Large Effect Research Articles

Place-based rural development programs and the labor allocation of farm households

PurposeRural development programs are widely used policy instruments mitigating rural-urban economic disparities. Yet, little research has examined their effect on rural labor. This study fills this knowledge gap by quantifying the causal impact of such programs on the labor allocation of farm households in Taiwan.Design/methodology/approachA theoretical framework based on the agricultural household model is constructed to guide the empirical specification. A unique dataset compiles administrative data on the program’s subsidies with farm household surveys across seven years. To cope with endogeneity bias, an instrumental variables model is applied. The eligibility rule for a township to participate in the program is used as the instrument.FindingsWe find that the program increases the labor supply of farm household members. These effects are more pronounced for off-farm work, particularly non-heads of farm households. The program’s subsidies supporting culture and promotion-related activities have larger effects. Finally, females benefited more from the program.Originality/valueWe focus on farm households since this group is the target of place-based rural development programs. In addition, we identify the causal impact of place-based development programs on rural labor. Finally, this study is relevant to the literature on intra-household models by demonstrating that place-based rural development programs can affect the labor supply of farm household members.

PUBLICITY, FACILITIES DIVERSITY AND WILLINGNESS TO PAY FOR HOUSEHOLD WASTE SORTING: NEW EVIDENCE FROM HETEROGENEITY REGRESSION

Household waste sorting is important to actively promote the construction of beautiful countryside and beautiful city via household waste reduction or recycling. The Law of China on the Prevention and Control of Solid Waste Environmental Pollution indicates that household waste treatment fee system follows the principle of “who produces, who pays”, reflecting differentiated management such as classified pricing and metering fees. This research mainly investigates the determinants of willingness to pay (WTP) for household waste sorting in China. This study mainly compares different effects of the waste sorting information publicity, waste sorting facilities diversity, perceived convenience and reference group behavior on WTP via multiple and logistic regression. It also explores gender and regional heterogeneity for WTP of household waste sorting in China. This study also analyzes how individuals respond to different levels of WTP fees of household waste sorting via logistic regression. The empirical results reveal that the facilities diversity of waste sorting has the highest effect on WTP for household waste sorting, followed by perceived convenience, publicity and reference group behaviors. Females have relatively lower WTP than males. Education has significant positive effects on males’ waste sorting WTP. In logistic regression, reference group has larger effect on WTP compared with other antecedents. It is important to enhance facilities and publicity of household waste sorting. This research is of great significance to increase the household waste sorting behavior, enhance the governance system of household waste sorting via the collaboration of government, medias, communities and individuals.

Pan-transcriptome reveals a large accessory genome contribution to gene expression variation in yeast.

Gene expression is an essential step in the translation of genotypes into phenotypes. However, little is known about the transcriptome architecture and the underlying genetic effects at the species level. Here we generated and analyzed the pan-transcriptome of ~1,000 yeast natural isolates across 4,977 core and 1,468 accessory genes. We found that the accessory genome is an underappreciated driver of transcriptome divergence. Global gene expression patterns combined with population structure showed that variation in heritable expression mainly lies within subpopulation-specific signatures, for which accessory genes are overrepresented. Genome-wide association analyses consistently highlighted that accessory genes are associated with proportionally more variants with larger effect sizes, illustrating the critical role of the accessory genome on the transcriptional landscape within and between populations.

Exploring the kynurenine pathway in mild traumatic brain injury: A longitudinal study.

