Attosecond field emission.

Field emission of electrons underlies great advances in science and technology, ranging from signal processing at ever higher frequencies1 to imaging of the atomic-scale structure of matter2 with picometre resolution. The advancing of electron microscopy techniques to enable the complete visualization of matter on the native spatial (picometre) and temporal (attosecond) scales of electron dynamics calls for techniques that can confine and examine the field emission on sub-femtosecond time intervals. Intense laser pulses have paved the way to this end3,4 by demonstrating femtosecond confinement5,6 and sub-optical cycle control7,8 of the optical field emission9 from nanostructured metals. Yet the measurement of attosecond electron pulses has remained elusive. We used intense, sub-cycle light transients to induce optical field emission of electron pulses from tungsten nanotips and a weak replica of the same transient to directly investigate the emission dynamics in real time. Access to the temporal properties of the electron pulses rescattering off the tip surface, including the duration τ = (53 as ± 5 as) and chirp, and the direct exploration of nanoscale near fields open new prospects for research and applications at the interface of attosecond physics and nano-optics.

The role of non-oropharyngeal biopsies in head and neck squamous cell carcinoma of unknown primary: A systematic review.

INTRODUCTION: This systematic review aims to evaluate the role of biopsies in non-oropharyngeal subsites in patients with cervical metastasis from head and neck squamous cell carcinoma of unknown primary (HNSCCUP). METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles that encompassed non-oropharyngeal biopsies in HNSCCUP as part of the diagnostic work-up were selected and analysed. RESULTS: A comprehensive search strategy was used to search relevant literature in PubMed from inception to October 2021. Eleven articles out of 860 were included, comprising 990 patients. There are no randomised control trials comparing the outcomes of survival and or locoregional control between patients who have or have not undergone non-targeted biopsies of non-oropharyngeal sub-sites for HNSCCUP. Several retrospective studies which showed an extremely low yield from random biopsies (range of yield, 0%-9%) of non-oropharyngeal subsites. Even targeted biopsies showed a low yield (range of yield, 0.6%-16.6%) from non-oropharyngeal subsites. The primary site identified for Epstein-Barr virus (EBV) positive cervical lymph nodes with an unknown primary is mainly the nasopharynx (51.7%). Narrow band imaging (NBI) (sensitivity range, 64%-91%) helps in the detection of primaries to target biopsies in non-oropharyngeal subsites. CONCLUSIONS: On the basis of this systematic review, it is not appropriate to offer biopsies of clinically and radiologically normal upper aerodigestive tract mucosa at non-oropharyngeal sites. Offer nasopharyngeal biopsies when the cervical node sampling reveals EBV-positive metastasis. Where available, NBI should be used to help detect and target biopsies in non-oropharyngeal subsites.

Is telemedicine a holy grail in healthcare policy: clinicians' and patients' perspectives from an Apex Institution in Western India.

BACKGROUND: This study aimed to explore the perception of doctors regarding telemedicine consultations and the level of patient satisfaction with the services received through teleconsultations. METHODS: This cross-sectional study was conducted on clinicians who provided teleconsultations and patients who received teleconsultations in an Apex healthcare institution in Western India. Semi-structured interview schedules were used to record the quantitative and qualitative information. Clinicians' perceptions and patients' satisfaction were assessed using two different 5-point Likert scales. Data were analyzed using SPSS v.23 using non-parametric tests (Kruskal Wallis and Mann-Whitney U). RESULTS: A total of 52 clinicians who delivered teleconsultations and 134 patients who received teleconsultations from those doctors were interviewed in this study. For 69% of doctors, telemedicine was feasible to implement, and for the rest, it was challenging. Doctors believe telemedicine is convenient for patients (77%) and prevents the transmission of infection (94.2%). Difficulty in clinical evaluation (73%), communication (55.7%), network connectivity (34%), diagnosis and investigations (32%), and patients' e-illiteracy (32%) were the most common challenges faced by clinicians. Patients' experiences were positive in terms of ease of registration (82.1%), audio quality (100%), freedom to discuss medicine (94.8%), and comprehension of the diagnoses (88.1%). Patients expressed satisfaction with the length of the teleconsultation (81.4%), the advice and care they received (78.4%), and the manner and communication of the clinicians (78.4%). CONCLUSIONS: Though there were some challenges in the implementation of telemedicine, the clinicians perceived it quite helpful. The majority of the patients were satisfied with teleconsultation services. Difficulty in registration, lack of communication, and a deep-rooted mindset of physical consultations were the primary concerns from the patient side.

