Introduction: During the 2016 Kumamoto earthquake, a grade 1–4 evacuation triage (Simple Triage and Rapid Treatment for Neonates, START-Neo) was used to determine the evacuation order at a tertiary neonatal intensive care unit (NICU). However, most newborns are classified as grade 2 or 3, which makes it difficult to determine the order of evacuation. A five-category, 0–12 scale (Neonatal Extrication Triage, NEXT) was developed to reflect the medical care provided. This retrospective observational study investigated whether the use of (i) a triage system (vs. random orders) and (ii) NEXT (vs. START-Neo) improved NICU evacuation efficiency. Methods: NEXT and START-Neo were assessed over 49 days. Given that the evacuation was performed in either ascending or descending order of patient severity, an efficient triage system was defined as one that precisely reflected patient severity. The severity of newborn patients at the time of triage assignment was determined using a Neonatal Therapeutic Intervention Scoring System (NTISS). The Total Evacuation Score (TES) was defined as the time integral of the NTISS scores of newborns waiting for evacuation and remaining within the NICU from the start to the completion of the evacuation. The TES was compared between (i) no triage, (ii) NEXT, and (iii) START-Neo. A computer-based evacuation simulation was conducted using all possible combinations of evacuation orders (NEXT and START-Neo) or randomly extracted combinations (no triage). Results: Compared to no-triage, both NEXT and START-Neo led to a reduction in TES throughout the study period. NEXT was superior to START-Neo on 34 of 49 days and showed no difference on 10 days. Conclusion: Triage systems are crucial for improving NICU evacuation efficiency. NEXT, an improved triage system, appears likely to reduce the overall risk of newborns remaining in a damaged NICU before transportation.

In this study, we proposed using Bayesian nonparametric quantile mixed-effects models (BNQMs) to estimate the nonlinear structure of quantiles in hierarchical data. Assuming that a nonlinear function representing a phenomenon of interest cannot be specified in advance, a BNQM can estimate the nonlinear function of quantile features using the basis expansion method. Furthermore, BNQMs adjust the smoothness to prevent overfitting by regularization. We also proposed a Bayesian regularization method using Gaussian process priors for the coefficient parameters of the basis functions, and showed that the problem of overfitting can be reduced when the number of basis functions is excessive for the complexity of the nonlinear structure. Although computational cost is often a problem in quantile regression modeling, BNQMs ensure the computational cost is not too high using a fully Bayesian method. Using numerical experiments, we showed that the proposed model can estimate nonlinear structures of quantiles from hierarchical data more accurately than the comparison models in terms of mean squared error. Finally, to determine the cortisol circadian rhythm in infants, we applied a BNQM to longitudinal data of urinary cortisol concentration collected at Kurume University. The result suggested that infants have a bimodal cortisol circadian rhythm before their biological rhythms are established.

Introduction: Hospitalized neonates are vulnerable to natural and man-made disasters because of their persistent requirement for medical resources and may need to be evacuated to safe locations when electricity and medical gas supply become unreliable. In Japan, a triage system for hospitalized neonates, or the Simple Triage and Rapid Treatment for Neonates, Revised (START-Neo-R), has been used to determine whether neonates are in suitable conditions for transportation. However, this scale is not useful to determine the evacuation order of neonates because a considerable number of evacuees are classified into the same categories. Study Objective: To solve this problem, a novel triage system, Neonatal Extrication Triage (NEXT) was developed. This study tested the validity and reproducibility of both triages and compared them with a standardized prognostic scoring system for hospitalized neonates, the Neonatal Therapeutic Intervention Scoring System (NTISS). Methods: In this retrospective observational study, physicians and nurses independently assessed each neonate hospitalized at a tertiary neonatal intensive care unit (NICU) twice weekly using NEXT and START-Neo-R. The NEXT system comprises six questionnaires regarding medical resources required during transition and transportation, providing composite scores on a 12-point scale. The START-Neo-R classified neonates into five levels based on the severity of disease and dependence on medical care. Inter-rater reliability of both systems was assessed using Cohen's kappa coefficient, whereas the criterion validity with NTISS was assessed using Spearman's correlation coefficient. Results: Overall, 162 neonates were assessed for 49 days, resulting in triage data for 1,079 accumulated patients. Both NEXT scores and START-Neo-R ranks were well-dispersed across different levels without excessive accumulation in specific categories. Inter-rater reliability of NEXT (kappa coefficient, 0.973; 95% confidence interval, 0.969-0.976) and START-Neo-R (kappa coefficient, 0.952; 95% confidence interval, 0.946-0.957) between physicians and nurses was sufficiently high. The correlation coefficient of NEXT and START-Neo-R scores with NTISS scores were 0.889 (P <.001) and 0.850 (P <.001), respectively. Conclusions: Both START-Neo-R and NEXT had good reproducibility and correlation with the severity of neonates indicated by NTISS. With its well-dispersed scores across different levels, the NEXT system might be a powerful tool to determine the priority of evacuation objectively.

