Influence of the quasi-biennial oscillation on the extratropical winter stratosphere in an atmospheric general circulation model and in reanalysis data

The interannual variability of the stratospheric polar vortex during winter in both hemispheres is observed to correlate strongly with the phase of the quasi-biennial oscillation (QBO) in tropical stratospheric winds. It follows that the lack of a spontaneously generated QBO in most atmospheric general circulation models (AGCMs) adversely affects the nature of polar variability in such models. This study examines QBO–vortex coupling in an AGCM in which a QBO is spontaneously induced by resolved and parameterized waves. The QBO–vortex coupling in the AGCM compares favorably to that seen in reanalysis data [from the 40-yr ECMWF Re-Analysis (ERA-40)], provided that careful attention is given to the definition of QBO phase. A phase angle representation of the QBO is employed that is based on the two leading empirical orthogonal functions of equatorial zonal wind vertical profiles. This yields a QBO phase that serves as a proxy for the vertical structure of equatorial winds over the whole depth of the stratosphere and thus provides a means of subsampling the data to select QBO phases with similar vertical profiles of equatorial zonal wind. Using this subsampling, it is found that the QBO phase that induces the strongest polar vortex response in early winter differs from that which induces the strongest late-winter vortex response. This is true in both hemispheres and for both the AGCM and ERA-40. It follows that the strength and timing of QBO influence on the vortex may be affected by the partial seasonal synchronization of QBO phase transitions that occurs both in observations and in the model. This provides a mechanism by which changes in the strength of QBO–vortex correlations may exhibit variability on decadal time scales. In the model, such behavior occurs in the absence of external forcings or interannual variations in sea surface temperatures

An unexpected disruption of the atmospheric quasi-biennial oscillation

One of the most repeatable phenomena seen in the atmosphere, the quasi-biennial oscillation (QBO) between prevailing eastward and westward wind jets in the equatorial stratosphere (approximately 16 to 50 kilometers altitude), was unexpectedly disrupted in February 2016. An unprecedented westward jet formed within the eastward phase in the lower stratosphere and cannot be accounted for by the standard QBO paradigm based on vertical momentum transport. Instead, the primary cause was waves transporting momentum from the Northern Hemisphere. Seasonal forecasts did not predict the disruption, but analogous QBO disruptions are seen very occasionally in some climate simulations. A return to more typical QBO behavior within the next year is forecast, although the possibility of more frequent occurrences of similar disruptions is projected for a warming climate

Population heterogeneity in Plasmodium vivax relapse risk

A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P vivax endemic regions and are thought to be influenced by factors such as febrile infections which may cause temporary changes in hypnozoite activation leading to ‘temporal heterogeneity’ in reactivation risk. In addition, immunity and variation in exposure to infection may be longer-term characteristics of individuals that lead to ‘popula-tion heterogeneity’ in hypnozoite activation. We analyze data on risk of P vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P vivax risk of recurrences. Trial Registration: ClinicalTrials.gov NCT01640574, NCT01074905, NCT02143934

Transcriptional profiling and immunophenotyping show sustained activation of blood monocyte in subpatent Plasmodium falciparum infection

Objectives Malaria, caused by Plasmodium infection, remains a major global health problem. Monocytes are integral to the immune response, yet their transcriptional and functional responses in primary Plasmodium falciparum infection and in clinical malaria are poorly understood. Methods The transcriptional and functional profiles of monocytes were examined in controlled human malaria infection with P. falciparum blood stages and in children and adults with acute malaria. Monocyte gene expression and functional phenotypes were examined by RNA sequencing and flow cytometry at peak infection and compared to pre‐infection or at convalescence in acute malaria. Results In subpatent primary infection, the monocyte transcriptional profile was dominated by an interferon (IFN) molecular signature. Pathways enriched included type I IFN signalling, innate immune response and cytokine‐mediated signalling. Monocytes increased TNF and IL‐12 production upon in vitro toll‐like receptor stimulation and increased IL‐10 production upon in vitro parasite restimulation. Longitudinal phenotypic analyses revealed sustained significant changes in the composition of monocytes following infection, with increased CD14+CD16− and decreased CD14−CD16+ subsets. In acute malaria, monocyte CD64/FcγRI expression was significantly increased in children and adults, while HLA‐DR remained stable. Although children and adults showed a similar pattern of differentially expressed genes, the number and magnitude of gene expression change were greater in children. Conclusions Monocyte activation during subpatent malaria is driven by an IFN molecular signature with robust activation of genes enriched in pathogen detection, phagocytosis, antimicrobial activity and antigen presentation. The greater magnitude of transcriptional changes in children with acute malaria suggests monocyte phenotypes may change with age or exposure

Variability in Serum Sodium Concentration and Prognostic Significance in Severe Traumatic Brain Injury: A Multicenter Observational Study.

