A bimodal burst energy distribution of a repeating fast radio burst source.

The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3-5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6-8. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h-1, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 1037 erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.

Arthralgia in midlife Singaporean women: the Integrated Women's Health Program (IWHP).

OBJECTIVE: Arthralgia is a common menopausal complaint in midlife women, and its causes remain unclear. We examined the prevalence of menopausal arthralgia with various factors including sleep quality, depression/anxiety, muscle strength and physical performance among midlife Singaporean women. METHODS: The Integrated Women's Health Program (IWHP) comprised 1120 healthy, community-dwelling women of Chinese, Malay or Indian ethnicities (aged 45-69 years) attending well-women clinics at the National University Hospital, Singapore. Sociodemographic, menopausal, reproductive and health data were obtained with validated questionnaires. Muscle strength, physical performance and dual-energy X-ray absorptiometry were measured. Women with moderate to very severe symptoms using the Menopause Rating Scale were classified as having arthralgia. Multivariable logistic regression analyses examined risk factors for arthralgia. RESULTS: One-third of the participants reported arthralgia, and 12.7%, 16.2% and 71.2% were in the premenopausal, perimenopausal and postmenopausal period, respectively. Menopausal symptoms, such as vaginal dryness (adjusted odds ratio [aOR]: 2.64, 95% confidence interval [CI]: 1.64, 4.24) and physical/mental exhaustion (aOR: 2.83, 95% CI: 1.79, 4.47), were independent risk factors for arthralgia. Poor muscle strength (aOR: 2.20, 95% CI: 1.29, 3.76), obesity (aOR: 1.94, 95% CI: 1.13, 3.32) and rheumatoid arthritis (aOR: 7.73, 95% CI: 4.47, 13.36) were also independently associated with arthralgia after adjustment for confounders. CONCLUSIONS: Arthralgia in midlife Singaporean women was associated with menopausal symptoms of vaginal dryness and physical and mental exhaustion. Women with poor muscle strength were more likely to experience menopausal arthralgia.

Second Data Release from the European Pulsar Timing Array: Challenging the Ultralight Dark Matter Paradigm.

Pulsar Timing Array experiments probe the presence of possible scalar or pseudoscalar ultralight dark matter particles through decade-long timing of an ensemble of galactic millisecond radio pulsars. With the second data release of the European Pulsar Timing Array, we focus on the most robust scenario, in which dark matter interacts only gravitationally with ordinary baryonic matter. Our results show that ultralight particles with masses 10^{-24.0} eV≲m≲10^{-23.3} eV cannot constitute 100% of the measured local dark matter density, but can have at most local density ρ≲0.3 GeV/cm^{3}.

Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy.

BACKGROUND: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid-A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short-course treatment of grass-pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. METHODS: In this exploratory, randomized, double-blind, placebo-controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre-seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18-65 years) with moderate-to-severe SAR with or without asthma that was well-controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ-S) and allergen-specific IgG4 response. RESULTS: The mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ-S for the extended regimen (mean change -0.72, p = .02). Both regimens were well-tolerated. CONCLUSIONS: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well-tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.

Interrater reliability of a customized submaximal cycle ergometer test.

