Alzheimer's Disease-Related Dementias Summit 2019: National research priorities for the investigation of traumatic brain injury as a risk factor for Alzheimer's Disease and Related Dementias

TBI is a risk factor for later life dementia. Clinical and preclinical studies have elucidated multiple mechanisms through which TBI may influence or exacerbate multiple pathological processes underlying Alzheimer’s Disease and Alzheimer’s Disease Related Dementias (AD/ADRD). The National Institutes of Health hosts triennial ADRD Summits to inform a national research agenda, and the 2019 ADRD Summit was the first to highlight ‘TBI and AD/ADRD Risk’ as an emerging topic in the field. A multidisciplinary committee of TBI researchers with relevant expertise reviewed extant literature, identified research gaps and opportunities, and proposed draft research recommendations at the 2019 ADRD Summit. These research recommendations, further refined after broad stakeholder input at the Summit, cover four overall areas: (1) Encourage crosstalk and interdisciplinary collaboration between TBI and dementia researchers, (2) Establish infrastructure to study TBI as a risk factor for AD/ADRD, (3) Promote basic and clinical research examining the development and progression of TBI AD/ADRD neuropathologies and associated clinical symptoms, and (4) Characterize the clinical phenotype of progressive dementia associated with TBI and develop non-invasive diagnostic approaches. These recommendations recognize a need to strengthen communication and build frameworks to connect the complexity of TBI with rapidly evolving AD/ADRD research. Recommendations acknowledge TBI as a clinically and pathologically heterogeneous disease whose associations with AD/ADRDs remain incompletely understood. The recommendations highlight the scientific advantage of investigating AD/ADRD in the context of a known TBI exposure, the study of which can directly inform on disease mechanisms and treatment targets for AD/ADRDs with shared common pathways

The chronic and evolving neurological consequences of traumatic brain injury.

Traumatic brain injury (TBI) can have lifelong and dynamic effects on health and wellbeing. Research on the long-term consequences emphasises that, for many patients, TBI should be conceptualised as a chronic health condition. Evidence suggests that functional outcomes after TBI can show improvement or deterioration up to two decades after injury, and rates of all-cause mortality remain elevated for many years. Furthermore, TBI represents a risk factor for a variety of neurological illnesses, including epilepsy, stroke, and neurodegenerative disease. With respect to neurodegeneration after TBI, post-mortem studies on the long-term neuropathology after injury have identified complex persisting and evolving abnormalities best described as polypathology, which includes chronic traumatic encephalopathy. Despite growing awareness of the lifelong consequences of TBI, substantial gaps in research exist. Improvements are therefore needed in understanding chronic pathologies and their implications for survivors of TBI, which could inform long-term health management in this sizeable patient population

Using Flow Specifications of Parameterized Cache Coherence Protocols for Verifying Deadlock Freedom

We consider the problem of verifying deadlock freedom for symmetric cache coherence protocols. In particular, we focus on a specific form of deadlock which is useful for the cache coherence protocol domain and consistent with the internal definition of deadlock in the Murphi model checker: we refer to this deadlock as a system- wide deadlock (s-deadlock). In s-deadlock, the entire system gets blocked and is unable to make any transition. Cache coherence protocols consist of N symmetric cache agents, where N is an unbounded parameter; thus the verification of s-deadlock freedom is naturally a parameterized verification problem. Parametrized verification techniques work by using sound abstractions to reduce the unbounded model to a bounded model. Efficient abstractions which work well for industrial scale protocols typically bound the model by replacing the state of most of the agents by an abstract environment, while keeping just one or two agents as is. However, leveraging such efficient abstractions becomes a challenge for s-deadlock: a violation of s-deadlock is a state in which the transitions of all of the unbounded number of agents cannot occur and so a simple abstraction like the one above will not preserve this violation. In this work we address this challenge by presenting a technique which leverages high-level information about the protocols, in the form of message sequence dia- grams referred to as flows, for constructing invariants that are collectively stronger than s-deadlock. Efficient abstractions can be constructed to verify these invariants. We successfully verify the German and Flash protocols using our technique

Energy security in a developing world

Energy security, a fuzzy concept, has traditionally been used to justify state control over energy and a reluctance to deal with energy issues at global level. However, over time, the concept is acquiring different meanings that are applicable at different levels of governance. Many of the elements of the new definitions also imply a number of inherent contradictions. Against this background, this article explores the dimensions of energy security with a special focus on the developing world. It argues that (1) within developing countries (DCs), energy security implies both access to modern energy services by the poorest as well as access by the rapidly developing industrial, services, and urban sectors. Lack of adequate resources has implied trade-offs in terms of who gets access and in terms of taking into account the social and ecological consequences of specific energy sources. Furthermore, (2) the growing DCs' need for energy is impacted by industrialized country perceptions of the various dimensions of energy security-recognizing the need for access to the poorest; industrialized countries are increasingly implicitly questioning the right of DCs to use fossil fuels because of its implications for climate change; or to build large dams because of ecological and social security concerns or expand nuclear energy because of its potential security implications. The development of reliable, continuous, affordable, and environmentally sound provision of energy services combined with a focus on energy efficiency and conservation is the only way of alleviating the various multi-level dimensions of energy security. © 2011 John Wiley & Sons, Ltd

