Introduction of non-invasive prenatal testing as a first-tier aneuploidy screening test: A survey among Dutch midwives about their role as counsellors.

PubMed

Martin, Linda; Gitsels-van der Wal, Janneke T; de Boer, Marjon A; Vanstone, Meredith; Henneman, Lidewij

2018-01-01

In 2014, non-invasive prenatal testing (NIPT) for trisomies 21, 18 and 13 was added to the Dutch prenatal screening program as part of the TRIDENT study. Most (85%) pregnant Dutch women are counselled for prenatal aneuploidy screening by primary care midwives. This will remain when NIPT is implemented as a first-tier screening test. We therefore investigated midwife counsellors': 1) Knowledge about NIPT; 2) Attitudes towards NIPT as first-tier screening test; and 3) Experiences with informing clients about NIPT. Between April-June 2015, an online questionnaire to assess knowledge about NIPT, attitudes towards NIPT, and experiences with NIPT was completed by 436 Dutch primary care midwives. We found that 59% midwives answered ≥7 of 8 knowledge questions correctly. Continuing professional education attendance and more positive attitudes towards prenatal screening for Down syndrome were positively associated with the total knowledge score (β = 0.261; p = 0.007 and β = 0.204; p = 0.015, respectively). The majority (67%) were in favor of replacing First trimester Combined Test with NIPT, although 41% preferred to maintain a nuchal translucency measurement alongside NIPT. We conclude that midwives demonstrated solid knowledge about NIPT that may still be improved in some areas. Dutch midwives overwhelmingly support the integration of NIPT as a first-tier screening test. Copyright © 2017 Elsevier Ltd. All rights reserved.

Validation of the CSI health station 6K blood pressure kiosk.

PubMed

Buxton, Iain L O; Adams, John Q; Gore, Mark; Sullivan, Charles R

2007-01-01

Established in 1978, Computerized Screening Inc. (CSI) is the manufacturer of medical kiosks that combine non-invasive & invasive preventive health-screening technology and services in the U.S. The centerpiece of CSl's health complement is the CSI Health Station, one-stop health information and screening using patented technology. The CSI Health Station (Model 6K) represents the corporation's evolution from its self-administered automated blood pressure monitors (Model 3K). CSI Health Stations also offer touch screen activated heart rate testing, patented, seated weight measurement and fitness evaluations plus other non-invasive features like BMI, resting metabolic rate, spirometry, pulse oximetry and customized health risk assessments or triage guidelines. Invasive testing such as urine analysis, cholesterol, and glucose is also accommodated in an attended setting. In addition, CSI Health Stations feature comprehensive, one-stop availability of health information, with access to a drug encyclopedia and an extensive library of health education videos, and information on local health providers and services. It also is web enabled and supports secure website access direct from the kiosk. The purpose of this study was to determine, using current standards from the Association for the Advancement of Medical Instrumentation (AAMI), whether or not the CSI 6K could accurately and reproducibly measure blood pressure in an ambulatory population in comparison to manual auscultation.

Multimodal noninvasive and invasive imaging of extracranial venous abnormalities indicative of CCSVI: Results of the PREMiSe pilot study

PubMed Central

2013-01-01

Background There is no established noninvasive or invasive diagnostic imaging modality at present that can serve as a ‘gold standard’ or “benchmark” for the detection of the venous anomalies, indicative of chronic cerebrospinal venous insufficiency (CCSVI). We investigated the sensitivity and specificity of 2 invasive vs. 2 noninvasive imaging techniques for the detection of extracranial venous anomalies in the internal jugular veins (IJVs) and azygos vein/vertebral veins (VVs) in patients with multiple sclerosis (MS). Methods The data for this multimodal imaging comparison pilot study was collected in phase 2 of the “Prospective Randomized Endovascular therapy in Multiple Sclerosis” (PREMiSe) study using standardized imaging techniques. Thirty MS subjects were screened initially with Doppler sonography (DS), out of which 10 did not fulfill noninvasive screening procedure requirements on DS that consisted of ≥2 venous hemodynamic extracranial criteria. Accordingly, 20 MS patients with relapsing MS were enrolled into the multimodal diagnostic imaging study. For magnetic resonance venography (MRV), IJVs abnormal findings were considered absent or pinpoint flow, whereas abnormal VVs flow was classified as absent. Abnormalities of the VVs were determined only using non-invasive testing. Catheter venography (CV) was considered abnormal when ≥50% lumen restriction was detected, while intravascular ultrasound (IVUS) was considered abnormal when ≥50% restriction of the lumen or intra-luminal defects or reduced pulsatility was found. Non-invasive and invasive imaging modality comparisons between left, right and total IJVs and between the VVs and azygos vein were performed. Because there is no reliable way of non-invasively assessing the azygos vein, the VVs abnormalities detected by the non-invasive testing were compared to the azygos abnormalities detected by the invasive testing. All image modalities were analyzed in a blinded manner by more than one viewer, upon which consensus was reached. The sensitivity and specificity were calculated using contingency tables denoting the presence or absence of vein-specific abnormality findings between all imaging modalities used individually as the benchmark. Results The sensitivity of CV + IVUS was 68.4% for the right and 90% for the left IJV and 85.7% for the azygos vein/VVs, compared to venous anomalies detected on DS. Compared to the venous anomalies detected on MRV, the sensitivity of CV + IVUS was 71.4% in right and 100% in left IJVs and 100% in the azygos vein/VVs; however, the specificity was 38.5%, 38.9% and 11.8%, respectively. The sensitivity between the two invasive imaging techniques, used as benchmarks, ranged from 72.7% for the right IJV to 90% for the azygos vein but the IVUS showed a higher rate of venous anomalies than the CV. There was excellent correspondence between identifying collateral veins on MRV and CV. Conclusions Noninvasive DS screening for the detection of venous anomalies indicative of CCSVI may be a reliable approach for identifying patients eligible for further multimodal invasive imaging testing of the IJVs. However, the noninvasive screening methods were inadequate to depict the total amount of azygos vein/VVs anomalies identified with invasive testing. This pilot study, with limited sample size, shows that both a non-invasive and invasive multimodal imaging diagnostic approach should be recommended to depict a range of extracranial venous anomalies indicative of CCSVI. However, lack of invasive testing on the study subjects whose results were negative on the DS screening and of healthy controls, limits further generalizibility of our findings. In addition, the findings from the 2 invasive techniques confirmed the existence of severe extracranial venous anomalies that significantly impaired normal blood outflow from the brain in this group of MS patients. PMID:24139135

Clinical, social and ethical issues associated with non-invasive prenatal testing for aneuploidy.

PubMed

Griffin, Blanche; Edwards, Samantha; Chitty, Lyn S; Lewis, Celine

2018-03-01

Non-invasive prenatal testing (NIPT), based on analysis of cell-free foetal DNA, is rapidly becoming a preferred method to screen for chromosomal aneuploidy with the technology now available in over 90 countries. This review provides an up-to-date discussion of the key clinical, social and ethical implications associated with this revolutionary technology. Stakeholders are positive about a test that is highly accurate, safe, can be perfomed early in pregnancy, identifies affected pregnancies that might otherwise have been missed and reduces the need for invasive testing. Nevertheless, professional societies currently recommend it as an advanced screening test due to the low false positive rate (FPR). Despite the practical and psychological benefits, a number of concerns have been raised which warrant attention. These include the potential for routinisation of testing and subsequent impact on informed decision-making, an "easy" blood test inadvertently contributing to women feeling pressured to take the test, fears NIPT will lead to less tolerance and support for those living with Down syndrome and the heightened expectation of having "perfect babies". These issues can be addressed to some extent through clinician education, patient information and establishing national and international consensus in the development of comprehensive and regularly updated guidelines. As the number of conditions we are able to test for non-invasively expands it will be increasingly important to ensure pre-test counselling can be delivered effectively supported by knowledgeable healthcare professionals.

Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance.

PubMed

Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

2015-01-01

A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations.

NON-INVASIVE MONITORING OF FOETAL ANAEMIA IN KELL SENSITIZED PREGNANCY.

PubMed

Memon, Zaibunnisa; Sheikh, Sana Sadiq

2015-01-01

We report a case of Kell sensitized pregnancy with good neonatal outcome. Anti-K antibodies were detected in maternal serum in early pregnancy as a part of routine antibody screening test. The middle cerebral artery doppler monitoring and serial titers were carried out to screen for foetal anaemia. Despite of rising antibody titers, serial middle cerebral artery doppler was normal and did not showed foetal anaemia. The pregnancy was carried out till term and patient delivered at 37 weeks of pregnancy with no evidence of foetal anaemia. This case underlines the need of general screening on rare antibodies in all pregnant women and that non-invasive monitoring of foetal anaemia can be done with anti-k titers and middle cerebral artery Doppler.

The effect of presenting information about invasive follow-up testing on individuals' noninvasive colorectal cancer screening participation decision: results from a discrete choice experiment.

PubMed

Benning, Tim M; Dellaert, Benedict G C; Severens, Johan L; Dirksen, Carmen D

2014-07-01

Many national colorectal cancer screening campaigns have a similar structure. First, individuals are invited to take a noninvasive screening test, and, second, in the case of a positive screening test result, they are advised to undergo a more invasive follow-up test. The objective of this study was to investigate how much individuals' participation decision in noninvasive screening is affected by the presence or absence of detailed information about invasive follow-up testing and how this effect varies over screening tests. We used a labeled discrete choice experiment of three noninvasive colorectal cancer screening types with two versions that did or did not present respondents with detailed information about the possible invasive follow-up test (i.e., colonoscopy) and its procedure. We used data from 631 Dutch respondents aged 55 to 75 years. Each respondent received only one of the two versions (N = 310 for the invasive follow-up test information specification version, and N = 321 for the no-information specification version). Mixed logit model results show that detailed information about the invasive follow-up test negatively affects screening participation decisions. This effect can be explained mainly by a decrease in choice shares for the most preferred screening test (a combined stool and blood sample test). Choice share simulations based on the discrete choice experiment indicated that presenting invasive follow-up test information decreases screening participation by 4.79%. Detailed information about the invasive follow-up test has a negative effect on individuals' screening participation decisions in noninvasive colorectal cancer screening campaigns. This result poses new challenges for policymakers who aim not only to increase uptake but also to provide full disclosure to potential screening participants. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

NEUROBEHAVIORAL TESTING IN ANIMALS AND THE APPLICATION TO RISK ASSESSMENT.

EPA Science Inventory

Neurobehavioral evaluations are emerging as a key component in neurotoxicity testing. The tests most often used for screening are the functional observational battery (FOB) and motor activity. The FOB is a series of non-invasive observational and manipulative measures which ass...

Prevention and control of Hb Bart's disease in Guangxi Zhuang Autonomous Region, China.

PubMed

He, Sheng; Zhang, Qiang; Li, Dongming; Chen, Shaoke; Tang, Yanqing; Chen, Qiuli; Zheng, Chenguang

2014-07-01

To demonstrate the performance of Hb Bart's Disease prevention in Guangxi Zhuang Autonomous Region, China. A prenatal control program for Hb Bart's disease was conducted from January 2006 to December 2012. A total of 17,555 pregnant women were screened for α-thalassemia in our prenatal screening program. Pregnancy at-risk for Hb Bart's disease was offered the choice of direct invasive testing or the non-invasive approach with serial ultrasonography. A total of 1425 at-risk couples attended the prenatal diagnosis. Three hundred ninety couples were screened at our own hospital, and the remaining 1035 couples were referred from other hospitals. Two hundred and three pregnant women chose non-invasive approach, and 1122 chose invasive testing. A total of 365 fetuses were diagnosed with Hb Bart's disease. All cases were finally confirmed by fetal DNA analysis. Eighty-two cases (22.4%) were diagnosed by chorionic villous sampling and 194 (53.2%) by amniocentesis samples. The other 89 (24.4%) cases were performed by cordocentesis. All of the affected pregnancies were terminated. Implementation of a prevention and control program accompanying with a referral system for prenatal diagnosis is technically feasible in Guangxi Zhuang Autonomous Region, China. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

CT colonography: accuracy, acceptance, safety and position in organised population screening.

PubMed

de Haan, Margriet C; Pickhardt, Perry J; Stoker, Jaap

2015-02-01

Colorectal cancer (CRC) is the second most common cancer and second most common cause of cancer-related deaths in Europe. The introduction of CRC screening programmes using stool tests and flexible sigmoidoscopy, have been shown to reduce CRC-related mortality substantially. In several European countries, population-based CRC screening programmes are ongoing or being rolled out. Stool tests like faecal occult blood testing are non-invasive and simple to perform, but are primarily designed to detect early invasive cancer. More invasive tests like colonoscopy and CT colonography (CTC) aim at accurately detecting both CRC and cancer precursors, thus providing for cancer prevention. This review focuses on the accuracy, acceptance and safety of CTC as a CRC screening technique and on the current position of CTC in organised population screening. Based on the detection characteristics and acceptability of CTC screening, it might be a viable screening test. The potential disadvantage of radiation exposure is probably overemphasised, especially with newer technology. At this time-point, it is not entirely clear whether the detection of extracolonic findings at CTC is of net benefit and is cost effective, but with responsible handling, this may be the case. Future efforts will seek to further improve the technique, refine appropriate diagnostic algorithms and study cost-effectiveness. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Initial experience with non-invasive prenatal testing of cell-free DNA for major chromosomal anomalies in a clinical setting.

PubMed

Comas, Carmina; Echevarria, Mónica; Rodríguez, M Angeles; Prats, Pilar; Rodríguez, Ignacio; Serra, Bernat

2015-07-01

To evaluate non-invasive prenatal testing (NIPT) of cell-free DNA (cfDNA) as a screening method for major chromosomal anomalies (CA) in a clinical setting. From January to December 2013, Panorama™ test or Harmony™ prenatal test were offered as advanced NIPT, in addition to first-trimester combined screening in singleton pregnancies. The cohort included 333 pregnant women with a mean maternal age (MA) of 37 years who underwent testing at a mean gestational age of 14.6 weeks. Eighty-four percent were low-risk pregnancies. Results were provided in 97.3% of patients at a mean reporting time of 12.9 calendar days. Repeat sampling was performed in six cases and results were obtained in five of them. No results were provided in four cases. Four cases of Down syndrome were detected and there was one discordant result of Turner syndrome. We found no statistical differences between commercial tests except in reporting time, fetal fraction and MA. The cfDNA fraction was statistically associated with test type, maternal weight, BMI and log βhCG levels. NIPT has the potential to be a highly effective screening method for major CA in a clinical setting.

Early Detection of Lung Cancer Using Nano-Nose - A Review

PubMed Central

Fernandes, M. P.; Venkatesh, S; Sudarshan, B. G

2015-01-01

Lung cancer is one of the malignancies causing deaths worldwide. The yet to be developed non-invasive diagnostic techniques, are a challenge for early detection of cancer before it progresses to its later stages. The currently available diagnostic methods are expensive or invasive, and are not fit for general screening purposes. Early identification not only helps in detecting primary cancer, but also in treating its secondaries; which creates a need for easily applicable tests to screen individuals at risk. A detailed review of the various screening methods, including the latest trend of breath analysis using gold nanoparticles, to identify cancer at its early stage, are studied here. The VOC based breath biomarkers are used to analyze the exhaled breath of the patients. These biomarkers are utilized by Chemiresistors coated with gold nanoparticles, which are found to be the most suited technique for early detection of lung cancer. This technique is highly accurate and is relatively easy to operate and was tested on smokers and non-smokers. This review also gives as an outline of the fabrication and working of the device Na-Nose. The Chemiresistors coated with Gold nanoparticles, show a great potential in being an non-invasive and cost-effective diagnostic technique for early detection of lung cancer. PMID:26628933

Early Detection of Lung Cancer Using Nano-Nose - A Review.

PubMed

Fernandes, M P; Venkatesh, S; Sudarshan, B G

2015-01-01

Lung cancer is one of the malignancies causing deaths worldwide. The yet to be developed non-invasive diagnostic techniques, are a challenge for early detection of cancer before it progresses to its later stages. The currently available diagnostic methods are expensive or invasive, and are not fit for general screening purposes. Early identification not only helps in detecting primary cancer, but also in treating its secondaries; which creates a need for easily applicable tests to screen individuals at risk. A detailed review of the various screening methods, including the latest trend of breath analysis using gold nanoparticles, to identify cancer at its early stage, are studied here. The VOC based breath biomarkers are used to analyze the exhaled breath of the patients. These biomarkers are utilized by Chemiresistors coated with gold nanoparticles, which are found to be the most suited technique for early detection of lung cancer. This technique is highly accurate and is relatively easy to operate and was tested on smokers and non-smokers. This review also gives as an outline of the fabrication and working of the device Na-Nose. The Chemiresistors coated with Gold nanoparticles, show a great potential in being an non-invasive and cost-effective diagnostic technique for early detection of lung cancer.

Summary of the evidence of breast cancer service screening outcomes in Europe and first estimate of the benefit and harm balance sheet.

PubMed

Paci, Eugenio

2012-01-01

To construct a European 'balance sheet' of key outcomes of population-based mammographic breast cancer screening, to inform policy-makers, stakeholders and invited women. From the studies reviewed, the primary benefit of screening, breast cancer mortality reduction, was compared with the main harms, over-diagnosis and false-positive screening results (FPRs). Pooled estimates of breast cancer mortality reduction among invited women were 25% in incidence-based mortality studies and 31% in case-control studies (38% and 48% among women actually screened). Estimates of over-diagnosis ranged from 1% to 10% of the expected incidence in the absence of screening. The combined estimate of over-diagnosis for screened women, from European studies correctly adjusted for lead time and underlying trend, was 6.5%. For women undergoing 10 biennial screening tests, the estimated cumulative risk of a FPR followed by non-invasive assessment was 17%, and 3% having an invasive assessment. For every 1000 women screened biennially from age 50-51 until age 68-69 and followed up to age 79, an estimated seven to nine lives are saved, four cases are over-diagnosed, 170 women have at least one recall followed by non-invasive assessment with a negative result and 30 women have at least one recall followed by invasive procedures yielding a negative result. The chance of saving a woman's life by population-based mammographic screening of appropriate quality is greater than that of over-diagnosis. Service screening in Europe achieves a mortality benefit at least as great as the randomized controlled trials. These outcomes should be communicated to women offered service screening in Europe.

Knowledge and future preference of Chinese women in a major public hospital in Hong Kong after undergoing non-invasive prenatal testing for positive aneuploidy screening: a questionnaire survey.

PubMed

Kou, Kam On; Poon, Chung Fan; Tse, Wai Ching; Mak, Shui Lam; Leung, Kwok Yin

2015-09-02

Despite the non-invasive nature of non-invasive prenatal testing (NIPT), there is still a need for a separate informed consent process before testing. The objectives of this study are to assess (a) knowledge and preferences of Chinese women in a major public hospital in Hong Kong who underwent NIPT, and (b) whether their knowledge and preferences differ depending on womens' characteristics and sources of information. Setting: Prenatal diagnosis and counselling clinic. Between February 2012 and September 2013, a questionnaire survey was distributed to all women who underwent NIPT after positive aneuploidy screening. As a pilot study, ten knowledge questions were designed based on the rapid response statement on Prenatal Detection of Down Syndrome using Massively Parallel Sequencing from the International Society for Prenatal Diagnosis in 2011. The source of women's knowledge and their preferences were also evaluated. While conventional screening was publicly funded, NIPT was not. Differences between subgroups were compared using chi square tests and logistic regression analysis. Of 152 women who underwent NIPT, 135 (88.8%) completed their questionnaires. More than 90% of women recognised the possibility of false positive and false negative results. Slightly more than 70% of women knew the inferior sensitivity of NIPT compared to an invasive test, and the possibility of an uninformative test result, but were not aware of the complicated aspects of NIPT. Pregnant women with an advanced level of education or those who underwent NIPT before 15 weeks provided answers that was more accurate by around 10-20% in two to three knowledge questions than those without. These associations were confirmed by multivariate logistic regression analysis. The women received information on NIPT largely from their private doctors (47.4%) and web (41.5%). In their future pregnancies, more women would opt for NIPT (a self-financed item) after positive screening ('free' in a public hospital) (57.8%) than as a primary screening (30.4%). It is feasible to use a questionnaire based on the ISPD statement on NIPT to assess women's knowledge of the test. The Chinese women who underwent NIPT recognised the limitations, but did not understand the complicated aspects. More information should be provided by health care professionals in order to facilitate an informed choice by patients. More women preferred NIPT as a contingent test than as a primary screening probably because of its high cost.

Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance

PubMed Central

Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

2015-01-01

A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations. PMID:26339413

Evaluation of recently validated non-invasive formula using basic lung functions as new screening tool for pulmonary hypertension in idiopathic pulmonary fibrosis patients

PubMed Central

Ghanem, Maha K.; Makhlouf, Hoda A.; Agmy, Gamal R.; Imam, Hisham M. K.; Fouad, Doaa A.

2009-01-01

BACKGROUND: A prediction formula for mean pulmonary artery pressure (MPAP) using standard lung function measurement has been recently validated to screen for pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) patients. OBJECTIVE: To test the usefulness of this formula as a new non invasive screening tool for PH in IPF patients. Also, to study its correlation with patients' clinical data, pulmonary function tests, arterial blood gases (ABGs) and other commonly used screening methods for PH including electrocardiogram (ECG), chest X ray (CXR), trans-thoracic echocardiography (TTE) and computerized tomography pulmonary angiography (CTPA). MATERIALS AND METHODS: Cross-sectional study of 37 IPF patients from tertiary hospital. The accuracy of MPAP estimation was assessed by examining the correlation between the predicted MPAP using the formula and PH diagnosed by other screening tools and patients' clinical signs of PH. RESULTS: There was no statistically significant difference in the prediction of PH using cut off point of 21 or 25 mm Hg (P = 0.24). The formula-predicted MPAP greater than 25 mm Hg strongly correlated in the expected direction with O2 saturation (r = −0.95, P < 0.000), partial arterial O2 tension (r = −0.71, P < 0.000), right ventricular systolic pressure measured by TTE (r = 0.6, P < 0.000) and hilar width on CXR (r = 0.31, P = 0.03). Chest symptoms, ECG and CTPA signs of PH poorly correlated with the same formula (P > 0.05). CONCLUSIONS: The prediction formula for MPAP using standard lung function measurements is a simple non invasive tool that can be used as TTE to screen for PH in IPF patients and select those who need right heart catheterization. PMID:19881164

Non-invasive carboxyhemoglobin monitoring: screening emergency medical services patients for carbon monoxide exposure.

PubMed

Nilson, Douglas; Partridge, Robert; Suner, Selim; Jay, Gregory

2010-01-01

Carbon monoxide (CO) toxicity is a significant health problem. The use of non-invasive pulse CO-oximetry screening in the emergency department has demonstrated that the rapid screening of numerous individuals for CO toxicity is simple and capable of identifying occult cases of CO toxicity. The objective of this study was to extend the use of this handheld device to the prehospital arena, assess carboxyhemoglobin (SpCO) levels in emergency medical services (EMS) patients, and correlate these levels with clinical and demographic data. This was a retrospective, observational, chart review of adult patients transported to hospital emergency departments by urban fire department EMS ambulances during a six-week period. Each ambulance used a non-invasive pulse CO-oximeter (Rad-57, Masimo Inc.) to record patients' COHb concentrations (SpCO) along with the standard EMS assessment data. Spearman's Rank Correlation tests and Student's t-tests were used to analyze the data and calculate relationships between SpCO and other variables (age, gender, respiratory rate, heart rate, mean arterial pressure, and oxygen saturation measured by pulse oximetry). A total of 36.4% of the patients transported during the study had SpCO documented. Of the 1,017 adults included in this group, 11 (1.1%) had an SpCO >15%. There was no correlation between SpCO and heart rate, ventilatory rate, mean arterial pressure, and oxygen saturation. Screening for CO toxicity in the EMS setting is possible, and may aid in the early detection and treatment of CO-poisoned patients.

Non-Invasive markers for hepatic fibrosis

PubMed Central

2011-01-01

With great advancements in the therapeutic modalities used for the treatment of chronic liver diseases, the accurate assessment of liver fibrosis is a vital need for successful individualized management of disease activity in patients. The lack of accurate, reproducible and easily applied methods for fibrosis assessment has been the major limitation in both the clinical management and for research in liver diseases. However, the problem of the development of biomarkers capable of non-invasive staging of fibrosis in the liver is difficult due to the fact that the process of fibrogenesis is a component of the normal healing response to injury, invasion by pathogens, and many other etiologic factors. Current non-invasive methods range from serum biomarker assays to advanced imaging techniques such as transient elastography and magnetic resonance imaging (MRI). Among non-invasive methods that gain strongest clinical foothold are FibroScan elastometry and serum-based APRI and FibroTest. There are many other tests that are not yet widely validated, but are none the less, promising. The rate of adoption of non-invasive diagnostic tests for liver fibrosis differs from country to country, but remains limited. At the present time, use of non-invasive procedures could be recommended as pre-screening that may allow physicians to narrow down the patients' population before definitive testing of liver fibrosis by biopsy of the liver. This review provides a systematic overview of these techniques, as well as both direct and indirect biomarkers based approaches used to stage fibrosis and covers recent developments in this rapidly advancing area. PMID:21849046

Antenatal screening for aneuploidy--surveying the current situation and planning for non-invasive prenatal diagnosis in New Zealand.

PubMed

Eastwood, Ashley; Webster, Dianne; Taylor, Juliet; Mckay, Richard; McEwen, Alison; Sullivan, Jan; Pope-Couston, Rachel; Stone, Peter

2016-01-29

To gauge clinical opinion about the current system and possible changes as well as providing a forum for education about Non-Invasive Prenatal Testing (NIPT). A series of workshops for doctors and midwives, supported by the National Screening Unit of the Ministry of Health and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, were held in the main centres of New Zealand. Following a brief education session, a structured evaluation of current screening and future possibilities was undertaken by questionnaire. One hundred and eight maternity carers participated in 5 workshops. Over 40% identified barriers to current screening. More than 60% would support NIPT in the first trimester. The majority of carers provided their own counselling support for women. The survey has shown general enthusiasm for the introduction of publically funded NIPT into prenatal screening in New Zealand. Barriers to utilisation of the current system have been identified and enhancements to screening performance with guidelines around conditions to be screened for would be supported.

Non-invasive coronary angiography for patients with acute atypical chest pain discharged after negative screening including maximal negative treadmill stress test. A prospective study.

PubMed

Bonello, L; Armero, S; Jacquier, A; Com, O; Sarran, A; Sbragia, P; Panuel, M; Arques, S; Paganelli, F

2009-05-01

Among patients admitted in the emergency department for acute atypical chest pain those with an acute coronary syndrome (ACS) who are mistakenly discharged home have high mortality. A recent retrospective study has demonstrated that multislice computed tomography (MSCT) coronary angiography could improve triage of these patients. We aimed to prospectively confirm these data on patients with a negative screening including maximal treadmill stress. 30 patients discharged from the emergency department after negative screening for an ACS were included. All patients underwent MSCT angiography of the coronary artery. Patients with coronary atheroma on MSCT had an invasive coronary angiography to confirm these findings. Seven patients (23%) had obstructive coronary artery disease on MSCT. Invasive coronary angiography (ICA) confirmed the diagnosis in all patients. In patients with no previously known coronary artery disease admitted to the emergency department with atypical acute chest pain and discharged after negative screening, including maximal treadmill stress test, MSCT coronary angiography is useful for the diagnosis of obstructive coronary artery disease.

NEUROBEHAVIORAL DATA INTERPRETATION IN NEUROTOXICITY STUDIES: FOB, MOTOR ACTIVITY AND FUNCTION

EPA Science Inventory

Neurobehavioral evaluations are emerging as a key component in neurotoxicity testing. The tests most often used for screening are the functional observational battery (FOB) and motor activity. The FOB is a series of non-invasive observational and manipulative measures which ass...

Model-based analysis of costs and outcomes of non-invasive prenatal testing for Down's syndrome using cell free fetal DNA in the UK National Health Service.

PubMed

Morris, Stephen; Karlsen, Saffron; Chung, Nancy; Hill, Melissa; Chitty, Lyn S

2014-01-01

Non-invasive prenatal testing (NIPT) for Down's syndrome (DS) using cell free fetal DNA in maternal blood has the potential to dramatically alter the way prenatal screening and diagnosis is delivered. Before NIPT can be implemented into routine practice, information is required on its costs and benefits. We investigated the costs and outcomes of NIPT for DS as contingent testing and as first-line testing compared with the current DS screening programme in the UK National Health Service. We used a pre-existing model to evaluate the costs and outcomes associated with NIPT compared with the current DS screening programme. The analysis was based on a hypothetical screening population of 10,000 pregnant women. Model inputs were taken from published sources. The main outcome measures were number of DS cases detected, number of procedure-related miscarriages and total cost. At a screening risk cut-off of 1∶150 NIPT as contingent testing detects slightly fewer DS cases, has fewer procedure-related miscarriages, and costs the same as current DS screening (around UK£280,000) at a cost of £500 per NIPT. As first-line testing NIPT detects more DS cases, has fewer procedure-related miscarriages, and is more expensive than current screening at a cost of £50 per NIPT. When NIPT uptake increases, NIPT detects more DS cases with a small increase in procedure-related miscarriages and costs. NIPT is currently available in the private sector in the UK at a price of £400-£900. If the NHS cost was at the lower end of this range then at a screening risk cut-off of 1∶150 NIPT as contingent testing would be cost neutral or cost saving compared with current DS screening. As first-line testing NIPT is likely to produce more favourable outcomes but at greater cost. Further research is needed to evaluate NIPT under real world conditions.

Potential of soluble CD26 as a serum marker for colorectal cancer detection

PubMed Central

Cordero, Oscar J; Imbernon, Monica; Chiara, Loretta De; Martinez-Zorzano, Vicenta S; Ayude, Daniel; de la Cadena, Maria Paez; Rodriguez-Berrocal, F Javier

2011-01-01

Colorectal cancer is characterized by a low survival rate even though the basis for colon cancer development, which involves the evolution of adenomas to carcinoma, is known. Moreover, the mortality rates continue to rise in economically transitioning countries although there is the opportunity to intervene in the natural history of the adenoma–cancer sequence through risk factors, screening, and treatment. Screening in particular accounted for most of the decline in colorectal cancer mortality achieved in the USA during the period 1975-2000. Patients show a better prognosis when the neoplasm is diagnosed early. Among the variety of screening strategies, the methods range from invasive and costly procedures such as colonoscopy to more low-cost and non-invasive tests such as the fecal occult blood test (guaiac and immunochemical). As a non-invasive biological serum marker would be of great benefit because of the performance of the test, several biomarkers, including cytologic assays, DNA and mRNA, and soluble proteins, have been studied. We found that the soluble CD26 (sCD26) concentration is diminished in serum of colorectal cancer patients compared to healthy donors, suggesting the potential utility of a sCD26 immunochemical detection test for early diagnosis. sCD26 originates from plasma membrane CD26 lacking its transmembrane and cytoplasmic domains. Some 90%–95% of sCD26 has been associated with serum dipeptidyl peptidase IV (DPP-IV) activity. DPP-IV, assigned to the CD26 cluster, is a pleiotropic enzyme expressed mainly on epithelial cells and lymphocytes. Our studies intended to validate this test for population screening to detect colorectal cancer and advanced adenomas are reviewed here. PMID:21773075

Uptake of non-invasive prenatal testing in Chinese women: money matters.

PubMed

Han, J; Zhen, L; Pan, M; Yang, X; Ou, Y-M; Liao, C; Li, D-Z

2015-12-01

To determine the influence of free invasive prenatal testing on the uptake of non-invasive prenatal testing (NIPT). Over a 2-year period at a Chinese tertiary prenatal diagnostic unit, women at risk of fetal trisomy were given the option of NIPT or invasive prenatal testing. Invasive prenatal testing was offered free of charge to women with a local Hukou (household registration); however, women without a local Hukou were charged for invasive prenatal testing. Both women with and without a local Hukou were charged for NIPT. During the first year, 2647 women with a positive trisomy 21 screening test were referred (474 women with a local Hukou and 2173 women without a local Hukou). Only 1.6% of the women with a local Hukou underwent NIPT, while this proportion was 20.6% in the women without a local Hukou. During the second year, the price of NIPT was reduced. The total number of women referred was 3047 (502 women with a local Hukou and 2545 women without a local Hukou). The uptake of NIPT in women without a local Hukou doubled, but the uptake of NIPT remained stable in women with a local Hukou. The financial impact on the uptake of NIPT should not be underestimated. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma.

PubMed

Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

2014-04-14

Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma.

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma

PubMed Central

Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

2014-01-01

Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma. PMID:24744577

A new discussion of the cutaneous vascular reactivity in sensitive skin: A sub-group of SS?

PubMed

Chen, S Y; Yin, J; Wang, X M; Liu, Y Q; Gao, Y R; Liu, X P

2018-02-02

Sensitive skin (SS) seems not to be a one-dimensional condition and many scholars concentrate on skin barrier disruption or sensorineural change, but few focus on its increased vascular reactivity. This study explored the possibility of using the different selection methods and measurement methods to verify a high vascular reactivity in SS without an impaired cutaneous barrier function. Sixty "self-perceived sensitive skin" volunteers were enlisted and each one completed three kinds of screening tests: assess cutaneous sensory using questionnaire survey and Lactic Acid Sting Test (LAST); assess barrier function using Sodium lauryl sulphate (SLS) skin irritation test and assess cutaneous vascular reactivity using 98% DMSO test and non-invasive measurement. Volunteers were divided into different groups based on response to SLS. The DMSO clinical score and the biophysical parameters obtained by non-invasive measurement were subsequently analysed. (1) The positive correlations could be seen between sum LAST score and sum DMSO score regardless of the observation time; (2) The biological parameters (CBF、a*values and L* values) are all keeping with DMSO score; (3) If the participants were divided into SLS reactors and non-reactors, a composition ratio of DMSO score was significant difference in these two groups and in SLS non-reactors, there were still seven participants showed high reaction to DMSO. There is a sub-group of SS for characteristics of a high vascular reactivity without an impaired cutaneous barrier function. The DMSO test and novel non-invasive measurements which are conducive to assess cutaneous vascular reactivity, combined with SLS skin irritation test could help us to screen this kind of SS. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Notes on testing non-inferiority under the partial verification design with a confirmatory procedure limited to screen positives.

PubMed

Lui, Kung-Jong

2012-05-01

When a new test with fewer invasions or less expenses to administer than the traditional test is developed, we may be interested in testing whether the former is non-inferior to the latter with respect to test accuracy. We define non-inferiority via both the odds ratio (OR) of correctly identifying a case and the OR of correctly identifying a non-case between two tests under comparison. We focus our discussion on testing the non-inferiority of a new screening test to a traditional screening test when a confirmatory procedure is performed only on patients with screen positives. On the basis of well-established methods for paired-sample data, we derive an asymptotic test procedure and an exact test procedure with respect to the two ORs defined here. Using Monte Carlo simulation, we evaluate the performance of these test procedures in a variety of situations. We note that the test procedures proposed here can also be applicable if we are interested in testing non-inferiority with respect to the ratio of sensitivities and the ratio of specificities. We discuss interval estimation of these ORs and sample size calculation based on the asymptotic test procedure considered here. We use the data taken from a study of the prostate-specific-antigen (PSA) test and the digital rectal examination (DRE) test to illustrate the practical use of these test procedures, interval estimators and sample size calculation formula. Copyright © 2012 Elsevier Inc. All rights reserved.

[Diagnostic work-up of pulmonary nodules : Management of pulmonary nodules detected with low‑dose CT screening].

PubMed

Wormanns, D

2016-09-01

Pulmonary nodules are the most frequent pathological finding in low-dose computed tomography (CT) scanning for early detection of lung cancer. Early stages of lung cancer are often manifested as pulmonary nodules; however, the very commonly occurring small nodules are predominantly benign. These benign nodules are responsible for the high percentage of false positive test results in screening studies. Appropriate diagnostic algorithms are necessary to reduce false positive screening results and to improve the specificity of lung cancer screening. Such algorithms are based on some of the basic principles comprehensively described in this article. Firstly, the diameter of nodules allows a differentiation between large (>8 mm) probably malignant and small (<8 mm) probably benign nodules. Secondly, some morphological features of pulmonary nodules in CT can prove their benign nature. Thirdly, growth of small nodules is the best non-invasive predictor of malignancy and is utilized as a trigger for further diagnostic work-up. Non-invasive testing using positron emission tomography (PET) and contrast enhancement as well as invasive diagnostic tests (e.g. various procedures for cytological and histological diagnostics) are briefly described in this article. Different nodule morphology using CT (e.g. solid and semisolid nodules) is associated with different biological behavior and different algorithms for follow-up are required. Currently, no obligatory algorithm is available in German-speaking countries for the management of pulmonary nodules, which reflects the current state of knowledge. The main features of some international and American recommendations are briefly presented in this article from which conclusions for the daily clinical use are derived.

Potential of mid-infrared spectroscopy as a non-invasive diagnostic test in urine for endometrial or ovarian cancer.

PubMed

Paraskevaidi, Maria; Morais, Camilo L M; Lima, Kássio M G; Ashton, Katherine M; Stringfellow, Helen F; Martin-Hirsch, Pierre L; Martin, Francis L

2018-06-07

The current lack of an accurate, cost-effective and non-invasive test that would allow for screening and diagnosis of gynaecological carcinomas, such as endometrial and ovarian cancer, signals the necessity for alternative approaches. The potential of spectroscopic techniques in disease investigation and diagnosis has been previously demonstrated. Here, we used attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy to analyse urine samples from women with endometrial (n = 10) and ovarian cancer (n = 10), as well as from healthy individuals (n = 10). After applying multivariate analysis and classification algorithms, biomarkers of disease were pointed out and high levels of accuracy were achieved for both endometrial (95% sensitivity, 100% specificity; accuracy: 95%) and ovarian cancer (100% sensitivity, 96.3% specificity; accuracy 100%). The efficacy of this approach, in combination with the non-invasive method for urine collection, suggest a potential diagnostic tool for endometrial and ovarian cancers.

Fetal sex determination in twin pregnancies using cell free fetal DNA analysis.

PubMed

Milan, Miguel; Mateu, Emilia; Blesa, David; Clemente-Ciscar, Monica; Simon, Carlos

2018-04-23

We sought to develop an accurate sex classification method in twin pregnancies using data obtained from a standard commercial non-invasive prenatal test. A total of 706 twin pregnancies were included in this retrospective analytical data study. Normalized chromosome values for chromosomes X and Y were used and adapted into a sex-score to predict fetal sex in each fetus, and results were compared with the clinical outcome at birth. Outcome information at birth for sex chromosomes was available for 232 twin pregnancies. From these, a total of 173 twin pregnancies with a Y chromosome identified in non-invasive pregnancy testing were used for the development of a predictive model. Global accuracy for sex classification in the testing set with 51 samples was 0.98 (95% confidence interval [0.90,0.99]), with a specificity and sensitivity of 1 (95% confidence interval [0.82,1.00]) and 0.97 (95% confidence interval [0.84,0.99]), respectively. While non-invasive prenatal testing is a screening method and confirmatory results must be obtained by ultrasound or genetic diagnosis, the sex-score determination presented herein offers an accurate and useful approach to characterizing fetus sex in twin pregnancies in a non-invasive manner early on in pregnancy. © 2018 John Wiley & Sons, Ltd.

[Meta-analyses on measurement precision of non-invasive hemodynamic monitoring technologies in adults].

PubMed

Pestel, G; Fukui, K; Higashi, M; Schmidtmann, I; Werner, C

2018-06-01

An ideal non-invasive monitoring system should provide accurate and reproducible measurements of clinically relevant variables that enables clinicians to guide therapy accordingly. The monitor should be rapid, easy to use, readily available at the bedside, operator-independent, cost-effective and should have a minimal risk and side effect profile for patients. An example is the introduction of pulse oximetry, which has become established for non-invasive monitoring of oxygenation worldwide. A corresponding non-invasive monitoring of hemodynamics and perfusion could optimize the anesthesiological treatment to the needs in individual cases. In recent years several non-invasive technologies to monitor hemodynamics in the perioperative setting have been introduced: suprasternal Doppler ultrasound, modified windkessel function, pulse wave transit time, radial artery tonometry, thoracic bioimpedance, endotracheal bioimpedance, bioreactance, and partial CO 2 rebreathing have been tested for monitoring cardiac output or stroke volume. The photoelectric finger blood volume clamp technique and respiratory variation of the plethysmography curve have been assessed for monitoring fluid responsiveness. In this manuscript meta-analyses of non-invasive monitoring technologies were performed when non-invasive monitoring technology and reference technology were comparable. The primary evaluation criterion for all studies screened was a Bland-Altman analysis. Experimental and pediatric studies were excluded, as were all studies without a non-invasive monitoring technique or studies without evaluation of cardiac output/stroke volume or fluid responsiveness. Most studies found an acceptable bias with wide limits of agreement. Thus, most non-invasive hemodynamic monitoring technologies cannot be considered to be equivalent to the respective reference method. Studies testing the impact of non-invasive hemodynamic monitoring technologies as a trend evaluation on outcome, as well as studies evaluating alternatives to the finger for capturing the raw signals for hemodynamic assessment, and, finally, studies evaluating technologies based on a flow time measurement are current topics of clinical research.

What Do Parents of Children with Down Syndrome Think about Non-Invasive Prenatal Testing (NIPT)?

PubMed

van Schendel, Rachèl V; Kater-Kuipers, Adriana; van Vliet-Lachotzki, Elsbeth H; Dondorp, Wybo J; Cornel, Martina C; Henneman, Lidewij

2017-06-01

This study explores the attitudes of parents of children with Down syndrome towards non-invasive prenatal testing (NIPT) and widening the scope of prenatal screening. Three focus groups (n = 16) and eleven individual interviews with Dutch parents (and two relatives) of children with Down syndrome were conducted. Safety, accuracy and earlier testing were seen as the advantages of NIPT. Some participants were critical about the practice of screening for Down syndrome, but acknowledged that NIPT enables people to know whether the fetus is affected and to prepare without risking miscarriage. Many feared uncritical use of NIPT and more abortions for Down syndrome. Concerns included the consequences for the acceptance of and facilities for children with Down syndrome, resulting in more people deciding to screen. Participants stressed the importance of good counseling and balanced, accurate information about Down syndrome. Testing for more disorders might divert the focus away from Down syndrome, but participants worried about "where to draw the line". They also feared a loss of diversity in society. Findings show that, while parents acknowledge that NIPT offers a better and safer option to know whether the fetus is affected, they also have concerns about NIPT's impact on the acceptance and care of children with Down syndrome.

Attitudes of women of advanced maternal age undergoing invasive prenatal diagnosis and the impact of genetic counselling

PubMed Central

Godino, Lea; Pompilii, Eva; D'Anna, Federica; Morselli-Labate, Antonio M; Nardi, Elena; Seri, Marco; Rizzo, Nicola; Pilu, Gianluigi; Turchetti, Daniela

2016-01-01

Despite the increasing availability and effectiveness of non-invasive screening for foetal aneuploidies, most women of advanced maternal age (AMA) still opt for invasive tests. A retrospective cross-sectional survey was performed on women of AMA undergoing prenatal invasive procedures, in order to explore their motivations and the outcome of preliminary genetic counselling according to the approach (individual or group) adopted. Of 687 eligible women, 221 (32.2%) participated: 117 had received individual counselling, while 104 had attended group sessions. The two groups did not differ by socio-demographic features. The commonest reported reason to undergo invasive tests was AMA itself (67.4%), while only 10.4% of women mentioned the opportunity of making informed choices. The majority perceived as clear and helpful the information received at counselling, and only 12.7% had doubts left that, however, often concerned non-pertinent issues. The impact of counselling on risk perception and decisions was limited: a minority stated their perceived risk of foetal abnormalities had either increased (6.8%) or reduced (3.6%), and only one eventually declined invasive test. The 52.6% of women expressed a preference toward individual counselling, which also had a stronger impact on perceived risk reduction (P=0.003). Nevertheless, group counselling had a more favourable impact on both clarity of understanding and helpfulness (P=0.0497 and P=0.035, respectively). The idea that AMA represents an absolute indication for invasive tests appears deeply rooted; promotion of non-invasive techniques may require extensive educational efforts targeted to both the general population and health professionals. PMID:26014424

Non-invasive prenatal screening for trisomy 21: what women want and are willing to pay.

PubMed

Verweij, E J Joanne; Oepkes, Dick; de Vries, Marieke; van den Akker, M E Elske; van den Akker, Eline S; de Boer, Marjon A

2013-12-01

To investigate the attitude among pregnant women regarding non-invasive prenatal testing (NIPT) for detecting trisomy 21 (T21) and to quantify their willingness to pay for NIPT. A questionnaire was administered to pregnant women who received counselling for first-trimester screening (FTS) in two hospitals and nine midwife practices in the Netherlands. A total of 147 women completed the questionnaire, yielding a response rate of 43%. If NIPT for detecting T21 were available, 81% stated they would choose to have this test, and 57% of women who elected not to undergo FTS in their current pregnancy would perform NIPT if available. Willingness to pay for NIPT was correlated with age and income, but not education level. The price that participants were willing to pay for NIPT was similar to the current price for FTS. The pregnant women in our study had a positive attitude regarding NIPT for T21, and more than half of the women who rejected prenatal screening would receive NIPT if available. Due to the elimination of iatrogenic miscarriage, caregivers should be aware that informed decision-making can change with respect to prenatal screening with the introduction of NIPT. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Plasma Septin9 versus fecal immunochemical testing for colorectal cancer screening: a prospective multicenter study.

PubMed

Johnson, David A; Barclay, Robert L; Mergener, Klaus; Weiss, Gunter; König, Thomas; Beck, Jürgen; Potter, Nicholas T

2014-01-01

Screening improves outcomes related to colorectal cancer (CRC); however, suboptimal participation for available screening tests limits the full benefits of screening. Non-invasive screening using a blood based assay may potentially help reach the unscreened population. To compare the performance of a new Septin9 DNA methylation based blood test with a fecal immunochemical test (FIT) for CRC screening. In this trial, fecal and blood samples were obtained from enrolled patients. To compare test sensitivity for CRC, patients with screening identified colorectal cancer (n = 102) were enrolled and provided samples prior to surgery. To compare test specificity patients were enrolled prospectively (n = 199) and provided samples prior to bowel preparation for screening colonoscopy. Plasma and fecal samples were analyzed using the Epi proColon and OC Fit-Check tests respectively. For all samples, sensitivity for CRC detection was 73.3% (95% CI 63.9-80.9%) and 68.0% (95% CI 58.2-76.5%) for Septin9 and FIT, respectively. Specificity of the Epi proColon test was 81.5% (95% CI 75.5-86.3%) compared with 97.4% (95% CI 94.1-98.9%) for FIT. For paired samples, the sensitivity of the Epi proColon test (72.2% -95% CI 62.5-80.1%) was shown to be statistically non-inferior to FIT (68.0%-95% CI 58.2-76.5%). When test results for Epi proColon and FIT were combined, CRC detection was 88.7% at a specificity of 78.8%. At a sensitivity of 72%, the Epi proColon test is non- inferior to FIT for CRC detection, although at a lower specificity. With negative predictive values of 99.8%, both methods are identical in confirming the absence of CRC. ClinicalTrials.gov NCT01580540.

Non-invasive, serum DNA pregnancy testing leading to incidental discovery of cancer: a good thing?

PubMed

Prasad, Vinay

2015-11-01

Cell-free DNA for perinatal screening is a growing industry. Non-invasive prenatal testing (NIPT) is based on the premise that foetal DNA is able to cross the placental barrier and enter the mother's circulation, where it can be examined for chromosomal abnormalities, such as trisomy 13, 18 or 21. Such tests are expected to be widely used by pregnant women, with the annual market expected to surpass $1 billion. Recently, a number of case reports have emerged in the haematology-oncology literature. The routine use of NIPT has led to the discovery of maternal neoplasms. Most writers have concluded that this is yet another benefit of the test; however, a closer examination of the cases reveals that this incidental detection may not improve patient outcomes. In some cases, early detection provides lead time bias, but does not change the ultimate clinical outcome, and in other cases, detection constitutes earlier knowledge of a cancer whose natural history cannot be altered. Here, we explore in detail cases where cancer was incidentally discovered among women undergoing routine non-invasive pregnancy testing, and investigate whether or not these women were benefitted by the discovery. Published by Elsevier Ltd.

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease

PubMed Central

Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

2015-01-01

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current “gold standard” for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence. PMID:26494961

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease.

PubMed

Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

2015-10-21

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.

Minimally invasive screening for colitis using attenuated total internal reflectance Fourier transform infrared spectroscopy

PubMed Central

Titus, Jitto; Viennois, Emilie; Merlin, Didier; Perera, A. G. Unil

2016-01-01

This article describes a rapid, simple and cost-effective technique that could lead to a screening method for colitis without the need for biopsies or in vivo measurements. This screening technique includes the testing of serum using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy for the colitis-induced increased presence of mannose. Chronic (Interleukin 10 knockout) and acute (Dextran Sodium Sulphate-induced) models for colitis are tested using the ATR-FTIR technique. Arthritis (Collagen Antibody Induced Arthritis) and metabolic syndrome (Toll like receptor 5 knockout) models are also tested as controls. The marker identified as mannose uniquely screens and distinguishes the colitic from the non-colitic samples and the controls. The reference or the baseline spectrum could be the pooled and averaged spectra of non-colitic samples or the subject's previous sample spectrum. This shows the potential of having individualized route maps of disease status, leading to personalized diagnosis and drug management. PMID:27094092

Airport testing an explosives detection portal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rhykerd, C.; Linker, K.; Hannum, D.

1998-08-01

At the direction of the US Congress, following the Pan Am 103 and TWA 800 crashes, the Federal Aviation Administration funded development of non-invasive techniques to screen airline passengers for explosives. Such an explosives detection portal, developed at Sandia National Laboratories, was field tested at the Albuquerque International airport in September 1997. During the 2-week field trial, 2,400 passengers were screened and 500 surveyed. Throughput, reliability, maintenance and sensitivity were studied. Follow-up testing at Sandia and at Idaho National Engineering and Environmental Laboratory was conducted. A passenger stands in the portal for five seconds while overhead fans blow air overmore » his body. Any explosive vapors or dislodged particles are collected in vents at the feet. Explosives are removed from the air in a preconcentrator and subsequently directed into an ion mobility spectrometer for detection. Throughput measured 300 passengers per hour. The non-invasive portal can detect subfingerprint levels of explosives residue on clothing. A survey of 500 passengers showed a 97% approval rating, with 99% stating that such portals, if effective, should be installed in airports to improve security. Results of the airport test, as well as operational issues, are discussed.« less

Pre- and post-test genetic counseling for chromosomal and Mendelian disorders.

PubMed

Fonda Allen, Jill; Stoll, Katie; Bernhardt, Barbara A

2016-02-01

Genetic carrier screening, prenatal screening for aneuploidy, and prenatal diagnostic testing have expanded dramatically over the past 2 decades. Driven in part by powerful market forces, new complex testing modalities have become available after limited clinical research. The responsibility for offering these tests lies primarily on the obstetrical care provider and has become more burdensome as the number of testing options expands. Genetic testing in pregnancy is optional, and decisions about undergoing tests, as well as follow-up testing, should be informed and based on individual patients' values and needs. Careful pre- and post-test counseling is central to supporting informed decision-making. This article explores three areas of technical expansion in genetic testing: expanded carrier screening, non-invasive prenatal screening for fetal aneuploidies using cell-free DNA, and diagnostic testing using fetal chromosomal microarray testing, and provides insights aimed at enabling the obstetrical practitioner to better support patients considering these tests. Copyright © 2016 Elsevier Inc. All rights reserved.

Unethical randomised controlled trial of cervical screening in India: US Freedom of Information Act disclosures.

PubMed

Suba, Eric J; Ortega, Robert E; Mutch, David G

2017-01-01

A randomised controlled trial conducted in Mumbai, India, compared invasive cervical cancer rates among women offered cervical screening with invasive cervical cancer rates among women offered no-screening. The US Office for Human Research Protections determined the Mumbai trial was unethical because informed consent was not obtained from trial participants. Reportedly, cervical screening in the Mumbai trial reduced invasive cervical cancer mortality rates, but not invasive cervical cancer incidence rates. Documents obtained through the US Freedom of Information Act disclose that the US National Cancer Institute funded the Mumbai trial from 1997 to 2015 to study 'visual inspection/downstaging' tests. However, 'visual inspection/downstaging' tests had been judged unsatisfactory for cancer control before the Mumbai trial began. 'Visual inspection/downstaging' tests failed to reduce invasive cervical cancer incidence rates in Mumbai because 'visual inspection/downstaging' tests, by design, failed to detect preinvasive cervical lesions. None of the 151 538 Mumbai trial participants, in either the intervention or control arms, received cervical screening tests that detected preinvasive cervical lesions. Because of missing/discrepant clinical staging data, it is uncertain whether 'visual inspection/downstaging' tests actually reduced invasive cervical cancer mortality rates in Mumbai. Documents obtained through the US Freedom of Information Act disclose that US National Cancer Institute leaders avoided accountability by making false and misleading statements to Congressional oversight staff. Our findings contradict assurances given to President Barack Obama that regulations pertaining to global health research supported by the US government adequately protect human participants from unethical treatment. US National Cancer Institute leaders should develop policies to compensate victims of unethical global health research. All surviving Mumbai trial participants should finally receive cervical screening tests that detect preinvasive cervical lesions.

Non-invasive prenatal screening versus prenatal diagnosis by array comparative genomic hybridization: a comparative retrospective study.

PubMed

Sotiriadis, Alexandros; Papoulidis, Ioannis; Siomou, Elisavet; Papageorgiou, Elena; Eleftheriades, Makarios; Papadopoulos, Vasilios; Alexiou, Maria; Manolakos, Emmanouil; Athanasiadis, Apostolos

2017-06-01

To calculate the proportion of array comparative genomic hybridization (aCGH) pathogenic results, that would not be detectable by non-invasive prenatal screening (NIPS). This is a comparative study using data from 2779 fetuses, which underwent invasive prenatal diagnosis, and the samples were analyzed using aCGH. The simulated NIPS assay would test for trisomies 21, 18, 13, monosomy X, 47, XXX, 47, XYY, and 47, XXY. Indications for invasive testing were grouped into categories and the absolute, relative rates of pathogenic/likely pathogenic results of aCGH analysis that would not be detectable by NIPS were calculated. The expected rate of aCGH-detected abnormalities that would not be detectable by NIPS was 28.0% (95% CI 14.3-47.6) for nuchal translucency (NT) 95 to 99th centile; 14.3% (95% 5.0-34.6) for NT > 99th centile; 34.2% (95% CI 21.1-50.1) for high-risk first-trimester results (regardless of NT); 52.4% (95% CI 32.4-71.7) for second-trimester markers; and 50.0% (95% CI 26.8-73.2) for advanced maternal age. The overall rate of aCGH pathogenic/likely pathogenic results was 5.0% and 44.0% (95% CI 36.0-52.2) of them would not be detected by NIPS. Approximately half of the abnormal aCGH results would not be detectable by standard NIPS assays, highlighting the necessity of pre-test counseling, and illustrating the limitations of NIPS. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Ultrahigh-resolution optical coherence microscopy accurately classifies precancerous and cancerous human cervix free of labeling

PubMed Central

Zeng, Xianxu; Zhang, Xiaoan; Li, Canyu; Wang, Xiaofang; Jerwick, Jason; Xu, Tao; Ning, Yuan; Wang, Yihong; Zhang, Linlin; Zhang, Zhan; Ma, Yutao; Zhou, Chao

2018-01-01

Cervical cancer remains the fourth most common cause of cancer worldwide and the third leading cause of cancer deaths for women in developing countries. Traditional screening tools, such as human papillomavirus and Pap tests, cannot provide results in real-time and cannot localize suspicious regions. Colposcopy-directed biopsies are invasive in nature and only a few sites of the cervix may be chosen for investigation. A non-invasive, label-free and real-time imaging method with a resolution approaching that of histopathology is desirable for early detection of the disease. Methods: Ultrahigh-resolution optical coherence microscopy (OCM) is an emerging imaging technique used to obtain 3-dimensional (3-D) “optical biopsies” of biological samples with cellular resolution. In this study, 497 3-D OCM datasets from 159 specimens were collected from 92 patients. Results: Distinctive patterns for normal cervix, squamocolumnar junction, ectropion, low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL) and invasive cervical lesions were clearly observed from OCM images, which matched well with corresponding histological slides. OCM images demonstrated a sensitivity of 80% (95% confidence interval, CI, 72%-86%) and a specificity of 89% (95% CI, 84%-93%) for detecting high-risk lesions (HSIL and invasive lesions) when blindly tested by three investigators. A substantial inter-observer agreement was observed (κ=0.627), which showed high diagnostic consistency among three investigators. Conclusion: These results laid the foundation for future non-invasive optical evaluation of cervical tissue in vivo, which could lead to a less invasive and more effective screening and “see-and-treat” strategy for the management of cervical cancer. PMID:29896305

A prospective clinical trial to compare the performance of dried blood spots prenatal screening for Down's syndrome with conventional non-invasive testing technology.

PubMed

Hu, Huiying; Jiang, Yulin; Zhang, Minghui; Liu, Shanying; Hao, Na; Zhou, Jing; Liu, Juntao; Zhang, Xiaojin; Ma, Liangkun

2017-03-01

To evaluate, side by side, the efficiency of dried blood spots (DBSs) against serum screening for Down's syndrome, and then, to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down's syndrome. One thousand eight hundred and thirty-seven low-risk Chinese women, with singleton pregnancy, were enrolled for the study. Alpha-fetoprotein and free beta human chorionic gonadotropin were measured for the serum as well as for the parallel DBS samples. Partial high-risk pregnant women identified by primary blood testing (n = 38) were also subject to the secondary cfDNA screening. Diagnostic amniocentesis was utilized to confirm the screening results. The true positive rate for Down's syndrome detection was 100% for both blood screening methods; however, the false-positive rate was 3.0% for DBS and 4.0% for serum screening, respectively. DBS correlated well with serum screening on Down's syndrome detection. Three out of 38 primary high-risk women displayed chromosomal abnormalities by cfDNA analysis, which were confirmed by amniocentesis. Either the true detection rate or the false-positive rate for Down's syndrome between DBS and the serum test is comparable. In addition, blood primary screening aligned with secondary cfDNA analysis, a "before and after" two-tier screening strategy, can massively decrease the false-positive rate, which, then, dramatically reduces the demand for invasive diagnostic operation. Impact statement Children born with Down's syndrome display a wide range of mental and physical disability. Currently, there is no effective treatment to ease the burden and anxiety of the Down's syndrome family and the surrounding society. This study is to evaluate the efficiency of dried blood spots against serum screening for Down's syndrome and to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down's syndrome. Results demonstrate that fetal cfDNA can significantly reduce false-positive rate close to none while distinguishing all true positives. Thus, we recommend that fetal cfDNA analysis to be utilized as a secondary screening tool atop of the primary blood protein screening to further minimize the capacity of undesirable invasive diagnostic operations.

Rationale, objectives, and design of the EUTrigTreat clinical study: a prospective observational study for arrhythmia risk stratification and assessment of interrelationships among repolarization markers and genotype

PubMed Central

Seegers, Joachim; Vos, Marc A.; Flevari, Panagiota; Willems, Rik; Sohns, Christian; Vollmann, Dirk; Lüthje, Lars; Kremastinos, Dimitrios T.; Floré, Vincent; Meine, Mathias; Tuinenburg, Anton; Myles, Rachel C.; Simon, Dirk; Brockmöller, Jürgen; Friede, Tim; Hasenfuß, Gerd; Lehnart, Stephan E.; Zabel, Markus

2012-01-01

Aims The EUTrigTreat clinical study has been designed as a prospective multicentre observational study and aims to (i) risk stratify patients with an implantable cardioverter defibrillator (ICD) for mortality and shock risk using multiple novel and established risk markers, (ii) explore a link between repolarization biomarkers and genetics of ion (Ca2+, Na+, K+) metabolism, (iii) compare the results of invasive and non-invasive electrophysiological (EP) testing, (iv) assess changes of non-invasive risk stratification tests over time, and (v) associate arrythmogenomic risk through 19 candidate genes. Methods and results Patients with clinical ICD indication are eligible for the trial. Upon inclusion, patients will undergo non-invasive risk stratification, including beat-to-beat variability of repolarization (BVR), T-wave alternans, T-wave morphology variables, ambient arrhythmias from Holter, heart rate variability, and heart rate turbulence. Non-invasive or invasive programmed electrical stimulation will assess inducibility of ventricular arrhythmias, with the latter including recordings of monophasic action potentials and assessment of restitution properties. Established candidate genes are screened for variants. The primary endpoint is all-cause mortality, while one of the secondary endpoints is ICD shock risk. A mean follow-up of 3.3 years is anticipated. Non-invasive testing will be repeated annually during follow-up. It has been calculated that 700 patients are required to identify risk predictors of the primary endpoint, with a possible increase to 1000 patients based on interim risk analysis. Conclusion The EUTrigTreat clinical study aims to overcome current shortcomings in sudden cardiac death risk stratification and to answer several related research questions. The initial patient recruitment is expected to be completed in July 2012, and follow-up is expected to end in September 2014. Clinicaltrials.gov identifier: NCT01209494. PMID:22117037

[Strategy for molecular testing in pulmonary carcinoma].

PubMed

Penault-Llorca, Frédérique; Tixier, Lucie; Perrot, Loïc; Cayre, Anne

2016-01-01

Nowadays, the analysis of theranostic molecular markers is central in the management of lung cancer. As those tumors are diagnosed in two third of the cases at an advanced stage, molecular screening is frequently performed on "small samples". The screening strategy starts by an accurate histopathological characterization, including on biopsies or cytological specimens. WHO 2015 provided a new classification for small biopsy and cytology, defining categories such as non-small cell carcinoma (NSCC), favor adenocarcinoma (TTF1 positive), or favor squamous cell carcinoma (p40 positive). Only the NSCC tumors, non-squamous, are eligible to molecular testing. A strategy aiming at tissue sparing for the small biopsies has to be organized. Tests corresponding to available drugs are prioritized. Blank slides will be prepared for immunohistochemistry and in situ hybridization based tests such as ALK. DNA will then be extracted for the other tests, EGFR mutation screening first associated or not to KRAS. Then, the emerging biomarkers (HER2, ROS1, RET, BRAF…) as well as potentially other markers in case of clinical trials, can been tested. The spread of next generation sequencing technologies, with a very sensitive all-in-one approach will allow the identification of minority clones. Eventually, the development of liquid biopsies will provide the opportunity to monitor the apparition of resistance clones during treatment. This non-invasive approach allows patients with a contraindication to perform biopsy or with non-relevant biopsies to access to molecular screening. Copyright © 2016. Published by Elsevier Masson SAS.

Non-invasive prediction of oesophageal varices in cirrhosis

PubMed Central

Sen, Sambit; Griffiths, William JH

2008-01-01

Non-invasive predictors of varices in cirrhosis would reduce the need for screening endoscopies. Platelet count and spleen size have been shown to be useful parameters, in mixed groups of cirrhotics with different aetiologies. We evaluated this in two homogeneous groups with cirrhosis due to hepatitis C and alcohol. Non-invasive predictors appear promising in the former group, but less so in the latter group. PMID:18416480

Plasma Septin9 versus Fecal Immunochemical Testing for Colorectal Cancer Screening: A Prospective Multicenter Study

PubMed Central

Johnson, David A.; Barclay, Robert L.; Mergener, Klaus; Weiss, Gunter; König, Thomas; Beck, Jürgen; Potter, Nicholas T.

2014-01-01

Background Screening improves outcomes related to colorectal cancer (CRC); however, suboptimal participation for available screening tests limits the full benefits of screening. Non-invasive screening using a blood based assay may potentially help reach the unscreened population. Objective To compare the performance of a new Septin9 DNA methylation based blood test with a fecal immunochemical test (FIT) for CRC screening. Design: In this trial, fecal and blood samples were obtained from enrolled patients. To compare test sensitivity for CRC, patients with screening identified colorectal cancer (n = 102) were enrolled and provided samples prior to surgery. To compare test specificity patients were enrolled prospectively (n = 199) and provided samples prior to bowel preparation for screening colonoscopy. Measurements Plasma and fecal samples were analyzed using the Epi proColon and OC Fit-Check tests respectively. Results For all samples, sensitivity for CRC detection was 73.3% (95% CI 63.9–80.9%) and 68.0% (95% CI 58.2–76.5%) for Septin9 and FIT, respectively. Specificity of the Epi proColon test was 81.5% (95% CI 75.5–86.3%) compared with 97.4% (95% CI 94.1–98.9%) for FIT. For paired samples, the sensitivity of the Epi proColon test (72.2% –95% CI 62.5–80.1%) was shown to be statistically non-inferior to FIT (68.0%–95% CI 58.2–76.5%). When test results for Epi proColon and FIT were combined, CRC detection was 88.7% at a specificity of 78.8%. Conclusions At a sensitivity of 72%, the Epi proColon test is non- inferior to FIT for CRC detection, although at a lower specificity. With negative predictive values of 99.8%, both methods are identical in confirming the absence of CRC. Trial Registration ClinicalTrials.gov NCT01580540 PMID:24901436

Comparative effectiveness of incorporating a hypothetical DCIS prognostic marker into breast cancer screening.

PubMed

Trentham-Dietz, Amy; Ergun, Mehmet Ali; Alagoz, Oguzhan; Stout, Natasha K; Gangnon, Ronald E; Hampton, John M; Dittus, Kim; James, Ted A; Vacek, Pamela M; Herschorn, Sally D; Burnside, Elizabeth S; Tosteson, Anna N A; Weaver, Donald L; Sprague, Brian L

2018-02-01

Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

Non-invasive prenatal diagnosis of achondroplasia and thanatophoric dysplasia: next-generation sequencing allows for a safer, more accurate, and comprehensive approach

PubMed Central

Chitty, Lyn S; Mason, Sarah; Barrett, Angela N; McKay, Fiona; Lench, Nicholas; Daley, Rebecca; Jenkins, Lucy A

2015-01-01

Abstract Objective Accurate prenatal diagnosis of genetic conditions can be challenging and usually requires invasive testing. Here, we demonstrate the potential of next-generation sequencing (NGS) for the analysis of cell-free DNA in maternal blood to transform prenatal diagnosis of monogenic disorders. Methods Analysis of cell-free DNA using a PCR and restriction enzyme digest (PCR–RED) was compared with a novel NGS assay in pregnancies at risk of achondroplasia and thanatophoric dysplasia. Results PCR–RED was performed in 72 cases and was correct in 88.6%, inconclusive in 7% with one false negative. NGS was performed in 47 cases and was accurate in 96.2% with no inconclusives. Both approaches were used in 27 cases, with NGS giving the correct result in the two cases inconclusive with PCR–RED. Conclusion NGS provides an accurate, flexible approach to non-invasive prenatal diagnosis of de novo and paternally inherited mutations. It is more sensitive than PCR–RED and is ideal when screening a gene with multiple potential pathogenic mutations. These findings highlight the value of NGS in the development of non-invasive prenatal diagnosis for other monogenic disorders. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. What's already known about this topic? Non-invasive prenatal diagnosis (NIPD) using PCR-based methods has been reported for the detection or exclusion of individual paternally inherited or de novo alleles in maternal plasma. What does this study add? NIPD using next generation sequencing provides an accurate, more sensitive approach which can be used to detect multiple mutations in a single assay and so is ideal when screening a gene with multiple potential pathogenic mutations. Next generation sequencing thus provides a flexible approach to non-invasive prenatal diagnosis ideal for use in a busy service laboratory. PMID:25728633

Cell-free DNA testing in the maternal blood in high-risk pregnancies after first-trimester combined screening.

PubMed

Persico, Nicola; Boito, Simona; Ischia, Benedetta; Cordisco, Adalgisa; De Robertis, Valentina; Fabietti, Isabella; Periti, Enrico; Volpe, Paolo; Fedele, Luigi; Rembouskos, Georgios

2016-03-01

The objective of this study was to investigate a strategy for clinical implementation of cell-free DNA (cfDNA) testing in high-risk pregnancies after first-trimester combined screening. In 259 singleton pregnancies undergoing invasive testing after first-trimester combined screening, a maternal blood sample was sent to the laboratory Natera for cfDNA testing using a single-nucleotide polymorphism-based methodology. The cfDNA test provided a result in 249 (96.1%) pregnancies and, among these, identified as being at high risk 35 of 36 cases of trisomy 21, 13 of 13 with trisomy 18, five of five with trisomy 13 and three of four with sex chromosome aneuploidies. A policy of performing an invasive test in women with a combined risk of ≥1 in 10 or NT ≥4 mm and offering cfDNA testing to the remaining cases would detect all cases of trisomy 21, 18 or 13, 80% of sex aneuploidies and 62.5% of other defects and would avoid an invasive procedure in 82.4% of euploid fetuses. In high-risk pregnancies after combined screening, a policy of selecting a subgroup for invasive testing and another for cfDNA testing would substantially reduce the number of invasive procedures and retain the ability to diagnose most of the observed aneuploidies. © 2016 John Wiley & Sons, Ltd.

Evaluation of commercial multi-drug oral fluid devices to identify 39 new amphetamine-designer drugs.

PubMed

Nieddu, Maria; Burrai, Lucia; Trignano, Claudia; Boatto, Gianpiero

2014-03-01

Recently, the diffusion on the black market of new psychoactive substances not controlled and often sold as 'legal highs', is exponentially increasing in Europe. Generally, the first analysis for these drugs involves an immunoassay screening in urine or plasma. Actually, there is growing interest in the use of oral fluid (OF) as alternative specimen over conventional biological fluids for drug testing, because of the significant advantages, as a non-invasive collection under direct observation without undue embarrassment or invasion of privacy, and a good correlation with plasma analytical data. Few assays have been developed for detection of new psychoactive compounds in biological samples, so it is important to investigate how they may or may not react in pre-existing commercial immunoassays. In this paper, two different multi-drugs oral fluid screen devices (OFDs) (Screen® Multi-Drug OFD and GIMA One Step Multi-Line Screen Test OFD) were evaluated to determine the cross-reactivity of thirty-nine new amphetamine designer drugs, including twelve substances officially recognized as illicit by italian legislation. Cross-reactivity towards most drugs analyzed was <1 in assays targeting amphetamine (AMP) or methamphetamine (MET). Only two (p-methoxyamphetamine and p-methoxymethamphetamine) of all tested amphetamines gave a positive result. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Phenotypes and genotypes of erythromycin-resistant Streptococcus pyogenes strains isolated from invasive and non-invasive infections from Mexico and the USA during 1999–2010

PubMed Central

Villaseñor-Sierra, Alberto; Katahira, Eva; Jaramillo-Valdivia, Abril N.; de los Angeles Barajas-García, María; Bryant, Amy; Morfín-Otero, Rayo; Márquez-Díaz, Francisco; Tinoco, Juan Carlos; Sánchez-Corona, José; Stevens, Dennis L.

2012-01-01

Summary Objective To compare the prevalence, phenotypes, and genes responsible for erythromycin resistance among Streptococcus pyogenes isolates from Mexico and the USA. Methods Eighty-nine invasive and 378 non-invasive isolates from Mexico, plus 148 invasive, 21 non-invasive, and five unclassified isolates from the USA were studied. Susceptibilities to penicillin, erythromycin, clindamycin, ceftriaxone, and vancomycin were evaluated according to Clinical and Laboratory Standards Institute (CLSI) standards. Phenotypes of erythromycin resistance were identified by triple disk test, and screening for mefA, ermTR, and ermB genes was carried out by PCR. Results All isolates were susceptible to penicillin, ceftriaxone, and vancomycin. Erythromycin resistance was found in 4.9% of Mexican strains and 5.2% of USA strains. Phenotypes in Mexican strains were 95% M and 5% cMLS; in strains from the USA, phenotypes were 33.3% iMLS, 33.3% iMLS-D, and 33.3% M. Erythromycin resistance genes in strains from Mexico were mefA (95%) and ermB (5%); USA strains harbored ermTR (56%), mefA (33%), and none (11%). In Mexico, all erythromycin-resistant strains were non-invasive, whereas 89% of strains from the USA were invasive. Conclusions Erythromycin resistance continues to exist at low levels in both Mexico and the USA, although the genetic mechanisms responsible differ between the two nations. These genetic differences may be related to the invasive character of the S. pyogenes isolated. PMID:22217469

Attitudes towards non-invasive prenatal diagnosis among obstetricians in Pakistan, a developing, Islamic country.

PubMed

Ahmed, Shenaz; Jafri, Hussain; Rashid, Yasmin; Mason, Gerald; Ehsan, Yasmin; Ahmed, Mushtaq

2017-03-01

Stakeholders' views are essential for informing implementation strategies for non-invasive prenatal testing (NIPT). Little is known about such views in developing countries. We explored attitudes towards NIPT among obstetricians in Pakistan, a developing, Islamic country. A 35-item questionnaire was distributed and collected at eight events (a national conference and seven workshops in five cities) for obstetric professionals on advances in fetal medicine. Responses from 113 obstetrician show positive attitudes towards implementation of NIPT: 95% agreed prevention of genetic conditions was a necessity, and 97% agreed public hospitals should provide prenatal screening tests. However, participants also agreed the availability of NIPT would increase social pressure on women to have prenatal screening tests and to terminate an affected pregnancy (53% and 63%, respectively). Most participants would not offer NIPT for sex determination (55%), although 31% would. The most valued aspects of NIPT were its safety, followed by its utility and then accuracy. Participants generally supported the implementation of NIPT but raised concerns about social implications. Therefore, national policy is needed to regulate the implementation of NIPT, and pretest information and post-test genetic counselling are needed to mitigate social pressure and support parents to make informed decisions. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Colon cancer screening: which non-invasive filter tests?

PubMed

Pox, Christian

2011-01-01

The following non-invasive stool tests for colorectal cancer (CRC) screening exist: guaiac or immunochemical fecal occult blood testing (FOBT), genetic stool tests and the M2-PK. Currently the most widely used tests are guaiac-based (gFOBT). Several randomized controlled trials have shown that gFOBT are able to achieve a reduction in CRC-related mortality. This reduction is achieved by detecting asymptomatic cancers at an early stage with a better prognosis. However, gFOBT have a low sensitivity for colorectal adenomas and are thus unlikely to be able to reduce the incidence of CRC. Furthermore, gFOBT are not specific for human blood and can be influenced by external factors. Immunochemical tests (iFOBT) only detect human blood in the stool. In two recent randomized studies from the Netherlands comparing guaiac and immunochemical tests in the asymptomatic population, iFOBT were found to detect more cancers than gFOBT. Furthermore, iFOBT were able to detect more advanced adenomas thus having the potential to be able to reduce the incidence of CRC as well as CRC-related mortality. In the recently released European CRC screening guidelines, iFOBT are considered the screening test of choice. Several questions remain however. It is currently unknown what the optimal cut-off value for an iFOBT to be considered positive should be and what the number of stool samples is that are required. Genetic stool tests detect mutations in stool that can be found in CRC. The original test testing for 21 genetic changes was found to be superior to gFOBT for the detection of cancers. However, the sensitivity was moderate (51.6%) and the sensitivity for advanced adenomas was low. In the meantime the test has been modified improving DNA extraction and reducing the number of mutations tested for as well as including a methylation marker. The efficacy of the modified test in the screening population is unknown. M2-PK is an isomer of the enzyme pyruvate kinase that is involved in glycolysis. Studies have found a good sensitivity for cancers, a low sensitivity for advanced adenomas with a specificity of around 80%. Further studies in the screening population are required. Copyright © 2011 S. Karger AG, Basel.

Acceptability of screening for early detection of liver disease in hazardous/harmful drinkers in primary care.

PubMed

Eyles, Caroline; Moore, Michael; Sheron, Nicholas; Roderick, Paul; O'Brien, Wendy; Leydon, Geraldine M

2013-08-01

It is estimated that one-quarter of adults in the UK drink at harmful/hazardous levels leading to increased mortality and alcohol liver disease (ALD). The Alcohol Liver Disease Detection Study (ALDDeS) aimed to test out in primary care the feasibility of alcohol misuse screening in adults, using the AUDIT questionnaire, and to assess screening harmful/hazardous alcohol users for ALD using newer non-invasive serum markers of fibrosis. To explore patients' experiences of taking part in ALDDeS and understanding of the delivery and process of screening for ALD using self-report questionnaires and feedback of liver fibrosis risk using levels of non-invasive serum markers. A nested qualitative study based in five primary care practices in the UK. From a sample of patients who were identified as drinking at harmful/hazardous levels, 30 participants were identified by maximum variation sampling for qualitative in-depth interviews. Using the principles of constant comparison the transcribed interviews were thematically analysed. Receiving a postal AUDIT questionnaire was viewed as acceptable by participants. For some completing the AUDIT increased awareness of their hazardous alcohol use and a positive blood test indicating liver fibrosis was a catalyst for behaviour change. For others, a negative blood test result provided a licence to continue drinking at hazardous levels. A limited understanding of safe drinking and of ALD was common. Educational and training needs of primary care professionals must be taken into account, so that patients with marker levels indicating low risk of fibrosis are correctly informed about the likely risks of continuing to drink at the same levels.

Transfer of stimulus control from a TFT to CRT screen.

PubMed

Railton, Renee Caron Richards; Foster, T Mary; Temple, William

2010-10-01

The use of television and computer screens for presenting stimuli to animals is increasing as it is non-invasive and can provide precise control over stimuli. Past studies have used cathode ray tube (CRT) screens; however, there is some evidence that these give different results to non-flickering thin film transistor (TFT) screens. Hens' critical flicker fusion frequency ranges between 80 and 90 Hz--above standard CRT screens. Thus, stimuli presented on CRT screens may appear distorted to hens. This study aimed to investigate whether changing the flicker rate of CRT screens altered hens' discrimination. Hens were trained (in a conditional discrimination) to discriminate between two stimuli on a TFT (flickerless) screen, and tested with the stimuli on a CRT screen at four flicker rates (60, 75, 85, and 100 Hz). The hens' accuracy generally decreased as the refresh rate of the CRT screen decreased. These results imply that the change in flicker rate changed the appearance of the stimuli enough to affect the hens' discrimination and stimulus control is disrupted when the stimuli appear to flicker. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Predicting invasiveness of species in trade: Climate match, trophic guild and fecundity influence establishment and impact of non-native freshwater fishes

USGS Publications Warehouse

Howeth, Jennifer G.; Gantz, Crysta A.; Angermeier, Paul; Frimpong, Emmanuel A.; Hoff, Michael H.; Keller, Reuben P.; Mandrak, Nicholas E.; Marchetti, Michael P.; Olden, Julian D.; Romagosa, Christina M.; Lodge, David M.

2016-01-01

AimImpacts of non-native species have motivated development of risk assessment tools for identifying introduced species likely to become invasive. Here, we develop trait-based models for the establishment and impact stages of freshwater fish invasion, and use them to screen non-native species common in international trade. We also determine which species in the aquarium, biological supply, live bait, live food and water garden trades are likely to become invasive. Results are compared to historical patterns of non-native fish establishment to assess the relative importance over time of pathways in causing invasions.LocationLaurentian Great Lakes region.MethodsTrait-based classification trees for the establishment and impact stages of invasion were developed from data on freshwater fish species that established or failed to establish in the Great Lakes. Fishes in trade were determined from import data from Canadian and United States regulatory agencies, assigned to specific trades and screened through the developed models.ResultsClimate match between a species’ native range and the Great Lakes region predicted establishment success with 75–81% accuracy. Trophic guild and fecundity predicted potential harmful impacts of established non-native fishes with 75–83% accuracy. Screening outcomes suggest the water garden trade poses the greatest risk of introducing new invasive species, followed by the live food and aquarium trades. Analysis of historical patterns of introduction pathways demonstrates the increasing importance of these trades relative to other pathways. Comparisons among trades reveal that model predictions parallel historical patterns; all fishes previously introduced from the water garden trade have established. The live bait, biological supply, aquarium and live food trades have also contributed established non-native fishes.Main conclusionsOur models predict invasion risk of potential fish invaders to the Great Lakes region and could help managers prioritize efforts among species and pathways to minimize such risk. Similar approaches could be applied to other taxonomic groups and geographic regions.

Liquid biopsy: A potential and promising diagnostic tool for advanced stage non-small cell lung cancer patients.

PubMed

Doval, D C; Deshpande, R; Dhabhar, B; Babu, K G; Prabhash, K; Chopra, R; Sripada, P V; Deshmukh, C; Suryavanshi, M

2017-12-01

More than 50% of non-small cell lung cancer (NSCLC) cases harbor an actionable mutation, and molecular testing at different intervals can help in personalized and targeted treatment. Core tissue biopsy and needle biopsy done at the time of diagnosis/disease progression are interventional, time-consuming and can affect the patients adversely. Noninterventional biomarker testing by liquid biopsy promises to revolutionize advanced stage cancer screening. The present report was formulated based on an expert panel meeting of renowned oncologists who gave their opinions for minimally invasive liquid biopsy to detect targetable molecular biomarkers in advanced NSCLC cases. An exhaustive literature search was done to support their recommendations. Clinical utility of minimally invasive liquid biopsy, for detection of molecular biomarkers in advanced stage NSCLC patients, was broadly discussed by the key opinion leaders.

Using population-based data to predict the impact of introducing noninvasive prenatal diagnosis for Down syndrome.

PubMed

Susman, Marleen R; Amor, David J; Muggli, Evelyne; Jaques, Alice M; Halliday, Jane

2010-05-01

To compare the number and types of chromosome abnormalities prenatally diagnosed and the number of invasive procedures between current prenatal testing pathways and a pathway where noninvasive prenatal diagnosis for Down syndrome replaces Down syndrome screening tests. Numbers and types of chromosome abnormalities for each referral category were extracted from prenatal diagnostic testing reports routinely collected in Victoria, Australia, in 2006 and 2007. These data were then applied to the proposed implementation strategy. If noninvasive prenatal diagnosis for Down syndrome had replaced Down syndrome screening tests in 2006 and 2007, in Victoria, there would have been 25 (7%) additional Down syndrome diagnosed, 6896 (84%) fewer invasive procedures, and 231 (56%) non-Down syndrome chromosome abnormalities no longer detected. These include trisomy 13, trisomy 18, sex chromosome abnormalities, balanced and unbalanced rearrangements, polyploidy, and mosaic results. The potential loss of information about chromosome abnormalities other than Down syndrome with noninvasive prenatal diagnosis compared with full karyotyping with traditional prenatal diagnosis should be considered when planning for the implementation of new technologies.

The Training and Field Work Experiences of Community Health Workers conducting non-invasive, population-based screening for Cardiovascular Disease in Four Communities in Low and Middle-Income Settings

PubMed Central

Denman, Catalina A.; Montano, Carlos Mendoza; Gaziano, Thomas A.; Levitt, Naomi; Rivera-Andrade, Alvaro; Carrasco, Diana Munguía; Zulu, Jabu; Khanam, Masuma Akter; Puoane, Thandi

2015-01-01

Background Cardiovascular disease (CVD) is on the rise in low- and middle-income countries (LMIC) and is proving difficult to combat due to the emphasis on improving outcomes in maternal and child health and infectious diseases, against a backdrop of severe human resource and infrastructure constraints. Effective task-sharing from physicians or nurses to community health workers (CHWs) to conduct population-based screening for persons at risk, has the potential to mitigate the impact of CVD on vulnerable populations. CHWs in Bangladesh, Guatemala, Mexico, and South Africa were trained to conduct non-invasive population-based screening for persons at high risk for CVD. Objective (s) The objectives of this study were to quantitatively assess the performance of CHWs during training and to qualitatively capture their training and fieldwork experiences while conducting non-invasive screening for cardiovascular disease (CVD) risk in their communities. Methods Written tests were used to assess CHWs’ acquisition of content knowledge during training, and focus group discussions conducted to capture their training and fieldwork experiences. Results Training was effective at increasing the CHWs’ content knowledge of cardiovascular disease (CVD) and this knowledge was largely retained up to six months after the completion of field work. Common themes which need to be addressed when designing task sharing with CHWs in chronic diseases are identified, including language, respect, and compensation. The importance of having intimate knowledge of the community receiving services from design to implementation is underscored. Conclusions Effective training for screening for CVD in community settings should have a strong didactic core that is supplemented with culture-specific adaptations in the delivery of instruction. The incorporation of expert and intimate knowledge of the communities themselves is critical, from the design to implementation phases of training. Challenges such as role definition, defining career paths, and providing adequate remuneration, must be addressed. PMID:25754566

Early clinical experience of cell-free DNA-based aneuploidy screening: A survey of obstetric sonologists in Australia and New Zealand.

PubMed

Hui, Lisa; Teoh, Mark; Piessens, Sofie; Walker, Susan P

2015-04-01

Cell-free DNA-based non-invasive prenatal testing for aneuploidy (NIPT) is now established as the most accurate screening test for trisomy 21. This test became clinically available on a patient-funded basis in Australia and New Zealand in 2013. To investigate the clinical implementation of NIPT use by members of the Australian Association of Obstetrical and Gynaecological Ultrasonologists (AAOGU) during its first year of local availability. Email invitations with an embedded link to an anonymous online survey were sent to all 140 members of the AAOGU in December 2013. We received 54 responses to the survey (39% response rate). Two thirds of respondents were subspecialists in obstetric and gynaecological ultrasound or maternal fetal medicine. The majority of respondents had already used NIPT in their practice (94%). There was no significant difference in the proportion of respondents offering NIPT to high-risk women in private versus public practice (95 versus 82%, P = 0.14). However, inequity of access due to cost was the most common ethical issue encountered. The vast majority continued to offer an 11-13 week ultrasound in addition to NIPT. Almost all respondents (96%) were also willing to offer NIPT to low-risk women in December 2013 after appropriate genetic counselling. Non-invasive prenatal testing was introduced into clinical care by obstetric sonologists with confidence and in accordance with the current recommended guidelines. These results may help inform future prenatal screening policy and cost-effectiveness analyses. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Phenotypes and genotypes of erythromycin-resistant Streptococcus pyogenes strains isolated from invasive and non-invasive infections from Mexico and the USA during 1999-2010.

PubMed

Villaseñor-Sierra, Alberto; Katahira, Eva; Jaramillo-Valdivia, Abril N; Barajas-García, María de los Angeles; Bryant, Amy; Morfín-Otero, Rayo; Márquez-Díaz, Francisco; Tinoco, Juan Carlos; Sánchez-Corona, José; Stevens, Dennis L

2012-03-01

To compare the prevalence, phenotypes, and genes responsible for erythromycin resistance among Streptococcus pyogenes isolates from Mexico and the USA. Eighty-nine invasive and 378 non-invasive isolates from Mexico, plus 148 invasive, 21 non-invasive, and five unclassified isolates from the USA were studied. Susceptibilities to penicillin, erythromycin, clindamycin, ceftriaxone, and vancomycin were evaluated according to Clinical and Laboratory Standards Institute (CLSI) standards. Phenotypes of erythromycin resistance were identified by triple disk test, and screening for mefA, ermTR, and ermB genes was carried out by PCR. All isolates were susceptible to penicillin, ceftriaxone, and vancomycin. Erythromycin resistance was found in 4.9% of Mexican strains and 5.2% of USA strains. Phenotypes in Mexican strains were 95% M and 5% cMLS; in strains from the USA, phenotypes were 33.3% iMLS, 33.3% iMLS-D, and 33.3% M. Erythromycin resistance genes in strains from Mexico were mefA (95%) and ermB (5%); USA strains harbored ermTR (56%), mefA (33%), and none (11%). In Mexico, all erythromycin-resistant strains were non-invasive, whereas 89% of strains from the USA were invasive. Erythromycin resistance continues to exist at low levels in both Mexico and the USA, although the genetic mechanisms responsible differ between the two nations. These genetic differences may be related to the invasive character of the S. pyogenes isolated. Copyright © 2011 International Society for Infectious Diseases. All rights reserved.

[Development of a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse tanscription polymerase chain reaction (qRT-PCR)].

