Parent Population Research Articles

Evaluation of seed yield, essential oil compositions, and fatty acid profiles in advanced fennel (Foeniculum vulgare Mill) breeding populations

Metabolites derived from bitter fennel serve as flavoring and healing agents in the pharmaceutical, food, and cosmetic sectors. Previously, we developed three fennel breeding populations (Early, Medium, and Late Maturity Synthetic Cultivars) with the potential to produce higher seed yield. This investigation aimed to assess the quality and quantity of the important metabolites in these three cultivars alongside their elite parental populations. Our results showed that the highest amounts of essential oil yield and seed yield were produced by, two breeding populations, Medium and Late Maturity Synthetic Cultivars. These cultivars showed positive seed yield heterosis rates of 28% and 20%, respectively, above the averages of their parental populations. GC-MS analysis of the essential oil samples identified 24 components in total. The major compounds in all genotypes were trans-anethole (34.09–77.84%), limonene (4.99–12.66%), methyl chavicol (1.35–38.69%), and fenchone (6–13.07%). The highest amount of trans-anethole belonged to Fasa and the Medium Maturity Synthetic with 77.84 % and 73.10%, respectively. The analysis of fatty acid compositions in the genotypes was conducted using GC-FID, which revealed the presence of 19 unique fatty acids, of which ten were saturated, and nine were unsaturated fatty acids. Petroselinic acid (67.11–78.44%), and linoleic acid (9.14–11.60%) were the major unsaturated fatty acids in fennel seeds. The Early Maturity Synthetic exhibited the least saturated fatty acid content (7.24%), while the highest levels of unsaturated fatty acids were found in both the Early Maturity Synthetic (89%) and Hashtgerd (88.55%). The genotypes were categorized into four groups using a heat map analysis with hierarchical clustering. Overall, the results showed that the three synthetic cultivars of fennel have outperformed the elite parental populations for seed and essential oil yields, concentration of the major industrial secondary metabolites such as trans-anethole, and higher proportions of unsaturated fatty acids. These cultivars show potential for usage in the pharmaceutical and healthcare industries.

On the feasibility of malaria hypothesis

In 1954, Allison proposed that hemoglobin S (HbS) gene causes protection against fatal malaria. This would explain the high HbS gene frequency observed in certain regions hyperendemic for malaria, so-called “malaria hypothesis”. This in silico study was conducted to examine the feasibility of the hypothesis under more realistic initial conditions, where a mutant gene with heterozygous advantage against malaria (e.g., HbS) was introduced in a group of Neolithic hunter-gatherers who decided to start agriculture nearby water where malaria killed a proportion of population. The tribe population size, number of children born to each woman in each generation, mortality from malaria and sickle cell disease, the protection factor provided by the gene carriers against malaria, the probability of mating between the members of the parent and offspring populations, population growth, and increased fertility in women heterozygous for HbS, were also considered. For effectively confer protection against malaria within the shortest possible period, the mutation needs to be happened in a small population. For a large population, the process would take around 100 generations (~ 2500 years) or more to provide an effective protection. Even then, the probability that the new gene could survive and propagate to future generations is about 35%. Conventional population genetics equations with differential or difference equations, give totally incorrect estimates of the gene frequency in small populations; discrete mathematics should be used, instead. After introduction of the advantageous mutation, the gene frequency increased until a steady state value. This value is far less than the gene frequency reported in certain tribes of Africa. It seems that the malaria hypothesis, per se, could not explain such a high observed gene frequency, unless HbS is associated with lower mortality from other causes too.

Mental Health, Parenting Stress, and Parenting Practices of Parents of Deaf or Hard of Hearing Children During the Pandemic.

The authors investigated parent mental health during the COVID-19 pandemic and its association with parenting behaviors of parents of children who are deaf or hard of hearing. An electronic survey was distributed to parents (N = 103). The results showed that they were experiencing elevated anxiety, depression, and symptoms of post-traumatic stress disorder. A combined model demonstrated that parental distress was significantly associated with depression and with parental reports of symptoms indicating significantly higher distress. Parental distress was also significantly associated with parenting strategies: Parents who endorsed positive strategies reported significantly lower levels of distress, while parents who endorsed negative strategies reporting significantly higher levels. It was found that screening protocols to identify parents in need of support are crucial, particularly among the parent population considered in the present study. Additionally, access to mental health services and evidence-based positive parenting programs is essential.

