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Background: Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels., Methods: The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined)., Findings: Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50)., Interpretation: There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke., Funding: The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke., Competing Interests: We declare no competing interests. Dr. Hans-Christoph Diener has reported receiving fees from Pfizer, Abbott, and Daiichi Sankyo. Dr. Denis Xavier reported receiving grants from Population Health Research Institute, Hamilton Health Science, Boehringer Ingelheim, Bristol Myers Squibb, Coco cola India, Indian Council of Medical Research, Pfizer, United Kingdom Medical Research Council and Welcome Trust., (© 2024 The Authors.)

Supercontinuum (SC) light source has advanced ultrafast laser spectroscopy in condensed matter science, biology, physics, and chemistry. Compared to the frequently used photonic crystal fibers and bulk materials, femtosecond laser filamentation in gases is damage-immune for supercontinuum generation. A bottleneck problem is the strong jitters from filament induced self-heating at kHz repetition rate level. We demonstrated stable kHz supercontinuum generation directly in air with multiple mJ level pulse energy. This was achieved by applying an external DC electric field to the air plasma filament. Beam pointing jitters of the 1 kHz air filament induced SC light were reduced by more than 2 fold. The stabilized high repetition rate laser filament offers the opportunity for stable intense SC generation and its applications in air., (© 2024. The Author(s).)

Background: The impact of concomitant coronary artery bypass grafting (CABG) on aortic valve replacement (AVR) in octogenarians is still debated. We analyzed the characteristics and long-term survival of octogenarians undergoing isolated AVR and AVR + CABG., Methods: All octogenarians who consecutively underwent AVR with or without concomitant CABG at our tertiary cardiac center between 2000 and 2022 were included. Patients with redo, emergent, or any other concomitant procedures were excluded. The primary endpoints were 30-day and long-term survival. The secondary endpoints were early postoperative outcomes and determinants of long-term survival. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of 30-day mortality, and Cox regression analysis was performed for predictors of adverse long-term survival., Results: A total of 1011 patients who underwent AVR (83.0 [81.0-85.0] years, 42.0% males) and 1055 with AVR + CABG (83.0 [81.2-85.4] years, 66.1% males) were included in our study. Survival at 30 days and at 1, 3, and 5 years in the AVR group was 97.9%, 91.5%, 80.5%, and 66.2%, respectively, while in the AVR + CABG group it was 96.2%, 89.6%, 77.7%, and 64.7%, respectively. There was no significant difference in median postoperative survival between the AVR and AVR + CABG groups (7.1 years [IQR: 6.7-7.5] vs. 6.6 years [IQR: 6.3-7.2], respectively, p = 0.21). Significant predictors of adverse long-term survival in the AVR group included age (hazard ratio (HR): 1.09; 95% CI: 1.06-1.12, p < 0.001), previous MI (HR: 2.08; 95% CI: 1.32-3.28, p = 0.002), and chronic kidney disease (HR 2.07; 95% CI: 1.33-3.23, p = 0.001), while in the AVR + CABG group they included age (HR: 1.06; 95% CI: 1.04-1.10, p < 0.001) and diabetes mellitus (HR: 1.48; 95% CI: 1.15-1.89, p = 0.002). Concomitant CABG was not an independent risk factor for adverse long-term survival (HR: 0.89; 95% CI: 0.77-1.02, p = 0.09)., Conclusions: The long-term survival of octogenarians who underwent AVR or AVR + CABG was similar and was not affected by adding concomitant CABG. However, octogenarians who underwent concomitant CABG with AVR had significantly higher in-hospital mortality. Each decision should be discussed within the heart team.

Breast-conserving surgery (BCS) is commonly used for the treatment of early-stage breast cancer. Following BCS, approximately 20% to 30% of patients require reexcision because postoperative histopathology identifies cancer in the surgical margins of the excised specimen. Quantitative micro-elastography (QME) is an imaging technique that maps microscale tissue stiffness and has demonstrated a high diagnostic accuracy (96%) in detecting cancer in specimens excised during surgery. However, current QME methods, in common with most proposed intraoperative solutions, cannot image cancer directly in the patient, making their translation to clinical use challenging. In this proof-of-concept study, we aimed to determine whether a handheld QME probe, designed to interrogate the surgical cavity, can detect residual cancer directly in the breast cavity in vivo during BCS. In a first-in-human study, 21 BCS patients were scanned in vivo with the QME probe by five surgeons. For validation, protocols were developed to coregister in vivo QME with postoperative histopathology of the resected tissue to assess the capability of QME to identify residual cancer. In four cavity aspects presenting cancer and 21 cavity aspects presenting benign tissue, QME detected elevated stiffness in all four cancer cases, in contrast to low stiffness observed in 19 of the 21 benign cases. The results indicate that in vivo QME can identify residual cancer by directly imaging the surgical cavity, potentially providing a reliable intraoperative solution that can enable more complete cancer excision during BCS., Significance: Optical imaging of microscale tissue stiffness enables the detection of residual breast cancer directly in the surgical cavity during breast-conserving surgery, which could potentially contribute to more complete cancer excision., (©2022 The Authors; Published by the American Association for Cancer Research.)

