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Forrester's book is a guide to relection and consideration for decision making in the twenty-first century. There's an intangible and invisible marketplace within our lives today where the products traded are four fold: attention, distraction, data and meaning. The stories and examples within Consider demonstrate that the best decisions, insights, ideas and outcomes result when we take sufficient time to think and reflect. While technology allows us to act and react more quickly than ever before, we are taking increasingly less time to consider our decisions before we make them. Reflection supplies an arsenal of ideas and solutions to the right problems. Including interviews with leaders such as General David Petraeus, attorney Brooksley Born and global investor Kyle Bass, Forrester shows us that taking time and giving ourselves the mental space for reflection can mean the difference between total success and total failure--Publisher's description.

It has been more than 15 years since the CompStat management model was first introduced by the New York City Police Department, sparking a movement that has profoundly affected public administration. CompStat has been successfully replicated in a wide variety of contexts in the US and abroad -- a testament to its valuable and lasting nature. CompStat was initially designed as a means of analyzing timely and accurate crime data to inform management decisions and to enhance organizational performance. It uses regularly scheduled meetings, whereby field commanders are called before the highest echelons of their agencies to review and discuss performance -- their ability to reduce crime. Crime data is openly shared, and managers are challenged to look for patterns or anomalies and provide explanations and solutions. With its roots grounded in human discourse, the Stat movement has a bright future.

World War II brought forth a generation of leaders who had scarce resources and global enemies to combat. Some of the most difficult battles in that war, such as D-day, featured political, military, and civilian leadership pushing down the decision making and authority to those closest to the enemy and the problem. This overauthorization gave rise to decentralized decision making, innovative leadership, transformation of operations, and, most important, victory.

Fractional Chern insulators (FCIs) are lattice analogues of fractional quantum Hall states that may provide a new avenue towards manipulating non-Abelian excitations. Early theoretical studies 1 – 7 have predicted their existence in systems with flat Chern bands and highlighted the critical role of a particular quantum geometry. However, FCI states have been observed only in Bernal-stacked bilayer graphene (BLG) aligned with hexagonal boron nitride (hBN) 8 , in which a very large magnetic field is responsible for the existence of the Chern bands, precluding the realization of FCIs at zero field. By contrast, magic-angle twisted BLG 9 – 12 supports flat Chern bands at zero magnetic field 13 – 17 , and therefore offers a promising route towards stabilizing zero-field FCIs. Here we report the observation of eight FCI states at low magnetic field in magic-angle twisted BLG enabled by high-resolution local compressibility measurements. The first of these states emerge at 5 T, and their appearance is accompanied by the simultaneous disappearance of nearby topologically trivial charge density wave states. We demonstrate that, unlike the case of the BLG/hBN platform, the principal role of the weak magnetic field is merely to redistribute the Berry curvature of the native Chern bands and thereby realize a quantum geometry favourable for the emergence of FCIs. Our findings strongly suggest that FCIs may be realized at zero magnetic field and pave the way for the exploration and manipulation of anyonic excitations in flat moiré Chern bands. A study using local compressibility measurements reports fractional Chern insulator states at low magnetic field in magic-angle twisted bilayer graphene, and establishes the applied magnetic field as a means to tune the Berry curvature distribution.