Unmasking of systemic lupus erythematosus in a patient with hemophagocytic lymphohistiocytosis- macrophage activation syndrome (HLA-MAS) and diffuse alveolar hemorrhage.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by macrophages and cytotoxic T cells with aberrant activation. The primary (genetic) form, which is caused by mutations that affect lymphocyte cytotoxicity and immune regulation, is most prevalent in children, whereas the secondary (acquired) form is prevalent in adults. Secondary HLH is commonly caused by infections or cancers, but it can also be caused by autoimmune disorders, in which case it is known as macrophage activation syndrome (MAS; or MAS-HLH). A 25-year-old female presented with a high-grade fever that lasted for two weeks. His laboratory results revealed pancytopenia, neutropenia, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. Based on the clinical presentation and laboratory findings, a provisional diagnosis of HLH has been made. A HLH protocol was utilized to treat the patient. During the course of hospitalization, systemic lupus erythematosus (SLE) was identified as the underlying cause. She improved dramatically after receiving an immunosuppressive regimen of etoposide, cyclosporine, and dexamethasone according to HLH protocol-2004 with individualized modifications. The clinician should be aware that HLH may be the initial manifestation of underlying SLE. Early diagnosis and aggressive, individualized treatment are the key to improving outcomes.

Heat Equilibration of Integer and Fractional Quantum Hall Edge Modes in Graphene.

Hole-conjugate states of the fractional quantum Hall effect host counterpropagating edge channels which are thought to exchange charge and energy. These exchanges have been the subject of extensive theoretical and experimental works; in particular, it is yet unclear if the presence of integer quantum Hall edge channels stemming from fully filled Landau levels affects heat equilibration along the edge. In this Letter, we present heat transport measurements in quantum Hall states of graphene demonstrating that the integer channels can strongly equilibrate with the fractional ones, leading to markedly different regimes of quantized heat transport that depend on edge electrostatics. Our results allow for a better comprehension of the complex edge physics in the fractional quantum Hall regime.

Epithelial-to-mesenchymal transition based diagnostic and prognostic signature markers in non-muscle invasive and muscle invasive bladder cancer patients.

BACKGROUND: Diagnostic and prognostic significance of epithelial-to-mesenchymal transition (EMT) associated biomarkers are evaluated in a cohort of NMIBC (non-muscle invasive bladder cancer) and MIBC (muscle invasive bladder cancer) patients. METHODS AND RESULTS: Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining were carried out in 100 tumor specimens (59 NMIBC and 41 MIBC). The expressions of the epithelial marker, mesenchymal markers and EMT-activating transcription factors (EMT-ATFs) were determined at transcriptome and protein level followed by their statistical associations with clinicohistopathological variables of the patients. Transcriptomic expression analysis showed statistical relevance of tumor stage with increased Twist and Zeb-1; tumor type with reduced E-cadherin and increased Snail; and smoking/tobacco chewing status (S/TC) of patients with increased N-cadherin and Snail in NMIBC patients. Tumor grade with reduced message E-cadherin, gain of N-cadherin, Snail, Twist and Zeb-1; patients' age with reduced E-cadherin and Twist gain; and tumor type with increased message N-cadherin exhibited associations in MIBC patients. Protein expression analysis identified statistical relevance of tumor grade with nuclear gain of Snail and Twist; and nuclear gain of Slug with S/TC status of NMIBC patients. Novel gain of membranous Vimentin deduced association with patients' age in MIBC patients. Survival analysis identified novel Vimentin as the positive predictor of short progression free survival (PFS) and short overall survival (OS) in MIBC patients. Study established altered EMT profile as the independent negative predictor of short recurrence free survival (RFS) in NMIBC patients and positive predictor of short PFS and OS in MIBC patients. CONCLUSIONS: EMT associated biomarkers could provide diagnostic and prognostic risk stratification and hence could be of importance in the clinical management of bladder cancer patients.

Multi-petahertz electronic metrology.

