Hosing of a Long Relativistic Particle Bunch in Plasma.

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing.

Acceleration of electrons in the plasma wakefield of a proton bunch.

High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration1-5, in which the electrons in a plasma are excited, leading to strong electric fields (so called 'wakefields'), is one such promising acceleration technique. Experiments have shown that an intense laser pulse6-9 or electron bunch10,11 traversing a plasma can drive electric fields of tens of gigavolts per metre and above-well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies5,12. The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage13. Long, thin proton bunches can be used because they undergo a process called self-modulation14-16, a particle-plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN17-19 uses high-intensity proton bunches-in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules-to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage20 means that our results are an important step towards the development of future high-energy particle accelerators21,22.

Utility of cranial MRI in non-traumatic headache patients with prior negative head CT within 1 month.

AIM: To investigate the importance of additional cranial magnetic resonance imaging (cMRI) in non-traumatic headache patients with a prior negative head computed tomography (CT) examination within 1 month. MATERIALS AND METHODS: This retrospective study analysed 162 adult patients with non-traumatic headache who underwent cMRI within 1 month of a negative initial head CT at the emergency department (ED). The diagnostic yield and false-referral rate were analysed according to the revisit duration (early [≤1 week] versus late [>1-4 weeks] revisits), patient care settings (ED versus outpatient clinics [OPC]), and clinical variables. Subsequent patient management change (PMC), such as admission and treatment (AT) or outpatient clinic treatment (OT), were also investigated. RESULTS: The overall diagnostic yield of cMRI was 17.3% (28/162) and the false-referral rate was 1.2% (2/162). The diagnostic yield of cMRI was significantly different according to the patient care settings (ED, 24.7% [21/85] versus OPC, 9.1% [7/77]; p=0.02). The diagnostic yield was highest in the ED-early-revisit group (25.4% [18/71]), 45% (9/20) in those with systemic signs, and 46.7% (14/30) in those with symptom change. Among patients with positive cMRI findings, 90% (27/30) received AT and 3.3% (1/30) received OT. Among OPC-revisit-negative cMRI patients, PMC occurred in 0% (0/50). CONCLUSION: The diagnostic yield of cMRI was relatively high for headache patients who revisited the ED earlier, especially in those with systemic signs or symptom change. Most positive cMRI cases experienced PMC. Negative cMRI in OPC-revisit patients might help clarify the benign nature of a condition.

Widening disparities in the national prevalence of diabetes mellitus for people with disabilities in South Korea.

OBJECTIVES: In Korea, diabetes mellitus has a high disease burden, based on disability-adjusted life years. However, the disease burden is disproportionately distributed, with people with disabilities (PWD) experiencing higher rates of health disparities. Our study investigated long-term trends in diabetes prevalence and risk according to disability status, grade, and type. STUDY DESIGN: Retrospective cohort study. METHODS: Approximately 10 million individuals aged ≥30 years were included yearly from the National Health Information Database (NHID) and national disability registration data in Korea between 2008 and 2017, corresponding to 40 % of those aged ≥30 years in Korea. In 2017, 12, 975, 757 individuals were included; 5.5 % had disabilities. We estimated annual diabetes age-standardized prevalence and used multiple logistic regression analyses to estimate the odds of having diabetes in 2017, according to disability status, severity, and type. RESULTS: Diabetes age-standardized prevalence consistently increased over 2008-2017 in PWD and people without disabilities. However, the prevalence increased more rapidly and was higher in all years among PWD, with widening disparities based on disability status. Additionally, diabetes prevalence was high in all years for specific subgroups, including women, individuals with intellectual or mental disabilities or autism, and individuals with severe disabilities, suggesting further disparities among PWD. CONCLUSIONS: Our findings reveal health disparities between those with and without disabilities and among PWD subgroups. In addition to timely prevention, diabetes screening and management among PWD is vital. Public investment in improving disparities in the root causes of diabetes is essential, including health behaviours, healthcare utilization, and self-care.

