Contingent screening for down syndrome is an efficient alternative to non-disclosure sequential screening

Objective To present a first and second trimester Down syndrome screening strategy, whereby second-trimester marker determination is contingent on the first-trimester results. Unlike non-disclosure sequential screening (the Integrated test), which requires all women to have markers in both trimesters, this allows a large proportion of the women to complete screening in the first trimester. Methods Two first-trimester risk cut-offs defined three types of results: positive and referred for early diagnosis; negative with screening complete; and intermediate, needing second-trimester markers. Multivariate Gaussian modelling with Monte Carlo simulation was used to estimate the false-positive rate for a fixed 85% detection rate. The false-positive rate was evaluated for various early detection rates and early test completion rates. Model parameters were taken from the SURUSS trial. Results Completion of screening in the first trimester for 75% of women resulted in a 30% early detection rate and a 55% second trimester detected rate (net 85%) with a false-positive rate only 0.1% above that achievable by the Integrated test. The screen-positive rate was 0.1% in the first trimester and 4.7% for those continuing to be tested in the second trimester. If the early detection rate were to be increased to 45% or the early completion rate were to be increased to 80%, there would be a further 0.1% increase in the false-positive rate. Conclusion Contingent screening can achieve results comparable with the Integrated test but with earlier completion of screening for most women. Both strategies need to be evaluated in large-scale prospective studies particularly in relation to psychological impact and practicability.

The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis.

Objective To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables. Methods Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the “gold standard measure,” chi-square, sensitivity, specificity, false-positive and-negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions. Results The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second-highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process. Conclusion We propose a provisional data-driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM.

Comparison of two polyclonal antibodies for the detection of 19-nortestosterone in bovine bile by ELISA

19-Nortestosterone (beta-NT) is banned for use as a growth promoter in food animals within the European Union. For regulatory control purposes, urine and bile samples are routinely screened by immunoassay. The aim of the present study was to compare the ability of two immunoassays, using two rabbit polyclonal antibodies raised against two different NT derivatives, to detect NT residues in bovine bile. One antiserum cross-reacted with both alpha-NT and beta-NT (alpha/beta-NT), whereas the other was specific for alpha-NT. Bile samples from 266 slaughtered cattle were deconjugated and analyzed using both antibodies, with all screening positives (>2 ng ml(-1)) confirmed by high resolution gas chromatography mass spectrometry. The alpha/beta-NT and alpha-NT antibody-based ELISAs screened 39 and 44 samples positive, respectively, with NT confirmed in 22 and 39, respectively. The alpha/beta-NT antibody-based ELISA produced a false-negative rate of 44% compared to 0% for the alpha-NT antibody-based ELISA. Supplementary investigations concluded that a matrix effect was a major cause of the marked differences in false-negative rates. This result underlines the necessity to validate immunoassays in the sample matrix.

Detecting Packed Executables using Steganalysis

This paper proposes a novel method of detecting packed executable files using steganalysis, primarily targeting the detection of obfuscated malware through packing. Considering that over 80% of malware in the wild is packed, detection accuracy and low false negative rates are important properties of malware detection methods. Experimental results outlined in this paper reveal that the proposed approach achieving an overall detection accuracy of greater than 99%, a false negative rate of 1% and a false positive rate of 0%.

Increasing detection rate of user-to-root attacks using genetic algorithms

An extensive set of machine learning and pattern classification techniques trained and tested on KDD dataset failed in detecting most of the user-to-root attacks. This paper aims to provide an approach for mitigating negative aspects of the mentioned dataset, which led to low detection rates. Genetic algorithm is employed to implement rules for detecting various types of attacks. Rules are formed of the features of the dataset identified as the most important ones for each attack type. In this way we introduce high level of generality and thus achieve high detection rates, but also gain high reduction of the system training time. Thenceforth we re-check the decision of the user-to- root rules with the rules that detect other types of attacks. In this way we decrease the false-positive rate. The model was verified on KDD 99, demonstrating higher detection rates than those reported by the state- of-the-art while maintaining low false-positive rate.