A potential source of novel biomarkers for mTBI is the kynurenine pathway (KP), a metabolic pathway of tryptophan (Trp), that is up-regulated by neuroinflammation and stress. Considering that metabolites of the KP (kynurenines) are implicated in various neuropsychiatric diseases, exploration of this pathway could potentially bridge the gap between physiological and psychological factors in the recovery process after mTBI. This study, therefore, set out to characterize the KP after mTBI and to examine associations with long-term outcome. Patients were prospectively recruited at the emergency department (ED), and blood samples were obtained in the acute phase (<24 h; N = 256) and at 1-month follow-up (N = 146). A comparison group of healthy controls (HC; N = 32) was studied at both timepoints. Trp, kynurenines, and interleukin (IL)-6 and IL-10 were quantified in plasma. Clinical outcome was measured at six months post-injury. Trp, xanthurenic acid (XA), and picolinic acid (PA) were significantly reduced in patients with mTBI relative to HC, corrected for age and sex. For Trp (d = -0.57 vs. d = -0.29) and XA (d = -0.98 vs. d = -0.32), larger effects sizes were observed during the acute phase compared to one-month follow-up, while for PA (d = -0.49 vs. d = -0.52) effect sizes remained consistent. Findings for other kynurenines (e.g., kynurenine, kynurenic acid, and quinolinic acid) were non-significant after correction for multiple testing. Within the mTBI group, lower acute Trp levels were significantly related to incomplete functional recovery and higher depression scores at 6 months post-injury. No significant relationships were found for Trp, XA, and PA with IL-6 or IL-10 concentrations. In conclusion, our findings indicate that perturbations of the plasma KP in the hyperacute phase of mTBI and 1 month later are limited to the precursor Trp, and glutamate system modulating kynurenines XA and PA. Correlations between acute reductions of Trp and unfavorable outcomes may suggest a potential substrate for pharmacological intervention.

The External Validity of College Remediation Effects: Caveats about Compliers in Fuzzy-discontinuity Designs

Abstract Fuzzy regression-discontinuity evaluations of college remediation often find negative and null estimates of local average treatments effects (LATEs), but with substantial heterogeneity. We find that a remedial quantitative skills course at Wellesley College has a modestly positive LATE on participation in mathematically intensive fields of study—including the sciences, mathematics, and economics courses. Yet, LATEs are a weighted average of average causal effects (at the passing cutoff) in two principal strata: students who voluntarily comply with remediation, and those who are coerced to comply after scoring below the cutoff on an optional retest. In the retest sample, we show that average causal effects are close to zero among (1) coerced compliers, and (2) never-takers. By implication, there are even larger effects among a smaller group of voluntary compliers at the cutoff. The results help interpret the mixed findings in the literature, in which compliance varies widely, and demonstrate methods for assessing external validity in fuzzy-discontinuity designs.

Menstrual cycle and strength levels in women: a pilot study

It is speculated that hormonal fluctuations during the different menstrual cycle (MC) phases can influence physiological systems, such as musculoskeletal, and can also impact physical performance and quality of life. The aimed to check and compare the effects of MC on women's strength levels. The sample was made up of 18-30 years old women, who were using (G1) or not (G2) Oral Contraceptives (OC). Hormonal concentrations were determined using blood extraction, while muscle strength (FM) was assessed through the maximal dynamic strength (1RM) and muscle power tests at 40%, 60%, and 80%. The data were processed using two-factor ANCOVA (group and time), at a significance level of p &lt; 0.05. Hormonal values showed greater significant differences in almost all hormones and G1 phases. The results of the FM tests showed a significant reduction of 1 RM (day 21) in G1, with a moderate effect size on days 21 and 11. In the G1 muscle power (MP) test, on day 01 there was a significant increase in 60% concerning day 11 and day 21. It can be considered that the hormonal behavior of both groups was maintained throughout the evaluations. Regarding FM manifestations, it is suggested that regular MC, without the use of OC, induces a reduction in FM levels during days 11 and 21 in women. However, the group that used OC had a larger effect size on 40% on day 01 and 40% on day 21.