PubMed

Pavlov, K A; Shkoporov, A N; Khokhlova, E V; Korchagina, A A; Sidorenkov, A V; Grigor'ev, M É; Pushkar', D Iu; Chekhonin, V P

2013-01-01

The wide introduction of prostatic specific antigen (PSA) determination into clinical practice has resulted in a larger number of prostate biopsies, while the lower age threshold for PSA has led to a larger number of unnecessary prostate biopsies. Hence, there is a need for new biomarkers that can detect prostate cancer. PCA3 is a noncoding messenger ribonucleic acid (mRNA) that is expressed exclusively in prostate cells. The aim of the study has been to develop a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of the study, a laboratory diagnostic test system prototype has been designed, an application methodology has been developed and specificity and sensitivity data of the method has been assessed. The diagnostic system has demonstrated its ability to detect significantly elevated levels of PCA 3/KLK 3 in samples from prostate cancer (PCa) patients compared with those from healthy men. The findings have shown relatively high diagnostic sensitivity, specificity and negative-predictive values for an early non-invasive screening of prostate cancer

Pre-Analytical Conditions in Non-Invasive Prenatal Testing of Cell-Free Fetal RHD

PubMed Central

Rieneck, Klaus; Krog, Grethe Risum; Nielsen, Leif Kofoed; Tabor, Ann; Dziegiel, Morten Hanefeld

2013-01-01

Background Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women. In Denmark, routine antenatal screening for the fetal RhD gene (RHD) directs the administration of antenatal anti-D prophylaxis only to women who carry an RhD positive fetus. Prophylaxis reduces the risk of immunization that may lead to hemolytic disease of the fetus and the newborn. The reliability of predicting the fetal RhD type depends on pre-analytical factors and assay sensitivity. We evaluated the testing setup in the Capital Region of Denmark, based on data from routine antenatal RHD screening. Methods Blood samples were drawn at gestational age 25 weeks. DNA extracted from 1 mL of plasma was analyzed for fetal RHD using a duplex method for exon 7/10. We investigated the effect of blood sample transportation time (n = 110) and ambient outdoor temperatures (n = 1539) on the levels of cffDNA and total DNA. We compared two different quantification methods, the delta Ct method and a universal standard curve. PCR pipetting was compared on two systems (n = 104). Results The cffDNA level was unaffected by blood sample transportation for up to 9 days and by ambient outdoor temperatures ranging from -10°C to 28°C during transport. The universal standard curve was applicable for cffDNA quantification. Identical levels of cffDNA were observed using the two automated PCR pipetting systems. We detected a mean of 100 fetal DNA copies/mL at a median gestational age of 25 weeks (range 10–39, n = 1317). Conclusion The setup for real-time PCR-based, non-invasive prenatal testing of cffDNA in the Capital Region of Denmark is very robust. Our findings regarding the transportation of blood samples demonstrate the high stability of cffDNA. The applicability of a universal standard curve facilitates easy cffDNA quantification. PMID:24204719

Pre-analytical conditions in non-invasive prenatal testing of cell-free fetal RHD.

PubMed

Clausen, Frederik Banch; Jakobsen, Tanja Roien; Rieneck, Klaus; Krog, Grethe Risum; Nielsen, Leif Kofoed; Tabor, Ann; Dziegiel, Morten Hanefeld

2013-01-01

Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women. In Denmark, routine antenatal screening for the fetal RhD gene (RHD) directs the administration of antenatal anti-D prophylaxis only to women who carry an RhD positive fetus. Prophylaxis reduces the risk of immunization that may lead to hemolytic disease of the fetus and the newborn. The reliability of predicting the fetal RhD type depends on pre-analytical factors and assay sensitivity. We evaluated the testing setup in the Capital Region of Denmark, based on data from routine antenatal RHD screening. Blood samples were drawn at gestational age 25 weeks. DNA extracted from 1 mL of plasma was analyzed for fetal RHD using a duplex method for exon 7/10. We investigated the effect of blood sample transportation time (n = 110) and ambient outdoor temperatures (n = 1539) on the levels of cffDNA and total DNA. We compared two different quantification methods, the delta Ct method and a universal standard curve. PCR pipetting was compared on two systems (n = 104). The cffDNA level was unaffected by blood sample transportation for up to 9 days and by ambient outdoor temperatures ranging from -10 °C to 28 °C during transport. The universal standard curve was applicable for cffDNA quantification. Identical levels of cffDNA were observed using the two automated PCR pipetting systems. We detected a mean of 100 fetal DNA copies/mL at a median gestational age of 25 weeks (range 10-39, n = 1317). The setup for real-time PCR-based, non-invasive prenatal testing of cffDNA in the Capital Region of Denmark is very robust. Our findings regarding the transportation of blood samples demonstrate the high stability of cffDNA. The applicability of a universal standard curve facilitates easy cffDNA quantification.

Testing times: do new prenatal tests signal the end of Down syndrome?

PubMed

Cole, Robert; Jones, Gareth

2013-03-01

Since 2010, prenatal screening for Down syndrome (DS) has been offered to all pregnant women in New Zealand. The programme has been criticised by several groups, on claims that screening is eugenic and discriminatory towards those with DS. Recently, tests have been developed that may one day prove more efficient than current screening methods. They are an example of 'Non-Invasive Prenatal Diagnosis' (NIPD), which enables diagnosis earlier in pregnancy with less risk of complications. If the current programme raises objections, what threats does this new and seemingly more attractive technology pose to the DS community? We argue that NIPD is simply an extension of current screening methods, raising similar ethical concerns. Presently, the programme shows little evidence of 'eugenics', demonstrated by moderate uptake rates and varying attitudes towards disability. We do not regard the offer of screening to be threatening, as women choose whether or not to be screened depending on their own personal circumstances. One day, prenatal testing may result in fewer people with DS; but past and present trends indicate these individuals will continue to be supported, irrespective of 'group size'. Care and respect for the disabled will remain essential, regardless of a woman's decision over her pregnancy.

Care standards for non-alcoholic fatty liver disease in the United Kingdom 2016: a cross-sectional survey.

PubMed

Sheridan, David A; Aithal, Guru; Alazawi, William; Allison, Michael; Anstee, Quentin; Cobbold, Jeremy; Khan, Shahid; Fowell, Andrew; McPherson, Stuart; Newsome, Philip N; Oben, Jude; Tomlinson, Jeremy; Tsochatzis, Emmanouil

2017-10-01

Guidelines for the assessment of non-alcoholic fatty liver disease (NAFLD) have been published in 2016 by National Institute for Health and Care Excellence and European Associations for the study of the Liver-European Association for the study of Diabetes-European Association for the study of Obesity. Prior to publication of these guidelines, we performed a cross-sectional survey of gastroenterologists and hepatologists regarding NAFLD diagnosis and management. An online survey was circulated to members of British Association for the Study of the Liver and British Society of Gastroenterology between February 2016 and May 2016. 175 gastroenterologists/hepatologists responded, 116 completing the survey, representing 84 UK centres. 22% had local NAFLD guidelines. 45% received >300 referrals per year from primary care for investigation of abnormal liver function tests (LFTs). Clinical assessment tended to be performed in secondary rather than primary care including body mass index (82% vs 26%) and non-invasive liver screen (86% vs 32%) and ultrasound (81% vs 37%). Widely used tools for non-invasive fibrosis risk stratification were aspartate transaminase (AST)/alanine transaminase (ALT) ratio (53%), Fibroscan (50%) and NAFLD fibrosis score (41%). 78% considered liver biopsy in selected cases. 50% recommended 10% weight loss target as first-line treatment. Delivery of lifestyle interventions was mostly handed back to primary care (56%). A minority have direct access to community weight management services (22%). Follow-up was favoured by F3/4 fibrosis (72.9%), and high-risk non-invasive fibrosis tests (51%). Discharge was favoured by simple steatosis at biopsy (30%), and low-risk non-invasive scores (25%). The survey highlights areas for improvement of service provision for NAFLD assessment including improved recognition of non-alcoholic steatohepatitis in people with type 2 diabetes, streamlining abnormal LFT referral pathways, defining non-invasive liver fibrosis assessment tools, use of liver biopsy, managing metabolic syndrome features and improved access to lifestyle interventions.

Stiffness at shear-wave elastography and patient presentation predicts upgrade at surgery following an ultrasound-guided core biopsy diagnosis of ductal carcinoma in situ.

PubMed

Evans, A; Purdie, C A; Jordan, L; Macaskill, E J; Flynn, J; Vinnicombe, S

2016-11-01

The aim of this study is to establish predictors of invasion in lesions yielding an ultrasound-guided biopsy diagnosis of ductal carcinoma in situ (DCIS). Patients subjected to ultrasound-guided core biopsy yielding DCIS were studied. At shear-wave elastography (SWE) a threshold of 50 kPa was used for mean elasticity (Emean) to dichotomise the elasticity data between invasive and non-invasive masses. Data recorded included the mammographic and ultrasound features, the referral source, and grade of DCIS in the biopsy. The chi-square test was used to detect statistical significance. Of 57 lesions, 24 (42%) had invasion at excision. Symptomatic patients and patients with stiff lesions were more likely to have invasion than patients presenting through screening and with soft lesions (58% [14 of 24] versus 30% [10 of 33], p=0.03) and (51% [20 of 39] versus 22% [4 of 18], p=0.04). No other factors showed a relationship with invasion. Combining the two predictors of invasion improved risk stratification with symptomatic and stiff lesions having a risk of invasion of 67% (12 of 18) and soft lesions presenting at screening having only a 17% (2 of 12) risk of invasion (p=0.02). Stiffness on SWE and the referral source of the patient are predictors of occult invasion in women with an ultrasound-guided core biopsy diagnosis of DCIS. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Non-invasive prenatal diagnosis of achondroplasia and thanatophoric dysplasia: next-generation sequencing allows for a safer, more accurate, and comprehensive approach.

PubMed

Chitty, Lyn S; Mason, Sarah; Barrett, Angela N; McKay, Fiona; Lench, Nicholas; Daley, Rebecca; Jenkins, Lucy A

2015-07-01

Accurate prenatal diagnosis of genetic conditions can be challenging and usually requires invasive testing. Here, we demonstrate the potential of next-generation sequencing (NGS) for the analysis of cell-free DNA in maternal blood to transform prenatal diagnosis of monogenic disorders. Analysis of cell-free DNA using a PCR and restriction enzyme digest (PCR-RED) was compared with a novel NGS assay in pregnancies at risk of achondroplasia and thanatophoric dysplasia. PCR-RED was performed in 72 cases and was correct in 88.6%, inconclusive in 7% with one false negative. NGS was performed in 47 cases and was accurate in 96.2% with no inconclusives. Both approaches were used in 27 cases, with NGS giving the correct result in the two cases inconclusive with PCR-RED. NGS provides an accurate, flexible approach to non-invasive prenatal diagnosis of de novo and paternally inherited mutations. It is more sensitive than PCR-RED and is ideal when screening a gene with multiple potential pathogenic mutations. These findings highlight the value of NGS in the development of non-invasive prenatal diagnosis for other monogenic disorders. © 2015 John Wiley & Sons, Ltd.

Non-invasive prenatal testing: a review of international implementation and challenges

PubMed Central

Allyse, Megan; Minear, Mollie A; Berson, Elisa; Sridhar, Shilpa; Rote, Margaret; Hung, Anthony; Chandrasekharan, Subhashini

2015-01-01

Noninvasive prenatal genetic testing (NIPT) is an advance in the detection of fetal chromosomal aneuploidies that analyzes cell-free fetal DNA in the blood of a pregnant woman. Since its introduction to clinical practice in Hong Kong in 2011, NIPT has quickly spread across the globe. While many professional societies currently recommend that NIPT be used as a screening method, not a diagnostic test, its high sensitivity (true positive rate) and specificity (true negative rate) make it an attractive alternative to the serum screens and invasive tests currently in use. Professional societies also recommend that NIPT be accompanied by genetic counseling so that families can make informed reproductive choices. If NIPT becomes more widely adopted, States will have to implement regulation and oversight to ensure it fits into existing legal frameworks, with particular attention to returning fetal sex information in areas where sex-based abortions are prevalent. Although there are additional challenges for NIPT uptake in the developing world, including the lack of health care professionals and infrastructure, the use of NIPT in low-resource settings could potentially reduce the need for skilled clinicians who perform invasive testing. Future advances in NIPT technology promise to expand the range of conditions that can be detected, including single gene disorders. With these advances come questions of how to handle incidental findings and variants of unknown significance. Moving forward, it is essential that all stakeholders have a voice in crafting policies to ensure the ethical and equitable use of NIPT across the world. PMID:25653560

Does sensitivity measured from screening test-sets predict clinical performance?

NASA Astrophysics Data System (ADS)

Soh, BaoLin P.; Lee, Warwick B.; Mello-Thoms, Claudia R.; Tapia, Kriscia A.; Ryan, John; Hung, Wai Tak; Thompson, Graham J.; Heard, Rob; Brennan, Patrick C.

2014-03-01

Aim: To examine the relationship between sensitivity measured from the BREAST test-set and clinical performance. Background: Although the UK and Australia national breast screening programs have regarded PERFORMS and BREAST test-set strategies as possible methods of estimating readers' clinical efficacy, the relationship between test-set and real life performance results has never been satisfactorily understood. Methods: Forty-one radiologists from BreastScreen New South Wales participated in this study. Each reader interpreted a BREAST test-set which comprised sixty de-identified mammographic examinations sourced from the BreastScreen Digital Imaging Library. Spearman's rank correlation coefficient was used to compare the sensitivity measured from the BREAST test-set with screen readers' clinical audit data. Results: Results shown statistically significant positive moderate correlations between test-set sensitivity and each of the following metrics: rate of invasive cancer per 10 000 reads (r=0.495; p < 0.01); rate of small invasive cancer per 10 000 reads (r=0.546; p < 0.001); detection rate of all invasive cancers and DCIS per 10 000 reads (r=0.444; p < 0.01). Conclusion: Comparison between sensitivity measured from the BREAST test-set and real life detection rate demonstrated statistically significant positive moderate correlations which validated that such test-set strategies can reflect readers' clinical performance and be used as a quality assurance tool. The strength of correlation demonstrated in this study was higher than previously found by others.

Short-Term Outcomes of Screening Mammography Using Computer-Aided Detection

PubMed Central

Fenton, Joshua J.; Xing, Guibo; Elmore, Joann G.; Bang, Heejung; Chen, Steven L.; Lindfors, Karen K.; Baldwin, Laura-Mae

2013-01-01

Background Computer-aided detection (CAD) has rapidly diffused into screening mammography practice despite limited and conflicting data on its clinical effect. Objective To determine associations between CAD use during screening mammography and the incidence of ductal carcinoma in situ (DCIS) and invasive breast cancer, invasive cancer stage, and diagnostic testing. Design Retrospective cohort study. Setting Medicare program. Participants Women aged 67 to 89 years having screening mammography between 2001 and 2006 in U.S. SEER (Surveillance, Epidemiology and End Results) regions (409 459 mammograms from 163 099 women). Measurements Incident DCIS and invasive breast cancer within 1 year after mammography, invasive cancer stage, and diagnostic testing within 90 days after screening among women without breast cancer. Results From 2001 to 2006, CAD prevalence increased from 3.6% to 60.5%. Use of CAD was associated with greater DCIS incidence (adjusted odds ratio [OR], 1.17 [95% CI, 1.11 to 1.23]) but no difference in invasive breast cancer incidence (adjusted OR, 1.00 [CI, 0.97 to 1.03]). Among women with invasive cancer, CAD was associated with greater likelihood of stage I to II versus III to IV cancer (adjusted OR, 1.27 [CI, 1.14 to 1.41]). In women without breast cancer, CAD was associated with increased odds of diagnostic mammography (adjusted OR, 1.28 [CI, 1.27 to 1.29]), breast ultrasonography (adjusted OR, 1.07 [CI, 1.06 to 1.09]), and breast biopsy (adjusted OR, 1.10 [CI, 1.08 to 1.12]). Limitation Short follow-up for cancer stage, potential unmeasured confounding, and uncertain generalizability to younger women. Conclusion Use of CAD during screening mammography among Medicare enrollees is associated with increased DCIS incidence, the diagnosis of invasive breast cancer at earlier stages, and increased diagnostic testing among women without breast cancer. Primary Funding Source Center for Healthcare Policy and Research, University of California, Davis. PMID:23588746

The potential impact of NIPT as a second-tier screen on the outcomes of high-risk pregnancies with rare chromosomal abnormalities.

PubMed

Maxwell, Susannah; Dickinson, Jan E; Murch, Ashleigh; O'Leary, Peter

2015-10-01

To describe the potential impact of using noninvasive prenatal testing (NIPT) as a second-tier test, on the diagnosis and outcomes of pregnancies identified as high risk through first trimester screening (FTS) in a cohort of real pregnancies. Western Australian FTS and diagnostic data (2007-2009) were linked to pregnancy outcomes. Karyotype results from invasive prenatal testing in high-risk women were analysed. The outcomes of abnormal results that would not be detected by NIPT, assuming a panel of trisomy 21/18/13 and sex chromosome aneuploidies, and the likelihood of diagnosis in a screening model using NIPT as a second-tier test are described. Abnormal karyotype results were reported in 224 of 1488 (15%) women with high-risk pregnancies having invasive diagnostic testing. NIPT potentially would have identified 85%. The 33 abnormalities unidentifiable by NIPT were triploidies (n = 7, 21%), balanced (n = 8, 24%) and unbalanced rearrangements (n = 10, 30%) and level III mosaicisms (n = 8, 24%). For conditions not identifiable by NIPT, fetal sonographic appearance was likely to have led to invasive testing for 10 of 17 (59%) pathogenic abnormalities. If a policy was adopted recommending invasive testing for FTS risk >1:50 and/or ultrasound detected abnormality, the residual risk of an unidentified pathogenic chromosomal abnormality in those without a diagnosis would have been 0.33% (95% CI 0.01-0.65%). A screening model with NIPT as a second-tier for high-risk pregnancies would be unlikely to have changed the outcome for the majority of pregnancies. Optimising the diagnosis of rare pathogenic abnormalities requires clear indicators for invasive testing over NIPT. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Use of the Analysis of the Volatile Faecal Metabolome in Screening for Colorectal Cancer

PubMed Central

2015-01-01

Diagnosis of colorectal cancer is an invasive and expensive colonoscopy, which is usually carried out after a positive screening test. Unfortunately, existing screening tests lack specificity and sensitivity, hence many unnecessary colonoscopies are performed. Here we report on a potential new screening test for colorectal cancer based on the analysis of volatile organic compounds (VOCs) in the headspace of faecal samples. Faecal samples were obtained from subjects who had a positive faecal occult blood sample (FOBT). Subjects subsequently had colonoscopies performed to classify them into low risk (non-cancer) and high risk (colorectal cancer) groups. Volatile organic compounds were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and then data were analysed using both univariate and multivariate statistical methods. Ions most likely from hydrogen sulphide, dimethyl sulphide and dimethyl disulphide are statistically significantly higher in samples from high risk rather than low risk subjects. Results using multivariate methods show that the test gives a correct classification of 75% with 78% specificity and 72% sensitivity on FOBT positive samples, offering a potentially effective alternative to FOBT. PMID:26086914

Biomarkers to Distinguish Aggressive Cancers from Non-aggressive or Non-progressing Cancer — EDRN Public Portal

Cancer.gov

Distinguishing aggressive cancers from non-aggressive or non-progressing cancers is an issue of both clinical and public health importance particularly for those cancers with an available screening test. With respect to breast cancer, mammographic screening has been shown in randomized trials to reduce breast cancer mortality, but given the limitations of its sensitivity and specificity some breast cancers are missed by screening. These so called interval detected breast cancers diagnosed between regular screenings are known to have a more aggressive clinical profile. In addition, of those cancers detected by mammography some are indolent while others are more likely to recur despite treatment. The pilot study proposed herein is highly responsive to the EDRN supplement titled “Biomarkers to Distinguish Aggressive Cancers from Nonaggressive or Non-progressing Cancers” in that it addresses both of the research objectives related to these issues outlined in the notice for this supplement: Aim 1: To identify biomarkers in tumor tissue related to risk of interval detected vs. mammography screen detected breast cancer focusing on early stage invasive disease. We will compare gene expression profiles using the whole genome-cDNA-mediated Annealing, Selection, extension and Ligation (DASL) assay of 50 screen detected cancers to those of 50 interval detected cancers. Through this approach we will advance our understanding of the molecular characteristics of interval vs. screen detected breast cancers and discover novel biomarkers that distinguish between them. Aim 2: To identify biomarkers in tumor tissue related to risk of cancer recurrence among patients with screen detected early stage invasive breast cancer. Using the DASL assay we will compare gene expression profiles from screen detected early stage breast cancer that either recurred within five years or never recurred within five years. These two groups of patients will be matched on multiple factors including tumor stage and treatments received. Our goal with this comparison is to identify novel biomarkers that discriminate between tumors that recur and are more aggressive compared to those that are less aggressive and do not recur. This project will evaluate well characterized tumor tissue specimens using a robust high dimensional laboratory approach and generate preliminary data that will motivate a larger scale study of high translational relevance.

A mixed methods study to assess the feasibility of a randomised controlled trial of invasive urodynamic testing versus clinical assessment and non-invasive tests prior to surgery for stress urinary incontinence in women: the INVESTIGATE-I study.

PubMed

Hilton, Paul; Armstrong, Natalie; Brennand, Catherine; Howel, Denise; Shen, Jing; Bryant, Andrew; Tincello, Douglas G; Lucas, Malcolm G; Buckley, Brian S; Chapple, Christopher R; Homer, Tara; Vale, Luke; McColl, Elaine

2015-09-08

The position of invasive urodynamic testing (IUT) in diagnostic pathways for urinary incontinence is unclear, and systematic reviews have called for further trials evaluating clinical utility. The objective of this study was to inform the decision whether to proceed to a definitive randomised trial of IUT compared to clinical assessment with non-invasive tests, prior to surgery in women with stress urinary incontinence (SUI) or stress-predominant mixed urinary incontinence (MUI). A mixed methods study comprising a pragmatic multicentre randomised pilot trial, a qualitative face-to face interview study with patients eligible for the trial, an exploratory economic evaluation including value of information study, a survey of clinicians' views about IUT, and qualitative telephone interviews with purposively sampled survey respondents. Only the first and second of these elements are reported here. Trial participants were randomised to either clinical assessment with non-invasive tests (control arm) or clinical assessment with non-invasive tests plus IUT (intervention arm). The main outcome measures of these feasibility studies were confirmation that units can identify and recruit eligible women, acceptability of investigation strategies and data collection tools, and acquisition of outcome data to determine the sample size for a definitive trial. The primary outcome proposed for a definitive trial was ICIQ-FLUTS (total score) 6 months after surgery or the start of nonsurgical treatment. Of 284 eligible women, 222 (78%) were recruited, 165/219 (75%) returned questionnaires at baseline, and 125/200 returned them (63%) at follow-up. Most women underwent surgery; management plans were changed in 19 (19%) participants following IUT. Participants interviewed were positive about the trial and the associated documentation. All elements of a definitive trial were rehearsed. Such a trial would require between 232 and 922 participants, depending on the target difference in the primary outcome. We identified possible modifications to our protocol for application in a definitive trial including clarity over inclusion/exclusions, screening processes, reduction in secondary outcomes, and modification to patient questionnaire booklets and bladder diaries. A definitive trial of IUT versus clinical assessment prior to surgery for SUI or stress predominant MUI is feasible and remains relevant. Current Controlled Trials: ISRCTN 71327395, registered 7 June 2010.

Saliva as a non-invasive diagnostic tool for inflammation and insulin-resistance

PubMed Central

Desai, Gauri S; Mathews, Suresh T

2014-01-01

Saliva has been progressively studied as a non-invasive and relatively stress-free diagnostic alternative to blood. Currently, saliva testing is used for clinical assessment of hormonal perturbations, detection of HIV antibodies, DNA analysis, alcohol screening, and drug testing. Recently, there has been increasing interest in evaluating the diagnostic potential of saliva in obesity, inflammation, and insulin-resistance. Current literature has demonstrated elevated levels of inflammatory biomarkers including C-reactive protein, tumor necrosis factor-α, interleukin-6, and interferon-γ in saliva of obese/overweight children and adults. Salivary antioxidant status has also been studied as a measure of oxidative stress in individuals with type 2 diabetes. Further, several studies have demonstrated correlations of salivary markers of stress and insulin resistance including cortisol, insulin, adiponectin, and resistin with serum concentrations. These findings suggest the potential diagnostic value of saliva in health screening and risk stratification studies, particularly in the pediatric population, with implications for inflammatory, metabolic and cardiovascular conditions. However, additional studies are required to standardize saliva collection and storage procedures, validate analytical techniques for biomarker detection, and establish reference ranges for routine clinical use. The purpose of this review is to summarize and evaluate recent advancements in using saliva as a diagnostic tool for inflammation and insulin-resistance. PMID:25512775

Detection of colorectal cancer (CRC) by urinary volatile organic compound analysis.

PubMed

Arasaradnam, Ramesh P; McFarlane, Michael J; Ryan-Fisher, Courtenay; Westenbrink, Erik; Hodges, Phoebe; Hodges, Paula; Thomas, Matthew G; Chambers, Samantha; O'Connell, Nicola; Bailey, Catherine; Harmston, Christopher; Nwokolo, Chuka U; Bardhan, Karna D; Covington, James A

2014-01-01

Colorectal cancer (CRC) is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs) signature(s) for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer). FAIMS is able to identify Inflammatory Bowel disease (IBD) patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK). Data was processed using Fisher Discriminant Analysis (FDA) after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS) with potential as a novel screening tool.

New non-invasive safe, quick, economical method of detecting various cancers was found using QRS complex or rising part of T-wave of recorded ECGs. Cancers can be screened along with their biochemical parameters & therapeutic effects of any cancer treatments can be evaluated using recorded ECGs of the same individual.

PubMed

Omura, Yoshiaki; Lu, Dominic; O'Young, Brian; Jones, Marilyn; Nihrane, Abdallah; Duvvi, Harsha; Shimotsuura, Yasuhiro; Ohki, Motomu

2015-01-01

There are many methods of detecting cancers including detection of cancer markers by blood test, (which is invasive, time consuming and relatively expensive), detection of cancers by non-invasive methods such as X-Ray, CT scan, and MRI & PET Scan (which are non-invasive and quick but very expensive). Our research was performed to develop new non-invasive, safe, quick economical method of detecting cancers and the 1st author already developed for clinically important non-invasive new methods including early stage of present method using his method of localizing accurate organ representation areas of face, eyebrows, upper lip, lower lip, surface and dorsal part of the tongue, surface backs, and palm side of the hands. This accurate localization of the organ representation area of the different parts of the body was performed using electromagnetic field resonance phenomenon between 2 identical molecules or tissues based on our US patented non-invasive method in 1993. Since year 2000, we developed the following non-invasive diagnostic methods that can be quickly identified by the patented simple non-invasive method without using expensive or bulky instrument at any office or field where there is no electricity or instrument available. The following are examples of non-invasive quick method of diagnosis and treatment of cancers using different approaches: 1) Soft red laser beam scanning of different parts of body; 2) By speaking voice; 3) Visible and invisible characteristic abnormalities on different organ representation areas of the different parts of the body, and 4) Mouth, Hand, and Foot Writings of both right and left side of the body. As a consequence of our latest research, we were able to develop a simple method of detecting cancer from existing recorded electrocardiograms. In this article, we are going to describe the method and result of clinical applications on many different cancers of different organs including lung, esophagus, breast, stomach, colon, uterus, ovary, prostate gland, as well as common bone marrow related malignancies such as Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Multiple Myeloma as well as Leukemia.

[Radionuclide evaluation of the mucociliary function of the mucosa of the nasal cavity in chronic lung diseases].

PubMed

Kasatkin, Iu N; Kaganov, S Iu; Vyrenkova, N Iu; Kramer, E F; Rozinova, N N

1987-02-01

The authors presented their first experience of radionuclide assessment of the nasal mucosal transport (NMT) in 39 patients with chronic bronchopulmonary pathology (14 adults and 25 children) to detect patients among them with suspected syndrome of primary ciliary dyskinesia (SPCD). In 18 patients the test was positive excluding SPCD as a cause of a chronic inflammatory pulmonary process. In 21 patients NMT was absent, 2 of these patients had Kartagener's triad serving as a kind of model confirming the data on NMT. The authors proposed the method as a screening test due to its non-invasiveness and simplicity in patients with chronic inflammatory pulmonary diseases in order to detect among them patients with suspected SPCD for further examination using invasive methods.

[Variations in the diagnostic confirmation process between breast cancer mass screening units].

PubMed

Natal, Carmen; Fernández-Somoano, Ana; Torá-Rocamora, Isabel; Tardón, Adonina; Castells, Xavier

2016-01-01

To analyse variations in the diagnostic confirmation process between screening units, variations in the outcome of each episode and the relationship between the use of the different diagnostic confirmation tests and the lesion detection rate. Observational study of variability of the standardised use of diagnostic and lesion detection tests in 34 breast cancer mass screening units participating in early-detection programmes in three Spanish regions from 2002-2011. The diagnostic test variation ratio in percentiles 25-75 ranged from 1.68 (further appointments) to 3.39 (fine-needle aspiration). The variation ratio in detection rates of benign lesions, ductal carcinoma in situ and invasive cancer were 2.79, 1.99 and 1.36, respectively. A positive relationship between rates of testing and detection rates was found with fine-needle aspiration-benign lesions (R(2): 0.53), fine-needle aspiration-invasive carcinoma (R(2): 0 28), core biopsy-benign lesions (R(2): 0.64), core biopsy-ductal carcinoma in situ (R(2): 0.61) and core biopsy-invasive carcinoma (R(2): 0.48). Variation in the use of invasive tests between the breast cancer screening units participating in early-detection programmes was found to be significantly higher than variations in lesion detection. Units which conducted more fine-needle aspiration tests had higher benign lesion detection rates, while units that conducted more core biopsies detected more benign lesions and cancer. Copyright © 2016 SESPAS. Published by Elsevier Espana. All rights reserved.

Non-invasive prenatal diagnosis using cell-free fetal DNA technology: applications and implications.

PubMed

Hall, Alison; Bostanci, A; Wright, C F

2010-01-01

Cell-free fetal DNA and RNA circulating in maternal blood can be used for the early non-invasive prenatal diagnosis (NIPD) of an increasing number of genetic conditions, both for pregnancy management and to aid reproductive decision-making. Here we present a brief review of the scientific and clinical status of the technology, and an overview of key ethical, legal and social issues raised by the analysis of cell-free fetal DNA for NIPD. We suggest that the less invasive nature of the technology brings some distinctive issues into focus, such as the possibility of broader uptake of prenatal diagnosis and access to the technology directly by the consumer via the internet, which have not been emphasised in previous work in this area. We also revisit significant issues that are familiar from previous debates about prenatal testing. Since the technology seems to transect existing distinctions between screening and diagnostic tests, there are important implications for the form and process involved in obtaining informed consent or choice. This analysis forms part of the work undertaken by a multidisciplinary group of experts which made recommendations about the implementation of this technology within the UK National Health Service. Copyright 2010 S. Karger AG, Basel.

Screening history of cervical cancers in Emilia-Romagna, Italy: defining priorities to improve cervical cancer screening.

PubMed

Rossi, Paolo Giorgi; Caroli, Stefania; Mancini, Silvia; de' Bianchi, Priscilla Sassoli; Finarelli, Alba C; Naldoni, Carlo; Bucchi, Lauro; Falcini, Fabio

2015-03-01

Most invasive cervical cancers in industrialized countries are due to the lack of Pap test coverage, very few are due to screening failures. This study aimed at quantifying the proportion of invasive cancers occurring in nonscreened or underscreened women and that in women with a previous negative screening, that is, screening failure, during the first two screening rounds (1996-2002) and in the following rounds (2003-2008) in the Emilia-Romagna region. All cases of invasive cancers registered in the regional cancer registry between 1996 and 2008 were classified according to screening history through a record linkage with the screening programme registry. The incidence significantly decreased from 11.6/100 000 to 8.7/100 000; this decrease is due to a reduction in squamous cell cancers (annual percentage change -6.2; confidence interval: -7.8, -4.6) and advanced cancers (annual percentage change -6.6; confidence interval: -8.8, -4.3), whereas adenocarcinomas and microinvasive cancers were essentially stable. The proportion of cancers among women not yet invited and among nonresponders decreased over the two periods, from 45.5 to 33.3%. In contrast, the proportion of women with a previous negative Pap test less than 5 years and 5 years or more before cancer incidence increased from 5.7 to 13.3% and from 0.3 to 5.5%, respectively. Although nonattendance of the screening programme remains the main barrier to cervical cancer control, the introduction of a more sensitive test, such as the human papillomavirus DNA test, could significantly reduce the burden of disease.

Development and validation of a measure of informed choice for women undergoing non-invasive prenatal testing for aneuploidy

PubMed Central

Lewis, Celine; Hill, Melissa; Skirton, Heather; Chitty, Lyn S

2016-01-01

Non-invasive prenatal testing (NIPT) using cell-free DNA for aneuploidy is a highly accurate screening test; however, concerns exist around the potential for routinisation of testing. The multidimensional measure of informed choice (MMIC) is a quantitative instrument developed to assess informed choice for Down syndrome screening (DSS). We have validated a modified MMIC for NIPT and measured informed choice among women offered NIPT in a public health service. The measure was distributed to women recruited across eight maternity units in the United Kingdom who had accepted DSS. Construct validity was assessed by simultaneously conducting qualitative interviews. Five hundred and eighty-five questionnaires were completed and 45 interviews conducted after blood-draw (or equivalent for those that declined NIPT). The measure demonstrated good internal consistency and internal validity. Results indicate the vast majority of women (89%) made an informed choice; 95% were judged to have good knowledge, 88% had a positive attitude and 92% had deliberated. Of the 11% judged to have made an uninformed choice, 55% had not deliberated, 41% had insufficient knowledge, and 19% had a negative attitude. Ethnicity (OR=2.78, P=0.003) and accepting NIPT (OR=16.05, P=0.021) were found to be significant predictors of informed choice. The high rate of informed choice is likely to reflect the importance placed on the provision of pre-test counselling in this study. It will be vital to ensure that this is maintained once NIPT is offered in routine clinical practice. PMID:26508572

Development and validation of a measure of informed choice for women undergoing non-invasive prenatal testing for aneuploidy.

PubMed

Lewis, Celine; Hill, Melissa; Skirton, Heather; Chitty, Lyn S

2016-06-01

Non-invasive prenatal testing (NIPT) using cell-free DNA for aneuploidy is a highly accurate screening test; however, concerns exist around the potential for routinisation of testing. The multidimensional measure of informed choice (MMIC) is a quantitative instrument developed to assess informed choice for Down syndrome screening (DSS). We have validated a modified MMIC for NIPT and measured informed choice among women offered NIPT in a public health service. The measure was distributed to women recruited across eight maternity units in the United Kingdom who had accepted DSS. Construct validity was assessed by simultaneously conducting qualitative interviews. Five hundred and eighty-five questionnaires were completed and 45 interviews conducted after blood-draw (or equivalent for those that declined NIPT). The measure demonstrated good internal consistency and internal validity. Results indicate the vast majority of women (89%) made an informed choice; 95% were judged to have good knowledge, 88% had a positive attitude and 92% had deliberated. Of the 11% judged to have made an uninformed choice, 55% had not deliberated, 41% had insufficient knowledge, and 19% had a negative attitude. Ethnicity (OR=2.78, P=0.003) and accepting NIPT (OR=16.05, P=0.021) were found to be significant predictors of informed choice. The high rate of informed choice is likely to reflect the importance placed on the provision of pre-test counselling in this study. It will be vital to ensure that this is maintained once NIPT is offered in routine clinical practice.

Electronic nose screening of ethanol release during sol-gel encapsulation. A novel non-invasive method to test silica polymerisation.

PubMed

Lovino, Magalí; Cardinal, M Fernanda; Zubiri, Diana B V; Bernik, Delia L

2005-12-15

Porous silica matrices prepared by sol-gel process yield biocompatible materials adequate for encapsulation of biomolecules or drugs. The procedure is simple and fast, but when alkoxyde precursors like tetraethoxysilane (TEOS) are used the polymerisation reaction leads to the formation of alcohol as a by-product, which can produce undesirable effects on the activity of entrapped enzymes or modify a drug release kinetic. Therefore, it is critical to determine that no remnant ethanol is left prior using or storing the obtained biomaterial. In this regard, the technique used in the alcohol determination should be non-invasive and non-destructive to preserve the encapsulation device intact and ready to use. In this work we have successfully used a portable electronic nose (e-nose) for the screening of silica polymerisation process during theophylline encapsulation. TEOS reaction was "smelt" since precursor pre-hydrolysis until the end of ethanol release, sensed directly at the headspace of matrices slabs. Measurements showed that ethanol was negligible since 10th day in polymeric slabs of 10 mm width and 2 cm diameter. This first use of e-nose following a polymerisation reaction opens a wide number of putative applications in pharmaceutical and biochemical fields.

Non-invasive molecular imaging for preclinical cancer therapeutic development

PubMed Central

O'Farrell, AC; Shnyder, SD; Marston, G; Coletta, PL; Gill, JH

2013-01-01

Molecular and non-invasive imaging are rapidly emerging fields in preclinical cancer drug discovery. This is driven by the need to develop more efficacious and safer treatments, the advent of molecular-targeted therapeutics, and the requirements to reduce and refine current preclinical in vivo models. Such bioimaging strategies include MRI, PET, single positron emission computed tomography, ultrasound, and optical approaches such as bioluminescence and fluorescence imaging. These molecular imaging modalities have several advantages over traditional screening methods, not least the ability to quantitatively monitor pharmacodynamic changes at the cellular and molecular level in living animals non-invasively in real time. This review aims to provide an overview of non-invasive molecular imaging techniques, highlighting the strengths, limitations and versatility of these approaches in preclinical cancer drug discovery and development. PMID:23488622

First-trimester contingent screening for trisomies 21, 18 and 13 by biomarkers and maternal blood cell-free DNA testing.

PubMed

Nicolaides, K H; Syngelaki, A; Poon, L C; Gil, M M; Wright, D

2014-01-01

To examine potential performance of screening for trisomies by cell-free (cf) DNA testing in maternal blood contingent on results of first-line testing by combinations of fetal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index (DV PIV), and serum-free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). Performance was estimated for firstly, screening by cfDNA in all pregnancies and secondly, cfDNA testing contingent on results of first-line testing by combinations of ultrasound and biochemical markers. In first-line screening by cfDNA testing, the detection rate for trisomy 21 and trisomies 18 or 13 would be 99 and 96%, respectively, after invasive testing in 1% of the population. In contingent screening, a detection rate of 98% for trisomy 21 and 96% for trisomy 18 or 13, at an invasive testing rate of 0.7%, can be achieved by carrying out cfDNA testing in about 35, 20 and 11% of cases identified by first-line screening with the combined test alone (age, NT, FHR, β-hCG, PAPP-A), the combined test plus PLGF and AFP and the combined test plus PLGF, AFP and DV PIV, respectively. Effective first-trimester screening for trisomies can be achieved by contingent screening incorporating biomarkers and cfDNA testing. © 2013 S. Karger AG, Basel.

Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women.

PubMed

Badeau, Mylène; Lindsay, Carmen; Blais, Jonatan; Nshimyumukiza, Leon; Takwoingi, Yemisi; Langlois, Sylvie; Légaré, France; Giguère, Yves; Turgeon, Alexis F; Witteman, William; Rousseau, François

2017-11-10

Common fetal aneuploidies include Down syndrome (trisomy 21 or T21), Edward syndrome (trisomy 18 or T18), Patau syndrome (trisomy 13 or T13), Turner syndrome (45,X), Klinefelter syndrome (47,XXY), Triple X syndrome (47,XXX) and 47,XYY syndrome (47,XYY). Prenatal screening for fetal aneuploidies is standard care in many countries, but current biochemical and ultrasound tests have high false negative and false positive rates. The discovery of fetal circulating cell-free DNA (ccfDNA) in maternal blood offers the potential for genomics-based non-invasive prenatal testing (gNIPT) as a more accurate screening method. Two approaches used for gNIPT are massively parallel shotgun sequencing (MPSS) and targeted massively parallel sequencing (TMPS). To evaluate and compare the diagnostic accuracy of MPSS and TMPS for gNIPT as a first-tier test in unselected populations of pregnant women undergoing aneuploidy screening or as a second-tier test in pregnant women considered to be high risk after first-tier screening for common fetal aneuploidies. The gNIPT results were confirmed by a reference standard such as fetal karyotype or neonatal clinical examination. We searched 13 databases (including MEDLINE, Embase and Web of Science) from 1 January 2007 to 12 July 2016 without any language, search filter or publication type restrictions. We also screened reference lists of relevant full-text articles, websites of private prenatal diagnosis companies and conference abstracts. Studies could include pregnant women of any age, ethnicity and gestational age with singleton or multifetal pregnancy. The women must have had a screening test for fetal aneuploidy by MPSS or TMPS and a reference standard such as fetal karyotype or medical records from birth. Two review authors independently carried out study selection, data extraction and quality assessment (using the QUADAS-2 tool). Where possible, hierarchical models or simpler alternatives were used for meta-analysis. Sixty-five studies of 86,139 pregnant women (3141 aneuploids and 82,998 euploids) were included. No study was judged to be at low risk of bias across the four domains of the QUADAS-2 tool but applicability concerns were generally low. Of the 65 studies, 42 enrolled pregnant women at high risk, five recruited an unselected population and 18 recruited cohorts with a mix of prior risk of fetal aneuploidy. Among the 65 studies, 44 evaluated MPSS and 21 evaluated TMPS; of these, five studies also compared gNIPT with a traditional screening test (biochemical, ultrasound or both). Forty-six out of 65 studies (71%) reported gNIPT assay failure rate, which ranged between 0% and 25% for MPSS, and between 0.8% and 7.5% for TMPS.In the population of unselected pregnant women, MPSS was evaluated by only one study; the study assessed T21, T18 and T13. TMPS was assessed for T21 in four studies involving unselected cohorts; three of the studies also assessed T18 and 13. In pooled analyses (88 T21 cases, 22 T18 cases, eight T13 cases and 20,649 unaffected pregnancies (non T21, T18 and T13)), the clinical sensitivity (95% confidence interval (CI)) of TMPS was 99.2% (78.2% to 100%), 90.9% (70.0% to 97.7%) and 65.1% (9.16% to 97.2%) for T21, T18 and T13, respectively. The corresponding clinical specificity was above 99.9% for T21, T18 and T13.In high-risk populations, MPSS was assessed for T21, T18, T13 and 45,X in 30, 28, 20 and 12 studies, respectively. In pooled analyses (1048 T21 cases, 332 T18 cases, 128 T13 cases and 15,797 unaffected pregnancies), the clinical sensitivity (95% confidence interval (CI)) of MPSS was 99.7% (98.0% to 100%), 97.8% (92.5% to 99.4%), 95.8% (86.1% to 98.9%) and 91.7% (78.3% to 97.1%) for T21, T18, T13 and 45,X, respectively. The corresponding clinical specificities (95% CI) were 99.9% (99.8% to 100%), 99.9% (99.8% to 100%), 99.8% (99.8% to 99.9%) and 99.6% (98.9% to 99.8%). In this risk group, TMPS was assessed for T21, T18, T13 and 45,X in six, five, two and four studies. In pooled analyses (246 T21 cases, 112 T18 cases, 20 T13 cases and 4282 unaffected pregnancies), the clinical sensitivity (95% CI) of TMPS was 99.2% (96.8% to 99.8%), 98.2% (93.1% to 99.6%), 100% (83.9% to 100%) and 92.4% (84.1% to 96.5%) for T21, T18, T13 and 45,X respectively. The clinical specificities were above 100% for T21, T18 and T13 and 99.8% (98.3% to 100%) for 45,X. Indirect comparisons of MPSS and TMPS for T21, T18 and 45,X showed no statistical difference in clinical sensitivity, clinical specificity or both. Due to limited data, comparative meta-analysis of MPSS and TMPS was not possible for T13.We were unable to perform meta-analyses of gNIPT for 47,XXX, 47,XXY and 47,XYY because there were very few or no studies in one or more risk groups. These results show that MPSS and TMPS perform similarly in terms of clinical sensitivity and specificity for the detection of fetal T31, T18, T13 and sex chromosome aneuploidy (SCA). However, no study compared the two approaches head-to-head in the same cohort of patients. The accuracy of gNIPT as a prenatal screening test has been mainly evaluated as a second-tier screening test to identify pregnancies at very low risk of fetal aneuploidies (T21, T18 and T13), thus avoiding invasive procedures. Genomics-based non-invasive prenatal testing methods appear to be sensitive and highly specific for detection of fetal trisomies 21, 18 and 13 in high-risk populations. There is paucity of data on the accuracy of gNIPT as a first-tier aneuploidy screening test in a population of unselected pregnant women. With respect to the replacement of invasive tests, the performance of gNIPT observed in this review is not sufficient to replace current invasive diagnostic tests.We conclude that given the current data on the performance of gNIPT, invasive fetal karyotyping is still the required diagnostic approach to confirm the presence of a chromosomal abnormality prior to making irreversible decisions relative to the pregnancy outcome. However, most of the gNIPT studies were prone to bias, especially in terms of the selection of participants.

[Significance of Septin9 gene methylation detection of plasma circulation DNA in colorectal cancer screening].

PubMed

Kang, Qian; Jin, Peng; Yang, Lang; Wang, Xin; An, Hejuan; Liu, Lili; Li, Na; Sheng, Jianqiu

2014-12-30

To explore the role of detecting the methylation status of gene Septin9 (SEPT9) in plasma for colorectal cancer screening in Chinese population. Patients were collected from Beijing Military General Hospital since September 2013 to February 2014. The performance of SEPT9 assay was validated in a single-blind study of 80 cases with colonoscopy and pathologically verified colorectal cancer and 52 normal controls. The detection of Septin9 gene methylation in peripheral blood was performed by fluorescence quantitative polymerase chain reaction (PCR). And immunoassay fecal occult blood test was conducted to compare the superiority of methylated Septin9 for screening colorectal cancer. The Septin9 assay successfully identified 75.0% (95%CI:64.7%-83.6%) of cancers at a specificity of 98.1% (95%CI:90.9%-99.9%). And it was superior to fecal occult blood screening for colorectal cancer (sensitivity 79.5% vs 53.8%, P < 0.05). Determination of SEPT9 methylation status is an innovative non-invasive plasma screening test for colorectal cancer.

Detection of fetal sex chromosome aneuploidy by massively parallel sequencing of maternal plasma DNA: initial experience in a Chinese hospital.

PubMed

Yao, H; Jiang, F; Hu, H; Gao, Y; Zhu, Z; Zhang, H; Wang, Y; Guo, Y; Liu, L; Yuan, Y; Zhou, L; Wang, J; Du, B; Qu, N; Zhang, R; Dong, Y; Xu, H; Chen, F; Jiang, H; Liu, Y; Zhang, L; Tian, Z; Liu, Q; Zhang, C; Pan, X; Yang, S; Zhao, L; Wang, W; Liang, Z

2014-07-01

To evaluate the performance of a massively parallel sequencing (MPS)-based test in detecting fetal sex chromosome aneuploidy (SCA) and to present a comprehensive clinical counseling protocol for SCA-positive patients. This was a retrospective study in a large patient cohort of 5950 singleton pregnancies which underwent MPS-based testing as a prenatal screening test for trisomies 21, 18 and 13, with X and Y chromosomes as secondary findings, in Southwest Hospital in China. MPS-based SCA-positive women were offered the choice of knowing whether their SCA results were positive and those who did commenced a two-stage post-test clinical counseling protocol. In Stage 1, general information about SCA was given, and women were given the option of invasive testing for confirmation of findings; in Stage 2, those who had chosen to undergo invasive testing were informed about the specific SCA affecting their fetus and their management options. Thirty-three cases were classified as SCA-positive by MPS-based testing. After Stage 1 of the two-stage post-test clinical counseling session, 33 (100%) of these pregnant women chose to know the screening test results, and 25 (75.76%) underwent an invasive diagnostic procedure and karyotype analysis, in one of whom karyotyping failed. In thirteen cases, karyotyping confirmed the MPS-based test results (two X0 cases, seven XXX cases, three XXY cases and one XYY case), giving a positive predictive value of 54.17% (13/24 cases confirmed by karyotyping). After post-test clinical counseling session Stage 2, seven women chose to terminate the pregnancy: one X0 case, two XXX cases, the three XXY cases and the single XYY case. Six women decided to continue with pregnancy: one X0 case and five XXX cases. Our study showed the feasibility of clinical application of the MPS-based test in the non-invasive detection of fetal SCA. Together with a two-stage post-test clinical counseling protocol, it leads to a well-informed decision-making procedure. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Valuing experience factors in the provision of Chlamydia screening: an application to women attending the family planning clinic.

PubMed

Watson, Verity; Ryan, Mandy; Watson, Emma

2009-06-01

To examine women's preferences for characteristics of chlamydia screening. Chlamydia trachomatis is the most common curable sexually transmitted disease. To design effective screening programs, it is important to fully capture the benefits of screening to patients. Thus, the value of experience factors must be considered alongside health outcomes. A self-complete discrete choice experiment questionnaire was administered to women attending a family planning clinic. Chlamydia screening was described by five characteristics: location of screening; type of screening test; cost of screening test; risk of developing pelvic inflammatory disease if chlamydia is untreated; and support provided when receiving results. One hundred twenty-six women completed the questionnaire. Respondents valued characteristics of the care experience. Screening was valued at 15 pound; less invasive screening tests increase willingness to pay by 7 pound, and more invasive tests reduce willingness to pay by 3.50 pound. The most preferred screening location was the family planning clinic, valued at 5 pound. The support of a trained health-care professional when receiving results was valued at 4 pound. Respondents under 25 years and those in a casual relationship were less likely to be screened. Women valued experience factors in the provision of chlamydia screening. To correctly value these screening programs and to predict uptake, cost-effectiveness studies should take such values into account. Failure to do this may result in incorrect policy recommendations.

Rapid detection and differentiation of Staphylococcus colonies using an optical scattering technology.

PubMed

Alsulami, Tawfiq S; Zhu, Xingyue; Abdelhaseib, Maha Usama; Singh, Atul K; Bhunia, Arun K

2018-05-24

Staphylococcus species are a major pathogen responsible for nosocomial infections and foodborne illnesses. We applied a laser-based BARDOT (bacterial rapid detection using optical scattering technology) for rapid colony screening and detection of Staphylococcus on an agar plate and differentiate these from non-Staphylococcus spp. Among the six growth media tested, phenol red mannitol agar (PRMA) was found most suitable for building the Staphylococcus species scatter image libraries. Scatter image library for Staphylococcus species gave a high positive predictive value (PPV 87.5-100%) when tested against known laboratory strains of Staphylococcus spp., while the PPV against non-Staphylococcus spp. was 0-38%. A total of nine naturally contaminated bovine raw milk and ready-to-eat chicken salad samples were tested, and BARDOT detected Staphylococcus including Staphylococcus aureus with 80-100% PPV. Forty-five BARDOT-identified bacterial isolates from naturally contaminated foods were further confirmed by tuf and nuc gene-specific PCR and 16S rRNA gene sequence. This label-free, non-invasive on-plate colony screening technology can be adopted by the food industries, biotechnology companies, and public health laboratories for Staphylococcus species detection including S. aureus from various samples for food safety and public health management. Graphical abstract.

Future microfluidic and nanofluidic modular platforms for nucleic acid liquid biopsy in precision medicine

PubMed Central

Egatz-Gomez, Ana; Wang, Ceming; Klacsmann, Flora; Pan, Zehao; Marczak, Steve; Wang, Yunshan; Sun, Gongchen; Senapati, Satyajyoti; Chang, Hsueh-Chia

2016-01-01

Nucleic acid biomarkers have enormous potential in non-invasive diagnostics and disease management. In medical research and in the near future in the clinics, there is a great demand for accurate miRNA, mRNA, and ctDNA identification and profiling. They may lead to screening of early stage cancer that is not detectable by tissue biopsy or imaging. Moreover, because their cost is low and they are non-invasive, they can become a regular screening test during annual checkups or allow a dynamic treatment program that adjusts its drug and dosage frequently. We briefly review a few existing viral and endogenous RNA assays that have been approved by the Federal Drug Administration. These tests are based on the main nucleic acid detection technologies, namely, quantitative reverse transcription polymerase chain reaction (PCR), microarrays, and next-generation sequencing. Several of the challenges that these three technologies still face regarding the quantitative measurement of a panel of nucleic acids are outlined. Finally, we review a cluster of microfluidic technologies from our group with potential for point-of-care nucleic acid quantification without nucleic acid amplification, designed to overcome specific limitations of current technologies. We suggest that integration of these technologies in a modular design can offer a low-cost, robust, and yet sensitive/selective platform for a variety of precision medicine applications. PMID:27190565

A case of placental trisomy 18 mosaicism causing a false negative NIPT result.

PubMed

Yang, Jiexia; Qi, Yiming; Guo, Fangfang; Hou, Yaping; Peng, Haishan; Wang, Dongmei; Oy, Haoxin; Yin, Aihua

2017-01-01

The non-invasive prenatal testing that evaluates circulating cell free DNA, and has been established as an additional pregnancy test for detecting the common fetal trisomies 21, 18 and 13 is rapidly revolutionizing prenatal screening as a result of its increased sensitivity and specificity. However, false positive and false negative results still exist. We presented a case in which the non-invasive prenatal testing results were normal at 15 gestational age (GA), but an ultrasound examination at 30GA showed that the fetus had heart abnormalities, and the third trimester ultrasound at 33GA noted multiple anomalies including a 3.0 mm ventricular septal defect. Along with cordocentesis at 33GA, the cord blood sample cytogenetics analysis showed a mos 47,XN,+18[61]/46,XN[39] T18 karyotype. Six placental biopsies confirmed that the chromosome 18 placenta chimerism ratio had changed from 33% to 72%. Ultimately, the pregnancy was interrupted at 34GA. We presented this case to highlight the need to clearly explain false positive or false negative results to patients. We believe that this information will also influence the development of future diagnostic test methodologies.

Diagnostic accuracy of functional, imaging and biochemical tests for patients presenting with chest pain to the emergency department: A systematic review and meta-analysis.

PubMed

Iannaccone, Mario; Gili, Sebastiano; De Filippo, Ovidio; D'Amico, Salvatore; Gagliardi, Marco; Bertaina, Maurizio; Mazzilli, Silvia; Rettegno, Sara; Bongiovanni, Federica; Gatti, Paolo; Ugo, Fabrizio; Boccuzzi, Giacomo G; Colangelo, Salvatore; Prato, Silvia; Moretti, Claudio; D'Amico, Maurizio; Noussan, Patrizia; Garbo, Roberto; Hildick-Smith, David; Gaita, Fiorenzo; D'Ascenzo, Fabrizio

2018-01-01

Non-invasive ischaemia tests and biomarkers are widely adopted to rule out acute coronary syndrome in the emergency department. Their diagnostic accuracy has yet to be precisely defined. Medline, Cochrane Library CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1 September 2016, end date 1 December 2016). Prospective studies (observational or randomised controlled trial) comparing functional/imaging or biochemical tests for patients presenting with chest pain to the emergency department were included. Overall, 77 studies were included, for a total of 49,541 patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T protocols did not show significant differences in their ability to detect acute coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95% confidence interval 0.79-0.94) and 0.84 (0.74-0.9) vs 0.89 (0.78-0.94) and 0.83 (0.70-0.92), respectively. The addition of copeptin to troponin increased sensitivity and reduced specificity, without improving diagnostic accuracy. The diagnostic value of non-invasive tests for patients without troponin increase was tested. Coronary computed tomography showed the highest level of diagnostic accuracy (sensitivity 0.93 (0.81-0.98) and specificity 0.90 (0.93-0.94)), along with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77-0.91) and specificity 0.92 (0.83-0.96)). Stress echography was inferior to coronary computed tomography but non-inferior to myocardial perfusion scintigraphy, while exercise testing showed the lower level of diagnostic accuracy. Fast and six-hour highly sensitive troponin T protocols provide an overall similar level of diagnostic accuracy to detect acute coronary syndrome. Among the non-invasive ischaemia tests for patients without troponin increase, coronary computed tomography and myocardial perfusion scintigraphy showed the highest sensitivity and specificity.

Antenatal diagnosis of Down syndrome: how good is state of the art.

PubMed

Mittal, Riju; Varghese, Raji Mathew; Puliyel, Jacob M

2009-01-01

A newborn with Down syndrome can be expected once in a thousand deliveries. Amniocentesis for karyotyping of foetal cells or detection of foetal cell in the maternal circulation ie, fluorescent in-situ hybridisation (FISH) and karyotyping, are definitive methods of making the diagnosis antenatally. The cost of doing this routinely in all pregnancies is prohibitive. This has led to dependence on screening tests, to select women more likely to be carrying a Down foetus, to offer karyotyping in a more cost efficient manner. Unfortunately, these screening criteria, namely maternal age, biochemical markers and ultrasound pointers, are rather insensitive and miss a large number of cases of Down syndrome. At the same time they are very non-specific, picking up a large number of false positive cases, resulting in undue anxiety and unnecessary alarm in a large number of mothers. Till a non-invasive, definitive test, like FISH can be routinely used in all pregnancies at affordable costs, accurate antenatal diagnosis on a community basis will be a hit and miss affair.

Time and travel costs incurred by women attending antenatal tests: A costing study.

PubMed

Verhoef, Talitha I; Daley, Rebecca; Vallejo-Torres, Laura; Chitty, Lyn S; Morris, Stephen

2016-09-01

to estimate the costs to women, their friends and family for different antenatal tests in the Down's syndrome (DS) screening pathway. questionnaire-based costing study. eight maternity clinics across the UK. pregnant women (n=574) attending an appointment for DS screening, NIPT or invasive testing between December 2013 and September 2014. using data collected from the questionnaires we calculated the total costs to women by multiplying the time spent at the hospital and travelling to and from it by the opportunity costs of the women and accompanying person and adding travel and childcare costs. Assumptions about the value of opportunity costs were tested in one-way sensitivity analyses. The main outcome measure was the mean cost to the women and friends/family for each test (DS screening, NIPT, and invasive testing). mean costs to women and their family/friend were £33.96 per visit, of which £22.47 were time costs, £9.15 were travel costs and £2.34 were childcare costs. Costs were lowest for NIPT (£22), £32 for DS screening (£44 if combined with NIPT), and highest for invasive testing (£60). Sensitivity analysis revealed that variations around the value of leisure time opportunity costs had the largest influence on the results. there are considerable costs to women, their friends and family when attending different tests in the DS screening pathway. when assessing the cost-effectiveness of changes to this pathway, costs to women should be considered. Copyright © 2016 Elsevier Ltd. All rights reserved.

Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS)

PubMed Central

Lee, Matthew M Y; Petrie, Mark C; Rocchiccioli, Paul; Simpson, Joanne; Jackson, Colette; Brown, Ammani; Corcoran, David; Mangion, Kenneth; McEntegart, Margaret; Shaukat, Aadil; Rae, Alan; Hood, Stuart; Peat, Eileen; Findlay, Iain; Murphy, Clare; Cormack, Alistair; Bukov, Nikolay; Balachandran, Kanarath; Papworth, Richard; Ford, Ian; Briggs, Andrew; Berry, Colin

2016-01-01

Introduction There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. Methods and analysis 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. Trial registration number NCT01895751 (ClinicalTrials.gov). PMID:27110377

Recent developments in genetics and medically assisted reproduction: from research to clinical applications.

PubMed

Harper, J C; Aittomäki, K; Borry, P; Cornel, M C; de Wert, G; Dondorp, W; Geraedts, J; Gianaroli, L; Ketterson, K; Liebaers, I; Lundin, K; Mertes, H; Morris, M; Pennings, G; Sermon, K; Spits, C; Soini, S; van Montfoort, A P A; Veiga, A; Vermeesch, J R; Viville, S; Macek, M

2018-01-01

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.

Rating of CCl(4)-induced rat liver fibrosis by blood serum glycomics.

PubMed

Desmyter, Liesbeth; Fan, Ye-Dong; Praet, Marleen; Jaworski, Tomasz; Vervecken, Wouter; De Hemptinne, Bernard; Contreras, Roland; Chen, Cuiying

2007-07-01

Non-invasive staging of human liver fibrosis is a desirable objective that remains under extensive evaluation. Animal model systems are often used for studying human liver disease and screening antifibrotic compounds. The aim of the present study was to investigate the potential use of serum N-glycan profiles to evaluate liver fibrosis in a rat model. Liver fibrosis and cirrhosis were induced in rats by oral administration of CCl(4). Liver injury was assessed biochemically (alanine aminotransferase [ALT] activity, aspartate aminotransferase [AST] activity and total bilirubin) and histologically. The N-glycan profile (GlycoTest) was performed using DNA sequencer-assisted-fluorophore-assisted carbohydrate electrophoresis technology. In parallel, the effect of cotreatment with antifibrotic interferon-gamma (IFN-gamma) was studied. The biopsy scoring system showed that CCl(4) induced early fibrosis (F < 1-2) in rats after 3 weeks of treatment, and cirrhosis (F4) after 12 weeks. Significant increases in ALT activity, AST activity and total bilirubin levels were detected only after 12 weeks of CCl(4) treatment. GlycoTest showed three glycans were significantly altered in the CCl(4)-goup. Peak 3 started at week 6, at an early stage in fibrosis development (F < 1-2), whereas peaks 4 and 5 occurred at week 9, at which time mild liver fibrosis (F = 1-2) had developed. The changes in the CCl(4)-IFN-gamma group were intermediate between the CCl(4)- and the control groups. The GlycoTest is much more sensitive than biochemical tests for evaluating liver fibrosis/cirrhosis in the rat model. The test can also be used as a non-invasive marker for screening and monitoring the antifibrotic activity of potential therapeutic compounds.

Comparison of non-invasive measures of cholinergic and allergic airway responsiveness in rats.

PubMed

Glaab, T; Hecker, H; Stephan, M; Baelder, R; Braun, A; Korolewitz, R; Krug, N; Hoymann, H G

2006-04-01

Non-invasive analysis of tidal expiratory flow parameters such as Tme/TE (time needed to reach peak expiratory flow divided by total expiratory time) or midexpiratory tidal flow (EF50) has been shown useful for phenotypic characterization of lung function in humans and animal models. In this study, we aimed to compare the utility of two non-invasive measures, EF50 and Tme/TE, to monitor bronchoconstriction to inhaled cholinergic and allergic challenges in Brown-Norway rats. Non-invasive measurements of Tme/TE and EF50 were paralleled by invasive recordings of Tme/TE, EF50 and pulmonary conductance (GL). First, dose-response studies with acetylcholine were performed in naive rats, showing that EF50 better than Tme/TE reflected the dose-related changes as observed with the classical invasive outcome parameter GL. The subsequent determination of allergen-specific early airway responsiveness (EAR) showed that ovalbumin-sensitized and -challenged rats exhibited airway inflammation and allergen-specific EAR. Again, EF50 was more sensitive than Tme/TE in detecting the allergen-specific EAR recorded with invasive and non-invasive lung function methods and agreed well with classical GL measurements. We conclude that non-invasive assessment of EF50 is significantly superior to Tme/TE and serves as a suitable and valid tool for phenotypic screening of cholinergic and allergic airway responsiveness in rats.

The role of chemical antifouling defence in the invasion success of Sargassum muticum: A comparison of native and invasive brown algae

PubMed Central

Schwartz, Nicole; Rohde, Sven; Dobretsov, Sergey; Hiromori, Shimabukuro; Schupp, Peter J.

2017-01-01

Competition and fouling defence are important traits that may facilitate invasions by non-indigenous species. The ‘novel weapons hypothesis’ (NWH) predicts that the invasive success of exotic species is closely linked to the possession of chemical defence compounds that the recipient community in the new range is not adapted to. In order to assess whether chemical defence traits contribute to invasion success, anti-bacterial, anti-quorum sensing, anti-diatom, anti-larval and anti-algal properties were investigated for the following algae: a) the invasive brown alga Sargassum muticum from both, its native (Japan) and invasive (Germany) range, b) the two non- or weak invasive species Sargassum fusiforme and Sargassum horneri from Japan, and c) Fucus vesiculosus, a native brown alga from Germany. Crude and surface extracts and lipid fractions of active extracts were tested against common fouling organisms and zygotes of a dominant competing brown alga. Extracts of the native brown alga F. vesiculosus inhibited more bacterial strains (75%) than any of the Sargassum spp. (17 to 29%). However, Sargassum spp. from Japan exhibited the strongest settlement inhibition against the diatom Cylindrotheca closterium, larvae of the bryozoan Bugula neritina and zygotes of the brown alga F. vesiculosus. Overall, extracts of S. muticum from the invasive range were less active compared to those of the native range suggesting an adaptation to lower fouling pressure and competition in the new range resulting in a shift of resource allocation from costly chemical defence to reproduction and growth. Non-invasive Sargassum spp. from Japan was equally defended against fouling and competitors like S. muticum from Japan indicating a necessity to include these species in European monitoring programs. The variable antifouling activity of surface and crude extracts highlights the importance to use both for an initial screening for antifouling activity. PMID:29267326

The role of chemical antifouling defence in the invasion success of Sargassum muticum: A comparison of native and invasive brown algae.

PubMed

Schwartz, Nicole; Rohde, Sven; Dobretsov, Sergey; Hiromori, Shimabukuro; Schupp, Peter J

2017-01-01

Competition and fouling defence are important traits that may facilitate invasions by non-indigenous species. The 'novel weapons hypothesis' (NWH) predicts that the invasive success of exotic species is closely linked to the possession of chemical defence compounds that the recipient community in the new range is not adapted to. In order to assess whether chemical defence traits contribute to invasion success, anti-bacterial, anti-quorum sensing, anti-diatom, anti-larval and anti-algal properties were investigated for the following algae: a) the invasive brown alga Sargassum muticum from both, its native (Japan) and invasive (Germany) range, b) the two non- or weak invasive species Sargassum fusiforme and Sargassum horneri from Japan, and c) Fucus vesiculosus, a native brown alga from Germany. Crude and surface extracts and lipid fractions of active extracts were tested against common fouling organisms and zygotes of a dominant competing brown alga. Extracts of the native brown alga F. vesiculosus inhibited more bacterial strains (75%) than any of the Sargassum spp. (17 to 29%). However, Sargassum spp. from Japan exhibited the strongest settlement inhibition against the diatom Cylindrotheca closterium, larvae of the bryozoan Bugula neritina and zygotes of the brown alga F. vesiculosus. Overall, extracts of S. muticum from the invasive range were less active compared to those of the native range suggesting an adaptation to lower fouling pressure and competition in the new range resulting in a shift of resource allocation from costly chemical defence to reproduction and growth. Non-invasive Sargassum spp. from Japan was equally defended against fouling and competitors like S. muticum from Japan indicating a necessity to include these species in European monitoring programs. The variable antifouling activity of surface and crude extracts highlights the importance to use both for an initial screening for antifouling activity.

Systematic review of cost-effectiveness of myocardial perfusion scintigraphy in patients with ischaemic heart disease: A report from the cardiovascular committee of the European Association of Nuclear Medicine. Endorsed by the European Association of Cardiovascular Imaging.

PubMed

Trägårdh, Elin; Tan, Siok Swan; Bucerius, Jan; Gimelli, Alessia; Gaemperli, Oliver; Lindner, Oliver; Agostini, Denis; Übleis, Christopher; Sciagrà, Roberto; Slart, Riemer H; Underwood, S Richard; Hyafil, Fabien; Hacker, Marcus; Verberne, Hein J

2017-05-01

Coronary artery disease (CAD) is a major cause of death and disability. Several diagnostic tests, such as myocardial perfusion scintigraphy (MPS), are accurate for the detection of CAD, as well as having prognostic value for the prediction of cardiovascular events. Nevertheless, the diagnostic and prognostic value of these tests should be cost-effective and should lead to improved clinical outcome. We have reviewed the literature on the cost-effectiveness of MPS in different circumstances: (i) the diagnosis and management of CAD; (ii) comparison with exercise electrocardiography (ECG) and other imaging tests; (iii) as gatekeeper to invasive coronary angiography (ICA), (iv) the impact of appropriate use criteria; (v) acute chest pain, and (vi) screening of asymptomatic patients with type-2 diabetes. In total 57 reports were included. Although most non-invasive imaging tests are cost-effective compared with alternatives, the data conflict on which non-invasive strategy is the most cost-effective. Different definitions of cost-effectiveness further confound the subject. Computer simulations of clinical diagnosis and management are influenced by the assumptions made. For instance, diagnostic accuracy is often defined against an anatomical standard that is wrongly assumed to be perfect. Conflicting data arise most commonly from these incorrect or differing assumptions. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Galactomannan, β-D-Glucan, and Polymerase Chain Reaction-Based Assays for the Diagnosis of Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

PubMed

Lehrnbecher, Thomas; Robinson, Paula D; Fisher, Brian T; Castagnola, Elio; Groll, Andreas H; Steinbach, William J; Zaoutis, Theoklis E; Negeri, Zelalem F; Beyene, Joseph; Phillips, Bob; Sung, Lillian

2016-11-15

We systematically reviewed and analyzed the available data for galactomannan (GM), β-D-glucan (BG), and polymerase chain reaction (PCR)-based assays to detect invasive fungal disease (IFD) in patients with pediatric cancer or undergoing hematopoietic stem cell transplantation when used as screening tools during immunosuppression or as diagnostic tests in patients presenting with symptoms such as fever during neutropenia (FN). Of 1532 studies screened, 25 studies reported on GM (n = 19), BG (n = 3), and PCR (n = 11). All fungal biomarkers demonstrated highly variable sensitivity, specificity, and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85% to 100% for screening and 70% to 100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of fungal biomarkers in pediatric cancer and HSCT. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Prenatal screening: an ethical agenda for the near future.

PubMed

de Jong, Antina; de Wert, Guido M W R

2015-01-01

Prenatal screening for foetal abnormalities such as Down's syndrome differs from other forms of population screening in that the usual aim of achieving health gains through treatment or prevention does not seem to apply. This type of screening leads to no other options but the choice between continuing or terminating the pregnancy and can only be morally justified if its aim is to provide meaningful options for reproductive choice to pregnant women and their partners. However, this aim should not be understood as maximizing reproductive choice per se. Only if understood as allowing prospective parents to avoid suffering related to living with (a child with) serious disorders and handicaps can prenatal screening be a publicly or collectively funded programme. The alternative of moving prenatal testing outside the healthcare system into the private sector is problematic, as it makes these tests accessible only to those who can afford to pay for it. New developments in prenatal screening will have to be assessed in terms of whether and to what extent they either contribute to or undermine the stated aim of providing meaningful options for reproductive choice. In the light of this criterion, this article discusses the introduction of the new non-invasive prenatal test (NIPT), the tendency to widen the scope of follow-up testing, as well as the possible future scenarios of genome-wide screening and 'prenatal personalised medicine'. The article ends with recommendations for further debate, research and analysis. © 2014 John Wiley & Sons Ltd.

What are the characteristics of breast cancers misclassified as benign by quantitative ultrasound shear wave elastography?

PubMed

Vinnicombe, S J; Whelehan, P; Thomson, K; McLean, D; Purdie, C A; Jordan, L B; Hubbard, S; Evans, A J

2014-04-01

Shear wave elastography (SWE) is a promising adjunct to greyscale ultrasound in differentiating benign from malignant breast masses. The purpose of this study was to characterise breast cancers which are not stiff on quantitative SWE, to elucidate potential sources of error in clinical application of SWE to evaluation of breast masses. Three hundred and two consecutive patients examined by SWE who underwent immediate surgery for breast cancer were included. Characteristics of 280 lesions with suspicious SWE values (mean stiffness >50 kPa) were compared with 22 lesions with benign SWE values (<50 kPa). Statistical significance of the differences was assessed using non-parametric goodness-of-fit tests. Pure ductal carcinoma in situ (DCIS) masses were more often soft on SWE than masses representing invasive breast cancer. Invasive cancers that were soft were more frequently: histological grade 1, tubular subtype, ≤10 mm invasive size and detected at screening mammography. No significant differences were found with respect to the presence of invasive lobular cancer, vascular invasion, hormone and HER-2 receptor status. Lymph node positivity was less common in soft cancers. Malignant breast masses classified as benign by quantitative SWE tend to have better prognostic features than those correctly classified as malignant. • Over 90 % of cancers assessable with ultrasound have a mean stiffness >50 kPa. • 'Soft' invasive cancers are frequently small (≤10 mm), low grade and screen-detected. • Pure DCIS masses are more often soft than invasive cancers (>40 %). • Large symptomatic masses are better evaluated with SWE than small clinically occult lesions. • When assessing small lesions, 'softness' should not raise the threshold for biopsy.

Epigenetic inactivation of VGF associated with Urothelial Cell Carcinoma and its potential as a non-invasive biomarker using urine.

PubMed

Hayashi, Masamichi; Bernert, Heike; Kagohara, Luciane Tsukamoto; Maldonado, Leonel; Brait, Mariana; Schoenberg, Mark; Bivalacqua, Trinity; Netto, George J; Koch, Wayne; Sidransky, David; Hoque, Mohammad O

2014-05-30

To identify new epigenetic markers and further characterize Urothelial Cell Carcinoma (UCC), we tested the promoter methylation (PM) status of 19 genes previously identified as cancer specific methylated genes in other solid tumors. We used bisulfite sequencing, methylation specific PCR and quantitative methylation specific PCR (QMSP) to test the PM status of 19 genes in urothelial cancer cell lines. Among the 19 genes tested, VGF was found to be completely methylated in several UCC cell lines. VGF QMSP analysis showed that methylation values of almost all the primary 19 UCC tissues were higher than the paired normal tissues (P=0.009). In another cohort, 12/35 (34.3%) of low grade UCC cases displayed VGF methylation. As a biomarker for non-invasive detection of UCC, VGF showed a significantly higher frequency of methylation in urine from UCC cases (8/20) compared to controls (1/20) (P=0.020). After treatment of cell lines with 5-Aza-2'-deoxycytidine, VGF was robustly re-expressed. Forced expression of VGF in bladder cancer cell lines inhibited cell growth. Selection of candidates from genome-wide screening approach in other solid tumors successfully identified UCC specific methylated genes.

On the Estimation of Disease Prevalence by Latent Class Models for Screening Studies Using Two Screening Tests with Categorical Disease Status Verified in Test Positives Only

PubMed Central

Chu, Haitao; Zhou, Yijie; Cole, Stephen R.; Ibrahim, Joseph G.

2010-01-01

Summary To evaluate the probabilities of a disease state, ideally all subjects in a study should be diagnosed by a definitive diagnostic or gold standard test. However, since definitive diagnostic tests are often invasive and expensive, it is generally unethical to apply them to subjects whose screening tests are negative. In this article, we consider latent class models for screening studies with two imperfect binary diagnostic tests and a definitive categorical disease status measured only for those with at least one positive screening test. Specifically, we discuss a conditional independent and three homogeneous conditional dependent latent class models and assess the impact of misspecification of the dependence structure on the estimation of disease category probabilities using frequentist and Bayesian approaches. Interestingly, the three homogeneous dependent models can provide identical goodness-of-fit but substantively different estimates for a given study. However, the parametric form of the assumed dependence structure itself is not “testable” from the data, and thus the dependence structure modeling considered here can only be viewed as a sensitivity analysis concerning a more complicated non-identifiable model potentially involving heterogeneous dependence structure. Furthermore, we discuss Bayesian model averaging together with its limitations as an alternative way to partially address this particularly challenging problem. The methods are applied to two cancer screening studies, and simulations are conducted to evaluate the performance of these methods. In summary, further research is needed to reduce the impact of model misspecification on the estimation of disease prevalence in such settings. PMID:20191614

Genetic counselors' experience with cell-free fetal DNA testing as a prenatal screening option for aneuploidy.

PubMed

Horsting, Julie M H; Dlouhy, Stephen R; Hanson, Katelyn; Quaid, Kimberly; Bai, Shaochun; Hines, Karrie A

2014-06-01

First identified in 1997, cell-free fetal DNA (cffDNA) has just recently been used to detect fetal aneuploidy of chromosomes 13, 18, and 21, showing its potential to revolutionize prenatal genetic testing as a non-invasive screening tool. Although this technological advancement is exciting and has certain medical applications, it has been unclear how it will be implemented in a clinical setting. Genetic counselors will likely be instrumental in answering that question, but to date, there is no published research regarding prenatal counselors' implementation of and experiences with cffDNA testing. We developed a 67 question survey to gather descriptive information from counselors regarding their personal opinions, experiences, thoughts, and concerns regarding the validity, usefulness, and implementation of this new technology. A total of 236 individuals completed a portion of the survey; not all respondents answered all questions. Qualitative questions complemented quantitative survey items, allowing respondents to voice their thoughts directly. Results indicate that counselors value cffDNA testing as a screening option but are concerned regarding how some obstetricians and patients make use of this testing. Further results, discussion, and practice implications are presented.

Aortic stiffness improves the prediction of both diagnosis and severity of coronary artery disease.

PubMed

Yannoutsos, Alexandra; Ahouah, Mathieu; Dreyfuss Tubiana, Céline; Topouchian, Jirar; Safar, Michel E; Blacher, Jacques

2018-02-01

Elective coronography has low diagnostic yield for obstructive coronary artery disease (CAD). We aim to determine whether non-invasive aortic stiffness assessment improves diagnostic accuracy of CAD screening by reducing the number of false-positive results from the cardiac stress test. A cross-sectional study was conducted from January 2013 to September 2014 in our medical center. Electrocardiogram (ECG) stress test coupled with nuclear imaging was performed in 367 consecutive patients routinely followed for myocardial ischemia screening. Aortic pulse wave velocity (PWV) was assessed by applanation tonometry in the overall population. Forty-two patients underwent elective coronography because of ischemia. Theoretical PWV was calculated according to age, blood pressure and gender. The results were expressed as an index ((measured PWV-theoretical PWV)/theoretical PWV) for each patient. Ten patients presented with obstructive CAD, 16 patients had non-obstructive CAD and 16 patients had normal coronary angiography. PWV index and severity of CAD were positively correlated (P=0.001). All patients with obstructive CAD had a positive PWV index. When considering the PWV index retrospectively, the false positive results of cardiac stress test were significantly reduced (P<0.001). Twenty-three procedures may have been avoided in the present study cohort. The salient finding of this study was that in patients with known or suspected CAD, routinely followed aortic PWV index may be considered clinically useful for reducing the rate of unnecessary invasive angiographies. The clinical relevance of this individualized decision approach should be confirmed in a large-scale study. Prospective studies have the potential to evaluate the PWV index as a marker of CAD.

Non-invasive prenatal testing for single gene disorders: exploring the ethics.

PubMed

Deans, Zuzana; Hill, Melissa; Chitty, Lyn S; Lewis, Celine

2013-07-01

Non-invasive prenatal testing for single gene disorders is now clearly on the horizon. This new technology offers obvious clinical benefits such as safe testing early in pregnancy. Before widespread implementation, it is important to consider the possible ethical implications. Four hypothetical scenarios are presented that highlight how ethical ideals of respect for autonomy, privacy and fairness may come into play when offering non-invasive prenatal testing for single gene disorders. The first scenario illustrates the moral case for using these tests for 'information only', identifying a potential conflict between larger numbers of women seeking the benefits of the test and the wider social impact of funding tests that do not offer immediate clinical benefit. The second scenario shows how the simplicity and safety of non-invasive prenatal testing could lead to more autonomous decision-making and, conversely, how this could also lead to increased pressure on women to take up testing. In the third scenario we show how, unless strong safeguards are put in place, offering non-invasive prenatal testing could be subject to routinisation with informed consent undermined and that woman who are newly diagnosed as carriers may be particularly vulnerable. The final scenario introduces the possibility of a conflict of the moral rights of a woman and her partner through testing for single gene disorders. This analysis informs our understanding of the potential impacts of non-invasive prenatal testing for single gene disorders on clinical practice and has implications for future policy and guidelines for prenatal care.

MicroRNAs derived from circulating exosomes as non-invasive biomarkers for screening and diagnose lung cancer

PubMed Central

Cazzoli, Riccardo; Buttitta, Fiamma; Di Nicola, Marta; Malatesta, Sara; Marchetti, Antonio; Pass, Harvey I.

2013-01-01

Introduction Lung cancer is formerly the highest cause of mortality among tumor pathologies worldwide. There are no validated techniques for an early detection of pulmonary cancer lesions other than low-dose helical CT-scan. Unfortunately, this method have some downside effects. Recent studies have laid the basis for development of exosomes-based techniques to screen/diagnose lung cancers. As the isolation of circulating exosomes is a minimally invasive procedure, this technique opens new possibilities for diagnostic applications. Methods We used a first set of 30 plasma samples from as many patients, including 10 patients affected by Lung Adenocarcinomas, 10 with Lung Granulomas and 10 healthy smokers matched for age and sex as negative controls. Wide range microRNAs analysis (742 microRNAs) was performed by quantitative RT-PCR. Data were compared by lesion characteristics using WEKA software for statistics and modeling. Subsequently, selected microRNAs were evaluated on an independent larger group of samples (105 specimens: 50 Lung Adenocarcinomas, 30 Lung Granulomas and 25 healthy smokers). Results This analysis led to the selection of 4 microRNAs to perform a screening test (miR-378a, miR-379, miR-139-5p and miR-200b-5p), useful to divide population into 2 groups: nodule (lung adenocarcinomas+carcinomas) and non-nodule (healthy former smokers). Six microRNAs (miR-151a-5p, miR-30a-3p, miR-200b-5p, miR-629, miR-100 and miR-154-3p) were selected for a second test on the “nodule” population to discriminate between lung adenocarcinoma and granuloma. Conclusions “Screening test” has shown 97.5% sensitivity, 72.0% specificity, AUC ROC of 90.8%. “Diagnostic test” had 96.0% sensitivity, 60.0% specificity, AUC ROC of 76.0%. Further evaluation is needed to confirm the predictive power of those models on higher cohorts of samples. PMID:23945385

Molecular markers for colorectal cancer screening

PubMed Central

Dickinson, Brandon T.; Kisiel, John; Ahlquist, David A.; Grady, William M.

2016-01-01

Colorectal cancer (CRC), although a significant cause of morbidity and mortality worldwide, has seen a declining incidence and mortality in countries with programmatic screening. Fecal occult blood testing (FOBT) and endoscopic approaches are the predominant screening methods currently. The discovery of the adenoma→carcinoma sequence and a greater understanding of the genetic and epigenetic changes that drive the formation of CRC have contributed to innovative research to identify molecular markers for highly accurate, non-invasive screening tests for CRC. DNA, proteins, messenger RNA, and micro-RNA have all been evaluated. The observation of tumor cell exfoliation into the mucocellular layer of the colonic epithelium and proven stability of DNA in a harsh stool environment make stool DNA a particularly promising marker. The development of a clinically useful stool DNA test has required numerous technical advances, including optimization in DNA stabilization, the development of assays with high analytical sensitivity, and the identification of specific and broadly informative molecular markers. A multi-target stool DNA (MT-sDNA) test, which combines both mutant and methylated DNA markers and a fecal immunochemical test (FIT), recently performed favorably in a large cross-sectional validation study and has been approved by the US Food and Drug Administration (FDA) for the screening of asymptomatic, average risk individuals. The ultimate way in which molecular marker screening assays will be used in clinical practice will require additional studies to determine optimal screening intervals, factors affecting compliance, management of false positive results, and the use of these assays in high-risk populations, as well as other considerations. PMID:25994221

Non-Invasive Detection of Anaemia Using Digital Photographs of the Conjunctiva.

PubMed

Collings, Shaun; Thompson, Oliver; Hirst, Evan; Goossens, Louise; George, Anup; Weinkove, Robert

2016-01-01

Anaemia is a major health burden worldwide. Although the finding of conjunctival pallor on clinical examination is associated with anaemia, inter-observer variability is high, and definitive diagnosis of anaemia requires a blood sample. We aimed to detect anaemia by quantifying conjunctival pallor using digital photographs taken with a consumer camera and a popular smartphone. Our goal was to develop a non-invasive screening test for anaemia. The conjunctivae of haemato-oncology in- and outpatients were photographed in ambient lighting using a digital camera (Panasonic DMC-LX5), and the internal rear-facing camera of a smartphone (Apple iPhone 5S) alongside an in-frame calibration card. Following image calibration, conjunctival erythema index (EI) was calculated and correlated with laboratory-measured haemoglobin concentration. Three clinicians independently evaluated each image for conjunctival pallor. Conjunctival EI was reproducible between images (average coefficient of variation 2.96%). EI of the palpebral conjunctiva correlated more strongly with haemoglobin concentration than that of the forniceal conjunctiva. Using the compact camera, palpebral conjunctival EI had a sensitivity of 93% and 57% and specificity of 78% and 83% for detection of anaemia (haemoglobin < 110 g/L) in training and internal validation sets, respectively. Similar results were found using the iPhone camera, though the EI cut-off value differed. Conjunctival EI analysis compared favourably with clinician assessment, with a higher positive likelihood ratio for prediction of anaemia. Erythema index of the palpebral conjunctiva calculated from images taken with a compact camera or mobile phone correlates with haemoglobin and compares favourably to clinician assessment for prediction of anaemia. If confirmed in further series, this technique may be useful for the non-invasive screening for anaemia.

Fatty acid ethyl esters (FAEEs) as markers for alcohol in meconium: method validation and implementation of a screening program for prenatal drug exposure.

PubMed

Hastedt, Martin; Krumbiegel, Franziska; Gapert, René; Tsokos, Michael; Hartwig, Sven

2013-09-01

Alcohol consumption during pregnancy is a widespread problem and can cause severe fetal damage. As the diagnosis of fetal alcohol syndrome is difficult, the implementation of a reliable marker for alcohol consumption during pregnancy into meconium drug screening programs would be invaluable. A previously published gas chromatography mass spectrometry method for the detection of fatty acid ethyl esters (FAEEs) as alcohol markers in meconium was optimized and newly validated for a sample size of 50 mg. This method was applied to 122 cases from a drug-using population. The meconium samples were also tested for common drugs of abuse. In 73 % of the cases, one or more drugs were found. Twenty percent of the samples tested positive for FAEEs at levels indicating significant alcohol exposure. Consequently, alcohol was found to be the third most frequently abused substance within the study group. This re-validated method provides an increase in testing sensitivity, is reliable and easily applicable as part of a drug screening program. It can be used as a non-invasive tool to detect high alcohol consumption in the last trimester of pregnancy. The introduction of FAEEs testing in meconium screening was found to be of particular use in a drug-using population.

National screening guidelines and developments in prenatal diagnoses and live births of Down syndrome in 1973-2016 in Denmark.

PubMed

Lou, Stina; Petersen, Olav B; Jørgensen, Finn S; Lund, Ida C B; Kjaergaard, Susanne; Vogel, Ida

2018-02-01

Denmark was the first country in the world to implement a national, free-for-all offer of prenatal screening for Down syndrome to all pregnant women. It has a high uptake (>90%) compared to other countries. Thus, Denmark offers an interesting case for investigating the consequences of implementing comprehensive, national prenatal screening guidelines. The aim of this study was to describe the historical developments in invasive procedures, pre-/postnatal diagnoses of Down syndrome and Down syndrome live births in the period 1973-2016 in Denmark. Data on invasive procedures, pre- and postnatal Down syndrome diagnoses were retrieved from the Danish Cytogenetic Central Registry. From 1973 to 1993, screening based on maternal age and high-risk indications resulted in a constant increase in invasive procedures. After the introduction of the triple test in 1994, invasive procedures decreased for the first time in 20 years. Following the introduction of an offer of combined screening to all pregnant women in 2004, the number of invasive procedures decreased markedly, while there was a concurrent increase in prenatal diagnoses of Down syndrome. Additionally, the number of Down syndrome live births decreased suddenly and significantly, but subsequently stabilized at 23-35 annual live births. Of these, the majority were diagnosed postnatally. Though prenatal screening technologies constantly improve, it was the introduction of and adherence to national guidelines that resulted in marked shifts in screening procedures and outcome in Denmark. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening.