Respiratory microbiome profiles are associated with distinct inflammatory phenotype and lung function in children with asthma.

BACKGROUND: Respiratory microbiome studies have fostered our understanding of various phenotypes and endotypes of heterogeneous asthma. However, the relationship between the respiratory microbiome and clinical phenotypes in children with asthma remains unclear. We aimed to identify microbiome-driven clusters reflecting the clinical features of asthma and their dominant microbiotas in children with asthma. METHODS: Induced sputum was collected from children with asthma, and microbiome profiles were generated via sequencing of the V3-V4 region of the 16S rRNA gene. Cluster analysis was performed using the partitioning around medoid clustering method. The dominant microbiota in each cluster was determined using the Linear Discriminant Effect Size analysis. Each cluster was analyzed for association among the dominant microbiota, clinical phenotype, and inflammatory cytokine. RESULTS: Eighty-three children diagnosed with asthma were evaluated. Among four clusters reflecting the clinical characteristics of asthma, cluster 1, dominated by Haemophilus and Neisseria, demonstrated lower post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) than that in the other clusters and more mixed granulocytic asthma. Neisseria negatively correlated with pre-BD and post-BD FEV1/FVC. Haemophilus and Neisseria positively correlated with programmed death-ligand (PD-L)1. CONCLUSION: To our knowledge, this study is the first to analyze the relationship between an unbiased microbiome-driven cluster and clinical phenotype in children with asthma. The cluster dominated by Haemophilus and Neisseria showed fixed airflow obstruction and mixed granulocytic asthma, which correlated with PD-L1 levels. Thus, microbiome-driven unbiased clustering can help identify new asthma phenotypes related to endotypes in childhood asthma.

Nationwide prevalence and trends in cigarette smoking among adult men with and without disabilities in South Korea between 2009 and 2017.

OBJECTIVES: Current smoking rates for people with and without disabilities vary among countries. This study analyzed smoking behavior over 9 years in adult South Korean men with disabilities, according to disability severity and type, and in those without disabilities. STUDY DESIGN: This was a cross-sectional study. METHODS: This analysis was conducted using national disability registration data and national general health checkup data for 2009-2017. Age-standardized smoking behaviors were analyzed for each year according to the presence, severity, and type of disability. The odds of current smoking were determined by multivariate logistic regression after adjusting for sociodemographic and clinical variables. RESULTS: The age-standardized smoking rate and average number of cigarettes for men with mild disabilities in the younger age group were 1.16 (43.0 vs 36.8%) and 1.05 (16.1 vs 15.3 cigarettes) times higher than in non-disabled men as of 2017. The highest smoking rate was observed in men with physical disabilities in the younger age. In the older age group, the highest smoking rate was that of men with intellectual or psychological disabilities. CONCLUSION: Smoking behaviors remained poorest in men with disabilities, especially those with mild, physical, and intellectual/psychological disabilities. Public health policies should focus on people with disabilities to promote health, prevent secondary conditions, and reduce health disparities by implementing antismoking health policies.

Facemask ventilation and vocal cord angle following neuromuscular blockade: a prospective observational study.

Numerous studies support the idea that neuromuscular blockade facilitates facemask ventilation after induction of anaesthesia. Although improved airway patency or pulmonary compliance and a resolution of laryngospasm have been suggested as possible causes, the exact mechanism remains unclear. We aimed to assess whether neuromuscular blockade improves facemask ventilation and to clarify whether this phenomenon is associated with the vocal cord angle. This prospective observational study included patients aged between 20 and 65 years scheduled for elective surgery under general anaesthesia. After induction of anaesthesia, patients' lungs were ventilated with pressure-controlled ventilation using a facemask. During facemask ventilation, a flexible bronchoscope was inserted through a self-sealing diaphragm at the elbow connector attached to the facemask and breathing circuit and positioned to allow a continuous view of the vocal cords. The mean tidal volume and vocal cord angle were measured before and after administration of neuromuscular blocking drugs. Of 108 patients, 100 completed the study. Mean (SD) tidal volume ((11.0 (3.9) ml.kg-1 vs. 13.6 (2.6) ml.kg-1 ; p < 0.001) and mean (SD) vocal cord angle (17° (10°) vs. 26° (5°); p < 0.001) increased significantly after neuromuscular blockade. The proportional increase in mean tidal volume after neuromuscular blockade was positively correlated with vocal cord angle (Spearman's ρ = 0.803; p < 0.001). In conclusion, neuromuscular blockade facilitated facemask ventilation, and the improvement was correlated with further opening of the vocal cords.

