Ultra-low-coverage genome-wide association study-insights into gestational age using 17,844 embryo samples with preimplantation genetic testing.

BACKGROUND: Very low-coverage (0.1 to 1×) whole genome sequencing (WGS) has become a promising and affordable approach to discover genomic variants of human populations for genome-wide association study (GWAS). To support genetic screening using preimplantation genetic testing (PGT) in a large population, the sequencing coverage goes below 0.1× to an ultra-low level. However, the feasibility and effectiveness of ultra-low-coverage WGS (ulcWGS) for GWAS remains undetermined. METHODS: We built a pipeline to carry out analysis of ulcWGS data for GWAS. To examine its effectiveness, we benchmarked the accuracy of genotype imputation at the combination of different coverages below 0.1× and sample sizes from 2000 to 16,000, using 17,844 embryo PGT samples with approximately 0.04× average coverage and the standard Chinese sample HG005 with known genotypes. We then applied the imputed genotypes of 1744 transferred embryos who have gestational ages and complete follow-up records to GWAS. RESULTS: The accuracy of genotype imputation under ultra-low coverage can be improved by increasing the sample size and applying a set of filters. From 1744 born embryos, we identified 11 genomic risk loci associated with gestational ages and 166 genes mapped to these loci according to positional, expression quantitative trait locus, and chromatin interaction strategies. Among these mapped genes, CRHBP, ICAM1, and OXTR were more frequently reported as preterm birth related. By joint analysis of gene expression data from previous studies, we constructed interrelationships of mainly CRHBP, ICAM1, PLAGL1, DNMT1, CNTLN, DKK1, and EGR2 with preterm birth, infant disease, and breast cancer. CONCLUSIONS: This study not only demonstrates that ulcWGS could achieve relatively high accuracy of adequate genotype imputation and is capable of GWAS, but also provides insights into the associations between gestational age and genetic variations of the fetal embryos from Chinese population.

Perceptual Voice and Speech Analysis after Supraglottic Laryngeal Closure for Chronic Aspiration in Head and Neck Cancer.

OBJECTIVES/HYPOTHESIS: To evaluate the voice and speech outcomes after tubed supraglottic laryngeal closure (TSLC) surgery to treat chronic aspiration after radiotherapy for head and neck cancer. STUDY DESIGN: A retrospective case-control study. METHODS: The data of patients who underwent radiotherapy for head and neck cancer and who later required total laryngectomy or TSLC for chronic aspiration between 2004 and 2017 were retrieved from a dysphagia clinic. Preoperative and postoperative voice and speech were assessed by the GRBAS and INFVo rating scales. Control subjects who underwent radiotherapy alone or total laryngectomy with a tracheoesophageal prosthesis for other indications were recruited for comparison. RESULTS: Of 15 patients who underwent a TSLC with a mean age of 57.3 years (45-75 years), 13 were male and 2 female. All patients had a history of nasopharyngeal carcinoma. The success rate of speech production using their own larynx following an intact TSLC was 64%. There was no statistically significant difference in voice and speech ratings between preoperative and TSLC subjects on the GRBAS (P = .32) and INFVo scales (P = .57), although the quality of voice appeared to deteriorate after TSLC. However, the INFVo scale for impression, intelligibility and unsteadiness of the voice after TSLC was statistically significantly better than for laryngectomy with tracheoesophageal speech. CONCLUSIONS: A tubed supraglottic laryngeal closure controls chronic aspiration while preserving the larynx for phonation, and results in a better voice and speech quality than a laryngectomy with a voice prosthesis. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1616-E1623, 2021.

Factors related to meeting physical activity guidelines in active college students: A social cognitive perspective.

