Three-dimensional collective charge excitations in electron-doped copper oxide superconductors.

High-temperature copper oxide superconductors consist of stacked CuO2 planes, with electronic band structures and magnetic excitations that are primarily two-dimensional1,2, but with superconducting coherence that is three-dimensional. This dichotomy highlights the importance of out-of-plane charge dynamics, which has been found to be incoherent in the normal state3,4 within the limited range of momenta accessible by optics. Here we use resonant inelastic X-ray scattering to explore the charge dynamics across all three dimensions of the Brillouin zone. Polarization analysis of recently discovered collective excitations (modes) in electron-doped copper oxides5-7 reveals their charge origin, that is, without mixing with magnetic components5-7. The excitations disperse along both the in-plane and out-of-plane directions, revealing its three-dimensional nature. The periodicity of the out-of-plane dispersion corresponds to the distance between neighbouring CuO2 planes rather than to the crystallographic c-axis lattice constant, suggesting that the interplane Coulomb interaction is responsible for the coherent out-of-plane charge dynamics. The observed properties are hallmarks of the long-sought 'acoustic plasmon', which is a branch of distinct charge collective modes predicted for layered systems8-12 and argued to play a substantial part in mediating high-temperature superconductivity10-12.

Perioperative outcomes of laparoscopic low anterior resection using ArtiSential® versus robotic approach in patients with rectal cancer: a propensity score matching analysis.

BACKGROUND: Total mesorectal excision using conventional straight fixed devices may be technically difficult because of the narrow and concave pelvis. Several laparoscopic articulating tools have been introduced as an alternative to robotic systems. The aim of this study was to compare perioperative outcomes between laparoscopic low anterior resection using ArtiSential® and robot-assisted surgery for rectal cancer. METHODS: This retrospective study included 682 patients who underwent laparoscopic or robotic low anterior resection  for rectal cancer from September 2018 to December 2021. Among them, 82 underwent laparoscopic surgery using ArtiSential® (group A) and 201 underwent robotic surgery (group B). A total of 73 [group A; 66.37 ± 11.62; group B 65.79 ± 11.34] patients were selected for each group using a propensity score matching analysis. RESULTS: There was no significant difference in the baseline characteristics between group A and B. Mean operative time was longer in group B than A (163.5 ± 61.9 vs 250.1 ± 77.6 min, p < 0.001). Mean length of hospital stay was not significantly different between the two groups (6.2 ± 4.7 vs 6.7 ± 6.1 days, p = 0.617). Postoperative complications, reoperation, and readmission within 30 days after surgery were similar between the two groups. Pathological findings revealed that the circumferential resection margins were above 10 mm in both groups (11.00 ± 7.47 vs 10.17 ± 6.25 mm, p = 0.960). At least 12 lymph nodes were sufficiently harvested, with no significant difference in the number harvested between the groups (20.5 ± 9.9 vs 19.7 ± 7.3, p = 0.753). CONCLUSIONS: Laparoscopic low anterior resection using ArtiSential® can achieve acceptable clinical and oncologic outcomes. ArtiSential®, a multi-joint and articulating device, may serve a feasible alternative approach to robotic surgery in rectal cancer.

Imaging findings of granular cell tumours of the head and neck.

AIM: To review the imaging characteristics of granular cell tumours in the head and neck and assess their associations with pathological findings. MATERIALS AND METHODS: Eleven patients (10 [91%] women, mean age 43 years) with histopathologically confirmed granular cell tumours were included in this study. Preoperative imaging studies were performed, including computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound. The location of the tumours, their imaging features, and histopathological findings were analysed. RESULTS: Among the 11 granular cell tumours, four (36%), three (27%), and two (18%) tumours were found in the submucosal layer, subcutaneous layer, and intramuscular area, respectively. On CT, all tumours exhibited homogeneous iso-attenuating enhancement compared with adjacent muscle, and nine out of the 11 tumours (81%) demonstrated well-defined margins. On T2-weighted imaging (T2WI), four out of five tumours (80%) demonstrated iso-signal intensity compared with adjacent muscles, and four tumours (80%) exhibited homogeneous signal intensity. The apparent diffusion coefficient (ADC) values ranged from 0.68-0.81 × 10-3 mm2/s. Histopathological examination revealed densely packed tumour cells with variable amounts of fibrous stroma. CONCLUSION: Granular cell tumours were characterised by well-defined and iso-signals on T2WI and low mean ADC values, and were predominantly located in the submucosal, subcutaneous, or intramuscular areas in middle-aged women. The characteristic locations, demographic characteristics, and imaging findings can help to differentiate granular cell tumours from other soft-tissue tumours in the head and neck.