Cost-effectiveness analysis of screening for lung cancer with low dose spiral CT (computed tomography) in the Australian setting

Introduction:
Low dose spiral computed tomography (CT) is a sensitive screening tool for lung cancer that is currently being evaluated in both non-randomised studies and randomised controlled trials.
Methods:
We conducted a quantitative decision analysis using a Markov model to determine whether, in the Australian setting, offering spiral CT screening for lung cancer to high risk individuals would be cost-effective compared with current practice. This exploratory analysis was undertaken predominantly from the perspective of the government as third-party funder. In the base-case analysis, the costs and health outcomes (life-years saved and quality-adjusted life years) were calculated in a hypothetical cohort of 10,000 male current smokers for two alternatives: (1) screen for lung cancer with annual CT for 5 years starting at age 60 year and treat those diagnosed with cancer or (2) no screening and treat only those who present with symptomatic cancer.
Results:
For male smokers aged 60–64 years, with an annual incidence of lung cancer of 552 per 100,000, the incremental cost-effectiveness ratio was $57,325 per life-year saved and $105,090 per QALY saved. For females aged 60–64 years with the same annual incidence of lung cancer, the cost-effectiveness ratio was $51,001 per life-year saved and $88,583 per QALY saved. The model was used to examine the relationship between efficacy in terms of the expected reduction in lung cancer mortality at 7 years and cost-effectiveness. In the base-case analysis lung cancer mortality was reduced by 27% and all cause mortality by 2.1%. Changes in the estimated proportion of stage I cancers detected by screening had the greatest impact on the efficacy of the intervention and the cost-effectiveness. The results were also sensitive to assumptions about the test performance characteristics of CT scanning, the proportion of lung cancer cases overdiagnosed by screening, intervention rates for benign disease, the discount rate, the cost of CT, the quality of life in individuals with early stage screen-detected cancer and disutility associated with false positive diagnoses. Given current knowledge and practice, even under favourable assumptions, reductions in lung cancer mortality of less than 20% are unlikely to be cost-effective, using a value of $50,000 per life-year saved as the threshold to define a “cost-effective” intervention.
Conclusion:
The most feasible scenario under which CT screening for lung cancer could be cost-effective would be if very high-risk individuals are targeted and screening is either highly effective or CT screening costs fall substantially.

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.

Distinguishing DDoS attacks from flash crowds using probability metrics

Both Flash crowds and DDoS (Distributed Denial-of-Service) attacks have very similar properties in terms of internet traffic, however Flash crowds are legitimate flows and DDoS attacks are illegitimate flows, and DDoS attacks have been a serious threat to internet security and stability. In this paper we propose a set of novel methods using probability metrics to distinguish DDoS attacks from Flash crowds effectively, and our simulations show that the proposed methods work well. In particular, these mathods can not only distinguish DDoS attacks from Flash crowds clearly, but also can distinguish the anomaly flow being DDoS attacks flow or being Flash crowd flow from Normal network flow effectively. Furthermore, we show our proposed hybrid probability metrics can greatly reduce both false positive and false negative rates in detection.

Malware variant detection using similarity search over sets of control flow graphs

Static detection of polymorphic malware variants plays an important role to improve system security. Control flow has shown to be an effective characteristic that represents polymorphic malware instances. In our research, we propose a similarity search of malware using novel distance metrics of malware signatures. We describe a malware signature by the set of control flow graphs the malware contains. We propose two approaches and use the first to perform pre-filtering. Firstly, we use a distance metric based on the distance between feature vectors. The feature vector is a decomposition of the set of graphs into either fixed size k-sub graphs, or q-gram strings of the high-level source after decompilation. We also propose a more effective but less computationally efficient distance metric based on the minimum matching distance. The minimum matching distance uses the string edit distances between programs' decompiled flow graphs, and the linear sum assignment problem to construct a minimum sum weight matching between two sets of graphs. We implement the distance metrics in a complete malware variant detection system. The evaluation shows that our approach is highly effective in terms of a limited false positive rate and our system detects more malware variants when compared to the detection rates of other algorithms.

Control flow-based malware variant detection

Static detection of malware variants plays an important role in system security and control flow has been shown as an effective characteristic that represents polymorphic malware. In our research, we propose a similarity search of malware to detect these variants using novel distance metrics. We describe a malware signature by the set of control flowgraphs the malware contains. We use a distance metric based on the distance between feature vectors of string-based signatures. The feature vector is a decomposition of the set of graphs into either fixed size k-subgraphs, or q-gram strings of the high-level source after decompilation. We use this distance metric to perform pre-filtering. We also propose a more effective but less computationally efficient distance metric based on the minimum matching distance. The minimum matching distance uses the string edit distances between programs' decompiled flowgraphs, and the linear sum assignment problem to construct a minimum sum weight matching between two sets of graphs. We implement the distance metrics in a complete malware variant detection system. The evaluation shows that our approach is highly effective in terms of a limited false positive rate and our system detects more malware variants when compared to the detection rates of other algorithms. © 2013 IEEE.

