A boarding school outbreak of pertussis in adolescents : value of laboratory diagnostic methods

Culture for Bordetella pertussis (B. pertussis) is the traditional gold standard for laboratory diagnosis of pertussis but is insensitive, especially later in the course of illness and in vaccinated persons. Interpretation of serology is limited by the lack of an appropriate reference standard. An outbreak of pertussis in a crowded boarding-school dormitory allowed evaluation of laboratory correlates of infection. Questionnaires, serum samples and throat swabs were collected from members of the exposed group. Serum samples from unexposed controls of a similar age group were used for comparison. B. pertussis PCR was performed on throat swabs, and sera were tested for IgA antibodies against whole-cell (WC) B. pertussis antigen and IgG antibodies to pertussis toxin (PT). The Centers for Disease Control and Prevention definition for pertussis was used to define clinical cases. We evaluated the use of a previously published cut-off for PT IgG of 125 EIA units (EU)/ml. Completed questionnaires were obtained from 115 students, of whom 85 (74%) reported coughing symptoms, including 32 (28%) who met the clinical case definition for pertussis. B. pertussis was detected by PCR in 17 (15%) and WC IgA in 22 (19%) students; neither correlated with symptoms, but dormitory of residence strongly predicted PCR status. The mean PT IgG geometric mean concentration, in this situation of high pertussis exposure, correlated with severity of symptoms and was significantly higher in both symptomatic and asymptomatic children exposed during the outbreak (P<0·001) than in control children. A cut-off for PT IgG of 125 EU/ml was too high in an outbreak situation to be sensitive enough to identify pertussis cases. A case of pertussis in a crowded boarding-school dormitory resulted rapidly in an outbreak. Serology and PCR were useful in identifying the outbreak and commencing disease control measures. The use of serology has mostly been evaluated in community serosurveys, where it is not possible to determine if immunity reflects vaccination, asymptomatic disease or symptomatic disease. This outbreak gave us the opportunity to evaluate the value of serology and PCR in the presence of confirmed exposure to pertussis.

Evaluation of Bayesian belief networks for diagnosis of psychotic disorders

The thesis examined the inter-rater reliability and procedural validity of four computerised Bayesian belief networks (BBNs) which were developed to assist with the diagnosis of psychotic disorders. The results of this research indicated that BBNs can significantly improve diagnostic reliability and may represent an important advance over current diagnostic methods. The professional portfolio investigated, through the presentation of case studies and review of literature relevant to each case study, how comorbidity and context of depression may impact on cognitive behavioural therapy treatment.

Recent insights into microbial catalases: isolation, production and purification

Catalase, an oxidoreductase enzyme, works as a detoxification system inside living cells against reactive oxygen species formed as a by-product of different metabolic reactions. The enzyme is found in a wide range of aerobic and anaerobic organisms. Catalase has also been employed in various analytical and diagnostic methods in the form of biosensors and biomarkers in addition to its other applications in textile, paper, food and pharmaceutical industries. New applications for catalases are constantly emerging thanks to their high turnover rate, distinct evolutionary origin, relatively simple and well-defined reaction mechanisms. The following review provides comprehensive information on isolation, production and purification of catalases with different techniques from various microbial sources along with their types, structure, mechanism of action and applications.

Isolation and polyphasic characterization of a novel hyper catalase producing thermophilic bacterium for the degradation of hydrogen peroxide.

A newly isolated microbial strain of thermophilic genus Geobacillus has been described with emphasis on polyphasic characterization and its application for degradation of hydrogen peroxide. The validation of this thermophilic strain of genus Geobacillus designated as BSS-7 has been demonstrated by polyphasic taxonomy approaches through its morphological, biochemical, fatty acid methyl ester profile and 16S rDNA sequencing. This thermophilic species of Geobacillus exhibited growth at broad pH and temperature ranges coupled with production of extraordinarily high quantities of intracellular catalase, the latter of which as yet not been reported in any member of this genus. The isolated thermophilic bacterial culture BSS-7 exhibited resistance against a variety of organic solvents. The immobilized whole cells of the bacterium successfully demonstrated the degradation of hydrogen peroxide (H2O2) in a packed bed reactor. This strain has potential application in various analytical and diagnostic methods in the form of biosensors and biomarkers in addition to applications in the textile, paper, food and pharmaceutical industries.

Depression and suicidal behavior in adolescents : a multi-informant and multi-methods approach to diagnostic classification

Informant discrepancies have been reported between parent and adolescent measures of depressive disorders and suicidality. We aimed to examine the concordance between adolescent and parent ratings of depressive disorder using both clinical interview and questionnaire measures and assess multi-informant and multi-method approaches to classification.