Background and Purpose: The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes., Methods: Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH)., Results: Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P<0.0001)., Conclusions: The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.

Anticoagulant therapeutics are a mainstay of modern surgery and of clotting disorder management such as venous thrombosis, yet performance and supply limitations exist for the most widely used agent - heparin. Herein we report the first synthesis, characterization, and performance of sulfated poly-amido-saccharides (sulPASs) as heparin mimetics. sulPASs inhibit the intrinsic pathway of coagulation, specifically FXa and FXIa, as revealed by ex vivo human plasma clotting assays and serine protease inhibition assays. sulPASs activity positively correlates with molecular weight and degree of sulfation. Importantly, sulPASs are not degraded by heparanases and are non-hemolytic. In addition, their activity is reversed by protamine sulfate, unlike small molecule anticoagulants. In an in vivo murine model, sulPASs extend clotting time in a dose dependent manner with bleeding risk comparable to heparin. These findings support continued development of synthetic anticoagulants to address the clinical risks and shortages associated with heparin., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Although low sodium intake (<2 g/day) and high potassium intake (>3.5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke., Methods: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes., Results: Compared with an estimated urinary sodium excretion of 2.8-3.5 g/day (reference), higher (>4.26 g/day) (odds ratio [OR] 1.81; 95% confidence interval [CI], 1.65-2.00) and lower (<2.8 g/day) sodium excretion (OR 1.39; 95% CI, 1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4.26 g/day) was significantly greater (P < 0.001) for intracerebral hemorrhage (ICH) (OR 2.38; 95% CI, 1.93-2.92) than for ischemic stroke (OR 1.67; 95% CI, 1.50-1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1.58 g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke., Conclusions: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake-rather than low sodium intake-combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Pulses at 744 nm with 90 fs duration, 6 mJ energy, and a weakly divergent wavefront propagate for more than 100 m and generate a filament followed by an unprecedently long high intensity (≥1 T W / c m 2 ) light channel. Over a 20 m long sub-section of this channel, the pulse energy is transferred continuously to the infrared wing, forming spectral humps that extend up to 850 nm. From 3D+time carrier-resolved simulations of 100 m pulse propagation, we show that spectral humps indicate the formation of a train of femtosecond pulses appearing at a predictable position in the propagation path.

Background: Previous studies reported an association of renal impairment with stroke, but there are uncertainties underpinning this association., Aims: We explored if the association is explained by shared risk factors or is independent and whether there are regional or stroke subtype variations., Methods: INTERSTROKE is a case-control study and the largest international study of risk factors for first acute stroke, completed in 27 countries. We included individuals with available serum creatinine values and calculated estimated glomerular filtration rate (eGFR). Renal impairment was defined as eGFR <60 mL/min/1.73 m2. Multivariable conditional logistic regression was used to determine the association of renal function with stroke., Results: Of 21,127 participants, 41.0% were female, the mean age was 62.3 ± 13.4 years, and the mean eGFR was 79.9 ± 23.5 mL/min/1.73 m2. The prevalence of renal impairment was higher in cases (22.9% vs. 17.7%, p < 0.001) and differed by region (p < 0.001). After adjustment, lower eGFR was associated with increased odds of stroke. Renal impairment was associated with increased odds of all stroke (OR 1.35; 95% CI: 1.24-1.47), with higher odds for intracerebral hemorrhage (OR 1.60; 95% CI: 1.35-1.89) than ischemic stroke (OR 1.29; 95% CI: 1.17-1.42) (pinteraction 0.12). The largest magnitudes of association were seen in younger participants and those living in Africa, South Asia, or South America (pinteraction < 0.001 for all stroke). Renal impairment was also associated with poorer clinical outcome (RRR 2.97; 95% CI: 2.50-3.54 for death within 1 month)., Conclusion: Renal impairment is an important risk factor for stroke, particularly in younger patients, and is associated with more severe stroke and worse outcomes., (© 2021 S. Karger AG, Basel.)

