A single-particle characterization of a mobile Versatile Aerosol Concentration Enrichment System for exposure studies

BACKGROUND: An Aerosol Time-of-Flight Mass Spectrometer (ATOFMS) was used to investigate the size and chemical composition of fine concentrated ambient particles (CAPs) in the size range 0.2–2.6 μm produced by a Versatile Aerosol Concentration Enrichment System (VACES) contained within the Mobile Ambient Particle Concentrator Exposure Laboratory (MAPCEL). The data were collected during a study of human exposure to CAPs, in Edinburgh (UK), in February-March 2004. The air flow prior to, and post, concentration in the VACES was sampled in turn into the ATOFMS, which provides simultaneous size and positive and negative mass spectral data on individual fine particles. RESULTS: The particle size distribution was unaltered by the concentrator over the size range 0.2–2.6 μm, with an average enrichment factor during this study of ~5 (after dilution of the final air stream). The mass spectra from single particles were objectively grouped into 20 clusters using the multivariate K-means algorithm and then further grouped manually, according to similarity in composition and time sequence, into 8 main clusters. The particle ensemble was dominated by pure and reacted sea salt and other coarse inorganic dusts (as a consequence of the prevailing maritime-source climatology during the study), with relatively minor contributions from carbonaceous and secondary material. Very minor variations in particle composition were noted pre- and post-particle concentration, but overall there was no evidence of any significant change in particle composition. CONCLUSION: These results confirm, via single particle analysis, the preservation of the size distribution and chemical composition of fine ambient PM in the size range 0.2–2.6 μm after passage through the VACES concentration instrumentation

Pain psychology in the 21st century: lessons learned and moving forward

Background and aims In the spring of 2019, Professor Steven J. Linton, the founder of the Center for Health and Medical Psychology (CHAMP) at Örebro University, Sweden, formally retired. As a tribute to his scholarly work covering decades of influence and inspiration to the field of pain psychology, the research center organized a topical conference titled “Pain in the 21st century: Where do we come from and where are we going?”, which resulted in this state-of the-art synthesis. The aim of this declaration is to highlight lessons learned but not in the least is meant to inspire and guide our continued journey forward, developing pain psychology into the 21st century. Methods Several collaborators of Professor Linton have summarized and reflected on the current state-of-the-art of pain psychology from the perspective of his input to the field, as well as on developments from the last years of advancements in pain psychology. Results The topics have been divided into six themed sections covering the fear avoidance model, transdiagnostics, secondary prevention, risk- and protective factors, communication and contextual factors. The sections cover a broad spectrum, from basic experimental studies, integrating emotion and motivational theories into current theoretical models, to applied research on the effect of early interventions as well as sophisticated emotion-focused treatment models for pain patients with concurrent emotional ill-health. Conclusions There have been major advancements within pain psychology research during the last decades, moving the field towards a more comprehensive picture, taking emotional and motivational aspects into account to understand pain sufferers. Although psychologically informed interventions in general mainly focus on the individual, it has been put forward that pain management is highly influenced by the surrounding environment, including communication with health care providers, and the occupational and social context. Implications Professor Steven J. Linton has been at the forefront of pain psychology research during the last decades, and inspired by his work this journey will continue into the 21st century, with the ultimate goal of enhancing the understanding and treatment for all people suffering from persistent and disabling pain

An Analysis of Resting-State Functional Transcranial Doppler Recordings from Middle Cerebral Arteries

Functional transcrannial Doppler (fTCD) is used for monitoring the hemodynamics characteristics of major cerebral arteries. Its resting-state characteristics are known only when considering the maximal velocity corresponding to the highest Doppler shift (so called the envelope signals). Significantly more information about the resting-state fTCD can be gained when considering the raw cerebral blood flow velocity (CBFV) recordings. In this paper, we considered simultaneously acquired envelope and raw CBFV signals. Specifically, we collected bilateral CBFV recordings from left and right middle cerebral arteries using 20 healthy subjects (10 females). The data collection lasted for 15 minutes. The subjects were asked to remain awake, stay silent, and try to remain thought-free during the data collection. Time, frequency and time-frequency features were extracted from both the raw and the envelope CBFV signals. The effects of age, sex and body-mass index were examined on the extracted features. The results showed that the raw CBFV signals had a higher frequency content, and its temporal structures were almost uncorrelated. The information-theoretic features showed that the raw recordings from left and right middle cerebral arteries had higher content of mutual information than the envelope signals. Age and body-mass index did not have statistically significant effects on the extracted features. Sex-based differences were observed in all three domains and for both, the envelope signals and the raw CBFV signals. These findings indicate that the raw CBFV signals provide valuable information about the cerebral blood flow which can be utilized in further validation of fTCD as a clinical tool. © 2013 Sejdić et al