MRI provides useful information regarding brain maturation and injury in newborn infants. However, MRI studies are generally restricted during acute phase, resulting in uncertainty around upstream clinical events responsible for subtle cerebral injuries. Time‐resolved near‐infrared spectroscopy non‐invasively provides the reduced scattering coefficient ( μs′ ), which theoretically reflects tissue structural complexity. This study aimed to test whether μs′ values of the newborn head reflected MRI findings.

If the brain structure is assessed at neonatal intensive care units, covert clinical events related with subtle brain injury might be identified. The reduced scattering coefficient of near-infrared light (μ S ’) obtained using time-resolved near-infrared spectroscopy from the forehead of infants is associated with gestational age, body weight and Apgar scores, presumably reflecting subtle changes of the brain related to foetal growth and birth transition. One hundred twenty-eight preterm and term infants were studied to test whether μ S ’ obtained from the head at term-equivalent age is associated with foetal growth, birth transition and nutritional status after birth, which are key independent variables of developmental outcomes. As potential independent variables of μ S ’, birth weight, Apgar scores, age at full enteral feeding and post-conceptional age at the study were assessed to represent foetal growth, birth transition and nutritional status after birth. Subsequently, higher μ S ’ values were associated with higher Apgar scores ( p = 0.003) and earlier establishment of enteral feeding ( p < 0.001). The scattering property of near-infrared light within the neonatal brain might reflect changes associated with birth transition and nutritional status thereafter, which might be used as a non-invasive biomarker to identify covert independent variables of brain injury in preterm infants.

a Tissue and Histopathology Section, b Biostatistics Section, Division of Scientific Data Registry, c Department of Hematology and d Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Science, Nagasaki University, Nagasaki, 852-8523, Japan; and e Department of Pathology, National Hospital Organization Nagasaki Medical Center, Omura, 856-8562, Nagasaki, Japan

Hippocampal atrophy is a proposed biomarker for Alzheimer's disease (AD). Yet the hippocampus—a key structure involved in learning and memory—is vulnerable to pathological deterioration in a number of non-AD conditions. Several modifiable factors are implicated in the pathophysiology of hippocampal atrophy such that primary prevention strategy is a promising strategy for hippocampal atrophy and associated cognitive impairment. Risk or protective factors for hippocampal atrophy include education, diabetes, hypertension, chronic kidney disease, alcohol, hearing loss, and depression. Furthermore, physical activity, healthy diet, and lifelong learning and cognitive training may protect against hippocampal atrophy. Hippocampal atrophy is also implicated in the preclinical phases of AD—e.g., subjective cognitive decline and mild cognitive impairment. Given that cerebrovascular disease and AD share modifiable risk factors related to cognitive decline and dementia, we also discuss the significance of hippocampal atrophy as it relates to cerebrovascular disease and white-matter lesions.