Identification of prey captures in Australian Fur Seals (Arctocephalus pusillus doriferus) using head-mounted accelerometers: field validation with animal-borne video cameras

This study investigated prey captures in free-ranging adult female Australian fur seals (Arctocephalus pusillus doriferus) using head-mounted 3-axis accelerometers and animal-borne video cameras. Acceleration data was used to identify individual attempted prey captures (APC), and video data were used to independently verify APC and prey types. Results demonstrated that head-mounted accelerometers could detect individual APC but were unable to distinguish among prey types (fish, cephalopod, stingray) or between successful captures and unsuccessful capture attempts. Mean detection rate (true positive rate) on individual animals in the testing subset ranged from 67-100%, and mean detection on the testing subset averaged across 4 animals ranged from 82-97%. Mean False positive (FP) rate ranged from 15-67% individually in the testing subset, and 26-59% averaged across 4 animals. Surge and sway had significantly greater detection rates, but also conversely greater FP rates compared to heave. Video data also indicated that some head movements recorded by the accelerometers were unrelated to APC and that a peak in acceleration variance did not always equate to an individual prey item. The results of the present study indicate that head-mounted accelerometers provide a complementary tool for investigating foraging behaviour in pinnipeds, but that detection and FP correction factors need to be applied for reliable field application.

Associação glicemia de jejum e fatores de risco como teste para rastreamento do diabete gestacional

OBJETIVOS: comparar dois testes de rastreamento do diabete gestacional. MÉTODOS: estudo prospectivo no qual foram avaliadas 356 gestantes, sem diagnóstico prévio do diabete melito, submetidas, de modo independente, a dois testes de rastreamento: associação glicemia de jejum e fator de risco (GJ+FR) e teste oral simplificado de tolerância à glicose (TTG50g). A comparação entre os métodos foi realizada pelos índices de sensibilidade (S), especificidade (E) e valores preditivos positivo (VPP) e negativo (VPN), resultados falsos, positivos (FP) e negativos (FN) e pela diferença dos resultados observados e esperados, avaliada pelo teste do Qui-quadrado (p<0,05). RESULTADOS: a associação GJ+FR determinou a confirmação diagnóstica em maior número de gestantes (187; 52,5%) que o TTG50g (49; 13,8%). Esta diferença foi significativa (p<0,05). A associação GJ+FR apresentou sensibilidade de 83,7% e valor preditivo negativo (VPN) de 95,3% em relação ao TTG50g. CONCLUSÕES: os índices elevados de sensibilidade e VPN da associação GJ+FR em relação ao TTG50g, sua simplicidade, praticidade, baixo custo e fácil replicação permitem sua indicação no rastreamento do diabete gestacional.

Comparison between 100-g glucose tolerance test and two other screening tests for gestational diabetes: combined fasting glucose with risk factors and 50-g glucose tolerance test