Objective: Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke., Methods: We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension., Results: Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (p-heterogeneity<0.0001). Untreated hypertension was associated with a higher OR for stroke (OR 5.25; 4.53 to 6.10) than treated hypertension (OR 2.60; 2.32 to 2.91) and younger age of first stroke (61.4 vs 65.4 years; p<0.01). Untreated hypertension was associated with a greater risk of intracerebral haemorrhage (OR 6.95; 5.61 to 8.60) than ischaemic stroke (OR 4.76; 3.99 to 5.68). The PAR associated with untreated hypertension was higher in lower-income regions, PAR 36.3%, 26.3%, 19.8% to 10.4% by increasing GNI of countries. Lifetime non-measurement of blood pressure was associated with stroke (OR 1.80; 1.32 to 2.46)., Conclusions: Deficits in knowledge, detection and treatment of hypertension contribute to higher risk of stroke, younger age of onset and larger proportion of intracerebral haemorrhage in lower-income countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Choosing which patients to recommend surgery for benign thyroid conditions can be difficult due to the subjective nature of compressive thyroid and hormonal symptoms. The aim of this prospective study was to analyse changes in quality of life (QOL) following thyroid surgery using a validated disease-specific assessment tool, the thyroid-related patient-reported outcome (ThyPRO) questionnaire., Methods: Participants undergoing elective thyroid surgery for benign conditions were recruited. Patient demographics and clinical data were collected. ThyPRO consists of 85 questions grouped into 13 physical, mental and social symptom domains. Patients completed a ThyPRO questionnaire pre-operatively and at 6 weeks and 6 months post-operatively. ThyPRO items were scored according to protocol to produce 13 subscales. Repeated measures linear models with no random effects were performed using data for each outcome., Results: Results were available for a total of 72 patients. The sample was predominately female (n = 63, 88%) with average age 49.8 years. The majority of patients underwent surgery for multi-nodular goitre. At 6 weeks post-operatively, significant improvement was demonstrated in the goitre, hypothyroid, hyperthyroid and anxiety symptom domains. At 6 months post-operatively, significant improvement was demonstrated in all but four domains. No domains demonstrated significant increase in impairment post-operatively., Conclusion: Patients had significant improvement in nine of 13 symptom domains following surgery. Patients did not experience a negative impact on QOL following surgery. Further studies with larger patient cohorts may be able to identify potential pre-operative predictive factors for a post-operative improvement in QOL for benign thyroid disease., (© 2020 Royal Australasian College of Surgeons.)

Inadequate margins in breast-conserving surgery (BCS) are associated with an increased likelihood of local recurrence of breast cancer. Currently, approximately 20% of BCS patients require repeat surgery due to inadequate margins at the initial operation. Implementation of an accurate, intraoperative margin assessment tool may reduce this re-excision rate. This study determined, for the first time, the diagnostic accuracy of quantitative micro-elastography (QME), an optical coherence tomography (OCT)-based elastography technique that produces images of tissue microscale elasticity, for detecting tumor within 1 mm of the margins of BCS specimens. Simultaneous OCT and QME were performed on the margins of intact, freshly excised specimens from 83 patients undergoing BCS and on dissected specimens from 7 patients undergoing mastectomy. The resulting three-dimensional images (45 × 45 × 1 mm) were coregistered with postoperative histology to determine tissue types present in each scan. Data from 12 BCS patients and the 7 mastectomy patients served to build a set of images for reader training. One hundred and fifty-four subimages (10 × 10 × 1 mm) from the remaining 71 BCS patients were included in a blinded reader study, which resulted in 69.0% sensitivity and 79.0% specificity using OCT images, versus 92.9% sensitivity and 96.4% specificity using elasticity images. The quantitative nature of QME also facilitated development of an automated reader, which resulted in 100.0% sensitivity and 97.7% specificity. These results demonstrate high accuracy of QME for detecting tumor within 1 mm of the margin and the potential for this technique to improve outcomes in BCS. SIGNIFICANCE: An optical imaging technology probes breast tissue elasticity to provide accurate assessment of tumor margin involvement in breast-conserving surgery., (©2020 American Association for Cancer Research.)

Nonuniform azimuthal distribution of N 2 + fluorescence emitted from the femtosecond laser filament in air was discovered. The fluorescence is stronger when the detector is placed perpendicular or parallel to the laser polarization. The experimental results have been confirmed by the theoretical calculation that the azimuthal distribution of fluorescence is reproduced by the convolution of the transition of the dipole and the molecular alignment in the strong laser field. The results would provide new insight into laser-molecule interactions during filamentation, which are important in practice for remote sensing using filamentation.

