Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

Purpose: Neurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild phenotype without any externally visible tumors. Methods: A total of 135 individuals from 103 unrelated families, all carrying the constitutional NF1 p.Met992del pathogenic variant and clinically assessed using the same standardized phenotypic checklist form, were included in this study. Results: None of the individuals had externally visible plexiform or histopathologically confirmed cutaneous or subcutaneous neurofibromas. We did not identify any complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors, mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning disabilities. In an individual with the NF1 constitutional c.2970_2972del and three astrocytomas, we provided proof that all were NF1-associated tumors given loss of heterozygosity at three intragenic NF1 microsatellite markers and c.2970_297

The evaluation of treatment services and systems for substance use disorders

Scientific research and program evaluation have not played a major role in shaping the development of treatment services and systems in most countries. This has led to disparities in the development, management and monitoring of national treatment systems. In the evaluation of treatment for substance use disorders, the evaluation practitioner will usually be working at one of five levels: single case, treatment activity, treatment service, treatment agency or treatment system. One of the major barriers to undertaking internal program evaluation is the belief that it is a complicated research process best left to those with specific research training. Program managers and staff can plan and initiate an evaluation process for their program if they have access to research expertise when needed for certain parts of the process. There are seven main components of an evaluation process that can be planned and implemented: need assessment; evaluation planning, process evaluation, cost analysis, client satisfaction evaluation, outcome evaluation and economic evaluation. However, evaluation is more than the techniques and technology required to implement these types of activities. It also involves the routine questioning of current practice even if the feedback may be less positive than anticipated. A healthy culture for evaluation is one in which feedback loops are woven into the fabric of the treatment service or system. There are many barriers to evaluation in substance abuse services but these barriers can be overcome with careful planning and commitment to the delivery of evidence-based services

Load transfer curves from a large-diameter pipe pile in silty soil

This paper presents load transfer curves interpreted from a static load test performed on a large-diameter pipe pile in silty soils. In large-diameter driven piles and drilled shafts, appreciable movement is needed to mobilize toe resistance and thus settlement may control the design. Advanced load transfer methods require the prediction of the load transfer behavior along the shaft (i.e. t-z curve) and beneath the toe (i.e. q-z curve) of the pile. A number of generic load transfer curves for sand and clay are reported in the literature but limited information is available for large diameter piles and intermediate soils such as silt. This study develops t-z and q-z curves for silty soils from the analysis of a static loading test performed on an 1.8-meter diameter pipe pile in Rhode Island. The t-z curves from the test pile showed a softer load-movement response in comparison to those from slender piles in the literature. The results suggest that use of existing empirical t-z curves developed from slender piles in sands could lead to inaccurate load transfer analyses in large-diameter piles in silty soils. © 2012 American Society of Civil Engineers