Sleep impairment in patients with empty nose syndrome.

BACKGROUND: Empty nose syndrome (ENS) is characterized by paradoxical nasal obstruction that usually occurs after turbinate surgery. Patients with ENS may also experience significant psychiatric symptoms and sleep dysfunction, which negatively affect the quality of life of affected subjects. This study aimed to evaluate sleep impairment and sleepiness in patients with ENS. METHODS: Patients with ENS and control participants were recruited prospectively. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Epworth Sleepiness Scale (EpSS), and modified sleep quality index (MSQI) were used to evaluate the participants before and after nasal surgery. RESULTS: Forty-eight patients with ENS and forty-eight age- and sex-matched control subjects were enrolled. The SNOT-25, ENS6Q, EpSS, and MSQI scores in the ENS group were all significantly higher than those in the control group before and after surgery. After surgery, ENS patients all exhibited significant improvements in SNOT-25, ENS6Q, EpSS, and MSQI scores. Regression analysis revealed that SNOT-25 score was a significant predictor of EpSS and MSQI in preoperative evaluations. ENS patients experiencing daytime sleepiness suffered from significantly more "dryness of nose" and "suffocation" than those not experiencing daytime sleepiness. CONCLUSIONS: Patients with ENS experienced significantly impaired sleep quality and sleepiness. Nasal reconstruction surgery improved the sleep quality of ENS patients. The severity of sleep dysfunction is associated with the severity of ENS symptoms. Recognizing individuals with significant sleep impairment and sleepiness and providing appropriate management are critical issues for ENS patients.

Familial risk for endometriosis and its interaction with smoking, age at menarche and body mass index: a population-based cohort study among siblings.

OBJECTIVE: To quantify familial risk of endometriosis among full siblings and examine interactions between family history and smoking, age at menarche or body mass index (BMI). DESIGN, SETTING AND POPULATION: Population-based nationwide cohort study. METHODS: Using data from the Korean National Health Insurance and Screening Programme databases on kinship, healthcare utilisation, lifestyle and anthropometrics, we identified 2 109 288 women with full siblings and their environmental risk factors from 2002 to 2018. Familial risks were estimated using Cox proportional-hazards models, represented as incidence risk ratios (IRR) with 95% CI. Interaction between family history and smoking, age at menarche or BMI were assessed on an additive scale. MAIN OUTCOME MEASURES: IRR of endometriosis among women with and without affected siblings. RESULTS: From 19 195 women with affected siblings, 1126 developed endometriosis with an incidence of 35.45/10 000 person-years. Familial risk of endometriosis with versus without affected siblings was increased to IRR 2.75 (95% CI 2.25-3.36), and the highest risk was with affected twins (IRR 6.98; 95% CI 4.19-11.62). Women with both a family history and either smoking, early menarche or low BMI had a significantly higher risk of endometriosis compared with the general population and can be regarded as a high-risk group, the IRRs were 4.28 (95% CI 2.43-7.55), 3.47 (95% CI 2.82-4.26) and 3.09 (95% CI 2.68-3.56), respectively. Substantial effect modification of the associations was noted by smoking and early menarche, as their combined risk with family history exceeded the sum of their individual risks, which was also statistically significant. CONCLUSION: Genetic factors are the primary contributor to the familial aggregation of endometriosis. Significant gene-environment interaction exists between family history and smoking or early menarche. TWEETABLE ABSTRACT: Significant gene-environment interaction exists between family history of endometriosis and smoking or early menarche.

