Age Window Research Articles

The PANDA score: External validation and modification of a simple upfront prediction tool for poor outcomes despite successful stroke thrombectomy.

While endovascular thrombectomy (EVT) has become standard of care for patients' acute ischemic stroke (AIS) due to large vessel occlusion (LVO), many patients still suffer profound neurological disability, also termed futile recanalization (FR). The BAND score, which incorporates baseline disability, age, stroke severity, and treatment time window, is derived as a simple tool for upfront prediction of FR prior to EVT. This study aims to externally validate the BAND score and to incorporate upfront imaging biomarkers into the prediction tool. Consecutive stroke thrombectomy patients with anterior circulation LVO who achieved successful recanalization (mTICI 2b or greater) were retrospectively identified at a single institution from 2019 to 2023. Clinical information, procedural details, and 90-day outcomes were recorded. The performance of the BAND score in predicting FR (90-day modified Rankin scale [mRS] >3) and loss of complete independence (LCID, 90-day mRS>2) was assessed. Then, Alberta stroke programme early CT score (ASPECTS) was added to create the PANDA score (pre-stroke disability, age, NIH stroke scale, delay from last known normal, and ASPECTS). The performance of PANDA to predict FR was assessed and compared with the original BAND score and also the widely validated THRIVE score. 296 patients were included; 36.5 % experienced FR. BAND had areas under the receiver-operating curve (AUCs) of 0.72 and 0.74 for predicting FR and LCID, respectively (both p < 0.001). The new PANDA score had AUCs of 0.76 and 0.78 for predicting FR and LCID, respectively (both p < 0.001), and it outperformed both BAND and THRIVE (all p < 0.05). Of the 30 patients (11.2 %) with high PANDA scores (≥7), 24 patients (80.0 %) suffered FR and 26 (86.7 %) suffered LCID. This external validation study confirmed the adequate performance of BAND in predicting FR. The improved PANDA score performed better than the original BAND score and the widely validated THRIVE score.

Timeliness of 24 childhood immunisations and evolution of vaccination delay: Analysis of data from 54 low- and middle-income countries.

Vaccination timeliness is often not considered among standard performance indicators of routine vaccination programmes, such as vaccination coverage, yet quantifying vaccination delay could inform policies to promote in-time vaccination and help design vaccination schedules. Here, we analysed vaccination timeliness for 24 routine childhood immunisations for 54 countries. We extracted individual vaccination status and timing from Demographic and Health Surveys data from 54 countries with surveys from 2010 onwards. Individual data was used to estimate age at vaccination for <5 year-old children. Recommended age of vaccination for each country and vaccine was compared to the age at vaccination to determine vaccination delay. The evolution of vaccination delay over time was described using estimates from different birth cohorts. To identify socio-demographic indicators associated with delayed vaccination, we used multivariable Cox regression models with country as random effect and estimated the Hazard Ratio for vaccination with each vaccine-dose for each week post recommended vaccination age. Vaccine coverage at the recommended age was highest for birth and first doses (e.g. 50.5% BCG, 18.5% DTP-D1) and lowest for later doses (e.g. 5.5% DTP-D3, 16.3% MCV-D1, 8.2% MCV-D2). Median delay was lowest for birth doses, e.g. BCG (1 week (IQR: 0 to 4)), and it increased with later doses in vaccination courses: 1 (0, 4) week for DTP-D1 versus 4 (2, 9) weeks for DTP-D3. Although the median delay for each vaccine-dose remained largely constant over time, the range of delay estimates moderately decreased. Children living in rural areas, their countries' poorer wealth quintiles and whose mothers had no formal education were more likely to received delayed vaccinations. Although we report most children are vaccinated within the recommended age window, we found little reduction on routine immunisation delays over the last decade and that children from deprived socioeconomic backgrounds are more likely to receive delayed vaccinations.

