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We prove the conjectured limiting normality for the number of crossings of a uniformly chosen set partition of [n] = {1,2,⋯,n}. The arguments use a novel stochastic representation and are also used to prove central limit theorems for the dimension index and the number of levels.

A dependent scattering effect is produced for unidirectional thermosetting composites, in the fibers of commercial filament wound structures due to the nearby fibers. The single-fiber extinction coefficient and the phase function can be changed by the dependent scattering, and a corresponding change in the radiative transfer of the fibers is also produced. The incident radiation perpendicular to the cylinder axis produces a maximum dependent scattering effect.

The temperatures and the degrees of cure in an infrared heat curing process for unidirectional thermosetting composites can be found. They depend on infrared heat source configurations, power input, mandrel winding speed and wound composite size. A two dimensional model results from this analysis. There is good agreement between the numerical and the experimental results.

Malignant bone disease can cause significant morbidity. Monthly zoledronic acid (ZOL) reduces skeletal complications; however, limited data are available regarding long‐term safety. We aimed to assess efficacy and safety of ZOL beyond 1 year of treatment. We prospectively evaluated 73 patients; breast cancer (n = 29), castrate‐resistant prostate cancer (n = 13), multiple myeloma (n = 31) from 2006 to 2008 in 19 cancer centres. All patients were diagnosed with bone disease and had completed 1–2 years of monthly ZOL (4 mg) and received a further 1–2 years of therapy following contemporary guidelines for managing risks of osteonecrosis of the jaw (ONJ) and renal toxicity. Overall rates of skeletal‐related events (SREs), renal impairment and ONJ were assessed. Over the additional 1 year of treatment, only 5.5% (n = 4) of patients developed a new SRE. The overall Kaplan–Meier estimate for SRE incidence after 48 weeks on study was 6.75% (95 CI: 2.5–17.3). Although 51% of patients reported serious adverse events, only two cases were suspected as ZOL related. No patients had confirmed ONJ. The observed incidence of new renal impairment was 11% (none due to ZOL). Our study confirms the benefit over risk of continuing monthly ZOL for at least 2 years in patients with advanced cancer involving bone. [ABSTRACT FROM AUTHOR]

Importance: Poorly differentiated cancer (PDC) and anaplastic thyroid cancer (ATC) have an aggressive course of disease with limited treatment options. The expression of programmed cell death ligand-1 (PD-L1) has been used to determine the responses of many cancers to immunotherapy. The aim of the study was to investigate the expression of PD-L1 in a cohort of patients with PDC and ATC to assess their suitability for immunotherapy. Data, settings, and participants: This study is a retrospective cohort review of patients treated for PDC and ATC treated at a tertiary referral institution during the period 2000-2020. PD-L1 22C3 pharmDx qualitative immunohistochemistry was performed on formalin-fixed, paraffin-embedded (FFPE) specimens of tumours to detect the presence of the PD-L1 protein., Main Outcome Measures: The percentage of tumours that were positive for PD-L1 immunohistochemistry and the PD-L1 protein expression as measured by using the Tumour Proportion Score (TPS). Secondary outcomes studied were the associations between demographic, clinicopathological, treatment and disease outcomes and PD-L1 expression., Results: Nineteen patients (12F:7M) with a mean age of 65.4 (±14.3 SD) years were diagnosed with PDC in 4 (21%) and fifteen were diagnosed with ATC (79%) during the study period. Fifteen (79%) patients underwent some form of surgery, with R0 resection achieved in only three of the fifteen (20%) patients. Overall, PD-L1 expression was seen in seven of the fifteen (47%) of the patients with ATC, with no positivity seen in the patients with PDC. PD-L1 expression had no impact on treatment modality and positive expression was not significantly associated with stage of disease, metastasis, or survival., Conclusion: Nearly half of patients with ATC express PD-L1 and may be amenable to immunotherapy with pembrolizumab.

