AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3

Inflammation that contributes to acute cerebrovascular disease is driven by the proinflammatory cytokine interleukin-1 and is known to exacerbate resulting injury. The activity of interleukin-1 is regulated by multimolecular protein complexes called inflammasomes. There are multiple potential inflammasomes activated in diverse diseases, yet the nature of the inflammasomes involved in brain injury is currently unknown. Here, using a rodent model of stroke, we show that the NLRC4 (NLR family, CARD domain containing 4) and AIM2 (absent in melanoma 2) inflammasomes contribute to brain injury. We also show that acute ischemic brain injury is regulated by mechanisms that require ASC (apoptosis-associated speck-like protein containing a CARD), a common adaptor protein for several inflammasomes, and that the NLRP3 (NLR family, pyrin domain containing 3) inflammasome is not involved in this process. These discoveries identify the NLRC4 and AIM2 inflammasomes as potential therapeutic targets for stroke and provide new insights into how the inflammatory response is regulated after an acute injury to the brain

The use of hyperspectral imaging for cake moisture prediction

In this paper, hyperspectral imaging is demonstrated to be a valid method for predicting the moisture content of baked sponge cakes. The application of this technology in the cake production environment, empowered by sophisticated signal & image processing techniques and prediction algorithms has the potential to provide on-line, real-time, non-destructive cake moisture monitoring

The Intrinsic Alignment of Dark Halo Substructures

We investigate the intrinsic alignments of dark halo substructures with their host halo major-axis orientations both analytically and numerically. Analytically, we derive the probability density distribution of the angles between the minor axes of the substructures and the major axes of their host halos from the physical principles, under the assumption that the substructure alignment on galaxy scale is a consequence of the tidal fields of the host halo gravitational potential. Numerically, we use a sample of four cluster-scale halos and their galaxy-scale substructures from recent high-resolution N-body simulations to measure the probability density distribution. We compare the numerical distribution with the analytic prediction, and find that the two results agree with each other very well. We conclude that our analytic model provides a quantitative physical explanation for the intrinsic alignment of dark halo substructures. We also discuss the possibility of discriminating our model from the anisotropic infall scenario by testing it against very large N-body simulations in the future.Comment: accepted version, ApJL in press, minor revision, 12 pages, 2 figure

Weak lensing surveys and the intrinsic correlation of galaxy ellipticities

We explore the possibility that an intrinsic correlation between galaxy ellipticities arising during the galaxy formation process may account for part of the shear signal recently reported by several groups engaged in weak lensing surveys. Using high resolution N-body simulations we measure the projected ellipticities of dark matter halos and their correlations as a function of pair separation. With this simplifying, but not necessarily realistic assumption (halo shapes as a proxy for galaxy shapes), we find a positive detection of correlations up to scales of at least 20 h^-1mpc (limited by the box size). The signal is not strongly affected by variations in the halo finding technique, or by the resolution of the simulations. We translate our 3d results into angular measurements of ellipticity correlation functions and shear variance which can be directly compared to observations. We also measure similar results from simulated angular surveys made by projecting our simulation boxes onto the plane of the sky and applying a radial selection function. Interestingly, the shear variance we measure is a small, but not entirely negligible fraction (from ~10-20 %) of that seen by the observational groups, and the ellipticity correlation functions approximately mimic the functional form expected to be caused by weak lensing. The amplitude depends on the width in redshift of the galaxy distribution. If photometric redshifts are used to pick out a screen of background galaxies with a small width, then the intrinsic correlation may become comparable to the weak lensing signal. Although we are dealing with simulated dark matter halos, whether there is a signal from real galaxies could be checked with a nearby sample with known redshifts.Comment: 12 pages, 11 ps figures, emulateapj.sty, submitted to Ap

DEVELOPMENT OF CLINICAL AND PATIENT-REPORTED QUALITY METRICS FOR MULTIPLE SCLEROSIS: A UK PILOT STUDY REPORT

BackgroundQuality standards (QS) for people with multiple sclerosis (PwMS) are suboptimal, ambiguous and restricted to certain patient subgroups and care pathways.AimDevelop and pilot MS metrics measuring service provision quality to identify areas for improvement.MethodsA multidisciplinary Working Group developed clinician and patient-reported metrics and standardised data collection forms through an iterative process.ResultsMetrics covered: referral; diagnosis; treatment; annual review; general management; education. Pilot (n=76) showed: 31% of PwMS were referred to MS specialist within 4 weeks of suspected/confirmed demyelination; 28% and 56% had uncomplicated MS confirmed and were offered specialist MS nurse appointment, respectively, within 4 weeks of specialist referral; 75% of eligible PwMS were offered disease-modifying therapy within 8 weeks of confirmed MS diagnosis; 85% had comprehensive multidisciplinary team (MDT) annual review; 90% had a defined point of contact within the MS service; 86% of unscheduled contacts by PwMS, MDT or general practitioners were responded to within 3 days; 53% of MS services maintained a single database of PwMS; and 76% of PwMS were offered ongoing education. Data collection continues and updated findings will be reported.DiscussionMS metrics/data forms are feasible for routine clinical settings, simple to interpret and provide a valuable benchmark for guiding MS service improvements

