Positive Carriers Research Articles

(Invited) Simulating Dynamic Excitons Via Quantum Molecular Dynamics: A Case Study in Lead Halide Perovskites

The ultrafast electronic and structural dynamics invoked by photoexcitation, i.e., “dynamic exciton” phenomena, not only are important in the context of practical applications such as solar cells, but also raise many questions from the viewpoint of fundamental science. Experimental measurement, computational simulations, and theoretical interpretation will be the three pillars for deciphering the dynamic exciton phenomena.From the viewpoint of computational simulations, molecular dynamics (MD) techniques combined with quantum chemical calculations, i.e., quantum molecular dynamics (QMD), has been the popular tool to simulate the dynamic exciton phenomena. The quantum chemical calculations, which are typically conducted on the basis of the density-functional theory (DFT), require the large computational resources and time. These have been the limiting factors for the accessible spatial and time scales by the QMD simulations.To extend the coverage of simulations to more complex, large-scale systems, we have developed efficient excited-state QMD methods that can include nonadiabatic effects. Our method combines the density-functional tight binding (DFTB) method, which is an approximate DFT, and the surface hopping method, which is a theoretical framework to incorporate the nonadiabatic effects into the QMD simulations. The method was further improved to be suitable for condensed-phase simulations explicitly including the environment, i.e., solvent, by using a “divide-and-conquer” style quantum chemical calculation technique. These theoretical framework enables us to simulate the coupled electronic–structural dynamics in excited states of systems consisting of 102–103 atoms[1,2,3].In addition, using the developed method, we conducted the real-time simulations of the ultrafast processes invoked by photoexcitation of lead iodide perovskites, which are known as the key materials for perovskite solar cells. The dissociation of the exciton into the positive and negative charge carriers was observed. Moreover, the hot carrier cooling, where the charge carriers dissipate excess energy via the electron–phonon coupling and relax to the band edges, was also tracked. Finally, the direct evidence of the polaron formation, where the structural deformation is induced by the presence of charge carriers, was observed. These results highlight the importance of the coupling between electronic and structural degrees of freedom.In the talk, recent improvements in the methodology and future perspectives will also be presented[5].

P-548 IMPORTANCE OF EXPANDED CARRIER SCREENING AMONG OOCYTE DONORS - questions and concerns

Abstract Study question To examine the utility of a range of expanded screening panels for oocyte donors. Summary answer Expanded carrier screening with NGS data identified that 86% of gamete donors were carriers of at least one condition while 302 genes were tested. What is known already The level of genetic testing for oocyte donors is not regulated in most countries. The use of expanded carrier screening is recommended more widely. If the egg donor is a carrier, there is a 50% chance that the offspring will also be carriers. Expanded carrier screening is performed to determine the potential effects of positive carrier status, which guarantees safety for future pregnancy. From practical experience, more genes are tested for a donor, more potential mutations are detected. Study design, size, duration A cohort of 92 potential oocyte donor applicants aged 18-30 years old, who were qualified for oocyte donation after full screening, tested negative on an initial cystic fibrosis carrier test for 11 most common CFTR mutations (PCR panel), was further screened with expanded commercial carrier testing panel (302 genes) using next-generation sequencing (NGS) data. Participants/materials, setting, methods A cohort of 92 potential oocyte donor applicants aged 18-30 years old, who tested negative on an initial cystic fibrosis carrier test for 11 most common CFTR mutations (PCR panel), was further screened with expanded commercial carrier testing panel (302 genes) using next-generation sequencing (NGS) data. Main results and the role of chance Genotyping results for all donors were analyzed; 38% (35/92) of donors were identified as carriers for one condition, 34% (31/92)- for two conditions, 7% (6/92)- for three conditions and 7% (6/92)- for four conditions, including cystic fibrosis. Among the most prevalent conditions in our study were: Hemochromatosis: Type 1: HFE Related- 22%, Cystic Fibrosis: CFTR-related conditions 11%, Biotinidase deficiency– 7,6%, 21-Hydroxilase-Deficient Congenital Nonclassical Adrenal Hyperplasia- 6,5%, Krabbe disease – 6,5%, Usher syndrome: USH2A-related conditions – 6,5%, Nonsyndromic deafness: GJB2- related conditions- 5,4% and Smith-Lemli-Opitz syndrome (5,4%). Limitations, reasons for caution Each donor was consented for genetic testing Wider implications of the findings This study shows a need to provide the explicit requirement for oocyte donor genetic testing and guidelines to satisfy quality and safety and not reduce the number of donors carries of mutations, but to implement a practice of genetic matching. Trial registration number not applicable