The frequency of electric currents associated with charge carriers moving in the electronic bands of solids determines the speed limit of electronics and thereby that of information and signal processing. The use of light fields to drive electrons promises access to vastly higher frequencies than conventionally used, as electric currents can be induced and manipulated on timescales faster than that of the quantum dephasing of charge carriers in solids. This forms the basis of terahertz (1012 hertz) electronics in artificial superlattices, and has enabled light-based switches and sampling of currents extending in frequency up to a few hundred terahertz. Here we demonstrate the extension of electronic metrology to the multi-petahertz (1015 hertz) frequency range. We use single-cycle intense optical fields (about one volt per ångström) to drive electron motion in the bulk of silicon dioxide, and then probe its dynamics by using attosecond (10-18 seconds) streaking to map the time structure of emerging isolated attosecond extreme ultraviolet transients and their optical driver. The data establish a firm link between the emission of the extreme ultraviolet radiation and the light-induced intraband, phase-coherent electric currents that extend in frequency up to about eight petahertz, and enable access to the dynamic nonlinear conductivity of silicon dioxide. Direct probing, confinement and control of the waveform of intraband currents inside solids on attosecond timescales establish a method of realizing multi-petahertz coherent electronics. We expect this technique to enable new ways of exploring the interplay between electron dynamics and the structure of condensed matter on the atomic scale.

Optical attosecond pulses and tracking the nonlinear response of bound electrons.

The time it takes a bound electron to respond to the electromagnetic force of light sets a fundamental speed limit on the dynamic control of matter and electromagnetic signal processing. Time-integrated measurements of the nonlinear refractive index of matter indicate that the nonlinear response of bound electrons to optical fields is not instantaneous; however, a complete spectral characterization of the nonlinear susceptibility tensors--which is essential to deduce the temporal response of a medium to arbitrary driving forces using spectral measurements--has not yet been achieved. With the establishment of attosecond chronoscopy, the impulsive response of positive-energy electrons to electromagnetic fields has been explored through ionization of atoms and solids by an extreme-ultraviolet attosecond pulse or by strong near-infrared fields. However, none of the attosecond studies carried out so far have provided direct access to the nonlinear response of bound electrons. Here we demonstrate that intense optical attosecond pulses synthesized in the visible and nearby spectral ranges allow sub-femtosecond control and metrology of bound-electron dynamics. Vacuum ultraviolet spectra emanating from krypton atoms, exposed to intense waveform-controlled optical attosecond pulses, reveal a finite nonlinear response time of bound electrons of up to 115 attoseconds, which is sensitive to and controllable by the super-octave optical field. Our study could enable new spectroscopies of bound electrons in atomic, molecular or lattice potentials of solids, as well as light-based electronics operating on sub-femtosecond timescales and at petahertz rates.

The role of infrared dermal thermometry in the management of neuropathic diabetic foot ulcers.

AIM: This prospective observational study evaluated the role of infrared (IR) dermal thermometry in the management of diabetic foot ulcers. METHODS: Thirty participants with unilateral neuropathic diabetic foot ulcers of University of Texas grade 1 or 2 (stage A) were followed up monthly for 1 year. At each visit, skin temperatures were measured with an IR dermal thermometer at corresponding sites on both feet, using the contralateral feet without ulcers as controls. RESULTS: Average temperature and ulcer temperature in affected feet were significantly higher than in unaffected feet, with a mean difference of 1.2 °C [95% confidence interval (CI) 0.7 to 1.7] and 3.1 °C (95% CI 2.3 to 3.9), respectively. Although the gradient between average temperature of affected foot and that of unaffected foot normalized (mean difference 0.2 °C, 95% CI -0.2 to 0.7) at healing, the temperature gradient between the ulcer and a corresponding site on the unaffected foot decreased but did not normalize (mean difference 2.1 °C, 95% CI 1.2 to 3.1) even at healing, as documented by skin closure, and persisted for up to 1 month after skin closure. A gradient of ≥1 °C between average temperature of affected foot and that of unaffected foot at initial presentation or at any time during ulcer healing was found to predict impaired healing and should alert clinicians to ulcers requiring more attention. An incremental trend in temperature gradient (median difference 2.2 °C; range 0.1-6.3 °C) at a site on the foot was predictive of a recurrent ulcer involving the same site. CONCLUSIONS: IR dermal thermometry may have a role in predicting diabetic foot ulcer healing, in determining the completeness of healing and in guiding the duration of offloading. Serial monitoring of the temperature gradient may predict the development of recurrent diabetic foot ulcers.

Extreme ultraviolet high-harmonic spectroscopy of solids.