PubMed

Cohen, Paul A; Flowers, Nicola; Tong, Stephen; Hannan, Natalie; Pertile, Mark D; Hui, Lisa

2016-08-24

Non-invasive prenatal testing (NIPT) identifies fetal aneuploidy by sequencing cell-free DNA in the maternal plasma. Pre-symptomatic maternal malignancies have been incidentally detected during NIPT based on abnormal genomic profiles. This low coverage sequencing approach could have potential for ovarian cancer screening in the non-pregnant population. Our objective was to investigate whether plasma DNA sequencing with a clinical whole genome NIPT platform can detect early- and late-stage high-grade serous ovarian carcinomas (HGSOC). This is a case control study of prospectively-collected biobank samples comprising preoperative plasma from 32 women with HGSOC (16 'early cancer' (FIGO I-II) and 16 'advanced cancer' (FIGO III-IV)) and 32 benign controls. Plasma DNA from cases and controls were sequenced using a commercial NIPT platform and chromosome dosage measured. Sequencing data were blindly analyzed with two methods: (1) Subchromosomal changes were called using an open source algorithm WISECONDOR (WIthin-SamplE COpy Number aberration DetectOR). Genomic gains or losses ≥ 15 Mb were prespecified as "screen positive" calls, and mapped to recurrent copy number variations reported in an ovarian cancer genome atlas. (2) Selected whole chromosome gains or losses were reported using the routine NIPT pipeline for fetal aneuploidy. We detected 13/32 cancer cases using the subchromosomal analysis (sensitivity 40.6 %, 95 % CI, 23.7-59.4 %), including 6/16 early and 7/16 advanced HGSOC cases. Two of 32 benign controls had subchromosomal gains ≥ 15 Mb (specificity 93.8 %, 95 % CI, 79.2-99.2 %). Twelve of the 13 true positive cancer cases exhibited specific recurrent changes reported in HGSOC tumors. The NIPT pipeline resulted in one "monosomy 18" call from the cancer group, and two "monosomy X" calls in the controls. Low coverage plasma DNA sequencing used for prenatal testing detected 40.6 % of all HGSOC, including 38 % of early stage cases. Our findings demonstrate the potential of a high throughput sequencing platform to screen for early HGSOC in plasma based on characteristic multiple segmental chromosome gains and losses. The performance of this approach may be further improved by refining bioinformatics algorithms and targeting selected cancer copy number variations.

Epi proColon® 2.0 CE: A Blood-Based Screening Test for Colorectal Cancer.

PubMed

Lamb, Yvette N; Dhillon, Sohita

2017-04-01

Epi proColon ® 2.0 CE is a blood-based test designed to aid in the early detection of colorectal cancer. The test comprises a qualitative assay for the polymerase chain reaction (PCR) detection of methylated Septin9 DNA, the presence of which is associated with colorectal cancer: however, positive results should be verified by colonoscopy or sigmoidoscopy. Epi proColon ® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with high clinical sensitivity and specificity in pivotal case-control studies. The sensitivity of the test did not appear to be affected by the tumour location or by patient age or gender. In addition, limited data suggest that Epi proColon ® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with higher sensitivity and generally similar specificity to that of the faecal immunochemical test, and with higher sensitivity and specificity to that of the guaiac-based faecal occult blood test (statistical data not available). In an observational study, most patients who refused colonoscopy for screening accepted a non-invasive test option as an alternative, and preferred Epi proColon ® 2.0 CE over a stool-based test. Large prospective trials of Epi proColon ® 2.0 CE in a screening setting will be required to further elucidate the cost-effectiveness of the test. Nevertheless, currently available data suggests that Epi proColon ® 2.0 CE has the potential to be a sensitive and convenient screening option for patients refusing screening by colonoscopy.

Assessing the impact of the SOGC recommendations to increase access to prenatal screening on overall use of health resources in pregnancy.

PubMed

Metcalfe, Amy; Lix, Lisa M; Johnson, Jo-Ann; Bernier, François; Currie, Gillian; Lyon, Andrew W; Tough, Suzanne C

2013-05-01

The recommendation by the Society of Obstetricians and Gynaecologists of Canada that prenatal screening for fetal aneuploidy be offered to all pregnant women is an important change in clinical obstetrics. However, it is unknown how this recommendation might affect the use of other health resources during pregnancy. Twelve clinical and administrative databases were linked, and care paths outlining typical service use in pregnancy were created based on the type of prenatal screening accessed (first trimester screening [FTS], maternal serum screening [MSS], invasive testing only, or no screening and/or diagnosis). Logistic, Poisson, and negative binomial models were applied to the data to examine the association between use of prenatal screening/diagnosis and other health services during pregnancy. Women who accessed prenatal screening/diagnosis were significantly more likely to have a consultation with a medical geneticist (FTS OR 2.42; 95% CI 1.75 to 3.33; MSS OR 4.84; 95% CI 2.92 to 8.03; and invasive testing OR 8.58; 95% CI 5.28 to 13.94), and women who accessed FTS had more prenatal visits (FTS incidence rate ratio 1.03; 95% CI 1.01 to 1.05) than women who did not access prenatal screening/diagnosis. Uptake of invasive tests did not differ between women who accessed FTS and those who accessed MSS. Use of prenatal screening/diagnosis was not significantly associated with use of most other health resources In a publicly funded health care system, understanding the impact of recommendations to increase access to a specific service on other services is important. Recommendations to increase access to prenatal screening services may have some unanticipated downstream effects on the use of other services during pregnancy. However, most aspects of health resource use in pregnancy do not appear to be influenced by the use of prenatal screening services.

Upgrade of ductal carcinoma in situ on core biopsies to invasive disease at final surgery: a retrospective review across the Scottish Breast Screening Programme.

PubMed

Sim, Y T; Litherland, J; Lindsay, E; Hendry, P; Brauer, K; Dobson, H; Cordiner, C; Gagliardi, T; Smart, L

2015-05-01

To identify factors affecting upgrade rates from B5a (non-invasive) preoperative core biopsies to invasive disease at surgery and ways to improve screening performance. This was a retrospective analysis of 1252 cases of B5a biopsies across all six Scottish Breast Screening Programmes (BSPs), ranging between 2004 and 2012. Final surgical histopathology was correlated with radiological and biopsy factors. Data were analysed using basic Microsoft Excel and standard Chi-squared test used for evaluating statistical significance. B5a upgrade rates for the units ranged from 19.2% to 29.2%, with an average of 23.6%. Mean sizes of invasive tumours were small (3-11 mm). The upgrade rate was significantly higher for cases where the main mammographic abnormality was mass, distortion, or asymmetry, compared with micro-calcification alone (33.2% versus 21.7%, p = 0.0004). The upgrade rate was significantly lower with the use of large-volume vacuum-assisted biopsy (VAB) devices than 14 G core needles (19.9% versus 26%, p = 0.013); in stereotactic than ultrasound-guided biopsies (21.2% versus 36.1%, p < 0.001). Heterogeneity of data from different centres limited evaluation of other potential factors. Upgrade rates are lower for cases with micro-calcification as the sole mammographic feature with the use of VAB devices. Nevertheless, there is variation in practice across Scottish BSPs, including first-line biopsy technique and/or device; and it is of interest that a few centres maintain low upgrade rates despite not using VAB routinely for biopsy of micro-calcification. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals

PubMed Central

Canto, Marcia Irene; Hruban, Ralph H.; Fishman, Elliot K.; Kamel, Ihab R.; Schulick, Richard; Zhang, Zhe; Topazian, Mark; Takahashi, Naoki; Fletcher, Joel; Petersen, Gloria; Klein, Alison P.; Axilbund, Jennifer; Griffin, Constance; Syngal, Sapna; Saltzman, John R.; Mortele, Koenraad J.; Lee, Jeffrey; Tamm, Eric; Vikram, Raghunandan; Bhosale, Priya; Margolis, Daniel; Farrell, James; Goggins, Michael

2012-01-01

BACKGROUND & AIMS The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, non-invasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRI). METHODS We screened 225 asymptomatic adult HRI at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS Ninety-two of 216 HRI (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n=5) by any of the imaging modalities. Fifty-one of the 84 HRI with a cyst (60.7%) had multiple lesions, typically small (mean 0.55 cm, range 2–39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects <50 years old, 34% of subjects 50–59 years old, and 53% of subjects 60–69 years old (P<.0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRI, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRI (82 intraductal papillary mucinous neoplasms [IPMN] and 3 pancreatic endocrine tumors). Three of 5 HRI who underwent pancreatic resection had high-grade dysplasia in <3 cm IPMNs and in multiple intraepithelial neoplasias. CONCLUSIONS Screening of asymptomatic HRI frequently detects small pancreatic cysts, including curable, non-invasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT. PMID:22245846

Non-Invasive Pneumothorax Detector

DTIC Science & Technology

2012-04-01

AD_________________ Award Number: W81XWH-09-2-0092 TITLE: Non-Invasive Pneumothorax Detector...REPORT TYPE Final 3. DATES COVERED 27 July 2009 – 31 August 2011 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Non-Invasive Pneumothorax ...that form the scope of work support the development and clinical testing of a non-invasive pneumothorax detector. Goal and objectives are reflected in

Prevalence and severity of non-alcoholic fatty liver disease are underestimated in clinical practice: impact of a dedicated screening approach at a large university teaching hospital.

PubMed

Marjot, T; Sbardella, E; Moolla, A; Hazlehurst, J M; Tan, G D; Ainsworth, M; Cobbold, J F L; Tomlinson, J W

2018-01-01

To define the attitudes and current clinical practice of diabetes specialists with regard to non-alcoholic fatty liver disease and, based on the results, implement an evidenced-based pathway for non-alcoholic fatty liver disease assessment. An online survey was disseminated to diabetes specialists. Based on findings from this survey, we sought a local solution by launching an awareness campaign and implementing a screening algorithm across all diabetes clinics at a secondary/tertiary referral centre. A total of 133 diabetes specialists responded to the survey. Fewer than 5% of responders correctly assessed the prevalence and severity of advanced fibrotic non-alcoholic fatty liver disease in people with diabetes as 50-75%. Whilst most clinicians performed liver function tests, only 5.7% responded stating that they would use, or had used, a non-invasive algorithm to stage the severity of non-alcoholic fatty liver disease. Implementing a local non-alcoholic fatty liver disease awareness campaign and screening strategy using pre-printed blood request forms, we ensured that 100% (n=395) of all people with Type 1 and Type 2 diabetes mellitus attending secondary/tertiary care diabetes clinics over a 6-month period were appropriately screened for advanced fibrotic non-alcoholic fatty liver disease using the Fib-4 index; 17.9% required further investigation or assessment. The prevalence and severity of non-alcoholic fatty liver disease are underestimated among diabetes specialists. The Fib-4 index can easily be incorporated into clinical practice in secondary/tertiary care to identify those individuals at risk of advanced fibrosis who require further assessment and who may benefit from a dedicated multidisciplinary approach to their management. © 2017 Diabetes UK.

Exhaled breath analysis for lung cancer

PubMed Central

Sutedja, Tom G.; Zimmerman, Paul V.

2013-01-01

Early diagnosis of lung cancer results in improved survival compared to diagnosis with more advanced disease. Early disease is not reliably indicated by symptoms. Because investigations such as bronchoscopy and needle biopsy have associated risks and substantial costs, they are not suitable for population screening. Hence new easily applicable tests, which can be used to screen individuals at risk, are required. Biomarker testing in exhaled breath samples is a simple, relatively inexpensive, non-invasive approach. Exhaled breath contains volatile and non-volatile organic compounds produced as end-products of metabolic processes and the composition of such compounds varies between healthy subjects and subjects with lung cancer. Many studies have analysed the patterns of these compounds in exhaled breath. In addition studies have also reported that the exhaled breath condensate (EBC) can reveal gene mutations or DNA abnormalities in patients with lung cancer. This review has summarised the scientific evidence demonstrating that lung cancer has distinct chemical profiles in exhaled breath and characteristic genetic changes in EBC. It is not yet possible to accurately identify individuals with lung cancer in at risk populations by any of these techniques. However, analysis of both volatile organic compounds in exhaled breath and of EBC have great potential to become clinically useful diagnostic and screening tools for early stage lung cancer detection. PMID:24163746

A Retrospective Assessment of Four Antigen Assays for the Detection of Invasive Candidiasis Among High-Risk Hospitalized Patients.

PubMed

Hartl, Barbara; Zeller, Iris; Manhart, Angelika; Selitsch, Brigitte; Lass-Flörl, Cornelia; Willinger, Birgit

2018-06-01

Because of their high mortality rates and non-specific symptoms, invasive Candida infections pose a huge diagnostic and therapeutic challenge. In this study, we evaluated the three mannan antigen assays Platelia, Platelia Plus and Serion, and the (1-3)-β-D-glucan assay Fungitell in a group of high-risk (hematological and surgical) patients. Test results of 305 patients hospitalized at the Vienna General Hospital and the University Hospital of Innsbruck were retrospectively analyzed. We assessed the test accuracy by means of descriptive statistics. Nine (2.95%) patients were affected by invasive candidiasis (IC), and 25 (8.2%) patients had a probable/possible infection. The majority of patients (271; 88.9%) showed no signs of infection. The Platelia and Serion mannan assays had a low sensitivity (65% and 52%, respectively), but high specificity (98% for both tests). The newer version of the Platelia assay, the Platelia Plus, had a higher sensitivity (85%) but a lower specificity (89%). The sensitivity of the Fungitell assay was high (100%), while its specificity was low (58%). The positive predictive values were 0.48 for the Platelia and 0.41 for the Serion assay, 0.26 for the Platelia Plus and 0.09 for the Fungitell assay. Our limited, retrospective study suggests the efficacy of mannan assays as screening (Platelia Plus) and confirmatory (Serion) tests, while the Fungitell assay can be used to exclude invasive Candida infections.

A real-time, non-invasive, micro-optrode technique for detecting seed viability by using oxygen influx.

PubMed

Xin, Xia; Wan, Yinglang; Wang, Wenjun; Yin, Guangkun; McLamore, Eric S; Lu, Xinxiong

2013-10-28

Quantifying seed viability is required for seed bank maintenance. The classical methods for detecting seed viability are time consuming and frequently cause seed damage and unwanted germination. We have established a novel micro-optrode technique (MOT) to measure seed viability in a quick and non-invasive manner by measuring the oxygen influxes of intact seeds, approximately 10 seconds to screen one seed. Here, we used soybean, wheat, and oilseed rape as models to test our method. After 3-hour imbibition, oxygen influxes were recorded in real-time with the total measurement taking less than 5 minutes. The results indicated a significantly positive correlation between oxygen influxes and viability in all 3 seed types. We also established a linear equation between oxygen influxes and seed viability for each seed type. For measurements, seeds were kept in the early imbibition stage without germination. Thus, MOT is a reliable, quick, and low-cost seed viability detecting technique.

First-trimester contingent screening for trisomy 21 by biomarkers and maternal blood cell-free DNA testing.

PubMed

Nicolaides, K H; Wright, D; Poon, L C; Syngelaki, A; Gil, M M

2013-07-01

To define risk cut-offs with corresponding detection rates (DR) and false-positive rates (FPR) in screening for trisomy 21 using maternal age and combinations of first-trimester biomarkers in order to determine which women should undergo contingent maternal blood cell-free (cf) DNA testing. From singleton pregnancies undergoing screening for aneuploidies at three UK hospitals between March 2006 and May 2012, we analyzed prospectively collected data on the following biomarkers: fetal nuchal translucency thickness (NT) and ductus venosus pulsatility index for veins (DV-PIV) at 11 + 0 to 13 + 6 weeks' gestation and serum free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and alpha-fetoprotein (AFP) at 8 + 0 to 13 + 6 weeks. Estimates of risk cut-offs, DRs and FPRs were derived for combinations of biomarkers and these were used to define the best strategy for contingent cfDNA testing. In contingent screening, detection of 98% of fetuses with trisomy 21 at an overall invasive testing rate < 0.5% can be potentially achieved by offering cfDNA testing to about 36%, 21% and 11% of cases identified by first-line screening using the combined test alone, using the combined test with the addition of serum PlGF and AFP and using the combined test with the addition of PlGF, AFP and DV-PIV, respectively. Effective first-trimester screening for trisomy 21, with DR of 98% and invasive testing rate < 0.5%, can be potentially achieved by contingent screening incorporating biomarkers and cfDNA testing. Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.

The circulating transcriptome as a source of non-invasive cancer biomarkers: concepts and controversies of non-coding and coding RNA in body fluids

PubMed Central

Fernandez-Mercado, Marta; Manterola, Lorea; Larrea, Erika; Goicoechea, Ibai; Arestin, María; Armesto, María; Otaegui, David; Lawrie, Charles H

2015-01-01

The gold standard for cancer diagnosis remains the histological examination of affected tissue, obtained either by surgical excision, or radiologically guided biopsy. Such procedures however are expensive, not without risk to the patient, and require consistent evaluation by expert pathologists. Consequently, the search for non-invasive tools for the diagnosis and management of cancer has led to great interest in the field of circulating nucleic acids in plasma and serum. An additional benefit of blood-based testing is the ability to carry out screening and repeat sampling on patients undergoing therapy, or monitoring disease progression allowing for the development of a personalized approach to cancer patient management. Despite having been discovered over 60 years ago, the clear clinical potential of circulating nucleic acids, with the notable exception of prenatal diagnostic testing, has yet to translate into the clinic. The recent discovery of non-coding (nc) RNA (in particular micro(mi)RNAs) in the blood has provided fresh impetuous for the field. In this review, we discuss the potential of the circulating transcriptome (coding and ncRNA), as novel cancer biomarkers, the controversy surrounding their origin and biology, and most importantly the hurdles that remain to be overcome if they are really to become part of future clinical practice. PMID:26119132

Assessment of non-invasive models for liver fibrosis in chronic hepatitis B virus related liver disease patients in resource limited settings.

PubMed

Shrivastava, Rakesh; Sen, Sourav; Banerji, Debabrata; Praharaj, Ashok K; Chopra, Gurvinder Singh; Gill, Satyajit Singh

2013-01-01

A total of 350 million individuals are affected by chronic hepatitis B virus infection world-wide. Historically, liver biopsy has been instrumental in adequately assessing patients with chronic liver disease. A number of non-invasive models have been studied world-wide. The aim of this study is to assess the utility of non-invasive mathematical models of liver fibrosis in chronic hepatitis B (CHB). Indian patients in a resource limited setting using routinely performed non-invasive laboratory investigations. A cross-sectional study carried out at a tertiary care center. A total of 52 consecutive chronic liver disease patients who underwent percutaneous liver biopsy and 25 healthy controls were enrolled in the study. Routine laboratory investigations included serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gama glutamyl transpeptidase (GGT), total bilirubin, total cholesterol, prothrombin time and platelet count. Three non-invasive models for namely aspartate aminotransferase to platelet ratio index (APRI), Fibrosis 4 (FIB-4) and Forn's index were calculated. Outcomes were compared for the assessment of best predictor of fibrosis by calculating the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each index. Medcalc online software and by Microsoft Excel Worksheet. Chi-square test was used for significance. P value < 0.05 was taken as significant. While the serum levels of AST, ALT and GGT were significantly higher in patients group as compare with the healthy controls (P < 0.01), the platelet counts were significantly lower in patient group as compared to the control group (P < 0.01). Mean value of all 3 indices were significantly higher in patients group as compare with the controls (P < 0.01). Out of the three indices, APRI index with a NPV of 95% appeared to be a better model for excluding significant liver fibrosis while FIB-4 with a PPV of 61% showed fair correlation with significant fibrosis. Thus, these two non-invasive models for predicting of liver fibrosis, namely APRI and FIB-4, can be utilized in combination as screening tools in monitoring of CHB patients, especially in resource limiting settings.

Dynamic infrared imaging for skin cancer screening

NASA Astrophysics Data System (ADS)

Godoy, Sebastián E.; Ramirez, David A.; Myers, Stephen A.; von Winckel, Greg; Krishna, Sanchita; Berwick, Marianne; Padilla, R. Steven; Sen, Pradeep; Krishna, Sanjay

2015-05-01

Dynamic thermal imaging (DTI) with infrared cameras is a non-invasive technique with the ability to detect the most common types of skin cancer. We discuss and propose a standardized analysis method for DTI of actual patient data, which achieves high levels of sensitivity and specificity by judiciously selecting pixels with the same initial temperature. This process compensates the intrinsic limitations of the cooling unit and is the key enabling tool in the DTI data analysis. We have extensively tested the methodology on human subjects using thermal infrared image sequences from a pilot study conducted jointly with the University of New Mexico Dermatology Clinic in Albuquerque, New Mexico (ClinicalTrials ID number NCT02154451). All individuals were adult subjects who were scheduled for biopsy or adult volunteers with clinically diagnosed benign condition. The sample size was 102 subjects for the present study. Statistically significant results were obtained that allowed us to distinguish between benign and malignant skin conditions. The sensitivity and specificity was 95% (with a 95% confidence interval of [87.8% 100.0%]) and 83% (with a 95% confidence interval of [73.4% 92.5%]), respectively, and with an area under the curve of 95%. Our results lead us to conclude that the DTI approach in conjunction with the judicious selection of pixels has the potential to provide a fast, accurate, non-contact, and non-invasive way to screen for common types of skin cancer. As such, it has the potential to significantly reduce the number of biopsies performed on suspicious lesions.

Non-invasive prenatal testing for aneuploidy: a systematic review of Internet advertising to potential users by commercial companies and private health providers.

PubMed

Skirton, Heather; Goldsmith, Lesley; Jackson, Leigh; Lewis, Celine; Chitty, Lyn S

2015-12-01

The development of non-invasive prenatal testing has increased accessibility of fetal testing. Companies are now advertising prenatal testing for aneuploidy via the Internet. The aim of this systematic review of websites advertising non-invasive prenatal testing for aneuploidy was to explore the nature of the information being provided to potential users. We systematically searched two Internet search engines for relevant websites using the following terms: 'prenatal test', 'antenatal test', 'non-invasive test', 'noninvasive test', 'cell-free fetal DNA', 'cffDNA', 'Down syndrome test' or 'trisomy test'. We examined the first 200 websites identified through each search. Relevant web-based text was examined, and key topics were identified, tabulated and counted. To analyse the text further, we used thematic analysis. Forty websites were identified. Whilst a number of sites provided balanced, accurate information, in the majority supporting evidence was not provided to underpin the information and there was inadequate information on the need for an invasive test to definitely diagnose aneuploidy. The information provided on many websites does not comply with professional recommendations. Guidelines are needed to ensure that companies offering prenatal testing via the Internet provide accurate and comprehensible information. © 2015 John Wiley & Sons, Ltd.

Combustion characteristics of north-eastern USA vegetation tested in the cone calorimeter: invasive versus non-invasive plants

Treesearch

Alison C. Dibble; Robert H. White; Patricia K. Lebow

2007-01-01

In the north-eastern United States, invasive plants alter forest fuels, but their combustion characteristics are largely unknown. We assessed unground samples of foliage and twigs in the cone calorimeter for 21 non-invasive, native species, paired with 21 invasive species (18 non-native). Variables included sustained ignition, peak heat release rate, total heat release...

Epigenetic inactivation of VGF associated with Urothelial Cell Carcinoma and its potential as a non-invasive biomarker using urine

PubMed Central

Kagohara, Luciane Tsukamoto; Maldonado, Leonel; Brait, Mariana; Schoenberg, Mark; Bivalacqua, Trinity; Netto, George J; Koch, Wayne; Sidransky, David; Hoque, Mohammad O.

2014-01-01

Background: To identify new epigenetic markers and further characterize Urothelial Cell Carcinoma (UCC), we tested the promoter methylation (PM) status of 19 genes previously identified as cancer specific methylated genes in other solid tumors. Methods: We used bisulfite sequencing, methylation specific PCR and quantitative methylation specific PCR (QMSP) to test the PM status of 19 genes in urothelial cancer cell lines. Results: Among the 19 genes tested, VGF was found to be completely methylated in several UCC cell lines. VGF QMSP analysis showed that methylation values of almost all the primary 19 UCC tissues were higher than the paired normal tissues (P=0.009). In another cohort, 12/35 (34.3%) of low grade UCC cases displayed VGF methylation. As a biomarker for non-invasive detection of UCC, VGF showed a significantly higher frequency of methylation in urine from UCC cases (8/20) compared to controls (1/20) (P=0.020). After treatment of cell lines with 5-Aza-2'-deoxycytidine, VGF was robustly re-expressed. Forced expression of VGF in bladder cancer cell lines inhibited cell growth. Conclusion: Selection of candidates from genome-wide screening approach in other solid tumors successfully identified UCC specific methylated genes. PMID:24830820

“I think we’ve got too many tests!”: Prenatal providers’ reflections on ethical and clinical challenges in the practice integration of cell-free DNA screening

PubMed Central

Gammon, B.L.; Kraft, S.A.; Michie, M.; Allyse, M.

2016-01-01

Background The recent introduction of cell-free DNA-based non-invasive prenatal screening (cfDNA screening) into clinical practice was expected to revolutionize prenatal testing. cfDNA screening for fetal aneuploidy has demonstrated higher test sensitivity and specificity for some conditions than conventional serum screening and can be conducted early in the pregnancy. However, it is not clear whether and how clinical practices are assimilating this new type of testing into their informed consent and counselling processes. Since the introduction of cfDNA screening into practice in 2011, the uptake and scope have increased dramatically. Prenatal care providers are under pressure to stay up to date with rapidly changing cfDNA screening panels, manage increasing patient demands, and keep up with changing test costs, all while attempting to use the technology responsibly and ethically. While clinical literature on cfDNA screening has shown benefits for specific patient populations, it has also identified significant misunderstandings among providers and patients alike about the power of the technology. The unique features of cfDNA screening, in comparison to established prenatal testing technologies, have implications for informed decision-making and genetic counselling that must be addressed to ensure ethical practice. Objectives This study explored the experiences of prenatal care providers at the forefront of non-invasive genetic screening in the United States to understand how this testing changes the practice of prenatal medicine. We aimed to learn how the experience of providing and offering this testing differs from established prenatal testing methodologies. These differences may necessitate changes to patient education and consent procedures to maintain ethical practice. Methods We used the online American Congress of Obstetricians and Gynecologists Physician Directory to identify a systematic sample of five prenatal care providers in each U.S. state and the District of Columbia. Beginning with the lowest zip code in each state, we took every fifth name from the directory, excluding providers who were retired, did not currently practice in the state in which they were listed, or were not involved in a prenatal specialty. After repeating this step twice and sending a total of 461 invitations, 37 providers expressed interest in participating, and we completed telephone interviews with 21 providers (4.6%). We developed a semi-structured interview guide including questions about providers’ use of and attitudes toward cfDNA screening. A single interviewer conducted and audio-recorded all interviews by telephone, and the interviews lasted approximately 30 minutes each. We collaboratively developed a codebook through an iterative process of transcript review and code application, and a primary coder coded all transcripts. Results Prenatal care providers have varying perspectives on the advantages of cfDNA screening and express a range of concerns regarding the implementation of cfDNA screening in practice. While providers agreed on several advantages of cfDNA, including increased accuracy, earlier return of results, and decreased risk of complications, many expressed concern that there is not enough time to adequately counsel and educate patients on their prenatal screening and testing options. Providers also agreed that demand for cfDNA screening has increased and expressed a desire for more information from professional societies, labs, and publications. Providers disagreed about the healthcare implications and future of cfDNA screening. Some providers anticipated that cfDNA screening would decrease healthcare costs when implemented widely and expressed optimism for expanded cfDNA screening panels. Others were concerned that cfDNA screening would increase costs over time and questioned whether the expansion to include microdeletions could be done ethically. Conclusions The perspectives and experiences of the providers in this study allow insight into the clinical benefit, burden on prenatal practice, and potential future of cfDNA screening in clinical practice. Given the likelihood that the scope and uptake of cfDNA screening will continue to increase, it is essential to consider how these changes will affect frontline prenatal care providers and, in turn, patients. Providers’ requests for additional guidance and data as well as their concerns with the lack of time available to explain screening and testing options indicate significant potential issues with patient care. It is important to ensure that the clinical integration of cfDNA screening is managed responsibly and ethically before it expands further, exacerbating pre-existing issues. As prenatal screening evolves, so should informed consent and the resources available to women making decisions. The field must take steps to maximize the advantages of cfDNA screening and responsibly manage its ethical issues. PMID:28180146

"I think we've got too many tests!": Prenatal providers' reflections on ethical and clinical challenges in the practice integration of cell-free DNA screening.

PubMed

Gammon, B L; Kraft, S A; Michie, M; Allyse, M

2016-01-01

The recent introduction of cell-free DNA-based non-invasive prenatal screening (cfDNA screening) into clinical practice was expected to revolutionize prenatal testing. cfDNA screening for fetal aneuploidy has demonstrated higher test sensitivity and specificity for some conditions than conventional serum screening and can be conducted early in the pregnancy. However, it is not clear whether and how clinical practices are assimilating this new type of testing into their informed consent and counselling processes. Since the introduction of cfDNA screening into practice in 2011, the uptake and scope have increased dramatically. Prenatal care providers are under pressure to stay up to date with rapidly changing cfDNA screening panels, manage increasing patient demands, and keep up with changing test costs, all while attempting to use the technology responsibly and ethically. While clinical literature on cfDNA screening has shown benefits for specific patient populations, it has also identified significant misunderstandings among providers and patients alike about the power of the technology. The unique features of cfDNA screening, in comparison to established prenatal testing technologies, have implications for informed decision-making and genetic counselling that must be addressed to ensure ethical practice. This study explored the experiences of prenatal care providers at the forefront of non-invasive genetic screening in the United States to understand how this testing changes the practice of prenatal medicine. We aimed to learn how the experience of providing and offering this testing differs from established prenatal testing methodologies. These differences may necessitate changes to patient education and consent procedures to maintain ethical practice. We used the online American Congress of Obstetricians and Gynecologists Physician Directory to identify a systematic sample of five prenatal care providers in each U.S. state and the District of Columbia. Beginning with the lowest zip code in each state, we took every fifth name from the directory, excluding providers who were retired, did not currently practice in the state in which they were listed, or were not involved in a prenatal specialty. After repeating this step twice and sending a total of 461 invitations, 37 providers expressed interest in participating, and we completed telephone interviews with 21 providers (4.6%). We developed a semi-structured interview guide including questions about providers' use of and attitudes toward cfDNA screening. A single interviewer conducted and audio-recorded all interviews by telephone, and the interviews lasted approximately 30 minutes each. We collaboratively developed a codebook through an iterative process of transcript review and code application, and a primary coder coded all transcripts. Prenatal care providers have varying perspectives on the advantages of cfDNA screening and express a range of concerns regarding the implementation of cfDNA screening in practice. While providers agreed on several advantages of cfDNA, including increased accuracy, earlier return of results, and decreased risk of complications, many expressed concern that there is not enough time to adequately counsel and educate patients on their prenatal screening and testing options. Providers also agreed that demand for cfDNA screening has increased and expressed a desire for more information from professional societies, labs, and publications. Providers disagreed about the healthcare implications and future of cfDNA screening. Some providers anticipated that cfDNA screening would decrease healthcare costs when implemented widely and expressed optimism for expanded cfDNA screening panels. Others were concerned that cfDNA screening would increase costs over time and questioned whether the expansion to include microdeletions could be done ethically. The perspectives and experiences of the providers in this study allow insight into the clinical benefit, burden on prenatal practice, and potential future of cfDNA screening in clinical practice. Given the likelihood that the scope and uptake of cfDNA screening will continue to increase, it is essential to consider how these changes will affect frontline prenatal care providers and, in turn, patients. Providers' requests for additional guidance and data as well as their concerns with the lack of time available to explain screening and testing options indicate significant potential issues with patient care. It is important to ensure that the clinical integration of cfDNA screening is managed responsibly and ethically before it expands further, exacerbating pre-existing issues. As prenatal screening evolves, so should informed consent and the resources available to women making decisions. The field must take steps to maximize the advantages of cfDNA screening and responsibly manage its ethical issues.

Feasibility of supervised self-testing using an oral fluid-based HIV rapid testing method: a cross-sectional, mixed method study among pregnant women in rural India.

PubMed

Sarkar, Archana; Mburu, Gitau; Shivkumar, Poonam Varma; Sharma, Pankhuri; Campbell, Fiona; Behera, Jagannath; Dargan, Ritu; Mishra, Surendra Kumar; Mehra, Sunil

2016-01-01

HIV self-testing can increase coverage of essential HIV services. This study aimed to establish the acceptability, concordance and feasibility of supervised HIV self-testing among pregnant women in rural India. A cross-sectional, mixed methods study was conducted among 202 consenting pregnant women in a rural Indian hospital between August 2014 and January 2015. Participants were provided with instructions on how to self-test using OraQuick(®) HIV antibody test, and subsequently asked to self-test under supervision of a community health worker. Test results were confirmed at a government-run integrated counselling and testing centre. A questionnaire was used to obtain information on patient demographics and the ease, acceptability and difficulties of self-testing. In-depth interviews were conducted with a sub-sample of 35 participants to understand their experiences. In total, 202 participants performed the non-invasive, oral fluid-based, rapid test under supervision for HIV screening. Acceptance rate was 100%. Motivators for self-testing included: ease of testing (43.4%), quick results (27.3%) and non-invasive procedure (23.2%). Sensitivity and specificity were 100% for 201 tests, and one test was invalid. Concordance of test result interpretation between community health workers and participants was 98.5% with a Cohen's Kappa (k) value of k=0.566 with p<0.001 for inter-rater agreement. Although 92.6% participants reported that the instructions for the test were easy to understand, 18.7% required the assistance of a supervisor to self-test. Major themes that emerged from the qualitative interviews indicated the importance of the following factors in influencing acceptability of self-testing: clarity and accessibility of test instructions; time-efficiency and convenience of testing; non-invasiveness of the test; and fear of incorrect results. Overall, 96.5% of the participants recommended that the OraQuick(®) test kits should become publicly available. Self-testing for HIV status using an oral fluid-based rapid test under the supervision of a community health worker was acceptable and feasible among pregnant women in rural India. Participants were supportive of making self-testing publicly available. Policy guidelines and implementation research are required to advance HIV self-testing for larger populations at scale.

Feasibility of supervised self-testing using an oral fluid-based HIV rapid testing method: a cross-sectional, mixed method study among pregnant women in rural India

PubMed Central

Sarkar, Archana; Mburu, Gitau; Shivkumar, Poonam Varma; Sharma, Pankhuri; Campbell, Fiona; Behera, Jagannath; Dargan, Ritu; Mishra, Surendra Kumar; Mehra, Sunil

2016-01-01

Introduction HIV self-testing can increase coverage of essential HIV services. This study aimed to establish the acceptability, concordance and feasibility of supervised HIV self-testing among pregnant women in rural India. Methods A cross-sectional, mixed methods study was conducted among 202 consenting pregnant women in a rural Indian hospital between August 2014 and January 2015. Participants were provided with instructions on how to self-test using OraQuick® HIV antibody test, and subsequently asked to self-test under supervision of a community health worker. Test results were confirmed at a government-run integrated counselling and testing centre. A questionnaire was used to obtain information on patient demographics and the ease, acceptability and difficulties of self-testing. In-depth interviews were conducted with a sub-sample of 35 participants to understand their experiences. Results In total, 202 participants performed the non-invasive, oral fluid-based, rapid test under supervision for HIV screening. Acceptance rate was 100%. Motivators for self-testing included: ease of testing (43.4%), quick results (27.3%) and non-invasive procedure (23.2%). Sensitivity and specificity were 100% for 201 tests, and one test was invalid. Concordance of test result interpretation between community health workers and participants was 98.5% with a Cohen's Kappa (k) value of k=0.566 with p<0.001 for inter-rater agreement. Although 92.6% participants reported that the instructions for the test were easy to understand, 18.7% required the assistance of a supervisor to self-test. Major themes that emerged from the qualitative interviews indicated the importance of the following factors in influencing acceptability of self-testing: clarity and accessibility of test instructions; time-efficiency and convenience of testing; non-invasiveness of the test; and fear of incorrect results. Overall, 96.5% of the participants recommended that the OraQuick® test kits should become publicly available. Conclusions Self-testing for HIV status using an oral fluid-based rapid test under the supervision of a community health worker was acceptable and feasible among pregnant women in rural India. Participants were supportive of making self-testing publicly available. Policy guidelines and implementation research are required to advance HIV self-testing for larger populations at scale. PMID:27630096

The utilization of circulating cell-free fetal DNA testing and decrease in invasive diagnostic procedures: an institutional experience.

PubMed

Pettit, K E; Hull, A D; Korty, L; Jones, M C; Pretorius, D H

2014-10-01

To characterize the patient population utilizing circulating cell-free fetal DNA (ccffDNA) testing at a large academic center and evaluate trends in the performance of invasive diagnostic procedures. A retrospective cohort study of all patients who underwent cell-free DNA testing from May to December 2012 was performed. During the study period, 206 patients had cell-free DNA testing. Of those, 75% (155/206) were of ages ⩾ 35 years. Of those undergoing ccffDNA testing, 41% had positive aneuploidy screening and 38% had abnormal ultrasound findings. Only 7% of the patients with negative ccffDNA testing opted for an invasive diagnostic procedure compared with 60% with positive testing (P<0.01). The rate of invasive procedures decreased from 5.9% of all visits to the center during a similar 8-month period in 2010 to 4.1% of all visits during the study period (P<0.01). Our data suggest that ccffDNA testing leads to reduced uptake of invasive procedures.

Projected future impact of HPV vaccination and primary HPV screening on cervical cancer rates from 2017-2035: Example from Australia.

PubMed

Hall, Michaela T; Simms, Kate T; Lew, Jie-Bin; Smith, Megan A; Saville, Marion; Canfell, Karen

2018-01-01

Many countries are transitioning from cytology-based to longer-interval HPV screening. Trials comparing HPV-based screening to cytology report an increase in CIN2/3 detection at the first screen, and longer-term reductions in CIN3+; however, population level year-to-year transitional impacts are poorly understood. We undertook a comprehensive evaluation of switching to longer-interval primary HPV screening in the context of HPV vaccination. We used Australia as an example setting, since Australia will make this transition in December 2017. Using a model of HPV vaccination, transmission, natural history and cervical screening, Policy1-Cervix, we simulated the planned transition from recommending cytology every two years for sexually-active women aged 18-20 to 69, to recommending HPV screening every five years for women aged 25-74 years. We estimated rates of CIN2/3, cervical cancer incidence, and mortality for each year from 2005 to 2035, considering ranges for HPV test accuracy and screening compliance in the context of HPV vaccination (current coverage ~82% in females; ~76% in males). Transient increases are predicted to occur in rates of CIN2/3 detection and invasive cervical cancer in the first two to three years following the screening transition (of 16-24% and 11-14% in respectively, compared to 2017 rates). However, by 2035, CIN2/3 and invasive cervical cancer rates are predicted to fall by 40-44% and 42-51%, respectively, compared to 2017 rates. Cervical cancer mortality rates are predicted to remain unchanged until ~2020, then decline by 34-45% by 2035. Over the period 2018-2035, switching to primary HPV screening in Australia is expected to avert 2,006 cases of invasive cervical cancer and save 587 lives. Transient increases in detected CIN2/3 and invasive cancer, which may be detectable at the population level, are predicted following a change to primary HPV screening. This is due to improved test sensitivity bringing forward diagnoses, resulting in longer term reductions in both cervical cancer incidence and mortality. Fluctuations in health outcomes due to the transition to a longer screening interval are predicted to occur for 10-15 years, but cervical cancer rates will be significantly reduced thereafter due to the impact of HPV vaccination and HPV screening. In order to maintain confidence in primary HPV screening through the transitional phase, it is important to widely communicate that an initial increase in CIN2/3 and perhaps even invasive cervical cancer is expected after a national transition to primary HPV screening, that this phenomenon is due to increased prevalent disease detection, and that this effect represents a marker of screening success.

Economic analysis of prenatal screening strategies for Down syndrome in singleton pregnancies in Turkey.

PubMed

Ökem, Zeynep Güldem; Örgül, Gökçen; Kasnakoglu, Berna Tari; Çakar, Mehmet; Beksaç, M Sinan

2017-12-01

To examine the costs and outcomes of different screening strategies for Down Syndrome (DS) in singleton pregnancies. A decision-analytic model was developed to compare the costs and the outcomes of different prenatal screening strategies. Five strategies were compared for women under 35-year of age: 1A) triple test (TT), 2A); combined test (CT), 3A) Non-invasive Prenatal Screening Test by using cell free fetal DNA (NIPT), 4A) and 5A) NIPT as a second-step screening for high-risk patients detected by either TT, or CT respectively. For women ≥35-year of age, 1B) implementing invasive test (amniocentesis -AC) and 2B) NIPT for all women were compared. Data was analyzed to obtain the outcomes, total costs, the cost per women and the incremental cost-effectiveness ratios (ICERs) for screening strategies. Among the current strategies for women under 35 years old, CT is clearly dominated to TT, as it is more effective and less costly. Although, the current routine practice (2A) is the least-costly strategy, implementing NIPT as a second step screening to high-risk women identified by CT (5A) would be more effective than 2A; leading to a 10.2% increase in the number of detected DS cases and a 96.3% reduction in procedural related losses (PRL). However, its cost to the Social Security Institution that is a public entity would be 17 times higher and increase screening costs by 1.5 times. Strategy 5A would result in an incremental cost effectiveness of 6,873,082 (PPP) US$ when compared to the current one (2A). Strategy 1B-for offering AC to all women ≥35-year of age is dominated over NIPT (2B), as it would detect more DS cases and would be less costly. On the other hand, there would be 206 PRL associated with AC, but NIPT provides clear clinical benefits as there would be no PRL with NIPT. NIPT leads to very high costs despite its high effectiveness in terms of detecting DS cases and avoiding PRL. The cost of NIPT should be decreased, otherwise, only individuals who can afford to pay from out-of-pocket could benefit. We believe that reliable cost-effective prenatal screening policies are essential in countries with low and smiddle income and high birth rates as well. Copyright © 2017 Elsevier B.V. All rights reserved.

First and second trimester serum tests with and without first trimester ultrasound tests for Down's syndrome screening.

PubMed

Alldred, S Kate; Takwoingi, Yemisi; Guo, Boliang; Pennant, Mary; Deeks, Jonathan J; Neilson, James P; Alfirevic, Zarko

2017-03-15

Down's syndrome occurs when a person has three copies of chromosome 21 (or the specific area of chromosome 21 implicated in causing Down's syndrome) rather than two. It is the commonest congenital cause of mental disability. Non-invasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing.  Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal) and false negative screening tests (i.e. a fetus with Down's syndrome will be missed). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have. To estimate and compare the accuracy of first and second trimester serum markers with and without first trimester ultrasound markers for the detection of Down's syndrome in the antenatal period, as combinations of markers. We conducted a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), the Database of Abstracts of Reviews of Effectiveness (the Cochrane Library 25 August 2011), MEDION (25 August 2011), the Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), the National Research Register (Archived 2007), and Health Services Research Projects in Progress database (25 August 2011). We did not apply a diagnostic test search filter. We did forward citation searching in ISI citation indices, Google Scholar and PubMed 'related articles'. We also searched reference lists of retrieved articles SELECTION CRITERIA: Studies evaluating tests of combining first and second trimester maternal serum markers in women up to 24 weeks of gestation for Down's syndrome, with or without first trimester ultrasound markers, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses. Twenty-two studies (reported in 25 publications) involving 228,615 pregnancies (including 1067 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high risk pregnancies. Ten studies made direct comparisons between tests. Thirty-two different test combinations were evaluated formed from combinations of eight different tests and maternal age; first trimester nuchal translucency (NT) and the serum markers AFP, uE3, total hCG, free βhCG, Inhibin A, PAPP-A and ADAM 12. We looked at tests combining first and second trimester markers with or without ultrasound as complete tests, and we also examined stepwise and contingent strategies.Meta-analysis of the six most frequently evaluated test combinations showed that a test strategy involving maternal age and a combination of first trimester NT and PAPP-A, and second trimester total hCG, uE3, AFP and Inhibin A significantly outperformed other test combinations that involved only one serum marker or NT in the first trimester, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate. However, the evidence was limited in terms of the number of studies evaluating this strategy, and we therefore cannot recommend one single screening strategy. Tests involving first trimester ultrasound with first and second trimester serum markers in combination with maternal age are significantly better than those without ultrasound, or those evaluating first trimester ultrasound in combination with second trimester serum markers, without first trimester serum markers. We cannot make recommendations about a specific strategy on the basis of the small number of studies available.

Non-invasive hemoglobin monitoring.

PubMed

Joseph, Bellal; Haider, Ansab; Rhee, Peter

2016-09-01

Technology has transformed the practice of medicine and surgery in particular over the last several decades. This change in practice has allowed diagnostic and therapeutic tests to be performed less invasively. Hemoglobin monitoring remains one of the most commonly performed diagnostic tests in the United States. Recently, non-invasive hemoglobin monitoring technology has gained popularity. The aim of this article is to review the principles of how this technology works, pros and cons, and the implications of non-invasive hemoglobin technology particularly in trauma surgery. Copyright © 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Predictive and prognostic biomarkers in colorectal cancer: A systematic review of recent advances and challenges.

PubMed

Das, Vishal; Kalita, Jatin; Pal, Mintu

2017-03-01

Colorectal cancer (CRC) is one of the leading cause of cancer deaths worldwide. Since CRC is largely asymptomatic until alarm features develop to advanced stages, the implementation of the screening programme is very much essential to reduce cancer incidence and mortality rates. CRC occurs predominantly from accumulation of genetic and epigenetic changes in colon epithelial cells, which later gets transformed into adenocarcinomas. The current challenges of screening paradigm and diagnostic ranges are from semi-invasive methods like colonoscopy to non-invasive stool-based test, have resulted in over-diagnosis and over-treatment of CRC. Hence, new screening initiatives and deep studies are required for early diagnosis of CRC. In this regard, we not only summarise current predictive and prognostic biomarkers with their potential for diagnostic and therapeutic applications, but also describe current limitations, future perspectives and challenges associated with the progression of CRC. Currently many potential biomarkers have already been successfully translated into clinical practice eg. Fecal haemoglobin, Carcinoembryonic antigen (CEA) and CA19.9, although these are not highly promising diagnostic target for personalized medicine. So there is a critical need for reliable, minimally invasive, highly sensitive and specific genetic markers of an individualised and optimised patient treatment at the earliest disease stage possible. Identification of a new biomarker, or a set of biomarkers to the development of a valid, and clinical sensible assay that can be served as an alternative tool for early diagnosis of CRC and open up promising new targets in therapeutic intervention strategies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Non-invasive indices for the estimation of the anaerobic threshold of oarsmen.

PubMed

Erdogan, A; Cetin, C; Karatosun, H; Baydar, M L

2010-01-01

This study compared four common non-invasive indices with an invasive index for determining the anaerobic threshold (AT) in 22 adult male rowers using a Concept2 rowing ergometer. A criterion-standard progressive incremental test (invasive method) measured blood lactate concentrations to determine the 4 mmol/l threshold (La4-AT) and Dmax AT (Dm-AT). This was compared with three indices obtained by analysis of respiratory gases and one that was based on the heart rate (HR) deflection point (HRDP) all of which used the Conconi test (non-invasive methods). In the Conconi test, the HRDP was determined whilst continuously increasing the power output (PO) by 25 W/min and measuring respiratory gases and HR. The La4-AT and Dm-AT values differed slightly with respect to oxygen uptake, PO and HR however, AT values significantly correlated with each other and with the four non-invasive methods. In conclusion, the non-invasive indices were comparable with the invasive index and could, therefore, be used in the assessment of AT during rowing ergometer use. In this population of elite rowers, Conconi threshold (Con-AT), based on the measurement of HRDP tended to be the most adequate way of estimating AT for training regulation purposes.

Screening Allelochemical-Resistant Species of the Alien Invasive Mikania micrantha for Restoration in South China

PubMed Central

Wu, Ai-Ping; Li, Zi-Li; He, Fei-Fei; Wang, Yan-Hong; Dong, Ming

2015-01-01

To screen allelochemical-resistant species of the alien invasive weed Mikania micrantha, we studied the allelopathic inhibition effects of the leaf aqueous extract (LAE) of Mikania on seed germination and seedling growth of the 26 species native or naturalized in the invaded region in South China. Seed germination was more strongly negatively affected by LAE than seedling growth. Responses of seed germination and seed growth to LAE differed differently among the target species. LAE more strongly negatively affected seed germination, but less strongly negatively affected seedling growth, in non-legume species than in legume species. LAE more strongly negatively affected seed germination and seedling growth in native species than naturalized exotic species. Therefore, naturalized exotic non-legume seedlings are more suitable than seeds of native legume species for restoration of Mikania-invaded habitats. PMID:26177031

Screening Allelochemical-Resistant Species of the Alien Invasive Mikania micrantha for Restoration in South China.

PubMed

Wu, Ai-Ping; Li, Zi-Li; He, Fei-Fei; Wang, Yan-Hong; Dong, Ming

2015-01-01

To screen allelochemical-resistant species of the alien invasive weed Mikania micrantha, we studied the allelopathic inhibition effects of the leaf aqueous extract (LAE) of Mikania on seed germination and seedling growth of the 26 species native or naturalized in the invaded region in South China. Seed germination was more strongly negatively affected by LAE than seedling growth. Responses of seed germination and seed growth to LAE differed differently among the target species. LAE more strongly negatively affected seed germination, but less strongly negatively affected seedling growth, in non-legume species than in legume species. LAE more strongly negatively affected seed germination and seedling growth in native species than naturalized exotic species. Therefore, naturalized exotic non-legume seedlings are more suitable than seeds of native legume species for restoration of Mikania-invaded habitats.

[Foetal therapy for Down syndrome: a pro-active ethical reflection].

PubMed

de Wert, G M W R; Dondorp, W J

2016-01-01

Prenatal screening for Down syndrome has to date focused on facilitating the informed choice to continue or not with a pregnancy. The non-invasive prenatal test (NIPT) for Down syndrome does potentially offer the option to apply foetal neurocognitive therapy for Down syndrome (FTDS). Current research in animal models looks promising and therefore a proactive ethical reflection in relation to clinical trials is urgently needed. This discussion includes an exploration of the ethical aspects of FTDS. There seem to be no convincing a priori objections on the basis of the social model of disability. Arguments in terms of (respect for) autonomy, wellbeing and justice seem to in principle support such therapy. Still, both the conditions for sound clinical trials and the implications of possible effective therapy for current prenatal screening need further scrutiny.

Non-invasive prenatal testing using massively parallel sequencing of maternal plasma DNA: from molecular karyotyping to fetal whole-genome sequencing.

PubMed

Lo, Y M Dennis

2013-12-01

The discovery of cell-free fetal DNA in maternal plasma in 1997 has stimulated a rapid development of non-invasive prenatal testing. The recent advent of massively parallel sequencing has allowed the analysis of circulating cell-free fetal DNA to be performed with unprecedented sensitivity and precision. Fetal trisomies 21, 18 and 13 are now robustly detectable in maternal plasma and such analyses have been available clinically since 2011. Fetal genome-wide molecular karyotyping and whole-genome sequencing have now been demonstrated in a number of proof-of-concept studies. Genome-wide and targeted sequencing of maternal plasma has been shown to allow the non-invasive prenatal testing of β-thalassaemia and can potentially be generalized to other monogenic diseases. It is thus expected that plasma DNA-based non-invasive prenatal testing will play an increasingly important role in future obstetric care. It is thus timely and important that the ethical, social and legal issues of non-invasive prenatal testing be discussed actively by all parties involved in prenatal care. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Non-invasive test using palmitate in patients with suspected fatty acid oxidation defects: disease-specific acylcarnitine patterns can help to establish the diagnosis.

PubMed

Janzen, Nils; Hofmann, Alejandro D; Schmidt, Gunnar; Das, Anibh M; Illsinger, Sabine

2017-12-21

The aim of the present study was to establish a non-invasive, fast and robust enzymatic assay to confirm fatty acid oxidation defects (FAOD) in humans following informative newborn-screening or for selective screening of patients suspected to suffer from FAOD. The reliability of this method was tested in whole blood from FAOD patients with specific enzymatic defects. Whole blood samples were assayed in 30 medium chain- (MCADD, age 0 to 17 years), 6 very long chain- (VLCADD, age 0 to 4 years), 6 long chain hydroxy- (LCHAD, age 1 to 6 years), 3 short chain- (SCADD, age 10 to 13 years) acyl-CoA-dehydrogenase- and 2 primary carnitine transporter deficiencies (CTD, age 3 to 5 years). Additionally, 26 healthy children (age 0 to 17 years) served as controls. Whole blood samples were incubated with stable end-labeled palmitate; labeled acylcarnitines were analyzed by tandem mass spectrometry and compared with controls and between patient groups (Mann-Whitney Rank Sum Test). Concentrations of specific labeled acylcarnitine metabolites were compared between particular underlying MCADD- (ANOVA), VLCADD- and LCHADD- genetic variants (descriptive data analysis). 11 different acylcarnitines were analyzed. MCADD- (C8-, C10-carnitine, C8/C10- and C8/C4-carnitine), VLCADD- (C12-, C14:1-, C14:2-carnitine, C14:1/C12- and C14:2/C12-carnitine), LCHADD (C16-OH-carnitine) as well as CTD- deficiency (sum of all acylcarnitines) samples could be clearly identified and separated from control values as well as other FAOD, whereas the sum of all acylcarnitines was not conclusive between FAOD samples. Furthermore, C4- (SCADD), C14- (VLCADD) and C14-OH-carnitines (LCHADD) were discriminating between the FAOD groups. Metabolic parameters did not differ significantly between underlying MCADD variants; similar results could be observed for VLCADD- and LCHADD- variants. This functional method in whole blood samples is relatively simple, non-invasive and little time consuming. It allows to identify MCADD-, VLCADD-, LCHADD- and carnitine transporter deficiencies. The genetic phenotypes of one enzyme defect did not result in differing acylcarnitine patterns in MCADD, VLCADD or LCHADD in vitro.

Trends in Detection of Invasive Cancer and Ductal Carcinoma In Situ at Biennial Screening Mammography in Spain: A Retrospective Cohort Study

PubMed Central

Román, Marta; Rué, Montse; Sala, Maria; Ascunce, Nieves; Baré, Marisa; Baroja, Araceli; De la Vega, Mariola; Galcerán, Jaume; Natal, Carmen; Salas, Dolores; Sánchez-Jacob, Mercedes; Zubizarreta, Raquel; Castells, Xavier

2013-01-01

Background Breast cancer incidence has decreased in the last decade, while the incidence of ductal carcinoma in situ (DCIS) has increased substantially in the western world. The phenomenon has been attributed to the widespread adaption of screening mammography. The aim of the study was to evaluate the temporal trends in the rates of screen detected invasive cancers and DCIS, and to compare the observed trends with respect to hormone replacement therapy (HRT) use along the same study period. Methods Retrospective cohort study of 1,564,080 women aged 45–69 years who underwent 4,705,681 screening mammograms from 1992 to 2006. Age-adjusted rates of screen detected invasive cancer, DCIS, and HRT use were calculated for first and subsequent screenings. Poisson regression was used to evaluate the existence of a change-point in trend, and to estimate the adjusted trends in screen detected invasive breast cancer and DCIS over the study period. Results The rates of screen detected invasive cancer per 100.000 screened women were 394.0 at first screening, and 229.9 at subsequent screen. The rates of screen detected DCIS per 100.000 screened women were 66.8 at first screen and 43.9 at subsequent screens. No evidence of a change point in trend in the rates of DCIS and invasive cancers over the study period were found. Screen detected DCIS increased at a steady 2.5% per year (95% CI: 1.3; 3.8), while invasive cancers were stable. Conclusion Despite the observed decrease in breast cancer incidence in the population, the rates of screen detected invasive cancer remained stable during the study period. The proportion of DCIS among screen detected breast malignancies increased from 13% to 17% throughout the study period. The rates of screen detected invasive cancer and DCIS were independent of the decreasing trend in HRT use observed among screened women after 2002. PMID:24376649

A preoperative cotininury test for abdominoplasty reduces peri-operative complications.

PubMed

Delaunay, F; Coquerel-Beghin, D; Magalon, G; Cohen, S R; Casanova, D; Niddam, J; Milliez, P-Y; Peillon, C; Delpierre, V; Auquit-Auckbur, I

2018-05-16

Smoking induces complications in plastic surgery, in particular wound healing delays. Despite a 4-weeks' abstinence asking before and after surgery, some patients denied or hid their consumption. The aim of this study was to evaluate the effectiveness of a cotininury detection test in terms of improvement in outcomes after an abdominoplasty. This retrospective cohort study included patients who underwent an abdominoplasty with umbilical transposition and lipoaspiration. Current smokers were asked to stop smoking 4 weeks before and after surgery. After 2013, we performed a preoperative cotininury test for patients having abdominoplasty, with a cancellation of surgery in case of positive result. We analyzed the test's effectiveness on delayed healing and on other complications. Two hundred and thirty-five patients were included; 80 were tested and 21,3% had a positive test. There was significantly less delayed healing in the "screening" group than in the "no screening": 20,3% versus 41,5% (P=0,002). Alike, complications were significantly less frequent in the "screening" group than in the "no screening": 18,1% versus 42,3% (P<0,001). The routine use of the cotininury test in preoperative abdominoplasties significantly reduces risk of delayed healing and other serious complications. It is an objective test, which is simple, quick and non-invasive. Smoking cessation must be at least 4 weeks before and after the surgery. Following medical advice to cease smoking by the surgeon and anesthetist, referral to an appropriate tobacco-addiction specialist clinic may be helpful for the patient who has difficulty stopping smoking. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Extensive analysis of native and non-native Centaurea solstitialis L. populations across the world shows no traces of polyploidization

PubMed Central

Montesinos, Daniel; Eren, Özkan; Lortie, Christopher J.; French, Kristine; Cavieres, Lohengrin A.; Sotes, Gastón J.; Hierro, José L.; Jorge, Andreia; Loureiro, João

2017-01-01

Centaurea solstitialis L. (yellow starthistle, Asteraceae) is a Eurasian native plant introduced as an exotic into North and South America, and Australia, where it is regarded as a noxious invasive. Changes in ploidy level have been found to be responsible for numerous plant biological invasions, as they are involved in trait shifts critical to invasive success, like increased growth rate and biomass, longer life-span, or polycarpy. C. solstitialis had been reported to be diploid (2n = 2x = 16 chromosomes), however, actual data are scarce and sometimes contradictory. We determined for the first time the absolute nuclear DNA content by flow cytometry and estimated ploidy level in 52 natural populations of C. solstitialis across its native and non-native ranges, around the world. All the C. solstitialis populations screened were found to be homogeneously diploid (average 2C value of 1.72 pg, SD = ±0.06 pg), with no significant variation in DNA content between invasive and non-invasive genotypes. We did not find any meaningful difference among the extensive number of native and non-native C. solstitialis populations sampled around the globe, indicating that the species invasive success is not due to changes in genome size or ploidy level. PMID:28828232

Extensive analysis of native and non-native Centaurea solstitialis L. populations across the world shows no traces of polyploidization.

PubMed

Irimia, Ramona-Elena; Montesinos, Daniel; Eren, Özkan; Lortie, Christopher J; French, Kristine; Cavieres, Lohengrin A; Sotes, Gastón J; Hierro, José L; Jorge, Andreia; Loureiro, João

2017-01-01

Centaurea solstitialis L. (yellow starthistle, Asteraceae) is a Eurasian native plant introduced as an exotic into North and South America, and Australia, where it is regarded as a noxious invasive. Changes in ploidy level have been found to be responsible for numerous plant biological invasions, as they are involved in trait shifts critical to invasive success, like increased growth rate and biomass, longer life-span, or polycarpy. C . solstitialis had been reported to be diploid (2 n  = 2 x  = 16 chromosomes), however, actual data are scarce and sometimes contradictory. We determined for the first time the absolute nuclear DNA content by flow cytometry and estimated ploidy level in 52 natural populations of C . solstitialis across its native and non-native ranges, around the world. All the C. solstitialis populations screened were found to be homogeneously diploid (average 2C value of 1.72 pg, SD = ±0.06 pg), with no significant variation in DNA content between invasive and non-invasive genotypes. We did not find any meaningful difference among the extensive number of native and non-native C . solstitialis populations sampled around the globe, indicating that the species invasive success is not due to changes in genome size or ploidy level.

Accuracy of indocyanine green pulse spectrophotometry clearance test for liver function prediction in transplanted patients

PubMed Central

Hsieh, Chung-Bao; Chen, Chung-Jueng; Chen, Teng-Wei; Yu, Jyh-Cherng; Shen, Kuo-Liang; Chang, Tzu-Ming; Liu, Yao-Chi

2004-01-01

AIM: To investigate whether the non-invasive real-time Indocynine green (ICG) clearance is a sensitive index of liver viability in patients before, during, and after liver transplantation. METHODS: Thirteen patients were studied, two before, three during, and eight following liver transplantation, with two patients suffering acute rejection. The conventional invasive ICG clearance test and ICG pulse spectrophotometry non-invasive real-time ICG clearance test were performed simultaneously. Using linear regression analysis we tested the correlation between these two methods. The transplantation condition of these patients and serum total bilirubin (T. Bil), alanine aminotransferase (ALT), and platelet count were also evaluated. RESULTS: The correlation between these two methods was excellent (r2 = 0.977). CONCLUSION: ICG pulse spectrophotometry clearance is a quick, non-invasive, and reliable liver function test in transplantation patients. PMID:15285026

Public stated preferences and predicted uptake for genome-based colorectal cancer screening

PubMed Central

2014-01-01

Background Emerging developments in nanomedicine allow the development of genome-based technologies for non-invasive and individualised screening for diseases such as colorectal cancer. The main objective of this study was to measure user preferences for colorectal cancer screening using a nanopill. Methods A discrete choice experiment was used to estimate the preferences for five competing diagnostic techniques including the nanopill and iFOBT. Alternative screening scenarios were described using five attributes namely: preparation involved, sensitivity, specificity, complication rate and testing frequency. Fourteen random and two fixed choice tasks, each consisting of three alternatives, were offered to 2225 individuals. Data were analysed using the McFadden conditional logit model. Results Thirteen hundred and fifty-six respondents completed the questionnaire. The most important attributes (and preferred levels) were the screening technique (nanopill), sensitivity (100%) and preparation (no preparation). Stated screening uptake for the nanopill was 79%, compared to 76% for iFOBT. In the case of screening with the nanopill, the percentage of people preferring not to be screened would be reduced from 19.2% (iFOBT) to 16.7%. Conclusions Although the expected benefits of nanotechnology based colorectal cancer screening are improved screening uptake, assuming more accurate test results and less preparation involved, the relative preference of the nanopill is only slightly higher than the iFOBT. Estimating user preferences during the development of diagnostic technologies could be used to identify relative performance, including perceived benefits and harms compared to competitors allowing for significant changes to be made throughout the process of development. PMID:24642027

Impact of Anthropogenic Disturbance on Native and Invasive Trypanosomes of Rodents in Forested Uganda.

PubMed

Salzer, Johanna S; Pinto, C Miguel; Grippi, Dylan C; Williams-Newkirk, Amanda Jo; Peterhans, Julian Kerbis; Rwego, Innocent B; Carroll, Darin S; Gillespie, Thomas R

2016-12-01

Habitat disturbance and anthropogenic change are globally associated with extinctions and invasive species introductions. Less understood is the impact of environmental change on the parasites harbored by endangered, extinct, and introduced species. To improve our understanding of the impacts of anthropogenic disturbance on such host-parasite interactions, we investigated an invasive trypanosome (Trypanosoma lewisi). We screened 348 individual small mammals, representing 26 species, from both forested and non-forested habitats in rural Uganda. Using microscopy and PCR, we identified 18% of individuals (order Rodentia) as positive for trypanosomes. Further phylogenetic analyses revealed two trypanosomes circulating-T. lewisi and T. varani. T. lewisi was found in seven species both native and invasive, while T. varani was identified in only three native forest species. The lack of T. varani in non-forested habitats suggests that it is a natural parasite of forest-dwelling rodents. Our findings suggest that anthropogenic disturbance may lead to spillover of an invasive parasite (T. lewisi) from non-native to native species, and lead to local co-extinction of a native parasite (T. varani) and native forest-dwelling hosts.

First-void urine: A potential biomarker source for triage of high-risk human papillomavirus infected women.

PubMed

Van Keer, Severien; Pattyn, Jade; Tjalma, Wiebren A A; Van Ostade, Xaveer; Ieven, Margareta; Van Damme, Pierre; Vorsters, Alex

2017-09-01

Great interest has been directed towards the use of first-void urine as a liquid biopsy for high-risk human papillomavirus DNA testing. Despite the high correlations established between urinary and cervical infections, human papillomavirus testing is unable to distinguish between productive and transforming high-risk infections that have the tendency to progress to cervical cancer. Thus far, investigations have been primarily confined to the identification of biomarkers for triage of high-risk human papillomavirus-positive women in cervicovaginal specimens and tissue biopsies. This paper reviews urinary biomarkers for cervical cancer and triage of high-risk human papillomavirus infections and elaborates on the opportunities and challenges that have emerged regarding the use of first-void urine as a liquid biopsy for the analysis of both morphological- (conventional cytology and novel immunohistochemical techniques) and molecular-based (HPV16/18 genotyping, host/viral gene methylation, RNA, and proteins) biomarkers. A literature search was performed in PubMed and Web of Science for studies investigating the use of urine as a biomarker source for cervical cancer screening. Five studies were identified reporting on biomarkers that are still in preclinical exploratory or clinical assay development phases and on assessments of non-invasive (urine) samples. Although large-scale validation studies are still needed, we conclude that methylation of both host and viral genes in urine has been proven feasible for use as a molecular cervical cancer triage and screening biomarker in phase two studies. This is especially promising and underscores our hypothesis that human papillomavirus DNA and candidate human and viral biomarkers are washed away with the initial, first-void urine, together with exfoliated cells, debris and impurities that line the urethra opening. Similar to the limitations of self-collected cervicovaginal samples, first-void urine will likely not fulfil the high-quality cellularity standards required for morphological biomarkers. Molecular biomarkers will likely overcome this issue to yield high-throughput, objective, and reproducible results. When using proper sampling, transport, storage, preanalytical biomarker concentration techniques, and clinically validated assays, first-void urine is expected to be a valuable source of molecular biomarkers for cervical cancer screening. Furthermore, as first-void urine can be easily and non-invasively collected, it is a highly preferred technique among women and offers the ability to test both primary high-risk human papillomavirus and biomarkers in the same sample. In addition, the use of first-void urine confers opportunities to reduce loss-to follow-up and non-adherence to screening subjects. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Non-invasive 13C-glucose breath test using residual gas analyzer-mass spectrometry: a novel tool for screening individuals with pre-diabetes and type 2 diabetes.

PubMed

Ghosh, Chiranjit; Maity, Abhijit; Banik, Gourab D; Som, Suman; Chakraborty, Arpita; Selvan, Chitra; Ghosh, Shibendu; Ghosh, Barnali; Chowdhury, Subhankar; Pradhan, Manik

2014-09-01

We report, for the first time, the clinical feasibility of a novel residual gas analyzer mass spectrometry (RGA-MS) method for accurate evaluation of the (13)C-glucose breath test ((13)C-GBT) in the diagnosis of pre-diabetes (PD) and type 2 diabetes mellitus (T2D). In T2D or PD, glucose uptake is impaired and results in blunted isotope enriched (13)CO2 production in exhaled breath samples. Using the Receiver operating characteristics (ROC) curve analysis, an optimal diagnostic cut-off point of the (13)CO2/(12)CO2 isotope ratios expressed as the delta-over-baseline (DOB) value, was determined to be δDOB(13)C‰ = 28.81‰ for screening individuals with non-diabetes controls (NDC) and pre-diabetes (PD), corresponding to a sensitivity of 100% and specificity of 94.4%. We also determined another optimal diagnostic cut-off point of δDOB(13)C‰ = 19.88‰ between individuals with PD and T2D, which exhibited 100% sensitivity and 95.5% specificity. Our RGA-MS methodology for the (13)C-GBT also manifested a typical diagnostic positive and negative predictive value of 96% and 100%, respectively. The diagnostic accuracy, precision and validity of the results were also confirmed by high-resolution optical cavity enhanced integrated cavity output spectroscopy (ICOS) measurements. The δDOB(13)C‰ values measured with RGA-MS method, correlated favourably (R(2) = 0.979) with those determined by the laser based ICOS method. Moreover, we observed that the effects of endogenous CO2 production related to basal metabolic rates in individuals were statistically insignificant (p = 0.37 and 0.73) on the diagnostic accuracy. Our findings suggest that the RGA-MS is a valid and sufficiently robust method for the (13)C-GBT which may serve as an alternative non-invasive point-of-care diagnostic tool for routine clinical practices as well as for large-scale diabetes screening purposes in real-time.

Bladder cancer biomarker discovery using global metabolomic profiling of urine.

PubMed

Wittmann, Bryan M; Stirdivant, Steven M; Mitchell, Matthew W; Wulff, Jacob E; McDunn, Jonathan E; Li, Zhen; Dennis-Barrie, Aphrihl; Neri, Bruce P; Milburn, Michael V; Lotan, Yair; Wolfert, Robert L

2014-01-01

Bladder cancer (BCa) is a common malignancy worldwide and has a high probability of recurrence after initial diagnosis and treatment. As a result, recurrent surveillance, primarily involving repeated cystoscopies, is a critical component of post diagnosis patient management. Since cystoscopy is invasive, expensive and a possible deterrent to patient compliance with regular follow-up screening, new non-invasive technologies to aid in the detection of recurrent and/or primary bladder cancer are strongly needed. In this study, mass spectrometry based metabolomics was employed to identify biochemical signatures in human urine that differentiate bladder cancer from non-cancer controls. Over 1000 distinct compounds were measured including 587 named compounds of known chemical identity. Initial biomarker identification was conducted using a 332 subject sample set of retrospective urine samples (cohort 1), which included 66 BCa positive samples. A set of 25 candidate biomarkers was selected based on statistical significance, fold difference and metabolic pathway coverage. The 25 candidate biomarkers were tested against an independent urine sample set (cohort 2) using random forest analysis, with palmitoyl sphingomyelin, lactate, adenosine and succinate providing the strongest predictive power for differentiating cohort 2 cancer from non-cancer urines. Cohort 2 metabolite profiling revealed additional metabolites, including arachidonate, that were higher in cohort 2 cancer vs. non-cancer controls, but were below quantitation limits in the cohort 1 profiling. Metabolites related to lipid metabolism may be especially interesting biomarkers. The results suggest that urine metabolites may provide a much needed non-invasive adjunct diagnostic to cystoscopy for detection of bladder cancer and recurrent disease management.

Three-hour analysis of non-invasive foetal sex determination: application of Plexor chemistry.

PubMed

Pietropolli, Adalgisa; Capogna, Maria Vittoria; Cascella, Raffaella; Germani, Chiara; Bruno, Valentina; Strafella, Claudia; Sarta, Simona; Ticconi, Carlo; Marmo, Giusy; Gallaro, Sara; Longo, Giuliana; Marsella, Luigi Tonino; Novelli, Antonio; Novelli, Giuseppe; Piccione, Emilio; Giardina, Emiliano

2016-04-04

The knowledge of the individual genetic "status" in the prenatal era is particularly relevant in the case of positive family history for genetic diseases, in advanced maternal age and in the general screening for foetal abnormalities. In this context, here, we report an innovative molecular assay which utilizes the cell-free foetal DNA (cffDNA) as a source for the early and fast detection of the foetal sex. The study involved 132 pregnant women in their first 3 months of pregnancy, who agreed to give a blood sample. All the collected samples were immediately subjected to the separation of the plasma, which was utilized for the extraction of the cffDNA. Successively, the extracted cffDNA was analysed by a quantitative PCR (qPCR) method based on Plexor-HY chemistry, which is able to simultaneously identify, quantify and discriminate the autosomal DNA from the sex-linked DNA. Overall, the Plexor-HY assay demonstrated to be sensitive and specific for the determination of low-template DNA, such as the cffDNA. In fact, the Plexor-HY assay has been successfully performed in all the samples, identifying 70 males and 62 females. As the foetal sex can be provided in 120 min just by utilizing a maternal blood sample as cffDNA source, the assay represents a very fast, safe and non-invasive prenatal method. The possibility of determining the foetal sex in the early prenatal life consents the application of our assay as a helpful screening test for subjects and families at risk of sex-linked disorders. Moreover, the early knowledge of the foetal sex may be of great help even for the specialist, who might promptly advise the patients concerning the foetal risk of inheriting sex-linked disorders and the clinical utility of performing an invasive prenatal diagnosis.

Residual gas analyzer mass spectrometry for human breath analysis: a new tool for the non-invasive diagnosis of Helicobacter pylori infection.

PubMed

Maity, Abhijit; Banik, Gourab D; Ghosh, Chiranjit; Som, Suman; Chaudhuri, Sujit; Daschakraborty, Sunil B; Ghosh, Shibendu; Ghosh, Barnali; Raychaudhuri, Arup K; Pradhan, Manik

2014-03-01

A residual gas analyzer (RGA) coupled with a high vacuum chamber is described for the non-invasive diagnosis of the Helicobacter pylori (H. pylori) infection through ¹³C-urea breath analysis. The present RGA-based mass spectrometry (MS) method is capable of measuring high-precision ¹³CO₂ isotope enrichments in exhaled breath samples from individuals harboring the H. pylori infection. The system exhibited 100% diagnostic sensitivity, and 93% specificity alongside positive and negative predictive values of 95% and 100%, respectively, compared with invasive endoscopy-based biopsy tests. A statistically sound diagnostic cut-off value for the presence of H. pylori was determined to be 3.0‰ using a receiver operating characteristic curve analysis. The diagnostic accuracy and validity of the results are also supported by optical off-axis integrated cavity output spectroscopy measurements. The δ¹³(DOB)C‰ values of both methods correlated well (R² = 0.9973 at 30 min). The RGA-based instrumental setup described here is simple, robust, easy-to-use and more portable and cost-effective compared to all other currently available detection methods, thus making it a new point-of-care medical diagnostic tool for the purpose of large-scale screening of the H. pylori infection in real time. The RGA-MS technique should have broad applicability for ¹³C-breath tests in a wide range of biomedical research and clinical diagnostics for many other diseases and metabolic disorders.

[Utilisation of salivary markers in nephrology].

PubMed

Podracká, Ľudmila; Celec, Peter; Šebeková, Katarína

2016-01-01

Saliva has a broad diagnostic potential which can be used for detection many pathological conditions including renal dysfunction. In saliva can be measured concentration of urea and creatinine as well as the other uremic markers. Saliva urea nitrogen and creatinine and blood urea and creatinine highly correlated therefore might be used for screening in patients with CKD. Saliva collection is truly non-invasive and is especially suitable for small children and elderly patients. Recently, semiquantitative saliva urea test strip is available. Saliva might become promising dia-gnostic biofluid in nephrological practice.Key words: chronic kidney disease - renal failure - salivary dipstick - salivary markers.

The Use of Climatic Niches in Screening Procedures for Introduced Species to Evaluate Risk of Spread: A Case with the American Eastern Grey Squirrel

PubMed Central

Di Febbraro, Mirko; Lurz, Peter W. W.; Genovesi, Piero; Maiorano, Luigi; Girardello, Marco; Bertolino, Sandro

2013-01-01

Species introduction represents one of the most serious threats for biodiversity. The realized climatic niche of an invasive species can be used to predict its potential distribution in new areas, providing a basis for screening procedures in the compilation of black and white lists to prevent new introductions. We tested this assertion by modeling the realized climatic niche of the Eastern grey squirrel Sciurus carolinensis. Maxent was used to develop three models: one considering only records from the native range (NRM), a second including records from native and invasive range (NIRM), a third calibrated with invasive occurrences and projected in the native range (RCM). Niche conservatism was tested considering both a niche equivalency and a niche similarity test. NRM failed to predict suitable parts of the currently invaded range in Europe, while RCM underestimated the suitability in the native range. NIRM accurately predicted both the native and invasive range. The niche equivalency hypothesis was rejected due to a significant difference between the grey squirrel’s niche in native and invasive ranges. The niche similarity test yielded no significant results. Our analyses support the hypothesis of a shift in the species’ climatic niche in the area of introductions. Species Distribution Models (SDMs) appear to be a useful tool in the compilation of black lists, allowing identifying areas vulnerable to invasions. We advise caution in the use of SDMs based only on the native range of a species for the compilation of white lists for other geographic areas, due to the significant risk of underestimating its potential invasive range. PMID:23843957

An assessment of community health workers’ ability to screen for cardiovascular disease risk with a simple, non-invasive risk assessment instrument in Bangladesh, Guatemala, Mexico, and South Africa: an observational study

PubMed Central

Gaziano, Thomas A; Abrahams-Gessel, Shafika; Denman, Catalina A; Montano, Carlos Mendoza; Khanam, Masuma; Puoane, Thandi; Levitt, Naomi S

2016-01-01

Summary Background Cardiovascular disease contributes substantially to the non-communicable disease (NCD) burden in low-income and middle-income countries, which also often have substantial health personnel shortages. In this observational study we investigated whether community health workers could do community-based screenings to predict cardiovascular disease risk as effectively as could physicians or nurses, with a simple, non-invasive risk prediction indicator in low-income and middle-income countries. Methods This observation study was done in Bangladesh, Guatemala, Mexico, and South Africa. Each site recruited at least ten to 15 community health workers based on usual site-specific norms for required levels of education and language competency. Community health workers had to reside in the community where the screenings were done and had to be fluent in that community’s predominant language. These workers were trained to calculate an absolute cardiovascular disease risk score with a previously validated simple, non-invasive screening indicator. Community health workers who successfully finished the training screened community residents aged 35–74 years without a previous diagnosis of hypertension, diabetes, or heart disease. Health professionals independently generated a second risk score with the same instrument and the two sets of scores were compared for agreement. The primary endpoint of this study was the level of direct agreement between risk scores assigned by the community health workers and the health professionals. Findings Of 68 community health worker trainees recruited between June 4, 2012, and Feb 8, 2013, 42 were deemed qualified to do fieldwork (15 in Bangladesh, eight in Guatemala, nine in Mexico, and ten in South Africa). Across all sites, 4383 community members were approached for participation and 4049 completed screening. The mean level of agreement between the two sets of risk scores was 96 8% (weighted κ =0 948, 95% CI 0 936–0 961) and community health workers showed that 263 (6%) of 4049 people had a 5-year cardiovascular disease risk of greater than 20%. Interpretation Health workers without formal professional training can be adequately trained to effectively screen for, and identify, people at high risk of cardiovascular disease. Using community health workers for this screening would free up trained health professionals in low-resource settings to do tasks that need high levels of formal, professional training. Funding US National Heart, Lung, and Blood Institute and National Institutes of Health, UnitedHealth Chronic Disease Initiative. PMID:26187361

An assessment of community health workers' ability to screen for cardiovascular disease risk with a simple, non-invasive risk assessment instrument in Bangladesh, Guatemala, Mexico, and South Africa: an observational study.

PubMed

Gaziano, Thomas A; Abrahams-Gessel, Shafika; Denman, Catalina A; Montano, Carlos Mendoza; Khanam, Masuma; Puoane, Thandi; Levitt, Naomi S

2015-09-01

Cardiovascular disease contributes substantially to the non-communicable disease (NCD) burden in low-income and middle-income countries, which also often have substantial health personnel shortages. In this observational study we investigated whether community health workers could do community-based screenings to predict cardiovascular disease risk as effectively as could physicians or nurses, with a simple, non-invasive risk prediction indicator in low-income and middle-income countries. This observation study was done in Bangladesh, Guatemala, Mexico, and South Africa. Each site recruited at least ten to 15 community health workers based on usual site-specific norms for required levels of education and language competency. Community health workers had to reside in the community where the screenings were done and had to be fluent in that community's predominant language. These workers were trained to calculate an absolute cardiovascular disease risk score with a previously validated simple, non-invasive screening indicator. Community health workers who successfully finished the training screened community residents aged 35-74 years without a previous diagnosis of hypertension, diabetes, or heart disease. Health professionals independently generated a second risk score with the same instrument and the two sets of scores were compared for agreement. The primary endpoint of this study was the level of direct agreement between risk scores assigned by the community health workers and the health professionals. Of 68 community health worker trainees recruited between June 4, 2012, and Feb 8, 2013, 42 were deemed qualified to do fieldwork (15 in Bangladesh, eight in Guatemala, nine in Mexico, and ten in South Africa). Across all sites, 4383 community members were approached for participation and 4049 completed screening. The mean level of agreement between the two sets of risk scores was 96·8% (weighted κ=0·948, 95% CI 0·936-0·961) and community health workers showed that 263 (6%) of 4049 people had a 5-year cardiovascular disease risk of greater than 20%. Health workers without formal professional training can be adequately trained to effectively screen for, and identify, people at high risk of cardiovascular disease. Using community health workers for this screening would free up trained health professionals in low-resource settings to do tasks that need high levels of formal, professional training. Copyright © 2015 Gaziano et al. Open Access article published under the terms of CC BY-NC-ND 4.0. Published by Elsevier Ltd.. All rights reserved.

Effectiveness of Computer-Aided Detection in Community Mammography Practice

PubMed Central

Abraham, Linn; Taplin, Stephen H.; Geller, Berta M.; Carney, Patricia A.; D’Orsi, Carl; Elmore, Joann G.; Barlow, William E.

2011-01-01

Background Computer-aided detection (CAD) is applied during screening mammography for millions of US women annually, although it is uncertain whether CAD improves breast cancer detection when used by community radiologists. Methods We investigated the association between CAD use during film-screen screening mammography and specificity, sensitivity, positive predictive value, cancer detection rates, and prognostic characteristics of breast cancers (stage, size, and node involvement). Records from 684 956 women who received more than 1.6 million film-screen mammograms at Breast Cancer Surveillance Consortium facilities in seven states in the United States from 1998 to 2006 were analyzed. We used random-effects logistic regression to estimate associations between CAD and specificity (true-negative examinations among women without breast cancer), sensitivity (true-positive examinations among women with breast cancer diagnosed within 1 year of mammography), and positive predictive value (breast cancer diagnosed after positive mammograms) while adjusting for mammography registry, patient age, time since previous mammography, breast density, use of hormone replacement therapy, and year of examination (1998–2002 vs 2003–2006). All statistical tests were two-sided. Results Of 90 total facilities, 25 (27.8%) adopted CAD and used it for an average of 27.5 study months. In adjusted analyses, CAD use was associated with statistically significantly lower specificity (OR = 0.87, 95% confidence interval [CI] = 0.85 to 0.89, P < .001) and positive predictive value (OR = 0.89, 95% CI = 0.80 to 0.99, P = .03). A non-statistically significant increase in overall sensitivity with CAD (OR = 1.06, 95% CI = 0.84 to 1.33, P = .62) was attributed to increased sensitivity for ductal carcinoma in situ (OR = 1.55, 95% CI = 0.83 to 2.91; P = .17), although sensitivity for invasive cancer was similar with or without CAD (OR = 0.96, 95% CI = 0.75 to 1.24; P = .77). CAD was not associated with higher breast cancer detection rates or more favorable stage, size, or lymph node status of invasive breast cancer. Conclusion CAD use during film-screen screening mammography in the United States is associated with decreased specificity but not with improvement in the detection rate or prognostic characteristics of invasive breast cancer. PMID:21795668

Proposed Application of Fast Fourier Transform in Near Infra Red Based Non Invasive Blood Glucose Monitoring System

NASA Astrophysics Data System (ADS)

Jenie, R. P.; Iskandar, J.; Kurniawan, A.; Rustami, E.; Syafutra, H.; Nurdin, N. M.; Handoyo, T.; Prabowo, J.; Febryarto, R.; Rahayu, M. S. K.; Damayanthi, E.; Rimbawan; Sukandar, D.; Suryana, Y.; Irzaman; Alatas, H.

2017-03-01

Worldwide emergence of glycaemic status related health disorders, such as diabetes and metabolic syndrome, is growing in alarming rate. The objective was to propose new methods for non invasive blood glucose level measurement system, based on implementation of Fast Fourier Transform methods. This was an initial-lab-scale-research. Data on non invasive blood glucose measurement are referred from Scopus, Medline, and Google Scholar, from 2011 until 2016, and was used as design references, combined with in house verification. System was developed in modular fashion, based on aforementioned compiled references. Several preliminary tests to understand relationship between LED and photo-diode responses have been done. Several references were used as non invasive blood glucose measurement tools design basis. Solution is developed in modular fashion. we have proven different sensor responses to water and glucose. Human test for non invasive blood glucose level measurement system is needed.

Non-invasive prenatal diagnosis (NIPD) for single gene disorders: cost analysis of NIPD and invasive testing pathways.

PubMed

Verhoef, Talitha I; Hill, Melissa; Drury, Suzanne; Mason, Sarah; Jenkins, Lucy; Morris, Stephen; Chitty, Lyn S

2016-07-01

Evaluate the costs of offering non-invasive prenatal diagnosis (NIPD) for single gene disorders compared to traditional invasive testing to inform NIPD implementation into clinical practice. Total costs of diagnosis using NIPD or invasive testing pathways were compared for a representative set of single gene disorders. For autosomal dominant conditions, where NIPD molecular techniques are straightforward, NIPD cost £314 less than invasive testing. NIPD for autosomal recessive and X-linked conditions requires more complicated technical approaches and total costs were more than invasive testing, e.g. NIPD for spinal muscular atrophy was £1090 more than invasive testing. Impact of test uptake on costs was assessed using sickle cell disorder as an example. Anticipated high uptake of NIPD resulted in an incremental cost of NIPD over invasive testing of £48 635 per 100 pregnancies at risk of sickle cell disorder. Total costs of NIPD are dependent upon the complexity of the testing technique required. Anticipated increased demand for testing may have economic implications for prenatal diagnostic services. Ethical issues requiring further consideration are highlighted including directing resources to NIPD when used for information only and restricting access to safe tests if it is not cost-effective to develop NIPD for rare conditions. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

The Present and Future of Prostate Cancer Urine Biomarkers

PubMed Central

Rigau, Marina; Olivan, Mireia; Garcia, Marta; Sequeiros, Tamara; Montes, Melania; Colás, Eva; Llauradó, Marta; Planas, Jacques; de Torres, Inés; Morote, Juan; Cooper, Colin; Reventós, Jaume; Clark, Jeremy; Doll, Andreas

2013-01-01

In order to successfully cure patients with prostate cancer (PCa), it is important to detect the disease at an early stage. The existing clinical biomarkers for PCa are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid over-treatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two thirds of the biopsies performed are still unnecessary. Thus the discovery of non-invasive PCa biomarkers remains urgent. In recent years, the utilization of urine has emerged as an attractive option for the non-invasive detection of PCa. Moreover, a great improvement in high-throughput “omic” techniques has presented considerable opportunities for the identification of new biomarkers. Herein, we will review the most significant urine biomarkers described in recent years, as well as some future prospects in that field. PMID:23774836

Cost-Effectiveness of High-Risk Human Papillomavirus Testing With Messenger RNA Versus DNA Under United States Guidelines for Cervical Cancer Screening.