Testing Paleomagnetic Dating on Pre‐Historic Flank Eruptions From SE Slope of Etna Volcano

AbstractDuring the last 20 kyr, the Etna volcano has been characterized by almost continuous summit eruptions and by less frequent—yet definitely more destructive—flank eruptions issuing at &lt;1,000 m asl altitudes and reaching the Ionian Sea. The chronological framework of pre‐historic (pre‐2,750 yr BP) flank eruptions is supported only by few radiometric and paleomagnetic ages. Here we paleomagnetically investigated 15 Holocene lava flows from SE Etna lower slopes and dated 12 of them. Paleomagnetic dating at Etna relies on best method pre‐requisites: European location where reference geomagnetic models are well defined, and detailed stratigraphic evidence is available. We sampled 45 sites (450 oriented cores) from lavas loosely constrained in the 19,000–2,000 yr BP age window. Ten eruptions yielded a minimum 40% refinement with respect to initial age constraints, with four lava flows achieving refinement up to 90%. We obtained 620–1,398 yr (998 yr on average) dating accuracy for three flows bracketed in relatively short (1,398–1,644 yr) independent age constraints. By contrast, five flows characterized by longer 6,567–7,439 yr initial age windows yielded multiple age solutions. Finally, four lava flows with 1,644–6,567 yr‐long initial age windows were tightly dated with 120–680 yr age ranges. We conclude that at volcanoes where best paleomagnetic dating pre‐requisite are fulfilled, singular solutions are expected for 30% of the analyzed flows and, significant refinements for the others. Seven kyr seems to represent an independent age window threshold length to get or not significant dating refinements.

Critical menarche age for late-life dementia and the role of education and socioeconomic status

ABSTRACT Estrogen exposure during menstrual years has been associated with late-life neuroprotection. We explored the presence of an age-sensitive menarche window for cognition in old age and the impact of socioeconomic status and education. We compared neuropsychological performance of 1082 older women [MeanAGE = 72.69 (5.48)] with menarche in childhood, early-, mid-, and late-adolescence and dementia prevalence, severity, and type, including the effects of education and socioeconomic status. Adjusting for covariates, menarche at 11–14 years of age was associated with better memory, executive and global cognitive functioning in old age, and stronger positive effects of education and socioeconomic status on cognition than those with menarche at 15–17 years. We found a critical age window for the neuroprotective effects of estrogens during early adolescence, putting women with later menarche at higher risk for cognitive decline. Effects of socioeconomic status and education in adulthood should be a focus of future research.

Relative Biological Effectiveness of Carbon Ion Beams for Induction of Medulloblastoma with Radiation-specific Chromosome 13 Deletion in Ptch1+/- Mice.

Carbon ion radiotherapy (CIRT) for pediatric cancer is currently limited because of the unknown risk of induction of secondary cancers. Medulloblastoma of Ptch1+/- mice offers a unique experimental system for radiation-induced carcinogenesis, in which tumors are classified into spontaneous and radiation-induced subtypes based on their features of loss of heterozygosity (LOH) that affect the wild-type Ptch1 allele. The present study aims to investigate in young Ptch1+/- mice the carcinogenic effect, and its age dependence, of the low-linear energy transfer (LET, ∼13 keV/µm) carbon ions, to which normal tissues in front of the tumor are exposed during therapy. We irradiated Ptch1+/- mice at postnatal day (P) 1, 4, or 10 with 290 MeV/u carbon ions (0.05-0.5 Gy; LET, 13 keV/µm) and monitored them for medulloblastoma development. Loss of heterozygosity of seven genetic markers on chromosome 13 (where Ptch1 resides) was studied to classify the tumors. Carbon ion exposure induced medulloblastoma most effectively at P1. The LOH patterns of tumors were either telomeric or interstitial, the latter occurring almost exclusively in the irradiated groups, allowing the use of interstitial LOH as a biomarker of radiation-induced tumors. Radiation-induced tumors developed during a narrow age window (most strongly at P1 and only moderately at P4, with suppressed tumorigenesis at P10). Calculated using previous results using 137Cs gamma rays, the values for relative biological effectiveness (RBE) regarding radiation-induced tumors were 4.1 (3.4, 4.8) and 4.3 (3.3, 5.2) (mean and 95% confidence interval) for exposure at P1 and 4, respectively. Thus, the RBE of carbon ions for medulloblastoma induction in Ptch1+/- mice was higher than the generally recognized RBE of 1-2 for cell killing, chromosome aberrations, and skin reactions.