Extreme ultraviolet (EUV) high-harmonic radiation emerging from laser-driven atoms, molecules or plasmas underlies powerful attosecond spectroscopy techniques and provides insight into fundamental structural and dynamic properties of matter. The advancement of these spectroscopy techniques to study strong-field electron dynamics in condensed matter calls for the generation and manipulation of EUV radiation in bulk solids, but this capability has remained beyond the reach of optical sciences. Recent experiments and theoretical predictions paved the way to strong-field physics in solids by demonstrating the generation and optical control of deep ultraviolet radiation in bulk semiconductors, driven by femtosecond mid-infrared fields or the coherent up-conversion of terahertz fields to multi-octave spectra in the mid-infrared and optical frequencies. Here we demonstrate that thin films of SiO2 exposed to intense, few-cycle to sub-cycle pulses give rise to wideband coherent EUV radiation extending in energy to about 40 electronvolts. Our study indicates the association of the emitted EUV radiation with intraband currents of multi-petahertz frequency, induced in the lowest conduction band of SiO2. To demonstrate the applicability of high-harmonic spectroscopy to solids, we exploit the EUV spectra to gain access to fine details of the energy dispersion profile of the conduction band that are as yet inaccessible by photoemission spectroscopy in wide-bandgap dielectrics. In addition, we use the EUV spectra to trace the attosecond control of the intraband electron motion induced by synthesized optical transients. Our work advances lightwave electronics in condensed matter into the realm of multi-petahertz frequencies and their attosecond control, and marks the advent of solid-state EUV photonics.

Sequelae of COVID-19 pneumonia: Is it correct to label everything as post-COVID lung fibrosis?

One of the common long-term consequences observed in survivors of COVID-19 pneumonia is the persistence of respiratory symptoms and/or radiological lung abnormalities. The exact prevalence of these post-COVID pulmonary changes is yet unclear. Few authors, based on their early observations, have labeled these persistent computed tomography (CT) abnormalities as post-COVID lung fibrosis, which appears to be an overstatement. Lately, it is being observed that many of the changes seen in post-COVID lungs are temporary and tend to show resolution on follow-up, with only a few developing into lung fibrosis. Thus, based on the presumptive diagnosis of lung fibrosis, these patients should not be blindly started on anti-fibrotic drugs. One must not forget that these drugs can do more harm than good, if used injudiciously. It is better to use the term "post-COVID interstitial lung changes", which covers a broader spectrum of pulmonary changes seen in patients who have recovered from COVID-19 pneumonia. At the same time, it is essential to identify the sub-set of COVID-19 survivors who are at an increased risk of developing lung fibrosis and to carefully chalk out management strategies so as to modify the course of the disease and prevent irreversible damage. Meticulous and systematic longitudinal follow-up studies consisting of clinical, laboratory, imaging, and pulmonary function tests are needed for the exact estimation of the burden of lung fibrosis, to understand the nature of residual pulmonary changes, and to predict the likelihood of development of lung fibrosis in COVID-19 survivors.

Vitamin D, body mass composition and metabolic risk factors in healthy young Indians.

BACKGROUND: Studies have linked vitamin D to risk factors for cardiovascular disease. Obesity is a potential confounder in these studies. This study examined the relationship of 25 (OH) cholecalciferol (25[OH] D3) with insulin resistance, blood glucose, and lipid profile in lean male adults. METHOD: We enrolled two hundred and thirty four military recruits before beginning of military training. Demographic and anthropometric data were collected from them. The participants underwent body mass composition analysis by dual energy X ray absorptiometry. Fasting samples were collected for measurement of blood glucose, lipid profile, 25(OH) D3, serum parathormone (PTH) and insulin. RESULTS: Vitamin D deficiency and insufficiency was found in 47.7% (107/224) and 31.6% (71/224) of participants, respectively. Using Pearson's correlation coefficient 25(OH) cholecalciferol and fasting blood glucose (FBG) were inversely correlated (p = 0.023). However, similar relation was not found between 25(OH) D3 and total cholesterol, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, homeostatic model assessment of insulin resistance and levels of PTH. On body composition analysis, there was no correlation of 25(OH) cholecalciferol with body mass index or fat mass index. CONCLUSION: This study showed that in lean young male population, 25(OH) cholecalciferol and FBG are inversely correlated but no association of 25(OH) D3 with other cardiometabolic risk factors could be demonstrated.

The effect of vitamin D supplementation on cardiorespiratory fitness and muscle strength in male adults undergoing basic military training.