PURPOSE: Graded exercise testing (GXTs) is used to determine maximum oxygen uptake ([Formula: see text]). Recently, customized submaximal exercise testing (CSET) completed on both treadmill and cycle ergometry were validated. METHODS: Interrater reliability of the CSET for cycle ergometry was examined. Thirteen participants (age 31 ± 10.2 y, weight 77.9 ± 10.5 kg, height 176.2 ± 9.9 cm, body mass index 25.1 ± 2.9) completed the 2-stage × 3-min CSET protocol performed by two separate testers. True [Formula: see text] was determined using the highest value derived by a GXT and verification bout. Skeletal muscle oxygen saturation ([Formula: see text]), measured using near-infrared spectrometry on the medial gastrocnemius muscle, and [Formula: see text] were monitored during each CSET; whereby, [Formula: see text] kinetics were modeled breath-by-breath data for each 3-min stage. Measurement agreement was quantified using intraclass coefficient (ICC), typical error (TE), and coefficient of variation (CV). RESULTS: "True" [Formula: see text] (ml·kg-1·min-1) between the GXT (41.3 ± 10.5) and verification (42.5 ± 11.5) was established (ICC = 0.98, TE: 0.98, CV 2.1%). Estimated [Formula: see text] by tester 1 (42.5 ± 9.8) and tester 2 (42.7 ± 8.9) did not differ from "true" [Formula: see text] (F2,36 = 0.02, p = 0.98, ηp2 = 0.00). The second stage evoked a [Formula: see text] slow component of 194 ± 124 ml·min-1 that corresponded with a time-dependent decline of [Formula: see text]. The mean [Formula: see text] from the two CSET testers were highly correlated (ICC = 0.91, TE: 4.1%, CV = 8.9%). CONCLUSIONS: The CSET is a reliable and valid procedure and [Formula: see text] is a useful tool for corroborating the second stage is in the heavy-intensity domain.

The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer.

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths. Among breast cancers (BC) subtypes, triple-negative (TN) BC is characterized by metastatic progression and poor patient prognosis. Although, TNBC is initially sensitive to chemotherapy, many TNBC patients rapidly develop resistance, at which point metastatic disease is highly lethal. Cancer cells present phenotypic changes or molecular signatures that distinguish them from healthy cells. The Tn antigen (GalNAc-O-Thr/Ser), which constitutes a powerful tool as tumor marker, was recently reported to contribute to tumor growth. However, its role in BC-derived metastasis has not yet been addressed. In this work, we generated a pre-clinical orthotopic Tn+ model of metastatic TNBC, which mimics the patient surgical treatment and is useful to study the role of Tn in metastasis and immunoregulation. We obtained two different cell clones, which differed in their Tn antigen expression: a high Tn-expressing and a non-expressing clone. Interestingly, the Tn-positive cell line generated significantly larger tumors and higher degree of lung metastases associated with a lower survival rate than the Tn-negative and parental cell line. Furthermore, we also found that both tumors and draining-lymph nodes from Tn+-tumor-bearing mice presented a higher frequency of CD4+ FoxP3+ T cells, while their splenocytes expressed higher levels of IL-10. In conclusion, this work suggests that the Tn antigen participates in breast tumor growth and spreading, favoring metastases to the lungs that are associated with an immunoregulatory state, suggesting that Tn-based immunotherapy could be a strategy of choice to treat these tumors.

Amphetamine or skin cream? The impact of the sampling site on the concentration of controlled substances: a case report.

This case report demonstrates the impact of different sampling sites on the quantification of narcotic substances. In 2020, officers secured a syringe containing a light-yellow paste-like substance, for which a drug pre-test indicated a positive result for amphetamine, inducing subsequent analyses of the sample by means of a gaschromatographic-mass spectrometric method (GC-MS) and liquid chromatography-(tandem) mass spectrometry (LC-MS/MS). Depending on the sample location, different results were obtained, with amphetamine not being detected in each sample. Amphetamine was particularly found at the outlet of the syringe, while amphetamine detection on the inside of the syringe at the plunger seal was only possible occasionally and, moreover, in lower concentrations. Based on this and with regard to the comparatively small amphetamine concentrations, contamination of the syringe (especially on the tip of the syringe) was assumed. Hence, the results strengthened the importance of the implication of different sampling sites, when either homogenization of the sample is not feasible or is not performed for reasons of plausibility checks concerning possible contamination of the sample.

The host galaxy of a fast radio burst.