Effect of Age on Sexual Behaviour, Scrotal Circumference and Scrotal Surface Temperature in Sahiwal Bulls

Age of the bull influences the sexual behaviour and quality of semen. The present study was conducted to find out the age window at which the bull shows best reproductive performance. Fifteen Sahiwal bulls were selected and classified into three age groups (n=5, in each group) - G1(2- 3.5), G2 (&gt;3.5-8) and G3 (&gt;8-12) years. The sexual behaviour was recorded at the time of semen collection by CCTV camera at 15 days interval. Scrotal circumference (by scrotal tape) and scrotal surface temperature (by IRT) were also taken at monthly interval. The data so obtained in the experiment was subjected to statistical analysis by one-way analysis of variance (ANOVA) using SPSS software version 26.0 to draw scientific interferences. The results revealed that the mean value of scrotal circumference was significantly (p&lt;0.05) low in G1 as compared to the other two groups. No significant difference was observed among the groups for scrotal surface temperature and scrotal temperature gradient. Most of the sexual behaviour parameters were significantly high in the G2 (&gt;3.5-8) group except for the time to enter arena from preparation site and total number of mountings. Therefore, it can be concluded from this study that sexual behaviour is influenced by age and adult (middle) aged bulls performed better as compared to young and old groups.

NFS-02. MEDULLOBLASTOMAS WITH ELP1 PATHOGENIC VARIANTS: A WEAKLY PENETRANT SYNDROME WITH A RESTRICTED SPECTRUM IN A LIMITED AGE WINDOW

Abstract BACKGROUND Medulloblastomas (MB) Sonic hedgehog (SHH) subtype are associated with a cancer predisposition syndrome (CPS) in about 15% of cases, the most frequent being related to ELP1 pathogenic variant (PV). The aim of our study is to better evaluate penetrance of this CPS and detail the characteristics of the related tumors. METHODS Twenty-nine ELP1-mutated MB identified in France were retrospectively reviewed. Molecular characteristics of the tumor and clinical features of the patients were collected; whenever possible, the germline DNA from patients and their relatives were sequenced. RESULTS All patients (sex ratio 16/13) presented with SHH-MB, mostly nodular desmoplastic (n=20/28), between 3 and 15 years of age (median 7.3). All mutations are found in the germline when a constitutional DNA sample was available (n=26). Most tumors (93%) showed a biallelic inactivation of PTCH1, other recurrent alterations concerned the TP53 pathway (including 1 somatic TP53 VP) and activation of MYCN/MYCL signaling. We observed that ELP1-mutated MB behave as sporadic cases, with similar distribution within clinical and molecular risk groups of MB, similar outcomes (5y-OS = 85%) and no unusual side effects of treatments. Three patients developed a second tumor (2 high-grade gliomas and 1 thyroid carcinoma) within the irradiation fields. All germline PV were inherited from one asymptomatic parent (11 trio). No specific morphological features were mentioned. Only two index cases from the 29 French patients had a previous familial history of MB (occurring in a cousin), with many asymptomatic carriers. Except the MB, no other cancer was significantly associated with the ELP1 PV. CONCLUSIONS the low penetrance, the ‘at risk’ age window limited to childhood and the narrow tumor spectrum, question the actual benefit of genetic screening in these patients and their family. Our results suggest restricting ELP1 germline sequencing to patients with MB, depending on the parents’ request.

A Study on the Nonsurgical Correction Treatment Age Window and Long-Term Follow-Up of Infants With Congenital Ear Anomalies in China.

To evaluate the efficacy of ear molding across various initial ages and analyze challenges encountered by infants beyond the optimal treatment age window. A retrospective review of 331 infants (527 ears) treated with EarWell was conducted over 5 years from January 2017 to March 2022 at a single center. The treatment duration of the ear molding, success rate, recurrence rate, and complication rate were analyzed among the 3 age groups. Concentrate on evaluating treatment outcomes for infants with an initial age exceeding 42 days. The mean age at initial treatment was 25±28 days. In addition, it includes a child with cryptotia who is 3.5 years old (1278d). The mean duration of treatment was 7±5 weeks. In the long-term follow-up, the overall treatment success rate was 92%, with 467 ears (88.6%) showing improvement without recurrence, 30 ears (5.7%) experiencing varying degrees of recurrence, and 30 ears (5.7%) showing no improvement or complete recurrence. A total of 20 infants (3%) developed mild skin complications during treatment. Ear molding is a safe and effective option for the treatment of congenital ear anomalies, with a low recurrence rate during long-term follow-up. For infants with congenital auricular anomalies aged over 42 days, ear molding remains a viable option. Treatment success may be influenced by the age at treatment, the subtype of anomalies, and relies on the assessment of a specialized otologist, expert procedural techniques, as well as thorough understanding and cooperation from parents.