Power grid planning and optimal dispatch based on intelligent optimization and genetic algorithm

Power grid planning is a prerequisite for optimal design, operation, and planning of the power grid. Based on the characteristics of the power system, this article explored a genetic algorithm-based power network optimization method. In genetic algorithms, simulated annealing algorithms were used to optimize candidate individuals, resulting in the optimal ratio of the number of selected individuals to the number of all mutated individuals. At the same time, a simulated annealing algorithm was added to the optimization process to improve the shortcomings of GA (Genetic Algorithm). When the genetic algorithm selected individuals from the parent population, a simulated annealing algorithm was used to optimize candidate individuals, making the ratio of the number of selected individuals to the number of all mutated individuals optimal. In order to overcome the shortcomings of GA, the tabu search algorithm was introduced into the optimization process, making it have better optimization ability. Through optimization experiments on 15 nodes, it was found that this method had good convergence speed. The final experiment also proved that the power planning based on the simulated annealing genetic algorithm was superior to other models (the load balance, power supply capacity matching, and coordination index scores of the substation based on the algorithm model in this article were 0.5111, 2.2693, and 120.215, respectively, which were higher than other schemes).

Integration of natural selection across the life cycle stabilizes a marine mussel hybrid zone.

Hybridization among related species is now recognized as common but it remains unclear how hybrid zones persist for prolonged periods. Here, we test the hypothesis that selection in different components of the life cycle may stabilize a hybrid zone. A hybrid zone occurs in southwest England between the marine mussels Mytilus edulis and M. galloprovincialis. Previous studies have found strong directional selection against alleles from M. edulis occurs among hybrids in the adult stage. Traditional hybrid zone models argue that alleles that are selected within the hybrid zone are replaced by migration from neighboring parental population into the hybrid zone. In this system, however, migration occurs out of this hybrid zone into neighboring parental populations. This hybrid zone should therefore be unstable and dissipate, yet this zone has persisted for more than 30 years. We tested and rejected the hypothesis that differences in fecundity may select for M. edulis alleles within this hybrid zone and thus counter the selection observed against these alleles among adults. We also tested the hypothesis that selection during the larval stage may counter selection against M. edulis alleles in the adult stage. We found that selection favors M. edulis alleles during the veliger stage of larval development. The direction and strength of selection during the larval stage are sufficient to counter strong selection during the adult portion of the life cycle. This hybrid zone is stabilized by opposing forms of directional selection operating in different portions of the life cycle.

The Contribution of Parents' Occupation on Students' Academic Achievements in Public Secondary Schools in Njombe Town Council

The parents are considered very important in their children's education, as they actively support the implementation of their children's education. The study sought to determine the contribution of parents' occupation on students' academic achievement in public secondary schools in Njombe Town Council. The study was guided by Maslow's Hierarchy of Needs Theory of Human Motivation. The study was conducted across 14 public secondary schools, analyzed 3113 targeted populations of students, teachers, school heads, and parents using an embedded research design, combining quantitative and qualitative data. The sample size consisted of 192 respondents; thus, five (5) school heads and ten (10) parents were purposively selected to take part in the interview guides, while 83 teachers and 94 students (form III and IV) were randomly selected to take part in the study through the questionnaires. The instruments' reliability (r= 0.78) was obtained using the Test-retest method. Quantitative data was analyzed using descriptive statistics with the help of the SPSS version 23, and results were presented in the table of frequencies and percentages. Meanwhile, qualitative data was analyzed thematically and presented through categories and themes' narration. The findings revealed that parents' occupation contributes to students' academic achievement through learning morale, absenteeism, child labor, and unconducive home environments. Parents influence monitoring and supervising children's academic progress at home and school. The study suggests that parents should be educated on their work-education relationship and invest in education based on their occupation. Policymakers and curriculum developers should re-consider making reforms to education financing policy to be more equitably favourable to students from poor families for sustainable academic achievement. Government and NGOs should ensure that all students from poor parental backgrounds are supported to receive quality education