Objectives: Uterine fibroids and adenomyosis are common gynecological conditions that often require surgical treatment. Minimally invasive interventions such as ultrasound-guided high-intensity focused ultrasound (USgHIFU) are gaining popularity as they avoid surgical morbidity and conserve the uterus. We present a single-center experience on the use of USgHIFU for the treatment of fibroids and adenomyosis., Materials and Methods: This was a retrospective study of 167 patients who underwent USgHIFU for uterine fibroids and adenomyosis between July 2018 and December 2020. Relevant demographic data and pre- and post-intervention fibroid volume, symptom severity scores (SSS), and health-related quality of life (QOL) scores were collected and compared. The paired t -test or Wilcoxon signed-rank test was used to compare the difference before and after treatment. P < 0.001 was considered statistically significant., Results: One hundred and sixty-seven patients with fibroids or adenomyosis were included in this study. The mean age of the cohort was 42-year-old. USgHIFU treatment led to a reduction in mean fibroid volume, improvement in SSS, and health-related QOL scores. The average reduction in mean fibroid volume was 68% and 75% at 6 and 12 months, respectively. There was a significant reduction in SSS (46.9 [pre] vs. 15.6 [post], P < 0.001) and improvement in health-related QOL scores at 6 months (58 [pre] vs. 86 [post], P < 0.001). The re-intervention rate following USgHIFU was 7.7% and successful pregnancy post USgHIFU was reported in 6 patients., Conclusion: USgHIFU is safe and effective. In women who desire fertility or are not suitable for surgery, it is a good alternative option. It should be included in the armamentarium for the treatment of uterine fibroids and adenomyosis., Competing Interests: Dr. Bernard Chern, an editorial board member at Gynecology and Minimally Invasive Therapy, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper., (Copyright: © 2023 Gynecology and Minimally Invasive Therapy.)