PubMed

Ting, Jie; Smith, Jennifer S; Myers, Evan R

2015-10-01

To compare the cost-effectiveness of high-risk human papillomavirus (hrHPV) testing using a hrHPV DNA and a hrHPV messenger RNA (mRNA) assay under current US cervical cancer screening guidelines. We constructed a Markov model for stochastic cost-effectiveness analysis using published data. We compared screening efficiency using DNA and mRNA testing for the following: (1) cotesting with cytology in women 30 to 65 years, and (2) triage of women with mild cervical cytological abnormalities (atypical squamous cells of undetermined significance [ASC-US]) in the United States. Screening end point is histologically confirmed high-grade lesions (cervical intraepithelial neoplasia grade 2, 3, or invasive cancer). Sensitivity and specificity estimates of DNA and mRNA testing to detect cervical intraepithelial neoplasia grade 2, 3, or invasive cancer were obtained from 2 published trials: the US Clinical Evaluation of APTIMA mRNA (CLEAR) study for ASC-US triage and the French APTIMA Screening Evaluation (FASE) study for cotesting. Costs of DNA and mRNA testing were assumed identical. Costs of screening, diagnosis, and treatment of cervical neoplasia and cancer were from previously published estimates, adjusted to 2012 US dollars. Inputs were modeled as distributions for Monte Carlo probabilistic sensitivity analysis. Model outcomes were costs per life-year saved for each strategy, discounted at 3% annually. For both cotesting and ASC-US triage, mRNA testing cost less than DNA testing, whereas life expectancies were widely overlapping. There was a 100% probability that DNA testing was not cost-effective at $100,000/life-year saved threshold for ASC-US triage and a 55% probability that DNA testing was not cost-effective at the same threshold for cotesting. Based on the available evidence, mRNA testing for cotesting or ASC-US triage is likely to be more efficient than DNA testing under current US cervical cancer screening guidelines.

[Interpretation of false positive results of biochemical prenatal tests].

PubMed

Sieroszewski, Piotr; Słowakiewicz, Katarzyna; Perenc, Małgorzata

2010-03-01

Modern, non-invasive prenatal diagnostics based on biochemical and ultrasonographic markers of fetal defects allows us to calculate the risk of fetal chromosomal aneuploidies with high sensitivity and specificity An introduction of biochemical, non-invasive prenatal tests turned out to result in frequent false positive results of these tests in cases when invasive diagnostics does not confirm fetal defects. However prospective analysis of these cases showed numerous complications in the third trimester of the pregnancies.

Non-invasive preimplantation genetic screening using array comparative genomic hybridization on spent culture media: a proof-of-concept pilot study.

PubMed

Feichtinger, Michael; Vaccari, Enrico; Carli, Luca; Wallner, Elisabeth; Mädel, Ulrike; Figl, Katharina; Palini, Simone; Feichtinger, Wilfried

2017-06-01

The aim of this pilot study was to assess if array comparative genomic hybridization (aCGH), non-invasive preimplantation genetic screening (PGS) on blastocyst culture media is feasible. Therefore, aCGH analysis was carried out on 22 spent blastocyst culture media samples after polar body PGS because of advanced maternal age. All oocytes were fertilized by intracytoplasmic sperm injection and all embryos underwent assisted hatching. Concordance of polar body analysis and culture media genetic results was assessed. Thirteen out of 18 samples (72.2%) revealed general concordance of ploidy status (euploid or aneuploid). At least one chromosomal aberration was found concordant in 10 out of 15 embryos found to be aneuploid by both polar body and culture media analysis. Overall, 17 out of 35 (48.6%) single chromosomal aneuploidies were concordant between the culture media and polar body analysis. By analysing negative controls (oocytes with fertilization failure), notable maternal contamination was observed. Therefore, non-invasive PGS could serve as a second matrix after polar body or cleavage stage PGS; however, in euploid results, maternal contamination needs to be considered and results interpreted with caution. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The population impact of screening for Down syndrome: audit of 19 326 invasive diagnostic tests in England and Wales in 2008.

PubMed

Morris, Joan K; Waters, Jonathan J; de Souza, E

2012-06-01

Pregnant women who receive a high screening risk result for Down, Edwards or Patau syndrome are offered diagnostic tests that carry a risk of miscarriage. This study determined how many women had such tests per syndrome diagnosis. The number of tests per Down, Edwards or Patau syndrome diagnosis adjusted for maternal and gestational age at diagnosis was calculated using routine data from 18 (95%) cytogenetic laboratories in England and Wales in 2008. There were 19,326 tests that identified 1118 diagnoses of Down syndrome and 615 of Edwards and Patau syndromes. There were eight chorionic villus samplings (CVS) per syndrome diagnosis compared with 16 amniocenteses (gestational age adjusted). The lowest number of tests per diagnosis (three for CVSs and for amniocentesis) resulted from an abnormal ultrasound scan. Among pregnant women, 2.9% had an invasive diagnostic test. If a CVS and an amniocentesis increase the risk of a miscarriage by 1% and 0.5%, respectively, approximately one miscarriage for every 14 Down, Edwards or Patau syndrome diagnosis would have occurred. A simple measurement of the population impact of screening for Down syndrome can be calculated using data already collected. Annual estimates should be produced to monitor the national fetal anomaly screening programme. © 2012 John Wiley & Sons, Ltd. © 2012 John Wiley & Sons, Ltd.

Projected future impact of HPV vaccination and primary HPV screening on cervical cancer rates from 2017–2035: Example from Australia

PubMed Central

Smith, Megan A.; Saville, Marion; Canfell, Karen

2018-01-01

Background Many countries are transitioning from cytology-based to longer-interval HPV screening. Trials comparing HPV-based screening to cytology report an increase in CIN2/3 detection at the first screen, and longer-term reductions in CIN3+; however, population level year-to-year transitional impacts are poorly understood. We undertook a comprehensive evaluation of switching to longer-interval primary HPV screening in the context of HPV vaccination. We used Australia as an example setting, since Australia will make this transition in December 2017. Methods Using a model of HPV vaccination, transmission, natural history and cervical screening, Policy1-Cervix, we simulated the planned transition from recommending cytology every two years for sexually-active women aged 18–20 to 69, to recommending HPV screening every five years for women aged 25–74 years. We estimated rates of CIN2/3, cervical cancer incidence, and mortality for each year from 2005 to 2035, considering ranges for HPV test accuracy and screening compliance in the context of HPV vaccination (current coverage ~82% in females; ~76% in males). Findings Transient increases are predicted to occur in rates of CIN2/3 detection and invasive cervical cancer in the first two to three years following the screening transition (of 16–24% and 11–14% in respectively, compared to 2017 rates). However, by 2035, CIN2/3 and invasive cervical cancer rates are predicted to fall by 40–44% and 42–51%, respectively, compared to 2017 rates. Cervical cancer mortality rates are predicted to remain unchanged until ~2020, then decline by 34–45% by 2035. Over the period 2018–2035, switching to primary HPV screening in Australia is expected to avert 2,006 cases of invasive cervical cancer and save 587 lives. Conclusions Transient increases in detected CIN2/3 and invasive cancer, which may be detectable at the population level, are predicted following a change to primary HPV screening. This is due to improved test sensitivity bringing forward diagnoses, resulting in longer term reductions in both cervical cancer incidence and mortality. Fluctuations in health outcomes due to the transition to a longer screening interval are predicted to occur for 10–15 years, but cervical cancer rates will be significantly reduced thereafter due to the impact of HPV vaccination and HPV screening. In order to maintain confidence in primary HPV screening through the transitional phase, it is important to widely communicate that an initial increase in CIN2/3 and perhaps even invasive cervical cancer is expected after a national transition to primary HPV screening, that this phenomenon is due to increased prevalent disease detection, and that this effect represents a marker of screening success. PMID:29444073

A new approach to epigenome-wide discovery of non-invasive methylation biomarkers for colorectal cancer screening in circulating cell-free DNA using pooled samples.

PubMed

Gallardo-Gómez, María; Moran, Sebastian; Páez de la Cadena, María; Martínez-Zorzano, Vicenta Soledad; Rodríguez-Berrocal, Francisco Javier; Rodríguez-Girondo, Mar; Esteller, Manel; Cubiella, Joaquín; Bujanda, Luis; Castells, Antoni; Balaguer, Francesc; Jover, Rodrigo; De Chiara, Loretta

2018-01-01

Colorectal cancer is the fourth cause of cancer-related deaths worldwide, though detection at early stages associates with good prognosis. Thus, there is a clear demand for novel non-invasive tests for the early detection of colorectal cancer and premalignant advanced adenomas, to be used in population-wide screening programs. Aberrant DNA methylation detected in liquid biopsies, such as serum circulating cell-free DNA (cfDNA), is a promising source of non-invasive biomarkers. This study aimed to assess the feasibility of using cfDNA pooled samples to identify potential serum methylation biomarkers for the detection of advanced colorectal neoplasia (colorectal cancer or advanced adenomas) using microarray-based technology. cfDNA was extracted from serum samples from 20 individuals with no colorectal findings, 20 patients with advanced adenomas, and 20 patients with colorectal cancer (stages I and II). Two pooled samples were prepared for each pathological group using equal amounts of cfDNA from 10 individuals, sex-, age-, and recruitment hospital-matched. We measured the methylation levels of 866,836 CpG positions across the genome using the MethylationEPIC array. Pooled serum cfDNA methylation data meets the quality requirements. The proportion of detected CpG in all pools (> 99% with detection p value < 0.01) exceeded Illumina Infinium methylation data quality metrics of the number of sites detected. The differential methylation analysis revealed 1384 CpG sites (5% false discovery rate) with at least 10% difference in the methylation level between no colorectal findings controls and advanced neoplasia, the majority of which were hypomethylated. Unsupervised clustering showed that cfDNA methylation patterns can distinguish advanced neoplasia from healthy controls, as well as separate tumor tissue from healthy mucosa in an independent dataset. We also observed that advanced adenomas and stage I/II colorectal cancer methylation profiles, grouped as advanced neoplasia, are largely homogenous and clustered close together. This preliminary study shows the viability of microarray-based methylation biomarker discovery using pooled serum cfDNA samples as an alternative approach to tissue specimens. Our strategy sets an open door for deciphering new non-invasive biomarkers not only for colorectal cancer detection, but also for other types of cancers.

[Breast cancer incidence related with a population-based screening program].

PubMed

Natal, Carmen; Caicoya, Martín; Prieto, Miguel; Tardón, Adonina

2015-02-20

To compare breast cancer cumulative incidence, time evolution and stage at diagnosis between participants and non-participant women in a population-based screening program. Cohort study of breast cancer incidence in relation to participation in a population screening program. The study population included women from the target population of the screening program. The source of information for diagnostics and stages was the population-based cancer registry. The analysis period was 1999-2010. The Relative Risk for invasive, in situ, and total cancers diagnosed in participant women compared with non-participants were respectively 1.16 (0.94-1.43), 2.98 (1.16-7.62) and 1.22 (0.99-1.49). The Relative Risk for participants versus non-participants was 2.47 (1.55-3.96) for diagnosis at stagei, 2.58 (1.67-3.99) for T1 and 2.11 (1.38-3.23) for negative lymph node involvement. The cumulative incidence trend had two joint points in both arms, with an Annual Percent of Change of 92.3 (81.6-103.5) between 1999-2001, 18.2 (16.1-20.3) between 2001-2005 and 5.9 (4.0-7.8) for the last period in participants arm, and 72.6 (58.5-87.9) between 1999-2001, 12.6 (7.9-17.4) between 2001-2005, and 8.6 (6.5-10.6) in the last period in the non-participant arm. Participating in the breast cancer screening program analyzed increased the in situ cumulative cancer incidence, but not the invasive and total incidence. Diagnoses were earlier in the participant arm. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

[Research on a non-invasive pulse wave detection and analysis system].

PubMed

Li, Ting; Yu, Gang

2008-10-01

A novel non-invasive pulse wave detection and analysis system has been developed, including the software and the hardware. Bi-channel signals can be acquired, stored and shown on the screen dynamically at the same time. Pulse wave can be reshown and printed after pulse wave analysis and pulse wave velocity analysis. This system embraces a computer which is designed for fast data saving, analyzing and processing, and a portable data sampling machine which is based on a singlechip. Experimental results have shown that the system is stable and easy to use, and the parameters are calculated accurately.

Breast and cervical cancers diagnosed and stage at diagnosis among women served through the National Breast and Cervical Cancer Early Detection Program.

PubMed

Miller, Jacqueline W; Royalty, Janet; Henley, Jane; White, Arica; Richardson, Lisa C

2015-05-01

To assess cancers diagnosed and the stage of cancer at the time of diagnosis among low-income, under-insured, or uninsured women who received services through the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Using the NBCCEDP database, we examined the number and percent of women diagnosed during 2009-2011 with in situ breast cancer, invasive breast cancer, and invasive cervical cancer by demographic and clinical characteristics, including age, race and ethnicity, test indication (screening or diagnostic), symptoms (for breast cancer), and screening history (for cervical cancer). We examined these characteristics by stage at diagnosis, a new variable included in the database obtained by linking with state-based central cancer registries. There were 11,569 women diagnosed with invasive breast cancer, 1,988 with in situ breast cancer, and 583 with invasive cervical cancer through the NBCCEDP. Women who reported breast symptoms or who had diagnostic mammography were more likely to be diagnosed with breast cancer, and at a later stage, than those who did not have symptoms or who had screening mammography. Women who had been rarely or never screened for cervical cancer were more likely to be diagnosed with cervical cancer, and at a later stage, than women who received regular screenings. Women served through the NBCCEDP who have not had prior screening or who have symptoms were more often diagnosed with late-stage disease.

Msi2 Regulates the Aggressiveness of Non-Small Cell Lung Cancer (NSCLC)

DTIC Science & Technology

2016-12-01

Non-small cell lung cancer, invasion, metastasis, pro-invasive signaling, RNA binding proteins, Musashi, TGF-beta, epithelial mesenchymal transition...Non-small cell lung cancer, invasion, metastasis, pro-invasive signaling, RNA binding proteins, Musashi, TGF- beta, epithelial mesenchymal...NOTCH-1 RNA and protein expression in 344SQ and 531LN2 cells (NICD protein level was tested in 344SQ cells as well), Fig. 2 D-F. Surprisingly

Non-destructive digital imaging in poplar allows detailed analysis of adventitious rooting dynamics

Treesearch

R.J. Kodrzycki; R.B. Michaels; A.L. Friend; R.S. Zalesny; Ch.P. Mawata; D.W. McDonald

2008-01-01

The dynamics of root formation are difficult to observe directly over time without disturbing the rooting environment. A novel system for a non-destructive, non-invasive root analysis (RootViz FS, Phenotype Screening Corp.) was evaluated for its ability to analyze root formation from cuttings over a 32 day period in three poplar genotypes (DN70, P. Deltoides x...

Schrodinger's scat: a critical review of the currently available tiger (Panthera Tigris) and leopard (Panthera pardus) specific primers in India, and a novel leopard specific primer.

PubMed

Maroju, Pranay Amruth; Yadav, Sonu; Kolipakam, Vishnupriya; Singh, Shweta; Qureshi, Qamar; Jhala, Yadvendradev

2016-02-09

Non-invasive sampling has opened avenues for the genetic study of elusive species, which has contributed significantly to their conservation. Where field based identity of non-invasive sample is ambiguous (e.g. carnivore scats), it is essential to establish identity of the species through molecular approaches. A cost effective procedure to ascertain species identity is to use species specific primers (SSP) for PCR amplification and subsequent resolution through agarose gel electrophoresis. However, SSPs if ill designed can often cross amplify non-target sympatric species. Herein we report the problem of cross amplification with currently published SSPs, which have been used in several recent scientific articles on tigers (Panthera tigris) and leopards (Panthera pardus) in India. Since these papers form pioneering research on which future work will be based, an early rectification is required so as to not propagate this error further. We conclusively show cross amplification of three of the four SSPs, in sympatric non-target species like tiger SSP amplifying leopard and striped hyena (Hyaena hyaena), and leopard SSP amplifying tiger, lion (Panthera leo persica) and clouded leopard (Neofelis nebulosa), with the same product size. We develop and test a non-cross-amplifying leopard specific primer pair within the mitochondrial cytochrome b region. We also standardize a duplex PCR method to screen tiger and leopard samples simultaneously in one PCR reaction to reduce cost and time. These findings suggest the importance of an often overlooked preliminary protocol of conclusive identification of species from non-invasive samples. The cross amplification of published primers in conspecifics suggests the need to revisit inferences drawn by earlier work.

Improvement of Olfactory Function With High Frequency Non-invasive Auricular Electrostimulation in Healthy Humans

PubMed Central

Maharjan, Ashim; Wang, Eunice; Peng, Mei; Cakmak, Yusuf O.

2018-01-01

In past literature on animal models, invasive vagal nerve stimulation using high frequencies has shown to be effective at modulating the activity of the olfactory bulb (OB). Recent advances in invasive vagal nerve stimulation in humans, despite previous findings in animal models, used low frequency stimulation and found no effect on the olfactory functioning. The present article aimed to test potential effects of non-invasive, high and low frequency vagal nerve stimulation in humans, with supplementary exploration of the orbitofrontal cortex using near-infrared spectroscopy (NIRS). Healthy, male adult participants (n = 18) performed two olfactory tests [odor threshold test (OTT) and supra-threshold test (STT)] before and after receiving high-, low frequency vagal nerve stimulation and placebo (no stimulation). Participant's olfactory functioning was monitored using NIRS, and assessed with two behavioral olfactory tests. NIRS data of separate stimulation parameters were statistically analyzed using repeated-measures ANOVA across different stages. Data from olfactory tests were analyzed using paired parametric and non-parametric statistical tests. Only high frequency, non-invasive vagal nerve stimulation was able to positively modulate the performance of the healthy participants in the STT (p = 0.021, Wilcoxon sign-ranked test), with significant differences in NIRS (p = 0.014, post-hoc with Bonferroni correction) recordings of the right hemispheric, orbitofrontal cortex. The results from the current article implore further exploration of the neurocircuitry involved under vagal nerve stimulation and the effects of non-invasive, high frequency, vagal nerve stimulation toward olfactory dysfunction which showcase in Parkinson's and Alzheimer's Diseases. Despite the sufficient effect size (moderate effect, correlation coefficient (r): 0.39 for the STT) of the current study, future research should replicate the current findings with a larger cohort. PMID:29740266

Improvement of Olfactory Function With High Frequency Non-invasive Auricular Electrostimulation in Healthy Humans.

PubMed

Maharjan, Ashim; Wang, Eunice; Peng, Mei; Cakmak, Yusuf O

2018-01-01

In past literature on animal models, invasive vagal nerve stimulation using high frequencies has shown to be effective at modulating the activity of the olfactory bulb (OB). Recent advances in invasive vagal nerve stimulation in humans, despite previous findings in animal models, used low frequency stimulation and found no effect on the olfactory functioning. The present article aimed to test potential effects of non-invasive, high and low frequency vagal nerve stimulation in humans, with supplementary exploration of the orbitofrontal cortex using near-infrared spectroscopy (NIRS). Healthy, male adult participants ( n = 18) performed two olfactory tests [odor threshold test (OTT) and supra-threshold test (STT)] before and after receiving high-, low frequency vagal nerve stimulation and placebo (no stimulation). Participant's olfactory functioning was monitored using NIRS, and assessed with two behavioral olfactory tests. NIRS data of separate stimulation parameters were statistically analyzed using repeated-measures ANOVA across different stages. Data from olfactory tests were analyzed using paired parametric and non-parametric statistical tests. Only high frequency, non-invasive vagal nerve stimulation was able to positively modulate the performance of the healthy participants in the STT ( p = 0.021, Wilcoxon sign-ranked test), with significant differences in NIRS ( p = 0.014, post-hoc with Bonferroni correction ) recordings of the right hemispheric, orbitofrontal cortex. The results from the current article implore further exploration of the neurocircuitry involved under vagal nerve stimulation and the effects of non-invasive, high frequency, vagal nerve stimulation toward olfactory dysfunction which showcase in Parkinson's and Alzheimer's Diseases. Despite the sufficient effect size (moderate effect, correlation coefficient (r): 0.39 for the STT) of the current study, future research should replicate the current findings with a larger cohort.

Strategies for Implementing Cell-Free DNA Testing.

PubMed

Cuckle, Howard

2016-06-01

Maternal plasma cell-free (cf) DNA testing has higher discriminatory power for aneuploidy than any conventional multi-marker screening test. Several strategies have been suggested for introducing it into clinical practice. Secondary cfDNA, restricted only to women with positive conventional screening test, is generally cost saving and minimizes the need for invasive prenatal diagnosis but leads to a small loss in detection. Primary cfDNA, replacing conventional screening or retaining the nuchal translucency scan, is not currently cost-effective for third-party payers. Contingent cfDNA, testing about 20% of women with the highest risks based on a conventional test, is the preferred approach. Copyright © 2016 Elsevier Inc. All rights reserved.

Decision-making for non-invasive prenatal testing for Down syndrome: Hong Kong Chinese women's preferences for individual vs relational autonomy.

PubMed

Lau, J Y C; Yi, H; Ahmed, S

2016-05-01

Individual autonomy in antenatal screening is internationally recognized and supported. Policy and practice guidelines in various countries place emphasis on the woman's right to make her own decision and are related to concepts such as self-determination, independence, and self-sufficiency. In contrast, the dominant perspective in Chinese medical ethics suggests that the family is pivotal in making medical decisions, hence providing support for relational autonomy. This study explored Hong Kong Chinese pregnant women's preferences for individual vs relational autonomy for non-invasive prenatal testing (NIPT) for Down syndrome. A qualitative study was carried out using semi-structured interviews with 36 women who had undertaken NIPT in Hong Kong. The findings show that most Hong Kong Chinese women valued aspects of both relational and individual autonomy in decision-making for NIPT. Women expected support from doctors as experts on the topic and wanted to involve their husband in decision-making while retaining control over the outcome. Somewhat surprisingly, the findings do not provide support for the involvement of family members in decision-making for NIPT. The adequacy of current interpretations of autonomy in prenatal testing policies as an individual approach needs discussion, where policy developers need to find a balance between individual and relational approaches. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acoustic analysis of snoring sounds recorded with a smartphone according to obstruction site in OSAS patients.

PubMed

Koo, Soo Kweon; Kwon, Soon Bok; Kim, Yang Jae; Moon, J I Seung; Kim, Young Jun; Jung, Sung Hoon

2017-03-01

Snoring is a sign of increased upper airway resistance and is the most common symptom suggestive of obstructive sleep apnea. Acoustic analysis of snoring sounds is a non-invasive diagnostic technique and may provide a screening test that can determine the location of obstruction sites. We recorded snoring sounds according to obstruction level, measured by DISE, using a smartphone and focused on the analysis of formant frequencies. The study group comprised 32 male patients (mean age 42.9 years). The spectrogram pattern, intensity (dB), fundamental frequencies (F 0 ), and formant frequencies (F 1 , F 2 , and F 3 ) of the snoring sounds were analyzed for each subject. On spectrographic analysis, retropalatal level obstruction tended to produce sharp and regular peaks, while retrolingual level obstruction tended to show peaks with a gradual onset and decay. On formant frequency analysis, F 1 (retropalatal level vs. retrolingual level: 488.1 ± 125.8 vs. 634.7 ± 196.6 Hz) and F 2 (retropalatal level vs. retrolingual level: 1267.3 ± 306.6 vs. 1723.7 ± 550.0 Hz) of retrolingual level obstructions showed significantly higher values than retropalatal level obstruction (p < 0.05). This suggests that the upper airway is more severely obstructed with retrolingual level obstruction and that there is a greater change in tongue position. Acoustic analysis of snoring is a non-invasive diagnostic technique that can be easily applied at a relatively low cost. The analysis of formant frequencies will be a useful screening test for the prediction of occlusion sites. Moreover, smartphone can be effective for recording snoring sounds.

[Effects, safety and cost-benefit analysis of Down syndrome screening in first trimester].

PubMed

Shengmou, Lin; Min, Chen; Chenhong, Wang; Shengli, Li; Jiansheng, Xie; Hui, Yuan; Dinghao, Lin; Xiaoxia, Wu; Wei, Wang; Hongyun, Zhang; Haiyan, Tang

2014-05-01

To investigate the effects, safety and cost-benefit analysis of Down syndrome screening in first trimester. From January 2009 to December 2012, 43 729 pregnant women undergoing 3 methods of Down syndrome traditional screening strategies in Shenzhen Maternity and Child Healthcare Hospital were studied retrospectively, including in 17 502 cases in pregnancy associated plasma protein A (PAPP-A) and free β-hCG measured biochemistry screening, 14 080 cases in nuchal translucency (NT) screening and 12 147 cases in combined screening, meanwhile, 7 389 cases on non-invasive fetal trisomy test (NIFTY) were performed in Huada Gene Research Institute(BGI). The effects and safety of four screening strategies were assessed throughout a decision tree. The economical characters of each screening strategy were compared by cost-effectiveness analysis as well as cost-benefit analysis. (1) The effects of four strategies are: NIFTY > combined screening > NT screening > biochemistry screening. (2) The safety of four strategies are: NIFTY > combined screening > NT screening > biochemistry screening. (3) Cost-effectiveness analysis and cost-benefit analysis:the biochemistry screening has lowest cost-effectiveness ratio (CER) and highest cost-benefit ratio (CBR), which performed a better economical efficiency. The incremental CER of three traditional screening strategies are all less than the economical burden of Down syndrome.NIFTY has highest CER and negative net present value (NPV), NPV would be positive and CBR would be more than 1 if the price of NIFTY reduce to 1 434 Yuan. Combined screening possess best screening efficiency, while biochemistry screening was demonstrated more economical in traditional screening.NIFTY is the future of Down syndrome screening.

Prenatal diagnostic decision-making in adolescents.

PubMed

Plaga, Stacey L; Demarco, Kristin; Shulman, Lee P

2005-04-01

We sought to evaluate the prenatal decision-making of pregnant adolescents identified at increased risk for identifiable fetal genetic abnormalities. A retrospective review of records of gravid women 19 years old or younger undergoing genetic counseling from 2001-2003 (inclusive) was undertaken. Hospital-based academic center. Thirty-seven women were identified; four cases did not meet inclusion criteria. None. Decision to undergo or forgo invasive prenatal testing. Of the 33 women included in this study, the average age was 17.6 years (range: 15-19). Eighteen were Latinas, eight were African-Americans, and seven were Caucasians. Sixteen women had positive maternal serum screening outcomes; nine women sought counseling because of personal/family histories of genetic abnormalities, seven sought counseling after fetal structural anomalies were detected by ultrasound, and one woman sought counseling because she and her partner were positive for Mendelian disorder screening (sickle cell disease). Sixteen of the women (48.5%) chose to undergo invasive testing (15 amniocenteses, one chorionic villus sampling) whereas 17 (51.5%) chose to forgo invasive testing. Adolescents offered invasive prenatal diagnosis will chose to undergo or forgo such testing based on diagnostic and personal criteria as do adult women. Nonetheless, unique adolescent issues may make the process by which information is obtained and communicated during counseling to be different from counseling provided to adults. The development of new genetic screening and diagnostic protocols has and will increase the number of pregnant adolescent women who will be offered genetic counseling during their pregnancies. Such an increase in numbers will place considerably more pressure on an already taxed genetic counseling system; accordingly, new counseling paradigms will need to be developed to provide service to an expanded patient population seeking information for an increasing number of genetic issues.

Could Digital PCR Be an Alternative as a Non-Invasive Prenatal Test for Trisomy 21: A Proof of Concept Study.

PubMed

El Khattabi, Laïla Allach; Rouillac-Le Sciellour, Christelle; Le Tessier, Dominique; Luscan, Armelle; Coustier, Audrey; Porcher, Raphael; Bhouri, Rakia; Nectoux, Juliette; Sérazin, Valérie; Quibel, Thibaut; Mandelbrot, Laurent; Tsatsaris, Vassilis; Vialard, François; Dupont, Jean-Michel

2016-01-01

NIPT for fetal aneuploidy by digital PCR has been hampered by the large number of PCR reactions needed to meet statistical requirements, preventing clinical application. Here, we designed an octoplex droplet digital PCR (ddPCR) assay which allows increasing the number of available targets and thus overcomes statistical obstacles. After technical optimization of the multiplex PCR on mixtures of trisomic and euploid DNA, we performed a validation study on samples of plasma DNA from 213 pregnant women. Molecular counting of circulating cell-free DNA was performed using a mix of hydrolysis probes targeting chromosome 21 and a reference chromosome. The results of our validation experiments showed that ddPCR detected trisomy 21 even when the sample's trisomic DNA content is as low as 5%. In a validation study of plasma samples from 213 pregnant women, ddPCR discriminated clearly between the trisomy 21 and the euploidy groups. Our results demonstrate that digital PCR can meet the requirements for non-invasive prenatal testing of trisomy 21. This approach is technically simple, relatively cheap, easy to implement in a diagnostic setting and compatible with ethical concerns regarding access to nucleotide sequence information. These advantages make it a potential technique of choice for population-wide screening for trisomy 21 in pregnant women.

Prostate-specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer.

PubMed

Hashimoto, Takeshi; Ohori, Makoto; Shimodaira, Kenji; Kaburaki, Naoto; Hirasawa, Yosuke; Satake, Naoya; Gondo, Tatsuo; Nakagami, Yoshihiro; Namiki, Kazunori; Ohno, Yoshio

2018-06-01

To clarify the impact of prostate-specific antigen screening on surgical outcomes of prostate cancer. Patients who underwent radical prostatectomy were divided into two groups according to prostate-specific antigen testing opportunity (group 1, prostate-specific antigen screening; group 2, non-prostate-specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank-sum and χ 2 -tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence-free survival. In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate-specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5-year biochemical recurrence-free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate-specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate-specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate-specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study. Detection by screening results in favorable outcomes after surgery. Prostate-specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer. © 2018 The Japanese Urological Association.

Non-invasive Prenatal Testing and the Unveiling of an Impaired Translation Process.

PubMed

Murdoch, Blake; Ravitsky, Vardit; Ogbogu, Ubaka; Ali-Khan, Sarah; Bertier, Gabrielle; Birko, Stanislav; Bubela, Tania; De Beer, Jeremy; Dupras, Charles; Ellis, Meika; Granados Moreno, Palmira; Joly, Yann; Kamenova, Kalina; Master, Zubin; Marcon, Alessandro; Paulden, Mike; Rousseau, François; Caulfield, Timothy

2017-01-01

Non-invasive prenatal testing (NIPT) is an exciting technology with the potential to provide a variety of clinical benefits, including a reduction in miscarriages, via a decline in invasive testing. However, there is also concern that the economic and near-future clinical benefits of NIPT have been overstated and the potential limitations and harms underplayed. NIPT, therefore, presents an opportunity to explore the ways in which a range of social pressures and policies can influence the translation, implementation, and use of a health care innovation. NIPT is often framed as a potential first tier screen that should be offered to all pregnant women, despite concerns over cost-effectiveness. Multiple forces have contributed to a problematic translational environment in Canada, creating pressure towards first tier implementation. Governments have contributed to commercialization pressure by framing the publicly funded research sector as a potential engine of economic growth. Members of industry have an incentive to frame clinical value as beneficial to the broadest possible cohort in order to maximize market size. Many studies of NIPT were directly funded and performed by private industry in laboratories lacking strong independent oversight. Physicians' fear of potential liability for failing to recommend NIPT may further drive widespread uptake. Broad social endorsement, when combined with these translation pressures, could result in the "routinization" of NIPT, thereby adversely affecting women's reproductive autonomy. Policymakers should demand robust independent evidence of clinical and public health utility relevant to their respective jurisdictions before making decisions regarding public funding for NIPT. Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

Non-Invasive Screening Techniques for Drugs of Abuse,

DTIC Science & Technology

1982-08-01

documentation. The system is capable of identifying all common drugs of abuse except cannabinoids, lysergic acid diethylamide (LSD), and psilocybin ...combined with LSD, diphenhydramine (Benadryl), mari- huana or other drugs. Methods of detection: TLC, GLC, EMIT, RIA. Psilocybin (’magic mushrooms

When Are Native Species Inappropriate for Conservation Plantings

EPA Science Inventory

Conservation agencies and organizations are generally reluctant to encourage the use of invasive plant species in conservation programs. Harsh lessons learned in the past have resulted in tougher screening protocols for non-indigenous species introductions and removal of many no...

Role of non-Invasive Tests for the Early Detection of Cancer | Division of Cancer Prevention

Cancer.gov

Speaker | Dr. Nickolas Papadopoulos will present "Role of non-Invasive Tests for the Early Detection of Cancers". Date: June 5, 2018; Time: 11:00am - 12:00pm; Location: NCI Shady Grove, Conference Room: Seminar 110 Terrace Level East

Effectiveness of VIA, Pap, and HPV DNA Testing in a Cervical Cancer Screening Program in a Peri-Urban Community in Andhra Pradesh, India

PubMed Central

Gravitt, Patti E.; Paul, Proma; Katki, Hormuzd A.; Vendantham, Haripriya; Ramakrishna, Gayatri; Sudula, Mrudula; Kalpana, Basany; Ronnett, Brigitte M.; Vijayaraghavan, K.; Shah, Keerti V.

2010-01-01

Background While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness. Methods and Findings A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity  =  78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures. Conclusions We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality. PMID:21060889

Identification of trisomy 18, trisomy 13, and Down syndrome from maternal plasma.

PubMed

Gekas, Jean; Langlois, Sylvie; Ravitsky, Vardit; Audibert, François; van den Berg, David-Gradus; Haidar, Hazar; Rousseau, François

2014-01-01

Current prenatal diagnosis for fetal aneuploidies (including trisomy 21 [T21]) generally relies on an initial biochemical serum-based noninvasive prenatal testing (NIPT) after which women who are deemed to be at high risk are offered an invasive confirmatory test (amniocentesis or chorionic villi sampling for a fetal karyotype), which is associated with a risk of fetal miscarriage. Recently, genomics-based NIPT (gNIPT) was proposed for the analysis of fetal genomic DNA circulating in maternal blood. The diffusion of this technology in routine prenatal care could be a major breakthrough in prenatal diagnosis, since initial research studies suggest that this novel approach could be very effective and could reduce substantially the number of invasive procedures. However, the limitations of gNIPT may be underappreciated. In this review, we examine currently published literature on gNIPT to highlight advantages and limitations. At this time, the performance of gNIPT is relatively well-documented only in high-risk pregnancies for T21 and trisomy 18. This additional screening test may be an option for women classified as high-risk of aneuploidy who wish to avoid invasive diagnostic tests, but it is crucial that providers carefully counsel patients about the test's advantages and limitations. The gNIPT is currently not recommended as a first-tier prenatal screening test for T21. Since gNIPT is not considered as a diagnostic test, a positive gNIPT result should always be confirmed by an invasive test, such as amniocentesis or chorionic villus sampling. Validation studies are needed to optimally introduce this technology into the existing routine workflow of prenatal care.

Prenatal screening for congenital anomalies: exploring midwives' perceptions of counseling clients with religious backgrounds.

PubMed

Gitsels-van der Wal, Janneke T; Manniën, Judith; Gitsels, Lisanne A; Reinders, Hans S; Verhoeven, Pieternel S; Ghaly, Mohammed M; Klomp, Trudy; Hutton, Eileen K

2014-07-19

In the Netherlands, prenatal screening follows an opting in system and comprises two non-invasive tests: the combined test to screen for trisomy 21 at 12 weeks of gestation and the fetal anomaly scan to detect structural anomalies at 20 weeks. Midwives counsel about prenatal screening tests for congenital anomalies and they are increasingly having to counsel women from religious backgrounds beyond their experience. This study assessed midwives' perceptions and practices regarding taking client's religious backgrounds into account during counseling. As Islam is the commonest non-western religion, we were particularly interested in midwives' knowledge of whether pregnancy termination is allowed in Islam. This exploratory study is part of the DELIVER study, which evaluated primary care midwifery in The Netherlands between September 2009 and January 2011. A questionnaire was sent to all 108 midwives of the twenty practices participating in the study. Of 98 respondents (response rate 92%), 68 (69%) said they took account of the client's religion. The two main reasons for not doing so were that religion was considered irrelevant in the decision-making process and that it should be up to clients to initiate such discussions. Midwives' own religious backgrounds were independent of whether they paid attention to the clients' religious backgrounds. Eighty midwives (82%) said they did not counsel Muslim women differently from other women. Although midwives with relatively many Muslim clients had more knowledge of Islamic attitudes to terminating pregnancy in general than midwives with relatively fewer Muslim clients, the specific knowledge of termination regarding trisomy 21 and other congenital anomalies was limited in both groups. While many midwives took client's religion into account, few knew much about Islamic beliefs on prenatal screening for congenital anomalies. Midwives identified a need for additional education. To meet the needs of the changing client population, counselors need more knowledge of religious opinions about the termination of pregnancy and the skills to approach religious issues with clients.

Prenatal screening for congenital anomalies: exploring midwives’ perceptions of counseling clients with religious backgrounds

PubMed Central

2014-01-01

Background In the Netherlands, prenatal screening follows an opting in system and comprises two non-invasive tests: the combined test to screen for trisomy 21 at 12 weeks of gestation and the fetal anomaly scan to detect structural anomalies at 20 weeks. Midwives counsel about prenatal screening tests for congenital anomalies and they are increasingly having to counsel women from religious backgrounds beyond their experience. This study assessed midwives’ perceptions and practices regarding taking client’s religious backgrounds into account during counseling. As Islam is the commonest non-western religion, we were particularly interested in midwives’ knowledge of whether pregnancy termination is allowed in Islam. Methods This exploratory study is part of the DELIVER study, which evaluated primary care midwifery in the Netherlands between September 2009 and January 2011. A questionnaire was sent to all 108 midwives of the twenty practices participating in the study. Results Of 98 respondents (response rate 92%), 68 (69%) said they took account of the client’s religion. The two main reasons for not doing so were that religion was considered irrelevant in the decision-making process and that it should be up to clients to initiate such discussions. Midwives’ own religious backgrounds were independent of whether they paid attention to the clients’ religious backgrounds. Eighty midwives (82%) said they did not counsel Muslim women differently from other women. Although midwives with relatively many Muslim clients had more knowledge of Islamic attitudes to terminating pregnancy in general than midwives with relatively fewer Muslim clients, the specific knowledge of termination regarding trisomy 21 and other congenital anomalies was limited in both groups. Conclusion While many midwives took client’s religion into account, few knew much about Islamic beliefs on prenatal screening for congenital anomalies. Midwives identified a need for additional education. To meet the needs of the changing client population, counselors need more knowledge of religious opinions about the termination of pregnancy and the skills to approach religious issues with clients. PMID:25037919

Clinical implications of the HPV-16 infection & 7 beneficial effects of optimal dose of Vitamin D3 in safe, effective cancer treatment: Non-invasive rapid cancer screening using "Mouth, Hand & Foot Writing Form" of 40 participants during 150- minute workshop on the Bi-Digital 0-ring Test, in the 1st day of European Congress for Integrative Medicine, September 9-11, 2016 in Budapest.

PubMed

Omura, Yoshiaki

During the 1st day of European Congress for Integrative Medicine held September 9-11, 2016, almost the entire 1st day was scheduled for the Bi-Digital O-Ring Test, which was originally developed by this author, & consists of 2 main parts for which a U.S. patent was issued in 1993. One is a non-invasive, detection of various molecules using very strong Electromagnetic Field (EMF) Resonance Phenomenon between 2 identical molecules with identical weight. Using this strong EMF Resonance Phenomenon, most molecules & microorganisms can be detected rapidly and non-invasively without directly contacting patients. We measured the HPV-16 infection of 70 participants non-invasively in the first 30 minutes, then screened cancers for 40 volunteers who completed one page "Mouth, Hand & Foot Writing Form," which took an average of 5∼10 minutes for each person to complete. Screening of 75 common cancers was made in 2-5 minutes for each patient. Analysis of 40 volunteers revealed 32 persons had some malignancies including 5 Anaplastic Astrocytomas of the L-brain, 3 Multiple Myelomas, 7 Hodgkin's Lymphomas, 8 Non-Hodgkin's Lymphomas, 2 rectum cancers (with chief complaints of worsening Irritable Bowel Syndrome). Although everyone had HPV-16 infections between about 6,000ng & 250ng, malignancy could not be found among those who had less than 1,200ng. Our individualized safe, effective and economical treatment of various cancers consists of optimal doses of Vitamin D3 with or without Taurine and/or PQQ depending on the positive synergetic compatibility among these 3 substances as normal parts of human tissue. The most serious 2 cases of rectum cancer with multiple metastasis, we confirmed very significant anti-cancer effects of their optimal doses of vitamin D3, which is increased to 800~1,000 I.U. (due to advanced cancer with multiple metastasis instead of the usual 400 I.U. for average adults). The unique 7 beneficial effects of optimal dose of Vitamin D3 (also Taurine or PQQ) include: 1) significant Anti-cancer effects without side effects; 2) marked decrease in DNA mutation as decreases in 8-OH-dG; 3) marked urinary excretion of Viruses, Bacteria, Fungi, & Toxic substances, including Asbestos & metals; 4) marked increase in Acetylcholine in the brain & the rest of the body; 5) marked increase in DHEA; 6) marked decrease in β-Amyloid (I-42); 7) marked decrease in Cardiac Troponin I. Optimal dose of Vitamin D3 is clinically most important for cancer, ischemic heart, and memory problems. Optimal dose of Taurine is 150∼175mg and PQQ is 5-7.5mg and should be taken 3-4 times a day, depending on the patient. Medications and supplements including excessive Vitamin C (as well as multivitamins) but also inhibited optimal doses of Vitamin D3, Taurine & PQQ. Often coffee, drinks containing high Vitamin C content (e.g., some green tea & orange juice), & multivitamins as well as pain medicine (e.g., Oxycodone), strong EMF from cellular phones, and strong negative BDORT underwear often completely eliminate the above beneficial effects of Vitamin D3 and promote growth of cancer.

A novel approach for noninvasive drug delivery and sensing through the amniotic sac.

PubMed

Azagury, Aharon; Amar-Lewis, Eliz; Mann, Ella; Goldbart, Riki; Traitel, Tamar; Jelinek, Raz; Hallak, Mordechai; Kost, Joseph

2014-06-10

Current invasive prenatal tests (amniocentesis and chorionic villus sampling) are known for their risk to the fetus. In the last decade, the use and awareness of these prenatal tests have increased, resulting in growing demand for a safe, non-invasive, and accurate prenatal test. Chemical penetration enhancers (CPEs) have long been used to increase transport phenomena across skin and other membranes (e.g., tympanic membrane). The amniotic sac membrane is called the chorioamnion (CA) membrane and serves as the physical barrier between the fetus and the mother. In this research, the effect of CPEs on human CA mass transport was evaluated both in vitro and ex vivo. The results show that the tested CPEs exhibit an enhancing effect on CA mass transport. Based on the permeability results, two mechanisms of action were suggested: "extractors" and "fluidizers". Fourier transform infrared (FTIR) and rapid colorimetric screening measurements supported the mechanisms, based on which, more potent compounds were designed and tested for their enhancing effect. The enhancing mass transport effect of CPEs on CA membrane may be used both for sampling of cell-free DNA and for noninvasively administering drugs and other biological agents to the amniotic sac. Copyright © 2014 Elsevier B.V. All rights reserved.

Design of and normative data for a new computer based test of ocular torsion.

PubMed

Vaswani, Reena S; Mudgil, Ananth V

2004-01-01

To evaluate a new clinically practical and dynamic test for quantifying torsional binocular eye alignment changes which may occur in the change from monocular to binocular viewing conditions. The test was developed using a computer with Lotus Freelance Software, binoculars with prisms and colored filters. The subject looks through binoculars at the computer screen two meters away. For monocular vision, six concentric blue circles, a blue horizontal line and a tilted red line were displayed on the screen. For binocular vision, white circles replaced blue circles. The subject was asked to orient the lines parallel to each other. The difference in tilt (degrees) between the subjective parallel and fixed horizontal position is the torsional alignment of the eye. The time to administer the test was approximately two minutes. In 70 Normal subjects, average age 16 years, the mean degree of cyclodeviation tilt in the right eye was 0.6 degrees for monocular viewing conditions and 0.7 degrees for binocular viewing conditions, with a standard deviation of approximately one degree. There was no "statistically significant" difference between monocular and binocular viewing. This computer based test is a simple, computerized, non-invasive test that has a potential for use in the diagnosis of cyclovertical strabismus. Currently, there is no commercially available test for this purpose.

Characterization of small microsatellite loci isolated in endangered Indiana bat (Myotis sodalis) for use in non-invasive sampling

USGS Publications Warehouse

Oyler-McCance, Sara J.; Fike, Jennifer A.

2011-01-01

Primers for 10 microsatellite loci were developed specifically to amplify low quantity and quality DNA in the endangered Indiana Bat (Myotis sodalis). In a screen of 20 individuals from a population in Missouri, the 10 loci were found to have levels of variability ranging from seven to 18 alleles. No loci were found to be linked, although two loci revealed significant departures from Hardy–Weinberg equilibrium. These microsatellite loci will be applicable for population genetic analyses and for use in mark-recapture studies that utilize DNA collected non-invasively from fecal pellets, which will ultimately aid in management efforts.

Tools for the diagnosis of hepatitis C virus infection and hepatic fibrosis staging

PubMed Central

Saludes, Verónica; González, Victoria; Planas, Ramon; Matas, Lurdes; Ausina, Vicente; Martró, Elisa

2014-01-01

Hepatitis C virus (HCV) infection represents a major public health issue. Hepatitis C can be cured by therapy, but many infected individuals are unaware of their status. Effective HCV screening, fast diagnosis and characterization, and hepatic fibrosis staging are highly relevant for controlling transmission, treating infected patients and, consequently, avoiding end-stage liver disease. Exposure to HCV can be determined with high sensitivity and specificity with currently available third generation serology assays. Additionally, the use of point-of-care tests can increase HCV screening opportunities. However, active HCV infection must be confirmed by direct diagnosis methods. Additionally, HCV genotyping is required prior to starting any treatment. Increasingly, high-volume clinical laboratories use different types of automated platforms, which have simplified sample processing, reduced hands-on-time, minimized contamination risks and human error and ensured full traceability of results. Significant advances have also been made in the field of fibrosis stage assessment with the development of non-invasive methods, such as imaging techniques and serum-based tests. However, no single test is currently available that is able to completely replace liver biopsy. This review focuses on approved commercial tools used to diagnose HCV infection and the recommended hepatic fibrosis staging tests. PMID:24707126

Potential diagnostic consequences of applying non-invasive prenatal testing: population-based study from a country with existing first-trimester screening.

PubMed

Petersen, O B; Vogel, I; Ekelund, C; Hyett, J; Tabor, A

2014-03-01

Targeted non-invasive prenatal testing (NIPT) tests for trisomies 21, 18 and 13 and sex chromosome aneuploidies and could be an alternative to traditional karyotyping. The aim of this study was to determine the risk of missing other abnormal karyotypes of probable phenotypic significance by NIPT. This was a retrospective population-based analysis of all singleton pregnancies booked for combined first-trimester screening (cFTS) in Denmark over a 4-year period. Data concerning maternal demographics, cFTS and prenatal or postnatal karyotypes were collected from the Danish Fetal Medicine database. Karyotypes were classified according to whether the chromosomal anomaly would have been detected by NIPT and whether it was likely to affect phenotype. cFTS was completed in 193638 pregnancies. 10205 (5.3%) had cytogenetic or molecular analysis performed. Of these, 1122 (11.0%) had an abnormal karyotype, of which 262 (23.4%) would have been missed by NIPT, but would probably have been clinically significant. The prevalence of such 'atypical abnormal karyotypes' was increased in women above 45 years of age, in pregnancies with increased nuchal translucency (NT) thickness (≥ 3.5 mm), with abnormal levels of free β-human chorionic gonadotropin (<0.2 or ≥ 5.0 multiples of the median (MoM)) or pregnancy-associated plasma protein-A<0.2 MoM. One or more of these factors was present in 3% of women, and the prevalence of atypical abnormal karyotypes in this high-risk cohort was 1.6%. A significant proportion of karyotypic abnormalities will be missed by targeted NIPT. Women of advanced maternal age, or with increased fetal NT or abnormal biochemistry, have a higher risk of having a fetus affected by an atypical abnormal karyotype and need to be counseled accordingly when considering NIPT. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Qualitative and quantitative dermatoglyphic traits in patients with breast cancer: a prospective clinical study

PubMed Central

Chintamani; Khandelwal, Rohan; Mittal, Aliza; Saijanani, Sai; Tuteja, Amita; Bansal, Anju; Bhatnagar, Dinesh; Saxena, Sunita

2007-01-01

Background Breast cancer is one of the most extensively studied cancers and its genetic basis is well established. Dermatoglyphic traits are formed under genetic control early in development but may be affected by environmental factors during first trimester of pregnancy. They however do not change significantly thereafter, thus maintaining stability not greatly affected by age. These patterns may represent the genetic make up of an individual and therefore his/her predisposition to certain diseases. Patterns of dermatoglyphics have been studied in various congenital disorders like Down's syndrome and Kleinfelter syndrome. The prints can thus represent a non-invasive anatomical marker of breast cancer risk and thus facilitate early detection and treatment. Methods The study was conducted on 60 histo-pathologically confirmed breast cancer patients and their digital dermatoglyphic patterns were studied to assess their association with the type and onset of breast cancer. Simultaneously 60 age-matched controls were also selected that had no self or familial history of a diagnosed breast cancer and the observations were recorded. The differences of qualitative (dermatoglyphic patterns) data were tested for their significance using the chi-square test, and for quantitative (ridge counts and pattern intensity index) data using the t- test. Results It was observed that six or more whorls in the finger print pattern were statistically significant among the cancer patients as compared to controls. It was also seen that whorls in the right ring finger and right little finger were found increased among the cases as compared to controls. The differences between mean pattern intensity index of cases and controls were found to be statistically significant. Conclusion The dermatoglyphic patterns may be utilized effectively to study the genetic basis of breast cancer and may also serve as a screening tool in the high-risk population. In a developing country like India it might prove to be an anatomical, non-invasive, inexpensive and effective tool for screening and studying the patterns in the high-risk population. PMID:17397524

Feasibility and Outcomes of Multiplex Ligation-Dependent Probe Amplification on Buccal Smears as a Screening Method for Microdeletions and Duplications among 300 Adults with an Intellectual Disability of Unknown Aetiology

ERIC Educational Resources Information Center

Peppink, D.; Douma-Kloppenburg, D. D.; de Rooij-Askes, E. S. P.; van Zoest, I. M.; Evenhuis, H. M.; Gille, J. J. P.; van Hagen, J. M.

2008-01-01

Background: Determining the aetiology of intellectual disability (ID) enables anticipation of specific comorbidity and can thus be beneficial. Blood sampling, however, is considered stressful for people with ID. Our aim was to evaluate the feasibility of a non-invasive screening technique of nine microdeletions/duplications among adults with ID of…

Mammographic screening in Sami speaking municipalities and a control group. Are early outcome measures influenced by ethnicity?

PubMed

Norum, Jan; Hofvind, Solveig; Nieder, Carsten; Schnell, Edrun Andrea; Broderstad, Ann Ragnhild

2012-04-16

Female citizens of Sami (the indigenous people of Norway) municipalities in northern Norway have a low risk of breast cancer. The objective of this study was to describe the attendance rate and outcome of the Norwegian Breast Cancer Screening Program (NBCSP) in the Sami-speaking municipalities and a control group. A retrospective registry-based study. The 8 municipalities included in the administration area of the Sami language law (Sami) were matched with a control group of 11 municipalities (non-Sami). Population data were accessed from Statistics Norway. Data regarding invitations and outcome in the NBCSP during the period 2001-2010 was derived from the Cancer Registry of Norway (CRN). The NBCSP targets women aged 50-69 years. Rates and percentages were compared using chi-square test with a p-value<0.05 as statistical significant. The attendance rate in the NBCSP was 78% in the Sami and 75% in the non-Sami population (p< 0.01). The recall rates were 2.4 and 3.3% in the Sami and non-Sami population, respectively (p<0.01). The rate of invasive screen detected cancer was not significantly lower in the Sami group (p=0.14). The percentage of all breast cancers detected in the NBCSP among the Sami (67%) was lower compared with the non-Sami population (86%, p=0.06). Despite a lower risk of breast cancer, the Sami attended the NBCSP more frequently than the control group. The recall and cancer detection rate was lower among the Sami compared with the non-Sami group.

Withdrawing low risk women from cervical screening programmes: mathematical modelling study.

PubMed

Sherlaw-Johnson, C; Gallivan, S; Jenkins, D

1999-02-06

To evaluate the impact of policies for removing women before the recommended age of 64 from screening programmes for cervical cancer in the United Kingdom. A mathematical model of the clinical course of precancerous lesions which accounts for the influence of infection with the human papillomavirus, the effects of screening on the progression of disease, and the accuracy of the testing procedures. Two policies are compared: one in which women are withdrawn from the programme if their current smear is negative and they have a recent history of regular, negative results and one in which women are withdrawn if their current smear test is negative and a simultaneous test is negative for exposure to high risk types of human papillomavirus. United Kingdom cervical screening programme. The incidence of invasive cervical cancer and the use of resources. Early withdrawal of selected women from the programme is predicted to give rise to resource savings of up to 25% for smear tests and 18% for colposcopies when withdrawal occurs from age 50, the youngest age considered in the study. An increase in the incidence of invasive cervical cancer, by up to 2 cases/100 000 women each year is predicted. Testing for human papillomavirus infection to determine which women should be withdrawn from the programme makes little difference to outcome. This model systematically analyses the consequences of screening options using available data and the clinical course of precancerous lesions. If further audit studies confirm the model's forecasts, a policy of early withdrawal might be considered. This would be likely to release substantial resources which could be channelled into other aspects of health care or may be more effectively used within the cervical screening programme to counteract the possible increase in cancer incidence that early withdrawal might bring.

Diagnosis of primary antibody and complement deficiencies in young adults after a first invasive bacterial infection.

PubMed

Sanges, S; Wallet, F; Blondiaux, N; Theis, D; Vérin, I; Vachée, A; Dessein, R; Faure, K; Viget, N; Senneville, E; Leroy, O; Maury, F; Just, N; Poissy, J; Mathieu, D; Prévotat, A; Chenivesse, C; Scherpereel, A; Smith, G; Lopez, B; Rosain, J; Frémeaux-Bacchi, V; Hachulla, E; Hatron, P-Y; Bahuaud, M; Batteux, F; Launay, D; Labalette, M; Lefèvre, G

2017-08-01

Screening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults. Eligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening. The study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively. PID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Non-invasive, non-radiological quantification of anteroposterior knee joint ligamentous laxity

PubMed Central

Russell, D. F.; Deakin, A. H.; Fogg, Q. A.; Picard, F.

2013-01-01

Objectives We performed in vitro validation of a non-invasive skin-mounted system that could allow quantification of anteroposterior (AP) laxity in the outpatient setting. Methods A total of 12 cadaveric lower limbs were tested with a commercial image-free navigation system using trackers secured by bone screws. We then tested a non-invasive fabric-strap system. The lower limb was secured at 10° intervals from 0° to 60° of knee flexion and 100 N of force was applied perpendicular to the tibia. Acceptable coefficient of repeatability (CR) and limits of agreement (LOA) of 3 mm were set based on diagnostic criteria for anterior cruciate ligament (ACL) insufficiency. Results Reliability and precision within the individual invasive and non-invasive systems was acceptable throughout the range of flexion tested (intra-class correlation coefficient 0.88, CR 1.6 mm). Agreement between the two systems was acceptable measuring AP laxity between full extension and 40° knee flexion (LOA 2.9 mm). Beyond 40° of flexion, agreement between the systems was unacceptable (LOA > 3 mm). Conclusions These results indicate that from full knee extension to 40° flexion, non-invasive navigation-based quantification of AP tibial translation is as accurate as the standard validated commercial system, particularly in the clinically and functionally important range of 20° to 30° knee flexion. This could be useful in diagnosis and post-operative evaluation of ACL pathology. Cite this article: Bone Joint Res 2013;2:233–7. PMID:24184443

Do native parasitic plants cause more damage to exotic invasive hosts than native non-invasive hosts? An implication for biocontrol.

PubMed

Li, Junmin; Jin, Zexin; Song, Wenjing

2012-01-01

Field studies have shown that native, parasitic plants grow vigorously on invasive plants and can cause more damage to invasive plants than native plants. However, no empirical test has been conducted and the mechanism is still unknown. We conducted a completely randomized greenhouse experiment using 3 congeneric pairs of exotic, invasive and native, non-invasive herbaceous plant species to quantify the damage caused by parasitic plants to hosts and its correlation with the hosts' growth rate and resource use efficiency. The biomass of the parasitic plants on exotic, invasive hosts was significantly higher than on congeneric native, non-invasive hosts. Parasites caused more damage to exotic, invasive hosts than to congeneric, native, non-invasive hosts. The damage caused by parasites to hosts was significantly positively correlated with the biomass of parasitic plants. The damage of parasites to hosts was significantly positively correlated with the relative growth rate and the resource use efficiency of its host plants. It may be the mechanism by which parasitic plants grow more vigorously on invasive hosts and cause more damage to exotic, invasive hosts than to native, non-invasive hosts. These results suggest a potential biological control effect of native, parasitic plants on invasive species by reducing the dominance of invasive species in the invaded community.

Raman spectroscopic studies on exfoliated cells of oral and cervix

NASA Astrophysics Data System (ADS)

Hole, Arti; Sahu, Aditi; Shaikh, Rubina; Tyagi, Gunjan; Murali Krishna, C.

2018-01-01

Visual inspection followed by biopsy is the standard procedure for cancer diagnosis. Due to invasive nature of the current diagnostic methods, patients are often non-compliant. Hence, it is necessary to explore less invasive and rapid methods for early detection. Exfoliative cytology is a simple, rapid, and less invasive technique. It is thus well accepted by patients and is suitable for routine applications in population screening programs. Raman spectroscopy (RS) has been increasingly explored for disease diagnosis in the recent past. In vivo RS has previously shown promise in management of both oral and cervix cancers. In vivo applications require on-site instrumentation and stringent experimental conditions. Hence, RS of less invasive samples like exfoliated cells has been explored, as this facilitates collection at multiple screening centers followed by analysis at a centralized facility. In the present study, efficacy of Raman spectroscopy in classification of 15 normal and 29 abnormal oral exfoliated cells specimens and 28 normal and 38 abnormal cervix specimens were explored. Spectra were acquired by Raman microprobe (HE 785, Horiba-Jobin-Yvon, France) from several areas to span the pellet. Spectral acquisition parameters were: microscopic objective: 40X, power: 40 mW, acquisition time: 15 s and average: 3. PCA and PC-LDA of pre-processed spectra was carried out on a 4-model system of normal and tumor of both cervix and oral specimens. Leave-one-out-cross-validation findings indicate 73 % correct classification. Findings suggest RS of exfoliated cells may serve as a patient-friendly, non-invasive, rapid and objective method for management of cervix and oral cancers.

Transient elastography (FibroScan®) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand?

PubMed Central

Mikolasevic, Ivana; Orlic, Lidija; Franjic, Neven; Hauser, Goran; Stimac, Davor; Milic, Sandra

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Currently, the routinely used modalities are unable to adequately determine the levels of steatosis and fibrosis (laboratory tests and ultrasonography) or cannot be applied as a screening procedure (liver biopsy). Among the non-invasive tests, transient elastography (FibroScan®, TE) with controlled attenuation parameter (CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD, the factors associated with the diagnosis and NAFLD progression. The method is fast, reliable and reproducible, with good intra- and interobserver levels of agreement, thus allowing for population-wide screening and disease follow-up. The initial inability of the procedure to accurately determine fibrosis and steatosis in obese patients has been addressed with the development of the obese-specific XL probe. TE with CAP is a viable alternative to ultrasonography, both as an initial assessment and during follow-up of patients with NAFLD. Its ability to exclude patients with advanced fibrosis may be used to identify low-risk NAFLD patients in whom liver biopsy is not needed, therefore reducing the risk of complications and the financial costs. PMID:27621571

Introduction of the colorectal cancer screening program: results from a single centre study.

PubMed

Vermeer, Nina C A; Bahadoer, Renu R; Bastiaannet, Esther; Holman, Fabian A; Meershoek-Klein Kranenbarg, Elma; Liefers, Gerrit-Jan; van de Velde, Cornelis J H; Peeters, Koen C M J

2018-06-19

In 2014, a national colorectal cancer (CRC) screening program was launched in the Netherlands. It is difficult to assess for the individual CRC patient whether the oncological benefits of surgery will outweigh the morbidity of the procedure, especially in early lesions. This study compares patient and tumour characteristics between screen-detected and non-screen-detected patients. Secondly, we present an overview of treatment options and clinical dilemmas when treating patients with early stage colorectal disease. Between January 2014 and December 2016, all patients with non-malignant polyps or CRC who were referred to the Department of Surgery of the Leiden University Medical Centre in the Netherlands were included. Baseline characteristics, type of treatment and short-term outcomes of patients with screen-detected and non-screen-detected colorectal tumours were compared. A total of 426 patients were included, of whom 240 (56.3%) were identified by screening. Non-screen-detected patients more often had comorbidity (p=0.03), the primary tumour was more often located in the rectum (p=0.001) and there was a higher rate of metastatic disease (p<0.001). Among 354 surgically treated patients, postoperative adverse events did not significantly differ between the two groups (p=0.38). Of 46 patients with T1 CRC in the endoscopic resection specimen, 23 underwent surgical resection of which only 30.4% had residual invasive disease at colectomy. Despite differences in comorbidity and stage, surgical outcome of patients with screen-detected tumours compared to non-screen-detected tumours was not significantly different. Considering its limited oncological benefits as well as the rate of adverse events, surgery for non-malignant polyps and T1 CRC should be considered carefully. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A pragmatic and scalable strategy using mobile technology to promote sustained lifestyle changes to prevent type 2 diabetes in India-Outcome of screening.

PubMed

Priscilla, Susairaj; Nanditha, Arun; Simon, Mary; Satheesh, Krishnamoorthy; Kumar, Sathish; Shetty, Ananth Samith; Snehalatha, Chamukuttan; Johnston, Desmond G; Godsland, Ian F; Wareham, Nicholas J; Ramachandran, Ambady

2015-12-01

We describe a two-step screening approach using non-invasive risk assessment and glycated hemoglobin (HbA1c) to identify participants for a diabetes prevention trial. A total of 6030 non-diabetic persons of 35-55 years were screened using risk assessment for diabetes. Those with three or more risk factors were screened using point of care HbA1c test. For this study, participants in HbA1c categories of 6.0% (42.1 mmol/mol)-6.4% (46.4 mmol/mol) were selected and their characteristics were analyzed. Among 6030 persons, 2835 (47%) had three or more risk factors for diabetes. Among those screened with HbA1c, 43.2% (1225) had HbA1c values of <6.0% (42.1 mmol/mol), 46.8% (1327) had HbA1c values between 6.0% (42.1 mmol/mol) and ≤ 6.4% (46.4 mmol/mol) and 10% (283) had undiagnosed diabetes with ≥6.5% (47.5 mmol/mol). Positive family history was present in 53.2%, 81.7% were obese and 14.8% were overweight. Opportunistic screening using a two-step approach: diabetes risk profile and HbA1c measurement detected a large percentage of individuals with prediabetes. Prediabetic persons recruited to the trial had higher percentage of obesity and presence of positive family history than those who had lower HbA1c values. Outcomes from this trial will enable comparisons with the previous prevention studies that used blood glucose levels as the screening criteria. Copyright © 2015. Published by Elsevier Ireland Ltd.

Use of Advanced Machine-Learning Techniques for Non-Invasive Monitoring of Hemorrhage

DTIC Science & Technology

2010-04-01

that state-of-the-art machine learning techniques when integrated with novel non-invasive monitoring technologies could detect subtle, physiological...decompensation. Continuous, non-invasively measured hemodynamic signals (e.g., ECG, blood pressures, stroke volume) were used for the development of machine ... learning algorithms. Accuracy estimates were obtained by building models using 27 subjects and testing on the 28th. This process was repeated 28 times

Cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal anti-D prophylaxis in RhD-negative pregnant women: a model-based analysis.

PubMed

Neovius, M; Tiblad, E; Westgren, M; Kublickas, M; Neovius, K; Wikman, A

2016-07-01

To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP. Model based on a population-based cohort study. The Swedish health service. Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010-2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008-2009 when standard care did not include RAADP (n = 7099). Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives. Additional cost per RhD immunisation averted. Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D. Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis. Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP. © 2015 Royal College of Obstetricians and Gynaecologists.

The role of pre-invasive disease in overdiagnosis: A microsimulation study comparing mass screening for breast cancer and cervical cancer.

PubMed

van Luijt, Paula A; Rozemeijer, Kirsten; Naber, Steffie K; Heijnsdijk, Eveline Am; van Rosmalen, Joost; van Ballegooijen, Marjolein; de Koning, Harry J

2016-12-01

Although early detection of cancer through screening can prevent cancer deaths, a drawback of screening is overdiagnosis. Overdiagnosis has been much debated in breast cancer screening, but less so in cervical cancer screening. We examined the impact of overdiagnosis by comparing two screening programmes in the Netherlands. We estimated overdiagnosis rates by microsimulation for breast cancer screening and cervical cancer screening, using a cohort of women born in 1982 with lifelong follow-up. Overdiagnosis estimates were made analogous to two definitions formed by the UK 2012 breast screening review. Pre-invasive disease was included in both definitions. Screening prevented 921 cervical cancers (-55%) and 378 cervical cancer deaths (-59%), and 169 (-1.3%) breast cancer cases and 970 breast cancer deaths (-21%). The cervical cancer overdiagnosis rate was 74.8% (including pre-invasive disease). Breast cancer overdiagnosis was estimated at 2.5% (including pre-invasive disease). For women of all ages in breast cancer screening, an excess of 207 diagnoses/100,000 women was found, compared with an excess of 3999 diagnoses/100,000 women in cervical cancer screening. For breast cancer, the frequency of overdiagnosis in screening is relatively low, but consequences are evident. For cervical cancer, the frequency of overdiagnosis in screening is high, because of detection of pre-invasive disease, but the consequences per case are relatively small due to less invasive treatment. This illustrates that it is necessary to present overdiagnosis in relation to disease stage and consequences. © The Author(s) 2016.

Cellular autofluorescence imaging for early diagnosis of cancers

NASA Astrophysics Data System (ADS)

Steenkeste, Karine; Deniset, Ariane; Lecart, Sandrine; Leveque-Fort, Sandrine; Fontaine-Aupart, Marie-Pierre; Ferlicot, Sophie; Eschwege, Pascal

2005-08-01

Urinary cytology is employed in diagnostic guidelines of bladder cancer in anatomo-pathological laboratories mostly for its ability to diagnose non detectable cancers using cystoscopy, but also because it is a non-invasive and non-constraining technique for a regular follow-up of the more exposed populations. The impossibility to detect such cancers is mainly due to their localization either in the bladder or in the upper urinary tract and the prostate. However, urinary cytology lacks sensitivity, especially for the detection of low grade low stage tumors due to inherent limitation of morphological criteria to distinguish low grade tumor cells from normal urothelial cells. For this purpose, we developed, in addition to urinary cytology, an original screening of these cytological slides by using spectrally-resolved and time-resolved fluorescence as a contrast factor, without changing any parameters in the cytological slide preparation. This method takes advantage of a femtosecond Ti:sapphire laser, continuously tunable in the spectral range 700-950 nm allowing the observation of most endogenous cellular chromophores by biphotonic excitation. A commercial confocal microscope was also used in the measurements allowing an excitation of the samples between 458 nm and 633 nm. We observed that the fluorescence emission is differentially distributed in normal and pathological urothelial cells. Spectral- and time-resolved measurements attested this difference over about one hundred cases which have been tested to confirm the high accuracy of this non-invasive technique.

A single mini-barcode test to screen for Australian mammalian predators from environmental samples

PubMed Central

MacDonald, Anna J; Sarre, Stephen D

2017-01-01

Abstract Identification of species from trace samples is now possible through the comparison of diagnostic DNA fragments against reference DNA sequence databases. DNA detection of animals from non-invasive samples, such as predator faeces (scats) that contain traces of DNA from their species of origin, has proved to be a valuable tool for the management of elusive wildlife. However, application of this approach can be limited by the availability of appropriate genetic markers. Scat DNA is often degraded, meaning that longer DNA sequences, including standard DNA barcoding markers, are difficult to recover. Instead, targeted short diagnostic markers are required to serve as diagnostic mini-barcodes. The mitochondrial genome is a useful source of such trace DNA markers because it provides good resolution at the species level and occurs in high copy numbers per cell. We developed a mini-barcode based on a short (178 bp) fragment of the conserved 12S ribosomal ribonucleic acid mitochondrial gene sequence, with the goal of discriminating amongst the scats of large mammalian predators of Australia. We tested the sensitivity and specificity of our primers and can accurately detect and discriminate amongst quolls, cats, dogs, foxes, and devils from trace DNA samples. Our approach provides a cost-effective, time-efficient, and non-invasive tool that enables identification of all 8 medium-large mammal predators in Australia, including native and introduced species, using a single test. With modification, this approach is likely to be of broad applicability elsewhere. PMID:28810700

Utility of arterial blood gas, CBC, biochemistry and cardiac hormones as evaluation parameters of cardiovascular disease in nonhuman primates.

PubMed

Nakayama, Shunya; Koie, Hiroshi; Kanayama, Kiichi; Katakai, Yuko; Ito-Fujishiro, Yasuyo; Sankai, Tadashi; Yasutomi, Yasuhiro; Ageyama, Naohide

2018-06-11

Cardiovascular disease (CVD) has a tremendous impact on the quality of life of humans. While experimental animals are valuable to medical research as models of human diseases, cardiac systems differ widely across various animal species. Thus, we examined a CVD model in cynomolgus monkeys. Laboratory primates are precious resources, making it imperative that symptoms of diseases and disorders are detected as early as possible. Thus, in this study we comprehensively examined important indicators of CVD in cynomolgus monkeys, including arterial blood gas, complete blood count (CBC), biochemistry, and cardiac hormones. The control group included 20 healthy macaques showing non-abnormal findings in screening tests, whereas the CVD group included 20 macaques with valvular disease and cardiomyopathy. An increase of red blood cell distribution width was observed in the CBC, indicating chronic inflammation related to CVD. An increase of HCO 3 was attributed to the correction of acidosis. Furthermore, development of the CVD model was supported by significant increases in natriuretic peptides. It is suggested that these results indicated a correlation between human CVD and the model in monkeys. Moreover, blood tests including arterial blood gas are non-invasive and can be performed more easily than other technical tests. CVD affected animals easily change their condition by anesthesia and surgical invasion. Pay attention to arterial blood gas and proper respond to their condition are important for research. This data may facilitate human research and aid in the management and veterinary care of nonhuman primates.

Non-invasive, transdermal, path-selective and specific glucose monitoring via a graphene-based platform

NASA Astrophysics Data System (ADS)

Lipani, Luca; Dupont, Bertrand G. R.; Doungmene, Floriant; Marken, Frank; Tyrrell, Rex M.; Guy, Richard H.; Ilie, Adelina

2018-06-01

Currently, there is no available needle-free approach for diabetics to monitor glucose levels in the interstitial fluid. Here, we report a path-selective, non-invasive, transdermal glucose monitoring system based on a miniaturized pixel array platform (realized either by graphene-based thin-film technology, or screen-printing). The system samples glucose from the interstitial fluid via electroosmotic extraction through individual, privileged, follicular pathways in the skin, accessible via the pixels of the array. A proof of principle using mammalian skin ex vivo is demonstrated for specific and `quantized' glucose extraction/detection via follicular pathways, and across the hypo- to hyper-glycaemic range in humans. Furthermore, the quantification of follicular and non-follicular glucose extraction fluxes is clearly shown. In vivo continuous monitoring of interstitial fluid-borne glucose with the pixel array was able to track blood sugar in healthy human subjects. This approach paves the way to clinically relevant glucose detection in diabetics without the need for invasive, finger-stick blood sampling.

Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip

PubMed Central

Hennig, Georg; Homann, Christian; Teksan, Ilknur; Hasbargen, Uwe; Hasmüller, Stephan; Holdt, Lesca M.; Khaled, Nadia; Sroka, Ronald; Stauch, Thomas; Stepp, Herbert; Vogeser, Michael; Brittenham, Gary M.

2016-01-01

Worldwide, more individuals have iron deficiency than any other health problem. Most of those affected are unaware of their lack of iron, in part because detection of iron deficiency has required a blood sample. Here we report a non-invasive method to optically measure an established indicator of iron status, red blood cell zinc protoporphyrin, in the microcirculation of the lower lip. An optical fibre probe is used to illuminate the lip and acquire fluorescence emission spectra in ∼1 min. Dual-wavelength excitation with spectral fitting is used to distinguish the faint zinc protoporphyrin fluorescence from the much greater tissue background fluorescence, providing immediate results. In 56 women, 35 of whom were iron-deficient, the sensitivity and specificity of optical non-invasive detection of iron deficiency were 97% and 90%, respectively. This fluorescence method potentially provides a rapid, easy to use means for point-of-care screening for iron deficiency in resource-limited settings lacking laboratory infrastructure. PMID:26883939

Effect of Diabetes Mellitus Type 2 on Salivary Glucose – A Systematic Review and Meta-Analysis of Observational Studies

PubMed Central

Mascarenhas, Paulo; Fatela, Bruno; Barahona, Isabel

2014-01-01

Background Early screening of type 2 diabetes mellitus (DM) is essential for improved prognosis and effective delay of clinical complications. However, testing for high glycemia often requires invasive and painful blood testing, limiting its large-scale applicability. We have combined new, unpublished data with published data comparing salivary glucose levels in type 2 DM patients and controls and/or looked at the correlation between salivary glucose and glycemia/HbA1c to systematically review the effectiveness of salivary glucose to estimate glycemia and HbA1c. We further discuss salivary glucose as a biomarker for large-scale screening of diabetes or developing type 2 DM. Methods and Findings We conducted a meta-analysis of peer-reviewed published articles that reported data regarding mean salivary glucose levels and/or correlation between salivary glucose levels and glycemia or HbA1c for type 2 DM and non-diabetic individuals and combined them with our own unpublished results. Our global meta-analysis of standardized mean differences on salivary glucose levels shows an overall large positive effect of type 2 DM over salivary glucose (Hedge's g = 1.37). The global correlation coefficient (r) between salivary glucose and glycemia was large (r = 0.49), with subgroups ranging from medium (r = 0.30 in non-diabetics) to very large (r = 0.67 in diabetics). Meta-analysis of the global correlation between salivary glucose and HbA1c showed an overall association of medium strength (r = 0.37). Conclusions Our systematic review reports an overall meaningful salivary glucose concentration increase in type 2 DM and a significant overall relationship between salivary glucose concentration and associated glycemia/HbA1c values, with the strength of the correlation increasing for higher glycemia/HbA1c values. These results support the potential of salivary glucose levels as a biomarker for type 2 DM, providing a less painful/invasive method for screening type 2 DM, as well as for monitoring blood glucose levels in large cohorts of DM patients. PMID:25025218

Cell-free DNA testing after combined test: factors affecting the uptake.

PubMed

Maiz, Nerea; Alzola, Irune; Murua, Emerson J; Rodríguez Santos, Javier

2016-11-01

First, to assess what was the uptake of cell free DNA (cfDNA) testing after a combined test and the maternal and fetal factors that influenced this decision, and second, to assess the uptake and factors that influence the choice of invasive testing. This observational retrospective study included 1083 singleton pregnancies who had a combined test for screening for Down syndrome between 11 (+) (0) and 13 (+) (6) weeks. Multivariate logistic regression analysis was used to determine which factors affected the uptake of cfDNA test and invasive testing among risk for trisomies 21, 18, and 13, maternal characteristics and fetal nuchal translucency (NT) thickness. Two-hundred fifty-seven (23.7%) women had a cfDNA test, 89 (8.2%) had an invasive test, and 737 (68.1%) had no further test. The uptake of cfDNA increased with the risk for trisomies (p < 0.001), maternal age (p = 0.013), and was higher in nulliparous women (p = 0.004). The uptake of invasive test increased with the risk for trisomies (p < 0.001) and NT thickness (p < 0.001). This study shows that the uptake of cfDNA testing increases with the risk for trisomies, maternal age, and is higher in nulliparous, whereas the uptake of invasive testing increases with the risk for trisomies and NT thickness.

Additional mailing phase for FIT after a medical offer phase: The best way to improve compliance with colorectal cancer screening in France.

PubMed

Piette, Christine; Durand, Gérard; Bretagne, Jean-François; Faivre, Jean

2017-03-01

Compliance with colorectal cancer screening is critical to its effectiveness. The organisation of the mass screening programme in France has recently been modified with no evaluation of the consequences. To evaluate the impact of the way the screening test is delivered on compliance. During the first six months of the screening campaign (Ille-Vilaine, Brittany), general practitioners were asked to propose a faecal immunochemical test (FIT), OC-Sensor, to individuals at average risk for colorectal cancer (n=152,097). A subset of non-participants in the medical phase (n=13,071) was randomly chosen to receive a reminder that included the screening test or a simple postal reminder without the screening test. Compliance was 31% if the screening test was proposed during a medical consultation. In non-participants during the medical phase, it was 45% in those receiving both a reminder and the screening test and 28% amongst those receiving a simple reminder. An estimated overall participation rate of 54% can be expected if non-participants in the medical phase are sent a reminder together with the screening test. In France, a compliance rate above the minimum uptake rate of 45% recommended by European Union experts can be achieved if the FIT is mailed to non-participants after the medical free-offer phase. Copyright © 2016. Published by Elsevier Ltd.

Quantifying swallowing function for healthy adults in different age groups using acoustic analysis

NASA Astrophysics Data System (ADS)

Leung, Man-Yin

Dysphagia is a medical condition that can lead to devastating complications including weight loss, aspiration pneumonia, dehydration, and malnutrition; hence, timely identification is essential. Current dysphagia evaluation tools are either invasive, time consuming, or highly dependent on the experience of an individual clinician. The present study aims to develop a non-invasive, quantitative screening tool for dysphagia identification by capturing acoustic data from swallowing and mastication. The first part of this study explores the feasibility of using acoustic data to quantify swallowing and mastication. This study then further identifies mastication and swallowing trends in a neurotypical adult population. An acoustic capture protocol for dysphagia screening is proposed. Finally, the relationship among speaking, lingual and mastication rates are explored. Results and future directions are discussed.

Multimodality cardiac imaging in Turner syndrome.

PubMed

Mortensen, Kristian H; Gopalan, Deepa; Nørgaard, Bjarne L; Andersen, Niels H; Gravholt, Claus H

2016-06-01

Congenital and acquired cardiovascular diseases contribute significantly to the threefold elevated risk of premature death in Turner syndrome. A multitude of cardiovascular anomalies and disorders, many of which deleteriously impact morbidity and mortality, is frequently left undetected and untreated because of poor adherence to screening programmes and complex clinical presentations. Imaging is essential for timely and effective primary and secondary disease prophylaxis that may alleviate the severe impact of cardiovascular disease in Turner syndrome. This review illustrates how cardiovascular disease in Turner syndrome manifests in a complex manner that ranges in severity from incidental findings to potentially fatal anomalies. Recommendations regarding the use of imaging for screening and surveillance of cardiovascular disease in Turner syndrome are made, emphasising the key role of non-invasive and invasive cardiovascular imaging to the management of all patients with Turner syndrome.

MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier (MSC) for Lung Cancer Screening.

PubMed

Mensah, Mavis; Borzi, Cristina; Verri, Carla; Suatoni, Paola; Conte, Davide; Pastorino, Ugo; Orazio, Fortunato; Sozzi, Gabriella; Boeri, Mattia

2017-10-26

The development of a minimally invasive test, such as liquid biopsy, for early lung cancer detection in its preclinical phase is crucial to improve the outcome of this deadly disease. MicroRNAs (miRNAs) are tissue specific, small, non-coding RNAs regulating gene expression, which may act as extracellular messengers of biological signals derived from the cross-talk between the tumor and its surrounding microenvironment. They could thus represent ideal candidates for early detection of lung cancer. In this work, a methodological workflow for the prospective validation of a circulating miRNA test using custom made microfluidic cards and quantitative Real-Time PCR in plasma samples of volunteers enrolled in a lung cancer screening trial is proposed. In addition, since the release of hemolysis-related miRNAs and more general technical issues may affect the analysis, the quality control steps included in the standard operating procedures are also presented. The protocol is reproducible and gives reliable quantitative results; however, when using large clinical series, both pre-analytical and analytical features should be cautiously evaluated.

Analysis of Invasion Dynamics of Matrix-Embedded Cells in a Multisample Format.

PubMed

Van Troys, Marleen; Masuzzo, Paola; Huyck, Lynn; Bakkali, Karima; Waterschoot, Davy; Martens, Lennart; Ampe, Christophe

2018-01-01

In vitro tests of cancer cell invasion are the "first line" tools of preclinical researchers for screening the multitude of chemical compounds or cell perturbations that may aid in halting or treating cancer malignancy. In order to have predictive value or to contribute to designing personalized treatment regimes, these tests need to take into account the cancer cell environment and measure effects on invasion in sufficient detail. The in vitro invasion assays presented here are a trade-off between feasibility in a multisample format and mimicking the complexity of the tumor microenvironment. They allow testing multiple samples and conditions in parallel using 3D-matrix-embedded cells and deal with the heterogeneous behavior of an invading cell population in time. We describe the steps to take, the technical problems to tackle and useful software tools for the entire workflow: from the experimental setup to the quantification of the invasive capacity of the cells. The protocol is intended to guide researchers to standardize experimental set-ups and to annotate their invasion experiments in sufficient detail. In addition, it provides options for image processing and a solution for storage, visualization, quantitative analysis, and multisample comparison of acquired cell invasion data.

Ocular biomarkers of Alzheimer's disease.

PubMed

Heaton, George R; Davis, Benjamin M; Turner, Lisa A; Cordeiro, Maria F

2015-01-01

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterised clinically by a progressive decline in executive functions, memory and cognition. Classic neuropathological hallmarks of AD include intracellular hyper-phosphorylated tau protein which forms neurofibrillary tangles (NFT), and extracellular deposits of amyloid β (Aβ) protein, the primary constituent of senile plaques (SP). The gradual process of pathogenic amyloid accumulation is thought to occur 10-20 years prior to symptomatic manifestation. Advance detection of these deposits therefore offers a highly promising avenue for prodromal AD diagnosis. Currently, the most sophisticated method of 'probable AD' diagnosis is via neuroimaging or cerebral spinal fluid (CSF) biomarker analysis. Whilst these methods have reported a high degree of diagnostic specificity and accuracy, they fall significantly short in terms of practicality; they are often highly invasive, expensive or unsuitable for large-scale population screening. In recent years, ocular screening has received substantial attention from the scientific community due to its potential for non-invasive and inexpensive central nervous system (CNS) imaging. In this appraisal we build upon our previous reviews detailing ocular structural and functional changes in AD (Retinal manifestations of Alzheimer's disease, Alzheimer's disease and Retinal Neurodegeneration) and consider their use as biomarkers. In addition, we present an overview of current advances in the use of fluorescent reporters to detect AD pathology through non-invasive retinal imaging.

Could Digital PCR Be an Alternative as a Non-Invasive Prenatal Test for Trisomy 21: A Proof of Concept Study

PubMed Central

El Khattabi, Laïla Allach; Rouillac-Le Sciellour, Christelle; Le Tessier, Dominique; Luscan, Armelle; Coustier, Audrey; Porcher, Raphael; Bhouri, Rakia; Nectoux, Juliette; Sérazin, Valérie; Quibel, Thibaut; Mandelbrot, Laurent; Tsatsaris, Vassilis

2016-01-01

Objective NIPT for fetal aneuploidy by digital PCR has been hampered by the large number of PCR reactions needed to meet statistical requirements, preventing clinical application. Here, we designed an octoplex droplet digital PCR (ddPCR) assay which allows increasing the number of available targets and thus overcomes statistical obstacles. Method After technical optimization of the multiplex PCR on mixtures of trisomic and euploid DNA, we performed a validation study on samples of plasma DNA from 213 pregnant women. Molecular counting of circulating cell-free DNA was performed using a mix of hydrolysis probes targeting chromosome 21 and a reference chromosome. Results The results of our validation experiments showed that ddPCR detected trisomy 21 even when the sample’s trisomic DNA content is as low as 5%. In a validation study of plasma samples from 213 pregnant women, ddPCR discriminated clearly between the trisomy 21 and the euploidy groups. Conclusion Our results demonstrate that digital PCR can meet the requirements for non-invasive prenatal testing of trisomy 21. This approach is technically simple, relatively cheap, easy to implement in a diagnostic setting and compatible with ethical concerns regarding access to nucleotide sequence information. These advantages make it a potential technique of choice for population-wide screening for trisomy 21 in pregnant women. PMID:27167625

Performance of Momguard, a new non-invasive prenatal testing protocol developed in Korea.

PubMed

Lee, Mi-Young; Cho, Dae-Yeon; Won, Hye-Sung; Hwang, Ah Reum; Jeong, Bada; Kim, Jihun; Oh, Mijin

2015-09-01

To evaluate the performance of Momguard, non-invasive prenatal test (NIPT) for detecting trisomy (T) 21, T18, T13, and sex-chromosome abnormalities recently developed in Korea. This preliminary study formed part of a large prospective cohort study conducted at Asan Medical Center, Seoul, Korea. Only pregnant women who underwent both NIPT and confirmatory karyotyping were included in this study. NIPT results were compared with those of karyotype analyses. Among 93 eligible cases, NIPT results could not be obtained in one case due to a low fetal cell-free DNA fraction. Based on NIPT, eight cases of fetal aneuploidies, including T21 (n=5), T18 (n=2), and T13 (n=1), were identified. For T21 and T18, the sensitivity and specificity of NIPT were both 100%, with a false-positive and false-negative rate of 0% and a positive-predictive value of 100%. One patient classified as having intermediate risk for T13 by NIPT was confirmed to have T13 by karyotyping, and there were no false-negative cases. No cases of sex-chromosome anomalies were detected by NIPT or karyotyping during the study period. Momguard is a reliable screening tool for detecting T21 and T18. For T13 and sex-chromosome anomalies, further prospective studies are necessary to confirm its utility.

NC-TEST: noncontact thermal emissions screening technique for drug and alcohol detection

NASA Astrophysics Data System (ADS)

Prokoski, Francine J.

1997-01-01

Drug abuse is highly correlated with criminal behavior. The typical drug-using criminal commits hundreds of crimes per year. The crime rate cannot be significantly reduced without a reduction in the percentage of the population abusing drugs and alcohol. Accurate and timely estimation of that percentage is important for policy decisions concerning crime control, public health measures, allocation of intervention resources for prevention and treatment, projections of criminal justice needs, and the evaluation of policy effectiveness. Such estimation is particularly difficult because self reporting is unreliable; and physical testing has to date required blood or urine analysis which is expensive and invasive, with the result that too few people are tested. MIKOS Ltd. has developed a non-contact, passive technique with the potential for automatic, real- time screening for drug and alcohol use. The system utilizes thermal radiation which is spontaneously and continuously emitted by the human body. Facial thermal patterns and changes in patterns are correlated with standardized effects of specific drugs and alcohol. A portable system incorporating the collection and analysis technique can be used episodically to collect data for estimating drug and alcohol use by general unknown populations such as crowds at airports, or it can be used for repetitive routine screening of specific known groups such as airline pilots, military personnel, school children, or persons on probation or parole.

Colorectal cancer: From prevention to personalized medicine

PubMed Central

Binefa, Gemma; Rodríguez-Moranta, Francisco; Teule, Àlex; Medina-Hayas, Manuel

2014-01-01

Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy. In recent years, the use of DNA, RNA and protein markers in different biological samples has been explored as strategies for CRC diagnosis. Although there is not yet sufficient evidence to recommend the analysis of biomarkers such as DNA, RNA or proteins in the blood or stool, it is likely that given the quick progression of technology tools in molecular biology, increasingly sensitive and less expensive, these tools will gradually be employed in clinical practice and will likely be developed in mass. PMID:24944469

Colorectal cancer: from prevention to personalized medicine.

PubMed

Binefa, Gemma; Rodríguez-Moranta, Francisco; Teule, Alex; Medina-Hayas, Manuel

2014-06-14

Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy. In recent years, the use of DNA, RNA and protein markers in different biological samples has been explored as strategies for CRC diagnosis. Although there is not yet sufficient evidence to recommend the analysis of biomarkers such as DNA, RNA or proteins in the blood or stool, it is likely that given the quick progression of technology tools in molecular biology, increasingly sensitive and less expensive, these tools will gradually be employed in clinical practice and will likely be developed in mass.

