Design and fabrication of a coupled high-Q photonic nanocavity system with large coupling coefficients.

In a previous work, we demonstrated a coupled cavity system where photons in one storage cavity can be transferred to another storage cavity at an arbitrary time by applying a voltage pulse to a third cavity placed in a p-i-n junction. In this work, we demonstrate methods to improve the transfer efficiency and photon lifetimes of such a coupled system. Firstly, we designed a photonic-crystal structure that achieves a large coupling coefficient without reducing the radiation quality factor compared to the previously proposed structure: The photonic-crystal design was changed to a more symmetric configuration to suppress radiation losses and then optimized using an automatic structure tuning method based on the Covariance Matrix Adaptive Evolutional Strategy (CMAES). Here we added two improvements to achieve an evolution toward the desired direction in the two-dimensional target parameter space (spanned by the coupling coefficient and the inverse radiation loss). Secondly, to improve the experimental cavity quality factors, we developed a fabrication process that reduces the surface contamination associated with the fabrication of the p-i-n junction: We covered the photonic structure with a SiO2 mask to avoid the contamination and the electrode material was changed from Al to Au/Cr to enable cleaning by a weak acid. Owing to these improvements of the cavity design and the fabrication process, the obtained system provides coupling strengths that are about three times stronger and photon lifetimes that are about two times longer, compared to the previously reported system.

The effect of nano hydroxyapatite coating implant surfaces on gene expression and osseointegration.

BACKGROUND: Hierarchical micro-nano structured topography along with surface chemistry modifications of dental implants have been suggested to positively contribute to the osseointegration process. However, the effect of such surface modifications on the molecular response as well as bone formation rate and quality are still unclear, especially in the early healing period. This study aimed to evaluate the effect of coating a double acid etched (DAE) implant surface with nano-sized (20 nm) hydroxyapatite (Nano) with respect to gene expression, histologic parameters, and nanomechanical properties when compared to DAE control at 1 and 2 weeks after implant placement in a rodent femur model. MATERIAL AND METHODS: Expression of bone-related genes was determined by qRT-PCR (Col-I, Runx-2, Osx, Opn, Ocn, Alp). Histomorphometric evaluation of bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within implant threads was performed using photomicrographs after histologic processing. Mechanical properties, reduced elastic modulus and hardness, were determined through nanoindentation. RESULTS: At 1 week, the Nano group demonstrated significantly higher expression of Col-I and Ocn compared to the DAE group, indicating upregulation of osteoprogenitor and osteoblast differentiation genes. At 2 weeks, Nano surface further exhibited enhanced gene expression of Col-I and Osx in comparison to the DAE surface, suggesting an increased mineralization of the newly formed bone. Nanoindentation analysis revealed that the Nano group presented no significant difference on the ranks of reduced elastic modulus and hardness compared to DAE for both timepoints. Histomorphometric analysis yielded no significant difference in the percentage of BIC and BAFO between the Nano and DAE surfaces at 1 and 2 weeks. However, Nano implants did present a higher mean value, ~50%, of BIC compared to DAE, ~30%, after 2 weeks in vivo. CONCLUSIONS: While no significant differences were observed in the amount and mechanical properties of newly formed bone, Nano surface positively and significantly increased the expression osteogenic genes compared to DAE surface at early healing periods.

Distribution of natural radionuclides in NORM samples from North Abu Rusheid area, Egypt.

