Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

Prevalence of Frailty in European Emergency Departments (FEED): an international flash mob study

Introduction Current emergency care systems are not optimized to respond to multiple and complex problems associated with frailty. Services may require reconfiguration to effectively deliver comprehensive frailty care, yet its prevalence and variation are poorly understood. This study primarily determined the prevalence of frailty among older people attending emergency care. Methods This cross-sectional study used a flash mob approach to collect observational European emergency care data over a 24-h period (04 July 2023). Sites were identified through the European Task Force for Geriatric Emergency Medicine collaboration and social media. Data were collected for all individuals aged 65 + who attended emergency care, and for all adults aged 18 + at a subset of sites. Variables included demographics, Clinical Frailty Scale (CFS), vital signs, and disposition. European and national frailty prevalence was determined with proportions with each CFS level and with dichotomized CFS 5 + (mild or more severe frailty). Results Sixty-two sites in fourteen European countries recruited five thousand seven hundred eighty-five individuals. 40% of 3479 older people had at least mild frailty, with countries ranging from 26 to 51%. They had median age 77 (IQR, 13) years and 53% were female. Across 22 sites observing all adult attenders, older people living with frailty comprised 14%. Conclusion 40% of older people using European emergency care had CFS 5 + . Frailty prevalence varied widely among European care systems. These differences likely reflected entrance selection and provide windows of opportunity for system configuration and workforce planning

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A common volatilization trend in Transantarctic Mountain and Australasian microtektites: Implications for their formation model and parent crater location

We studied the variations of the volatile major elements Na and K in Transantarctic Mountain microtektites and Australasian microtektites with distance from the putative source crater location in Indochina. The dataset includes 169 normal-type Australasian microtektites (101 from this study and 68 from the literature) from 24 deep-sea sediment cores up to 8000km from Indochina, and 54 Transantarctic Mountain microtektites from northern Victoria Land, 11000km due southeast of Indochina. Normal-type (MgO8000km are 4.27±0.67wt.% (n=84), 3.20±1.21wt.% (n=50), 2.10±0.25wt.% (n=35) and 1.25±0.25wt.% (n=54), respectively. The trend highlights a relationship between increasing loss of volatiles in microtektites with longer trajectories and higher temperature-time regimes which should be taken into account in microtektite formation modeling. The trend is consistent with a previous hypothesis that Transantarctic Mountain microtektites belong to the Australasian strewn field and that Indochina is the target region for the parent catastrophic impact

Upper Eocene tektite and impact ejecta layer on the continental slope off New Jersey

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155817/1/Glass_et_al_1998_Upper_eocene.pd

DDE-NBSR Status Report of Conceptual Design Activities

The Design Demonstration Experiment for the National Bureau of Standard Reactor (DDE-NBSR) is intended to facilitate Low Enriched Uranium (LEU) conversion of the NBSR by demonstrating the performance and fabrication of the LEU fuel element design through an irradiation test in the Advanced Test Reactor center flux trap. At the time this report was prepared the resources for furthering DDE design work were expected to be postponed. As such, the conceptual design effort to date is summarized herein in order to provide the status of key objectives, notable results, and provisions for future design work. These demonstrate that the DDE-NBSR design effort is well on the path to producing a suitable irradiation experiment, but also exhibits several challenges for which timely resolution is recommend in order to facilitate success of the irradiation campaign and ultimate conversion of the NBSR

A Muong Nong-type Georgia tektite

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155791/1/Glass_et_al_1995_Muong_nong.pd