Tree effects on urban microclimate: diurnal, seasonal, and climatic temperature differences explained by separating radiation, evapotranspiration, and roughness effects

Increasing urban tree cover is an often proposed mitigation strategy against urban heat as trees are expected to cool cities through evapotranspiration and shade provision. However, trees also modify wind flow and urban aerodynamic roughness, which can potentially limit heat dissipation. Existing studies show a varying cooling potential of urban trees in different climates and times of the day. These differences are so far not systematically explained as partitioning the individual tree effects is challenging and impossible through observations alone. Here, we conduct numerical experiments removing and adding radiation, evapotranspiration, and aerodynamic roughness effects caused by urban trees using a mechanistic urban ecohydrological model. Simulations are presented for four cities in different climates (Phoenix, Singapore, Melbourne, Zurich) considering the seasonal and diurnal cycles of air and surface temperatures. Results show that evapotranspiration of well-watered trees alone can decrease local 2 m air temperature at maximum by 3.1 – 5.8 °C in the four climates during summer. Further cooling is prevented by stomatal closure at peak temperatures as high vapour pressure deficits limit transpiration. While shading reduces surface temperatures, the interaction of a non-transpiring tree with radiation can increase 2 m air temperature by up to 1.6 – 2.1 °C in certain hours of the day at local scale, thus partially counteracting the evapotranspirative cooling effect. Furthermore, in the analysed scenarios, which do not account for tree wind blockage effects, trees lead to a decrease in urban roughness, which inhibits turbulent energy exchange and increases air temperature during daytime. At night, single tree effects are variable likely due to differences in atmospheric stability within the urban canyon. These results explain reported diurnal, seasonal and climatic differences in the cooling effects of urban trees, and can guide future field campaigns, planning strategies, and species selection aimed at improving local microclimate using urban greenery

In utero exposure to cigarette smoke dysregulates human fetal ovarian developmental signalling

STUDY QUESTION How does maternal cigarette smoking disturb development of the human fetal ovary?<p></p> SUMMARY ANSWER Maternal smoking increases fetal estrogen titres and dysregulates several developmental processes in the fetal ovary.<p></p> WHAT IS KNOWN ALREADY Exposure to maternal cigarette smoking during gestation reduces human fetal ovarian cell numbers, germ cell proliferation and subsequent adult fecundity.<p></p> STUDY DESIGN, SIZE, DURATION The effects of maternal cigarette smoking on the second trimester human fetal ovary, fetal endocrine signalling and fetal chemical burden were studied. A total of 105 fetuses were studied, 56 from mothers who smoked during pregnancy and 49 from those who did not.<p></p> PARTICIPANTS/MATERIALS, SETTING METHODS Ovary, liver and plasma samples were collected from electively terminated, normally progressing, second trimester human fetuses. Circulating fetal hormones, levels of 73 fetal ovarian transcripts, protein localization, density of oocytes/primordial follicles and levels of 16 polycyclic aromatic hydrocarbons (PAHs) in the fetal liver were determined.<p></p> MAIN RESULTS AND THE ROLE OF CHANCE Circulating fetal estrogen levels were very high and were increased by maternal smoking (ANOVA, P = 0.055–0.004 versus control). Smoke exposure also dysregulated (two-way ANOVA, smoking versus gestation weeks interaction, P = 0.046–0.023) four fetal ovarian genes (cytochrome P450 scc [CYP11A1], NOBOX oogenesis homeobox [NOBOX], activator of apoptosis harakiri [HRK], nuclear receptor subfamily 2, group E, member 1 [NR2E1]), shifted the ovarian Inhibin βA/inhibin α ratio (NHBA/INHA) transcript ratio in favour of activin (ANOVA, P = 0.049 versus control) and reduced the proportion of dominant-negative estrogen receptor 2 (ERβ: ESR2) isoforms in half the exposed fetuses. PAHs, ligands for the aryl hydrocarbon receptor (AHR), were increased nearly 6-fold by maternal smoking (ANOVA, P = 0.011 versus control). A fifth transcript, COUP transcription factor 1 (nuclear receptor subfamily 2, group F, member 1: NR2F1, which contains multiple AHR-binding sites), was both significantly increased (ANOVA, P = 0.026 versus control) and dysregulated by (two-way ANOVA, smoking versus gestation weeks interaction, P = 0.021) maternal smoking. NR2F1 is associated with repression of FSHR expression and smoke-exposed ovaries failed to show the normal increase in FSHR expression during the second trimester. There was a significantly higher number of DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 (DDX4) VASA-positive (ANOVA, P = 0.016 versus control), but not POU domain, class 1, transcription factor 1 (POU5F1) OCT3/4-positive, oocytes in smoke-exposed fetuses and this matched with a significantly higher number of primordial follicles (ANOVA, P = 0.024 versus control).<p></p> LIMITATIONS, REASONS FOR CAUTION The effects of maternal smoking on establishment of the maximum fetal primordial follicle pool cannot be reliably studied in our population since the process is not completed until 28 weeks of gestation and normal fetuses older than 21 weeks of gestation are not available for study. Our data suggest that some fetal ovaries are affected by smoke exposure while others are not, indicating that additional studies, with larger numbers, may show more significant effects.<p></p> WIDER IMPLICATIONS OF THE FINDINGS Fetal exposure to chemicals in cigarette smoke is known to lead to reduced fecundity in women. Our study suggests, for the first time, that this occurs via mechanisms involving activation of AHR, disruption of inhibin/activin and estrogen signalling, increased exposure to estrogen and dysregulation of multiple molecular pathways in the exposed human fetal ovary. Our data also suggest that alterations in the ESR2 positive and dominant negative isoforms may be associated with reduced sensitivity of some fetuses to increased estrogens and maternal smoking

