Modelling Germline Mosaicism and Different New Mutation Rates Simultaneously for Appropriate Risk Calculations in Families with Duchenne Muscular Dystrophy

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations.     

Functioning and disability 6–15 years after traumatic brain injuries in northern Sweden

Objectives –  To assess long‐term functioning and disability after traumatic brain injury (TBI). Material and methods –  Individuals (n = 88) in Norrbotten, northern Sweden, who had been transferred for neurosurgical care were assessed with internationally established TBI outcome measures 6–15 years post‐injury. Results –  There was an improvement in overall outcome from discharge from inpatient rehabilitation to follow‐up. Many individuals had a high degree of motor and cognitive functioning, which enabled them to live independently in their own home without assistance, but there remained a disability related to community reintegration and social participation. This affected their productivity and to some degree their marital stability. The remaining disability and reduced productivity were related to the age at injury and the injury severity. Conclusions –  Our data showed that individuals with a TBI can achieve and maintain a high degree of functioning many years after the injury. Increasing age and a greater injury severity contributed to their long‐term disability.     

Children's categorisation of play and learning based on social context

While much time has been spent deliberating about the definition of play, little emphasis has been placed on what children themselves perceive as play. The aim of the present study was to examine social context as a cue for children's perceptions of play and learning. Ninety-two children aged between four and six years (mean four years nine months) participated in the study and completed the Activity Apperception Story Procedure. Children were asked to sort photographic stimuli into those they believed depicted play/not play and learning/not learning. Each of the stimuli were identified by independent raters as containing one of the following social cues; teacher absence (solitary activity, parallel activity or cooperative activity) or teacher presence (teacher involved activity or teacher directed activity). Findings revealed that children associated teacher absence with play. More specifically, children made links between play and the presence of peers (parallel and cooperative activity). Findings are discussed in relation to play in the early years curriculum, differences in children's early educational experiences and the importance of understanding children's perceptions of play.     

Central Sensitization Theory of Migraine: Clinical Implications

The clinical science of migraine headache continues to evolve. Theories of the pathophysiology of migraine have progressed from the early vascular basis of migraine to more complex current theories that emphasize the centrality of neuronal dysfunction. The most recently articulated theory of migraine is the central sensitization hypothesis, which proposes that altered processing of sensory input in the brainstem, principally the trigeminal nucleus caudalis, could account for many of the temporal and symptomatic features of migraine, as well as its poor response to triptan therapy when such treatment is initiated hours after the onset of pain. Both preclinical and clinical data support the central sensitization theory. A critical clinical implication of this theory is that drugs that are capable of either aborting or arresting the process of central sensitization, most prominently dihydroergotamine, may have a unique role in the treatment of migraine. An additional, and highly practical, implication is based upon the finding that cutaneous allodynia—pain arising from innocuous stimulation of the skin, as in hair brushing or the application of cosmetics—is an easily identifiable marker of central sensitization. Thus, the presence or absence of cutaneous allodynia can be integrated into the routine clinical assessment of migraine and utilized as a determinant of treatment. Future basic and clinical research on central sensitization is likely to be of ongoing importance to the field.     

Quality of life after total mesorectal excision for rectal cancer

BACKGROUND: After total mesorectal excision for rectal cancer, many surgeons try to avoid an abdominoperineal resection (APR) by performing a transanally double stapled low colo-rectal anastomosis (LRA), frequently without a pouch. This policy is mainly based on the assumption that the quality of life after such LRA is higher than after APR. It has been suggested that a better functional outcome and therefore a higher quality of life might be achieved by a colo-anal J-pouch anastomosis (CPA). The aim of this study was to assess quality of life among disease-free survivors after APR, LRA and CPA. METHODS: The charts of 301 consecutive patients who had undergone surgery for cancer in the middle or lower third of the rectum were analysed. Two hundred four patients were eligible for inclusion. The quality of life among these patients was assessed using one generic (EQ-5D) and two disease-specific questionnaires (EORTC QLQ-C30 and EORTC QLQ-CR38). RESULTS: The response rate was 82%. The median follow-up was 31 months. Overall, quality of life was good but CPA patients had better quality of life scores than APR and LRA patients. This difference was not only due to the better functional outcome but also to the lower incidence of disturbed micturition and sexual problems in the CPA group. CONCLUSION: The quality of life after colo-anal J-pouch anastomosis is better than after abdominoperineal resection (APR) and low colo-rectal anastomosis (LRA). The quality of life after APR is similar to that after LRA.     

第一产程胎心监护异常226例的相关因素分析

目的探讨第一产程胎心监护异常的相关因素，提示处理措施。方法2004年1月1日。12月31日对我院226例第一产程胎心监护异常的相关因素进行回顾性分析。结果第一产程胎心监护异常为综合因素所致，胎儿高危因素为91.59％，母体高危因素为65．49％，产程处理因素为42．92％。结论第一产程胎心监护异常主要与胎儿因素、母体因素有关，提高产前检查质量、加强产程监护、正确选择分娩方式极为重要。