IQCB1 (NPHP5)-Retinopathy: Clinical and Genetic Characterization and Natural History

To describe the clinical and genetic features, and explore the natural history of retinopathy associated with IQCB1 variants in children and adults with retinopathy. Retrospective cohort study at a single tertiary care referral center. The study recruited 19 patients with retinopathy, harboring likely disease-causing variants in IQCB1. Demographic data and clinical presentation, best corrected visual acuity (BCVA), fundus appearance, optical coherence tomography (OCT) and autofluorescence features, electroretinography (ERG) and molecular genetics are reported. Ten patients had best corrected visual acuity better than 1.0 LogMAR, and BCVA remained stable till the last review. Seven patients had a vision of hand movements or worse in at least one eye at presentation. There was no correlation found between age of onset and severity of vision loss. Nine patients (47.4%) had a diagnosis of end-stage renal failure at presentation. The other 10 patients (52.6%) had a diagnosis of non-syndromic IQCB1-retinopathy and maintained normal renal function until the last follow-up. The mean age at diagnosis of renal failure was 26.3 ±19.8 years. OCT showed ellipsoid zone (EZ) disruption with foveal sparing in 8/13 patients. All patients had stable OCT findings. Full-field ERGs in four adults revealed a severe cone-rod dystrophy and three children had extinguished ERGs. We identified 17 IQCB1 variants, all predicted to cause loss of function. IQCB1-retinopathy is a severe early-onset cone-rod dystrophy. The dissociation between severely decreased retinal function and relative preservation of retinal structure over a wide age window makes the disease a candidate for gene therapy.

Change in the perceived reproductive age window and delayed fertility in Europe

While extensive literature documents the massive fertility delay of recent decades, knowledge about whether and how attitudes towards the timing of births have changed in Europe remains limited. Using data from two rounds of the European Social Survey, we investigate these changes and their association with macro-level fertility indicators in 21 countries. Between 2006–07 and 2018–19, societal consensus regarding the existence of optimal childbearing ages remained strong and became more in favour of later parenthood. Decomposition analyses show that these shifts were driven only partially by changes in population composition, supporting the idea that a general attitudinal change in favour of later childbearing is underway. We also find a trend towards gender convergence in upper age limits driven by the increasing social recognition of an age deadline for men’s childbearing. Although shifts in perceived reproductive age windows occurred during periods of birth postponement, they corresponded only loosely to country-level changes in fertility.

Medulloblastomas with ELP1 pathogenic variants: A weakly penetrant syndrome with a restricted spectrum in a limited age window.

ELP1 pathogenic variants (PV) have been recently identified as the most frequent variants predisposing to Sonic Hedgehog (SHH) medulloblastomas (MB); however, guidelines are still lacking for genetic counseling in this new syndrome. We retrospectively reviewed clinical and genetic data of a French series of 29 ELP1-mutated MB. All patients developed SHH-MB, with a biallelic inactivation of PTCH1 found in 24 tumors. Other recurrent alterations encompassed the TP53 pathway and activation of MYCN/MYCL signaling. The median age at diagnosis was 7.3 years (range: 3-14). ELP1-mutated MB behave as sporadic cases, with similar distribution within clinical and molecular risk groups and similar outcomes (5 y - OS = 86%); no unusual side effect of treatments was noticed. Remarkably, a germline ELP1 PV was identified in all patients with available constitutional DNA (n = 26); moreover, all tested familial trio (n = 11) revealed that the PVs were inherited. Two of the 26 index cases from the French series had a family history of MB; pedigrees from these patients and from 1 additional Dutch family suggested a weak penetrance. Apart from MB, no cancer was associated with ELP1 PVs; second tumors reported in 4 patients occurred within the irradiation fields, in the usual time-lapse for expected radiotherapy-induced neoplasms. The low penetrance, the "at risk' age window limited to childhood and the narrow tumor spectrum, question the actual benefit of genetic screening in these patients and their family. Our results suggest restricting ELP1 germline sequencing to patients with SHH-MB, depending on the parents" request.

