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Sample records for non-invasive prenatal testing

  1. Physician liability and non-invasive prenatal testing.

    PubMed

    Toews, Maeghan; Caulfield, Timothy

    2014-10-01

    Although non-invasive prenatal testing (NIPT) marks a notable development in the field of prenatal genetic testing, there are some physician liability considerations raised by this technology. As NIPT is still emerging as the standard of care and is just starting to receive provincial funding, the question arises of whether physicians are obligated to disclose the availability of NIPT to eligible patients as part of the physician-patient discussion about prenatal screening and diagnosis. If NIPT is discussed with patients, it is important to disclose the limitations of this technology with respect to its accuracy and the number of disorders that it can detect when compared with invasive diagnostic options. A failure to sufficiently disclose these limitations could leave patients with false assurances about the health of their fetuses and could raise informed consent and liability issues, particularly if a child is born with a disability as a result.

  2. [Non-invasive prenatal testing: challenges for future implementation].

    PubMed

    Henneman, Lidewij; Page-Chrisiaens, G C M L Lieve; Oepkes, Dick

    2015-01-01

    The non-invasive prenatal test (NIPT) is an accurate and safe test in which blood from the pregnant woman is used to investigate if the unborn child possibly has trisomy 21 (Down's syndrome), trisomy 18 (Edwards' syndrome) or trisomy 13 (Patau syndrome). Since April 2014 the NIPT has been available in the Netherlands as part of the TRIDENT implementation project for those in whom the first trimester combined test showed an elevated risk (> 1:200) of trisomy, or on medical indication, as an alternative to chorionic villous sampling or amniocentesis. Since the introduction of the NIPT the use of these invasive tests, which are associated with a risk of miscarriage, has fallen steeply. The NIPT may replace the combined test. Also the number of conditions that is tested for can be increased. Modification of current prenatal screening will require extensive discussion, but whatever the modification, careful counseling remains essential to facilitate pregnant women's autonomous reproductive decision making.

  3. Non-invasive prenatal testing: ethics and policy considerations.

    PubMed

    Vanstone, Meredith; King, Carol; de Vrijer, Barbra; Nisker, Jeff

    2014-06-01

    New technologies analyzing fetal DNA in maternal blood have led to the wide commercial availability of non-invasive prenatal testing (NIPT). We present here for clinicians the ethical and policy issues related to an emerging practice option. Although NIPT presents opportunities for pregnant women, particularly women who are at increased risk of having a baby with an abnormality or who are otherwise likely to access invasive prenatal testing, NIPT brings significant ethics and policy challenges. The ethical issues include multiple aspects of informed decision-making, such as access to counselling about the possible results of the test in advance of making a decision about participation in NIPT. Policy considerations include issues related to offering and promoting a privately available medical strategy in publicly funded institutions. Ethics and policy considerations merge in NIPT with regard to sex selection and support for persons living with disabilities.

  4. Non-invasive prenatal testing: ethical issues explored

    PubMed Central

    de Jong, Antina; Dondorp, Wybo J; de Die-Smulders, Christine E M; Frints, Suzanne G M; de Wert, Guido M W R

    2010-01-01

    This paper explores the ethical implications of introducing non-invasive prenatal diagnostic tests (NIPD tests) in prenatal screening for foetal abnormalities. NIPD tests are easy and safe and can be performed early in pregnancy. Precisely because of these features, it is feared that informed consent may become more difficult, that both testing and selective abortion will become ‘normalized', and that there will be a trend towards accepting testing for minor abnormalities and non-medical traits as well. In our view, however, the real moral challenge of NIPD testing consists in the possibility of linking up a technique with these features (easy, safe and early) with new genomic technologies that allow prenatal diagnostic testing for a much broader range of abnormalities than is the case in current procedures. An increase in uptake and more selective abortions need not in itself be taken to signal a thoughtless acceptance of these procedures. However, combining this with considerably enlarging the scope of NIPD testing will indeed make informed consent more difficult and challenge the notion of prenatal screening as serving reproductive autonomy. If broad NIPD testing includes later-onset diseases, the ‘right not to know' of the future child will become a new issue in the debate about prenatal screening. With regard to the controversial issue of selective abortion, it may make a morally relevant difference that after NIPD testing, abortion can be done early. A lower moral status may be attributed to the foetus at that moment, given the dominant opinion that the moral status of the foetus progressively increases with its development. PMID:19953123

  5. Public viewpoints on new non-invasive prenatal genetic tests.

    PubMed

    Farrimond, Hannah R; Kelly, Susan E

    2013-08-01

    Prenatal screening programmes have been critiqued for their routine implementation according to clinical rationale without public debate. A new approach, non-invasive prenatal diagnosis (NIPD), promises diagnosis of fetal genetic disorders from a sample of maternal blood without the miscarriage risk of current invasive prenatal tests (e.g. amniocentesis). Little research has investigated the attitudes of wider publics to NIPD. This study used Q-methodology, which combines factor analysis with qualitative comments, to identify four distinct "viewpoints" amongst 71 UK men and women: 1. NIPD as a new tool in the ongoing societal discrimination against the disabled; 2. NIPD as a positive clinical application offering peace of mind in pregnancy; 3. NIPD as a medical option justified for severe disorders only; and 4. NIPD as a valid expansion of personal choice. Concerns included the "trivialisation of testing" and the implications of commercial/direct-to-consumer tests. Q-methodology has considerable potential to identify viewpoints and frame public debate about new technologies.

  6. Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening.

    PubMed

    Dondorp, Wybo; de Wert, Guido; Bombard, Yvonne; Bianchi, Diana W; Bergmann, Carsten; Borry, Pascal; Chitty, Lyn S; Fellmann, Florence; Forzano, Francesca; Hall, Alison; Henneman, Lidewij; Howard, Heidi C; Lucassen, Anneke; Ormond, Kelly; Peterlin, Borut; Radojkovic, Dragica; Rogowski, Wolf; Soller, Maria; Tibben, Aad; Tranebjærg, Lisbeth; van El, Carla G; Cornel, Martina C

    2015-11-01

    This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non

  7. Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening

    PubMed Central

    Dondorp, Wybo; de Wert, Guido; Bombard, Yvonne; Bianchi, Diana W; Bergmann, Carsten; Borry, Pascal; Chitty, Lyn S; Fellmann, Florence; Forzano, Francesca; Hall, Alison; Henneman, Lidewij; Howard, Heidi C; Lucassen, Anneke; Ormond, Kelly; Peterlin, Borut; Radojkovic, Dragica; Rogowski, Wolf; Soller, Maria; Tibben, Aad; Tranebjærg, Lisbeth; van El, Carla G; Cornel, Martina C

    2015-01-01

    This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non

  8. Implementation of non-invasive prenatal testing by semiconductor sequencing in a genetic laboratory.

    PubMed

    Dheedene, Annelies; Sante, Tom; De Smet, Matthias; Vanbellinghen, Jean-François; Grisart, Bernard; Vergult, Sarah; Janssens, Sandra; Menten, Björn

    2016-08-01

    To implement non-invasive prenatal testing (NIPT) for fetal aneuploidies with semiconductor sequencing in an academic cytogenomic laboratory and to evaluate the first 15-month experience on clinical samples. We validated a NIPT protocol for cell-free fetal DNA sequencing from maternal plasma for the detection of trisomy 13, 18 and 21 on a semiconductor sequencing instrument. Fetal DNA fraction calculation for all samples and several quality parameters were implemented in the workflow. One thousand eighty-one clinical NIPT samples were analysed, following the described protocol. Non-invasive prenatal testing was successfully implemented and validated on 201 normal and 74 aneuploid samples. From 1081 clinical samples, 17 samples showed an abnormal result: 14 trisomy 21 samples, one trisomy 18 and one trisomy 16 were detected. Also a maternal copy number variation on chromosome 13 was observed, which could potentially lead to a false positive trisomy 13 result. One sex discordant result was reported, possibly attributable to a vanishing twin. Moreover, our combined fetal fraction calculation enabled a more reliable risk estimate for trisomy 13, 18 and 21. Non-invasive prenatal testing for trisomy 21, 18 and 13 has a very high specificity and sensitivity. Because of several biological phenomena, diagnostic invasive confirmation of abnormal results remains required. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

  9. Effect of non-invasive prenatal testing as a contingent approach on the indications for invasive prenatal diagnosis and prenatal detection rate of Down's syndrome.

    PubMed

    Kou, K O; Poon, C F; Kwok, S L; Chan, K Yk; Tang, M Hy; Kan, A Sy; Leung, K Y

    2016-06-01

    In Hong Kong, universal combined first-trimester screening for Down's syndrome was started as a 'free service' in July 2010. Non-invasive prenatal testing was available as a self-financed item in August 2011. This study aimed to determine whether the introduction of non-invasive prenatal testing as a contingent approach influenced the indications for invasive prenatal diagnosis and the consequent prenatal detection of Down's syndrome. This historical cohort study was conducted at the Prenatal Diagnosis Clinic of Queen Elizabeth Hospital in Hong Kong. We compared the indications for invasive prenatal diagnosis and prenatal detection of Down's syndrome in singleton pregnancies 1 year before and 2 years following the availability of non-invasive prenatal testing as a contingent test after a positive aneuploidy test. All pregnant women who attended our hospital for counselling about universal Down's syndrome screening between August 2010 and July 2013 were recruited. A total of 16 098 women were counselled. After the introduction of non-invasive prenatal testing, the invasive prenatal diagnosis rate for a positive aneuploidy screening reduced from 77.7% in 2010-11 to 68.8% in 2012-13. The new combined conventional plus non-invasive prenatal testing strategy was associated with a lower false-positive rate (6.9% in 2010-11 vs 5.2% in 2011-12 and 4.9% in 2012-13). There was no significant increase in invasive prenatal diagnosis for structural anomalies over the years. There was no significant trend in the overall prenatal detection rate of Down's syndrome (100% 1 year before vs 89.1% 2 years after introduction of non-invasive prenatal testing). Four (2.6%) of 156 women who underwent non-invasive prenatal testing for a screen-positive result had a high-risk result for trisomy 21, which was subsequently confirmed by invasive prenatal diagnosis. There were no false-negative cases. The introduction of non-invasive prenatal testing as a contingent approach reduced the invasive

  10. Best Ethical Practices for Clinicians and Laboratories in the Provision of Non-Invasive Prenatal Testing

    PubMed Central

    Allyse, MA; Sayres, LC; Havard, M; King, JS; Greely, HT; Hudgins, L; Taylor, J; Norton, ME; Cho, MK; Magnus, D; Ormond, KE

    2014-01-01

    Objective To provide an ethical framework for clinicians and companies providing non-invasive prenatal testing using cell-free fetal DNA or whole fetal cells. Method In collaboration with an NIH-supported research ethics consultation committee, together with feedback from an inter-disciplinary group of clinicians, members of industry, legal experts and genetic counselors we developed a set of best practices for the provision of non-invasive prenatal genetic testing. Results Principal recommendations include the amendment of current informed consent procedures to include attention to the non-invasive nature of new testing and the potential for a broader range of results earlier in the pregnancy. We strongly recommend that tests should only be provided through licensed medical providers and not direct-to-consumer. Conclusion Prenatal tests, including new methods using cell-free fetal DNA, are not currently regulated by government agencies and limited professional guidance is available. In the absence of regulation, companies and clinicians should cooperate to adopt responsible best ethical practices in the provision of these tests. PMID:23613322

  11. SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy

    PubMed Central

    Samango-Sprouse, Carole; Banjevic, Milena; Ryan, Allison; Sigurjonsson, Styrmir; Zimmermann, Bernhard; Hill, Matthew; Hall, Megan P.; Westemeyer, Margaret; Saucier, Jennifer; Demko, Zachary; Rabinowitz, Matthew

    2013-01-01

    Objective To develop a single nucleotide polymorphism- and informatics-based non-invasive prenatal test that detects sex chromosome aneuploidies early in pregnancy. Methods Fifteen aneuploid samples, including thirteen 45,X, two 47,XXY, and one 47,XYY, along with 185 euploid controls, were analyzed. Cell-free DNA was isolated from maternal plasma, amplified in a single multiplex PCR assay that targeted 19,488 polymorphic loci covering chromosomes 13, 18, 21, X, and Y, and sequenced. Sequencing results were analyzed using a Bayesian-based maximum likelihood statistical method to determine copy number of interrogated chromosomes, calculating sample-specific accuracies. Results Of the samples that passed a stringent quality control metric (93%), the algorithm correctly identified copy number at all five chromosomes in all 187 samples, for 934/935 correct calls as early as 9.4 weeks of gestation. We detected 45,X with 91.7% sensitivity (CI: 61.5-99.8%) and 100% specificity (CI: 97.9-100%), and 47,XXY and 47,XYY. The average calculated accuracy was 99.78%. Conclusion This method non-invasively detected 45,X, 47,XXY, and 47,XYY fetuses from cfDNA isolated from maternal plasma with high calculated accuracies, and thus offers a non-invasive method with the potential to function as a routine screen allowing for early prenatal detection of rarely diagnosed yet commonly occurring sex aneuploidies. PMID:23712453

  12. Diagnostic performance and costs of contingent screening models for trisomy 21 incorporating non-invasive prenatal testing.

    PubMed

    Maxwell, Susannah; O'Leary, Peter; Dickinson, Jan E; Suthers, Graeme K

    2017-08-01

    Contingent screening for trisomy 21 using non-invasive prenatal testing has the potential to reduce invasive diagnostic testing and increase the detection of trisomy 21. To describe the diagnostic and economic performance of prenatal screening models for trisomy 21 that use non-invasive prenatal testing as a contingent screen across a range of combined first trimester screening risk cut-offs from a public health system perspective. Using a hypothetical cohort of 300 000 pregnancies, we modelled the outcomes of 25 contingent non-invasive prenatal testing screening models and compared these to conventional screening, offering women with a high-risk (1 > 300) combined first trimester screening result an invasive test. The 25 models used a range of risk cut-offs. High-risk women were offered invasive testing. Intermediate-risk women were offered non-invasive prenatal testing. We report the cost of each model, detection rate, costs per diagnosis, invasive tests per diagnosis and the number of fetal losses per diagnosis. The cost per prenatal diagnosis of trisomy 21 using the conventional model was $51 876 compared to the contingent models which varied from $49 309-66 686. The number of diagnoses and cost per diagnosis increased as the intermediate-risk threshold was lowered. Results were sensitive to trisomy 21 incidence, uptake of testing and cost of non-invasive prenatal testing. Contingent non-invasive prenatal testing models using more sensitive combined first trimester screening risk cut-offs than conventional screening improved the detection rate of trisomy 21, reduced procedure-related fetal loss and could potentially be provided at a lower cost per diagnosis than conventional screening. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  13. 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.

  14. Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening.

    PubMed

    van Schendel, Rachèl V; Kleinveld, Johanna H; Dondorp, Wybo J; Pajkrt, Eva; Timmermans, Danielle R M; Holtkamp, Kim C A; Karsten, Margreet; Vlietstra, Anne L; Lachmeijer, Augusta M A; Henneman, Lidewij

    2014-12-01

    Non-invasive prenatal testing (NIPT) and its potential to test for multiple disorders has received much attention. This study explores attitudes of women and men towards NIPT, and their views on widening the scope of prenatal testing in a country with a low uptake of prenatal screening (The Netherlands). Five focus groups with low-risk pregnant women (n=28), three focus groups with men (n=19) and 13 interviews with high- and low-risk pregnant women were conducted. Participants felt that current prenatal screening has great disadvantages such as uncertain results and risk of miscarriage from follow-up diagnostics. Characteristics of NIPT (accurate, safe and early testing) could therefore diminish these disadvantages of prenatal screening and help lower the barrier for participation. This suggests that NIPT might allow couples to decide about prenatal testing based mostly on their will to test or not, rather than largely based on fear of miscarriage risk or the uncertainty of results. The lower barrier for participation was also seen as a downside that could lead to uncritical use or pressure to test. Widening the scope of prenatal testing was seen as beneficial for severe disorders, although it was perceived difficult to determine where to draw the line. Participants argued that there should be a limit to the scope of NIPT, avoiding testing for minor abnormalities. The findings suggest that NIPT could enable more meaningful decision-making for prenatal screening. However, to ensure voluntary participation, especially when testing for multiple disorders, safeguards on the basis of informed decision-making will be of utmost importance.

  15. Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening

    PubMed Central

    van Schendel, Rachèl V; Kleinveld, Johanna H; Dondorp, Wybo J; Pajkrt, Eva; Timmermans, Danielle R M; Holtkamp, Kim C A; Karsten, Margreet; Vlietstra, Anne L; Lachmeijer, Augusta M A; Henneman, Lidewij

    2014-01-01

    Non-invasive prenatal testing (NIPT) and its potential to test for multiple disorders has received much attention. This study explores attitudes of women and men towards NIPT, and their views on widening the scope of prenatal testing in a country with a low uptake of prenatal screening (The Netherlands). Five focus groups with low-risk pregnant women (n=28), three focus groups with men (n=19) and 13 interviews with high- and low-risk pregnant women were conducted. Participants felt that current prenatal screening has great disadvantages such as uncertain results and risk of miscarriage from follow-up diagnostics. Characteristics of NIPT (accurate, safe and early testing) could therefore diminish these disadvantages of prenatal screening and help lower the barrier for participation. This suggests that NIPT might allow couples to decide about prenatal testing based mostly on their will to test or not, rather than largely based on fear of miscarriage risk or the uncertainty of results. The lower barrier for participation was also seen as a downside that could lead to uncritical use or pressure to test. Widening the scope of prenatal testing was seen as beneficial for severe disorders, although it was perceived difficult to determine where to draw the line. Participants argued that there should be a limit to the scope of NIPT, avoiding testing for minor abnormalities. The findings suggest that NIPT could enable more meaningful decision-making for prenatal screening. However, to ensure voluntary participation, especially when testing for multiple disorders, safeguards on the basis of informed decision-making will be of utmost importance. PMID:24642832

  16. Non-invasive prenatal testing for trisomy 13: more harm than good?

    PubMed

    Verweij, E J; de Boer, M A; Oepkes, D

    2014-07-01

    A 35-year-old primigravida, pregnant after in-vitro fertilization, was seen because of a trisomy 13/trisomy 18 (T13/T18) risk of 1:55, based on the result of her first-trimester combined test. She elected for non-invasive prenatal testing (NIPT) at 14 + 5 weeks' gestation, which was positive for T13. After counseling, the patient elected to undergo amniocentesis. Quantitative fluorescence polymerase chain reaction (QF-PCR) showed no signs of trisomy, and full karyotyping confirmed a normal 46,XY result. Analysis of the published literature on NIPT for T13 gives an overall detection rate of 91.6%, with a false-positive rate of 0.097%. Based on this detection rate, hypothetical calculations show that the positive predictive value is highly dependent on the prevalence of the disease, resulting in an unfavorable balance between benefit and harm in a general population.

  17. 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.

  18. Non-invasive prenatal testing: impact on invasive prenatal diagnosis at a mainland Chinese tertiary medical center.

    PubMed

    Li, Dong-Zhi; Zhen, Li; Pan, Min; Han, Jin; Yang, Xin; Ou, Yan-Mei

    2016-11-01

    We describe the changes over a 4-year period in the number of diagnostic testing after the introduction of non-invasive prenatal testing (NIPT). The rate of NIPT as an indication in women who received amniocentesis, and the number of amniocentesis required for detection of one case with major aneuploidy were compared between a 1-year baseline period before the introduction of NIPT, and the 3 years following NIPT introduction. A total of 7536 amniocentesis procedures were performed over the 4-year study period. During the baseline period of the year 2011, the number of invasive testing required for detection of one common trisomy was 57. During the first 2 years that NIPT was offered, NIPT averaged 1.7 percent of the total indications for amniocentesis, and the required number of invasive testing decreased to 30. With the increase of the percentage of NIPT during the 3rd year, the required number of invasive testing further decreased to 26. After the clinical introduction of NIPT, invasive prenatal diagnostic testing had not decreased at a Chinese prenatal diagnostic unit, but a remarkably improved detection rate of major aneuploidies in diagnostic procedures was observed.

  19. Comparative evaluation of the Minimally-Invasive Karyotyping (MINK) algorithm for non-invasive prenatal testing.

    PubMed

    Chu, Tianjiao; Shaw, Patricia A; Yeniterzi, Suveyda; Dunkel, Mary; Rajkovic, Aleksander; Hogge, W Allen; Bunce, Kimberly D; Peters, David G

    2017-01-01

    Minimally Invasive Karyotyping (MINK) was communicated in 2009 as a novel method for the non-invasive detection of fetal copy number anomalies in maternal plasma DNA. The original manuscript illustrated the potential of MINK using a model system in which fragmented genomic DNA obtained from a trisomy 21 male individual was mixed with that of his karyotypically normal mother at dilutions representing fetal fractions found in maternal plasma. Although it has been previously shown that MINK is able to non-invasively detect fetal microdeletions, its utility for aneuploidy detection in maternal plasma has not previously been demonstrated. The current study illustrates the ability of MINK to detect common aneuploidy in early gestation, compares its performance to other published third party methods (and related software packages) for prenatal aneuploidy detection and evaluates the performance of these methods across a range of sequencing read inputs. Plasma samples were obtained from 416 pregnant women between gestational weeks 8.1 and 34.4. Shotgun DNA sequencing was performed and data analyzed using MINK RAPIDR and WISECONDOR. MINK performed with greater accuracy than RAPIDR and WISECONDOR, correctly identifying 60 out of 61 true trisomy cases, and reporting only one false positive in 355 normal pregnancies. Significantly, MINK achieved accurate detection of trisomy 21 using just 2 million aligned input reads, whereas WISECONDOR required 6 million reads and RAPIDR did not achieve complete accuracy at any read input tested. In conclusion, we demonstrate that MINK provides an analysis pipeline for the detection of fetal aneuploidy in samples of maternal plasma DNA.

  20. Comparative evaluation of the Minimally-Invasive Karyotyping (MINK) algorithm for non-invasive prenatal testing

    PubMed Central

    Chu, Tianjiao; Shaw, Patricia A.; Yeniterzi, Suveyda; Dunkel, Mary; Rajkovic, Aleksander; Hogge, W. Allen; Bunce, Kimberly D.; Peters, David G.

    2017-01-01

    Minimally Invasive Karyotyping (MINK) was communicated in 2009 as a novel method for the non-invasive detection of fetal copy number anomalies in maternal plasma DNA. The original manuscript illustrated the potential of MINK using a model system in which fragmented genomic DNA obtained from a trisomy 21 male individual was mixed with that of his karyotypically normal mother at dilutions representing fetal fractions found in maternal plasma. Although it has been previously shown that MINK is able to non-invasively detect fetal microdeletions, its utility for aneuploidy detection in maternal plasma has not previously been demonstrated. The current study illustrates the ability of MINK to detect common aneuploidy in early gestation, compares its performance to other published third party methods (and related software packages) for prenatal aneuploidy detection and evaluates the performance of these methods across a range of sequencing read inputs. Plasma samples were obtained from 416 pregnant women between gestational weeks 8.1 and 34.4. Shotgun DNA sequencing was performed and data analyzed using MINK RAPIDR and WISECONDOR. MINK performed with greater accuracy than RAPIDR and WISECONDOR, correctly identifying 60 out of 61 true trisomy cases, and reporting only one false positive in 355 normal pregnancies. Significantly, MINK achieved accurate detection of trisomy 21 using just 2 million aligned input reads, whereas WISECONDOR required 6 million reads and RAPIDR did not achieve complete accuracy at any read input tested. In conclusion, we demonstrate that MINK provides an analysis pipeline for the detection of fetal aneuploidy in samples of maternal plasma DNA. PMID:28306738

  1. NIPTRIC: an online tool for clinical interpretation of non-invasive prenatal testing (NIPT) results

    PubMed Central

    Sikkema-Raddatz, Birgit; Johansson, Lennart F.; de Boer, Eddy N.; Boon, Elles M. J.; Suijkerbuijk, Ron F.; Bouman, Katelijne; Bilardo, Catia M.; Swertz, Morris A.; Dijkstra, Martijn; van Langen, Irene M.; Sinke, Richard J.; te Meerman, Gerard J.