BACKGROUND: Vitamin D deficiency (VDD) is ubiquitous in the Indian subcontinent. VDD has been shown to impair muscle functions. However, the association of VDD with cardiorespiratory endurance is uncertain. Hence, we enrolled and supplemented vitamin D in military recruits with VDD with an aim to evaluate effect of supplementation on cardiorespiratory endurance and muscle strength. METHOD: We enrolled 90 military recruits with VDD and randomly allotted them to two groups equally. The group I received cholecalciferol granules 60,000 IU every fortnight for twelve weeks (cases), and the group II was observed as control. Muscle strength and cardiorespiratory endurance was assessed with a battery of tests (standing broad jump, bent arm hang test, 20 m shuttle run) at baseline and repeated at the end of training (nineteen weeks). Blood samples were collected for measurement of serum 25(OH)D and parathyroid hormone. RESULTS: In Group I and Group II, there was significant increase in 25(OH) D levels (25.8 ± 7.1 and 17.3 ± 3.5 ng/ml, respectively), and in VO2 max (9.8 ± 8.8 and 12.7 ± 8.6 ml/kg/min, respectively) compared with the baseline values. However, no significant change was observed in muscle strength after supplementation. There was no difference between the groups in VO2 max and muscle strength at baseline and at the end of training. CONCLUSION: Vitamin D supplementation did not improve muscle strength and cardiorespiratory endurance in military recruits with VDD. A significant rise in 25(OH) D was observed even in those not supplemented with vitamin D.

Training and accrediting international surgeons.

BACKGROUND: Formal international medical programmes (IMPs) represent an evolution away from traditional medical volunteerism, and are based on the foundation of bidirectional exchange of knowledge, experience and organizational expertise. The intent is to develop multidirectional collaborations and local capacity that is resilient in the face of limited resources. Training and accreditation of surgeons continues to be a challenge to IMPs, including the need for mutual recognition of competencies and professional certification. METHODS: MEDLINE, Embase and Google Scholar™ were searched using the following terms, alone and in combination: 'credentialing', 'education', 'global surgery', 'international medicine', 'international surgery' and 'training'. Secondary references cited by original sources were also included. The authors, all members of the American College of Academic International Medicine group, agreed advice on training and accreditation of international surgeons. RESULTS AND CONCLUSION: The following are key elements of training and accrediting international surgeons: basic framework built upon a bidirectional approach; consideration of both high-income and low- and middle-income country perspectives; sourcing funding from current sources based on existing IMPs and networks of IMPs; emphasis on predetermined cultural competencies and a common set of core surgical skills; a decentralized global system for verification and mutual recognition of medical training and certification. The global medical system of the future will require the assurance of high standards for surgical education, training and accreditation.

Elevated plasma ferritin in elderly individuals with high neocortical amyloid-ß load.

Ferritin, an iron storage and regulation protein, has been associated with Alzheimer's disease (AD); however, it has not been investigated in preclinical AD, detected by neocortical amyloid-ß load (NAL), before cognitive impairment. Cross-sectional analyses were carried out for plasma and serum ferritin in participants in the Kerr Anglican Retirement Village Initiative in Aging Health cohort. Subjects were aged 65-90 years and were categorized into high and low NAL groups via positron emission tomography using a standard uptake value ratio cutoff=1.35. Ferritin was significantly elevated in participants with high NAL compared with those with low NAL, adjusted for covariates age, sex, apolipoprotein E ɛ4 carriage and levels of C-reactive protein (an inflammation marker). Ferritin was also observed to correlate positively with NAL. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished high from low NAL (area under the curve (AUC)=0.766), but was outperformed when plasma ferritin was added to the base model (AUC=0.810), such that at 75% sensitivity, the specificity increased from 62 to 71% on adding ferritin to the base model, indicating that ferritin is a statistically significant additional predictor of NAL over and above the base model. However, ferritin's contribution alone is relatively minor compared with the base model. The current findings suggest that impaired iron mobilization is an early event in AD pathogenesis. Observations from the present study highlight ferritin's potential to contribute to a blood biomarker panel for preclinical AD.

A systematic understanding of signaling by ErbB2 in cancer using phosphoproteomics.

ErbB2 is an important receptor tyrosine kinase and a member of the ErbB family. Although it does not have a specific ligand, it transmits signals downstream by heterodimerization with other receptors in the family. It plays a major role in a variety of cellular responses like proliferation, differentiation, and adhesion. ErbB2 is amplified at the DNA level in breast cancer (20%-30%) and gastric cancer (10%-20%), and trastuzumab is effective as a therapeutic antibody. This review is a critical analysis of the currently published data on the signaling pathways of ErbB2 and the interacting proteins. It also focuses on the techniques that are currently available to evaluate the entire phosphoproteome following activation of ErbB2. Identification of new and relevant phosphoproteins can not only serve as new therapeutic targets but also as a surrogate marker in patients to assess the activity of compounds that inhibit ErbB2. Overall, such analysis will improve understanding of signaling by ErbB2.

