Evaluation at the Endgame: Evaluating Sustainability and the SDGs by Moving Past Dominion and Institutional Capture

Three facts underlay this chapter. First, the human system and all our ambitions for improving the human system depend on sustainable natural systems. Second, we do not have much time. On track to fall well short of all sustainability goals, the climate and sustainability crises grow and extinction looms. Third, up to this point evaluation has shown little interest in sustainability, yet evaluation potentially addresses the very questions that are central to informing and guiding rapid adaptation of human behavior to successfully surmounting extinction.Business-as-usual evaluation will not suffice. At the endgame with extinction looming, we need an evaluation that is more nimble, keeps up with rapidly accelerating knowledge, is relentlessly use-seeking and that guides the way to joined-up approaches. The evaluation we need will systematically mainstream sustainability across all evaluations and interventions, in all evaluation criteria and standards. For this, all evaluations will always address nexus where human and natural systems join and incorporate knowledge and methods from both systems. Existing evaluation knowledge is well suited to this task, as are knowledges in biophysical sciences. We know and promote knowledge processes for integrative evaluation and are starting to shift toward the requirements for evaluation at the nexus. As this chapter shows, the anchors holding us back are political, not technical.

Matrix integrals & finite holography

We explore the conjectured duality between a class of large N matrix integrals, known as multicritical matrix integrals (MMI), and the series (2m − 1, 2) of non-unitary minimal models on a fluctuating background. We match the critical exponents of the leading order planar expansion of MMI, to those of the continuum theory on an S2 topology. From the MMI perspective this is done both through a multi-vertex diagrammatic expansion, thereby revealing novel combinatorial expressions, as well as through a systematic saddle point evaluation of the matrix integral as a function of its parameters. From the continuum point of view the corresponding critical exponents are obtained upon computing the partition function in the presence of a given conformal primary. Further to this, we elaborate on a Hilbert space of the continuum theory, and the putative finiteness thereof, on both an S2 and a T2 topology using BRST cohomology considerations. Matrix integrals support this finiteness.

Interdisciplinary Lessons Learned While Researching Fake News

The misleading and propagandistic tendencies in American news reporting have been a part of public discussion from its earliest days as a republic (Innis, 2007; Sheppard, 2007). “Fake news” is hardly new (McKernon, 1925), and the term has been applied to a variety of distinct phenomenon ranging from satire to news, which one may find disagreeable (Jankowski, 2018; Tandoc et al., 2018). However, this problem has become increasingly acute in recent years with the Macquarie Dictionary declaring “fake news” the word of the year in 2016 (Lavoipierre, 2017). The international recognition of fake news as a problem (Pomerantsev and Weiss, 2014; Applebaum and Lucas, 2016) has led to a number of initiatives to mitigate perceived causes, with varying levels of success (Flanagin and Metzger, 2014; Horne and Adali, 2017; Sample et al., 2018). The inability to create a holistic solution continues to stymie researchers and vested parties. A significant contributor to the problem is the interdisciplinary nature of digital deception. While technology enables the rapid and wide dissemination of digitally deceptive data, the design and consumption of data rely on a mixture of psychology, sociology, political science, economics, linguistics, marketing, and fine arts. The authors for this effort discuss deception’s history, both old and new, from an interdisciplinary viewpoint and then proceed to discuss how various disciplines contribute to aiding in the detection and countering of fake news narratives. A discussion of various fake news types (printed, staged events, altered photographs, and deep fakes) ensues with the various technologies being used to identify these; the shortcomings of those technologies and finally the insights offered by the other disciplines can be incorporated to improve outcomes. A three-point evaluation model that focuses on contextual data evaluation, pattern spread, and archival analysis of both the author and publication archives is introduced. While the model put forth cannot determine fact from fiction, the ability to measure distance from fact across various domains provides a starting point for evaluating the veracity of a new story.

Single 225μg/Kg Dose Treatment with Eptacog Beta (Factor VIIa, Recombinant) Results in Rapid Hemostasis in Joint Bleeds for Persons with Hemophilia Α or Β with Inhibitors: A PERSEPT1 Subset Analysis