Dominance relation selection and angle-based distribution evaluation for many-objective evolutionary algorithm

In many-objective optimization, most existing evolutionary algorithms struggle to effectively balance the convergence and diversity of population. Given the failure of Pareto-dominance-based selection mechanism in high-dimensional spaces and the growing recognition of the advantages of angle-based similarity evaluation, we propose a Many-objective Evolutionary Algorithm using Dominance Relation Selection and Angle-based Distribution Evaluation (DSAE). Firstly, based on both traditional Pareto dominance and a newly proposed Angle-dominance with higher selection pressure, a Dominance Relation Selection (DRS) strategy is designed, which dynamically adjusts the selection pressure by assessing the overall proximity between parent and offspring populations. Then, an Angle-based Distribution Evaluation is proposed to determine the distribution levels of solutions, so as to adaptively maintain promising distribution performance of population in objective space. Furthermore, a Pareto-dominance-based global optimal solution set is introduced to save solutions with the best diversity throughout the iteration as the final output. Finally, DSAE is compared with 7 state-of-the-art algorithms by using benchmark test suites DTLZ and WFG with 5, 8 and 10 objectives, and the experimental results demonstrate that DSAE has the most advanced performance.

What Influences Parents on Their Decision to Vaccinate Their Daughters Against HPV?

Study ObjectiveTo investigate and compare the attitudes of parents who initiated their daughters’ HPV vaccination with parents who did not. MethodsData were collected through telephone interviews with a close-end questionnaire on parents’ knowledge, attitudes towards the vaccine, and the reasons for vaccinating or not their daughters against HPV. The sample was random, stratified by geographic region and urbanization level, national, and representative of the general population of parents of girls aged 11-18 in Greece. Statistical analysis consisted of descriptives, an inferential analysis with hypothesis testing, and a logistic regression model. ResultsOverall, 996 parents were included in the analysis, 99.0% of which were women. Forty-seven percent of them initiated their daughters’ HPV vaccination, with physician recommendation stated as the most important reason for this decision (50.2%). For those who had not initiated their daughters’ HPV vaccination (53%), lack of information was the most important reason (25.6%). In the hypothesis testing, parents with unvaccinated daughters agreed more with the statements “I do not have enough information for the HPV vaccine to decide,” and “My child is very young to be vaccinated for an STD” (P < .05), but no significant difference found for the statement “It's more possible for a vaccinated girl to begin sexual activities” (P > .05). ConclusionsLack of information, young age of the daughter, and perceived effectiveness of the vaccine are the most important hesitation factors. Physician recommendation is the most important reason to initiate vaccination.

Late‐heading parental selection in orchardgrass (Dactylis glomerata L.)

AbstractDactylis glomerata L., orchardgrass or cocksfoot, is frequently planted as a companion crop in perennial forage legumes such as alfalfa (Medicago sativa L.). However, many commercial orchardgrass cultivars flower earlier than legumes, resulting in a reduction in grass yield and nutritional value if harvested to maximize the legume. Additionally, during orchardgrass seed production over years, later flowering can gradually shift to earlier flowering. In this study, we employed parental selection based on half‐sib family (HS‐family) trait values for dry matter yield (DMY) and heading date (HD), and augmented it with marker‐assisted selection to enrich for late‐heading‐associated alleles in six vernalization and flowering time candidate genes. The parent population resulted from polycrossing three late‐heading orchardgrass germplasm sources and evaluating 94 HS‐families. HDs differed by years and locations for both the parent and HS‐family populations. Of the 313 single‐nucleotide polymorphisms (SNPs) identified within the candidate genes, 16 were associated with HD with a range of effects from 0.48 to 3.37 days to heading. An SNP detected across multiple years and locations in this study was also found in a previous study, within the intron of the Constans 1 gene (DgCO1). DMY was not highly significant in this study, highlighting a large environmental effect alongside lower variation across the HS‐families. However, parental plants fixed for the SNP within DgCO1 showed a trend to later heading as well as higher DMY.