CONTEXTO E OBJETIVO: A falta de consenso sobre os protocolos de rastreamento e diagnóstico do diabetes gestacional, associada às dificuldades na realização do teste oral simplificado do diabete gestacional (o teste de tolerância a 100 g de glicose, considerado padrão-ouro) justificam a comparação com alternativas. O objetivo deste trabalho é comparar o teste padrão-ouro a dois testes de rastreamento: associação de glicemia de jejum e fatores de risco (GJ + FR) e o teste oral simplificado de tolerância a 50 g de glicose (TTG 50 g), com o teste de tolerância a 100 g de glicose (TTG 100 g). TIPO DE ESTUDO E LOCAL: Estudo de coorte longitudinal, prospectivo, realizado no Serviço de Ginecologia e Obstetrícia do Hospital Universitário da Universidade Federal de Mato Grosso do Sul. MÉTODOS: 341 gestantes foram submetidas aos três testes. Calcularam-se os índices de sensibilidade (S), especificidade (E), valores preditivos (VPP e VPN), razões de probabilidade (RPP e RPN) e resultados falsos (FP e FN), positivos e negativos da associação GJ + FR e do TTG 50 g em relação ao TTG 100 g. Compararam-se as médias das glicemias de uma hora pós-sobrecarga (1hPS) com 50 e 100 g. Na análise estatística, empregou-se o teste t de Student, com limite de significância de 5%. RESULTADOS: A associação GJ + FR encaminhou mais gestantes (53,9%) para a confirmação diagnóstica que o TTG 50 g (14,4%). Os dois testes foram equivalentes nos índices de S (86,4 e 76,9%), VPN (98,7 e 98,9%), RPN (0,3 e 0,27) e FN (15,4 e 23,1%). As médias das glicemias 1hPS foram semelhantes, 106,8 mg/dl para o TTG 50 g e 107,5 mg/dl para o TTG 100 g. CONCLUSÕES: Os resultados da eficiência diagnóstica associados à simplicidade, praticabilidade e custo referendaram a associação GJ + FR como o mais adequado para o rastreamento. A equivalência das glicemias de 1hPS permitiram a proposição de um novo protocolo de rastreamento e diagnóstico do diabete gestacional, com menores custo e desconforto.

Microbiological evaluation of milk samples positive to California Mastitis Test in dairy buffalo cows (Buballus bubalis)

In order to observe the microbiological status of CMT positive samples, 734 apparently health mammary quarters from buffalo cows were submitted to physical evaluation, strip cup test and CMT. After milk samples inoculation in 10% ovine blood agar base media and in MacConkey agar and incubation under aerobic condition for 72 hours at 37 degrees C, identification was proceeded. According to CMT, 227 quarters (30,93%) were positive, among them 73 (32,16%) presented 1+ reaction, 53 (23,35%) were 2+ and 101 (44,49%) were 3+. Microbiological exams of such samples were positive in 147 (64,76%) out of 227 CMT positive samples and among the remaining 72 (31,72%) were negative and 8 (3,52) were contaminated. In the 147 microbiological positive samples 204 bacteria were found in pure or associated growth and the most frequent agents were: Corynebacterium sp (59,25%); Staphylococcus sp (17,65%) among which 86,11% were coagulase negative and 13,89% were coagulase positive; and Micrococcus sp (6,37%). The results revealed that, excluding the eight contaminated samples, 147 (67,12%) quarters out of 219 CMT positive could be considered as bacteria-carrier and that even in a smaller percentage false-positive results can cause problems in a sanitary program for mastitis control in dairy buffalo cows.

Validade da citologia cervicovaginal na detecção de lesões pré-neoplásicas e neoplásicas de colo de útero

Introdução: O exame colpocitológico ou teste de Papanicolaou permite o diagnóstico precoce do câncer de colo do útero. O êxito no rastreamento desta doença dependerá, além de outros fatores, da acuidade diagnóstica do exame colpocitológico. Objetivos: Avaliar a acurácia diagnóstica da citologia cervicovaginal na detecção de lesões cervicais através da comparação citoistopatológica. Material e métodos: Avaliou-se o grau de concordância entre os exames citológico e histopatológico de 373 pacientes atendidas em um hospital universitário no período de 1990 a 1997 e foram calculados os indicadores: sensibilidade, especificidade, valores preditivos positivos e negativos e as taxas de falsos positivos e falsos negativos do exame. Resultados: A taxa bruta de concordância citoistopatológica foi de 65,1%. A sensibilidade do exame foi alta (96,0%), no entanto sua especificidade foi baixa (51,5%), significando a inclusão de muitos resultados falsos positivos. A taxa de falsos positivos foi de 48,4%, enquanto a de falsos negativos foi de 4%. Discussão: Apesar de a sensibilidade do teste ser alta, sua especificidade é baixa, significando que muitas mulheres seriam falsamente diagnosticadas como doentes, levando a um número elevado de resultados falsos positivos e custos desnecessários, além do potencial caráter iatrogênico que esta ação poderia assumir. No entanto, um exame altamente sensível é o teste de escolha para programas de rastreamento de câncer cervical na população feminina. Conclusões: Para garantir a acuidade diagnóstica do teste de Papanicolaou são essenciais atividades de controle de qualidade nos laboratórios, tanto do procedimento colpocitológico quanto do histopatológico, permitindo, assim, o êxito na detecção precoce e no tratamento das lesões cervicais.