Beneficial cardiovascular effects of reducing exposure to particulate air pollution with a simple facemask

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollution is an important risk factor for cardiovascular morbidity and mortality, and is associated with increased blood pressure, reduced heart rate variability, endothelial dysfunction and myocardial ischaemia. Our objectives were to assess the cardiovascular effects of reducing air pollution exposure by wearing a facemask.</p> <p>Methods</p> <p>In an open-label cross-over randomised controlled trial, 15 healthy volunteers (median age 28 years) walked on a predefined city centre route in Beijing in the presence and absence of a highly efficient facemask. Personal exposure to ambient air pollution and exercise was assessed continuously using portable real-time monitors and global positional system tracking respectively. Cardiovascular effects were assessed by continuous 12-lead electrocardiographic and ambulatory blood pressure monitoring.</p> <p>Results</p> <p>Ambient exposure (PM_2.586 ± 61 <it>vs </it>140 ± 113 μg/m³; particle number 2.4 ± 0.4 <it>vs </it>2.3 ± 0.4 × 10⁴particles/cm³), temperature (29 ± 1 <it>vs </it>28 ± 3°C) and relative humidity (63 ± 10 <it>vs </it>64 ± 19%) were similar (P > 0.05 for all) on both study days. During the 2-hour city walk, systolic blood pressure was lower (114 ± 10 <it>vs </it>121 ± 11 mmHg, P < 0.01) when subjects wore a facemask, although heart rate was similar (91 ± 11 <it>vs </it>88 ± 11/min; P > 0.05). Over the 24-hour period heart rate variability increased (SDNN 65.6 ± 11.5 <it>vs </it>61.2 ± 11.4 ms, P < 0.05; LF-power 919 ± 352 <it>vs </it>816 ± 340 ms², P < 0.05) when subjects wore the facemask.</p> <p>Conclusion</p> <p>Wearing a facemask appears to abrogate the adverse effects of air pollution on blood pressure and heart rate variability. This simple intervention has the potential to protect susceptible individuals and prevent cardiovascular events in cities with high concentrations of ambient air pollution.</p

On the experimental verification of quantum complexity in linear optics

The first quantum technologies to solve computational problems that are beyond the capabilities of classical computers are likely to be devices that exploit characteristics inherent to a particular physical system, to tackle a bespoke problem suited to those characteristics. Evidence implies that the detection of ensembles of photons, which have propagated through a linear optical circuit, is equivalent to sampling from a probability distribution that is intractable to classical simulation. However, it is probable that the complexity of this type of sampling problem means that its solution is classically unverifiable within a feasible number of trials, and the task of establishing correct operation becomes one of gathering sufficiently convincing circumstantial evidence. Here, we develop scalable methods to experimentally establish correct operation for this class of sampling algorithm, which we implement with two different types of optical circuits for 3, 4, and 5 photons, on Hilbert spaces of up to 50,000 dimensions. With only a small number of trials, we establish a confidence >99% that we are not sampling from a uniform distribution or a classical distribution, and we demonstrate a unitary specific witness that functions robustly for small amounts of data. Like the algorithmic operations they endorse, our methods exploit the characteristics native to the quantum system in question. Here we observe and make an application of a "bosonic clouding" phenomenon, interesting in its own right, where photons are found in local groups of modes superposed across two locations. Our broad approach is likely to be practical for all architectures for quantum technologies where formal verification methods for quantum algorithms are either intractable or unknown.Comment: Comments welcom

Safety and feasibility of switching from phenytoin to levetiracetam monotherapy for glioma-related seizure control following craniotomy: a randomized phase II pilot study

