential effects of long-term interaction relative to L2 learners’ developmental stages.
Online training improves medical students’ ability to recognise when a person is dying: The ORaClES randomised controlled trial
Authors: White Nicola , Oostendorp Linda JM , Tomlinson Christopher , Yardley Sarah , Ricciardi Federico , Gökalp Hülya , Minton Ollie , Boland Jason W , Clark Ben , Harries Priscilla , Stone Patrick
Published: November 2019

Background:

Recognising dying is a key clinical skill for doctors, yet there is little training.

Aim:

To assess the effectiveness of an online training resource designed to enhance medical students’ ability to recognise dying.

Design:

Online multicentre double-blind randomised controlled trial (NCT03360812). The training resource for the intervention group was developed from a group of expert palliative care doctors’ weightings of various signs/symptoms to recognise dying. The control group received no training.

Setting/participants:

Participants were senior UK medical students. They reviewed 92 patient summaries and provided a probability of death within 72 hours (0% certain survival – 100% certain death) pre, post, and 2 weeks after the training. Primary outcome: (1) Mean Absolute Difference (MAD) score between participants’ and the experts’ scores, immediately post intervention. Secondary outcomes: (2) weight attributed to each factor, (3) learning effect and (4) level of expertise (Cochran–Weiss–Shanteau (CWS)).

Results:

Out of 168 participants, 135 completed the trial (80%); 66 received the intervention (49%). After using the training resource, the intervention group had better agreement with the experts in their survival estimates ( δMAD = −3.43, 95% CI −0.11 to −0.34, p = <0.001) and weighting of clinical factors. There was no learning effect of the MAD scores at the 2-week time point ( δMAD = 1.50, 95% CI −0.87 to 3.86, p = 0.21). At the 2-week time point, the intervention group was statistically more expert in their decision-making versus controls (intervention CWS = 146.04 (SD 140.21), control CWS = 110.75 (SD 104.05); p = 0.01).

Conclusion:

The online training resource proved effective in altering the decision-making of medical students to agree more with expert decision-making.
Using an Online, Modified Delphi Approach to Engage Patients and Caregivers in Determining the Patient-Centeredness of Duchenne Muscular Dystrophy Care Considerations
Authors: Khodyakov Dmitry , Grant Sean , Denger Brian , Kinnett Kathi , Martin Ann , Booth Marika , Armstrong Courtney , Dao Emily , Chen Christine , Coulter Ian , Peay Holly , Hazlewood Glen , Street Natalie
Published: November 2019

Purpose. To determine the patient-centeredness of endocrine and bone health Duchenne muscular dystrophy (DMD) care considerations using the RAND/PPMD Patient-Centeredness Method (RPM), which is a novel, online, modified-Delphi approach to engaging patients and caregivers in clinical guideline development. Methods. We solicited input on the patient-centeredness of care considerations from 28 individuals with DMD and 94 caregivers, randomly assigned to 1 of 2 mixed panels. During a 3-round online modified-Delphi process, participants rated the importance and acceptability of 19 DMD care considerations (round 1), reviewed and discussed the initial results (round 2), and revised their original ratings (round 3). Patient-centeredness was operationalized as importance and acceptability of recommendations. We considered a care consideration to be patient-centered if both panels deemed it important and acceptable. Results. Ninety-five panelists (78%) participated in this study. Of these, 88 (93%) participated in round 1, 74 (78%) in round 2, and 56 (59%) in round 3. Panelists deemed 12 care considerations to be patient-centered: 3 weight management, 3 bone health, 4 vertical growth, and 2 puberty recommendations. Seven care considerations did not meet patient-centeredness criteria. Common reasons were lack of evidence specific to DMD and concerns about insurance coverage, access to treatment, and patient safety. Conclusions. Using the RPM, Duchenne families considered most care considerations to be patient-centered. Besides being clinically appropriate, these considerations are likely to be consistent with the preferences, needs, and values of Duchenne families. While all relevant care considerations should be discussed during patient-provider encounters, those that did not meet patient-centeredness criteria in particular should be carefully considered as part of joint decision making between Duchenne families and their providers. Study Registration: HSRProj 20163126.
Conceptualising animal exploitation in capitalism: Getting terminology straight
Authors: Stache Christian
Published: November 2019