Early cleaving embryos result in blastocysts with increased aspartate and glucose consumption, which exhibit different metabolic gene expression that persists in placental and fetal tissues.

OBJECTIVES: Using time-lapse microscopy, previous research has shown that IVF mouse embryos that cleave earlier at the first division ('fast') develop into blastocysts with increased glucose consumption and lower likelihood of post-implantation loss as compared to slower cleaving embryos ('slow'). Further, metabolomics analysis employing LC-MS conducted on groups of 'fast' blastocysts revealed that more aspartate was consumed. With the worldwide adoption of single blastocyst transfer as the standard of care, the need for quantifiable biomarkers of viability, such as metabolism of specific nutrients, would greatly assist in embryo selection for transfer. METHODS: Here we describe the development of a targeted enzymatic assay to quantitate aspartate uptake of single blastocysts. RESULTS: Results demonstrate that the rates of aspartate and glucose consumption were significantly higher in individual 'fast' blastocysts. Blastocysts, together with placental and fetal liver tissue collected following transfer, were analysed for the expression of genes involved in aspartate and carbohydrate metabolism. In 'fast' blastocysts, expressions of B3gnt5, Slc2a1, Slc2a3, Got1 and Pkm2 were found to be significantly higher. In placental tissue derived from 'fast' blastocysts, expression of Slc2a1, Got1 and Pkm2 were significantly higher, while levels of Got1 and Pkm2 were lower in fetal liver tissue compared to tissue from 'slow' blastocysts. CONCLUSIONS: Importantly, this study shows that genes regulating aspartate and glucose metabolism were increased in blastocysts that have higher viability, with differences maintained in resultant placentae and fetuses. Consequently, the analysis of aspartate uptake in combination with glucose represents biomarkers of development and may improve embryo selection efficacy and pregnancy rates.

PIN1 is a new therapeutic target of craniosynostosis.

Gain-of-function mutations in fibroblast growth factor receptors (FGFRs) cause congenital skeletal anomalies, including craniosynostosis (CS), which is characterized by the premature closure of craniofacial sutures. Apert syndrome (AS) is one of the severest forms of CS, and the only treatment is surgical expansion of prematurely fused sutures in infants. Previously, we demonstrated that the prolyl isomerase peptidyl-prolyl cis-trans isomerase interacting 1 (PIN1) plays a critical role in mediating FGFR signaling and that Pin1+/- mice exhibit delayed closure of cranial sutures. In this study, using both genetic and pharmacological approaches, we tested whether PIN1 modulation could be used as a therapeutic regimen against AS. In the genetic approach, we crossbred Fgfr2S252W/+, a mouse model of AS, and Pin1+/- mice. Downregulation of Pin1 gene dosage attenuated premature cranial suture closure and other phenotypes of AS in Fgfr2S252W/+ mutant mice. In the pharmacological approach, we intraperitoneally administered juglone, a PIN1 enzyme inhibitor, to pregnant Fgfr2S252W/+ mutant mice and found that this treatment successfully interrupted fetal development of AS phenotypes. Primary cultured osteoblasts from Fgfr2S252W/+ mutant mice expressed high levels of FGFR2 downstream target genes, but this phenotype was attenuated by PIN1 inhibition. Post-translational stabilization and activation of Runt-related transcription factor 2 (RUNX2) in Fgfr2S252W/+ osteoblasts were also attenuated by PIN1 inhibition. Based on these observations, we conclude that PIN1 enzyme activity is important for FGFR2-induced RUNX2 activation and craniofacial suture morphogenesis. Moreover, these findings highlight that juglone or other PIN1 inhibitors represent viable alternatives to surgical intervention for treatment of CS and other hyperostotic diseases.

Effect of cholinergic pathway disruption on cortical and subcortical volumes in subcortical vascular cognitive impairment.

