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Objectives To investigate the association between multimorbidity during pregnancy and neurodevelopmental delay in offspring using data from a Japanese nationwide birth cohort study.Design This study was a prospective birth cohort study.Setting This study population included 104 059 fetal records who participated in The Japan Environment and Children’s Study from 2011 to 2014.Participants Pregnant women whose children had undergone developmental testing were included in this analysis.Primary and secondary outcome measures Neurodevelopment of offspring was assessed using the Japanese version of the Ages and Stages Questionnaire, third edition, comprising five developmental domains. The number of comorbidities among the pregnant women was categorised as zero, single disease or multimorbidity (two or more diseases). Maternal chronic conditions included in multimorbidity were defined as conditions with high prevalence among women of reproductive age. A multivariate logistic regression analysis was conducted to examine the association between multimorbidity in pregnant women and offspring development.Results Pregnant women with multimorbidity, single disease and no disease accounted for 3.6%, 30.6% and 65.8%, respectively. The ORs for neurodevelopmental impairment during the follow-up period were similar for infants of mothers with no disease comorbidity and those with a single disease comorbidity. However, the ORs for neurodevelopmental impairment were significantly higher for children born to mothers with multimorbidity compared with those born to healthy mothers.Conclusion An association was observed between the number of comorbidities in pregnant women and developmental delay in offspring. Multimorbidity in pregnant women may be associated with neurodevelopmental delay in their offspring. Further research is required in this regard in many other regions of the world.

We present robust pixel design methodologies for a vertical avalanche photodiode-based CMOS image sensor, taking account of three critical practical factors: (i) “guard-ring-free” pixel isolation layout, (ii) device characteristics “insensitive” to applied voltage and temperature, and (iii) stable operation subject to intense light exposure. The “guard-ring-free” pixel design is established by resolving the tradeoff relationship between electric field concentration and pixel isolation. The effectiveness of the optimization strategy is validated both by simulation and experiment. To realize insensitivity to voltage and temperature variations, a global feedback resistor is shown to effectively suppress variations in device characteristics such as photon detection efficiency and dark count rate. An in-pixel overflow transistor is also introduced to enhance the resistance to strong illumination. The robustness of the fabricated VAPD-CIS is verified by characterization of 122 different chips and through a high-temperature and intense-light-illumination operation test with 5 chips, conducted at 125 °C for 1000 h subject to 940 nm light exposure equivalent to 10 kLux.

IntroductionThe efficacy of second-line immune checkpoint inhibitor (ICI) therapy is limited in non-small cell lung cancer (NSCLC) patients with ≤ 49% PD-L1 expression. Although chemoimmunotherapy is a promising strategy, platinum-based chemotherapy followed by ICI monotherapy is often used to avoid synergistic adverse events. However, predictors of the efficacy of ICI monotherapy after platinum-based chemotherapy in NSCLC with ≤ 49% PD-L1 expression remain scarce.MethodsThis multicenter retrospective study evaluated 54 advanced or recurrent NSCLC patients with ≤ 49% PD-L1 expression who were treated with second-line ICI monotherapy following disease progression on first-line platinum-based chemotherapy at nine hospitals in Japan. The impact of response to platinum-based chemotherapy on the efficacy of subsequent ICI monotherapy was investigated.ResultsThe response to first-line platinum-based chemotherapy was divided into two groups: the non-progressive disease (PD) group, which included patients who did not experience disease progression after four cycles of chemotherapy, and the PD group, which included patients who showed initial PD or could not maintain disease control during the four cycles of chemotherapy and switched to second-line ICI monotherapy. Among the 54 patients, 32 and 22 were classified into the non-PD and PD groups, respectively. The non-PD group showed better response rates (p = 0.038) and longer overall survival (OS) with ICI monotherapy (p = 0.023) than the PD group. Multivariate analysis identified that maintaining a non-PD status after four cycles of chemotherapy was an independent prognostic factor for ICI monotherapy (p = 0.046). Moreover, patients with a modified Glasgow Prognostic Score (mGPS) of 0 showed a tendency for longer OS with ICI monotherapy (p = 0.079), and there was a significant correlation between maintaining non-PD after four cycles of chemotherapy and an mGPS of 0 (p = 0.045).ConclusionMaintaining a non-PD status after four cycles of platinum-based chemotherapy was a predictor of OS after second-line ICI monotherapy. These findings will help physicians select the most suitable treatment option for NSCLC patients who were treated with platinum-based chemotherapy and switched to second-line treatment. Those who experienced early PD during platinum-based chemotherapy should not be treated with ICI monotherapy in the second-line setting.

Objective: To investigate the incidence of umbilical cord prolapse (UCP) and its influence on infant prognosis in pregnant women with preterm premature rupture of membranes (PPROM). Materials and methods: We conducted a retrospective cohort study in a single tertiary perinatal center between 2009 and 2017. Singleton pregnancies with PPROM that occurred between 22 and 33 weeks of gestation were included. Infantile composite adverse outcome consisted of death, severe intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis, and sepsis before discharge. Infantile outcomes were compared between pregnancies that were complicated by UCP and those that were not. Results: Out of 208 singleton pregnancies included in the analysis, UCP occurred in 12 (5.8%) cases. The gestational age of pregnancies with UCP was significantly lesser than that of those without UCP. The incidence of infantile composite adverse outcome in patients with UCP was 16.7%, and this was not significantly higher than the incidence in patients without UCP (6.6%, P = 0.21). UCP was not shown to be associated with infantile composite adverse outcome in a multivariate regression model. Gestational age

Abstract Background The extremes of maternal pre-pregnancy body mass index (BMI) are known to be risk factors associated with obstetric and adverse perinatal outcomes. Among Japanese women aged 20 years or older, the prevalence of underweight (BMI

We present a long range (~250 m) time-of flight (TOF) system with suppressed (nearly-free) mutual-interference. The system is based on a $1296\times960$ pixels vertical avalanche photodiodes (VAPD) CMOS image sensor (CIS). Real-time long-range 3D-imaging with 30 fps speed (450 fps for 2D imaging) is demonstrated. Designs and operation principles of the core circuits, i.e., a photon counting circuit and a global shutter driver, are fully described. The ranging method is based on a sub-range synthesis (SRS) where a range is set by the phase of exposure pulses with respect to that of the light source of the system. The depth resolution is configurable in that the minimum sub-range width limited by the light source pulse width of 10 ns or 1.5 m can be reduced to a 10 cm by introducing an indirect-TOF operation. Furthermore, by employing a random flight timing (RFT), mutual-interference in raw signal level is suppressed by 35 dB when 2 cameras are simultaneously operated. By simulation, the present system is estimated to be tolerant up to a case of 27 cameras operation.

A [12]Cyclo-p-phenylene 9 composed of dinaphthofuran units and biphenyl units was synthesized through reductive elimination of the corresponding trinuclear complex by applying Yamago's method. The X-ray crystallographic analyses of 9 revealed that it adopts a zigzag conformation in the solid state. The UV-vis and fluorescence measurements of compound 9 indicated that it also preferentially took a zigzag conformation in the solution state. [ABSTRACT FROM AUTHOR]

The construction of dinaphtho[2,1-b;2',3'-d]furan-6-ol was developed via a dehydration reaction involving two molecules of 2,3-dihydroxynaphthalene in the presence of a strong acid. Starting from the dinaphthofuran, a variety of butterfly shaped derivatives were synthesized. The optical properties of these compounds were investigated with special attention to the dihedral angle formed by adjacent dinaphthofuran rings and/or the sizes of the fused aromatic rings. [ABSTRACT FROM AUTHOR]