Protocol for the Prognostication of Consciousness Recovery Following a Brain Injury

Individuals who have suffered a severe brain injury typically require extensive hospitalization in intensive care units (ICUs), where critical treatment decisions are made to maximize their likelihood of recovering consciousness and cognitive function. These treatment decisions can be difficult when the neurological assessment of the patient is limited by unreliable behavioral responses. Reliable objective and quantifiable markers are lacking and there is both (1) a poor understanding of the mechanisms underlying the brain’s ability to reconstitute consciousness and cognition after an injury and (2) the absence of a reliable and clinically feasible method of tracking cognitive recovery in ICU survivors. Our goal is to develop and validate a clinically relevant EEG paradigm that can inform the prognosis of unresponsive, brain-injured patients in the ICU. This protocol describes a study to develop a point-of-care system intended to accurately predict outcomes of unresponsive, brain-injured patients in the ICU. We will recruit 200 continuously-sedated brain-injured patients across five ICUs. Between 24 h and 7 days post-ICU admission, high-density EEG will be recorded from behaviorally unresponsive patients before, during and after a brief cessation of pharmacological sedation. Once patients have reached the waking stage, they will be asked to complete an abridged Cambridge Brain Sciences battery, a web-based series of neurocognitive tests. The test series will be repeated every day during acute admission (ICU, ward), or as often as possible given the constraints of ICU and ward care. Following discharge, patients will continue to complete the same test series on weekly, and then monthly basis, for up to 12 months following injury. Functional outcomes will also be assessed up to 12 months post-injury. We anticipate our findings will lead to an increased ability to identify patients, as soon as possible after their brain injury, who are most likely to survive, and to make accurate predictions about their long-term cognitive and functional outcome. In addition to providing critically needed support for clinical decision-making, this study has the potential to transform our understanding of key functional EEG networks associated with consciousness and cognition

Resources, Capabilities, and Routines in Public Organizations

States, state agencies, multilateral agencies, and other non-market actors are relatively under-studied in strategic management and organization science. While important contributions to the study of public actors have been made within the agency-theoretic and transaction-cost traditions, there is little research in political economy that builds on resource-based, dynamic capabilities, and behavioral approaches to the firm. Yet public organizations can be characterized as stocks of human and non-human resources, including routines and capabilities; they can possess excess capacity in these resources; and they may grow and diversify in predictable patterns according to behavioral and Penrosean logic. This paper shows how resource-based, dynamic capabilities, and behavioral approaches to understanding public agencies and organizations shed light on their nature and governance

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

High contrast, isotropic, and uniform 3D-imaging of centimeter-scale scattering samples using structured illumination light-sheet microscopy with axial sweeping

Light-sheet fluorescent microscopy (LSFM) has, in recent years, allowed for rapid 3D-imaging of cleared biomedical samples at larger and larger scale. However, even in cleared samples, multiple light scattering often degrades the imaging contrast and widens the optical sectioning. Accumulation of scattering intensifies these negative effects as light propagates inside the tissue, which accentuates the issues when imaging large samples. With axially swept light-sheet microscopy (ASLM), centimeter-scale samples can be scanned with a uniform micrometric optical sectioning. But to fully utilize these benefits for 3D-imaging in biomedical tissue samples, suppression of scattered light is needed. Here, we address this by merging ASLM with light-sheet based structured illumination into Structured Illumination Light-sheet Microscopy with Axial Sweeping (SILMAS). The SILMAS method thus enables high-contrast imaging, isotropic micrometric resolution and uniform optical sectioning in centimeter-scale scattering samples, creating isotropic 3D-volumes of e.g., whole mouse brains without the need for any computation-heavy post-processing. We demonstrate the effectiveness of the approach in agarose gel phantoms with fluorescent beads, and in an PFF injected alpha-synuclein transgenic mouse model tagged with a green fluorescent protein (SynGFP). SILMAS imaging is compared to standard ASLM imaging on the same samples and using the same optical setup, and is shown to increase contrast by as much as 370% and reduce widening of optical sectioning by 74%. With these results, we show that SILMAS improves upon the performance of current state-of-the-art light-sheet microscopes for large and imperfectly cleared tissue samples and is a valuable addition to the LSFM family