In the last three decades, the interchange between Marxism and critical human–animalism has gratifyingly picked up. Scholars use Marxist categories to analyse and criticise the exploitation and oppression of animals in capitalism. But the application of Marx’s original concepts often rests on fragile analogies and judgements. To conceptualise the exploitation of animals accurately and substantiate the common class struggle for humans and animals theoretically, the present article serves to get the terminology straight with respect to four interrelated topics. First, the common charge against Marx’s theory to build on a human–animal dualism is refuted by showing that he understands the relationship between humans and animals as a historical materialist, socio-practical and dialectical differentiation. Second, based on a relational understanding of the capitalist mode of production, I argue that animals are not wage labourers, slaves or super-exploited commodities. Rather, as nature in general, they are super-exploited and despotically oppressed by the capitalist class. This capital–animal relation turns animals into private property and means of production at the hands of capital. It also has significant consequences for a value theory of animal labour. Animals, third, do not create value or surplus value and they do not produce commodities. They produce products and these as well as their labour are appropriated by capital for free. Finally, fourth, I defend the transfer of the concept of alienation to animals in general. But animal alienation has to be derived from the form of social labour as in the human case and it has to include the estrangement from body and life as well due to the special form of animal exploitation in capitalism.
Bad Timing: The Temporal Dimensions of Economic Insecurity
Authors: Banks Marcus , Bowman Dina
Published: November 2019

In this article, we draw on a recent Australian study to illustrate how social time in precariously employed or low-income households is increasingly riven by uncertainty and risk. We apply two concepts, riskscapes and timescapes, to examine how these households respond to and are buffeted by the economic and temporal insecurities they experience in labour, welfare and finance markets. Using May and Thrift’s four categories of time, – representations, technologies, social disciplines and rhythms – we highlight how household timescapes interact with their riskscapes to exacerbate economic insecurity.
Neuromyelitis optica spectrum disorder and systemic lupus erythematosus
Authors: Thabah M M , D Sekar , Pranov R , Moulitej M M V , Ramesh A , Kadhiravan T
Published: November 2019

Neuromyelitis optica spectrum disorder is an inflammatory syndrome that is associated with many autoimmune conditions. We present the case of a patient who had longitudinally extensive transverse myelitis and antibodies to aquaporin 4 IgG (AQP4-IgG). Based on presence of lymphopenia, further workup revealed strong ANA positivity, anti-Sm antibodies, and low serum complements suggesting presence of systemic lupus erythematosus. The patient promptly responded to intravenous pulse methylprednisolone and five sessions of plasma exchange. At 1 year, she is on maintenance treatment with low dose prednisolone, azathioprine, and hydroxychloroquine, she has had no relapse and no other clinical features of lupus. This case is an illustration that neuromyelitis optica spectrum disorder can be the first manifestation of systemic lupus erythematosus.
Episomal Induced Pluripotent Stem Cells: Functional and Potential Therapeutic Applications
Authors: Wang Aline Yen Ling , Loh Charles Yuen Yung
Published: November 2019

The term episomal induced pluripotent stem cells (EiPSCs) refers to somatic cells that are reprogrammed into induced pluripotent stem cells (iPSCs) using non-integrative episomal vector methods. This reprogramming process has a better safety profile compared with integrative methods using viruses. There is a current trend toward using episomal plasmid reprogramming to generate iPSCs because of the improved safety profile. Clinical reports of potential human cell sources that have been successfully reprogrammed into EiPSCs are increasing, but no review or summary has been published. The functional applications of EiPSCs and their potential uses in various conditions have been described, and these may be applicable to clinical scenarios. This review summarizes the current direction of EiPSC research and the properties of these cells with the aim of explaining their potential role in clinical applications and functional restoration.
CGPL—Survival Through Engagement at a Time of Turbulence
Authors: Choudhury Shyam Sundar , Chatterjee Devjani
Published: November 2019

This is a case of organizational development at Coastal Gujarat Power Ltd. (CGPL), Mundra in Gujarat, India. CGPL was formed as 100% subsidiary of Tata Power in April 2007. CGPL is India's first Ultra Mega Power Plant of 4000 MW capacity. CGPL has put India into global power map by utilizing the best technology & operating at benchmark levels of lowest cost of power generation. This paper focus on the management and development of employee engagement, which was at an all-time low. This level of engagement has been attributed to a diverse workforce, inadequate leadership communication, ambiguity is people policies, uncertainties on the financial health of the plant, remote location and lack of individual career plan at the time of project demobilization. This case addresses the use of an engagement model and was customized holistically through active participation of employees and all stakeholders to address the issues and enhancing engagement level of employees to 71%. This case reinforces various literature that employee engagement has positive impact on business results. The case provides possibilities and questions regarding what and how an organizational development initiative facilitates the change within the organization despite various challenges.
Are Degree-Awarding Institutions Doing Enough to Support the Implementation of Quality Assurance in Transnational Higher Education Partnerships?
Authors: Bordogna Claudia M.
Published: November 2019