Direct evidence of barrier inhomogeneities at metal/AlGaN/GaN interfaces using nanoscopic electrical characterizations.

The existence of barrier inhomogeneities at metal-semiconductor interfaces is believed to be one of the reasons for the non-ideal behaviour of Schottky contacts. In general, barrier inhomogeneities are modelled using a Gaussian distribution of barrier heights of nanoscale patches having low and high barrier heights, and the standard deviation of this distribution roughly estimates the level of barrier inhomogeneities. In the present work, we provide direct experimental evidence of barrier inhomogeneities by performing electrical characterizations on individual nanoscale patches and, further, obtaining the magnitude of these inhomogeneities. Localized current-voltage measurements on individual nanoscale patches were performed using conducting atomic force microscopy (CAFM) whereas surface potential variations on nanoscale dimensions were investigated using Kelvin probe force microscopy (KPFM) measurements. The CAFM measurements revealed the distribution of barrier heights, which is attributed to surface potential variations at nanoscale dimensions, as obtained from KPFM measurements. The present work is an effort to provide direct evidence of barrier inhomogeneities, finding their origin and magnitude by combining CAFM and KPFM techniques and correlating their findings.

Protective role of Aloe vera against X-ray induced testicular dysfunction.

The present investigation was carried out to evaluate the possible radioprotective potential of an Aloe vera extract against whole-body X-ray irradiation-induced testicular alterations in mice. Male balb/c mice were divided into four groups: control, A. vera, X-ray and A. vera pre-treated + X-ray irradiated. Histopathological examination revealed significant structural alterations in testes after X-ray exposure, which was also associated with the presence of apoptotic cells as assessed by TUNEL assay. X-ray irradiation resulted in elevation in the levels of reactive oxygen species, lipid peroxidation, a reduction in glutathione concentration and enhanced activities of antioxidant enzymes such as glutathione reductase, glutathione peroxidase, catalase, superoxide dismutase and glutathione-S-transferase. Sperm count/motility and testosterone levels were significantly decreased in the irradiated group. Irradiated animals pre-treated with A. vera extract revealed an improvement in antioxidant status, inhibition of lipid peroxides, apoptotic cell formation and enhanced testicular parameters when compared to the X-ray-exposed group. These findings suggest that A. vera extract could ameliorate X-ray-induced damage due to its free radical scavenging properties and its potential to boost cellular antioxidant defence machinery.

Sex hormones and systemic inflammation are modulators of the obese-asthma phenotype.

BACKGROUND: Both systemic inflammation and sex hormones have been proposed as potential mediators of the obese-asthma phenotype. The aim of this study was to examine the associations between sex hormones, oral contraceptive pill (OCP) use, systemic inflammation and airway inflammation in adults with asthma. METHODS: Obese (n = 39) and nonobese (n = 42) females and obese (n = 24) and nonobese (n = 25) males with asthma were recruited. Females were further categorized as reproductive-aged (<50 years old; n = 36) or older (>50 years old; n = 45). Thirteen (36.1%) reproductive-aged females were using the OCP. Participants had induced sputum cell counts measured and blood analysed for sex hormones and inflammatory markers. RESULTS: Obese reproductive-aged females had higher sputum %neutrophils than nonobese reproductive-aged females (45.4 ± 24.3% vs 27.5 ± 17.5%, P = 0.016); however, there was no difference in sputum neutrophils in obese compared with nonobese males (P = 0.620) or older females (P = 0.087). Multiple linear regression analysis found testosterone and OCP use to be negative predictors of sputum %neutrophils, while C-reactive protein and IL-6 were positive predictors of sputum %neutrophils. BMI and age were not significant predictors in the multivariate model. Reproductive-aged females using the OCP had significantly lower sputum %neutrophils than those not using the OCP (23.2 ± 12.6% vs 42.1 ± 23.8%, P = 0.015). CONCLUSIONS: This study suggests that sex hormones and systemic inflammation may be mediating the obese-asthma phenotype. The observation that OCP use was associated with lower sputum %neutrophils in reproductive-aged females warrants further investigation.

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.