Did the COVID-19 experience change U.S. parents’ attitudes towards HPV vaccination? Results from a national survey

BackgroundIn the U.S., uptake of the HPV vaccine remains below coverage goals. There is concern that negative reactions to emergency initiatives during the COVID-19 pandemic, including vaccination, may have increased some parents’ hesitancy towards all vaccines, including HPV. Understanding how different parent populations view routine vaccination post-pandemic is key to strategic efforts to maintaining and increasing uptake of HPV vaccine. MethodsIn early 2022, we recruited an online panel of English-speaking U.S. parents and caregivers, who used the social media platform Twitter and had HPV vaccine-eligible but unvaccinated children age 9–14 years. Respondents completed a 20-minute survey measuring knowledge, attitudes and intentions regarding HPV vaccination for their child, as well as background socio-demographics and health information-seeking practices. Questions regarding experiences during the COVID-19 pandemic included changes in access to preventive care, and perceptions of whether pandemic experiences had positively or negatively affected their attitudes about routine vaccination, with open text capturing reasons for this change. ResultsAmong 557 respondents, 81 % were definitely or likely to vaccinate their child against HPV, with 12 % being uncertain, and 7 % unlikely to vaccinate. Regarding routine vaccination, most (70 %) felt their attitudes had not changed, while 26 % felt more positively, and only 4 % felt more negatively. Reasons for positive attitude change included increased appreciation for vaccines overall, and motivation to proactively seek preventive care for their child. Negative attitude changes stemmed from distrust of COVID-19 public health efforts including vaccine development, and disillusionment with vaccines’ ability to prevent disease. In multivariable models, intention to vaccinate was greater among parents reporting greater education, Democratic affiliation, greater religiosity, and urban residence. Negative attitude change due to the pandemic independently predicted reduced HPV vaccination intention, while positive attitude change predicted positive intention. ConclusionsPost-pandemic, most U.S. parents remain committed to vaccinating their children against HPV. However, addressing residual COVID-19 concerns could improve uptake among vaccine-hesitant parents.

Co-Packaged PARP inhibitor and photosensitizer for targeted photo-chemotherapy of 3D ovarian cancer spheroids

BackgroundWithin the last decade, poly(ADP-ribose) polymerase inhibitors (PARPi) have emerged in the clinic as an effective treatment for numerous malignancies. Preclinical data have demonstrated powerful combination effects of PARPi paired with photodynamic therapy (PDT), which involves light-activation of specialized dyes (photosensitizers) to stimulate cancer cell death through reactive oxygen species generation.ResultsIn this report, the most potent clinical PARP inhibitor, talazoparib, is loaded into the core of a polymeric nanoparticle (NP-Tal), which is interfaced with antibody-photosensitizer conjugates (photoimmunoconjugates, PICs) to form PIC-NP-Tal. In parallel, a new 3D fluorescent coculture model is developed using the parental OVCAR-8-DsRed2 and the chemo-resistant subline, NCI/ADR-RES-EGFP. This model enables quantification of trends in the evolutionary dynamics of acquired chemoresistance in response to various treatment regimes. Results reveal that at a low dosage (0.01 μM), NP-Tal kills the parental cells while sparing the chemo-resistant subline, thereby driving chemoresistance. Next, PIC-NP-Tal and relevant controls are evaluated in the 3D coculture model at multiple irradiation doses to characterize effects on total spheroid ablation and relative changes in parental and subline cell population dynamics. Total spheroid ablation data shows potent combination effects when PIC and NP-Tal are co-administered, but decreased efficacy with the conjugated formulation (PIC-NP-Tal). Analysis of cell population dynamics reveals that PIC, BPD + NP-Tal, PIC + NP-Tal, and PIC-NP-Tal demonstrate selection pressures towards chemoresistance.ConclusionsThis study provides key insights into manufacturing parameters for PARPi-loaded nanoparticles, as well as the potential role of PDT-based combination therapies in the context of acquired drug resistance.

Simulations of multiple breeding strategy scenarios in common bean for assessing genomic selection accuracy and model updating.