Tractable bayesian estimation of smooth transition vector autoregressive models

Abstract We develop a tractable way of estimating the parameters ruling the nonlinearity in the popular Smooth Transition VAR model, and identify structural shocks using external instruments. This jointly offers an alternative to the option of identifying shocks recursively and calibrating key parameters. In an illustration, we show that monetary policy shocks generate larger effects on economic activity during economic expansions compared to economic recessions. We then document that calibrating rather than estimating the parameters ruling the nonlinearity of the model can lead to values for which the key results are lost. This suggests caution in the calibration of these parameters.

Reading abilities in preterm children: a systematic review and meta-analysis.

It is well recognized that children born preterm have specific learning difficulties. The objective of this study is to carry out a systematic review and meta-analysis on preterm children's reading ability performance. Of the 486 studies identified, 53 met the inclusion criteria, resulting in 143 effect sizes. 33,500 children between 5 and 18years were included of whom 13,765 were preterm infants and 19,735 were full-term infants. Among preterm-born children without neurodevelopmental disorders significant differences and larger effect sizes were found in the reading subcategories, letter-word knowledge, reading comprehension, and spelling, whereas no significant differences were found in phonological awareness and rapid automatized naming. Extremely preterm children showed larger effect size. The present meta-analysis, which includes a much larger number of studies, shows that preterm children have lower performance than full-term children in reading and spelling. This fact underlines the need to design, develop and implement neuroeducational programs that take into account the characteristics of preterm born students.

Examining the association of hysterectomy with and without oophorectomy on cardiovascular disease and all-cause, cardiovascular or cancer mortality: A systematic review and meta-analysis.

The associations between hysterectomy and cardiovascular disease (CVD) and mortality remains unlcear and a meta-analysis with cohort studies is lacking. This study aimed to conduct a systematic review and meta-analysis of cohort studies to investigate the relationship between hysterectomy and CVD, coronary heart disease (CHD), stroke, heart failure, and all-cause, cardiovascular and cancer mortality. We further explored the effect of oophorectomy on the association between hysterectomy and these health outcomes. PubMed, EMBASE and Web of Science were searched up to 24 July 2023. Cohort studies. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were pooled using a random-effects model. We used I2 to assess the heterogeneity between studies. Forty-three studies were included in the meta-analysis. Hysterectomy was significantly associated with an increased risk of CVD (pooled HR 1.11, 95% CI 1.09-1.13; n = 6; I2 = 0) and stroke (HR 1.09, 95% CI 1.04-1.14; n = 7; I2 = 52%), but with a decreased risk of cancer mortality (HR 0.93, 95% CI 0.86-1.00; n = 4; I2 = 81%). No significant association was observed between hysterectomy and CHD (n = 10; I2 = 83%), all-cause mortality (n = 8; I2 = 81%) or cardiovascular mortality (n = 7; I2 = 89%). Hysterectomy with and without oophorectomy was significantly associated with CVD and stroke risk, but showed a larger effect size for hysterectomy with oophorectomy. A significantly increased risk of CHD was observed in the subgroup of hysterectomy with oophorectomy, but not for the subgroup of hysterectomy alone. Hysterectomy may increase the risk of CVD, CHD and stroke, but not all-cause, cardiovascular or cancer mortality. Hysterectomy with oophorectomy may have a higher risk of CVD, CHD and stroke than hysterectomy alone. However, the results on CHD and mortality related to hysterectomy should be interpreted cautiously because of the high level of heterogeneity and unstable subgroup analyses.

Assessment of Gray Matter Microstructural Alterations in Alzheimer's Disease by Free Water Imaging.

