PCR bias Toward the wild-type k-ras and p53 sequences: Implications for PCR detection of mutations and cancer diagnosis

PCR-based cancer diagnosis requires detection of rare mutations in k- ras, p53 or other genes. The assumption has been that mutant and wild-type sequences amplify with near equal efficiency, so that they are eventually present in proportions representative of the starting material. Work on factor IX suggests that this assumption is invalid for one case of near- sequence identity. To test the generality of this phenomenon and its relevance to cancer diagnosis, primers distant from point mutations in p53 and k-ras were used to amplify wild-type and mutant sequences from these genes. A substantial bias against PCR amplification of mutants was observed for two regions of the p53 gene and one region of k-ras. For k-ras and p53, bias was observed when the wild-type and mutant sequences were amplified separately or when mixed in equal proportions before PCR. Bias was present with proofreading and non-proofreading polymerase. Mutant and wild-type segments of the factor V, cystic fibrosis transmembrane conductance regulator and prothrombin genes were amplified and did not exhibit PCR bias. Therefore, the assumption of equal PCR efficiency for point mutant and wild-type sequences is invalid in several systems. Quantitative or diagnostic PCR will require validation for each locus, and enrichment strategies may be needed to optimize detection of mutants.

Condition monitoring and diagnosis of injector faults in a diesel engine using in-cylinder pressure and acoustic emission techniques

Failing injectors are one of the most common faults in diesel engines. The severity of these faults could have serious effects on diesel engine operations such as engine misfire, knocking, insufficient power output or even cause a complete engine breakdown. It is thus essential to prevent such faults from occurring by monitoring the condition of these injectors. In this paper, the authors present the results of an experimental investigation on identifying the signal characteristics of a simulated incipient injector fault in a diesel engine using both in-cylinder pressure and acoustic emission (AE) techniques. A time waveform event driven synchronous averaging technique was used to minimize or eliminate the effect of engine speed variation and amplitude fluctuation. It was found that AE is an effective method to detect the simulated injector fault in both time (crank angle) and frequency (order) domains. It was also shown that the time domain in-cylinder pressure signal is a poor indicator for condition monitoring and diagnosis of the simulated injector fault due to the small effect of the simulated fault on the engine combustion process. Nevertheless, good correlations between the simulated injector fault and the lower order components of the enveloped in-cylinder pressure spectrum were found at various engine loading conditions.

Applications of medical image processing in the diagnosis and treatment of spinal deformity

In Chapter 10, Adam and Dougherty describe the application of medical image processing to the assessment and treatment of spinal deformity, with a focus on the surgical treatment of idiopathic scoliosis. The natural history of spinal deformity and current approaches to surgical and non-surgical treatment are briefly described, followed by an overview of current clinically used imaging modalities. The key metrics currently used to assess the severity and progression of spinal deformities from medical images are presented, followed by a discussion of the errors and uncertainties involved in manual measurements. This provides the context for an analysis of automated and semi-automated image processing approaches to measure spinal curve shape and severity in two and three dimensions.

Integrated approach for HP-LNG pump diagnosis and prognostics based on health state probability estimation

This paper presents an innovative prognostics model based on health state probability estimation embedded in the closed loop diagnostic and prognostic system. To employ an appropriate classifier for health state probability estimation in the proposed prognostic model, the comparative intelligent diagnostic tests were conducted using five different classifiers applied to the progressive fault levels of three faults in HP-LNG pump. Two sets of impeller-rubbing data were employed for the prediction of pump remnant life based on estimation of discrete health state probability using an outstanding capability of SVM and a feature selection technique. The results obtained were very encouraging and showed that the proposed prognosis system has the potential to be used as an estimation tool for machine remnant life prediction in real life industrial applications.