The aim of this study was to evaluate the accuracy of the ridge regression best linear unbiased prediction model across different traits, parent population sizes, and breeding strategies when estimating breeding values in common bean (Phaseolus vulgaris). Genomic selection was implemented to make selections within a breeding cycle and compared across five different breeding strategies (single seed descent, mass selection, pedigree method, modified pedigree method, and bulk breeding) following 10 breeding cycles. The model was trained on a simulated population of recombinant inbreds genotyped for 1010 single nucleotide polymorphism markers including 38 known quantitative trait loci identified in the literature. These QTL included 11 for seed yield, eight for white mold disease incidence, and 19 for days to flowering. Simulation results revealed that realized accuracies fluctuate depending on the factors investigated: trait genetic architecture, breeding strategy, and the number of initial parents used to begin the first breeding cycle. Trait architecture and breeding strategy appeared to have a larger impact on accuracy than the initial number of parents. Generally, maximum accuracies (in terms of the correlation between true and estimated breeding value) were consistently achieved under a mass selection strategy, pedigree method, and single seed descent method depending on the simulation parameters being tested. This study also investigated model updating, which involves retraining the prediction model with a new set of genotypes and phenotypes that have a closer relation to the population being tested. While it has been repeatedly shown that model updating generally improves prediction accuracy, it benefited some breeding strategies more than others. For low heritability traits (e.g., yield), conventional phenotype-based selection methods showed consistent rates of genetic gain, but genetic gain under genomic selection reached a plateau after fewer cycles. This plateauing is likely a cause of faster fixation of alleles and a diminishing of genetic variance when selections are made based on estimated breeding value as opposed to phenotype.

Could hybridization increase the establishment success of the biological control agent Aphalara itadori (Hemiptera: Aphalaridae) against invasive knotweeds?

Intraspecific hybridization between distinct populations could increase the fitness and adaptive potential of biological control agents that often have low genetic diversity and can be inbred due to long-term laboratory rearing often at small population sizes. Hybridization can also alter host preference and performance when the parental insect populations are adapted to different host plants. We investigated the effects of hybridization between two populations (Northern and Southern) of the psyllid, Aphalara itadori, that have different fitness on three invasive knotweed species (Japanese, giant, and Bohemian). Fecundity, host choice, and developmental success of second-generation reciprocal hybrids and the parental psyllid populations were compared on the three knotweed species in multiple-choice tests. Hybridization did not increase fecundity. All three knotweed species were accepted for oviposition without preference by the Southern and the two hybrid psyllid populations. The northern psyllid population laid the most eggs on Bohemian knotweeds but those were maladaptive choices since almost all eggs failed to develop. The developmental success of the parental psyllid populations was highest on the knotweed species they were originally collected from, on Japanese knotweed of the Southern psyllids and giant knotweed of the Northern psyllids. Hybrids had intermediate or higher survival on given knotweed hosts compared to their parents. These results can inform release tactics of A. itadori in different regions especially where there appear to be climatic and/or host mismatches such as in Michigan. In southern Michigan, based on climate the Northern psyllid population should be released. However, the most common knotweed species in the region are Bohemian and Japanese knotweeds that do not support the development of the Northern psyllids. In this case, hybrids that may carry cold adaptations of the Northern psyllids but have better developmental success on the prevailing knotweed species may be considered for release to increase establishment success.

Abstract B037: ClonMapper Duo: An scRNAseq compatible lineage tracing method to track cell-cell fusion at single-cell resolution