BACKGROUND/OBJECTIVE: Dysnatremia is common in severe traumatic brain injury (TBI) patients and may contribute to mortality. However, serum sodium variability has not been studied in TBI patients. We hypothesized that such variability would be independently associated with mortality. METHODS: We collected 6-hourly serum sodium levels for the first 7 days of ICU admission from 240 severe TBI patients in 14 neurotrauma ICUs in Europe and Australia. We evaluated the association between daily serum sodium standard deviation (dNaSD), an index of variability, and 28-day mortality. RESULTS: Patients were 46 ± 19 years of age with a median initial GCS of 6 [4-8]. Overall hospital mortality was 28%. Hypernatremia and hyponatremia occurred in 64% and 24% of patients, respectively. Over the first 7 days in ICU, serum sodium standard deviation was 2.8 [2.0-3.9] mmol/L. Maximum daily serum sodium standard deviation (dNaSD) occurred at a median of 2 [1-4] days after admission. There was a significant progressive decrease in dNaSD over the first 7 days (coefficient - 0.15 95% CI [- 0.18 to - 0.12], p < 0.001). After adjusting for baseline TBI severity, diabetes insipidus, the use of osmotherapy, the occurrence of hypernatremia, and hyponatremia and center, dNaSD was significantly independently associated with 28-day mortality (HR 1.27 95% CI (1.01-1.61), p = 0.048). CONCLUSIONS: Our study demonstrates that daily serum sodium variability is an independent predictor of 28-day mortality in severe TBI patients. Further prospective investigations are necessary to confirm the significance of sodium variability in larger cohorts of TBI patients and test whether attenuating such variability confers outcome benefits to such patients

Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation

Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection. pDC responsiveness to TLR7 and TLR9 stimulation was assessed in-vitro. Circulating pDC remained transcriptionally stable with gene expression altered for 8 genes (FDR < 0.07). There was no upregulation of co-stimulatory molecules CD86, CD80, CD40, and reduced surface expression of HLA-DR and CD123 (IL-3R-α). pDC loss from the circulation was associated with active caspase-3, suggesting pDC apoptosis during primary infection. pDC remained responsive to TLR stimulation, producing IFN-α and upregulating HLA-DR, CD86, CD123 at peak-infection. In clinical malaria, pDC retained HLA-DR but reduced CD123 expression compared to convalescence. These data demonstrate pDC retain function during a first blood-stage P. falciparum exposure despite sub-microscopic parasitaemia downregulating HLA-DR. The lack of evident pDC activation in both early infection and malaria suggests little response of circulating pDC to infection

Early Osmotherapy in Severe Traumatic Brain Injury : An International Multicenter Study

The optimal osmotic agent to treat intracranial hypertension in patients with severe traumatic brain injury (TBI) remains uncertain. We aimed to test whether the choice of mannitol or hypertonic saline (HTS) as early (first 96 h) osmotherapy in these patients might be associated with a difference in mortality. We retrospectively analyzed data from 2015 from 14 tertiary intensive care units (ICUs) in Australia, UK, and Europe treating severe TBI patients with intracranial pressure (ICP) monitoring and compared mortality in those who received mannitol only versus HTS only. We performed multi-variable analysis adjusting for site and illness severity (Injury Severity Score, extended IMPACT score, and mean ICP over the first 96 h) using Cox proportional hazards regression. We collected data on 262 patients and compared patients who received early osmotherapy with mannitol alone (n = 46) with those who received HTS alone (n = 46). Mannitol patients were older (median age, 49.2 (19.2) vs. 40.5 (16.8) years; p = 0.02), with higher Injury Severity Scores (42 (15.9) vs. 32.1 [11.3]; p = 0.001), and IMPACT-TBI predicted 6-month mortality (34.5% [23-46] vs. 25% [13-38]; p = 0.02), but had similar APACHE-II scores, and mean and maximum ICPs over the first 96 h. The unadjusted hazard ratio for in-hospital mortality in patients receiving only mannitol was 3.35 (95% confidence interval [CI], 1.60-7.03; p = 0.001). After adjustment for key mortality predictors, the hazard ratio for in-hospital mortality in patients receiving only mannitol was 2.64 (95% CI, 0.96-7.30; p = 0.06). The choice of early osmotherapy in severe TBI patients may affect survival, or simply reflect clinician beliefs about their different roles, and warrants controlled investigation.Peer reviewe