BACKGROUND AND PURPOSE: The brain's cholinergic network has various interconnections with the cortical and subcortical structures. Disruption of cholinergic pathways by white matter hyperintensities (WMH) may cause pathologic changes within brain regions. Thus, WMH may represent an important pathological contributor to subcortical vascular cognitive impairment (scVCI). We aimed to investigate associations between the magnitude of WMH and volumetric changes in cortical and subcortical regions innervated by cholinergic neurons in patients with scVCI. METHODS: We enrolled patients with scVCI, defined as moderate to severe WMH or multiple (>2) lacunar infarcts outside the brainstem. Cholinergic Pathway HyperIntensities Scale (CHIPS) scores were used to quantify the magnitude of cholinergic pathway disruptions by WMH. We measured cortical thickness and subcortical volumes of 11 brain regions innervated by cholinergic neurons. Partial correlation of brain region volumes with total CHIPS scores was obtained using multiple linear regression. RESULTS: In total, 80 patients were enrolled. The mean age was 78.4 ± 6.5 years, median Mini-Mental State Examination score was 17 (interquartile range, 13-20) and median CHIPS score was 11 (interquartile range, 7-17). CHIPS scores were positively correlated with subcortical volumes of the putamen (r' = 0.46, P = 0.002) and pallidum (r' = 0.45, P = 0.002), and were negatively associated with inferior temporal (r' = -0.35, P = 0.002) and medial orbitofrontal (r' = -0.32, P = 0.002) cortical thickness. CONCLUSION: Our study suggested that WMH in cholinergic pathways may contribute to volumetric structural changes in cortical and subcortical structures innervated by cholinergic neurons.

The association between vaginal bacterial composition and miscarriage: a nested case-control study.

OBJECTIVE: To characterise vaginal bacterial composition in early pregnancy and investigate its relationship with first and second trimester miscarriages. DESIGN: Nested case-control study. SETTING: Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London. POPULATION: 161 pregnancies: 64 resulting in first trimester miscarriage, 14 in second trimester miscarriage and 83 term pregnancies. METHODS: Prospective profiling and comparison of vaginal bacteria composition using 16S rRNA gene-based metataxonomics from 5 weeks' gestation in pregnancies ending in miscarriage or uncomplicated term deliveries matched for age, gestation and body mass index. MAIN OUTCOME MEASURES: Relative vaginal bacteria abundance, diversity and richness. Pregnancy outcomes defined as first or second trimester miscarriage, or uncomplicated term delivery. RESULTS: First trimester miscarriage associated with reduced prevalence of Lactobacillus spp.-dominated vaginal microbiota classified using hierarchical clustering analysis (65.6 versus 87.7%; P = 0.005), higher alpha diversity (mean Inverse Simpson Index 2.5 [95% confidence interval 1.8-3.0] versus 1.5 [1.3-1.7], P = 0.003) and higher richness 25.1 (18.5-31.7) versus 16.7 (13.4-20), P = 0.017), compared with viable pregnancies. This was independent of vaginal bleeding and observable before first trimester miscarriage diagnosis (P = 0.015). Incomplete/complete miscarriage associated with higher proportions of Lactobacillus spp.-depleted communities compared with missed miscarriage. Early pregnancy vaginal bacterial stability was similar between miscarriage and term pregnancies. CONCLUSIONS: These findings associate the bacterial component of vaginal microbiota with first trimester miscarriage and indicate suboptimal community composition is established in early pregnancy. While further studies are required to elucidate the mechanism, vaginal bacterial composition may represent a modifiable risk factor for first trimester miscarriage. TWEETABLE ABSTRACT: Vaginal bacterial composition in first trimester miscarriage is associated with reduced Lactobacillus spp. abundance and is independent of vaginal bleeding.

Development of Novel Continuous and Interval Exercise Programs by Applying the FITT-VP Principle in Dogs.