Do Native Parasitic Plants Cause More Damage to Exotic Invasive Hosts Than Native Non-Invasive Hosts? An Implication for Biocontrol

PubMed Central

Li, Junmin; Jin, Zexin; Song, Wenjing

2012-01-01

Field studies have shown that native, parasitic plants grow vigorously on invasive plants and can cause more damage to invasive plants than native plants. However, no empirical test has been conducted and the mechanism is still unknown. We conducted a completely randomized greenhouse experiment using 3 congeneric pairs of exotic, invasive and native, non-invasive herbaceous plant species to quantify the damage caused by parasitic plants to hosts and its correlation with the hosts' growth rate and resource use efficiency. The biomass of the parasitic plants on exotic, invasive hosts was significantly higher than on congeneric native, non-invasive hosts. Parasites caused more damage to exotic, invasive hosts than to congeneric, native, non-invasive hosts. The damage caused by parasites to hosts was significantly positively correlated with the biomass of parasitic plants. The damage of parasites to hosts was significantly positively correlated with the relative growth rate and the resource use efficiency of its host plants. It may be the mechanism by which parasitic plants grow more vigorously on invasive hosts and cause more damage to exotic, invasive hosts than to native, non-invasive hosts. These results suggest a potential biological control effect of native, parasitic plants on invasive species by reducing the dominance of invasive species in the invaded community. PMID:22493703

Costs and clinical outcomes for non-invasive versus invasive diagnostic approaches to patients with suspected in-stent restenosis.

PubMed

Min, James K; Hasegawa, James T; Machacz, Susanne F; O'Day, Ken

2016-02-01

This study compared costs and clinical outcomes of invasive versus non-invasive diagnostic evaluations for patients with suspected in-stent restenosis (ISR) after percutaneous coronary intervention. We developed a decision model to compare 2 year diagnosis-related costs for patients who presented with suspected ISR and were evaluated by: (1) invasive coronary angiography (ICA); (2) non-invasive stress testing strategy of myocardial perfusion imaging (MPI) with referral to ICA based on MPI; (3) coronary CT angiography-based testing strategy with referral to ICA based on CCTA. Costs were modeled from the payer's perspective using 2014 Medicare rates. 56 % of patients underwent follow-up diagnostic testing over 2 years. Compared to ICA, MPI (98.6 %) and CCTA (98.1 %) exhibited lower rates of correct diagnoses. Non-invasive strategies were associated with reduced referrals to ICA and costs compared to an ICA-based strategy, with diagnostic costs lower for CCTA than MPI. Overall 2-year costs were highest for ICA for both metallic as well as BVS stents ($1656 and $1656, respectively) when compared to MPI ($1444 and $1411) and CCTA. CCTA costs differed based upon stent size and type, and were highest for metallic stents >3.0 mm followed by metallic stents <3.0 mm, BVS < 3.0 mm and BVS > 3.0 mm ($1466 vs. $1242 vs. $855 vs. $490, respectively). MPI for suspected ISR results in lower costs and rates of complications than invasive strategies using ICA while maintaining high diagnostic performance. Depending upon stent size and type, CCTA results in lower costs than MPI.

Comparison of first-tier cell-free DNA screening for common aneuploidies with conventional publically funded screening.

PubMed

Langlois, Sylvie; Johnson, JoAnn; Audibert, François; Gekas, Jean; Forest, Jean-Claude; Caron, André; Harrington, Keli; Pastuck, Melanie; Meddour, Hasna; Tétu, Amélie; Little, Julian; Rousseau, François

2017-12-01

This study evaluates the impact of offering cell-free DNA (cfDNA) screening as a first-tier test for trisomies 21 and 18. This is a prospective study of pregnant women undergoing conventional prenatal screening who were offered cfDNA screening in the first trimester with clinical outcomes obtained on all pregnancies. A total of 1198 pregnant women were recruited. The detection rate of trisomy 21 with standard screening was 83% with a false positive rate (FPR) of 5.5% compared with 100% detection and 0% FPR for cfDNA screening. The FPR of cfDNA screening for trisomies 18 and 13 was 0.09% for each. Two percent of women underwent an invasive diagnostic procedure based on screening or ultrasound findings; without the cfDNA screening, it could have been as high as 6.8%. Amongst the 640 women with negative cfDNA results and a nuchal translucency (NT) ultrasound, only 3 had an NT greater or equal to 3.5 mm: one had a normal outcome and two lost their pregnancy before 20 weeks. cfDNA screening has the potential to be a highly effective first-tier screening approach leading to a significant reduction of invasive diagnostic procedures. For women with a negative cfDNA screening result, NT measurement has limited clinical utility. © 2017 John Wiley & Sons, Ltd.

Supplemental Screening for Breast Cancer in Women with Dense Breasts: A Systematic Review for the U.S. Preventive Services Task Force

PubMed Central

Melnikow, Joy; Fenton, Joshua J.; Whitlock, Evelyn P.; Miglioretti, Diana L.; Weyrich, Meghan S.; Thompson, Jamie H.; Shah, Kunal

2016-01-01

Background Screening mammography has lower sensitivity and specificity in women with dense breasts, who experience higher breast cancer risk. Purpose Systematic review of: reproducibility of BI-RADS density categorization; test performance and clinical outcomes of supplemental screening with breast ultrasound, magnetic resonance imaging (MRI), and digital breast tomosynthesis (DBT) in women with dense breasts and negative mammography. Data Sources MEDLINE, PubMed, Embase, and Cochrane January 2000–July 2015. Study Selection Studies reporting BI-RADS density reproducibility or supplemental screening results for women with dense breasts. Data Extraction Quality assessment and abstraction of twenty-four studies from seven countries; six were good quality. Data Synthesis Three good-quality studies reported reproducibility of BI-RADS density; 13–19% of women were re-categorized between “dense” and “non-dense” at subsequent screening. Two good-quality studies reported ultrasound sensitivity for women with negative mammography ranging from 80–83%; specificity 86–94%; and positive predictive value (PPV) 3–8%. MRI sensitivity ranged from 75–100%, specificity 78–94%, and PPV 3–33% (3 studies). Ultrasound additional cancer detection rates were 4.4 per 1,000 exams (89–93% invasive); recall rates were 14%. MRI detected 3.5–28.6 additional cancers per 1,000 exams (34–86% invasive); recall rates were 12–24 %. DBT cancer detection rates increased by 1.4–2.5 per 1000 exams compared to mammography alone (3 studies). Recall rates ranged from 7–11%, compared to 7–17% with mammography alone. No studies examined breast cancer outcomes. Limitations Good quality evidence was sparse. Studies were small and confidence intervals were wide. Definitions of recall were absent or inconsistent. Conclusions Density ratings may be re-categorized on serial screening mammograms. Supplemental screening of women with dense breasts finds additional breast cancers, but increases false-positives. DBT may reduce recall rates. Supplemental screening impacts on breast cancer outcomes remain unclear. Primary Funding Source Agency for Healthcare Research and Quality PMID:26757021

A foetus with 18p11.32-q21.2 duplication and Xp22.33-p11.1 deletion derived from a maternal reciprocal translocation t(X;18)(q13;q21.3).

PubMed

Chen, Jun-Kun; Liu, Ping; Hu, Li-Qin; Xie, Qing; Huang, Quan-Fei; Liu, Hai-Liang

2018-01-01

Non-invasive prenatal testing (NIPT) evaluates circulating cell-free DNA (cfDNA) and has been widely applied, with highly accurate results for detecting foetal trisomies 21, 18 and 13. Recently, increasing attention has been paid to the clinical application of the non-invasive detection of foetal sub-chromosomal duplications and deletions beyond common aneuploidies. A 32-year-old healthy pregnant woman was referred to the Medical Genetic Centre of Ganzhou Maternal and Child Health Care Hospital. As routine practice, ultrasound examination at a gestational age of 16 weeks showed that the foetus is normal. To avoid invasive prenatal diagnosis procedures, an NIPT was offered to further screen for common foetal chromosomal abnormalities. The result showed that there was an approximately 50.94 Mb duplication in p11.32-q21.2 of chromosome 18 and an approximately 58.46 Mb deletion in p22.33-p11.1 of chromosome X. In addition, the chromosome karyotypes of the parents and foetus were also analysed. Chromosome karyotype analysis results showed that foetal karyotype was 46,X,der(18), the maternal karyotype was 46,XX,t(X;18)(q13;q21.3), and the paternal karyotype revealed no obvious abnormality. In this case, we successfully detected a healthy pregnant woman with balanced translocation X;18(q13;q21.3) and described the foetal karyotype as 46,X,der(18)t(X;18)(q11;q21.1)mat. Our report illustrated these cases which present complex X;autosome balance translocation and X;autosome unbalance translocation which may contribute to severe clinical phenotypes. In addition, our report also proved that the interruption of genes in the Xq critical region is not only reason of primary infertility. Finally, we prompted that NIPT might play a role in the first trimester screening of sub-chromosomal rearrangement.

Can intracranial pressure be measured non-invasively bedside using a two-depth Doppler-technique?

PubMed

Koskinen, Lars-Owe D; Malm, Jan; Zakelis, Rolandas; Bartusis, Laimonas; Ragauskas, Arminas; Eklund, Anders

2017-04-01

Measurement of intracranial pressure (ICP) is necessary in many neurological and neurosurgical diseases. To avoid lumbar puncture or intracranial ICP probes, non-invasive ICP techniques are becoming popular. A recently developed technology uses two-depth Doppler to compare arterial pulsations in the intra- and extra-cranial segments of the ophthalmic artery for non-invasive estimation of ICP. The aim of this study was to investigate how well non-invasively-measured ICP and invasively-measured cerebrospinal fluid (CSF) pressure correlate. We performed multiple measurements over a wide ICP span in eighteen elderly patients with communicating hydrocephalus. As a reference, an automatic CSF infusion apparatus was connected to the lumbar space. Ringer's solution was used to create elevation to pre-defined ICP levels. Bench tests of the infusion apparatus showed a random error (95 % CI) of less than ±0.9 mmHg and a systematic error of less than ±0.5 mmHg. Reliable Doppler signals were obtained in 13 (72 %) patients. An infusion test could not be performed in one patient. Thus, twelve patients and a total of 61 paired data points were studied. The correlation between invasive and non-invasive ICP measurements was good (R = 0.74), and the 95 % limits of agreements were -1.4 ± 8.8 mmHg. The within-patient correlation varied between 0.47 and 1.00. This non-invasive technique is promising, and these results encourage further development and evaluation before the method can be recommended for use in clinical practice.

Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: prospective cohort study of a nationwide programme in the Netherlands.

PubMed

de Haas, Masja; Thurik, Florentine F; van der Ploeg, Catharina P B; Veldhuisen, Barbera; Hirschberg, Hoang; Soussan, Aicha Ait; Woortmeijer, Heleen; Abbink, Frithjofna; Page-Christiaens, Godelieve C M L; Scheffer, Peter G; Ellen van der Schoot, C

2016-11-07

 To determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD DESIGN:  Prospectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined.  Nationwide screening programme, the Netherlands. Tests are performed in a centralised setting.  25 789 RhD negative pregnant women.  Sensitivity, specificity, false negative rate, and false positive rate of fetal RHD testing compared with serological cord blood typing; proportion of technical failures; and compliance to the screening programme.  A fetal RHD test result and serological cord blood result were available for 25 789 pregnancies. Sensitivity for detection of fetal RHD was 99.94% (95% confidence interval 99.89% to 99.97%) and specificity was 97.74% (97.43% to 98.02%). Nine false negative results for fetal RHD testing were registered (0.03%, 95% confidence interval 0.01% to 0.06%). In two cases these were due to technical failures. False positive fetal RHD testing results were registered for 225 samples (0.87%, 0.76% to 0.99%). Weak RhD expression was shown in 22 of these cases, justifying anti-D immunoglobulin use. The negative and positive predictive values were 99.91% (95% confidence interval 99.82% to 99.95%) and 98.60% (98.40% to 98.77%), respectively. More than 98% of the women participated in the screening programme.  Fetal RHD testing in week 27 of pregnancy as part of a national antenatal screening programme is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Summary of the 2014 Beam-Halo Monitoring Workshop

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, Alan

2015-09-25

Understanding and controlling beam halo is important for high-intensity hadron accelerators, for high-brightness electron linacs, and for low-emittance light sources. This can only be achieved by developing suitable diagnostics. The main challenge faced by such instrumentation is the high dynamic range needed to observe the halo in the presence of an intense core. In addition, measurements must often be made non-invasively. This talk summarizes the one-day workshop on Beam-Halo Monitoring that was held at SLAC on September 19 last year, immediately following IBIC 2014 in Monterey. Workshop presentations described invasive techniques using wires, screens, or crystal collimators, and non-invasive measurementsmore » with gas or scattered electrons. Talks on optical methods showed the close links between observing halo and astronomical problems like observing the solar corona or directly observing a planet orbiting another star.« less

Test of a non-physical barrier consisting of light, sound, and bubble screen to block upstream movement of sea lamprey in an experimental raceway

USGS Publications Warehouse

Miehls, Scott M.; Johnson, Nicholas S.; Hrodey, Pete J.

2017-01-01

Control of the invasive Sea Lamprey Petromyzon marinus is critical for management of commercial and recreational fisheries in the Laurentian Great Lakes. Use of physical barriers to block Sea Lampreys from spawning habitat is a major component of the control program. However, the resulting interruption of natural streamflow and blockage of nontarget species present substantial challenges. Development of an effective nonphysical barrier would aid the control of Sea Lampreys by eliminating their access to spawning locations while maintaining natural streamflow. We tested the effect of a nonphysical barrier consisting of strobe lights, low-frequency sound, and a bubble screen on the movement of Sea Lampreys in an experimental raceway designed as a two-choice maze with a single main channel fed by two identical inflow channels (one control and one blocked). Sea Lampreys were more likely to move upstream during trials when the strobe light and low-frequency sound were active compared with control trials and trials using the bubble screen alone. For those Sea Lampreys that did move upstream to the confluence of inflow channels, no combination of stimuli or any individual stimulus significantly influenced the likelihood that Sea Lampreys would enter the blocked inflow channel, enter the control channel, or return downstream.

Motivations for Undertaking DNA Sequencing-Based Non-Invasive Prenatal Testing for Fetal Aneuploidy: A Qualitative Study with Early Adopter Patients in Hong Kong

PubMed Central

Yi, Huso; Hallowell, Nina; Griffiths, Sian; Yeung Leung, Tak

2013-01-01

Background A newly introduced cell-free fetal DNA sequencing based non-invasive prenatal testing (DNA-NIPT) detects Down syndrome with sensitivity of 99% at early gestational stage without risk of miscarriage. Attention has been given to its public health implications; little is known from consumer perspectives. This qualitative study aimed to explore women’s motivations for using, and perceptions of, DNA-NIPT in Hong Kong. Methods and Findings In-depth interviews were conducted with 45 women who had undertaken DNA-NIPT recruited by purposive sampling based on socio-demographic and clinical characteristics. The sample included 31 women identified as high-risk from serum and ultrasound based Down syndrome screening (SU-DSS). Thematic narrative analysis examined informed-decision making of the test and identified the benefits and needs. Women outlined a number of reasons for accessing DNA-NIPT: reducing the uncertainty associated with risk probability-based results from SU-DSS, undertaking DNA-NIPT as a comprehensive measure to counteract risk from childbearing especially at advanced age, perceived predictive accuracy and absence of risk of harm to fetus. Accounts of women deemed high-risk or not high-risk are distinctive in a number of respects. High-risk women accessed DNA-NIPT to get a clearer idea of their risk. This group perceived SU-DSS as an unnecessary and confusing procedure because of its varying, protocol-dependent detection rates. Those women not deemed high-risk, in contrast, undertook DNA-NIPT for psychological assurance and to reduce anxiety even after receiving the negative result from SU-DSS. Conclusions DNA-NIPT was regarded positively by women who chose this method of screening over the routine, less expensive testing options. Given its perceived utility, health providers need to consider whether DNA-NIPT should be offered as part of universal routine care to women at high-risk for fetal aneuploidy. If this is the case, then further development of guidelines and quality assurance will be needed to provide a service suited to patients’ needs. PMID:24312358

Predictors of Cervical Cancer Screening for Rarely or Never Screened Rural Appalachian Women

PubMed Central

Hatcher, Jennifer; Studts, Christina R.; Dignan, Mark; Turner, Lisa M.; Schoenberg, Nancy E.

2011-01-01

Background and Purpose Women who have not had a Papanicolaou test in five years or more have increased risk of developing invasive cervical cancer. This study compares Appalachian women whose last screening was more than one year ago but less than five years ago with those not screened for the previous five years or more. Methods Using PRECEDE/PROCEED as a guide, factors related to obtaining Pap tests were examined using cross-sectional data from 345 Appalachian Kentucky women. Bivariate and multivariate analyses were conducted to identify predictors of screening. Results Thirty-four percent of participants were rarely- or never-screened. In multiple logistic regression analyses, several factors increased those odds, including belief that cervical cancer has symptoms, and not having a regular source of medical care. Conclusion The findings from this study may lead to the development of effective intervention and policies that increase cervical cancer screening in this population. PMID:21317514

Decision aids that support decisions about prenatal testing for Down syndrome: an environmental scan.

PubMed

Leiva Portocarrero, Maria Esther; Garvelink, Mirjam M; Becerra Perez, Maria Margarita; Giguère, Anik; Robitaille, Hubert; Wilson, Brenda J; Rousseau, François; Légaré, France

2015-09-24

Prenatal screening tests for Down syndrome (DS) are routine in many developed countries and new tests are rapidly becoming available. Decisions about prenatal screening are increasingly complex with each successive test, and pregnant women need information about risks and benefits as well as clarity about their values. Decision aids (DAs) can help healthcare providers support women in this decision. Using an environmental scan, we aimed to identify publicly available DAs focusing on prenatal screening/diagnosis for Down syndrome that provide effective support for decision making. Data sources searched were the Decision Aids Library Inventory (DALI) of the Ottawa Patient Decision Aids Research Group at the Ottawa Health Research Institute; Google searches on the internet; professional organizations, academic institutions and other experts in the field; and references in existing systematic reviews on DAs. Eligible DAs targeted pregnant women, focused on prenatal screening and/or diagnosis, applied to tests for fetal abnormalities or aneuploidies, and were in French, English, Spanish or Portuguese. Pairs of reviewers independently identified eligible DAs and extracted characteristics including the presence of practical decision support tools and features to aid comprehension. They then performed quality assessment using the 16 minimum standards established by the International Patient Decision Aids Standards (IPDASi v4.0). Of 543 potentially eligible DAs (512 in DALI, 27 from experts, and four on the internet), 23 were eligible and 20 were available for data extraction. DAs were developed from 1996 to 2013 in six countries (UK, USA, Canada, Australia, Sweden, and France). Five DAs were for prenatal screening, three for prenatal diagnosis and 12 for both). Eight contained values clarification methods (personal worksheets). The 20 DAs scored a median of 10/16 (range 6-15) on the 16 IPDAS minimum standards. None of the 20 included DAs met all 16 IPDAS minimum standards, and few included practical decision support tools or aids to comprehension. Our results indicate there is a need for DAs that effectively support decision making regarding prenatal testing for Down syndrome, especially in light of the recently available non-invasive prenatal screening tests.

The role of invasive and non-invasive procedures in diagnosing fever of unknown origin.

PubMed

Mete, Bilgul; Vanli, Ersin; Yemisen, Mucahit; Balkan, Ilker Inanc; Dagtekin, Hilal; Ozaras, Resat; Saltoglu, Nese; Mert, Ali; Ozturk, Recep; Tabak, Fehmi

2012-01-01

The etiology of fever of unknown origin has changed because of the recent advances in and widespread use of invasive and non-invasive diagnostic tools. However, undiagnosed patients still constitute a significant number. To determine the etiological distribution and role of non-invasive and invasive diagnostic tools in the diagnosis of fever of unknown origin. One hundred patients who were hospitalized between June 2001 and 2009 with a fever of unknown origin were included in this study. Clinical and laboratory data were collected from the patients' medical records retrospectively. Fifty three percent of the patients were male, with a mean age of 45 years. The etiology of fever was determined to be infectious diseases in 26, collagen vascular diseases in 38, neoplastic diseases in 14, miscellaneous in 2 and undiagnosed in 20 patients. When the etiologic distribution was analyzed over time, it was noted that the rate of infectious diseases decreased, whereas the rate of rheumatological and undiagnosed diseases relatively increased because of the advances in imaging and microbiological studies. Seventy patients had a definitive diagnosis, whereas 10 patients had a possible diagnosis. The diagnoses were established based on clinical features and non-invasive tests for 61% of the patients and diagnostic benefit was obtained for 49% of the patients undergoing invasive tests. Biopsy procedures contributed a rate of 42% to diagnoses in patients who received biopsies. Clinical features (such as detailed medical history-taking and physical examination) may contribute to diagnoses, particularly in cases of collagen vascular diseases. Imaging studies exhibit certain pathologies that guide invasive studies. Biopsy procedures contribute greatly to diagnoses, particularly for malignancies and infectious diseases that are not diagnosed by non-invasive procedures.

Client views and attitudes to non-invasive prenatal diagnosis for sickle cell disease, thalassaemia and cystic fibrosis.

PubMed

Hill, Melissa; Compton, Cecilia; Karunaratna, Madhavi; Lewis, Celine; Chitty, Lyn

2014-12-01

In the near future the availability of non-invasive prenatal diagnosis (NIPD) for single gene disorders will change the prenatal diagnosis options available to couples who are carriers of conditions such as cystic fibrosis, sickle cell disorder and thalassaemia. Client opinions about NIPD are needed to inform the implementation of NIPD for single gene disorders. This qualitative study used two focus groups (n = 12) and one-to-one interviews (n = 16) with carriers and support group representatives of sickle cell disease, thalassaemia and cystic fibrosis. Discussions were digitally recorded, transcribed verbatim and analysed using thematic analysis. Opinions about NIPD were very positive and participants valued the opportunity to have safe and early testing. Uptake of prenatal testing is likely to increase as women who had previously declined invasive testing expressed interest in having NIPD. Participant concerns about NIPD centred on the need for accuracy to be high to be used for subsequent decision making about termination of pregnancy. Participants also raised concerns that less thought may be given to having a blood test compared to an invasive test and that the perceived ease of a blood test may bring increased pressure to have testing. Participants thought NIPD should be offered through existing specialist services to ensure appropriate genetic counseling and support. Maintaining all testing options is important as some people may prefer invasive testing over NIPD if invasive testing was more accurate or if invasive testing could give information about other conditions such as Down syndrome.

Non-invasive diagnostic platforms in management of non-small cell lung cancer: opportunities and challenges

PubMed Central

Pennell, Nathan A.

2017-01-01

Several non-invasive diagnostic platforms are already being incorporated in routine clinical practice in the work up and monitoring of patients with lung cancer. These approaches have great potential to improve patient selection and monitor patients while on therapy, however several challenges exist in clinical validation and standardization of such platforms. In this review, we summarize the current technologies available for non-invasive diagnostic evaluation from the blood of patients with non-small cell lung cancer (NSCLC), and discuss the technical and logistical challenges associated incorporating such testing in clinical practice. PMID:29057238

Diagnosis of cirrhosis and portal hypertension: imaging, non-invasive markers of fibrosis and liver biopsy

PubMed Central

Procopet, Bogdan

2017-01-01

Abstract The concept of ‘cirrhosis’ is evolving and it is now clear that compensated and decompensated cirrhosis are completely different in terms of prognosis. Furthermore, the term ‘advanced chronic liver disease (ACLD)’ better reflects the continuum of histological changes occurring in the liver, which continue to progress even after cirrhosis has developed, and might regress after removing the etiological factor causing the liver disease. In compensated ACLD, portal hypertension marks the progression to a stage with higher risk of clinical complication and requires an appropriate evaluation and treatment. Invasive tests to diagnose cirrhosis (liver biopsy) and portal hypertension (hepatic venous pressure gradient measurement and endoscopy) remain of crucial importance in several difficult clinical scenarios, but their need can be reduced by using different non-invasive tests in standard cases. Among non-invasive tests, the accepted use, major limitations and major benefits of serum markers of fibrosis, elastography and imaging methods are summarized in the present review. PMID:28533906

Non-Invasive Seismic Methods for Earthquake Site Classification Applied to Ontario Bridge Sites

NASA Astrophysics Data System (ADS)

Bilson Darko, A.; Molnar, S.; Sadrekarimi, A.

2017-12-01

How a site responds to earthquake shaking and its corresponding damage is largely influenced by the underlying ground conditions through which it propagates. The effects of site conditions on propagating seismic waves can be predicted from measurements of the shear wave velocity (Vs) of the soil layer(s) and the impedance ratio between bedrock and soil. Currently the seismic design of new buildings and bridges (2015 Canadian building and bridge codes) requires determination of the time-averaged shear-wave velocity of the upper 30 metres (Vs30) of a given site. In this study, two in situ Vs profiling methods; Multichannel Analysis of Surface Waves (MASW) and Ambient Vibration Array (AVA) methods are used to determine Vs30 at chosen bridge sites in Ontario, Canada. Both active-source (MASW) and passive-source (AVA) surface wave methods are used at each bridge site to obtain Rayleigh-wave phase velocities over a wide frequency bandwidth. The dispersion curve is jointly inverted with each site's amplification function (microtremor horizontal-to-vertical spectral ratio) to obtain shear-wave velocity profile(s). We apply our non-invasive testing at three major infrastructure projects, e.g., five bridge sites along the Rt. Hon. Herb Gray Parkway in Windsor, Ontario. Our non-invasive testing is co-located with previous invasive testing, including Standard Penetration Test (SPT), Cone Penetration Test and downhole Vs data. Correlations between SPT blowcount and Vs are developed for the different soil types sampled at our Ontario bridge sites. A robust earthquake site classification procedure (reliable Vs30 estimates) for bridge sites across Ontario is evaluated from available combinations of invasive and non-invasive site characterization methods.

Improved 5-year survival of patients with immunochemical faecal blood test-screen-detected colorectal cancer versus non-screening cancers in northern Italy.

PubMed

Parente, Fabrizio; Vailati, Cristian; Boemo, Cinzia; Bonoldi, Emanuela; Ardizzoia, Antonio; Ilardo, Antonina; Tortorella, Franco; Cereda, Danilo; Cremaschini, Marco; Moretti, Roberto

2015-01-01

Colorectal cancer screening may reduce disease-related mortality by early-stage detection of cancers. To study the effect of a single immunochemical faecal occult blood test (i-FOBt) screening round on reduction in colorectal cancer-related-mortality among average risk subjects. Comparison of 5-year mortality rates in 3 cohorts from a Northern Italian province: (1) colorectal cancers detected at the 1st biennial round of a mass-screening programme targeting 50-69 years old subjects, (2) non-screening cancers symptomatically diagnosed during the same time period, and (3) cancers detected in the pre-screening biennium. Multivariate analyses were performed with the Cox regression model including tumour node metastasis (TNM) stage at diagnosis, anatomical distribution of cancers, age at diagnosis, gender and patient group. Kaplan-Meyer survival estimates and log-rank test for equality of survivor functions were calculated. Stage distribution significantly differed between screening and non-screening colorectal cancers: 73% of screen-detected colorectal cancers were stages I and II versus 43% and 40% of non-screening and pre-screening colorectal cancers. Cumulative 5-year mortality rate was significantly lower in screening compared to non-screening or pre-screening colorectal cancers patients (19% versus 37% and 41%, p < 0.001). Colorectal cancers were detected at earlier stages in i-FOBT-positive subjects in comparison with non-screening patients; colorectal cancers found at screening had a significantly improved 5-year survival. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Excreted Thiocyanate Detects Live Reef Fishes Illegally Collected Using Cyanide—A Non-Invasive and Non-Destructive Testing Approach

PubMed Central

Vaz, Marcela C. M.; Rocha-Santos, Teresa A. P.; Rocha, Rui J. M.; Lopes, Isabel; Pereira, Ruth; Duarte, Armando C.; Rubec, Peter J.; Calado, Ricardo

2012-01-01

Cyanide fishing is a method employed to capture marine fish alive on coral reefs. They are shipped to markets for human consumption in Southeast Asia, as well as to supply the marine aquarium trade worldwide. Although several techniques can be used to detect cyanide in reef fish, there is still no testing method that can be used to survey the whole supply chain. Most methods for cyanide detection are time-consuming and require the sacrifice of the sampled fish. Thiocyanate anion (SCN−) is a metabolite produced by the main metabolic pathway for cyanide anion (CN−) detoxification. Our study employed an optical fiber (OF) methodology (analytical time <6 min) to detect SCN− in a non-invasive and non-destructive manner. Our OF methodology is able to detect trace levels (>3.16 µg L−1) of SCN− in seawater. Given that marine fish exposed to cyanide excrete SCN− in the urine, elevated levels of SCN− present in the seawater holding live reef fish indicate that the surveyed specimens were likely exposed to cyanide. In our study, captive-bred clownfish (Amphiprion clarkii) pulse exposed for 60 s to either 12.5 or 25 mg L−1 of CN− excreted up to 6.96±0.03 and 9.84±0.03 µg L−1 of SCN−, respectively, during the 28 days following exposure. No detectable levels of SCN− were recorded in the water holding control organisms not exposed to CN−, or in synthetic seawater lacking fish. While further research is necessary, our methodology can allow a rapid detection of SCN− in the holding water and can be used as a screening tool to indicate if live reef fish were collected with cyanide. PMID:22536375

Excreted thiocyanate detects live reef fishes illegally collected using cyanide--a non-invasive and non-destructive testing approach.

PubMed

Vaz, Marcela C M; Rocha-Santos, Teresa A P; Rocha, Rui J M; Lopes, Isabel; Pereira, Ruth; Duarte, Armando C; Rubec, Peter J; Calado, Ricardo

2012-01-01

Cyanide fishing is a method employed to capture marine fish alive on coral reefs. They are shipped to markets for human consumption in Southeast Asia, as well as to supply the marine aquarium trade worldwide. Although several techniques can be used to detect cyanide in reef fish, there is still no testing method that can be used to survey the whole supply chain. Most methods for cyanide detection are time-consuming and require the sacrifice of the sampled fish. Thiocyanate anion (SCN(-)) is a metabolite produced by the main metabolic pathway for cyanide anion (CN(-)) detoxification. Our study employed an optical fiber (OF) methodology (analytical time <6 min) to detect SCN(-) in a non-invasive and non-destructive manner. Our OF methodology is able to detect trace levels (>3.16 µg L(-1)) of SCN(-) in seawater. Given that marine fish exposed to cyanide excrete SCN(-) in the urine, elevated levels of SCN(-) present in the seawater holding live reef fish indicate that the surveyed specimens were likely exposed to cyanide. In our study, captive-bred clownfish (Amphiprion clarkii) pulse exposed for 60 s to either 12.5 or 25 mg L(-1) of CN(-) excreted up to 6.96±0.03 and 9.84±0.03 µg L(-1) of SCN(-), respectively, during the 28 days following exposure. No detectable levels of SCN(-) were recorded in the water holding control organisms not exposed to CN(-), or in synthetic seawater lacking fish. While further research is necessary, our methodology can allow a rapid detection of SCN(-) in the holding water and can be used as a screening tool to indicate if live reef fish were collected with cyanide.

Creatinine measurement on dry blood spot sample for chronic kidney disease screening.

PubMed

Silva, Alan Castro Azevedo E; Gómez, Juan Fidel Bencomo; Lugon, Jocemir Ronaldo; Graciano, Miguel Luis

2016-03-01

Chronic kidney disease (CKD) screening is advisable due to its high morbidity and mortality and is usually performed by sampling blood and urine. Here we present an innovative and simpler method, by measuring creatinine on a dry blood spot on filter paper. One-hundred and six individuals at high risk for CKD were enrolled. The creatinine values obtained using both tests and the demographic data of each participant allowed us to determinate the eGFR. The adopted cutoff for CKD was an eGFR < 60 ml/min. Mean age was 57 ± 12 years, 74% were female, 40% white, and 60% non-white. Seventy-six percent were hypertensive, 30% diabetic, 37% had family history of CKD, and 22% of smoking. The BMI was 29.5 ± 6.9 kg/m2, median systolic blood pressure was 125 mmHg (IQR 120-140 mmHg) and median diastolic blood pressure was 80 mmHg (IQR 70-80 mmHg). According to MDRD equation, sensitivity was 96%, specificity 55%, predictive positive value 96%, predictive negative value 55% and accuracy 92%. By the CKD-EPI equation the sensitivity was 94%, specificity 55%, predictive positive value 94%, predictive negative value 55% and accuracy 90%. A Bland and Altman analysis showed a relatively narrow range of creatinine values differences (+ 0.68mg/dl to -0.55mg/dl) inside the ± 1.96 SD, without systematic differences. Measurement of creatinine on dry blood sample is an easily feasible non-invasive diagnostic test with good accuracy that may be useful to screen chronic kidney disease.

Screening for invasion of the individual human brain tumour in an autologous confrontation system in vitro.

PubMed

de Ridder, L

1999-01-01

Invasiveness is the major cause of death in patients bearing a brain tumour. The invasiveness or infiltrative capacity of a primary brain tumour has a prognostic value for the evaluation of the process in vivo. So a model to imitate invasion might give information on the in vivo behaviour and outcome of the disease for the individual patient. The developed in vitro model represents an assay in which the patients' brain tumour-derived cells are confronted with connective tissue from the patient himself, i.e. an autologous system to evaluate the individual behaviour of the tumour, in contrast to other invasion models. The test can be applied with tumour-derived material collected by a stereotactic biopsy.

An easy test but a hard decision: ethical issues concerning non-invasive prenatal testing for autosomal recessive disorders

PubMed Central

Skirton, Heather; Goldsmith, Lesley; Chitty, Lyn S

2015-01-01

Prenatal testing based on cell-free fetal DNA in maternal serum is now possible for specific monogenic conditions, and studies have shown that the use of non-invasive testing is supported by prospective parents and health professionals. However, some ethical issues have been raised concerning informed consent and paternal rights. The objective of this study was to explore ethical aspects of the use of non-invasive prenatal diagnostic testing for autosomal recessive disorders. We used a qualitative cross-sectional design, based on Thematic Analysis, and recruited 27 individuals of reproductive age who were carriers of one of four conditions: thalassaemia, sickle cell disease, cystic fibrosis or spinal muscular atrophy. Data were collected via focus groups or interviews. Participants were aware of the potential for such tests to be viewed as routine and suggested that obtaining written consent and allowing time for consideration is needed to facilitate autonomous choice and informed consent. All participants felt that mothers should be able to request such tests, but fathers who declined carrier testing should be made aware that fetal test results may reveal their status. We suggest that a written record of consent for non-invasive prenatal diagnosis should be used as a standard to help reinforce the serious nature of the test results. Where the father's carrier status could be revealed through fetal testing, he should be made aware of this before the results are available. Health professionals should discuss with the pregnant woman the best way to manage unsought information about the father's carrier status to minimise family disruption. PMID:25351779

Anthropometric Variables Accurately Predict Dual Energy X-Ray Absorptiometric-Derived Body Composition and Can Be Used to Screen for Diabetes

PubMed Central

Yavari, Reza; McEntee, Erin; McEntee, Michael; Brines, Michael

2011-01-01

The current world-wide epidemic of obesity has stimulated interest in developing simple screening methods to identify individuals with undiagnosed diabetes mellitus type 2 (DM2) or metabolic syndrome (MS). Prior work utilizing body composition obtained by sophisticated technology has shown that the ratio of abdominal fat to total fat is a good predictor for DM2 or MS. The goals of this study were to determine how well simple anthropometric variables predict the fat mass distribution as determined by dual energy x-ray absorptometry (DXA), and whether these are useful to screen for DM2 or MS within a population. To accomplish this, the body composition of 341 females spanning a wide range of body mass indices and with a 23% prevalence of DM2 and MS was determined using DXA. Stepwise linear regression models incorporating age, weight, height, waistline, and hipline predicted DXA body composition (i.e., fat mass, trunk fat, fat free mass, and total mass) with good accuracy. Using body composition as independent variables, nominal logistic regression was then performed to estimate the probability of DM2. The results show good discrimination with the receiver operating characteristic (ROC) having an area under the curve (AUC) of 0.78. The anthropometrically-derived body composition equations derived from the full DXA study group were then applied to a group of 1153 female patients selected from a general endocrinology practice. Similar to the smaller study group, the ROC from logistical regression using body composition had an AUC of 0.81 for the detection of DM2. These results are superior to screening based on questionnaires and compare favorably with published data derived from invasive testing, e.g., hemoglobin A1c. This anthropometric approach offers promise for the development of simple, inexpensive, non-invasive screening to identify individuals with metabolic dysfunction within large populations. PMID:21915276

Potential secondary poisoning risks to non-targets from a sodium nitrite toxic bait for invasive wild pigs.

PubMed

Snow, Nathan P; Foster, Justin A; VanNatta, Eric H; Horak, Katherine E; Humphrys, Simon T; Staples, Linton D; Hewitt, David G; VerCauteren, Kurt C

2018-01-01

An acute and orally delivered toxic bait containing micro-encapsulated sodium nitrite (MESN), is under development to provide a novel and humane technology to help curtail damage caused by invasive wild pigs (Sus scrofa). We evaluated potential secondary risks for non-target species by: testing whether four different types of micro-encapsulation coatings could reduce vomiting by invasive wild pigs, testing the levels of residual sodium nitrite (SN) in tissues of invasive wild pigs, testing the environmental persistence of SN in vomitus, and conducting a risk assessment for scavengers. Micro-encapsulation coatings did not affect the frequency of vomiting. We identified no risk of secondary poisoning for non-target scavengers that consume muscle, eyes, and livers of invasive wild pig carcasses because residual SN from the toxic bait was not detected in those tissues. The risk of secondary poisoning from consuming vomitus appeared low because ∼90% of the SN was metabolized or broken down prior to vomiting, and continued to degrade after being exposed to the environment. Secondary poisoning could occur for common scavengers that consume approximately ≥15% of their daily dietary requirements of digestive tract tissues or undigested bait from carcasses of invasive wild pigs in a rapid, single-feeding event. The likelihood of this occurring in a natural setting is unknown. The digestive tracts of poisoned invasive wild pigs contained an average of ∼4.35 mg/g of residual SN. Data from this study suggest no risks of secondary poisoning for non-target species (including humans) that consume muscle, liver, or eyes of invasive wild pigs poisoned with a MESN toxic bait. More species-specific testing for scavengers that consume digestive tract tissues and undigested bait is needed to reduce uncertainty about these potential risks. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Microfluidic platform for electrophysiological recordings from host-stage hookworm Ascaris suum larvae: a new tool for anthelmenthic research

USDA-ARS?s Scientific Manuscript database

The screening of candidate compounds and natural products for anthelmintic activity is a key component of discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device (‘chip’) that records non-invasively the tiny electrophysiologic...

Screening of microbial volatile organic compounds for detection of disease in cattle: development of lab-scale method

USDA-ARS?s Scientific Manuscript database

The quest to find unique marker volatile organic compounds (VOCs) associated with human, livestock and wildlife diseases (Ellis et al., 2014) requires development of diagnostic non-invasive point-of-care tools and field surveillance technologies and strategies. The objective of this research was to ...

Point of care hemoglobin testing in plateletpheresis donors: Noninvasive versus invasive methods.

PubMed

Mallhi, R S; Pawar, Amit; Kushwaha, Neerja; Kumar, Sudeep; Dimri, Ujjwal

2016-10-01

Predonation hemoglobin (Hb) for plateletpheresis donors is estimated by presently available invasive methods. Venous samples of only those donors whose Hb is more than 12.5 g/dl are screened for complete blood count and transfusion transmissible infections. There is a pressing need to substitute this invasive Hb test with noninvasive one to reduce donor discomfort and avoid further pricking the donor. We therefore went ahead with the aim of comparing a noninvasive Hb estimation method NBM 200 with the invasive method - Hemocue, taking SYSMEX KX-21 as a gold standard. 500 voluntary consenting plateletpheresis donors qualifying the laid down criteria for platelet donation were included in the study. Hb readings obtained by the NBM 200 and Hemocue were compared to those obtained from the fully automated hematology analyzer SYSMEX KX-21. Coefficients of correlation were found to be statistically significant at <0.0001 level of confidence. Results of Friedman's test on the three methods also showed significant difference in means. Bland-Altman plots and mountain plots also confirm the same. NBM 200 was found to be more sensitive, specific, and precise than Hemocue in detecting ineligible donors. NBM 200 was found to be more sensitive, specific, and precise as compared to Hemocue for predonation screening of Hb in plateletpheresis donors and the prime benefit it offers is that it is 'noninvasive' thereby assisting in stemming the platelet donor pool. The onus lies on the blood transfusion services to make use of appropriately validated gadgets that reduce the donor discomfort.

Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy

PubMed Central

Li, Lu; Douville, Christopher; Wang, Yuxuan; Cohen, Joshua David; Taheri, Diana; Silliman, Natalie; Schaefer, Joy; Ptak, Janine; Dobbyn, Lisa; Papoli, Maria; Kinde, Isaac; Afsari, Bahman; Tregnago, Aline C; Bezerra, Stephania M; VandenBussche, Christopher; Fujita, Kazutoshi; Ertoy, Dilek; Cunha, Isabela W; Yu, Lijia; Bivalacqua, Trinity J; Grollman, Arthur P; Diaz, Luis A; Karchin, Rachel; Danilova, Ludmila; Huang, Chao-Yuan; Shun, Chia-Tung; Turesky, Robert J; Yun, Byeong Hwa; Rosenquist, Thomas A; Pu, Yeong-Shiau; Hruban, Ralph H; Tomasetti, Cristian; Papadopoulos, Nickolas; Kinzler, Ken W

2018-01-01

Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer. PMID:29557778

Rapid diagnosis of tinea incognito using handheld reflectance confocal microscopy: a paradigm shift in dermatology?

PubMed

Navarrete-Dechent, Cristián; Bajaj, Shirin; Marghoob, Ashfaq A; Marchetti, Michael A

2015-06-01

Dermatophytoses are common skin infections. Traditional diagnostic tests such as skin scrapings for light microscopy examination, fungal cultures and biopsies remain imperfect due to false-negative test results, cost, time required to perform the procedure, time delays in test results and/or a requirement for an invasive procedure. Herein, we present a case of an 80-year-old female whose tinea incognito was non-invasively diagnosed within seconds using handheld reflectance confocal microscopy (RCM). As non-invasive skin imaging continues to improve, we expect light-based office microscopy to be replaced with technologies such as RCM, which has multiple and continually expanding diagnostic applications. © 2015 Blackwell Verlag GmbH.

Comparative Proteomic Analysis of Whole-Gut Lavage Fluid and Pancreatic Juice Reveals a Less Invasive Method of Sampling Pancreatic Secretions

PubMed Central

Rocker, Jana M; Tan, Marcus C; Thompson, Lee W; Contreras, Carlo M; DiPalma, Jack A; Pannell, Lewis K

2016-01-01

OBJECTIVES: There are currently no reliable, non-invasive screening tests for pancreatic ductal adenocarcinoma. The fluid secreted from the pancreatic ductal system (“pancreatic juice”) has been well-studied as a potential source of cancer biomarkers. However, it is invasive to collect. We recently observed that the proteomic profile of intestinal effluent from the bowel in response to administration of an oral bowel preparation solution (also known as whole-gut lavage fluid, WGLF) contains large amounts of pancreas-derived proteins. We therefore hypothesized that the proteomic profile is similar to that of pancreatic juice. In this study, we compared the proteomic profiles of 77 patients undergoing routine colonoscopy with the profiles of 19 samples of pure pancreatic juice collected during surgery. METHODS: WGLF was collected from patients undergoing routine colonoscopy, and pancreatic juice was collected from patients undergoing pancreatic surgery. Protein was isolated from both samples using an optimized method and analyzed by LC-MS/MS. Identified proteins were compared between samples and groups to determine similarity of the two fluids. We then compared our results with literature reports of pancreatic juice-based studies to determine similarity. RESULTS: We found 104 proteins in our pancreatic juice samples, of which 90% were also found in our WGLF samples. The majority (67%) of the total proteins found in the WGLF were common to pancreatic juice, with intestine-specific proteins making up a smaller proportion. CONCLUSIONS: WGLF and pancreatic juice appear to have similar proteomic profiles. This supports the notion that WGLF is a non-invasive, surrogate bio-fluid for pancreatic juice. Further studies are required to further elucidate its role in the diagnosis of pancreatic cancer. PMID:27228405

Effect of prophylactic non-invasive mechanical ventilation on functional capacity after heart valve replacement: a clinical trial

PubMed Central

de Araújo-Filho, Amaro Afrânio; de Cerqueira-Neto, Manoel Luiz; de Assis Pereira Cacau, Lucas; Oliveira, Géssica Uruga; Cerqueira, Telma Cristina Fontes; de Santana-Filho, Valter Joviniano

2017-01-01

OBJECTIVE: During cardiac surgery, several factors contribute to the development of postoperative pulmonary complications. Non-invasive ventilation is a promising therapeutic tool for improving the functionality of this type of patient. The aim of this study is to evaluate the functional capacity and length of stay of patients in a nosocomial intensive care unit who underwent prophylactic non-invasive ventilation after heart valve replacement. METHOD: The study was a controlled clinical trial, comprising 50 individuals of both sexes who were allocated by randomization into two groups with 25 patients in each group: the control group and experimental group. After surgery, the patients were transferred to the intensive care unit and then participated in standard physical therapy, which was provided to the experimental group after 3 applications of non-invasive ventilation within the first 26 hours after extubation. For non-invasive ventilation, the positive pressure was 10 cm H2O, with a duration of 1 hour. The evaluation was performed on the 7th postoperative day/discharge and included a 6-minute walk test. The intensive care unit and hospitalization times were monitored in both groups. Brazilian Registry of Clinical Trials (REBeC): RBR number 8bxdd3. RESULTS: Analysis of the 6-minute walk test showed that the control group walked an average distance of 264.34±76 meters and the experimental group walked an average distance of 334.07±71 meters (p=0.002). The intensive care unit and hospitalization times did not differ between the groups. CONCLUSION: Non-invasive ventilation as a therapeutic resource was effective toward improving functionality; however, non-invasive ventilation did not influence the intensive care unit or hospitalization times of the studied cardiac patients. PMID:29160424

Using pre-screening methods for an effective and reliable site characterization at megasites.

PubMed

Algreen, Mette; Kalisz, Mariusz; Stalder, Marcel; Martac, Eugeniu; Krupanek, Janusz; Trapp, Stefan; Bartke, Stephan

2015-10-01

This paper illustrates the usefulness of pre-screening methods for an effective characterization of polluted sites. We applied a sequence of site characterization methods to a former Soviet military airbase with likely fuel and benzene, toluene, ethylbenzene, and xylene (BTEX) contamination in shallow groundwater and subsoil. The methods were (i) phytoscreening with tree cores; (ii) soil gas measurements for CH4, O2, and photoionization detector (PID); (iii) direct-push with membrane interface probe (MIP) and laser-induced fluorescence (LIF) sensors; (iv) direct-push sampling; and (v) sampling from soil and from groundwater monitoring wells. Phytoscreening and soil gas measurements are rapid and inexpensive pre-screening methods. Both indicated subsurface pollution and hot spots successfully. The direct-push sensors yielded 3D information about the extension and the volume of the subsurface plume. This study also expanded the applicability of tree coring to BTEX compounds and tested the use of high-resolution direct-push sensors for light hydrocarbons. Comparison of screening results to results from conventional soil and groundwater sampling yielded in most cases high rank correlation and confirmed the findings. The large-scale application of non- or low-invasive pre-screening can be of help in directing and focusing the subsequent, more expensive investigation methods. The rapid pre-screening methods also yielded useful information about potential remediation methods. Overall, we see several benefits of a stepwise screening and site characterization scheme, which we propose in conclusion.

Non-invasive ventilation (NIV) as an aid to rehabilitation in acute respiratory disease.

PubMed

Dyer, Fran; Flude, Lizzie; Bazari, Farid; Jolley, Caroline; Englebretsen, Catherine; Lai, Dilys; Polkey, Michael I; Hopkinson, Nicholas S

2011-12-16

Non-invasive ventilation (NIV) can increase exercise tolerance, reduce exercise induced desaturation and improve the outcome of pulmonary rehabilitation in patients with chronic respiratory disease. It is not known whether it can be applied to increase exercise capacity in patients admitted with non-hypercapnic acute exacerbations of COPD (AECOPD). We investigated the acceptability and feasibility of using NIV for this purpose. On a single occasion, patients admitted with an acute exacerbation of chronic respiratory disease who were unable to cycle for five minutes at 20 watts attempted to cycle using NIV and their endurance time (T(lim)) was recorded. To determine feasibility of this approach in clinical practice patients admitted with AECOPD were screened for participation in a trial of regular NIV assisted rehabilitation during their hospital admission. In 12 patients tested on a single occasion NIV increased T(lim) from 184(65) seconds to 331(229) seconds (p = 0.04) and patients desaturated less (median difference = 3.5%, p = 0.029). In the second study, 60 patients were admitted to hospital during a three month period of whom only 18(30)% were eligible to participate and of these patients, only four (7%) consented to participate. NIV improves exercise tolerance in patients with acute exacerbations of chronic respiratory disease but the applicability of this approach in routine clinical practice may be limited. http://www.controlled-trials.com/ISRCTN35692743.

Molecular Detection of Invasive Species in Heterogeneous Mixtures Using a Microfluidic Carbon Nanotube Platform

PubMed Central

Mahon, Andrew R.; Barnes, Matthew A.; Senapati, Satyajyoti; Feder, Jeffrey L.; Darling, John A.; Chang, Hsueh-Chia; Lodge, David M.

2011-01-01

Screening methods to prevent introductions of invasive species are critical for the protection of environmental and economic benefits provided by native species and uninvaded ecosystems. Coastal ecosystems worldwide remain vulnerable to damage from aquatic species introductions, particularly via ballast water discharge from ships. Because current ballast management practices are not completely effective, rapid and sensitive screening methods are needed for on-site testing of ships in transit. Here, we describe a detection technology based on a microfluidic chip containing DNA oligonucleotide functionalized carbon nanotubes. We demonstrate the efficacy of the chip using three ballast-transported species either established (Dreissena bugensis) or of potential threat (Eriocheir sinensis and Limnoperna fortuneii) to the Laurentian Great Lakes. With further refinement for on-board application, the technology could lead to real-time ballast water screening to improve ship-specific management and control decisions. PMID:21364993

Non-invasive assessment of hemispheric language dominance by optical topography during a brief passive listening test: a pilot study.

PubMed

Bembich, Stefano; Demarini, Sergio; Clarici, Andrea; Massaccesi, Stefano; Grasso, Domenico Loenardo

2011-12-01

The Wada test is usually used for pre-surgical assessment of language lateralization. Considering its invasiveness and risk of complications, alternative methods have been proposed but they are not always applicable to non-cooperative patients. In this study we explored the possibility of using optical topography (OT)--a multichannel near-infrared system--for non-invasive assessment of hemispheric language dominance during passive listening. Cortical activity was monitored in a sample of healthy, adult Italian native speakers, all right-handed. We assessed changes in oxy-haemoglobin concentration in temporal, parietal and posterior frontal lobes during a passive listening of bi-syllabic words and vowel-consonant-vowel syllables lasting less then 3 minutes. Activated channels were identified by t tests. Left hemisphere showed significant activity only during the passive listening of bi-syllabic words. Specifically, the superior temporal gyrus, the supramarginal gyrus and the posterior inferior parietal lobe were activated. During passive listening of bi-syllabic words, right handed healthy adults showed a significant activation in areas already known to be involved in speech comprehension. Although more research is needed, OT proved to be a promising alternative to the Wada test for non-invasive assessment of hemispheric language lateralization, even if using a particularly brief trial, which has been designed for future applications with non-cooperative subjects.

Novel minimally invasive multi-modality monitoring modalities in neurocritical care.

PubMed

Al-Mufti, Fawaz; Smith, Brendan; Lander, Megan; Damodara, Nitesh; Nuoman, Rolla; El-Ghanem, Mohammad; Kamal, Naveed; Al-Marsoummi, Sarmad; Alzubaidi, Basim; Nuoaman, Halla; Foreman, Brandon; Amuluru, Krishna; Gandhi, Chirag D

2018-07-15

Elevated intracranial pressure (ICP) following brain injury contributes to poor outcomes for patients, primarily by reducing the caliber of cerebral vasculature, and thereby reducing cerebral blood flow. Careful monitoring of ICP is critical in these patients in order to determine prognosis, implement treatment when ICP becomes elevated, and to judge responsiveness to treatment. Currently, the gold standard for monitoring is invasive pressure transducers, usually an intraventricular monitor, which presents significant risk of infection and hemorrhage. These risks made discovering non-invasive methods for monitoring ICP and cerebral perfusion a priority for researchers. Herein we sought to review recent publications on novel minimally invasive multi-modality monitoring techniques that provide surrogate data on ICP, cerebral oxygenation, metabolism and blood flow. While limitations in various forms preclude them from supplanting the use of invasive monitors, these modalities represent useful screening tools within our armamentarium that may be invaluable when the risks of invasive monitoring outweigh the associated benefits. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of gingival blood as a minimally invasive screening tool for diabetes mellitus among 40-59-year-old adults in dental clinics: A cross-sectional study.

PubMed

Partheeban, Indumathi K; Chaly, Preetha; Priyadarshni, Indra; Junaid, Mohammed; Nijesh, J E; Vaishnavi, S

2017-01-01

To evaluate a quick, safe, and minimally invasive method to screen for diabetes using gingival blood with the help of self-monitoring glucometer during periodontal examination. A hospital-based, cross-sectional comparative study was conducted among 40-59-year-old diabetic and nondiabetic population who had come for their master health examination to a private tertiary care hospital (Global Hospital and Health City) in Chennai. Among them, those who fulfilled the inclusion criteria were selected for the study. Thirty diabetic and thirty nondiabetic patients with moderate to severe gingivitis were enrolled and subjected to routine clinical periodontal examination. Blood samples of two sites were analyzed using a glucose self-monitoring device (Accu-Check). Patients were tested for venous fasting blood sugar (VFBS), venous postprandial blood sugar (VPPS), gingival fasting blood sugar (GFBS) level, gingival postprandial blood sugar (GPPS) level, peripheral fingerstick fasting blood sugar (PFBS) level, and peripheral fingerstick postprandial sugar (PPPS) level. Data obtained were statistically analyzed using Student's t-test, ANOVA, and Pearson's correlation test. A significant positive correlation was found between GFBS and VFBS, GFBS and PFBS, GPPS and VPPS, and GPPS and PPPS (P < 0.01) in both diabetic and nondiabetic patients correlation. Using venous blood glucose level as a gold standard, the sensitivity and specificity of GFBS was 93% and 100%, respectively, whereas in GPPS, the sensitivity and specificity was 80% and 96%, respectively. Gingival blood glucometry can be used as a minimally invasive screening tool for diabetes mellitus in dental clinics.

A Comparative Evaluation of the Effect of Bonding Agent on the Tensile Bond Strength of Two Pit and Fissure Sealants Using Invasive and Non-invasive Techniques: An in-vitro Study.

PubMed

Singh, Shamsher; Adlakha, Vivek; Babaji, Prashant; Chandna, Preetika; Thomas, Abi M; Chopra, Saroj

2013-10-01

Newer technologies and the development of pit and fissure sealants have shifted the treatment philosophy from 'drill and fill' to that of 'seal and heal'. The purpose of this in-vitro study was to evaluate the effects of bonding agents on the tensile bond strengths of two pit and fissure sealants by using invasive and non-invasive techniques. One hundred and twenty bicuspids were collected and teeth were divided into two groups: Group-I (Clinpro) and Group-II (Conseal f) with 60 teeth in each group. For evaluating tensile bond strengths, occlusal surfaces of all the teeth were flattened by reducing buccal and lingual cusps without disturbing fissures. Standardised polyvinyl tube was bonded to occlusal surfaces with respective materials. Sealants were applied, with or without bonding agents, in increments and they were light cured. Tensile bond strengths were determined by using Universal Testing Machine. Data were then statistically analysed by using Student t-test for comparison. A statistically significant difference was found in tensile bond strength in invasive with bonding agent group than in non-invasive with bonding agent group. This study revealed that invasive techniques increase the tensile bond strengths of sealants as compared to non- invasive techniques and that the use of a bonding agent as an intermediate layer between the tooth and fissure sealant is beneficial for increasing the bond strength.

 Usefulness of acoustic radiation force impulse and fibrotest in liver fibrosis assessment after liver transplant.

PubMed

Bignulin, Sara; Falleti, Edmondo; Cmet, Sara; Cappello, Dario; Cussigh, Annarosa; Lenisa, Ilaria; Dissegna, Denis; Pugliese, Fabio; Vivarelli, Cinzia; Fabris, Carlo; Fabris, Carlo; Toniutto, Pierluigi

2016-01-01

 Background and rationale. Acoustic radiation force impulse (ARFI) is a non-invasive tool used in the evaluation of liver fibrosis in HCV positive immune-competent patients. This study aimed to assess the accuracy of ARFI in discriminating liver transplanted patients with different graft fibrosis severity and to verify whether ARFI, eventually combined with non-invasive biochemical tests, could spare liver biopsies. This prospective study included 51 HCV positive liver transplanted patients who consecutively underwent to annual liver biopsy concomitantly with ARFI and blood chemistry tests measurements needed to calculate several non-invasive liver fibrosis tests. Overall ARFI showed an AUC of 0.885 in discriminating between patients without or with significant fibrosis (Ishak score 0-2vs. 3-6). Using a cut-off of 1.365 m/s, ARFI possesses a negative predictive value of 100% in identifying patients without significant fibrosis. AUC for Fibrotest was 0.848 in discriminating patients with Ishak fibrosis score 0-2 vs. 3-6. The combined assessment of ARFI and Fibro-test did not improve the results obtained by ARFI alone. ARFI measurement in HCV positive liver transplanted patients can be considered an easy and accurate non-invasive tool in identify patients with a benign course of HCV recurrence.

Non-invasive pulmonary function test on Morquio Patients

PubMed Central

Kubaski, Francyne; Tomatsu, Shunji; Patel, Pravin; Shimada, Tsutomu; Xie, Li; Yasuda, Eriko; Mason, Robert; Mackenzie, William G.; Theroux, Mary; Bober, Michael B.; Oldham, Helen M.; Orii, Tadao; Shaffer, Thomas H.

2015-01-01

In clinical practice, respiratory function tests are difficult to perform in Morquio syndrome patients due to their characteristic skeletal dysplasia, small body size and lack of cooperation of young patients, where in some cases, conventional spirometry for pulmonary function is too challenging. To establish feasible clinical pulmonary endpoints and determine whether age impacts lung function in Morquio patients non-invasive pulmonary tests and conventional spirometry were evaluated. The non-invasive pulmonary tests: impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography in conjunction with conventional spirometry were evaluated in twenty-two Morquio patients (18 Morquio A and 4 Morquio B) (7 males), ranging from 3 and 40 years of age. Twenty-two patients were compliant with non-invasive tests (100%) with exception of IOS (81.8%–18 patients). Seventeen patients (77.3%) were compliant with spirometry testing. All subjects had normal vital signs at rest including > 95% oxygen saturation, end tidal CO2 (38–44 mmHg), and age-appropriate heart rate (mean=98.3, standard deviation=19) (two patients were deviated). All patients preserved normal values in impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography, although predicted forced expiratory volume total (72.8 ± 6.9 SE%) decreased with age and was below normal; phase angle (35.5 ± 16.5 Degrees), %Rib Cage (41.6 ± 12.7%), resonant frequency, and forced expiratory volume in one second/forced expiratory volume total (110.0 ± 3.2 SE%) were normal and not significantly impacted by age. The proposed non-invasive pulmonary function tests are able to cover a greater number of patients (young patients and/or wheel-chair bound), thus providing a new diagnostic approach for the assessment of lung function in Morquio syndrome which in many cases may be difficult to evaluate. Morquio patients studied herein demonstrated no clinical or functional signs of restrictive and/or obstructive lung disease. PMID:26116954

Rapid and direct screening of H:C ratio in Archean kerogen via microRaman Spectroscopy

NASA Astrophysics Data System (ADS)

Ferralis, N.; Matys, E. D.; Allwood, A.; Knoll, A. H.; Summons, R. E.

2015-12-01

Rapid evaluation of the preservation of biosignatures in ancient kerogens is essential for the evaluation of the usability of Earth analogues as proxies of Martian geological materials. No single, non-destructive and non-invasive technique currently exists to rapidly determine such state of preservation of the organic matter in relation to its geological and mineral environment. Due to its non-invasive nature, microRaman spectroscopy is emerging as a candidate technique for the qualitative determination maturity of organic matter, by correlating Raman spectral features and aromatic carbon cluster size. Here we will present a novel quantitative method in which before-neglected Raman spectral features are correlated directly and with excellent accuracy with the H:C ratio. In addition to providing a chemical justification of the found direct correlation, we will show its applicability and predictive capabilities in evaluating H:C in Archean kerogens. This novel method opens new opportunities for the use of Raman spectroscopy and mapping. This includes the non-invasively determination of kerogen preservation and microscale chemical diversity within a particular Earth analogue, to be potentially extended to evaluate Raman spectra acquired directly on Mars.

Development and experimental test of support vector machines virtual screening method for searching Src inhibitors from large compound libraries.

PubMed

Han, Bucong; Ma, Xiaohua; Zhao, Ruiying; Zhang, Jingxian; Wei, Xiaona; Liu, Xianghui; Liu, Xin; Zhang, Cunlong; Tan, Chunyan; Jiang, Yuyang; Chen, Yuzong

2012-11-23

Src plays various roles in tumour progression, invasion, metastasis, angiogenesis and survival. It is one of the multiple targets of multi-target kinase inhibitors in clinical uses and trials for the treatment of leukemia and other cancers. These successes and appearances of drug resistance in some patients have raised significant interest and efforts in discovering new Src inhibitors. Various in-silico methods have been used in some of these efforts. It is desirable to explore additional in-silico methods, particularly those capable of searching large compound libraries at high yields and reduced false-hit rates. We evaluated support vector machines (SVM) as virtual screening tools for searching Src inhibitors from large compound libraries. SVM trained and tested by 1,703 inhibitors and 63,318 putative non-inhibitors correctly identified 93.53%~ 95.01% inhibitors and 99.81%~ 99.90% non-inhibitors in 5-fold cross validation studies. SVM trained by 1,703 inhibitors reported before 2011 and 63,318 putative non-inhibitors correctly identified 70.45% of the 44 inhibitors reported since 2011, and predicted as inhibitors 44,843 (0.33%) of 13.56M PubChem, 1,496 (0.89%) of 168 K MDDR, and 719 (7.73%) of 9,305 MDDR compounds similar to the known inhibitors. SVM showed comparable yield and reduced false hit rates in searching large compound libraries compared to the similarity-based and other machine-learning VS methods developed from the same set of training compounds and molecular descriptors. We tested three virtual hits of the same novel scaffold from in-house chemical libraries not reported as Src inhibitor, one of which showed moderate activity. SVM may be potentially explored for searching Src inhibitors from large compound libraries at low false-hit rates.

Further statistics in dentistry, Part 5: Diagnostic tests for oral conditions.

PubMed

Petrie, A; Bulman, J S; Osborn, J F

2002-12-07

A diagnostic test is a simple test, sometimes based on a clinical measurement, which is used when the gold-standard test providing a definitive diagnosis of a given condition is too expensive, invasive or time-consuming to perform. The diagnostic test can be used to diagnose a dental condition in an individual patient or as a screening device in a population of apparently healthy individuals.

Pre-operative factors indicating risk of multiple operations versus a single operation in women undergoing surgery for screen detected breast cancer.

PubMed

O'Flynn, E A M; Currie, R J; Mohammed, K; Allen, S D; Michell, M J

2013-02-01

We aim to identify preoperative factors at diagnosis which could predict whether women undergoing wide local excision (WLE) would require further operations. 1593 screen-detected invasive and non-invasive breast cancers were reviewed. Age, presence of ductal carcinoma in situ (DCIS), invasive cancer size on mammography, mammographic sign, tumour type, grade and confidence of the radiologist in malignancy were compared. 83%(1315/1593) of women had a WLE. Of these, 70%(919/1315) had a single operation, and 30%(396/1315) multiple operations. These included repeat WLE to clear margins (60%(238/396)), mastectomy (34%(133/396)) and axillary dissection (6%(25/396)). The presence of mammographic microcalcification, lobular carcinoma and grade 2 malignancy on core biopsy were independent risk factors for multiple operations on multivariate analysis. Women with mammographic DCIS >30 mm were 3.4 times more likely to undergo repeat surgery than those with smaller foci. The multidisciplinary team should pay particular attention to these factors when planning surgery. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cumulative Incidence of False-Positive Results in Repeated, Multimodal Cancer Screening

PubMed Central

Croswell, Jennifer Miller; Kramer, Barnett S.; Kreimer, Aimee R.; Prorok, Phil C.; Xu, Jian-Lun; Baker, Stuart G.; Fagerstrom, Richard; Riley, Thomas L.; Clapp, Jonathan D.; Berg, Christine D.; Gohagan, John K.; Andriole, Gerald L.; Chia, David; Church, Timothy R.; Crawford, E. David; Fouad, Mona N.; Gelmann, Edward P.; Lamerato, Lois; Reding, Douglas J.; Schoen, Robert E.

2009-01-01

PURPOSE Multiple cancer screening tests have been advocated for the general population; however, clinicians and patients are not always well-informed of screening burdens. We sought to determine the cumulative risk of a false-positive screening result and the resulting risk of a diagnostic procedure for an individual participating in a multimodal cancer screening program. METHODS Data were analyzed from the intervention arm of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial to determine the effects of prostate, lung, colorectal, and ovarian cancer screening on disease-specific mortality. The 68,436 participants, aged 55 to 74 years, were randomized to screening or usual care. Women received serial serum tests to detect cancer antigen 125 (CA-125), transvaginal sonograms, posteroanterior-view chest radiographs, and flexible sigmoidoscopies. Men received serial chest radiographs, flexible sigmoidoscopies, digital rectal examinations, and serum prostate-specific antigen tests. Fourteen screening examinations for each sex were possible during the 3-year screening period. RESULTS After 14 tests, the cumulative risk of having at least 1 false-positive screening test is 60.4% (95% CI, 59.8%–61.0%) for men, and 48.8% (95% CI, 48.1%–49.4%) for women. The cumulative risk after 14 tests of undergoing an invasive diagnostic procedure prompted by a false-positive test is 28.5% (CI, 27.8%–29.3%) for men and 22.1% (95% CI, 21.4%–22.7%) for women. CONCLUSIONS For an individual in a multimodal cancer screening trial, the risk of a false-positive finding is about 50% or greater by the 14th test. Physicians should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer screening. PMID:19433838

A new diagnostic technique for tinea incognito: in vivo reflectance confocal microscopy. Report of five cases.

PubMed

Turan, Enver; Erdemir, Asli Turgut; Gurel, Mehmet Salih; Yurt, Nurdan

2013-02-01

In vivo confocal laser scanning microscopy (CLSM) is a modern non-invasive method for investigation of the skin that allows real-time visualization of individual cells and subcellular structures with the highest resolution imaging comparable to the routine histopathology. Our aim was to demonstrate the potential of CLSM for non-invasive diagnosis of difficult tinea incognito cases. Clinically atypical lesions in five cases of tinea incognito due to dermatophyte spp. were demonstrated using reflectance confocal laser scanning microscopy (RCM), parallel to KOH preparation and fungal culture of skin scrapings performed in the same patients. The morphological features characteristic for tinea incognito, namely linear branched hyphae in the intercellular area of the stratum corneum, were readily detectable by means of CLSM. In vivo tissue imaging were performed at three different wavelengths (785, 658, 445 nm) and the best images of fungal elements were obtained at 445 nm. All of our five cases had similar reflectance confocal microscopical findings. Our findings suggest the potential of CLSM as a non-invasive tool for the diagnosis of tinea incognito having atypical clinical appearance. Although at present the reflectance confocal microscopy cannot replace the current diagnostic standards for tinea incognito, it may be successfully used as in vivo non-invasive screening tool to facilitate the diagnosis and point to the need for further investigation of the patient. © 2012 John Wiley & Sons A/S.

Non-Invasive Monitoring of Streptococcus pyogenes Vaccine Efficacy Using Biophotonic Imaging

PubMed Central

Alam, Faraz M.; Bateman, Colin; Turner, Claire E.; Wiles, Siouxsie; Sriskandan, Shiranee

2013-01-01

Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 105 bacterial colony forming units (CFU) in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines. PMID:24278474

New non-invasive method for early detection of metabolic syndrome in the working population.

PubMed

Romero-Saldaña, Manuel; Fuentes-Jiménez, Francisco J; Vaquero-Abellán, Manuel; Álvarez-Fernández, Carlos; Molina-Recio, Guillermo; López-Miranda, José

2016-12-01

We propose a new method for the early detection of metabolic syndrome in the working population, which was free of biomarkers (non-invasive) and based on anthropometric variables, and to validate it in a new working population. Prevalence studies and diagnostic test accuracy to determine the anthropometric variables associated with metabolic syndrome, as well as the screening validity of the new method proposed, were carried out between 2013 and 2015 on 636 and 550 workers, respectively. The anthropometric variables analysed were: blood pressure, body mass index, waist circumference, waist-height ratio, body fat percentage and waist-hip ratio. We performed a multivariate logistic regression analysis and obtained receiver operating curves to determine the predictive ability of the variables. The new method for the early detection of metabolic syndrome we present is based on a decision tree using chi-squared automatic interaction detection methodology. The overall prevalence of metabolic syndrome was 14.9%. The area under the curve for waist-height ratio and waist circumference was 0.91 and 0.90, respectively. The anthropometric variables associated with metabolic syndrome in the adjusted model were waist-height ratio, body mass index, blood pressure and body fat percentage. The decision tree was configured from the waist-height ratio (⩾0.55) and hypertension (blood pressure ⩾128/85 mmHg), with a sensitivity of 91.6% and a specificity of 95.7% obtained. The early detection of metabolic syndrome in a healthy population is possible through non-invasive methods, based on anthropometric indicators such as waist-height ratio and blood pressure. This method has a high degree of predictive validity and its use can be recommended in any healthcare context. © The European Society of Cardiology 2016.

Adhesion and invasion to epithelial cells and motility of extended-spectrum β-lactamase-producing Escherichia coli reveal ST131 superiority: a comparative in vitro study of extraintestinal pathogenic E. coli lineages.

PubMed

Kondratyeva, Kira; Wollman, Ayala; Gerlitz, Gabi; Navon-Venezia, Shiri

2017-09-01

Extended-spectrum β-lactamase (ESBL)-producing extraintestinal pathogenic Escherichia coli (ExPEC) sequence type ST131 is pandemic, and it is the major contributor to antibiotic resistance in E. coli. Despite its epidemiological superiority, the physiological reasons that decipher its success remain elusive. We aimed to compare the adhesion, invasion and motility potential of ST131 versus other E. coli lineages. In this in vitro comparative study, 14 ESBL-producing ExPEC community-onset bacteremia isolates were chosen from a reported clinical collection (Karfunkel D, Carmeli Y, Chmelnitsky I, Kotlovsky T, Navon-Venezia S. Eur J Clin Microbiol Infect Dis 2013;32:513-521). Isolates were divided into two groups, ST131 (n=7) and 'non-ST131', sporadic sequence types (STs) (n=7). Virulence and adhesion genes were screened by PCR in all isolates. Virotyping and serotyping were performed for ST131 isolates. Adhesion and invasion to Caco-2 epithelial cells, and motility on semi-solid agar were quantified and compared between the two groups. Fluorescence microscopy using anti-LPS E. coli antibodies was used for visualization and confirmation of adhesion and invasion. ST131 isolates belonged to the O25b:H4-B2 subclone. Two ST131 virotypes were found, A (two blaCTX-M-15 H30-Rx) and C (two blaCTX-M-15 H30-Rx and three blaCTX-M-14 H30 isolates). The average number of adhesion and virulence genes carried by ExPEC ST131 isolates and non-ST131 isolates was 5.3 and 3.7, respectively (P<0.05). Group analysis showed that ST131 surpassed non-ST131 lineages in all three physiological properties: adherence (17.1 vs 13.1 %, P<0.001), invasion (0.4 vs 0.17 %, P<0.01), and swarming motility on all media tested (P<0.05). This study demonstrates ST131 superiority that may explain its improved gut-colonization and dissemination capabilities within the host. These insights are an important step in our understanding of ST131 epidemiological success.

Lung Function Measurements in Rodents in Safety Pharmacology Studies

PubMed Central

Hoymann, Heinz Gerd

2012-01-01

The ICH guideline S7A requires safety pharmacology tests including measurements of pulmonary function. In the first step – as part of the “core battery” – lung function tests in conscious animals are requested. If potential adverse effects raise concern for human safety, these should be explored in a second step as a “follow-up study”. For these two stages of safety pharmacology testing, both non-invasive and invasive techniques are needed which should be as precise and reliable as possible. A short overview of typical in vivo measurement techniques is given, their advantages and disadvantages are discussed and out of these the non-invasive head-out body plethysmography and the invasive but repeatable body plethysmography in orotracheally intubated rodents are presented in detail. For validation purposes the changes in the respective parameters such as tidal midexpiratory flow (EF50) or lung resistance have been recorded in the same animals in typical bronchoconstriction models and compared. In addition, the technique of head-out body plethysmography has been shown to be useful to measure lung function in juvenile rats starting from day two of age. This allows safety pharmacology testing and toxicological studies in juvenile animals as a model for the young developing organism as requested by the regulatory authorities (e.g., EMEA Guideline 1/2008). It is concluded that both invasive and non-invasive pulmonary function tests are capable of detecting effects and alterations on the respiratory system with different selectivity and area of operation. The use of both techniques in a large number of studies in mice and rats in the last years have demonstrated that they provide useful and reliable information on pulmonary mechanics in safety pharmacology and toxicology testing, in investigations of respiratory disorders, and in pharmacological efficacy studies. PMID:22973226

Droplet digital PCR combined with minisequencing, a new approach to analyze fetal DNA from maternal blood: application to the non-invasive prenatal diagnosis of achondroplasia.

PubMed

Orhant, Lucie; Anselem, Olivia; Fradin, Mélanie; Becker, Pierre Hadrien; Beugnet, Caroline; Deburgrave, Nathalie; Tafuri, Gilles; Letourneur, Franck; Goffinet, François; Allach El Khattabi, Laïla; Leturcq, France; Bienvenu, Thierry; Tsatsaris, Vassilis; Nectoux, Juliette

2016-05-01

Achondroplasia is generally detected by abnormal prenatal ultrasound findings in the third trimester of pregnancy and then confirmed by molecular genetic testing of fetal genomic DNA obtained by aspiration of amniotic fluid. This invasive procedure presents a small but significant risk for both the fetus and mother. Therefore, non-invasive procedures using cell-free fetal DNA in maternal plasma have been developed for the detection of the fetal achondroplasia mutations. To determine whether the fetus carries the de novo mis-sense genetic mutation at nucleotide 1138 in FGFR3 gene involved in >99% of achondroplasia cases, we developed two independent methods: digital-droplet PCR combined with minisequencing, which are very sensitive methods allowing detection of rare alleles. We collected 26 plasmatic samples from women carrying fetus at risk of achondroplasia and diagnosed to date a total of five affected fetuses in maternal blood. The sensitivity and specificity of our test are respectively 100% [95% confidence interval, 56.6-100%] and 100% [95% confidence interval, 84.5-100%]. This novel, original strategy for non-invasive prenatal diagnosis of achondroplasia is suitable for implementation in routine clinical testing and allows considering extending the applications of these technologies in non-invasive prenatal diagnosis of many other monogenic diseases. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

Single Cell Assay for Analyzing Single Cell Exosome and Endocrine Secretion and Cancer Markers

NASA Astrophysics Data System (ADS)

Chiu, Yu-Jui

To understand the inhomogeneity of cells in biological systems, there is a growing demand for the capability to characterize the properties of individual single cells. Since single cell studies require continuous monitoring of the cell behaviors instead of a snapshot test at a single time point, an effective single-cell assay that can support time lapsed studies in a high throughput manner is desired. Most currently available single-cell technologies cannot provide proper environments to sustain cell growth and cannot provide, for appropriate cell types, proliferation of single cells and convenient, non-invasive tests of single cell behaviors from molecular markers. In this dissertation, I present a highly versatile single-cell assay that can accommodate different cellular types, enable easy and efficient single cell loading and culturing, and be suitable for the study of effects of in-vitro environmental factors in combination with drug screening. The salient features of the assay are the non-invasive collection and surveying of single cell secretions at different time points and massively parallel translocation of single cells by user defined criteria, producing very high compatibility to the downstream process such as single cell qPCR and sequencing. Above all, the acquired information is quantitative -- for example, one of the studies is measured by the number of exosomes each single cell secretes for a given time period. Therefore, our single-cell assay provides a convenient, low-cost, and enabling tool for quantitative, time lapsed studies of single cell properties.

Case report of vasovagal syncope associated with single pulse transcranial magnetic stimulation in a healthy adult participant.

PubMed

Gillick, Bernadette T; Rich, Tonya; Chen, Mo; Meekins, Gregg D

2015-12-01

Non-invasive brain stimulation-related seizures or syncopal events are rare. However, we report on a syncopal event in a healthy female during a transcranial magnetic stimulation single-pulse testing session. A 47-year-old healthy female presented for a transcranial magnetic stimulation session involving single-pulse assessment of cortical excitability. During the session, the participant appeared to have a brief event involving fainting and myoclonic jerks of the upper extremities. Orthostatic assessment was performed after the event and physician evaluation determined that this was a vasovagal syncopal event. The ethical aspects of this neurophysiology testing protocol were reviewed by the University of Minnesota Institutional Review Board (IRB), and formal IRB approval was deemed unnecessary for single-pulse assessment of healthy control participants not directly involved in a research study. Informed consent was obtained by the participant, including review of potential adverse events. Although rare and rarely reported, vasovagal syncopal events surrounding non-invasive brain stimulation do occur. Thorough pre-screening should incorporate assessment of history of syncope and a plan for risk mitigation if such an event should occur. A complete assessment of the impact of stimulation on the autonomic nervous system is unknown. As such studies expand into patients with myriad neurologic diagnoses, further studies on this effect, in both healthy control and patient populations, are warranted. Such knowledge could contribute to identification of the optimal study participant, and improvements in techniques of stimulation administration.

DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.

PubMed

Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

2014-09-01

Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Grey-scale ultrasonography for monitoring industrial exposure to hepatotoxic agents.

PubMed

Taylor, K J; Williams, D M; Smith, P M; Duck, B W

1975-05-31

Industrial exposure to several potentially hepatotoxic agents, such as vinyl-chloride monomer may occur, and there is a need for non-vasive, diagnostic techniques to detect and monitor progressive pathological processes in liver or spleen. Grey-scale ultrasonography permits display of detailed anatomy and pathology in the liver, portal veins, and spleen. The combination of fine resolution, non-invasiveness, absence of ionising radiation hazard, and portable equipment makes the technique ideal for screening populations at risk.

A stepwise algorithm using an at-a-glance first-line test for the non-invasive diagnosis of advanced liver fibrosis and cirrhosis.

PubMed

Boursier, Jérôme; de Ledinghen, Victor; Leroy, Vincent; Anty, Rodolphe; Francque, Sven; Salmon, Dominique; Lannes, Adrien; Bertrais, Sandrine; Oberti, Frederic; Fouchard-Hubert, Isabelle; Calès, Paul

2017-06-01

Chronic liver diseases (CLD) are common, and are therefore mainly managed by non-hepatologists. These physicians lack access to the best non-invasive tests of liver fibrosis, and consequently cannot accurately determine the disease severity. Referral to a hepatologist is then needed. We aimed to implement an algorithm, comprising a new first-line test usable by all physicians, for the detection of advanced liver fibrosis in all CLD patients. Diagnostic study: 3754 CLD patients with liver biopsy were 2:1 randomized into derivation and validation sets. Prognostic study: longitudinal follow-up of 1275 CLD patients with baseline fibrosis tests. Diagnostic study: the easy liver fibrosis test (eLIFT), an "at-a-glance" sum of points attributed to age, gender, gamma-glutamyl transferase, aspartate aminotransferase (AST), platelets and prothrombin time, was developed for the diagnosis of advanced fibrosis. In the validation set, eLIFT and fibrosis-4 (FIB4) had the same sensitivity (78.0% vs. 76.6%, p=0.470) but eLIFT gave fewer false positive results, especially in patients ≥60years old (53.8% vs. 82.0%, p<0.001), and was thus more suitable as screening test. FibroMeter with vibration controlled transient elastography (VCTE) was the most accurate among the eight fibrosis tests evaluated. The sensitivity of the eLIFT-FM VCTE algorithm (first-line eLIFT, second-line FibroMeter VCTE ) was 76.1% for advanced fibrosis and 92.1% for cirrhosis. Prognostic study: patients diagnosed as having "no/mild fibrosis" by the algorithm had excellent liver-related prognosis with thus no need for referral to a hepatologist. The eLIFT-FM VCTE algorithm extends the detection of advanced liver fibrosis to all CLD patients and reduces unnecessary referrals of patients without significant CLD to hepatologists. Blood fibrosis tests and transient elastography accurately diagnose advanced liver fibrosis in the large population of patients having chronic liver disease, but these non-invasive tests are only currently available in specialized centers. We have developed an algorithm including the easy liver fibrosis test (eLIFT), a new simple and widely available blood test. It is used as a first-line procedure that selects at-risk patients who need further evaluation with the FibroMeter VCTE , an accurate fibrosis test combining blood markers and transient elastography result. This new algorithm, called the eLIFT-FM VCTE , accurately identifies the patients with advanced chronic liver disease who need referral to a specialist, and those with no or mild liver lesions who can remain under the care of their usual physician. No registration (analysis of pooled data from previously published diagnostic studies). Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

[Update on the respiratory management of patients with chronic neuromuscular disease].

PubMed

Priou, P; Trzepizur, W; Meslier, N; Gagnadoux, F

2017-12-01

Neuromuscular diseases include a wide range of conditions that may involve potentially life-threatening respiratory complications (infection, respiratory failure). For patients with neuromuscular diseases, clinical assessment of respiratory function and regular pulmonary function tests are needed to screen for nocturnal respiratory disorders, weakness of the diaphragm and potential restrictive disorders and/or chronic hypercapnic respiratory insufficiency, possibly with couch deficiency. MANAGEMENT OF NOCTURNAL RESPIRATORY DISORDERS AND CHRONIC RESPIRATORY FAILURE: Nocturnal respiratory assistance is an important phase of care for nocturnal respiratory disorders and chronic respiratory failure. This may involve continuous positive airway pressure, adaptative servo-ventilation or non-invasive ventilation with a facial or nasal mask. As needed, diurnal assistance may be proposed by mouthpiece ventilation. Should non-invasive ventilation prove insufficient, or if significant swallowing disorders or recurrent bronchial obstruction develop, or in case of prolonged intubation, tracheotomy may be required. In case of lower airway infection with ineffective cough, physical therapy, associated with air stacking, intermittent positive pressure breathing or mechanical in-exsufflation may be proposed. Care for swallowing disorders, nutritional counseling (cachexia, obesity), vaccinations and therapeutic education are integral elements of patient-centered management aiming to prevent the negative impact of infection and to manage respiratory failure of chronic neuromuscular disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Analysis of RTEL1 and PCDHGB6 promoter methylation in circulating-free DNA of lung cancer patients using liquid biopsy: A pilot study.

PubMed

Powrózek, Tomasz; Krawczyk, Paweł; Kuźnar-Kamińska, Barbara; Batura-Gabryel, Halina; Milanowski, Janusz

2016-08-01

Analysis of epigenetic alterations such as methylation of circulating-free DNA (cf-DNA) expression significantly broadened perspectives of lung cancer (LC) screening. Moreover, methylation of tumor suppressor genes may be analyzed with non-invasive manner in patients' blood samples (liquid biopsy), what underline necessity of detailed investigation of tumor cf-DNA. The purpose of current study was to assess methylation of RTEL1 and PCDHGB6 promoter regions in cf-DNA of 70 LC patients and 80 healthy individuals using qMSP-PCR technique. Methylation status of both genes has not been investigated in cf-DNA of LC patients before. PCDHGB6 promoter methylation was found in 41.4% of LC patients and in 1.3% of healthy individuals, whereas promoter of RTEL1 was found methylated in 51.4% of LC patients and in 8.8% of healthy individuals. Combined analysis of two markers improved test sensitivity up to 62.9% and specificity up to 90% with area under the curve (AUC) in receiver operating curve (ROC) of 0.755. The evaluation of RTEL1 and PCDHGB6 promoter methylation may be an useful tool for non-invasive diagnosis of LC in liquid biopsy.

The effects of water and lipids on NIR optical breast measurements

NASA Astrophysics Data System (ADS)

Cerussi, Albert E.; Bevilacqua, Frederic; Shah, Natasha; Jakubowski, Dorota B.; Berger, Andrew J.; Lanning, Ryan M.; Tromberg, Bruce J.

2001-06-01

Near infrared diffuse optical spectroscopy and imaging may enhance existing technologies for breast cancer screening, diagnosis, and treatment. NIR spectroscopy yields quantitative functional information that cannot be obtained with other non-invasive radiological techniques. In this study we focused upon the origins of this contrast in healthy breast, especially from water and lipids.

Patient factors associated with non-attendance at colonoscopy after a positive screening faecal occult blood test.

PubMed

Plumb, Andrew A; Ghanouni, Alex; Rainbow, Sandra; Djedovic, Natasha; Marshall, Sarah; Stein, Judith; Taylor, Stuart A; Halligan, Steve; Lyratzopoulos, Georgios; von Wagner, Christian

2017-03-01

Background Screening participants with abnormal faecal occult blood test results who do not attend further testing are at high risk of colorectal cancer, yet little is known about their reasons for non-attendance. Methods We conducted a medical record review of 170 patients from two English Bowel Cancer Screening Programme centres who had abnormal guaiac faecal occult blood test screening tests between November 2011 and April 2013 but did not undergo colonoscopy. Using information from patient records, we coded and categorized reasons for non-attendance. Results Of the 170 patients, 82 were eligible for review, of whom 66 had at least one recorded reason for lack of colonoscopy follow-up. Reasons fell into seven main categories: (i) other commitments, (ii) unwillingness to have the test, (iii) a feeling that the faecal occult blood test result was a false positive, (iv) another health issue taking priority, (v) failing to complete bowel preparation, (vi) practical barriers (e.g. lack of transport), and (vii) having had or planning colonoscopy elsewhere. The most common single reasons were unwillingness to have a colonoscopy and being away. Conclusions We identify a range of apparent reasons for colonoscopy non-attendance after a positive faecal occult blood test screening. Education regarding the interpretation of guaiac faecal occult blood test findings, offer of alternative confirmatory test options, and flexibility in the timing or location of subsequent testing might decrease non-attendance of diagnostic testing following positive faecal occult blood test.

A new method to address verification bias in studies of clinical screening tests: cervical cancer screening assays as an example.

PubMed

Xue, Xiaonan; Kim, Mimi Y; Castle, Philip E; Strickler, Howard D

2014-03-01

Studies to evaluate clinical screening tests often face the problem that the "gold standard" diagnostic approach is costly and/or invasive. It is therefore common to verify only a subset of negative screening tests using the gold standard method. However, undersampling the screen negatives can lead to substantial overestimation of the sensitivity and underestimation of the specificity of the diagnostic test. Our objective was to develop a simple and accurate statistical method to address this "verification bias." We developed a weighted generalized estimating equation approach to estimate, in a single model, the accuracy (eg, sensitivity/specificity) of multiple assays and simultaneously compare results between assays while addressing verification bias. This approach can be implemented using standard statistical software. Simulations were conducted to assess the proposed method. An example is provided using a cervical cancer screening trial that compared the accuracy of human papillomavirus and Pap tests, with histologic data as the gold standard. The proposed approach performed well in estimating and comparing the accuracy of multiple assays in the presence of verification bias. The proposed approach is an easy to apply and accurate method for addressing verification bias in studies of multiple screening methods. Copyright © 2014 Elsevier Inc. All rights reserved.