Lifetime of Photogenerated Positive Charges in Hybrid Cerium Oxide-Based Materials from Space and Mirror Charge Effects in Time-Resolved Photoemission Spectroscopy

Space and mirror charge effects in time-resolved photoemission spectroscopy can be modeled to obtain relevant information on the recombination dynamics of charge carriers. We successfully extracted from these phenomena the reneutralization characteristic time of positive charges generated by photoexcitation in CeO2-based films. For the above-band-gap excitation, a large fraction of positive carriers with a lifetime that exceeds 100 ps are generated. Otherwise, the sub-band-gap excitation induces the formation of a significantly smaller fraction of charges with lifetimes of tens of picoseconds, ascribed to the excitation of defect sites or to multiphoton absorption. When the oxide is combined with Ag nanoparticles, the sub-band-gap excitation of localized surface plasmon resonances leads to reneutralization times longer than 300 ps. This was interpreted by considering the electronic unbalance at the surface of the nanoparticles generated by the injection of electrons, via localized surface plasmon resonance (LSPR) decay, into CeO2. This study represents an example of how to exploit the space charge effect in gaining access to the surface carrier dynamics in CeO2 within the picosecond range of time, which is fundamental to describe the photocatalytic processes.

Reflex single-gene non-invasive prenatal testing is associated with markedly better detection of fetuses affected with single-gene recessive disorders at lower cost

Objective To evaluate the clinical benefits and achievable cost savings associated with the adoption of a carrier screen with reflex single-gene non-invasive prenatal test (sgNIPT) in prenatal care. Method A decision-analytic model was developed to compare carrier screen with reflex sgNIPT (maternal carrier status and fetal risk reported together) as first-line carrier screening to the traditional carrier screening workflow (positive maternal carrier screen followed by paternal screening to evaluate fetal risk). The model compared the clinical outcomes and healthcare costs associated with the two screening methods. These results were used to simulate appropriate pricing for reflex sgNIPT. Results Reflex sgNIPT carrier screening-detected 108 of 110 affected pregnancies per 100,000 births (98.5% sensitivity), whereas traditional carrier screening-detected 46 of 110 affected pregnancies (41.5% sensitivity). The cost to identify one affected pregnancy was reduced by 62% in the reflex sgNIPT scenario compared to the traditional scenario. Adding together the testing cost savings and the savings from earlier clinical intervention made possible by reflex sgNIPT, the total cost savings was $37.6 million per 100,000 pregnancies. Based on these cost savings, we simulated appropriate reflex sgNIPT pricing range: if the cost to identify one affected pregnancy is the unit cost, carrier screening with reflex sgNIPT can be priced up to $1,859 per test (or $7,233 if sgNIPT is billed separately); if the cost per 100,000 pregnancies is the unit cost, carrier screening with sgNIPT can be priced up to $1,070 per test (or $2,336 if sgNIPT is billed separately). Conclusion Using the carrier screen with reflex sgNIPT as first-line screening improves the detection of affected fetuses by 2.4-fold and can save costs for the healthcare system. A real-life experience will be needed to assess the clinical utility and exact cost savings of carrier screen with reflex sgNIPT.

EP461: Barriers to prenatal genetic testing for male partners at a Los Angeles County public teaching hospital

eP461: Barriers to prenatal genetic testing for male partners at a Los Angeles County public teaching hospital

Piezoelectric BaTiO3 with the milling treatment for highly efficient piezocatalysis under vibration

The hydrothermally-synthesized barium titanate (BaTiO3) nanofibers are mechanically milled and used to for the piezocatalytic RhB dye decomposition. It is found that the mechanical milling can improve the piezocatalytic performance of BaTiO3 nanofibers. With the increasing of the milling time from 0 to 120 min, the RhB dye decomposition ratio of BaTiO3 nanofibers first increases and then decreases. When the milling time is 30 min, for the 20 min vibration time, the RhB decomposition ratio of BaTiO3 is 94%, which is much higher than that (~65%) of the unmilled BaTiO3. On one hand, the enhancement in piezocatalysis of BaTiO3 may be originated from the exposure of active sites due to the increasement of the specific surface area after the mechanical milling. On the other hand, it is also found that the ferroelectric polarization strength of BaTiO3 nanofibers obviously increases after the mechanical milling, which is helpful to reduce the recombination of these positive and negative carriers in the catalytic process, resulting in the enhanced piezocatalysis performance. The mechanical milling provides a convenient, fast, and effective method for improving the piezocatalytic activity of BaTiO3 nanofibers.