Although proper exercise training induces positive physiological effects, improper exercise can lead to injury, fatigue, and poor performance. The frequency, intensity, time/duration, type, volume, and progression (FITT-VP) are the essential components of exercise training to maintain or improve physical fitness and health. The purpose of this study was to develop specific exercise programs by applying the FITT-VP principle and to examine the effects on heart rate (HR) and hematological and biochemical parameters in dogs. The healthy male Beagles (n = 4) included in this study performed continuous and interval exercises, comprising 12 protocols. The HR monitoring elicited an affirmative response to activities but varied depending on the protocols. The hematologic parameters (e.g., red blood cell count, white blood cell count, hemoglobin, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration) were within the reference ranges both before and after exercise. The creatine kinase level significantly increased, and the cholesterol level decreased after exercises. In conclusion, the continuous and interval exercise program elicits an appropriate HR reaction, has no adverse effects on the serum parameters, and provides valuable insight for healthcare in dogs.

MicroRNA miR-252 targets mbt to control the developmental growth of Drosophila.

Developmental growth is an intricate process involving the coordinated regulation of the expression of various genes, and microRNAs (miRNAs) play crucial roles in diverse processes throughout animal development. The ecdysone-responsive miRNA, miR-252, is normally upregulated during the pupal and adult stages of Drosophila development. Here, we found that overexpression of miR-252 in the larval fat body decreased total tissue mass through a reduction in both cell size and cell number, causing a concomitant decrease in larval size. Furthermore, miR-252 overexpression led to a delayed larval-to-pupal transition with defective anterior spiracle eversion, as well as a decrease in adult size and mass. Conversely, adult flies lacking miR-252 showed an increase in mass compared with control flies. We found that miR-252 directly targeted mbt, encoding a p21-activated kinase, to repress its expression. Notably, co-overexpression of mbt rescued the developmental and growth defects associated with miR-252 overexpression, indicating that mbt is a biologically relevant target of miR-252. Overall, our data support a role for the ecdysone/miR-252/mbt regulatory axis in growth control during Drosophila development.

Left ventricular ejection fraction is associated with small vessel disease in ischaemic stroke patients.

BACKGROUND AND PURPOSE: The purpose was to evaluate the association between the left ventricular ejection fraction (LVEF) and cerebral small vessel disease (cSVD) in ischaemic stroke patients. METHODS: Consecutive first-ever ischaemic stroke patients between 2010 and 2013 were included. White matter hyperintensity (WMH) volumes were rated using both the Fazekas score and quantitative methods on fluid-attenuated inversion recovery images. As spectra of cSVD, lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVSs) were also evaluated. To assess the dose-response relationship between LVEF and cSVD, the burdens of each radiological marker and the total cSVD score were rated. RESULTS: A total of 841 patients were included [median WMH volume 2.98 (1.22-10.50) ml; the frequencies of lacunes, CMBs and moderate to severe EPVSs were 38%, 31% and 35%, respectively]. In the multivariate analysis about predictors of WMH volumes, the LVEF (B = -0.052, P < 0.001) remained significant after adjusting for confounders. LVEF was also a predictor of lacunes [adjusted odds ratio (aOR) 0.978, P = 0.012], CMBs (aOR = 0.96, P < 0.001) and moderate to severe EPVSs (aOR = 0.94, P < 0.001) after adjusting for their confounders. The LVEF values were negatively correlated with the burdens of lacunes (P = 0.026), CMBs (P < 0.001) and EPVSs (P = 0.002). The total cSVD score also showed a negative association with LVEF in a dose-response manner (P < 0.001). CONCLUSIONS: The burden of cSVD is negatively correlated with the LVEF in a dose-response manner. Our results suggest clues for further studies about determining the pathophysiology of cSVD.

Prospective observational study of vaginal microbiota pre- and post-rescue cervical cerclage.