OBJECTIVE: To examine the relations of sex, exercise self-efficacy, outcome expectations, and social support with meeting physical activity guidelines (PAGs). PARTICIPANTS: Three hundred ninety-six college students participated in this study in the summer 2013. METHODS: Students completed online questionnaires that assessed physical activity behaviors and psychosocial factors (ie, self-efficacy, outcome expectancies, and social support). Students' physical activity profile was categorized as meeting no PAGs, meeting aerobic PAGs only, meeting muscle-strengthening PAGs only, or meeting both PAGs. RESULTS: A multinomial logistic regression revealed that students' sex and psychosocial factors significantly affected the odds of meeting any and all PAGs. Sex significantly moderated the relationship between outcome expectancy and meeting aerobic PAGs and between outcome expectancy meeting muscle-strengthening PAGs. CONCLUSIONS: Results indicate that interventions designed to increase psychosocial factors may increase the likelihood of students meeting any and all PAGs. Social support may be especially beneficial for increasing muscle-strengthening activity.

Haemoglobin level, proportion of haemoglobin Bart's and haemoglobin Portland in fetuses affected by homozygous α0-thalassemia from 12 to 40 weeks' gestation.

OBJECTIVES: To determine haematological parameters in fetuses affected by homozygous α(0)-thalassemia. METHODS: This was a cross-sectional retrospective study reviewing 546 blood samples (268 fetal and 278 neonatal cord) being collected between 1993 and 2006, from 12 weeks' gestation onwards for any indication, including the prenatal diagnosis of homozygous α(0)-thalassemia, other haematological disorders, hydrops or aneuploidy. The proportion of haemoglobin (Hb) fractions was determined by electrophoresis of haemolysate on cellulose acetate in all samples. RESULTS: There were significant differences in the haematological parameters between homozygous α(0)-thalassemia (n = 183) and control (n = 363) which were either heterozygous α(0)-thalassemia (alpha thalassemia trait) or normal. In homozygous α(0)-thalassemia, the median Hb level, proportion of Hb Bart's (γ(4)) and Hb Portland 1(ζ(2)γ(2)) were 6.4 g/dL, 77.5% and 22.5%, respectively. While the Hb level and the proportion of Hb Bart's increased significantly with gestation, the proportion of Hb Portland 1 decreased. The Hb level contributed by Hb Portland 1 remained around 1.4 g/dL throughout gestation. The proportion of mild, moderate and severe anaemia in the affected fetuses was 27.5, 32.7 and 39.8%, respectively. There was no significant difference in these proportions across different gestation (P = 0.231). There were no differences in the haematological parameters between hydropic and non-hydropic fetuses. CONCLUSION: Although the degree of anaemia is mild in around one-quarter of the affected fetuses, the contribution by Hb Portland 1 (ζ(2)γ(2)) to the Hb level was very low throughout gestation, and the affected fetuses may therefore be at risk for hypoxia.

Effects of low back pain on the relationship between the movements of the lumbar spine and hip.

Previous research had examined the effects of back pain on spinal movements, but information concerning movement coordination between the lumbar spine and hips was limited. The purpose of this study was to examine the effects of back pain and limitation in straight leg raise on the relationship between the movements of the lumbar spine and hip. An electromagnetic tracking system was employed to measure the movements of these joints in asymptomatic subjects (n = 20), and back pain subjects with (n = 24) and without (n = 17) limitation in straight leg raise. Subjects were requested to perform forward, backward and side bending, and twisting of the trunk. Back pain subjects were found to exhibit significant reductions in the magnitude of spine movements in all directions. Back pain was also associated with decrease in the magnitude of hip flexion but not hip movements in other directions. Cross-correlation analysis showed that there were changes in the strength of correlation and the time lag between lumbar spine and hip motions in normal and back pain subjects. In addition, back pain and limitation in straight leg raise were found to cause significant increases in the time required to complete the trunk movements. It was concluded that clinical assessment and treatment planning should take into account of the effects of back pain on the relationship between spine and hip movements.

Relationship between the movements of the lumbar spine and hip.

Movements of the lumbar spine and hips were measured in 20 healthy subjects using an electromagnetic tracking device. Movement sensors were attached to the L1 spinous process, the sacrum and the thighs. Each subject was requested to perform the following movements of the trunk: forward and backward bending, lateral bending and twisting. The ratio of the maximum magnitude of spine movement to that of the hip was determined. Angle-angle plot and cross-correlation were used to examine the relationship between the movements of the spine and hip. It was shown that during forward and backward bending of the trunk, the overall contributions of the lumbar spine and hip were similar, but the spine had a greater contribution to the early stage of the movement. Lateral bending of the trunk was found to be primarily accomplished by movement of the spine, whereas the hips were the predominate sources of movement for twisting. Moreover, it was shown that in the sagittal and horizontal planes, the movement patterns of the spine and hip were in phase, whereas in the coronal plane, the spine generally moved earlier than the hips. It is concluded that clinical examination of the back should include kinematic measures of both the lumbar spine and hips.

Developmental features of rapid aiming arm movements across the lifespan.

Using a lifespan approach, the authors investigated developmental features of the control of ballistic aiming arm movements by manipulating movement complexity, response uncertainty, and the use of precues. Four different age groups of participants (6- and 9-year-old boys and girls and 24- and 73-year-old men and women, 20 participants in each age group) performed 7 types of rapid aiming arm movements on the surface of a digitizer. Their movement characteristics such as movement velocity, normalized jerk, relative timing, movement linearity, and intersegment intervals were profiled. Analyses of variance with repeated measures were conducted on age and task effects in varying movement complexity (Study 1), response uncertainty (Study 2), and precue use (Study 3) conditions. Young children and senior adults had slower, more variant, less smooth, and less linear arm movements than older children and young adults. Increasing the number of movement segments resulted in slower and more variant responses. Movement accuracy demands or response uncertainty interacted with age so that the 6- and 74-year-old participants had poorer performances but responded similarly to the varying treatments. Even though older children and young adults had better performances than young children and senior adults, their arm movement performance declined when response uncertainty increased. The analyses suggested that young children's and senior adults' performances are poorer because less of their movement is under central control, and they therefore use on-line adjustments. In addition, older children and young adults use a valid precue more effectively to prepare for subsequent movements than do young children and senior adults, suggesting that older children and young adults are more capable of organizing motor responses than are young children and senior adults.

Periodic fever syndrome in children.

OBJECTIVES: To describe the presentation, clinical course, therapeutic response, and long-term follow-up of patients with a syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA). STUDY DESIGN: Patients with PFAPA (n = 94) referred over a 10-year period completed a registry form and provided medical records. Follow-up telephone calls were made in late 1997 to determine the persistence of episodes and sequelae. RESULTS: PFAPA episodes lasted 4.8 days (95% confidence interval 4.5 to 5.1) and recurred every 28 days (confidence interval 26 to 30), with a maximal temperature of 40.5 degrees C (confidence interval 40. 4 degrees to 40.6 degrees ). Of the 83 children available for follow-up, 34 no longer had episodes. In the remainder the episodes did not differ in character but recurred less frequently over time. The affected children had no long-term sequelae. Glucocorticoids were highly effective in controlling symptoms. Tonsillectomy and cimetidine treatment were associated with remission in a small number of patients. CONCLUSIONS: PFAPA is a not uncommon cause of periodic fever in children. In some children the syndrome resolves, whereas symptoms in others persist. Long-term sequelae do not develop. The syndrome is easily diagnosed when regularly recurring episodes of fever are associated with aphthous stomatitis, pharyngitis, or cervical adenitis.

A generalized rank-order method for nonparametric analysis of data from exercise science: a tutorial.

Frequent violations of the assumption that data are normally distributed occur in exercise science and other life and behavioral sciences. When this assumption is violated, parametric statistical analyses may be inappropriate for data analysis. We provide a rationale for using a generalized form of nonparametric analyses based on the Puri and Sen (1985) L treated as a chi 2 approximation. If data do not meet the assumption of normality, this nonparametric approach has substantial power and is easy to use. An advantage of this generalized technique is that ranked data may be used in standard parametric statistical programs widely available on desktop and mainframe computers, for example, regression, analysis of variance (ANOVA), multivariate analysis of variance (MANOVA) within BioMed, SAS, SPSS. Once the data are ranked and analyzed with these programs, the only adjustment required is to use a standard formula to calculate the nonparametric test statistic, L, instead of the parametric test statistic (e.g., F). Thus, rank-order nonparametric models become parallel with their parametric counterparts allowing the researcher to select between them based on characteristics of the data distribution. Examples of this approach are provided using data from exercise science for regression, ANOVA (including repeated measures) and MANOVA techniques from SPSSPC. Using these procedures, researchers can easily examine data distributions and make an appropriate decision about parametric or nonparametric analyses while continuing to use their regular statistical packages.

Assessment of overweight and obese patients.

The increasing prevalence of overweight and obesity in the United States has significant impact on the assessment, diagnosis, and treatment skill requirements of clinicians. There are a number of parameters that are used in the appropriate assessment of overweight and obesity. These include knowledge of basic body composition, measurement techniques for the assessment of total and regional body fat, and awareness of cultural influences on overweight and obesity. The focus of this article is to define overweight and obesity and delineate appropriate assessment parameters for those conditions.

Ethnic and age trends for body composition in women residing in the U.S. Southwest: I. Regional fat.

The study described regional fat distribution and anthropometric variables in an ethnically diverse sample of women (N = 143) who were between 20 and 30 (premenopausal) or 40 and 50 (perimenopausal) yr of age and of normal weight for height. Measurements included 11 skinfolds (abdomen, biceps, calf, forearm, midaxillary, pectoral, subscapular, suprailiac, suprapatellar, thigh, and triceps), waist and hip circumferences, height and mass. Regional fat distribution for African American, Mexican American, and Caucasian women was described as gluteal femoral. African American women had the smallest waist-to-hip ratio, with larger absolute measures for both the waist and gluteal C than the Caucasians or Mexican Americans. Native American women had an abdominal fat distribution pattern which was explained by more fat on the abdomen rather than less fat on the gluteal-femoral area. Native Americans had a different fat distribution from the other ethnic groups. Caucasians are not a good comparison group for African Americans or Native Americans because there are large differences as indicated by effect sizes in regional fat distribution. Variation within the ethnic groups was larger than differences between the groups for most variables. The distribution within ethnic groups was biased by extreme scores; thus 50-70% of the subjects were similar regardless of ethnic group.

Ethnic and age trends for body composition in women residing in the U.S. Southwest: II. Total fat.

This study assessed body density (BD) in an ethnically diverse sample of women (African American, Caucasian, Mexican American and Native American) (N = 139) who were between 20 and 30 or 40 and 50 yr of age and of normal weight for their height. BD was assessed using three methods: hydrostatically determined density (UWW), total body potassium (TBK) and the Jackson et al. (1980) sum of seven SF with gluteal circumference (SF). Ethnic differences in BD were detected by TBK and UWW. BD from SF did not detect ethnic differences, and the SEE was unacceptable. Based on multiple regression, the prediction equation was: BD = 1.1197794 - 0.000224382 (X3) + 0.006999 (e2) - 0.000320177 (X2) - 0.001892 (e1) + 0.001750 (e3) - 0.000537005 (x1) (where x1 = gluteal C, x2 = age in years, x3 = sum of 7 SF and e1, e2, and e3 describe ethnicity). This formula had a reduced SEE, a higher correlation with hydrostatically determined BD, and was sensitive to ethnic differences detected with other measures of BD. A 24-mmol decrease in potassium was found when comparing the older Caucasian women with the younger Caucasian women, while the difference for the African, Mexican, and Native American groups was 200-300 mmol.

Variables related to obesity and body fat: avenues to change.

Obesity and overweight constitute major health concerns in this country today. This article provides a description of the terms overweight and obese, variables contributing to diet and exercise adherence, and practice implications for nurse practitioners.

Measurement of body fat and fat distribution.

Overweight and obesity are increasing in prevalent and thus an important area for intervention and investigation. Researchers and clinicians have a variety of measurement techniques to assess body fatness and regional fat. These techniques are chosen for their accuracy and precision in light of their cost, convenience, and safety. This article introduces techniques for the measurement of body fatness and regional fat, their advantages and disadvantages and accuracy. Recommended measurement techniques for investigators and clinicians are provided.