The use of Cohort Size Shrinkage Index (CSSI) to quantify regional famine intensity during the Chinese famine of 1959-61

There has been a growing interest in studying the causes and impact of the Great Chinese Famine of 1959-61. The Cohort Size Shrinkage Index (CSSI) is the most widely used measure to examine famine intensity and was used in at least 28 Chinese famine studies to date. We examined the potential impact of violations of three requirements for a valid CSSI measure: reliable information on cohort size by year of birth; a stable trend of cohort size by year of birth; and the absence of significant regional migration. We used data from the 1% China 2000 Census to examine the trend of cohort size over time and concentrated on the time window between 1950-70 to exclude policies and events with a large impact on birth trends other than the famine itself. Across China we established a significant difference in cohort size trends between pre-famine births and post-famine births, violating one of the main requirements for a valid CSSI measure. This leads to systematic differences in CSSI depending on what non-famine years are selected for comparison. At the province level, CSSIs estimated based on pre- & post-famine births tend to overestimate famine intensity at higher exposure levels and underestimate intensity at lower levels compared to CSSIs based on pre-famine births alone. This is problematic and demonstrates that the CSSI is not as robust an estimator of famine intensity as had been assumed previously. We recommend therefore that all CSSI should be based on pre-famine birth trends. Using data from Sichuan province, we demonstrate a less pronounced dose-response relation between famine intensity and tuberculosis outcomes using pre-famine based CSSI as compared to reported patterns based on pre- & post-famine based CSSI. We encourage researchers to re-examine their results of Chinese famine studies as local differences in cohort size of pre-famine and post-famine births may lead to significant discrepancies of CSSI estimation and change the interpretation of their findings.

Stroke Aetiology and Collateral Status in Acute Ischemic Stroke Patients Receiving Reperfusion Therapy—A Meta-Analysis

Background: The interplay between collateral status and stroke aetiology may be crucial in the evaluation and management of acute ischemic stroke (AIS). Our understanding of this relationship and its level of association remains sub-optimal. This study sought to examine the association of pre-intervention collateral status with stroke aetiology, specifically large artery atherosclerosis (LAA) and cardio-embolism (CE), in AIS patients receiving reperfusion therapy, by performing a meta-analysis. Methods: Relevant search terms were explored on Medline/PubMed, Embase and Cochrane databases. Studies were included using the following inclusion criteria: (a) patients aged 18 or above; (b) AIS patients; (c) patients receiving reperfusion therapy; (d) total cohort size of >20, and (e) qualitative or quantitative assessment of pre-intervention collateral status on imaging using a grading scale. Random-effects meta-analysis was performed to investigate the association of aetiology with pre-intervention collateral status, and forest plots of risk ratio (RR) were generated. Results: A meta-analysis was conducted on seven studies, with a cumulative cohort of 1235 patients, to assess the association of pre-intervention collateral status with stroke aetiology. Patients with LAA were associated significantly with an increased rate of good collaterals (RR 1.24; 95% CI 1.04–1.50; p = 0.020, z = 2.33). Contrarily, CE aetiology was associated significantly with a decreased rate of good collaterals (RR 0.83; 95% CI 0.71–0.98; p = 0.027, z = −2.213). Conclusions: This study demonstrates that, in AIS patients receiving reperfusion therapy, LAA and CE aetiologies are associated significantly with collateral status.