Background Sepsis-associated encephalopathy (SAE), a diffuse cerebral dysfunction in the absence of direct CNS infection, is associated with increased rates of mortality and morbidity in patients with sepsis. Increased cytokine production and disruption of the blood-brain barrier (BBB) are implicated in the pathogenesis of SAE. The induction of pro-inflammatory mediators is driven, in part, by activation of NF-κΒ. Lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, potently activates NF-κΒ and its downstream targets, including cyclooxygenase-2 (Cox-2). Cox-2 catalyzes prostaglandin synthesis and in the brain prostaglandin, E2 is capable of inducing endothelial permeability. Depletion of polymerase δ-interacting protein 2 (Poldip2) has previously been reported to attenuate BBB disruption, possibly via regulation of NF-κΒ, in response to ischemic stroke. Here we investigated Poldip2 as a novel regulator of NF-κΒ/cyclooxygenase-2 signaling in an LPS model of SAE. Methods Intraperitoneal injections of LPS (18 mg/kg) were used to induce BBB disruption in Poldip2 +/+ and Poldip2 +/− mice. Changes in cerebral vascular permeability and the effect of meloxicam, a selective Cox-2 inhibitor, were assessed by Evans blue dye extravasation. Cerebral cortices of Poldip2 +/+ and Poldip2 +/− mice were further evaluated by immunoblotting and ELISA. To investigate the role of endothelial Poldip2, immunofluorescence microscopy and immunoblotting were performed to study the effect of siPoldip2 on LPS-mediated NF-κΒ subunit p65 translocation and Cox-2 induction in rat brain microvascular endothelial cells. Finally, FITC-dextran transwell assay was used to assess the effect of siPoldip2 on LPS-induced endothelial permeability. Results Heterozygous deletion of Poldip2 conferred protection against LPS-induced BBB permeability. Alterations in Poldip2 +/+ BBB integrity were preceded by induction of Poldip2, p65, and Cox-2, which was not observed in Poldip2 +/− mice. Consistent with these findings, prostaglandin E2 levels were significantly elevated in Poldip2 +/+ cerebral cortices compared to Poldip2 +/− cortices. Treatment with meloxicam attenuated LPS-induced BBB permeability in Poldip2 +/+ mice, while having no significant effect in Poldip2 +/− mice. Moreover, silencing of Poldip2 in vitro blocked LPS-induced p65 nuclear translocation, Cox-2 expression, and endothelial permeability. Conclusions These data suggest Poldip2 mediates LPS-induced BBB disruption by regulating NF-κΒ subunit p65 activation and Cox-2 and prostaglandin E2 induction. Consequently, targeted inhibition of Poldip2 may provide clinical benefit in the prevention of sepsis-induced BBB disruption.

Chronic diseases contribute to high rates of disability and mortality. Patient engagement in chronic disease self-management is an essential component of chronic disease models of health care. Wearables provide patient-centered health data in real time, which can help inform self-management decision-making. Despite the perceived benefits of wearables in improving chronic disease self-management, their influence on health care outcomes remains poorly understood. This review aimed to examine the influence of wearables on health care outcomes in individuals with chronic diseases through a systematic review of the literature. A narrative systematic review was conducted by searching 6 databases for randomized and observational studies published between January 1, 2016, and July 1, 2021, that included the use of a wearable intervention in a chronic disease group to assess its impact on a predefined outcome measure. These outcomes were defined as any influence on the patient or clinician experience, cost-effectiveness, or health care outcomes as a result of the wearable intervention. Data from the included studies were extracted based on 6 key themes, which formed the basis for a narrative qualitative synthesis. All outcomes were mapped against each component of the Quadruple Aim of health care. The guidelines of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement were followed in this study. A total of 30 articles were included; studies reported 2446 participants (mean age: range 10.1-74.4 years), and the influence of 14 types of wearables on 18 chronic diseases was presented. The most studied chronic diseases were type 2 diabetes (4/30, 13%), Parkinson disease (3/30, 10%), and chronic lower back pain (3/30, 10%). The results were mixed when assessing the impact on a predefined primary outcome, with 50% (15/30) of studies finding a positive influence on the studied outcome and 50% (15/30) demonstrating a nil effect. There was a positive effect of 3D virtual reality systems on chronic pain in 7% (2/30) of studies that evaluated 2 distinct chronic pain syndromes. Mixed results were observed in influencing exercise capacity; weight; and biomarkers of disease, such as hemoglobin A , in diabetes. In total, 155 outcomes were studied. Most (139/155, 89.7%) addressed the health care outcomes component. This included pain (11/155, 7.5%), quality of life (7/155, 4.8%), and physical function (5/155, 3.4%). Approximately 7.7% (12/155) of outcome measures represented the patient experience component, with 1.3% (2/155) addressing the clinician experience and cost. Given their popularity and capability, wearables may play an integral role in chronic disease management. However, further research is required to generate a strong evidence base for safe and effective implementation. PROSPERO International Prospective Register of Systematic Reviews CRD42021244562; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=244562.