AgI-type pyrotechnics are widely used in the field of weather modification, as a kind of artificial ice nuclei. However, their precipitation yield remains an intensively studied area. In this paper, we present a study of AgI-type pyrotechnic nucleant-induced water condensation promoted by femtosecond laser filaments in a cloud chamber. It is found that when 50-ml sample was irradiated by the laser filaments, the particles condensed on the glass slide are more soluble and slightly larger (5-15 μm). The irradiation of the laser filament on the nucleant rarely induces the generation of particles of sizes larger than 1 μm; however, it increases the decay time of particles from 13 to 18 min by the creation of numerous small particles. The amount of snow on the cold bottom plate increases by 4.2-13.1% in 2 h, compared to that without the irradiation of the laser filament. These results are associated with the production of high-concentration HNO 3 by the laser filament. The concentration of HNO 3 in the melt water increases by more than ten times when the sample was irradiated by the laser filaments.

Personal lubricants can increase user satisfaction with male condoms by reducing friction and yielding a slippery sensation. However, lubricants pose disadvantages of dilution in physiologic fluids and sloughing away over repeated articulations. To address these drawbacks, a latex surface modification, which becomes lubricious in the presence of physiologic fluid, has been developed and evaluated. This study assesses (i) the frictional performance of the lubricious coating compared to non-coated latex and latex lubricated by personal lubricant, (ii) the level of agreement between human-perceived slipperiness and machine-measured friction, and (iii) human preference for a hypothetical male condom containing the lubricious coating. Friction coefficient of the lubricious coating was 53% lower than that of non-coated latex and approximately equal to that afforded by personal lubricant. A touch test and survey of a small population sample ( N = 33) revealed a strong correlation ( R 2 = 0.83) between human-perceived slipperiness and machine-measured friction. A majority of participants (73%) expressed a preference for a condom containing the lubricious coating, agreeing that an inherently slippery condom that remained slippery for a long duration would increase their condom usage. Such a coating shows potential to be an effective strategy for decreasing friction-associated pain, increasing user satisfaction and increasing condom usage., Competing Interests: A patent application was filed by Boston University on this technology.

We report on a method to experimentally generate ionic wind by coupling an external large electric field with an intense femtosecond laser induced air plasma channel. The measured ionic wind velocity could be as strong as >4 m/s. It could be optimized by increasing the strength of the applied electric field and the volume of the laser induced plasma channel. The experimental observation was qualitatively confirmed by a numerical simulation of spatial distribution of the electric field. The ionic wind can be generated outside a high-voltage geometry, even at remote distances.

Background: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels., Methods: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month., Findings: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics., Interpretation: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes., Funding: Chest, Heart and Stroke Scotland., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We demonstrate the generation of filament array with orthogonal polarizations in air by using specifically designed wedge-type birefringent quartz plates. Experimental results show that the number of the generated filaments can be expressed as N = 2n wherenis the number of quartz plates inserted in the laser propagation path. By manipulating the optic axis of the quartz plates with respect to the polarization direction of the input laser pulse, the generated filaments can be separated into two parts with the polarization directions perpendicular with each other. The separation distance between the adjacent filaments is found to be linearly dependent on the focal length of external focusing lens. Our results provide a simple and efficient way to generate regular and reproductive femtosecond filament array in air.

Currently, 20-30% of patients undergoing breast-conserving surgery require a second surgery due to insufficient surgical margins in the initial procedure. We have developed a wide-field quantitative micro-elastography system for the assessment of tumor margins. In this technique, we map tissue elasticity over a field-of-view of ~46 × 46 mm. We performed wide-field quantitative micro-elastography on thirteen specimens of freshly excised tissue acquired from patients undergoing a mastectomy. We present wide-field optical coherence tomography (OCT) images, qualitative (strain) micro-elastograms and quantitative (elasticity) micro-elastograms, acquired in 10 minutes. We demonstrate that wide-field quantitative micro-elastography can extend the range of tumors visible using OCT-based elastography by providing contrast not present in either OCT or qualitative micro-elastography and, in addition, can reduce imaging artifacts caused by a lack of contact between tissue and the imaging window. Also, we describe how the combined evaluation of OCT, qualitative micro-elastograms and quantitative micro-elastograms can improve the visualization of tumor., Competing Interests: BFK: OncoRes Medical (F,I), LC, AC, KMK, BL and CMS: OncoRes Medical (I). The other authors declare that there are no conflicts of interest related to this article.

Water condensation and precipitation induced by 22-TW 800-nm laser pulses at 1 Hz in an open cloud chamber were investigated in a time-resolved manner. Two parts of precipitation in two independent periods of time were observed directly following each laser shot. One part started around the filament zone at t < 500 μs and ended at t ≅ 1.5 ms after the arrival of the femtosecond laser pulse. The other following the laser-induced energetic air motion (turbulence), started at t ≅ 20 ms and ended at t ≅ 120 ms. Meanwhile, the phase transitions of large-size condensation droplets with diameters of 400-500 μm from liquid to solid (ice) in a cold area (T < -30 °C) were captured at t ≅ 20 ms.