Carpal tunnel syndrome: diagnostic usefulness of sonography

PURPOSE: To prospectively evaluate accuracy of sonography for diagnosis of carpal tunnel syndrome (CTS) in patients clinically suspected of having the disease in one or both hands.
MATERIALS AND METHODS: A prospective cohort of 133 patients suspected of having CTS were referred to a teaching hospital between October 2001 and June 2002 for electrodiagnostic study. One hundred twenty patients (98 women, 22 men; mean age, 49 years; range, 19–83 years) underwent sonography within 1 week after electrodiagnostic study. Radiologist was blinded to electrodiagnostic study results. Seventy-five patients had bilateral symptoms; 23 patients, right-hand symptoms; and 22 patients, left-hand symptoms (total, 195 symptomatic hands). Cross-sectional area of median nerve was measured at three levels: immediately proximal to carpal tunnel inlet, at carpal tunnel inlet, and at carpal tunnel outlet. Flexor retinaculum was used as a landmark to margins of carpal tunnel. Optimal threshold levels (determined with classification and regression tree analysis) for areas proximal to and at tunnel inlet and at tunnel outlet were used to discriminate between patients with and patients without disease. Sensitivity, specificity, and false-positive and false-negative rates were derived on the basis of final diagnosis, which was determined with clinical history and electrodiagnostic study results as reference standard.
RESULTS: For right hands, sonography had sensitivity of 94% (66 of 70); specificity, 65% (17 of 26); false-positive rate, 12% (nine of 75); and false-negative rate, 19% (four of 21) (cutoff, 0.09 cm2 proximal to tunnel inlet and 0.12 cm2 at tunnel outlet). For left hands, sensitivity was 83% (53 of 64); specificity, 73% (24 of 33); false-positive rate, 15% (nine of 62); and false-negative rate, 31% (11 of 35) (cutoff, 0.10 cm2 proximal to tunnel inlet).
CONCLUSION: Sonography is comparable to electrodiagnostic study in diagnosis of CTS and should be considered as initial test of choice for patients suspected of having CTS.

Spurious precision : variability in procedural validity of diagnostic procedures in psychotic disorders and implications for research and treatment

Very few studies have quantified the level of agreement among alternative diagnostic procedures that use a common set of fixed operational criteria. The authors examined the procedural validity of four independent methods of assigning DSM-III-R diagnoses of psychotic disorders. METHOD: The research was conducted as a satellite study to the DSM-IV Field Trial for Schizophrenia and Related Psychotic Disorders. The setting was the National Health and Medical Research Council Schizophrenia Research Unit's Early Psychosis Prevention and Intervention Centre, which focuses on first-episode psychosis. Consecutively admitted patients (N = 50) were assessed by independent raters who used four different procedures to determine a DSM-III-R diagnosis. These procedures were 1) the diagnostic instrument developed for the DSM-IV field trial, 2) the Royal Park Multidiagnostic Instrument for Psychosis, 3) the Munich Diagnostic Checklists, and 4) a consensus DSM-III-R diagnosis assigned by a team of clinician researchers who were expert in the use of diagnostic criteria. RESULTS: Concordance between pairs of diagnostic procedures was only moderate. Corresponding levels of percent agreement, however, ranged from 66% to 76%, with converse misclassification rates of 24%-34% (assuming one procedure to be "correct"). CONCLUSIONS: These findings have significant research and clinical implications. Despite the introduction of operationally defined diagnoses, there remained an appreciable level of differential classification or misclassification arising from variability in the method of assigning the diagnostic criteria rather than the criteria themselves. Such misclassification may impede neurobiological research and have harmful clinical effects on patients with first-episode psychosis.

Robust-diagnostic regression : a prelude for inducing reliable knowledge from regression