As transnational education grows in complexity, it is imperative degree-awarding institutions develop ways to ensure the quality of their offshore provision. Although agencies, such as the Quality Assurance Agency (QAA) in the United Kingdom and Tertiary Education Quality and Standards Agency (TEQSA) in Australia, safeguard standards through guidelines and reviews, it is vital degree-awarding institutions consider their own actions in the pursuit of academic quality. Although codes of conduct can guide quality assurance, this article suggests these documents are not enough to ensure quality education occurs. Offering a study of two Chinese–British transnational partnerships, this article identifies two key challenges that can affect the implementation of quality assurance at the operational level: time and cultural difference. The findings suggest that senior managers at degree-awarding institutions should consider how their structures and policies encourage and support the implementation of quality assurance at the operational level.
Rational reconstructions and the question of function
Authors: Eriksson Lina
Published: November 2019

Social norm emergence is commonly explained by stating that norms serve certain functions – for example, solving cooperation or coordination problems. But critics argue that examples of norms that do not seem to serve functions show that functions cannot explain social norms. However, both sides tend to make assumptions about how explanations of social norms in terms of functions would work. By discussing four problems for these assumptions, I will show that they are over-simplified. Instead of asking whether norms serve functions, we need to ask more specific questions about the relationship between the norm and the function it supposedly serves.
Penile Invasive Squamous Cell Carcinoma: Analysis of Incidence, Mortality Trends, and Geographic Distribution in Canada
Authors: Lagacé François , Ghazawi Feras M. , Le Michelle , Savin Evgeny , Zubarev Andrei , Powell Mathieu , Moreau Linda , Sasseville Denis , Popa Ioana , Litvinov Ivan V.
Published: November 2019

Background

Penile invasive squamous cell carcinoma (SCC) is a rare disease with several known risk factors. However, few studies have assessed its incidence, mortality, and temporal trends.

Objective

Our objectives are to analyze the epidemiology of penile SCC in Canada and to examine patient distribution with this cancer across Canada in order to elucidate population risk factors.

Methods

Three independent cancer registries were used to retrospectively analyze demographic data from Canadian men diagnosed with penile invasive SCC between 1992 and 2010. The Canadian Census of Population was used to calculate incidence and mortality rates at the province and Forward Sortation Area levels.

Results

The overall age-adjusted incidence rate was 6.08 cases per million males. Four provinces with statistically significantly higher incidence rates were identified. The national crude incidence rates increased linearly between 1992 and 2010, whereas the age-adjusted incidence rates showed no significant increase during this time period. The overall age-adjusted mortality rate was 1.88 deaths per million males per year. The province of Saskatchewan had significantly higher mortality rates. There was no increase in crude or age-adjusted mortality rates between 1992 and 2010. There was a significant positive correlation between incidence rates and obesity, Caucasian ethnicity, and lower socioeconomic status.

Conclusion

This study was able to establish geographic variation for this malignancy at the provincial level. Although there are many established risk factors for penile SCC, our results suggest that the increase in crude incidence rates observed is largely due to the aging population.
YouTube as a resource for evaluating the unmet needs of caregivers of stroke survivors
Authors: Denham Alexandra MJ , Baker Amanda L , Spratt Neil J , Wynne Olivia , Hunt Sally A , Bonevski Billie , Kumar Ratika
Published: November 2019

Content produced by caregivers of stroke survivors on the online video-sharing platform YouTube may be a good source of knowledge regarding caregivers’ unmet needs. We aimed to examine the content, quantity and quality of YouTube videos that target and discuss the needs and concerns of caregivers of stroke survivors. YouTube was systematically searched using six search strings, and the first 20 videos retrieved from each search were screened against the inclusion criteria. A pre-determined coding schedule was used to report the rate of unmet needs in each video. Twenty-six videos were included in the analysis. In total, 291 unmet needs were reported by caregivers of stroke survivors, an average of 11.2 unmet needs per video. The most common unmet needs domain was ‘Impact of Caregiving on Daily Activities’ (44%). Most videos were developed in the United States (61.5%) and featured spouses of stroke survivors (65.47%). Content produced by caregivers of stroke survivors on YouTube may be used as a tool for caregivers to provide and receive support through online communication. YouTube videos offer insight into the unmet needs of caregivers of stroke survivors and may be used as an additional resource for stroke services to support caregivers.
AFP, EFE and dpa as international news agencies
Authors: Surm Jasmin
Published: November 2019