The North Abu Rusheid area in Egypt is a well-known high background natural radiation area (HBNRA) due to the existence of naturally occurring radioactive materials (NORMs) in mylonitic rocks. In this study, 27 rock samples were selected for dose estimation studies. 238U and 232Th were measured using inductively coupled plasma mass spectrometry (ICP-MS) and 40K was measured using sodium iodide (thallium) gamma-ray spectroscopy. The ranges of activity concentrations (Bq/kg) of 238U, 232Th and 40K in the samples varied from 270 ± 2 to 2120 ± 29, 350 ± 2 to 1840 ± 27 and 20 ± 2 to 1390 ± 35 with mean values of 980 ± 349, 770 ± 351, and 640 ± 402 Bq/kg, respectively. The radiological hazard parameters were estimated from activity concentrations of 238U, 232Th and 40K and compared to United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) values. The present study revealed that the hazard parameters were several times higher than the worldwide averages. The U/Th concentration ratio ranged from 0.7 to 3 and could be attributed to the presence of kasolite, uranothorite, zircon, and columbite in mylonitic rocks. From the radiological protection viewpoint, it is necessary to monitor natural radionuclides in these rocks prior to their use in residential and commercial construction materials.

Search for the Majorana Nature of Neutrinos in the Inverted Mass Ordering Region with KamLAND-Zen.

The KamLAND-Zen experiment has provided stringent constraints on the neutrinoless double-beta (0νßß) decay half-life in ^{136}Xe using a xenon-loaded liquid scintillator. We report an improved search using an upgraded detector with almost double the amount of xenon and an ultralow radioactivity container, corresponding to an exposure of 970 kg yr of ^{136}Xe. These new data provide valuable insight into backgrounds, especially from cosmic muon spallation of xenon, and have required the use of novel background rejection techniques. We obtain a lower limit for the 0νßß decay half-life of T_{1/2}^{0ν}>2.3×10^{26} yr at 90% C.L., corresponding to upper limits on the effective Majorana neutrino mass of 36-156 meV using commonly adopted nuclear matrix element calculations.

Influence of using history of immune checkpoint inhibitor therapy for neutropenia caused by combination therapy of ramucirumab and docetaxel.

Recently, pretreatment with immune checkpoint inhibitors (ICIs) has been shown to enhance the therapeutic effects of the combination therapy of ramucirumab (RAM) and docetaxel (DTX); however, its influence on the drug's side effects remains unclear. This study investigated the influence of pretreatment with ICIs on the incidence of neutropenia caused by RAM + DTX therapy in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC who received RAM + DTX therapy at Gifu Prefectural General Medical Center between April 2016 and December 2020 were enrolled. Retrospective data regarding age, sex, performance status and detailed treatment history, among others, at treatment initiation were collected from the patients' electronic medical records. Additionally, data on the course number of RAM + DTX therapy, supportive therapy and blood biochemical parameters, including leukocyte and neutrocyte counts, during the treatment period were collected. We identified 41 patients receiving RAM + DTX therapy. Among the more than grade 3 adverse events caused by this therapy, neutropenia was the most common (78.1%). Despite the fact that all previous risk factors influencing this incidence rate had corresponded, the only factor influencing the incidence rate of neutropenia more than grade 3 was ICI treatment history. A difference in the incidence of neutropenia more than grade 3 in the Kaplan-Meier curve was observed between patients with and without ICI pretreatment history (p = 0.037). The pretreatment history of ICI therapy affects the incidence of neutropenia caused by RAM + DTX therapy in patients with NSCLC.

The use of video games, smartphones, and PCs/tablet PCs based on a survey of students' lifestyles: necessary actions.

OBJECTIVES: Addictions to video gaming, smartphones, and Personal Computer (PCs)/tablets have become serious public health problems worldwide. METHODS: We distributed a lifestyle survey to sixth-grade students (aged 11-12 years) during the 10-year period 2008-2017 and compared their responses in the first 5-year period (2008-2012) with those during the second 5-year period (2013-2017). The survey asked whether the student was (1) in a good mood upon waking, (2) the time that the student woke up, (3) the time that he/she went to bed, (4) the hours of TV watched per day, (5) the hours of video games played per day, (6) the hours of smartphone use per day, (7) the hours of PC or tablet PC use per day, (8) whether the student had a positive sense of self, (9) the number of times the student ate breakfast each week, and (10) how often the student turned off the TV during meals. RESULTS: Compared with the first 5-year period, during the second period significantly more students reported waking up before 6:30 a.m. (P < 0.01), going to bed before 10:00 p.m. (P < 0.05), and watching TV for <1 h (P < 0.001), and significantly fewer students reported playing video games for <1 h (P < 0.05), using a smartphone for <1 h (P < 0.001), and using a PC or tablet PC for <1 h (P < 0.001). CONCLUSIONS: Educational campaigns should specifically address the use of addictive technologies among adolescents.

