Systematic reanalysis of genomic data improves quality of variant interpretation.

As genomic sequencing expands, so does our knowledge of the link between genetic variation and disease. Deeper catalogs of variant frequencies improve identification of benign variants, while sequencing affected individuals reveals disease-associated variation. Accumulation of human genetic data thus makes reanalysis a means to maximize the benefits of clinical sequencing. We implemented pipelines to systematically reassess sequencing data from 494 individuals with developmental disability. Reanalysis yielded pathogenic or likely pathogenic (P/LP) variants that were not initially reported in 23 individuals, 6 described here, comprising a 16% increase in P/LP yield. We also downgraded 3 LP and 6 variants of uncertain significance (VUS) due to updated population frequency data. The likelihood of identifying a new P/LP variant increased over time, as ~22% of individuals who did not receive a P/LP variant at their original analysis subsequently did after 3 years. We show here that reanalysis and data sharing increase the diagnostic yield and accuracy of clinical sequencing.

Coordinated, multi-joint, fatigue-resistant feline stance produced with intrafascicular hind limb nerve stimulation.

The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.

Characteristics of volunteers and families in a neonatal home visitation project: the Kempe Community Caring Program.

OBJECTIVE: The purpose of this paper is to review literature related to home visitation support for new families using volunteer visitors and to describe characteristics of volunteers of the Kempe Community Caring Program, a home visitor support program for first time parents. Suggestions for effectively utilizing volunteers in family support programs are made. METHOD: Program data was collected and reviewed on 592 volunteer home visitors and the 1,144 families they served. Several evaluations and assessments were performed in order to attempt to measure the success of the intervention. Motivation for volunteering, longevity with program, and the extent of sociodemographic match between visitor and client were reviewed and discussed. RESULTS: Information on matched volunteer-client pairs was limited; however, speculations were made that neither motivation to participate nor sociodemographic match were critical factors in determining success of the intervention. Duration of volunteer participation was influenced by marital status, but not by age. Married volunteers stayed with the program significantly longer than unmarried volunteers. Low risk families demonstrated slightly improved confidence in parental function after receiving home visitation by a volunteer. CONCLUSION: This program suggests that new mothers may benefit from receiving the services of a volunteer home visitor; specifically, their confidence as parents and ability to establish positive relationships show slight improvement. Likewise, volunteers and families felt satisfied with the supportive relationships generated. In addition, a volunteer profile emerged which may be beneficial to similar programs' recruiting efforts.

Volunteer services for vulnerable families and at-risk elderly.

OBJECTIVE: The purpose of this paper is to explore the role of the volunteer with vulnerable populations, specifically, new parents and their infants and at-risk elderly. As demand for volunteer services increases due to budgetary and personnel reductions, a better understanding of volunteers as service providers is imperative. METHOD: A review of the literature related to volunteers who work with these two populations was conducted. Volunteer characteristics, roles, needs of populations served, recruitment, and training issues were addressed, specifically as they relate to the two populations. RESULTS: Studies indicate that the socio-demographic range of volunteers is wide, as are the motivations for volunteering. Similarities between the needs of new families and the elderly exist, and volunteers for both populations often provide supportive and pragmatic services. Volunteers for both populations are further challenged to maintain a client-focused intervention, a task which may be more difficult in the home. Training of volunteers was found to be both client and volunteer driven, with the needs of the population being served and the role of the volunteer within a specific service domain of prime importance. CONCLUSION: Similarities between infant and elder populations exist, as do volunteer interventions with these populations. A theoretical framework for defining motivation, designing need-based training, and addressing the role of volunteers is discussed. The use of volunteers as compassionate and cost-effective service providers for populations across the lifespan not only provides an increase in the number of skilled workers involved with these vulnerable populations, but also allows professional staff to expand the care which they are able to provide.

Differences in program implementation between nurses and paraprofessionals providing home visits during pregnancy and infancy: a randomized trial.

OBJECTIVES: This study examined differences between nurses and paraprofessionals in implementation of a home visiting program for low-income, first-time parents during pregnancy and the first 2 years of the child's life. METHODS: Mothers were randomly assigned to either a nurse-visited (n = 236) or a paraprofessional-visited (n = 244) condition. Nurse- and paraprofessional-visited families were compared on number and length of visits, topics covered, number of program dropouts, and relationship with home visitor. RESULTS: On average, nurses completed more visits than paraprofessionals (28 vs 23; P < .001) and spent a greater proportion of time on physical health issues during pregnancy (38% vs 27%; P < .001) and on parenting issues during infancy (46% vs 32%; P < .001). Paraprofessionals conducted visits that lasted longer and spent a greater proportion of time on environmental health and safety issues (15% vs 7% pregnancy; 15% vs 8% infancy; P < .001). While home visitors were viewed equally positively by mothers, nurses had fewer dropouts than did paraprofessionals (38% vs 48%; P = .04). More paraprofessional-visited families than nurse-visited families experienced staff turnover. CONCLUSIONS: Nurses and paraprofessionals, even when using the same model, provide home visiting services in different ways.

Limbness in the early chick embryo lateral plate.

In order for the limb to be useful in the evaluation of early determinants of morphogenesis, it is necessary to understand some of the characteristics associated with "limbness" and, more importantly at the beginning at least, it is necessary to know what regions of the early embryo exhibit limbness qualities. Previous investigators have assumed, without direct experimental evidence, that the flank does not have limbness qualities, even at early stages of development. However, there are a few studies suggesting that the early flank does possess limbness qualities. The purpose of the present study was to determine how extensively the qualities of limbness exist in the early chick embryo. Tissues from the future neck, wing, flank, and leg regions were grafted to host celoms and evaluated for their abilities to form limbs. Limbs developed from all four regions of stage 11-14 embryos, but after stage 14 only grafts from the wing and leg regions formed limbs.

Direction of gaze and emergence of speech in the second year.

Orienting to the right member of a pair of identical pictures increased monotonically with age in a longitudinal sample of 14 infants seen monthly from 13 to 22 months. The magnitude of the correlation between this orientation bias and a measure of language development also rose with age reaching a peak at 20 months and then declining. It was suggested that the acceleration of vocabulary and maturational changes in the central nervous system that occur between 16 and 22 months are associated with a special excitatory state in the temporal cortex of the left hemisphere.

Management of a mandibular high-flow vascular malformation.

A case of a high-flow mandibular vascular malformation successfully treated with combined selective embolization, resection, and reconstruction is reported.

Facial patterning and infant emotional expression: happiness, surprise, and fear.

Although recent studies have convincingly demonstrated that emotional expressions can be judged reliably from actor-posed facial displays, there exists little evidence that facial expressions in lifelike settings are similar to actor-posed displays, are reliable across situations designed to elicit the same emotion, or provide sufficient information to mediate consistent emotion judgments by raters. The present study therefore investigated these issues as they related to the emotions of happiness, surprise, and fear. 27 infants between 10 and 12 months of age (when emotion masking is not likely to confound results) were tested in 2 situations designed to elicit hapiness (peek-a-boo game and a collapsing toy), 2 to elicit surprise (a toy-switch and a vanishing-object task), and 2 to elicit fear (the visual cliff and the approach of a stranger. Dependent variables included changes in 28 facial response components taken from previous work using actor poses, as well as judgments of the presence of 6 discrete emotions. In addition, instrumental behaviors were used to verify with other than facial expression responses whether the predicted emotion was elicited. In contrast to previous conclusions on the subject, we found that judges were able to make all facial expression judgments reliably, even in the absence of contextual information. Support was also obtained for at least some degree of specificity of facial component response patterns, especially for happiness and surprise. Emotion judgments by raters were found to be a function of the presence of discrete facial components predicted to be linked to those emotions. Finally, almost all situations elicited blends, rather than discrete emotions.