A technique is presented to create uninterrupted long ultraviolet filaments in air using appropriately structured transmission mesh. The mesh with different cell sizes was inserted into 10-cm parallel beam of 0.2-J, 248-nm, and 870-fs pulse propagating along ~100-m corridor. Transverse positions of multiple filaments formed by the optimum size cells were reproducible within at least 15 m along the propagation path. 3D+time simulations confirmed uninterrupted plasma channels with fixed positions in the transverse space similar to the experiment. Unoptimized cell size resulted in filaments shifting towards the cell center and destruction of uninterrupted filaments.

Artificial rainmaking is in strong demand especially in arid regions. Traditional methods of seeding various Cloud Condensation Nuclei (CCN) into the clouds are costly and not environment friendly. Possible solutions based on ionization were proposed more than 100 years ago but there is still a lack of convincing verification or evidence. In this report, we demonstrated for the first time the condensation and precipitation (or snowfall) induced by a corona discharge inside a cloud chamber. Ionic wind was found to have played a more significant role than ions as extra CCN. In comparison with another newly emerging femtosecond laser filamentation ionization method, the snow precipitation induced by the corona discharge has about 4 orders of magnitude higher wall-plug efficiency under similar conditions.

Importance: YARS2 mutations have been associated with a clinical triad of myopathy, lactic acidosis, and sideroblastic anemia in predominantly Middle Eastern populations. However, the identification of new patients expands the clinical and molecular spectrum of mitochondrial disorders., Objectives: To review the clinical, molecular, and genetic features of YARS2-related mitochondrial disease and to demonstrate a new Scottish founder variant., Design, Setting, and Participants: An observational case series study was conducted at a national diagnostic center for mitochondrial disease in Newcastle upon Tyne, England, and review of cases published in the literature. Six adults in a well-defined mitochondrial disease cohort and 11 additional cases described in the literature were identified with YARS2 variants between January 1, 2000, and January 31, 2015., Main Outcome and Measures: The spectrum of clinical features and disease progression in unreported and reported patients with pathogenic YARS2 variants., Results: Seventeen patients (median [interquartile range] age at onset, 1.5 [9.8] years) with YARS2-related mitochondrial myopathy were identified. Fifteen individuals (88%) exhibited an elevated blood lactate level accompanied by generalized myopathy; only 12 patients (71%) manifested with sideroblastic anemia. Hypertrophic cardiomyopathy (9 [53%]) and respiratory insufficiency (8 [47%]) were also prominent clinical features. Central nervous system involvement was rare. Muscle studies showed global cytochrome-c oxidase deficiency in all patients tested and severe, combined respiratory chain complex activity deficiencies. Microsatellite genotyping demonstrated a common founder effect shared between 3 Scottish patients with a p.Leu392Ser variant. Immunoblotting from fibroblasts and myoblasts of an affected Scottish patient showed normal YARS2 protein levels and mild respiratory chain complex defects. Yeast modeling of novel missense YARS2 variants closely correlated with the severity of clinical phenotypes., Conclusions and Relevance: The p.Leu392Ser variant is likely a newly identified founder YARS2 mutation. Testing for pathogenic YARS2 variants should be considered in patients presenting with mitochondrial myopathy, characterized by exercise intolerance and muscle weakness even in the absence of sideroblastic anemia irrespective of ethnicity. Regular surveillance and early treatment for cardiomyopathy and respiratory muscle weakness is advocated because early treatment may mitigate the significant morbidity and mortality associated with this genetic disorder.

We present a novel method based on plasma-guided corona discharges to probe the plasma density longitudinal distribution, which is particularly good for the weakly ionized plasmas (~10 14 cm -3 ). With this method, plasma density longitudinal distribution inside both a weakly ionized plasma and a filament were characterized. When a high voltage electric field was applied onto a plasma channel, the original ionization created by a laser pulse would be enhanced and streamer coronas formed along the channel. By measuring the fluorescence of enhanced ionization, in particular, on both ends of a filament, the weak otherwise invisible plasma regions created by the laser pulse were identified. The observed plasma guided coronas were qualitatively understood by solving a 3D Maxwell equation through finite element analysis. The technique paves a new way to probe low density plasma and to precisely measure the effective length of plasma inside a filament.