    2016-01-01

    To properly interpret the result of a pregnant woman’s non-invasive prenatal test (NIPT), her a priori risk must be taken into account in order to obtain her personalised a posteriori risk (PPR), which more accurately expresses her true likelihood of carrying a foetus with trisomy. Our aim was to develop a tool for laboratories and clinicians to calculate easily the PPR for genome-wide NIPT results, using diploid samples as a control group. The tool takes the a priori risk and Z-score into account. Foetal DNA percentage and coefficient of variation can be given default settings, but actual values should be used if known. We tested the tool on 209 samples from pregnant women undergoing NIPT. For Z-scores < 5, the PPR is considerably higher at a high a priori risk than at a low a priori risk, for NIPT results with the same Z-score, foetal DNA percentage and coefficient of variation. However, the PPR is effectively independent under all conditions for Z-scores above 6. A high PPR for low a priori risks can only be reached at Z-scores > 5. Our online tool can assist clinicians in understanding NIPT results and conveying their true clinical implication to pregnant women, because the PPR is crucial for individual counselling and decision-making. PMID:27917919

  2. 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

  3. Open source non-invasive prenatal testing platform and its performance in a public health laboratory.

    PubMed

    Johansen, Peter; Richter, Stine R; Balslev-Harder, Marie; Miltoft, Caroline B; Tabor, Ann; Duno, Morten; Kjaergaard, Susanne

    2016-06-01

    The objective of this study was to introduce non-invasive prenatal testing (NIPT) for fetal autosomal trisomies and gender in a Danish public health setting, using semi-conductor sequencing and published open source scripts for analysis. Plasma-derived DNA from a total of 375 pregnant women (divided into three datasets) was whole-genome sequenced on the Ion Proton™ platform and analyzed using a pipeline based on WISECONDOR for fetal autosomal aneuploidy detection and SeqFF for fetal DNA fraction estimation. We furthermore validated a fetal sex determination analysis. The pipeline correctly detected 27/27 trisomy 21, 4/4 trisomy 18, and 3/3 trisomy 13 fetuses. Neither false negatives nor false positives (chromosomes 13, 18, and 21) were observed in our validation dataset. Fetal sex was identified correctly in all but one triploid fetus (172/173). SeqFF showed a strong correlation (R(2)  = 0.72) to Y-chromosomal content of the male fetus samples. We have implemented NIPT into Danish health care using published open source scripts for autosomal aneuploidy detection and fetal DNA fraction estimation showing excellent false negative and false positive rates. SeqFF provides a good estimation of fetal DNA fraction. This coupled with an analysis of fetal sex that provides a complete NIPT workflow, which may easily be adapted for implementation in other public health laboratories. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  4. 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.

  5. Expanding non-invasive prenatal testing beyond chromosomes 21, 18, 13, X and Y.

    PubMed

    Benn, P

    2016-12-01

    Non-invasive prenatal testing (NIPT) based on cell-free DNA in maternal plasma is being expanded to include additional chromosome abnormalities beyond those involving chromosomes 21, 18, 13, X and Y. Review of population cytogenetic data provides insight into the likely number of additional abnormalities detectable. Additional clinically significant and cytogenetically recognizable abnormalities are present in less than 0.1% of newborns but clinically significant, or potentially significant, sub-microscopic imbalances are expected to be present in 1.7%. Cytogenetic studies on chorionic villus samples suggests that after excluding abnormalities involving chromosomes 21, 18, 13, X and Y, approximately 0.6% of NIPT results may be positive for an unbalanced abnormality attributable to mosaicism but most of these will not be confirmed at amniocentesis or in newborns. NIPT has also been developed for specific microdeletion syndromes and initial experience is now available. Laboratory procedures such as deeper sequencing and additional data analytics are rapidly evolving but even with existing protocols, it is already clear that NIPT does not necessarily need to be limited to trisomies 21, 18, 13 and the sex-chromosome abnormalities. Patient educational materials and genetic counseling services need to be available for women offered expanded NIPT. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Non-invasive prenatal testing for fetal chromosome abnormalities: review of clinical and ethical issues

    PubMed Central

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

    2016-01-01

    Genomics-based non-invasive prenatal screening using cell-free DNA (cfDNA screening) was proposed to reduce the number of invasive procedures in current prenatal diagnosis for fetal aneuploidies. We review here the clinical and ethical issues of cfDNA screening. To date, it is not clear how cfDNA screening is going to impact the performances of clinical prenatal diagnosis and how it could be incorporated in real life. The direct marketing to users may have facilitated the early introduction of cfDNA screening into clinical practice despite limited evidence-based independent research data supporting this rapid shift. There is a need to address the most important ethical, legal, and social issues before its implementation in a mass setting. Its introduction might worsen current tendencies to neglect the reproductive autonomy of pregnant women. PMID:26893576

  7. Limited Clinical Utility of Non-invasive Prenatal Testing for Subchromosomal Abnormalities

    PubMed Central

    Lo, Kitty K.; Karampetsou, Evangelia; Boustred, Christopher; McKay, Fiona; Mason, Sarah; Hill, Melissa; Plagnol, Vincent; Chitty, Lyn S.

    2016-01-01

    The use of massively parallel sequencing of maternal cfDNA for non-invasive prenatal testing (NIPT) of aneuploidy is widely available. Recently, the scope of testing has increased to include selected subchromosomal abnormalities, but the number of samples reported has been small. We developed a calling pipeline based on a segmentation algorithm for the detection of these rearrangements in maternal plasma. The same read depth used in our standard pipeline for aneuploidy NIPT detected 15/18 (83%) samples with pathogenic rearrangements > 6 Mb but only 2/10 samples with rearrangements < 6 Mb, unless they were maternally inherited. There were two false-positive calls in 534 samples with no known subchromosomal abnormalities (specificity 99.6%). Using higher read depths, we detected 29/31 fetal subchromosomal abnormalities, including the three samples with maternally inherited microduplications. We conclude that test sensitivity is a function of the fetal fraction, read depth, and size of the fetal CNV and that at least one of the two false negatives is due to a low fetal fraction. The lack of an independent method for determining fetal fraction, especially for female fetuses, leads to uncertainty in test sensitivity, which currently has implications for this technique’s future as a clinical diagnostic test. Furthermore, to be effective, NIPT must be able to detect chromosomal rearrangements across the whole genome for a very low false-positive rate. Because standard NIPT can only detect the majority of larger (>6 Mb) chromosomal rearrangements and requires knowledge of fetal fraction, we consider that it is not yet ready for routine clinical implementation. PMID:26708752

  8. 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.

  9. For your interest? The ethical acceptability of using non-invasive prenatal testing to test 'purely for information'.

    PubMed

    Deans, Zuzana; Clarke, Angus J; Newson, Ainsley J

    2015-01-01

    Non-invasive prenatal testing (NIPT) is an emerging form of prenatal genetic testing that provides information about the genetic constitution of a foetus without the risk of pregnancy loss as a direct result of the test procedure. As with other prenatal tests, information from NIPT can help to make a decision about termination of pregnancy, plan contingencies for birth or prepare parents to raise a child with a genetic condition. NIPT can also be used by women and couples to test purely 'for information'. Here, no particular action is envisaged following the test; it is motivated entirely by an interest in the result. The fact that NIPT can be performed without posing a risk to the pregnancy could give rise to an increase in such requests. In this paper, we examine the ethical aspects of using NIPT 'purely for information', including the competing interests of the prospective parents and the future child, and the acceptability of testing for 'frivolous' reasons. Drawing on several clinical scenarios, we claim that arguments about testing children for genetic conditions are relevant to this debate. In addition, we raise ethical concerns over the potential for objectification of the child. We conclude that, in most cases, using NIPT to test for adult-onset conditions, carrier status or non-serious traits presenting in childhood would be unacceptable. © 2014 John Wiley & Sons Ltd.

  10. 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.

  11. Women's Experiences of Publicly Funded Non-Invasive Prenatal Testing in Ontario, Canada: Considerations for Health Technology Policy-Making.

    PubMed

    Vanstone, Meredith; Yacoub, Karima; Giacomini, Mita; Hulan, Danielle; McDonald, Sarah

    2015-08-01

    Non-invasive prenatal testing (NIPT) via fetal DNA in maternal blood has been publicly funded in Ontario, Canada, for high-risk women since 2014. We solicited women's experiences and values related to this new health technology to describe how this test is currently being used in Ontario and to provide information about patient priorities to inform future policy decisions about the use of NIPT. Guided by constructivist grounded theory methodology, we interviewed 38 women who had diverse personal experiences with NIPT. Participants' accounts of their values for decision making about NIPT heavily relied on three mutually modulating factors: timing, accuracy, and risk. The values expressed by women conflict with the way that publicly funded NIPT has typically been implemented in Ontario. We offer recommendations for how NIPT might be integrated into prenatal care pathways in a way more consistent with women's values.

  12. Study of the extent of information desired by women undergoing non-invasive prenatal testing following positive prenatal Down-syndrome screening test results.

    PubMed

    Lo, Tsz-Kin; Chan, Kelvin Yuen-Kwong; Kan, Anita Sik-Yau; So, Po-Lam; Kong, Choi-Wah; Mak, Shui-Lam; Lee, Chung-Nin

    2017-03-12

    In addition to common trisomies, the inclusion of sex chromosomes and atypical autosomal anomalies in non-invasive prenatal tests (NIPTs) is becoming increasingly common; this is the result of limited screening alternatives that can identify them [1]. It has been recommended that healthcare practitioners understand patient preferences thoroughly [1], and that, given the complexity of NIPTs, patients be given the option to accept or reject this additional information [2, 3]. However, how much information patients want from NIPTs in a real-life clinical setting remains unknown. This article is protected by copyright. All rights reserved.

  13. Positive Attitudes towards Non-Invasive Prenatal Testing (NIPT) in a Swedish Cohort of 1,003 Pregnant Women

    PubMed Central

    Nordenskjöld, Magnus; Gustavsson, Peter; Wincent, Josephine

    2016-01-01

    Objective The clinical utilization of non-invasive prenatal testing (NIPT) for identification of fetal aneuploidies is expanding worldwide. The aim of this study was to gain an increased understanding of pregnant women’s awareness, attitudes, preferences for risk information and decision-making concerning prenatal examinations with emphasis on NIPT, before its introduction into Swedish healthcare. Method Pregnant women were recruited to fill in a questionnaire, including multiple-choice questions and Likert scales, at nine maternity clinics located in different areas of Stockholm, Sweden. Results In total, 1,003 women participated in the study (86% consent rate). The vast majority (90.7%) considered examinations aiming to detect fetal abnormalities to be good. Regarding NIPT, 59.8% stated that they had heard about the method previously, yet 74.0% would like to use the test if available. The main factor affecting the women’s decision to undergo prenatal chromosomal screening was worry about the baby’s health (82.5%), followed by the urge to have as much information as possible about the fetus (54.5%). Most women (79.9%) preferred to receive NIPT information orally. Conclusion The overwhelming majority of a cohort of 1,003 pregnant women considered prenatal examinations good. Moreover, the majority had a positive attitude towards NIPT and would like to use the test if available. PMID:27195496

  14. Positive Attitudes towards Non-Invasive Prenatal Testing (NIPT) in a Swedish Cohort of 1,003 Pregnant Women.

    PubMed

    Sahlin, Ellika; Nordenskjöld, Magnus; Gustavsson, Peter; Wincent, Josephine; Georgsson, Susanne; Iwarsson, Erik

    2016-01-01

    The clinical utilization of non-invasive prenatal testing (NIPT) for identification of fetal aneuploidies is expanding worldwide. The aim of this study was to gain an increased understanding of pregnant women's awareness, attitudes, preferences for risk information and decision-making concerning prenatal examinations with emphasis on NIPT, before its introduction into Swedish healthcare. Pregnant women were recruited to fill in a questionnaire, including multiple-choice questions and Likert scales, at nine maternity clinics located in different areas of Stockholm, Sweden. In total, 1,003 women participated in the study (86% consent rate). The vast majority (90.7%) considered examinations aiming to detect fetal abnormalities to be good. Regarding NIPT, 59.8% stated that they had heard about the method previously, yet 74.0% would like to use the test if available. The main factor affecting the women's decision to undergo prenatal chromosomal screening was worry about the baby's health (82.5%), followed by the urge to have as much information as possible about the fetus (54.5%). Most women (79.9%) preferred to receive NIPT information orally. The overwhelming majority of a cohort of 1,003 pregnant women considered prenatal examinations good. Moreover, the majority had a positive attitude towards NIPT and would like to use the test if available.

  15. A survey on awareness of genetic counseling for non-invasive prenatal testing: the first year experience in Japan.

    PubMed

    Yotsumoto, Junko; Sekizawa, Akihiko; Suzumori, Nobuhiro; Yamada, Takahiro; Samura, Osamu; Nishiyama, Miyuki; Miura, Kiyonori; Sawai, Hideaki; Murotsuki, Jun; Kitagawa, Michihiro; Kamei, Yoshimasa; Masuzaki, Hideaki; Hirahara, Fumiki; Endo, Toshiaki; Fukushima, Akimune; Namba, Akira; Osada, Hisao; Kasai, Yasuyo; Watanabe, Atsushi; Katagiri, Yukiko; Takeshita, Naoki; Ogawa, Masaki; Okai, Takashi; Izumi, Shunichiro; Hamanoue, Haruka; Inuzuka, Mayuko; Haino, Kazufumi; Hamajima, Naoki; Nishizawa, Haruki; Okamoto, Yoko; Nakamura, Hiroaki; Kanegawa, Takeshi; Yoshimatsu, Jun; Tairaku, Shinya; Naruse, Katsuhiko; Masuyama, Hisashi; Hyodo, Maki; Kaji, Takashi; Maeda, Kazuhisa; Matsubara, Keiichi; Ogawa, Masanobu; Yoshizato, Toshiyuki; Ohba, Takashi; Kawano, Yukie; Sago, Haruhiko

    2016-12-01

    The purpose of this study is to summarize the results from a survey on awareness of genetic counseling for pregnant women who wish to receive non-invasive prenatal testing (NIPT) in Japan. As a component of a clinical study by the Japan NIPT Consortium, genetic counseling was conducted for women who wished to receive NIPT, and a questionnaire concerning both NIPT and genetic counseling was given twice: once after pre-test counseling and again when test results were reported. The responses of 7292 women were analyzed. They expressed high satisfaction with the genetic counseling system of the NIPT Consortium (94%). The number of respondents who indicated that genetic counseling is necessary for NIPT increased over time. Furthermore, they highly valued genetic counseling provided by skilled clinicians, such as clinical geneticists or genetic counselors. The vast majority (90%) responded that there was sufficient opportunity to consider the test ahead of time. Meanwhile, women who received positive test results had a poor opinion and expressed a low-degree satisfaction. We confirmed that the pre-test genetic counseling that we conducted creates an opportunity for pregnant women to sufficiently consider prenatal testing, promotes its understanding and has possibilities to effectively facilitate informed decision making after adequate consideration. A more careful and thorough approach is considered to be necessary for women who received positive test results.

  16. Implementing non-invasive prenatal testing for aneuploidy in a national healthcare system: global challenges and national solutions.

    PubMed

    van Schendel, Rachèl V; van El, Carla G; Pajkrt, Eva; Henneman, Lidewij; Cornel, Martina C

    2017-09-19

    Since the introduction of non-invasive prenatal testing (NIPT) in 2011, mainly by commercial companies, a growing demand for NIPT from the public and healthcare professionals has been putting pressure on the healthcare systems of various countries. This study identifies the challenges of establishing a responsible implementation of NIPT for aneuploidy in prenatal healthcare, by looking at the Netherlands. A mixed methods approach involving 13 stakeholder interviews, document analysis and (participatory) observations of the Dutch NIPT Consortium meetings were used. The Diffusion of Innovation Theory and a Network of Actors model were used to interpret the findings. Implementation of NIPT was facilitated by several factors. The set-up of a national NIPT Consortium enabled discussion and collaboration between stakeholders. Moreover, it led to the plan to offer NIPT through a nationwide research setting (TRIDENT studies), which created a learning phase for careful implementation. The Dutch legal context was perceived as a delaying factor, but eventually gave room for the parties involved to organise themselves and their practices. This study shows that implementing advanced technologies with profound effects on prenatal care benefit from a learning phase that allows time to carefully evaluate the technical performance and women's experiences and to enable public debate. Such a coordinated learning phase, involving all stakeholders, will stimulate the process of responsible and sustainable implementation.

  17. 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.

  18. 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

  19. How do the trends in the prenatal diagnosis of aneuploidy change after a non-invasive prenatal test becomes available? A Japanese single center study.

    PubMed

    Hasegawa, Junichi; Nakamura, Masamitsu; Sekizawa, Akihiko

    2015-04-01

    To clarify the trends in the use of the prenatal diagnosis of and screening for aneuploidy after a non-invasive prenatal test (NIPT) was made available at a single Japanese hospital. The subjects included consecutive pregnant females who visited our hospital for maternal checkups and delivery between January 2012 and April 2014. After the subjects were divided into those who desired a prenatal diagnosis or screening before the availability of NIPT and those who did after the availability of NIPT, the frequencies of various prenatal diagnosis and screening procedures were compared between the two groups. A total of 544 patients who visited the hospital before NIPT was available and 703 who visited the hospital after NIPT became available were analyzed. While only 16.2 % of pregnant females received a prenatal diagnosis or screening before the NIPT was available, 27.5 % of them considered undergoing a prenatal diagnosis or screening after the NIPT was available before genetic counseling, and 24.0 % ultimately received a prenatal diagnosis or screening following genetic counseling. Of these patients, 7.7 % underwent NIPT. First trimester ultrasound screening for chromosomal abnormalities was unlikely to be selected (from 12.9 to 10.5 %, p = 0.212), although the rate of amniocentesis significantly increased after genetic counseling (from 1.5 to 3.7 %, p = 0.021). Since NIPT became available in 2013, pregnant females have demonstrated a deep interest in obtaining a prenatal diagnosis and screening. Whereas some patients choose to forgo a screening after receiving genetic counseling, others prefer invasive diagnostic tests in contrast to screening.

  20. 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.

  1. Advantages and Disadvantages of Different Implementation Strategies of Non-Invasive Prenatal Testing in Down Syndrome Screening Programmes.

    PubMed

    Mersy, Elke; de Die-Smulders, Christine E M; Coumans, Audrey B C; Smits, Luc J M; de Wert, Guido M W R; Frints, Suzanna G M; Veltman, Joris A

    2015-01-01

    Implementation of non-invasive prenatal testing (NIPT) in Down syndrome screening programmes requires health policy decisions about its combination with other tests and its timing in pregnancy. Our aim was to aid health policy decision makers by conducting a quantitative analysis of different NIPT implementation strategies. Decision trees were created to illustrate all plausible alternatives in a theoretical cohort of 100,000 pregnant women in five screening programmes: classical screening by the first-trimester combined test (FCT), pre-selection of high-risk women prior to NIPT by the FCT, NIPT as the first screening test at 10 weeks and at 13 weeks, and the simultaneous conductance of NIPT and the FCT. Pre-selection by FCT prior to NIPT reduces the number of amniocenteses to a minimum because of a reduction of false-positive NIPT results. If NIPT is the first screening test, it detects almost all fetal Down syndrome cases. NIPT at 10 weeks reassures women early in pregnancy, while NIPT at 13 weeks prevents unnecessary tests due to spontaneous miscarriages and allows for immediate confirmation by amniocentesis. Every implementation strategy has its advantages and disadvantages. The most favourable implementation strategy may be NIPT as the first screening test at 13 weeks, offering the most accurate screening test for Down syndrome, when the risk for spontaneous miscarriage has declined remarkably and timely confirmation by amniocentesis can be performed. © 2015 S. Karger AG, Basel.

  2. Primer-introduced restriction analysis polymerase chain reaction method for non-invasive prenatal testing of β-thalassemia.

    PubMed

    Liu, Saijun; Chen, Liyuan; Zhang, Xiandong; Li, Jian; Lin, Haiying; Liu, Louhui; Xie, Jiansheng; Ge, Huijuan; Ye, Minglan; Chen, Caifen; Ji, Xingwen; Zhang, Caifen; Xu, Fengping; Jiang, Hui; Zhen, Hefu; Chen, Shiping; Wang, Wei

    2015-01-01

    We have developed a new method for non-invasive prenatal testing (NIPT) of paternally inherited fetal mutants for β-thalassemia (β-thal). Specially designed primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) were used to detect four major mutations [IVS-II-654, HBB: c.316-197C > T; codon 17 (A > T), HBB: c.52A > T; -28 (A > G), HBB: c.-78A > G and codons 41/42 (-TTCT), HBB: c.126_129delCTTT] causing β-thal in China. The PIRA-PCR assay was first tested in a series of mixed DNA with different concentrations and mixed proportions. Subsequently, this assay was further tested in 10 plasma DNA samples collected from pregnant women. In the DNA mixture simulation test, the PIRA-PCR assay was able to detect 3.0% target genomic DNA (gDNA) mixed in 97.0% wild-type gDNA isolated from whole blood. For plasma DNA testing, the results detected by PIRA-PCR assay achieved 100.0% consistency with those obtained from the amniocentesis analysis. This new method could potentially be used for NIPT of paternally inherited fetal mutants for β-thal.

  3. An Optimized Method for Accurate Fetal Sex Prediction and Sex Chromosome Aneuploidy Detection in Non-Invasive Prenatal Testing

    PubMed Central

    Li, Haibo; Ding, Jie; Wen, Ping; Zhang, Qin; Xiang, Jingjing; Li, Qiong; Xuan, Liming; Kong, Lingyin; Mao, Yan; Zhu, Yijun; Shen, Jingjing; Liang, Bo; Li, Hong

    2016-01-01

    Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing. PMID:27441628

  4. 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.

  5. The consequences of implementing non-invasive prenatal testing in Dutch national health care: a cost-effectiveness analysis.

    PubMed

    Beulen, Lean; Grutters, Janneke P C; Faas, Brigitte H; Feenstra, Ilse; van Vugt, John M G; Bekker, Mireille N

    2014-11-01

    Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy. Clinical trials have shown high sensitivity and specificity for trisomy 21 (T21) in both high-risk and average-risk populations. Although its great potential for prenatal medicine is evident, more information regarding the consequences of implementing NIPT in a national programme for prenatal screening is required. A decision-analytic model was developed to compare costs and outcomes of current clinical practice in The Netherlands using conventional screening only, with two alternatives: implementing NIPT as an optional secondary screening test for those pregnancies complicated by a high risk for T21, and implementing NIPT as primary screening test, replacing conventional screening. Probability estimates were derived from a systematic review of international literature. Costs were determined from a health-care perspective. Data were analysed to obtain outcomes, total costs, relative costs and incremental cost-effectiveness ratios (ICERs) for the different strategies. Sensitivity analysis was used to assess the impact of assumptions on model results. Implementing NIPT as an optional secondary, or as primary screening test will increase T21 detection rate by 36% (from 46.8% to 63.5%) and 54% (from 46.8% to 72.0%), simultaneously decreasing the average risk of procedure-related miscarriage by 44% (from 0.0168% to 0.0094% per pregnant woman) and 62% (from 0.0168% to 0.0064% per pregnant woman), respectively. None of the strategies clearly dominated: current clinical practice is the least costly, whereas implementing NIPT will cause total costs of the programme to increase by 21% (from €257.09 to €311.74 per pregnant woman), leading to an ICER of k€94 per detected case of T21, when utilised as an optional secondary screening test and by 157% (from €257.09 to €660.94 per pregnant woman), leading to an ICER of k€460 per

  6. 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.