Altered distributions in circulating follicular helper and follicular regulatory T cells accountable for imbalanced cytokine production in multiple sclerosis.

Follicular T helper (Tfh) and regulatory (Tfr) cells are distinct subsets of CD4+ T lymphocytes, regulating humoral immune responses in the germinal center. It is widely accepted that dysregulated Tfh and Tfr cells are associated with autoimmunity. In this study, we evaluated the frequencies of circulating chemokine receptor (CXCR)5+ programmed cell death 1 (PD-1+ ) Tfh (cTfh) and CXCR5+ PD-1+ forkhead box protein 3 (FoxP3+ ) CD25+ Tfr (cTfr) cells, and their corresponding cytokines from the peripheral blood mononuclear cells of 28 patients with relapsing-remitting multiple sclerosis (MS) and 16 age- and sex-matched healthy controls (HC). Subsets of cTfh cells by Th1- and Th17-related surface markers (CXCR3 and CCR6) were also evaluated. We found that the frequency of cTfh cells was significantly higher in MS patients compared to that of HC. Conversely, the frequency of cTfr cells was lower in MS patients than that of HC. Interleukin (IL)-21-producing cTfh cells were significantly increased in MS patients, while IL-10-secreting cTfr cells were lower in MS patients compared to levels in HC. Among cTfh cells, cTfh17.1 cells were the major subtypes that were significantly increased in MS patients compared to HC, with the frequency of IL-21-secreting cells being the highest. These results suggest that an imbalanced distribution of cTfh and cTfr exist in MS patients, which contributes to the reciprocally altered IL-21 and IL-10 production.

Transition between Instability and Seeded Self-Modulation of a Relativistic Particle Bunch in Plasma.

We use a relativistic ionization front to provide various initial transverse wakefield amplitudes for the self-modulation of a long proton bunch in plasma. We show experimentally that, with sufficient initial amplitude [≥(4.1±0.4) MV/m], the phase of the modulation along the bunch is reproducible from event to event, with 3%-7% (of 2π) rms variations all along the bunch. The phase is not reproducible for lower initial amplitudes. We observe the transition between these two regimes. Phase reproducibility is essential for deterministic external injection of particles to be accelerated.

Diagnostic accuracy of the jetting sign and a dilatation ratio of left renal vein in CT urography for detecting anterior nutcracker syndrome.

AIM: To investigate the diagnostic value of computed tomography (CT) urography findings of anterior nutcracker syndrome (NCS). MATERIALS AND METHODS: The study included patients with left renal vein (LRV) compression at the aortomesenteric portion at CT urography who underwent renal venography or cystoscopy. Patients with a renocaval pressure gradient of ≥3 mmHg on renal venography or bloody urine jetting from the left ureteral orifice on cystoscopy were defined as the NCS group; the remaining patients comprised the non-NCS group. CT findings were analysed using the jetting of contrast medium flow from the LRV to the inferior vena cava (jetting sign), aortomesenteric distance, presence of collateral veins, and a dilatation ratio of LRV diameter at the aortomesenteric portion (arterial phase/delayed phases). Clinical findings, including age, gender, and body-mass-index, were also analysed. CT features and clinical findings were compared between the NCS and non-NCS groups. Diagnostic performance of CT parameters was assessed using receiver operating characteristic curve analysis. RESULTS: A total of 70 patients (21 men, mean age 44.4 ± 17.2 years) with NCS (n=13) and non-NCS (n=57) were included. Younger age (<40 years), presence of the jetting sign, and a lower dilatation ratio of LRV diameter between the arterial and delayed phases (<1.7) were found to be significant independent factors for predicting the NCS group (OR 24.5, 18.9, 19.4, respectively, p<0.05 for all). The combination of the presence of the jetting sign and a dilatation ratio of LRV diameter of <1.7 obtained the highest AUC of 0.88. CONCLUSION: The jetting sign and the dilatation ratio of LRV diameter between the arterial and delayed phases can both be very useful in the diagnosis of anterior nutcracker syndrome during CT urography.