Cognitive and Tactile Factors Affecting Human Haptic Performance in Later Life

Background: Vision and haptics are the key modalities by which humans perceive objects and interact with their environment in a target-oriented manner. Both modalities share higher-order neural resources and the mechanisms required for object exploration. Compared to vision, the understanding of haptic information processing is still rudimentary. Although it is known that haptic performance, similar to many other skills, decreases in old age, the underlying mechanisms are not clear. It is yet to be determined to what extent this decrease is related to the age-related loss of tactile acuity or cognitive capacity. Methodology/Principal Findings: We investigated the haptic performance of 81 older adults by means of a cross-modal object recognition test. Additionally, we assessed the subjects ’ tactile acuity with an apparatus-based two-point discrimination paradigm, and their cognitive performance by means of the non-verbal Raven-Standard-Progressive matrices test. As expected, there was a significant age-related decline in performance on all 3 tests. With the exception of tactile acuity, this decline was found to be more distinct in female subjects. Correlation analyses revealed a strong relationship between haptic and cognitive performance for all subjects. Tactile performance, on the contrary, was only significantly correlated with male subjects ’ haptic performance. Conclusions: Haptic object recognition is a demanding task in old age, especially when it comes to the exploration o

Increased Asymmetric Dimethylarginine in Severe Falciparum Malaria: Association with Impaired Nitric Oxide Bioavailability and Fatal Outcome

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is a predictor of mortality in critical illness. Severe malaria (SM) is associated with decreased NO bioavailability, but the contribution of ADMA to the pathogenesis of impaired NO bioavailability and adverse outcomes in malaria is unknown. In adults with and without falciparum malaria, we tested the hypotheses that plasma ADMA would be: 1) increased in proportion to disease severity, 2) associated with impaired vascular and pulmonary NO bioavailability and 3) independently associated with increased mortality. We assessed plasma dimethylarginines, exhaled NO concentrations and endothelial function in 49 patients with SM, 78 with moderately severe malaria (MSM) and 19 healthy controls (HC). Repeat ADMA and endothelial function measurements were performed in patients with SM. Multivariable regression was used to assess the effect of ADMA on mortality and NO bioavailability. Plasma ADMA was increased in SM patients (0.85 µM; 95% CI 0.74–0.96) compared to those with MSM (0.54 µM; 95%CI 0.5–0.56) and HCs (0.64 µM; 95%CI 0.58–0.70; p<0.001). ADMA was an independent predictor of mortality in SM patients with each micromolar elevation increasing the odds of death 18 fold (95% CI 2.0–181; p = 0.01). ADMA was independently associated with decreased exhaled NO (rs = −0.31) and endothelial function (rs = −0.32) in all malaria patients, and with reduced exhaled NO (rs = −0.72) in those with SM. ADMA is increased in SM and associated with decreased vascular and pulmonary NO bioavailability. Inhibition of NOS by ADMA may contribute to increased mortality in severe malaria

Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis.

Monitoring and optimisation of brain tissue oxygen tension (PbtO2) has been associated with improved neurological outcome and survival in observational studies of severe traumatic brain injury (TBI). We carried out a systematic review of randomized controlled trials to determine if PbtO2-guided management is associated with differential neurological outcomes, survival, and adverse events. Searches were carried out to 10 February 2022 in Medline (OvidSP), 11 February in EMBASE (OvidSP) and 8 February in Cochrane library. Randomized controlled trials comparing PbtO2 and ICP-guided management to ICP-guided management alone were included. The primary outcome was survival with favourable neurological outcome at 6-months post injury. Data were extracted by two independent authors and GRADE certainty of evidence assessed. There was no difference in the proportion of patients with favourable neurological outcomes with PbtO2-guided management (relative risk [RR] 1.42, 95% CI 0.97 to 2.08; p = 0.07; I2 = 0%, very low certainty evidence) but PbtO2-guided management was associated with reduced mortality (RR 0.54, 95% CI 0.31 to 0.93; p = 0.03; I2 = 42%; very low certainty evidence) and ICP (mean difference (MD) - 4.62, 95% CI - 8.27 to - 0.98; p = 0.01; I2 = 63%; very low certainty evidence). There was no significant difference in the risk of adverse respiratory or cardiovascular events. PbtO2-guided management in addition to ICP-based care was not significantly associated with increased favourable neurological outcomes, but was associated with increased survival and reduced ICP, with no difference in respiratory or cardiovascular adverse events. However, based on GRADE criteria, the certainty of evidence provided by this meta-analysis was consistently very low. MESH: Brain Ischemia; Intensive Care; Glasgow Outcome Scale; Randomized Controlled Trial; Craniocerebral Trauma