Objective: To examine the prevalence of a history of polycystic ovary syndrome (PCOS) in women with type 2 diabetes (DM2) and to compare metabolic and reproductive outcomes between women with and without PCOS., Design: Cross-sectional study., Setting: Tertiary hospital., Patient(s): Female inpatients age 18-75 years with DM2., Intervention(s): A face-to-face questionnaire was administered., Main Outcome Measure(s): Age at diagnosis of diabetes, history of gestational diabetes, family history of diabetes, and reproductive history, fertility history, number of miscarriages, and morbidity in pregnancy., Result(s): One hundred seventy-one inpatients with DM2 participated. The prevalence of a history of PCOS was 37%. Women with PCOS had an earlier mean age of diagnosis of DM2 (44.2 vs. 48.8 years), higher recalled peak body mass index (BMI; 43.1 kg/m 2 vs. 36.8 kg/m 2 ), higher rate of gestational diabetes (28% vs. 18%), and higher rate of hypertension in pregnancy (40% vs. 22%). Women with PCOS were less likely to have a family history of DM2 than those without PCOS (45% vs. 67%)., Conclusion(s): A history of PCOS in women with DM2 is associated with earlier onset of DM2, higher BMI, and a more severe phenotype. Since PCOS subjects were less likely to have a family history of DM2, lack of a family history of DM2 in women with PCOS is not reassuring for DM2 risk. We recommend identifying PCOS in early life and intervening to reduce the risk of diabetes and its comorbidities and suboptimal reproductive outcomes., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

We investigated water condensation in a laboratory cloud chamber induced by picosecond (ps) laser pulses at ~350 ps (800 nm/1-1000 Hz) with a maximum peak power of ~25 MW. The peak power was much lower than the critical power for self-focusing in air (~3-10 GW depending on the pulse duration). Sparks, airflow and snow formation were observed under different laser energies or repetition rates. It was found that weaker ps laser pulses can also induce water condensation by exploding and breaking down ice crystals and/or water droplets into tiny particles although there was no formation of laser filament. These tiny particles would grow until precipitation in a super-saturation zone due to laser-induced airflow in a cold region with a large temperature gradient.

Background: Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke., Methods: We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals., Findings: Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001)., Interpretation: Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke., Funding: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Laser filamentation produced by the propagation of intense laser pulses in flames is opening up new possibility in application to combustion diagnostics that can provide useful information on understanding combustion processes, enhancing combustion efficiency and reducing pollutant products. Here we present simultaneous identification of multiple combustion intermediates by femtosecond filament excitation for five alkanol-air flames fueled by methanol, ethanol, n-propanol, n-butanol, and n-pentanol. We experimentally demonstrate that the intensities of filament-induced photoemission signals from the combustion intermediates C, C2, CH, CN increase with the increasing number of carbons in the fuel molecules, and the signal ratios between the intermediates (CH/C, CH/C2, CN/C, CH/C2, CN/CH) are different for different alkanol combustion flames. Our observation provides a way for sensing multiple combustion components by femtosecond filament excitation in various combustion conditions that strongly depend on the fuel species.

Poly-amido-saccharides (PAS) are carbohydrate-based, enantiopure synthetic polymers in which sugar repeat units are joined by amide linkages. This unique and relatively rigid pyranose backbone contributes to their defined helical secondary structure and remarkable chemical properties. Glucose- (glc-) and galactose- (gal-) PAS 10-mer structures are synthesized and investigated with molecular dynamics (MD) simulations and experimental measurements. Quantum mechanical DFT energy minimization calculations, as well as experimental observables including circular dichroism, (1)H,(13)C-HSQC, and (1)H,(1)H-NOESY 2D-NMR studies, validated the all-atom simulation models produced using a modified CHARMM force field. Water radial distribution functions show distinct differences in the glc- and gal-PAS systems that correlate well with observed differences in solubility between gal-PASs and glc-PASs. The computational analysis and MD simulations are in good agreement with experimental results, validating the proposed models as reliable representations of novel glc- and gal-PASs.

A unified picture of femtosecond laser induced precipitation in a cloud chamber is proposed. Among the three principal consequences of filamentation from the point of view of thermodynamics, namely, generation of chemicals, shock waves and thermal air flow motion (due to convection), the last one turns out to be the principal cause. Much of the filament induced chemicals would stick onto the existing background CCN's (Cloud Condensation Nuclei) through collision making the latter more active. Strong mixing of air having a large temperature gradient would result in supersaturation in which the background CCN's would grow efficiently into water/ice/snow. This conclusion was supported by two independent experiments using pure heating or a fan to imitate the laser-induced thermal effect or the strong air flow motion, respectively. Without the assistance of any shock wave and chemical CCN's arising from laser filament, condensation and precipitation occurred. Meanwhile we believe that latent heat release during condensation /precipitation would enhance the air flow for mixing.