412. Estimating the Impact of School Classroom Sizes on the Probability of Severe Acute Respiratory Syndrome Coronavirus-2 Infectivity or Exposure

Background Despite schools reopening across the United States in communities with low and high Coronavirus disease 2019 (COVID-19) prevalence, data remain scarce about the effect of classroom size on the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) within schools. This study estimates the effect of classroom size on the risk of COVID-19 infection in a closed classroom cohort for varying age groups locally in Durham, North Carolina. Total number of Coronavirus Disease 2019 (COVID-19) infections over a 28-day follow-up period for varying classroom reproduction number (R0) and varying classroom cohort sizes of 15 students, 30 students and 100 students in Durham County, North Carolina. Methods Using publicly available population and COVID-19 case count data from Durham County, we calculated a weekly average number of new confirmed COVID-19 cases per week between May 3, 2020 and August 22, 2020 according to age categories: < 5 years, 5-9 years, 10-14 years, and 15-19 years. We collated average classroom cohort sizes and enrollment data for each age group by grade level of education for the first month of the 2019-2020 academic school year. Then, using a SEIR compartmental model, we calculated the number of susceptible (S), exposed (E), infectious (I) and recovered (R) students in a cohort size of 15, 30 and 100 students, modelling for classroom reproduction number (R0) of 0.5, 1.5 and 2.5 within a closed classroom cohort over a 14-day and 28-day follow-up period using age group-specific COVID-19 prevalence rates. Results The SEIR model estimated that the increase in cohort size resulted in up to 5 new COVID-19 infections per 10,000 students whereas the classroom R0 had a stronger effect, with up to 88 new infections per 10,000 students in a closed classroom cohort over time. When comparing different follow-up periods in a closed cohort with R0 of 0.5, we estimated 12 more infected students per 10,000 students over 28 days as compared to 14 days irrespective of cohort size. With a R0 of 2.5, there were 49 more infected students per 10,000 students over 28 days as compared to 14 days. Conclusion Classroom R0 had a stronger impact in reducing school-based COVID-19 transmission events as compared to cohort size. Additionally, earlier isolation of newly infected students in a closed cohort resulted in fewer new COVID-19 infections within that group. Mitigation strategies should target promoting safe practices within the school setting including early quarantine of newly identified contacts and minimizing COVID-19 community prevalence. Disclosures Michael J. Smith, MD, M.S.C.E, Merck (Grant/Research Support)Pfizer (Grant/Research Support)

P–551 Blastocyst cohort size is not associated with embryo aneuploidy: comprehensive multi-centre data from current preimplantation genetic testing cycles