  7. Introducing the non-invasive prenatal test for trisomy 21 in Belgium: a cost-consequences analysis.

    PubMed

    Neyt, Mattias; Hulstaert, Frank; Gyselaers, Wilfried

    2014-11-07

    The first- and second-trimester screening for trisomy 21 (T21) are reimbursed for all pregnant women in Belgium. Using a cut-off risk of 1:300 for T21, about 5% of all pregnant women are referred for definitive prenatal diagnosis using an invasive test, at a sensitivity of (only) 72.5%. The sensitivity and specificity of the non-invasive prenatal test (NIPT) are over 99% but come at a cost of €460 (£373) per test. The objective is to estimate the consequences of introducing NIPT for the detection of T21. A cost-consequences analysis was performed presenting the impact on benefits, harms and costs. Context-specific real-world information was available to set up a model reflecting the current screening situation in Belgium. This model was used to construct the second and first line NIPT screening scenarios applying information from the literature on NIPT's test accuracy. Introducing NIPT in the first or second line reduces harm by decreasing the number of procedure-related miscarriages after invasive testing. In contrast with NIPT in the second line, offering NIPT in the first line additionally will miss fewer cases of T21 due to less false-negative test results. The introduction of NIPT in the second line results in cost savings, which is not true for NIPT at the current price in the first line. If NIPT is offered to all pregnant women, the price should be lowered to about €150 to keep the screening cost per T21 diagnosis constant. In Belgium, the introduction and reimbursement of NIPT as a second line triage test significantly reduces procedure-related miscarriages without increasing the short-term screening costs. Offering and reimbursing NIPT in the first line to all pregnant women is preferred in the long term, as it would, in addition, miss fewer cases of T21. However, taking into account the government's limited resources for universal reimbursement, the price of NIPT should first be lowered substantially before this can be realised. Published by the BMJ

  8. 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

  9. 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

  10. Hypermethylated ERG as a cell-free fetal DNA biomarker for non-invasive prenatal testing of Down syndrome.

    PubMed

    Chen, Xi; Xiong, Likuan; Zeng, Ting; Xiao, Kelin; Huang, Yanping; Guo, Hui; Ren, Jinghui

    2015-04-15

    Previous reports have shown that the ERG gene is hypermethylated in the placenta and hypomethylated in maternal blood cells. In this study, we explore the feasibility of hypermethylated ERG as a cell-free fetal (cff) DNA biomarker for non-invasive prenatal testing (NIPT) of Down syndrome. We randomly selected 90 healthy pregnant women, including 30 cases at each trimester of pregnancy. In addition, 15 pregnant women were recruited as the case group whose fetuses had been confirmed to have trisomy 21 by amniotic fluid analysis at 18th to 26th week gestation. Using HpaII, MspІ to digest cell-free maternal plasma DNA, we performed SYBR Green PCR to detect methylated sites of ERG sequences, and analyzed the concentrations of cff DNA in maternal plasma in different gestational trimesters and the case group. The ERG median concentrations of the maternal plasma after Hpa II digestion (LG copies/ml) in first, second and third-trimesters were 5.38, 6.10, and 7.04, respectively (Kruskal-Wallis, P<0.01); and that in the trisomy 21 case group was 6.85, which was higher than the second-trimester (Mann-Whitney, P<0.01). The study demonstrated that ERG gene is hypermethylated in cff DNA but hypomethylated in maternal DNA; and the median concentration of ERG gene in the trisomy 21 case group is higher than that in the gestational trimester matched normal group. ERG gene, as a fetal DNA biomarker, may be useful for NIPT of Down syndrome. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. New trend in non-invasive prenatal diagnosis.

    PubMed

    Ferrari, M; Carrera, P; Lampasona, V; Galbiati, S

    2015-12-07

    The presence of fetal DNA in maternal plasma represents a source of genetic material which can be obtained non-invasively. To date, the translation of noninvasive prenatal diagnosis from research into clinical practice has been rather fragmented, and despite the advances in improving the analytical sensitivity of methods, distinguishing between fetal and maternal sequences remains very challenging. Thus, the field of noninvasive prenatal diagnosis of genetic diseases has yet to attain a routine application in clinical diagnostics. On the contrary, fetal sex determination in pregnancies at high risk of sex-linked disorders, tests for fetal RHD genotyping and non-invasive assessment of chromosomal aneuploidies are now available worldwide. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Non-invasive prenatal diagnostic test accuracy for fetal sex using cell-free DNA a review and meta-analysis.

    PubMed

    Wright, Caroline F; Wei, Yinghui; Higgins, Julian P T; Sagoo, Gurdeep S

    2012-09-01

    Cell-free fetal DNA (cffDNA) can be detected in maternal blood during pregnancy, opening the possibility of early non-invasive prenatal diagnosis for a variety of genetic conditions. Since 1997, many studies have examined the accuracy of prenatal fetal sex determination using cffDNA, particularly for pregnancies at risk of an X-linked condition. Here we report a review and meta-analysis of the published literature to evaluate the use of cffDNA for prenatal determination (diagnosis) of fetal sex. We applied a sensitive search of multiple bibliographic databases including PubMed (MEDLINE), EMBASE, the Cochrane library and Web of Science. Ninety studies, incorporating 9,965 pregnancies and 10,587 fetal sex results met our inclusion criteria. Overall mean sensitivity was 96.6% (95% credible interval 95.2% to 97.7%) and mean specificity was 98.9% (95% CI = 98.1% to 99.4%). These results vary very little with trimester or week of testing, indicating that the performance of the test is reliably high. Based on this review and meta-analysis we conclude that fetal sex can be determined with a high level of accuracy by analyzing cffDNA. Using cffDNA in prenatal diagnosis to replace or complement existing invasive methods can remove or reduce the risk of miscarriage. Future work should concentrate on the economic and ethical considerations of implementing an early non-invasive test for fetal sex.

  13. Detection of fetal chromosomal anomalies: does nuchal translucency measurement have added value in the era of non-invasive prenatal testing?

    PubMed

    Lichtenbelt, K D; Diemel, B D M; Koster, M P H; Manten, G T R; Siljee, J; Schuring-Blom, G H; Page-Christiaens, G C M L

    2015-07-01

    The objective of this study is to determine what percentage of fetal chromosomal anomalies remains undetected when first trimester combined testing is replaced by non-invasive prenatal testing for trisomies 13, 18, and 21. We focused on the added clinical value of nuchal translucency (NT) measurement. Data on fetal karyotype, ultrasound findings, and pregnancy outcome of all pregnancies with an NT measurement ≥3.5 mm were retrospectively collected from a cohort of 25,057 singleton pregnancies in which first trimester combined testing was performed. Two hundred twenty-five fetuses (0.9 %) had an NT ≥3.5 mm. In 24 of these pregnancies, a chromosomal anomaly other than trisomy 13, 18, or 21 was detected. Eleven resulted in fetal demise, and ten showed fetal ultrasound anomalies. In three fetuses with normal ultrasound findings, a chromosomal anomaly was detected, of which one was a triple X. In three out of 25,057 pregnancies (0.01%), non-invasive prenatal testing and fetal ultrasound would have missed a chromosomal anomaly that would have been identified by NT measurement. © 2015 John Wiley & Sons, Ltd. © 2015 John Wiley & Sons, Ltd.

  14. Discordant results between fetal karyotyping and non-invasive prenatal testing by maternal plasma sequencing in a case of uniparental disomy 21 due to trisomic rescue.

    PubMed

    Pan, Min; Li, Fa Tao; Li, Yan; Jiang, Fu Man; Li, Dong Zhi; Lau, Tze Kin; Liao, Can

    2013-06-01

    Uniparental disomy (UPD) is an uncommon chromosome condition, but UPD involving chromosome 21 is rarely reported. We reported here a case who had first trimester screening test for Down syndrome, chorionic villus sampling for fetal karyotyping, quantitative fluorescence polymerase chain reaction (QF-PCR), as well as non-invasive prenatal testing (NIPT) by maternal plasma sequencing. There were discordant results between fetal karyotyping and NIPT due to UPD 21combined with confined placental mosaicism of trisomy 21. This demonstrated that it is possible to detect placental mosaicism by NIPT, but further studies are required to confirm its sensitivity. Therefore, all positive NIPT results must be confirmed by conventional invasive test and karyotyping. QF-PCR has the additional benefit in diagnosing UPD. © 2013 John Wiley & Sons, Ltd.

  15. Obstetric professionals' perceptions of non-invasive prenatal testing for Down syndrome: clinical usefulness compared with existing tests and ethical implications.

    PubMed

    Ngan, Olivia Miu Yung; Yi, Huso; Wong, Samuel Yeung Shan; Sahota, Daljit; Ahmed, Shenaz

    2017-09-05

    While non-invasive prenatal testing (NIPT) for fetal aneuploidy is commercially available in many countries, little is known about how obstetric professionals in non-Western populations perceive the clinical usefulness of NIPT in comparison with existing first-trimester combined screening (FTS) for Down syndrome (DS) or invasive prenatal diagnosis (IPD), or perceptions of their ethical concerns arising from the use of NIPT. A cross-sectional survey among 327 obstetric professionals (237 midwives, 90 obstetricians) in Hong Kong. Compared to FTS, NIPT was believed to: provide more psychological benefits and enable earlier consideration of termination of pregnancy. Compared to IPD, NIPT was believed to: provide less psychological stress for high-risk women and more psychological assurance for low-risk women, and offer an advantage to detect chromosomal abnormalities earlier. Significant differences in perceived clinical usefulness were found by profession and healthcare sector: (1) obstetricians reported more certain views towards the usefulness of NIPT than midwives and (2) professionals in the public sector perceived less usefulness of NIPT than the private sector. Beliefs about earlier detection of DS using NIPT were associated with ethical concerns about increasing abortion. Participants believing that NIPT provided psychological assurance among low-risk women were less likely to be concerned about ethical issues relating to informed decision-making and pre-test consultation for NIPT. Our findings suggest the need for political debate initially on how to ensure pregnant women accessing public services are informed about commercially available more advanced technology, but also on the potential implementation of NIPT within public services to improve access and equity to DS screening services.

  16. The first 3,000 Non-Invasive Prenatal Tests (NIPT) with the Harmony test in Belgium and the Netherlands.

    PubMed

    Willems, P J; Dierickx, H; Vandenakker, Es; Bekedam, D; Segers, N; Deboulle, K; Vereecken, A

    2014-01-01

    As the classical first trimester Down syndrome screening (FTS, combination test) has a false-negative rate of 20-25% and > 95% of the abnormal FTS results are false-positive, we evaluated the new Non-Invasive Prenatal Test (NIPT) in Belgium and the Netherlands. The study population consisted of 3000 consecutive pregnancies in Belgium and the Netherlands in which NIPT was performed using the Harmony test. In 57 (1.9%) of the 3000 pregnancies an abnormal NIPT result was found. This included 51 fetuses with trisomy 21, 4 fetuses with trisomy 18 and 2 fetuses with trisomy 13. In 47 of the 57 the NIPT result was confirmed by genetic testing of material obtained by amniocentesis or chorionic biopsy, and no false-positive results were recorded. The false-negative rate as determined on more than 2000 women that had delivered at the time of reporting was low, and so far only 2 false-negative results were reported (one trisomy 18 and one trisomy 21). The failure rate where no NIPT result could be obtained after repeated sampling was 0.90%. In this large clinical series, NIPT using the Harmony test proves to be a very reliable prenatal test to detect fetal trisomies 21, 18 and 13 in maternal blood in Belgium and the Netherlands.

  17. 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.

  18. Diagnosis for choroideremia in a large Chinese pedigree by next-generation sequencing (NGS) and non-invasive prenatal testing (NIPT)

    PubMed Central

    Zhu, Li; Cheng, Jingliang; Zhou, Boxu; Wei, Chunli; Yang, Weichan; Jiang, Dong; Ijaz, Iqra; Tan, Xiaojun; Chen, Rui; Fu, Junjiang

    2017-01-01

    To develop an effective strategy to isolate and use cell-free fetal DNA (cffDNA) for the combined use of next-generation sequencing (NGS) for diagnosing choroideremia and non-invasive prenatal testing (NIPT) for Y chromosome determination, a large Chinese family with an X-linked recessive disease, choroideremia, was recruited. Cell-free DNA was extracted from maternal plasma, and SRY polymerase chain reaction amplification was performed using NIPT. Sanger sequencing was subsequently used for fetal amniotic fluid DNA verification. A nonsense mutation (c.C799T:p.R267X) of the CHM gene on the X chromosome of the proband (IV:7) and another 5 males with choroideremia were detected, while 3 female carriers with no symptoms were also identified. The fetus (VI:7) was identified as female from the cffDNA, and the same heterozygous nonsense mutation present in her mother was also confirmed. At one and a half years of age, the female baby did not present with any associated symptoms of choroideremia. Therefore, cffDNA was successfully used for the combined use of NGS for diagnosing choroideremia in a large Chinese pedigree, and NIPT for Y chromosome determination. This approach should result in a markedly increased use of prenatal diagnosis and improvement, and more sophisticated clinical management of diseases in China and other developing countries. The establishment of a highly accurate method for prenatal gene diagnosis will allow for more reliable gene diagnosis, improved genetic counseling, and personalized clinical management of our patients. PMID:28098911

  19. 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.

  20. Clinical utility and cost of non-invasive prenatal testing with cfDNA analysis in high-risk women based on a US population

    PubMed Central

    Song, Ken; Musci, Thomas J.; Caughey, Aaron B.

    2013-01-01

    Objective Evaluate the clinical and economic consequences of fetal trisomy 21 (T21) screening with non-invasive prenatal testing (NIPT) in high-risk pregnant women. Methods Using a decision-analytic model, we estimated the number of T21 cases detected, the number of invasive procedures performed, corresponding euploid fetal losses and total costs for three screening strategies: first trimester combined screening (FTS), integrated screening (INT) or NIPT, whereby NIPT was performed in high-risk patients (women 35 years or older or women with a positive conventional screening test). Modeling was based on a 4 million pregnant women cohort in the US. Results NIPT, at a base case price of $795, was more clinically effective and less costly (dominant) over both FTS and INT. NIPT detected 4823 T21 cases based on 5330 invasive procedures. FTS detected 3364 T21 cases based on 108 364 procedures and INT detected 3760 cases based on 108 760 procedures. NIPT detected 28% and 43% more T21 cases compared to INT and FTS, respectively, while reducing invasive procedures by >95% and reducing euploid fetal losses by >99%. Total costs were $3786M with FTS, $3919M with INT and $3403M with NIPT. Conclusions NIPT leads to improved T21 detection and reduction in euploid fetal loss at lower total healthcare expenditures. PMID:23356557

  1. Mosaic embryo transfer after oocyte in vitro maturation in combination with non-invasive prenatal testing (NIPT)-first report of a euploid live birth.

    PubMed

    Inoue, Naomi; Lopez, Rosmary; Delgado, Andrea; Nuñez, Denisse; Portella, Jimmy; Noriega-Hoces, Luis; Guzmán, Luis

    2017-06-24

    The purpose of this study is to describe a healthy life birth after a mosaic embryo transfer in oocyte in vitro maturation (IVM). Patient received minimal stimulation, starting on day 3 after menstrual period. No hCG trigger was administered. Oocyte retrieval was performed and oocytes were matured for 30 h. After denuding, mature oocytes were inseminated by ICSI. Embryos were cultured until blastocyst stage and biopsied. One euploid embryo after array comprehensive genome hybridization (aCGH) was diagnostic. However, the next-generation sequencing (NGS) re-analysis showed that embryo was a mosaic for chromosome 13 and 21. Nevertheless, pregnancy ultrasound scans and non-invasive prenatal test (NIPT-Verifi-Illumina) indicated a normal fetus development. Finally, a healthy baby was born after 38 weeks. Its weight was 4480 g, head circumference 36 cm, and total length of 51 cm. To confirm that the baby was chromosomically normal, an NGS test was performed in buccal cells, a normal profile was obtained. Our finding confirmed that mosaic embryo transfer would bring a healthy offspring.

  2. 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

  3. 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.

  4. Women’s Experiences and Preferences for Service Delivery of Non-Invasive Prenatal Testing for Aneuploidy in a Public Health Setting: A Mixed Methods Study

    PubMed Central

    Lewis, Celine; Hill, Melissa; Chitty, Lyn S.

    2016-01-01

    Non-invasive prenatal testing (NIPT) for aneuploidy is currently only available in the UK through the private sector outside of the research arena. As part of an implementation study in the UK National Health Service we conducted a mixed methods study to assess women’s experience of being offered NIPT using validated measures of decisional conflict, decisional regret and anxiety. Clinical service preferences were also explored. Women with a Down syndrome screening risk >1:1000 were invited to take part in the study and offered NIPT, NIPT and invasive testing (for women with a risk above 1:150) or no further testing. A cross-sectional survey and semi-structured interviews were conducted at two time points; at the time of testing and one month following receipt of results (or equivalent for NIPT decliners). In total, 845 questionnaires and 81 interviews were analysed. The main motivation to accept NIPT was for reassurance (30.8%). Decisional conflict occurred in a minimal number of cases (3.8%), however, none of the participants experienced decisional regret. Around a third (29.9%) of women had elevated anxiety at the time of testing, including intermediate risk women who traditionally would not be offered further testing (54.4% high risk; 20.1% medium risk), a finding supported through the qualitative interviews where prolonged or additional anxiety was found to occur in some medium risk cases. Women were overwhelmingly positive about the opportunity to have a test that was procedurally safe, accurate, reduced the need for invasive testing and identified cases of Down syndrome that might otherwise have been missed. Reassurance was identified as the main motivator for accepting NIPT, particularly amongst medium risk women, with high risk women inclined to accept NIPT to inform decisions around invasive testing. The current turnaround time for test result was identified as a key limitation. All the women interviewed thought NIPT should be adopted as part of NHS

  5. Women's Experiences and Preferences for Service Delivery of Non-Invasive Prenatal Testing for Aneuploidy in a Public Health Setting: A Mixed Methods Study.

    PubMed

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

    2016-01-01

    Non-invasive prenatal testing (NIPT) for aneuploidy is currently only available in the UK through the private sector outside of the research arena. As part of an implementation study in the UK National Health Service we conducted a mixed methods study to assess women's experience of being offered NIPT using validated measures of decisional conflict, decisional regret and anxiety. Clinical service preferences were also explored. Women with a Down syndrome screening risk >1:1000 were invited to take part in the study and offered NIPT, NIPT and invasive testing (for women with a risk above 1:150) or no further testing. A cross-sectional survey and semi-structured interviews were conducted at two time points; at the time of testing and one month following receipt of results (or equivalent for NIPT decliners). In total, 845 questionnaires and 81 interviews were analysed. The main motivation to accept NIPT was for reassurance (30.8%). Decisional conflict occurred in a minimal number of cases (3.8%), however, none of the participants experienced decisional regret. Around a third (29.9%) of women had elevated anxiety at the time of testing, including intermediate risk women who traditionally would not be offered further testing (54.4% high risk; 20.1% medium risk), a finding supported through the qualitative interviews where prolonged or additional anxiety was found to occur in some medium risk cases. Women were overwhelmingly positive about the opportunity to have a test that was procedurally safe, accurate, reduced the need for invasive testing and identified cases of Down syndrome that might otherwise have been missed. Reassurance was identified as the main motivator for accepting NIPT, particularly amongst medium risk women, with high risk women inclined to accept NIPT to inform decisions around invasive testing. The current turnaround time for test result was identified as a key limitation. All the women interviewed thought NIPT should be adopted as part of NHS

  6. Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis

    PubMed Central

    Taylor-Phillips, Sian; Freeman, Karoline; Geppert, Julia; Agbebiyi, Adeola; Uthman, Olalekan A; Madan, Jason; Clarke, Angus; Quenby, Siobhan; Clarke, Aileen

    2016-01-01

    Objective To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy. Design Systematic review and meta-analysis of published studies. Data sources PubMed, Ovid Medline, Ovid Embase and the Cochrane Library published from 1997 to 9 February 2015, followed by weekly autoalerts until 1 April 2015. Eligibility criteria for selecting studies English language journal articles describing case–control studies with ≥15 trisomy cases or cohort studies with ≥50 pregnant women who had been given NIPT and a reference standard. Results 41, 37 and 30 studies of 2012 publications retrieved were included in the review for Down, Edwards and Patau syndromes. Quality appraisal identified high risk of bias in included studies, funnel plots showed evidence of publication bias. Pooled sensitivity was 99.3% (95% CI 98.9% to 99.6%) for Down, 97.4% (95.8% to 98.4%) for Edwards, and 97.4% (86.1% to 99.6%) for Patau syndrome. The pooled specificity was 99.9% (99.9% to 100%) for all three trisomies. In 100 000 pregnancies in the general obstetric population we would expect 417, 89 and 40 cases of Downs, Edwards and Patau syndromes to be detected by NIPT, with 94, 154 and 42 false positive results. Sensitivity was lower in twin than singleton pregnancies, reduced by 9% for Down, 28% for Edwards and 22% for Patau syndrome. Pooled sensitivity was also lower in the first trimester of pregnancy, in studies in the general obstetric population, and in cohort studies with consecutive enrolment. Conclusions NIPT using cell-free fetal DNA has very high sensitivity and specificity for Down syndrome, with slightly lower sensitivity for Edwards and Patau syndrome. However, it is not 100% accurate and should not be used as a final diagnosis for positive cases. Trial registration number CRD42014014947. PMID:26781507

  7. 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.

  8. The accuracy of cell-free fetal DNA-based non-invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta-analysis.

    PubMed

    Mackie, F L; Hemming, K; Allen, S; Morris, R K; Kilby, M D

    2017-01-01

    Cell-free fetal DNA (cffDNA) non-invasive prenatal testing (NIPT) is rapidly expanding, and is being introduced at varying rates depending on country and condition. Determine accuracy of cffDNA-based NIPT for all conditions. Evaluate influence of other factors on test performance. Medline, Embase, CINAHL, Cochrane Library, from 1997 to April 2015. Cohort studies reporting cffDNA-based NIPT performance in singleton pregnancies. Bivariate or univariate meta-analysis and subgroup analysis performed to explore influence of test type and population risk. A total of 117 studies were included that analysed 18 conditions. Bivariate meta-analysis demonstrated sensitivities and specificities, respectively, for: fetal sex, 0.989 (95% CI 0.980-0.994) and 0.996 (95% CI 0.989-0.998), 11 179 tests; rhesus D, 0.993 (95% CI 0.982-0.997) and 0.984 (95% CI 0.964-0.993), 10 290 tests; trisomy 21, 0.994 (95% CI 0.983-0.998) and 0.999 (95% CI 0.999-1.000), 148 344 tests; trisomy 18, 0.977 (95% CI 0.952-0.989) and 0.999 (95% CI 0.998-1.000), 146 940 tests; monosomy X, 0.929 (95% CI 0.741-0.984) and 0.999 (95% CI 0.995-0.999), 6712 tests. Trisomy 13 was analysed by univariate meta-analysis, with a summary sensitivity of 0.906 (95% CI 0.823-0.958) and specificity of 1.00 (95% CI 0.999-0.100), from 134 691 tests. False and inconclusive results were poorly reported across all conditions. Although the test type affected both sensitivity and specificity, there was no evidence that population risk had any effect. Performance of cffDNA-based NIPT is affected by condition under investigation. For fetal sex and rhesus D status, NIPT can be considered diagnostic. For trisomy 21, 18, and 13, the lower sensitivity, specificity, and disease prevalence, combined with the biological influence of confined placental mosaicism, designates it a screening test. These factors must be considered when counselling patients and assessing the cost of introduction into routine care

  9. 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

  10. Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis.