We investigated femtosecond laser-filamentation-induced airflow, water condensation and snow formation in a cloud chamber filled respectively with air, argon and helium. The mass of snow induced by laser filaments was found being the maximum when the chamber was filled with argon, followed by air and being the minimum with helium. We also discussed the mechanisms of water condensation in different gases. The results show that filaments with higher laser absorption efficiency, which result in higher plasma density, are beneficial for triggering intense airflow and thus more water condensation and precipitation.

We report on measurements of both the critical power for self-focusing of a Ti: Sapphire 800 nm femtosecond laser and the peak intensity clamped inside a single filament in an ethanol-air flame on an alcohol burner array. By observing the shift of focal position of femtosecond laser pulses, we determine the critical power in the flame to be 2.2 ± 0.3 GW, which is 4-5 times smaller than the usually quoted one in air. The clamped laser intensity inside the filament is measured to be roughly half of that in air. Our results provide insights into the understanding of femtosecond laser filamentation in flames for practical application of combustion diagnostics.

We have solved the long-standing problem of the mechanism of terahertz (THz) generation by a two-color filament in air and found that both neutrals and plasma contribute to the radiation. We reveal that the contribution from neutrals by four-wave mixing is much weaker and higher in frequency than the distinctive plasma lower-frequency contribution. The former is in the forward direction while the latter is in a cone and reveals an abrupt down-shift to the plasma frequency. Ring-shaped spatial distributions of the THz radiation are shown to be of universal nature and they occur in both collimated and focusing propagation geometries. Experimental measurements of the frequency-angular spectrum generated by 130-fs laser pulses agree with numerical simulations based on a unidirectional pulse propagation model.

Laser based lightning control holds a promising way to solve the problem of the long standing disaster of lightning strikes. But it is a challenging project due to insufficient understanding of the interaction between laser plasma channel and high voltage electric filed. In this work, a direct observation of laser guided corona discharge is reported. Laser filament guided streamer and leader types of corona discharges were observed. An enhanced ionization took place in the leader (filament) through the interaction with the high voltage discharging field. The fluorescence lifetime of laser filament guided corona discharge was measured to be several microseconds, which is 3 orders of magnitude longer than the fluorescence lifetime of laser filaments. This work could be advantageous towards a better understanding of laser assisted leader development in the atmosphere.

The gastrointestinal (GI) transit behavior of and absorption from an amphotericin B (AmB) solid lipid nanoformulation (SLN) in rats was investigated. We aimed to estimate the gastric emptying time (GET) and cecal arrival time (CAT) of AmB SLN in rats as animal models. From these two parameters, an insight on the absorption window of AmB was ascertained. Three types of SLNs, AmB, paracetamol (PAR), and sulfasalazine (SSZ), were similarly formulated using beeswax/theobroma oil composite as the lipid matrix and characterized with regard to size, viscosity, density, migration propensity within agarose gel, in vitro drug release, morphology, gastrointestinal transit, and in vivo absorption. The GET and CAT were estimated indirectly using marker drugs: PAR and sulfapyridine (SP). All three types of SLNs exhibited identical properties with regard to z-average, viscosity, relative density, and propensity to migrate. PAR was absorbed rapidly from the small intestine following emptying of the SLNs giving the T50E (time for 50% absorption of PAR) to be 1.6 h. SP was absorbed after release and microbial degradation of SSZ from SLN in the colon with a lag time of 2 h post-administration, serving as the estimated cecal arrival time of the SLNs. AmB within SLN was favorably absorbed from the small intestine, albeit slowly.

The polarization evolution and control of a femtosecond laser pulse in the wake of molecular alignment inside a laser filament was investigated. A weak probe pulse was delayed with respect to the field-free revivals of the pre-excited rotational wave-packets created by an infrared filamenting pulse in nitrogen gas. 30° was set between the pump and probe's initial linear polarization directions in order to control the output probe's polarization ellipse. The detailed physical response of the probe's polarization states was analyzed in the wake of alignment and dephasing of molecular N(2). The probe's polarization was modulated by varying the retarded time between the pump and probe pulses.

The synthesis of novel carbohydrate-based polymers allows the structure to be tailored at the monomer level for a specific property and expands the range of available structures beyond those found in nature. Using a controlled anionic polymerization, a new type of carbohydrate polymer is synthesized in which glucose-derived monomers are joined by an α-1,2 amide linkage to give enantiopure poly-amido-saccharides (PASs). To investigate the effect of adding ionizable carboxylic acid groups, such as those found in natural polysaccharides containing glucuronic acid, the oxidation of the primary alcohol at the C6-position of the repeat unit to a carboxylic acid is reported. TEMPO-mediated oxidation provides control over the degree of oxidation in excellent yield. Based on circular dichroism, the oxidized polymers possess an ordered helical secondary structure in aqueous solution. Finally, oxidized PASs stabilize lysozyme toward dehydration and freezing stresses better than a current, widely used protein stabilizing agent, trehalose.