Study question Does blastocyst cohort size impact aneuploidy rates, evaluated by next generation sequencing (NGS)? Summary answer Embryo aneuploidy rates were independent of blastocyst cohort size across all patient ages. What is known already The effects of ovarian response on oocyte and embryo quality remain controversial. Several studies have proposed that a high response to ovarian stimulation may negatively impact oocyte competence. Alternatively, irrespective of maternal age, a poor ovarian response may potentially compromise embryo quality. Using blastocyst cohort size as an indirect measure of ovarian response, previous studies applying array comparative genomic hybridisation (aCGH) have demonstrated that the number of embryos available for biopsy does not impact embryo aneuploidy rates. Nevertheless, these findings remain to be confirmed in a comprehensive cohort, using current approaches for preimplantation genetic testing for aneuploidies (PGT-A). Study design, size, duration Retrospective, international, cohort study of 3998 patients from 16 clinics undergoing PGT-A from 2016–2020. We evaluated 11665 blastocysts, tested using trophectoderm (TE) biopsy and next generation sequencing (NGS). To eliminate bias of multiple treatments, we considered only the first PGT-A cycle for all patients. Both autologous and donation cycles were included in the analysis. Cycles were excluded if they utilised preimplantation genetic testing for monogenic disorders (PGT-M) or preimplantation genetic testing for structural rearrangements (PGT-SR). Participants/materials, setting, methods We evaluated aneuploidy and mosaicism rates, as well as the proportion of patients who had at least one euploid embryo suitable for transfer. Findings were stratified according to SART-defined maternal age groups, <35 (n = 698/2622 patients/blastocysts), 35–37 (n = 988/3141 patients/blastoycsts), 38–40 (n = 1447/3939 patients/blastocysts), 41–42 (653/1562 patients/blastocysts) and >42 (212/401 patients/blastocysts) and blastoycst cohort size (1–2, 3–5, 6–9 and 10 or more biopsied blastocysts). Main results and the role of chance The mean maternal age was 37.0±3.7. The overall embryo aneuploidy rate was 50.6% (5904/11665), while mosaicism was established in 4.0% (469/11665) of blastocysts. As expected, the proportion of aneuploid embryos increased steadily with advancing maternal age (31.8%, 41.5%, 58.4%, 71.2%, 87.8%; p < 0.0001), while mosaicism rates did not vary significantly (p = 0.2). Within each age group, we observed no association between the number of blastocysts biopsied and aneuploidy or mosaicism rates. However, as previously suggested, the chance of having at least one euploid embryo increased linearly with the number of embryos biopsied. We observed that young patients (<35) with 1–2 blastocysts had a 70.4% of having at least one embryo suitable for transfer, which increased to 96.4% and 99.2% with 3–5 and 6–9 blastocysts, respectively. Similar trends were observed in the 36–38 and 39–40 age groups. Patients in the 40–41 age group had a significantly lower chance of having a suitable embryo for transfer. Nevertheless, the chance increased from 27.2% with 1–2 embryos to 61.2% with 3–5 blastocysts. Patients with >10 embryos had at least one euploid embryo in 100% of cases, across all ages. Albeit, the numbers of patients within this category was low, and decreased significantly with advancing maternal age. Limitations, reasons for caution While blastocyst cohort size is considered to be an indirect measure of ovarian reserve, the number of oocytes retrieved was not evaluated. Our study only included the first PGT-A cycle for all patients. Subsequent, alterations in stimulation protocols may have resulted in an improved response in some patients. Wider implications of the findings: The comprehensive nature of the study, based on current PGT-A approaches and a large number of cycles across 16 centres increases clinical confidence in the notion that ovarian response is independent of embryo aneuploidy. Importantly, our findings may serve as a valuable clinical resource to guide patient counselling strategies. Trial registration number NA

P–413 The combination of endometrial injury and Freeze-All strategy in women with repeated implantation failures

Study question Can the combination of hysteroscopic endometrial injury (EI) and freeze-all strategy improve pregnancy parameters, mainly live birth, in women with repeated implantation failures (RIF)? Summary answer The combination of Endometrial Injury and freeze-all strategy has no significant effect on live birth, clinical and miscarriage rates in RIF patients undergoing ART. What is known already A variety of strategies and approaches for RIF patients undergoing ART have been used and proposed. Currently there is insufficient evidence in the literature concerning the effect of either EI or freeze-all strategy in IVF cycles and very limited on the combination of these two approaches in RIF patients. Study design, size, duration This is a two-center two-arm cohort study conducted at both University and Private Assisted Reproductive Units in Greece, encompassing 60 cycles with vitrification as the cryopreservation method from 60 participants during the last three years. Participants/materials, setting, methods The study group comprised of 30 patients with RIF and underwent a hysteroscopic endometrial injury in the menstrual cycle prior that to the embryo transfer. The control group comprised of patients with RIF and underwent a standard cycle with no adjuvant treatment. Our primary analysis was performed to provide a direct comparison between groups. Logistic and Poisson Regression models were further employed to examine possible confounding effects. Main results and the role of chance Live birth did not differ between groups (p = 0.0953); similarly, clinical pregnancy and miscarriage rates were comparable among them (p = 0.3472 and p = 0.2542, respectively). The number of retrieved oocytes was the only significant confounder for biochemical pregnancy (p = 0.0481, 95% CI: (0.0014, 0.3223)]. Limitations, reasons for caution Limitations of the study include the lack of randomization that is linked with known and unknown biases and the small cohort size. Wider implications of the findings: The combination of both endometrial injury and freeze-all strategy does not appear to improve pregnancy rates, including live birth, in patients with RIF undergoing ART. The number of retrieved oocytes was the only significant confounder for biochemical pregnancy. Trial registration number NCT04597463