Motivation Learning Achievement in Open Distance Learning (ODL) Environment: Skills, Beliefs, Self-Direction and Interaction of University Students

The COVID-19 pandemic in Malaysia has seen the number of positive carriers rise day by day, prompting the government to issue a movement control order (MCO), compelling Malaysians to stay at home to prevent the virus from spreading quickly in the year 2020-2021. The MCO has an impact on students. This situation forces them to stay at home while the learning process continues in Online Distance Learning (ODL) mode. The institution is concerned about the implications of online learning as a teaching technique that is intended to improve students' academic performance by increasing computer self-efficacy and other factors such as student satisfaction and e-learning outcomes. Therefore, this study aims to examine the motivation learning achievement in ODL among university students. A total of 290 volunteer students from both genders of diploma and bachelor degree students participated in this study. The study found that there were significant relationships on the factors of motivation learning achievement. There were differences in motivation learning achievement (skills, beliefs, self-direction and interaction) between genders. Whilst, there were no significant differences on the factors of motivation learning achievement (skills, beliefs, self-direction and interaction) between diploma and bachelor degree students. Thus, the ODL appears to be new standards that should not obstruct potential interactive learning for optimal academic performance and accomplishment. In other words, this research provides a new perception to lecturers, faculty management, and the institution, as well as serving as the standard practice of ODL in the future.

Assessing rodents as carriers of pathogenic Leptospira species in the U.S. Virgin Islands and their risk to animal and public health

Leptospirosis is a global zoonotic disease caused by pathogenic bacteria of the genus Leptospira. We sought to determine if rodents in U.S. Virgin Islands (USVI) are carriers of Leptospira. In total, 140 rodents were sampled, including 112 Mus musculus and 28 Rattus rattus. A positive carrier status was identified for 64/140 (45.7%); 49 (35.0%) were positive by dark-field microscopy, 60 (42.9%) by culture, 63 (45.0%) by fluorescent antibody testing, and 61 (43.6%) by real-time polymerase chain reaction (rtPCR). Molecular typing indicated that 48 isolates were L. borgpetersenii and 3 were L. kirschneri; the remaining nine comprised mixed species. In the single culture-negative sample that was rtPCR positive, genotyping directly from the kidney identified L. interrogans. Serotyping of L. borgpetersenii isolates identified serogroup Ballum and L. kirschneri isolates as serogroup Icterohaemorrhagiae. These results demonstrate that rodents are significant Leptospira carriers and adds to understanding the ecoepidemiology of leptospirosis in USVI.

Computational study of phase stability, electronic, magnetic and thermoelectric properties of a new quaternary Heusler alloy CrCoIrGa

Exploring new materials with interesting physical properties plays a vital role in the development of modern technologies. Herein, using density functional theory based first-principles calculations, we present a study on the structural, electronic, magnetic and thermoelectric properties of a new quaternary Heusler alloy CrCoIrGa. The structure stability determined in terms of cohesive energy, formation energy and phonons dispersion curves confirms that alloy is stable and can be considered in experiments. The structural optimization in non-magnetic, ferromagnetic and antiferromagnetic state proves that alloy is ferromagnetic in the ground state with optimized lattice constant of 5.93 Å. The electronic band structure and density of states show that alloy is nearly half-metal (NHF) with 96% spin-polarization at the Fermi level. The effect of pressure on the electronic and magnetic properties investigated in the range 0–25 GPa, reveals that complete half-metallic character at the Fermi level can be obtained for pressure ≥10 GPa with a half-metallic gap of about 1 eV in the minority spin channel and a magnetic moment (Mt) of 3.0 μB/f.u., in agreement with Slater-Pauling rule (Mt = Zt-24). In addition, the electronic structures determined using DFT+U approach exhibit nearly half-metallic property such that amount of spin-polarization increases with increasing Hubbard parameter U. Finally, thermoelectric properties are examined by computing Seebeck coefficient (S), electrical conductivity (σ/τ), electronic thermal conductivity (κ) and power factor (PF) up to 800 K temperature. The positive value of S conveys that heat transport is carried by positive charge carriers. The room temperature values of S, σ/τ, κe/τ and PF are found to be about 5.9 μV/K, 3.06 × 1020 Ω−1m−1s−1, 2.27 × 1015 WK−1m−1s−1 and 1 WK−2m−1s−1, respectively. Collectively, these findings suggest that CrCoIrGa could play a useful role for the development of spintronics and energy production applications.