OBJECTIVE: To investigate the relation between vaginal microbiota composition and outcome of rescue cervical cerclage. DESIGN: Prospective observational study. SETTING: Queen Charlotte's and Chelsea Hospital, London. POPULATION: Twenty singleton pregnancies undergoing a rescue cervical cerclage. METHODS: Vaginal microbiota composition was analysed in women presenting with a dilated cervix and exposed fetal membranes before and 10 days following rescue cervical cerclage and was correlated with clinical outcomes. MAIN OUTCOME MEASURES: Composition of vaginal bacteria was characterised by culture-independent next generation sequencing. Successful cerclage was defined as that resulting in the birth of a neonate discharged from hospital without morbidity. Unsuccessful cerclage was defined as procedures culminating in miscarriage, intrauterine death, neonatal death or significant neonatal morbidity. RESULTS: Reduced Lactobacillus spp. relative abundance was observed in 40% of cases prior to rescue cerclage compared with 10% of gestation age-matched controls (8/20, 40% versus 3/30, 10%, P = 0.017). Gardnerella vaginalis was over-represented in women presenting with symptoms (3/7, 43% versus 0/13, 0%, P = 0.03, linear discriminant analysis, LDA (log 10) and cases culminating in miscarriage (3/6, 50% versus 0/14, 0%, P = 0.017). In the majority of cases (10/14, 71%) bacterial composition was unchanged following cerclage insertion and perioperative interventions. CONCLUSIONS: Reduced relative abundance of Lactobacillus spp. is associated with premature cervical dilation, whereas high levels of G. vaginalis are associated with unsuccessful rescue cerclage cases. The insertion of a rescue cerclage does not affect the underlying bacterial composition in the majority of cases. TWEETABLE ABSTRACT: Preterm cervical dilatation associates with reduced Lactobacillus spp. Presence of Gardnerella vaginalis predicts rescue cerclage failure.

Molecular and cellular mechanisms of learning disabilities: a focus on NF1.

Neurofibromatosis Type I (NF1) is a single-gene disorder characterized by a high incidence of complex cognitive symptoms, including learning disabilities, attention deficit disorder, executive function deficits, and motor coordination problems. Because the underlying genetic cause of this disorder is known, study of NF1 from a molecular, cellular, and systems perspective has provided mechanistic insights into the etiology of higher-order cognitive symptoms associated with the disease. In particular, studies of animal models of NF1 indicated that disruption of Ras regulation of inhibitory networks is critical to the etiology of cognitive deficits associated with NF1. Animal models of Nf1 identified mechanisms and pathways that are required for cognition, and represent an important complement to the complex neuropsychological literature on learning disabilities associated with this condition. Here, we review findings from NF1 animal models and human populations affected by NF1, highlighting areas of potential translation and discussing the implications and limitations of generalizing findings from this single-gene disease to idiopathic learning disabilities.

Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma.

Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT + RT; RT + CT) and concurrent modalities (CCRT; CCRT + CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P = 0.027), prognostic index for NK/T-cell lymphoma (PINK) (P = 0.026) and types of initial treatment (P = 0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P = 0.021) and PINK-EBV DNA (PINK-E) (P = 0.002) significantly impacted on PFS; whereas ECOG performance score (P = 0.008) and stage (P < 0.001) significantly impacted on OS. For comparing CCRT ± CT and sequential CT + RT, CCRT ± CT patients (n = 190) were similar to sequential CT + RT patients (n = 54) in all evaluated clinicopathologic parameters except two significantly superior features (higher proportion of undetectable circulating EBV DNA on diagnosis and lower PINK-E scores). Despite more favorable pre-treatment characteristics, CCRT ± CT patients had CR rate, PFS and OS comparable with sequential CT + RT patients on multivariate and Cox regression analyses. Conclusions: In stage I/II NK/T-cell lymphomas, when effective chemotherapeutic regimens were used, CCRT and sequential CT + RT gave similar outcome.

Modifiable risk factors in the first 1000 days for subsequent risk of childhood overweight in an Asian cohort: significance of parental overweight status.