Regression lies heart in statistics, it is the one of the most important branch of multivariate techniques available for extracting knowledge in almost every field of study and research. Nowadays, it has drawn a huge interest to perform the tasks with different fields like machine learning, pattern recognition and data mining. Investigating outlier (exceptional) is a century long problem to the data analyst and researchers. Blind application of data could have dangerous consequences and leading to discovery of meaningless patterns and carrying to the imperfect knowledge. As a result of digital revolution and the growth of the Internet and Intranet data continues to be accumulated at an exponential rate and thereby importance of detecting outliers and study their costs and benefits as a tool for reliable knowledge discovery claims perfect attention. Investigating outliers in regression has been paid great value for the last few decades within two frames of thoughts in the name of robust regression and regression diagnostics. Robust regression first wants to fit a regression to the majority of the data and then to discover outliers as those points that possess large residuals from the robust output whereas in regression diagnostics one first finds the outliers, delete/correct them and then fit the regular data by classical (usual) methods. At the beginning there seems to be much confusion but now the researchers reach to the consensus, robustness and diagnostics are two complementary approaches to the analysis of data and any one is not good enough. In this chapter, we discuss both of them under the unique spectrum of regression diagnostics. Chapter expresses the necessity and views of regression diagnostics as well as presents several contemporary methods through numerical examples in linear regression within each aforesaid category together with current challenges and possible future research directions. Our aim is to make the chapter self-explained maintaining its general accessibility.

Comparative evaluation of multi-label classification methods

This paper presents a comparative evaluation of popular multi-label classification methods on several multi-label problems from different domains. The methods include multi-label k-nearest neighbor, binary relevance, label power set, random k-label set ensemble learning, calibrated label ranking, hierarchy of multi-label classifiers and triple random ensemble multi-label classification algorithms. These multi-label learning algorithms are evaluated using several widely used MLC evaluation metrics. The evaluation results show that for each multi-label classification problem a particular MLC method can be recommended. The multi-label evaluation datasets used in this study are related to scene images, multimedia video frames, diagnostic medical report, email messages, emotional music data, biological genes and multi-structural proteins categorization.

Incidence, clinical spectrum, diagnostic features, treatment and predictors of paradoxical reactions during antibiotic treatment of Mycobacterium ulcerans infections

Background: Paradoxical reactions from antibiotic treatment of Mycobacterium ulcerans have recently been recognized. Data is lacking regarding their incidence, clinical and diagnostic features, treatment, outcomes and risk factors in an Australian population.

Methods: Data was collected prospectively on all confirmed cases of M. ulcerans infection managed at Barwon Health Services, Australia, from 1/1/1998-31/12/2011. Paradoxical reactions were defined on clinical and histological criteria and cases were determined by retrospectively reviewing the clinical history and histology of excised lesions. A Poisson regression model was used to examine associations with paradoxical reactions.

Results: Thirty-two of 156 (21%) patients developed paradoxical reactions a median 39 days (IQR 20-73 days) from antibiotic initiation. Forty-two paradoxical episodes occurred with 26 (81%) patients experiencing one and 6 (19%) multiple episodes. Thirty-two (76%) episodes occurred during antibiotic treatment and 10 (24%) episodes occurred a median 37 days after antibiotic treatment. The reaction site involved the original lesion (wound) in 23 (55%), was separate to but within 3 cm of the original lesion (local) in 11 (26%) and was more than 3 cm from the original lesion (distant) in 8 (19%) episodes. Mycobacterial cultures were negative in 33/33 (100%) paradoxical episodes. Post-February 2009 treatment involved more cases with no antibiotic modifications (12/15 compared with 11/27, OR 5.82, 95% CI 1.12-34.07, p = 0.02) and no further surgery (9/15 compared with 2/27, OR 18.75, 95% CI 2.62-172.73, p < 0.001). Six severe cases received prednisone with marked clinical improvement. On multivariable analysis, age ≥ 60 years (RR 2.84, 95% CI 1.12-7.17, p = 0.03), an oedematous lesion (RR 3.44, 95% CI 1.11-10.70, p=0.03) and use of amikacin in the initial antibiotic regimen (RR 6.33, 95% CI 2.09-19.18, p < 0.01) were associated with an increased incidence of paradoxical reactions.

Conclusions: Paradoxical reactions occur frequently during or after antibiotic treatment of M. ulcerans infections in an Australian population and may be increased in older adults, oedematous disease forms, and in those treated with amikacin. Recognition of paradoxical reactions led to changes in management with less surgery, fewer antibiotic modifications and use of prednisolone for severe reactions.

A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways

Background
Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach.

Methods
The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with ‘biopsy-confirmed’ CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology.

Results
Only five ‘biopsy-confirmed’ patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively.

Conclusions
Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.

Analysis of operating environments: A diagnostic model for linking science, society and policy for sustainability

Through analysis of the dynamics between science and decision-making, we argue that diagnosing fit-for purpose approaches to linking science and decision-making may be possible. Such diagnosis should enable identification of appropriate processes, institutions, objects (e.g. tools, information products) and relationships that can facilitate outcomes. We begin the paper by unsettling the traditional constructions that science must distance itself from debates about values and what is at stake, and so from policy making. Then, drawing from mixed methods case studies in coastal South-eastern Australia, we describe how scientific research has had a bearing on decisions affecting society and the environment. These analyses suggest that the willingness and capacity of research organisations, programmes or projects to actively reflect on and participate in the evolution of the 'operating environment' for their research is integral to their ability to inform outcomes through science. © 2014 Elsevier Ltd.