In recent years, millisecond-duration radio signals originating in distant galaxies appear to have been discovered in the so-called fast radio bursts. These signals are dispersed according to a precise physical law and this dispersion is a key observable quantity, which, in tandem with a redshift measurement, can be used for fundamental physical investigations. Every fast radio burst has a dispersion measurement, but none before now have had a redshift measurement, because of the difficulty in pinpointing their celestial coordinates. Here we report the discovery of a fast radio burst and the identification of a fading radio transient lasting ~6 days after the event, which we use to identify the host galaxy; we measure the galaxy's redshift to be z = 0.492 ± 0.008. The dispersion measure and redshift, in combination, provide a direct measurement of the cosmic density of ionized baryons in the intergalactic medium of ΩIGM = 4.9 ± 1.3 per cent, in agreement with the expectation from the Wilkinson Microwave Anisotropy Probe, and including all of the so-called 'missing baryons'. The ~6-day radio transient is largely consistent with the radio afterglow of a short γ-ray burst, and its existence and timescale do not support progenitor models such as giant pulses from pulsars, and supernovae. This contrasts with the interpretation of another recently discovered fast radio burst, suggesting that there are at least two classes of bursts.

Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers.

The prevalence of allergic disorders has increased drastically over the last 50 years to the extent that they can be considered epidemic. At present, allergen-specific immunotherapy (AIT) is the only therapy that targets the underlying cause of allergic disorders, and evidence of its superiority is based on data accumulated from clinical trials and observational studies demonstrating efficacy and safety. However, several aspects remain unresolved, such as harmonization and standardization of manufacturing and quantification procedures across manufacturers, homogeneous reporting of strength, and the establishment of international reference standards for many allergens. This article discusses issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison of products from different manufacturers is an appropriate basis for selecting a specific AIT product. Allergen standardization in immunotherapy products is critical for ensuring quality and, thereby, safety and efficacy. However, lack of harmonization in manufacturing processes, allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that the comparison of AIT products based solely on major allergen amounts is not rational and, in fact, impossible. Moreover, when rating the information given for a specific product, it is necessary to take into account further inherent characteristics of products and their application in clinical practice, such as the state of extract modification, addition of adjuvant or adjuvant system, route of administration (sublingual/ subcutaneous), and cumulative dose as per posology (including the volume per administration). Finally, only convincing clinical data can serve as the basis for product-specific evaluation and cross-product comparability of individual products.

Retrospective evaluation of surgical technique, complications and long-term outcome of lateral and medial humeral condylar fractures in 80 dogs.

CASE HISTORY: Medical records from a single veterinary teaching hospital in Giessen, Germany were retrospectively reviewed for dogs presenting with medial or lateral humeral condylar fractures (HCF) between 2007 and 2019. Data regarding surgical technique and complications were collected from the medical records. These were supplemented through information obtained from telephone interviews with referral veterinarians and from an owner questionnaire completed ≥12 months after surgical repair, which also provided data regarding the outcome. CLINICAL FINDINGS: Eighty dogs with 85 HCF were identified: 13 (15.3%) HCF were medial (bilateral in two dogs) and 72 (84.7%) were lateral (bilateral in three dogs). French Bulldogs (n = 19/80; 23.8%) were most commonly affected. Patients were predominantly skeletally immature and light-weight, with a median age at the time of presentation of 3 (min 2, max 118) months and with a median body weight of 6.4 (min 1, max 46) kg. There were 38 female (47.5%) and 42 male (52.5%) dogs. Fractures developed most frequently secondary to minor trauma (67/77; 87.0%). Dogs were presented in 35/84 (41.7%) cases more than 24 hours after fracture occurrence. TREATMENT AND OUTCOME: Surgical treatment was performed in 80/85 (94.1%) HCF. An open reduction and internal fixation approach was chosen in all cases. A transcondylar screw (TS) combined with a supracondylar (SC) K-wire (67/80; 83.8%) was the most frequently used fixation technique. Considering all fracture fixation methods, complications (26/80; 32.5%) were classed as minor in 10 (12.5%), major in 14 (17.5%) and catastrophic in two (2.5%) of the 80 surgically treated HCF. Long-term outcome was excellent in 68.6% (24/35 HCF) and very good in 22.9% (8/35 HCF) of the cases for which follow-up information was obtained. Additionally, owner information revealed that 85.7% of dogs (30/35 HCF) were free of lameness in the long-term. CLINICAL RELEVANCE: This case series demonstrates that surgical repair of lateral and medial HCF with a TS and SC K-wire is a viable option to consider in skeletally immature and light-weight patients. Complications occur frequently after surgical fixation of HCF, but owners can expect a very good to excellent long-term outcome in the majority of cases.