The diagnostic accuracy of telegeriatrics for the diagnosis of dementia via video conferencing

Introduction The suitability of video conferencing (VC) technology for clinical purposes relevant to geriatric medicine is still being established. This project aimed to determine the validity of the diagnosis of dementia via VC. Methods This was a multisite, noninferiority, prospective cohort study. Patients, aged 50 years and older, referred by their primary care physician for cognitive assessment, were assessed at 4 memory disorder clinics. All patients were assessed independently by 2 specialist physicians. They were allocated one face-to-face (FTF) assessment (Reference standard – usual clinical practice) and an additional assessment (either usual FTF assessment or a VC assessment) on the same day. Each specialist physician had access to the patient chart and the results of a battery of standardized cognitive assessments administered FTF by the clinic nurse. Percentage agreement (P0) and the weighted kappa statistic with linear weight (Kw) were used to assess inter-rater reliability across the 2 study groups on the diagnosis of dementia (cognition normal, impaired, or demented). Results The 205 patients were allocated to group: Videoconference (n = 100) or Standard practice (n = 105); 106 were men. The average age was 76 (SD 9, 51–95) and the average Standardized Mini-Mental State Examination Score was 23.9 (SD 4.7, 9–30). Agreement for the Videoconference group (P0= 0.71; Kw = 0.52; P < .0001) and agreement for the Standard Practice group (P0= 0.70; Kw = 0.50; P < .0001) were both statistically significant (P < .05). The summary kappa statistic of 0.51 (P = .84) indicated that VC was not inferior to FTF assessment. Conclusions Previous studies have shown that preliminary standardized assessment tools can be reliably administered and scored via VC. This study focused on the geriatric assessment component of the interview (interpretation of standardized assessments, taking a history and formulating a diagnosis by medical specialist) and identified high levels of agreement for diagnosing dementia. A model of service incorporating either local or remote administered standardized assessments, and remote specialist assessment, is a reliable process for enabling the diagnosis of dementia for isolated older adults.

Using optical coherence tomography for differential diagnosis of a pigmented choroidal lesion

Clinicians regularly face the confronting challenge of differentiating a choroidal naevus from a melanoma. Uveal naevi are a relatively common finding during routine eye examinations: a prevalence of 6.5 per cent has been reported.1 In contrast, malignant melanomata are uncommon, being found in six persons per million population, but they can have devastating implications and consequences.2 Differential diagnoses can be difficult to make with certainty; any additional information that can assist in this process is advantageous...

Clinical utility of mental state screening as a predictor of intellectual outcomes 6 months after diagnosis of type 1 diabetes

Background Screening tests of basic cognitive status or ‘mental state’ have been shown to predict mortality and functional outcomes in adults. This study examined the relationship between mental state and outcomes in children with type 1 diabetes. Objective We aimed to determine whether mental state at diagnosis predicts longer term cognitive function of children with a new diagnosis of type 1 diabetes. Methods Mental state of 87 patients presenting with newly diagnosed type 1 diabetes was assessed using the School-Years Screening Test for the Evaluation of Mental Status. Cognitive abilities were assessed 1 wk and 6 months postdiagnosis using standardized tests of attention, memory, and intelligence. Results Thirty-seven children (42.5%) had reduced mental state at diagnosis. Children with impaired mental state had poorer attention and memory in the week following diagnosis, and, after controlling for possible confounding factors, significantly lower IQ at 6 months compared to those with unimpaired mental state (p < 0.05). Conclusions Cognition is impaired acutely in a significant number of children presenting with newly diagnosed type 1 diabetes. Mental state screening is an effective method of identifying children at risk of ongoing cognitive difficulties in the days and months following diagnosis. Clinicians may consider mental state screening for all newly diagnosed diabetic children to identify those at risk of cognitive sequelae.

RCA method for fault diagnosis in digital substations of power systems

The authors present a Cause-Effect fault diagnosis model, which utilises the Root Cause Analysis approach and takes into account the technical features of a digital substation. The Dempster/Shafer evidence theory is used to integrate different types of fault information in the diagnosis model so as to implement a hierarchical, systematic and comprehensive diagnosis based on the logic relationship between the parent and child nodes such as transformer/circuit-breaker/transmission-line, and between the root and child causes. A real fault scenario is investigated in the case study to demonstrate the developed approach in diagnosing malfunction of protective relays and/or circuit breakers, miss or false alarms, and other commonly encountered faults at a modern digital substation.