Urine tests for Down's syndrome screening.

PubMed

Alldred, S Kate; Guo, Boliang; Takwoingi, Yemisi; Pennant, Mary; Wisniewski, Susanna; Deeks, Jonathan J; Neilson, James P; Alfirevic, Zarko

2015-12-10

Down's syndrome occurs when a person has three copies of chromosome 21, or the specific area of chromosome 21 implicated in causing Down's syndrome, rather than two. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life. The risk of a Down's syndrome affected pregnancy increases with advancing maternal age.Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have. To estimate and compare the accuracy of first and second trimester urine markers for the detection of Down's syndrome. We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), EMBASE (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2011, Issue 7), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (archived 2007), Health Services Research Projects in Progress database (25 August 2011). We studied reference lists and published review articles. Studies evaluating tests of maternal urine in women up to 24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC (receiver operating characteristic) meta-analytical methods to analyse test performance and compare test accuracy. We performed analysis of studies allowing direct comparison between tests. We investigated the impact of maternal age on test performance in subgroup analyses. We included 19 studies involving 18,013 pregnancies (including 527 with Down's syndrome). Studies were generally of high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Twenty-four test combinations were evaluated formed from combinations of the following seven different markers with and without maternal age: AFP (alpha-fetoprotein), ITA (invasive trophoblast antigen), ß-core fragment, free ßhCG (beta human chorionic gonadotrophin), total hCG, oestriol, gonadotropin peptide and various marker ratios. The strategies evaluated included three double tests and seven single tests in combination with maternal age, and one triple test, two double tests and 11 single tests without maternal age. Twelve of the 19 studies only evaluated the performance of a single test strategy while the remaining seven evaluated at least two test strategies. Two marker combinations were evaluated in more than four studies; second trimester ß-core fragment (six studies), and second trimester ß-core fragment with maternal age (five studies).In direct test comparisons, for a 5% false positive rate (FPR), the diagnostic accuracy of the double marker second trimester ß-core fragment and oestriol with maternal age test combination was significantly better (ratio of diagnostic odds ratio (RDOR): 2.2 (95% confidence interval (CI) 1.1 to 4.5), P = 0.02) (summary sensitivity of 73% (CI 57 to 85) at a cut-point of 5% FPR) than that of the single marker test strategy of second trimester ß-core fragment and maternal age (summary sensitivity of 56% (CI 45 to 66) at a cut-point of 5% FPR), but was not significantly better (RDOR: 1.5 (0.8 to 2.8), P = 0.21) than that of the second trimester ß-core fragment to oestriol ratio and maternal age test strategy (summary sensitivity of 71% (CI 51 to 86) at a cut-point of 5% FPR). Tests involving second trimester ß-core fragment and oestriol with maternal age are significantly more sensitive than the single marker second trimester ß-core fragment and maternal age, however, there were few studies. There is a paucity of evidence available to support the use of urine testing for Down's syndrome screening in clinical practice where alternatives are available.

Non-invasive prenatal testing using cell-free fetal DNA in maternal circulation.

PubMed

Liao, Gary J W; Gronowski, Ann M; Zhao, Zhen

2014-01-20

The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible. Maternal plasma cell free DNA is a mixture of maternal and fetal DNA, of which, fetal DNA represents a minor population in maternal plasma. Therefore, methods with high sensitivity and precision are required to detect and differentiate fetal DNA from the large background of maternal DNA. In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future. This review briefly summarizes the technical aspects of the NIPT and application of NIPT in clinical practice.

Assessing blood vessel perfusion and vital signs through retinal imaging photoplethysmography.

PubMed

Hassan, Harnani; Jaidka, Sheila; Dwyer, Vincent M; Hu, Sijung

2018-05-01

One solution to the global challenge of increasing ocular disease is a cost-effective technique for rapid screening and assessment. Current ophthalmic imaging techniques, e.g. scanning and ocular blood flow systems, are expensive, complex to operate and utilize invasive contrast agents during assessment. The work presented here demonstrates a simple retinal imaging photoplethysmography (iPPG) system with the potential to provide screening, diagnosis, monitoring and assessment that is non-invasive, painless and radiationless. Time series of individual retinal blood vessel images, captured with an eye fundus camera, are processed using standard filtering, amplitude demodulation and principle component analysis (PCA) methods to determine the values of the heart rate (HR) and respiration rate (RR), which are in compliance with simultaneously obtained measurements using commercial pulse oximetry. It also seems possible that some information on the dynamic changes in oxygen saturation levels ( SpO 2 ) in a retinal blood vessel may also be obtained. As a consequence, the retinal iPPG modality system demonstrates a potential avenue for rapid ophthalmic screening, and even early diagnosis, against ocular disease without the need for fluorescent or contrast agents.

Rapid screening of serum-free media for the growth of adherent Vero cells by using a small-scale and non-invasive tool.

PubMed

Petiot, Emma; Fournier, Frantz; Gény, Cécile; Pinton, Hervé; Marc, Annie

2010-03-01

The paper proposes a rapid screening method for a first step improvement of an animal component-free medium dedicated to the growth of the anchorage-dependent Vero cell line. A new, rapid, and non-invasive technique is presented to specifically monitor cultures of adherent cells in 96-well plates. The operating conditions of an image analyzer are adapted to take into account the decrease of cell size when the attached cell density increases. An experimental design is carried out to assess the influence of ten component groups in the original medium. Two groups including protein extracts, growth factor, insulin, glucose, and pyruvate show significant positive effects. The groups with vitamins and molecules related to nitrogenous bases display a less pronounced influence. The mixture of amino acids, B(1) vitamin, magnesium sulfate, and sodium phosphate as well as the couple sodium citrate and ferric chloride lead to a downward trend. The screening results are proved to be scalable in stirred cultures with cells on microcarriers. An improved serum-free medium, with some component groups being removed or added, can be rapidly formulated to reach respectively similar or 1.6 times higher cell density than in the original medium. The results from this global approach could be helpful to further focus experiments on identified medium components.

Next Generation Programmable Bio-Nano-Chip System for On-Site Detection in Oral Fluids.

PubMed

Christodoulides, Nicolaos; De La Garza, Richard; Simmons, Glennon W; McRae, Michael P; Wong, Jorge; Newton, Thomas F; Kosten, Thomas R; Haque, Ahmed; McDevitt, John T

2015-11-23

Current on-site drug of abuse detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. Test confirmation and quantitative assessment of a presumptive positive are then provided by remote laboratories, an inefficient and costly process decoupled from the initial sampling. Recently, a new noninvasive oral fluid sampling approach that is integrated with the chip-based Programmable Bio-Nano-Chip (p-BNC) platform has been developed for the rapid (~ 10 minutes), sensitive detection (~ ng/ml) and quantitation of 12 drugs of abuse. Furthermore, the system can provide the time-course of select drug and metabolite profiles in oral fluids. For cocaine, we observed three slope components were correlated with cocaine-induced impairment using this chip-based p-BNC detection modality. Thus, this p-BNC has significant potential for roadside drug testing by law enforcement officers. Initial work reported on chip-based drug detection was completed using 'macro' or "chip in the lab" prototypes, that included metal encased "flow cells", external peristaltic pumps and a bench-top analyzer system instrumentation. We now describe the next generation miniaturized analyzer instrumentation along with customized disposables and sampling devices. These tools will offer real-time oral fluid drug monitoring capabilities, to be used for roadside drug testing as well as testing in clinical settings as a non-invasive, quantitative, accurate and sensitive tool to verify patient adherence to treatment.

Characterization of small microsatellite loci for use in non invasive sampling studies of Gunnison Sage-grouse (Centrocercus minimus)

USGS Publications Warehouse

Oyler-McCance, Sara J.; St. John, Judy

2010-01-01

Primers for 10 microsatellite loci were developed specifically to amplify low quantity and quality DNA for Gunnison Sage-grouse (Centrocercus minimus), a species that has been petitioned for listing under the US Endangered Species Act. In a screen of 20 individuals from the largest population in the Gunnison Basin, Colorado, the 10 loci were found to have levels of variability ranging from two to seven alleles. No loci were found to be linked, although one locus revealed significant departures from Hardy–Weinberg equilibrium. These microsatellite loci will be applicable for population genetic analyses and for use in mark recapture studies that utilize DNA collected non invasively from feathers and fecal pellets, which will ultimately aid in management efforts.

An image based vibration sensor for soft tissue modal analysis in a Digital Image Elasto Tomography (DIET) system.

PubMed

Feng, Sheng; Lotz, Thomas; Chase, J Geoffrey; Hann, Christopher E

2010-01-01

Digital Image Elasto Tomography (DIET) is a non-invasive elastographic breast cancer screening technology, based on image-based measurement of surface vibrations induced on a breast by mechanical actuation. Knowledge of frequency response characteristics of a breast prior to imaging is critical to maximize the imaging signal and diagnostic capability of the system. A feasibility analysis for a non-invasive image based modal analysis system is presented that is able to robustly and rapidly identify resonant frequencies in soft tissue. Three images per oscillation cycle are enough to capture the behavior at a given frequency. Thus, a sweep over critical frequency ranges can be performed prior to imaging to determine critical imaging settings of the DIET system to optimize its tumor detection performance.

Human leukocyte antigen typing using buccal swabs as accurate and non-invasive substitute for venipuncture in children at risk for celiac disease.

PubMed

Adriaanse, Marlou P M; Vreugdenhil, Anita C E; Vastmans, Véronique; Groeneveld, Lisette; Molenbroeck, Stefan; Schott, Dina A; Voorter, Christina E M; Tilanus, Marcel G J

2016-10-01

Human leukocyte antigen (HLA) typing is an important step in the diagnostic algorithm for celiac disease (CD) and is also used for screening purposes. Collection of blood is invasive and accompanied with emotional impact especially in children. Genetic technological progress now enables HLA typing from buccal cell samples. This study evaluated the reliability and feasibility of HLA typing for CD-associated HLA polymorphisms using buccal swabs as routine test in high-risk individuals. Blood and buccal swabs of 77 children and adolescents with high risk for CD were prospectively collected in this cohort study. Buccal swab collection was performed either by the investigator at the outpatient clinic or by the patient or its parents at home. To evaluate the possibility of self-administration, three families performed the test at home. DNA was extracted using an adapted QIAamp method. Quantity, quality, and purity of DNA were recorded. HLA-DRB1, HLA-DQA1, and HLA-DQB1 typing was examined on buccal cell-derived and blood-derived DNA at low and, if necessary, high resolution level, using sequence-specific oligonucleotide and sequence-based typing, respectively. DNA isolation using buccal swabs yielded a good quality and sufficient quantity of DNA to perform HLA-DQ typing in all individuals. HLA typing results on buccal cell-derived DNA were identical to typing on blood-derived DNA, also for the self-administered samples. Introduction of the buccal swab test for HLA typing of CD risk in routine diagnostics can omit the current venipuncture and enables self-administration at home. Therefore, the buccal swab test is beneficial for individuals with a clinical suspicion for CD, as well as for screening purposes in high-risk populations. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Patients' perception of risk: informed choice in prenatal testing for foetal aneuploidy.

PubMed

Choolani, Mahesh; Biswas, Arijit

2012-10-01

Each of us perceives risk differently, and so do our patients. This perception of risk gets even more complex when multiple individuals and interactions are involved: the doctor, the patient-pregnant mother, the spouse-father and the foetus-unborn child. In this review, we address the relationship between different levels of information gathering, from clinical data to experiential knowledge - data, information, knowledge, perception, attitude, wisdom - and how these would impact the perception of risk and informed consent. We discuss how patients might interpret the risks of the same event differently based upon past experiences, and suggest how risk data could be presented more meaningfully for patients and family to assimilate for informed decision making. Finally, we demonstrate how patients' expectations and risk management can impact scientific research and clinical progress by way of the most topical subject of risk screening in pregnancy - non-invasive prenatal testing using cell-free DNA in maternal plasma.

Telefetalcare: a first prototype of a wearable fetal electrocardiograph.

PubMed

Fanelli, A; Signorini, M G; Ferrario, M; Perego, P; Piccini, L; Andreoni, G; Magenes, G

2011-01-01

Fetal heart rate monitoring is fundamental to infer information about fetal health state during pregnancy. The cardiotocography (CTG) is the most common antepartum monitoring technique. Abdominal ECG recording represents the most valuable alternative to cardiotocography, as it allows passive, non invasive and long term fetal monitoring. Unluckily fetal ECG has low SNR and needs to be extracted from abdominal recordings using ad hoc algorithms. This work describes a prototype of a wearable fetal ECG electrocardiograph. The system has flat band frequency response between 1-60 Hz and guarantees good signal quality. It was tested on pregnant women between the 30(th) and 34(th) gestational week. Several electrodes configurations were tested, in order to identify the best solution. Implementation of a simple algorithm for FECG extraction permitted the reliable detection of maternal and fetal QRS complexes. The system will allow continuative and deep screening of fetal heart rate, introducing the possibility of home fetal monitoring.

Hyperventilation and cold-pressor stress echocardiography combined with automated functional imaging non-invasively detected vasospastic angina

PubMed Central

Suzuki, Kengo; Akashi, Yoshihiro J; Mizukoshi, Kei; Kou, Seisyou; Takai, Manabu; Izumo, Masaki; Shimozato, Takashi; Hayashi, Akio; Ohtaki, Eiji; Nobuoka, Sachihiko; Miyake, Fumihiko

2010-01-01

A 47-year-old male presented with chest discomfort while sleeping. The patient was suspected of having vasospastic angina (VSA) and underwent hyperventilation and cold-pressor stress echocardiography. No chest pain, ECG changes or decreased wall motion was found. However, automated function imaging (AFI) showed decreased peak systolic strain at the apex and postsystolic shortening at both the apex and inferior wall, which was not found before the test. The provocation test revealed 99% stenosis in the right coronary artery #2 at a dose of 50 μg acetylcholine and 90% stenosis in the left coronary artery #8 at a dose of 100 μg. The patient was thus diagnosed as having VSA. The present case demonstrates the usefulness of AFI combined with hyperventilation and cold-pressor stress echocardiography as a screening examination for VSA. PMID:22798093

Anal cancer and intraepithelial neoplasia screening: A review

PubMed Central

Leeds, Ira L; Fang, Sandy H

2016-01-01

This review focuses on the early diagnosis of anal cancer and its precursor lesions through routine screening. A number of risk-stratification strategies as well as screening techniques have been suggested, and currently little consensus exists among national societies. Much of the current clinical rationale for the prevention of anal cancer derives from the similar tumor biology of cervical cancer and the successful use of routine screening to identify cervical cancer and its precursors early in the disease process. It is thought that such a strategy of identifying early anal intraepithelial neoplasia will reduce the incidence of invasive anal cancer. The low prevalence of anal cancer in the general population prevents the use of routine screening. However, routine screening of selected populations has been shown to be a more promising strategy. Potential screening modalities include digital anorectal exam, anal Papanicolaou testing, human papilloma virus co-testing, and high-resolution anoscopy. Additional research associating high-grade dysplasia treatment with anal cancer prevention as well as direct comparisons of screening regimens is necessary to develop further anal cancer screening recommendations. PMID:26843912

Trait Values, Not Trait Plasticity, Best Explain Invasive Species' Performance in a Changing Environment

PubMed Central

Matzek, Virginia

2012-01-01

The question of why some introduced species become invasive and others do not is the central puzzle of invasion biology. Two of the principal explanations for this phenomenon concern functional traits: invasive species may have higher values of competitively advantageous traits than non-invasive species, or they may have greater phenotypic plasticity in traits that permits them to survive the colonization period and spread to a broad range of environments. Although there is a large body of evidence for superiority in particular traits among invasive plants, when compared to phylogenetically related non-invasive plants, it is less clear if invasive plants are more phenotypically plastic, and whether this plasticity confers a fitness advantage. In this study, I used a model group of 10 closely related Pinus species whose invader or non-invader status has been reliably characterized to test the relative contribution of high trait values and high trait plasticity to relative growth rate, a performance measure standing in as a proxy for fitness. When grown at higher nitrogen supply, invaders had a plastic RGR response, increasing their RGR to a much greater extent than non-invaders. However, invasive species did not exhibit significantly more phenotypic plasticity than non-invasive species for any of 17 functional traits, and trait plasticity indices were generally weakly correlated with RGR. Conversely, invasive species had higher values than non-invaders for 13 of the 17 traits, including higher leaf area ratio, photosynthetic capacity, photosynthetic nutrient-use efficiency, and nutrient uptake rates, and these traits were also strongly correlated with performance. I conclude that, in responding to higher N supply, superior trait values coupled with a moderate degree of trait variation explain invasive species' superior performance better than plasticity per se. PMID:23119098

Inhibition of gold nanoparticles (AuNPs) on pathogenic biofilm formation and invasion to host cells.

PubMed

Yu, Qilin; Li, Jianrong; Zhang, Yueqi; Wang, Yufan; Liu, Lu; Li, Mingchun

2016-05-25

Owing to the growing infectious diseases caused by eukaryotic and prokaryotic pathogens, it is urgent to develop novel antimicrobial agents against clinical pathogenic infections. Biofilm formation and invasion into the host cells are vital processes during pathogenic colonization and infection. In this study, we tested the inhibitory effect of Au nanoparticles (AuNPs) on pathogenic growth, biofilm formation and invasion. Interestingly, although the synthesized AuNPs had no significant toxicity to the tested pathogens, Candida albicans and Pseudomonas aeruginosa, the nanoparticles strongly inhibited pathogenic biofilm formation and invasion to dental pulp stem cells (DPSCs). Further investigations revealed that AuNPs abundantly bound to the pathogen cells, which likely contributed to their inhibitory effect on biofilm formation and invasion. Moreover, treatment of AuNPs led to activation of immune response-related genes in DPSCs, which may enhance the activity of host immune system against the pathogens. Zeta potential analysis and polyethylene glycol (PEG)/polyethyleneimine (PEI) coating tests further showed that the interaction between pathogen cells and AuNPs is associated with electrostatic attractions. Our findings shed novel light on the application of nanomaterials in fighting against clinical pathogens, and imply that the traditional growth inhibition test is not the only way to evaluate the drug effect during the screening of antimicrobial agents.

Demographic factors influencing consensus opinion on the recall for women screened by mobile mammography unit in taiwan.

PubMed

Yu-Mei, Lee; Hsueh-Hua, Yao

2013-09-01

The incidence of breast cancer has had a four-fold increase from 1980 to 2005 in Taiwan. Limited data have been available on mobile breast screening in the Taiwanese population since 2009. This study aims at investigating the factors influencing consensus opinion on the recall for mobile breast screening in Taiwan. The factors were categorized by individual health background, socioeconomic status and knowledge about breast screening. There were 502 questionnaires collected from Taiwanese women examined on mobile mammography screening vehicle. Data were then analyzed by SPSS 12 via analysis of variance (ANOVA), F-test, t-test or chi-square test. Strong participation was associated with a younger age, higher educational level, higher incomes, previous history of cancer, previous family history of cancer, one or two prior mammographies, more correct recognitions of mammography, recall rate, and breast cancer risk. If the false-positive result occurred, 83.9%, 81.9% and 77.3% of the women agreed or strongly agreed to participate in noninvasive and invasive testing and screening mammography, respectively. The policy makers should notify the importance of demographic factors affecting further examination for early detection of breast cancer in Taiwan.

Non-invasive assessment of liver fibrosis: Between prediction/prevention of outcomes and cost-effectiveness.

PubMed

Stasi, Cristina; Milani, Stefano

2016-01-28

The assessment of the fibrotic evolution of chronic hepatitis has always been a challenge for the clinical hepatologist. Over the past decade, various non-invasive methods have been proposed to detect the presence of fibrosis, including the elastometric measure of stiffness, panels of clinical and biochemical parameters, and combinations of both methods. The aim of this review is to analyse the most recent data on non-invasive techniques for the evaluation of hepatic fibrosis with particular attention to cost-effectiveness. We searched for relevant studies published in English using the PubMed database from 2009 to the present. A large number of studies have suggested that elastography and serum markers are useful techniques for diagnosing severe fibrosis and cirrhosis and for excluding significant fibrosis in hepatitis C virus patients. In addition, hepatic stiffness may also help to prognosticate treatment response to antiviral therapy. It has also been shown that magnetic resonance elastography has a high accuracy for staging and differentiating liver fibrosis. Finally, studies have shown that non-invasive methods are becoming increasingly precise in either positively identifying or excluding liver fibrosis, thus reducing the need for liver biopsy. However, both serum markers and transient elastography still have "grey area" values of lower accuracy. In this case, liver biopsy is still required to properly assess liver fibrosis. Recently, the guidelines produced by the World Health Organization have suggested that the AST-to-platelet ratio index or FIB-4 test could be utilised for the evaluation of liver fibrosis rather than other, more expensive non-invasive tests, such as elastography or FibroTest.

Non-invasive assessment of liver fibrosis: Between prediction/prevention of outcomes and cost-effectiveness

PubMed Central

Stasi, Cristina; Milani, Stefano

2016-01-01

The assessment of the fibrotic evolution of chronic hepatitis has always been a challenge for the clinical hepatologist. Over the past decade, various non-invasive methods have been proposed to detect the presence of fibrosis, including the elastometric measure of stiffness, panels of clinical and biochemical parameters, and combinations of both methods. The aim of this review is to analyse the most recent data on non-invasive techniques for the evaluation of hepatic fibrosis with particular attention to cost-effectiveness. We searched for relevant studies published in English using the PubMed database from 2009 to the present. A large number of studies have suggested that elastography and serum markers are useful techniques for diagnosing severe fibrosis and cirrhosis and for excluding significant fibrosis in hepatitis C virus patients. In addition, hepatic stiffness may also help to prognosticate treatment response to antiviral therapy. It has also been shown that magnetic resonance elastography has a high accuracy for staging and differentiating liver fibrosis. Finally, studies have shown that non-invasive methods are becoming increasingly precise in either positively identifying or excluding liver fibrosis, thus reducing the need for liver biopsy. However, both serum markers and transient elastography still have “grey area” values of lower accuracy. In this case, liver biopsy is still required to properly assess liver fibrosis. Recently, the guidelines produced by the World Health Organization have suggested that the AST-to-platelet ratio index or FIB-4 test could be utilised for the evaluation of liver fibrosis rather than other, more expensive non-invasive tests, such as elastography or FibroTest. PMID:26819535

Non-invasive cortical stimulation improves post-stroke attention decline.

PubMed

Kang, Eun Kyoung; Baek, Min Jae; Kim, Sangyun; Paik, Nam-Jong

2009-01-01

Attention decline after stroke is common and hampers the rehabilitation process, and non-invasive transcranial direct current stimulation (tDCS) has the potential to elicit behavioral changes by modulating cortical excitability. The authors tested the hypothesis that a single session of non-invasive cortical stimulation with excitatory anodal tDCS applied to the left dorsolateral prefrontal cortex (DLPFC) can improve attention in stroke patients. Ten patients with post-stroke cognitive decline (MMSE 25) and 10 age-matched healthy controls participated in this double blind, sham-controlled, crossover study involving the administration of real (2 mA for 20 min) or sham stimulation (2 mA for 1 min) to the left DLPFC. Attention was measured using a computerized Go/No-Go test before and after intervention. Improvements in accuracy and speed after stimulation relative to baseline were compared for real and sham stimulations. In healthy controls, no significant improvement in Go/No-Go test was observed after either real or sham stimulation. However, in stroke patients, tDCS led to a significant improvement in response accuracy at 1 hour post-stimulation relative to baseline, and this improvement was maintained until 3 hours post-stimulation (P< 0.05), whereas sham stimulation did not lead to a significant improvement in response accuracy (P> 0.05). Changes in reaction times were comparable for the two stimulations (P> 0.05). Non invasive anodal tDCS applied to the left DLPFC was found to improve attention versus sham stimulation in stroke patients, which suggests that non-invasive cortical intervention could potentially be used during rehabilitative training to improve attention.

Comparison of accuracy of fibrosis degree classifications by liver biopsy and non-invasive tests in chronic hepatitis C.

PubMed

Boursier, Jérôme; Bertrais, Sandrine; Oberti, Frédéric; Gallois, Yves; Fouchard-Hubert, Isabelle; Rousselet, Marie-Christine; Zarski, Jean-Pierre; Calès, Paul

2011-11-30

Non-invasive tests have been constructed and evaluated mainly for binary diagnoses such as significant fibrosis. Recently, detailed fibrosis classifications for several non-invasive tests have been developed, but their accuracy has not been thoroughly evaluated in comparison to liver biopsy, especially in clinical practice and for Fibroscan. Therefore, the main aim of the present study was to evaluate the accuracy of detailed fibrosis classifications available for non-invasive tests and liver biopsy. The secondary aim was to validate these accuracies in independent populations. Four HCV populations provided 2,068 patients with liver biopsy, four different pathologist skill-levels and non-invasive tests. Results were expressed as percentages of correctly classified patients. In population #1 including 205 patients and comparing liver biopsy (reference: consensus reading by two experts) and blood tests, Metavir fibrosis (FM) stage accuracy was 64.4% in local pathologists vs. 82.2% (p < 10-3) in single expert pathologist. Significant discrepancy (≥ 2FM vs reference histological result) rates were: Fibrotest: 17.2%, FibroMeter2G: 5.6%, local pathologists: 4.9%, FibroMeter3G: 0.5%, expert pathologist: 0% (p < 10-3). In population #2 including 1,056 patients and comparing blood tests, the discrepancy scores, taking into account the error magnitude, of detailed fibrosis classification were significantly different between FibroMeter2G (0.30 ± 0.55) and FibroMeter3G (0.14 ± 0.37, p < 10-3) or Fibrotest (0.84 ± 0.80, p < 10-3). In population #3 (and #4) including 458 (359) patients and comparing blood tests and Fibroscan, accuracies of detailed fibrosis classification were, respectively: Fibrotest: 42.5% (33.5%), Fibroscan: 64.9% (50.7%), FibroMeter2G: 68.7% (68.2%), FibroMeter3G: 77.1% (83.4%), p < 10-3 (p < 10-3). Significant discrepancy (≥ 2 FM) rates were, respectively: Fibrotest: 21.3% (22.2%), Fibroscan: 12.9% (12.3%), FibroMeter2G: 5.7% (6.0%), FibroMeter3G: 0.9% (0.9%), p < 10-3 (p < 10-3). The accuracy in detailed fibrosis classification of the best-performing blood test outperforms liver biopsy read by a local pathologist, i.e., in clinical practice; however, the classification precision is apparently lesser. This detailed classification accuracy is much lower than that of significant fibrosis with Fibroscan and even Fibrotest but higher with FibroMeter3G. FibroMeter classification accuracy was significantly higher than those of other non-invasive tests. Finally, for hepatitis C evaluation in clinical practice, fibrosis degree can be evaluated using an accurate blood test.

Comparison of accuracy of fibrosis degree classifications by liver biopsy and non-invasive tests in chronic hepatitis C

PubMed Central

2011-01-01

Background Non-invasive tests have been constructed and evaluated mainly for binary diagnoses such as significant fibrosis. Recently, detailed fibrosis classifications for several non-invasive tests have been developed, but their accuracy has not been thoroughly evaluated in comparison to liver biopsy, especially in clinical practice and for Fibroscan. Therefore, the main aim of the present study was to evaluate the accuracy of detailed fibrosis classifications available for non-invasive tests and liver biopsy. The secondary aim was to validate these accuracies in independent populations. Methods Four HCV populations provided 2,068 patients with liver biopsy, four different pathologist skill-levels and non-invasive tests. Results were expressed as percentages of correctly classified patients. Results In population #1 including 205 patients and comparing liver biopsy (reference: consensus reading by two experts) and blood tests, Metavir fibrosis (FM) stage accuracy was 64.4% in local pathologists vs. 82.2% (p < 10-3) in single expert pathologist. Significant discrepancy (≥ 2FM vs reference histological result) rates were: Fibrotest: 17.2%, FibroMeter2G: 5.6%, local pathologists: 4.9%, FibroMeter3G: 0.5%, expert pathologist: 0% (p < 10-3). In population #2 including 1,056 patients and comparing blood tests, the discrepancy scores, taking into account the error magnitude, of detailed fibrosis classification were significantly different between FibroMeter2G (0.30 ± 0.55) and FibroMeter3G (0.14 ± 0.37, p < 10-3) or Fibrotest (0.84 ± 0.80, p < 10-3). In population #3 (and #4) including 458 (359) patients and comparing blood tests and Fibroscan, accuracies of detailed fibrosis classification were, respectively: Fibrotest: 42.5% (33.5%), Fibroscan: 64.9% (50.7%), FibroMeter2G: 68.7% (68.2%), FibroMeter3G: 77.1% (83.4%), p < 10-3 (p < 10-3). Significant discrepancy (≥ 2 FM) rates were, respectively: Fibrotest: 21.3% (22.2%), Fibroscan: 12.9% (12.3%), FibroMeter2G: 5.7% (6.0%), FibroMeter3G: 0.9% (0.9%), p < 10-3 (p < 10-3). Conclusions The accuracy in detailed fibrosis classification of the best-performing blood test outperforms liver biopsy read by a local pathologist, i.e., in clinical practice; however, the classification precision is apparently lesser. This detailed classification accuracy is much lower than that of significant fibrosis with Fibroscan and even Fibrotest but higher with FibroMeter3G. FibroMeter classification accuracy was significantly higher than those of other non-invasive tests. Finally, for hepatitis C evaluation in clinical practice, fibrosis degree can be evaluated using an accurate blood test. PMID:22129438

Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay

PubMed Central

Grützmann, Robert; Molnar, Bela; Pilarsky, Christian; Habermann, Jens K.; Schlag, Peter M.; Saeger, Hans D.; Miehlke, Stephan; Stolz, Thomas; Model, Fabian; Roblick, Uwe J.; Bruch, Hans-Peter; Koch, Rainer; Liebenberg, Volker; deVos, Theo; Song, Xiaoling; Day, Robert H.; Sledziewski, Andrew Z.; Lofton-Day, Catherine

2008-01-01

Background Colorectal cancer (CRC) is the second leading cause of cancer deaths despite the fact that detection of this cancer in early stages results in over 90% survival rate. Currently less than 45% of at-risk individuals in the US are screened regularly, exposing a need for better screening tests. We performed two case-control studies to validate a blood-based test that identifies methylated DNA in plasma from all stages of CRC. Methodology/Principal Findings Using a PCR assay for analysis of Septin 9 (SEPT9) hypermethylation in DNA extracted from plasma, clinical performance was optimized on 354 samples (252 CRC, 102 controls) and validated in a blinded, independent study of 309 samples (126 CRC, 183 controls). 168 polyps and 411 additional disease controls were also evaluated. Based on the training study SEPT9-based classification detected 120/252 CRCs (48%) and 7/102 controls (7%). In the test study 73/126 CRCs (58%) and 18/183 control samples (10%) were positive for SEPT9 validating the training set results. Inclusion of an additional measurement replicate increased the sensitivity of the assay in the testing set to 72% (90/125 CRCs detected) while maintaining 90% specificity (19/183 for controls). Positive rates for plasmas from the other cancers (11/96) and non-cancerous conditions (41/315) were low. The rate of polyp detection (>1 cm) was ∼20%. Conclusions/Significance Analysis of SEPT9 DNA methylation in plasma represents a straightforward, minimally invasive method to detect all stages of CRC with potential to satisfy unmet needs for increased compliance in the screening population. Further clinical testing is warranted. PMID:19018278

Estimating disease prevalence in two-phase studies.

PubMed

Alonzo, Todd A; Pepe, Margaret Sullivan; Lumley, Thomas

2003-04-01

Disease prevalence is ideally estimated using a 'gold standard' to ascertain true disease status on all subjects in a population of interest. In practice, however, the gold standard may be too costly or invasive to be applied to all subjects, in which case a two-phase design is often employed. Phase 1 data consisting of inexpensive and non-invasive screening tests on all study subjects are used to determine the subjects that receive the gold standard in the second phase. Naive estimates of prevalence in two-phase studies can be biased (verification bias). Imputation and re-weighting estimators are often used to avoid this bias. We contrast the forms and attributes of the various prevalence estimators. Distribution theory and simulation studies are used to investigate their bias and efficiency. We conclude that the semiparametric efficient approach is the preferred method for prevalence estimation in two-phase studies. It is more robust and comparable in its efficiency to imputation and other re-weighting estimators. It is also easy to implement. We use this approach to examine the prevalence of depression in adolescents with data from the Great Smoky Mountain Study.

Can one blood draw replace transrectal ultrasonography-estimated prostate volume to predict prostate cancer risk?

PubMed

Carlsson, Sigrid V; Peltola, Mari T; Sjoberg, Daniel; Schröder, Fritz H; Hugosson, Jonas; Pettersson, Kim; Scardino, Peter T; Vickers, Andrew J; Lilja, Hans; Roobol, Monique J

2013-09-01

To explore whether a panel of kallikrein markers in blood: total, free and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2, could be used as a non-invasive alternative for predicting prostate cancer on biopsy in a screening setting. The study cohort comprised previously unscreened men who underwent sextant biopsy owing to elevated PSA (≥3 ng/mL) in two different centres of the European Randomized Study of Screening for Prostate Cancer, Rotterdam (n = 2914) and Göteborg (n = 740). A statistical model, based on kallikrein markers, was compared with one based on established clinical factors for the prediction of biopsy outcome. The clinical tests were found to be no better than blood markers, with an area under the curve in favour of the blood measurements of 0.766 vs. 0.763 in Rotterdam and 0.809 vs. 0.774 in Göteborg. Adding digital rectal examination (DRE) or DRE plus transrectal ultrasonography (TRUS) volume to the markers improved discrimination, although the increases were small. Results were similar for predicting high-grade cancer. There was a strong correlation between the blood measurements and TRUS-estimated prostate volume (Spearman's correlation 0.60 in Rotterdam and 0.57 in Göteborg). In previously unscreened men, each with indication for biopsy, a statistical model based on kallikrein levels was similar to a clinical model in predicting prostate cancer in a screening setting, outside the day-to-day clinical practice. Whether a clinical approach can be replaced by laboratory analyses or used in combination with decision models (nomograms) is a clinical judgment that may vary from clinician to clinician depending on how they weigh the different advantages and disadvantages (harms, costs, time, invasiveness) of both approaches. © 2013 BJU International.

Effectiveness of FISK, an invasiveness screening tool for non-native freshwater fishes, to perform risk identification assessments in the Iberian Peninsula.

PubMed

Almeida, David; Ribeiro, Filipe; Leunda, Pedro M; Vilizzi, Lorenzo; Copp, Gordon H

2013-08-01

Risk assessments are crucial for identifying and mitigating impacts from biological invasions. The Fish Invasiveness Scoring Kit (FISK) is a risk identification (screening) tool for freshwater fishes consisting of two subject areas: biogeography/history and biology/ecology. According to the outcomes, species can be classified under particular risk categories. The aim of this study was to apply FISK to the Iberian Peninsula, a Mediterranean climate region highly important for freshwater fish conservation due to a high level of endemism. In total, 89 fish species were assessed by three independent assessors. Results from receiver operating characteristic analysis showed that FISK can discriminate reliably between noninvasive and invasive fishes for Iberia, with a threshold of 20.25, similar to those obtained in several regions around the world. Based on mean scores, no species was categorized as "low risk," 50 species as "medium risk," 17 as "moderately high risk," 11 as "high risk," and 11 as "very high risk." The highest scoring species was goldfish Carassius auratus. Mean certainty in response was above the category "mostly certain," ranging from tinfoil barb Barbonymus schwanenfeldii with the lowest certainty to eastern mosquitofish Gambusia holbrooki with the highest level. Pair-wise comparison showed significant differences between one assessor and the other two on mean certainty, with these two assessors showing a high coincidence rate for the species categorization. Overall, the results suggest that FISK is a useful and viable tool for assessing risks posed by non-native fish in the Iberian Peninsula and contributes to a "watch list" in this region. © 2013 Crown copyright This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

Uterine molecular changes for non-invasive embryonic attachment in the marsupials Macropus eugenii (Macropodidae) and Trichosurus vulpecula (Phalangeridae).

PubMed

Laird, Melanie K; Dargan, Jessica R; Paterson, Lillian; Murphy, Christopher R; McAllan, Bronwyn M; Shaw, Geoff; Renfree, Marilyn B; Thompson, Michael B

2017-10-01

Pregnancy in mammals requires remodeling of the uterus to become receptive to the implanting embryo. Remarkably similar morphological changes to the uterine epithelium occur in both eutherian and marsupial mammals, irrespective of placental type. Nevertheless, molecular differences in uterine remodeling indicate that the marsupial uterus employs maternal defences, including molecular reinforcement of the uterine epithelium, to regulate embryonic invasion. Non-invasive (epitheliochorial) embryonic attachment in marsupials likely evolved secondarily from invasive attachment, so uterine defences in these species may prevent embryonic invasion. We tested this hypothesis by identifying localization patterns of Talin, a key basal anchoring molecule, in the uterine epithelium during pregnancy in the tammar wallaby (Macropus eugenii; Macropodidae) and the brush tail possum (Trichosurus vulpecula; Phalangeridae). Embryonic attachment is non-invasive in both species, yet Talin undergoes a clear distributional change during pregnancy in M. eugenii, including recruitment to the base of the uterine epithelium just before attachment, that closely resembles that of invasive implantation in the marsupial species Sminthopsis crassicaudata. Basal localization occurs throughout pregnancy in T. vulpecula, although, as for M. eugenii, this pattern is most specific prior to attachment. Such molecular reinforcement of the uterine epithelium for non-invasive embryonic attachment in marsupials supports the hypothesis that less-invasive and non-invasive embryonic attachment in marsupials may have evolved via accrual of maternal defences. Recruitment of basal molecules, including Talin, to the uterine epithelium may have played a key role in this transition. © 2017 Wiley Periodicals, Inc.

Clonal Structure and Characterization of Staphylococcus aureus Strains from Invasive Infections in Paediatric Patients from South Poland: Association between Age, spa Types, Clonal Complexes, and Genetic Markers

PubMed Central

Ilczyszyn, Weronika M.; Sabat, Artur J.; Akkerboom, Viktoria; Szkarlat, Anna; Klepacka, Joanna; Sowa-Sierant, Iwona; Wasik, Barbara; Kosecka-Strojek, Maja; Buda, Aneta; Miedzobrodzki, Jacek; Friedrich, Alexander W.

2016-01-01

The aim of current study was to examine clonal structure and genetic profile of invasive Staphylococcus aureus isolates recovered from infants and children treated at the Jagiellonian University Children’s Hospital of Krakow, Poland. The 107 invasive S. aureus isolates, collected between February 2012 and August 2014, were analysed retrospectively. Antimicrobial susceptibility testing, spa typing and DNA microarray analysis were performed to determine clonal distribution, diversity and gene content in regard to patients characteristics. In total, 107 isolates were recovered from 88 patients with clinical symptoms of invasive bacterial infection. The final set of 92 non-duplicate samples included 38 MRSA isolates. Additionally, a set of 54 S. aureus isolates collected during epidemiological screening was genotyped and analysed. There were 72 healthcare-associated (HCA) and 20 community-onset (CO) infection events caused by 33 and 5 MRSA isolates, respectively. The majority of isolates were affiliated with the major European clonal complexes CC5 (t003, spa-CC 002), CC45 (spa-CC 015), CC7 or CC15 (t084, t091, spa-CC 084). Two epidemic clones (CC5-MRSA-II or CC45-MRSA-IV) dominated among MRSA isolates, while MSSA population contained 15 different CCs. The epidemiological screening isolates belonged to similar genetic lineages as those collected from invasive infection cases. The HCA infection events, spa types t003, t2642 or CC5 were significantly associated with infections occurring in neonates and children under 5 years of age. Moreover, carriage of several genetic markers, including erm(A), sea (N315), egc-cluster, chp was significantly higher in isolates obtained from children in this age group. The spa types t091 and t008 were underrepresented among patients aged 5 years or younger, whereas spa type t008, CC8 and presence of splE was associated with infection in children aged 10 years or older. The HCA-MRSA strains were most frequently found in children under 5 years, although the majority of invasive infections was associated with MSSA strains. Moreover, an association between age group of children from the study population and a specific strain genotype (spa type, clonal complex or genetic content) was observed among the patients. PMID:26992009

Detection of HPV related oropharyngeal cancer in oral rinse specimens

PubMed Central

Rosenthal, Matthew; Huang, Bin; Katabi, Nora; Migliacci, Jocelyn; Bryant, Robert; Kaplan, Samuel; Blackwell, Timothy; Patel, Snehal; Yang, Liying; Pei, Zhiheng; Tang, Yi-Wei; Ganly, Ian

2017-01-01

Background The majority of patients diagnosed with oropharyngeal squamous cell cancer (OPSCC) are due to HPV infection. At present, there are no reliable tests for screening HPV in patients with OPSCC. The objective of this study was to assess the Cobas® HPV Test on oral rinse specimens as an early, non-invasive tool for HPV-related OPSCC. Methods Oral rinse specimens were collected from 187 patients (45 with OPSCC, 61 with oral cavity SCC (OCSCC) and 81 control patients who had benign or malignant thyroid nodules) treated at MSKCC. The Cobas® HPV Test was used to detect 14 high-risk HPV types in these samples. Performance of the HPV Test was correlated with p16 tumor immunohistochemistry as gold standard. Results 91.1% of the oropharynx cancer patients had p16 positive tumors compared to 3.3% of oral cavity cancer. Of the 81 control patients, 79 (97.5%) had no HPV in their oral rinse giving a specificity of the HPV test of 98%. For the combined oral cavity oropharynx cancer cohort, the sensitivity, specificity, positive predictive value and negative predictive value of the HPV Test were 79.1%, 90.5%, 85.0% and 86.4% respectively when p16 immunohistochemistry was used as the reference. Conclusion The Cobas® HPV Test on oral rinse is a highly specific and potentially sensitive test for oropharyngeal cancer and may be a potentially useful screening test for early oropharyngeal cancer. Impact We describe an oral rinse test for the detection of HPV related oropharyngeal cancer. PMID:29312616

Participation in colorectal cancer screening trials after first-time invitation: a systematic review.

PubMed

Khalid-de Bakker, C; Jonkers, D; Smits, K; Mesters, I; Masclee, A; Stockbrügger, R

2011-12-01

Colorectal cancer (CRC) screening is implemented by an increasing number of countries. Participation rates of screening programs influence the health benefit and cost-effectiveness of the applied method. The aim was to systematically review participation rate after first-time invitation for CRC screening with fecal occult blood test (FOBT), sigmoidoscopy, colonoscopy, and/or computed tomography (CT) colonography. A systematic literature search was performed prior to October 1 2009. Prospective CRC screening studies of unselected populations reporting participation rates were included. After meta-analyses, overall participation rates were found to be 47 % for FOBT, 42 % for fecal immunologic tests (FITs), 35 % for sigmoidoscopy, 41 % for sigmoidoscopy combined with FIT/FOBT, 28 % for colonoscopy, and 22 % for CT colonography. Studies comparing screening methods showed higher participation rates for less invasive methods. Studies comparing invitation methods showed higher participation rates with general practitioner involvement, a more personalized recruitment approach, and reduction of barriers that discourage participation. Knowledge of identified factors affecting CRC screening participation can be used to improve screening programs. © Georg Thieme Verlag KG Stuttgart · New York.

Comparison of Hemispheric Activation during Mental Word and Rhyme Generation Using Transcranial Doppler Sonography

ERIC Educational Resources Information Center

Krach, Soren; Hartje, Wolfgang

2006-01-01

The Wada test is at present the method of choice for preoperative assessment of patients who require surgery close to cortical language areas. It is, however, an invasive test with an attached morbidity risk. By now, an alternative to the Wada test is to combine a lexical word generation paradigm with non-invasive imaging techniques. However,…

Calcium score of coronary artery stratifies the risk of obstructive coronary artery diseases.

PubMed

Ibrahim, O; Oteh, M; Anwar, I R; Che Hassan, H H; Choor, C K; Hamzaini, A H; Rahman, M M

2013-01-01

Coronary heart disease is a major health problem in Malaysia with high morbidity and mortality. Common primary screening tool of cardiovascular risk stratification is exercise treadmill test (ETT). This communication is to determine the performance of coronary artery calcium score a new method to stratify the presence of obstructive coronary artery disease (CAD) in comparison to traditional ETT in patients having coronary artery diseases. Patients between 30 to 60 years old attended the ETT to screen for ischemic heart disease were recruited for Agatston coronary artery calcium score (CACS) of multi-sliced computed tomography (MSCT). Subsequently all patients underwent a full MSCT coronary angiography. The major determinant was the state of CAD whether obstructive (50% stenosis or more) or non-obstructive (less than 50% stenosis). All patients diagnosed with obstructive CAD on MSCT coronary angiogram were subjected to invasive coronary angiogram (ICA) to confirm the findings and planned the need for revascularization. The CACS was 100% sensitivity and 97.5% specificity in detecting obstructive CAD at the optimal cut-off value of 106.5 and above. The positive predictive value (PPV) at CACS ≥ 106 was 71.4% and the negative predictive value (NPV) was consistent at 100%. Compare to ETT, the CACS discriminative value and diagnostic performance was much better (PPV 71.4% vs. 45.5%), respectively. CACS can be a good diagnostic screening tool in patients suspected of CAD, and particularly within the non-diagnostic ETT subgroup with low to moderate cardiovascular risks.

Expanded Enlistment Eligibility Metrics (EEEM): Recommendations on a Non-Cognitive Screen for New Soldier Selection

DTIC Science & Technology

2010-07-01

applicants and is pursing further research on the WPA. An operational test and evaluation ( IOT &E) has been initiated to evaluate the new screen...initial operational test and evaluation ( IOT &E) starting in fall 2009. vii EXPANDED ENLISTMENT ELIGIBILITY METRICS (EEEM): RECOMMENDATIONS ON A NON...Evaluation of a Performance Screen for IOT &E ..................................... 49 Approach

Development and evaluation of training resources to prepare health professionals for counselling pregnant women about non-invasive prenatal testing for Down syndrome: a mixed methods study.

PubMed

Oxenford, Kerry; Daley, Rebecca; Lewis, Celine; Hill, Melissa; Chitty, Lyn S

2017-04-27

The availability of non-invasive prenatal testing (NIPT) for aneuploidies is expanding rapidly throughout the world. Training health professionals to offer NIPT in a way that supports informed choice is essential for implementation. The aim of this study was to develop and evaluate a training package for health professionals to support the introduction of NIPT into clinical practice. Training on NIPT was offered to health professionals, primarily midwives, involved in Down syndrome screening and testing in eight hospitals located in England and Scotland as part of a research study evaluating the implementation of NIPT in the UK National Health Service. Training was evaluated using a mixed methods approach that included quantitative questionnaires at three time points and post-training qualitative interviews. The questionnaires measured confidence, self-perceived knowledge and actual knowledge about NIPT for Down syndrome. Interviews explored opinions about the training and experiences of offering NIPT. The training provided to the health professionals was found to positively impact on their confidence in discussing NIPT with women in their clinic, and both their perceived and actual knowledge and understanding of NIPT was improved. Knowledge remained weak in four areas; cell-free fetal DNA levels increase with gestation; turnaround time for NIPT results; cell-free fetal DNA is placental in origin; and NIPT false positive rate. Training materials, including a lesson plan, PowerPoint presentation and written factsheet on NIPT, have been developed and evaluated for use in educating midwives and supporting the introduction of NIPT. Implementation of training should include a greater focus on the areas where knowledge remained low. Some groups of midwives will need additional training or support to optimise their confidence in discussing NIPT with women.

The inclusion of N-terminal pro-brain natriuretic peptide in a sensitive screening strategy for systemic sclerosis-related pulmonary arterial hypertension: a cohort study

PubMed Central

2013-01-01

Introduction Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accuracy of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with pulmonary function tests (PFT) (‘proposed’ algorithm) in a screening algorithm for SSc-PAH. Methods We evaluated our proposed algorithm (PFT with NT-proBNP) on 49 consecutive SSc patients with suspected pulmonary hypertension undergoing right heart catherisation (RHC). The predictive accuracy of the proposed algorithm was compared with existing screening recommendations, and is presented as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results Overall, 27 patients were found to have pulmonary hypertension (PH) at RHC, while 22 had no PH. The sensitivity, specificity, PPV and NPV of the proposed algorithm for PAH was 94.1%, 54.5%, 61.5% and 92.3%, respectively; current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines achieved a sensitivity, specificity, PPV and NPV of 94.1%, 31.8%, 51.6% and 87.5%, respectively. In an alternate case scenario analysis, estimating a PAH prevalence of 10%, the proposed algorithm achieved a sensitivity, specificity, PPV and NPV for PAH of 94.1%, 54.5%, 18.7% and 98.8%, respectively. Conclusions The combination of NT-proBNP with PFT is a sensitive, yet simple and non-invasive, screening strategy for SSc-PAH. Patients with a positive screening result can be referred for echocardiography, and further confirmatory testing for PAH. In this way, it may be possible to shift the burden of routine screening away from echocardiography. The findings of this study should be confirmed in larger studies. PMID:24246100

The impact of illiteracy on the assessment of cognition and dementia: a critical issue in the developing countries.

PubMed

Noroozian, Maryam; Shakiba, Alia; Iran-nejad, Shahrzad

2014-12-01

Dementia and Alzheimer's disease (AD) is considered a major public health challenge in this decade and in the future. Early detection of AD through appropriate screening tools would be valuable approach in facing the burden of disease specifically in developing societies with insufficient resources. Selecting a screening tool which is non-expensive, non-invasive and implementable by trained primary healthcare providers is the first and probably the most important step in detecting high risk individuals. The goal of this review is to address the key issues in assessment tools in developing countries with a high level of illiteracy. We set about a review on literature on the subject of cognitive function assessment among minorities, people with low or no education, and people who live in underdeveloped societies. We also reviewed the studies on validation of such tests in a new society. The most popular assessment tools are more or less biased by the level of education; not all of them are useful for any type of dementia as they assess only some domains of cognitive function. Even though people with lower level of education have a higher rate of developing dementia, cognitive function cannot be accurately assessed because of limitations of current available tools. It is strongly suggested that special attention be paid to assess them by functional scales and activity daily living scales. For a more efficient assessment, cognitive tests can also benefit from illustrative questions, proverbs, metaphors, traditions, religious rituals and historical events.

A neurotoxic pesticide changes the outcome of aggressive interactions between native and invasive ants

PubMed Central

Barbieri, Rafael F.; Lester, Philip J.; Miller, Alexander S.; Ryan, Ken G.

2013-01-01

Neurotoxic pesticides, such as neonicotinoids, negatively affect the cognitive capacity and fitness of non-target species, and could also modify interspecific interactions. We tested whether sublethal contamination with neonicotinoid could affect foraging, colony fitness and the outcome of behavioural interactions between a native (Monomorium antarcticum) and an invasive ant species (Linepithema humile). The foraging behaviour of both ants was not affected by neonicotinoid exposure. Colonies of the invasive species exposed to the neonicotinoid produced significantly fewer brood. In interspecific confrontations, individuals of the native species exposed to the neonicotinoid lowered their aggression towards the invasive species, although their survival probability was not affected. Exposed individuals of the invasive species interacting with non-exposed native ants displayed increased aggression and had their survival probability reduced. Non-exposed individuals of the invasive species were less aggressive but more likely to survive when interacting with exposed native ants. These results suggest that non-target exposure of invaders to neonicotinoids could either increase or decrease the probability of survival according to the exposure status of the native species. Given that, in any community, different species have different food preferences, and thus different exposure to pesticides, non-target exposure could potentially change the dynamics of communities and influence invasion success. PMID:24266038

The long non-coding RNA MALAT1 promotes the migration and invasion of hepatocellular carcinoma by sponging miR-204 and releasing SIRT1.

PubMed

Hou, Zhouhua; Xu, Xuwen; Zhou, Ledu; Fu, Xiaoyu; Tao, Shuhui; Zhou, Jiebin; Tan, Deming; Liu, Shuiping

2017-07-01

Increasing evidence supports the significance of long non-coding RNA in cancer development. Several recent studies suggest the oncogenic activity of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in hepatocellular carcinoma. In this study, we explored the molecular mechanisms by which MALAT1 modulates hepatocellular carcinoma biological behaviors. We found that microRNA-204 was significantly downregulated in sh-MALAT1 HepG2 cell and 15 hepatocellular carcinoma tissues by quantitative real-time polymerase chain reaction analysis. Through bioinformatic screening, luciferase reporter assay, RNA-binding protein immunoprecipitation, and RNA pull-down assay, we identified microRNA-204 as a potential interacting partner for MALAT1. Functionally, wound-healing and transwell assays revealed that microRNA-204 significantly inhibited the migration and invasion of hepatocellular carcinoma cells. Notably, sirtuin 1 was recognized as a direct downstream target of microRNA-204 in HepG2 cells. Moreover, si-SIRT1 significantly inhibited cell invasion and migration process. These data elucidated, by sponging and competitive binding to microRNA-204, MALAT1 releases the suppression on sirtuin 1, which in turn promotes hepatocellular carcinoma migration and invasion. This study reveals a novel mechanism by which MALAT1 stimulates hepatocellular carcinoma progression and justifies targeting metastasis-associated lung adenocarcinoma transcript 1 as a potential therapy for hepatocellular carcinoma.

Withdrawing low risk women from cervical screening programmes: mathematical modelling study

PubMed Central

Sherlaw-Johnson, C; Gallivan, S; Jenkins, D

1999-01-01

Objective To evaluate the impact of policies for removing women before the recommended age of 64 from screening programmes for cervical cancer in the United Kingdom. Design A mathematical model of the clinical course of precancerous lesions which accounts for the influence of infection with the human papillomavirus, the effects of screening on the progression of disease, and the accuracy of the testing procedures. Two policies are compared: one in which women are withdrawn from the programme if their current smear is negative and they have a recent history of regular, negative results and one in which women are withdrawn if their current smear test is negative and a simultaneous test is negative for exposure to high risk types of human papillomavirus. Setting United Kingdom cervical screening programme. Main outcome measures The incidence of invasive cervical cancer and the use of resources. Results Early withdrawal of selected women from the programme is predicted to give rise to resource savings of up to 25% for smear tests and 18% for colposcopies when withdrawal occurs from age 50, the youngest age considered in the study. An increase in the incidence of invasive cervical cancer, by up to 2 cases/100 000 women each year is predicted. Testing for human papillomavirus infection to determine which women should be withdrawn from the programme makes little difference to outcome. Conclusions This model systematically analyses the consequences of screening options using available data and the clinical course of precancerous lesions. If further audit studies confirm the model’s forecasts, a policy of early withdrawal might be considered. This would be likely to release substantial resources which could be channelled into other aspects of health care or may be more effectively used within the cervical screening programme to counteract the possible increase in cancer incidence that early withdrawal might bring. Key messagesIn the United Kingdom there is concern that the cervical screening programme uses a large amount of resources to screen postmenopausal women who are at low risk of cervical cancerThere may be advantages to withdrawing these women from the screening programme before they reach the recommended age of 64A mathematical modelling approach can be used to evaluate the effectiveness of different policies for early withdrawal from screening with or without an additional test for human papillomavirus DNAEarly withdrawal could lead to a substantial reduction in the resources devoted to screening which could be channelled more effectively into other aspects of health careEarly withdrawal is likely to increase the overall incidence of cervical cancer unless other steps are taken to compensate PMID:9933195

Comparison of non-invasive assessment to diagnose liver fibrosis in chronic hepatitis B and C patients.

PubMed

Stibbe, Krista J M; Verveer, Claudia; Francke, Jan; Hansen, Bettina E; Zondervan, Pieter E; Kuipers, Ernst J; de Knegt, Robert J; van Vuuren, Anneke J

2011-07-01

Chronic viral hepatitis B and C cause liver fibrosis, leading to cirrhosis. Fibrosis assessment is essential to establish prognosis and treatment indication. We compared seven non-invasive tests, separately and in combination, in chronic hepatitis patients to detect early stages of fibrosis according to the Metavir score in liver biopsy. Galactose and methacetin breath tests (GBT and MBT), biomarkers (hyaluronic acid (HA), aspartate aminotransferase platelet ratio index (APRI), FibroTest, and Fib-4) and transient elastography (TE) were evaluated in 89 patients. Additionally, 31 healthy controls were included for evaluation of breath tests and biomarkers. Serum markers (HA, APRI, FibroTest, and Fib-4) and elastography significantly distinguished non-cirrhotic (F0123) from cirrhotic (F4) patients (p < 0.001, p = 0.015, p < 0.001, p = 0.005, p = 0.006, respectively). GBT, HA, APRI, FibroTest, Fib-4, and TE detected F01 from F234 (p = 0.04, p = 0.011, p = 0.009, p < 0.001, p < 0.001, and p < 0.001, respectively). A combination of different tests (TE, HA, and FibroTest) improved the performance statistically, area under the curve (AUC) = 0.87 for F234, 0.92 for F34, and 0.90 for F4. HA, APRI, FibroTest, Fib-4, and TE reliably distinguish non-cirrhotic and cirrhotic patients. Except for MBT, all tests discriminate between mild and moderate fibrosis. As single tests: FibroTest, Fib-4, and TE were the most accurate for detecting early fibrosis; combining different non-invasive tests increased the accuracy for detection of liver fibrosis to such an extent and thus might be acceptable to replace liver biopsy.

Non-invasive pressure difference estimation from PC-MRI using the work-energy equation

PubMed Central

Donati, Fabrizio; Figueroa, C. Alberto; Smith, Nicolas P.; Lamata, Pablo; Nordsletten, David A.

2015-01-01

Pressure difference is an accepted clinical biomarker for cardiovascular disease conditions such as aortic coarctation. Currently, measurements of pressure differences in the clinic rely on invasive techniques (catheterization), prompting development of non-invasive estimates based on blood flow. In this work, we propose a non-invasive estimation procedure deriving pressure difference from the work-energy equation for a Newtonian fluid. Spatial and temporal convergence is demonstrated on in silico Phase Contrast Magnetic Resonance Image (PC-MRI) phantoms with steady and transient flow fields. The method is also tested on an image dataset generated in silico from a 3D patient-specific Computational Fluid Dynamics (CFD) simulation and finally evaluated on a cohort of 9 subjects. The performance is compared to existing approaches based on steady and unsteady Bernoulli formulations as well as the pressure Poisson equation. The new technique shows good accuracy, robustness to noise, and robustness to the image segmentation process, illustrating the potential of this approach for non-invasive pressure difference estimation. PMID:26409245

Correlation of Michigan neuropathy screening instrument, United Kingdom screening test and electrodiagnosis for early detection of diabetic peripheral neuropathy.

PubMed

Fateh, Hamid R; Madani, Seyed Pezhman; Heshmat, Ramin; Larijani, Bagher

2015-01-01

Almost half of Diabetic Peripheral Neuropathies (DPNs) are symptom-free. Methods including questionnaires and electrodiagnosis (EDx) can be fruitful for easy reach to early diagnosis, correct treatments of diabetic neuropathy, and so decline of complications for instance diabetic foot ulcer and prevention of high costs. The goal of our study was to compare effectiveness of the Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST) and electrophysiological evaluation in confirming diabetic peripheral neuropathy. One hundred twenty five known diabetes mellitus male and female subjects older than 18 with or without symptoms of neuropathy comprised in this research. All of them were interviewed in terms of demographic data, lipid profile, HbA1C, duration of disease, and history of retinopathy, so examined by Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST), and nerve conduction studies (NCS). The collected data were analyzed by SPSS software 18. One hundred twenty five diabetic patients (70 female, 55 male) were recruited in this study with a mean age of 58.7 ± 10.2, and mean duration of diabetes was 10.17 ± 6.9 years. The mean neuropathy score of MNSI and UKST were 2.3 (1.7) and 4.16 (2.9), respectively. Each instrument detected the peripheral neuropathy in 78 (69 %) and 91 (73 %) of patients, respectively. There was a significant relationship between number of neuropathies and mean of diabetes duration and development of retinopathy in both questionnaire evaluations and NCS. By nerve conduction study, neuropathy was detected in 121 (97 %) diabetic patients were reported in order 15 (12 %) mononeuropathy (as 33 % sensory and 67 % motor neuropathy) and 106 (85 %) polyneuropathy (as 31 % motor and 69 % sensorimotor neuropathy). As regards NCS is an objective, simple, and non-invasive tool and also can determine level of damage and regeneration in peripheral nerves, this study suggests electrodiagnosis as a convenient option for screening, confirming, and follow up of diabetic peripheral neuropathy.

Hepatitis B in Moroccan-Dutch: a quantitative study into determinants of screening participation.

PubMed

Hamdiui, Nora; Stein, Mart L; Timen, Aura; Timmermans, Danielle; Wong, Albert; van den Muijsenbergh, Maria E T C; van Steenbergen, Jim E

2018-03-29

In November 2016, the Dutch Health Council recommended hepatitis B (HBV) screening for first-generation immigrants from HBV endemic countries. However, these communities show relatively low attendance rates for screening programmes, and our knowledge on their participation behaviour is limited. We identified determinants associated with the intention to request an HBV screening test in first-generation Moroccan-Dutch immigrants. We also investigated the influence of non-refundable costs for HBV screening on their intention. Offline and online questionnaires were distributed among first- and second/third-generation Moroccan-Dutch immigrants using respondent-driven sampling. Random forest analyses were conducted to determine which determinants had the greatest impact on (1) the intention to request an HBV screening test on one's own initiative, and (2) the intention to participate in non-refundable HBV screening at €70,-. Of the 379 Moroccan-Dutch respondents, 49.3% intended to request a test on their own initiative, and 44.1% were willing to attend non-refundable screening for €70,-. Clarity regarding infection status, not having symptoms, fatalism, perceived self-efficacy, and perceived risk of having HBV were the strongest predictors to request a test. Shame and stigma, fatalism, perceived burden of screening participation, and social influence of Islamic religious leaders had the greatest predictive value for not intending to participate in screening at €70,- non-refundable costs. Perceived severity and possible health benefit were facilitators for this intention measure. These predictions were satisfyingly accurate, as the random forest method retrieved area under the curve scores of 0.72 for intention to request a test and 0.67 for intention to participate in screening at €70,- non-refundable costs. By the use of respondent-driven sampling, we succeeded in studying screening behaviour among a hard-to-reach minority population. Despite the limitations associated with correlated data and the sampling method, we recommend to (1) incorporate clarity regarding HBV status, (2) stress the risk of an asymptomatic infection, (3) emphasise mother-to-child transmission as the main transmission route, and (4) team up with Islamic religious leaders to help decrease elements of fatalism, shame, and stigma to enhance screening uptake of Moroccan immigrants in the Netherlands.

RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy

PubMed Central

Lo, Kitty K.; Boustred, Christopher; Chitty, Lyn S.; Plagnol, Vincent

2014-01-01

Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice. RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods. The input to RAPIDR is a set of sequence alignment files in the BAM format, and the outputs are calls for aneuploidy, including trisomies 13, 18, 21 and monosomy X as well as fetal sex. RAPIDR has been extensively tested with a large sample set as part of the RAPID project in the UK. The package contains quality control steps to make it robust for use in the clinical setting. Availability and implementation: RAPIDR is implemented in R and can be freely downloaded via CRAN from here: http://cran.r-project.org/web/packages/RAPIDR/index.html. Contact: kitty.lo@ucl.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24990604

Comparing self- and provider-collected swabbing for HPV DNA testing in female-to-male transgender adult patients: a mixed-methods biobehavioral study protocol.

PubMed

Reisner, Sari L; Deutsch, Madeline B; Peitzmeier, Sarah M; White Hughto, Jaclyn M; Cavanaugh, Timothy; Pardee, Dana J; McLean, Sarah; Marrow, Elliot J; Mimiaga, Matthew J; Panther, Lori; Gelman, Marcy; Green, Jamison; Potter, Jennifer

2017-06-23

Cervical cancer, nearly all cases of which are caused by one of several high-risk strains of the human papillomavirus (hr-HPV), leads to significant morbidity and mortality in individuals with a cervix. Trans masculine (TM) individuals were born with female reproductive organs and identify as male, man, transgender man, or another diverse gender identity different from their female assigned sex at birth. Routine preventive sexual health screening of TM patients is recommended, including screening for cervical cancer and other sexually transmitted infections (STIs); however, as many as one in three TM patients are not up-to-date per recommended U.S. Among cisgender (non-transgender) women, self-swab hr.-HPV DNA testing as a primary cervical cancer screening method and self-swab specimen collection for other STIs have high levels of acceptability. No study has yet been conducted to compare the performance and acceptability of self- and provider-collected swabs for hr.-HPV DNA testing and other STIs in TM patients. This article describes the study protocol for a mixed-methods biobehavioral investigation enrolling 150 sexually active TM to (1) assess the clinical performance and acceptability of a vaginal self-swab for hr.-HPV DNA testing compared to provider cervical swab and cervical cytology, and (2) gather acceptability data on self-collected specimens for other STIs. Study participation entails a one-time clinical visit at Fenway Health in Boston, MA comprised of informed consent, quantitative assessment, venipuncture for syphilis testing and HIV (Rapid OraQuick) testing, randomization, collection of biological specimens/biomarkers, participant and provider satisfaction survey, and qualitative exit interview. Participants are compensated $100. The primary study outcomes are concordance (kappa statistic) and performance (sensitivity and specificity) of self-collected vaginal HPV DNA specimens vs provider-collected cervical HPV swabs as a gold standard. This study addresses critical gaps in current clinical knowledge of sexual health in TM patients, including comparing alternative strategies for screening and diagnosis of cervical cancer, hr.-HPV, and other STIs. Findings have implications for improving the delivery of sexual health screening to this often overlooked and underserved patient population. Less-invasive patient-centered strategies may also generalize to other at-risk cisgender female populations that face barriers to timely and needed STI and cervical cancer screening. ClinicalTrials.gov ID: NCT02401867.

Fruit fate, seed germination and growth of an invasive vine - an experimental test of 'sit and wait' strategy

Treesearch

Cathryn H. Greenberg; Lindsay M. Smith; Douglas J. Levey

2001-01-01

Oriental bittersweet (Celastrus orbiculutus Thunb.) is a non-indigenous, invasive woody vine in North America that proliferates in disturbed open sites. Unlike most invasive species, C. orbiculatus exhibits a `sit and wait' strategy by establishing and persisting indefinitely in undisturbed, closed canopy forest and...

Contraband detection using acoustic technology

NASA Astrophysics Data System (ADS)

George, Robert D.; Gauthier, Ronald D.; Denslow, Kayte D.; Cinson, Anthony M.; Diaz, Aaron A.; Griffin, Molly

2008-03-01

Maritime security personnel have a need for advanced technologies to address issues such as identification, confirmation or classification of substances and materials in sealed containers, both non-invasively and nondestructively in field and first response operations. Such substances include items such as hazardous/flammable liquids, drugs, contraband, and precursor chemicals used in the fabrication of illicit materials. Our initial efforts focused specifically on a commercial portable acoustic detector technology that was evaluated under operational conditions in a maritime environment. Technical/operational limitations were identified and enhancements were incorporated that would address these limitations. In this paper, application-specific improvements and performance testing/evaluation results will be described. Such enhancements will provide personnel/users of the detector a significantly more reliable method of screening materials for contraband items that might be hidden in cargo containers.

Pre-operative Screening and Manual Drilling Strategies to Reduce the Risk of Thermal Injury During Minimally Invasive Cochlear Implantation Surgery.

PubMed

Dillon, Neal P; Fichera, Loris; Kesler, Kyle; Zuniga, M Geraldine; Mitchell, Jason E; Webster, Robert J; Labadie, Robert F

2017-09-01

This article presents the development and experimental validation of a methodology to reduce the risk of thermal injury to the facial nerve during minimally invasive cochlear implantation surgery. The first step in this methodology is a pre-operative screening process, in which medical imaging is used to identify those patients that present a significant risk of developing high temperatures at the facial nerve during the drilling phase of the procedure. Such a risk is calculated based on the density of the bone along the drilling path and the thermal conductance between the drilling path and the nerve, and provides a criterion to exclude high-risk patients from receiving the minimally invasive procedure. The second component of the methodology is a drilling strategy for manually-guided drilling near the facial nerve. The strategy utilizes interval drilling and mechanical constraints to enable better control over the procedure and the resulting generation of heat. The approach is tested in fresh cadaver temporal bones using a thermal camera to monitor temperature near the facial nerve. Results indicate that pre-operative screening may successfully exclude high-risk patients and that the proposed drilling strategy enables safe drilling for low-to-moderate risk patients.

A new ethical landscape of prenatal testing: individualizing choice to serve autonomy and promote public health: a radical proposal.

PubMed

Munthe, Christian

2015-01-01

A new landscape of prenatal testing (PNT) is presently developing, including new techniques for risk-reducing, non-invasive sampling of foetal DNA and drastically enhanced possibilities of what may be rapidly and precisely analysed, surrounded by a growing commercial genetic testing industry and a general trend of individualization in healthcare policies. This article applies a set of established ethical notions from past debates on PNT for analysing PNT screening-programmes in this new situation. While some basic challenges of PNT stay untouched, the new development supports a radical individualization of how PNT screening is organized. This reformation is, at the same time, difficult to reconcile with responsible spending of resources in a publicly funded healthcare context. Thus, while the ethical imperative of individualization holds and applies to PNT, the new landscape of PNT provides reasons to start rolling back the type of mass-screening programmes currently established in many countries. Instead, more limited offers are suggested, based on considerations of severity of conditions and optimized to simultaneously serve reproductive autonomy and public health within an acceptable frame of priorities. The new landscape of PNT furthermore underscores the ethical importance of supporting and including people with disabilities. For the very same reason, no ban on what may be analysed using PNT in the new landscape should be applied, although private offers must, of course, conform to strict requirements of respecting reproductive autonomy and what that means in terms of counselling. © 2014 John Wiley & Sons Ltd.

Reasons for non-uptake and subsequent participation in the NHS Bowel Cancer Screening Programme: a qualitative study.

PubMed

Palmer, C K; Thomas, M C; von Wagner, C; Raine, R

2014-04-02

Screening for bowel cancer using the guaiac faecal occult blood test offered by the NHS Bowel Cancer Screening Programme (BCSP) is taken up by 54% of the eligible population. Uptake ranges from 35% in the most to 61% in the least deprived areas. This study explores reasons for non-uptake of bowel cancer screening, and examines reasons for subsequent uptake among participants who had initially not taken part in screening. Focus groups with a socio-economically diverse sample of participants were used to explore participants' experience of invitation to and non-uptake of bowel cancer screening. Participants described sampling faeces and storing faecal samples as broaching a cultural taboo, and causing shame. Completion of the test kit within the home rather than a formal health setting was considered unsettling and reduced perceived importance. Not knowing screening results was reported to be preferable to the implications of a positive screening result. Feeling well was associated with low perceived relevance of screening. Talking about bowel cancer screening with family and peers emerged as the key to subsequent participation in screening. Initiatives to normalise discussion about bowel cancer screening, to link the BCSP to general practice, and to simplify the test itself may lead to increased uptake across all social groups.

[Human papillomavirus testing in cervical cancer screening at a public health service of Santiago, Chile].

PubMed

Terrazas, Solana; Ibáñez, Carolina; Lagos, Marcela; Poggi, Helena; Brañes, Jorge; Barriga, María Isabel; Cartagena, Jaime; Núñez, Felipe; González, Francisca; Cook, Paz; Van De Wyngard, Vanessa; Ferreccio, Catterina

2015-01-01

Molecular techniques for human papillomavirus (HPV) detection have a good performance as screening tests and could be included in cervical cancer early detection programs. We conducted a population-based trial comparing HPV detection and Papanicolaou as primary screening tests, in a public health service in Santiago, Chile. To describe the experience of implementing this new molecular test and present the main results of the study. Women aged 25 to 64 enrolled in three public health centers were invited to participate. In all women, samples were collected for Papanicolaou and HPV DNA testing, and naked-eye visual inspection of the cervix with acetic acid was performed. Women with any positive screening test were referred to the local area hospital for diagnostic confirmation with colposcopy and biopsy of suspicious lesions. Screening results were obtained for 8265 women, of whom 931 (11.3%) were positive to any test. The prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was 1.1%; nine women had invasive cervical cancer. Sensitivities for the detection of CIN2+ were 22.1% (95% confidence interval (CI) 16.4-29.2) for Papanicolaou and 92.7% (95% CI 84.4-96.8) for HPV testing; specificities were 98.9% (95% CI 98.7-99.0) and 92.0% (95% CI 91.4-92.6) respectively. This experience showed that the implementation of a molecular test for cervical cancer screening is not a major challenge in Chile: it was well accepted by both the health team and the participants, and it may improve the effectiveness of the screening program.

Executive summary of the SEPAR recommendations for the diagnosis and treatment of non-small cell lung cancer.

PubMed

Villar Álvarez, Felipe; Muguruza Trueba, Ignacio; Belda Sanchis, José; Molins López-Rodó, Laureano; Rodríguez Suárez, Pedro Miguel; Sánchez de Cos Escuín, Julio; Barreiro, Esther; Borrego Pintado, M Henar; Disdier Vicente, Carlos; Flandes Aldeyturriaga, Javier; Gámez García, Pablo; Garrido López, Pilar; León Atance, Pablo; Izquierdo Elena, José Miguel; Novoa Valentín, Nuria M; Rivas de Andrés, Juan José; Royo Crespo, Íñigo; Salvatierra Velázquez, Ángel; Seijo Maceiras, Luís M; Solano Reina, Segismundo; Aguiar Bujanda, David; Avila Martínez, Régulo J; de Granda Orive, Jose Ignacio; de Higes Martinez, Eva; Diaz-Hellín Gude, Vicente; Embún Flor, Raúl; Freixinet Gilart, Jorge L; García Jiménez, María Dolores; Hermoso Alarza, Fátima; Hernández Sarmiento, Samuel; Honguero Martínez, Antonio Francisco; Jimenez Ruiz, Carlos A; López Sanz, Iker; Mariscal de Alba, Andrea; Martínez Vallina, Primitivo; Menal Muñoz, Patricia; Mezquita Pérez, Laura; Olmedo García, María Eugenia; Rombolá, Carlos A; San Miguel Arregui, Iñigo; de Valle Somiedo Gutiérrez, María; Triviño Ramírez, Ana Isabel; Trujillo Reyes, Joan Carles; Vallejo, Carmen; Vaquero Lozano, Paz; Varela Simó, Gonzalo; Zulueta, Javier J

2016-07-01

The Thoracic Surgery and Thoracic Oncology groups of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) have backed the publication of a handbook on recommendations for the diagnosis and treatment of non-small cell lung cancer. Due to the high incidence and mortality of this disease, the best scientific evidence must be constantly updated and made available for consultation by healthcare professionals. To draw up these recommendations, we called on a wide-ranging group of experts from the different specialties, who have prepared a comprehensive review, divided into 4 main sections. The first addresses disease prevention and screening, including risk factors, the role of smoking cessation, and screening programs for early diagnosis. The second section analyzes clinical presentation, imaging studies, and surgical risk, including cardiological risk and the evaluation of respiratory function. The third section addresses cytohistological confirmation and staging studies, and scrutinizes the TNM and histological classifications, non-invasive and minimally invasive sampling methods, and surgical techniques for diagnosis and staging. The fourth and final section looks at different therapeutic aspects, such as the role of surgery, chemotherapy, radiation therapy, a multidisciplinary approach according to disease stage, and other specifically targeted treatments, concluding with recommendations on the follow-up of lung cancer patients and surgical and endoscopic palliative interventions in advanced stages. Copyright © 2016 SEPAR. Published by Elsevier Espana. All rights reserved.

Lessons from Training and Supervision of Community Health Workers conducting non-invasive, population-based screening for Cardiovascular Disease in Four Communities in Low and Middle-Income Settings: Implications for Scaling Up

PubMed Central

Denman, Catalina A.; Montano, Carlos Mendoza; Gaziano, Thomas A.; Levitt, Naomi; Rivera-Andrade, Alvaro; Carrasco, Diana Munguía; Zulu, Jabu; Khanam, Masuma Akter; Puoane, Thandi

2015-01-01

Background Community health workers (CHWs) can screen for cardiovascular disease (CVD) risk as well as health professionals using a non-invasive screening tool (data unpublished). However, this demonstrated success does not guarantee effective scaling of the intervention to a population level. Objectives To report lessons learned from supervisors’ experiences monitoring CHWs and perceptions of other stakeholders regarding features for successful scaling of interventions which incorporate task-sharing with CHWs. Methods We conducted a qualitative analysis of in-depth interviews to explore stakeholder perceptions. Data was collected through interviews of 36 supervisors and administrators at non-governmental organizations contracted to deliver and manage primary care services using CHWs, directors and staff at the government health care clinics, and officials from the departments of health responsible for the implementation of health policy. Results CHWs are recognized for their value in offsetting severe human resource shortages and for their expert community knowledge. There is a lack of clear definitions for roles, expectations, and career paths for CHWs. Formal evaluation and supervisory systems are highly desirable but nonexistent or poorly implemented, creating a critical deficit for effective implementation of programs utilizing task sharing. There is acknowledgement of environmental challenges (e.g. safety) and systemic challenges (e.g. respect from trained health professionals) that hamper the effectiveness of CHWs. The government-community relationships presumed to form the basis of redesigned health care services have to be supported more explicitly and consistently on both sides in order to increase the acceptability of CHWs and their effectiveness. Conclusions The criteria critical for successful scaling of CHW led screening are consistent with evidence for scaling up communicable disease programs. Policy makers have to commit appropriate levels of resources and political will to ensure successful scaling of this intervention. PMID:25754565

Confocal fluorometer for diffusion tracking in 3D engineered tissue constructs

NASA Astrophysics Data System (ADS)

Daly, D.; Zilioli, A.; Tan, N.; Buttenschoen, K.; Chikkanna, B.; Reynolds, J.; Marsden, B.; Hughes, C.

2016-03-01

We present results of the development of a non-contacting instrument, called fScan, based on scanning confocal fluorometry for assessing the diffusion of materials through a tissue matrix. There are many areas in healthcare diagnostics and screening where it is now widely accepted that the need for new quantitative monitoring technologies is a major pinch point in patient diagnostics and in vitro testing. With the increasing need to interpret 3D responses this commonly involves the need to track the diffusion of compounds, pharma-active species and cells through a 3D matrix of tissue. Methods are available but to support the advances that are currently only promised, this monitoring needs to be real-time, non-invasive, and economical. At the moment commercial meters tend to be invasive and usually require a sample of the medium to be removed and processed prior to testing. This methodology clearly has a number of significant disadvantages. fScan combines a fiber based optical arrangement with a compact, free space optical front end that has been integrated so that the sample's diffusion can be measured without interference. This architecture is particularly important due to the "wet" nature of the samples. fScan is designed to measure constructs located within standard well plates and a 2-D motion stage locates the required sample with respect to the measurement system. Results are presented that show how the meter has been used to evaluate movements of samples through collagen constructs in situ without disturbing their kinetic characteristics. These kinetics were little understood prior to these measurements.

Mid-Infrared Photoacoustic Detection of Glucose in Human Skin: Towards Non-Invasive Diagnostics

PubMed Central

Kottmann, Jonas; Rey, Julien M.; Sigrist, Markus W.

2016-01-01

Diabetes mellitus is a widespread metabolic disease without cure. Great efforts are being made to develop a non-invasive monitoring of the blood glucose level. Various attempts have been made, including a number of non-optical approaches as well as optical techniques involving visible, near- and mid-infrared light. However, no true breakthrough has been achieved so far, i.e., there is no fully non-invasive monitoring device available. Here we present a new study based on mid-infrared spectroscopy and photoacoustic detection. We employ two setups, one with a fiber-coupled photoacoustic (PA) cell and a tunable quantum cascade laser (QCL), and a second setup with two QCLs at different wavelengths combined with PA detection. In both cases, the PA cells are in direct skin contact. The performance is tested with an oral glucose tolerance test. While the first setup often gives reasonable qualitative agreement with ordinary invasive blood glucose measurements, the dual-wavelength approach yields a considerably improved stability and an uncertainty of only ±30 mg/dL of the blood glucose concentration level at a confidence level of 90%. This result is achieved without advanced data treatment such as principal component analysis involving extended wavelength ranges. PMID:27735878

Lung cancer: diagnosis, treatment principles, and screening.

PubMed

Latimer, Kelly M; Mott, Timothy F

2015-02-15

Lung cancer is classified histologically into small cell and non-small cell lung cancers. The most common symptoms of lung cancer are cough, dyspnea, hemoptysis, and systemic symptoms such as weight loss and anorexia. High-risk patients who present with symptoms should undergo chest radiography. If a likely alternative diagnosis is not identified, computed tomography and possibly positron emission tomography should be performed. If suspicion for lung cancer is high, a diagnostic evaluation is warranted. The diagnostic evaluation has three simultaneous steps (tissue diagnosis, staging, and functional evaluation), all of which affect treatment planning and determination of prognosis. The least invasive method possible should be used. The diagnostic evaluation and treatment of a patient with lung cancer require a team of specialists, including a pulmonologist, medical oncologist, radiation oncologist, pathologist, radiologist, and thoracic surgeon. Non-small cell lung cancer specimens are tested for various mutations, which, if present, can be treated with new targeted molecular therapies. The family physician should remain involved in the patient's care to ensure that the values and wishes of the patient and family are considered and, if necessary, to coordinate end-of-life care. Early palliative care improves quality of life and may prolong survival. Family physicians should concentrate on early recognition of lung cancer, as well as prevention by encouraging tobacco cessation at every visit. The U.S. Preventive Services Task Force recommends lung cancer screening using low-dose computed tomography in high-risk patients. However, the American Academy of Family Physicians concludes that the evidence is insufficient to recommend for or against screening. Whether to screen high-risk patients should be a shared decision between the physician and patient.

Advanced breast cancer rates in the epoch of service screening: The 400,000 women cohort study from Italy.

PubMed

Puliti, Donella; Bucchi, Lauro; Mancini, Silvia; Paci, Eugenio; Baracco, Susanna; Campari, Cinzia; Canuti, Debora; Cirilli, Claudia; Collina, Natalina; Conti, Giovanni Maria; Di Felice, Enza; Falcini, Fabio; Michiara, Maria; Negri, Rossella; Ravaioli, Alessandra; Sassoli De' Bianchi, Priscilla; Serafini, Monica; Zorzi, Manuel; Caldarella, Adele; Cataliotti, Luigi; Zappa, Marco

2017-04-01

The objective of this study was to evaluate if mammography screening attendance is associated with a reduction in late-stage breast cancer incidence. The cohort included over 400,000 Italian women who were first invited to participate in regional screening programmes during the 1990s and were followed for breast cancer incidence for 13 years. We obtained individual data on their exposure to screening and correlated this with total and stage-specific breast cancer incidence. Socio-economic status and pre-screening incidence data were used to assess the presence of self-selection bias. Overall, screening attendance was associated with a 10% excess risk of in situ and invasive breast cancer (IRR = 1.10; 95% confidence interval (CI): 1.06-1.14), which dropped to 5% for invasive cancers only (IRR = 1.05; 95% CI: 1.01-1.09). There were significant reductions among attenders for specific cancer stages; we observed a 39% reduction for T2 or larger (IRR = 0.61; 95% CI: 0.57-0.66), 19% for node positives (IRR = 0.81; 95% CI: 0.76-0.86) and 28% for stage II and higher (IRR = 0.72; 95% CI: 0.68-0.76). Our data suggest that the presence of self-selection bias is limited and, overall, invited women experienced a 17% reduction of advanced cancers compared with pre-screening rates. Comparing attenders' and non-attenders' stage-specific breast cancer incidence, we have estimated that screening attendance is associated with a reduction of nearly 30% for stages II+. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Comparison of Parallel and Integrated Models for Implementation of Routine HIV Screening in a Large, Urban Emergency Department.

PubMed

Hankin, Abigail; Freiman, Heather; Copeland, Brittney; Travis, Natasha; Shah, Bijal

2016-01-01

This study compared two approaches for implementation of non-targeted HIV screening in the emergency department (ED): (1) designated HIV counselors screening in parallel with ED care and (2) nurse-based screening integrated into patient triage. A retrospective analysis was performed to compare parallel and integrated screening models using data from the first 12 months of each program. Data for the parallel screening model were extracted from information collected by HIV test counselors and the electronic medical record (EMR). Integrated screening model data were extracted from the EMR and supplemented by data collected by HIV social workers during patient interaction. For both programs, data included demographics, HIV test offer, test acceptance or declination, and test result. A Z-test between two proportions was performed to compare screening frequencies and results. During the first 12 months of parallel screening, approximately 120,000 visits were made to the ED, with 3,816 (3%) HIV tests administered and 65 (2%) new diagnoses of HIV infection. During the first 12 months of integrated screening, 111,738 patients were triaged in the ED, with 16,329 (15%) patients tested and 190 (1%) new diagnoses. Integrated screening resulted in an increased frequency of HIV screening compared with parallel screening (0.15 tests per ED patient visit vs. 0.03 tests per ED patient visit, p<0.001) and an increase in the absolute number of new diagnoses (190 vs. 65), representing a slight decrease in the proportion of new diagnoses (1% vs. 2%, p=0.007). Non-targeted, integrated HIV screening, with test offer and order by ED nurses during patient triage, is feasible and resulted in an increased frequency of HIV screening and a threefold increase in the absolute number of newly identified HIV-positive patients.

Multi-modality image registration for effective thermographic fever screening

NASA Astrophysics Data System (ADS)

Dwith, C. Y. N.; Ghassemi, Pejhman; Pfefer, Joshua; Casamento, Jon; Wang, Quanzeng

2017-02-01

Fever screening based on infrared thermographs (IRTs) is a viable mass screening approach during infectious disease pandemics, such as Ebola and Severe Acute Respiratory Syndrome (SARS), for temperature monitoring in public places like hospitals and airports. IRTs have been found to be powerful, quick and non-invasive methods for detecting elevated temperatures. Moreover, regions medially adjacent to the inner canthi (called the canthi regions in this paper) are preferred sites for fever screening. Accurate localization of the canthi regions can be achieved through multi-modality registration of infrared (IR) and white-light images. Here we propose a registration method through a coarse-fine registration strategy using different registration models based on landmarks and edge detection on eye contours. We have evaluated the registration accuracy to be within +/- 2.7 mm, which enables accurate localization of the canthi regions.

A technology roadmap of smart biosensors from conventional glucose monitoring systems.

PubMed

Shende, Pravin; Sahu, Pratiksha; Gaud, Ram

2017-06-01

The objective of this review article is to focus on technology roadmap of smart biosensors from a conventional glucose monitoring system. The estimation of glucose with commercially available devices involves analysis of blood samples that are obtained by pricking finger or extracting blood from the forearm. Since pain and discomfort are associated with invasive methods, the non-invasive measurement techniques have been investigated. The non-invasive methods show advantages like non-exposure to sharp objects such as needles and syringes, due to which there is an increase in testing frequency, improved control of glucose concentration and absence of pain and biohazard materials. This review study is aimed to describe recent invasive techniques and major noninvasive techniques, viz. biosensors, optical techniques and sensor-embedded contact lenses for glucose estimation.