    PubMed

    Taylor-Phillips, Sian; Freeman, Karoline; Geppert, Julia; Agbebiyi, Adeola; Uthman, Olalekan A; Madan, Jason; Clarke, Angus; Quenby, Siobhan; Clarke, Aileen

    2016-01-18

    To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy. Systematic review and meta-analysis of published studies. PubMed, Ovid Medline, Ovid Embase and the Cochrane Library published from 1997 to 9 February 2015, followed by weekly autoalerts until 1 April 2015. English language journal articles describing case-control studies with ≥ 15 trisomy cases or cohort studies with ≥ 50 pregnant women who had been given NIPT and a reference standard. 41, 37 and 30 studies of 2012 publications retrieved were included in the review for Down, Edwards and Patau syndromes. Quality appraisal identified high risk of bias in included studies, funnel plots showed evidence of publication bias. Pooled sensitivity was 99.3% (95% CI 98.9% to 99.6%) for Down, 97.4% (95.8% to 98.4%) for Edwards, and 97.4% (86.1% to 99.6%) for Patau syndrome. The pooled specificity was 99.9% (99.9% to 100%) for all three trisomies. In 100,000 pregnancies in the general obstetric population we would expect 417, 89 and 40 cases of Downs, Edwards and Patau syndromes to be detected by NIPT, with 94, 154 and 42 false positive results. Sensitivity was lower in twin than singleton pregnancies, reduced by 9% for Down, 28% for Edwards and 22% for Patau syndrome. Pooled sensitivity was also lower in the first trimester of pregnancy, in studies in the general obstetric population, and in cohort studies with consecutive enrolment. NIPT using cell-free fetal DNA has very high sensitivity and specificity for Down syndrome, with slightly lower sensitivity for Edwards and Patau syndrome. However, it is not 100% accurate and should not be used as a final diagnosis for positive cases. CRD42014014947. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  11. Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down’s syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units

    PubMed Central

    Wright, David; Hill, Melissa; Verhoef, Talitha I; Daley, Rebecca; Lewis, Celine; Mason, Sarah; McKay, Fiona; Jenkins, Lucy; Howarth, Abigail; Cameron, Louise; McEwan, Alec; Fisher, Jane; Kroese, Mark; Morris, Stephen

    2016-01-01

    Objective To investigate the benefits and costs of implementing non-invasive prenatal testing (NIPT) for Down’s syndrome into the NHS maternity care pathway. Design Prospective cohort study. Setting Eight maternity units across the United Kingdom between 1 November 2013 and 28 February 2015. Participants All pregnant women with a current Down’s syndrome risk on screening of at least 1/1000. Main outcome measures Outcomes were uptake of NIPT, number of cases of Down’s syndrome detected, invasive tests performed, and miscarriages avoided. Pregnancy outcomes and costs associated with implementation of NIPT, compared with current screening, were determined using study data on NIPT uptake and invasive testing in combination with national datasets. Results NIPT was prospectively offered to 3175 pregnant women. In 934 women with a Down’s syndrome risk greater than 1/150, 695 (74.4%) chose NIPT, 166 (17.8%) chose invasive testing, and 73 (7.8%) declined further testing. Of 2241 women with risks between 1/151 and 1/1000, 1799 (80.3%) chose NIPT. Of 71 pregnancies with a confirmed diagnosis of Down’s syndrome, 13/42 (31%) with the diagnosis after NIPT and 2/29 (7%) after direct invasive testing continued, resulting in 12 live births. In an annual screening population of 698 500, offering NIPT as a contingent test to women with a Down’s syndrome screening risk of at least 1/150 would increase detection by 195 (95% uncertainty interval −34 to 480) cases with 3368 (2279 to 4027) fewer invasive tests and 17 (7 to 30) fewer procedure related miscarriages, for a non-significant difference in total costs (£−46 000, £−1 802 000 to £2 661 000). The marginal cost of NIPT testing strategies versus current screening is very sensitive to NIPT costs; at a screening threshold of 1/150, NIPT would be cheaper than current screening if it cost less than £256. Lowering the risk threshold increases the number of Down’s syndrome cases detected and

  12. Fetal cells in maternal blood: state of the art for non-invasive prenatal diagnosis.

    PubMed

    Ho, S S; O'Donoghue, K; Choolani, M

    2003-09-01

    In Singapore, 1 in 5 pregnancies occur in mothers > 35 years old and genetic diseases, such as thalassaemia, are common. Current methods for the diagnosis of aneuploidy and monogenic disorders require invasive testing by amniocentesis, chorion villus biopsy or fetal blood sampling. These tests carry a procedure-related risk of miscarriage that is unacceptable to many couples. Development of non-invasive methods for obtaining intact fetal cells would allow accurate prenatal diagnosis for aneuploidy and single gene disorders, without the attendant risks associated with invasive testing, and would increase the uptake of prenatal diagnosis by women at risk. Isolation of fetal erythroblasts from maternal blood should allow accurate non-invasive prenatal diagnosis of both aneuploidies and monogenic disorders. Expression of gamma-globin in maternal erythroblasts and the inability to locate fetal erythroblasts reliably in all pregnancies have prevented its clinical application. In the absence of a highly specific fetal cell marker, enrichment, identification and diagnosis--the 3 components of non-invasive prenatal diagnosis--have clearly defined objectives. Since fetal cells are rare in maternal blood, the sole purpose of enrichment is yield--to recover as many fetal cells as possible--even if purity is compromised at this stage. In contrast, the primary goal of identification is specificity; absolute certainty of fetal origin is required at this stage if the ultimate objective of diagnosis, accuracy, is to be achieved. This review summarises the current state of the art of non-invasive prenatal diagnosis using fetal erythroblasts enriched from maternal blood.

  13. Non-invasive prenatal diagnosis of thalassemias using maternal plasma cell free DNA.

    PubMed

    Hudecova, Irena; Chiu, Rossa W K

    2017-02-01

    Non-invasive prenatal testing (NIPT) using maternal plasma cell free DNA has already reshaped the existing prenatal care system for pregnancies screened for common chromosomal aneuploidies. On the other hand, much progress has been made in developing NIPT for monogenic diseases. Thalassemia served as a disease model to develop strategies for NIPT of monogenic traits. One approach focuses on the detection or exclusion of paternally inherited fetal mutations that are absent from the mother's genome. The assessment of maternally inherited mutations in maternal plasma requires the use of highly sensitive DNA quantification techniques. The relative mutation dosage (RMD) or the relative haplotype dosage (RHDO) approach provides a powerful tool to elucidate the fetal mutational status even in populations with lower genetic diversity, where the parents share the same mutation. With expected decrease in sequencing costs, NIPT for monogenic diseases is becoming an affordable option in prenatal care. Copyright © 2016. Published by Elsevier Ltd.

  14. Non-Invasive Prenatal Diagnosis of Lethal Skeletal Dysplasia by Targeted Capture Sequencing of Maternal Plasma

    PubMed Central

    Wang, Yaoshen; Chen, Chao; Gao, Changxin; Yu, Song; Liu, Yan; Song, Wei; Asan; Zhu, Hongmei; Yang, Ling; Deng, Hongmei; Su, Yue; Yi, Xin

    2016-01-01

    Background Since the discovery of cell-free foetal DNA in the plasma of pregnant women, many non-invasive prenatal testing assays have been developed. In the area of skeletal dysplasia diagnosis, some PCR-based non-invasive prenatal testing assays have been developed to facilitate the ultrasound diagnosis of skeletal dysplasias that are caused by de novo mutations. However, skeletal dysplasias are a group of heterogeneous genetic diseases, the PCR-based method is hard to detect multiple gene or loci simultaneously, and the diagnosis rate is highly dependent on the accuracy of the ultrasound diagnosis. In this study, we investigated the feasibility of using targeted capture sequencing to detect foetal de novo pathogenic mutations responsible for skeletal dysplasia. Methodology/Principal Findings Three families whose foetuses were affected by skeletal dysplasia and two control families whose foetuses were affected by other single gene diseases were included in this study. Sixteen genes related to some common lethal skeletal dysplasias were selected for analysis, and probes were designed to capture the coding regions of these genes. Targeted capture sequencing was performed on the maternal plasma DNA, the maternal genomic DNA, and the paternal genomic DNA. The de novo pathogenic variants in the plasma DNA data were identified using a bioinformatical process developed for low frequency mutation detection and a strict variant interpretation strategy. The causal variants could be specifically identified in the plasma, and the results were identical to those obtained by sequencing amniotic fluid samples. Furthermore, a mean of 97% foetal specific alleles, which are alleles that are not shared by maternal genomic DNA and amniotic fluid DNA, were identified successfully in plasma samples. Conclusions/Significance Our study shows that capture sequencing of maternal plasma DNA can be used to non-invasive detection of de novo pathogenic variants. This method has the potential

  15. Impact of fetal or child loss on parents' perceptions of non-invasive prenatal diagnosis for autosomal recessive conditions.

    PubMed

    Pisnoli, Laura; O'Connor, Anita; Goldsmith, Lesley; Jackson, Leigh; Skirton, Heather

    2016-03-01

    to explore parents' personal attitudes towards non-invasive prenatal diagnosis in the context of their own experiences caring for a child affected with a genetic condition or after the loss of a fetus, infant, or child due to the condition. we collected in-depth data from parents via either focus groups or individual interviews. this was a cross-sectional interpretive study based on grounded theory. United Kingdom. 17 parents (13 women and four men) who were carriers of a serious autosomal recessive condition: spinal muscular atrophy, cystic fibrosis or thalassaemia. All had a child (living or deceased) with the condition. parents experienced changes in reproductive self-identity due to their experiences of having an affected child: this influenced their views of non-invasive prenatal testing. They began their reproductive journeys 'naively', but described feelings of reproductive vulnerability after the diagnosis of the child and consequent realisation of risks to future children. They viewed non-invasive prenatal testing as a way to reduce threats to unborn children, while allowing prenatal diagnosis. when parents lose a child they may use emotional guarding, delayed pregnancy disclosure and avoidance of harmful activities to cope in future pregnancies. Parents who want to consider early prenatal testing are less able to utilise these strategies, but non-invasive methods allow them to reduce the risk. midwives should be sensitive to parents' reproductive vulnerability after genetic diagnosis of a child and ensure they are supported to consider the option of non-invasive prenatal testing if appropriate. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Non-invasive Prenatal Diagnosis for BRCA Mutations - a Qualitative Pilot Study of Health Professionals' Views.

    PubMed

    Bennett, Jade; Chitty, Lyn; Lewis, Celine

    2016-02-01

    Non-invasive prenatal diagnosis (NIPD) is a rapidly advancing approach that allows diagnostic testing based on analysis of cell free DNA in maternal plasma. This study aimed to explore the views of health professionals regarding the use of NIPD for BRCA1/2 mutations. Qualitative semi-structured interviews were conducted with eight participants. Whilst participants viewed NIPD in general as a positive step forward in prenatal testing, they were cautious about its use for BRCA testing. Significant ethical concerns emerged regarding testing prenatally for an adult onset condition, that is not fully penetrant, and the possibility of abrogating the rights of the future child to genetic autonomy. Nevertheless, participants did identify some situations whereby the test might be beneficial, such as for individuals with very negative and traumatic personal experiences of cancer desiring reassurance or wanting to prevent passing on the condition. NIPD was also seen as having benefits over invasive testing and pre-implantation genetic diagnosis, the only other options currently available to test prenatally for this condition. Exploring the views of a wider range of clinical specialties as well as patients at risk of hereditary breast cancer would be beneficial.

  17. Evaluating the culture of fetal erythroblasts from maternal blood for non-invasive prenatal diagnosis.

    PubMed

    Chen, H; Griffin, D K; Jestice, K; Hackett, G; Cooper, J; Ferguson-Smith, M A

    1998-09-01

    Fetal erythroblasts circulating in maternal blood are important candidate cells for non-invasive prenatal diagnosis. We have cultured erythroblasts from 16 maternal blood samples, both with and without prior enrichment by magnetic activated cell sorting (MACS), in a semi-solid medium containing growth factors. Individual colonies were examined by PCR with sex chromosome-specific primers and microsatellite marker primers. No conclusive Y-chromosome specific amplification could be demonstrated in any of the 16 cases, even when the mother was confirmed to be carrying a male fetus. All colonies tested by microsatellite marker PCR were of maternal origin. Our results suggest that the probability of obtaining fetal colonies from fetal erythroblasts circulating in maternal blood is very low and that approaches for culturing fetal erythroblasts in vitro cannot yet be used reliably for prenatal diagnosis using current methods for fetal cell enrichment.

  18. 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.

  19. Targeted capture enrichment assay for non-invasive prenatal testing of large and small size sub-chromosomal deletions and duplications

    PubMed Central

    Tsangaras, Kyriakos; Kypri, Elena; Loizides, Charalambos; Ioannides, Marios; Achilleos, Achilleas; Mina, Petros; Keravnou, Anna; Sismani, Carolina; Koumbaris, George; Patsalis, Philippos C.

    2017-01-01

    Noninvasive prenatal testing (NIPT) using whole genome and targeted sequencing has become increasingly accepted for clinical detection of Trisomy 21 and sex chromosome aneuploidies. Few studies have shown that sub-chromosomal deletions or duplications associated with genetic syndromes can also be detected in the fetus noninvasively. There are still limitations on these methodologies such as the detection of variants of unknown clinical significance, high number of false positives, and difficulties to detect small aberrations. We utilized a recently developed targeted sequencing approach for the development of a NIPT assay, for large and small size deletions/duplications, which overcomes these existing limitations. Artificial pregnancies with microdeletion/microduplication syndromes were created by spiking DNA from affected samples into cell free DNA (cfDNA) from non-pregnant samples. Unaffected spiked samples and normal pregnancies were used as controls. Target Capture Sequences (TACS) for seven syndromes were designed and utilized for targeted capture enrichment followed by sequencing. Data was analyzed using a statistical pipeline to identify deletions or duplications on targeted regions. Following the assay development a proof of concept study using 33 normal pregnancies, 21 artificial affected and 17 artificial unaffected pregnancies was carried out to test the sensitivity and specificity of the assay. All 21 abnormal spiked-in samples were correctly classified as subchromosomal aneuploidies while the 33 normal pregnancies or 17 normal spiked-in samples resulted in a false positive result. We have developed an NIPT assay for the detection of sub-chromosomal deletions and duplications using the targeted capture enrichment technology. This assay demonstrates high accuracy, high read depth of the genomic region of interest, and can identify deletions/duplications as small as 0.5 Mb. NIPT of fetal microdeletion/microduplication syndromes can be of enormous benefit

  20. 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.

  1. Systematic review and meta-analysis of non-invasive prenatal DNA testing for trisomy 21: implications for implementation in China.

    PubMed

    Jin, Jiajie; Yang, Junwen; Chen, Yingyao; Huang, Jiayan

    2017-07-07

    To systematically review clinical validation studies of massive parallel sequencing (MPS) technology in prenatal screening for trisomy 21 and to explore the potential implementation strategies in China compared with those in developing countries. Searches of the Cochrane Library, Medline, EMBASE, Web of Science, Biosis Previews, and three major Chinese databases were performed to identify all the peer-reviewed articles published between 1 January 2011 and 15 October 2016. We also reviewed and discussed the potential challenges and risks in the future promotion of MPS technology in China compared with those in developing countries. The weighted pooled sensitivity and specificity of MPS technology for the prenatal detection of trisomy 21 were 99.7% (95% CI 98.3-99.9%) and 100.0% (95% CI 99.9-100.0%), respectively, based on a meta-analysis of 44 included studies. An additional meta-analysis was conducted based on the 25 included studies that were performed in medical/genetic sequencing institutions in mainland China, showing a weighted pooled sensitivity and specificity of MPS technology as 99.5% (95% CI 98.7-99.8%) and 100% (95% CI 99.9-100%), respectively. MPS technology offers effective screening performance for trisomy 21 but should be cautiously promoted due to its clinical limitations and challenges that stem from the ethics and business aspects. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

  2. The Role of RNAs and microRNAs in Non-Invasive Prenatal Diagnosis

    PubMed Central

    Farina, Antonio

    2014-01-01

    In this paper, all possible clinical applications of circulating mRNA and miRNA for non-invasive prenatal diagnosis appearing in the medical literature so far are described. Data from the literature have also been reported and commented on along with some possible future applications. PMID:26237384

  3. 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 Central

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

    2014-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:24714162

  4. 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

  5. Bisulfite Conversion of DNA: Performance Comparison of Different Kits and Methylation Quantitation of Epigenetic Biomarkers that Have the Potential to Be Used in Non-Invasive Prenatal Testing

    PubMed Central

    Leontiou, Chrysanthia A.; Hadjidaniel, Michael D.; Mina, Petros; Antoniou, Pavlos; Ioannides, Marios; Patsalis, Philippos C.

    2015-01-01

    Introduction Epigenetic alterations, including DNA methylation, play an important role in the regulation of gene expression. Several methods exist for evaluating DNA methylation, but bisulfite sequencing remains the gold standard by which base-pair resolution of CpG methylation is achieved. The challenge of the method is that the desired outcome (conversion of unmethylated cytosines) positively correlates with the undesired side effects (DNA degradation and inappropriate conversion), thus several commercial kits try to adjust a balance between the two. The aim of this study was to compare the performance of four bisulfite conversion kits [Premium Bisulfite kit (Diagenode), EpiTect Bisulfite kit (Qiagen), MethylEdge Bisulfite Conversion System (Promega) and BisulFlash DNA Modification kit (Epigentek)] regarding conversion efficiency, DNA degradation and conversion specificity. Methods Performance was tested by combining fully methylated and fully unmethylated λ-DNA controls in a series of spikes by means of Sanger sequencing (0%, 25%, 50% and 100% methylated spikes) and Next-Generation Sequencing (0%, 3%, 5%, 7%, 10%, 25%, 50% and 100% methylated spikes). We also studied the methylation status of two of our previously published differentially methylated regions (DMRs) at base resolution by using spikes of chorionic villus sample in whole blood. Results The kits studied showed different but comparable results regarding DNA degradation, conversion efficiency and conversion specificity. However, the best performance was observed with the MethylEdge Bisulfite Conversion System (Promega) followed by the Premium Bisulfite kit (Diagenode). The DMRs, EP6 and EP10, were confirmed to be hypermethylated in the CVS and hypomethylated in whole blood. Conclusion Our findings indicate that the MethylEdge Bisulfite Conversion System (Promega) was shown to have the best performance among the kits. In addition, the methylation level of two of our DMRs, EP6 and EP10, was confirmed

  6. Bisulfite Conversion of DNA: Performance Comparison of Different Kits and Methylation Quantitation of Epigenetic Biomarkers that Have the Potential to Be Used in Non-Invasive Prenatal Testing.

    PubMed

    Leontiou, Chrysanthia A; Hadjidaniel, Michael D; Mina, Petros; Antoniou, Pavlos; Ioannides, Marios; Patsalis, Philippos C

    2015-01-01

    Epigenetic alterations, including DNA methylation, play an important role in the regulation of gene expression. Several methods exist for evaluating DNA methylation, but bisulfite sequencing remains the gold standard by which base-pair resolution of CpG methylation is achieved. The challenge of the method is that the desired outcome (conversion of unmethylated cytosines) positively correlates with the undesired side effects (DNA degradation and inappropriate conversion), thus several commercial kits try to adjust a balance between the two. The aim of this study was to compare the performance of four bisulfite conversion kits [Premium Bisulfite kit (Diagenode), EpiTect Bisulfite kit (Qiagen), MethylEdge Bisulfite Conversion System (Promega) and BisulFlash DNA Modification kit (Epigentek)] regarding conversion efficiency, DNA degradation and conversion specificity. Performance was tested by combining fully methylated and fully unmethylated λ-DNA controls in a series of spikes by means of Sanger sequencing (0%, 25%, 50% and 100% methylated spikes) and Next-Generation Sequencing (0%, 3%, 5%, 7%, 10%, 25%, 50% and 100% methylated spikes). We also studied the methylation status of two of our previously published differentially methylated regions (DMRs) at base resolution by using spikes of chorionic villus sample in whole blood. The kits studied showed different but comparable results regarding DNA degradation, conversion efficiency and conversion specificity. However, the best performance was observed with the MethylEdge Bisulfite Conversion System (Promega) followed by the Premium Bisulfite kit (Diagenode). The DMRs, EP6 and EP10, were confirmed to be hypermethylated in the CVS and hypomethylated in whole blood. Our findings indicate that the MethylEdge Bisulfite Conversion System (Promega) was shown to have the best performance among the kits. In addition, the methylation level of two of our DMRs, EP6 and EP10, was confirmed. Finally, we showed that bisulfite

  7. Non-invasive prenatal diagnosis for single gene disorders: experience of patients.

    PubMed

    Lewis, C; Hill, M; Chitty, L S

    2014-04-01

    The aim of this study is to explore women's experiences of using newly developed non-invasive prenatal diagnosis (NIPD) for single gene disorders. Methods used in this study include qualitative one-to-one interviews with eight women with pregnancies at risk of achondroplasia, Apert syndrome, thanatophoric dysplasia or a neuromuscular condition. The results of the study show that the women were positive about an accurate, safe, and early test. Where the foetus was at increased risk of inheriting a genetic condition, the benefits of NIPD over invasive testing were that it reduced the period of uncertainty and worry by being conducted within the first trimester. For those women for whom there was a low recurrence risk, the period of uncertainty could be reduced and pregnancy 'normalized' earlier. For women who would not have risked invasive testing, NIPD enabled them to have an early diagnostic test that was more accurate than ultrasound. Where ultrasound abnormalities were detected, NIPD ended the 'diagnostic odyssey', enabling women to make practical and psychological preparations for the birth. NIPD conducted through specialist services was considered most appropriate. NIPD for these particular single gene disorders was appreciated by women and appears to be satisfactory. Further exploration of stakeholder views may be required to inform more widespread implementation of NIPD for a broader range of genetic conditions. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Non-invasive prenatal diagnosis of spinal muscular atrophy by relative haplotype dosage.

    PubMed

    Parks, Michael; Court, Samantha; Bowns, Benjamin; Cleary, Siobhan; Clokie, Samuel; Hewitt, Julie; Williams, Denise; Cole, Trevor; MacDonald, Fiona; Griffiths, Mike; Allen, Stephanie

    2017-04-01

    Although technically possible, few clinical laboratories across the world have implemented non-invasive prenatal diagnosis (NIPD) for selected single-gene disorders, mostly owing to the elevated costs incurred. Having previously proven that NIPD for X-linked disorders can be feasibly implemented in clinical practice, we have now developed a test for the NIPD of an autosomal-recessive disorder, spinal muscular atrophy (SMA). Cell-free DNA was extracted from maternal blood and prepared for massively parallel sequencing on an Illumina MiSeq by targeted capture enrichment of single-nucleotide polymorphisms across a 6 Mb genomic window on chromosome 5 containing the SMN1 gene. Maternal, paternal and proband DNA samples were also tested for haplotyping purposes. Sequencing data was analysed by relative haplotype dosage (RHDO). Six pregnant SMA carriers and 10 healthy pregnant donors were recruited through the NIPSIGEN study. Inheritance of the maternally and paternally derived alleles of the affected SMN1 gene was determined in the foetus by RHDO analysis for autosomal-recessive disorders. DNA from the proband (for SMA carriers) or an invasively obtained foetal sample (for healthy pregnant donors) was used to identify the maternal and paternal reference haplotypes associated with the affected SMN1 gene. Results for all patients correlated with known outcomes and showed a testing specificity and sensitivity of 100%. On top of showing high accuracy and reliability throughout the stages of validation, our novel test for NIPD of SMA is also affordable and viable for implementation into clinical service.

  9. Non-Invasive Prenatal Detection of Trisomy 13 Using a Single Nucleotide Polymorphism- and Informatics-Based Approach

    PubMed Central

    Hall, Megan P.; Hill, Matthew; Zimmermann, Bernhard; Sigurjonsson, Styrmir; Westemeyer, Margaret; Saucier, Jennifer; Demko, Zachary; Rabinowitz, Matthew

    2014-01-01

    Purpose To determine how a single nucleotide polymorphism (SNP)- and informatics-based non-invasive prenatal aneuploidy test performs in detecting trisomy 13. Methods Seventeen trisomy 13 and 51 age-matched euploid samples, randomly selected from a larger cohort, were analyzed. Cell-free DNA was isolated from maternal plasma, amplified in a single multiplex polymerase chain reaction assay that interrogated 19,488 SNPs covering chromosomes 13, 18, 21, X, and Y, and sequenced. Analysis and copy number identification involved a Bayesian-based maximum likelihood statistical method that generated chromosome- and sample-specific calculated accuracies. Results Of the samples that passed a stringent DNA quality threshold (94.1%), the algorithm correctly identified 15/15 trisomy 13 and 49/49 euploid samples, for 320/320 correct copy number calls. Conclusions This informatics- and SNP-based method accurately detects trisomy 13-affected fetuses non-invasively and with high calculated accuracy. PMID:24805989

  10. 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.

  11. 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.

  12. Identification of fetal mesenchymal stem cells in maternal blood: implications for non-invasive prenatal diagnosis.

    PubMed

    O'Donoghue, K; Choolani, M; Chan, J; de la Fuente, J; Kumar, S; Campagnoli, C; Bennett, P R; Roberts, I A G; Fisk, N M

    2003-08-01

    Strategies for genetic prenatal diagnosis on fetal cells in the maternal circulation have been limited by lack of a cell type present only in fetal blood. However, the recent identification of mesenchymal stem cells (MSC) in first trimester fetal blood offers the prospect of targeting MSC for non-invasive prenatal diagnosis. We developed protocols for fetal MSC enrichment from maternal blood and determined sensitivity and specificity in mixing experiments of male fetal MSC added to female blood, in dilutions from 1 in 10(5) to 10(8). We then used the optimal protocol to isolate fetal MSC from maternal blood in the first trimester, using blood taken after surgical termination of pregnancy as a model of increased feto-maternal haemorrhage. In model mixtures, we could amplify one male fetal MSC in 2.5 x 10(7) adult female nucleated cells, yielding a 100% pure population of fetal cells, but not one fetal MSC in 10(8) nucleated cells. Fetal MSC were identified in one of 20 post-termination maternal blood samples and confirmed as fetal MSC by XY fluorescence in-situ hybridization (FISH), immunophenotyping and osteogenic and adipogenic differentiation. We report the isolation of fetal MSC from maternal blood; however, their rarity in post-termination blood suggests they are unlikely to have a role in non-invasive prenatal diagnosis. Failure to locate these cells routinely may be attributed to their low frequency in maternal blood, to sensitivity limitations of enrichment technology, and/or to their engraftment in maternal tissues soon after transplacental passage. We speculate that gender microchimerism in post-reproductive maternal tissues might result from feto-maternal trafficking of MSC in early pregnancy.