Early acquisition of syntactic variation: Lexical conditioning of Spanish variable clitic placement

Abstract This paper examines how children acquire Spanish variable clitic placement (VCP), a lexically conditioned phenomenon whereby clitics may precede or follow complex verb phrases. Research on how children acquire truly syntactic variable phenomena suggests that they either generalize one variant initially or they match the variation in the input from the beginning. Here I examine how children acquire the lexical conditioning of Spanish VCP. A corpus study of naturalistic conversations between parents and young children suggests that from the earliest ages examined (2;0-3;0) children display lexically-specific patterns that seem to be fine-tuned by the early school years. Experimental results using two different elicitation techniques with children ages 4;0-7;0 provide further support for early acquisition of the lexical conditioning of VCP and some evidence for fine-tuning during this age window. Thus, methodological triangulation enables detection of variable use where children would otherwise show categorical use of variants with infrequent syntactic phenomena, such as Spanish VCP.

Time-Varying Determinants of Graft Failure in Pediatric Kidney Transplantation in Europe.

Little is known about the time-varying determinants of kidney graft failure in children. We performed a retrospective study of primary pediatric kidney transplant recipients (younger than 18 years) from the Eurotransplant registry (1990-2020). Piece-wise exponential additive mixed models were applied to analyze time-varying recipient, donor, and transplant risk factors. Primary outcome was death-censored graft failure. We report on 4528 kidney transplantations, of which 68% with deceased and 32% with living donor. One thousand six hundred and thirty-eight recipients experienced graft failure, and 168 died with a functioning graft. Between 2011 and 2020, the 5-year graft failure risk was 10% for deceased donor and 4% for living donor kidney transplant recipients. Risk of graft failure decreased five-fold from 1990 to 2020. The association between living donor transplantation and the lower risk of graft failure was strongest in the first month post-transplant (adjusted hazard ratio, 0.58; 95% confidence interval, 0.46 to 0.73) and remained statistically significant until 12 years post-transplant. Risk factors for graft failure in the first 2 years were deceased donor younger than 12 years or older than 46 years, potentially recurrent kidney disease, and panel-reactive antibody >0%. Other determinants of graft failure included dialysis before transplantation (until 5 years post-transplant), human leukocyte antigen mismatch 2-4 (0-15 years post-transplant), human leukocyte antigen mismatch 5-6 (2-12 years post-transplant), and hemodialysis (8-14 years post-transplant). Recipients older than 11 years at transplantation had a higher risk of graft failure 1-8 years post-transplant compared with other age groups, whereas young recipients had a lower risk throughout follow-up. Analysis of the combined effect of post-transplant time and recipient age showed a higher rate of graft failure during the first 5 years post-transplant in adolescents compared with young transplant recipients. In contrast to deceased donor younger than 12 years, deceased donor older than 46 years was consistently associated with a higher graft failure risk. We report a long-term inverse association between living donor kidney transplantation and the risk of graft failure. The determinants of graft failure varied with time. There was a significant cumulative effect of adolescence and time post-transplant. The ideal donor age window was dependent on time post-transplant.