1 kHz, 2 mJ, 45 fs, 800 nm laser pulses were fired into a laboratory diffusion cloud chamber through a subsaturated zone (relative humidity ∼73%, T ∼ 4.3 °C). After 60 min of laser irradiation, an oval-shaped snow pile was observed right below the filament center and weighed ∼12.0 mg. The air current velocity at the edge of the vortices was estimated to be ∼16.5 cm/s. Scattering scenes recorded from the side show that filament-induced turbulence were formed inside the cloud chamber with two vortices below the filament. Two-dimensional simulations of the air flow motion in two cross sections of the cloud chamber confirm that the turbulent vortices exist below the filament. Based upon this simulation, we deduce that the vortices indeed have a three-dimensional elliptical shape. Hence, we propose that inside vortices where the humidity was supersaturated or saturated the condensation nuclei, namely, HNO(3), N(2)(+), O(2)(+) and other aerosols and impurities, were activated and grew in size. Large-sized particles would eventually be spun out along the fast moving direction towards the cold plate and formed an oval-shaped snow pile at the end.

The first synthesis of poly-amido-saccharides (PASs) from a galactose(gal)-derived β-lactam sugar monomer is reported. The polymers are prepared using a controlled anionic ring-opening polymerization and characterized by NMR, optical rotation, IR, and GPC. Galactose-derived PASs display high solubility in aqueous solutions and are noncytotoxic to HepG2, CHO, and HeLa cell lines. To evaluate whether gal-derived PASs are recognized by the gal-specific lectin present on human hepatocytes, cellular uptake of rhodamine-labeled polymers is assessed using flow cytometry and fluorescence microscopy. Based on these results, the polymers are taken into cells via endocytosis that is not dependent on the gal-specific receptor on hepatocytes. Neutral, hydrophilic polymers, such as gal-derived PASs, are desirable materials for a range of biomedical applications, such as drug delivery, surface passivation, and hydrogel formation.

We demonstrate that the two basic physical mechanisms of terahertz (THz) generation in a femtosecond filament, namely, the free electron photocurrent and the nonlinear polarization of neutrals, can be identified through the spectral analysis of THz radiation. The contribution from the photocurrent peaks at the units of THz, while the neutrals yield the peak at the tens of THz. We suggest the practical implementation of such spectral analysis by varying the initial transform-limited laser pulse duration.

We numerically simulated the air-flow motion in a diffusion cloud chamber induced by femtosecond laser filaments for different chopping rates. A two dimensional model was employed, where the laser filaments were treated as a heat flux source. The simulated patterns of flow fields and maximum velocity of updraft compare well with the experimental results for the chopping rates of 1, 5, 15 and 150 Hz. A quantitative inconsistency appears between simulated and experimental maximum velocity of updraft for 1 kHz repetition rate although a similar pattern of flow field is obtained, and the possible reasons were analyzed. Based on the present simulated results, the experimental observation of more water condensation/snow at higher chopping rate can be explained. These results indicate that the specific way of laser filament heating plays a significant role in the laser-induced motion of air flow, and at the same time, our previous conclusion of air flow having an important effect on water condensation/snow is confirmed.

Recently, amplification of harmonic-seeded radiation generated through femtosecond laser filamentation in air has been observed, giving rise to coherent emissions at wavelengths corresponding to transitions between different vibrational levels of the electronic B(2)Σ(u)(+) and X(2)Σ(g)(+) states of molecular nitrogen ions [Phys. Rev. A. 84, 051802(R) (2011)]. Here, we carry out systematic investigations on its physical mechanism. Our experimental results do not support the speculation that such excellent coherent emissions could originate from nonlinear optical processes such as four-wave mixing or stimulated Raman scattering, leaving stimulated amplification of harmonic seed due to the population inversion generated in molecular nitrogen ions the most likely mechanism.

We report on the investigation on harmonic-seeded remote laser emissions at 391 nm wavelength from strong-field ionized nitrogen molecules in three different gas mixtures, i.e., N₂-Ar, N₂-Xe and N₂-Ne. We observed a decrease in the remote laser intensity in the N₂-Xe mixture because of the decreased clamped intensity in the filament; whereas in the N₂-Ne mixture, the remote laser intensity slightly increases because of the increased clamped intensity within the filament. Remarkably, although the clamped intensity in the filament remains nearly unchanged in the N₂-Ar mixture because of the similar ionization potentials of N₂ and Ar, a significant enhancement of the lasing emission is realized in the N₂-Ar mixture. The enhancement is attributed to the stronger third harmonic seed, and longer gain medium due to the extended filament.