Purpose of Review: While the predominant cause for morbidity and mortality with SARS-CoV-2 infection is the lower respiratory tract manifestations of the disease, the effects of SARS-CoV-2 infection on the sinonasal tract have also come to the forefront especially with the increased recognition of olfactory symptom. This review presents a comprehensive summary of the mechanisms of action of the SARS-CoV-2 virus, sinonasal pathophysiology of COVID-19, and the correlation with the clinical and epidemiological impact on olfactory dysfunction., Recent Findings: ACE2 and TMPRSS2 receptors are key players in the mechanism of infection of SARS-CoV-2. They are present within both the nasal respiratory as well as olfactory epithelia. There are however differences in susceptibility between different groups of individuals, as well as between the different SARS-CoV-2 variants. The sinonasal cavity is an important route for SARS-CoV-2 infection. While the mechanism of infection of SARS-CoV-2 in nasal respiratory and olfactory epithelia is similar, there exist small but significant differences in the susceptibility of these epithelia and consequently clinical manifestations of the disease. Understanding the differences and nuances in sinonasal pathophysiology in COVID-19 would allow the clinician to predict and counsel patients suffering from COVID-19. Future research into molecular pathways and cytokine responses at different stages of infection and different variants of SARS-CoV-2 would evaluate the individual clinical phenotype, prognosis, and possibly response to vaccines and therapeutics., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Previous studies suggested mean arterial pressure (MAP) had moderate predictive values in the first and second trimesters for the prediction of preeclampsia. However, the performance of MAP in Asian women is still unclear. The objective of this study was to examine the predictive values of MAP in Asian population throughout gestation, and to compare the performance of MAP, angiogenic factors and uterine artery Doppler in the prediction of preeclampsia., Design: A prospective cohort study., Setting: KK Women's and Children's Hospital, Singapore., Participants: A total of 926 women with singleton pregnancy less than 14 weeks of gestation were included in the prospective Neonatal and Obstetrics Risks Assessment cohort between September 2010 and October 2014. Maternal blood pressure levels, uterine artery pulsatility index (UtA-PI), serum soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and sFlt-1/PlGF ratio were measured at 11-14, 18-22, 28-32 and 34 weeks onward, respectively., Primary and Secondary Outcomes: Preeclampsia was the main pregnancy outcome., Results: A total of 20 women developed preeclampsia, who had significantly lower levels of PlGF, higher levels of sFlt-1/PlGF ratio and MAP throughout pregnancy than women without preeclampsia. Compared with angiogenic factors and UtA-PI, MAP had significantly higher area under the receiver operating characteristic curves (AUCs) for predicting preeclampsia and term preeclampsia throughout gestation. For predicting preeclampsia, MAP had AUCs of 0.86 (95% CI 0.78 to 0.95), 0.87 (95% CI 0.80 to 0.95) and 0.91 (95% CI 0.85 to 0.98) at 11-14, 18-22 and 28-32 weeks, respectively. For predicting term preeclampsia, MAP yielded AUCs of 0.87 (95% CI 0.75 to 0.99), 0.87 (95% CI 0.76 to 0.98) and 0.90 (95% CI 0.80 to 0.99) at 11-14, 18-22 and 28-32 weeks, respectively. For predicting preterm preeclampsia, the performance of MAP and PlGF was similar., Conclusion: MAP is a good predictor for preeclampsia, especially term preeclampsia, in Asian women., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To elucidate the association between sleep disturbances and blood pressure as well as uterine artery Doppler during pregnancy in women with no pre-existing hypertension., Design: Prospective cohort study., Setting: Outpatient specialist clinics at KK Women's and Children's Hospital, Singapore., Population: Women with viable singleton pregnancies confirmed by ultrasonography at less than 14 weeks of amenorrhoea at first visit., Methods: In all, 926 subjects were recruited for this study in the outpatient specialist clinics at KK Women's and Children's Hospital, Singapore, between 1 September 2010 and 31 August 2014. They were followed up throughout pregnancy with sleep quality, blood pressure and uterine artery Doppler assessed at each visit., Main Outcome Measures: Sleep quality, blood pressure and uterine artery Doppler., Results: Sleep progressively worsened as pregnancy advanced. Shorter sleep duration and poorer sleep efficiency were associated with higher blood pressure, especially in the first trimester. Mixed model analysis demonstrated an overall positive association between sleep quality represented by Pittsburgh Sleep Quality Index (PSQI) score and diastolic blood pressure (DBP) (P < 0.001) and mean arterial pressure (MAP) (P = 0.005) during pregnancy after considering all trimesters. Sleep duration was found to be negatively associated with both systolic blood pressure (SBP) (P = 0.029) and DBP (P = 0.002), whereas sleep efficiency was negatively correlated with DBP (P = 0.002) only. Overall poor sleep during pregnancy was also found to be associated with a higher uterine artery pulsatility index., Conclusion: Our prospective study demonstrated that poor sleep quality is significantly associated with higher blood pressure and uterine artery pulsatility index during pregnancy., Tweetable Abstract: Poor sleep quality is significantly associated with higher blood pressure and higher uterine artery pulsatility index during pregnancy., (© 2020 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: Preterm birth (birth before 37 weeks of completed gestation) is the leading cause of neonatal death, and has an incidence of 5-13% which is believed to be on the rise. The objective of this study was to determine the rate of spontaneous preterm birth and investigate the relationship between preterm birth and cervical length in a pregnant Asian population., Materials and Methods: A prospective observational study between September 2010 and November 2013 was performed at KK Women's and Children's Hospital, Singapore. 1013 women with single viable pregnancies were recruited at less than 14 weeks of gestation between September 2010 and November 2013, excluding those with multiple gestation, pre-existing autoimmune or renal disease or those with current pregnancies complicated by aneuploidy or fetal anomalies. Participant characteristics were obtained from an interviewer-administered questionnaire at the first recruitment visit. Cervical length was measured using ultrasound at each of the 4 antenatal visits (Visit 1: < 14 weeks, Visit 2: 18-22 weeks, Visit 3: 28-32 weeks and Visit 4: > 34 weeks) using the Fetal Medicine Foundation protocol. Data on pregnancy outcomes were obtained from obstetric case notes and records. The main outcome measure examined in this study was that of spontaneous preterm birth and its relationship to cervical length., Results: There was a significantly shorter cervical length both in the 2nd trimester (18 to 22 weeks) and the 3rd trimester (28 to 32 weeks) in the preterm birth group compared to the term birth group (p = 0.028 and p < 0.001 respectively). In the first trimester (11 to 14 weeks), there was no statistically significant difference in cervical length between the two groups (p = 0.425). ROC curve analysis for cervical length in the preterm birth group for 18 to 22 weeks and 28 to 32 weeks showed an AUC of 0.605 and 0.725 respectively. At 28 to 32 weeks of gestation, a cut-off level at 2.49 cm has a sensitivity of 54.8%, specificity of 82.5%, negative predictive value of 97.9% and positive predictive value of 11.1%., Conclusion: There is a significantly shorter cervical length in the 2nd and 3rd trimester in the preterm birth group. Cervical length is a moderate predictor of preterm birth with good negative predictive value and a relatively good specificity. Ultrasound cervical length screening for pregnant Asian women between 18 and 22 weeks of gestation with a cutoff of ≥ 2.48cm can help to identify a group of women who are at risk for preterm birth., Competing Interests: The authors have declared that no competing interests exist.