  13. Non-invasive pulmonary function test on Morquio patients.

    PubMed

    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

    2015-08-01

    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 to 40 years of age. Twenty-two patients were compliant with non-invasive tests (100%) with the 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 the impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography, although predicted forced expiratory total (72.8±6.9 SE%) decreased with age and was below normal; phase angle (35.5±16.5°), %rib cage (41.6±12.7%), resonant frequency, and forced expiratory volume in 1 s/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

  14. Non-invasive prenatal diagnosis of single-gene disorders from maternal blood.

    PubMed

    Bustamante-Aragonés, Ana; Rodríguez de Alba, Marta; Perlado, Sara; Trujillo-Tiebas, María José; Arranz, Javier Plaza; Díaz-Recasens, Joaquín; Troyano-Luque, Juan; Ramos, Carmen

    2012-08-01

    Prenatal diagnosis (PD) is available for pregnancies at risk of monogenic disorders. However, PD requires the use of invasive obstetric techniques for fetal-sample collection and therefore, involves a risk of fetal loss. Circulating fetal DNA in the maternal bloodstream is being used to perform non-invasive prenatal diagnosis (NIPD). NIPD is a challenging discipline because of the biological features of the maternal blood sample. Maternal blood is an unequal mixture of small (and fragmented) amounts of fetal DNA within a wide background of maternal DNA. For this reason, initial NIPD studies have been based on the analysis of specific paternally inherited fetal tracts not present in the maternal genome so as to ensure their fetal origin. Following this strategy, different NIPD studies have been carried out, such as fetal-sex assessment for pregnancies at risk of X-linked disorders, RhD determination, and analysis of single-gene disorders with a paternal origin. The study of the paternal mutation can be used for fetal diagnosis of dominant disorders or to more accurately assess the risk of an affected child in case of recessive diseases. Huntington's disease, cystic fibrosis, or achondroplasia are some examples of diseases studied using NIPD. New technologies are opening NIPD to the analysis of maternally inherited fetal tracts. NIPD of trisomy 21 is the latest study derived from the use of next-generation sequencing (NGS). Copyright © 2012 Elsevier B.V. All rights reserved.

  15. 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.

  16. 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

  17. An optical approach for non-invasive blood clot testing

    NASA Astrophysics Data System (ADS)

    Kalchenko, Vyacheslav; Brill, Alexander; Fine, Ilya; Harmelin, Alon

    2007-02-01

    Physiological blood coagulation is an essential biological process. Current tests for plasma coagulation (clotting) need to be performed ex vivo and require fresh blood sampling for every test. A recently published work describes a new, noninvasive, in vivo approach to assess blood coagulation status during mechanical occlusion1. For this purpose, we have tested this approach and applied a controlled laser beam to blood micro-vessels of the mouse ear during mechanical occlusion. Standard setup for intravital transillumination videomicroscopy and laser based imaging techniques were used for monitoring the blood clotting process. Temporal mechanical occlusion of blood vessels in the observed area was applied to ensure blood flow cessation. Subsequently, laser irradiation was used to induce vascular micro-injury. Changes in the vessel wall, as well as in the pattern of blood flow, predispose the area to vascular thrombosis, according to the paradigm of Virchow's triad. In our experiments, two elements of Virchow's triad were used to induce the process of clotting in vivo, and to assess it optically. We identified several parameters that can serve as markers of the blood clotting process in vivo. These include changes in light absorption in the area of illumination, as well as changes in the pattern of the red blood cells' micro-movement in the vessels where blood flow is completely arrested. Thus, our results indicate that blood coagulation status can be characterized by non-invasive, in vivo methodologies.

  18. 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.

  19. 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.

  20. A Cost-Effectiveness Analysis of First Trimester Non-Invasive Prenatal Screening for Fetal Trisomies in the United States

    PubMed Central

    Walker, Brandon S.; Nelson, Richard E.; Jackson, Brian R.; Grenache, David G.; Ashwood, Edward R.; Schmidt, Robert L.

    2015-01-01

    Background Non-invasive prenatal testing (NIPT) is a relatively new technology for diagnosis of fetal aneuploidies. NIPT is more accurate than conventional maternal serum screening (MSS) but is also more costly. Contingent NIPT may provide a cost-effective alternative to universal NIPT screening. Contingent screening used a two-stage process in which risk is assessed by MSS in the first stage and, based on a risk cutoff, high-risk pregnancies are referred for NIPT. The objective of this study was to (1) determine the optimum MSS risk cutoff for contingent NIPT and (2) compare the cost effectiveness of optimized contingent NIPT to universal NIPT and conventional MSS. Study Design Decision-analytic model using micro-simulation and probabilistic sensitivity analysis. We evaluated cost effectiveness from three perspectives: societal, governmental, and payer. Results From a societal perspective, universal NIPT dominated both contingent NIPT and MSS. From a government and payer perspective, contingent NIPT dominated MSS. Compared to contingent NIPT, adopting a universal NIPT would cost $203,088 for each additional case detected from a government perspective and $263,922 for each additional case detected from a payer perspective. Conclusions From a societal perspective, universal NIPT is a cost-effective alternative to MSS and contingent NIPT. When viewed from narrower perspectives, contingent NIPT is less costly than universal NIPT and provides a cost-effective alternative to MSS. PMID:26133556

  1. Prenatal Genetic Diagnostic Tests

    MedlinePlus

    ... disorders and mutations. Only embryos that do not test positive for the disorders are transferred. How are the cells analyzed in prenatal diagnostic testing? A number of technologies are used in prenatal diagnostic testing. Your obstetrician ...

  2. Prenatal Tests

    MedlinePlus

    ... genetic counselor to help you look at the history of problems in your family and to determine the risk to your children. To decide which tests are right for you, it's important to carefully discuss with ...

  3. Prenatal Tests

    MedlinePlus

    ... pregnant with multiples (more than one baby, like twins or triplets). The test is called noninvasive because ... us to hear how you can make a difference and let your friends know you are helping ...

  4. Personalized management of cirrhosis by non-invasive tests of liver fibrosis

    PubMed Central

    Wong, Grace Lai-Hung; Espinosa, Wendell Zaragoza

    2015-01-01

    Owing to the high prevalence of various chronic liver diseases, cirrhosis is one of the leading causes of morbidity and mortality worldwide. In recent years, the development of non-invasive tests of fibrosis allows accurate diagnosis of cirrhosis and reduces the need for liver biopsy. In this review, we discuss the application of these non-invasive tests beyond the diagnosis of cirrhosis. In particular, their role in the selection of patients for hepatocellular carcinoma surveillance and varices screening is highlighted. PMID:26523265

  5. Views and preferences for the implementation of non-invasive prenatal diagnosis for single gene disorders from health professionals in the United Kingdom.

    PubMed

    Hill, Melissa; Karunaratna, Madhavi; Lewis, Celine; Forya, Frida; Chitty, Lyn

    2013-07-01

    Non-invasive prenatal diagnosis (NIPD) will offer new options in prenatal diagnosis for carriers of single gene disorders. This will affect carrier couples and health professionals involved in prenatal care. The aim of this study was to determine health professional opinions on NIPD for single gene disorders to guide development of infrastructure required for implementation. A qualitative approach was adopted using focus groups (N = 17) and one-to-one interviews (N = 30) with health professionals from a range of backgrounds involved in caring for carriers of single gene disorders. Data were digitally recorded, transcribed verbatim and analyzed using thematic analysis. Participants were very positive about the introduction of NIPD, describing benefits arising from no risk of miscarriage, earlier testing and a simple procedure. A number of concerns for implementation were raised. Participants emphasized the need for the new test to be highly accurate and thoroughly validated. There was concern that people may not give as much thought to having a blood test compared to an invasive test or that it may be viewed as routine and as such NIPD may negatively impact on informed consent. In addition there was concern that the simplicity of a blood test may lead to increased pressure to test and terminate. However, participants felt these concerns could be overcome with thorough pre- and post-test counseling. To ensure high quality care, offering NIPD through genetics or other specialist services is essential. Ongoing education and training of health professionals will be important, and guidelines and regulation are needed for effective implementation.

  6. [Non invasive prenatal diagnosis. Fetal nucleic acid analysis in maternal blood].

    PubMed

    Sesarini, Carla; Argibay, Pablo; Otaño, Lucas

    2010-01-01

    Current prenatal diagnosis of monogeneic and chromosomal diseases, includes invasive procedures which carry a small but significant risk. For many years, analysis of fetal cells in maternal circulation has been studied, however it has failed its clinical use due to the scarcity of these cells and their persistance after delivery. For more than a decade, the presence of cell-free fetal DNA in maternal blood has been identified. These fetal DNA fragments would derive from the placenta and are not detected after delivery, making them a source of fetal material for carrying out diagnosis techniques using maternal blood. However, the vast majority of cell free DNA in maternal circulation is of maternal origin, with the fetal component contributing from 3% to 6% and rising towards term. Available methodologies do not allow separation of fetal from maternal cell free DNA, so current applications have been focused on the analysis of genes not present in the mother, such as Y chromosome sequences, or RHD gene in RhD-negative women, or paternal or de novo mutations. Also, the detection of cell-free fetal RNA in maternal blood offers the possibility of obtaining information regarding genetic expression profiles of embrionic tissues, and using genes expressed only at the feto-placental unit, controls for the presence of fetal material could be established, regardless of maternal genetic tissue. The present article describes the evidences regarding the passage of fetal nucleic acids to maternal circulation, its current prenatal diagnosis application and possible future perspectives.

  7. Rapid non-invasive tests for diagnostics of infectious diseases

    NASA Astrophysics Data System (ADS)

    Malamud, Daniel

    2014-06-01

    A rapid test for an infectious disease that can be used at point-of-care at a physician's office, a pharmacy, or in the field is critical for the prompt and appropriate therapeutic intervention. Ultimately by treating infections early on will decrease transmission of the pathogen. In contrast to metabolic diseases or cancer where multiple biomarkers are required, infectious disease targets (e.g. antigen, antibody, nucleic acid) are simple and specific for the pathogen causing the disease. Our laboratory has focused on three major infectious disease; HIV, Tuberculosis, and Malaria. These diseases are pandemic in much of the world thus putting natives, tourists and military personnel at risk for becoming infected, and upon returning to the U.S., transmitting these diseases to their contacts. Our devices are designed to detect antigens, antibodies or nucleic acids in blood or saliva samples in less than 30 minutes. An overview describing the current status of each of the three diagnostic platforms is presented. These microfluidic point-of-care devices will be relatively inexpensive, disposable, and user friendly.

  8. Cell-Free DNA-Based Non-invasive Prenatal Screening for Common Aneuploidies in a Canadian Province: A Cost-Effectiveness Analysis.

    PubMed

    Nshimyumukiza, Léon; Beaumont, J A; Duplantie, J; Langlois, S; Little, J; Audibert, F; McCabe, C; Gekas, J; Giguère, Y; Gagné, C; Reinharz, D; Rousseau, F

    2017-08-04

    Yearly, 450 000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. Different screening strategies select approximately 4% of women for invasive fetal chromosome testing. Non-invasive prenatal testing (NIPT) using maternal blood cell-free DNA could reduce those invasive procedures but is expensive. This study evaluated the cost-effectiveness of NIPT strategies compared with conventional strategies. This study used a decision analytic model to estimate the cost-effectiveness of 13 prenatal screening strategies for fetal aneuploidies: six frequently used strategies, universal NIPT, and six strategies incorporating NIPT as a second-tier test. The study considered a virtual cohort of pregnant women of similar size and age as women in Quebec. Model data were obtained from published sources and government databases. The study predicted the number of chromosomal anomalies detected (trisomies 21, 13, and 18), invasive procedures and euploid fetal losses, direct costs, and incremental cost-effectiveness ratios. Of the 13 strategies compared, eight identified fewer cases at a higher cost than at least one of the remaining five strategies. Integrated serum screening with conditional NIPT had the lowest cost, and the cost per case detected was $63 139, with a 90% reduction of invasive procedures. The number of cases identified was improved with four other screening strategies, but with increasing of incremental costs per case (from $61 623 to $1 553 615). Results remained robust, except when NIPT costs and risk cut-offs varied. NIPT as a second-tier test for high-risk women is likely to be cost-effective as compared with screening algorithms not involving NIPT. Copyright © 2017 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

  9. Next generation sequencing of SNPs for non-invasive prenatal diagnosis: challenges and feasibility as illustrated by an application to β-thalassaemia

    PubMed Central

    Papasavva, Thessalia; van IJcken, Wilfred F J; Kockx, Christel E M; van den Hout, Mirjam C G N; Kountouris, Petros; Kythreotis, Loukas; Kalogirou, Eleni; Grosveld, Frank G; Kleanthous, Marina

    2013-01-01

    β-Thalassaemia is one of the most common autosomal recessive single-gene disorder worldwide, with a carrier frequency of 12% in Cyprus. Prenatal tests for at risk pregnancies use invasive methods and development of a non-invasive prenatal diagnostic (NIPD) method is of paramount importance to prevent unnecessary risks inherent to invasive methods. Here, we describe such a method by assessing a modified version of next generation sequencing (NGS) using the Illumina platform, called ‘targeted sequencing', based on the detection of paternally inherited fetal alleles in maternal plasma. We selected four single-nucleotide polymorphisms (SNPs) located in the β-globin locus with a high degree of heterozygosity in the Cypriot population. Spiked genomic samples were used to determine the specificity of the platform. We could detect the minor alleles in the expected ratio, showing the specificity of the platform. We then developed a multiplexed format for the selected SNPs and analysed ten maternal plasma samples from pregnancies at risk. The presence or absence of the paternal mutant allele was correctly determined in 27 out of 34 samples analysed. With haplotype analysis, NIPD was possible on eight out of ten families. This is the first study carried out for the NIPD of β-thalassaemia using targeted NGS and haplotype analysis. Preliminary results show that NGS is effective in detecting paternally inherited alleles in the maternal plasma. PMID:23572027

  10. Postnatal and non-invasive prenatal detection of β-thalassemia mutations based on Taqman genotyping assays.

    PubMed

    Breveglieri, Giulia; Travan, Anna; D'Aversa, Elisabetta; Cosenza, Lucia Carmela; Pellegatti, Patrizia; Guerra, Giovanni; Gambari, Roberto; Borgatti, Monica

    2017-01-01

    The β-thalassemias are genetic disorder caused by more than 200 mutations in the β-globin gene, resulting in a total (β0) or partial (β+) deficit of the globin chain synthesis. The most frequent Mediterranean mutations for β-thalassemia are: β039, β+IVSI-110, β+IVSI-6 and β0IVSI-1. Several molecular techniques for the detection of point mutations have been developed based on the amplification of the DNA target by polymerase chain reaction (PCR), but they could be labor-intensive and technically demanding. On the contrary, TaqMan® genotyping assays are a simple, sensitive and versatile method suitable for the single nucleotide polymorphism (SNP) genotyping affecting the human β-globin gene. Four TaqMan® genotyping assays for the most common β-thalassemia mutations present in the Mediterranean area were designed and validated for the genotype characterization of genomic DNA extracted from 94 subjects comprising 25 healthy donors, 33 healthy carriers and 36 β-thalassemia patients. In addition, 15 specimens at late gestation (21-39 gestational weeks) and 11 at early gestation (5-18 gestational weeks) were collected from pregnant women, and circulating cell-free fetal DNAs were extracted and analyzed with these four genotyping assays. We developed four simple, inexpensive and versatile genotyping assays for the postnatal and prenatal identification of the thalassemia mutations β039, β+IVSI-110, β+IVSI-6, β0IVSI-1. These genotyping assays are able to detect paternally inherited point mutations in the fetus and could be efficiently employed for non-invasive prenatal diagnosis of β-globin gene mutations, starting from the 9th gestational week.

  11. Postnatal and non-invasive prenatal detection of β-thalassemia mutations based on Taqman genotyping assays

    PubMed Central

    Breveglieri, Giulia; Travan, Anna; D’Aversa, Elisabetta; Cosenza, Lucia Carmela; Pellegatti, Patrizia; Guerra, Giovanni; Gambari, Roberto

    2017-01-01

    The β-thalassemias are genetic disorder caused by more than 200 mutations in the β-globin gene, resulting in a total (β0) or partial (β+) deficit of the globin chain synthesis. The most frequent Mediterranean mutations for β-thalassemia are: β039, β+IVSI-110, β+IVSI-6 and β0IVSI-1. Several molecular techniques for the detection of point mutations have been developed based on the amplification of the DNA target by polymerase chain reaction (PCR), but they could be labor-intensive and technically demanding. On the contrary, TaqMan® genotyping assays are a simple, sensitive and versatile method suitable for the single nucleotide polymorphism (SNP) genotyping affecting the human β-globin gene. Four TaqMan® genotyping assays for the most common β-thalassemia mutations present in the Mediterranean area were designed and validated for the genotype characterization of genomic DNA extracted from 94 subjects comprising 25 healthy donors, 33 healthy carriers and 36 β-thalassemia patients. In addition, 15 specimens at late gestation (21–39 gestational weeks) and 11 at early gestation (5–18 gestational weeks) were collected from pregnant women, and circulating cell-free fetal DNAs were extracted and analyzed with these four genotyping assays. We developed four simple, inexpensive and versatile genotyping assays for the postnatal and prenatal identification of the thalassemia mutations β039, β+IVSI-110, β+IVSI-6, β0IVSI-1. These genotyping assays are able to detect paternally inherited point mutations in the fetus and could be efficiently employed for non-invasive prenatal diagnosis of β-globin gene mutations, starting from the 9th gestational week. PMID:28235086

  12. Non-invasive prenatal diagnosis for fetal sex determination: benefits and disadvantages from the service users' perspective

    PubMed Central

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

    2012-01-01

    Prenatal fetal sex determination is clinically indicated for women who are at risk of having a child with a serious genetic disorder affecting a particular sex. Ultrasound has been the traditional method used, but early fetal sex determination using non-invasive prenatal diagnosis (NIPD) can now be performed using cell-free fetal DNA in maternal plasma. The study aim was to assess the views and experiences of service users who had used NIPD for fetal sex determination. In this paper, we report on the perceived benefits and disadvantages. A qualitative approach using semi-structured interviews was used. A total of 44 participants (38 women and 6 partners of participating women) were recruited. Participants' views and experiences of NIPD were overwhelmingly positive. Concerning benefits over traditional methods, three themes emerged: (1) technical aspects of technology; (2) timing; and (3) enhanced decision-making. Practical advantages of NIPD included avoiding miscarriage, and there were a number of psychological advantages associated with timing such as perceived control, early re-engagement, normalization of pregnancy and peace of mind. Participants also valued NIPD as it enabled a stepwise approach to decision-making. A number of disadvantages were discussed including concerns about social sexing and increased bonding at a time in pregnancy when miscarriage risk is high. However, participants felt these were fairly minor in comparison with the advantages of NIPD. Until definitive genetic diagnosis using NIPD is available, NIPD for fetal sex determination is perceived as a good interim measure with a number of notable advantages over traditional methods. PMID:22453293

  13. Development of a Novel, Non-Invasive Diagnostic Test for Prostate Cancer

    DTIC Science & Technology

    2007-01-01

    Invasive Diagnostic Test for Prostate Cancer PRINCIPAL INVESTIGATOR: Robert Gardiner, M.D...Novel, Non-Invasive Diagnostic Test for Prostate Cancer 5b. GRANT NUMBER W81XWH-05-1-0092 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...patients with prostate cancer so that transrectal ultrasound guided biopsies can be restricted to men harboring PCa. Our broad strategy will involve

  14. Understanding Prenatal Tests

    MedlinePlus

    ... several things, particularly the risk of Down Syndrome. Rh Incompatibility This test determines whether the mother and ... at the first prenatal visit. If there is Rh incompatibility, treatments can help prevent later complications. Ultrasound ...

  15. Clinical experience with single-nucleotide polymorphism-based non-invasive prenatal screening for 22q11.2 deletion syndrome.

    PubMed

    Gross, S J; Stosic, M; McDonald-McGinn, D M; Bassett, A S; Norvez, A; Dhamankar, R; Kobara, K; Kirkizlar, E; Zimmermann, B; Wayham, N; Babiarz, J E; Ryan, A; Jinnett, K N; Demko, Z; Benn, P

    2016-02-01

    To evaluate the performance of a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for the detection of fetal 22q11.2 deletion syndrome in clinical practice, assess clinical follow-up and review patient choices for women with high-risk results. In this study, 21 948 samples were submitted for screening for 22q11.2 deletion syndrome using a SNP-based NIPT and subsequently evaluated. Follow-up was conducted for all cases with a high-risk result. Ninety-five cases were reported as high risk for fetal 22q11.2 deletion. Diagnostic testing results were available for 61 (64.2%) cases, which confirmed 11 (18.0%) true positives and identified 50 (82.0%) false positives, resulting in a positive predictive value (PPV) of 18.0%. Information regarding invasive testing was available for 84 (88.4%) high-risk cases: 57.1% (48/84) had invasive testing and 42.9% (36/84) did not. Ultrasound anomalies were present in 81.8% of true-positive and 18.0% of false-positive cases. Two additional cases were high risk for a maternal 22q11.2 deletion; one was confirmed by diagnostic testing and one had a positive family history. There were three pregnancy terminations related to screening results of 22q11.2 deletion, two of which were confirmed as true positive by invasive testing. Clinical experience with this SNP-based non-invasive screening test for 22q11.2 deletion syndrome indicates that these deletions have a frequency of approximately 1 in 1000 in the referral population with most identifiable through this test. Use of this screening method requires the availability of counseling and other management resources for high-risk pregnancies. © 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd. on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

  16. Prenatal Genetic Testing Chart

    MedlinePlus

    ... www.acog.org/Patients/FAQs/Prenatal-Genetic-Diagnostic-Tests › › Resources & Publications Committee Opinions Practice Bulletins Patient Education Green Journal Clinical Updates Practice Management Coding Health Info Technology Professional Liability Managing Your Practice Patient Safety & Quality ...

  17. Prenatal Tests for Down Syndrome

    MedlinePlus

    PRENATAL TESTS FOR DOWN SYNDROME S HARE W ITH W OMEN PRENATAL TESTS FOR DOWN SYNDROME What Is Down Syndrome? Down syndrome is a common birth defect that includes mental retardation and— often— heart ...

  18. Reliable Detection of Paternal SNPs within Deletion Breakpoints for Non-Invasive Prenatal Exclusion of Homozygous α0-Thalassemia in Maternal Plasma

    PubMed Central

    Yan, Ti-Zhen; Mo, Qiu-Hua; Cai, Ren; Chen, Xue; Zhang, Cui-Mei; Liu, Yan-Hui; Chen, Ya-Jun; Zhou, Wan-Jun; Xiong, Fu; Xu, Xiang-Min

    2011-01-01

    Reliable detection of large deletions from cell-free fetal DNA (cffDNA) in maternal plasma is challenging, especially when both parents have the same deletion owing to a lack of specific markers for fetal genotyping. In order to evaluate the efficacy of a non-invasive prenatal diagnosis (NIPD) test to exclude α-thalassemia major that uses SNPs linked to the normal paternal α-globin allele, we established a novel protocol to reliably detect paternal SNPs within the (−−SEA) breakpoints and performed evaluation of the diagnostic potential of the protocol in a total of 67 pregnancies, in whom plasma samples were collected prior to invasive obstetrics procedures in southern China. A group of nine SNPs identified within the deletion breakpoints were scanned to select the informative SNPs in each of the 67 couples DNA by multiplex PCR based mini-sequencing technique. The paternally inherited SNP allele from cffDNA was detected by allele specific real-time PCR. A protocol for reliable detection of paternal SNPs within the (−−SEA) breakpoints was established and evaluation of the diagnostic potential of the protocol was performed in a total of 67 pregnancies. In 97% of the couples one or more different SNPs within the deletion breakpoint occurred between paternal and maternal alleles. Homozygosity for the (−−SEA) deletion was accurately excluded in 33 out of 67 (49.3%, 95% CI, 25.4–78.6%) pregnancies through the implementation of the protocol. Protocol was completely concordant with the traditional reference methods, except for two cases that exhibited uncertain results due to sample hemolysis. This method could be used as a routine NIPD test to exclude gross fetal deletions in α-thalassemia major, and could further be employed to test for other diseases due to gene deletion. PMID:21980356

  19. Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis.

    PubMed

    Bischoff, Farideh Z; Sinacori, Mina K; Dang, Dianne D; Marquez-Do, Deborah; Horne, Cassandra; Lewis, Dorothy E; Simpson, Joe Leigh

    2002-01-01

    Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.