Differential proteomic expression of equine cardiac and lamellar tissue during insulin-induced laminitis

Endocrinopathic laminitis is pathologically similar to the multi-organ dysfunction and peripheral neuropathy found in human patients with metabolic syndrome. Similarly, endocrinopathic laminitis has been shown to partially result from vascular dysfunction. However, despite extensive research, the pathogenesis of this disease is not well elucidated and laminitis remains without an effective treatment. Here, we sought to identify novel proteins and pathways underlying the development of equine endocrinopathic laminitis. Healthy Standardbred horses (n = 4/group) were either given an electrolyte infusion, or a 48-h euglycemic-hyperinsulinemic clamp. Cardiac and lamellar tissues were analyzed by mass spectrometry (FDR = 0.05). All hyperinsulinemic horses developed laminitis despite being previously healthy. We identified 514 and 709 unique proteins in the cardiac and lamellar proteomes, respectively. In the lamellar tissue, we identified 14 proteins for which their abundance was significantly increased and 13 proteins which were significantly decreased in the hyperinsulinemic group as compared to controls. These results were confirmed via real-time reverse-transcriptase PCR. A STRING analysis of protein-protein interactions revealed that these increased proteins were primarily involved in coagulation and complement cascades, platelet activity, and ribosomal function, while decreased proteins were involved in focal adhesions, spliceosomes, and cell-cell matrices. Novel significant differentially expressed proteins associated with hyperinsulinemia-induced laminitis include talin−1, vinculin, cadherin-13, fibrinogen, alpha-2-macroglobulin, and heat shock protein 90. In contrast, no proteins were found to be significantly differentially expressed in the heart of hyperinsulinemic horses compared to controls. Together, these data indicate that while hyperinsulinemia induced, in part, microvascular damage, complement activation, and ribosomal dysfunction in the lamellae, a similar effect was not seen in the heart. In brief, this proteomic investigation of a unique equine model of hyperinsulinemia identified novel proteins and signaling pathways, which may lead to the discovery of molecular biomarkers and/or therapeutic targets for endocrinopathic laminitis

Assessing Cognitive Outcomes in Coma Survivors: A Literature Review

(1) Background: Although cognitive impairments in coma survivors are common, methods of measuring long-term cognitive outcomes in this population are inconsistent, precluding the development of a strong evidence-base to support clinical decision making. In this literature review, we identify and characterize the measures used to track cognitive recovery in coma survivors to data. (2) Methods: We extracted the instrument used for cognitive assessment, the cognitive domains assessed, methods administration and scoring, and timing of assessment from 134 of 996 screened records. (3) Results: A total of 133 unique cognitive tests and cognitive testing batteries were identified, with 97 cognitive instruments used in less than three articles. The instruments assessed 20 different cognitive domains, with 73 articles also using tests that assess general “cognitive ability”. Cognitive instruments ranged from subjective assessments to comprehensive cognitive batteries. There were inconsistent points of reference for the timing of assessment across studies, with few studies repeating assessments at more than one time point, and arbitrary time intervals between tests. (4) Conclusions: Overall, this review illustrates the enormous disparity between studies that track cognitive outcome in coma survivors, and the need for a systematic, patient-accessible method of assessing cognitive functioning in future studies with this population

Synthesis and Electronic Properties of Fluoreno[2,1‑<i>a</i>]fluorenedione and Fluoreno[1,2‑<i>a</i>]fluorenedione

The [2,1-<i>a</i>]- and [1,2-<i>a</i>]-isomers of fluorenofluorenedione have been synthesized via intramolecular Friedel–Crafts acylations. DFT calculations indicate that the [1,2-<i>a</i>]-isomer adopts a twisted, helical <i>C</i>₂-symmetric structure and that its protonated form is the thermodynamic product of the Friedel–Crafts acylation in hot sulfuric acid. Absorption spectroscopy and cyclic voltammetry measurements provide experimental estimations of frontier molecular orbital energy levels, which are reported and discussed