105 The Mustaq Method: Could This be The Simplest Shoulder Dislocation Reduction Method?

Introduction The Mushtaq Method is a new shoulder reduction technique. It is a simple, reliable, and less traumatic time modulated procedure. Method Patients are placed in the supine position if plausible. Fully adducting the affected arm with the elbow at right angle. The practitioner applies gentle traction above the elbow with the other hand placed deep into the axilla, palpation of the humeral head is followed by lateral pressure resulting in a successful relocation. Internal rotation and a broad arm sling complete the technique. No assistants are needed, and simple analgesia was often enough. Results 95% had a successful reduction within 5 minutes. 75% required analgesia alone, and no periprocedural complications were observed. Conclusions With so many options already, available it is essential to understand what dictates the success and failures of these methods. We have a new, safe, easy to use method requiring minimal force. We hope to increase our cohort size in the future to draw firm conclusions.

Work-Based Learning (WBL) Model to Develop Self-Directed Learners in Optometry Education - An Evaluation

Purpose: This paper evaluated the effectiveness of work-based learning (WBL) model to develop self-directed learning skills in optometry education. Methods: ‘WBL cohort 1’ in Academic year (AY) 1819S1 (n = 20) and ‘WBL cohort 2’ in AY1920S1 (n = 65) were studied and compared with a ‘traditional cohort’ (n = 42). The following were investigated: (i) Student Survey (SS); (ii) Focus Group Interview (FGI); (iii) adjunct lecturer survey and (iv) Final Module Score (FMS) in four core modules. Results: Through SS, >60% reported that WBL enabled them to be selfdirected learners and >80% felt that it helped to develop useful optometry skills and knowledge. Through FGI, 83% of the ‘WBL cohort 1’ and 54% of the ‘WBL cohort 2’ reported that it trained them to be self-directed learners. More than 60% of the adjunct lecturers surveyed reported that students who underwent the WBL model had exhibited good interpersonal skills, critical thinking and good traits of an independent optometrist. However, these were not as clearly evident when the cohort size was increased. Based on academic performance (with FMS as an indicator), WBL produced variable results in the four core modules surveyed, with WBL cohorts 1 and 2 performing differently. Conclusion: WBL model was able to develop self-directed learners and professional dispositions as well as generic employability skills. To scale WBL for larger cohorts, considerations must be given to faculty and resource availability, which it demands.

Cross-Disorder Analysis of De Novo Variants Increases the Power of Prioritising Candidate Genes

De novo variants (DNVs) are critical to the treatment of neurodevelopmental disorders (NDDs). However, effectively identifying candidate genes in small cohorts is challenging in most NDDs because of high genetic heterogeneity. We hypothesised that integrating DNVs from multiple NDDs with genetic similarity can significantly increase the possibility of prioritising the candidate gene. We catalogued 66,186 coding DNVs in 50,028 individuals with nine types of NDDs in cohorts with sizes spanning from 118 to 31,260 from Gene4Denovo database to validate this hypothesis. Interestingly, we found that integrated DNVs can effectively increase the number of prioritised candidate genes for each disorder. We identified 654 candidate genes including 481 shared candidate genes carrying putative functional variants in at least two disorders. Notably, 13.51% (65/481) of shared candidate genes were prioritised only via integrated analysis including 44.62% (29/65) genes validated in recent large cohort studies. Moreover, we estimated that more novel candidate genes will be prioritised with the increase in cohort size, in particular for some disorders with high putative functional DNVs per individual. In conclusion, integrated DNVs may increase the power of prioritising candidate genes, which is important for NDDs with small cohort size.

External Habits Formation and the Environment

The present paper presents a standard overlapping generations model with external habits formation and environmental quality in the utility function. Our main objective is to study the impact of external habits on capital accumulation and environmental quality on the intertemporal competitive equilibrium. We notice that striving for status leads to environment worsening and capital increasing when the cohort size is large.