Scenario analysis is a key component of the advanced measurement approach AMA to estimating the capital charge for operational risk.
This article has been cited by other articles in PMC. It is an aetiologically heterogeneous group of disorders that affects about per cent of the general population.
Collectively, in up to 50 per cent of the cases, a genetic aetiology has been implicated. Despite extensive evaluation cause for MR remains unknown in about per cent of cases which is highly frustrating both for the treating clinician and parents.
Over the past 20 years, continuous advancement in various molecular and cytogenetic techniques has revolutionized the field of clinical genetics by improving the diagnostic yield and unraveling various genetic syndromes. Genomic imbalances or copy number variations CNVs as a group have now increasingly been implicated in the aetiology of mental retardation.
These are defined as DNA segments of more than 1 Kb length, which show a variable copy number compared with a reference genome 2. Such cryptic rearrangements are too small to be detected by conventional cytogenetics.
Initially, high resolution cytogenetics and FISH studies were considered the gold standard. However, over the years the use of MLPA and CMA has become the choice of diagnostic tests for the evaluation of idiopathic mental retardation. MLPA is especially useful in situations where a clinically well defined microdeletion or microduplication syndrome is suspected by a clinical geneticist, whereas CMA examines the whole genome at a variable resolution for all the cases of idiopathic MR.
CMA has resulted in the delineation of various mental retardation syndromes which otherwise would have been unrecognized based solely on the clinical acumen.
Both these techniques are not useful in the detection of balanced rearrangements like translocations or inversion as there is no copy number change as such.
MLPA is a PCR based multiplex technique that studies several genomic regions in a single reaction and allows multiple samples to be handled simultaneously.
This method has been reported to be accurate and reliable for identifying deletions and duplications for other genetic disorders such as Duchenne muscular dystrophy 3. As compared to FISH, it is an efficient, rapid, less labour intensive and cost-effective alternative for the evaluation of unexplained MR.
In various studies, based upon the usage of preselection criteria 4number of patients, the number and types of MLPA kits used, the yield has ranged from 5. CMA analysis is also used for the determination of genomic imbalances but performance is at a much higher resolution.
The CMA analysis covers either the target regions that are known to contain clinically significant CNVs or the whole genome depending upon the platform used.
The frequency of disease causing CNVs using CMA in patients with unexplained mental retardation with or without dysmorphism has been reported to be as high as 20 per cent 789. Although whole genome array allows the characterization of new genetic syndromes, yet it has a potential for the high number of uncertain results, as benign CNVs are quite prevalent in the phenotypically normal population Next-generation sequencing NGS is a latest emerging technique that allows detection of single-nucleotide changes through the whole genome.
Application of this technique has deciphered the aetiology of various mental retardation syndromes viz. In this study, use of follow up MLPA kits has allowed the determination of the approximate size in two thirds of subtelomeric imbalances.
With the rapid advancements of DNA based tests and their increasing utility in the clinical practice even for the common health problems, it is important to remember for the physicians that the choice of any genetic test depends upon the accurate clinical diagnosis, specific syndrome, availability of tests, accuracy and reliability of test, diagnostic yield and the cost of the test.
There is no single test that covers all the disorders.Scenario planning, also called scenario thinking or scenario analysis, is a strategic planning method that some organizations use to make flexible long-term plans.
It is in large part an adaptation and generalization of classic methods used by military intelligence . Developmental Analysis of Big: A Psychosocial Approach. Kaitlin Bettencourt FSCJ DEP Spring A12 Psycho-Social Development in Big In the movie Big, Tom Hanks is an adolescent boy who gets frustrated with the limitations that come with being only 12 years old.
A critical issue for scenario analysis is the quality of model input. The key information required for each risk class is the expected annual frequency (λ) of the loss events and the economic impact of each event, evaluated in terms of typical loss (M) and worst case (WC) scenario.
Global developmental delay (GDD) refers to the delay in two or more developmental domains (gross motor/fine motor, cognitive, speech/language, personal/social, activities of daily living) in young children less than 5 years of age. Mental retardation (MR) is defined by the American Association on.
A critical issue for scenario analysis is the quality of model input. The key information required for each risk class is the expected annual frequency (λ) of the loss events and the economic impact of each event, evaluated in .
Global developmental delay (GDD) refers to the delay in two or more developmental domains (gross motor/fine motor, cognitive, speech/language, personal/social, activities of daily living) in young children less than 5 years of age.
Mental retardation (MR) is defined by the American Association on.