Importance:Weight cycling is associated with the risk of mortality from heart disease, but many studies have not distinguished between simple nonlinear (monotone) weight changes and more complex changes that reflect fluctuations.Objective:To assess whether extreme body weight variation is associated with mortality after controlling for nonlinear weight changes.Design, Setting, and Participants:In this prospective clinical cohort study, 4796 Japanese atomic bomb survivors were examined in the clinic as part of a biennial health examination and research program. The study consisted of a 20-year longitudinal baseline period (July 1, 1958, to June 30, 1978) and subsequent mortality follow-up of 27 years (July 1, 1978, to June 30, 2005) Participants were initially between the ages of 20 and 49 years during the baseline period and, throughout the baseline period, had no diagnoses of cardiovascular disease (CVD) or cancer and attended at least 7 of 10 scheduled examinations. Data analysis was performed from October 16, 2015, to May 13, 2016.Exposures:Residual variability in body mass index (BMI) during the baseline period.Main Outcomes and Measures:Outcomes were mortality from ischemic heart disease, cerebrovascular disease, other CVDs combined, other causes (except cancer), and cancer. Root mean squared error was calculated to capture individual residual variation in BMI after adjustment for baseline BMI trends, and the association of magnitude of residual variation with mortality was calculated as relative risk.Results:In total, 4796 persons (mean [SD] age, 35.0 [7.3] years at first baseline examination; 3252 [67.8%] female; mean [SD] BMI, 21.2 [2.8] at first baseline visit [20.6 (2.4) among men and 21.5 (2.9) among women]) participated in the study. During follow-up, 1550 participants died: 82 (5.3% of all deaths) of ischemic heart disease, 181 (11.7%) of cerebrovascular disease, 186 (12.0%) of other CVDs, 615 (39.7%) of cancer, and 486 (31.3%) of other causes. Magnitude of residual variation in weight was associated with all-cause mortality (relative risk, 1.25 for 1 U of additional variation; 95% CI, 1.06-1.47) and ischemic heart disease mortality (relative risk, 2.49; 95% CI, 1.41-4.38).Conclusions and Relevance:The findings suggest that an association exists between weight variation and heart disease mortality and that weight loss interventions, if deemed to be necessary, should be considered carefully.

We propose a functional classification method with high-dimensional image predictors using a combination of logistic discrimination and basis expansions with sparse principal component analysis (PCA). Our model is an extension of the existing functional generalized linear models with image predictors using functional principal component regression to L1-regularized principal components. This extension enables us to create a more flexible prognostic region that does not depend on the shape of basis functions. Monte Carlo simulations were conducted to examine the method’s efficiency when compared with several possible classification techniques. Our method was shown to be the best in terms of both sensitivity and specificity for detecting the shape of interests and classifying groups. In addition, our model was applied to data on Alzheimer’s disease. Our model detected the prognostic brain region and was used to classify early-stage Alzheimer patients efficiently, based on three-dimensional structural magnetic resonance imaging (sMRI).

AIM To determine the usefulness of assigning narrow-band imaging (NBI) scores for predicting tumor grade and invasion depth in colorectal tumors. METHODS A total of 161 colorectal lesions were analyzed from 138 patients who underwent endoscopic or surgical resection after conventional colonoscopy and magnifying endoscopy with NBI. The relationships between the surface and vascular patterns of the lesions, as visualized with NBI, and the tumor grade and depth of submucosa (SM) invasion were determined histopathologically. Scores were assigned to distinct features of the surface microstructures of tubular and papillary-type lesions. Using a multivariate analysis, a model was developed for predicting the tumor grade and depth of invasion based on NBI-finding scores. RESULTS NBI findings that correlated with a high tumor grade were associated with the “regular/irregular” (P < 0.0001) surface patterns and the “avascular area” pattern (P = 0.0600). The vascular patterns of “disrupted vessels” (P = 0.0714) and “thick vessels” (P = 0.0133) but none of the surface patterns were associated with a depth of invasion of ≥ 1000 μm. In our model, a total NBI-finding score ≥ 1 was indicative of a high tumor grade (sensitivity: 0.97; specificity: 0.24), and a total NBI-finding score ≥ 9 (sensitivity: 0.56; specificity: 1.0) was predictive of a SM invasion depth ≥ 1000 μm. Scores less than these cutoff values signified adenomas and a SM invasion depth < 1000 μm, respectively. Associations were also noted between selected NBI findings and tumor tissue architecture and histopathology. CONCLUSION Our multivariate statistical model for predicting tumor grades and invasion depths from NBI-finding scores may help standardize the diagnosis of colorectal lesions and inform therapeutic strategies.