Abstract Spontaneous cell-cell fusion in cancer can generate genetic heterogeneity and often leads to more pathological phenotypes. While the consequences of cell-cell fusion in cancer continue to be revealed, few tools exist to determine the mechanisms and cell states which promote cell-cell fusion. To meet this need, we engineered ClonMapper Duo, a two-color, two-index expressed barcoding system which allows tracking of cell-cell fusion using live-cell imaging and lineage tracing of fusion cells in scRNAseq. The ClonMapper Duo system was created by modifying the ClonMapper DNA barcoding system to express indexed barcodes on either H2B-GFP or H2B-mCherry. Briefly, 8 unique 5-nucleotide sequences were designed by maximizing Hamming distance and 4 sequences were assigned to GFP and mCherry each. The index sequences were placed adjacent to a 15N random nucleotide in the expressed barcode region of the construct. Low-diversity GFP and mCherry barcoded cell libraries were created through lentiviral transduction of HCC1806, MDA-MB-231, and MCF-7 cells. Diversity and evenness of each library was confirmed via targeted barcode sequencing. For each cell line, homotypic GFP and mCherry barcoded cells were cocultured together for 1 week. A parallel culture was monitored using live-cell imaging to measure the rate of spontaneous cell-cell fusion and the probability of different fates (e.g. death, hybrid formation, senescence) for each cell line. Spontaneously fused cells identified by expression of both GFP and mCherry were enriched by FACS. Enriched fusion cells were expanded in parallel with the parental cocultures until ~1e5 fusion cells or 1 week was reached. Fusion and parental populations for each cell line were multiplexed for scRNAseq using the 10X Genomics 3’ CellPlex Kit. FACS enriched multibarcoded fusion cells were further bioinformatically distinguished from cell multiplets and the barcodes of spontaneously fused cells were traced to their single-barcoded cell lineage of origin. From this data set we ask: 1. Are certain cell lineages more primed for fusion than others, i.e. does a more fusogenic cell phenotype exist or is fusion random? 2. Is there a convergent state of post-fusion cells or does fusion tend to diversify phenotypes? Here, we will present the first results from this two-color, two-index live-cell imaging and scRNAseq lineage tracing system toward understanding cancer cell-cell fusion at a single cell resolution. Combining lineage traced transcriptomic data from scRNAseq with fusion rates and outcomes from live-cell imaging using ClonMapper Duo provides an unprecedented look into the causes and consequences of spontaneous cell-cell fusion in cancer. Citation Format: Andrea L. Gardner, Lan Zheng, Daylin Morgan, Kennedy Howland, Amy Brock. ClonMapper Duo: An scRNAseq compatible lineage tracing method to track cell-cell fusion at single-cell resolution [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B037.

The Scavenger Hunt for Quasar Samples to Be Used as Cosmological Tools

Although the Λ Cold Dark Matter model is the most accredited cosmological model, information at high redshifts (z) between type Ia supernovae (z=2.26) and the Cosmic Microwave Background (z=1100) is crucial to validate this model further. To this end, we have discovered a sample of 1132 quasars up to z=7.54 exhibiting a reduced intrinsic dispersion of the relation between ultraviolet and X-ray fluxes, δF=0.22 vs. δF=0.29 (24% less), than the original sample. This gold sample, once we correct the luminosities for selection biases and redshift evolution, enables us to determine the matter density parameter ΩM with a precision of 0.09. Unprecedentedly, this quasar sample is the only one that, as a standalone cosmological probe, yields such tight constraints on ΩM while being drawn from the same parent population of the initial sample.

Impact of Childhood Cancer on Family Functioning and Family Quality of Life in the Western Region of Saudi Arabia.

Childhood cancer affects families and friends and causes lifestyle changes that become overwhelming for them. Childhood cancer may cause decreased physical, emotional, and social health-related quality of life (QOL). Childhood cancer may cause strain on the financial status of the family and shape their coping strategy to the disease. The extent of the impact of childhood cancer on families is associated with several demographic characteristics of the family such as diagnosis, phase of treatment, and parent's educational level, employment, and marital status of the parents. The objective of this study was to explore the impact of childhood cancer on family functioning and family quality of life (QOL) in the Western Region of Saudi Arabia. This study was a quantitative, randomized, cross-sectional study. 187 participants were randomly selected from the population of parents whose children have cancer and treated at Princess Noorah Oncology Center in King Abdulaziz Medical City, Jeddah. A survey was used to collect data for this study. Healthcare and social systems may have to consider the impact of childhood cancer in the care plans of the patients. Leukemia represents the highest disease prevalence followed by brain tumor. The highest score of the impact on the family survey was familial social concerns domains followed by financial burden with mean scores of 3.59 (98.8%) and 3.56 (98.0%), respectively. Then, mastery domain mean score is 3.43 (85.8%) and finally personal strain with mean score of 3.21 (980.3%). The QOL of the family results indicated that the highest was physical/material well-being with mean score of 3.84 (76.8%) and family interaction with mean score of 3.82 (76.4%), followed by emotional well-being with mean score of 3.54 (70.8%) and parenting with mean score of 3.53 (70.6.%). Significant differences were found between the overall scales of QOL and the scale of impact on the family and some demographic characteristics of children and their parents. Childhood cancer has a substantial effect on family functioning and the family's QOL. In addition, both were significantly associated with some demographic characteristics of the child and his parents.

Suicide attempt and death by suicide among parents of young individuals with cancer: A population-based study in Denmark and Sweden.

The psychological toll on parents of a child receiving a cancer diagnosis is known to be high, but there is a knowledge gap regarding suicidal behavior among these parents. The aim of this study was to investigate the risk of suicide attempt and death by suicide in relation to having a child with cancer. We performed a binational population-based and sibling-controlled cohort study, including all parents with a child diagnosed with cancer in Denmark (1978 to 2016) or Sweden (1973 to 2014), 10 matched unexposed parents per exposed parent (population comparison), and unaffected full siblings of the exposed parents (sibling comparison). Suicide attempt was identified through the Patient Register and the Psychiatric Central Register in Denmark and the Patient Register in Sweden, whereas death by suicide was identified through the Danish Causes of Death Register and the Swedish Causes of Death Register. In population comparison, we used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of suicide attempt and death by suicide associated with cancer diagnosis of a child, adjusting for sex, age, country of residence, calendar year, marital status, highest attained educational level, household income, history of cancer, history of psychiatric disorder, and family history of psychiatric disorder. The sibling comparison was performed to assess the role of familial confounding in the studied associations. The population comparison consisted of 106,005 exposed parents and 1,060,050 matched unexposed parents, with a median age of 56 at cohort entry and 46.9% male. During the median follow-up of 7.3 and 7.2 years, we observed 613 (incidence rate [IR], 58.8 per 100,000 person-years) and 5,888 (IR, 57.1 per 100,000 person-years) cases of first-onset suicide attempt among the exposed and unexposed parents, respectively. There was an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis (HR, 1.15; 95% CI, [1.03, 1.28]; p = 0.01), particularly when the child was 18 or younger at diagnosis (HR, 1.25; 95% CI, [1.08, 1.46]; p = 0.004), when the child was diagnosed with a highly aggressive cancer (HR, 1.60; 95% CI, [1.05, 2.43]; p = 0.03), or when the child died due to cancer (HR, 1.63; 95% CI, [1.29, 2.06]; p < 0.001). The increased risk did not, however, maintain thereafter (HR, 0.86; 95% CI: [0.75, 0.98]; p = 0.03), and there was no altered risk of parental death by suicide any time after the child's cancer diagnosis. Sibling comparison corroborated these findings. The main limitation of the study is the potential residual confounding by factors not shared between full siblings. In this study, we observed an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis, especially when the child was diagnosed during childhood, or with an aggressive or fatal form of cancer. There was, however, no altered risk of parental death by suicide at any time after a child's cancer diagnosis. Our findings suggest extended clinical awareness of suicide attempt among parents of children with cancer, especially during the first few years after cancer diagnosis.

Being a "Good Parent" to a NICU Infant With a Major Congenital Anomaly.

In the United States, up to one-third of infants with a congenital anomaly require neonatal intensive care unit (NICU) hospitalization. Parents of these infants may have different decision-making priorities, which may be influenced by the timing of the infant's diagnosis. (1) To compare the ranked importance of decision-making beliefs for parents of infants who received a prenatal versus postnatal congenital diagnosis and (2) explore how parents describe their decision-making beliefs. A cross-sectional, sequential mixed-methods pilot design was applied to collect quantitative data using the Good Parent Ranking Exercise and further explore parents' decision-making beliefs through qualitative interviews. Maximum difference scaling/hierarchical Bayes estimation and content analysis were used to analyze the quantitative and qualitative data, respectively. Forty mothers completed the Good Parent Ranking Exercise and 20 mothers completed qualitative interviews. Four of the top 5 ranked parenting beliefs were shared by mothers in the prenatal and postnatal groups. Mothers in the postnatal group ranked "focusing on my child's quality of life" higher. Qualitative interviews revealed that previously identified decision-making beliefs were consistent in this NICU parent population, with 1 additional belief identified. Mixed-methods analysis revealed high concordance between the prenatal and postnatal groups. NICU nurses need to know that decision-making beliefs for parents who receive a prenatal versus postnatal congenital diagnosis, while largely similar, may have differences. Future research should explore decision-making beliefs in demographically diverse parent groups (ie, fathers, partnered vs nonpartnered couples) and effective strategies for promoting NICU parents' decision-making beliefs.

Dynamics aspects and bifurcations of a tumor-immune system interaction under stationary immunotherapy

We consider a three-dimensional mathematical model that describes the interaction between the effector cells, tumor cells, and the cytokine (IL-2) of a patient. This is called the Kirschner–Panetta model. Our objective is to explain the tumor oscillations in tumor sizes as well as long-term tumor relapse. We then explore the effects of adoptive cellular immunotherapy on the model and describe under what circumstances the tumor can be eliminated or can remain over time but in a controlled manner. Nonlinear dynamics of immunogenic tumors are given, for example: we prove that the trajectories of the associated system are bounded and defined for all positive time; there are some invariant subsets; there are open subsets of parameters, such that the system in the first octant has at most five equilibrium solutions, one of them is tumor-free and the others are of co-existence. We are able to prove the existence of transcritical and pitchfork bifurcations from the tumor-free equilibrium point. Fixing an equilibrium and introducing a small perturbation, we are able to show the existence of a Hopf periodic orbit, showing a cyclic behavior among the population, with a strong dominance of the parental anomalous growth cell population. The previous information reveals the effects of the parameters. In our study, we observe that our mathematical model exhibits a very rich dynamic behavior and the parameter μ̃ (death rate of the effector cells) and p̃1 (production rate of the effector cell stimulated by the cytokine IL-2) plays an important role. More precisely, in our approach the inequality μ̃2>p̃1 is very important, that is, the death rate of the effector cells is greater than the production rate of the effector cell stimulated by the cytokine IL-2. Finally, medical implications and a set of numerical simulations supporting the mathematical results are also presented.

Evaluation of the genetic basis of familial-associated early-onset hematologic cancers in an ancestral/ethnically diverse population.

Genetic predisposition to hematologic malignancies has historically been addressed utilizing patients recruited from clinical trials and pedigrees constructed at major treatment centers. Such efforts leave unexplored the genetic basis of variations in risk by race/ethnic group shown in population-based surveillance data where cancer registration, compulsory by law, delivers universal enrollment. To address this, we performed exome sequencing on DNA isolated from newborn bloodspots derived from sibling pairs with early-onset cancers across California in which at least one of the siblings developed a hematologic cancer, using unbiased recruitment from the full state population. We identified pathogenic/likely pathogenic (P/ LP) variants among 1,172 selected cancer genes that were private or present at low allele frequencies in reference populations. Within 64 subjects from 32 families, we found 9 LP variants shared between siblings, and an additional 7 such variants in singleton children (not shared with their sibling). In 8 of the shared cases, the ancestral origin of the local haplotype that carries P/LP variants matched the dominant global ancestry of study participant families. This was the case for Latino sibling pairs on FLG and CBLB, non-Latino White sibling pairs in TP53 and NOD2, and a shared GATA2 variant for a non-Latino Black sibling pair. A new inherited mutation in HABP2 was identified in a sibling pair, one with diffuse large B-cell lymphoma and the other with neuroblastoma. Overall, the profile of P/LP germline variants across ancestral/ethnic groups suggests that rare alleles contributing to hematologic diseases originate within their race/ethnic origin parental populations, demonstrating the value of this discovery process in diverse, population-based registries.