Negative food dilution and positive biofilm carrier effects of microplastic ingestion by D. magna cause tipping points at the population level

Ingestion of microplastics by aquatic organisms is often harmful due to the dilution of their regular food with low-calorie microplastic particles, but can also be beneficial if nutritious biofilms are present on the microplastic surface. This begs the question: is ingestion of microplastic harmful or beneficial and can the net effect of the two mechanisms be quantified? Here, we quantified these harmful and beneficial effects on Daphnia magna, using dose-response tests with clean and biofouled microplastic respectively, and determined the trade-off between these counteracting effects. A population model was developed to calculate the isoclines for zero population growth, separating the regime where adverse food dilution dominated from that where the beneficial biofilm vector mechanism dominated. Our results show that the organisms grew better when exposed to biofouled microplastic compared to pristine microplastic. Very good model predictions (R2 = 0.868–0.991) of the effects of biofouled microplastic were obtained based on literature parameter values, with optimization required only for the two sub-model parameters driving the dose-effect relationships for pristine microplastic. These results contradict previous sudies were only pristine microplastic were used and demonstrate that the ruling paradigm of unambiguously adverse microplastic effects is not ecologically justifiable.

Area‐level deprivation is associated with rate of memory decline in late life within a community‐based cohort

AbstractBackgroundResiding in a disadvantaged neighborhood is associated with adverse health outcomes, as well as increased risk for dementia. However, it remains unclear whether area‐level deprivation impacts the rate of age‐related memory decline, especially in community‐based populations.MethodWe quantified late life neighborhood level disadvantage using the 2013 Area Deprivation Index (ADI) for 2,554 participants with complete data of interest within the Wisconsin Longitudinal Study – a same‐aged, community‐based cohort of randomly selected 1957 Wisconsin high school graduates. Delayed recall for a 10‐item word list was assessed at two timepoints in mid to late life (Time 1 (∼2004): age 64.39 + 0.74 years; and Time 2 (∼2011): age 71.28 + 0.97 years). We used multivariate linear regression models to evaluate whether ADI was associated with memory performance at each time point, and with the annualized rate of change in memory performance over time.ResultIncreasing ADI was significantly correlated with lower adolescent IQ, less educational attainment, lower net worth, higher vascular risk scores, elevated depression metrics, and increasing age (all p<0.001). Mean ADI did not differ by sex, but was significantly higher in ApoE‐4 positive carriers (t(2552) =2.257, p=0.024). Results of multivariate regression indicated that greater area‐level deprivation (higher ADI) was not associated with delayed recall performance at Time 1 (b = 0.001; 95% CI: ‐0.003 to 0.005, P=0.790), but was associated with poorer delayed recall performance at Time 2 (B = ‐0.004; 95% CI: ‐0.007 to ‐0.001, P=0.019). Higher ADI also predicted greater annualized rate of decline in delayed recall between timepoints (B = ‐0.001; 95% CI: ‐0.001 to ‐9.9^10‐5, P=0.025). These findings held after controlling for individual‐level demographic and socioeconomic variables (age, sex, adolescent IQ, years of education, net worth), genetic risk (ApoE‐4 carrier status), depression, hearing loss, and a modified CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) risk score calculated at Time 1.ConclusionEven after accounting for established individual‐level demographic, socioeconomic, health, and genetic risk factors for cognitive decline, greater neighborhood disadvantage is associated with an accelerated rate of annualized decline in delayed recall performance across mid to late life in a community sample.

Highly Efficient Piezoelectrets through Ultra-Soft Elastomeric Spacers.

Piezoelectrets are artificial ferroelectrics that are produced from non-polar air-filled porous polymers by symmetry breaking through high-voltage-induced Paschen breakdown in air. A new strategy for three-layer polymer sandwiches is introduced by separating the electrical from the mechanical response. A 3D-printed grid of periodically spaced thermoplastic polyurethane (TPU) spacers and air channels was sandwiched between two thin fluoroethylene propylene (FEP) films. After corona charging, the air-filled sections acted as electroactive elements, while the ultra-soft TPU sections determined the mechanical stiffness. Due to the ultra-soft TPU sections, very high quasi-static (22,000 pC N−1) and dynamic (7500 pC N−1) coefficients were achieved. The isothermal stability of the coefficients showed a strong dependence on poling temperature. Furthermore, the thermally stimulated discharge currents revealed well-known instability of positive charge carriers in FEP, thereby offering the possibility of stabilization by high-temperature poling. The dependences of the dynamic coefficient on seismic mass and acceleration showed high coefficients, even at accelerations approaching that of gravity. An advanced analytical model rationalizes the magnitude of the obtained quasi-static coefficients of the suggested structure indicating a potential for further optimization.

Prevalence of Hepatitis B Carrier Status and Its Negative Association with Hypertensive Disorders in Pregnancy.

Results In a total cohort of 87889 deliveries over a period of 20 years, the prevalence rate of HBV fell from around 10-11% to around 6-7% in the last 5 years of the study. A negative association between chronic HBV carrier status and all gestational hypertensive disorders could be demonstrated. An apparent protective effect of HBV carrier status was apparently more robust against preeclampsia than gestational hypertension, as the negative association with preeclampsia was consistently observed throughout the study period. A logistic regression model showed that advanced maternal age, multiple pregnancies, obesity, and significant medical disorders were positively correlated with gestational hypertensive disorders, while multiparity and positive HBV carrier status were negatively correlated. Conclusion Chronic HBV carrier status appeared to have a protective effect against the development of preeclampsia and gestational hypertension in an endemic area with high HBV prevalence rates.

A new method for Synthetic Impulse and Aperture Radar transmitting waveform design based on non‐sequential positive, negative and random carrier frequency coding with dot product approach

Synthetic Impulse and Aperture Radar (SIAR) is a kind of Multiple Input Multiple Output (MIMO) radar. It is a four-dimensional radar that has advantages against stealth targets, multi targets, anti-radiated missile, reconnaissance and interference, as well as valuable features in high range resolution and high detection probability. SIAR uses special frequency coding separately in each antenna. This code has an essential function in SIAR, such as separating frequency bandwidth, satisfying orthogonality in transmitted signals, suppressing range-angle and range-Doppler frequency coupling. Pulse-to-pulse frequency code agility is a kind of radar signal coding that is used to suppress the sidelobes in range-Doppler frequency. In this study, a design method is suggested to transmit waveform based on non-sequential positive, negative and random carrier frequency coding with the dot product approach in pulse-to-pulse frequency code agility, to reduce sidelobes in range-Doppler frequency coupling. The simulation results showed that this method could effectively remove the strong coupling between range-Doppler frequency. Removing coupling in the range-Doppler frequency decreases the sidelobes.

Development and Validation of a Tool for the Prediction of Vancomycin-Resistant Enterococci Colonization Persistence-the PREVENT Score.

ABSTRACTVancomycin-resistant enterococci (VRE) are nosocomial pathogens with increasing prevalence worldwide. Extensive hygiene measures have been established to prevent infection transmission in hospitals. Here, we developed a predictive score system (the predictive vancomycin-resistant enterococci [PREVENT] score) to identify the clearance or persistence in patients with a history of VRE carrier status at readmission. Over a cumulative 3-year period, patients with a positive VRE carrier status were included. The study population was recruited in two successive time periods and separated into training data for predictive score development and validation data for evaluation of the predictive power. The risk factors for persistent VRE colonization were analyzed in a univariable analysis before development of a logistic regression model based on the potential risk factors. The score points were determined proportionally to the beta coefficients of the logistic regression model. The data from 448 (79%) patients were used as the training data, and those from 119 (21%) as the validation data. Multivariable analysis revealed the following variables as independent risk factors: age of ≥60 years, hemato-oncological disease, cumulative antibiotic treatment for >4 weeks, and a VRE infection. The resulting logistic regression model exhibited an acceptable area under the curve (AUC) of 0.81 (95% confidence interval [CI], 0.72 to 0.91). The predictive score system had a sensitivity of 82% (95% CI, 65 to 93%) and a specificity of 77% (95% CI, 66 to 85%). The developed predictive score system is a useful tool to assess the VRE carrier status of patients with a history of VRE colonization. On the basis of this risk assessment, more focused and cost-effective infection control measures can be implemented.IMPORTANCE Given the increasing relevance of VRE as nosocomial pathogens worldwide, infection prevention and control measures, including patient isolation and contact precautions, are indispensable to avoid their spread in the hospital setting. In this study, we developed and validated the PREVENT score, a tool for rapid risk assessment of VRE persistence in patients with a history of previous VRE colonization. The score is designed to be easily performed, employing clinical information available in a regular admission setting and immediately providing information to inform the decision of whether to adopt patient isolation and contact precautions during the hospital stay. After validation, the score was shown to accurately identify patients with persistent VRE colonization upon admission, representing a suitable option as (i) a complementary method yielding preliminary results significantly more quickly than culture-based VRE detection techniques and (ii) an alternative strategy for VRE detection in settings in which microbiological VRE screening is not routinely performed due to limited resources.

Is Industry Size a Carrier for Wage Inequality? A Panel Study Addressing Independent Variables of Inherently Different Sizes across Units

We address how independent variables of inherently different sizes across units, e.g., small vs. large industries, in panel regression is an advantage interpretively. Analyzing a Norwegian industry panel, we find that wage inequality is a function of industry size, particularly size increase, in an absolute number of firms. A possible reason is that specialized skilled employees negotiate higher wages when there are many legal entities. The findings can also imply that wage inequality is more sensitive to random change, particularly an increase, in large rather than small industries. We conclude that particularly large industries are positive carriers of wage inequality and discuss potential underlying causal mechanisms such as monopolistic competition.

Molecular ordering dependent charge transport in [formula omitted]-stacked triphenylene based discotic liquid crystals and its correlation with dielectric properties

We investigate the charge transport in triphenylene core based homologous series of discotic mesogens (HATn) by the time-of-flight method. HAT5, HAT6 and HAT8 exhibit Colh phase whereas HAT4 shows Colhp phase. For the investigated homologous series, we have observed a single transit in the transient photocurrent curves corresponding to positive charge carriers having the mobility in order of 10-2 to 10-4 cm2/vs. The hole mobility decreases with increasing the number of carbon atoms (n) in the alkyl chain attached to the triphenylene core, which follows the empirical exponential relationship: μ≈a.exp(-b/n). Furthermore, the dielectric measurement has been done on these compounds to bring a correlation between the molecular ordering by varying the alkyl chain of the HATn compounds. In the light of structure-property correlation, we have noticed that the hole mobility and permittivity vary according to the length of alkyl chain attached to the triphenylene core. The molecular ordering is also discussed via phase behaviour of compounds and confirmed by polarized optical textures. The change in entropy also decreases with increasing alkyl chain length of the HATn compounds rendering an agreement with that of the mobility and dielectric measurements. The HATn compounds show their potential applications in opto-electronics and could serve as organic semiconductors; however, the poor conductivity remains as a futuristic challenge.

Counseling for personal health implications identified during reproductive genetic carrier screening

Preconception and prenatal carrier screening is designed to provide reproductive risk information, but carriers for some autosomal recessive or X-linked conditions also have personal health risks. This study investigated the prevalence of and inclusion of personal health implications in pre- and post-test counseling. Twelve genetic conditions with personal health risks for carriers includedon carrier screening panels but not otherwise screened routinely were identified (e.g., Gaucher disease with Parkinson's disease risk). A retrospective review was performed of patients with a positive carrier screen for one of these conditions at our center from 2012 to 2019. Of 6147 individuals that had carrier screening for one of the twelve conditions, 96 (1.56%) did not report a known family history and screened positive for one of the conditions. Testing was ordered largely by reproductive endocrinologists (51.0%) and genetic counselors (35.4%). Most individuals did not receive pre- (96.8%) or post-test (64.6%) counseling about personal health risks. Post-test counseling was performed principally by genetic counselors (97.1%). For carriers of conditions with guidelines for specialist referral, most individuals (75.9%) were referred. Expanded genetic carrier screening increasingly identifies individuals with personal health implications, but patients are frequently not counseled before or after testing. These findings stress the importance of developing guidelines for practitioners about expanded carrier screening counseling and follow-up.

EXPANDED CARRIER SCREENING AND CLINICAL DECISION MAKING IN 2020

To assess how often clinical management is altered using expanded carrier screening (ECS) panels that analyze 283 genes. All couples who underwent expanded carrier screening with one test provider (SEMA4) in 2020 at a large assisted reproductive center were evaluated, with a focus on those with at least one partner with a positive carrier screen at risk for disease. A high-risk result was defined as any result that provided patients with information that was medically actionable, including the potential use of PGT-M for the selection of an unaffected embryo. The overall rate of positive ECS results and the number of couples who were considered high-risk were evaluated. From this data set, the proportion that underwent preimplantation genetic testing for monogenic/single gene disorders were analyzed. A total of 9,444 individuals were tested, with 4,722 couples tested in total. Of those, 3,471 (73.5%) of the couples had a positive result for at least one gene in one of the partners. 391 patients (11% of those with at least one positive test) were considered high-risk for genetic disorders that were potentially actionable. Some patients/couples had multiple actionable results. Out of the couples with at least one partner with an abnormal ECS, 145 (4% of positive tests, 37% of high-risk) underwent PGT-M testing. Five couples declined PGT-M even though they were considered high-risk, however they all underwent preimplantation genetic testing for aneuploidy (PGT-A). From this data, expanded carrier screening informed and/or affected clinical decision making 4.1% of the time, 391 times after 9,444 tests with 4,722 couples. The utilization of expanded carrier screening continues to increase in reproductive medicine populations. Prior studies have suggested that ECS will identify at least 1/300 couples (0.3%) who will have risk for a severe genetic disease for which PGT-M will prevent transmission. With our dataset, expanded carrier screening identifies approximately four percent of couples who have increased reproductive risk or personal health risk. The rate of positivity for at least one gene is likely to increase as ECS providers continue to expand testing panels. Further research is needed to understand the decision-making regarding couples who are eligible to do PGT-M but choose to proceed with only PGT-A.

Genetic Carrier Screening for Cystic Fibrosis, Fragile X Syndrome, Hemoglobinopathies, and Spinal Muscular Atrophy


 People generally describe wanting access to carrier screening because knowing about the risk of passing along a genetic condition is considered important and supportive of their desires to be prepared. In the context of expanded carrier screening programs, this could mean that an increased number of people would want to access these programs.
 Supporting people who are considering carrier screening can be challenging and is likely to be more involved than simply sharing high-level descriptive information about testing details and potential outcomes. Descriptive information is important to help people understand the screening process and the types of results that could emerge from testing; however, programs might be more supportive of informed decision-making if the providers take a proactive role and are open to facilitating speculative conversations about potential ramifications in people’s actual lives. This is challenging given the expressed desire by health care providers, clinical geneticists in particular, to provide “neutral information” that patients would not experience as prescriptive.
 Given the challenge of supporting people making decisions about whether or not to pursue carrier screening, and the likely increase in people who would consider carrier screening if targeted programs were expanded to population-level screening, it is important to ensure that health care providers are both aware of jurisdictional carrier screening programs and competent in what carrier screening can offer their patients in terms of clinical actionability. Although this is particularly true for general practitioners who are often the primary point of contact with the health care system for their patients, it is also important for people who work in family planning clinics and women’s health clinics.
 Having the option to engage with carrier screening at the preconception stage was universally preferred by participants across the included studies. Compared with prenatal carrier screening, preconception carrier screening was seen as providing prospective parents with more reproductive options. Health care providers were concerned that offering carrier screening during pregnancy might lead pregnant people and their partners to confuse it with other prenatal testing which would limit people’s ability to be truly informed before deciding whether or not to pursue screening. However, if offered as a prenatal option, most people consider it important to do so as early as possible because it could be paired with other prenatal tests. Although not referred to specifically by any of the included studies, we note that offering carrier screening prenatally rather than at preconception, could place the responsibility to make the decision on cisgender women and non-binary or transgender people with uteruses.
 Sequentially designed carrier screening programs were the most common across the included studies; however, people moving through programs with this design found the interim period between receiving their positive carrier results and receiving their partners’ results difficult. This was particularly true for people who were already pregnant because this interim period forced them to reimagine both their relationship with the fetus and the future they had imagined with that child. Of course, this reimagining might be necessary if both partners’ screening results came back positive for the condition in question, but to stagger the return of the results could put undue anxiety on potential parents.
 Carrier screening will not affect everyone in the same way, and reproductive decision-making will still be complex and difficult. As such, the opportunity to engage with genetic counsellors on reproductive options following positive carrier status result is considered valuable.