64 The Biomarker-Based Etiological Diagnosis of Neurocognitive Disorders: the European Inter-Societal Delphi Consensus

Objective:In the field of neurocognitive disorders, the perspective offered by new disease-modifying therapy increases the importance of etiological diagnosis. The prescription of cerebrospinal fluid analysis (CSF) and imaging biomarkers is a common practice in the clinic but is often driven more by personal expertise and local availability of diagnostic tools than by evidence of efficacy and cost-effectiveness analysis. This leads to a widely heterogeneous dementia care across Europe. Therefore, a European initiative is currently being conducted to establish a consensus for biomarker-based diagnosis of patients with mild cognitive impairment (MCI) and mild dementia.Participants and Methods:Since November 2020, a European multidisciplinary task force of 22 experts from 11 scientific societies have been defining a diagnostic workflow for the efficient use of biomarkers. The Delphi consensus procedure was used to bridge the gaps of incomplete scientific evidence on biomarker prioritization. The project has been in two phases. During Phase 1, we conducted a literature review on the accuracy of imaging, CSF, neurophysiological and blood biomarkers in predicting the clinical progression or in defining the underpinning aetiology of main neurocognitive disorders. Evidence was provided to support the panelists’ decisions. In phase 2, a modified Delphi procedure was implemented, and consensus was reached at a threshold of 70% agreement, or 50%+1 when a question required rediscussion.Results:In phase 1, 167 out of 2,200 screened papers provided validated measures of biomarker diagnostic accuracy compared with a gold standard or in predicting progression or conversion of MCI to the dementia stage (i.e., MRI, CSF, FDG-PET, DaT-imaging, amyloid-PET, tau-PET, and myocardial MIBG-scintigraphy and EEG). During phase 2, panelists agreed on the clinical workspace of the workflow, the stage of application, and the patient age window. The workflow is patient-centered and features three levels of assessment (W): W1 defines eleven clinical profiles based on integrated results of neuropsychology, MRI atrophy patterns, and blood tests; W2 describes the first-line biomarkers according to W1 versus clinical suspicion; and W3 suggests the second-line biomarkers when the results of first-line biomarkers are inconsistent with the diagnostic hypothesis, uninformative or inconclusive. CSF biomarkers are first-line in the suspect of Alzheimer’s disease (AD) and when inconsistent neuropsychological and MRI findings hinder a clear diagnostic hypothesis; dopamine SPECT/PET for those leading to suspect Lewy body spectrum. FDG-PET is first-line for the clinical profiles leading to suspect frontotemporal lobar degeneration and motor tauopathies and is followed by CSF biomarkers in the case of atypical metabolic patterns, when an underlying AD etiology is conceivable.Conclusions:The workflow will promote consistency in diagnosing neurocognitive disorders across countries and rational use of resources. The initiative has some limitations, mainly linked to the Delphi procedure (e.g., kickoff questions were driven by the moderators, answers are driven by the Delphi panel composition, a subtle phrasing of the questions may drive answers, and 70% threshold for convergence is conventional). However, the diagnostic workflow will be able to help clinicians achieve an early and sustainable etiological diagnosis and enable the use of disease-modifying drugs as soon as they become available.

Pilot feasibility study of a digital technology approach to the systematic electronic capture of parent-reported data on cognitive and language development in children aged 2 years

BackgroundThe assessment of language and cognition in children at risk of impaired neurodevelopment following neonatal care is a UK standard of care but there is no national, systematic approach for...

European Inter‐Societal Delphi Consensus for the biomarker‐based etiological diagnosis of neurocognitive disorders in the mild stage

AbstractBackgroundCSF and imaging biomarkers are needed for the etiological diagnosis of neurocognitive disorders, but evidence is incomplete on their rational use in the clinic. Since October 2020, a European task force has been defining an evidence‐based diagnostic workflow, where incomplete evidence is filled by the opinion of experts. Herein, we report the preliminary results through January 2022.MethodA Delphi method was used to reach consensus. Eleven pertinent European scientific societies delegated two panelists each to join Delphi rounds and voting. Consensus was set at 70% of consistent responses.ResultIn the 5 voting rounds completed so far, panelists defined clinical setting (specialist outpatient service) and stage of application (prodromal and mild dementia) of the workflow, patients’ age window of biomarkers use (strongly encouraged below 70 years and of limited usefulness over 85). Workflow is configurated to be patient‐centered and structured on three levels of assessment (W): W1, definition of clinical profiles based on the combined results of MRI, neuropsychology, blood tests; W2, choice of first‐line biomarkers according to the main clinical suspicion (i.e., FDG‐PET for frontotemporal lobar degeneration and motor tauopathies, dopamine SPECT/PET for Lewy body spectrum disorders, and CSF biomarkers either for Alzheimer’s disease or in cases with inconclusive neuropsychological and/or MRI findings, whereas no biomarker was indicated in suspected vascular cognitive impairment); W3, selection of a second‐line biomarker when results of first‐line biomarkers are inconsistent with diagnostic hypothesis (i.e., not typical FDG‐PET pattern) or uninformative (i.e., borderline CSF amyloid results) or not sufficient to rule out other etiologies (i.e., amyloid‐positive and tau‐negative CSF results) or when a diagnosis remains possible despite a negative first‐line biomarker (e.g., normal dopamine SPECT/PET in suspected prodromal dementia with Lewy bodies).ConclusionThe task force is currently defining the second‐line biomarkers of W3 and the project it set to deliver the final algorithm by June 2022. The workflow will promote consistency in diagnosing neurocognitive disorders across countries, and rational use of resources. The initiative has an impact in preparing clinicians to work in the upcoming clinical space where etiological disease‐modifying drugs are expected to be available.