Assessment of the albumin-bilirubin grade as a prognostic factor in patients with non-small-cell lung cancer receiving anti-PD-1-based therapy.

INTRODUCTION: The albumin-bilirubin (ALBI) grade is a novel indicator of the liver function. Some studies showed that the ALBI grade was a prognostic and predictive biomarker for the efficacy of chemotherapy in cancer patients. The association between the ALBI grade and outcomes in patients with non-small-cell lung cancer (NSCLC) treated with cancer immunotherapy, however, is poorly understood. METHODS: We retrospectively enrolled 452 patients with advanced or recurrent NSCLC who received anti-programmed cell death protein 1 (PD-1)-based therapy between 2016 and 2019 at three medical centers in Japan. The ALBI score was calculated from albumin and bilirubin measured at the time of treatment initiation and was stratified into three categories, ALBI grade 1-3, with reference to previous reports. We examined the clinical impact of the ALBI grade on the outcomes of NSCLC patients receiving anti-PD-1-based therapy using Kaplan-Meier survival curve analysis with log-rank test and Cox proportional hazards regression analysis. RESULTS: The classifications of the 452 patients were as follows: grade 1, n = 158 (35.0%); grade 2, n = 271 (60.0%); and grade 3, n = 23 (5.0%). Kaplan-Meier survival curve analysis showed that the ALBI grade was significantly associated with progression-free survival and overall survival. Moreover, Cox regression analysis revealed that the ALBI grade was an independent prognostic factor for progression-free survival and overall survival. CONCLUSION: The ALBI grade was an independent prognostic factor for survival in patients with advanced or recurrent NSCLC who receive anti-PD-1-based therapy. These findings should be validated in a prospective study with a larger sample size.

Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study.

BACKGROUND: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting. PATIENTS AND METHODS: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Subsequently, patients without disease progression during induction therapy were administered cisplatin and docetaxel (40 mg/m2 each) on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy. The primary endpoint was the 2-year overall survival (OS) rate, which was hypothesized to reach 85%, with a threshold of the lower limit of 60%. RESULTS: Twenty patients (median age: 66 years; male/female: 9/11; histology: 20 adenocarcinoma; stage IIIA/IIIB: 9/11; and exon 19/21: 10/10) were enrolled. The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively. Grade ≥3 adverse events (>10%) included hepatic toxicity during the induction phase and neutropenia and febrile neutropenia in the CRT phase. Radiation pneumonitis grade ≥3 or treatment-related death did not occur. CONCLUSIONS: This is the first prospective study to demonstrate the favorable efficacy and safety of EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III NSCLC. Further confirmatory studies are needed.

Geochemical characterization of monazite sands based on rare earth elements, thorium and uranium from a natural high background radiation area in Tamil Nadu, India.

The Kanyakumari coastal area in the southernmost part of Tamil Nadu, India is a well-known natural high background radiation area due to the abundance of monazite in beach placer deposits. In the present study, the concentrations of major oxides, rare earth elements (REEs), Th and U were measured to understand geochemical characteristics of these monazite sands. Based on the ambient dose rate, 23 locations covering an area of about 60 km along the coast were selected for sample collection. The concentrations of U and Th ranged from 1.1 to 737.8 µg g-1 and 25.2-12250.6 µg g-1, respectively. The Th/U ratio ranged from 2.2 to 61.6, which clearly indicated that Th was the dominant contributing radionuclide to the enhanced natural radioactivity in this coastal region. The chondrite-normalized REEs pattern of the placer deposits showed enrichment in light REEs and depletion in heavy REEs with a negative Eu anomaly that indicated the monazite sands were derived from granite, charnockite, and granitoid rocks from the Nagercoil and the Trivandrum Blocks of the Southern Granulite Terrain.

Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1.

BACKGROUND: Activation of the phosphatidylinositol-3-kinase (PI3K) pathway via PIK3CA mutations occurs in 28%-46% of hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancers (ABCs) and is associated with poor prognosis. The SOLAR-1 trial showed that the addition of alpelisib to fulvestrant treatment provided statistically significant and clinically meaningful progression-free survival (PFS) benefit in PIK3CA-mutated, HR+, HER2- ABC. PATIENTS AND METHODS: Men and postmenopausal women with HR+, HER2- ABC whose disease progressed on or after aromatase inhibitor (AI) were randomized 1 : 1 to receive alpelisib (300 mg/day) plus fulvestrant (500 mg every 28 days and once on day 15) or placebo plus fulvestrant. Overall survival (OS) in the PIK3CA-mutant cohort was evaluated by Kaplan-Meier methodology and a one-sided stratified log-rank test was carried out with an O'Brien-Fleming efficacy boundary of P ≤ 0.0161. RESULTS: In the PIK3CA-mutated cohort (n = 341), median OS [95% confidence interval (CI)] was 39.3 months (34.1-44.9) for alpelisib-fulvestrant and 31.4 months (26.8-41.3) for placebo-fulvestrant [hazard ratio (HR) = 0.86 (95% CI, 0.64-1.15; P = 0.15)]. OS results did not cross the prespecified efficacy boundary. Median OS (95% CI) in patients with lung and/or liver metastases was 37.2 months (28.7-43.6) and 22.8 months (19.0-26.8) in the alpelisib-fulvestrant and placebo-fulvestrant arms, respectively [HR = 0.68 (0.46-1.00)]. Median times to chemotherapy (95% CI) for the alpelisib-fulvestrant and placebo-fulvestrant arms were 23.3 months (15.2-28.4) and 14.8 months (10.5-22.6), respectively [HR = 0.72 (0.54-0.95)]. No new safety signals were observed with longer follow-up. CONCLUSIONS: Although the analysis did not cross the prespecified boundary for statistical significance, there was a 7.9-month numeric improvement in median OS when alpelisib was added to fulvestrant treatment of patients with PIK3CA-mutated, HR+, HER2- ABC. Overall, these results further support the statistically significant prolongation of PFS observed with alpelisib plus fulvestrant in this population, which has a poor prognosis due to a PIK3CA mutation. CLINICALTRIALS. GOV ID: NCT02437318.

Gender differences in self-perceived changes among Japanese workers with depression.

BACKGROUND: The number of patients living with depression continues to increase in Japan. The economic effects of depression include loss of productivity due to both absenteeism and presenteeism. Gender differences have been reported in prevalence, onset pathways and subjective symptoms of depression. AIMS: To understand how workers with major depressive disorder (MDD) perceive problems in the workplace and examine gender differences in their self-perceived levels of functioning at work, noticed during the initial stages of depression. METHODS: This is a cross-sectional study of Japanese workers with MDD. Participants' self-perceived changes in the level of functioning at work were surveyed after the diagnosis during the first visit. The relationship between gender and changes in the level of functioning at work as initially perceived by the participants themselves was analysed using the chi-square test, supplemented by a residual analysis. RESULTS: We administered the survey to 147 workers with MDD. In terms of gender differences in initial self-perceived changes in the level of functioning at work, the proportion of men reporting reduced work efficiency was significantly higher than that of women, while the proportion of women reporting deterioration in relationships with colleagues and superiors was significantly higher than that of men. CONCLUSIONS: The findings suggest that greater attention to reduced work efficiency by men and to deterioration in work relationships by women with MDD should be essential components of self-care. Managers need to pay attention to the level of functioning and provide adequate social support for employees.