Excess mortality after hip fracture: fracture or pre-fall comorbidity?

Comorbidity and hip fracture independently increased mortality risk for 9 years in both sexes, with a significant additive interaction in the first year among women and through 6 years among men. INTRODUCTION: Hip fracture is associated with a persistently elevated mortality risk, but it is unknown whether the elevated risk is due to the fracture or to pre-fracture comorbidity. METHODS: In a population-based study in Singapore with 9 years of follow-up, patients age > 50 with first hip fracture from 2008 to 2017 were pair-matched to a cohort without hip fracture by age, sex, ethnicity, and pre-fracture Charlson Comorbidity Index (CCI). We investigated additive interaction using the relative excess risk due to interaction (RERI) and multiplicative interaction using the ratio of relative risks. RESULTS: Twenty-two thousand five hundred ninety of 22,826 patients with a first hip fracture in 2008-2017 were successfully matched. Hip fracture and comorbidity independently increased mortality risk for 9 years in both sexes. After adjustment for comorbidity, excess mortality risk continued to persist for 9 years post-fracture in both men and women. Women with a hip fracture and pre-fracture CCI > 4 had a higher relative risk (RR) of mortality at 9 years of 3.29 [95% confidence interval (CI) 3.01, 3.59] than those without comorbidity (RR 1.51, 95%CI 1.36, 1.68) compared to the referent without hip fracture or comorbidity. An additive interaction between hip fracture and pre-fracture CCI > 4 was observed in the first post-fracture year` [relative excess risk due to interaction (RERI) 1.99, 95%CI 0.97, 3.01]. For men with CCI ≥ 4, the positive additive interaction was observed through 6 years. CONCLUSIONS: Excess mortality risks post-fracture are attributable to both the fracture and pre-fracture comorbidity. Early interventions in hip fracture patients with high comorbidity could reduce their excess mortality.

Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy.

BACKGROUND: Continuous spike and wave of sleep with encephalopathy (CSWS) is a rare and severe developmental electroclinical epileptic encephalopathy characterized by seizures, abundant sleep activated interictal epileptiform discharges, and cognitive regression or deceleration of expected cognitive growth. The cause of the cognitive symptoms is unknown, and efforts to link epileptiform activity to cognitive function have been unrevealing. Converging lines of evidence implicate thalamocortical circuits in these disorders. Sleep spindles are generated and propagated by the same thalamocortical circuits that can generate spikes and, in healthy sleep, support memory consolidation. As such, sleep spindle deficits may provide a physiologically relevant mechanistic biomarker for cognitive dysfunction in epileptic encephalopathies. CASE PRESENTATION: We describe the longitudinal course of a child with CSWS with initial cognitive regression followed by dramatic cognitive improvement after treatment. Using validated automated detection algorithms, we analyzed electroencephalograms for epileptiform discharges and sleep spindles alongside contemporaneous neuropsychological evaluations over the course of the patient's disease. We found that sleep spindles increased dramatically with high-dose diazepam treatment, corresponding with marked improvements in cognitive performance. We also found that the sleep spindle rate was anticorrelated to spike rate, consistent with a competitively shared underlying thalamocortical circuitry. CONCLUSIONS: Epileptic encephalopathies are challenging electroclinical syndromes characterized by combined seizures and a deceleration or regression in cognitive skills over childhood. This report identifies thalamocortical circuit dysfunction in a case of epileptic encephalopathy and motivates future investigations of sleep spindles as a biomarker of cognitive function and a potential therapeutic target in this challenging disease.

Increasing facility delivery through maternity waiting homes for women living far from a health facility in rural Zambia: a quasi-experimental study.

OBJECTIVE: To report on the effectiveness of a standardised core Maternity Waiting Home (MWH) model to increase facility deliveries among women living >10 km from a health facility. DESIGN: Quasi-experimental design with partial randomisation at the cluster level. SETTING: Seven rural districts in Zambia. POPULATION: Women delivering at 40 health facilities between June 2016 and August 2018. METHODS: Twenty intervention and 20 comparison sites were used to test whether MWHs increased facility delivery for women living in rural Zambia. Difference-in-differences (DID) methodology was used to examine the effectiveness of the core MWH model on our identified outcomes. MAIN OUTCOME MEASURES: Differences in the change from baseline to study period in the percentage of women living >10 km from a health facility who: (1) delivered at the health facility, (2) attended a postnatal care (PNC) visit and (3) were referred to a higher-level health facility between intervention and comparison group. RESULTS: We detected a significant difference in the percentage of deliveries at intervention facilities with the core MWH model for all women living >10 km away (DID 4.2%, 95% CI 0.6-7.6, P = 0.03), adolescent women (<18 years) living >10 km away (DID 18.1%, 95% CI 6.3-29.8, P = 0.002) and primigravida women living >10 km away (DID 9.3%, 95% CI 2.4-16.4, P = 0.01) and for women attending the first PNC visit (DID 17.8%, 95% CI 7.7-28, P < 0.001). CONCLUSION: The core MWH model was successful in increasing rates of facility delivery for women living >10 km from a healthcare facility, including adolescent women and primigravidas and attendance at the first PNC visit. TWEETABLE ABSTRACT: A core MWH model increased facility delivery for women living >10 km from a health facility including adolescents and primigravidas in Zambia.

Maternal risk factors and adverse birth outcomes associated with HELLP syndrome: a population-based study.

OBJECTIVES: We assessed the incidence, risk factors and adverse birth outcomes associated with elevated liver enzymes and low platelets (HELLP) syndrome. DESIGN: A retrospective population-based cohort study. SETTING: Canada (excluding Quebec), 2012/2013-2015/2016. POPULATION: Mothers with a singleton hospital live birth or stillbirth at ≥24 weeks' gestation (n = 1 078 323). METHODS: HELLP syndrome was identified using ICD-10-CA diagnostic code from delivery hospitalisation data. We used logistic regression to identify independent risk factors for HELLP syndrome by obtaining adjusted odds ratios (AOR) and 95% confidence intervals (CI), and to assess the associations with adverse outcomes. MAIN OUTCOME MEASURES: Adverse maternal (e.g. eclampsia) and fetal/neonatal outcomes (e.g. intraventricular haemorrhage, perinatal death). RESULTS: The incidence of HELLP syndrome was 2.5 per 1000 singleton deliveries (n = 2663). Risk factors included: age ≥35 years, rural residence, nulliparity, parity ≥4, pre-pregnancy and gestational hypertension and diabetes, assisted reproduction, chronic cardiac conditions, systemic lupus erythematosus, obesity, chronic hepatic conditions, placental disorders (e.g. fetomaternal transfusion) and congenital anomalies. PROM and age <25 years were inversely associated with HELLP syndrome (P-values <0.05). Women with the syndrome had a 10-fold higher maternal mortality (95% CI 1.6-84.3) and elevated severe maternal morbidity (9.6 versus 121.7 per 1000; AOR 12.5, 95% CI 11.1-14.1); and higher perinatal mortality (4.3 versus 21.0 per 1000; AOR 4.5, 95% CI 3.5-5.9) and perinatal mortality/severe neonatal morbidity (21.2 versus 202.4 per 1000; AOR 10.7, 95% CI 9.7-11.8). CONCLUSION: HELLP syndrome is associated with specific pre-pregnancy and pregnancy risk factors, higher rates of maternal death, and substantially higher severe maternal morbidity, perinatal mortality and severe neonatal morbidity. TWEETABLE ABSTRACT: HELLP syndrome is associated with higher maternal death rate, and substantially higher severe maternal and neonatal morbidity, and perinatal mortality.

