Impact of Nonpharmacological Interventions on Severe Acute Respiratory Infections in Children: From the National Surveillance Database.

BACKGROUND: Nonpharmacological interventions (NPIs) reduce the incidence of respiratory infections. After NPIs imposed during the coronavirus disease 2019 pandemic ceased, respiratory infections gradually increased worldwide. However, few studies have been conducted on severe respiratory infections requiring hospitalization in pediatric patients. This study compares epidemiological changes in severe respiratory infections during pre-NPI, NPI, and post-NPI periods in order to evaluate the effect of that NPI on severe respiratory infections in children. METHODS: We retrospectively studied data collected at 13 Korean sentinel sites from January 2018 to October 2022 that were lodged in the national Severe Acute Respiratory Infections (SARIs) surveillance database. RESULTS: A total of 9,631 pediatric patients were admitted with SARIs during the pre-NPI period, 579 during the NPI period, and 1,580 during the post-NPI period. During the NPI period, the number of pediatric patients hospitalized with severe respiratory infections decreased dramatically, thus from 72.1 per 1,000 to 6.6 per 1,000. However, after NPIs ceased, the number increased to 22.8 per 1,000. During the post-NPI period, the positive test rate increased to the level noted before the pandemic. CONCLUSION: Strict NPIs including school and daycare center closures effectively reduced severe respiratory infections requiring hospitalization of children. However, childcare was severely compromised. To prepare for future respiratory infections, there is a need to develop a social consensus on NPIs that are appropriate for children.

Change in Severity and Clinical Manifestation of MIS-C Over SARS-CoV-2 Variant Outbreaks in Korea.

BACKGROUND: There is difference in the incidence of multi-system inflammatory syndrome in children (MIS-C) in patients with different variants of severe acute respiratory syndrome coronavirus 2, however, little is known about the epidemiology in Asian countries. We investigated and compared the epidemiology of the MIS-C during omicron-dominant period with that of previous periods in South Korea. METHODS: We obtained clinical, epidemiological and laboratory data on MIS-C cases from national MIS-C surveillance in South Korea. We defined pre-delta period as January 2020-May 2021; delta period as June 2021-December 2021; and omicron period as January 2022-April 2022. We describe the clinical characteristics and outcomes of MIS-C patients by period. RESULTS: A total of 91 cases were assessed to be MIS-C cases. Number of MIS-C cases have increased from six cases during pre-delta period to 66 cases during omicron period, while the incidence rate (the number of MIS-C cases per 100,000 cases of reported coronavirus disease 2019) has decreased from 38.5 cases per 100,000 (95% confidence interval [CI], 14.1-83.9) during pre-delta period to 1.6 cases per 100,000 (95% CI, 1.2-2.0) during omicron periods. During pre-delta period, 66.7% and 100% had hypotension and gastrointestinal involvement, respectively; while during omicron period, 12.1% and 6.1% had such clinical manifestations. Fifty percent of pre-delta MIS-C patients were taken intensive care unit (ICU) cares, while 10.6% of patients during omicron periods were in ICUs. CONCLUSION: Omicron period were associated with less severe clinical manifestation compared to pre-delta and delta periods. Although incidence rate of MIS-C was lower for the omicron period than pre-delta and delta periods, number of patients reported with MIS-C may pose a substantial clinical burden.

Twenty-Five Year Trend Change in the Etiology of Pediatric Invasive Bacterial Infections in Korea, 1996-2020.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has contributed to the change in the epidemiology of many infectious diseases. This study aimed to establish the pre-pandemic epidemiology of pediatric invasive bacterial infection (IBI). METHODS: A retrospective multicenter-based surveillance for pediatric IBIs has been maintained from 1996 to 2020 in Korea. IBIs caused by eight bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species) in immunocompetent children > 3 months of age were collected at 29 centers. The annual trend in the proportion of IBIs by each pathogen was analyzed. RESULTS: A total of 2,195 episodes were identified during the 25-year period between 1996 and 2020. S. pneumoniae (42.4%), S. aureus (22.1%), and Salmonella species (21.0%) were common in children 3 to 59 months of age. In children ≥ 5 years of age, S. aureus (58.1%), followed by Salmonella species (14.8%) and S. pneumoniae (12.2%) were common. Excluding the year 2020, there was a trend toward a decrease in the relative proportions of S. pneumoniae (rs = -0.430, P = 0.036), H. influenzae (rs = -0.922, P < 0.001), while trend toward an increase in the relative proportion of S. aureus (rs = 0.850, P < 0.001), S. agalactiae (rs = 0.615, P = 0.001), and S. pyogenes (rs = 0.554, P = 0.005). CONCLUSION: In the proportion of IBIs over a 24-year period between 1996 and 2019, we observed a decreasing trend for S. pneumoniae and H. influenzae and an increasing trend for S. aureus, S. agalactiae, and S. pyogenes in children > 3 months of age. These findings can be used as the baseline data to navigate the trend in the epidemiology of pediatric IBI in the post COVID-19 era.

A Numerical Method of Aligning the Optical Stacks for All Pixels.

Reducing performance verification time is significant in product launch and production costs. This is especially true because aligning the optical stacks of off-axis pixels is a time-consuming task, but it is important to maintain sensitivity. In this paper, a numerical method to align the optical stacks of off-axis pixels is suggested in order to reduce performance test time. The components of the numerical method are the optical stack height, refractive index, and chief ray angle in order to calculate the optical stacks' optimal shift distance. The proposed method was investigated to confirm effectiveness by using optical simulation. The sub-micron backside illumination (BSI) pixels were simulated, having 2 × 2 microlens, quad-color filter array, and in-pixel deep trench isolation (DTI). Moreover, the proposed method was evaluated for various pixel pitches, microlens shapes, and CRAs. As a result, the optical stacks were optimized by using the numerical method and validated via optical simulation. Therefore, the proposed numerical method is expected to help reduce the time and cost.

Genome-wide meta-analysis revealed several genetic loci associated with serum uric acid levels in Korean population: an analysis of Korea Biobank data.

The serum uric acid (SUA) level is an important determinant of gout, hypertension, metabolic syndrome, and cardiovascular disease. Although previous genome-wide studies have identified multiple genetic variants associated with SUA, most genetic analyses have focused on individuals with European ancestry; thus, understanding of the genetic architecture of SUA is currently limited for Asian populations. We conducted a genome-wide meta-analysis based on Korea Biobank data consistent with three cohorts; namely, the Korean Genome and Epidemiology Study (KoGES) Ansan and Ansung, KoGES Health Examinee, and KoGES Cardiovascular Disease Association studies. In total, 60,585 participants aged ≥40 years were included in the analysis of the three cohorts. We used logistic regression analyses to perform genome-wide association study (GWAS) adjustments for confounding variables. Subsequently, a meta-analysis was conducted by combining the analyses of the three GWASs. We identified 8,105 variants at 22 genetic loci with a P value < 5 × 10-8. Among these, six novel genetic loci associated with SUA in the Korean population were identified (rs4715517 in HCRTR2, rs145099458 in 3.2 kb 3' of MLXIPL, rs1137642 in B4GALT1, rs659107 in LOC105378410, rs7919329 in LOC107984274, and rs2240751 in MFSD12). Our meta-analysis provides insights into the genetic architecture of SUA in the Korean population. Further studies are warranted to replicate the study results and elucidate the specific role of these variants in SUA homeostasis.

Immunogenicity after outbreak response immunization activities among young healthcare workers with secondary vaccine failure during the measles epidemic in Korea, 2019.

BACKGROUND: Despite high vaccination coverage, measles outbreaks have been reported in measles elimination countries, especially among healthcare workers in their 20 and 30 s. This study was designed to identify measles-susceptible individuals and to evaluate whether primary or secondary vaccine failure occurred during measles outbreak response immunization (ORI) activities. METHODS: The study population was divided into three groups as follows: natural immunity group (Group 1), vaccine-induced immunity group (Group 2), and vaccine failure group (Group 3). We evaluated the immunogenicity of measles among healthcare workers using three methods-enzyme-linked immunoassays, plaque reduction neutralization tests, and avidity assays. The results were assessed at baseline, 4 weeks after, and 6 months after the completion of measles-mumps-rubella (MMR) vaccination. RESULTS: In total, 120 subjects were enrolled, with 40 subjects in each group. The median age of Group 3 was 29 years, which was significantly lower than that of the other groups. The baseline negative measles virus (MeV) IgG in Group 3 increased to a median value of 165 AU/mL at 4 weeks after ORI and was lower than that in Groups 1 and 2. The median neutralizing antibody titer was highest in Group 1, and this was significantly different from that in Group 2 or Group 3 at 4 weeks (944 vs. 405 vs. 482 mIU/mL, P = 0.001) and 6 months (826 vs. 401 vs. 470, P = 0.011) after ORI. The rates of high MeV avidity IgG were highest in Group 2, and these were significantly different from those in Groups 1 or 3 at 4 weeks (77.5 vs. 90% vs. 88.6%, P = 0.03) and 6 months (81 vs. 94.8 vs. 82.1%, P = 0.01) after ORI. CONCLUSIONS: Considering the MeV-neutralizing antibodies and IgG avidity after MMR vaccination in measles-susceptible group, vaccine failure is inferred as secondary vaccine failure, and further data regarding the maintenance of immunogenicity are needed based on long-term data. The MeV-neutralizing antibody levels were highest in the natural immunity group, and the primary vaccine-induced immunity group showed the highest rates of high MeV IgG avidity.

COVID-19 vaccination-related small vessel vasculitis with multiorgan involvement.

Since its first outbreak in 2019, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, has been ongoing, and the pandemic is not over yet. Vaccines developed against COVID-19 have been approved and widely used since 2020; however, vaccine safety concerns need to be addressed. Autoimmune symptoms have been reported as a side effect of many COVID-19 vaccines. In particular, several cases of COVID-19 vaccine-induced vasculitis have recently been reported. Herein, we report the case of a 77-year-old woman who developed small-vessel vasculitis with multiorgan involvement after receiving the BNT162b2 COVID-19 vaccine (Pfizer and BioNTech, New York City, NY, USA).

Associations of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Monocyte-to-Lymphocyte Ratio with Osteoporosis and Incident Vertebral Fracture in Postmenopausal Women with Rheumatoid Arthritis: A Single-Center Retrospective Cohort Study.

Background and Objectives: We investigated whether nutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphoycte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are associated with the presence of osteoporosis (OP) and vertebral fractures in patients with rheumatoid arthritis (RA). Materials and Methods: This retrospective cohort study included 413 postmenopausal patients with RA and 200 healthy controls who underwent dual-energy X-ray absorptiometry (DEXA) between January 2005 and December 2017. DEXA examination data were defined as the index date, and all laboratory values were measured within one month from the index date. OP was defined as a T-score < −2.5, and incident vertebral fractures were defined as the first occurrence of non-traumatic fractures after the index date. NLR, PLR, and MLR measures were dichotomized by a median split (low vs. high). Results: The median NLR, PLR, and MLR in RA patients were significantly higher than those in controls. The frequencies of OP of the lumbar spine, hip, and either site in postmenopausal patients with RA were 24.7%, 15.5%, and 32%, respectively, and were significantly higher than those in controls. After adjusting for confounding factors, a high baseline NLR was significantly associated with OP at either site (OR = 1.61, p = 0.041). In addition, high baseline NLR (OR = 2.11, p = 0.025) and PLR (OR = 2.3, p = 0.011) were related with the presence OP at hip. During the follow-up period, 53 (12.8%) patients with RA developed vertebral fractures incidentally. In multivariable Cox regression models, a high baseline NLR (HR = 4.72, p < 0.001), PLR (HR = 1.96, p = 0.024), and MLR (HR = 2.64, p = 0.002) were independently associated with a higher risk of incidental vertebral fractures. Conclusions: Our data suggest that NLR, PLR, and MLR can be used as potential markers of systemic bone loss among individuals with RA.

Surveillance of COVID-19-Associated Multisystem Inflammatory Syndrome in Children, South Korea.

A concerning development during the coronavirus disease pandemic has been multisystem inflammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem inflammatory syndrome in children. All case-patients were hospitalized and survived with no major disease sequelae.

Coronavirus Disease 2019 Cases at Universities and Colleges in Seoul Metropolitan Area.

BACKGROUND: To facilitate evidence-based policy-making on safe reopening of higher education facilities, there is an urgent need to assess baseline profile of coronavirus disease 2019 (COVID-19) incidents within the university/college settings. We aimed to describe the epidemiology of COVID-19 in universities/colleges in Seoul Metropolitan Area during COVID-19 pandemic period. METHODS: Among the 38 universities in Seoul, 23 have agreed to participate in the study. Confirmed COVID-19 cases were identified from individual-level case reports submitted to the universities and to the health authorities from February 1, 2020, to June 30, 2021. Through the linkage with the Central Disease Control Headquarters' database, number of secondary infected cases (both within and outside of the campus) were counted. RESULTS: Between February 2020 and June 2021, a total of 827 COVID-19 cases were confirmed and reported in the universities across Seoul Metropolitan City. Generally, the community-associated cases had peaks preceding the university/college-associated. Of those with the documented clinical parameters, 38.6% of the cases were asymptomatic. Among them, 93% were potentially exposed off-campus, and 87.7% of the cases had not produced the secondary infection cases. CONCLUSION: In the setting of rigorous infection prevention measures in combination with on- and off- hybrid classes, COVID-19 incidences and outbreaks were limited in university and college campus area across Seoul Metropolitan Area. The evidence around the infection preventive measures in higher education facilities in Seoul Metropolitan Area, suggest insignificant impact on community transmission.

Yukmijihwang-Tang Suppresses Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Mediated Bone Loss.

Yukmijihwang-tang (YJ) has been used to treat diabetes mellitus, renal disorders, and cognitive impairment in traditional medicine. This study aimed to evaluate the anti-osteoporotic effect of YJ on ovariectomy (OVX)-induced bone loss in a rat and receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclast differentiation in bone marrow macrophages (BMMs). YJ reduced the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) in an osteoclast/osteoblast co-culture system by regulating the ratio of RANKL/osteoprotegerin (OPG) by osteoblasts. Overall, YJ reduced TRAP-positive cell formation and TRAP activity and F-actin ring formation. Analysis of the underlying mechanisms indicated that YJ inhibited the activation of the nuclear factor of activated T cell cytoplasmic 1 (NFATc1) and c-Fos, resulting in the suppression of osteoclast differentiation-related genes such as TRAP, ATPase, H+ transporting, lysosomal 38 kDa, V0 subunit d2, osteoclast-associated receptor, osteoclast-stimulatory transmembrane protein, dendritic cell-specific transmembrane protein, matrix metalloproteinase-9, cathepsin K, and calcitonin receptor. YJ also inhibited the nuclear translocation of NFATc1. Additionally, YJ markedly inhibited RANKL-induced phosphorylation of signaling pathways activated in the early stages of osteoclast differentiation including the p38, JNK, ERK, and NF-κB. Consistent with these in vitro results, the YJ-administered group showed considerably attenuated bone loss in the OVX-mediated rat model. These results provide promising evidence for the potential novel therapeutic application of YJ for bone diseases such as osteoporosis.

Eleutherococcus sessiliflorus Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss.

The aim of this study was to evaluate the effects of root bark of Eleutherococcus sessiliflorus (ES) on osteoclast differentiation and function in vitro and in vivo. In vitro, we found that ES significantly inhibited the RANKL-induced formation of TRAP-positive multinucleated osteoclasts and osteoclastic bone resorption without cytotoxic effects. ES markedly downregulated the expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1); c-Fos; and osteoclast-related marker genes, such as TRAP, osteoclast-associated receptor (OSCAR), matrix metalloproteinase-9 (MMP-9), calcitonin receptor, cathepsin K, the 38 kDa d2 subunit of the vacuolar H+-transporting lysosomal ATPase (Atp6v0d2), dendritic cell-specific transmembrane protein (DC-STAMP), and osteoclast-stimulatory transmembrane protein (OC-STAMP). These effects were achieved by inhibiting the RANKL-mediated activation of MAPK signaling pathway proteins, including p38, ERK, and JNK. In vivo, ES attenuated OVX-induced decrease in bone volume to tissue volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and bone mineral density, but increased trabecular separation (Tb.Sp) in the femur. Collectively, our findings showed that ES inhibited RANKL-activated osteoclast differentiation in bone marrow macrophages and prevented OVX-mediated bone loss in rats. These findings suggest that ES has the potential to be used as a therapeutic agent for bone-related diseases, such as osteoporosis.

Platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as potential makers for digital ulcers and interstitial lung disease in patients with systemic sclerosis: cross-sectional analysis of data from a prospective cohort study.

In this study, we aimed to investigate the association of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) with clinical manifestations in patients with systemic sclerosis (SSc). We conducted a cross-sectional analysis of data collected from a cohort study of 114 female patients with SSc and of 304 age-matched, healthy, female controls recruited from a tertiary rheumatology center. Patients with digital ulcers (DU) included those with either active or healed ulcers. Interstitial lung disease (ILD) was diagnosed on detection of diffuse ground-glass opacity or pulmonary fibrosis on chest X-ray or on high-resolution computed tomography. Patients with SSc had significantly higher PLR and NLR than ealthy controls. Of 114 patients with SSc, 35 (30.7%) and 54 (47.4%) patients had DU (active: 12, healed: 23) and ILD, respectively. PLR and NLR in SSc patients with concurrent DU or ILD were significantly higher than that in those without these respective complications. The PLR (OR = 1.008, 95% CI 1.002-1.015), but not the NLR, was independently associated with the presence of DU in SSc patients, based on multivariable logistic regression models. Additionally, both PLR (OR = 1.008, 95% CI 1.001-1.014) and NLR (OR = 1.515, 95% CI 1.066-2.155) correlated independently with the presence of ILD. However, both the PLR and NLR showed no significant association with the modified Rodnan skin score, pulmonary arterial hypertension, and gastrointestinal involvement. Our results suggest that PLR and NLR could be considered as potential biomarkers of DU and ILD, in patients with SSc.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio as predictors of 12-week treatment response and drug persistence of anti-tumor necrosis factor-α agents in patients with rheumatoid arthritis: a retrospective chart review analysis.

Data are scarce regarding the association of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with treatment response and persistence of anti-TNF-α agents in patients with rheumatoid arthritis (RA). Thus, we investigated whether baseline NLR and PLR could predict 12-week treatment response and long-term persistence of anti-TNF-α agents in RA patients. This is a retrospective chart review analysis of 82 women with RA who started anti-TNF-α agents as the first-line biologic therapy and 328 healthy age-matched women. RA patients were divided into high and low baseline NLR or PLR subgroups using the median split. European League against Rheumatism (EULAR) treatment response was evaluated at 12 weeks. RA patients had significantly higher NLR and PLR than controls. High baseline NLR and PLR groups showed higher 12-week EULAR non-response rate than low NLR (30% vs 7.1%, p = 0.01) and PLR groups (27.5% vs 9.5%, p = 0.047), respectively. After adjusting for confounding factors, high baseline NLR (OR 5.57, p = 0.014) and PLR (OR 4.24, p = 0.04) were significantly associated with a higher risk of EULAR non-response at 12 weeks. During the study period, 47 (57.3%) RA patients (lack of efficacy: n = 31; adverse events: n = 16) discontinued anti-TNF-α agents. High baseline NLR was associated with an increased risk of anti-TNF-α agent withdrawal due to lack of efficacy (HR 2.12, p = 0.045). Our data suggest that baseline NLR and PLR are useful markers for predicting the treatment outcome of anti-TNF-α agents in RA patients.

Increased serum uric acid levels are associated with digital ulcers in patients with systemic sclerosis.

Endothelial injury/dysfunction is thought to be one of the earliest events in the development of vascular diseases in systemic sclerosis (SSc). Although hyperuricemia is also known to induce endothelial dysfunction and vascular inflammation, the effect of uric acid on the microvascular involvement in SSc has not been well established. We investigated whether increased serum uric acid (SUA) levels are associated with digital ulcers (DUs) in SSc. In this cross-sectional study, we consecutively recruited 71 women with SSc and 349 age- and sex-matched healthy subjects, and SUA levels were measured in all study subjects. SSc patients had significantly higher mean SUA levels than healthy subjects (4.5 ± 1 mg/dL vs 4.2 ± 0.9 mg/dL, p = 0.017), although a significantly lower body mass index (BMI) was observed in SSc patients than in controls. Among 71 SSc patients, 22 (31%) had DUs ever (active DUs, 8; healed DUs, 14). SSc patients presenting with DUs ever showed significantly higher SUA levels than those without this feature (median, 5.2 mg/dL vs 4.1 mg/dL, p = 0.009). In multivariable logistic regression models adjusted for confounders such as BMI and estimated glomerular filtration rate, increased SUA levels were associated with a significantly higher risk for the presence of DUs ever (OR 2.3, 95% CI 1.16-4.57, p = 0.018). Our data revealed that elevated SUA levels are independently associated with the presence of DUs in SSc patients, thereby suggesting the potential role of hyperuricemia in the pathogenesis of SSc vasculopathy.

Pediatric intensive care unit admission due to respiratory syncytial virus: Retrospective multicenter study.

BACKGROUND: We investigated the characteristics and clinical outcomes of respiratory syncytial virus (RSV)-related pediatric intensive care unit (PICU) hospitalization and assessed the palivizumab (PZ) prophylaxis eligibility according to different guidelines from Korea, EU, and USA. METHODS: In this multicenter study, children <18 years of age hospitalized in six PICU from different hospitals due to severe RSV infection between September 2008 and March 2013 were included. A retrospective chart review was performed. RESULTS: A total of 92 patients were identified. The median length of PICU stay was 6 days (range, 1-154 days) and median PICU care cost was USD2,741 (range, USD556-98 243). Of 62 patients who were <2 years old at the beginning of the RSV season, 33 (53.2%) were high-risk patients for severe RSV infection. Hemodynamically significant congenital heart disease (22.6%) was the most common risk factor, followed by chronic lung disease (11.3%), neuromuscular disease or congenital abnormality of the airway (NMD/CAA) (11.3%), and prematurity (8.1%). The percentage of patients eligible for PZ prophylaxis ranged from 38.7% to 48.4% based on the guidelines, but only two (2.2%) received PZ ≤30 days prior to PICU admission. The median duration of mechanical ventilation was longer in children with NDM/CAA than in those without risk factors (26 days; range, 24-139 days vs 6 days, range, 2-68 days, P = 0.033). RSV-attributable mortality was 5.4%. CONCLUSIONS: Children <2 years old with already well-known high risks represent a significant proportion of RSV-related PICU admissions. Increasing of the compliance for PZ prophylaxis practice among physicians is needed. Further studies are needed to investigate the burden of RSV infection in patients hospitalized in PICU, including children with NMD/CAA.

Front-Inner Lens for High Sensitivity of CMOS Image Sensors.

Due to the continuing improvements in camera technology, a high-resolution CMOS image sensor is required. However, a high-resolution camera requires that the pixel pitch is smaller than 1.0 µm in the limited sensor area. Accordingly, the optical performance of the pixel deteriorates with the aspect ratio. If the pixel depth is shallow, the aspect ratio is enhanced. Also, optical performance can improve if the sensitivity in the long wavelengths is guaranteed. In this current work, we propose a front-inner lens structure that enhances the sensitivity to the small pixel size and the shallow pixel depth. The front-inner lens was located on the front side of the backside illuminated pixel for enhancement of the absorption. The proposed structures in the 1.0 µm pixel pitch were investigated with 3D optical simulation. The pixel depths were 3.0, 2.0, and 1.0 µm. The materials of the front-inner lens were varied, including air and magnesium fluoride (MgF2). For analysis of the sensitivity enhancement, we compared the typical pixel with the suggested pixel and confirmed that the absorption rate of the suggested pixel was improved by a maximum of 7.27%, 10.47%, and 29.28% for 3.0, 2.0, and 1.0 µm pixel depths, respectively.

High-Sensitivity Pixels with a Quad-WRGB Color Filter and Spatial Deep-Trench Isolation.

The demand for a high-resolution metal-oxide-semiconductor (CMOS) image sensor has increased in recent years, and pixel size has shrunk below 1.0 µm to allow accumulation of numerous pixels in a limited area. However, shrinking the pixel size lowers the sensitivity and increases crosstalk because the aspect ratio is worsened by maintaining the height of the pixel. This work introduces a high-sensitivity pixel with a quad-WRGB (White, Red, Green, Blue) color filter array (CFA), spatial deep-trench isolation (S-DTI), and a spatial tungsten grid (S-WG). The optical performance of the suggested pixel was analyzed by performing 3D optical simulations at 1.0, 0.9, and 0.8 µm pixel pitches as small-sized pixels. The quad-WRGB CFA is compared with the quad-Bayer CFA, and the S-DTI and S-WG are compared with the conventional DTI and WG. We confirmed an improvement in the sensitivity of the suggested pixel using the quad-WRGB CFA with S-DTI and S-WG to a maximum of 58.2%, 67.0%, and 66.3% for 1.0, 0.9, and 0.8 µm pixels, respectively.

Cognitive function of patients with rheumatoid arthritis is associated with disease activity but not carotid atherosclerotic changes.

OBJECTIVES: Although the relationship between atherosclerosis and cognitive impairment has been studied and replicated, whether cognitive deficits in RA can be attributed to atherosclerotic changes is not well understood. This study investigated cognitive function in patients with RA and evaluated whether cognitive function was affected by carotid arterial atherosclerosis. METHODS: We examined 70 RA patients and 40 healthy controls. RA activity was assessed by disease activity score with 28 joint-erythrocyte sedimentation rate (DAS28-ESR). Cognitive function was assessed by the Korean version of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K) neuropsychological battery. Carotid arteries were scanned for the presence of plaques and to assess intima-media thickness (IMT). We assessed potential risk factors of cognitive impairment in RA patients using regression analyses. RESULTS: There was a significant difference between RA patients and healthy controls in the verbal fluency (p=0.004) and Boston naming test (p=0.035). Carotid ultrasound revealed significantly more plaque in RA patients than in healthy controls (p=0.017). RA patients with memory impairment had significantly higher DAS28-ESR scores (p<0.001), age (p=0.009), and mean cIMT (p=0.027) than RA patients without memory impairment. In multivariable regression analysis, CERAD-K total score showed a significant negative correlation with age (ß=-0.415, p<0.001) or DAS28-ESR (ß=-4.685, p<0.001), but no correlation was found between CERAD-K total score and presence of plaque or cIMT. CONCLUSIONS: Our results indicate that disease activity of RA and aging contribute to cognitive dysfunction, but there was no association between cognitive function and carotid atherosclerotic changes in RA patients.

Genetic structures of invasive Streptococcus pneumoniae isolates from Korean children obtained between 1995 and 2013.

BACKGROUND: Understanding the population genetics of pneumococci will allow detection of changes in the prevalence of circulating genotypes and evidence for capsular switching. We aimed to analyze the genetic structure of invasive pneumococcal isolates obtained from children before and after the use of pneumococcal conjugate vaccines (PCVs) in Korea. METHODS: A total of 285 invasive pneumococcal isolates were analyzed using serotyping, multilocus sequence typing, and antimicrobial susceptibility testing. We classified the isolation year to pre-PCV7 (1995-2003; n = 70), post-PCV7 (2004-2010; n = 142), and post-PCV13 (2011-2013; n = 73) periods. RESULTS: Of the 10 clonal complexes (CCs), antibiotic-resistant international clones, CC320 (31.6%), CC81 (14.7%), and CC166 (6.7%) were the main complexes. Serotype 19A was the main serotype of CC320 throughout the periods. Serotypes of CC81 mainly comprised of 23F (53.3%) in pre-PCV7 period and replaced by non-vaccine types (NVTs; 6C [10%], 13 [30%], 15A [40%], and 15B/C [20%]) in post-PCV13 period. The main serotype responsible for CC166 also changed from 9 V (80%) in pre-PCV7 to NVT 11A (50%) in post-PCV13 periods. Non-susceptibility to penicillin (42.3%) was the highest in CC320, increasing from 0 to 76%. CONCLUSION: The genetic structures of invasive pneumococcal isolates in Korean children have changed concomitantly with serotype after the implementation of PCVs.