Cervical cancer screening: A never-ending developing program

PubMed Central

Comparetto, Ciro; Borruto, Franco

2015-01-01

With the term “oncological screening”, we define the overall performances made to detect early onset of tumors. These tests are conducted on a population that does not have any signs or symptoms related to a neoplasm. The whole population above a certain age, only one sex, only subjects with a high risk of developing cancer due to genetic, professional, discretionary reasons may be involved. Screening campaigns should be associated, when risk factors that can be avoided are known, with campaigns for the prevention of cancer by means of suitable behavior. The goal of cancer screening cannot however be limited to the diagnosis of a greater number of neoplasms. Screening will be useful only if it leads to a reduction in overall mortality or at least in mortality related to the tumor. Screening should then allow the diagnosis of the disease at a stage when there is a possibility of healing, possibility that is instead difficult when the disease is diagnosed at the appearance of signs or symptoms. This is the reason why not all campaigns of cancer screening have the same effectiveness. In Italy, every year there are about 150000 deaths due to cancer. Some of these tumors can be cured with a very high percentage of success if diagnosed in time. Cervical cancer can be diagnosed with non-invasive tests. The screening test used all over the world is Papanicolaou (Pap) test. This test may be carried out over the entire healthy population potentially exposed to the risk of contracting cancer. Public health has begun the screening campaigns in the hope of saving many of the approximately 270000 new cases of cancer reported each year. Screening is done following protocols that guarantee quality at the national level: these protocols are subject to change over time to reflect new realities or to correct any errors in the system. A simplified sketch of a possible route of cancer screening is as follows: (1) after selecting the target population, for example all women between 25 and 64 years (in the case of monitoring of cervical cancer), an invitation letter with the date and time of the appointment, planned according to the acceptance capacity of the hospital, is sent to all individuals; (2) an examination, which depending on the individual and the type of cancer to be monitored, for example, can be a Pap smear, is performed and the patient can go home; (3) once available the results of examinations, if negative, they shall be communicated to the person concerned that will be notified by mail and will be recalled for a second test at a few years of distance, in the case of non-negativity, instead, the patient is contacted by telephone and informed of the need to carry out further examinations: it is said that the patient is in the “phase two” of the screening pathway; (4) in phase two, reached by only a small portion of the interested parties (usually less than 3%-5%), more in-depth tests are carried out, which, depending on the individual and the type of cancer, can be: cytological and colposcopic examinations, the removal of a fragment of tissue (biopsy) and subsequent histological examination, additional tests such as ultrasound, radiography, or others such as computerized tomography, magnetic resonance imaging, positron emission tomography, etc., in case of negativity, the concerned person will be called for new control tests at a a few years of distance, in case of non-negativity, it will be proposed instead an oncologic therapeutic plan and/or surgery to treat the diagnosed tumor; and (5) once the treatment plan is completed, the individual enters the follow-up protocol, which is monitored over time to see if the tumor has been completely removed or if instead it is still developing. Cervical cancer is undoubtedly the most successful example of a cancer screening campaign. Paradoxically, its effectiveness is one of the strongest reasons to criticize the usefulness of vaccination against human papillomavirus (HPV) in countries where the screening service with Pap test is organized in an efficient manner. Cervical cancer screening protocols are directed to sexually active women aged 25-64 years: they provide the Pap test performed by examining under a microscope or by staining with a specific “thin prep” the material taken from the cervix with a small spatula and a brush. It is recommended to repeat the test every two or three years. It is important to emphasize that women vaccinated against HPV must continue the screening with Pap test. Although some screening programs (e.g., Pap smears) have had remarkable success in reducing mortality from a specific cancer, any kind of screening is free from inherent limitations. The screening methods are in fact applied to large parts of the apparently healthy population. In particular, the limits for certain cancers may be as obvious as to prohibit the introduction of an organized screening program. Potential limitations of organized screenings are basically of two types: organizational and medical. The limits of organizational type relate to the ability of a program to recruit the whole target population. Although well organized, a screening program will hardly be able to exceed a coverage of 70%-80% of the target population, and in fact the results of the current programs are often much smaller. The limits of medical type are represented by the possibility of reducing the overall mortality, or specific mortality, using a specific screening campaign. PMID:26244153

Non-invasive imaging of oxygen extraction fraction in adults with sickle cell anaemia.

PubMed

Jordan, Lori C; Gindville, Melissa C; Scott, Allison O; Juttukonda, Meher R; Strother, Megan K; Kassim, Adetola A; Chen, Sheau-Chiann; Lu, Hanzhang; Pruthi, Sumit; Shyr, Yu; Donahue, Manus J

2016-03-01

Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2-56.8 ml/100 g/min; oxygen extraction fraction = 0.39-0.50) relative to controls (interquartile range cerebral blood flow = 40.8-46.3 ml/100 g/min; oxygen extraction fraction = 0.33-0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the premise that magnetic resonance imaging-based assessment of elevated oxygen extraction fraction might be a viable screening tool for evaluating stroke risk in adults with sickle cell anaemia. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Non-invasive imaging of oxygen extraction fraction in adults with sickle cell anaemia

PubMed Central

Gindville, Melissa C.; Scott, Allison O.; Juttukonda, Meher R.; Strother, Megan K.; Kassim, Adetola A.; Chen, Sheau-Chiann; Lu, Hanzhang; Pruthi, Sumit; Shyr, Yu; Donahue, Manus J.

2016-01-01

Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2–56.8 ml/100 g/min; oxygen extraction fraction = 0.39–0.50) relative to controls (interquartile range cerebral blood flow = 40.8–46.3 ml/100 g/min; oxygen extraction fraction = 0.33–0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the premise that magnetic resonance imaging-based assessment of elevated oxygen extraction fraction might be a viable screening tool for evaluating stroke risk in adults with sickle cell anaemia. PMID:26823369

Cervical Cancer Screening Preferences Among Trans-Masculine Individuals: Patient-Collected Human Papillomavirus Vaginal Swabs Versus Provider-Administered Pap Tests.

PubMed

McDowell, Michal; Pardee, Dana J; Peitzmeier, Sarah; Reisner, Sari L; Agénor, Madina; Alizaga, Natalie; Bernstein, Ida; Potter, Jennifer

2017-08-01

Trans-masculine (TM, i.e., persons who have a masculine spectrum gender identity, but were assigned female sex at birth) individuals face disparities in cervical cancer screening rates compared to cisgender women. Some unique barriers to screening in this population are specific to Pap tests. Introduction of self-collected frontal (i.e., vaginal) swabs for human papillomavirus (HPV) testing as a screening strategy may obviate these barriers. This study elucidates cervical cancer screening preferences among TM individuals. TM individuals participated in in-depth interviews (n = 31) and online surveys (n = 32) to explore perceptions and experiences regarding cervical cancer screening, including the acceptability of self-collected frontal HPV swabs for cervical cancer screening compared to provider-administered Pap tests. Provider-collected frontal HPV swab acceptability was also explored. Most TM individuals (94% in-person and 91% online participants) preferred either the self- or provider-collected frontal HPV swab to the Pap test. Participants perceived self- and provider-collected frontal HPV swabs to be less invasive, provoke less gender discordance, and promote a greater sense of agency compared to Pap tests. However, some participants expressed concern about HPV swab accuracy and, regarding the self-collected swab, discomfort about the need to engage with genitals they may not want to acknowledge. Individuals who reported positive provider relationships found Pap tests and provider-collected frontal swabs more acceptable than those who did not. Frontal HPV swabs have the potential to promote regular cervical cancer screening among TM individuals and to narrow screening disparities. Work is ongoing to establish swab accuracy and develop shared decision-making tools.

Genomic futures of prenatal screening: ethical reflection.

PubMed

Dondorp, W J; Page-Christiaens, G C M L; de Wert, G M W R

2016-05-01

The practice of prenatal screening is undergoing important changes as a result of the introduction of genomic testing technologies at different stages of the screening trajectory. It is expected that eventually it will become possible to routinely obtain a comprehensive 'genome scan' of all fetuses. Although this will still take several years, there are clear continuities between present developments and this future scenario. As this review shows, behind the still limited scope of screening for common aneuploidies, a rapid widening of the range of conditions tested for is already taking shape at the invasive testing stage. But the continuities are not just technical; they are also ethical. If screening for Down's syndrome is a matter of providing autonomous reproductive choice, then why would providing the choice to have a full fetal genome scan be something entirely different? There is a clear need for a sustainable normative framework that will have to answer three challenges: the indeterminateness of the autonomy paradigm, the need to acknowledge the future child as an interested stakeholder, and the prospect of broad-scope genomic prenatal screening with a double purpose: autonomy and prevention. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Indications, Utility and Appropriateness of Echocardiography in Outpatient Cardiology

PubMed Central

Orsini, Enrico; Antoncecchi, Ettore; Carbone, Vincenzo; Dato, Achille; Monducci, Igor; Nistri, Stefano; Zito, Giovanni Battista

2013-01-01

Objective: Respect of “appropriateness” is considered an essential requirement, both on the clinical and the economic profile, and also as it helps to shorten the waiting list. However, only a few studies have dealt with the control of appropriateness in clinical practice, and most of them have focused only on hospital admissions and invasive procedures. Materials and Methods: INDICARD-out is a prospective, multicenter study carried out by A.R.C.A. (Associazioni Regionali Cardiologi Ambulatoriali) cardiologists from 13 Italian Regions, providing information on indications, utility and appropriateness of echocardiography in outpatient cardiology. Results: A total of 2110 prescriptions for echocardiogram were evaluated. Hypertension (23%) and the screening of asymptomatic subjects (17%) by far were the most frequent indications to echocardiography. Overall, 54% of the tests resulted appropriate, 30% were of uncertain appropriateness and 16% were inappropriate. Besides, 31% of the echocardiograms were not useful, and 28% were non pertinent for patient management. The vast majority of prescriptions (72%) came from non-cardiologist physicians (54% from general practitioners). The echocardiograms prescribed by cardiologists were significantly more appropriate, more useful and more pertinent than the tests prescribed by non-cardiologists. Conclusions: The appropriateness, utility and pertinence of the echocardiography are still suboptimal in practice cardiology, especially when indicated by non-cardiologists. The cardiologist, from mere executor of tests prescribed and managed by other physicians, should gain the role of the clinician who takes care of all the cardiologic needs of the patient community. PMID:28465880

Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances.

PubMed

Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

2016-02-07

Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments.

Trial by Dutch laboratories for evaluation of non‐invasive prenatal testing. Part II—women's perspectives†

PubMed Central

van Schendel, Rachèl V.; Page‐Christiaens, G. C. (Lieve); Beulen, Lean; Bilardo, Catia M.; de Boer, Marjon A.; Coumans, Audrey B. C.; Faas, Brigitte H.; van Langen, Irene M.; Lichtenbelt, Klaske D.; van Maarle, Merel C.; Macville, Merryn V. E.; Oepkes, Dick; Pajkrt, Eva

2016-01-01

Abstract Objective To evaluate preferences and decision‐making among high‐risk pregnant women offered a choice between Non‐Invasive Prenatal Testing (NIPT), invasive testing or no further testing. Methods Nationwide implementation study (TRIDENT) offering NIPT as contingent screening test for women at increased risk for fetal aneuploidy based on first‐trimester combined testing (>1:200) or medical history. A questionnaire was completed after counseling assessing knowledge, attitudes and participation following the Multidimensional Measure of Informed Choice. Results A total of 1091/1253 (87%) women completed the questionnaire. Of these, 1053 (96.5%) underwent NIPT, 37 (3.4%) invasive testing and 1 (0.1%) declined testing. 91.7% preferred NIPT because of test safety. Overall, 77.9% made an informed choice, 89.8% had sufficient knowledge and 90.5% had positive attitudes towards NIPT. Women with intermediate (odds ratio (OR) = 3.51[1.70–7.22], p < 0.001) or high educational level (OR = 4.36[2.22–8.54], p < 0.001) and women with adequate health literacy (OR = 2.60[1.36–4.95], p = 0.004) were more likely to make an informed choice. Informed choice was associated with less decisional conflict and less anxiety (p < 0.001). Intention to terminate the pregnancy for Down syndrome was higher among women undergoing invasive testing (86.5%) compared to those undergoing NIPT (58.4%) (p < 0.001). Conclusions The majority of women had sufficient knowledge and made an informed choice. Continuous attention for counseling is required, especially for low‐educated and less health‐literate women. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. PMID:27739584

Smartphone-based fluorescence spectroscopy device aiding in preliminary skin screening

NASA Astrophysics Data System (ADS)

Sahoo, Aparajita; Wahi, Akshat; Das, Anshuman

2018-02-01

Preliminary diagnosis of closely resembling skin conditions can be highly subjective for dermatologists. In ambiguous cases, it often leads to performing invasive procedures like biopsies. Different skin conditions, however, have varying concentrations of fluorophores (like collagen, NADH) and chromophores (like melanin, hemoglobin) which can alter their fluorescence spectra. We demonstrate a handheld, portable, smartphone-based spectrometer that leverages these alterations in skin autofluorescence spectra for rapid screening of skin conditions. This methodology involves excitation of affected skin areas with ultraviolet (UV-A) 385 nm light, capturing the generated fluorescence spectra and sending the data wirelessly to a companion mobile application for data storage, analysis and visualization. By collecting the fluorescence spectral signals from healthy and unhealthy skin conditions, we establish that the signals collected using this portable device can be used to develop a classification method to help in differentially diagnosing these conditions. It shows promise as a useful skin screening tool for both dermatologists and primary health care workers. This device can enable quick, non-invasive and a more objective preliminary examination. We envision the device to be especially useful in primary healthcare centers of developing countries where availability of dermatologists is limited.

[Antibiotic resistance analysis of Streptococcus pneumoniae isolates from the hospitalized children in Shanxi Children's Hospital from 2012 to 2014].

PubMed

Ge, L L; Han, Z Y; Liu, A H; Zhu, L; Meng, J H

2017-02-02

Objective: To investigate the antibiotic resistance status of Streptococcus pneumoniae isolates from hospitalized children in Shanxi Children's Hospital. Method: E-test and Kirby-Bauer methods were applied to determine drug sensitivity of the isolates collected from the body fluid specimens of hospitalized children in Shanxi Children's Hospital from January 2012 to December 2014. The antimicrobial sensitivity and minimum inhibitory concentration (MIC) of Streptococcus pneumoniae to the conventional antibiotics were analyzed, in order to compare the annual trends of non-invasive isolates, while the differentiation of sensitivity from specimens. The comparison of rates was performed by Chi-squared test and Fisher's exact test. Result: A total of 671 isolates of streptococcus pneumoniae were obtained, which could be divided as non-invasive isolates(607), invasive isolates from non-cerebrospinal fluid(non-CSF)(40) and invasive isolates from cerebrospinal fluid(CSF)(24). The antimicrobial sensitivity(isolates(%)) of the 671 isolates were respectively vancomycin 671(100.0%), linezolid 671(100.0%), levofloxacin 665(99.1%), penicillin 595(88.7%), ceftriaxone 516(76.9%), cefotaxime 512(76.3%), sulfamethoxazole-trimethoprin(SMZ-TMP) 103(15.4%), clindamycin 28(4.2%), tetracycline 26(3.9%), erythromycin 12(1.8%). From 2012 to 2014, the susceptibility rates of non-invasive isolates to penicillin every year were 95.0%(96/101), 97.3%(110/113), 87.3%(343/393), respectively, and there was significant difference among the three years(χ(2)=13.266, P <0.05), and the values of MIC(50, )MIC(90) and the maximum values of MIC(mg/L) of penicillin were 0.064, 2.000, 6.000 in 2012, which grew up to 1.000, 3.000, 16.000 in 2014. There was no significant difference in the susceptibility rate of non-invasive isolates to ceftriaxone and cefotaxime during these three years, (χ(2)=1.172, 1.198, both P >0.05). On the other hand, the values of MIC(50, )MIC(90) and the maximum value of MIC(mg/L) of ceftriaxone and cefotaxime both increased from 0.500, 2.000, 8.000 in 2012 to 0.750, 4.000, 32.000 in 2014. There was no significant difference in the susceptibility rate of non-invasive isolates to the rest antibiotic. Based on the same examining standard of CSF, the antimicrobial sensitivity(isolates(%)) of the non-invasive isolates to ceftriaxone, cefotaxime, SMZ-TMP were respectively 281(46.3%), 278(45.8%), 78(12.9%), were significantly lower than the susceptibility rate of the invasive isolates from non-CSF (28(70%), 28(70%), 14(35%), χ(2)=8.453, 8.817, 15.094, all P <0.012 5), and lower than the invasive isolates from CSF (18(75%), 18(75%), χ(2)=7.631, 7.905, P <0.012 5; 11(45.8%), P =0.001). The sensitivity of the isolates to the rest antibiotics were similar( P >0.05). Conclusion: More than 95.0% strains of the streptococcus pneumoniae isolates from the hospitalized children in Shanxi Children's Hospital were sensitive to vancomycin, linezolid, levofloxacin, and the susceptibility rate of penicillin, ceftriaxone, cefotaxime were 88.7%, 76.9%, 76.3%. However, less than 20.0% of streptococcus pneumoniae were sensitive to erythromycin, clindamycin, SMZ-TMP and tetracycline. The susceptibility rate of penicillin of non-invasive Streptococcus pneumoniae declined by these years, and the differences to ceftriaxone and cefotaxime can be neglected, but the values of MIC(50, )MIC(90) and the maximum value of MIC of all were linearly rising. The susceptibility rate of antibiotics to ceftriaxone and cefotaxime of the non-invasive isolates was lower than the invasive isolates.

Stroop Color-Word Test: A Screening Measure of Selective Attention to Differentiate LD From Non LD Children.

ERIC Educational Resources Information Center

Lazarus, Philip J.; And Others

1984-01-01

Used the Stroop Color-Word Test to measure selective attention in learning disabled (N=45) and nonLD (N=50) children. Results indicated that LD children have a significant weakness in the process of selective attention compared to the nonLD children. Findings suggested that the Stroop is an effective screening measure. (JAC)

Non-invasive health status detection system using Gabor filters based on facial block texture features.

PubMed

Shu, Ting; Zhang, Bob

2015-04-01

Blood tests allow doctors to check for certain diseases and conditions. However, using a syringe to extract the blood can be deemed invasive, slightly painful, and its analysis time consuming. In this paper, we propose a new non-invasive system to detect the health status (Healthy or Diseased) of an individual based on facial block texture features extracted using the Gabor filter. Our system first uses a non-invasive capture device to collect facial images. Next, four facial blocks are located on these images to represent them. Afterwards, each facial block is convolved with a Gabor filter bank to calculate its texture value. Classification is finally performed using K-Nearest Neighbor and Support Vector Machines via a Library for Support Vector Machines (with four kernel functions). The system was tested on a dataset consisting of 100 Healthy and 100 Diseased (with 13 forms of illnesses) samples. Experimental results show that the proposed system can detect the health status with an accuracy of 93 %, a sensitivity of 94 %, a specificity of 92 %, using a combination of the Gabor filters and facial blocks.

Effect of enhanced information, values clarification, and removal of financial barriers on use of prenatal genetic testing: a randomized clinical trial.

PubMed

Kuppermann, Miriam; Pena, Sherri; Bishop, Judith T; Nakagawa, Sanae; Gregorich, Steven E; Sit, Anita; Vargas, Juan; Caughey, Aaron B; Sykes, Susan; Pierce, Lasha; Norton, Mary E

2014-09-24

Prenatal genetic testing guidelines recommend providing patients with detailed information to allow informed, preference-based screening and diagnostic testing decisions. The effect of implementing these guidelines is not well understood. To analyze the effect of a decision-support guide and elimination of financial barriers to testing on use of prenatal genetic testing and decision making among pregnant women of varying literacy and numeracy levels. Randomized trial conducted from 2010-2013 at prenatal clinics at 3 county hospitals, 1 community clinic, 1 academic center, and 3 medical centers of an integrated health care delivery system in the San Francisco Bay area. Participants were English- or Spanish-speaking women who had not yet undergone screening or diagnostic testing and remained pregnant at 11 weeks' gestation (n = 710). A computerized, interactive decision-support guide and access to prenatal testing with no out-of-pocket expense (n = 357) or usual care as per current guidelines (n = 353). The primary outcome was invasive diagnostic test use, obtained via medical record review. Secondary outcomes included testing strategy undergone, and knowledge about testing, risk comprehension, and decisional conflict and regret at 24 to 36 weeks' gestation. Women randomized to the intervention group, compared with those randomized to the control group, were less likely to have invasive diagnostic testing (5.9% vs 12.3%; odds ratio [OR], 0.45 [95% CI, 0.25-0.80]) and more likely to forgo testing altogether (25.6% vs 20.4%; OR, 3.30 [95% CI, 1.43-7.64], reference group screening followed by invasive testing). Women randomized to the intervention group also had higher knowledge scores (9.4 vs 8.6 on a 15-point scale; mean group difference, 0.82 [95% CI, 0.34-1.31]) and were more likely to correctly estimate the amniocentesis-related miscarriage risk (73.8% vs 59.0%; OR, 1.95 [95% CI, 1.39-2.75]) and their estimated age-adjusted chance of carrying a fetus with trisomy 21 (58.7% vs 46.1%; OR, 1.66 [95% CI, 1.22-2.28]). Significant differences did not emerge in decisional conflict or regret. Full implementation of prenatal testing guidelines using a computerized, interactive decision-support guide in the absence of financial barriers to testing resulted in less test use and more informed choices. If validated in additional populations, this approach may result in more informed and preference-based prenatal testing decision making and fewer women undergoing testing. clinicaltrials.gov Identifier: NCT00505596.

An Overview on Prenatal Screening for Chromosomal Aberrations.

PubMed

Hixson, Lucas; Goel, Srishti; Schuber, Paul; Faltas, Vanessa; Lee, Jessica; Narayakkadan, Anjali; Leung, Ho; Osborne, Jim

2015-10-01

This article is a review of current and emerging methods used for prenatal detection of chromosomal aneuploidies. Chromosomal anomalies in the developing fetus can occur in any pregnancy and lead to death prior to or shortly after birth or to costly lifelong disabilities. Early detection of fetal chromosomal aneuploidies, an atypical number of certain chromosomes, can help parents evaluate their pregnancy options. Current diagnostic methods include maternal serum sampling or nuchal translucency testing, which are minimally invasive diagnostics, but lack sensitivity and specificity. The gold standard, karyotyping, requires amniocentesis or chorionic villus sampling, which are highly invasive and can cause abortions. In addition, many of these methods have long turnaround times, which can cause anxiety in mothers. Next-generation sequencing of fetal DNA in maternal blood enables minimally invasive, sensitive, and reasonably rapid analysis of fetal chromosomal anomalies and can be of clinical utility to parents. This review covers traditional methods and next-generation sequencing techniques for diagnosing aneuploidies in terms of clinical utility, technological characteristics, and market potential. © 2015 Society for Laboratory Automation and Screening.

De Novo Design of Skin-Penetrating Peptides for Enhanced Transdermal Delivery of Peptide Drugs.

PubMed

Menegatti, Stefano; Zakrewsky, Michael; Kumar, Sunny; De Oliveira, Joshua Sanchez; Muraski, John A; Mitragotri, Samir

2016-03-09

Skin-penetrating peptides (SPPs) are attracting increasing attention as a non-invasive strategy for transdermal delivery of therapeutics. The identification of SPP sequences, however, currently performed by experimental screening of peptide libraries, is very laborious. Recent studies have shown that, to be effective enhancers, SPPs must possess affinity for both skin keratin and the drug of interest. We therefore developed a computational process for generating and screening virtual libraries of disulfide-cyclic peptides against keratin and cyclosporine A (CsA) to identify SPPs capable of enhancing transdermal CsA delivery. The selected sequences were experimentally tested and found to bind both CsA and keratin, as determined by mass spectrometry and affinity chromatography, and enhance transdermal permeation of CsA. Four heptameric sequences that emerged as leading candidates (ACSATLQHSCG, ACSLTVNWNCG, ACTSTGRNACG, and ACSASTNHNCG) were tested and yielded CsA permeation on par with previously identified SPP SPACE (TM) . An octameric peptide (ACNAHQARSTCG) yielded significantly higher delivery of CsA compared to heptameric SPPs. The safety profile of the selected sequences was also validated by incubation with skin keratinocytes. This method thus represents an effective procedure for the de novo design of skin-penetrating peptides for the delivery of desired therapeutic or cosmetic agents. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Outcomes of non-invasive diagnostic modalities for the detection of coronary artery disease: network meta-analysis of diagnostic randomised controlled trials

PubMed Central

Siontis, George CM; Mavridis, Dimitris; Greenwood, John P; Coles, Bernadette; Nikolakopoulou, Adriani; Jüni, Peter; Salanti, Georgia

2018-01-01

Abstract Objective To evaluate differences in downstream testing, coronary revascularisation, and clinical outcomes following non-invasive diagnostic modalities used to detect coronary artery disease. Design Systematic review and network meta-analysis. Data sources Medline, Medline in process, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, SCOPUS, WHO International Clinical Trials Registry Platform, and Clinicaltrials.gov. Eligibility criteria for selecting studies Diagnostic randomised controlled trials comparing non-invasive diagnostic modalities in patients presenting with symptoms suggestive of low risk acute coronary syndrome or stable coronary artery disease. Data synthesis A random effects network meta-analysis synthesised available evidence from trials evaluating the effect of non-invasive diagnostic modalities on downstream testing and patient oriented outcomes in patients with suspected coronary artery disease. Modalities included exercise electrocardiograms, stress echocardiography, single photon emission computed tomography-myocardial perfusion imaging, real time myocardial contrast echocardiography, coronary computed tomographic angiography, and cardiovascular magnetic resonance. Unpublished outcome data were obtained from 11 trials. Results 18 trials of patients with low risk acute coronary syndrome (n=11 329) and 12 trials of those with suspected stable coronary artery disease (n=22 062) were included. Among patients with low risk acute coronary syndrome, stress echocardiography, cardiovascular magnetic resonance, and exercise electrocardiograms resulted in fewer invasive referrals for coronary angiography than coronary computed tomographic angiography (odds ratio 0.28 (95% confidence interval 0.14 to 0.57), 0.32 (0.15 to 0.71), and 0.53 (0.28 to 1.00), respectively). There was no effect on the subsequent risk of myocardial infarction, but estimates were imprecise. Heterogeneity and inconsistency were low. In patients with suspected stable coronary artery disease, an initial diagnostic strategy of stress echocardiography or single photon emission computed tomography-myocardial perfusion imaging resulted in fewer downstream tests than coronary computed tomographic angiography (0.24 (0.08 to 0.74) and 0.57 (0.37 to 0.87), respectively). However, exercise electrocardiograms yielded the highest downstream testing rate. Estimates for death and myocardial infarction were imprecise without clear discrimination between strategies. Conclusions For patients with low risk acute coronary syndrome, an initial diagnostic strategy of stress echocardiography or cardiovascular magnetic resonance is associated with fewer referrals for invasive coronary angiography and revascularisation procedures than non-invasive anatomical testing, without apparent impact on the future risk of myocardial infarction. For suspected stable coronary artery disease, there was no clear discrimination between diagnostic strategies regarding the subsequent need for invasive coronary angiography, and differences in the risk of myocardial infarction cannot be ruled out. Systematic review registration PROSPERO registry no CRD42016049442. PMID:29467161

Polygenic susceptibility to testicular cancer: implications for personalised health care.

PubMed

Litchfield, Kevin; Mitchell, Jonathan S; Shipley, Janet; Huddart, Robert; Rajpert-De Meyts, Ewa; Skakkebæk, Niels E; Houlston, Richard S; Turnbull, Clare

2015-11-17

The increasing incidence of testicular germ cell tumour (TGCT) combined with its strong heritable basis suggests that stratified screening for the early detection of TGCT may be clinically useful. We modelled the efficiency of such a personalised screening approach, based on genetic risk profiling in combination with other diagnostic tools. We compared the number of cases potentially detectable in the population under a number of screening models. The polygenic risk scoring (PRS) model was assumed to have a log-normal relative risk distribution across the 19 currently known TGCT susceptibility variants. The diagnostic performance of testicular biopsy and non-invasive semen analysis was also assessed, within a simulated combined screening programme. The area under the curve for the TGCT PRS model was 0.72 with individuals in the top 1% of the PRS having a nine-fold increased TGCT risk compared with the population median. Results from population-screening simulations only achieved a maximal positive predictive value (PPV) of 60%, highlighting broader clinical factors that challenge such strategies, not least the rare nature of TGCT. In terms of future improvements, heritability estimates suggest that a significant number of additional genetic risk factors for TGCT remain to be discovered, identification of which would potentially yield improvement of the PPV to 80-90%. While personalised screening models may offer enhanced TGCT risk discrimination, presently the case for population-level testing is not compelling. However, future advances, such as more routine generation of whole genome data is likely to alter the landscape. More targeted screening programs may plausibly then offer clinical benefit, particularly given the significant survivorship issues associated with the successful treatment of TGCT.

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): a mixed-methods study to assess the feasibility of a future randomised controlled trial of invasive urodynamic testing prior to surgery for stress urinary incontinence in women.

PubMed

Hilton, Paul; Armstrong, Natalie; Brennand, Catherine; Howel, Denise; Shen, Jing; Bryant, Andrew; Tincello, Douglas G; Lucas, Malcolm G; Buckley, Brian S; Chapple, Christopher R; Homer, Tara; Vale, Luke; McColl, Elaine

2015-02-01

The position of invasive urodynamic testing in the diagnostic pathway for urinary incontinence (UI) is unclear. Systematic reviews have called for further trials evaluating clinical utility, although a preliminary feasibility study was considered appropriate. To inform the decision whether or not to proceed to a definitive randomised trial of invasive urodynamic testing compared with clinical assessment with non-invasive tests, prior to surgery in women with stress UI (SUI) or stress predominant mixed UI (MUI). A mixed-methods study comprising a pragmatic multicentre randomised pilot trial; economic evaluation; survey of clinicians' views about invasive urodynamic testing; qualitative interviews with clinicians and trial participants. Urogynaecology, female urology and general gynaecology units in Newcastle, Leicester, Swansea, Sheffield, Northumberland, Gateshead and South Tees. Trial recruits were women with SUI or stress predominant MUI who were considering surgery after unsuccessful conservative treatment. Relevant clinicians completed two online surveys. Subsets of survey respondents and trial participants took part in separate qualitative interview studies. Pilot trial participants were randomised to undergo clinical assessment with non-invasive tests (control arm); or assessment as controls, plus invasive urodynamic testing (intervention arm). Confirmation that units can identify and recruit eligible women; acceptability of investigation strategies and data collection tools; acquisition of outcome data to determine the sample size for a definitive trial. The proposed primary outcome for the definitive trial was International Consultation on Incontinence Modular Questionnaire (ICIQ) Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) (total score) 6 months after surgery or the start of non-surgical treatment; secondary outcomes included: ICIQ-FLUTS (subscales); ICIQ Urinary Incontinence Short Form; ICIQ Lower Urinary Tract Symptoms Quality of Life; Urogenital Distress Inventory; EuroQol-5D; costs, quality-adjusted life-years (QALYs) and incremental cost per QALY, Short Form 12; 3-day bladder diary. Of 284 eligible women, 222 (78%) were recruited; 165/219 (75%) returned questionnaires at baseline and 125/200 (63%) who were sent questionnaires at follow-up. There were few missing data items in returned questionnaires, with individual outcome scales calculable for 81%-94%. Most women underwent surgery; management plans were changed in 19 (19%) participants following invasive urodynamic testing. Participant Costs Questionnaires were returned by 53% 6 months after treatment; complete data to undertake cost-utility analysis were available in 27% (intervention) and 47% (control). While insufficient to recommend changes in practice, the results suggest further research would be valuable. All clinicians responding to the survey had access to invasive urodynamic testing, and most saw it as essential prior to surgery in women with SUI with or without other symptoms; nevertheless, 70% considered the research question underlying INVESTIGATE important and most were willing to randomise patients in a definitive trial. Participants interviewed were positive about the trial and associated documentation; the desire of some women to avoid invasive urodynamic testing contrasted with opinions expressed by clinicians through both survey and interview responses. All elements of a definitive trial and economic evaluation were rehearsed; several areas for protocol modification were identified. Such a trial would require to 400-900 participants, depending on the difference in primary outcome sought. A definitive trial of invasive urodynamic testing versus clinical assessment prior to surgery for SUI or stress predominant MUI should be undertaken. Current Controlled Trials ISRCTN71327395. The National Institute for Health Research Health Technology Assessment programme.

A superhydrophobic cone to facilitate the xenomonitoring of filarial parasites, malaria, and trypanosomes using mosquito excreta/feces.

PubMed

Cook, Darren A N; Pilotte, Nils; Minetti, Corrado; Williams, Steven A; Reimer, Lisa J

2017-11-06

Background: Molecular xenomonitoring (MX), the testing of insect vectors for the presence of human pathogens, has the potential to provide a non-invasive and cost-effective method for monitoring the prevalence of disease within a community. Current MX methods require the capture and processing of large numbers of mosquitoes, particularly in areas of low endemicity, increasing the time, cost and labour required. Screening the excreta/feces (E/F) released from mosquitoes, rather than whole carcasses, improves the throughput by removing the need to discriminate vector species since non-vectors release ingested pathogens in E/F. It also enables larger numbers of mosquitoes to be processed per pool. However, this new screening approach requires a method of efficiently collecting E/F. Methods: We developed a cone with a superhydrophobic surface to allow for the efficient collection of E/F. Using mosquitoes exposed to either Plasmodium falciparum , Brugia malayi or Trypanosoma brucei brucei, we tested the performance of the superhydrophobic cone alongside two other collection methods. Results: All collection methods enabled the detection of DNA from the three parasites. Using the superhydrophobic cone to deposit E/F into a small tube provided the highest number of positive samples (16 out of 18) and facilitated detection of parasite DNA in E/F from individual mosquitoes. Further tests showed that following a simple washing step, the cone can be reused multiple times, further improving its cost-effectiveness. Conclusions: Incorporating the superhydrophobic cone into mosquito traps or holding containers could provide a simple and efficient method for collecting E/F. Where this is not possible, swabbing the container or using the washing method facilitates the detection of the three parasites used in this study.

Millimeter-Wave Sensing of Diabetes-Relevant Glucose Concentration Changes in Pigs

NASA Astrophysics Data System (ADS)

Cano-Garcia, Helena; Saha, Shimul; Sotiriou, Ioannis; Kosmas, Panagiotis; Gouzouasis, Ioannis; Kallos, Efthymios

2018-06-01

The paper presents the first in vivo glucose monitoring animal study in a pig, which correlates radio frequency signal transmission changes with changes in blood glucose concentration in the 58-62 GHz frequency range. The presented non-invasive glucose sensing system consists of two opposite facing patch antennas sandwiching glucose-loaded samples. Prior to the animal study, the system was tested using saline solution samples, for which a linear relationship between changes in transmitted signal and glucose concentration was observed. In the animal study, glucose concentration changes were induced by injecting a known glucose solution in the blood stream. The non-invasive transmission measurements were compared to the glucose levels obtained invasively from the animal. Our results suggest that the system can detect spikes in glucose concentration in the blood, which is an important milestone towards non-invasive glucose monitoring.

A novel wearable device for continuous, non-invasion blood pressure measurement.

PubMed

Xin, Qin; Wu, Jianping

2017-08-01

In this paper, we have developed a wearable cuffless device for daily blood pressure (BP) measurement. We incorporated the light based sensor and other hard wares in a small volume for BP detection. With optimized algorithm, the real-time BP reading could be achieved, the data could be presented in the screen and be transmitted by internet of things (IoT) for history data comparison and multi-terminal viewing. Thus, further analysis provides the probability for diet or sports suggestion and alarm. We have measured BP from more than 60 subjects, compare to traditional mercury blood pressure meter, no obvious error in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) are detected. Such device can be used for continues non-invasion BP detection, and further data docking and health analysis could be achieved. Copyright © 2017. Published by Elsevier Ltd.

A multiplexed chip-based assay system for investigating the functional development of human skeletal myotubes in vitro.

PubMed

Smith, A S T; Long, C J; Pirozzi, K; Najjar, S; McAleer, C; Vandenburgh, H H; Hickman, J J

2014-09-20

This report details the development of a non-invasive in vitro assay system for investigating the functional maturation and performance of human skeletal myotubes. Data is presented demonstrating the survival and differentiation of human myotubes on microscale silicon cantilevers in a defined, serum-free system. These cultures can be stimulated electrically and the resulting contraction quantified using modified atomic force microscopy technology. This system provides a higher degree of sensitivity for investigating contractile waveforms than video-based analysis, and represents the first system capable of measuring the contractile activity of individual human muscle myotubes in a reliable, high-throughput and non-invasive manner. The development of such a technique is critical for the advancement of body-on-a-chip platforms toward application in pre-clinical drug development screens. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical Utility of Fungal Screening Assays in Adults with Severe Burns

DTIC Science & Technology

2013-01-01

available test, FungitellTM Glucan Assay for (1,3) b D glucan (BG) in serum (Associates of Cape Cod Inc., East Falmouth, MA), is a qualitative...considered a positive test in the United States and was used as a positive value in this study. A positive test is reported with a b D glucan concentration... Glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous

Ultrasonography assessment of vocal cords mobility in children after cardiac surgery.

PubMed

Shaath, Ghassan A; Jijeh, Abdulraouf; Alkurdi, Ahmad; Ismail, Sameh; Elbarbary, Mahmoud; Kabbani, Mohamed S

2012-07-01

Upper airway obstruction after pediatric cardiac surgery is not uncommon. In the cardiac surgical population, an important etiology is vocal cord paresis or paralysis following extubation. In this study, we aimed to evaluate the feasibility and accuracy of ultrasonography (US) assessment of the vocal cords mobility and compare it to fiber-optic laryngoscope (FL). A prospective pilot study has been conducted in Pediatric Cardiac ICU (PCICU) at King Abdulaziz Cardiac Center (KACC) from the 1st of June 2009 till the end of July 2010. Patients who had cardiac surgery manifested with significant signs of upper airway obstruction were included. Each procedure was performed by different operators who were blinded to each other report. Results of invasive (FL) and non-invasive ultrasonography (US) investigations were compared. Ten patients developed persistent significant upper airway obstruction after cardiac surgery were included in the study. Their mean ± SEM of weight and age were 4.6 ± 0.4 kg and 126.4 ± 51.4 days, respectively. All patients were referred to bedside US screening for vocal cord mobility. The results of US were compared subsequently with FL findings. Results were identical in nine (90%) patients and partially different in one (10%). Six patients showed abnormal glottal movement while the other four patients demonstrated normal vocal cords mobility by FL. Sensitivity of US was 100% and specificity of 80%. US assessment of vocal cord is simple, non-invasive and reliable tool to assess vocal cords mobility in the critical care settings. This screening tool requires skills that can be easily obtained.

Non-invasive fibrosis tests are correlated with necroinflammatory actvity of liver in patients with chronic hepatitis B.

PubMed

Ozyalvacli, G; Kucukbayrak, A; Kurt, M; Gurel, K; Gunes, O; Ustun, C; Akdeniz, H

2014-01-01

The gold standarda method used for assessing necroinflammatory activity and fibrosis in the liver is a liver biopsy which has many disadvantages. Therefore, many investigators have been trying to develop non-invasive tests for predicting liver fibrosis score (LFS) of these patients. The aim of this study is to describe the relationship between certain non-invasive fibrosis markers with LFS and histological activity index (HAI) detected histopathologically by liver biopsy in chronic hepatitis B patients. A total of 54 patients who had undergone a liver biopsy with the diagnosis of chronic HBV infection were included in the study. Ishak scoring was used for the evaluation of liver fibrosis, and a modified Knodell HAI was used for demonstration of necroinflammation. In this study, non-invasive fibrosis tests were calculated as described in previous studies. Histological acitivity index was positively correlated with age, age/platelet index, cirrhosis discriminant score (CDS), AST/platelet ratio index (APRI), AST/platelet/GGT/AFP index (APGA), fibro-quotient (Fibro-Q), Goteburg University Cirrhosis Index (Guci), and Platelet/Age/Phosphatase/AFP/AST index (PAPAS). When divided into two groups according to HAI, Guci and APGA were found significantly different both in >4 and >4 HAI groups than the other group. In ROC analysis performed for LFS; PAPAS, APGA, FFI and APRI were the markers having the highest AUC levels, and in ROC analysis performed for HAI; Guci, APRI and APGA were the markers with the highest AUC levels. APRI, APGA and GUCI tests may be helpful in prediction of necroinflammatory scores in the liver.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belinsky, Steven A; Palmisano, William A

A molecular marker-based method for monitoring and detecting cancer in humans. Aberrant methylation of gene promoters is a marker for cancer risk in humans. A two-stage, or "nested" polymerase chain reaction method is disclosed for detecting methylated DNA sequences at sufficiently high levels of sensitivity to permit cancer screening in biological fluid samples, such as sputum, obtained non-invasively. The method is for detecting the aberrant methylation of the p16 gene, O 6-methylguanine-DNA methyltransferase gene, Death-associated protein kinase gene, RAS-associated family 1 gene, or other gene promoters. The method offers a potentially powerful approach to population-based screening for the detection ofmore » lung and other cancers.« less

Chinese tallow (Triadica sebifera) invasion in maritime forests: the role of anthropogenic disturbance and its management implication

Treesearch

Lauren S. Pile; G. Geoff Wang; Benjamin O. Knapp; Joan L. Walker; Michael C. Stambaugh

2017-01-01

Land-use and forest management practices may facilitate the invasion success of non-native plants in forests. In this study, we tested if agricultural land abandonment and subsequent forest management contributed to the invasion success of Chinese tallow (Triadica sebifera (L.) Small) in the maritime forest of Parris Island, SC. We compared the...

Multifaceted bench comparative evaluation of latest intensive care unit ventilators.

PubMed

Garnier, M; Quesnel, C; Fulgencio, J-P; Degrain, M; Carteaux, G; Bonnet, F; Similowski, T; Demoule, A

2015-07-01

Independent bench studies using specific ventilation scenarios allow testing of the performance of ventilators in conditions similar to clinical settings. The aims of this study were to determine the accuracy of the latest generation ventilators to deliver chosen parameters in various typical conditions and to provide clinicians with a comprehensive report on their performance. Thirteen modern intensive care unit ventilators were evaluated on the ASL5000 test lung with and without leakage for: (i) accuracy to deliver exact tidal volume (VT) and PEEP in assist-control ventilation (ACV); (ii) performance of trigger and pressurization in pressure support ventilation (PSV); and (iii) quality of non-invasive ventilation algorithms. In ACV, only six ventilators delivered an accurate VT and nine an accurate PEEP. Eleven devices failed to compensate VT and four the PEEP in leakage conditions. Inspiratory delays differed significantly among ventilators in invasive PSV (range 75-149 ms, P=0.03) and non-invasive PSV (range 78-165 ms, P<0.001). The percentage of the ideal curve (concomitantly evaluating the pressurization speed and the levels of pressure reached) also differed significantly (range 57-86% for invasive PSV, P=0.04; and 60-90% for non-invasive PSV, P<0.001). Non-invasive ventilation algorithms efficiently prevented the decrease in pressurization capacities and PEEP levels induced by leaks in, respectively, 10 and 12 out of the 13 ventilators. We observed real heterogeneity of performance amongst the latest generation of intensive care unit ventilators. Although non-invasive ventilation algorithms appear to maintain adequate pressurization efficiently in the case of leakage, basic functions, such as delivered VT in ACV and pressurization in PSV, are often less reliable than the values displayed by the device suggest. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Is there a role for antibody testing in the diagnosis of invasive candidiasis?

PubMed

Quindós, Guillermo; Moragues, María Dolores; Pontón, José

2004-03-01

During the last decades, the use of antibody tests for the diagnosis of invasive mycoses has declined as a consequence of the general belief that they are insensitive and non-specific. However, there is a clear evidence that antibodies can be detected in highly immunodeficient patients (such as bone marrow transplant recipients), and that those antibodies are useful for the diagnosis. Antibody tests are currently in use as diagnostic tools for some primary mycoses, such as the endemic mycoses, aspergilloma, allergic bronchopulmonary aspergilosis and sporothrichosis. For invasive candidiasis, diagnostic methods must differentiate Candida colonization of mucous membranes or superficial infection from tissue invasion by this microorganism. Substantial progress has been made in diagnosis of invasive candidiasis with the development of a variety of methods for the detection of antibodies and antigens. However, no single test has found widespread clinical use and there is a consensus that diagnosis based on a single specimen lacks sensitivity. It is necessary to test sequential samples taken while the patient is at greatest risk for developing invasive candidiasis to optimize the diagnosis. Results obtained from a panel of diagnostic tests in association with clinical aspects will likely be the most useful strategy for early diagnosis and therapy.

Gender-specific Differences in Recurrence of Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis.

PubMed

Uhlig, Annemarie; Strauss, Arne; Seif Amir Hosseini, Ali; Lotz, Joachim; Trojan, Lutz; Schmid, Marianne; Uhlig, Johannes

2017-09-06

The incidence of urothelial carcinoma of the bladder (UCB) is lower in women; however, women tend to present with more advanced disease. To date, there is no quantitative synthesis of studies reporting gender-specific outcomes in non-muscle-invasive UCB. To conduct a meta-analysis evaluating gender-specific differences in recurrence of non-muscle-invasive urinary bladder cancer (NMIBC). An unrestricted systematic literature search of the MEDLINE, EMBASE, and Cochrane libraries was conducted. Studies evaluating the impact of gender on disease recurrence after local treatment of NMIBC using multivariable Cox proportional hazard models were included. Random effect meta-analysis, subgroup analyses, meta-influence, and cumulative meta-analyses were conducted. Publication bias was assessed via a funnel plot and Eggeŕs test. Of 609 studies screened, 27 comprising 23 754 patients were included. Random effect meta-analyses indicated women at increased risk for UCB recurrence compared with men (hazard ratio [HR]=1.11, 95% confidence interval [CI]: 1.01-1.23, p=0.03). Subgroup analyses yielded estimates between HR=0.99 and HR=1.68. Gender-specific differences in UCB recurrence were most pronounced in studies administering exclusively bacillus Calmette-Guerin (BCG; HR=1.64, 95% CI: 1.13-2.39, p=0.01), especially in a long-term treatment regimen (HR=1.68, 95% CI: 1.32-2.15, p<0.001). Sensitivity analyses confirmed female patients at increased risk for UCB recurrence. Women are at increased risk for disease recurrence after local treatment of NMIBC compared with male patients. Reduced effectiveness of BCG treatment might underlie this observation. Gender-specific differences were evident across various subgroups and proved robust upon sensitivity analyses. In this report, we combined several studies on gender-specific differences in relapse of superficial bladder cancer. Women were more likely to experience cancer relapse than men. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Clinical expression of C282Y homozygous HFE haemochromatosis at 14 years of age.

PubMed

Rossi, Enrico; Wallace, Daniel F; Subramaniam, V Nathan; St Pierre, Timothy G; Mews, Catherine; Jeffrey, Gary P

2006-05-01

A 14-year-old boy who presented with debilitating lethargy was shown to have an elevated serum ferritin of 572 microg/L and a C282Y homozygous HFE genotype. Liver iron concentration was measured non-invasively by magnetic resonance imaging, which revealed a liver iron concentration of 59 micromol/g dry weight (children's reference range < 14). The early phenotypic expression was further investigated by screening genomic DNA for the presence of co-inherited mutations in genes responsible for non-HFE haemochromatosis. Coding regions and splice sites in genes encoding hepcidin and haemojuvelin were sequenced and previously described mutations in ferroportin 1 and transferrin receptor 2 genes were screened. Although no mutations were found, the most likely cause for the early expression is the presence of novel mutations or gene(s).

Ecology of invasive mosquitoes: effects on resident species and on human health

PubMed Central

Juliano, Steven A.; Lounibos, L. Philip

2007-01-01

Investigations of biological invasions focus on patterns and processes that are related to introduction, establishment, spread and impacts of introduced species. This review focuses on the ecological interactions operating during invasions by the most prominent group of insect vectors of disease, mosquitoes. First, we review characteristics of non-native mosquito species that have established viable populations, and those invasive species that have spread widely and had major impacts, testing whether biotic characteristics are associated with the transition from established non-native to invasive. Second, we review the roles of interspecific competition, apparent competition, predation, intraguild predation and climatic limitation as causes of impacts on residents or as barriers to invasion. We concentrate on the best-studied invasive mosquito, Aedes albopictus, evaluating the application of basic ecological theory to invasions by Aedes albopictus. We develop a model based on observations of Aedes albopictus for effects of resource competition and predation as barriers to invasion, evaluating which community and ecosystem characteristics favour invasion. Third, we evaluate the ways in which invasive mosquitoes have contributed to outbreaks of human and animal disease, considering specifically whether invasive mosquitoes create novel health threats, or modify disease transmission for existing pathogen–host systems. PMID:17637849

Development and experimental test of support vector machines virtual screening method for searching Src inhibitors from large compound libraries

PubMed Central

2012-01-01

Background Src plays various roles in tumour progression, invasion, metastasis, angiogenesis and survival. It is one of the multiple targets of multi-target kinase inhibitors in clinical uses and trials for the treatment of leukemia and other cancers. These successes and appearances of drug resistance in some patients have raised significant interest and efforts in discovering new Src inhibitors. Various in-silico methods have been used in some of these efforts. It is desirable to explore additional in-silico methods, particularly those capable of searching large compound libraries at high yields and reduced false-hit rates. Results We evaluated support vector machines (SVM) as virtual screening tools for searching Src inhibitors from large compound libraries. SVM trained and tested by 1,703 inhibitors and 63,318 putative non-inhibitors correctly identified 93.53%~ 95.01% inhibitors and 99.81%~ 99.90% non-inhibitors in 5-fold cross validation studies. SVM trained by 1,703 inhibitors reported before 2011 and 63,318 putative non-inhibitors correctly identified 70.45% of the 44 inhibitors reported since 2011, and predicted as inhibitors 44,843 (0.33%) of 13.56M PubChem, 1,496 (0.89%) of 168 K MDDR, and 719 (7.73%) of 9,305 MDDR compounds similar to the known inhibitors. Conclusions SVM showed comparable yield and reduced false hit rates in searching large compound libraries compared to the similarity-based and other machine-learning VS methods developed from the same set of training compounds and molecular descriptors. We tested three virtual hits of the same novel scaffold from in-house chemical libraries not reported as Src inhibitor, one of which showed moderate activity. SVM may be potentially explored for searching Src inhibitors from large compound libraries at low false-hit rates. PMID:23173901

Use of Ultrasound in Male Infertility: Appropriate Selection of Men for Scrotal Ultrasound.

PubMed

Armstrong, Joseph M; Keihani, Sorena; Hotaling, James M

2018-05-28

Male factor infertility is a complex and multifaceted problem facing the modern urologist and is identified in 30-40% of infertile couples. This review focuses on the use of ultrasound, as an adjunct screening tool, in the initial evaluation of male infertility. Access to male reproductive urologist for assessment of male infertility is limited and about a quarter of infertile couples do not complete the male component in their infertility assessment. Ultrasound evaluation of the infertile male is low-cost and non-invasive and helps uncover underlying pathologies that may be missed during the initial assessment. The addition of ultrasound allows the physician to accurately assess testicular anatomy and dimensions, as well as vascular environments, which may help guide treatment decisions. Scrotal ultrasound evaluation, in conjunction with a semen analysis and as an adjunct to physical exam, can be offered in the initial assessment of men who present for infertility consultation given its low cost, non-invasive nature, and ability to detect and discriminate between various etiologies of male infertility. Further, when directed by physical exam and semen analysis findings, it provides a valuable tool to select men for referral to a reproductive urologist, especially for infertile couples who are only screened by reproductive endocrinologists and female infertility specialists.

Laboratory screening markers in gastroenterology--state of the art.

PubMed

Kocna, Petr; Vanickova, Zdislava; Zima, Tomas

2013-06-01

Screening tests for gastrointestinal diseases acceptable for population with a high sensitivity and high specificity can now be offered by clinical laboratories. This paper summarizes major recent advances in this area of laboratory medicine. Relevant articles published within the last 5 years in the NLM (National Library of Medicine) PubMed - Medline database covering the three gastrointestinal diseases - colorectal cancer, coeliac disease, and atrophic gastritis were included for this overview. In Europe, colorectal cancer (CRCA) is the second most frequent malignant disease. Quantitative immunochemical analysis of the stool for haemoglobin provides the best screening test to date, with both sensitivity and specificity approaching 95%. Even though coeliac disease (CD) affects approximately 1% of the general population, it remains largely unrecognised. Recommended methods for screening currently involve the detection of IgA and IgG antibodies against tissue transglutaminase and deamidated gliadin peptide. Evaluations of screening are now discussed for other diseases of the gastrointestinal tract - such as chronic atrophic gastritis (CAG), and inflammatory bowel disease (IBD). Detection of infection by Helicobacter pylori and stomach-specific plasmatic biomarkers, especially pepsinogen I/II ratio, could help with the prevention of gastric carcinomas. The use of faecal calprotectin as a screening test could substantially reduce the number of invasive methods necessary for the diagnostic work-up of patients with IBD. Screening tests for CRCA and CD have been used worldwide for many years. Screening strategies for gastrointestinal diseases are suggested in the text, based on recent basic science, clinical papers as well as our own experience.

Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study.

PubMed

Wang, Jiangrong; Andrae, Bengt; Sundström, Karin; Ström, Peter; Ploner, Alexander; Elfström, K Miriam; Arnheim-Dahlström, Lisen; Dillner, Joakim; Sparén, Pär

2016-02-11

To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. Nationwide population based cohort study. Cancer and population registries in Sweden. 3,054,328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2,899,968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment within six months, much less than after HSIL (86%). Among women with histology assessment within six months, the incidence rate of cervical cancer after AGC was significantly higher than that after HSIL for up to 6.5 years. AGC found at cervical screening is associated with a high and persistent risk of cervical cancer for up to 15 years, particularly for cervical adenocarcinoma and women with AGC at age 30-39. Compared with the reduction in risk of cancer seen after HSIL management, management of AGC seems to have been suboptimal in preventing cervical cancer. Research to optimise management is needed, and a more aggressive assessment strategy is warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study

PubMed Central

Andrae, Bengt; Sundström, Karin; Ström, Peter; Ploner, Alexander; Elfström, K Miriam; Arnheim-Dahlström, Lisen; Dillner, Joakim; Sparén, Pär

2016-01-01

Objectives To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. Design Nationwide population based cohort study. Setting Cancer and population registries in Sweden. Participants 3 054 328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2 899 968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. Main outcome measures Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. Results The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment within six months, much less than after HSIL (86%). Among women with histology assessment within six months, the incidence rate of cervical cancer after AGC was significantly higher than that after HSIL for up to 6.5 years. Conclusions AGC found at cervical screening is associated with a high and persistent risk of cervical cancer for up to 15 years, particularly for cervical adenocarcinoma and women with AGC at age 30-39. Compared with the reduction in risk of cancer seen after HSIL management, management of AGC seems to have been suboptimal in preventing cervical cancer. Research to optimise management is needed, and a more aggressive assessment strategy is warranted. PMID:26869597

An electrochemical immunoassay for the screening of celiac disease in saliva samples.

PubMed

Adornetto, Gianluca; Fabiani, Laura; Volpe, Giulia; De Stefano, Alessia; Martini, Sonia; Nenna, Raffaella; Lucantoni, Federica; Bonamico, Margherita; Tiberti, Claudio; Moscone, Danila

2015-09-01

A highly sensitive electrochemical immunoassay for the initial diagnosis of celiac disease (CD) in saliva samples that overcomes the problems related to its high viscosity and to the low concentration of anti-transglutaminase antigen (tTG) IgA in this medium has been developed for the first time. The system uses magnetic beads (MBs) covered with tTG, which reacts with the anti-tTG IgA antibodies present in positive saliva samples. An anti-human IgA, conjugated with alkaline phosphate (AP) enzyme, was used as the label and a strip of eight magnetized screen-printed electrodes as the electrochemical transducer. In particular, two different immunoassay approaches were optimized and blindly compared to analyze a large number of saliva samples, whose anti-tTG IgA levels were independently determined by the radioimmunoassay (RIA) method. The obtained results, expressed as Ab index, were used to perform a diagnostic test evaluation through the construction of receiver operating characteristic (ROC) curves. The approach, involving a pre-incubation between the anti-human IgA-AP and saliva samples prior to the addition of MBs-tTG, showed a cutoff of 0.022 with 95% clinical sensitivity and 96% clinical specificity. The area under the ROC curve is equal to 1, a result that classifies our test as "perfect." This study demonstrates that it is possible to perform the screening of CD with a rapid, simple, inexpensive, and sensitive method able to detect anti-tTG antibodies in saliva samples, which are easily obtained by non-invasive techniques. This aspect is of fundamental importance to screen a large number of subjects, especially in the pediatric age.

The Cell-CT 3D Cell Imaging Technology Platform Enables the Detection of Lung Cancer Using the Non-Invasive LuCED Sputum Test

PubMed Central

Meyer, Michael G.; Hayenga, Jon; Neumann, Thomas; Katdare, Rahul; Presley, Chris; Steinhauer, David; Bell, Timothy; Lancaster, Christy; Nelson, Alan C.

2015-01-01

The war against cancer has yielded important advances in the early diagnosis and treatment of certain cancer types, but the poor detection rate and 5-year survival rate for lung cancer remains little changed over the past 40 years. Early detection through emerging lung cancer screening programs promises the most reliable means of improving mortality. Sputum cytology has been tried without success because sputum contains few malignant cells that are difficult for cytologists to detect. However, research has shown that sputum contains diagnostic malignant cells and could serve as a means of lung cancer detection if those cells could be detected and correctly characterized. Recently, the National Lung Cancer Screening Trial reported that screening by three consecutive low-dose X-ray CT scans provides a 20% reduction in lung cancer mortality compared to chest X-ray. This reduction in mortality, however, comes with an unacceptable false positive rate that increases patient risks and the overall cost of lung cancer screening. This article reviews the LuCED® test for detecting early lung cancer. LuCED is based on patient sputum that is enriched for bronchial epithelial cells. The enriched sample is then processed on the Cell-CT®, which images cells in three dimensions with sub-micron resolution. Algorithms are applied to the 3D cell images to extract morphometric features that drive a classifier to identify cells that have abnormal characteristics. The final status of these candidate abnormal cells is established by the pathologist's manual review. LuCED promotes accurate cell classification which could enable cost effective detection of lung cancer. PMID:26148817

Comparison of the Abbott RealTime High Risk HPV test and the Roche cobas 4800 HPV test using urine samples.

PubMed

Lim, Myong Cheol; Lee, Do-Hoon; Hwang, Sang-Hyun; Hwang, Na Rae; Lee, Bomyee; Shin, Hye Young; Jun, Jae Kwan; Yoo, Chong Woo; Lee, Dong Ock; Seo, Sang-Soo; Park, Sang-Yoon; Joo, Jungnam

2017-05-01

Human papillomavirus (HPV) testing based on cervical samples is important for use in cervical cancer screening. However, cervical sampling is invasive. Therefore, non-invasive methods for detecting HPV, such as urine samples, are needed. For HPV detection in urine samples, two real-time PCR (RQ-PCR) tests, Roche cobas 4800 test (Roche_HPV; Roche Molecular Diagnostics) and Abbott RealTime High Risk HPV test (Abbott_HPV; Abbott Laboratories) were compared to standard cervical samples. The performance of Roche_HPV and Abbott_HPV for HPV detection was evaluated at the National Cancer Center using 100 paired cervical and urine samples. The tests were also compared using urine samples stored at various temperatures and for a range of durations. The overall agreement between the Roche_HPV and Abbott_HPV tests using urine samples for any hrHPV type was substantial (86.0% with a kappa value of 0.7173), and that for HPV 16/18 was nearly perfect (99.0% with a kappa value of 0.9668). The relative sensitivities (based on cervical samples) for HPV 16/18 detection using Roche_HPV and Abbott_HPV with urine samples were 79.2% (95% CI; 57.9-92.9%) and 81.8% (95% CI; 59.7-94.8%), respectively. When the cut-off C T value for Abbott_HPV was extended to 40 for urine samples, the relative sensitivity of Abbott_HPV increased to 91.7% from 81.8% for HPV16/18 detection and to 87.0% from 68.5% for other hrHPV detection. The specificity was not affected by the change in the C T threshold. Roche_HPV and Abbott_HPV showed high concordance. However, HPV DNA detection using urine samples was inferior to HPV DNA detection using cervical samples. Interestingly, when the cut-off C T value was set to 40, Abbott_HPV using urine samples showed high sensitivity and specificity, comparable to those obtained using cervical samples. Fully automated DNA extraction and detection systems, such as Roche_HPV and Abbott_HPV, could reduce the variability in HPV detection and accelerate the standardization of HPV detection in urine. Thus, urine samples may be an effective alternative for HPV detection in women who hesitate to participate in cervical cancer screening programs. Copyright © 2017 Elsevier B.V. All rights reserved.

Systematic Review of Health Economic Evaluations of Diagnostic Tests in Brazil: How accurate are the results?

PubMed

Oliveira, Maria Regina Fernandes; Leandro, Roseli; Decimoni, Tassia Cristina; Rozman, Luciana Martins; Novaes, Hillegonda Maria Dutilh; De Soárez, Patrícia Coelho

2017-08-01

The aim of this study is to identify and characterize the health economic evaluations (HEEs) of diagnostic tests conducted in Brazil, in terms of their adherence to international guidelines for reporting economic studies and specific questions in test accuracy reports. We systematically searched multiple databases, selecting partial and full HEEs of diagnostic tests, published between 1980 and 2013. Two independent reviewers screened articles for relevance and extracted the data. We performed a qualitative narrative synthesis. Forty-three articles were reviewed. The most frequently studied diagnostic tests were laboratory tests (37.2%) and imaging tests (32.6%). Most were non-invasive tests (51.2%) and were performed in the adult population (48.8%). The intended purposes of the technologies evaluated were mostly diagnostic (69.8%), but diagnosis and treatment and screening, diagnosis, and treatment accounted for 25.6% and 4.7%, respectively. Of the reviewed studies, 12.5% described the methods used to estimate the quantities of resources, 33.3% reported the discount rate applied, and 29.2% listed the type of sensitivity analysis performed. Among the 12 cost-effectiveness analyses, only two studies (17%) referred to the application of formal methods to check the quality of the accuracy studies that provided support for the economic model. The existing Brazilian literature on the HEEs of diagnostic tests exhibited reasonably good performance. However, the following points still require improvement: 1) the methods used to estimate resource quantities and unit costs, 2) the discount rate, 3) descriptions of sensitivity analysis methods, 4) reporting of conflicts of interest, 5) evaluations of the quality of the accuracy studies considered in the cost-effectiveness models, and 6) the incorporation of accuracy measures into sensitivity analyses.

ESHRE Task Force on ethics and Law 20: sex selection for non-medical reasons.

PubMed

Dondorp, W; De Wert, G; Pennings, G; Shenfield, F; Devroey, P; Tarlatzis, B; Barri, P; Diedrich, K

2013-06-01

This Task Force document revisits the debate about the ethics of sex selection for non-medical reasons in the light of relevant new technological developments. First, as a result of improvement of the Microsort® flow cytometry method, there is now a proven technique for preconception sex selection that can be combined both with IVF and IUI. Secondly, the scenario where new approaches that are currently being developed for preimplantation genetic screening (PGS) may lead to such screening becoming a routine part of all IVF treatment. In that scenario professionals will more often be confronted with parental requests for transfer of an embryo of a specific sex. Thirdly, the recent development of non-invasive prenatal testing based on cell-free fetal DNA in maternal plasma allows for easy and safe sex determination in the early stages of pregnancy. While stressing the new urgency that these developments give to the debate, the Task Force did not come to a unanimous position with regard to the acceptability of sex selection for non-medical reasons in the context of assisted reproduction. Whereas some think maintaining the current ban is the best approach, others are in favour of allowing sex selection for non-medical reasons under conditions that take account of societal concerns about the possible impact of the practice. By presenting these positions, the document reflects the different views about this issue that also exist in the field. Specific recommendations include the need for a wider delineation of accepted 'medical reasons' than in terms of avoiding a serious sex-linked disorder, and for a clarification of the legal position with regard to answering parental requests for 'additional sex selection' in the context of medically indicated preimplantation genetic diagnosis, or routine PGS.

Screening and Testing Phytochemicals in Eastern Redcedar (Juniperus virginiana) for Development of Potential Entrepreneurial Opportunities

USDA-ARS?s Scientific Manuscript database

Eastern redcedar (Juniperus virginiana) is often considered a “trash or nuisance” tree. In some states, this species has been declared invasive and management strategies have been adopted to destroy it. However, value-added phytochemical products from eastern redcedar have the potential to create n...

The Clinical and Economic Benefits of Co-Testing Versus Primary HPV Testing for Cervical Cancer Screening: A Modeling Analysis.

PubMed

Felix, Juan C; Lacey, Michael J; Miller, Jeffrey D; Lenhart, Gregory M; Spitzer, Mark; Kulkarni, Rucha

2016-06-01

Consensus United States cervical cancer screening guidelines recommend use of combination Pap plus human papillomavirus (HPV) testing for women aged 30 to 65 years. An HPV test was approved by the Food and Drug Administration in 2014 for primary cervical cancer screening in women age 25 years and older. Here, we present the results of clinical-economic comparisons of Pap plus HPV mRNA testing including genotyping for HPV 16/18 (co-testing) versus DNA-based primary HPV testing with HPV 16/18 genotyping and reflex cytology (HPV primary) for cervical cancer screening. A health state transition (Markov) model with 1-year cycling was developed using epidemiologic, clinical, and economic data from healthcare databases and published literature. A hypothetical cohort of one million women receiving triennial cervical cancer screening was simulated from ages 30 to 70 years. Screening strategies compared HPV primary to co-testing. Outcomes included total and incremental differences in costs, invasive cervical cancer (ICC) cases, ICC deaths, number of colposcopies, and quality-adjusted life years for cost-effectiveness calculations. Comprehensive sensitivity analyses were performed. In a simulation cohort of one million 30-year-old women modeled up to age 70 years, the model predicted that screening with HPV primary testing instead of co-testing could lead to as many as 2,141 more ICC cases and 2,041 more ICC deaths. In the simulation, co-testing demonstrated a greater number of lifetime quality-adjusted life years (22,334) and yielded $39.0 million in savings compared with HPV primary, thereby conferring greater effectiveness at lower cost. Model results demonstrate that co-testing has the potential to provide improved clinical and economic outcomes when compared with HPV primary. While actual cost and outcome data are evaluated, these findings are relevant to U.S. healthcare payers and women's health policy advocates seeking cost-effective cervical cancer screening technologies.

Controversies in colorectal cancer screening.

PubMed

Pox, Christian P

2014-01-01

Colorectal cancer (CRC) is one of the most common cancers worldwide and a good candidate for screening programmes. However, there is controversy concerning which of the available screening tests should be used. There is general agreement that screening for CRC in the asymptomatic population should begin at the age of 50. Several different screening methods are available which can be separated into those that mainly detect cancers: faecal occult blood tests [guaiac (FOBT) and immunochemical (FIT)], genetic stool tests, blood tests and the M2-pyruvate kinase (M2-PK) test. Methods that detect cancers and polyps are colonoscopy, sigmoidoscopy, CT-colonography (CT-C) and colon capsule endoscopy. The only tests for which a reduction in CRC mortality compared to no screening have been proven in randomized trials are FOBT and sigmoidoscopy. Several trials suggest that FIT are superior to FOBT in terms of detection rates of cancers and advanced adenomas and possibly compliance. There is indirect evidence suggesting efficacy of colonoscopy as a screening test. The role of CT-C is controversial. There is data suggesting a good sensitivity for neoplasia >9 mm with a lower sensitivity for smaller neoplasia. However, radiation exposure is considered a major limitation in some countries. Unresolved questions include the lesion cut-off for referral to colonoscopy and work-up of extracolonic findings. For other methods, like genetic stool testing using newer markers, blood tests, capsule endoscopy and M2-PK, there is currently insufficient data on screening of the asymptomatic population. Key Messages: Colorectal screening is recommended and should be performed in the form of an organized programme. If detection of early-stage cancers is the aim of a screening programme, FIT seem to be superior to FOBT. If detection and removal of adenomas is the aim of a screening programme, endoscopic methods seem to be good alternatives. Sigmoidoscopy is easier to perform but will likely only have an effect on distal cancers. Colonoscopy is more invasive but enables inspection of the whole colon. The role of CT-C, capsule endoscopy, genetic stool tests, blood tests and M2-PK is currently unknown. © 2014 S. Karger AG, Basel.

Non-invasive prenatal testing (NIPT): Europe's first multicenter post-market clinical follow-up study validating the quality in clinical routine.

PubMed

Flöck, Anne; Tu, Ngoc-Chi; Rüland, Anna; Holzgreve, Wolfgang; Gembruch, Ulrich; Geipel, Annegret

2017-11-01

Non-invasive prenatal tests (NIPT) for the determination of fetal aneuploidies from maternal blood are firmly established in clinical routine. For the first time, the accuracy of an NIPT for the determination of trisomies 21, 18 and 13 in singleton pregnancies was assessed by means of a prospective German-wide multicenter post-market clinical follow-up study, to reliably evaluate the quality in clinical routine. The study covered the indications for testing, the test results, the rate of invasive diagnostics and the pregnancy outcome. 2232 cases were tested for trisomy 21. Of these, 1946 cases were additionally examined for trisomy 18 and 13. Sensitivity and specificity for trisomy 21 (43/43) and for trisomy 13 (2/2) were 100%, for trisomy 18 the sensitivity was 80% (4/5) with a specificity of 99.8%. Three false-positive results for trisomy 18 were observed (FPR 0.15%). The no-call rate was 0.5%. In this subgroup, 27.3% (3/11) aneuploidies were diagnosed. The rate of invasive procedures was 2.6%. NIPT provides a very high quality for the fetal trisomies 21, 13 and 18 in clinical routine. The results support the recommendation that NIPT should be offered after genetic counseling and only in conjunction with a qualified ultrasound examination.

An advanced design of non-radioactive image capturing and management system for applications in non-invasive skin disorder diagnosis

NASA Astrophysics Data System (ADS)

Liu, Carol Y. B.; Luk, David C. K.; Zhou, Kany S. Y.; So, Bryan M. K.; Louie, Derek C. H.

2015-03-01

Due to the increasing incidences of malignant melanoma, there is a rising demand for assistive technologies for its early diagnosis and improving the survival rate. The commonly used visual screening method is with limited accuracy as the early phase of melanoma shares many clinical features with an atypical nevus, while conventional dermoscopes are not user-friendly in terms of setup time and operations. Therefore, the development of an intelligent and handy system to assist the accurate screening and long-term monitoring of melanocytic skin lesions is crucial for early diagnosis and prevention of melanoma. In this paper, an advanced design of non-invasive and non-radioactive dermoscopy system was reported. Computer-aided simulations were conducted for optimizing the optical design and uniform illumination distribution. Functional prototype and the software system were further developed, which could enable image capturing at 10x amplified and general modes, convenient data transmission, analysis of dermoscopic features (e.g., asymmetry, border irregularity, color, diameter and dermoscopic structure) for assisting the early detection of melanoma, extract patient information (e.g. code, lesion location) and integrate with dermoscopic images, thus further support long term monitoring of diagnostic analysis results. A clinical trial study was further conducted on 185 Chinese children (0-18 years old). The results showed that for all subjects, skin conditions diagnosed based on the developed system accurately confirmed the diagnoses by conventional clinical procedures. Besides, clinical analysis on dermoscopic features and a potential standard approach by the developed system to support identifying specific melanocytic patterns for dermoscopic examination in Chinese children were also reported.

Cell-free DNA noninvasive prenatal screening for aneuploidy versus conventional screening: A systematic review of economic evaluations.

PubMed

Nshimyumukiza, L; Menon, S; Hina, H; Rousseau, F; Reinharz, D

2018-07-01

Although noninvasive prenatal testing (NIPT) for aneuploidies using cell-free fetal DNA in maternal blood has been reported to have a high accuracy, only little evidence about its cost-effectiveness is available. We systematically reviewed and assessed quality of economic evaluation studies published between January 1, 2009 and January 1, 2016 where NIPT was compared to the current screening practices consisting of biochemical markers with or without nuchal translucency (NT) and/or maternal age. We included 16 studies and we found that, at current level of NIPT prices, contingent NIPT provide the best value for money, especially for publicly funded screening programs. NIPT as first-line test was found not cost-effective in the majority of studies. The NIPT unit cost, the risk cut-offs for current screening practice, the screening uptake rates (first- and second-line screening) as well as the costs and uptake rates of invasive diagnostic screening were the most common uncertain variables. The overall quality of included studies was fair. Considering a possible drop in prices and an ongoing NIPT expansion to include other chromosomes abnormalities other than T21, T18, T13 and sex chromosomes aneuploidies, future research are needed to examine the potential cost-effectiveness of implementing NIPT as first-line test. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Non-target effects of broadleaf herbicide on a native perennial forb: a demographic framework for assessing and minimizing impacts

Treesearch

Elizabeth E. Crone; Marilyn Marler; Dean E. Pearson

2009-01-01

Invasive species are one of the leading threats to biodiversity worldwide. Therefore, chemical herbicides are increasingly used to control invasive plants in natural and semi-natural areas. Little is known about the non-target impacts of these chemicals on native species. We conducted an experiment to test the demographic effects of the herbicide picloram on a native...

Tumor and Plasma Met Levels in Non-Metastatic Prostate Cancer.

PubMed

Kaye, Deborah R; Pinto, Peter A; Cecchi, Fabiola; Reilly, Joseph; Semerjian, Alice; Rabe, Daniel C; Gupta, Gopal; Choyke, Peter L; Bottaro, Donald P

2016-01-01

To measure Met protein content in prostate biopsies guided by fused magnetic resonance and ultrasound imaging, and to measure soluble Met (sMet) protein concentration in plasma samples from patients presenting evidence of prostate cancer. 345 patients had plasma samples drawn prior to image-guided biopsy of the prostate. Of these, 32% had benign biopsies. Of the 236 that were positive for prostate adenocarcinoma (PCa), 132 treated by total prostatectomy had Gleason scores of 6 (17%), 7, (55%), 8 (16%), or 9-10 (12%). 23% had evidence of local invasion. Plasma samples were also obtained from 80 healthy volunteers. Tissue Met and plasma sMet were measured by two-site immunoassay; values were compared among clinically defined groups using non-parametric statistical tests to determine significant differences or correlations. PCa tumor Met correlated significantly with plasma sMet, but median values were similar among benign and malignant groups. Median plasma sMet values were also similar among those groups, although both medians were significantly above normal. Median Met content in primary PCa tumors and sMet concentrations were independent of Gleason score, final pathologic stage and age. Plasma sMet is not predictive of PCa or its severity in patients with organ-confined or locally invasive disease. Quantitative analysis of Met protein content and activation state in PCa tumor biopsy samples was highly feasible and may have value in follow-up to genomic and/or transcriptomic-based screens that show evidence of oncogenically relevant MET gene features that occur at relatively low frequency in non-metastatic PCa.

Transmission spectroscopy of dengue viral infection Transmission spectroscopy of dengue viral infection

NASA Astrophysics Data System (ADS)

Firdous, S.; Ahmed, M.; Rehman, A.; Nawaz, M.; Anwar, S.; Murtaza, S.

2012-04-01

We presented the rapid diagnostic test for dengue infection based on light spectrum of human blood. The transmission spectra of dengue infected whole blood samples have been recorded in ultra violet to near infrared range (400 - 800 nm) of about 30 conformed infected patients and compared to normal blood samples. Transmission spectra of dengue infected blood illustrate a strong band from 400 - 600 nm with prominant peaks at 540 and 580 nm, where is in case of normal blood below 600 nm, total absorption has been observed. These prominent peaks from 400 - 600 nm are characteristics of cells damage and dangue virus antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) produced against dengue antigen. The presented diagnostic method is non invasive, cost effective, easy and fast screening technique for dengue infected patients.

Maternal arterial elasticity in the first trimester as a predictor of birthweight.

PubMed

O'Connor, Clare; O'Higgins, Amy; Segurado, Ricardo; Turner, Michael J; Stuart, Bernard; Kennelly, Máireád M

2016-07-01

The early detection of foetal growth restriction and macrosomia is an important goal of modern obstetric care. Aberrant foetal growth is an important cause of perinatal morbidity and mortality. Current modalities for detecting the abnormal foetal growth are often inadequate. Pulse wave analysis using applanation tonometry is a simple and non-invasive test that provides information about the cardiovascular system. Arterial elasticity has previously been implicated in the pathophysiology of pre-eclampsia and cardiovascular disease. Our study examined the relationship between maternal arterial elasticity and birthweight by using pulse wave analysis. We discovered that increased large artery elasticity predicted a larger baby at birth. Large artery elasticity therefore has the potential to act as a useful screening tool which may help in the prediction of women who are at risk of aberrant foetal growth.

Analysis of DNA Methylation Status in Bodily Fluids for Early Detection of Cancer

PubMed Central

Yokoi, Keigo; Yamashita, Keishi; Watanabe, Masahiko

2017-01-01

Epigenetic alterations by promoter DNA hypermethylation and gene silencing in cancer have been reported over the past few decades. DNA hypermethylation has great potential to serve as a screening marker, a prognostic marker, and a therapeutic surveillance marker in cancer clinics. Some bodily fluids, such as stool or urine, were obtainable without any invasion to the body. Thus, such bodily fluids were suitable samples for high throughput cancer surveillance. Analyzing the methylation status of bodily fluids around the cancer tissue may, additionally, lead to the early detection of cancer, because several genes in cancer tissues are reported to be cancer-specifically hypermethylated. Recently, several studies that analyzed the methylation status of DNA in bodily fluids were conducted, and some of the results have potential for future development and further clinical use. In fact, a stool DNA test was approved by the U.S. Food and Drug Administration (FDA) for the screening of colorectal cancer. Another promising methylation marker has been identified in various bodily fluids for several cancers. We reviewed studies that analyzed DNA methylation in bodily fluids as a less-invasive cancer screening. PMID:28358330

Maternal cfDNA screening for Down syndrome--a cost sensitivity analysis.

PubMed

Cuckle, Howard; Benn, Peter; Pergament, Eugene

2013-07-01

This study aimed to determine the principal factors contributing to the cost of avoiding a birth with Down syndrome by using cell-free DNA (cfDNA) to replace conventional screening. A range of unit costs were assigned to each item in the screening process. Detection rates were estimated by meta-analysis and modeling. The marginal cost associated with the detection of additional cases using cfDNA was estimated from the difference in average costs divided by the difference in detection. The main factor was the unit cost of cfDNA testing. For example, replacing a combined test costing $150 with 3% false-positive rate and invasive testing at $1000, by cfDNA tests at $2000, $1500, $1000, and $500, the marginal cost is $8.0, $5.8, $3.6, and $1.4m, respectively. Costs were lower when replacing a quadruple test and higher for a 5% false-positive rate, but the relative importance of cfDNA unit cost was unchanged. A contingent policy whereby 10% to 20% women were selected for cfDNA testing by conventional screening was considerably more cost-efficient. Costs were sensitive to cfDNA uptake. Universal cfDNA screening for Down syndrome will only become affordable by public health purchasers if costs fall substantially. Until this happens, the contingent use of cfDNA is recommended. © 2013 John Wiley & Sons, Ltd.

In vitro inhibition of Eimeria tenella sporozoite invasion into host cells by probiotics.

PubMed

Hessenberger, S; Schatzmayr, G; Teichmann, K

2016-10-15

The aim was to study the effects of probiotics isolated from the intestinal tract of livestock animals on Eimeria tenella invasion into Madin-Darby bovine kidney (MDBK) cells in vitro. E. tenella sporozoites were purified and labeled with 5(6)-carboxyfluorescein diacetate N-succinimidyl ester before seeding on cell cultures, and invasion was evaluated by fluorescence microscopy. Two protocols (A and B) were used. In protocol A, Enterococcus faecium # 589 or Lactobacillus salivarius subsp. salivarius # 505 were added together with sporozoites to MDBK cell cultures and invasion was evaluated after incubation for approximately 20h. Viable, dead, or spent culture supernatants of probiotics were tested. In protocol B, viable probiotics were incubated with MDBK cells for one hour before sporozoites were added and invasion was evaluated after two more hours of incubation. Parasite invasion of viable, dead, or spent culture supernatant of E. faecium # 589 was assessed. Using protocol A, it was shown that parasite invasion was inhibited by viable (80%) or dead (75%) E. faecium # 589. While inhibition by viable L. salivarius subsp. salivarius # 505 was not valid at the highest concentration and not significant at the other test concentrations, dead cells inhibited parasite invasion up to 45%. Spent culture supernatants of both probiotics had no influence on parasite invasion. Using protocol B, it was shown that viable Bifidobacterium animalis subsp. animalis # 503, E. faecium # 497, E. faecium # 589, L. reuteri # 514, L. salivarius subsp. salivarius # 505, and Bacillus subtilis # 588 inhibited parasite invasion into MDBK cells up to 80%. Anticoccidial activity was strain-specific for E. faecium strains, and the strongest effect was shown by E. faecium # 589. Anticoccidial effects of some of the tested probiotics have already been shown in vivo, which makes them candidates to prevent coccidiosis. These findings have now been confirmed in vitro. The used parasite invasion assay is a fast and inexpensive tool to screen probiotics for prevention of coccidiosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparing outcomes and costs between contingent and combined first-trimester screening strategies for Down's syndrome.

PubMed

Martín, I; Gibert, M J; Aulesa, C; Alsina, M; Casals, E; Bauça, J M

2015-06-01

To compare a contingent strategy with a combined strategy for prenatal detection of Down's syndrome (DS) in terms of cost, outcomes and safety. The contingent strategy was based on a simulation, removing measurement of the free beta subunit of human chorionic gonadotropin (free βhCG) and calculating the DS risk retrospectively in 32,371 pregnant women who had been screened with the combined strategy in the first trimester. In the contingent strategy, a risk between 1:31 and 1:1000 in the first trimester indicated further testing in the second trimester (alpha-fetoprotein, inhibin A, unconjugated oestriol and free βhCG). The cut-off risk values for the contingent and combined strategies in the first trimester were 1:30 and 1:250, respectively, and the cut-off risk value for integrated screening in the second trimester was 1:250. Costs were compared in terms of avoided DS births, and the ratio of loss of healthy fetuses following invasive procedures per avoided DS birth was calculated. The combined strategy had sensitivity of 40/44 (90.9%) and a false-positive rate of 2.8%. Corresponding values for the contingent strategy were 39/44 (88.6%) and 1.3%, respectively. Only 11% of pregnant women required tests in the second trimester, and the approximate cost reduction for each avoided DS birth was 5000€. The ratio of lost healthy fetuses following invasive procedures per avoided DS birth improved by up to 0.65. The contingent strategy has similar effectiveness to the combined strategy, but has lower costs and fewer invasive procedures. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Guide for diagnosis and treatment of hepatocellular carcinoma

PubMed Central

Attwa, Magdy Hamed; El-Etreby, Shahira Aly

2015-01-01

Hepatocellular carcinoma (HCC) is ranked as the 5th common type of cancer worldwide and is considered as the 3rd common reason for cancer-related deaths. HCC often occurs on top of a cirrhotic liver. The prognosis is determined by several factors; tumour extension, alpha-fetoprotein (AFP) concentration, histologic subtype of the tumour, degree of liver dysfunction, and the patient’s performance status. HCC prognosis is strongly correlated with diagnostic delay. To date, no ideal screening modality has been developed. Analysis of recent studies showed that AFP assessment lacks adequate sensitivity and specificity for effective surveillance and diagnosis. Many tumour markers have been tested in clinical trials without progressing to routine use in clinical practice. Thus, surveillance is still based on ultrasound (US) examination every 6 mo. Imaging studies for diagnosis of HCC can fall into one of two main categories: routine non-invasive studies such as US, computed tomography (CT), and magnetic resonance imaging, and more specialized invasive techniques including CT during hepatic arteriography and CT arterial portography in addition to the conventional hepatic angiography. This article provides an overview and spotlight on the different diagnostic modalities and treatment options of HCC. PMID:26140083

Visual and Ocular Manifestations of Alzheimer’s Disease and Their Use as Biomarkers for Diagnosis and Progression

PubMed Central

Javaid, Fatimah Zara; Brenton, Jonathan; Guo, Li; Cordeiro, Maria F.

2016-01-01

Alzheimer’s disease (AD) is the most common form of dementia affecting the growing aging population today, with prevalence expected to rise over the next 35 years. Clinically, patients exhibit a progressive decline in cognition, memory, and social functioning due to deposition of amyloid β (Aβ) protein and intracellular hyperphosphorylated tau protein. These pathological hallmarks of AD are measured either through neuroimaging, cerebrospinal fluid analysis, or diagnosed post-mortem. Importantly, neuropathological progression occurs in the eye as well as the brain, and multiple visual changes have been noted in both human and animal models of AD. The eye offers itself as a transparent medium to cerebral pathology and has thus potentiated the development of ocular biomarkers for AD. The use of non-invasive screening, such as retinal imaging and visual testing, may enable earlier diagnosis in the clinical setting, minimizing invasive and expensive investigations. It also potentially improves disease management and quality of life for AD patients, as an earlier diagnosis allows initiation of medication and treatment. In this review, we explore the evidence surrounding ocular changes in AD and consider the biomarkers currently in development for early diagnosis. PMID:27148157

Direct Saliva Real Time Polymerase Chain Reaction Assay Shows Low Birth Prevalence of Congenital CMV Infection in Urban Western India.

PubMed

Viswanathan, Rajlakshmi; Bafna, Sanjay; Mergu, Ravikanth; Deshpande, Gururajrao; Gunjikar, Rashmi; Gaikwad, Shivshankar; Mullick, Jayati

2018-05-09

Congenital cytomegalovirus infection is the leading infectious cause of mental retardation, developmental delay and sensorineural deafness. Non primary infection plays a major role in transmission of this infection in countries with high maternal seroprevalence. Non invasive sampling and testing is a useful alternative to traditional methods of laboratory detection of congenital CMV infection. The present study was conducted to understand birth prevalence of congenital cytomegalovirus (cCMV) infection using molecular techniques, in an urban setting of a developing country with evidence of high maternal seroprevalence. Universal newborn screening for cCMV was performed for 750 infants born at a tertiary care centre in Western India. Real-time PCR was directly carried out on saliva samples. Follow up laboratory testing of saliva, urine and blood was performed for neonates identified as positive. Sequential clinical follow up was offered to the affected infants. A birth prevalence of 0.4% (95% CI 0.13-1.2) was observed with 3 of 750 babies confirmed to be positive for cCMV infection. All three babies were born to seropositive mothers (anti CMV IgG positive). One of the babies detected was symptomatic with sepsis like features. All of them survived and did not develop any sequelae upto one year of age. The use of direct real-time PCR of saliva samples can be considered as a feasible option for newborn screening of congenital CMV infection in developing countries. Relatively low birth prevalence of cCMV infection was observed in our study, which needs to be corroborated through further studies.

Non-invasive assessment of low- and intermediate-risk patients with chest pain

PubMed Central

Balfour, Pelbreton C.; Gonzalez, Jorge A.; Kramer, Christopher M.

2016-01-01

Coronary artery disease (CAD) remains a significant global public health burden despite advancements in prevention and therapeutic strategies. Common non-invasive imaging modalities, anatomic and functional, are available for the assessment of patients with stable chest pain. Exercise electrocardiography is a long-standing method for evaluation for CAD and remains the initial test for the majority of patients who can exercise adequately with a baseline interpretable electrocardiogram. The addition of cardiac imaging to exercise testing provides incremental benefit for accurate diagnosis for CAD and is particularly useful in patients who are unable to exercise adequately and/or have uninterpretable electrocardiograms. Radionuclide myocardial perfusion imaging and echocardiography with exercise or pharmacological stress provide high sensitivity and specificity in the detection and further risk stratification of patients with CAD. Recently, coronary computed tomography angiography has demonstrated its growing role to rule out significant CAD given its high negative predictive value. Although less available, stress cardiac magnetic resonance provides a comprehensive assessment of cardiac structure and function and provides a high diagnostic accuracy in the detection of CAD. The utilization of non-invasive testing is complex due to various advantages and limitations, particularly in the assessment of low- and intermediate-risk patients with chest pain, where no single study is suitable for all patients. This review will describe currently available non-invasive modalities, along with current evidence-based guidelines and appropriate use criteria in the assessment of low- and intermediate-risk patients with suspected, stable CAD. PMID:27717538

National Disparities in Colorectal Cancer Screening Among Obese Adults.

PubMed

Seibert, Ryan G; Hanchate, Amresh D; Berz, Jonathan P; Schroy, Paul C

2017-08-01

Obesity is a major risk factor for colorectal cancer (CRC), particularly among men. The purpose of this study was to characterize the prevalence of guideline-adherent CRC screening among obese adults using nationally representative data, assess trends in screening strategies, and identify obesity-specific screening barriers. Data from 8,550 respondents aged 50-75 years in the 2010 National Health Interview Survey, representing >70 million adults, were analyzed in 2015 using multivariable logistic regression. Prevalence of guideline-adherent CRC screening, endoscopic versus fecal occult blood test screening, and reasons for non-adherence were compared across BMI categories. Obese class III men (BMI ≥40), compared with normal-weight men, were significantly less likely to be adherent to screening guidelines (38.7% vs 55.8%, AOR=0.35, 95% CI=0.17, 0.75); less likely to have used an endoscopic test (36.7% vs 53.0%, AOR=0.37, 95% CI=0.18, 0.79); and had a trend toward lower fecal occult blood test use (4.2% vs 8.9%, AOR=0.42, 95% CI=0.14, 1.27). Among women, odds of guideline adherence and use of different screening modalities were similar across all BMI categories. Reasons for non-adherence differed by gender and BMI; lacking a physician screening recommendation differed significantly among men (29.7% obese class III vs 15.4% non-obese, p=0.04), and pain/embarrassment differed significantly among women (11.6% obese class III vs 2.6% non-obese, p=0.002). Despite elevated risk, severely obese men were significantly under-screened for CRC. Addressing the unique screening barriers of obese adults may promote screening uptake and lessen disparities among the vulnerable populations most affected by obesity. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Broad-Spectrum Molecular Detection of Fungal Nucleic Acids by PCR-Based Amplification Techniques.

PubMed

Czurda, Stefan; Lion, Thomas

2017-01-01

Over the past decade, the incidence of life-threatening invasive fungal infections has dramatically increased. Infections caused by hitherto rare and emerging fungal pathogens are associated with significant morbidity and mortality among immunocompromised patients. These observations render the coverage of a broad range of clinically relevant fungal pathogens highly important. The so-called panfungal or, perhaps more correctly, broad-range nucleic acid amplification techniques do not only facilitate sensitive detection of all clinically relevant fungal species but are also rapid and can be applied to analyses of any patient specimens. They have therefore become valuable diagnostic tools for sensitive screening of patients at risk of invasive fungal infections. This chapter summarizes the currently available molecular technologies employed in testing of a wide range of fungal pathogens, and provides a detailed workflow for patient screening by broad-spectrum nucleic acid amplification techniques.

[Practical problems in breast screening. Columnar cell lesions including flat epithelial atypia and lobular neoplasia].

PubMed

Nährig, J

2008-11-01

Columnar cell lesions (CCL) and lobular neoplasia (LN) are encountered with increasing frequency in breast screening biopsies. CCLs are frequently associated with microcalcifications, whereas LN is an incidental finding in most cases. Flat epithelia atypia (FEA) the atypical variant of CLL, LN and atypical ductal hyperplasia (ADH) are frequently associated lesions. Molecular genetic studies of CCL, ductal carcinoma in situ (DCIS) and low grade invasive carcinomas revealed similar chromosomal alterations supporting the assumption that CCLs are neoplastic proliferations. The frequent association of FEA together with well differentiated invasive carcinomas provides further evidence of this concept. There is no internationally accepted classification of CCLs at present. CDH1-gene mutations are the cardinal feature of LN and invasive lobular carcinoma. In immunohistochemically CDH1-positive cases, alternative genetic alterations of the CDH1 pathway can lead to functional loss of CDH1. In our opinion morphologically and immunohistochemically hybrid lesions may represent this group of lobular lesions. Recent follow-up data suggest a higher rate of ipsilateral carcinomas in patients with previously diagnosed LN. It is currently an open question whether FEA and LN are members of a common family of intralobular proliferations, which are non-obligatory precursors of a low nuclear grade breast neoplasia family.

Capacitive Sensing for Non-Invasive Breathing and Heart Monitoring in Non-Restrained, Non-Sedated Laboratory Mice.

PubMed

González-Sánchez, Carlos; Fraile, Juan-Carlos; Pérez-Turiel, Javier; Damm, Ellen; Schneider, Jochen G; Zimmermann, Heiko; Schmitt, Daniel; Ihmig, Frank R

2016-07-07

Animal testing plays a vital role in biomedical research. Stress reduction is important for improving research results and increasing the welfare and the quality of life of laboratory animals. To estimate stress we believe it is of great importance to develop non-invasive techniques for monitoring physiological signals during the transport of laboratory animals, thereby allowing the gathering of information on the transport conditions, and, eventually, the improvement of these conditions. Here, we study the suitability of commercially available electric potential integrated circuit (EPIC) sensors, using both contact and contactless techniques, for monitoring the heart rate and breathing rate of non-restrained, non-sedated laboratory mice. The design has been tested under different scenarios with the aim of checking the plausibility of performing contactless capture of mouse heart activity (ideally with an electrocardiogram). First experimental results are shown.

Non-Invasive Tension Measurement Devices for Parachute Cordage

NASA Technical Reports Server (NTRS)

Litteken, Douglas A.; Daum, Jared S.

2016-01-01

The need for lightweight and non-intrusive tension measurements has arisen alongside the development of high-fidelity computer models of textile and fluid dynamics. In order to validate these computer models, data must be gathered in the operational environment without altering the design, construction, or performance of the test article. Current measurement device designs rely on severing a cord and breaking the load path to introduce a load cell. These load cells are very reliable, but introduce an area of high stiffness in the load path, directly affecting the structural response, adding excessive weight, and possibly altering the dynamics of the parachute during a test. To capture the required data for analysis validation without affecting the response of the system, non-invasive measurement devices have been developed and tested by NASA. These tension measurement devices offer minimal impact to the mass, form, fit, and function of the test article, while providing reliable, axial tension measurements for parachute cordage.

Protocol for Compass: a randomised controlled trial of primary HPV testing versus cytology screening for cervical cancer in HPV-unvaccinated and vaccinated women aged 25-69 years living in Australia.

PubMed

Canfell, Karen; Saville, Marion; Caruana, Michael; Gebski, Val; Darlington-Brown, Jessica; Brotherton, Julia; Heley, Stella; Castle, Philip E

2018-01-26

Australia's National Cervical Screening Program (NCSP) currently recommends 2-year cytology in women aged 18-69 years. Following a review of the NCSP prompted by the implementation of human papillomavirus (HPV) vaccination, the programme will transition in 2017 to 5-year primary HPV screening with partial genotyping for HPV16/18 in women aged 25-74 years. Compass is a sentinel experience for the renewed NCSP and the first prospectively randomised trial of primary HPV screening compared with cytology to be conducted in a population with high uptake of HPV vaccination. This protocol describes the main Compass trial, which commenced after a pilot study of ~5000 women completed recruitment. Women aged 25-69 years will be randomised at a 1:2 allocation to (1) 2.5-year image-read, liquid-based cytology (LBC) screening with HPV triage of low-grade smears (active control Arm A) or (2) 5-year HPV screening with partial genotyping and referral of HPV16/18-positive women to colposcopy (intervention Arm B). Women in Arm B positive for other oncogenic HPV (not 16/18) will undergo secondary randomisation at a 1:1 allocation to either LBC or dual-stained (p16 INK4a and Ki-67) cytology testing (dual-stained cytology). The primary outcome is cumulative CIN3+ (CIN3, adenocarcinoma in situ and invasive cervical cancer) following a 5-year HPV exit testing round in both arms, in women randomised to the HPV arm versus women randomised to the LBC arm, based on an intention-to-treat analysis. The primary outcome will first be tested for non-inferiority and if declared, the primary outcome will be tested for superiority. A total of 36 300 women in birth cohorts not offered vaccination and 84 700 women in cohorts offered vaccination will be recruited, bringing the final sample size to 121 000. The trial is powered for the secondary outcome of cumulative CIN3+ in screen-negative women, adjusted for censoring after CIN2+ treatment and hysterectomy. Approved by the Bellberry Ethics Committee (2014-11-592). Findings will be reported in peer-reviewed journals and presented at scientific meetings. NCT02328872; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Genome-Wide siRNA Screen Implicates Spire1/2 in SipA-Driven Salmonella Typhimurium Host Cell Invasion

PubMed Central

Andritschke, Daniel; Dilling, Sabrina; Emmenlauer, Mario; Welz, Tobias; Schmich, Fabian; Misselwitz, Benjamin; Rämö, Pauli; Rottner, Klemens; Kerkhoff, Eugen; Wada, Teiji; Penninger, Josef M.; Beerenwinkel, Niko; Horvath, Peter; Dehio, Christoph; Hardt, Wolf-Dietrich

2016-01-01

Salmonella Typhimurium (S. Tm) is a leading cause of diarrhea. The disease is triggered by pathogen invasion into the gut epithelium. Invasion is attributed to the SPI-1 type 3 secretion system (T1). T1 injects effector proteins into epithelial cells and thereby elicits rearrangements of the host cellular actin cytoskeleton and pathogen invasion. The T1 effector proteins SopE, SopB, SopE2 and SipA are contributing to this. However, the host cell factors contributing to invasion are still not completely understood. To address this question comprehensively, we used Hela tissue culture cells, a genome-wide siRNA library, a modified gentamicin protection assay and S. TmSipA, a sopBsopE2sopE mutant which strongly relies on the T1 effector protein SipA to invade host cells. We found that S. TmSipA invasion does not elicit membrane ruffles, nor promote the entry of non-invasive bacteria "in trans". However, SipA-mediated infection involved the SPIRE family of actin nucleators, besides well-established host cell factors (WRC, ARP2/3, RhoGTPases, COPI). Stage-specific follow-up assays and knockout fibroblasts indicated that SPIRE1 and SPIRE2 are involved in different steps of the S. Tm infection process. Whereas SPIRE1 interferes with bacterial binding, SPIRE2 influences intracellular replication of S. Tm. Hence, these two proteins might fulfill non-redundant functions in the pathogen-host interaction. The lack of co-localization hints to a short, direct interaction between S. Tm and SPIRE proteins or to an indirect effect. PMID:27627128

Single non-invasive model to diagnose non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

PubMed

Otgonsuren, Munkhzul; Estep, Michael J; Hossain, Nayeem; Younossi, Elena; Frost, Spencer; Henry, Linda; Hunt, Sharon; Fang, Yun; Goodman, Zachary; Younossi, Zobair M

2014-12-01

Non-alcoholic steatohepatitis (NASH) is the progressive form of non-alcoholic fatty liver disease (NAFLD). A liver biopsy is considered the "gold standard" for diagnosing/staging NASH. Identification of NAFLD/NASH using non-invasive tools is important for intervention. The study aims were to: develop/validate the predictive performance of a non-invasive model (index of NASH [ION]); assess the performance of a recognized non-invasive model (fatty liver index [FLI]) compared with ION for NAFLD diagnosis; determine which non-invasive model (FLI, ION, or NAFLD fibrosis score [NFS]) performed best in predicting age-adjusted mortality. From the National Health and Nutrition Examination Survey III database, anthropometric, clinical, ultrasound, laboratory, and mortality data were obtained (n = 4458; n = 861 [19.3%] NAFLD by ultrasound) and used to develop the ION model, and then to compare the ION and FLI models for NAFLD diagnosis. For validation and diagnosis of NASH, liver biopsy data were used (n = 152). Age-adjusted Cox proportional hazard modeling estimated the association among the three non-invasive tests (FLI, ION, and NFS) and mortality. FLI's threshold score > 60 and ION's threshold score > 22 had similar specificity (FLI = 80% vs ION = 82%) for NAFLD diagnosis; FLI < 30 (80% sensitivity) and ION < 11 (81% sensitivity) excluded NAFLD. An ION score > 50 predicted histological NASH (92% specificity); the FLI model did not predict NASH or mortality. The ION model was best in predicting cardiovascular/diabetes-related mortality; NFS predicted overall or diabetes-related mortality. The ION model was superior in predicting NASH and mortality compared with the FLI model. Studies are needed to validate ION. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

European multicentre validation study of the accuracy of E/e' ratio in estimating invasive left ventricular filling pressure: EURO-FILLING study.

PubMed

Galderisi, Maurizio; Lancellotti, Patrizio; Donal, Erwan; Cardim, Nuno; Edvardsen, Thor; Habib, Gilbert; Magne, Julien; Maurer, Gerald; Popescu, Bogdan A

2014-07-01

The non-invasive estimation of left ventricular filling pressures (LVFPs) represents a main goal in the clinical setting. Current recommendations encourage the use of pulsed-wave Tissue Doppler for calculating the ratio between the preload-dependent transmitral E velocity and the average of septal and lateral early diastolic velocities (e') of the mitral annulus. Despite its wide use, real utility of the E/e' ratio has been recently challenged in patients with either very advanced heart failure or preserved left ventricular (LV) ejection fraction. However, only few studies performed the invasive and non-invasive estimation of LVFP simultaneously. The EURO-FILLING Study will validate the E/e' ratio (and additional non-invasive estimates) against simultaneously measured LVFP obtained by left heart catheterization in a multicentre study involving reference European echo laboratories collecting a wide population sample size of cardiac patients with and without heart failure. The EURO-FILLING study is a large, prospective observational study in which simultaneous assessment of invasive and non-invasive measurements of LVFP will be acquired in eight reference European centres. Centralized reading of the collected parameters will be performed in a core laboratory. Not only standardized echo Doppler measurements but also novel echo parameters such as LV global longitudinal strain and global atrial strain (obtainable by two-dimensional speckle tracking echocardiography) will be tested for predicting invasive measurements of LVFP. The EURO-FILLING study is expected to provide important information on non-invasive assessment of LVFP and to contribute to the standardization of this assessment in clinical practice. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

A randomized controlled trial in non-responders from Newcastle upon Tyne invited to return a self-sample for Human Papillomavirus testing versus repeat invitation for cervical screening.

PubMed

Cadman, Louise; Wilkes, Scott; Mansour, Diana; Austin, Janet; Ashdown-Barr, Lesley; Edwards, Rob; Kleeman, Michelle; Szarewski, Anne

2015-03-01

Non-attenders for cervical screening are at increased risk of cervical cancer. Studies offering self-sampling for high-risk Human Papillomavirus (HrHPV) testing have shown greater uptake than sending another invitation for cytology. To explore whether uptake would increase in a less diverse, more stable population than the previous English study, which demonstrated a lower response rate than other studies. The primary objective was whether non-attenders were more likely to respond to a postal invitation, including kit, to collect a self-sample compared with a further invitation for cytology screening. The secondary objective was whether women with an abnormal result would attend for follow-up. 6000 non-attenders for screening in this pragmatic, randomized (1:1) controlled trial in Newcastle-upon-Tyne were sent an HPV self-sample kit (intervention) or a further invitation for cytology screening (comparator). 411(13%) responded to the intervention, returning a self-sample (247(8%)) or attending for cytology (164(5%)), compared with 183(6%) attending for cytology, relative risk 2.25 (95% CI 1.90-2.65) (comparator arm). Of those testing hrHPV positive (32(13%)), 19(59%) subsequently attended cytology screening. Of those in the intervention group who attended for cytology screening without returning an hrHPV self-sample (n = 164), 5% (n = 8) were referred for colposcopy - all attended. In the comparator group eight of the nine referred for colposcopy attended. Persistent non-responders to invitations for cervical screening are significantly more likely to respond to a postal invitation to return a self-collected sample for HPV testing than a further invitation for cytology screening. However, just over half followed up on this positive HPV result. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

GERD questionnaire for diagnosis of gastroesophageal reflux disease in systemic sclerosis.

PubMed

Chunlertrith, K; Noiprasit, A; Foocharoen, C; Mairiang, P; Sukeepaisarnjaroen, W; Sangchan, A; Sawadpanitch, K

2014-01-01

Gastroesophageal reflux disease (GERD) is clinically-identified in patients with systemic sclerosis (SSc). The GERD-questionnaire (GERD-Q) score is a sensitive, non-invasive, diagnostic screening tool for diagnosis of GERD in general patients, but it has been not investigated for use in SSc. Our aim was to evaluate the proper cut-off GERD-Q score, sensitivity and specificity for a diagnosis of GERD in SSc patients. A cross-sectional study using the GERD-Q was performed during May 2012-January 2013 on patients over 18 with the diffuse SSc subset. Both esophago-gastro-duodenoscopy (EGD) and 24-hr pH-monitoring (24hr-pH) were performed as the gold standard tests for both symptomatic and asymptomatic GERD. A total of 75 SSc patients completed the GERD-Q, EGD and 24hr-pH. We identified 22 males (29.3%), 53 females (70.7%) with a mean age of 54.2 years. The respective number of symptomatic and asymptomatic GERD was 69 and 6 cases. For a GERD diagnosis, a cut-off GERD-Q score of 4 provided the best balance between sensitivity and specificity (96.9% and 50%, respectively). Of 48 participants (69.6%) with symptomatic GERD (i.e. positive for both EGD and 24hr-pH), 65 (94.2%) were positive for either EGD or 24hr-pH, and 4 (5.8%) were negative for both EGD and 24hr-pH. A respective majority (83%) vs. one-third of the asymptomatic group had reflux as detected by 24hr-pH vs. A GERD-Q score of 4 or higher indicates a high sensitivity for a diagnosis of GERD in SSc. It can thus be used as a non-invasive screening tool for diagnosing GERD in cases where EGD and 24hr-pH are unavailable.

Gestational Diabetes Mellitus Risk score: A practical tool to predict Gestational Diabetes Mellitus risk in Tanzania.

PubMed

Patrick Nombo, Anna; Wendelin Mwanri, Akwilina; Brouwer-Brolsma, Elske M; Ramaiya, Kaushik L; Feskens, Edith

2018-05-28

Universal screening for hyperglycemia during pregnancy may be in-practical in resource constrained countries. Therefore, the aim of this study was to develop a simple, non-invasive practical tool to predict undiagnosed Gestational diabetes mellitus (GDM) in Tanzania. We used cross-sectional data of 609 pregnant women, without known diabetes, collected in six health facilities from Dar es Salaam city (urban). Women underwent screening for GDM during ante-natal clinics visit. Smoking habit, alcohol consumption, pre-existing hypertension, birth weight of the previous child, high parity, gravida, previous caesarean section, age, MUAC ≥28 cm, previous stillbirth, haemoglobin level, gestational age (weeks), family history of type 2 diabetes, intake of sweetened drinks (soda), physical activity, vegetables and fruits consumption were considered as important predictors for GDM. Multivariate logistic regression modelling was used to create the prediction model, using a cut-off value of 2.5 to minimise the number of undiagnosed GDM (false negatives). Mid-upper arm circumference (MUAC) ≥28 cm, previous stillbirth, and family history of type 2 diabetes were identified as significant risk factors of GDM with a sensitivity, specificity, positive predictive value, and negative predictive value of 69%, 53%, 12% and 95%, respectively. Moreover, the inclusion of these three predictors resulted in an area under the curve (AUC) of 0.64 (0.56-0.72), indicating that the current tool correctly classifies 64% of high risk individuals. The findings of this study indicate that MUAC, previous stillbirth, and family history of type 2 diabetes significantly predict GDM development in this Tanzanian population. However, the developed non-invasive practical tool to predict undiagnosed GDM only identified 6 out of 10 individuals at risk of developing GDM. Thus, further development of the tool is warranted, for instance by testing the impact of other known risk factors such as maternal age, pre-pregnancy BMI, hypertension during or before pregnancy and pregnancy weight gain. Copyright © 2018. Published by Elsevier B.V.

Lettuce flavonoids screening and phenotyping by chlorophyll fluorescence excitation ratio.

PubMed

Zivcak, Marek; Brückova, Klaudia; Sytar, Oksana; Brestic, Marian; Olsovska, Katarina; Allakhverdiev, Suleyman I

2017-06-01

Environmentally induced variation and the genotypic differences in flavonoid and phenolic content in lettuce can be reliably detected using the appropriate parameters derived from the records of rapid non-invasive fluorescence technique. The chlorophyll fluorescence excitation ratio method was designed as a rapid and non-invasive tool to estimate the content of UV-absorbing phenolic compounds in plants. Using this technique, we have assessed the dynamics of accumulation of flavonoids related to developmental changes and environmental effects. Moreover, we have tested appropriateness of the method to identify the genotypic differences and fluctuations in total phenolics and flavonoid content in lettuce. Six green and two red genotypes of lettuce (Lactuca sativa L.) grown in pots were exposed to two different environments for 50 days: direct sunlight (UV-exposed) and greenhouse conditions (low UV). The indices based on the measurements of chlorophyll fluorescence after red, green and UV excitation indicated increase of the content of UV-absorbing compounds and anthocyanins in the epidermis of lettuce leaves. In similar, the biochemical analyses performed at the end of the experiment confirmed significantly higher total phenolic and flavonoid content in lettuce plants exposed to direct sun compared to greenhouse conditions and in red compared to green genotypes. As the correlation between the standard fluorescence indices and the biochemical records was negatively influenced by the presence of red genotypes, we proposed the use of a new parameter named Modified Flavonoid Index (MFI) taking into an account both absorbance changes due to flavonol and anthocyanin content, for which the correlation with flavonoid and phenolic content was relatively good. Thus, our results confirmed that the fluorescence excitation ratio method is useful for identifying the major differences in phenolic and flavonoid content in lettuce plants and it can be used for high-throughput pre-screening and phenotyping of leafy vegetables in research and breeding applications towards improvement of vegetable health effects.

Towards an ethically sensitive implementation of non invasive prenatal screening in the global context

PubMed Central

Mozersky, Jessica; Ravitsky, Vardit; Rapp, Rayna; Michie, Marsha; Chandrasekharan, Subhashini; Allyse, Megan

2017-01-01

Cell-free DNA (cfDNA) screening is an emerging prenatal technology available in 90 countries. Despite its rapid global diffusion, there is a gap in knowledge about its implementation outside of North America and Europe including low to middle income countries. To address this, we organized an international comparative workshop to explore the ethical and social implications of the global expansion of cfDNA screening. We describe 8 key insights that arose from discussions to illustrate how bioethical discussions and normative frameworks that originate and reflect North American and European ethical priorities can be enriched by attending to the importance of local context. The utility and ethical implications of cfDNA screening are highly variable and dependent upon local healthcare systems, cultural, economic, and socio-political contexts and needs. We call for a more subtle, dynamic and contextual understanding of the international spread of cfDNA screening, which will evoke diverse challenges across different contexts. PMID:28301696

Whole exome sequencing identifies driver mutations in asymptomatic computed tomography-detected lung cancers with normal karyotype.

PubMed

Belloni, Elena; Veronesi, Giulia; Rotta, Luca; Volorio, Sara; Sardella, Domenico; Bernard, Loris; Pece, Salvatore; Di Fiore, Pier Paolo; Fumagalli, Caterina; Barberis, Massimo; Spaggiari, Lorenzo; Pelicci, Pier Giuseppe; Riva, Laura

2015-04-01

The efficacy of curative surgery for lung cancer could be largely improved by non-invasive screening programs, which can detect the disease at early stages. We previously showed that 18% of screening-identified lung cancers demonstrate a normal karyotype and, following high-density genome scanning, can be subdivided into samples with 1) numerous; 2) none; and 3) few copy number alterations. Whole exome sequencing was applied to the two normal karyotype, screening-detected lung cancers, constituting group 2, as well as normal controls. We identified mutations in both tumors, including KEAP1 (commonly mutated in lung cancers) in one, and TP53, PMS1, and MSH3 (well-characterized DNA-repair genes) in the other. The two normal karyotype screening-detected lung tumors displayed a typical lung cancer mutational profile that only next generation sequencing could reveal, which offered an additional contribution to the over-diagnosis bias concept hypothesized within lung cancer screening programs. Copyright © 2015 Elsevier Inc. All rights reserved.

The impact of new trends in POCTs for companion diagnostics, non-invasive testing and molecular diagnostics.

PubMed

Huckle, David

2015-06-01

Point-of-care diagnostics have been slowly developing over several decades and have taken on a new importance in current healthcare delivery for both diagnostics and development of new drugs. Molecular diagnostics have become a key driver of technology change and opened up new areas in companion diagnostics for use alongside pharmaceuticals and in new clinical approaches such as non-invasive testing. Future areas involving smartphone and other information technology advances, together with new developments in molecular biology, microfluidics and surface chemistry are adding to advances in the market. The focus for point-of-care tests with molecular diagnostic technologies is focused on advancing effective applications.

Association between cervical screening and prevention of invasive cervical cancer in Ontario: a population-based case-control study.

PubMed

Vicus, Danielle; Sutradhar, Rinku; Lu, Yan; Kupets, Rachel; Paszat, Lawrence

2015-01-01

The aim of this study was to estimate the effect of cervical screening in the prevention of invasive cervical cancer among age groups, using a population-based case-control study in the province of Ontario, Canada. Exposure was defined as cervical cytology history greater than 3 months before the diagnosis date of cervical cancer (index date). Cases were women who were diagnosed with cervical cancer between January 1, 1998, and December 31, 2008. Controls were women without a diagnosis of cervical cancer on, or before, December 31, 2008. Two controls were matched to each case on year of birth and income quintile, as of the index date. Conditional logistic regression was used to estimate the odds ratio for having been screened among those with cervical cancer. Cervical cancer screening performed between 3 and 36 months before the index date was protective against invasive cervical cancer in women aged 40 through 69 years. In women younger than 40 years, cervical cancer screening performed 3 to 36 months before the index date was not protective. Cervical screening is associated with a reduced risk for invasive cervical cancer among women older than 40 years. Cervical cancer resources should be focused on maximizing the risk reduction.

Incidence of breast cancer and estimates of overdiagnosis after the initiation of a population-based mammography screening program.

PubMed

Coldman, Andrew; Phillips, Norm

2013-07-09

There has been growing interest in the overdiagnosis of breast cancer as a result of mammography screening. We report incidence rates in British Columbia before and after the initiation of population screening and provide estimates of overdiagnosis. We obtained the numbers of breast cancer diagnoses from the BC Cancer Registry and screening histories from the Screening Mammography Program of BC for women aged 30-89 years between 1970 and 2009. We calculated age-specific rates of invasive breast cancer and ductal carcinoma in situ. We compared these rates by age, calendar period and screening participation. We obtained 2 estimates of overdiagnosis from cumulative cancer rates among women between the ages of 40 and 89 years: the first estimate compared participants with nonparticipants; the second estimate compared observed and predicted population rates. We calculated participation-based estimates of overdiagnosis to be 5.4% for invasive disease alone and 17.3% when ductal carcinoma in situ was included. The corresponding population-based estimates were -0.7% and 6.7%. Participants had higher rates of invasive cancer and ductal carcinoma in situ than nonparticipants but lower rates after screening stopped. Population incidence rates for invasive cancer increased after 1980; by 2009, they had returned to levels similar to those of the 1970s among women under 60 years of age but remained elevated among women 60-79 years old. Rates of ductal carcinoma in situ increased in all age groups. The extent of overdiagnosis of invasive cancer in our study population was modest and primarily occurred among women over the age of 60 years. However, overdiagnosis of ductal carcinoma in situ was elevated for all age groups. The estimation of overdiagnosis from observational data is complex and subject to many influences. The use of mammography screening in older women has an increased risk of overdiagnosis, which should be considered in screening decisions.

Utilisation of cancer screening services by disabled women in Chile

PubMed Central

Rotarou, Elena S.

2017-01-01

Background Research has shown that women with disabilities face additional challenges in accessing and using healthcare services compared to non-disabled women. However, relatively little is known about the utilisation of cancer screening services for women with disabilities. This study addresses this gap by examining the utilisation of the Papanicolaou test and mammography for disabled women in Chile. Methods We used cross-sectional data, taken from a 2015 nationally-representative survey. Initially, we employed logistic regressions to test for differences in utilisation rates for the Papanicolaou test (66,281 observations) and the mammogram (35,294 observations) between disabled and non-disabled women. Next, logistic regressions were used to investigate the demographic, socioeconomic, and health-related factors affecting utilisation rates for cancer screening services for disabled women (sample sizes: 5,823 observations for the Papanicolaou test and 5,731 observations for the mammogram). Results Disabled women were less likely to undergo screening tests than non-disabled women. For the Papanicolaou test and mammography, the multivariable regression models showed that living in rural areas, having higher education, being affiliated with a private health insurance company, giving a good health self-assessment score, and being under medical treatment for other illnesses were associated with higher utilisation rates. On the other hand, being single, inactive with regard to employment, and having a better income were linked with lower utilisation. While utilisation rates for both disabled and non-disabled women have increased since 2006, the utilisation disparity has slightly increased. Conclusions This study shows the influence of various factors in the utilisation rates of preventive cancer screening services for disabled women. To develop effective initiatives targeting inequalities in the utilisation of cancer screening tests, it is important to move beyond an exclusively single-disease approach and acknowledge the complexity of the patient population. PMID:28459874

Utilisation of cancer screening services by disabled women in Chile.

PubMed

Sakellariou, Dikaios; Rotarou, Elena S

2017-01-01

Research has shown that women with disabilities face additional challenges in accessing and using healthcare services compared to non-disabled women. However, relatively little is known about the utilisation of cancer screening services for women with disabilities. This study addresses this gap by examining the utilisation of the Papanicolaou test and mammography for disabled women in Chile. We used cross-sectional data, taken from a 2015 nationally-representative survey. Initially, we employed logistic regressions to test for differences in utilisation rates for the Papanicolaou test (66,281 observations) and the mammogram (35,294 observations) between disabled and non-disabled women. Next, logistic regressions were used to investigate the demographic, socioeconomic, and health-related factors affecting utilisation rates for cancer screening services for disabled women (sample sizes: 5,823 observations for the Papanicolaou test and 5,731 observations for the mammogram). Disabled women were less likely to undergo screening tests than non-disabled women. For the Papanicolaou test and mammography, the multivariable regression models showed that living in rural areas, having higher education, being affiliated with a private health insurance company, giving a good health self-assessment score, and being under medical treatment for other illnesses were associated with higher utilisation rates. On the other hand, being single, inactive with regard to employment, and having a better income were linked with lower utilisation. While utilisation rates for both disabled and non-disabled women have increased since 2006, the utilisation disparity has slightly increased. This study shows the influence of various factors in the utilisation rates of preventive cancer screening services for disabled women. To develop effective initiatives targeting inequalities in the utilisation of cancer screening tests, it is important to move beyond an exclusively single-disease approach and acknowledge the complexity of the patient population.

Consistency of histopathological reporting of breast lesions detected by screening: findings of the U.K. National External Quality Assessment (EQA) Scheme. U. K. National Coordinating Group for Breast Screening Pathology.

PubMed

Sloane, J P; Ellman, R; Anderson, T J; Brown, C L; Coyne, J; Dallimore, N S; Davies, J D; Eakins, D; Ellis, I O; Elston, C W

1994-01-01

The aim of the scheme was to determine consistency of histopathological reporting in the United Kingdom National Breast Screening Programme. This external quality assessment scheme involved 51 sets of 12 slides which were circulated to 186-251 pathologists at intervals of 6 months for 3 years. Participants recorded their diagnoses on standard reporting forms, which were submitted to the U.K. National Cancer Screening Evaluation Unit for analysis. A high level of consistency was achieved in diagnosing major categories of breast disease including invasive carcinoma and the important borderline lesions, radial scar and ductal carcinoma in situ (DCIS), the latter exceeding a national target set prior to the onset of the scheme. Atypical hyperplasia (AH) was reported with much less consistency although, where it was the majority opinion, over 86% of diagnoses were of benign disorders and only 14% were of DCIS. Inconsistency was encountered in subtyping and measuring DCIS, the former apparently due to current uncertainties about classification and the latter to poor circumscription, variation in size in different sections and merging with zones of AH. Reporting prognostic features of invasive carcinomas was variable. Measurement of size was achieved with adequate consistency except in a small number of very poorly circumscribed tumours. Grading and subtyping were inconsistent although the latter was not specifically tested and will be the subject of future study. Members of the National Coordinating Group achieved greater uniformity than the remainder of the participants in all diagnostic categories, but both groups experienced similar types of problem. Our findings suggest that participation in the scheme improves diagnostic consistency. In conclusion, consistency in diagnosing invasive carcinoma and radial scar is excellent, and good in DCIS, but improvements are desirable in diagnosing atypical hyperplasia, classifying DCIS and reporting certain prognostic features of invasive tumours. Such improvements will require further research, the development of improved diagnostic criteria and the dissemination of clearer guidelines.

Talking Points: Women's Information Needs for Informed Decision-Making About Noninvasive Prenatal Testing for Down Syndrome.

PubMed

Dane, Aimée C; Peterson, Madelyn; Miller, Yvette D

2018-03-17

Adequate knowledge is a vital component of informed decision-making; however, we do not know what information women value when making decisions about noninvasive prenatal testing (NIPT). The current study aimed to identify women's information needs for decision-making about NIPT as a first-tier, non-contingent test with out-of-pocket expense and, in turn, inform best practice by specifying the information that should be prioritized when providing pre-test counseling to women in a time-limited scenario or space-limited decision support tool. We asked women (N = 242) in Australia to indicate the importance of knowing 24 information items when making a decision about NIPT and to choose two information items they would most value. Our findings suggest that women value having complete information when making decisions about NIPT. Information about the accuracy of NIPT and the pros and cons of NIPT compared to other screening and invasive tests were perceived to be most important. The findings of this study can be used to maximize the usefulness of time-limited discussions or space-limited decision support tools, but should not be routinely relied upon as a replacement for provision of full and tailored information when feasible.

Non-invasive determination of the complete elastic moduli of spider silks

NASA Astrophysics Data System (ADS)

Koski, Kristie J.; Akhenblit, Paul; McKiernan, Keri; Yarger, Jeffery L.

2013-03-01

Spider silks possess nature’s most exceptional mechanical properties, with unrivalled extensibility and high tensile strength. Unfortunately, our understanding of silks is limited because the complete elastic response has never been measured—leaving a stark lack of essential fundamental information. Using non-invasive, non-destructive Brillouin light scattering, we obtain the entire stiffness tensors (revealing negative Poisson’s ratios), refractive indices, and longitudinal and transverse sound velocities for major and minor ampullate spider silks: Argiope aurantia, Latrodectus hesperus, Nephila clavipes, Peucetia viridans. These results completely quantify the linear elastic response for all possible deformation modes, information unobtainable with traditional stress-strain tests. For completeness, we apply the principles of Brillouin imaging to spatially map the elastic stiffnesses on a spider web without deforming or disrupting the web in a non-invasive, non-contact measurement, finding variation among discrete fibres, junctions and glue spots. Finally, we provide the stiffness changes that occur with supercontraction.

Non-invasive assessment of respiratory muscle function and its relationship to exercise tolerance in patients with chronic obstructive pulmonary disease.

PubMed

Chlumský, J; Filipova, P; Terl, M

2006-01-01

Most patients with chronic obstructive pulmonary disease (COPD) have impaired respiratory muscle function. Maximal oesophageal pressure correlates closely with exercise tolerance and seems to predict the distance walked during the 6-min walk test. This study assessed the non-invasive parameters of respiratory muscle function in 41 patients with COPD to investigate their relationship to pulmonary function tests and exercise tolerance. The COPD patients, who demonstrated the full range of airway obstruction severity, had a mean forced expiratory volume in 1 s of 42.5% predicted (range, 20 - 79% predicted). Both the maximal inspiratory muscle strength and non-invasive tension-time index were significantly correlated with the degree of lung hyperinflation, as expressed by the ratio of residual volume to total lung capacity, and the distance walked in 6 min. We conclude that respiratory muscle function was influenced mainly by lung hyperinflation and that it had an important effect on exercise tolerance in COPD patients.

Real-time Quaking-induced Conversion Assay for Detection of CWD Prions in Fecal Material.

PubMed

Cheng, Yo Ching; Hannaoui, Samia; John, Theodore Ralph; Dudas, Sandor; Czub, Stefanie; Gilch, Sabine

2017-09-29

The RT-QuIC technique is a sensitive in vitro cell-free prion amplification assay based mainly on the seeded misfolding and aggregation of recombinant prion protein (PrP) substrate using prion seeds as a template for the conversion. RT-QuIC is a novel high-throughput technique which is analogous to real-time polymerase chain reaction (PCR). Detection of amyloid fibril growth is based on the dye Thioflavin T, which fluoresces upon specific interaction with ᵦ-sheet rich proteins. Thus, amyloid formation can be detected in real time. We attempted to develop a reliable non-invasive screening test to detect chronic wasting disease (CWD) prions in fecal extract. Here, we have specifically adapted the RT-QuIC technique to reveal PrP Sc seeding activity in feces of CWD infected cervids. Initially, the seeding activity of the fecal extracts we prepared was relatively low in RT-QuIC, possibly due to potential assay inhibitors in the fecal material. To improve seeding activity of feces extracts and remove potential assay inhibitors, we homogenized the fecal samples in a buffer containing detergents and protease inhibitors. We also submitted the samples to different methodologies to concentrate PrP Sc on the basis of protein precipitation using sodium phosphotungstic acid, and centrifugal force. Finally, the feces extracts were tested by optimized RT-QuIC which included substrate replacement in the protocol to improve the sensitivity of detection. Thus, we established a protocol for sensitive detection of CWD prion seeding activity in feces of pre-clinical and clinical cervids by RT-QuIC, which can be a practical tool for non-invasive CWD diagnosis.

The diagnostic process of cervical cancer; areas of good practice, and windows of opportunity.

PubMed

Zaal, Afra; de Wilde, Marlieke A; Duk, M Jitze; Graziosi, G C; van Haaften, Maarten; von Mensdorff-Pouilly, Silvia; van Diest, Paul J; Zweemer, Ronald P; Peeters, Petra H; Verheijen, René H M

2015-08-01

Despite an extensive screening programme in The Netherlands, some cases of cervical cancer are still diagnosed in late stages of disease. The aim of the present study was to investigate which elements in the diagnostic process of cervical cancer may be improved. This is a retrospective study of 120 patients with cervical cancer diagnosed between January 1st 2008 and June 1st 2010 at the University Medical Center Utrecht. Patient charts, referral information, and pathology results were analyzed. 39.1% of cancer cases were screen or interval detected; the other 60.9% of patients had not been screened, either due to non-attendance or because they fell outside the age range for screening. The final diagnosis of cervical cancer was established by biopsy in 77 (64.2%) and by excision of the cervical transformation zone in 35 (29.2%) of the patients. Fifteen (43%) of these excisions could have been avoided if biopsies would have been taken at the first examination, and had shown invasive cancer. Cervical cancer screening aims at early detection of precursor lesions to decrease the incidence of cancer. This in-depth analysis suggests that improvement of quality of care is to be expected from correct recognition of cervical cancer by physicians and adjustments of the screening programme to reach younger women and non-responders. Copyright © 2015 Elsevier Inc. All rights reserved.

Technology-enabled examinations of cardiac rhythm, optic nerve, oral health, tympanic membrane, gait and coordination evaluated jointly with routine health screenings: an observational study at the 2015 Kumbh Mela in India

PubMed Central

Gupta, Otkrist; Patalano II, Vincent; Mohit, Mrinal; Merchant, Rikin; Subramanian, S V

2018-01-01

Objectives Technology-enabled non-invasive diagnostic screening (TES) using smartphones and other point-of-care medical devices was evaluated in conjunction with conventional routine health screenings for the primary care screening of patients. Design Dental conditions, cardiac ECG arrhythmias, tympanic membrane disorders, blood oxygenation levels, optic nerve disorders and neurological fitness were evaluated using FDA-approved advanced smartphone powered technologies. Routine health screenings were also conducted. A novel remote web platform was developed to allow expert physicians to examine TES data and compare efficacy with routine health screenings. Setting The study was conducted at a primary care centre during the 2015 Kumbh Mela in Maharashtra, India. Participants 494 consenting 18–90 years old adults attending the 2015 Kumbh Mela were tested. Results TES and routine health screenings identified unique clinical conditions in distinct patients. Intraoral fluorescent imaging classified 63.3% of the population with dental caries and periodontal diseases. An association between poor oral health and cardiovascular illnesses was also identified. Tympanic membrane imaging detected eardrum abnormalities in 13.0% of the population, several with a medical history of hearing difficulties. Gait and coordination issues were discovered in eight subjects and one subject had arrhythmia. Cross-correlations were observed between low oxygen saturation and low body mass index (BMI) with smokers (p=0.0087 and p=0.0122, respectively), and high BMI was associated with elevated blood pressure in middle-aged subjects. Conclusions TES synergistically identified clinically significant abnormalities in several subjects who otherwise presented as normal in routine health screenings. Physicians validated TES findings and used routine health screening data and medical history responses for comprehensive diagnoses for at-risk patients. TES identified high prevalence of oral diseases, hypertension, obesity and ophthalmic conditions among the middle-aged and elderly Indian population, calling for public health interventions. PMID:29678964

Utility and reliability of non-invasive muscle function tests in high-fat-fed mice.

PubMed

Martinez-Huenchullan, Sergio F; McLennan, Susan V; Ban, Linda A; Morsch, Marco; Twigg, Stephen M; Tam, Charmaine S

2017-07-01

What is the central question of this study? Non-invasive muscle function tests have not been validated for use in the study of muscle performance in high-fat-fed mice. What is the main finding and its importance? This study shows that grip strength, hang wire and four-limb hanging tests are able to discriminate the muscle performance between chow-fed and high-fat-fed mice at different time points, with grip strength being reliable after 5, 10 and 20 weeks of dietary intervention. Non-invasive tests are commonly used for assessing muscle function in animal models. The value of these tests in obesity, a condition where muscle strength is reduced, is unclear. We investigated the utility of three non-invasive muscle function tests, namely grip strength (GS), hang wire (HW) and four-limb hanging (FLH), in C57BL/6 mice fed chow (chow group, n = 48) or a high-fat diet (HFD group, n = 48) for 20 weeks. Muscle function tests were performed at 5, 10 and 20 weeks. After 10 and 20 weeks, HFD mice had significantly reduced GS (in newtons; mean ± SD: 10 weeks chow, 1.89 ± 0.1 and HFD, 1.79 ± 0.1; 20 weeks chow, 1.99 ± 0.1 and HFD, 1.75 ± 0.1), FLH [in seconds per gram body weight; median (interquartile range): 10 weeks chow, 2552 (1337-4964) and HFD, 1230 (749-1994); 20 weeks chow, 2048 (765-3864) and HFD, 1036 (717-1855)] and HW reaches [n; median (interquartile range): 10 weeks chow, 4 (2-5) and HFD, 2 (1-3); 20 weeks chow, 3 (1-5) and HFD, 1 (0-2)] and higher falls [n; median (interquartile range): 10 weeks chow, 0 (0-2) and HFD, 3 (1-7); 20 weeks chow, 1 (0-4) and HFD, 8 (5-10)]. Grip strength was reliable in both dietary groups [intraclass correlation coefficient (ICC) = 0.5-0.8; P < 0.05], whereas FLH showed good reliability in chow (ICC = 0.7; P < 0.05) but not in HFD mice after 10 weeks (ICC < 0.5). Our data demonstrate that non-invasive muscle function tests are valuable and reliable tools for assessment of muscle strength and function in high-fat-fed mice. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Chick Heart Invasion Assay for Testing the Invasiveness of Cancer Cells and the Activity of Potentially Anti-invasive Compounds.

PubMed

Bracke, Marc E; Roman, Bart I; Stevens, Christian V; Mus, Liselot M; Parmar, Virinder S; De Wever, Olivier; Mareel, Marc M

2015-06-06

The goal of the chick heart assay is to offer a relevant organ culture method to study tumor invasion in three dimensions. The assay can distinguish between invasive and non-invasive cells, and enables study of the effects of test compounds on tumor invasion. Cancer cells - either as aggregates or single cells - are confronted with fragments of embryonic chick heart. After organ culture in suspension for a few days or weeks the confronting cultures are fixed and embedded in paraffin for histological analysis. The three-dimensional interaction between the cancer cells and the normal tissue is then reconstructed from serial sections stained with hematoxylin-eosin or after immunohistochemical staining for epitopes in the heart tissue or the confronting cancer cells. The assay is consistent with the recent concept that cancer invasion is the result of molecular interactions between the cancer cells and their neighbouring stromal host elements (myofibroblasts, endothelial cells, extracellular matrix components, etc.). Here, this stromal environment is offered to the cancer cells as a living tissue fragment. Supporting aspects to the relevance of the assay are multiple. Invasion in the assay is in accordance with the criteria of cancer invasion: progressive occupation and replacement in time and space of the host tissue, and invasiveness and non-invasiveness in vivo of the confronting cells generally correlates with the outcome of the assay. Furthermore, the invasion pattern of cells in vivo, as defined by pathologists, is reflected in the histological images in the assay. Quantitative structure-activity relation (QSAR) analysis of the results obtained with numerous potentially anti-invasive organic congener compounds allowed the study of structure-activity relations for flavonoids and chalcones, and known anti-metastatic drugs used in the clinic (e.g., microtubule inhibitors) inhibit invasion in the assay as well. However, the assay does not take into account immunological contributions to cancer invasion.

Understanding Your Test Results

MedlinePlus

... consuming. MRI (magnetic resonance imaging) MRI is a non-invasive study that uses mag- netic energy, not ... 1. Disease recurrence. 2. Disease that is technically non-secretory (so low level that it cannot be ...

Impact of gender on decisions to participate in faecal immunochemical test-based colorectal cancer screening: a qualitative study.

PubMed

Clarke, Nicholas; Gallagher, Pamela; Kearney, Patricia M; McNamara, Deirdre; Sharp, Linda

2016-12-01

Faecal immunochemical tests (FITs) are increasingly being used in population-based colorectal cancer-screening programmes. Uptake of FIT is lower in men than women; however, the reasons for this are not well understood. We aimed to explore gender differences in influences on decisions to participate in FIT screening. This is a qualitative study using in-depth face-to-face interviews of four groups of screening invitees (male and female screening users and male and female screening non-users), purposively sampled from the database of a population-based FIT screening programme. Recruitment continued until saturation was reached. Interviews were audio recorded and transcribed verbatim. Thematic analysis using the framework approach was employed with the theoretical domains framework guiding analysis. Forty-seven screening invitees were interviewed. Six theoretical domains influenced screening uptake: 'environmental context and resources', 'beliefs about capabilities', 'beliefs about consequences', 'emotions', 'social influences' and 'knowledge'. Male non-users were often fatalistic, less knowledgeable and misinformed about cancer and FIT screening compared with other groups. Female non-users expressed negative attitudes, beliefs and emotions towards FIT screening, cancer, social influences and the medical profession and were over-confident about their health. Negative attitudes and emotions to screening dominated non-user decision-making but differed by gender. Opportunities to improve uptake in men and women exist. Greater national discussions on the benefits of FIT screening, and development of screening materials tackling negative attitudes and beliefs while recognising male/female differences, may improve screening uptake. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Non-invasive characterization of real-time bladder sensation using accelerated hydration and a novel sensation meter: An initial experience

PubMed Central

Nagle, Anna S.; Speich, John E.; De Wachter, Stefan G.; Ghamarian, Peter P.; Le, David M.; Colhoun, Andrew F.; Ratz, Paul H.; Barbee, Robert W.; Klausner, Adam P.

2016-01-01

AIMS The purpose of this investigation was to develop a non-invasive, objective, and unprompted method to characterize real-time bladder sensation. METHODS Volunteers with and without overactive bladder (OAB) were prospectively enrolled in a preliminary accelerated hydration study. Participants drank 2L Gatorade-G2® and recorded real-time sensation (0–100% scale) and standardized verbal sensory thresholds using a novel, touch-screen “sensation meter.” 3D bladder ultrasound images were recorded throughout fillings for a subset of participants. Sensation data were recorded for two consecutive complete fill-void cycles. RESULTS Data from 14 normal and 12 OAB participants were obtained (ICIq-OAB-5a = 0 vs. ≥3). Filling duration decreased in fill2 compared to fill1, but volume did not significantly change. In normals, adjacent verbal sensory thresholds (within fill) showed no overlap, and identical thresholds (between fill) were similar, demonstrating effective differentiation between degrees of %bladder capacity. In OAB, within-fill overlaps and between-fill differences were identified. Real-time %capacity-sensation curves left shifted from fill1 to fill2 in normals, consistent with expected viscoelastic behavior, but unexpectedly right shifted in OAB. 3D ultrasound volume data showed that fill rates started slowly and ramped up with variable end points. CONCLUSIONS This study establishes a non-invasive means to evaluate real-time bladder sensation using a two-fill accelerated hydration protocol and a sensation meter. Verbal thresholds were inconsistent in OAB, and the right shift in OAB %capacity–sensation curve suggests potential biomechanical and/or sensitization changes. This methodology could be used to gain valuable information on different forms of OAB in a completely non-invasive way. PMID:27654469

Non-invasive characterization of real-time bladder sensation using accelerated hydration and a novel sensation meter: An initial experience.

PubMed

Nagle, Anna S; Speich, John E; De Wachter, Stefan G; Ghamarian, Peter P; Le, David M; Colhoun, Andrew F; Ratz, Paul H; Barbee, Robert W; Klausner, Adam P

2017-06-01

The purpose of this investigation was to develop a non-invasive, objective, and unprompted method to characterize real-time bladder sensation. Volunteers with and without overactive bladder (OAB) were prospectively enrolled in a preliminary accelerated hydration study. Participants drank 2L Gatorade-G2® and recorded real-time sensation (0-100% scale) and standardized verbal sensory thresholds using a novel, touch-screen "sensation meter." 3D bladder ultrasound images were recorded throughout fillings for a subset of participants. Sensation data were recorded for two consecutive complete fill-void cycles. Data from 14 normal and 12 OAB participants were obtained (ICIq-OAB-5a = 0 vs. ≥3). Filling duration decreased in fill2 compared to fill1, but volume did not significantly change. In normals, adjacent verbal sensory thresholds (within fill) showed no overlap, and identical thresholds (between fill) were similar, demonstrating effective differentiation between degrees of %bladder capacity. In OAB, within-fill overlaps and between-fill differences were identified. Real-time %capacity-sensation curves left shifted from fill1 to fill2 in normals, consistent with expected viscoelastic behavior, but unexpectedly right shifted in OAB. 3D ultrasound volume data showed that fill rates started slowly and ramped up with variable end points. This study establishes a non-invasive means to evaluate real-time bladder sensation using a two-fill accelerated hydration protocol and a sensation meter. Verbal thresholds were inconsistent in OAB, and the right shift in OAB %capacity-sensation curve suggests potential biomechanical and/or sensitization changes. This methodology could be used to gain valuable information on different forms of OAB in a completely non-invasive way. © 2016 Wiley Periodicals, Inc.

Visual in vivo degradation of injectable hydrogel by real-time and non-invasive tracking using carbon nanodots as fluorescent indicator.

PubMed

Wang, Lei; Li, Baoqiang; Xu, Feng; Li, Ying; Xu, Zheheng; Wei, Daqing; Feng, Yujie; Wang, Yaming; Jia, Dechang; Zhou, Yu

2017-11-01

Visual in vivo degradation of hydrogel by fluorescence-related tracking and monitoring is crucial for quantitatively depicting the degradation profile of hydrogel in a real-time and non-invasive manner. However, the commonly used fluorescent imaging usually encounters limitations, such as intrinsic photobleaching of organic fluorophores and uncertain perturbation of degradation induced by the change in molecular structure of hydrogel. To address these problems, we employed photoluminescent carbon nanodots (CNDs) with low photobleaching, red emission and good biocompatibility as fluorescent indicator for real-time and non-invasive visual in vitro/in vivo degradation of injectable hydrogels that are mixed with CNDs. The in vitro/in vivo toxicity results suggested that CNDs were nontoxic. The embedded CNDs in hydrogels did not diffuse outside in the absence of hydrogel degradation. We had acquired similar degradation kinetics (PBS-Enzyme) between gravimetric and visual determination, and established mathematical equation to quantitatively depict in vitro degradation profile of hydrogels for the predication of in vivo hydrogel degradation. Based on the in vitro data, we developed a visual platform that could quantitatively depict in vivo degradation behavior of new injectable biomaterials by real-time and non-invasive fluorescence tracking. This fluorescence-related visual imaging methodology could be applied to subcutaneous degradation of injectable hydrogel with down to 7 mm depth in small animal trials so far. This fluorescence-related visual imaging methodology holds great potentials for rational design and convenient in vivo screening of biocompatible and biodegradable injectable hydrogels in tissue engineering. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cell-Free DNA Analysis of Targeted Genomic Regions in Maternal Plasma for Non-Invasive Prenatal Testing of Trisomy 21, Trisomy 18, Trisomy 13, and Fetal Sex.

PubMed

Koumbaris, George; Kypri, Elena; Tsangaras, Kyriakos; Achilleos, Achilleas; Mina, Petros; Neofytou, Maria; Velissariou, Voula; Christopoulou, Georgia; Kallikas, Ioannis; González-Liñán, Alicia; Benusiene, Egle; Latos-Bielenska, Anna; Marek, Pietryga; Santana, Alfredo; Nagy, Nikoletta; Széll, Márta; Laudanski, Piotr; Papageorgiou, Elisavet A; Ioannides, Marios; Patsalis, Philippos C

2016-06-01

There is great need for the development of highly accurate cost effective technologies that could facilitate the widespread adoption of noninvasive prenatal testing (NIPT). We developed an assay based on the targeted analysis of cell-free DNA for the detection of fetal aneuploidies of chromosomes 21, 18, and 13. This method enabled the capture and analysis of selected genomic regions of interest. An advanced fetal fraction estimation and aneuploidy determination algorithm was also developed. This assay allowed for accurate counting and assessment of chromosomal regions of interest. The analytical performance of the assay was evaluated in a blind study of 631 samples derived from pregnancies of at least 10 weeks of gestation that had also undergone invasive testing. Our blind study exhibited 100% diagnostic sensitivity and specificity and correctly classified 52/52 (95% CI, 93.2%-100%) cases of trisomy 21, 16/16 (95% CI, 79.4%-100%) cases of trisomy 18, 5/5 (95% CI, 47.8%-100%) cases of trisomy 13, and 538/538 (95% CI, 99.3%-100%) normal cases. The test also correctly identified fetal sex in all cases (95% CI, 99.4%-100%). One sample failed prespecified assay quality control criteria, and 19 samples were nonreportable because of low fetal fraction. The extent to which free fetal DNA testing can be applied as a universal screening tool for trisomy 21, 18, and 13 depends mainly on assay accuracy and cost. Cell-free DNA analysis of targeted genomic regions in maternal plasma enables accurate and cost-effective noninvasive fetal aneuploidy detection, which is critical for widespread adoption of NIPT. © 2016 American Association for Clinical Chemistry.

Establishing an EGFR mutation screening service for non-small cell lung cancer - sample quality criteria and candidate histological predictors.

PubMed

Leary, Alexandra F; Castro, David Gonzalez de; Nicholson, Andrew G; Ashley, Sue; Wotherspoon, Andrew; O'Brien, Mary E R; Popat, Sanjay

2012-01-01

EGFR screening requires good quality tissue, sensitivity and turn-around time (TAT). We report our experience of routine screening, describing sample type, TAT, specimen quality (cellularity and DNA yield), histopathological description, mutation result and clinical outcome. Non-small cell lung cancer (NSCLC) sections were screened for EGFR mutations (M+) in exons 18-21. Clinical, pathological and screening outcome data were collected for year 1 of testing. Screening outcome alone was collected for year 2. In year 1, 152 samples were tested, most (72%) were diagnostic. TAT was 4.9 days (95%confidence interval (CI)=4.5-5.5). EGFR-M+ prevalence was 11% and higher (20%) among never-smoking women with adenocarcinomas (ADCs), but 30% of mutations occurred in current/ex-smoking men. EGFR-M+ tumours were non-mucinous ADCs and 100% thyroid transcription factor (TTF1+). No mutations were detected in poorly differentiated NSCLC-not otherwise specified (NOS). There was a trend for improved overall survival (OS) among EGFR-M+ versus EGFR-M- patients (median OS=78 versus 17 months). In year 1, test failure rate was 19%, and associated with scant cellularity and low DNA concentrations. However 75% of samples with poor cellularity but representative of tumour were informative and mutation prevalence was 9%. In year 2, 755 samples were tested; mutation prevalence was 13% and test failure only 5.4%. Although samples with low DNA concentration (<2 ng/μL) had more test failures (30% versus 3.9% for [DNA]>2.2 ng/μL), the mutation rate was 9.2%. Routine epidermal growth factor receptor (EGFR) screening using diagnostic samples is fast and feasible even on samples with poor cellularity and DNA content. Mutations tend to occur in better-differentiated non-mucinous TTF1+ ADCs. Whether these histological criteria may be useful to select patients for EGFR testing merits further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prevalence of high-risk human papilloma virus genotypes and associated risk of cervical precancerous lesions in a large U.S. screening population: data from the ATHENA trial.

PubMed

Monsonego, Joseph; Cox, J Thomas; Behrens, Catherine; Sandri, Maria; Franco, Eduardo L; Yap, Poh-Sin; Huh, Warner

2015-04-01

We assessed the age-related prevalence of high risk human papillomavirus (HR-HPV) genotypes and the genotype-associated risk for high-grade cervical intraepithelial neoplasia (CIN) in a large U.S. screening population. A total of 40,901 women aged ≥25 years were screened with liquid-based cytology and HPV testing in the ATHENA (Addressing the Need for Advanced HPV Diagnostics) trial. Genotyping was performed using the LINEAR ARRAY HPV Genotyping Test. HPV16 was the most prevalent genotype in all age groups, ranging from 3.5% to 0.8% in women aged 25-29 and ≥50 years, respectively. The next most prevalent genotypes were HPV52, HPV31 and HPV18. In the overall population, HPV16 conferred the greatest absolute risk of ≥CIN3 both in women aged 25-29 and ≥30 years (14.2% and 15.1%, respectively) followed by HPV31 (8.0% and 7.9%), HPV52 (6.7% and 4.4%) and HPV18 (2.7% and 9.0%). Similar trends were seen in women with negative cytology. The percent positivity increased markedly with disease progression for HPV16 and HPV18 which were responsible for 45.6% and 8.4% of ≥CIN3, respectively. Of note, HPV 18 was responsible for 50% of adenocarcinoma in situ (AIS) and 50% of invasive cancer cases. HPV16 played a major role in the development of ≥CIN3 irrespective of age, supporting the identification of HPV16 in primary screening for all women. Identification of HPV18 is also warranted, given its significant contribution to AIS and cancer. Identification of non-16/18 genotypes as a pool should provide sufficient information for screening. Copyright © 2015. Published by Elsevier Inc.

Simulation models in population breast cancer screening: A systematic review.

PubMed

Koleva-Kolarova, Rositsa G; Zhan, Zhuozhao; Greuter, Marcel J W; Feenstra, Talitha L; De Bock, Geertruida H

2015-08-01

The aim of this review was to critically evaluate published simulation models for breast cancer screening of the general population and provide a direction for future modeling. A systematic literature search was performed to identify simulation models with more than one application. A framework for qualitative assessment which incorporated model type; input parameters; modeling approach, transparency of input data sources/assumptions, sensitivity analyses and risk of bias; validation, and outcomes was developed. Predicted mortality reduction (MR) and cost-effectiveness (CE) were compared to estimates from meta-analyses of randomized control trials (RCTs) and acceptability thresholds. Seven original simulation models were distinguished, all sharing common input parameters. The modeling approach was based on tumor progression (except one model) with internal and cross validation of the resulting models, but without any external validation. Differences in lead times for invasive or non-invasive tumors, and the option for cancers not to progress were not explicitly modeled. The models tended to overestimate the MR (11-24%) due to screening as compared to optimal RCTs 10% (95% CI - 2-21%) MR. Only recently, potential harms due to regular breast cancer screening were reported. Most scenarios resulted in acceptable cost-effectiveness estimates given current thresholds. The selected models have been repeatedly applied in various settings to inform decision making and the critical analysis revealed high risk of bias in their outcomes. Given the importance of the models, there is a need for externally validated models which use systematical evidence for input data to allow for more critical evaluation of breast cancer screening. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-invasive prenatal diagnosis for cystic fibrosis: detection of paternal mutations, exploration of patient preferences and cost analysis.

PubMed

Hill, Melissa; Twiss, Philip; Verhoef, Talitha I; Drury, Suzanne; McKay, Fiona; Mason, Sarah; Jenkins, Lucy; Morris, Stephen; Chitty, Lyn S

2015-10-01

We aim to develop non-invasive prenatal diagnosis (NIPD) for cystic fibrosis (CF) and determine costs and implications for implementation. A next-generation sequencing assay was developed to detect ten common CF mutations for exclusion of the paternal mutation in maternal plasma. Using uptake data from a study exploring views on NIPD for CF, total test-related costs were estimated for the current care pathway and compared with those incorporating NIPD. The assay reliably predicted mutation status in all control and maternal plasma samples. Of carrier or affected adults with CF (n = 142) surveyed, only 43.5% reported willingness to have invasive testing for CF with 94.4% saying they would have NIPD. Using these potential uptake data, the incremental costs of NIPD over invasive testing per 100 pregnancies at risk of CF are £9025 for paternal mutation exclusion, and £26,510 for direct diagnosis. We have developed NIPD for risk stratification in around a third of CF families. There are economic implications due to potential increased test demand to inform postnatal management rather than to inform decisions around termination of an affected pregnancy. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Non-invasive prenatal diagnosis for cystic fibrosis: detection of paternal mutations, exploration of patient preferences and cost analysis

PubMed Central

Hill, Melissa; Twiss, Philip; Verhoef, Talitha I; Drury, Suzanne; McKay, Fiona; Mason, Sarah; Jenkins, Lucy; Morris, Stephen; Chitty, Lyn S

2015-01-01

Abstract Objectives We aim to develop non-invasive prenatal diagnosis (NIPD) for cystic fibrosis (CF) and determine costs and implications for implementation. Methods A next-generation sequencing assay was developed to detect ten common CF mutations for exclusion of the paternal mutation in maternal plasma. Using uptake data from a study exploring views on NIPD for CF, total test-related costs were estimated for the current care pathway and compared with those incorporating NIPD. Results The assay reliably predicted mutation status in all control and maternal plasma samples. Of carrier or affected adults with CF (n = 142) surveyed, only 43.5% reported willingness to have invasive testing for CF with 94.4% saying they would have NIPD. Using these potential uptake data, the incremental costs of NIPD over invasive testing per 100 pregnancies at risk of CF are £9025 for paternal mutation exclusion, and £26 510 for direct diagnosis. Conclusions We have developed NIPD for risk stratification in around a third of CF families. There are economic implications due to potential increased test demand to inform postnatal management rather than to inform decisions around termination of an affected pregnancy. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. PMID:25708280

Near-Infrared Spectroscopy as a Novel Non-Invasive Tool to Assess Spiny Lobster Nutritional Condition

PubMed Central

Rodemann, Thomas; Carter, Chris G.

2016-01-01

Rapid non-invasive monitoring of spiny lobster nutritional condition has considerable application in the established fishery, live market and prospective aquaculture. The aim of this research was to test the feasibility of near-infrared spectroscopy (NIRS) as a novel non-invasive tool to assess the nutritional condition of three lobster species. Lobster (n = 92) abdominal muscle dry matter (AMDM) and carbon content (AMC) correlated significantly with indices of nutritional condition including hepatopancreas dry matter (HPDM; rho = 0.83, 0.78), total lipid content (HPTL; rho = 0.85, 0.87) and haemolymph total protein (TP; rho = 0.89, 0.87 respectively). Abdominal muscle nitrogen content (AMN) was a poor correlate of nutritional condition. Models based on FT-NIR scanning of whole lobster tails successfully predicted AMDM, AMN and AMC (RMSECV = 1.41%, 0.35% and 0.91%; R2 = 0.75, 0.65, 0.77, respectively), and to a lower accuracy HPDM, HPTL and TP (RMSECV = 6.22%, 8.37%, 18.4 g l-1; R2 = 0.51, 0.70, 0.83, respectively). NIRS was applied successfully to assess the condition of spiny lobsters non-invasively. This pilot study paves the way for the development of crustacean condition models using portable non-invasive devices in the laboratory or in the field. PMID:27442242

Liquid biopsy: a step forward towards precision medicine in urologic malignancies.

PubMed

Di Meo, Ashley; Bartlett, Jenni; Cheng, Yufeng; Pasic, Maria D; Yousef, George M

2017-04-14

There is a growing trend towards exploring the use of a minimally invasive "liquid biopsy" to identify biomarkers in a number of cancers, including urologic malignancies. Multiple aspects can be assessed in circulating cell-free DNA, including cell-free DNA levels, integrity, methylation and mutations. Other prospective liquid biopsy markers include circulating tumor cells, circulating RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have also emerged as non-invasive cancer biomarkers. These circulating molecules can be detected in various biological fluids, including blood, urine, saliva and seminal plasma. Liquid biopsies hold great promise for personalized medicine due to their ability to provide multiple non-invasive global snapshots of the primary and metastatic tumors. Molecular profiling of circulating molecules has been a stepping-stone to the successful introduction of several non-invasive multi-marker tests into the clinic. In this review, we provide an overview of the current state of cell-free DNA-based kidney, prostate and bladder cancer biomarker research and discuss the potential utility other circulating molecules. We will also discuss the challenges and limitations facing non-invasive cancer biomarker discovery and the benefits of this growing area of translational research.

Allelochemical Control of Non-Indigenous Invasive Plant Species Affecting Military Testing and Training Activities

DTIC Science & Technology

2010-10-01

Evolution in invasive plants : implications for biological control. Trends in Ecology & Evolution . 19:417-422. Newingham, B.A. and R.M. Callaway...2008. Soil ecological interactions of spotted knapweed and native plant species. M.S. Thesis. Colorado State University. Fort Collins, CO...weapons and exotic plant invasions. NSF workshop on ecology and biochemical interactions , Lima. Peru. May. Keynote presentation. Callaway, R.M

Screening for Barrett’s Esophagus and Esophageal Adenocarcinoma: Rationale, Recent Progress, Challenges and Future Directions

PubMed Central

Sami, Sarmed S.; Ragunath, Krish; Iyer, Prasad G.

2014-01-01

As the incidence and mortality of esophageal adenocarcinoma continue to increase, strategies to counter this need to be explored. Screening for Barrett’s esophagus, which is the known precursor of a large majority of adenocarcinomas, has been debated without a firm consensus. Given evidence for and against perceived benefits of screening, the multitude of challenges in the implementation of such a strategy and in the downstream management of subjects with Barrett’s esophagus who could be diagnosed by screening, support for screening has been modest. Recent advances in form of development and initial accuracy of non-invasive tools for screening, risk assessment tools and biomarker panels to risk stratify subjects with BE, have spurred renewed interest in the early detection of Barrett’s esophagus and related neoplasia, particularly with the advent of effective endoscopic therapy. In this review, we explore in depth, the potential rationale for screening for Barrett’s esophagus, recent advances which have the potential of making screening feasible and also highlight some of the challenges which will have to be overcome to develop an effective approach to improve the outcomes of subjects with esophageal adenocarcinoma. PMID:24887058

Cell-free fetal DNA versus maternal serum screening for trisomy 21 in pregnant women with and without assisted reproduction technology: a prospective interventional study.

PubMed

Costa, Jean-Marc; Letourneau, Alexandra; Favre, Romain; Bidat, Laurent; Belaisch-Allart, Joelle; Jouannic, Jean-Marie; Quarello, Edwin; Senat, Marie-Victoire; Broussin, Bernard; Tsatsaris, Vassilis; Demain, Adèle; Kleinfinger, Pascale; Lohmann, Laurence; Agostini, Hélène; Bouyer, Jean; Benachi, Alexandra

2018-03-01

PurposeCell-free DNA (cfDNA) as a primary screening test has been available for years but few studies have addressed this option in a prospective manner. The question is of interest after reports that maternal serum screening (MSS) is less accurate for pregnancies resulting from assisted reproduction technologies (ART) than for spontaneous pregnancies (SP).MethodsA prospective interventional study was designed to address the performances of cfDNA compared with MSS in pregnancies with or without ART. Each patient was offered both MSS and cfDNA testing. The primary analysis cohort ultimately included 794 patients with a spontaneous pregnancy (SP) (n = 472) or pregnancy obtained after ART (n = 322).ResultsOverall, the false-positive rate and positive predictive value were 6.6% and 8.8% for MSS but 0% and 100% for cfDNA. MSS false-positive rate and positive predictive values were clearly poorer in the ART group (11.7% and 2.6%) than in the SP group (3.2% and 21.1%). The global rates of invasive procedures were 1.9% (15/794) with cfDNA but 8.4% (65/794) if MSS alone was proposed.ConclusioncfDNA achieved better performance than MSS in both spontaneous and ART pregnancies, thus decreasing the number of invasive procedures. Our findings suggest that cfDNA should be considered for primary screening, especially in pregnancies obtained after ART.GENETICS in MEDICINE advance online publication, 1 March 2018; doi:10.1038/gim.2018.4.

[Value of non-invasive models of liver fibrosis in judgment of treatment timing in chronic hepatitis B patients with ALT < 2×upper limit of normal].

PubMed

Zhou, Q Q; Hu, Y B; Zhou, K; Zhang, W W; Li, M H; Dong, P; Di, J G; Hong, L; Du, Q W; Xie, Y; Sun, Q F

2016-09-20

Objective: To investigate the value of non-invasive liver fibrosis models, FIB-4, S index, aspartate aminotransferase to platelet ratio index(APRI), globulin-platelet(GP)model, aspartate aminotransferase/platelet/gamma-glutamyl transpeptidase/alpha-fetoprotein(APGA), and platelet/age/phosphatase/alpha-fetoprotein/aspartate aminotransferase(PAPAS), in the diagnosis of marked liver fibrosis in chronic hepatitis B(CHB)patients with ALT < 2×upper limit of normal(ULN), as well as treatment timing for this population. Methods: A total of 389 CHB patients with ALT < 2×ULN who were admitted to Beijing Ditan Hospital and whose treatment timing was difficult to judge were enrolled. Transdermal liver biopsy was performed to obtain pathological results, and routine serological tests were performed, including routine blood test, serum biochemical parameters, hepatitis B virus(HBV)markers, and HBV DNA. According to liver pathology, the patients were divided into non-marked liver fibrosis group(S < 2)with 324 patients and marked liver fibrosis group(S≥2)with 65 patients. The non-invasive models for predicting liver fibrosis was established with reference to original articles. SPSS 19.0 software was used for statistical analysis, and the receiver operating characteristic(ROC)curve was used to compare the value of different non-invasive models in predicting marked liver fibrosis in this population. Results: All the non-invasive models had a certain diagnostic value for liver fibrosis degree in these patients, and the areas under the ROC curve for APRI, FIB-4, APGA, S index, PAPAS, and GP model were 0.718, 0.691, 0.758, 0.729, 0.673, and 0.691, respectively. APGA had the largest area under the ROC curve(0.758, 95% CI 0.673-0.844), and gamma-glutamyl transpeptidase was significantly positively correlated with liver fibrosis degree. Conclusion: The non-invasive models of liver fibrosis can identify marked liver fibrosis in CHB patients with ALT < 2×ULN in whom it is difficult to judge treatment timing and help to determine treatment timing for them. APGA model has the highest value and can reduce the need for liver biopsy to the certain degree.

Nested methylation-specific polymerase chain reaction cancer detection method

DOEpatents

Belinsky, Steven A [Albuquerque, NM; Palmisano, William A [Edgewood, NM

2007-05-08

A molecular marker-based method for monitoring and detecting cancer in humans. Aberrant methylation of gene promoters is a marker for cancer risk in humans. A two-stage, or "nested" polymerase chain reaction method is disclosed for detecting methylated DNA sequences at sufficiently high levels of sensitivity to permit cancer screening in biological fluid samples, such as sputum, obtained non-invasively. The method is for detecting the aberrant methylation of the p16 gene, O 6-methylguanine-DNA methyltransferase gene, Death-associated protein kinase gene, RAS-associated family 1 gene, or other gene promoters. The method offers a potentially powerful approach to population-based screening for the detection of lung and other cancers.

Non-invasive tool for foetal sex determination in early gestational age.

PubMed

Mortarino, M; Garagiola, I; Lotta, L A; Siboni, S M; Semprini, A E; Peyvandi, F

2011-11-01

Free foetal DNA in maternal blood during early pregnancy is an ideal source of foetal genetic material for non-invasive prenatal diagnosis. The aim of this study was to evaluate the use of free foetal DNA analysis at early gestational age as pretest for the detection of specific Y-chromosome sequences in maternal plasma of women who are carriers of X-linked disorders, such as haemophilia. Real-time quantitative PCR analysis of maternal plasma was performed for the detection of the SRY or DYS14 sequence. A group of 208 pregnant women, at different gestational periods from 4 to 12 weeks, were tested to identify the optimal period to obtain an adequate amount of foetal DNA for prenatal diagnosis. Foetal gender was determined in 181 pregnant women sampled throughout pregnancy. Pregnancy outcome and foetal gender were confirmed using karyotyping, ultrasonography or after birth. The sensitivity, which was low between 4th and 7th week (mean 73%), increased significantly after 7+1th weeks of gestation (mean 94%). The latter sensitivity after 7+1th week of gestation is associated to a high specificity (100%), with an overall accuracy of 96% for foetal gender determination. This analysis demonstrates that foetal gender determination in maternal plasma is reliable after the 9th week of gestation and it can be used, in association with ultrasonography, for screening to determine the need for chorionic villus sampling for prenatal diagnosis of X-linked disorders, such as haemophilia. © 2011 Blackwell Publishing Ltd.

Epigenetic regulation of EFEMP1 in prostate cancer: biological relevance and clinical potential

PubMed Central

Almeida, Mafalda; Costa, Vera L; Costa, Natália R; Ramalho-Carvalho, João; Baptista, Tiago; Ribeiro, Franclim R; Paulo, Paula; Teixeira, Manuel R; Oliveira, Jorge; Lothe, Ragnhild A; Lind, Guro E; Henrique, Rui; Jerónimo, Carmen

2014-01-01

Epigenetic alterations are common in prostate cancer (PCa) and seem to contribute decisively to its initiation and progression. Moreover, aberrant promoter methylation is a promising biomarker for non-invasive screening. Herein, we sought to characterize EFEMP1 as biomarker for PCa, unveiling its biological relevance in prostate carcinogenesis. Microarray analyses of treated PCa cell lines and primary tissues enabled the selection of differentially methylated genes, among which EFEMP1 was further validated by MSP and bisulfite sequencing. Assessment of biomarker performance was accomplished by qMSP. Expression analysis of EFEMP1 and characterization of histone marks were performed in tissue samples and cancer cell lines to determine the impact of epigenetic mechanisms on EFEMP1 transcriptional regulation. Phenotypic assays, using transfected cell lines, permitted the evaluation of EFEMP1’s role in PCa development. EFEMP1 methylation assay discriminated PCa from normal prostate tissue (NPT; P < 0.001, Kruskall–Wallis test) and renal and bladder cancers (96% sensitivity and 98% specificity). EFEMP1 transcription levels inversely correlated with promoter methylation and histone deacetylation, suggesting that both epigenetic mechanisms are involved in gene regulation. Phenotypic assays showed that EFEMP1 de novo expression reduces malignant phenotype of PCa cells. EFEMP1 promoter methylation is prevalent in PCa and accurately discriminates PCa from non-cancerous prostate tissues and other urological neoplasms. This epigenetic alteration occurs early in prostate carcinogenesis and, in association with histone deacetylation, progressively leads to gene down-regulation, fostering cell proliferation, invasion and evasion of apoptosis. PMID:25211630

Interval cancers in a population-based screening program for colorectal cancer in catalonia, Spain.

PubMed

Garcia, M; Domènech, X; Vidal, C; Torné, E; Milà, N; Binefa, G; Benito, L; Moreno, V

2015-01-01

Objective. To analyze interval cancers among participants in a screening program for colorectal cancer (CRC) during four screening rounds. Methods. The study population consisted of participants of a fecal occult blood test-based screening program from February 2000 to September 2010, with a 30-month follow-up (n = 30,480). We used hospital administration data to identify CRC. An interval cancer was defined as an invasive cancer diagnosed within 30 months of a negative screening result and before the next recommended examination. Gender, age, stage, and site distribution of interval cancers were compared with those in the screen-detected group. Results. Within the study period, 97 tumors were screen-detected and 74 tumors were diagnosed after a negative screening. In addition, 17 CRC (18.3%) were found after an inconclusive result and 2 cases were diagnosed within the surveillance interval (2.1%). There was an increase of interval cancers over the four rounds (from 32.4% to 46.0%). When compared with screen-detected cancers, interval cancers were found predominantly in the rectum (OR: 3.66; 95% CI: 1.51-8.88) and at more advanced stages (P = 0.025). Conclusion. There are large numbers of cancer that are not detected through fecal occult blood test-based screening. The low sensitivity should be emphasized to ensure that individuals with symptoms are not falsely reassured.

Analysis of anabolic steroids in human hair using LC-MS/MS.

PubMed

Deshmukh, Nawed; Hussain, Iltaf; Barker, James; Petroczi, Andrea; Naughton, Declan P

2010-10-01

New highly sensitive, specific, reliable, reproducible and robust LC-MS/MS methods were developed to detect the anabolic steroids, nandrolone and stanozolol, in human hair for the first time. Hair samples from 180 participants (108 males, 72 females, 62% athletes) were screened using ELISA which revealed 16 athletes as positive for stanozolol and 3 for nandrolone. Positive samples were confirmed on LC-MS/MS in selective reaction monitoring (SRM) mode. The assays for stanozolol and nandrolone showed good linearity in the range 1-400pg/mg and 5-400pg/mg, respectively. The methods were validated for LLOD, interday precision, intraday precision, specificity, extraction recovery and accuracy. The assays were capable of detecting 0.5pg stanozolol and 3.0pg nandrolone per mg of hair, when approximately 20mg of hair were processed. Analysis using LC-MS/MS confirmed 11 athletes' positive for stanozolol (5.0pg/mg to 86.3pg/mg) and 1 for nandrolone (14.0pg/mg) thus avoiding false results from ELISA screening. The results obtained demonstrate the application of these hair analysis methods to detect both steroids at low concentrations, hence reducing the amount of hair required significantly. The new methods complement urinalysis or blood testing and facilitate improved doping testing regimes. Hair analysis benefits from non-invasiveness, negligible risk of infection and facile sample storage and collection, whilst reducing risks of tampering and cross-contamination. Owing to the wide detection window, this approach may also offer an alternative approach for out-of-competition testing.

Liquid biopsy based biomarkers in non-small cell lung cancer for diagnosis and treatment monitoring.

PubMed

Pérez-Callejo, David; Romero, Atocha; Provencio, Mariano; Torrente, María

2016-10-01

Advances in the knowledge of the biology of non-small cell lung cancer (NSCLC) have revealed molecular information used for systemic cancer therapy targeting metastatic disease, with an important impact on patients overall survival (OS) and quality of life. However, a biopsy of overt metastases is an invasive procedure limited to certain locations and not easily acceptable in the clinic. Moreover, a single biopsy cannot reflect the clonal heterogeneity of the tumor. The analysis of peripheral blood samples of cancer patients represents a new source of cancer-derived material, known as liquid biopsy, and its components can be obtained from almost all body fluids. These components have shown to reflect characteristics of the status of both the primary and metastatic diseases, helping the clinicians to move towards a personalized medicine. The present review focuses on the liquid biopsy components: circulating tumor cells (CTCS), circulating free DNA (cfDNA), exosomes and tumor-educated platelets (TEP); the isolation technologies used and their potential use for non-invasive screening, early diagnosis, prognosis, response to treatment and real time monitoring of the disease, in NSCLC patients.

Liquid biopsy based biomarkers in non-small cell lung cancer for diagnosis and treatment monitoring

PubMed Central

Pérez-Callejo, David; Provencio, Mariano

2016-01-01

Advances in the knowledge of the biology of non-small cell lung cancer (NSCLC) have revealed molecular information used for systemic cancer therapy targeting metastatic disease, with an important impact on patients overall survival (OS) and quality of life. However, a biopsy of overt metastases is an invasive procedure limited to certain locations and not easily acceptable in the clinic. Moreover, a single biopsy cannot reflect the clonal heterogeneity of the tumor. The analysis of peripheral blood samples of cancer patients represents a new source of cancer-derived material, known as liquid biopsy, and its components can be obtained from almost all body fluids. These components have shown to reflect characteristics of the status of both the primary and metastatic diseases, helping the clinicians to move towards a personalized medicine. The present review focuses on the liquid biopsy components: circulating tumor cells (CTCS), circulating free DNA (cfDNA), exosomes and tumor-educated platelets (TEP); the isolation technologies used and their potential use for non-invasive screening, early diagnosis, prognosis, response to treatment and real time monitoring of the disease, in NSCLC patients. PMID:27826527

Gene therapy for inherited retinal and optic nerve degenerations.

PubMed

Moore, Nicholas A; Morral, Nuria; Ciulla, Thomas A; Bracha, Peter

2018-01-01

The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity. Areas covered: This review covers Leber's congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, Stargardt disease, Leber's hereditary optic neuropathy, Achromatopsia, and X-linked retinoschisis. Expert opinion: Despite great potential, gene therapy for IRD raises many questions, including the potential for less invasive intravitreal versus subretinal delivery, efficacy, safety, and longevity of response, as well as acceptance of novel study endpoints by regulatory bodies, patients, clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will require widespread genetic screening to identify and diagnose patients based on genotype instead of phenotype.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weier, Jingly F.; Ferlatte, Christy; Baumgartner, Adolf

Numerical chromosome aberrations in gametes typically lead to failed fertilization, spontaneous abortion or a chromosomally abnormal fetus. By means of preimplantation genetic diagnosis (PGD), we now can screen human embryos in vitro for aneuploidy before transferring the embryos to the uterus. PGD allows us to select unaffected embryos for transfer and increases the implantation rate in in vitro fertilization programs. Molecular cytogenetic analyses using multi-color fluorescence in situ hybridization (FISH) of blastomeres have become the major tool for preimplantation genetic screening of aneuploidy. However, current FISH technology can test for only a small number of chromosome abnormalities and hitherto failedmore » to increase the pregnancy rates as expected. We are in the process of developing technologies to score all 24 chromosomes in single cells within a 3 day time limit, which we believe is vital to the clinical setting. Also, human placental cytotrophoblasts (CTBs) at the fetal-maternal interface acquire aneuploidies as they differentiate to an invasive phenotype. About 20-50% of invasive CTB cells from uncomplicated pregnancies were found aneuploidy, suggesting that the acquisition of aneuploidy is an important component of normal placentation, perhaps limiting the proliferative and invasive potential of CTBs. Since most invasive CTBs are interphase cells and possess extreme heterogeneity, we applied multi-color FISH and repeated hybridizations to investigate individual CTBs. In summary, this study demonstrates the strength of Spectral Imaging analysis and repeated hybridizations, which provides a basis for full karyotype analysis of single interphase cells.« less

Design and rationale of the MR-INFORM study: stress perfusion cardiovascular magnetic resonance imaging to guide the management of patients with stable coronary artery disease.

PubMed

Hussain, Shazia T; Paul, Matthias; Plein, Sven; McCann, Gerry P; Shah, Ajay M; Marber, Michael S; Chiribiri, Amedeo; Morton, Geraint; Redwood, Simon; MacCarthy, Philip; Schuster, Andreas; Ishida, Masaki; Westwood, Mark A; Perera, Divaka; Nagel, Eike

2012-09-19

In patients with stable coronary artery disease (CAD), decisions regarding revascularisation are primarily driven by the severity and extent of coronary luminal stenoses as determined by invasive coronary angiography. More recently, revascularisation decisions based on invasive fractional flow reserve (FFR) have shown improved event free survival. Cardiovascular magnetic resonance (CMR) perfusion imaging has been shown to be non-inferior to nuclear perfusion imaging in a multi-centre setting and superior in a single centre trial. In addition, it is similar to invasively determined FFR and therefore has the potential to become the non-invasive test of choice to determine need for revascularisation. The MR-INFORM study is a prospective, multi-centre, randomised controlled non-inferiority, outcome trial. The objective is to compare the efficacy of two investigative strategies for the management of patients with suspected CAD. Patients presenting with stable angina are randomised into two groups: 1) The FFR-INFORMED group has subsequent management decisions guided by coronary angiography and fractional flow reserve measurements. 2) The MR-INFORMED group has decisions guided by stress perfusion CMR. The primary end-point will be the occurrence of major adverse cardiac events (death, myocardial infarction and repeat revascularisation) at one year. Clinical trials.gov identifier NCT01236807. MR INFORM will assess whether an initial strategy of CMR perfusion is non-inferior to invasive angiography supplemented by FFR measurements to guide the management of patients with stable coronary artery disease. Non-inferiority of CMR perfusion imaging to the current invasive reference standard (FFR) would establish CMR perfusion imaging as an attractive non-invasive alternative to current diagnostic pathways.

Organization and evolution of organized cervical cytology screening in Thailand.

PubMed

Khuhaprema, Thiravud; Attasara, Pattarawin; Srivatanakul, Petcharin; Sangrajrang, Suleeporn; Muwonge, Richard; Sauvaget, Catherine; Sankaranarayanan, Rengaswamy

2012-08-01

To describe phase 1 of an organized cytology screening project initiated in Thailand by the Ministry of Public Health and the National Health Security Office. Women aged 35-60 years were encouraged to undergo cervical screening in primary care units and hospitals through awareness programs. Papanicolaou smears were processed and reported at district or provincial cytology laboratories. Women with normal test results were advised to undergo repeat screening after 5 years, while those with precancerous and cancerous lesions were referred for colposcopy, biopsy, and treatment. Information on screening, referral, investigations, and therapy were logged in a computer database. Between 2005 and 2009, 69.2% of the 4030833 targeted women were screened. In all, 20991 women had inadequate smears; 27253 had low-grade squamous intraepithelial lesions; 15706 had high-grade squamous intraepithelial lesions; and 2920 had invasive cancers. Information on the management of precancerous lesions was available for only 17.4% of women referred for colposcopy. Although follow-up data on women with positive test results were inadequately documented, the present findings indicate that provision of cytology services through the existing healthcare system is feasible. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Certain performance values arising from mammographic test set readings correlate well with clinical audit.

PubMed

Soh, BaoLin Pauline; Lee, Warwick Bruce; Mello-Thoms, Claudia; Tapia, Kriscia; Ryan, John; Hung, Wai Tak; Thompson, Graham; Heard, Rob; Brennan, Patrick

2015-08-01

Test sets have been increasingly utilised to augment clinical audit in breast screening programmes; however, their relationship has never been satisfactorily understood. This study examined the relationship between mammographic test set performance and clinical audit data. Clinical audit data over a 2-year period was generated for each of 20 radiologists. Sixty mammographic examinations, consisting of 40 normal and 20 cancer cases, formed the test set. Readers located any identifiable cancer, and levels of confidence were scored from 2 to 5, where a score of 3 and above is considered a recall rating. Jackknifing free response operating characteristic (JAFROC) figure-of-merit (FOM), location sensitivity and specificity were calculated for individual readers and then compared with clinical audit values using Spearman's rho. JAFROC FOM showed significant correlations to: recall rate at a first round of screening (r = 0.51; P = 0.02); rate of small invasive cancers per 10 000 reads (r = 0.5; P = 0.02); percentage of all cancers read that were not recalled (r = -0.51; P = 0.02); and sensitivity (r = 0.51; P = 0.02). Location sensitivity demonstrated significant correlations with: rate of small invasive cancers per 10 000 reads (r = 0.46; P = 0.04); rate of DCIS (ductal carcinoma in situ) per 10 000 reads (r = 0.44; P = 0.05); detection rate of all invasive cancers and DCIS per 10 000 reads (r = 0.54; P = 0.01); percentage of all cancers read that were not recalled (r = -0.57; P = 0.009); and sensitivity (r = 0.57; P = 0.009). No other significant relationships were noted. Performance indicators from test set demonstrate significant correlations with specific aspects of clinical performance, although caution needs to be exercised when generalising test set specificity to the clinical situation. © 2015 The Royal Australian and New Zealand College of Radiologists.