Background: Although several studies have reported an association between parity and increased risk of stroke, this relationship remains controversial. Aims: The present study aimed to determine whether parity is associated with silent brain infarction (SBI), independent of other confounders. Methods: We analyzed the brain magnetic resonance imaging findings in 576 of community-dwelling older adults with a mean age of 72.1 years. All female participants were asked to provide information regarding the total number of live births, their age at the last parity, and their age at menopause. Results: The prevalence of SBI and the number of infarcts per participant were higher in men than in women. Although all women who had given birth (0, 1-2, 3-4, or 5+ times) exhibited lower age-adjusted odds ratios (ORs) for SBI than men, a significant difference was observed between women with ≧5 births and men after adjustment for common vascular risk factors (OR: .348, 95% confidence interval [95% CI]: .123-.986). Among women who had given birth, the relationship between fertility and SBI was attenuated, but was enhanced after adjustment for age at the last parity (OR: .300, 95% CI: .102-.886). Conclusions: Our findings indicate that fertile women may be protected against SBI or cerebral small vessel disease via the biological effects associated with reproductive activity, and that high fertility may be a marker of protection against SBI. However, late childbearing may blunt protective effects of fertility against SBI.

Background: Our previous study showed that there were significant correlations between the hippocampal atrophy and both of the Rivermead Behavioral Memory Test (RBMT) and Mini-Mental State Examination (MMSE) in community-dwelling elderly subjects (Brain Behav 2016; 7: e00620).

Recent advances in cancer treatment have steadily improved the overall survival rate, and enhancing the quality of life of cancer survivors is the challenge faced at present. One of the major topics in studies on cancer survivors is work-related issues, and the government has been focusing on improving the circumstances of the working population and children. In 2015, the Cancer Control Accelerating Plan set adolescent and young adult(AYA)cancer survivors as the top priority for this plan. Work-related issues of AYA cancer survivors are highly individualized and complicated, mainly because of three characteristics: 1 ) Cancer treatments and/or outpatient follow-ups are accompanied by major life-stage transitions, 2 ) Treatments are prone to be nonstandardized in "rare cancers" or "advanced-stage cancers" and 3 ) Achieving economic independence is difficult because of high medical costs. This article provides some tips for medical professionals working in hospitals on how to support AYA cancer survivors along with their main responsibilities. It also provides an overview of online and offline resources available for supporting this population.

Therapeutic hypothermia is recommended for moderate and severe neonatal encephalopathy, but is being applied to a wider range of neonates than originally envisaged. To examine the clinical use of therapeutic hypothermia, data collected during the first 3 years (2012–2014) of the Baby Cooling Registry of Japan were analysed. Of 485 cooled neonates, 96.5% were ≥36 weeks gestation and 99.4% weighed ≥1,800 g. Severe acidosis (pH < 7 or base deficit ≥16 mmol/L) was present in 68.9%, and 96.7% required resuscitation for >10 min. Stage II/III encephalopathy was evident in 88.3%; hypotonia, seizures and abnormal amplitude-integrated electroencephalogram were observed in the majority of the remainder. In-hospital mortality was 2.7%; 90.7% were discharged home. Apgar scores and severity of acidosis/encephalopathy did not change over time. The time to reach the target temperature was shorter in 2014 than in 2012. The proportion undergoing whole-body cooling rose from 45.4% to 81.6%, while selective head cooling fell over time. Mortality, duration of mechanical ventilation and requirement for tube feeding at discharge remained unchanged. Adherence to standard cooling protocols was high throughout, with a consistent trend towards cooling being achieved more promptly. The mortality rate of cooled neonates was considerably lower than that reported in previous studies.