  20. Recent advances in prenatal genetic screening and testing.

    PubMed

    Van den Veyver, Ignatia B

    2016-01-01

    The introduction of new technologies has dramatically changed the current practice of prenatal screening and testing for genetic abnormalities in the fetus. Expanded carrier screening panels and non-invasive cell-free fetal DNA-based screening for aneuploidy and single-gene disorders, and more recently for subchromosomal abnormalities, have been introduced into prenatal care. More recently introduced technologies such as chromosomal microarray analysis and whole-exome sequencing can diagnose more genetic conditions on samples obtained through amniocentesis or chorionic villus sampling, including many disorders that cannot be screened for non-invasively. All of these options have benefits and limitations, and genetic counseling has become increasingly complex for providers who are responsible for guiding patients in their decisions about screening and testing before and during pregnancy.

  1. Recent advances in prenatal genetic screening and testing

    PubMed Central

    Van den Veyver, Ignatia B.

    2016-01-01

    The introduction of new technologies has dramatically changed the current practice of prenatal screening and testing for genetic abnormalities in the fetus. Expanded carrier screening panels and non-invasive cell-free fetal DNA-based screening for aneuploidy and single-gene disorders, and more recently for subchromosomal abnormalities, have been introduced into prenatal care. More recently introduced technologies such as chromosomal microarray analysis and whole-exome sequencing can diagnose more genetic conditions on samples obtained through amniocentesis or chorionic villus sampling, including many disorders that cannot be screened for non-invasively. All of these options have benefits and limitations, and genetic counseling has become increasingly complex for providers who are responsible for guiding patients in their decisions about screening and testing before and during pregnancy. PMID:27853526

  2. Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests

    PubMed Central

    Felipo, Vicente; Urios, Amparo; Giménez-Garzó, Carla; Cauli, Omar; Andrés-Costa, Maria-Jesús; González, Olga; Serra, Miguel A; Sánchez-González, Javier; Aliaga, Roberto; Giner-Durán, Remedios; Belloch, Vicente; Montoliu, Carmina

    2014-01-01

    AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy. METHODS: Blood flow (BF) was analyzed by arterial spin labeling (ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy (MHE). Images were collected using a 3 Tesla MR scanner (Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score (PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention were evaluated using the Stroop test. Patients and controls also performed visuo-motor and bimanual coordination tests. Several biochemical parameters were measured: serum pro-inflammatory interleukins (IL-6 and IL-18), 3-nitrotyrosine, cGMP and nitrates+nitrites in plasma, and blood ammonia. Bivariate correlations were evaluated. RESULTS: In patients with MHE, BF was increased in cerebellar hemisphere (P = 0.03) and vermis (P = 0.012) and reduced in occipital lobe (P = 0.017). BF in cerebellar hemisphere was also increased in patients without MHE (P = 0.02). Bimanual coordination was impaired in patients without MHE (P = 0.05) and much more in patients with MHE (P < 0.0001). Visuo-motor coordination was impaired only in patients with MHE (P < 0.0001). Attention was slightly affected in patients without MHE and more strongly in patients with MHE (P < 0.0001). BF in cerebellar hemisphere and vermis correlated with performance in most tests of PHES [(number connection tests A (NCT-A), B (NCT-B)and line tracing test] and in the congruent task of Stroop test. BF in frontal lobe correlated with NCT-A. Performance in bimanual and visuomotor coordination tests correlated only with BF in cerebellar hemisphere. BF in occipital lobe correlates with performance in the PHES battery and with

  3. A robust and reliable non-invasive test for stress responsivity in mice

    PubMed Central

    Zimprich, Annemarie; Garrett, Lillian; Deussing, Jan M.; Wotjak, Carsten T.; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabě; Wurst, Wolfgang; Hölter, Sabine M.

    2014-01-01

    Stress and an altered stress response have been associated with many multifactorial diseases, such as psychiatric disorders or neurodegenerative diseases. As currently mouse mutants for each single gene are generated and phenotyped in a large-scale manner, it seems advisable also to test these mutants for alterations in their stress responses. Here we present the determinants of a robust and reliable non-invasive test for stress-responsivity in mice. Stress is applied through restraining the mice in tubes and recording behavior in the Open Field 20 min after cessation of the stress. Two hours, but not 15 or 50 min of restraint lead to a robust and reproducible increase in distance traveled and number of rearings during the first 5 min in the Open Field in C57BL/6 mice. This behavioral response is blocked by the corticosterone synthesis inhibitor metyrapone, but not by RU486 treatment, indicating that it depends on corticosteroid secretion, but is not mediated via the glucocorticoid receptor type II. We assumed that with a stress duration of 15 min one could detect hyper-responsivity, and with a stress duration of 2 h hypo-responsivity in mutant mouse lines. This was validated with two mutant lines known to show opposing effects on corticosterone secretion after stress exposure, corticotropin-releasing hormone (CRH) over-expressing mice and CRH receptor 1 knockout (KO) mice. Both lines showed the expected phenotype, i.e., increased stress responsivity in the CRH over-expressing mouse line (after 15 min restraint stress) and decreased stress responsivity in the CRHR1-KO mouse line (after 2 h of restraint stress). It is possible to repeat the acute stress test several times without the stressed animal adapting to it, and the behavioral response can be robustly evoked at different ages, in both sexes and in different mouse strains. Thus, locomotor and rearing behavior in the Open Field after an acute stress challenge can be used as reliable, non-invasive indicators of

  4. A non-invasive cardiac output measurement as an alternative to the test bolus technique during CT angiography.

    PubMed

    Nijhof, W H; Hilbink, M; Jager, G J; Slump, C H; Rutten, M J C M

    2016-09-01

    To investigate the association between a non-invasive cardiac output (CO) measurement and the scan delay, as derived from a test bolus injection protocol. The secondary objective was to determine which factors affect the relationship between the CO and scan delay. Fifty-five patients referred for a contrast-enhanced (thorax-)abdomen CT examination were included in this feasibility study. A test bolus examination was performed prior to the abdominal CT. During the test bolus injection, the CO of the patient was measured using a non-invasive finger-cuff measurement. Associations were analysed using linear regression analyses. Age, gender, height, weight, and blood pressure were included as potential confounders. Linear regression analysis showed a negative and significant association between CO and delay. The regression formula was as follows: scan delay (seconds) = 26.8-1.6 CO (l/min), with a 95% CI between -2.3 and -1.0 (p<0.001). Weight appeared to be a confounder in this relation, and gender and blood pressure were effect modifiers. There was no interaction between scan delay and age, height and weight. There is a negative and significant association between the non-invasive CO measurement and the CT scan delay; however, to validate these findings a larger cohort study is needed to investigate whether the non-invasively determined scan delay is as accurate as the use of a test bolus. Copyright © 2016. Published by Elsevier Ltd.

  5. Development of an Arm Phantom for Testing Non-Invasive Blood Pressure Monitors

    NASA Astrophysics Data System (ADS)

    Anderson-Jackson, LaTecia D.

    Approximately one in every three adults age 20 older are diagnosed with high blood pressure or hypertension. It is estimated that hypertension affects 78 million people in the United States, is equally prevalent in both men and woman (Crabtree, Stuart-Shor, & McAllister, 2013). In the United States, around 78% of people suffering from hypertension are aware of their condition, with only 68% using hypertensive medications to control their blood pressure (Writing Group et al., 2010). Clinically, blood pressure measurements may lack accuracy, which can be attributed to various factors, including device limitations, cuff mis-sizing and misplacement, white-coat effect, masked hypertension, and lifestyle factors. The development of an arm phantom to simulate physiologic properties of a human arm and arterial BP waveforms may allow us to better assess the accuracy of non-invasive blood pressure (NIBP) monitors. The objective of this study are to: (1) Develop an arm phantom to replicate physiological properties of the human arm, and (2) Incorporate the arm phantom into a mock circulatory flow loop to simulate different physiological blood pressure readings on the bench. A tissue mimicking material, styrene-ethylene-butylene-styrene (SEBS), a co-block polymer was used to develop the arm phantom for in-vitro testing. To determine the optimal mechanical properties for the arm phantom, individual arm components were isolated and tested. A protocol was developed to evaluate various components for optimal arm phantom development. Mechanical testing was conducted on 10%, 15%, and 20% SEBS gel samples for modulus of elasticity measurements in order to simulate physiological properties of the human arm. As a result of the SEBS polymer being a new material for this application, this investigation will contribute to resolving the limitations that occurred during experimentation. In this study, we demonstrated that although SEBS polymer may be an ideal material to use for simulating

  6. Offering prenatal diagnostic tests: European guidelines for clinical practice [corrected].

    PubMed

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

    2014-05-01

    For over four decades, it has been possible to offer prenatal diagnostic testing for fetal abnormalities. Prenatal testing is now available for a wide range of monogenic disorders as well as chromosomal abnormalities and should be provided within the ethical framework of informed consent and autonomous choice. However, there are no published guidelines for health professionals from varied disciplines who offer prenatal diagnosis (PND) in a range of possible settings including departments of maternity, obstetrics and clinical genetics. We used an Expert Group technique to develop a set of guidelines for provision of prenatal diagnostic services. Thirteen European health professionals, all experts in PND, participated in a workshop to develop the guidelines, which were then subjected to a wide consultation process. The objective of PND was defined as providing prenatal diagnostic testing services (for genetic conditions) that enable families to make informed choices consistent with their individual needs and values and which support them in dealing with the outcome of such testing. General principles, logistical considerations, clinical care and counselling topics are all described and are equally applicable to invasive and non-invasive testing. These guidelines provide a framework for ethical clinical care; however, they are flexible enough to enable practitioners to adapt them to their particular setting. Ideally, an individualised approach to each family is required to ensure autonomous choice and informed consent regarding prenatal diagnostic testing within the local ethical and legal framework.

  7. Invasive Prenatal Testing

    PubMed Central

    Hunter, A.

    1988-01-01

    Invasive prenatal diagnosis is a major diagnostic tool which is used in modern obstetrical care. A synopsis of these techniques is provided to assist the family practitioner in providing this information to his patients. PMID:21253097

  8. Prenatal Genetic Diagnostic Tests

    MedlinePlus

    ... offered to couples who are using in vitro fertilization to become pregnant and who are at increased ... The stage of prenatal development that starts at fertilization (joining of an egg and sperm) and lasts ...

  9. Non-invasive prenatal determination of fetal gender using QF-PCR analysis of cell-free fetal DNA in maternal plasma.

    PubMed

    Kim, Shin Young; Lim, Ji Hyae; Park, So Yeon; Kim, Moon Young; Choi, June Seek; Ryu, Hyun Mee

    2012-03-22

    Detection of cell-free fetal DNA (cffDNA) in maternal plasma has given rise to the possibility of new non-invasive approaches for early prenatal diagnoses. We evaluated the feasibility and accuracy of non-invasive fetal gender determination using quantitative fluorescent-polymerase chain reaction (QF-PCR) analysis of circulating cffDNA in the first-trimester maternal plasma. Plasma samples were prospectively collected from 202 singleton pregnancies at 4 to 13 weeks of gestation. Fetal gender was determined by QF-PCR with the sex-determining region Y (SRY) and amelogenin X/Y (AMELX/Y) genes. The result was confirmed by fetal karyotyping or phenotype at birth. Of the 202 pregnancies, 162 had pregnancy outcomes available and could be included in our evaluation. The accuracies of AMELX/Y, SRY, and combined AMELX/Y+SRY analysis for fetal gender determination were 83.3%, 82.1%, and 97.5%, respectively, compared with those of the invasive approach and the fetal gender outcome at birth (82 males and 80 females). Combined AMELX/Y+SRY analysis had the highest sensitivity (98.8%) for fetal gender determination with a specificity of 96.3%. Moreover, fetal gender detection by the combined AMELX/Y+SRY analysis at 11 to 13 weeks of gestation was 100% correct. Fetal gender determination could be accurately determined from maternal cffDNA in the first-trimester using QF-PCR analysis of combined AMELX/Y+SRY. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. [Evaluation of the appropriateness of prescribing non-invasive cardiologic tests].

    PubMed

    Lorenzoni, Roberto; Baldini, Paolo; Bernardi, Daniele; Bonatti, Vincenzo; Dabizzi, Roberto; Del Citerna, Federico; De Tommasi, Mario; Galli, Michele; Giannini, Raffaella; Macrì, Rocco; Mandorla, Sara; Mazzoni, Vincenzo; Micheli, Giovanni; Nannini, Eugenio; Pesola, Antonio; Severi, Silva; Tartarini, Giuseppe; Tonelli, Luigi; Vergoni, William; Vergassola, Rossano; Zuppiroli, Alfredo

    2002-06-01

    We evaluated the appropriateness of the prescription of echocardiography, exercise testing, Holter monitoring and vascular sonography for ambulatory patients, performed during 4 weeks in 21 outpatient laboratories in Tuscany and Umbria, Italy. We collected the following data: the appropriateness of the prescription (according to the guidelines of the Italian Federation of Cardiology), the prescribing physician (cardiologist vs noncardiologist), the synthetic result (normal vs abnormal) and the clinical utility (useful vs useless) of each exam. We evaluated 5614 prescriptions (patients: 3027 males, 2587 females; mean age 63 years, range 14-96 years). The indication to the test was of class I (appropriate) in 45.3%, of class II (doubtfully appropriate) in 34.8% and of class III (inappropriate) in 19.9% of the cases. The test was abnormal in 58.3% of class I exams vs 17% of class III exams (p < 0.05). The test was useful in 72.4% of class I exams vs 17.1% of class III exams (p < 0.05). The test was prescribed by a cardiologist in 1882 cases (33.5%). Cardiologist-prescribed exams were of class I in 57.3%, of class II in 32.4% and of class III in 10.3% of the cases vs 39.2, 36.1 and 24.7% of non-cardiologist-prescribed exams (p < 0.05). Cardiologist-prescribed exams were abnormal in 53.4% of the cases vs 39% of those of non-cardiologists' (odds ratio 1.76, 95% confidence interval 1.58-1.97; p < 0.05). Cardiologist-prescribed exams were useful in 64.7% of the cases vs 44.4% of those of non-cardiologists' (odds ratio 2.26, 95% confidence interval 2.02-2.53; p < 0.05). In Tuscany and Umbria, Italy, less than half of the prescriptions for non-invasive diagnostic tests are appropriate: appropriately prescribed exams more often provide abnormal and useful results; cardiologist-prescribed exams are more often appropriate, abnormal and useful.

  11. An open-source framework for stress-testing non-invasive foetal ECG extraction algorithms.

    PubMed

    Andreotti, Fernando; Behar, Joachim; Zaunseder, Sebastian; Oster, Julien; Clifford, Gari D

    2016-05-01

    Over the past decades, many studies have been published on the extraction of non-invasive foetal electrocardiogram (NI-FECG) from abdominal recordings. Most of these contributions claim to obtain excellent results in detecting foetal QRS (FQRS) complexes in terms of location. A small subset of authors have investigated the extraction of morphological features from the NI-FECG. However, due to the shortage of available public databases, the large variety of performance measures employed and the lack of open-source reference algorithms, most contributions cannot be meaningfully assessed. This article attempts to address these issues by presenting a standardised methodology for stress testing NI-FECG algorithms, including absolute data, as well as extraction and evaluation routines. To that end, a large database of realistic artificial signals was created, totaling 145.8 h of multichannel data and over one million FQRS complexes. An important characteristic of this dataset is the inclusion of several non-stationary events (e.g. foetal movements, uterine contractions and heart rate fluctuations) that are critical for evaluating extraction routines. To demonstrate our testing methodology, three classes of NI-FECG extraction algorithms were evaluated: blind source separation (BSS), template subtraction (TS) and adaptive methods (AM). Experiments were conducted to benchmark the performance of eight NI-FECG extraction algorithms on the artificial database focusing on: FQRS detection and morphological analysis (foetal QT and T/QRS ratio). The overall median FQRS detection accuracies (i.e. considering all non-stationary events) for the best performing methods in each group were 99.9% for BSS, 97.9% for AM and 96.0% for TS. Both FQRS detections and morphological parameters were shown to heavily depend on the extraction techniques and signal-to-noise ratio. Particularly, it is shown that their evaluation in the source domain, obtained after using a BSS technique, should be

  12. Stress testing and non-invasive coronary angiography in patients with suspected coronary artery disease: time for a new paradigm

    PubMed Central

    Arbab-Zadeh, Armin

    2012-01-01

    Diagnosis and management of coronary artery disease represents major challenges to our health care system, affecting millions of patients each year. Until recently, the diagnosis of coronary artery disease was possible only through cardiac catheterization and invasive coronary angiography. To avoid the risks of an invasive procedure, stress testing is often employed for an initial assessment of patients with suspected coronary artery disease, serving as a gatekeeper for cardiac catheterization. With the emergence of non-invasive coronary angiography, the question arises if such a strategy is still sensible, particularly, in view of only a modest agreement between stress testing results and the presence of coronary artery disease established by cardiac catheterization. Much data in support of the diagnostic accuracy and prognostic value of non-invasive coronary angiography by computed tomography have emerged within the last few years. These data challenge the role of stress testing as the initial imaging modality in patients with suspected coronary artery disease. This article reviews the clinical utility, limitations, as well as the hazards of stress testing compared with non-invasive coronary artery imaging by computed tomography. Finally, the implications of this review are discussed in relation to clinical practice. PMID:22690295

  13. The Glass Slide Extraction System Snap Card Improves Non-Invasive Prenatal Genotyping in Pregnancies with Antibodies.

    PubMed

    Adamczyk, Thomasz; Doescher, Andrea; Haydock, Paul V; Aldrich, Russ; Petershofen, Eduard K; Müller, Thomas H

    2015-11-01

    Determination of fetal blood groups in maternal plasma samples critically depends on adequate pre-analytical steps for optimal amplification of fetal DNA. We compared the extraction of cell-free DNA by binding on a glass surface (BCSI SNAP™ Card) with an automated system based on bead technology (MagnaPure compact™). Maternal blood samples from 281 pregnancies (7th-39th week of gestation) with known antibodies were evaluated in this study. Both the SNAP card and the MagnaPure method were applied to isolate DNA in order to directly compare the amplification in a single base extension assay and/or real-time PCR. The mean concentration of total DNA obtained by the SNAP card (33.8 ng/µl) exceeded more than twofold that of MagnaPure extraction (15.7 ng/µl). SNAP card-extracted samples allowed to detect 3.7 single nucleotide polymorphisms (SNPs) versus 2.5 SNPs in MagnaPure extracts to control for traces of fetal DNA. This difference is highest for samples from 7th-13th week of gestation. The SNAP card system improves DNA extraction efficacy for prenatal diagnosis in maternal blood samples and provides an at least eightfold higher total amount of DNA for the ensuing analysis. Its advantage is most evident for samples from early stages of pregnancy and thus especially valuable for pregnancies with antibodies.

  14. A non-invasive test for receptor binding applied to nephrogenic diabetes insipidus.

    PubMed Central

    Britton, K. E.; Tedder, R. S.; Khokhar, A. M.; Brown, N. J.; Davison, A.; Slater, J. D.

    1977-01-01

    Studies in animals have determined the importance of specific receptors to the action of many hormones and drugs. In man, a non-invasive external counting technique has been used and absence of receptor function has been demonstrated in a patient with nephrogenic diabetes insipidus using radioactively labelled arginine vasopressin. This is in contrast to the findings in a patient with pituitary diabetes insipidus and a normal control. These results suggest a model for the study of hormone and drug kinetics in man avoiding multiple samplings of biological fluids. PMID:196275

  15. 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.

  16. A field test study of our non-invasive thermal image analyzer for deceptive detection

    NASA Astrophysics Data System (ADS)

    Sumriddetchkajorn, Sarun; Somboonkaew, Armote; Sodsong, Tawee; Promduang, Itthipol; Sumriddetchkajorn, Niti

    2007-07-01

    We have developed a non-invasive thermal image analyzer for deceptive detection (TAD2) where the far-infrared data around the periorbital and nostril areas are simultaneously analyzed. Measured change in maximum skin temperature around two periorbital regions is converted to a relative blood flow velocity. A respiration pattern is also simultaneously determined via the ratio of the measured maximum and minimum temperatures in the nostril area. In addition, our TAD2 employs a simple normalized cross correlation scheme to independently track locations of the two periorbital and nostril areas. Our field case study from 7 subjects in two real crime scenes and with the use of our baseline classification criteria shows two-fold improvement in classification rate compared to our analysis using either the periorbital or nostril area alone.

  17. An innovative test for non-invasive Kell genotyping on circulating fetal DNA by means of the allelic discrimination of K1 and K2 antigens.

    PubMed

    Cro', Fabiana; Lapucci, Cristina; Vicari, Emilio; Salsi, Ginevra; Rizzo, Nicola; Farina, Antonio

    2016-12-01

    The aim of this study was to present a new method for fetal Kell genotyping by means of the allelic discrimination of K1 and K2 in real-time polymerase chain reaction (PCR). Real-time quantitative polymerase chain reaction incorporating an allele-specific primer was developed for detecting the K allele of KEL. By means of this method, the K1/K2 genotype was able to be determined in all blood samples analyzed. Results using cell-free fetal DNA (cffDNA) from two Kell-negative pregnant women confirmed the Kell-positive genotype of fetuses. The real-time PCR analysis also allowed the determination of the fetal fraction using the quantification of Kell-positive DNA. An efficient and reliable strategy for Kell genotyping is herein presented. The method was optimized on cffDNA to create a non-invasive prenatal test which could be routinely used for the prevention of hemolytic disease of the fetus and the newborn (HDFN). © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Gene expression test for the non-invasive diagnosis of bladder cancer: A prospective, blinded, international and multicenter validation study.

    PubMed

    Ribal, Maria J; Mengual, Lourdes; Lozano, Juan J; Ingelmo-Torres, Mercedes; Palou, Joan; Rodríguez-Faba, Oscar; Witjes, Johannes A; Van der Heijden, Antoine G; Medina, Rafael; Conde, Jose M; Marberger, Michael; Schmidbauer, Joerg; Fernández, Pedro L; Alcaraz, Antonio

    2016-02-01

    This study aimed to validate, in a prospective, blinded, international and multicenter cohort, our previously reported four non-invasive tests for bladder cancer (BC) diagnosis based on the gene expression patterns of urine. Consecutive voided urine samples from BC patients and controls were prospectively collected in five European centres (n=789). Finally, 525 samples were successfully analysed. Gene expression values were quantified using TaqMan Arrays and previously reported diagnostic algorithms were applied to gene expression data. Results from the most accurate gene signature for BC diagnosis were associated with clinical parameters using analysis of variance test. High diagnostic accuracy for the four gene signatures was found in the independent validation set (area under curve [AUC]=0.903-0.918), with the signature composed of two genes (GS_D2) having the best performance (sensitivity: 81.48%; specificity: 91.26%; AUC: 0.918). The diagnostic accuracy of GS_D2 was not affected by the number of tumours (p=0.58) but was statistically associated with tumour size (p=0.008). Also, GS_D2 diagnostic accuracy increases with increasing BC tumour risk. We found no differences in the performance of the GS_D2 test among the populations and centres in detecting tumours (p=0.7) and controls (p=0.2). Our GS_D2 test is non-invasive, non-observer dependent and non-labour-intensive, and has demonstrated diagnostic accuracy in an independent, international and multicenter study, equal or superior to the current gold standard (cystoscopy combined with cytology). Additionally, it has higher sensitivity than cytology while maintaining its specificity. Consequently, it meets the requirements for consideration as a molecular test applicable to clinical practice in the management of BC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Prenatal Genetic Screening Tests

    MedlinePlus

    ... until the second trimester. What is cell-free DNA testing? Cell-free DNA is the small amount of DNA that is released from the placenta into a pregnant woman’s bloodstream. The cell-free DNA in a sample of a woman’s blood can ...

  20. Assessment of various parameters using simple non-invasive tests in patients with cardiovascular diseases with or without cardiac rehabilitation.