Development of interatomic potential for Al-Tb alloys using a deep neural network learning method.

An interatomic potential for the Al-Tb alloy around the composition of Al90Tb10 is developed using the deep neural network (DNN) learning method. The atomic configurations and the corresponding total potential energies and forces on each atom obtained from ab initio molecular dynamics (AIMD) simulations are collected to train a DNN model to construct the interatomic potential for the Al-Tb alloy. We show that the obtained DNN model can well reproduce the energies and forces calculated by AIMD simulations. Molecular dynamics (MD) simulations using the DNN interatomic potential also accurately describe the structural properties of the Al90Tb10 liquid, such as partial pair correlation functions (PPCFs) and bond angle distributions, in comparison with the results from AIMD simulations. Furthermore, the developed DNN interatomic potential predicts the formation energies of the crystalline phases of the Al-Tb system with an accuracy comparable to ab initio calculations. The structure factors of the Al90Tb10 metallic liquid and glass obtained by MD simulations using the developed DNN interatomic potential are also in good agreement with the experimental X-ray diffraction data. The development of short-range order (SRO) in the Al90Tb10 liquid and the undercooled liquid is also analyzed and three dominant SROs, i.e., Al-centered distorted icosahedron (DISICO) and Tb-centered '3661' and '15551' clusters, respectively, are identified.

[Routine outcome monitoring (ROM) early in treatment and disorder specific. Observational study into generic and specific questionnaires to measure the early change in depression treatment]. / ROM vroeg in de behandeling en specifiek; observationeel onderzoek naar generieke en specifieke vragenlijsten bij meten van vroege verandering bij depressiebehandeling.

BACKGROUND: Mental health care institutions use routine outcome monitoring (ROM) to determine whether a patient responds well to treatment. However, it has been still unanswered whether disorder specific or generic measurement instruments can best be used for this purpose. In addition, little is known about when a first indication can be given for the outcome of the treatment.
AIM: To provide insight into the sensitivity to change of two questionnaires: a generic and a specific one, which were both used for clients with a depressive disorder. An additional objective is to provide insight into when a first indication can be given for the outcome of the treatment.
METHOD: An observational cohort study with data from 518 patients with a depressive disorder. The Outcome Questionnaire (OQ-45.2) and the Inventory of Depressive Symptomatology (IDS-SR) were used to measure the course of treatment.
RESULTS: The depression specific IDS-SR appeared to be more sensitive to change than the generic OQ-45.2, especially at the beginning of treatment. With a measurement frequency of once every four weeks, the best time to get a first indication on the outcome of the treatment was between week 4 and week 8.
CONCLUSION: For clients and practitioners whose treatment focus is reducing depressive symptoms, a disorder specific questionnaire is preferable to monitor this. The measurement between 4 and 8 weeks is important for, if necessary, adjusting the treatment, and to improve the treatment outcome.

Fecundity among women with polycystic ovary syndrome (PCOS)-a population-based study.

STUDY QUESTION: Does the long-term fecundity of women with polycystic ovary syndrome (PCOS) differ from those without PCOS? SUMMARY ANSWER: Cumulative probability of childbirth is similar between women with and without PCOS. WHAT IS KNOWN ALREADY: PCOS is the main cause of anovulatory infertility in women after menarche. Previous studies indirectly suggest that fecundity in women with PCOS over the longer term may not be lower than in women without PCOS. STUDY DESIGN, SIZE, DURATION: This is a population-based study using four linked Swedish national registries. A total of 45 395 women with PCOS and 217 049 non-PCOS women were included. Follow-up began at the age of 18 years and continued for a maximum of 26 years, from 1989 to the end of 2015. Childbirth was the main outcome, as identified from the Medical Birth Register. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women born between 1971 and 1997 who were identified with a PCOS diagnosis in the Swedish Patient Registry between 1 January 2001 and 31 December 2016 were included in the study population. Five controls per women with PCOS were randomly drawn from the Total Population Registry. The control women were born in the same year and living in the same municipality as the patient. The fecundity ratio (FR) was calculated by clustered Cox regression using a robust variance, adjusted for maternal birth period, country of birth and level of education. MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative probability of childbirth was 80.2% (95% CI, 79.5-80.9%) in women with PCOS and 78.2% (95% CI, 77.9-78.5%) in those without PCOS. Adjusted FR was 0.81 (95% CI, 0.80-0.82) for first childbirth and 0.58 (95% CI, 0.57-0.60) for first childbirth following a spontaneous pregnancy. The FR for second childbirth was 0.79 (95% CI, 0.77-0.80). Women with PCOS had more than one child less frequently than the comparison group. Within the PCOS group, early age at diagnosis, later birth year, Nordic country of origin and low educational level positively influenced the FR. LIMITATIONS, REASONS FOR CAUTION: Results are not adjusted for BMI, and time from intention to conceive to first childbirth could not be captured. Data on pregnancies, miscarriages or abortions and fertility treatment are unknown for women who did not give birth during the study period. Women with PCOS who did not seek medical assistance might have been incorrectly classified as not having the disease. Such misclassification would lead to an underestimation of the true association between PCOS and outcomes. WIDER IMPLICATIONS OF THE FINDINGS: While cumulative probability of childbirth is similar between groups, women with PCOS need longer time to achieve their first childbirth. Women with PCOS have a lower FR and give birth to fewer children per woman than women without PCOS. Early diagnosis of and information about PCOS may improve affected women's reproductive potential. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Swedish Society of Medicine. Inger Sundström Poromaa has, over the past 3 years, received compensation as a consultant and lecturer for Bayer Schering Pharma, MSD, Gedeon Richter, Peptonics and Lundbeck A/S. The other authors declare no competing interests.

Hip fractures in Singapore: ethnic differences and temporal trends in the new millennium.

Despite an increase in absolute numbers, the age-standardized incidence of hip fractures in Singapore declined in the period 2000 to 2017. Among the three major ethnic groups, Chinese women had the highest fracture rates but were the only group to show a temporal decline. INTRODUCTION: A study published in 2001 predicted a 30-50% increase in Singapore hip fracture incidence rates over the ensuing 30 years. To test that prediction, we examined the incidence of hip fracture in Singapore from 2000 to 2017. METHODS: We carried out a population-based study of hip fractures among Singapore residents aged ≥ 50 years. National medical insurance claims data were used to identify admissions with a primary discharge diagnosis of hip fracture. Age-adjusted rates, based on the age distribution of the Singapore population of 2000, were analyzed separately by sex and ethnicity (Chinese, Malay, or Indian). RESULTS: Over the 18-year study period, 36,082 first hip fractures were recorded. Total hip fracture admissions increased from 1487 to 2729 fractures/year in the years 2000 to 2017. Despite this absolute increase, age-adjusted fracture rates declined, with an average annual change of - 4.3 (95% CI - 5.0, - 3.5) and - 1.1 (95% CI - 1.7, - 0.5) fractures/100,000/year for women and men respectively. Chinese women had 1.4- and 1.9-fold higher age-adjusted rates than Malay and Indian women: 264 (95% CI 260, 267) versus 185 (95% CI 176, 193) and 141 (95% CI 132, 150) fractures/100,000/year, respectively. Despite their higher fracture rates, Chinese women were the only ethnic group exhibiting a decline, most evident in those ≥ 85 years, in age-adjusted fracture rate of - 5.3 (95% CI - 6.0, - 4.5) fractures/100,000/year. CONCLUSION: Although the absolute number of fractures increased, steep drops in elderly Chinese women drove a reduction in overall age-adjusted hip fracture rates. Increases in the older population will lead to a rise in total number of hip fractures, requiring budgetary planning and new preventive strategies.