While earlier news agency studies have often concentrated on Reuters in the United Kingdom (now in Canada) and on the Associated Press in the United States as the leading international news agencies, there is less up-to-date research in English on international agencies outside the Anglo-American sphere. This article intends to help bridge that research gap and to analyse the recent development of Agence France-Presse in France, EFE in Spain and Deutsche Presse-Agentur in Germany. The article uses a case study approach, employing in-depth interviews with agency representatives. The results of the analysis show that all three agencies fulfil the criteria for an international agency. However, to do so, they all not only need a large domestic market, together with linguistic and cultural markets outside their home countries, but also state support, in case of Agence France-Presse and EFE. The findings emphasize the relevance of diversification and innovation in response to the changing structure and demands of national and international markets.
The Association Between Mating Performance, Marital Status, and the Length of Singlehood: Evidence From Greece and China
Authors: Apostolou Menelaos , Wang Yan
Published: November 2019

A considerable proportion of people in postindustrial societies experience difficulties in intimate relationships and spend considerable time being single. In the current research, we attempted to examine mating performance, and occurrence and length of singlehood in a Greek ( N = 884) and a Chinese ( N = 2,041) sample. We found that, in both samples, about half of the participants experienced difficulties in intimate relationships. In addition, more than half of the participants were single, and nearly one in four participants indicated that they were single because they faced difficulties attracting a partner. Moreover, more than one in five singles in the Greek sample were without a partner for more than 3 years, and almost half of the singles in the Chinese sample had never been in a relationship. Mating performance predicted marital status, with low scorers being more likely to be single because they faced difficulties in attracting a partner than high scorers. Mating performance predicted also the length of singlehood, with low scorers spending more time being single than high scorers. In addition, singles who faced difficulties in attracting partners experienced lengthier spells of singlehood than other categories of singles. Furthermore, there were significantly more participants who preferred to be single and who never had a relationship in the Chinese than in the Greek sample. Overall, in both samples, a considerable proportion of participants experienced low mating performance, which was associated with increased incidence of prolonged spells of singlehood.
The psychology of experimental psychologists: Overcoming cognitive constraints to improve research: The 47th Sir Frederic Bartlett Lecture
Authors: Bishop Dorothy VM
Published: November 2019

Like many other areas of science, experimental psychology is affected by a “replication crisis” that is causing concern in many fields of research. Approaches to tackling this crisis include better training in statistical methods, greater transparency and openness, and changes to the incentives created by funding agencies, journals, and institutions. Here, I argue that if proposed solutions are to be effective, we also need to take into account human cognitive constraints that can distort all stages of the research process, including design and execution of experiments, analysis of data, and writing up findings for publication. I focus specifically on cognitive schemata in perception and memory, confirmation bias, systematic misunderstanding of statistics, and asymmetry in moral judgements of errors of commission and omission. Finally, I consider methods that may help mitigate the effect of cognitive constraints: better training, including use of simulations to overcome statistical misunderstanding; specific programmes directed at inoculating against cognitive biases; adoption of Registered Reports to encourage more critical reflection in planning studies; and using methods such as triangulation and “pre mortem” evaluation of study design to foster a culture of dialogue and criticism.
The methodological requirements for clinical examination and patient-reported outcomes, and how to test them
Authors: Rosales Roberto S. , Atroshi Isam
Published: November 2019

This article presents the methodological requirements for clinical examination and patient-reported outcomes measurements. The assessment of any measurement for clinical research in hand surgery is difficult. A method of measuring a criterion could be 100% reliable but 100% invalid. Bias may be present in our assessment if we do not take into account the methodological requirements related to reliability, validity, and responsiveness of our measures. Reliability refers to intra-observer agreement, inter-observer agreement, or agreement between two methods of assessment, and, for patient-reported measures, internal consistency and test–retest reliability. Validity is the capability of a clinical method to measure what it proposes to measure. Assessing validity involves comparing a measure with one or more other measures, and, if possible, with a reference standard criterion. Responsiveness is the ability to detect important clinical change. The Consensus-based Standards for the Selection of Health Measurement Instruments provides the standards required for design and recommended statistical analyses of patient-reported outcome measures.
Strategic Insights for Capacity Development on Forest Landscape Restoration: Implications for Addressing Global Commitments
Authors: Bloomfield Gillian , Meli Paula , Brancalion Pedro H. S. , Terris Eli , Guariguata Manuel R. , Garen Eva
Published: November 2019