Seizures are common in patients with gliomas, and phenytoin (PHT) is frequently used to control tumor-related seizures. PHT, however, has many undesirable side effects (SEs) and drug interactions with glioma chemotherapy. Levetiracetam (LEV) is a newer antiepileptic drug (AED) with fewer SEs and essentially no drug interactions. We performed a pilot study testing the safety and feasibility of switching patients from PHT to LEV monotherapy for postoperative control of glioma-related seizures. Over a 13-month period, 29 patients were randomized in a 2:1 ratio to initiate LEV therapy within 24 h of surgery or to continue PHT therapy. 6 month follow-up data were available for 15 patients taking LEV and for 8 patients taking PHT. In the LEV group, 13 patients (87%) were seizure-free. In the PHT group, 6 patients (75%) were seizure-free. Reported SEs at 6 months was as follows (%LEV/%PHT group): dizziness (0/14), difficulty with coordination (0/29), depression (7/14) lack of energy or strength (20/43), insomnia (40/43), mood instability (7/0). The pilot data presented here suggest that it is safe to switch patients from PHT to LEV monotherapy following craniotomy for supratentorial glioma. A large-scale, double-blinded, randomized control trial of LEV versus PHT is required to determine seizure control equivalence and better assess differences in SEs

Mutations in linker for activation of T cells (LAT) lead to a novel form of severe combined immunodeficiency

BACKGROUND: Signaling through the T-cell receptor (TCR) is critical for T-cell development and function. Linker for activation of T cells (LAT) is a transmembrane adaptor signaling molecule that is part of the TCR complex and essential for T-cell development, as demonstrated by LAT-deficient mice, which show a complete lack of peripheral T cells. OBJECTIVE: We describe a pedigree affected by a severe combined immunodeficiency phenotype with absent T cells and normal B-cell and natural killer cell numbers. A novel homozygous frameshift mutation in the gene encoding for LAT was identified in this kindred. METHODS: Genetic, molecular, and functional analyses were used to identify and characterize the LAT defect. Clinical and immunologic analysis of patients was also performed and reported. RESULTS: Homozygosity mapping was used to identify potential defective genes. Sanger sequencing of the LAT gene showed a mutation that resulted in a premature stop codon and protein truncation leading to complete loss of function and loss of expression of LAT in the affected family members. We also demonstrate loss of LAT expression and lack of TCR signaling restoration in LAT-deficient cell lines reconstituted with a synthetic LAT gene bearing this severe combined immunodeficiency mutation. CONCLUSION: For the first time, the results of this study show that inherited LAT deficiency should be considered in patients with combined immunodeficiency with T-cell abnormalities

Plasmodium vivax Adherence to Placental Glycosaminoglycans

BACKGROUND: Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear. METHODOLOGY: The adherence properties of P. vivax infected red blood cells (PvIRBC) were evaluated under static and flow conditions. PRINCIPAL FINDINGS: P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA) and hyaluronic acid (HA), the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5). Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD) shear stress reducing maximum attachment by 50% was 0.06 (0.02) Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37 °C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39 °C adherence began earlier and peaked at 24 hours. SIGNIFICANCE: Adherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation

Measured adiposity in relation to head and neck cancer risk in the European Prospective Investigation into Cancer and Nutrition

BACKGROUND: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer (HNC). However, most studies have used self-reported anthropometry which is prone to error. METHODS: Among 363 094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of HNC. HNC risk was examined in relation to body mass index (BMI) [lean: 30 kg/m²], waist circumference (WC), hip circumference (HC) and waist to hip ratio (WHR) using Cox proportional hazards models. RESULTS: Among men, a BMI < 22.5 kg/m² was associated with higher HNC risk [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.23 - 2.12)]; BMI was not associated with HNC among women. WC and WHR were associated with greater risk of HNC among women, (WC per 5 cm: HR 1.08, 95% CI 1.02 - 1.15; WHR per 0.1 unit: HR 1.64, 95% CI 1.38 - 1.93). After stratification by smoking status, the association for WHR was present only among smokers (p interaction 0.004). Among men, WC and WHR were associated with HNC only upon additional adjustment for BMI (WC per 5 cm: HR 1.16, 95% CI 1.07 - 1.26; WHR per 0.1 unit: HR 1.42, 95% CI 1.21 - 1.65). CONCLUSION: Central adiposity, particularly among women, may have a stronger association with HNC risk than previously estimated. IMPACT: Strategies to reduce obesity may beneficially impact HNC incidence.The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC- 2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; , PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to K.T. Khaw, N.J. Wareham; C570/A16491 to R.C. Travis and C8221/A19170 to Tim Key (EPIC-Oxford), Medical Research Council (1000143 to K.T. Khaw, N.J. Wareham, MR/M012190/1 to Tim Key (EPIC-Oxford)) (United Kingdom)