Association between benign paroxysmal positional vertigo and osteoporosis: two nested case-control studies.

Benign paroxysmal positional vertigo (BPPV) was related to a 1.28 times higher risk of osteoporosis. In addition, osteoporosis was associated with a 1.34 times higher risk of BPPV. This bidirectional relation was maintained after adjusting past medical histories and lifestyle factors, including obesity, smoking, and alcohol consumption. To our knowledge, this is the first study to explore the reciprocal association between BPPV and osteoporosis. In subgroup analyses, only women showed a reciprocal association between BPPV and osteoporosis. INTRODUCTION: A previous population cohort study suggested an association between osteoporosis and benign paroxysmal positional vertigo (BPPV). This study aimed to investigate the bidirectional association between BPPV and osteoporosis. METHODS: The Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2013 were used. In study I, the 50,897 osteoporosis patients were 1:1 matched with control I participants for age, sex, income, and region of residence. The previous histories of BPPV were analyzed in both groups using conditional logistic regression analysis. In study II, 9621 BPPV patients were 1:4 matched with control II participants. The previous histories of osteoporosis were analyzed in both groups using conditional logistic regression analysis. According to age and sex, subgroup analyses were achieved in both studies I and II. RESULTS: A total of 1.6% (822/50,897) of osteoporosis patients and 1.3% (644/50,897) of control I participants had BPPV. The osteoporosis patients demonstrated a 1.28 times higher chance of developing BPPV (95% confidence intervals [95% CI] = 1.16-1.42, P < 0.001). In study II, 21.2% (2040/9621) of BPPV patients and 17.6% (6790/38,484) of control II participants had osteoporosis. The BPPV patients showed 1.34 times higher chance of having osteoporosis (95% CI = 1.26-1.43, P < 0.001). In the analysis of the women subgroup, these relations were reliable. CONCLUSION: Osteoporosis patients had increased odds of having BPPV. On the other hand, BPPV patients had increased odds of having osteoporosis. This bidirectional relation was consistent only in the women subgroup.

Search for Sub-eV Sterile Neutrinos at RENO.

We report a search result for a light sterile neutrino oscillation with roughly 2200 live days of data in the RENO experiment. The search is performed by electron antineutrino (ν[over ¯]_{e}) disappearance taking place between six 2.8 GW_{th} reactors and two identical detectors located at 294 m (near) and 1383 m (far) from the center of the reactor array. A spectral comparison between near and far detectors can explore reactor ν[over ¯]_{e} oscillations to a light sterile neutrino. An observed spectral difference is found to be consistent with that of the three-flavor oscillation model. This yields limits on sin^{2}2θ_{14} in the 10^{-4}≲|Δm_{41}^{2}|≲0.5 eV^{2} region, free from reactor ν[over ¯]_{e} flux and spectrum uncertainties. The RENO result provides the most stringent limits on sterile neutrino mixing at |Δm_{41}^{2}|≲0.002 eV^{2} using the ν[over ¯]_{e} disappearance channel.

Dermatologist-level classification of malignant lip diseases using a deep convolutional neural network.