Introduction Joint bleeding events (BEs) have cumulative, irreversible and debilitating consequences for persons with hemophilia A or B with inhibitors (PwHABI) due to synovitis and joint iron deposition. To limit the long-term consequences of bleeding into joints, early bleed resolution is a primary treatment goal. Eptacog beta (Sevenfact®, HEMA Biologics and LFB) is a new bypassing agent indicated for the treatment and control of BEs in adults and adolescents with hemophilia A or B with inhibitors. In a prospective, randomized, cross-over, phase 3 clinical trial (PERSEPT 1, NCT#02020369) in the first 24 hours following bleed onset, eptacog beta demonstrated dose-dependent improvements in successful clinical response with 2 initial dose regimens (IDRs) (75 µg/kg IDR: 75 µg/kg q3h; and 225 µg/kg IDR: 225 µg/kg followed by 75 µg/kg q3h after 9 hours if necessary; Figure 1). 91% of all mild or moderate BEs achieved hemostatic efficacy at 12 hours (225 µg/kg IDR), as did 82% at 12 hours in the 75 µg/kg IDR. The majority (85%) of mild/moderate BEs treated in PERSEPT 1 were joint BEs. Aims A subset analysis of mild or moderate joint BE data from the PERSEPT 1 trial was performed to investigate the effect of 2 IDRs on clinical response at 3, 9, 12 and 24 hours on joint BEs in PwHABI. IRB approval and informed consent were obtained. Methods At enrollment, male PwHABI (n=27) were randomized to receive BE treatment on either the 75 µg/kg IDR or the 225 µg/kg IDR (Figure 1) for the first 3 months of treatment; subjects were crossed over to the alternate IDR every 3 months. The 12-hour composite endpoint subset analysis for joint BEs used the same success criteria that were used for the primary efficacy endpoint (for all BEs at 12 hours) in PERSEPT 1. Hemostatic efficacy at all other intermediate timepoints and at 24 hours was assessed using a 4-point evaluation scale (an excellent or good evaluation being considered hemostatic efficacy, and moderate or poor being considered a lack of hemostatic efficacy.) BE treatment continued until bleeding ceased as determined by the subject or physician to discontinue treatment. Results A subset of 396 mild/moderate joint BEs were analyzed. The proportion of successfully treated BEs (composite endpoint) at 12 hours was 91.5% [95% CI: 83.4%, 99.6%] on the 225 µg/kg IDR and 80.6% [95% CI: 69.6%, 91.6%] on the 75 µg/kg IDR. At 9 hours, the proportion of BEs with hemostatic efficacy (using the 4-point evaluation scale) from the first dose in the 225 µg/kg IDR was 86.5%; 3- and 24-hour data are shown in Table 1. Conclusions The joint BE success proportion following a first dose in the 225µg/kg IDR at 3 hours was 85.2%; joint BEs treated by the 75µg/kg IDR demonstrated a 26.4% 3-hour success proportion. These success proportions demonstrate a dose-dependent onset of action; this effect on efficacy was also observed in the 12- and 24-hour data. At 9 hours, sustained hemostatic efficacy from a single 225 µg/kg dose was observed (86.5%). Overall, both initial dose regimens showed successful resolution of joint BEs with early hemostatic success proportions. Further, the onset of action data supports the concept that a larger initial thrombin burst may result in an earlier effective clot that drives earlier bleed resolution. Further observations of this type are needed to understand the role of rFVIIa in hemostatic clot formation. Disclosures Hermans: Bayer: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; CAF-DCF: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; LFB: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau; Kedrion: Speakers Bureau; EAHAD: Other; WFH: Other. Ducore:Octapharma: Consultancy; Bayer: Consultancy, Honoraria, Speakers Bureau; HEMA Biologics: Consultancy, Honoraria. Escobar:Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Young:BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria; Bayer, CSL Behring, Freeline, UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding. Wang:Bayer: Honoraria; Takeda: Honoraria; Genentech: Honoraria; Biomarin: Honoraria; CSL Behring: Honoraria; Bioverativ Inc: Honoraria. Quon:Shire/Takeda: Speakers Bureau; Octapharma: Honoraria; Biomarin: Honoraria, Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Bayer: Honoraria; Orthopaedic Institute for Children: Current Employment; Bioverativ/Sanofi: Honoraria, Speakers Bureau. Alexander:HEMA Biologics, LLC: Current Employment, Patents & Royalties: No royalties or benefits. Mitchell:HEMA Biologics: Consultancy. Al-Sabbagh:LFB: Current Employment. Bonzo:International Association for Statistical Computing: Other; International Statistics Institute: Other; American Statistical Association: Other; LFB USA, Inc.: Current Employment.

Impact of COVID-19-Related Lockdown on Psychosocial, Cognitive, and Functional Well-Being in Adults With Down Syndrome

People with Down Syndrome (DS) have a high prevalence of physical and psychiatric comorbidities and experience early-onset dementia. With the outbreak of CoVID-19 pandemic, strict social isolation measures have been necessary to prevent the spreading of the disease. Effects of this lockdown period on behavior, mood and cognition in people with DS have not been assessed so far. In the present clinical study, we investigated the impact of CoVID-19-related lockdown on psychosocial, cognitive and functional well-being in a sample population of 46 adults with DS. The interRAI Intellectual Disability standardized assessment instrument, which includes measures of social withdrawal, functional impairment, aggressive behavior and depressive symptoms, was used to perform a three time-point evaluation (two pre-lockdown and one post-lockdown) in 37 subjects of the study sample, and a two time point evaluation (one pre- and one post-lockdown) in 9 subjects. Two mixed linear regression models – one before and one after the lockdown – have been fitted for each scale in order to investigate the change in the time-dependent variation of the scores. In the pre-lockdown period, significant worsening over time (i.e., per year) was found for the Depression Rating Scale score (β = 0.55; 95% CI 0.34; 0.76). In the post-lockdown period, a significant worsening in social withdrawal (β = 3.05, 95% CI 0.39; 5.70), instrumental activities of daily living (β = 1.13, 95% CI 0.08; 2.18) and depression rating (β = 1.65, 95% CI 0.33; 2.97) scales scores was observed, as was a significant improvement in aggressive behavior (β = −1.40, 95% CI −2.69; −0.10). Despite the undoubtful importance of the lockdown in order to reduce the spreading of the CoVID-19 pandemic, the related social isolation measures suggest an exacerbation of depressive symptoms and a worsening in functional status in a sample of adults with DS. At the opposite, aggressive behavior was reduced after the lockdown period. This finding could be related to the increase of negative and depressive symptoms in the study population. Studies with longer follow-up period are needed to assess persistence of these effects.