Cortical neurodegenerative processes may precede the emergence of disease symptoms in patients with Alzheimer's disease (AD) by many years. No study has evaluated the free water of patients with AD using gray matter-based spatial statistics. The aim of this study was to explore cortical microstructural changes within the gray matter in AD by using free water imaging with gray matter-based spatial statistics. Seventy-one participants underwent multi-shell diffusion magnetic resonance imaging, 11C-Pittsburgh compound B positron emission tomography, and neuropsychological evaluations. The patients were divided into two groups: healthy controls (n = 40) and the AD spectrum group (n = 31). Differences between the groups were analyzed using voxel-based morphometry, diffusion tensor imaging, and free water imaging with gray matter-based spatial statistics. Voxel-based morphometry analysis revealed gray matter volume loss in the hippocampus of patients with AD spectrum compared to that in controls. Furthermore, patients with AD spectrum exhibited significantly greater free water, mean diffusivity, and radial diffusivity in the limbic areas, precuneus, frontal lobe, temporal lobe, right putamen, and cerebellum than did the healthy controls. Overall, the effect sizes of free water were greater than those of mean diffusivity and radial diffusivity, and the larger effect sizes of free water were thought to be strongly correlated with AD pathology. This study demonstrates the utility of applying voxel-based morphometry, gray matter-based spatial statistics, free water imaging and diffusion tensor imaging to assess AD pathology and detect changes in gray matter.

Microplastic exposure is associated with epigenomic effects in the model organism Pimephales promelas (fathead minnow).

Microplastics have evolutionary and ecological impacts across species, affecting organisms' development, reproduction, and behavior along with contributing to genotoxicity and stress. As plastic pollution is increasing and ubiquitous, gaining a better understanding of organismal responses to microplastics is necessary. Epigenetic processes such as DNA methylation are heritable forms of molecular regulation influenced by environmental conditions. Therefore, determining such epigenetic responses to microplastics will reveal potential chronic consequences of this environmental pollutant. We performed an experiment across two generations of fathead minnows (Pimephales promelas) to elucidate transgenerational epigenetic effects of microplastic exposure. We exposed the first generation of fish to four different treatments of microplastics: two concentrations of each of pre-consumer polyethylene (PE) and PE collected from Lake Ontario. We then raised the first filial generation with no microplastic exposure. We used enzymatic methylation sequencing on adult liver tissue and homogenized larvae to evaluate DNA methylation differences among treatments, sexes, and generations. Our findings show the origin of the plastic had a larger effect in female minnows whereas the effect of concentration was stronger in the males. We also observed transgenerational effects, highlighting a mechanism in which parents can pass on the effects of microplastic exposure to their offspring. Many of the genes found within differentially methylated regions in our analyses are known to interact with estrogenic chemicals associated with plastic and are related to metabolism. This study highlights the persistent and potentially serious impacts of microplastic pollution on gene regulation in freshwater systems.

Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birthcohortanalysis, aimed to determine if repeated exposure to anticholinergic medicationswas associated with greater decline, and whether decline was reversed with medication reduction. From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified bythe Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantifiedby theWord Learning Test [WLT], and processing speed quantified by theTimed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms. Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p<0.01). Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.

Data envelopment analysis for identification of bank branches appropriate locations in terms of their efficient operation

One of the main banking activities is the branch network. It provides the effective banking, the profitability. Choosing the right location of branches is very important for the bank effective operation. Random or intuitively locations can have a negative impact on key performance indicators in the future. The correct and thoughtful choice of the bank branch location ultimately determines its maximum efficiency. The paper concerns with the determining of the bank branch location in terms of thorough mathematical calculation and many factors influencing bank activity. We developed a special calculation method using the DEA (Data Envelope Analysis) methodology, considering financial, branch location, location features, etc. The paper dwells on the issue of one large branch effectiveness comparing to several smaller branches covering a wider consumer area on the example of the branch on A. Sharifzade street, Baku, Azerbaijan. Indeed, it is important to consider the location in terms of its geolocation and landscape. However, one of the main issues is expediency of establishing one large or several small branches in densely populated areas. Moreover, it is necessary to take into account the infrastructure to improve the bank performance. To consider this issue, we use both hypothetical and statistical data of Capital Bank. It is one of the largest banks in Azerbaijan. Also it has a large network of branches. The article examines expediency of establishing one large or several small branches in the area close to the existing branch of Capital Bank on A. Sharifzade street. The efficiency of the current operating branch was compared with the total efficiency of virtual branches in several combinations. We analysed the indicators of the Inshaatchylar branch and virtual branches in different combinations in different locations in accordance with DEA CRS (Constant Return to Scale) method. Additionally, we determined the effectiveness of both the Inshaatchylar branch and virtual branches in various combinations. Thus, the highest score is the most effective one.