Deciphering the Influence of Estradiol and Estrogen Receptors on Cognitive Function: A Bibliometric Analysis and Emerging Research Trends.

BACKGROUND The cognitive impact of estradiol (E2), a sex steroid hormone, particularly its unique characteristics mediated through different estrogen receptors (ERs), is garnering research interest to optimize estrogen replacement therapy (ERT) and mitigate adverse effects. However, a systematic bibliometric investigation elucidating the connection between E2/ERs and cognition is lacking. This study examines 3502 Web of Science Core Collection publications using CiteSpace to unveil trends in this research field. MATERIAL AND METHODS The primary goal was to analyze highly co-cited articles characterized by extensive citation, centrality, Sigma index, and burst strength. We identified six research themes and directions from ten distinct, highly credible clusters (Q=0.8266; S=0.978), established by frequently employed keywords. Secondly, we sought to highlight the most contributing countries, institutions, and authors in this domain. RESULTS The study unveiled that the 'critical age window period' hypothesis of ERT, hippocampus-derived E2, the mediating role of GPER, and crosstalk among ERs are the current hotspots in this field. Future research is likely to explore the links between E2/ERs and the hippocampus, various memory types, sex specificity, and receptor specificity. The United States and the University of Wisconsin have the most publications, while Scotland and Stanford University have the highest centrality. The most influential authors are Woolley CS, Frick KM, Tuscher JJ, and Espeland MA. CONCLUSIONS These findings inform prospective research directions and hint at potential E2 targets for cognitive enhancement.

Assessment of gestational age at antenatal care visits among Kenyan women to inform delivery of a maternal respiratory syncytial virus (RSV) vaccine in low- and middle-income countries.

Background: Maternal respiratory syncytial virus (RSV) vaccines that are likely to be implementable in low- and middle-income countries (LMICs) are in final stages of clinical trials. Data on the number of women presenting for antenatal care (ANC) per day and proportion attending within the proposed gestational window for vaccine delivery, is a prerequisite to guide development of vaccine vial size and inform vaccine uptake in this setting. Methods: We undertook administrative review and abstraction of ANC attendance records from 2019 registers of 24 selected health facilities, stratified by the level of care, from Kilifi, Siaya and Nairobi counties in Kenya. Additional data were obtained from Mother and Child Health (MCH) booklets of women in each of the Health and Demographic Surveillance System (HDSS) areas of Kilifi, Nairobi and Siaya. Data analysis involved descriptive summaries of the number (mean, median) and proportion of women attending ANC within the gestational window period of 28-32 weeks and 24-36 weeks. Results: A total of 62,153 ANC records were abstracted, 33,872 from Kilifi, 19,438 from Siaya and 8,943 from Nairobi Counties. The median (Interquartile range, IQR) number of women attending ANC per day at a gestational age window of 28-32 and 24-36 weeks, respectively, were: 4 (2-6) and 7 (4-12) in dispensaries, 5 (2-9) and 10 (4-19) in health centres and 6 (4-11) and 16 (10-26) in county referral hospitals. In the HDSS areas of Kilifi, Siaya and Nairobi, pregnant women attending at least one ANC visit, within a window of 28-32 weeks, were: 77% (360/470), 75% (590/791) and 67% (547/821), respectively. Conclusions: About 70% of pregnant women across three distinct geographical regions in Kenya, attend ANC within 28-32 weeks of gestation. A multidose vial size with about five doses per vial, approximates daily ANC attendance and would not incur possible wastage in similar settings.