Using a quality of life (QoL)-monitor: preliminary results of a randomized trial in Dutch patients with early breast cancer.

PURPOSE: The diagnosis and treatment of cancer negatively affect patients' physical, functional and psychological wellbeing. Patients' needs for care cannot be addressed unless they are recognized by healthcare providers (HCPs). The use of quality of life (QoL) assessments with feedback to HCPs might facilitate the identification and discussion of QoL-topics. METHODS: 113 patients with stage I-IIIB breast cancer treated with chemotherapy were included in this randomized controlled trial. Patients were randomly allocated to receive either usual care, or usual care with an intervention consisting of a QoL-monitor assessing QoL, distress and care needs before every chemotherapy cycle visit. Patients completed questionnaires regarding QoL, illness perceptions, self-efficacy, and satisfaction with communication. From the 2nd visit onwards, patients in the intervention arm and their HCPs received a copy of the QoL overview and results were shown in patients' medical files. Audio-recordings and patients' self-reports were used to investigate effects on communication, patient management and patient-wellbeing. A composite score for communication was calculated by summing the number of QoL-topics discussed during each consultation. RESULTS: Use of the QoL-monitor resulted in a higher communication score (0.7 topics increase per visit, p = 0.04), especially regarding the disease-specific and psychosocial issues (p < 0.01). There were no differences in patient management, QoL, illness perceptions or distress. Patients in the experimental arm (n = 60) had higher scores on satisfaction with communication (p < 0.05). CONCLUSIONS: Use of a QoL-monitor during chemotherapy in patients with early breast cancer might result in a more frequent discussion of QoL-topics, associated with high levels of patients' satisfaction.

SELF-ASSESSED COMPETENCE IN PROVIDING CARE TO THE SEVERELY ILL PATIENTS AMONG NURSES AND RELATIVES/CAREGIVERS IN KAZAKHSTAN.

The growing demands have been placed on nurses working in public healthcare system, mostly due to expanding set of required competence. The presented cross-sectional study is aimed to investigate the level of self-assessed competence of community nurses in three primary health care establishments of Kazakhstan and to identify the relatives' perception of competence needed to provide medical care to their severely ill family members. The subjects enrolled into the study were 115 nurses employed in three primary healthcare establishments of Kazakhstan and 58 relatives/caregivers registered at the same establishments. Stoma care appeared to be the most problematic task for nurses in addition to providing of the first aid in different emergency situations, such as dyspnea, cardiac pain, vomiting, and pain attack. Relatives/caregivers reported satisfactory levels of such competence as feeding a bedridden patient, maintenance of basic hygiene, performing a simple physical therapy and instillation of eye/ear drops. Our results could be useful for healthcare managers in obtaining a clear vision of which educational areas require prioritization and guide public health interventions to overcome the identified problems.

Monoclonal anti-dsDNA antibody 2C10 escorts DNA to intracellular DNA sensors in normal mononuclear cells and stimulates secretion of multiple cytokines implicated in lupus pathogenesis.

There have been many studies on the mechanisms of internalization of DNA-anti-DNA immune complexes by cells, including the one used for rheumatoid factor-expressing mouse B cells. In parallel, studies on the role of intracellular DNA sensors in the pathogenesis of systemic lupus erythematosus (SLE) have been conducted, including the one using a mouse model lacking one of the sensors. These and other data have established a framework for understanding the pathogenic role of anti-DNA antibodies, but studies on normal cells are limited. Here, we used the monoclonal anti-dsDNA antibody 2C10, 2-kbp dsDNA and healthy human peripheral blood mononuclear cells (PBMCs) to test whether and how 2C10 and/or DNA cause pathology in normal cells. We found that on culture with PBMCs, 2C10 preferentially entered monocytes and that DNA enhanced this internalization. In contrast, DNA alone was not significantly internalized by monocytes, but 2C10 facilitated its internalization. This was suppressed by cytochalasin D, but not by methyl-ß-cyclodextrin, chloroquine or an Fc blocker, suggesting the involvement of macropinocytosis in this process. Internalization of 2C10 and DNA together resulted in production of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1ß, IL-6, IL-10 and IL-33 by PBMCs. Cytokine production was suppressed by chloroquine and shikonin, but not by RU.521, suggesting dependence on activation of the Toll-like receptor (TLR)-9 and absent in melanoma 2 (AIM-2) pathways. These results established a simple model to demonstrate that anti-DNA antibodies can cause dysregulation of cytokine network mimicking systemic lupus erythematosus in culture of normal PBMCs, and emphasize again the importance of maintaining anti-DNA antibodies at low levels by treatment.