BACKGROUND: Deep convolutional neural networks (DCNNs) can classify skin diseases at a level equivalent to a dermatologist, but their performance in specific areas requires further research. OBJECTIVE: To evaluate the performance of a trained DCNN-based algorithm in classifying benign and malignant lip diseases. METHODS: A training set of 1629 images (743 malignant, 886 benign) was used with Inception-Resnet-V2. Performance was evaluated using another set of 344 images and 281 images from other hospitals. Classifications by 44 participants (six board-certified dermatologists, 12 dermatology residents, nine medical doctors not specialized in dermatology and 17 medical students) were used for comparison. RESULTS: The outcomes based on the area under curve, sensitivity and specificity were 0·827 [95% confidence interval (CI) 0·782-0·873], 0·755 (95% CI 0·673-0·827) and 0·803 (95% CI 0·752-0·855), respectively, for the set of 344 images; and 0·774 (95% CI 0·699-0·849), 0·702 (95% CI 0·579-0·808) and 0·759 (95% CI 0·701-0·813), respectively, for the set of 281 images. The DCNN was equivalent to the dermatologists and superior to the nondermatologists in classifying malignancy. After referencing the DCNN result, the mean ± SD Youden index increased significantly for nondermatologists, from 0·201 ± 0·156 to 0·322 ± 0·141 (P < 0·001). CONCLUSIONS: DCNNs can classify lip diseases at a level similar to dermatologists. This will help unskilled physicians discriminate between benign and malignant lip diseases. What's already known about this topic? Deep convolutional neural networks (DCNNs) can classify malignant and benign skin diseases at a level equivalent to dermatologists. The lips are a unique feature in terms of histology and morphology. Previous studies of DCNNs have not investigated tumours on specific locations. What does this study add? This study shows that DCNNs can distinguish rare malignant and benign lip disorders at the same rate as dermatologists. DCNNs can help nondermatologists to distinguish malignant lip diseases. What are the clinical implications of this work? DCNNs can distinguish malignant and benign skin diseases even at specific locations such as the lips, as well as board-certified dermatologists. Malignant lip diseases are rare and difficult for less trained doctors to differentiate them from benign lesions. This study shows that in dermatology, DCNN can help improve decision-making processes for rare skin diseases in specific areas of the body.

Female reproductive factors and the risk of dementia: a nationwide cohort study.

BACKGROUND AND PURPOSE: The aim was to investigate whether female reproductive factors are associated with dementia. METHODS: In all, 4 696 633 post-menopausal women without dementia were identified using the Korean National Health Insurance System database. Data on reproductive factors were collected using a self-administered questionnaire. Dementia was determined using dementia diagnosis codes and anti-dementia drug prescription. Cox proportional hazards regression was conducted to assess the hazard ratio (HR) for dementia according to reproductive factors. RESULTS: During a median follow-up of 5.74 years, there were 212 227 new cases of all-cause dementia (4.5%), 162 901 cases of Alzheimer's disease (3.5%) and 24 029 cases of vascular dementia (0.5%). The HR of dementia was 1.15 [95% confidence interval (CI) 1.03-1.16] for menarcheal age ≥17 years compared with menarcheal age 13-14 years, 0.79 (0.77-0.81) for menopausal age ≥55 years compared with menopausal age <40 years, and 0.81 (0.79-0.82) for fertility duration ≥40 years compared with fertility duration <30 years. Whilst being of parity one (HR 0.89, 95% CI 0.85-0.94) and breastfeeding <6 months (HR 0.92, 95% CI 0.88-0.95) was associated with lower risk of dementia, being of parity two or more (HR 1.04, 95% CI 0.99-1.05) and breastfeeding ≥12 months (HR 1.14, 95% CI 1.01-1.07) was associated with a higher risk of dementia than women without parity or breastfeeding history. Use of hormone replacement therapy and oral contraceptives independently reduced the dementia risk by 15% and 10%, respectively. CONCLUSIONS: Female reproductive factors are independent risk factors for dementia incidence, with higher risk associated with shorter lifetime endogenous estrogen exposure.

Dynamic predictive model for postoperative nausea and vomiting for intravenous fentanyl patient-controlled analgesia.