BACKGROUND/OBJECTIVE: Many studies have identified early-life risk factors for subsequent childhood overweight/obesity, but few have evaluated how they combine to influence risk of childhood overweight/obesity. We examined associations, individually and in combination, of potentially modifiable risk factors in the first 1000 days after conception with childhood adiposity and risk of overweight/obesity in an Asian cohort. METHODS: Six risk factors were examined: maternal pre-pregnancy overweight/obesity (body mass index (BMI) ⩾25 kg m-2), paternal overweight/obesity at 24 months post delivery, maternal excessive gestational weight gain, raised maternal fasting glucose during pregnancy (⩾5.1 mmol l-1), breastfeeding duration <4 months and early introduction of solid foods (<4 months). Associations between number of risk factors and adiposity measures (BMI, waist-to-height ratio (WHtR), sum of skinfolds (SSFs), fat mass index (FMI) and overweight/obesity) at 48 months were assessed using multivariable regression models. RESULTS: Of 858 children followed up at 48 months, 172 (19%) had none, 274 (32%) had 1, 244 (29%) had 2, 126 (15%) had 3 and 42 (5%) had ⩾4 risk factors. Adjusting for confounders, significant graded positive associations were observed between number of risk factors and adiposity outcomes at 48 months. Compared with children with no risk factors, those with four or more risk factors had s.d. unit increases of 0.78 (95% confidence interval 0.41-1.15) for BMI, 0.79 (0.41-1.16) for WHtR, 0.46 (0.06-0.83) for SSF and 0.67 (0.07-1.27) for FMI. The adjusted relative risk of overweight/obesity in children with four or more risk factors was 11.1(2.5-49.1) compared with children with no risk factors. Children exposed to maternal pre-pregnancy (11.8(9.8-13.8)%) or paternal overweight status (10.6(9.6-11.6)%) had the largest individual predicted probability of child overweight/obesity. CONCLUSIONS: Early-life risk factors added cumulatively to increase childhood adiposity and risk of overweight/obesity. Early-life and preconception intervention programmes may be more effective in preventing overweight/obesity if they concurrently address these multiple modifiable risk factors.

Which anthropometric measures best reflect neonatal adiposity?

BACKGROUND: Studying the determinants and the long-term consequences of fetal adipose accretion requires accurate assessment of neonatal body composition. In large epidemiological studies, in-depth body composition measurement methods are usually not feasible for cost and logistical reasons, and there is a need to identify anthropometric measures that adequately reflect neonatal adiposity. METHODS: In a multiethnic Asian mother-offspring cohort in Singapore, anthropometric measures (weight, length, abdominal circumference, skinfold thicknesses) were measured using standardized protocols in newborn infants, and anthropometric indices (weight/length, weight/length2 (body mass index, BMI), weight/length3 (ponderal index, PI)) derived. Neonatal total adiposity was measured using air displacement plethysmography (ADP) and abdominal adiposity using magnetic resonance imaging (MRI). Correlations of the anthropometric measures with ADP- and MRI-based adiposity were assessed using Pearson's correlation coefficients (rp), including in subsamples stratified by sex and ethnicity. RESULTS: Study neonates (n=251) had a mean (s.d.) age of 10.2 (2.5) days. Correlations between ADP-based fat mass (ADPFM) and anthropometric measures were moderate (rp range: 0.44-0.67), with the strongest being with weight/length, weight, BMI and sum of skinfolds (rp=0.67, 0.66, 0.62, 0.62, respectively, all P<0.01). All anthropometric measures except skinfold thicknesses correlated more strongly with ADP-based fat-free mass than ADPFM, indicating that skinfold measures may have more discriminative power in terms of neonatal total body adiposity. For MRI-based measures, weight and weight/length consistently showed strong positive correlations (rp⩾0.7) with abdominal adipose tissue compartments. These correlations were consistent in boys and girls, across different ethnic groups, and when conventional determinants of neonatal adiposity were adjusted for potential confounding. Abdominal circumference was not strongly associated with ADPFM or abdominal fat mass. CONCLUSIONS: Simple anthropometric measures (weight and weight/length) correlated strongly with neonatal adiposity, with some evidence for greater discriminative power for skinfold measures. These simple measures could be of value in large epidemiological studies.

Female adiposity and time-to-pregnancy: a multiethnic prospective cohort.