Simultaneous measurement of p53:Mdm2 and p53:Mdm4 protein-protein interactions in whole cells using fluorescence labelled foci.

In this report we describe the development of a Fluorescent Protein-Protein Interaction-visualization (FLUOPPI) to enable the simultaneous measurement of both Mdm2:p53 and Mdm4:p53 interactions in order to assess the relative efficiencies of mimetic molecules of the p53 peptide helix against both PPIs. Mdm2 and Mdm4 overexpression frequently leads to the inactivation of non-mutated p53 in human cancers, via inhibition of its transcriptional activity, enhancing its degradation by the proteasome or by preventing its nuclear import. Development of inhibitors to disrupt the binding of one or both of these protein interactions have been the subject of intensive pharmaceutical development for anti-cancer therapies. Using the bimodal FLUOPPI system we have characterised compounds that were either monospecific for Mdm2 or bispecific for both Mdm2 and Mdm4. We have also demonstrated that the FLUOPPI assay can reliably differentiate between specific and non-specific disruption of these protein complexes via accurate assessment and normalization to the cell population under measurement. We envision that this methodology will increase the efficiency of identifying compounds that are either specific against a single PPI from a closely related family of interactions or compounds that interact across multiple related PPI pairs, depending on which is more desirable.

IMPACT ON ABSORBED DOSE RATE IN AIR IN KANTO REGION BY FUKUSHIMA DAIICHI NUCLEAR POWER PLANT ACCIDENT.

Absorbed dose rates in air were measured for the whole area of the Kanto region in 2015, 2016 and 2017 (n = 31 147). The mean absorbed dose rates in air for each prefecture measured by car-borne surveys were from 44 to 67 nGy h-1 (13-289 nGy h-1). The absorbed dose rate in air from artificial radionuclides (134Cs + 137Cs) measured by fixed-point observation (n = 507) was from 1 to 14 nGy h-1 (0-105 nGy h-1), and meaning that the contribution ratios of 134Cs and 137Cs were 3-22%. The deposited location of artificial radionuclides was less than 1000 m from ground level and depended on the topography, wind direction and precipitation field.

Precision Analysis of the

We present a precision analysis of the ^{136}Xe two-neutrino ßß electron spectrum above 0.8 MeV, based on high-statistics data obtained with the KamLAND-Zen experiment. An improved formalism for the two-neutrino ßß rate allows us to measure the ratio of the leading and subleading 2νßß nuclear matrix elements (NMEs), ξ_{31}^{2ν}=-0.26_{-0.25}^{+0.31}. Theoretical predictions from the nuclear shell model and the majority of the quasiparticle random-phase approximation (QRPA) calculations are consistent with the experimental limit. However, part of the ξ_{31}^{2ν} range allowed by the QRPA is excluded by the present measurement at the 90% confidence level. Our analysis reveals that predicted ξ_{31}^{2ν} values are sensitive to the quenching of NMEs and the competing contributions from low- and high-energy states in the intermediate nucleus. Because these aspects are also at play in neutrinoless ßß decay, ξ_{31}^{2ν} provides new insights toward reliable neutrinoless ßß NMEs.