Preschool and child health: Evidence from China's universal child care reform

Early childhood education programs have been found to effectively promote children's social and cognitive development. However, the health impact of these programs is less understood. Using a quasi-experiment of the first universal child care reform in China from 2010, this paper aims to identify whether the preschool reform produces any short-term effects on health-related outcomes of preschoolers (3-6 years old). Specifically, this reform expands access to affordable preschools that provide full-day center-based education, with school meals and essential health services on campus. I exploit the variation in the number of newly established preschools across provinces and implement difference-in-differences and triple-difference strategies. Results confirm the effectiveness of this reform by showing a strong and positive impact on preschool attendance. This paper then documents the benefits to alleviating underweight among preschoolers. Estimates show a larger effect in rural areas, suggesting that the reform narrows rural-urban disparities in education access and undernutrition prevention. I also explore the impact on caregivers’ health consciousness and find improved health-seeking behavior when children get sick.

Does Digital Intergroup Contact Reduce Prejudice? A Meta-Analysis.

With the ubiquity of technology in the modern life, contact between different social groups via different digital means is an everyday reality. Can such a digital intergroup contact reduce prejudice, or does it exacerbate it? In this study, we summarize the present evidence on the links between intergroup digital contact and prejudice in a variety of intergroup contexts. We meta-analyzed experimental and correlational evidence from 88 independent samples (n = 9,385). Digital intergroup contact showed a small but significant effect consistent with prejudice reduction (g = 0.25). Direct digital contact showed larger effect than indirect forms of contact, and contact via computer-mediated communication showed larger effects than contact achieved via other activities such as interacting with nonplayable characters or embodiment. The effects were similar regardless of the type of out-group targeted by prejudice. Overall, meta-analytical results suggest that digital intergroup contact may reduce prejudice.

What makes public transit demand management programmes successful? A systematic review of ex-post evidence

ABSTRACT Transit crowding results in negative experiences and mode change for transit riders and operational challenges for operators. The COVID-19 pandemic initiated an ongoing transformation of how, when, and where people travel, yet the challenge of balancing demand and supply in transportation remained topical. The pandemic has also exposed the traditional approach of infrastructure expansion for being too slow to respond to the challenges of crowding in a timely manner. As such, this paper provides a systematic literature review of the ex-post studies that evaluated the impact of transit demand management strategies. The paper synthesises the findings from 13 different programmes analysed in 20 studies. It is concluded that at least within the scope of the limited number of identified ex-post studies, the practice of alternative work schedules that allow employees greater freedom when to travel is the demand management approach that can bring the most significant crowding reduction. Once that flexibility is expanded, other strategies that appeal to riders’ preferences might have a larger effect as well. The findings of this review aim to encourage transit agencies to develop collaborations with large employers that can introduce alternative work schedules.

Locally adaptive inversions in structured populations.