Background: Physical inactivity is one of the modifiable risk factors for hippocampal atrophy and Alzheimer's disease. We investigated the relationship between physical activity, hippocampal atrophy, and memory using structural equation modeling (SEM).Materials and Methods: We examined 213 community-dwelling elderly subjects (99 men and 114 women with a mean age of 68.9years) without dementia or clinically apparent depression. All participants underwent Mini-Mental State Examination (MMSE) and Rivermead Behavioral Memory Test (RBMT). Physical activities were assessed with a structured questionnaire. We evaluated the degree of hippocampal atrophy (z-scorereferred to as ZAdvance hereafter), using a free software programthe voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) based on statistical parametric mapping 8 plus Diffeomorphic Anatomical Registration Through an Exponentiated Lie algebra.Results: Routine magnetic resonance imaging findings were as follows: silent brain infarction, n=24 (11.3%); deep white matter lesions, n=72 (33.8%); periventricular hyperintensities, n=35 (16.4%); and cerebral microbleeds, n=14 (6.6%). Path analysis based on SEM indicated that the direct paths from leisure-time activity to hippocampal atrophy (=-.18, p<.01) and from hippocampal atrophy to memory dysfunction (RBMT) (=-.20, p<.01) were significant. Direct paths from hippocampus gray matter volume to RBMT and MMSE were highly significant, while direct paths from whole brain gray matter volume to RBMT and MMSE were not significant. The presented SEM model fit the data reasonably well.Conclusion: Based on the present SEM analysis, we found that hippocampal atrophy was associated with age and leisure-time physical inactivity, and hippocampal atrophy appeared to cause memory dysfunction, although we are unable to infer a causal or temporal association between hippocampal atrophy and memory dysfunction from the present observational study.

BACKGROUND AND PURPOSE:The purpose of this study was to determine the complex associations among chronic kidney disease (CKD), subclinical brain infarction (SBI), and cognitive impairment. METHODS:We used structural equation modeling (SEM) to examine the complex relationships among CKD, SBI, and cognitive function with Mini-Mental State Examination (MMSE; global function) and modified Stroop test (executive function) in a population-based cohort of 560 non-demented elderly subjects. RESULTS:Path analysis based on SEM revealed that the direct paths from estimated glomerular filtration rate (eGFR) to SBI and from SBI to executive function were significant (β = -.10, P = .027, and β = .16, P < .001, respectively). Furthermore, the direct path from eGFR to executive function was also significant (β = -.12, P = .006), indicating that the effects of CKD on executive function are independent of SBI. The direct paths from age and education to global cognitive function were highly significant (β = -.17 and .22, respectively, P < .001), whereas the direct path from eGFR to MMSE was not significant. CONCLUSIONS:Our findings indicate that CKD confers a risk of vascular cognitive impairment or executive dysfunction through mechanisms dependent and independent of SBI. Treating CKD may be a potential strategy to protect against vascular cognitive impairment or executive dysfunction in healthy elderly subjects.