Computational methods for breast cancer diagnosis, prognosis, and treatment prediction

The research presented here develops a robust reliability algorithm for the identification of reliable protein interactions that can be incorporated with a gene expression dataset to improve the algorithm performance, and novel breast cancer based diagnostic, prognostic and treatment prediction algorithms, respectively, which take into account the existing issues in order to provide a fair estimation of their performance.

Foot-and-mouth disease in red deer - experimental infection and test methods performance

Summary: The aim of this study was to evaluate a number of foot-and-mouth disease (FMD) test methods for use in red deer. Ten animals were intranasally inoculated with the FMD virus (FMDV) O UKG 11/2001, monitored for clinical signs, and samples taken regularly (blood, serum, oral swabs, nasal swabs, probang samples and lesion swabs, if present) over a 4-week period. Only one animal, deer 1103, developed clinical signs (lesions under the tongue and at the coronary band of the right hind hoof). It tested positive by 3D and IRES real-time reverse transcription polymerase chain reaction (rRT-PCR) in various swabs, lesion materials and serum. In a non-structural protein (NSP) in-house ELISA (NSP-ELISA-IH), one commercial ELISA (NSP-ELISA-PR) and a commercial antibody NSP pen side test, only deer 1103 showed positive results from day post-inoculation (dpi) 14 onwards. Two other NSP-ELISAs detected anti-NSP serum antibodies with lower sensitivity. It also showed rising antibody levels in the virus neutralization test (VNT), the in-house SPO-ELISA-IH and the commercial SPO-ELISA-PR at dpi 9, and in another two commercial SPO-ELISAs at dpi 12 (SPO-ELISA-IV) and dpi 19 (SPO-ELISA-IZ), respectively. Six of the red deer that had been rRT-PCR and antibody negative were re-inoculated intramuscularly with the same O-serotype FMDV at dpi 14. None of these animals became rRT-PCR or NSP-ELISA positive, but all six animals became positive in the VNT, the in-house SPO-ELISA-IH and the commercial SPO-ELISA-PR. Two other commercial SPO-ELISAs were less sensitive or failed to detect animals as positive. The rRT-PCRs and the four most sensitive commercial ELISAs that had been used for the experimentally inoculated deer were further evaluated for diagnostic specificity (DSP) using 950 serum samples and 200 nasal swabs from non-infected animals. DSPs were 100% for the rRT-PCRs and between 99.8 and 100% for the ELISAs.

The diagnostic validity and reliability of an internet-based clinical assessment program for mental disorders

BACKGROUND: Internet-based assessment has the potential to assist with the diagnosis of mental health disorders and overcome the barriers associated with traditional services (eg, cost, stigma, distance). Further to existing online screening programs available, there is an opportunity to deliver more comprehensive and accurate diagnostic tools to supplement the assessment and treatment of mental health disorders. OBJECTIVE: The aim was to evaluate the diagnostic criterion validity and test-retest reliability of the electronic Psychological Assessment System (e-PASS), an online, self-report, multidisorder, clinical assessment and referral system. METHODS: Participants were 616 adults residing in Australia, recruited online, and representing prospective e-PASS users. Following e-PASS completion, 158 participants underwent a telephone-administered structured clinical interview and 39 participants repeated the e-PASS within 25 days of initial completion. RESULTS: With structured clinical interview results serving as the gold standard, diagnostic agreement with the e-PASS varied considerably from fair (eg, generalized anxiety disorder: κ=.37) to strong (eg, panic disorder: κ=.62). Although the e-PASS' sensitivity also varied (0.43-0.86) the specificity was generally high (0.68-1.00). The e-PASS sensitivity generally improved when reducing the e-PASS threshold to a subclinical result. Test-retest reliability ranged from moderate (eg, specific phobia: κ=.54) to substantial (eg, bulimia nervosa: κ=.87). CONCLUSIONS: The e-PASS produces reliable diagnostic results and performs generally well in excluding mental disorders, although at the expense of sensitivity. For screening purposes, the e-PASS subclinical result generally appears better than a clinical result as a diagnostic indicator. Further development and evaluation is needed to support the use of online diagnostic assessment programs for mental disorders. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG).