Integration of airborne and ground observations of nitryl chloride in the Seoul metropolitan area and the implications on regional oxidation capacity during KORUS-AQ 2016

Nitryl chloride (ClNO2) is a radical reservoir species that releases chlorine radicals upon photolysis. An integrated analysis of the impact of ClNO2 on regional photochemistry in the Seoul metropolitan area (SMA) during the Korea-United States Air Quality Study (KORUS-AQ) 2016 field campaign is presented. Comprehensive multiplatform observations were conducted aboard the NASA DC-8 and at two ground sites (Olympic Park, OP; Taehwa Research Forest, TRF), representing an urbanized area and a forested suburban region, respectively. Positive correlations between daytime Cl2 and ClNO2 were observed at both sites, the slope of which was dependent on O3 levels. The possible mechanisms are explored through box model simulations constrained with observations. The overall diurnal variations in ClNO2 at both sites appeared similar but the nighttime variations were systematically different. For about half of the observation days at the OP site the level of ClNO2 increased at sunset but rapidly decreased at around midnight. On the other hand, high levels were observed throughout the night at the TRF site. Significant levels of ClNO2 were observed at both sites for 4-5 h after sunrise. Airborne observations, box model calculations, and back-trajectory analysis consistently show that these high levels of ClNO2 in the morning are likely from vertical or horizontal transport of air masses from the west. Box model results show that chlorine-radical-initiated chemistry can impact the regional photochemistry by elevating net chemical production rates of ozone by 25% in the morning

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

Statistically derived contributions of diverse human influences to twentieth-century temperature changes

The warming of the climate system is unequivocal as evidenced by an increase in global temperatures by 0.8 °C over the past century. However, the attribution of the observed warming to human activities remains less clear, particularly because of the apparent slow-down in warming since the late 1990s. Here we analyse radiative forcing and temperature time series with state-of-the-art statistical methods to address this question without climate model simulations. We show that long-term trends in total radiative forcing and temperatures have largely been determined by atmospheric greenhouse gas concentrations, and modulated by other radiative factors. We identify a pronounced increase in the growth rates of both temperatures and radiative forcing around 1960, which marks the onset of sustained global warming. Our analyses also reveal a contribution of human interventions to two periods when global warming slowed down. Our statistical analysis suggests that the reduction in the emissions of ozone-depleting substances under the Montreal Protocol, as well as a reduction in methane emissions, contributed to the lower rate of warming since the 1990s. Furthermore, we identify a contribution from the two world wars and the Great Depression to the documented cooling in the mid-twentieth century, through lower carbon dioxide emissions. We conclude that reductions in greenhouse gas emissions are effective in slowing the rate of warming in the short term.F.E. acknowledges financial support from the Consejo Nacional de Ciencia y Tecnologia (http://www.conacyt.gob.mx) under grant CONACYT-310026, as well as from PASPA DGAPA of the Universidad Nacional Autonoma de Mexico. (CONACYT-310026 - Consejo Nacional de Ciencia y Tecnologia; PASPA DGAPA of the Universidad Nacional Autonoma de Mexico

Lifshitz-like space-time from intersecting branes in string/M theory

We construct 1/4 BPS, threshold F-D$p$ bound states (with $0\leq p \leq 5$) of type II string theories by applying S- and T-dualities to the D1-D5 system of type IIB string theory. These are different from the known 1/2 BPS, non-threshold F-D$p$ bound states. The near horizon limits of these solutions yield Lifshitz-like space-times with varying dynamical critical exponent $z=2(5-p)/(4-p)$, for $p\neq 4$, along with the hyperscaling violation exponent $\theta = p - (p-2)/(4-p)$, showing how Lifshitz-like space-time can be obtained from string theory. The dilatons are in general non-constant (except for $p=1$). We discuss the holographic RG flows and the phase structures of these solutions. For $p=4$, we do not get a Lifshitz-like space-time, but the near horizon limit in this case leads to an AdS$_2$ space.Comment: 20 pages, no figure, v2: proper identification of hyperscaling violation exponent has been made, abstract and the text has been changed accordingly, note added, v3: minor changes, refs added, version to appear in JHE

Atrial Fibrillation Specific Exercise Rehabilitation: Are We There Yet?