Inversions have been proposed to facilitate local adaptation, by linking together locally coadapted alleles at different loci. Prior work addressing this question theoretically has considered the spread of inversions in "continent-island" scenarios in which there is a unidirectional flow of maladapted migrants into the island population. In this setting, inversions capturing locally adaptive haplotypes are most likely to invade when selection is weak, because stronger local selection i) more effectively purges maladaptive alleles, and ii) generates linkage disequilibrium between adaptive alleles, thus lessening the advantage of inversions. We show this finding only holds under limited conditions by studying the establishment of inversions in a more general two-deme model, which explicitly considers the dynamics of allele frequencies in both populations linked by bidirectional migration. In this model, the level of symmetry between demes can be varied from complete asymmetry (continent-island) to complete symmetry. For symmetric selection and migration, strong selection increases the allele frequency divergence between demes thereby increasing the frequency of maladaptive alleles in migrants, favouring inversions-the opposite of the pattern seen in the asymmetric continent-island scenario. We also account for the likelihood that a new inversion captures an adaptive haplotype in the first instance. When considering the combined process of capture and invasion in "continent island" and symmetric scenarios, relatively strong selection increases inversion establishment probability. Migration must also be low enough that the inversion is likely to capture an adaptive allele combination, but not so low as to eliminate the inversion's advantage. Overall, our analysis suggests that inversions are likely to harbour larger effect alleles that experience relatively strong selection.

High salt diet induces microbiome dysregulation, neuroinflammation, and anxiety in the chronic period after mild repetitive closed head injury in adolescent mice

Abstract The associations between human concussions and subsequent sequelae of chronic neuropsychiatric and cardiovascular such as hypertension have been reported; however, little is known about the underlying biological processes. We hypothesized that dietary changes, including a high salt diet, disrupt the bidirectional gut-brain axis, resulting in worsening neuroinflammation and emergence of cardiovascular and behavioral phenotypes in the chronic period after repetitive closed head injury in adolescent mice. Adolescent mice were subjected to three daily closed head injuries, recovered for 12 weeks, and then maintained on a high salt diet or a normal diet for an additional 12 weeks. Experimental endpoints were hemodynamics, behavior, microglial gene expression (bulk RNA sequencing), brain inflammation (brain tissue quantitative PCR), and microbiome diversity (16S RNA sequencing). High salt diet did not affect systemic blood pressure or heart rate in Sham or injured mice. High salt diet increased anxiety-like behavior in injured mice compared to Sham mice fed with high salt diet and injured mice fed with normal diet. Increased anxiety in injured mice that received a high salt diet was associated with microgliosis and a proinflammatory microglial transcriptomic signature, including upregulation in interferon-gamma (IFN-γ), interferon beta (IFN- β), and oxidative stress related pathways. Accordingly, we found upregulation of tumor necrosis factor-alpha (TNF-α) and IFN-γ mRNA in the brain tissue of high salt diet-fed injured mice. High salt diet had a larger effect on the gut microbiome composition than repetitive close head injury. Increases in gut microbes in the families Lachnospiraceae, Erysipelotrichaceae, and Clostridiaceae were positively correlated with anxiety-like behaviors. In contrast, Muribaculaceae, Acholeplasmataceae, and Lactobacillaceae were negatively correlated with anxiety in injured mice that received a high salt diet, a time-dependent effect. The findings suggest that high salt diet, administered after a recovery period, may affect neurologic outcomes following mild repetitive head injury, including the development of anxiety. This effect was linked to microbiome dysregulation and an exacerbation of microglial inflammation, which may be physiological targets to prevent behavioral sequelae in the chronic period after mild repetitive head injury. The data suggest an important contribution of diet in determining long-term outcomes after mild repetitive head injury.

Structure-Photoreactivity Studies of BODIPY Photocages: Limitations of the Activation Barrier for Optimizing Photoreactions.

BODIPY photocages are photoreactive chromophores that release covalently linked cargo upon absorption of visible light. Here, we used computations of the T1 photoheterolysis barrier to ascertain whether a computational approach could assist in a priori structure design by identifying new structures with higher quantum yields of photorelease. The electronic structure-photoreactivity relationships were elucidated for boron-substituted and core-functionalized 2-substituted BODIPY photocages as well as aryl substitutions at the meso-methyl position. Although there is a clear trend for the 2-substituted derivatives, with donor-substituted derivatives featuring both lower computed barriers and higher experimental quantum yields, no trend in the quantum yield with the computed activation barrier is found for the meso-methyl-substituted or boron-substituted derivatives. The lack of a correlation between the experimental quantum yield with the computed barrier in the latter two substitution cases is attributed to the substituents having larger effects on the rates of competing channels (internal conversion and competitive photoreactions) than on the rate of the photoheterolysis channel. Thus, although in some cases computed photoreaction barriers can aid in identifying structures with higher quantum yields, the ignored impacts of how changing the structure affects the rates of competing photophysical/photochemical channels limit the effectiveness of this single-parameter approach.

