Parental questions about sex chromosome aneuploidies regarding sex, gender, and sexual orientation as reported by genetic counselors in a prenatal setting.

The introduction of cell-free DNA screening has resulted in increased prenatal identification of sex chromosome aneuploidies (SCAs). This study aimed to evaluate genetic counselor experiences disclosing SCAs positive prenatal screening or testing results and genetic counselor-reported parental questions regarding sex, gender, and sexual orientation. Forty-eight prenatal genetic counselors completed the survey. When asked to quantify their experiences, 97.9% of counselors reported disclosing a SCAs positive screen result within the previous year, and 81.3% disclosed a diagnostic result. Of those counselors, 53.8% reported always or often receiving parental questions about sex, 33% always or often about gender, and 25% always or often regarding sexual orientation. Counselors were asked to share examples of parental questions following a positive screen or diagnostic testing for SCAs. Parental questions were stratified by karyotype and content analysis revealed questions about the fetus' sex, anatomy, reproduction, being cisgender, gender expression, behavior, being transgender, and sexual orientation. The examples of parental questions provided by genetic counselors suggested some parents may have misconceptions about the intersection of SCAs with sex, gender, and sexual orientation following prenatal screening or diagnostic testing. The majority of counselors (83.3%) agreed to some extent that they desired further education on responding to parental questions about SCAs. Findings from this research suggest a need for genetic counseling strategies that accurately and respectfully discuss SCAs in the context of sex, gender, and sexual orientation with prenatal patients.

Group meditation, addressing stigma, and "mental health days": Recommendations for integrating self-awareness practices into genetic counseling graduate programs.

Genetic counseling graduate programs provide a rigorous curriculum comprised of coursework encompassing counseling and medical genetics, fieldwork, and research experience. Students face similar emotional and mental demands as practicing genetic counselors while also experiencing stressors commonly associated with graduate study. Increased self-awareness may help combat these stressors. This mixed-methods study surveyed 154 genetic counseling graduate students to determine the types of self-awareness practices they would like to have included in their graduate training and surveyed 11 program faculty regarding the feasibility of implementing these practices. The students' most preferred practices were self-reflection (n = 73, 47.4%), support from peers, colleagues, and/or supervisors (n = 71, 46.1%), and mental health counseling (n = 71, 46.1%). Analysis of responses to open-ended questions capturing students' recommendations for programs yielded six recurrent themes: (1) Consistent, Structured Practice with Accountability, (2) Emphasis on Mental Health, (3) Practical Techniques, (4) Access to Resources, (5) Encouragement and Support, and (6) Barriers to Implementation. Many students suggested that programs should incorporate repetitive exercises that could be implemented on a schedule with an emphasis on consistency (Theme 1). Students also emphasized the importance of providing exposure to multiple examples of self-awareness practices, so they could find an approach that was most beneficial on an individual basis (Theme 3). These findings were shared with program faculty via a presentation at the Association for Genetic Counseling Program Directors annual meeting, and attendees were subsequently surveyed regarding self-awareness practices currently integrated into their curriculum, as well as the feasibility and likelihood of integrating new practices. Program faculty respondents indicated that most of the recommended practices were included in their curriculum already or would be feasible and likely to incorporate. These results provide insight into the attitudes of genetic counseling students toward structured practice in self-awareness and how genetic counseling graduate programs might integrate such practices into the curriculum.

Something to chat about: An analysis of genetic counseling via asynchronous messaging following direct-to-consumer genetic testing.

Advances in technology, decreasing cost of genetic testing, and growing public interest in genetics marked by an increased uptake of genetic testing, particularly direct-to-consumer genetic testing (DTC-GT), have led to an overwhelming demand for genetic counseling services. As such, various alternative service delivery models have been proposed to increase access to genetic counseling. Some service delivery models, such as asynchronous messaging, remain unexplored in the genetic counseling literature. The purpose of this study was to assess communication during genetic counseling for DTC-GT through asynchronous messaging. A thematic analysis was conducted on 34 de-identified chat transcripts between genetic counselors and clients who underwent DTC-GT. Six categories of communication were identified and were grouped based on communication sources from either the client or the genetic counselor. Categories observed in client communication were motivations for seeking DTC testing and/or genetic counseling services, questions posed to the genetic counselor, responses provided during the session, and psychosocial aspects of the session related to the clients' mental, emotional, social, and spiritual needs. Categories of communication that emerged from the genetic counselors' communications were educational aspects of the session and counseling strategies to address concerns that are not related to educational or informational needs. Most clients had specific questions about variants detected or specific conditions. Many clients asked about appropriate subsequent steps related to additional testing or medical management. Genetic counselors discussed the limitations of DTC-GT and recommendations for clinical grade testing in almost all chat transcripts. In several chats, the genetic counselor provided advice to the client related to minimizing time sorting through likely benign results and refraining from altering medical management. Results suggest that genetic counselors are able to provide genetic information to clients and respond to their mental and emotional needs through asynchronous chat following DTC-GT. Findings from this study provide initial insight into a unique genetic counseling delivery model and reveal the informational and counseling needs of clients following DTC-GT.