Postoperative nausea and vomiting is the most common side-effect of opioid-based intravenous patient-controlled analgesia. Apfel's simplified risk score is popular but it has some limitations. We developed and validated a dynamic predictive model for nausea or vomiting up to 48 postoperative hours, available as an online web application. Fentanyl was used by 22,144 adult patients for analgesia after non-cardiac surgery under general anaesthesia: we randomly divided them into development (80%) and validation (20%) cohorts, repeated 100 times. We used linear discriminant analysis to select variables for multivariate logistic regression. The incidences of postoperative nausea or vomiting were: 0-48 h, 5691/22,144 (26%); 0-6 h, 2749/22,144 (12%); 6-12 h, 2687/22,144 (12%); 12-18 h, 2624/22,144 (12%); 18-24 h, 1884/22,144 (9%); and 24-48 h, 1082/22,144 (5%). The median (95%CI) area under the receiver operating characteristic curve was 0.72 (0.71-0.73) up to 48 postoperative hours compared with 0.65 (0.64-0.66) for the Apfel model, p < 0.001. The equivalent areas for 0-6 h, 6-12 h, 12-18 h, 18-24 h and 24-48 h were: 0.70 (0.69-0.72); 0.71 (0.69-0.73); 0.69 (0.68-0.71); 0.70 (0.67-0.72); and 0.69 (0.66-0.71), respectively. Our web application allows clinicians to calculate incidences of nausea and vomiting in patients receiving intravenous fentanyl for patient-controlled analgesia.

Fuel-Composition Dependent Reactor Antineutrino Yield at RENO.

We report a fuel-dependent reactor electron antineutrino (ν[over ¯]_{e}) yield using six 2.8 GW_{th} reactors in the Hanbit nuclear power plant complex, Yonggwang, Korea. The analysis uses 850 666 ν[over ¯]_{e} candidate events with a background fraction of 2.0% acquired through inverse beta decay (IBD) interactions in the near detector for 1807.9 live days from August 2011 to February 2018. Based on multiple fuel cycles, we observe a fuel ^{235}U dependent variation of measured IBD yields with a slope of (1.51±0.23)×10^{-43} cm^{2}/fission and measure a total average IBD yield of (5.84±0.13)×10^{-43} cm^{2}/fission. The hypothesis of no fuel-dependent IBD yield is ruled out at 6.6σ. The observed IBD yield variation over ^{235}U isotope fraction does not show significant deviation from the Huber-Mueller (HM) prediction at 1.3 σ. The measured fuel-dependent variation determines IBD yields of (6.15±0.19)×10^{-43} and (4.18±0.26)×10^{-43} cm^{2}/fission for two dominant fuel isotopes ^{235}U and ^{239}Pu, respectively. The measured IBD yield per ^{235}U fission shows the largest deficit relative to the HM prediction. Reevaluation of the ^{235}U IBD yield per fission may mostly solve the reactor antineutrino anomaly (RAA) while ^{239}Pu is not completely ruled out as a possible contributor to the anomaly. We also report a 2.9 σ correlation between the fractional change of the 5 MeV excess and the reactor fuel isotope fraction of ^{235}U.

Proton-driven plasma wakefield acceleration in AWAKE.

In this article, we briefly summarize the experiments performed during the first run of the Advanced Wakefield Experiment, AWAKE, at CERN (European Organization for Nuclear Research). The final goal of AWAKE Run 1 (2013-2018) was to demonstrate that 10-20 MeV electrons can be accelerated to GeV energies in a plasma wakefield driven by a highly relativistic self-modulated proton bunch. We describe the experiment, outline the measurement concept and present first results. Last, we outline our plans for the future. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

What influences use of dental services by the Korean disabled people? The role of perceived barriers in dental care system.

OBJECTIVE: To identify the perceived barriers to dental care for disabled people in South Korea using the revised Andersen's model of access to health care. BASIC RESEARCH DESIGN: Cross-sectional analytic interview study. PARTICIPANTS: Korean people with a disability residing in residential facilities, or those at home who attend vocational rehabilitation facilities, special schools, or welfare facilities, were sampled from Seoul and non-Seoul areas in 2016 and were interviewed face-to-face. In total, 456 disabled Koreans, or their primary caregivers participated. RESULTS: Household income, disability duration and perceived barriers in the dental care system were perceived to impact on dental care utilisation, while the need for dental care services did not significantly explain the use of dental care by disabled people in South Korea. Those with low household incomes were less likely to use dental care services, compared to people with moderate and high household incomes. As disability duration increased, disabled people were more likely to use dental services. Those who perceived the barriers to dental care as higher were less likely to use dental services. CONCLUSION: These data suggest that policies are needed to support disabled people with low household incomes. Lowering barriers in the dental care system may encourage people with disabilities to access timely and adequate dental services.