Medical nutrition therapy and clinical outcomes in critically ill adults: a European multinational, prospective observational cohort study (EuroPN)

BACKGROUND: Medical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European intensive care units (ICU) and their importance for clinical outcomes. METHODS: Prospective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low:  20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV). RESULTS: A total of 1172 patients with median [Q1;Q3] APACHE II score of 18.5 [13.0;26.0] were included, and 24% died within 90 days. Median length of ICU stay was 10.0 [7.0;16.0] days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% [59;107] and 65% [41;91] of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 [95% CI: 1.60;3.25] for calorie intake, 0.14 [0.09;0.20] for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (− 2.74 [− 3.28; − 2.21] and − 0.12 [− 0.15; − 0.09], respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 [95% CI: 1.5;14.09] on day 12; for protein: maximum HR 2.60 [1.09;6.23] on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, [0.05;0.39] on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements. CONCLUSIONS: Calorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes. Trial registration NCT04143503, registered on October 25, 2019. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-022-03997-z

Acute Ischemic Stroke After Moderate to Severe Traumatic Brain Injury: Incidence and Impact on Outcome

Background and Purpose—Traumatic brain injury (TBI) leads to nearly 300 000 annual US hospitalizations and increased lifetime risk of acute ischemic stroke (AIS). Occurrence of AIS immediately after TBI has not been well characterized. We evaluated AIS acutely after TBI and its impact on outcome. Methods—A prospective database of moderate to severe TBI survivors, admitted to inpatient rehabilitation at 22 Traumatic Brain Injury Model Systems centers and their referring acute-care hospitals, was analyzed. Outcome measures were AIS incidence, duration of posttraumatic amnesia, Functional Independence Measure, and Disability Rating Scale, at rehabilitation discharge. Results—Between October 1, 2007, and March 31, 2015, 6488 patients with TBI were enrolled in the Traumatic Brain Injury Model Systems National Database. One hundred and fifty-nine (2.5%) patients had a concurrent AIS, and among these, median age was 40 years. AIS was associated with intracranial mass effect and carotid or vertebral artery dissection. High-velocity events more commonly caused TBI with dissection. AIS predicted poorer outcome by all measures, accounting for a 13.3-point reduction in Functional Independence Measure total score (95% confidence interval, −16.8 to −9.7; P<0.001), a 1.9-point increase in Disability Rating Scale (95% confidence interval, 1.3–2.5; P<0.001), and an 18.3-day increase in posttraumatic amnesia duration (95% confidence interval, 13.1–23.4; P<0.001). Conclusions—Ischemic stroke is observed acutely in 2.5% of moderate to severe TBI survivors and predicts worse functional and cognitive outcome. Half of TBI patients with AIS were aged ≤40 years, and AIS patients more often had cervical dissection. Vigilance for AIS is warranted acutely after TBI, particularly after high-velocity events

Inheritance of Temporal Logic Properties

Abstract. Inheritance is one of the key features for the success of object-oriented languages. Inheritance (or specialisation) supports incremental design and re-use of already written specifications or programs. In a for-mal approach to system design the interest does not only lie in re-use of class definitions but also in re-use of correctness proofs. If a provably correct class is specialised we like to know those correctness properties which are preserved in the subclass. This can avoid re-verification of already proven properties and may thus substantially reduce the verifi-cation effort. In this paper we study the question of inheritance of correctness prop-erties in the context of state-based formalisms, using a temporal logic (CTL) to formalise requirements on classes. Given a superclass and its specialised subclass we develop a technique for computing the set of for-mulas which are preserved in the subclass. For specialisation we allow addition of attributes, modification of existing as well as extension with new methods.

Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury

Identification and characterization of 3.8 min 134mI

The [gamma]-ray spectra of iodine fractions rapidly separated from the products of slow neutron fission of 235U were studied. A 3.8 +/- 0.2 min species was found and was identified as 134mI from observations of corresponding growth in the intensities of the prominent 847 and 884 keV [gamma]-rays of 53 min 134I. This isomer is analogous to the 2.9 h isomer 134mCs and decays by the sequence 134mI (J[pi] = 8-)(J[pi] = 5+)134I (J[pi] = 4+) by transitions of and 44.4 +/- 0.1 keV(), respectively. For a 316 keV cross-over [gamma]-ray an upper limit of 1 % was obtained, and is near the intensity predicted by M4 systematics. A low-intensity [gamma]-ray of 234.3 +/- 0.5 keV was found This [gamma]-ray is interpreted as evidence for [beta]-decay (2%) of the isomer, possibly to the 0.29 sec 7- isomeric level in 134Xe.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34159/1/0000445.pd