Global initiatives such as the Aichi Targets and Bonn Challenge have inspired governments to pledge to restore millions of hectares of degraded lands. Many of these calls to action and policy frameworks identify capacity development as important for implementing and scaling-up restoration activities to meet global targets. However, there is little explanation about what capacity development actually involves. How is capacity development approached in the context of restoration? What makes it more or less effective? This article aims to help fill that gap by identifying four components of what an effective approach to capacity development might look like, drawing upon a number of examples in practice. We believe that capacity development initiatives can more effectively support stakeholders to address the complex nature of forest landscape restoration (FLR) if they include the following four components: (a) activities tailored to stakeholder needs and context, (b) knowledge and applied experience from diverse sources and disciplines, (c) skill sets for selecting among a suite of restoration interventions, and (d) inclusion of multiple subjects and skill sets (e.g., social, financial, legal, etc.) in addition to technical or ecological themes. As exemplified by the organizations discussed in this article, these four elements of capacity development can help to support restoration professionals and other stakeholders to think holistically, moving from the scale of an individual farm or plot to the landscape scale where they must address more diverse stakeholder interests, societal trade-offs, and socioecological heterogeneity. This more holistic approach to FLR planning and implementation is needed to more effectively accomplish ambitious FLR targets worldwide.
From Government Office to Private PR: Career Patterns of Special Ministerial Advisers and the Privatization of Politics
Authors: Blach-Ørsten Mark , Mayerhöffer Eva , Willig Ida
Published: November 2019

This article presents a study on special ministerial advisers examining their careers beyond their role in the machinery of government. Applying a theoretical framework derived from the literature on the sociology of work and the transformation of the organization of politics in the Nordic welfare states, we make two theoretical points. First, special advisers are part of an emerging group of partisan policy professionals, and second, the characteristics of this group are best analyzed through the lens of the boundaryless career. By combining these two positions, we contribute to studies on special advisers by offering a longer career perspective, and we contribute to studies on the boundaryless career by analyzing a job market other than the dot-com and cultural industries. Mapping the entire career paths of all Danish special ministerial advisers from 2000 to 2017 ( n = 144), we show that the position of special adviser serves as a stepping-stone to a new labor market that typically culminates with a position in private public relations. This conclusion lends fresh support to concerns about the privatization of politics changing policy formation in the Nordic welfare states.
Lower DLco% identifies exercise pulmonary hypertension in patients with parenchymal lung disease referred for dyspnea
Authors: Zou Richard H. , Wallace William D. , Nouraie S. Mehdi , Chan Stephen Y. , Risbano Michael G.
Published: November 2019

Exercise pulmonary hypertension is an underappreciated form of physical limitation related to early pulmonary vascular disease. A low diffusing capacity of lungs for carbon monoxide (DLco) can be seen in patients with resting pulmonary hypertension as well as parenchymal lung disease. It remains unclear whether low DLco% identifies early pulmonary vascular disease. We hypothesize that a reduced DLco% differentiates the presence of exercise pulmonary hypertension in patients with parenchymal lung disease. Fifty‐six patients referred for unexplained exertional dyspnea with pulmonary function tests within six months of hemodynamic testing underwent exercise right heart catheterization. Exclusion criteria included resting pulmonary arterial or venous hypertension. Receiver operator characteristic curve determined the optimal DLco% cutoffs based on the presence or absence of parenchymal lung disease. Twenty‐one (37%) patients had parenchymal lung disease, most common manifesting as chronic obstructive lung disease or interstitial lung disease. In patients with parenchymal lung disease, a DLco of 46% demonstrated 100% sensitivity and 73% specificity for detecting exercise pulmonary hypertension. In patients without parenchymal lung disease, a DLco of 73% demonstrated 58% sensitivity and 94% specificity for detecting exercise pulmonary hypertension. In both cohorts, DLco% below the optimum cutoffs were associated with higher peak mean pulmonary arterial pressure and peak total pulmonary resistance consistent with the hemodynamic definition of exercise pulmonary hypertension. Patients with a DLco < 46% were more often treated with pulmonary vasodilators and had a trend to higher mortality and lung transplant. DLco% is a simple non‐invasive screening test for the presence of exercise pulmonary hypertension in our mixed referral population with progressive exertional dyspnea. DLco < 46% with parenchymal lung disease and DLco < 73% without parenchymal lung disease may play a role in differentiating the presence of pulmonary vascular disease prior to invasive hemodynamic testing.
Platform Practices in the Cultural Industries: Creativity, Labor, and Citizenship
Authors: Duffy Brooke Erin , Poell Thomas , Nieborg David B.
Published: November 2019

The rise of contemporary platforms—from GAFAM in the West to the “three kingdoms” of the Chinese Internet—is reconfiguring the production, distribution, and monetization of cultural content in staggering and complex ways. Given the nature and extent of these transformations, how can we systematically examine the platformization of cultural production? In this introduction, we propose that a comprehensive understanding of this process is as much institutional (markets, governance, and infrastructures), as it is rooted in everyday cultural practices. It is in this vein that we present fourteen original articles that reveal how platformization involves key shifts in practices of labor, creativity, and citizenship. Diverse in their methodological approaches and topical foci, these contributions allow us to see how platformization is unfolding across cultural, geographic, and sectoral-industrial contexts. Despite their breadth and scope, these articles can be mapped along four thematic clusters: continuity and change; diversity and creativity; labor in an age of algorithmic systems; and power, autonomy, and citizenship.
Activating TP53 by Dual Inhibition of MDMX and MDM2
Authors: Steidl Ulrich G.
Published: November 2019