STUDY QUESTION: Are higher overall and central adiposity associated with reduced fecundability, measured by time-to-pregnancy (TTP), in Asian women? SUMMARY ANSWER: Higher overall adiposity, but not central adiposity, was associated with longer TTP in Asian women. WHAT IS KNOWN ALREADY: High body mass index (BMI) has been associated with a longer TTP, although the associations of body composition and distribution with TTP are less clear. There are no previous studies of TTP in Asian women, who have a relatively higher percentage of body fat and abdominal fat at relatively lower BMI. STUDY DESIGN, SIZE, DURATION: Prospective preconception cohort using data from 477 Asian (Chinese, Malay and Indian) women who were planning to conceive and enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) study, 2015-2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women's mean age was 30.7 years. Overall adiposity was assessed by BMI, sum of 4-site skinfold thicknesses (SFT) and total body fat percentage (TBF%, measured using air displacement plethysmography); central adiposity was assessed by waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and A body Shape Index (ABSI). Pregnancy occurring within one year from recruitment was ascertained by ultrasonography. Those who did not conceive within one year of recruitment, were lost to follow-up, or initiated fertility treatment were censored. TTP was measured in cycles. Discrete-time proportional hazards models were used to estimate the fecundability ratio (FR) and 95% confidence interval (CI) for each anthropometric measure in association with fecundability, adjusting for confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to women with a normal BMI of 18.5-22.9 kg/m2, women with higher BMI of 23-27.4 and ≥27.5 kg/m2 showed lower FR of 0.66 (95% CI 0.45, 0.97) and 0.53 (0.31, 0.89), respectively. Compared to women in the lowest quartile of SFT (25-52.9 mm), those in the highest quartile of ≥90.1 mm showed lower FR of 0.58 (95% CI 0.36, 0.95). Compared to women in the lowest quartile of TBF% (13.6-27.2%), those in the upper two quartiles of 33.0-39.7% and ≥39.8% showed lower FR of 0.56 (95% CI 0.32, 0.98) and 0.43 (0.24, 0.80), respectively. Association of high BMI with reduced fecundability was particularly evident among nulliparous women. Measures of central adiposity (WC, WHR, WHtR, ABSI) were not associated with fecundability. LIMITATIONS REASONS FOR CAUTION: Small sample size could restrict power of analysis.The analysis was confined to planned pregnancies, which could limit generalizability of findings to non-planned pregnancies, estimated at around 44% in Singapore. Information on the date of last menstrual period for each month was not available, hence the accuracy of self-reported menstrual cycle length could not be validated, potentially introducing error into TTP estimation. Measures of exposures and covariates such as cycle length were not performed repeatedly over time; cycle length might have changed during the period before getting pregnant. WIDER IMPLICATIONS OF THE FINDINGS: Other than using BMI as the surrogate measure of body fat, we provide additional evidence showing that higher amounts of subcutaneous fat that based on the measure of SFT at the sites of biceps, triceps, suprailiac and subscapular, and TBF% are associated with longer TTP. Achieving optimal weight and reducing total percentage body fat may be a potential intervention target to improve female fertility. The null results observed between central adiposity and TTP requires confirmation in further studies. STUDY FUNDING/COMPETING INTEREST(S): This research is supported by Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council, (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. Y.S.C., K.M.G., F.Y. and Y.S.L. have received reimbursement to speak at conferences sponsored by companies selling nutritional products. Y.S.C., K.M.G. and S.Y.C. are part of an academic consortium that has received research funding from Abbott, Nutrition, Nestle and Danone. Other authors declared no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Violet-blue emission property of the cerium-ion doped CaHfO3 : Doping and temperature dependence.

We investigated the emission property of perovskite CaHfO3 polycrystals with various concentrations of cerium ion (Ce3+ ). With a wide range of UV photoexcitation, we observed a strong emission near 430 nm which should originate from 5d-4f transitions in the Ce3+ ions. Combining these emission spectra with the photoluminescence excitation spectra, we estimated the Stokes shift to be 6700 cm-1 , irrespective of the Ce3+ ion doping concentration. We found that the violet-blue emissions in Ce3+ ions showed non-trivial temperature dependence in their peak position and intensity. We found interesting low-temperature behavior of the violet-blue emission, which might be attributed to the thermal lattice effect in CaHfO3 . We also discussed our results with those of the similar materials, perovskite zirconates. Our systematic studies provide useful information on the host material CaHfO3 for a future study on the violet-blue emission of Ce3+ ions.