    PubMed

    Ueda, Takashi; Miura, Shin-Ichiro; Fujimi, Kanta; Ishida, Toshihisa; Matsuda, Takuro; Fujita, Masaomi; Ura, Yoshiyuki; Kaino, Kouji; Sakamoto, Maya; Horita, Tomoe; Arimura, Tadaaki; Shiga, Yuhei; Kuwano, Takashi; Kitajima, Ken; Saku, Keijiro

    2016-09-01

    Cardiac rehabilitation (CR) improves cardiac function and exercise capacity in patients with cardiovascular disease (CVD). Simpler techniques are needed for use by physicians in the examination room to assess the usefulness of CR. We enrolled 46 consecutive CVD patients in a CR program (CR group) and prospectively followed them for 3 months. We compared them to 18 age-, gender- and body mass index-matched CVD patients without CR (non-CR group). Various parameters were measured at baseline and after 3 months using 3 simple non-invasive tests: severity of atherosclerosis [arterial velocity pulse index and arterial pressure volume index (API)] were determined using PASESA®, an autonomic nerve total activity amount index and a coefficient of variation of the R-R interval (CVRR) were determined using eHEART®, and peripheral resistance index, pressure rate product, stroke volume and cardiac index were determined using nico®]. There were no significant differences in patient characteristics including percentages (%) of ischemic heart disease and heart failure between the non-CR and CR groups. Systolic blood pressure (SBP), diastolic BP, heart rate and API at baseline significantly decreased and CVRR at baseline significantly increased after 3 months in the CR group, but not in the non-CR group. In addition, ΔAPI (Δ = the value after 3 months minus the value at baseline) was positively associated with ΔSBP in the CR group. In conclusion, CR significantly decreased BP and improved atherosclerosis and sympathetic nerve activity. These findings suggest that simple non-invasive tests may be useful for assessing the effects of CR.

  1. Non-invasive panel tests for gastrointestinal motility monitoring within the MARS-500 Project

    PubMed Central

    Roda, Aldo; Mirasoli, Mara; Guardigli, Massimo; Simoni, Patrizia; Festi, Davide; Afonin, Boris; Vasilyeva, Galina

    2013-01-01

    AIM: To develop an integrated approach for monitoring gastrointestinal motility and inflammation state suitable for application in long-term spaceflights. METHODS: Breath tests based on the oral administration of 13C-labeled or hydrogen-producing substrates followed by the detection of their metabolites (13CO2 or H2) in breath were used to measure gastrointestinal motility parameters during the 520-d spaceflight ground simulation within the MARS-500 Project. In particular, the gastric emptying rates of solid and liquid contents were evaluated by 13C-octanoic acid and 13C-acetate breath tests, respectively, whereas the orocecal transit time was assessed by an inulin H2-breath test, which was performed simultaneously with the 13C-octanoic acid breath test. A ready-to-eat, standardized pre-packaged muffin containing 100 mg of 13C-octanoic acid was used in the 13C-octanoic acid breath test to avoid the extemporaneous preparation of solid meals. In addition, a cassette-type lateral flow immunoassay was employed to detect fecal calprotectin, a biomarker of intestinal inflammation. Because no items could be introduced into the simulator during the experiment, all materials and instrumentation required for test performance during the entire mission simulation had to be provided at the beginning of the experiment. RESULTS: The experiments planned during the simulation of a manned flight to Mars could be successfully performed by the crewmembers without any external assistance. No evident alterations (i.e., increasing or decreasing trends) in the gastric emptying rates were detected using the 13C-breath tests during the mission simulation, as the gastric emptying half-times were in the range of those reported for healthy subjects. In contrast to the 13C-breath tests, the results of the inulin H2-breath test were difficult to interpret because of the high variability of the H2 concentration in the breath samples, even within the same subject. This variability suggested that

  2. Validation of a field test for the non-invasive determination of badminton specific aerobic performance

    PubMed Central

    Wonisch, M; Hofmann, P; Schwaberger, G; von Duvillard, S P; Klein, W

    2003-01-01

    Aim: To develop a badminton specific test to determine on court aerobic and anaerobic performance. Method: The test was evaluated by using a lactate steady state test. Seventeen male competitive badminton players (mean (SD) age 26 (8) years, weight 74 (10) kg, height 179 (7) cm) performed an incremental field test on the badminton court to assess the heart rate turn point (HRTP) and the individual physical working capacity (PWCi) at 90% of measured maximal heart rate (HRmax). All subjects performed a 20 minute steady state test at a workload just below the PWCi. Results: Significant correlations (p<0.05) for Pearson's product moment coefficient were found between the two methods for HR (r = 0.78) and velocity (r = 0.93). The HR at the PWCi (176 (5.5) beats/min) was significantly lower than the HRTP (179 (5.5) beats/min), but no significant difference was found for velocity (1.44 (0.3) m/s, 1.38 (0.4) m/s). The constant exercise test showed steady state conditions for both HR (175 (9) beats/min) and blood lactate concentration (3.1 (1.2) mmol/l). Conclusion: The data indicate that a valid determination of specific aerobic and anaerobic exercise performance for the sport of badminton is possible without HRTP determination. PMID:12663351

  3. Identification of an 18 bp deletion in the TWIST1 gene by CO-amplification at lower denaturation temperature-PCR (COLD-PCR) for non-invasive prenatal diagnosis of craniosynostosis: first case report.

    PubMed

    Galbiati, Silvia; Stenirri, Stefania; Sbaiz, Luca; Barberis, Marco; Cremonesi, Laura; Restagno, Gabriella; Ferrari, Maurizio

    2014-04-01

    Non-invasive prenatal diagnosis has found application in a limited number of genetic diseases due to the difficulty in detecting a few copies of fetal mutated sequences in the presence of a large excess of wild-type maternal alleles, even in the case of single-base mutations. We developed conditions for the enrichment of fetal mutated alleles in maternal plasma based on CO-amplification at lower denaturation temperature-PCR (COLD-PCR). In particular, we applied a full COLD-PCR protocol to the identification of a p.A87_G92del mutation in the TWIST1 gene causing craniosynostosis in a couple at risk for the disease. The use of the COLD-PCR protocol coupled with direct sequencing enabled correct identification of the fetal paternally inherited mutated allele, in accordance with the result obtained on DNA extracted from chorionic villi. COLD-PCR proved to be a simple and powerful tool for the identification of minority mutated alleles even in the case of a moderately large deletion (18 bp) and confirmed to be very suitable for non-invasive prenatal diagnosis of a variety of genetic diseases.

  4. Silicon-rich mineral water as a non-invasive test of the 'aluminum hypothesis' in Alzheimer's disease.

    PubMed

    Davenward, Samantha; Bentham, Peter; Wright, Jan; Crome, Peter; Job, Deborah; Polwart, Anthony; Exley, Christopher

    2013-01-01

    There has been a plausible link between human exposure to aluminum and Alzheimer's disease for several decades. We contend that the only direct and ethically acceptable experimental test of the 'aluminum hypothesis', which would provide unequivocal data specific to the link, is to test the null hypothesis that a reduction in the body burden of aluminum to its lowest practical limit would have no influence upon the incidence, progression, or severity of Alzheimer's disease. Herein we are testing the hypothesis that silicon-rich mineral waters can be used as non-invasive methods to reduce the body burden of aluminum in individuals with Alzheimer's disease and a control group consisting of their carers and partners. We have shown that drinking up to 1 L of a silicon-rich mineral water each day for 12 weeks facilitated the removal of aluminum via the urine in both patient and control groups without any concomitant affect upon the urinary excretion of the essential metals, iron and copper. We have provided preliminary evidence that over 12 weeks of silicon-rich mineral water therapy the body burden of aluminum fell in individuals with Alzheimer's disease and, concomitantly, cognitive performance showed clinically relevant improvements in at least 3 out of 15 individuals. This is a first step in a much needed rigorous test of the 'aluminum hypothesis of Alzheimer's disease' and a longer term study involving many more individuals is now warranted.

  5. Non-invasive prediction of blood lactate response to constant power outputs from incremental exercise tests.

    PubMed

    Sullivan, C S; Casaburi, R; Storer, T W; Wasserman, K

    1995-01-01

    We determined the ability of gas exchange analyses during incremental exercise tests (IXT) to predict blood lactate levels associated with a range of constant power output cycle ergometer tests. Twenty-seven healthy young men performed duplicate IXT and four 15-min constant power output tests at intensities ranging from moderate to very severe, before and after a training program. End-exercise blood lactate levels were approximated from superficial venous samples obtained 60 s after each constant power output test. From IXT, the power outputs corresponding to peak oxygen uptake (Wmax) and lactic acidosis threshold (WLAT), were determined. We examined the ability of four measures of exercise intensity to predict blood lactate levels for power outputs above the LAT: (1) power output (W), (2) power difference (W-WLAT), (3) power fraction (W/Wmax) and (4) power difference to delta ratio [(W-WLAT)/(Wmax-WLAT)]. Correlation coefficients were r = 0.38, 0.69, 0.75, and 0.81, respectively. The best linear regression prediction equation was: lactate (mmol.l-1) = 12.2[(W-WLAT)/(Wmax-WLAT)] + 0.7 mmol.l-1. This relationship was not significantly affected by training, despite increased values of LAT and peak oxygen uptake. Normalizing exercise intensity to the range of power outputs between WLAT and Wmax provided an estimate of blood lactate response to constant power outputs with a standard error of the estimate of 1.66 mmol.l-1.

  6. 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.

  7. Assessing receptivity in the endometrium: the need for a rapid, non-invasive test.

    PubMed

    Edgell, Tracey A; Rombauts, Luk J F; Salamonsen, Lois A

    2013-11-01

    Successful implantation of an embryo into the uterus requires synchrony between the blastocyst and the endometrium. Endometrial preparedness, or receptivity, occurs only for a very short time during the mid-secretory phase of the menstrual cycle in fertile women. Failure to achieve receptivity results in infertility and is a rate-limiting step for IVF success. Frozen embryo transfer in non-stimulation cycles is already improving live birth rates. However, an important tool that is missing in the armoury of reproductive specialists is a means to rapidly assess endometrial receptivity, either during initial assessment or immediately prior to embryo transfer. The development of a wealth of omics technologies now opens the way for identifying potential receptivity markers, although validation of these is still a major issue. This review assesses the current state of the field and the requirements to proceed to a valid clinical test.

  8. Perioperative Non-Invasive Indocyanine Green-Clearance Testing to Predict Postoperative Outcome after Liver Resection

    PubMed Central

    Haegele, Stefanie; Reiter, Silvia; Wanek, David; Offensperger, Florian; Pereyra, David; Stremitzer, Stefan; Fleischmann, Edith; Brostjan, Christine; Gruenberger, Thomas; Starlinger, Patrick

    2016-01-01

    Background Postoperative liver dysfunction may lead to morbidity and mortality after liver resection. Preoperative liver function assessment is critical to identify preexisting liver dysfunction in patients prior to resection. The aim of this study was to evaluate the predictive potential of perioperative indocyanine green (ICG)-clearance testing to prevent postoperative liver dysfunction and morbidity using standardized outcome parameters in a routine Western-clinical-setting. Study Design 137 patients undergoing partial hepatectomy between 2011 and 2013, at the general hospital of Vienna, were included. ICG-clearance was recorded one day prior to surgery as well as on the first and fifth postoperative day. Postoperative liver dysfunction was defined according to the International Study Group of Liver Surgery and evaluation of morbidity was based on the Dindo-Clavien classification. Statistical analyses were based on non-parametric tests. Results Preoperative reduced ICG—plasma disappearance rate (PDR) as well as increased ICG—retention rate at 15 min (R15) were able to significantly predict postoperative liver dysfunction (Area under the curve = PDR: 0.716, P = 0.018; R15: 0.719, P = 0.016). Furthermore, PDR <17%/min. or R15 >8%, were able to accurately predict postoperative complications prior to surgery. In addition to this, ICG-clearance on postoperative day 1 comparably predicted postoperative liver dysfunction (Area under the curve = PDR: 0.895; R15: 0.893; both P <0.001), specifically, PDR <10%/min or R15 >20% on postoperative day 1 predicted poor postoperative outcome. Conclusion PDR and R15 may represent useful parameters to distinguish preoperative high and low risk patients in a Western collective as well as on postoperative day 1, to identify patients who require closer monitoring for potential complications. PMID:27812143

  9. Prognostic Implications of Non-Invasive Vascular Function Tests in High-Risk Atherosclerosis Patients.

    PubMed

    Kusunose, Kenya; Sato, Mitsuyo; Yamada, Hirotsugu; Saijo, Yoshihito; Bando, Mika; Hirata, Yukina; Nishio, Susumu; Hayashi, Shuji; Sata, Masataka

    2016-01-01

    The aim of this study was to assess the role of clinically available vascular function tests as predictors of cardiovascular events and decline in kidney function. One hundred and fourteen patients who had at least 2 cardiovascular risk factors were recruited for vascular function assessment including ankle-brachial blood pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), cardio-ankle vascular index (CAVI) and flow-mediated vasodilatation (%FMD). During a median period of 51 months, 35 patients reached the primary endpoint (29 cardiovascular events and 6 cardiac deaths), and 30 patients reached the secondary endpoint (decline in kidney function: defined as a 5% per year decline of estimated glomerular filtration rate). In sequential Cox models, a model on the basis of the Framingham risk score, hemoglobin, and high-sensitivity C-reactive protein (chi-squared, 16.6) was improved by the ABI (chi-squared: 21.5; P=0.047). The baPWV (hazard ratio: 1.42 per 1 SD increase; P=0.025) and the CAVI (hazard ratio: 1.52 per 1 SD increase; P=0.040) were associated with the secondary endpoint. The %FMD was only slightly associated with the primary and secondary endpoints. Both ABI and baPWV are significantly associated with future cardiovascular events in high-risk patients with cardiovascular disease. The predictive capabilities of these parameters are greater than that of other parameters in this cohort.

  10. Relationship between non-invasive haemodynamic responses and cardiopulmonary exercise testing in patients with coronary artery disease.

    PubMed

    Sperling, Milena Pelosi Rizk; Caruso, Flávia Cristina Rossi; Mendes, Renata Gonçalves; Dutra, Daniela Bassi; Arakelian, Vivian Maria; Bonjorno, José Carlos; Catai, Aparecida Maria; Arena, Ross; Borghi-Silva, Audrey

    2016-03-01

    Non-invasive assessment of haemodynamic function by impedance cardiography (IC) constitutes an interesting approach to monitor cardiac function in patients with coronary artery disease (CAD). However, such measurements are most often performed at rest, whereas symptoms are also possible during exertion, particularly at higher intensities. In addition, the association between IC during exertion and cardiopulmonary exercise testing (CPX) is not well understood in these patients, which was the aim of this study. Nineteen men (age = 62 ± 6 years) with CAD [left ventricular ejection fraction (LVEF) = 61 ± 10%] underwent a CPX using an incremental protocol on a cycle ergometer, with simultaneous measurement of IC. Cardiac output (CO), stroke volume (SV), cardiac index (CI), peak oxygen consumption (VO2 ), the oxygen uptake efficiency slope (OUES), circulatory power and ventilatory power were determined. Pearson product-moment correlation analysis revealed peak VO2 (r = 0·46) was significantly related to CO. Peak oxygen pulse (0·52) was associated with SV. OUES was associated with resting SV (0·47) and with peak SV (r = 0·52). These findings suggest that IC indices are associated with certain, but not all, established CPX measures in patients with stable CAD. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  11. Non-invasive diagnosis of H pylori infection: Evaluation of serological tests with and without current infection marker CIM

    PubMed Central

    Rahman, Sufi HZ; Azam, M Golam; Rahman, M Anisur; Arfin, MS; Alam, M Mahbub; Bhuiyan, Tareq M; Ahmed, Nasim; Rahman, Motiur; Nahar, Shamsun; Hassan, MS

    2008-01-01

    AIM: To evaluate the performance of commercially available immunochromatographic (ICT) and immunoblot tests covering the current infection marker CIM and conventional ELISA for the diagnosis of H pylori infection in adult dyspeptic patients. METHODS: Consecutive non-treated dyspeptic patients undergoing diagnostic endoscopy were tested for H pylori infection by culture, rapid urease test, and histology of gastric biopsy specimens. Serum from 61 H pylori infected and 21 non-infected patients were tested for anti-H pylori IgG antibodies by commercial ELISA (AccuBindTM ELISA, Monobind, USA), ICT (Assure® H pylori Rapid Test, Genelabs Diagnostics, Singapore), and immunoblot (Helico Blot 2.1, Genelabs Diagnostics, Singapore) assays. ICT and immunoblot kits cover CIM among other parameters and their performance with and without CIM was evaluated separately. RESULTS: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of ELISA were 96.7%, 42.8%, 83.1%, 81.8%, and 82.9%, of ICT were 90.1%, 80.9%, 93.2%, 73.9%, and 87.8%, of ICT with CIM were 88.5%, 90.4%, 96.4%, 73.0%, and 89.0%, of immunoblot were 98.3%, 80.9%, 93.7%, 94.4%, and 93.9%, and of immunoblot with CIM were 98.3%, 90.4%, 96.7%, 95.0%, and 96.3%, respectively. CONCLUSION: Immunoblot with CIM had the best performance. ICT with CIM was found to be more specific and accurate than the conventional ELISA and may be useful for non-invasive diagnosis of H pylori infection. PMID:18300349

  12. Development of new non-invasive tests for colorectal cancer screening: The relevance of information on adenoma detection

    PubMed Central

    Haug, Ulrike; Knudsen, Amy B.; Lansdorp-Vogelaar, Iris; Kuntz, Karen M.

    2014-01-01

    Researchers are actively pursuing the development of a new non-invasive test (NIT) for colorectal cancer (CRC) screening as an alternative to fecal occult blood tests (FOBTs). The majority of pilot studies focus on the detection of invasive CRC rather than precursor lesions (i.e., adenomas). We aimed to explore the relevance of adenoma detection for the viability of an NIT for CRC screening by considering a hypothetical test that does not detect adenomas beyond chance. We used the Simulation Model of Colorectal Cancer (SimCRC) to estimate the effectiveness of CRC screening and the lifetime costs (payers’ perspective) for a cohort of US 50-year-olds to whom CRC screening is offered from age 50–75. We compared annual screening with guaiac and immunochemical FOBTs (with sensitivities up to 70% and 24% for CRC and adenomas, respectively) to annual screening with a hypothetical NIT (sensitivity of 90% for CRC, no detection of adenomas beyond chance, specificity and cost similar to FOBTs). Screening with the NIT was not more effective, but was 29–44% more costly than screening with FOBTs. The findings were robust to varying the screening interval, the NIT’s sensitivity for CRC, adherence rates favoring the NIT, and the NIT’s unit cost. A comparative modelling approach using a model that assumes a shorter adenoma dwell time (MISCAN-COLON) confirmed the superiority of the immunochemical FOBT over a NIT with no ability to detect adenomas. Information on adenoma detection is crucial to determine whether a new NIT is a viable alternative to FOBTs for CRC screening. Current evidence thus lacks an important piece of information to identify marker candidates that hold real promise and deserve further (large-scale) evaluation. PMID:25403937

  13. Development of new non-invasive tests for colorectal cancer screening: the relevance of information on adenoma detection.

    PubMed

    Haug, Ulrike; Knudsen, Amy B; Lansdorp-Vogelaar, Iris; Kuntz, Karen M

    2015-06-15

    Researchers are actively pursuing the development of a new non-invasive test (NIT) for colorectal cancer (CRC) screening as an alternative to fecal occult blood tests (FOBTs). The majority of pilot studies focus on the detection of invasive CRC rather than precursor lesions (i.e., adenomas). We aimed to explore the relevance of adenoma detection for the viability of an NIT for CRC screening by considering a hypothetical test that does not detect adenomas beyond chance. We used the Simulation Model of Colorectal Cancer (SimCRC) to estimate the effectiveness of CRC screening and the lifetime costs (payers' perspective) for a cohort of US 50-years-old persons to whom CRC screening is offered from age 50-75. We compared annual screening with guaiac and immunochemical FOBTs (with sensitivities up to 70 and 24% for CRC and adenomas, respectively) to annual screening with a hypothetical NIT (sensitivity of 90% for CRC, no detection of adenomas beyond chance, specificity and cost similar to FOBTs). Screening with the NIT was not more effective, but was 29-44% more costly than screening with FOBTs. The findings were robust to varying the screening interval, the NIT's sensitivity for CRC, adherence rates favoring the NIT, and the NIT's unit cost. A comparative modelling approach using a model that assumes a shorter adenoma dwell time (MISCAN-COLON) confirmed the superiority of the immunochemical FOBT over an NIT with no ability to detect adenomas. Information on adenoma detection is crucial to determine whether a new NIT is a viable alternative to FOBTs for CRC screening. Current evidence thus lacks an important piece of information to identify marker candidates that hold real promise and deserve further (large-scale) evaluation. © 2014 UICC.

  14. Non-Invasive Cytology Brush PCR Diagnostic Testing in Mucosal Leishmaniasis: Superior Performance to Conventional Biopsy with Histopathology

    PubMed Central

    Veland, Nicolas; Pilar Ramos, Ana; Calderon, Flor; Arevalo, Jorge; Low, Donald E.; Llanos-Cuentas, Alejandro

    2011-01-01

    Background Traditional methods of diagnosing mucosal leishmaniasis (ML), such as biopsy with histopathology, are insensitive and require collection of an invasive diagnostic specimen. Methods We compared standard invasive procedures including biopsy histopathology, biopsy PCR, and leishmanin skin test (LST) to a novel, non-invasive, cytology-brush based PCR for the diagnosis of ML in Lima, Peru. Consensus reference standard was 2/4 tests positive, and outcome measures were sensitivity and specificity. Leishmania species identification was performed by PCR-based assays of positive specimens. Results Twenty-eight patients were enrolled, 23 of whom fulfilled criteria for a diagnosis of ML. Sensitivity and specificity of biopsy with histopathology were 21.7% [95% CI 4.9–38.5%] and 100%; 69.6% [95% CI 50.8–88.4%] and 100% for LST; 95.7% [95% CI 87.4–100%] and 100% for biopsy PCR; and 95.7% [95% CI 87.4–100%] and 90% [95% CI 71.4–100%] for cytology brush PCR using both Cervisoft® and Histobrush® cervical cytology brushes. Represented species identified by PCR-RFLP included: L. (V). braziliensis (n = 4), and L. (V). peruviana (n = 3). Conclusions Use of commercial grade cytology brush PCR for diagnosis of ML is sensitive, rapid, well tolerated, and carries none of the risks of invasive diagnostic procedures such as biopsy. Further optimization is required for adequate species identification. Further evaluation of this method in field and other settings is warranted. PMID:22046280

  15. Prenatal Testing: MedlinePlus Health Topic

    MedlinePlus

    ... Reliable Is Laboratory Testing? (American Association for Clinical Chemistry) Prenatal Testing: Is It Right for You? (Mayo ... Spanish Amniotic Fluid Analysis (American Association for Clinical Chemistry) Biophysical Profile (Mayo Foundation for Medical Education and ...

  16. 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...

  17. Time-resolved diffuse optical tomography for non-invasive flap viability assessment: pre-clinical tests on rats

    NASA Astrophysics Data System (ADS)

    Di Sieno, L.; Bettega, G.; Berger, M.; Hamou, C.; Aribert, M.; Dalla Mora, A.; Puszka, A.; Grateau, H.; Contini, D.; Hervé, L.; Coll, J.-L.; Dinten, J.-M.; Pifferi, A.; Planat-Chrétien, A.

    2015-07-01

    We present a new setup for time-resolved diffuse optical tomography based on multiple source-detector acquisitions analysed by means of the Mellin-Laplace transform. The proposed setup has been used to perform pre-clinical measurements on rats in order to show its suitability for non-invasive assessment of flap viability.

  18. In-vivo testing of a non-invasive prototype device for the continuous monitoring of intracerebral hemorrhage

    PubMed Central

    Kandadai, Madhuvanthi A.; Korfhagen, Joseph; Beiler, Shauna; Beiler, Chris; Wagner, Kenneth; Adeoye, Opeolu M.; Shaw, George J.

    2014-01-01

    Background Intracerebral hemorrhage (ICH) is a stroke subtype with the highest mortality rate. Hematoma expansion and re-bleeding post-ICH are common and exacerbate the initial cerebral insult. There is a need for continuous monitoring of the neurologic status of patients with an ICH injury. New Method A prototype device for non-invasive continuous monitoring of an ICH was developed and tested in-vivo using a porcine ICH model. The device consists of receiving and transmitting antennae in the 400–1000 MHz frequency range, placed directly in line with the site of the ICH. The device exploits the differences in the dielectric properties and geometry of tissue media of a healthy brain and a brain with an ICH injury. The power received by the receiving antenna is measured and the percent change in power received immediately after infusion of blood and 30 minutes after the infusion, allowing for the blood to clot, is calculated. Results An increase in the received power in the presence of an ICH is observed at 400 MHz, consistent with previous in-vitro studies. Frequency sweep experiments show a maximum percent change in received power in the 750–1000 MHz frequency range. Comparison with existing methods Currently, CT, MRI and catheter angiography (CA) are the main clinical neuroimaging modalities. However, these techniques require specialized equipment and personnel, substantial time, and patient- transportation to a radiology suite to obtain results. Moreover, CA is invasive and uses intra-venous dye or vascular catheters to accomplish the imaging. Conclusions The device has the potential to significantly improve neurologic care in the critically ill brain-injured patient. PMID:24997340

  19. Non-invasive prenatal diagnosis of β-thalassemia by detection of the cell-free fetal DNA in maternal circulation: a systematic review and meta-analysis.