Abstract PO4-03-11: Discerning the impact of ctDNA detection on patient decisions in early-stage breast cancer

Abstract Background: Detection of circulating tumor DNA (ctDNA) after neoadjuvant therapy for triple negative breast cancer (TNBC) is associated with increased risk of recurrence. Ongoing trials aim to determine whether knowledge of specific genomic mutations in ctDNA can inform targeted adjuvant therapy to improve prognosis. The impact of knowledge of ctDNA status on patient treatment decisions weighing benefit and toxicity is unknown. Methods: 401 women were recruited via the Research Advocacy Network from Young Survivors’ Coalition, Living Beyond Breast Cancer, and Pink-4-Ever Ending Disparities. Participants had to self-report a history of non-metastatic breast cancer and have received chemotherapy in the prior 6 months to 10 years to be eligible. Participants completed a 27 question Qualtrics survey detailing demographics and experience with prior chemotherapy. Based on estimations from prior data, participants were presented with scenarios mimicking residual TNBC and unknown, negative, or positive ctDNA status with corresponding risk of recurrence of 40%, 20%, or 55% respectively. Participants were then presented with 12 scenarios (in random order) combining various degrees of absolute risk reduction (5%, 15%, 35%) with established toxicity profiles of four possible post-neoadjuvant therapies (capecitabine, immunotherapy, PARP inhibitor, and PI3K inhibitor). Participants rated scenarios in terms of acceptability from 0-100. A general linear model with repeated measures (3 × 4) was used to determine the contributions of risk reduction and toxicity to acceptability. Models were also run with the addition of between subject factors: age group (&amp;lt; 40; &amp;gt;40), stage of cancer (Stage 1; Stage 2/3), and previous experience with toxicity (Yes; No), to examine whether any of these factors moderated the effects of risk reduction and toxicity. Effect sizes were determined by partial h2. Results: 286 eligible respondents completed the survey with evaluable responses. Average age was 41.2 (range 27-75). When the hypothetical risk of recurrence decreased from 40% (ctDNA-unknown) to 20% (ctDNA-negative), significantly less participants preferred adjuvant capecitabine vs. no therapy (95.1% versus 63.3%, p&amp;lt; 0.001). Across the 12 scenarios, both benefit (F=448.5, p&amp;lt; 0.001; preference for greater benefit) and toxicity (F=33.64, p&amp;lt; 0.001; preference for lower toxicity) significantly influenced acceptability, but benefit had a much larger effect size than toxicity (h2=0.76 and 0.26, respectively). There was no significant interaction effect, and the pattern of results was not moderated by age, stage of cancer, or prior experience with chemotherapy toxicity. The most preferred scenario (greatest benefit, lowest toxicity) had a mean rating of 87.8/100; however, even when presented with the scenario with the lowest benefit and highest toxicity, the mean rating was still 31.5/100, suggesting that this combination would be acceptable to some individuals. Conclusions: Knowledge of ctDNA-negative status significantly reduced the number of participants preferring adjuvant capecitabine over no further therapy. When faced with ctDNA-positive status, participants preferred maximum risk reduction regardless of toxicity profile. As genomic technology advances, it is imperative that researchers and treating physicians understand its impact on patient decision making. Citation Format: Tarah Ballinger, Gregory Zimet, Elda Railey, Mary Lou Smith, Bryan Schneider. Discerning the impact of ctDNA detection on patient decisions in early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-11.