Impact of genomic alterations on lapatinib treatment outcome and cell-free genomic landscape during HER2 therapy in HER2+ gastric cancer patients.

Background: To identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics. Patients and methods: We prospectively evaluated the efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer. A parallel biomarker study was conducted by simultaneously performing immunohistochemistry and next-generation sequencing (NGS) with tumor and blood samples. Results: Complete response was confirmed in 7/32 patients (21.8%), 2 of whom received radical surgery with pathologic-confirmed complete response. Fifteen partial responses (46.8%) were observed, resulting in a 68.6% overall response rate. NGS of the 16 tumor specimens demonstrated that the most common co-occurring copy number alteration was CCNE1 amplification, which was present in 40% of HER2+ tumors. The relationship between CCNE1 amplification and lack of response to HER2-targeted therapy trended toward statistical significance (66.7% of non-responders versus 22.2% of responders harbored CCNE1 amplification; P = 0.08). Patients with high level ERBB2 amplification by NGS were more likely to respond to therapy, compared with patients with low level ERBB2 amplification (P = 0.02). Analysis of cfDNA showed that detectable ERBB2 copy number amplification in plasma was predictive to the response (100%, response rate) and changes in plasma-detected genomic alterations were associated with lapatinib sensitivity and/or resistance. The follow-up cfDNA genomics at disease progression demonstrated that there are emergences of other genomic aberrations such as MYC, EGFR, FGFR2 and MET amplifications. Conclusions: The present study showed that HER2+ GC patients respond differently according to concomitant genomic aberrations beyond ERBB2, high ERBB2 amplification by NGS or cfDNA can be a positive predictor for patient selection, and tumor genomic alterations change significantly during targeted agent therapy.

Activated leucocyte cell adhesion molecule (ALCAM/CD166) regulates T cell responses in a murine model of food allergy.

Food allergy is a major public health problem. Studies have shown that long-term interactions between activated leucocyte cell adhesion molecule (ALCAM/CD166) on the surface of antigen-presenting cells, and CD6, a co-stimulatory molecule, influence immune responses. However, there are currently no studies on the functions of ALCAM in food allergy. Therefore, we aimed to identify the functions of ALCAM in ovalbumin (OVA)-induced food allergy using ALCAM-deficient mice. Wild-type (WT) and ALCAM-deficient (ALCAM-/- ) mice were sensitized intraperitoneally and with orally fed OVA. The mice were killed, and parameters related to food allergy and T helper type 2 (Th2) immune responses were analysed. ALCAM serum levels increased and mRNA expression decreased in OVA-challenged WT mice. Serum immunoglobulin (Ig)E levels, Th2 cytokine mRNA and histological injuries were higher in OVA-challenged WT mice than in control mice, and these were attenuated in ALCAM-/- mice. T cell proliferation of total cells, CD3+ CD4+ T cells and activated T cells in immune tissues were diminished in OVA-challenged ALCAM-/- mice. Proliferation of co-cultured T cells and dendritic cells (DCs) was decreased by the anti-CD6 antibody. In addition, WT mice sensitized by adoptive transfer of OVA-pulsed ALCAM-/- BM-derived DCs showed reduced immune responses. Lastly, serum ALCAM levels were higher in children with food allergy than in control subjects. In this study, serum levels of ALCAM were elevated in food allergy-induced WT mice and children with food allergy. Moreover, immune responses and T cell activation were attenuated in OVA-challenged ALCAM-/- mice. These results indicate that ALCAM regulates food allergy by affecting T cell activation.