Adult patients frequently suffer from serious respiratory complications during therapeutic hypothermia. During therapeutic hypothermia, respiratory gases are humidified close to saturated vapor at 37°C (44 mg/L) despite that saturated vapor reduces considerably depending on temperature reduction. Condensation may cause serious adverse events, such as bronchial edema, mucosal dysfunction, and ventilator-associated pneumonia during cooling. To determine clinical variables associated with inadequate humidification of respiratory gases during cooling, humidity of inspiratory gases was measured in 42 cumulative newborn infants who underwent therapeutic hypothermia. Three humidifier settings of 37-default (chamber outlet, 37°C; distal circuit, 40°C), 33.5-theoretical (chamber outlet, 33.5°C; distal circuit, 36.5°C), and 33.5-adjusted (optimized setting to achieve 36.6 mg/L using feedback from a hygrometer) were tested to identify independent variables of excessively high humidity >40.7 mg/L and low humidity <32.9 mg/L. The mean (SD) humidity at the Y-piece was 39.2 (5.2), 33.3 (4.1), and 36.7 (1.2) mg/L for 37-default, 33.5-theoretical, and 33.5-adjusted, respectively. The incidence of excessive high humidity was 10.3% (37-default, 31.0%; 33.5-theoretical, 0.0%; 33.5-adjusted, 0.0%), which was positively associated with the use of a counter-flow humidifier (p < 0.001), 37-default (compared with 33.5-theoretical and 33.5-adjusted, both p < 0.001) and higher fraction of inspired oxygen (p = 0.003). The incidence of excessively low humidity was 17.5% (37-default, 7.1%; 33.5-theoretical, 45.2%; 33.5-adjusted, 0.0%), which was positively associated with the use of a pass-over humidifier and 33.5-theoretical (both p < 0.001). All patients who used a counter-flow humidifier achieved the target gas humidity at the Y-piece (36.6 ± 0.5 mg/L) required for 33.5-adjusted with 33.5-theoretical. During cooling, 37-default is associated with excessively high humidity, whereas 33.5-theoretical leads to excessively low humidity. Future studies are needed to assess whether a new regimen with optimized Y-piece temperature and humidity control reduces serious respiratory adverse events during cooling.

Regional brain sizes of very-preterm infants at term-equivalent age differ from those of term-born peers, which have been linked with later cognitive impairments. However, dependence of regional brain volume loss on gestational age has not been studied in detail. To investigate the spatial pattern of brain growth in neonates without destructive brain lesions, head MRI of 189 neonates with a wide range of gestational age (24–42 weeks gestation) was assessed using simple metrics measurements. Dependence of MRI findings on gestational age at birth (Agebirth) and the corrected age at MRI scan (AgeMRI) were assessed. The head circumference was positively correlated with AgeMRI, but not Agebirth. The bi-parietal width, deep grey matter area and the trans-cerebellar diameter were positively correlated with both Agebirth and AgeMRI. The callosal thickness (positive), atrial width of lateral ventricle (negative) and the inter-hemispheric distance (negative) were exclusively correlated with Agebirth. The callosal thickness and cerebral/cerebellar transverse diameters showed predominant dependence on Agebirth over AgeMRI, suggesting that brain growth after preterm-birth was considerably restricted or even became negligible compared with that in utero. Such growth restriction after preterm birth may extensively affect relatively more matured infants, considering the linear relationships observed between brain sizes and Agebirth.

MRI of preterm infants at term commonly reveals subtle brain lesions such as diffuse white matter injury, which are linked with later cognitive impairments. The timing and mechanism of such injury remains unclear. The reduced scattering coefficient of near-infrared light (μ s ’) has been shown to correlate linearly with gestational age in neonates. To identify clinical variables associated with brain μ s ’, 60 preterm and full-term infants were studied within 7 days of birth. Dependence of μ s ’ obtained from the frontal head on clinical variables was assessed. In the univariate analysis, smaller μ s ’ was associated with antenatal glucocorticoid, emergency Caesarean section, requirement for mechanical ventilation, smaller gestational age, smaller body sizes, low 1- and 5-minute Apgar scores, higher cord blood pH and PO 2 , and higher blood HCO 3 − at the time of study. Multivariate analysis revealed that smaller gestational age, requirement for mechanical ventilation, and higher HCO 3 − at the time of study were correlated with smaller μ s ’. Brain μ s ’ depended on variables associated with physiological maturation and pathological conditions of the brain. Further longitudinal studies may help identify pathological events and clinical conditions responsible for subtle brain injury and subsequent cognitive impairments following preterm birth.