A prospective study of the impact of serial troponin measurements on the diagnosis of myocardial infarction and hospital and six-month mortality in patients admitted to ICU with non-cardiac diagnoses.

INTRODUCTION: Troponin T (cTnT) elevation is common in patients in the Intensive Care Unit (ICU) and associated with morbidity and mortality. Our aim was to determine the epidemiology of raised cTnT levels and contemporaneous electrocardiogram (ECG) changes suggesting myocardial infarction (MI) in ICU patients admitted for non-cardiac reasons. METHODS: cTnT and ECGs were recorded daily during week 1 and on alternate days during week 2 until discharge from ICU or death. ECGs were interpreted independently for the presence of ischaemic changes. Patients were classified into four groups: (i) definite MI (cTnT ≥15 ng/L and contemporaneous changes of MI on ECG), (ii) possible MI (cTnT ≥15 ng/L and contemporaneous ischaemic changes on ECG), (iii) troponin rise alone (cTnT ≥15 ng/L), or (iv) normal. Medical notes were screened independently by two ICU clinicians for evidence that the clinical teams had considered a cardiac event. RESULTS: Data from 144 patients were analysed (42% female; mean age 61.9 (SD 16.9)). A total of 121 patients (84%) had at least one cTnT level ≥15 ng/L. A total of 20 patients (14%) had a definite MI, 27% had a possible MI, 43% had a cTNT rise without contemporaneous ECG changes, and 16% had no cTNT rise. ICU, hospital and 180-day mortality was significantly higher in patients with a definite or possible MI. CONCLUSIONS: The majority of critically ill patients (84%) had a cTnT rise and 41% met criteria for a possible or definite MI of whom only 20% were recognised clinically. Mortality up to 180 days was higher in patients with a cTnT rise

Informal healthcare provision in Lebanon: an adaptive mechanism among displaced Syrian health professionals in a protracted crisis

Abstract: Background: Syrian healthcare workers (HCWs) are among those who fled the Syrian conflict only to face further social and economic challenges in host countries. In Lebanon, this population group cannot formally practice, yet many are believed to be operating informally. These activities remain poorly documented and misunderstood by the academic, policy and humanitarian communities. This study aims to understand mechanisms of informal provision of services, the facilitators and barriers for such practices and to present policy recommendations for building on this adaptive mechanism. Method: A qualitative descriptive study based on an in-depth interview approach with a sample of Syrian informal healthcare workers (IHCWs) residing in Lebanon was adopted. Known sponsor networks followed by snowball sampling approaches were used to recruit participants. Data collection occurred between September and December 2017. All interviews were audio-recorded, transcribed and translated into English. An inductive thematic analysis was used. Results: Twenty-two participants were recruited. Motivational factors that led HCWs to practice informally were personal (e.g. source of income/livelihood), societal (cultural competency), and need to fulfill a gap in the formal health service sector. Being connected to a network of IHCWs facilitated initiation of the informal practice until eventually becoming part of a community of informal practice. The central challenge was the informal nature of their practice and its negative consequences. Most IHCWs were afraid of arrest by the government upon identification. Most interviewees indicated being discriminated against by host communities in the form of differential wages and tense interpersonal relationships. Almost all recommended a change in policy allowing them to practice formally under a temporary registration until their return to Syria. Conclusion: Our study confirmed the presence of IHCWs operating in Lebanon. Despite its informal nature, participants perceived that this practice was filling a gap in the formal health system and was helping to alleviate the burden of IHCWs and refugee health needs. In line with interviewees’ views, we recommend that policy decision makers within humanitarian agencies and the Government of Lebanon explore the possibilities for allowing temporary registration of displaced Syrian IHCW to benefit local host communities and refugee populations