TP53 is often inactivated by mutations or other mechanisms in human cancers. Recent work has demonstrated that its endogenous inhibitor MDMX (or MDM4) is frequently overexpressed in patients with hematologic malignancies including AML, lymphoid malignancies, as well as other cancers. Pharmacological disruption of the interactions of TP53 with both its endogenous inhibitors (MDMX and MDM2) has long been sought after as an attractive strategy to restore p53-dependent tumor suppressor activity. However, selective targeting of this pathway has previously been limited to MDM2-only small-molecule inhibitors, which lack affinity for MDMX. More recently, pharmacological dual targeting of MDMX/MDM2 has become feasible through stapled peptides and is currently being tested in clinical trials. This presentation will discuss such MDMX/MDM2 dual-targeting strategies as well as new insights into MDMX-mediated mechanisms of tumor progression at the stem cell level, which have emerged from recent studies.

Disclosures

Steidl: Aileron Therapeutics: Consultancy, Research Funding; Stelexis Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Scientific Co-Founder; Pieries Pharmaceuticals: Consultancy; Celgene: Consultancy; BayerHealthcare: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; GlaxoSmithKline: Research Funding.
MCL1 Inhibitors in Multiple Myeloma
Authors: Vanderkerken Karin , De Veirman Kim , Maes Ken , Menu Eline , De Bruyne Elke
Published: November 2019

Apoptosis plays a key role, not only in normal homeostasis but also in protection against genomic instability. Protection against apoptosis is a hallmark of cancer and is mainly regulated by the overexpression of anti-apoptotic proteins such as Bcl-2, Bcl-Xl or Mcl-1. This results in increased survival of the tumor cells and resistance to therapy.

This presentation will focus on MCL-1 (myeloid cell leukemia 1), its expression and its role as potential target in multiple myeloma (MM). MCL1 gene regions are one the most amplified gene regions in several human cancers and Mcl-1 activity is often associated with therapy resistance and relapse. Mcl-1 binds to and sequesters the pro-apoptotic BH3 proteins, thereby preventing apoptosis.

Mcl-1 is overexpressed on MM cells from newly diagnosed patients compared to normal plasma cells and in MM cells at relapse. This overexpression is furthermore associated with a shorter survival of these patients. Increased Mcl-1 expression can result either from genetic lesions or by induction through interaction with the bone marrow microenvironment. Its expression is correlated with the molecular heterogeneity of the myeloma patients; while the CCDN1 group has high BCL2 and low MCL-1 expression; the MMSET and MAF group has high MCL-1 and low BCL2 expression. Unlike Bcl-2 and Bcl-Xl, Mcl-1 has a large unstructured aminoterminus and its activity is mainly dependent on posttranslational modifications. The bone marrow microenvironment, by producing high levels of interleukin 6, also induces the upregulation of Mcl-1. Furthermore, our group recently demonstrated that not only stromal cells in the bone marrow microenvironment, but also MDSC (myeloid derived suppressor cells) induce survival of MM cells by increasing Mcl-1 levels through the AMPK pathway.

As such, these data suggest the potential therapeutic benefit of targeting Mcl-1 in MM patients. Developing the first-generation inhibitors appeared to be challenging, especially in view of the occurrence of unwanted off target effects. Recent preclinical data with new, selective Mcl-1 inhibitors show promising anti-tumor effects both in vitro and in in vivo myeloma models, either alone or in combination with the Bcl-2 selective inhibitor, venetoclax, especially as it was demonstrated that high levels of MCL-1 are associated with venetoclax resistance in MM. In addition, it was also shown that proteasome inhibition can trigger Mcl-1 accumulation, further pointing to the importance of Mcl-1 inhibition. Induction of NOXA, as an inhibitor of Mcl-1, is also suggested as a therapeutic option, especially in combinations with other drugs.

Clinically, following preclinical results, several new Mcl-1 inhibitors have entered phase I trials. Most of them are still recruiting patients, and as such too early to have results.