Regular physical activity and exercise training are integral for the secondary prevention of cardiovascular disease. Despite recent advances in more holistic care pathways for people with atrial fibrillation (AF), exercise rehabilitation is not provided as part of routine care. The most recent European Society of Cardiology report for AF management states that patients should be encouraged to undertake moderate-intensity exercise and remain physically active to prevent AF incidence or recurrence. The aim of this review was to collate data from primary trials identified in three systematic reviews and recent real-world cohort studies to propose an AF-specific exercise rehabilitation guideline. Collating data from 21 studies, we propose that 360-720 metabolic equivalent (MET)-minutes/week, corresponding to ~60-120 min of exercise per week at moderate-to-vigorous intensity, could be an evidence-based recommendation for patients with AF to improve AF-specific outcomes, quality of life, and possibly prevent long-term major adverse cardiovascular events. Furthermore, non-traditional, low-moderate intensity exercise, such as Yoga, seems to have promising benefits on patient quality of life and possibly physical capacity and should, therefore, be considered in a personalised rehabilitation programme. Finally, we discuss the interesting concepts of short-term exercise-induced cardioprotection and 'none-response' to exercise training with reference to AF rehabilitation

SUPPORT Tools for evidence-informed health Policymaking (STP) 14: Organising and using policy dialogues to support evidence-informed policymaking

This article is part of a series written for people responsible for making decisions about health policies and programmes and for those who support these decision makers

Hamstring stretch reflex:could it be a reproducible objective measure of functional knee stability?"

Background: The anterior cruciate ligament (ACL) plays an important role in anterior knee stability by preventing anterior translation of the tibia on the femur. Rapid translation of the tibia with respect to the femur produces an ACL-hamstring stretch reflex which may provide an object measure of neuromuscular function following ACL injury or reconstruction. The aim of this study was to determine if the ACL-hamstring stretch reflex could be reliably and consistently obtained using the KT-2000 arthrometer.  Methods: A KT-2000 arthrometer was used to translate the tibia on the femur while recording the electromyography over the biceps femoris muscle in 20 participants, all with intact ACLs. In addition, a sub-group comprising 4 patients undergoing a knee arthroscopy for meniscal pathology, were tested before and after anaesthetic and with direct traction on the ACL during arthroscopy. The remaining 16 participants underwent testing to elicit the reflex using the KT-2000 only.  Results: A total number of 182 trials were performed from which 70 trials elicited stretch reflex (38.5 %). The mean onset latency of the hamstring stretch reflexes was 58.9 ± 17.9 ms. The average pull force was 195 ± 47 N, stretch velocity 48 ± 35 mm/s and rate of force 19.7 ± 6.4 N/s. Conclusions Based on these results, we concluded that the response rate of the anterior cruciate ligament-hamstring reflex is too low for it to be reliably used in a clinical setting, and thus would have limited value in assessing the return of neuromuscular function following ACL injuries

Robust markers and sample sizes for multi‐centre trials of Huntington's disease

Objective: The identification of sensitive biomarkers is essential to validate therapeutics for Huntington disease (HD). We directly compare structural imaging markers across the largest collective imaging HD dataset to identify a set of imaging markers robust to multicenter variation and to derive upper estimates on sample sizes for clinical trials in HD. Methods: We used 1 postprocessing pipeline to retrospectively analyze T1-weighted magnetic resonance imaging (MRI) scans from 624 participants at 3 time points, from the PREDICT-HD, TRACK-HD, and IMAGE-HD studies. We used mixed effects models to adjust regional brain volumes for covariates, calculate effect sizes, and simulate possible treatment effects in disease-affected anatomical regions. We used our model to estimate the statistical power of possible treatment effects for anatomical regions and clinical markers. Results: We identified a set of common anatomical regions that have similarly large standardized effect sizes (>0.5) between healthy control and premanifest HD (PreHD) groups. These included subcortical, white matter, and cortical regions and nonventricular cerebrospinal fluid (CSF). We also observed a consistent spatial distribution of effect size by region across the whole brain. We found that multicenter studies were necessary to capture treatment effect variance; for a 20% treatment effect, power of >80% was achieved for the caudate (n = 661), pallidum (n = 687), and nonventricular CSF (n = 939), and, crucially, these imaging markers provided greater power than standard clinical markers. Interpretation: Our findings provide the first cross-study validation of structural imaging markers in HD, supporting the use of these measurements as endpoints for both observational studies and clinical trial

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures