Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.

PURPOSE: The goal of this study was to identify new candidate genes and genomic copy-number variations associated with a rare, severe, and persistent speech disorder termed childhood apraxia of speech. Childhood apraxia of speech is the speech disorder segregating with a mutation in FOXP2 in a multigenerational London pedigree widely studied for its role in the development of speech-language in humans. METHODS: A total of 24 participants who were suspected to have childhood apraxia of speech were assessed using a comprehensive protocol that samples speech in challenging contexts. All participants met clinical-research criteria for childhood apraxia of speech. Array comparative genomic hybridization analyses were completed using a customized 385K Nimblegen array (Roche Nimblegen, Madison, WI) with increased coverage of genes and regions previously associated with childhood apraxia of speech. RESULTS: A total of 16 copy-number variations with potential consequences for speech-language development were detected in 12 or half of the 24 participants. The copy-number variations occurred on 10 chromosomes, 3 of which had two to four candidate regions. Several participants were identified with copy-number variations in two to three regions. In addition, one participant had a heterozygous FOXP2 mutation and a copy-number variation on chromosome 2, and one participant had a 16p11.2 microdeletion and copy-number variations on chromosomes 13 and 14. CONCLUSION: Findings support the likelihood of heterogeneous genomic pathways associated with childhood apraxia of speech.

Array comparative genomic hybridization analysis in patients with anophthalmia, microphthalmia, and coloboma.

PURPOSE: The goal of our study was to determine whether genomic copy number abnormalities (deletions and duplications) affecting genes involved in eye development contributed to the etiology of anophthalmia, microphthalmia, and coloboma. METHODS: The affected individuals were evaluated for the presence of deletions and duplications in genomic DNA by a very high-resolution array comparative genomic hybridization. RESULTS: Array analysis of 32 patients detected one case with a deletion encompassing the renal-coloboma syndrome associated gene PAX2. Nonpolymorphic copy number changes were also observed at several candidate chromosomal regions, including 6p12.3, 8q23.1q23.2, 13q31.3, 15q11.2q13.1, 16p13.13, and 20q13.13. CONCLUSIONS: This study identified the first patient with the typical phenotype of the renal-coloboma syndrome caused by a submicroscopic deletion of the coding region of the PAX2 gene. The finding suggests that PAX2 deletion testing should be performed in addition to gene sequencing as a part of molecular evaluation for the renal-coloboma syndrome. Array comparative genomic hybridization testing of 32 affected individuals showed that genomic deletions and duplications are not a common cause of nonsyndromic anophthalmia, microphthalmia, or coloboma but undoubtedly contribute to the etiology of these eye anomalies. Therefore, array comparative genomic hybridization testing represents an important and valuable addition to candidate gene sequencing in research and diagnostics of ocular birth defects.

Burn injuries among children from a region-wide paediatric burns unit.

Burns are known to be a cause of the most severe childhood injuries. The purpose of this retrospective study was to investigate socio-demographic and other factors involved in children being presented to a burns unit for treatment. This is the first reported comprehensive audit of burns admissions highlighting factors that may relate to the occurrence of burns in children. Raw data was obtained from the data service unit (DSU) and the ward registers of a paediatric burns unit. Of 1249 admissions, 1156 cases (92.5%) had clearly specified causes. The number of annual admissions ranged from 225 to 281 with a mean of 250 ± 25 per year. Eighty-eight percent of burns were superficial and covered less than 10% of body surface area. The majority of cases were males (744 cases; 60%). The mean age of cases was 4 years ± 1.8 years. The major causes of burns were 'spill' (765 cases; 61%) and 'contact' (150 cases; 12%). The largest group was white British (787 cases; 63%) followed by Asian (353 cases; 28%). Mixed and African population groups made up the remaining 9%. The risk of burns injuries is higher among younger children, during the early evening, and is disproportionately high in the Asian/Asian British groups. It is suggested that there is a need to increase injury prevention towards those at greatest risk.

Work-Life and Well-Being in U.K. Therapeutic Prison Officers: A Thematic Analysis.

Previous research has clearly demonstrated the positive impact of therapeutic interventions on offenders' well-being. Much less is known about the impact on prison staff facilitating and delivering such interventions. We employed qualitative methodology to capture a deeper understanding of the work of therapeutic prison officers. Seven prison officers working in a U.K. Category B therapeutic community prison were interviewed about their working lives, including their own participation in therapy. Following a thematic analysis approach, key findings indicated that the physical and cultural work environment was very important to staff; the therapeutic element of their job role, although demanding, was both satisfying and rewarding; and that working in a therapeutic prison environment provided the opportunity for personal as well as professional development. We conclude that further attention should be given to the unique nature of therapeutic prison work and the positive impact it can have on well-being at work.

Childhood Apraxia of Speech (CAS) in two patients with 16p11.2 microdeletion syndrome.

We report clinical findings that extend the phenotype of the ~550 kb 16p11.2 microdeletion syndrome to include a rare, severe, and persistent pediatric speech sound disorder termed Childhood Apraxia of Speech (CAS). CAS is the speech disorder identified in a multigenerational pedigree ('KE') in which half of the members have a mutation in FOXP2 that co-segregates with CAS, oromotor apraxia, and low scores on a nonword repetition task. Each of the two patients in the current report completed a 2-h assessment protocol that provided information on their cognitive, language, speech, oral mechanism, motor, and developmental histories and performance. Their histories and standard scores on perceptual and acoustic speech tasks met clinical and research criteria for CAS. Array comparative genomic hybridization analyses identified deletions at chromosome 16p11.2 in each patient. These are the first reported cases with well-characterized CAS in the 16p11.2 syndrome literature and the first report of this microdeletion in CAS genetics research. We discuss implications of findings for issues in both literatures.

Prevalence of fatigue among commercial pilots.

BACKGROUND: Short-haul pilots have largely been neglected in studies of fatigue, sleep loss and circadian disruption created by flight operations, but anecdotal evidence from pilots suggests that with the increasing amount of low-cost air travel, commercial pilots working short-haul operations may be becoming seriously fatigued. AIMS: This study attempted to ascertain how much subjective fatigue short-haul pilots reported, and makes comparisons between low-cost and scheduled airline pilots. METHODS: Pilots completed anonymous questionnaires (encompassing aviation factors, flight experience and a fatigue scale) posted on the Professional Pilots' Rumours Network website. RESULTS: Data were collected from 162 short-haul pilots and statistical adjustment for operational factors was made. Seventy-five percent reported severe fatigue and 81% reported the fatigue to be worse than 2 years ago. Eighty percent considered their thought processes were reduced while flying. Severe fatigue was reported more frequently by low-cost airline pilots than scheduled airline pilots (P = 0.05) and fatigue ratings were higher in this group (P = 0.03). Pilots who reported regularly flying into their 'discretion' hours had lower physical and psychological health, and overall fatigue scores, and poorer self-rated general health. Flying into discretion time occurred no more frequently in low-cost airline pilots than scheduled airline pilots. CONCLUSIONS: Identifiable fatigue problems are reported by short-haul pilots, but this cannot be attributed solely to the work schedules of low-cost airlines as regular use of discretion time appears to be associated with fatigue regardless of airline.

Reassessment of a midwestern Lyme disease focus for Borrelia burgdorferi and the human granulocytic ehrlichiosis agent.

Previous studies from the late 1980s defined the risk of human Lyme disease by determining the prevalence of Borrelia burgdorferi infection in Ixodes scapularis ticks and Peromyscus sp. mice captured from areas around La Crosse, Wis. High percentages of B. burgdorferi-infected I. scapularis ticks and P. leucopus mice were common in areas located north of Interstate 90 but were not detected in areas south of this major east-west thoroughfare. In this study, we reevaluated the extent of B. burgdorferi infection. High percentages of mice captured from sites north of the interstate were still infected with B. burgdorferi. In addition, B. burgdorferi was recovered from 12 (67%) of 18 mice captured from a site well south of the highway. However, none of 104 mice or 713 I. scapularis ticks captured from the study sites were infected with Ehrlichia spp. The results confirmed the continued high risk for humans to contract infection with B. burgdorferi and the significant southward expansion of the area in which Lyme disease is endemic. In contrast, the risk of acquiring human granulocytic ehrlichiosis remains minimal despite the abundance of appropriate vector ticks and reservoir rodents.