Early Results from GLASS-JWST. XVI. Discovering a Bluer z ∼ 4–7 Universe through UV Slopes

We use the GLASS-JWST Early Release Science NIRCam parallel observations to provide a first view of the UV continuum properties of NIRCam/F444W selected galaxies at 4 < z < 7. By combining multiwavelength NIRCam observations, we constrain the UV continuum slope for a sample of 401 galaxies with stringent quality controls. We find that >99% of the galaxies are blue star-forming galaxies with very low levels of dust (Av β ∼ 0.01 ± 0.33). We find no statistically significant correlation for UV slope with redshift or UV magnitude. However, we find that in general galaxies at higher redshifts and fainter UV magnitudes have steeper UV slopes. We find a statistically significant correlation for UV slope with stellar mass, with galaxies with higher stellar mass showing shallower UV slopes. Individual fits to some of our galaxies reach the bluest UV slopes of β ∼ −3.1 allowed by stellar population models used in this analysis. Therefore, it is likely that stellar population models with a higher amount of Lyman continuum leakage, active galactic nucleus effects, and/or Population III contributions are required to accurately reproduce the rest-UV and optical properties of some of our bluest galaxies. This dust-free early view confirms that our current cosmological understanding of gradual mass + dust buildup of galaxies with cosmic time is largely accurate to describe the ∼0.7–1.5 Gyr age window of the universe. The abundance of a large population of UV faint dust-poor systems may point to a dominance of low-mass galaxies at z > 6 playing a vital role in cosmic reionization.

Age and Genetic Risk Score and Rates of Blood Lipid Changes in China

Blood lipids are the primary cause of atherosclerosis. However, little is known about relationships between rates of blood lipid changes and age and genetic risk. To evaluate associations of blood lipid change rates with age and polygenic risk. This cohort is from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China, which was established from 1998 to 2008. Participants were followed up until 2020 (mean [SD] follow-up, 13.8 [4.3] years) and received 4 repeated lipid measurements. Data analysis was performed from June to August 2022. A total of 47 691 participants with available genotype data were recruited, and 37 317 participants aged 18 years or older were included in the final analysis after excluding participants who were lost to follow-up or with major chronic diseases, and those without blood lipid measurements at baseline and any follow-up survey. Age and polygenic risk scores based on 126 lipid-related genetic variants. The estimated annual changes (EAC) of blood lipids in milligrams per deciliter. This study evaluated 37 317 participants (mean [SD] age of 51.37 [10.82] years; 15 664 [41.98%] were male). The associations of EACs of blood lipids with age differed substantially between male and female participants. Male participants experienced declining change as they got older for total cholesterol (EAC, 0.34 [95% CI, 0.14 to 0.54] mg/dL for age <40 years vs 0.01 [95% CI, -0.11 to 0.13] mg/dL for age ≥60 years), triglyceride (EAC, 3.28 [95% CI, 2.50 to 4.07] mg/dL for age <40 years vs -1.70 [95% CI, -2.02 to -1.38] mg/dL for age ≥60 years), and low-density lipoprotein cholesterol (LDL-C) (EAC, 0.15 [95% CI, -0.02 to 0.32] mg/dL for age <40 years vs 0.01 [95% CI, -0.10 to 0.11] mg/dL for age ≥60 years). Female participants had inverse V-shaped associations and the greatest rate of change appeared in the age group of 40 to 49 years (EAC for total cholesterol, 1.33 [95% CI, 1.22 to 1.44] mg/dL; EAC for triglyceride, 2.28 [95% CI, 1.94 to 2.62] mg/dL; and EAC for LDL-C, 0.94 [95% CI, 0.84 to 1.03] mg/dL). Change in levels of blood lipids were also associated with polygenic risk. Participants at low polygenic risk tended to shift toward lower blood lipid levels, with EACs of -0.16 (95% CI, -0.25 to -0.07) mg/dL; -1.58 (95% CI, -1.78 to -1.37) mg/dL; and -0.13 (95% CI, -0.21 to -0.06) mg/dL for total cholesterol, triglyceride, and LDL-C, respectively. Participants with high polygenic risk had the greatest rates of change for total cholesterol, triglyceride, and LDL-C (EAC, 1.12 [95% CI, 1.03 to 1.21] mg/dL; EAC, 3.57 [95% CI, 3.24 to 3.91] mg/dL; and EAC, 0.73 [95% CI, 0.65 to 0.81] mg/dL, respectively). Similar patterns were also observed across sex and age groups. In this cohort study, EACs of blood lipids were significantly associated with age and polygenic risk, suggesting that prevention strategies for lipids should focus on individuals with high genetic risk and in the critical age window.