CRISPR/Cas9 has revolutionized our ability to engineer genomes and conduct genome-wide screens in human cells 1 – 3 . Whereas some cell types are amenable to genome engineering, genomes of human pluripotent stem cells (hPSCs) have been difficult to engineer, with reduced efficiencies relative to tumour cell lines or mouse embryonic stem cells 3 – 13 . Here, using hPSC lines with stable integration of Cas9 or transient delivery of Cas9-ribonucleoproteins (RNPs), we achieved an average insertion or deletion (indel) efficiency greater than 80%. This high efficiency of indel generation revealed that double-strand breaks (DSBs) induced by Cas9 are toxic and kill most hPSCs. In previous studies, the toxicity of Cas9 in hPSCs was less apparent because of low transfection efficiency and subsequently low DSB induction 3 . The toxic response to DSBs was P53/TP53 -dependent, such that the efficiency of precise genome engineering in hPSCs with a wild-type P53 gene was severely reduced. Our results indicate that Cas9 toxicity creates an obstacle to the high-throughput use of CRISPR/Cas9 for genome engineering and screening in hPSCs. Moreover, as hPSCs can acquire P53 mutations 14 , cell replacement therapies using CRISPR/Cas9-enginereed hPSCs should proceed with caution, and such engineered hPSCs should be monitored for P53 function. CRISPR–Cas9-induced DNA damage triggers p53 to limit the efficiency of gene editing in human pluripotent cells.

Both human health and the health systems we depend on are increasingly threatened by a range of environmental crises, including climate change. Paradoxically, health care provision is a significant driver of environmental pollution, with surgical and anesthetic services among the most resource-intensive components of the health system. This analysis aimed to summarize the state of life cycle assessment (LCA) practice as applied to surgical and anesthetic care via review of extant literature assessing environmental impacts of related services, procedures, equipment, and pharmaceuticals. A state-of-the-science review was undertaken following a registered protocol and a standardized, LCA-specific reporting framework. Three bibliographic databases (Scopus®, PubMed, and Embase®) and the gray literature were searched. Inclusion criteria were applied, eligible entries critically appraised, and key methodological data and results extracted. From 1,316 identified records, 44 studies were eligible for inclusion. The annual climate impact of operating surgical suites ranged between 3,200,000 and . The climate impact of individual surgical procedures varied considerably, with estimates ranging from . Anesthetic gases; single-use equipment; and heating, ventilation, and air conditioning system operation were the main emissions hot spots identified among operating room- and procedure-specific analyses. Single-use equipment used in surgical settings was generally more harmful than equivalent reusable items across a range of environmental parameters. Life cycle inventories have been assembled and associated climate impacts calculated for three anesthetic gases ( ) and 20 injectable anesthetic drugs ( ). Despite the recent proliferation of surgical and anesthesiology-related LCAs, extant studies address a miniscule fraction of the numerous services, procedures, and products available today. Methodological heterogeneity, external validity, and a lack of background life cycle inventory data related to many essential surgical and anesthetic inputs are key limitations of the current evidence base. This review provides an indication of the spectrum of environmental impacts associated with surgical and anesthetic care at various scales. https://doi.org/10.1289/EHP8666.

Typical tropospheric temperatures render possible phase states of amorphous organic aerosol (OA) particles of solid, semisolid, and liquid. This will affect the multiphase oxidation kinetics involving the organic condensed-phase and gaseous oxidants and radicals. To quantify this effect, we determined the reactive uptake coefficients (γ) ofO3, NO3, and OH by substrate films composed of single and binary OA surrogate species under dry conditions for temperatures from 213 to 313 K. A temperature-controlled coated-wall flow reactor coupled to a chemical ionization mass spectrometer was applied to determine γ with consideration of gas diffusion transport limitation and gas flow entrance effects, which can impact heterogeneous reaction kinetics. The phase state of the organic substrates was probed via the poke-flow technique, allowing the estimation of the substrates' glass transition temperatures. γ values for O3 and OH uptake to a canola oil substrate, NO3 uptake to a levoglucosan and a levoglucosan / xylitol substrate, and OH uptake to a glucose and glucose / 1,2,6-hexanetriol substrate have been determined as a function of temperature. We observed the greatest changes in γ with temperature for substrates that experienced the largest changes in viscosity as a result of a solid-to-liquid phase transition. Organic substrates that maintain a semisolid or solid phase state and as such a relatively higher viscosity do not display large variations in heterogeneous reactivity. From 213 to 293 K, γ values of O3 with canola oil, of NO3 with a levoglucosan / xylitol mixture, and of OH with a glucose / 1,2,6-hexanetriol mixture and canola oil, increase by about a factor of 34, 3, 2, and 5, respectively, due to a solid-to-liquid phase transition of the substrate. These results demonstrate that the surface and bulk lifetime of the OA surrogate species can significantly increase due to the slowed heterogeneous kinetics when OA species are solid or highly viscous in the middle and upper troposphere. This experimental study will further our understanding of the chemical evolution of OA particles with subsequent important consequences for source apportionment, air quality, and climate.