Disclosures

No relevant conflicts of interest to declare.
Genetic Engineering in Hematopoietic Stem Cells for Gene Therapy of Hemoglobinopathies
Authors: Ferrari Giuliana
Published: November 2019

Beta-thalassemia and sickle cell disease (SCD) are congenital anemias caused by mutations in the beta-globin gene, resulting in either reduced/absent production of globin chains or abnormal hemoglobin structure. At present, the definitive cure is represented by allogeneic hematopoietic stem cell transplantation, with a probability to find a well-matched donor of <25%.

Experimental gene therapy for hemoglobinopathies is based on transplantation of autologous hematopoietic stem cells genetically modified to express therapeutic hemoglobin levels. Approaches to genetically modify HSCs for treatment of hemoglobinopathies include: 1) the addition of globin genes by lentiviral vectors and 2) gene editing by nucleases to reactivate fetal hemoglobin either through inhibition of repressors or by reproducing mutations associated with high fetal hemoglobin levels.

The outcomes of early clinical trials are showing the safety and potential efficacy, as well as the hurdles still limiting a general application.Current challenges and improved strategies will be presented and discussed.

Disclosures

No relevant conflicts of interest to declare.

OffLabel Disclosure:

Plerixafor
Developmental Biology of the Blood System
Authors: Speck Nancy , Zhu Qin , Gao Peng , Tober Joanna , Bennett Laura , Chen Changya , Uzun Yasin , Li Yan , Tan Kai
Published: November 2019

Hematopoietic stem and progenitor cells (HSPCs) in the bone marrow are derived from a small population of hemogenic endothelial (HE) cells located in the yolk sac and major caudal arteries of the mammalian embryo. HE cells undergo an endothelial to hematopoietic cell transition, giving rise to HSPCs that accumulate in intra-arterial clusters before colonizing the fetal liver. To examine the molecular transitions between endothelial cells, HE, and intra-arterial cluster cells, and the heterogeneity of HSPCs within the intra-arterial clusters, we profiled ~40,000 cells from the caudal arteries (dorsal aorta, umbilical, vitelline) of embryonic day 9.5 to 11.5 mouse embryos by single-cell RNA sequencing (scRNA-seq) and single-cell chromatin accessibility sequencing (scATAC-Seq). A continuous developmental trajectory leads from endothelial cells to intra-arterial cluster cells, with identifiable intermediate stages between endothelial cells and HE. The intermediate endothelial stages most proximal to HE are characterized by elevated expression of genes regulated by GATA and SOX transcription factors. Developmental bottlenecks separate endothelial cells from HE cells, with the efficiency of transit through one of the last bottleneck regulated by RUNX1 dosage. Distinct developmental trajectories within intra-arterial cluster cells result in two populations of CD45+HSPCs; an initial wave of multi-lineage committed progenitors followed by precursors of hematopoietic stem cells (pre-HSCs). These and other insights gained from single cell analyses of HSPC formation from arterial endothelium will be presented.

Disclosures

No relevant conflicts of interest to declare.
Post-Treatment FDG-Avid Splenic Lesions in DLBCL: Clinical and Radiographic Characteristics for Risk Assessment
Authors: Nachmias Boaz , Godefroy Geremy , Ganzel Chezi , Goldschmidt Neta , Rozenbach Eyal , Bar-Shalom Rachel , Libster Diana , Vainstein Vladimir
Published: November 2019

PET-CT has been widely incorporated in the treatment of diffuse large B cell lymphoma (DLBCL) and Hodgkin's lymphoma (HD) both for staging at diagnosis and for evaluation of response to therapy. Residual FDG-avid lesions at the end of treatment (EOT) are often due to infectious or inflammatory process and not due to refractory lymphoma. Nonetheless, such lesions prompt diagnostic and therapeutic interventions. In the present study, we evaluate clinical and radiological characteristics of patients with EOT FDG-avid splenic lesions in hope to provide better tools to discern false from true lesions.

The study cohort included patients with DLBCL or HD who had residual EOT FDG-avid splenic lesion with no evidence of active disease in other sites. Patients were concluded as false positive or true positive according to pathological results or long-term follow-up. Clinical and PET-CT characteristics were compared between the two groups.

Our cohort included 9 patients with DLBCL and 2 with HD, of which 6 patients were determined to have false positive lesions and 5 true positive.

Comparing metabolic volume (MV) ratio between EOT to interim (EOT/interim) tests showed a marked difference between false positive and true positive lesions (0.5 vs 3.6, p= 0.02). Notably, comparing EOT to diagnosis (EOT/Dx) MV showed a similar trend that did not reach statistical significance, highlighting MV EOT/interim ratio as a parameter with higher discriminative ability. EOT SUVmax was also significantly different between false positive and true positive (7 vs. 19, p=0.02). A MV EOT/interim ratio >3 has a 75% sensitivity and 100% specificity for the true positive group. Other clinical and PET-CT characteristics were not found to statistically differ between the groups.