Objective: It remains unclear what roles placenta-originated angiogenic factors play in the pathogenesis of preeclampsia among hypertensive women. We compared maternal soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) levels throughout pregnancy in women with normal blood pressure (BP), elevated BP and hypertension in early pregnancy and their risks of developing preeclampsia., Design: A prospective cohort study., Setting: KK Women's and Children's Hospital, Singapore., Participants: 923 women with singleton pregnancy <14 weeks of gestation were included in the prospective Neonatal and Obstetrics Risks Assessment cohort between September 2010 and October 2014. Systolic, diastolic, mean arterial blood pressure (MAP) were measured at 11-14 weeks., Primary and Secondary Outcomes: Maternal serum sFlt-1, PlGF and sFlt-1/PlGF ratio were tested at 11-14, 18-22, 28-32 and 34 weeks onwards of gestation. Preeclampsia was main pregnancy outcome., Results: Women were divided based on their BP in early pregnancy: normal (n=750), elevated BP (n=98) and hypertension (n=75). Maternal sFlt-1 levels and sFlt-1/PlGF ratios were higher in hypertensive women throughout pregnancy, but maternal PlGF levels were not significantly lower. Rise in maternal systolic, diastolic BP and MAP at 11-14 weeks were significantly associated with higher sFlt-1/PlGF ratios during pregnancy. A 10 mm Hg increase in MAP was associated with a 5.6-fold increase in risk of preterm preeclampsia and a 3.3-fold increase in risk of term preeclampsia, respectively., Conclusion: Women with elevated BP in early pregnancy already had a higher sFlt-1/PlGF ratio in early gestation and throughout pregnancy, and an increased risk of preeclampsia. In contrast, PlGF levels in these women remained normal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Coordinating eating schedules with day-night cycles has been shown to improve glucose regulation in adults, but its association with gestational glycaemia is less clear. A better understanding on how eating time can influence glucose levels in pregnancy may improve strategies for gestational glycaemic control. This study aims to examine the association of maternal night-eating pattern with glucose tolerance in the second trimester of pregnancy, and to investigate how lifestyle factors may be related to night-eating pattern., Methods and Analysis: This is an observational longitudinal study that targets to recruit 200 pregnant women at 18-24 weeks' gestation from the KK Women's and Children's Hospital in Singapore. Data collection includes sociodemographics, lifestyle habits and obstetric information. Maternal dietary intake is collected using the 4-day food diary and food frequency questionnaire; while 24-hour physical activity, sedentary behaviour, sleep and light exposure are captured using the accelerometer at 18-24 weeks' gestation. Continuous glucose monitoring at 18-24 weeks' gestation, oral glucose tolerance test and insulin test at 24-28 weeks' gestation are performed to assess glycaemic outcomes. Multivariable generalised linear models will be used to analyse the association of maternal night-eating pattern (consumption of meal and snack during 1900-0659 hours) with glycaemic measures, and the associated factors of night-eating pattern, controlling for potential confounders. Recruitment began in March 2019 and is estimated to end in November 2020., Ethics and Dissemination: Ethical approval has been granted by the Centralised Institutional Review Board of SingHealth, Singapore (reference 2018/2529). The results will be presented at conferences and disseminated in journal articles., Trial Registration Number: NCT03803345., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background To establish gestational specific cutoffs for the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio as a diagnostic tool for pre-eclampsia (PE) in an Asian population. Methods 82 subjects (48 PE patients and 34 controls) were recruited. sFlt-1 and PlGF were analysed on the Roche Cobas e411 analyzer and their ratio was calculated. Diagnostic performance was evaluated using receiver-operating characteristics (ROC) curves. Optimal cutoffs for sFlt-1/PlGF ratio were determined for different gestation phases. Results The most optimal cut-off for the study group is 32 with a sensitivity and specificity of 85.1% and 100% and Youden Index (J) of 0.85. Applying this cutoff for early-onset PE (EO-PE), sensitivity increased to 95.8% while specificity remains at 100% (J=0.96). However, for late onset PE (LO-PE), sensitivity decreases to 73.9% while specificity remains at 100% (J=0.74). Two cutoffs were further determined for EO-PE and LO-PE - the first focusing on high sensitivity; the second focusing on high specificity. For EO-PE, cutoff <17 yielded sensitivity of 100% and specificity of 94.4% (J=0.94) while cutoff ≥32 yielded sensitivity of 95.8% and specificity of 100% (J=0.95). For LO-PE, cutoff <22 has a sensitivity of 82.6% and a specificity of 91.7% (J=0.74) while cutoff ≥32 yielded sensitivity of 73.9% and specificity of 100% (J=0.74). Conclusion While our study found an overall cutoff at 32 regardless of gestation age, it has limited diagnostic accuracy for LO-PE in our study. Multiple cutoffs focusing on either high sensitivity or high specificity enhance the performance of the sFlt-1/PlGF ratio as a diagnostic tool for PE and contribute to the identification of women at risk of PE in our Asian region.