Nondestructive Detection of Codling Moth Infestation in Apples Using Pixel-Based NIR Hyperspectral Imaging with Machine Learning and Feature Selection.

Codling moth (CM) (Cydia pomonella L.), a devastating pest, creates a serious issue for apple production and marketing in apple-producing countries. Therefore, effective nondestructive early detection of external and internal defects in CM-infested apples could remarkably prevent postharvest losses and improve the quality of the final product. In this study, near-infrared (NIR) hyperspectral reflectance imaging in the wavelength range of 900-1700 nm was applied to detect CM infestation at the pixel level for three organic apple cultivars, namely Gala, Fuji and Granny Smith. An effective region of interest (ROI) acquisition procedure along with different machine learning and data processing methods were used to build robust and high accuracy classification models. Optimal wavelength selection was implemented using sequential stepwise selection methods to build multispectral imaging models for fast and effective classification purposes. The results showed that the infested and healthy samples were classified at pixel level with up to 97.4% total accuracy for validation dataset using a gradient tree boosting (GTB) ensemble classifier, among others. The feature selection algorithm obtained a maximum accuracy of 91.6% with only 22 selected wavelengths. These findings indicate the high potential of NIR hyperspectral imaging (HSI) in detecting and classifying latent CM infestation in apples of different cultivars.

SCA2 presenting as a focal dystonia.

BACKGROUND: Spinocerebellar ataxia 2 (SCA2) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansions in ATXN2 on chromosome 12q24. Patients present with adult-onset progressive gait ataxia, slow saccades, nystagmus, dysarthria and peripheral neuropathy. Dystonia is known to occur as SCA2 advances, but is rarely the presenting symptom. CASE PRESENTATION: A 43-year-old right handed woman presented with focal dystonia of the right hand which started two years earlier with difficulty writing. There were only mild cerebellar signs. Her mother was reported to have a progressive gait disorder and we subsequently learned that she had SCA2. A total of 10 maternal family members were similarly affected. Over the course of 10 years, the patient's cerebellar signs progressed only mildly however the dystonia worsened to the extent of inability to use her right hand. Dystonia did not improve significantly with botulinum toxin, levodopa or trihexyphenidyl, but has shown marked improvement since DBS implantation in the GPi. CONCLUSIONS: We describe a patient with SCA2 who presented with focal dystonia of the right upper extremity. Subtle cerebellar signs as well as the family history became especially important given the absence of predominant gait ataxia. Our case emphasizes that focal dystonia is not only a feature of SCA2, but can also rarely be the presenting sign as well as the most prominent feature during the disease course.

Cationic PCP iridaepoxide and carbene complexes for facile water elimination and activation processes.

Iridaepoxide dihydride complexes of a PCP ligand bearing benzo[b]thiophene linkers are synthesized through ligand coopertive N2O and H2 activations. These neutral complexes also eliminate water at elevated temperatures to form the corresponding PCcarbeneP complexes which results in the formal hydrogenation of N2O to water. The synthesis of cationic iridaepoxide dihydride complexes are reported herein where the room temperature elimination of water is observed when a donating solvent is used. This supports a previously proposed mechanism for this water elimination where hydrides cis to the epoxide are required. Ir(i) and Ir(iii) cationic PCcarbeneP complexes are also synthesized through protonation and through O-H oxidation additions of water and phenol.

Cationic mono and dicarbonyl pincer complexes of rhodium and iridium to assess the donor properties of PCcarbeneP ligands.

The donor properties of five different PCcarbeneP ligands are assessed by evaluation of the CO stretching frequencies in iridium(i) and rhodium(i) carbonyl cations. The ligands feature dialkyl phosphine units (R = (i)Pr or (t)Bu) linked to the central benzylic carbon by either an ortho-phenylene bridge, or a 2,3-benzo[b]thiophene linker; in the former, substituent patterns on the phenyl linker are varied. The carbonyl complexes are synthesized from the (PCcarbeneP)M-Cl starting materials via abstraction of the chlorides in the presence of CO gas. In addition to the expected mono carbonyl cations, products with two carbonyl ligands are produced, and for the rhodium example, a novel product in which the second carbonyl ligand adds reversibly across the Rh[double bond, length as m-dash]C bond to give an η(2) ketene moiety was characterized. The IR data for the complexes shows the 2,3-benzo[b]thiophene linked system to be the poorest overall donor, while the phenyl bridged ligands incorporating electron donating dialkyl amino groups para to the anchoring carbene are very strongly donating pincer arrays.

Maternal blood pressures during pregnancy and the risk of delivering a small-for-gestational-age neonate.

OBJECTIVE: To determine the relationship between maternal blood pressures throughout pregnancy and the risk of delivering a small-for-gestational-age (SGA) neonate. METHODS: Women were prospectively enrolled at 9-14 weeks and had serial blood pressure measurements throughout pregnancy. SGA prevalence was compared to maternal blood pressure at enrollment, average blood pressure during each trimester, and blood pressure trends throughout gestation. Blood pressure was categorized as normotension, prehypertension, or hypertension using Joint National Committee on Hypertension-7 (JNC-7) definitions. Information on preeclampsia prevalence was also obtained due to its frequent concurrence with SGA. RESULTS: A total of 758 women had 8438 blood pressure measurements taken (average 11.1, range 3-14) and 65 (8.6%) delivered an SGA neonate. Forty-two of 514 (8.2%) normotensive women at enrollment and 23/244 (9.4%) women with enrollment prehypertension or hypertension delivered an SGA neonate. Women with persistent hypertensive range blood pressures had an SGA rate 2-3 times higher than other women (p = 0.272) as well as a significantly higher preeclampsia rate (p < 0.001). Women with elevated enrollment blood pressures did not have an increased SGA rate if their blood pressures improved throughout pregnancy. Logistic regression identified enrollment uterine artery Doppler, pregnancy-associated plasma protein-A levels, and ethnicity as primary contributors to SGA. CONCLUSION: Blood pressure improvement throughout pregnancy decreases the preeclampsia rate without increasing SGA frequency. Theoretical risks of fetal growth delay should not prevent investigations into improved maternal blood pressure control, possibly at thresholds lower than commonly used in obstetric practice, beginning in the first trimester of pregnancy.

Mechanistic studies on the addition of hydrogen to iridaepoxide complexes with subsequent elimination of water.

Iridium complexes of the PCsp2 P ligand in which the donors are linked by 2,3-benzo[b]thiophene groups engage in the cooperative activation of N2O and the resulting iridaepoxides can be treated with dihydrogen to effect elimination of water and regeneration of the starting iridium complex. The mechanism of the steps in this reaction have been investigated using low temperature NMR investigations that reveal H/D exchange processes that point to a highly reactive kinetic product of hydrogen addition to the iridaepoxide. This intermediate is also involved in the water elimination pathway, and model compounds have been synthesized to provide further evidence for the mechanistic proposals for water elimination. The adaptable donor properties of the PCsp2 P ligand framework, particularly the anchoring carbene donor, plays a significant role in the ability of these compounds to mediate the transformation of N2O in this way.

Ligand cooperation in the formal hydrogenation of N2O using a PC(sp2)P iridium pincer complex.

A new PC(carbene)P pincer ligand with 2,3-benzo[b]thiophene linkers connecting the flanking dialkyl phosphine donors to the central carbene can be attached to Ir(I). The chloro derivative reacts with N2O with loss of N2 to form an iridaepoxide species by addition of an oxygen atom to the Ir═C linkage. This compound reacts with H2 to afford the oxidative addition product, in which the hydride ligands are trans to the Ir-O bond. Heating this dihydride results in slow release of H2O; kinetic and spectroscopic studies show that conversion of the dihydride to its isomer, in which the hydrides are cis to the Ir-O bond, is required for H2O elimination to take place. Together, these reactions constitute the stoichiometric conversion of N2O and H2 to N2 and H2O; further mechanistic studies suggest ways to make the system catalytic.

First trimester prediction of maternal glycemic status.

OBJECTIVE: To predict gestational diabetes mellitus (GDM) or normoglycemic status using first trimester maternal characteristics. METHODS: We used data from a prospective cohort study. First trimester maternal characteristics were compared between women with and without GDM. Association of these variables with sugar values at glucose challenge test (GCT) and subsequent GDM was tested to identify key parameters. A predictive algorithm for GDM was developed and receiver operating characteristics (ROC) statistics was used to derive the optimal risk score. We defined normoglycemic state, when GCT and all four sugar values at oral glucose tolerance test, whenever obtained, were normal. Using same statistical approach, we developed an algorithm to predict the normoglycemic state. RESULTS: Maternal age, race, prior GDM, first trimester BMI, and systolic blood pressure (SBP) were all significantly associated with GDM. Age, BMI, and SBP were also associated with GCT values. The logistic regression analysis constructed equation and the calculated risk score yielded sensitivity, specificity, positive predictive value, and negative predictive value of 85%, 62%, 13.8%, and 98.3% for a cut-off value of 0.042, respectively (ROC-AUC - area under the curve 0.819, CI - confidence interval 0.769-0.868). The model constructed for normoglycemia prediction demonstrated lower performance (ROC-AUC 0.707, CI 0.668-0.746). CONCLUSIONS: GDM prediction can be achieved during the first trimester encounter by integration of maternal characteristics and basic measurements while normoglycemic status prediction is less effective.

Second-trimester prediction of delivery of a small-for-gestational-age neonate: integrating sequential Doppler information, fetal biometry, and maternal characteristics.

OBJECTIVE: The aim of this study was to investigate the predictive accuracy of second-trimester ultrasound parameters, maternal characteristics, and sequential Doppler changes between first and second trimesters for the prediction of small-for-gestational-age (SGA) infants (birth weight < 10th percentile). METHODS: We conducted a prospective study of singleton pregnancies enrolled in the first trimester with subsequent second-trimester follow-up. Maternal characteristics, uterine artery (UtA) pulsatility index (PI), fetal biometry, and umbilical artery (UA)-PI were ascertained. UtA and UA-PI change from first to second trimester was calculated (ΔUtA-PI and ΔUA-PI). These parameters were tested for their ability to predict delivery of an SGA infant. RESULTS: Among 1982 women, 172 delivered an SGA neonate. African-American ethnicity, nulliparity, tobacco use, and low abdominal circumference (AC) z-score were independent predictors of SGA. No difference was found in the magnitude of ΔUtA-PI and ΔUA-PI between SGA and no-SGA. Receiver-operating characteristics curve analysis yielded an area under the curve of 0.700 for AC z-score. The combination of low AC and bilateral notching had high specificity (99%) but low sensitivity (7%) for SGA prediction. CONCLUSIONS: A small second-trimester fetal AC is a specific marker for SGA when found with bilateral UtA notching. Only a small proportion is predicted by the factors studied, suggesting a small contributory role or later evolution of SGA.

Prediction of preeclampsia utilizing the first trimester screening examination.

OBJECTIVE: To derive a prediction rule for preeclampsia and early onset preeclampsia requiring delivery <34 weeks using first trimester maternal, ultrasound, and serum markers. STUDY DESIGN: Prospective cohort study of women enrolled at first trimester screening. Maternal history, demographics, anthropometry, ultrasound parameters, and serum analytes were compared between women with preeclampsia and normal outcome. The prediction rule was derived by Lasso logistic regression analysis. RESULTS: In 2441 women, 108 (4.4%) women developed preeclampsia, and 18 (0.7%) early preeclampsia. Nulliparity, prior hypertension, diabetes, prior preeclampsia, mean arterial pressure, and the log pregnancy-associate pregnancy protein-A multiples of the median were primary risk factors. Prediction rules for preeclampsia/early preeclampsia had an area under the curve of 0.82/0.83 respectively. Preeclampsia was predicted with 49% sensitivity and early preeclampsia with 55% sensitivity for a 10% false positive rate. CONCLUSION: First trimester prediction rules using parameters currently available at first trimester screening identify a significant proportion of women with subsequent preeclampsia.

First-trimester prediction of small-for-gestational age neonates incorporating fetal Doppler parameters and maternal characteristics.

OBJECTIVE: First-trimester screening for subsequent delivery of a small-for-gestational-age (SGA) infant typically focuses on maternal risk factors and uterine artery (UtA) Doppler. Our aim is to test if incorporation of fetal umbilical artery (UA) and ductus venosus (DV) Doppler improves SGA prediction. STUDY DESIGN: Prospective screening study of singletons at 11-14 weeks. Maternal characteristics, serum concentrations of pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin are ascertained and UtA Doppler, UA, and DV Doppler studies are performed. These parameters are tested for their ability to predict subsequent delivery of a SGA infant. RESULTS: Among 2267 enrolled women, 191 (8.4%) deliver an SGA infant. At univariate analysis women with SGA neonates are younger, more frequently African-American (AA), nulliparous, more likely to smoke, have lower PAPP-A and free ß-human chorionic gonadotropin levels. They have a higher incidence of UtA Doppler bilateral notching, higher mean UtA Doppler-pulsatility index z-scores (P < .001) and UA pulsatility index z-scores (P = .03), but no significant difference in DV-pulsatility index z-scores or in the incidence of abnormal qualitative UA and DV patterns. Multivariate logistic regression analysis identifies nulliparity and AA ethnicity (P < .001), PAPP-A multiple of the median and bilateral notching (P < .05) as determinants of SGA infant. Predictive sensitivity was low; receiver operating characteristic curve analysis yields areas under the curve of 0.592 (95% confidence interval, 0.548-0.635) for the combination of UtA Doppler and UA pulsatility index z-scores. CONCLUSION: Delivery of a SGA infant is most frequent in nulliparous women of AA ethnicity. Despite the statistical association with UtA Doppler first-trimester SGA prediction is poor and not improved by the incorporation of fetal Doppler.

First-trimester risk factors for preeclampsia development in women initiating aspirin by 16 weeks of gestation.

OBJECTIVE: The residual risk of preeclampsia in high-risk women on aspirin prophylaxis exceeds that of low-risk populations, and this study aimed to identify first-trimester maternal characteristics associated with aspirin prophylaxis failure. METHODS: This is a nested cohort study of prospectively enrolled women with verified initiation of risk-indicated aspirin prophylaxis by 16 weeks of gestation. First-trimester maternal history, demographics, anthropometry, ultrasound parameters, and serum analytes were compared between women who developed preeclampsia and those who did not. Blood pressure measurements were classified as prehypertension or hypertension according to the Joint National Committee on Hypertension guidelines. Chi square, nonparametric, and logistic regression analyses were used to determine the contributors to preeclampsia development. RESULTS: Six hundred fourteen women prospectively enrolled at 9-14 weeks of gestation initiated aspirin by 16 weeks of gestation. The 59 (9.6%) women who developed preeclampsia were more likely to have chronic hypertension, diabetes, and obesity and had higher first-trimester blood pressure and lower serum pregnancy-associated plasma protein-A concentrations (all P<.05). Having first-trimester Joint National Committee on Hypertension prehypertension or hypertension was associated with a 2.18-fold increased risk of developing preeclampsia, whereas normotension was associated with a reduction of risk of 56%. CONCLUSION: Women who develop preeclampsia while taking aspirin prophylaxis are more likely to have elevated first-trimester blood pressures. Conversely, first-trimester normotension is associated with a reduced risk of preeclampsia.

First trimester maternal characteristics, Doppler parameters and serum analytes after preeclampsia.

OBJECTIVE: To evaluate the impact of prior preeclampsia on first trimester assessment in subsequent pregnancy. METHODS: A total of 1283 parous patients were prospectively enrolled at 9-14 weeks of gestation. Maternal biophysical characteristics, ultrasound parameters and placental analytes were compared between women with and without prior preeclampsia. RESULTS: There is no association between prior preeclampsia and the first trimester ultrasound parameters or placental analytes studied. The effects of prior preeclampsia in subsequent pregnancy are exaggerated by increasing parity and are predominantly blood pressure-related, independent of other cardiovascular risk factors. CONCLUSION: There is a potential role for lifestyle modification and stricter pregnancy blood pressure control in patients with prior preeclampsia.

Selective formation of angular tricyclic compounds by ruthenium-mediated ring-rearrangement metathesis.

Unsaturated spirocyclic substrates bearing two alkenyl chains underwent ruthenium-mediated ring-rearrangement metathesis through relaying cyclohexene and cycloheptene moieties to give angularly fused tricyclics. In some instances where two products were expected, high degrees of selectivity were observed. In one instance the structural parameter leading to selectivity was very subtle; in others the transformation favoured the formation of products with a cis-fused cyclohexene moiety. An unusual transformation involving ring-opening, double-bond migration, and then ring-closing was observed.