To date, this is the first report showing predictive ability of PET-CT characteristics to discern true from false positive residual FDG-avid splenic lesions. Our cohort is of small numbers, nonetheless, EOT/interim MV shows a clear opposite ratio with a decrease in the false positive compared to an increase in the true positive groups. We suggest EOT/interim MV ratio might be a tool to identify patients at low risk of refractory disease allowing non-invasive surveillance. Further larger studies will be needed to validate the role MV EOT/interim ratio as a tool to discriminate residual disease from false positive FDG-avid lesions.

Disclosures

No relevant conflicts of interest to declare.
Cost-Effectiveness of Venetoclax and Rituximab Combination Therapy in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) in Argentina
Authors: Elgart Jorge Federico , Glancszpigel Mariana , Kanevsky Diego , Godar Maria , Touliet Valeria , Albaytero Natalia
Published: November 2019

OBJETIVE: To estimate the cost- effectiveness of Venetoclax + Rituximab (VEN + R) versus ibrutinib in the treatment of Relapsed/Refractory (R/R) Chronic Lymphocytic Leukaemia (CLL), in Argentina from the Social Security perspective."

METHODS: A three-state partitioned survival model (including pre-progression, post-progression and death) developed in accordance with the NICE Guide to the Methods of Technology Appraisal and the ISPOR decision modelling guidelines was adapted to Argentina setting. Population inputs are derived from the MURANO trial. Efficacy and safety data for treatments in R/R CLL were obtained from the literature. The cost of medication was based on country level drug prices. Costs of resources used for routine medical attention and the management of adverse events were based on tariffs from social security system of Argentina. Costs were expressed in US dollars ($) (exchange rate 1$ = 37.10 AR$, November 2018). A 30-year time horizon and the Social Security's payer's perspective were assumed. Costs and health outcomes were discounted at 5%. Deterministic and probabilistic sensitivity analyses (PAS) were performed.

RESULTS: Over a 30-year time horizon, VEN + R regimen generates a significantly lower total treatment cost in comparison to Ibrutinib (- US dollars ($) 312.679,37). In QALYs the result is higher in VEN + R related to the comparator (5.83 vs. 4.18). These show that VEN + R is a dominant treatment strategy over Ibutrinib in patients with R/R CLL. The univariate sensitivity and scenario analysis confirm the robustness of this result. Likewise, the probabilistic sensitivity analysis shows that there is a 100% probability that VEN + R is a cost-effective strategy against Ibrutinib.

CONCLUSIONS: This study shows that in Argentina, VEN+R would be dominant treatment option (better results and lower costs) compared with ibrutinib in R/R CLL patients.

Disclosures

Elgart: 3eff: Consultancy. Glancszpigel:3eff: Employment. Kanevsky:Abbvie: Employment. Godar:Abbvie: Employment. Touliet:Abbvie: Employment. Albaytero:3eff: Employment.
Comparison of the DONOR Lymphocyte Infusion and Second Allogeneic STEM-CELL Transplantation in the Treatment of First Hematological Relapse after Allogeneic STEM-CELL Transplantation in Adults with ACUTE Leukemia
Authors: Demiroglu Haluk , Aladag Elifcan , Chao Nelson J. , Buyukasik Yahya , Goker Hakan
Published: November 2019

Purpose: Relapse after allogeneic hematopoietic bone marrow transplantation (AHSCT) in acute leukemia is a poor prognosis indicator. Although there is no definite opinion about the optimal treatment chemotherapy, second allogeneic hematopoietic stem cell transplantation (AHSCT2) or donor lymphocyte infusion (DLI) are among the treatment options. Relapse after allogeneic transplantation remains unfortunately quite common and we frequently face difficult management decisions. The decision to offer either option is based on several factors, including donor availability, remission status, presence of disabling comorbidities, and center or physician preference. The aim of this study was to investigate the effect of AHBMT2 or DLI on survival in relapsed transplant patients suffers from acute leukemia. Method:We here in report a retrospective analysis of single-center experience with AHBMT2 and DLI to treat patients relapsing from acute leukemia after a first AHBMT from 2003 to 2018.We enrolled the study 20 patients who underwent DLI and 6 patients who underwent AHBMT2. Result:There was no significant difference in OS between the groups afterward intervention (p:0,9) The 2-year survival rate was 33% in the AHBMT2 group and 43% in the DLI group. After intervention, chronic GVHD was observed only in DLI group. Conclusion: DLI can be considered after relapse as a safer and less toxic method than AHBMT2.

Disclosures

No relevant conflicts of interest to declare.