Background: Thyroid disorders are common during pregnancy. To date, a limited number of studies have reported differences in serum thyroid hormone concentrations between different ethnic groups. We sought to establish gestational age-specific reference intervals for serum levels of thyroid hormones in a multi-ethnic population and investigate whether separate reference intervals should be used for different ethnic groups., Methods: A total of 926 pregnant women from multiple ethnic groups attended four separate study visits spanning the three trimesters. Venous blood samples were taken at 9 to 14 weeks, 18 to 22 weeks, 28 to 32 weeks, and 34 to 39 weeks of gestation. Serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (T4), free triiodothyronine (T3), total T4, total T3, thyroid peroxidase antibody and thyroglobulin antibody were measured using Abbott Architect immunoassays. A total of 562 women with singleton pregnancies were found to be negative for both thyroid autoantibodies at all four study visits and thus included in the reference sample group for the establishment of reference intervals (2.5th to 97.5th percentiles)., Results: Reference intervals for serum thyroid hormones at 9-14 weeks of gestation derived from the combined group of pregnant women are as follows: TSH, 0.01-2.39 mIU/L; free T4, 11.4-19.5 pmol/L; free T3, 4.23-6.69 pmol/L; total T4, 77.8-182.4 nmol/L; total T3, 1.39-2.97 nmol/L. No differences in the five thyroid parameters' reference intervals are detectable among the ethnic groups except that at study visit 3 (28-32 weeks of gestation), the upper reference limit of total T3 in Malays (3.20 nmol/L; 90% CI, 2.99-3.76 nmol/L) is slightly higher than that in Chinese (2.86 nmol/L; 90% CI, 2.70-2.98 nmol/L)., Conclusions: The findings from this study on a multi-ethnic cohort highlight the importance of establishing locally derived and gestational age-specific reference intervals for the five thyroid hormone parameters.

Wider use of chemotherapy and targeted agents can be associated with posterior reversible encephalopathy syndrome (PRES). This syndrome is most commonly found in metastatic adenocarcinoma treated with platinum-based analogs and is managed with cessation of the precipitating medication. We present the first case of PRES in early-stage breast cancer and discuss the further management of this condition. Recognition of this condition and correction of identifiable precipitating factor including cessation of relevant medications remains important in its management., (© 2015 Wiley Periodicals, Inc.)

Objective: To present our experience of laparoscopic management of cornual ectopic pregnancy., Design: Retrospective review of 53 cases of cornual pregnancy treated laparoscopically., Setting: K.K. Women's and Children's Hospital, Singapore., Patient(s): Patients who were treated for cornual pregnancy via laparoscopic surgery from 2001 to 2006., Intervention(s): Laparoscopic surgery as a treatment modality for cornual pregnancy., Main Outcome Measure(s): Success rate of laparoscopic surgery and future reproductive outcome., Result(s): Fifty-two cases were managed by laparoscopy, and one was converted to laparotomy. Laparoscopic wedge resection was carried out in 33 patients, cornuostomy in 13 patients, and salpingectomy in 7 patients. Nine patients received methotrexate injection after surgery because of persistently high serum beta-hCG. Eighteen patients became pregnant, four had early miscarriages, and ten had pregnancies beyond 24 weeks' gestation. Five delivered vaginally, and three had cesarean section at term. Two patients traveled back to their native countries for delivery. There were no cases of uterine rupture or dehiscence reported., Conclusion(s): Laparoscopic treatment of cornual pregnancy can be safely carried out with good results in an institution with trained laparoscopist and adequate facilities.