    PubMed

    Zafari, Mandana; Kosaryan, Mehrnoush; Gill, Pooria; Alipour, Abbass; Shiran, Mohammadreza; Jalalli, Hossein; Banihashemi, Ali; Fatahi, Fatemeh

    2016-08-01

    The discovery of fetal DNA (f-DNA) opens the possibility of early non-invasive procedure for detection of paternally inherited mutation of beta-thalassemia. Since 2002, some studies have examined the sensitivity and specificity of this method for detection of paternally inherited mutation of thalassemia in pregnant women at risk of having affected babies. We conducted a systematic review of published articles that evaluated using this method for early detection of paternally inherited mutation in maternal plasma. A sensitive search of multiple databases was done in which nine studies met our inclusion criteria. The sensitivity and specificity was 99 and 99 %, respectively. The current study found that detection of paternally inherited mutation of thalassemia using analysis of cell-free fetal DNA is highly accurate. This method could replace conventional and invasive methods.

  20. Tomorrow's prenatal genetic testing. Should we test for 'minor' diseases?

    PubMed

    Strong, C

    1993-11-01

    New genetic knowledge will make it possible to test prenatally for a wide range of fetal genetic characteristics. One consequence will be an expansion of potential reasons for selective abortion following prenatal testing. It will likely become possible for patients to request prenatal testing and abortion not only for serious diseases but also relatively mild diseases, late-onset diseases, treatable diseases, elevated risks for common diseases, and eventually nondisease characteristics, such as height and body build. Two main ethical views concerning prenatal testing have been advocated: (1) Prenatal testing should be restricted to the "most severe" disorders, involving profound retardation, severe physical handicaps, or prolonged physical suffering and (2) Patients' requests for prenatal tests should be honored except for diseases considered to be "too minor." At least two additional views can be identified: (3) Physicians should honor requests for prenatal testing for diseases, including relatively minor ones, but not requests pertaining to nondisease characteristics and (4) All requests for prenatal tests should be honored. A difficulty with the first and second views is that they deviate from the norm of nondirectiveness in prenatal testing and counseling. The problems with the fourth view are that it leads to abortions for morally trivial reasons and that attempts to design our children could adversely affect parent-child relationships and exacerbate current social inequities. These considerations support the third view, which holds that the future role of reproductive genetic testing and counseling should be based on the imperfect, but helpful, distinction between disease and nondisease.

  1. [Non invasive prenatal genetic diagnosis of fetal RhD and sex through the analysis of free fetal DNA in maternal plasma].

    PubMed

    Sesarini, Carla; Giménez, María Laura; Redal, María Ana; Izbizky, Gustavo; Aiello, Horacio; Argibay, Pablo; Otaño, Lucas

    2009-10-01

    The analysis of free fetal DNA in maternal plasma allows the assessment of fetal genetic material avoiding the necessity of invasive procedures during pregnancy. To evaluate the feasibility and the diagnostic performance of fetal sex and fetal RhD detection through the analysis of free fetal DNA in maternal plasma using standard reagents in molecular biology. A hundred and nine blood samples of pregnant women were obtained. Amplification by real time PCR a sequence from the RhD gene in Rh negative patients and a Y-chromosome sequence, for the diagnosis of fetal Rh and sex respectively, were performed. Results were compared with neonatal outcomes. From the 109 samples, 26 are still ongoing, 4 ended in spontaneous abortions and in 3 were lost to follow up. From the remaining 76 samples with neonatal result, the determination of fetal Rh from the RhD gene was performed in 65 Rh negative women, whereas in 66 samples the fetal sex analysis was evaluated. Overall, 15 samples had not conclusive results and were excluded from the study. The predictive values for RhD positive and negative were 85% and 90%, respectively, while the prediction for male sex was 94.3% and for female sex 95%. The non invasive determination of fetal RhD and sex in maternal plasma using standard reagents in molecular biology was feasible in the majority of the samples, with a diagnostic performance similar to the reported in the literature.

  2. A non-invasive platform for functional characterization of stem-cell-derived cardiomyocytes with applications in cardiotoxicity testing.

    PubMed

    Maddah, Mahnaz; Heidmann, Julia D; Mandegar, Mohammad A; Walker, Chase D; Bolouki, Sara; Conklin, Bruce R; Loewke, Kevin E

    2015-04-14

    We present a non-invasive method to characterize the function of pluripotent stem-cell-derived cardiomyocytes based on video microscopy and image analysis. The platform, called Pulse, generates automated measurements of beating frequency, beat duration, amplitude, and beat-to-beat variation based on motion analysis of phase-contrast images captured at a fast frame rate. Using Pulse, we demonstrate recapitulation of drug effects in stem-cell-derived cardiomyocytes without the use of exogenous labels and show that our platform can be used for high-throughput cardiotoxicity drug screening and studying physiologically relevant phenotypes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Occurrence and prenatal exposure to persistent organic pollutants using meconium in Korea: Feasibility of meconium as a non-invasive human matrix.

    PubMed

    Jeong, Yunsun; Lee, Sunggyu; Kim, Sunmi; Choi, Sung-Deuk; Park, Jeongim; Kim, Hai-Joong; Lee, Jeong Jae; Choi, Gyuyeon; Choi, Sooran; Kim, Sungjoo; Kim, Su Young; Kim, Young Don; Cho, Geumjoon; Suh, Eunsook; Kim, Sung Koo; Eun, So-Hee; Eom, Soyong; Kim, Seunghyo; Kim, Gun-Ha; Kim, Sungkyoon; Choi, Kyungho; Moon, Hyo-Bang

    2016-05-01

    Prenatal exposure to persistent organic pollutants (POPs) is of great concern due to the vulnerability of fetus. Nineteen Polychlorinated biphenyls (PCBs), 18 organochlorine pesticides (OCPs) including DDTs, HCHs, chlordanes, and hexachlorobenzene, and 22 polybrominated diphenyl ethers (PBDEs) were measured in meconium samples from 72 newborn infants using high resolution gas chromatography/mass spectrometry. The median concentrations (on wet weight basis) of PCBs, OCPs, and PBDEs were 26.8pg/g, 66.7pg/g, and 2.32pg/g, respectively. Highly significant correlations were observed among the compounds of PCBs and OCPs, suggesting their similar sources and kinetic behaviors. BDE 47 had significant correlations with PCBs and OCPs, whereas BDE 209 was not correlated with any of the contaminants due to different exposure sources. The concentrations of p,p'-DDE, β-HCH, and trans-nonaCHL between paired maternal blood-meconium and cord blood-meconium showed significant correlations, while PCBs and PBDEs were not significantly correlated in the paired samples. Maternal age and gestational age were demographic parameters affecting POP levels in meconium. Multiple regression analysis showed that the levels of several OCPs in cord and maternal serum were contributing factors governing the levels of these contaminants in meconium. Our results indicate that meconium can be utilized as a human matrix for prenatal exposure to several OCPs. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Non-invasive neurosensory testing used to diagnose and confirm successful surgical management of lower extremity deep distal posterior compartment syndrome

    PubMed Central

    2009-01-01

    Background Chronic exertional compartment syndrome (CECS) is characterized by elevated pressures within a closed space of an extremity muscular compartment, causing pain and/or disability by impairing the neuromuscular function of the involved compartment. The diagnosis of CECS is primarily made on careful history and physical exam. The gold standard test to confirm the diagnosis of CECS is invasive intra-compartmental pressure measurements. Sensory nerve function is often diminished during symptomatic periods of CECS. Sensory nerve function can be documented with the use of non-painful, non-invasive neurosensory testing. Methods Non-painful neurosensory testing of the myelinated large sensory nerve fibers of the lower extremity were obtained with the Pressure Specified Sensory Device™ in a 25 year old male with history and invasive compartment pressures consistent with CECS both before and after running on a tread mill. After the patient's first operation to release the deep distal posterior compartment, the patient failed to improve. Repeat sensory testing revealed continued change in his function with exercise. He was returned to the operating room where a repeat procedure revealed that the deep posterior compartment was not completely released due to an unusual anatomic variant, and therefore complete release was accomplished. Results The patient's symptoms numbness in the plantar foot and pain in the distal calf improved after this procedure and his repeat sensory testing performed before and after running on the treadmill documented this improvement. Conclusion This case report illustrates the principal that non-invasive neurosensory testing can detect reversible changes in sensory nerve function after a provocative test and may be a helpful non-invasive technique to managing difficult cases of persistent lower extremity symptoms after failed decompressive fasciotomies for CECS. It can easily be performed before and after exercise and be repeated at

  5. Non-invasive Pregnancy Diagnosis from Urine by the Cuboni Reaction and the Barium Chloride Test in Donkeys (Equus asinus) and Alpacas (Vicugna pacos).

    PubMed

    Kubátová, A; Fedorova, T; Skálová, I; Hyniová, L

    2016-09-01

    The aim of the research was to evaluate two chemical tests for non-invasive pregnancy diagnosis from urine, the Cuboni reaction and the barium chloride test, in donkeys (Equus asinus) and alpacas (Vicugna pacos). The research was carried out from April 2013 to September 2014. Urine samples were collected on five private Czech farms from 18 jennies and 12 alpaca females. Urine was collected non-invasively into plastic cups fastened on a telescopic rod, at 6-9 week intervals. In total, 60 and 54 urine samples from alpacas and jennies, respectively, were collected. The Cuboni reaction was performed by the State Veterinary Institute Prague. The barium chloride test was done with 5 ml of urine mixed together with 5 ml of 1% barium chloride solution. Results of the Cuboni reaction were strongly influenced by the reproductive status of jennies; the test was 100% successful throughout the second half of pregnancy. However, no relationship was found between the real reproductive status of alpaca females and results of the Cuboni reaction. It was concluded that the barium chloride test is not suitable for pregnancy diagnosis either in donkeys, due to significant influence of season on the results, or in alpacas, because no relationship between results of the test and the reproductive status of alpaca females was found. In conclusion, the Cuboni reaction has potential to become a standard pregnancy diagnostic method in donkeys.

  6. A cost-effective, non-invasive system for pressure monitoring during epidural needle insertion: Design, development and bench tests.

    PubMed

    Tesei, M; Saccomandi, P; Massaroni, C; Quarta, R; Carassiti, M; Schena, E; Setola, R

    2016-08-01

    Epidural blockade procedures have gained large acceptance during last decades. However, the insertion of the needle during epidural blockade procedures is challenging, and there is an increasing alarming risk in accidental dural puncture. One of the most popular approaches to minimize the mentioned risk is to detect the epidural space on the base of the loss of resistance (LOR) during the epidural needle insertion. The aim of this paper is to illustrate an innovative and non-invasive system able to monitor the pressure exerted during the epidural blockade procedure in order to detect the LOR. The system is based on a Force Sensing Resistor (FSR) sensor arranged on the top of the syringe's plunger. Such a sensor is able to register the resistance opposed to the needle by the different tissues transducing the pressure exerted on the plunger into a change of an electrical resistance. Hence, on the base of a peculiar algorithm, the system automatically detects LOR providing visual and acoustic feedbacks to the operator improving the safety of the procedure. Experiments have been performed to characterize the measurement device and to validate the whole system. Notice that the proposed solution is able to perform an effective detection of the LOR.

  7. A simulation test of the effectiveness of several methods for error-checking non-invasive genetic data

    USGS Publications Warehouse

    Roon, David A.; Waits, L.P.; Kendall, K.C.

    2005-01-01

    Non-invasive genetic sampling (NGS) is becoming a popular tool for population estimation. However, multiple NGS studies have demonstrated that polymerase chain reaction (PCR) genotyping errors can bias demographic estimates. These errors can be detected by comprehensive data filters such as the multiple-tubes approach, but this approach is expensive and time consuming as it requires three to eight PCR replicates per locus. Thus, researchers have attempted to correct PCR errors in NGS datasets using non-comprehensive error checking methods, but these approaches have not been evaluated for reliability. We simulated NGS studies with and without PCR error and 'filtered' datasets using non-comprehensive approaches derived from published studies and calculated mark-recapture estimates using CAPTURE. In the absence of data-filtering, simulated error resulted in serious inflations in CAPTURE estimates; some estimates exceeded N by ??? 200%. When data filters were used, CAPTURE estimate reliability varied with per-locus error (E??). At E?? = 0.01, CAPTURE estimates from filtered data displayed < 5% deviance from error-free estimates. When E?? was 0.05 or 0.09, some CAPTURE estimates from filtered data displayed biases in excess of 10%. Biases were positive at high sampling intensities; negative biases were observed at low sampling intensities. We caution researchers against using non-comprehensive data filters in NGS studies, unless they can achieve baseline per-locus error rates below 0.05 and, ideally, near 0.01. However, we suggest that data filters can be combined with careful technique and thoughtful NGS study design to yield accurate demographic information. ?? 2005 The Zoological Society of London.

  8. Validation of AshTest as a Non-Invasive Alternative to Transjugular Liver Biopsy in Patients with Suspected Severe Acute Alcoholic Hepatitis

    PubMed Central

    Rudler, Marika; Mouri, Sarah; Charlotte, Frederic; Cluzel, Philippe; Ngo, Yen; Munteanu, Mona; Lebray, Pascal; Ratziu, Vlad; Thabut, Dominique; Poynard, Thierry

    2015-01-01

    Background/Aims According to guidelines, the histological diagnosis of severe alcoholic steatohepatitis (ASH) can require liver biopsy if a specific treatment is needed. The blood test AshTest (BioPredictive, Paris, France) has been initially validated for the non-invasive diagnosis of ASH in a large population of heavy drinkers. The aim was to validate the AshTest accuracy in the specific context of use of patients with suspected severe ASH, in order to reduce the need for transjugular biopsy before deciding treatment. Methods The reference was liver biopsy, performed using the transjugular route, classified according to its histological severity as none, minimal, moderate or severe. Biopsies were assessed by the same experienced pathologist, blinded to simultaneous AshTest results. Results A total of 123 patients with severe clinical ASH (recent jaundice and Maddrey function greater or equal to 32) were included, all had cirrhosis and 80% had EASL histological definition of ASH. 95% of patients received prednisolone; and the 2-year mortality was 63%. The high AshTest performance was confirmed both for the binary outcome [AUROC = 0.803 (95%CI 0.684–0.881)] significantly higher than the AST/ALT AUROC [0.603 (0.462–0.714); P<0.001], and for the severity of ASH-score system by the Obuchowski measures for [mean (SE) 0.902 (0.017) vs. AST/ALT 0.833 (0.023); P = 0.01], as well as for the diagnosis and severity of ballooning, PMN and Mallory bodies. According to attributability of discordances, AshTest had a 2–7% risk of 2 grades misclassification. Conclusion These results confirmed the diagnostic performance of AshTest in cirrhotic patients with severe clinical ASH, in the specific context of use of corticosteroid treatment. AshTest is an appropriate non-invasive alternative to transjugular liver biopsy. PMID:26252713

  9. Non-invasive ventilation for cystic fibrosis.

    PubMed

    Moran, Fidelma; Bradley, Judy M; Piper, Amanda J

    2017-02-20

    capacity (interface used was unclear) and did not reported on any of the review's primary outcomes. The trial found no clear differences between non-invasive ventilation compared to no non-invasive ventilation for any of our outcomes.Three trials reported on adverse effects. One trial, evaluating non-invasive ventilation for airway clearance, reported that a participant withdrew at the start of the trial due to pain on respiratory muscle testing. One trial evaluating non-invasive ventilation for overnight support reported that one participant could not tolerate an increase in inspiratory positive airway pressure. A second trial evaluating non-invasive ventilation in this setting reported that one participant did not tolerate the non-invasive ventilation mask, one participant developed a pneumothorax when breathing room air and two participants experienced aerophagia which resolved when inspiratory positive airway pressure was decreased. Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with cystic fibrosis who have difficulty expectorating sputum. Non-invasive ventilation, used in addition to oxygen, may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. The effect of NIV on exercise is unclear. These benefits of non-invasive ventilation have largely been demonstrated in single treatment sessions with small numbers of participants. The impact of this therapy on pulmonary exacerbations and disease progression remain unclear. There is a need for long-term randomised controlled trials which are adequately powered to determine the clinical effects of non-invasive ventilation in cystic fibrosis airway clearance and exercise.

  10. Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y.

    PubMed

    Nicolaides, K H; Syngelaki, A; Gil, M; Atanasova, V; Markova, D

    2013-06-01

    To assess the performance of cell-free DNA (cfDNA) testing in maternal blood for detection of fetal aneuploidy of chromosomes 13, 18, 21, X, and Y using targeted sequencing of single-nucleotide polymorphisms. Prospective study in 242 singleton pregnancies undergoing chorionic villus sampling at 11 to 13 weeks. Maternal blood was collected before chorionic villus sampling and sent to Natera (San Carlos, CA, USA). cfDNA was isolated from maternal plasma, and targeted multiplex PCR amplification followed by sequencing of 19 488 polymorphic loci covering chromosomes 13, 18, 21, X, and Y was performed. Sequencing data were analyzed using the NATUS algorithm that determines the copy number and calculates a sample-specific accuracy for each of the five chromosomes tested. Laboratory personnel were blinded to fetal karyotype. Results were provided for 229 (94.6%) of the 242 cases. Thirty-two cases were correctly identified as aneuploid, including trisomy 21 [n = 25; sensitivity = 100% (CI: 86.3-100%), specificity = 100% (CI: 98.2-100%)], trisomy 18 (n = 3), trisomy 13 (n = 1), Turner syndrome (n = 2), and triploidy (n = 1), with no false positive or false negative results. Median accuracy was 99.9% (range: 96.0-100%). cfDNA testing in maternal blood using targeted sequencing of polymorphic loci at chromosomes 13, 18, 21, X, and Y holds promise for accurate detection of fetal autosomal trisomies, sex chromosome aneuploidies, and triploidy. © 2013 John Wiley & Sons, Ltd.

  11. Non-Invasive Screening Tools for Down’s Syndrome: A Review

    PubMed Central

    Sillence, Kelly A.; Madgett, Tracey E.; Roberts, Llinos A.; Overton, Timothy G.; Avent, Neil D.

    2013-01-01

    Down’s syndrome (DS) is the most common genetic cause of developmental delay with an incidence of 1 in 800 live births, and is the predominant reason why women choose to undergo invasive prenatal diagnosis. However, as invasive tests are associated with around a 1% risk of miscarriage new non-invasive tests have been long sought after. Recently, the most promising approach for non-invasive prenatal diagnosis (NIPD) has been provided by the introduction of next generation sequencing (NGS) technologies. The clinical application of NIPD for DS detection is not yet applicable, as large scale validation studies in low-risk pregnancies need to be completed. Currently, prenatal screening is still the first line test for the detection of fetal aneuploidy. Screening cannot diagnose DS, but developing a more advanced screening program can help to improve detection rates, and therefore reduce the number of women offered invasive tests. This article describes how the prenatal screening program has developed since the introduction of maternal age as the original “screening” test, and subsequently discusses recent advances in detecting new screening markers with reference to both proteomic and bioinformatic techniques. PMID:26835682

  12. Non-invasive Evaluation of NAFLD with Indocyanine Green Clearance Test: a Preliminary Study in Morbidly Obese Patients Undergoing Bariatric Surgery.

    PubMed

    Danin, Pierre Eric; Anty, Rodolphe; Patouraux, Stephanie; Raucoules-Aimé, Marc; Gugenheim, Jean; Tran, Albert; Gual, Philippe; Iannelli, Antonio

    2017-09-05

    Overweight and obesity dramatically increased in the last years. Hepatic complication of obesity, integrated in the term of non-alcoholic fatty liver disease (NAFLD), is a spectrum of abnormality ranging from steatosis to non-alcoholic steatohepatitis (NASH), potentially leading to cirrhosis. Liver biopsy remains the gold standard to evaluate the stage of NAFLD; however, the procedure is invasive. The indocyanine green (ICG) clearance test is performed since years to assess hepatic function before partial hepatectomy, or after liver transplantation. This study was designed to detect liver complications with the ICG clearance test in a population of obese patients scheduled for bariatric surgery. In a prospective cohort study, morbidly obese individuals receiving bariatric surgery with scheduled hepatic biopsies were investigated. Liver function was determined by the ICG test preoperatively, and blood samples were collected. Liver biopsy specimens were obtained for each patient and classified according to the NAFLD activity score (NAS) by a single pathologist that was blinded to the results of the ICG test. Twenty-six patients were included (7 male and 19 female). The mean age of participants was 45.8 years; the mean body mass index was 41.4 kg/m(2). According to the NAS, 6 (23.1%) patients revealed manifest NASH, and 5 patients were considered borderline (19.2%). A closed correlation was observed between the ICG clearance test and hepatic steatosis (r = 0.43, p = 0.03), NAS (r = 0.44, p = 0.025), and fibrosis (r = 0.49, p = 0.01). In obese patients, non-invasive evaluation of liver function with the indocyanine green clearance test correlated with histological features of NAFLD. This may detect non-invasively hepatopathy in obese population and could motive biopsy.

  13. Preferences for prenatal tests for Down syndrome: an international comparison of the views of pregnant women and health professionals.

    PubMed

    Hill, Melissa; Johnson, Jo-Ann; Langlois, Sylvie; Lee, Hyun; Winsor, Stephanie; Dineley, Brigid; Horniachek, Marisa; Lalatta, Faustina; Ronzoni, Luisa; Barrett, Angela N; Advani, Henna V; Choolani, Mahesh; Rabinowitz, Ron; Pajkrt, Eva; van Schendel, Rachèl V; Henneman, Lidewij; Rommers, Wieke; Bilardo, Caterina M; Rendeiro, Paula; Ribeiro, Maria João; Rocha, José; Bay Lund, Ida Charlotte; Petersen, Olav B; Becher, Naja; Vogel, Ida; Stefánsdottir, Vigdis; Ingvarsdottir, Sigrun; Gottfredsdottir, Helga; Morris, Stephen; Chitty, Lyn S

    2016-07-01

    Non-invasive prenatal testing is increasingly available worldwide and stakeholder viewpoints are essential to guide implementation. Here we compare the preferences of women and health professionals from nine different countries towards attributes of non-invasive and invasive prenatal tests for Down syndrome. A discrete choice experiment was used to obtain participants' stated preference for prenatal tests that varied according to four attributes: accuracy, time of test, risk of miscarriage, and type of information. Pregnant women and health professionals were recruited from Canada, Denmark, Iceland, Israel, Italy, the Netherlands, Portugal, Singapore, and the United Kingdom. A total of 2666 women's and 1245 health professionals' questionnaires were included in the analysis. Differences in preferences were seen between women and health professionals within and between countries. Overall, women placed greater emphasis on test safety and comprehensive information than health professionals, who emphasised accuracy and early testing. Differences between women's and health professionals' preferences are marked between countries. Varied approaches to implementation and service delivery are therefore needed and individual countries should develop guidelines appropriate for their own social and screening contexts.

  14. Prenatal HIV tests. Routine testing or informed choice?

    PubMed Central

    Guenter, Dale; Kaczorowski, Janusz; Carroll, June; Sellors, John

    2003-01-01

    OBJECTIVE: To examine how prenatal care providers responded to a new provincial policy of offering HIV testing to all prenatal patients, and to determine factors associated with self-reported high testing rates. DESIGN: Cross-sectional mailed survey. SETTING: Outpatient practices in three Ontario health-planning regions. PARTICIPANTS: Prenatal care providers: 784 family physicians, 200 obstetricians, and 103 midwives were sent questionnaires and were eligible to participate. MAIN OUTCOME MEASURES: Self-reported testing of 80% or more prenatal patients ("high testers") and associated practice characteristics, attitudes, and counseling practices. RESULTS: Response rate was 57% (622/1087): 43% of respondents were high testers. Family physicians were most likely and midwives least likely to be high testers. High testers tended to report that they had adequate knowledge of HIV testing, that HIV risk among their patients warranted testing all of them, and that testing should be routine. Encouraging women to test and not providing written information or choice were independently associated with high testing rates. CONCLUSION: Strongest predictors of high prenatal HIV testing rates were attitudes and practices that favoured a routine approach to testing and that placed little emphasis on informed consent. PMID:14594102

  15. Noninvasive prenatal testing: more caution in counseling is needed in high risk pregnancies with ultrasound abnormalities.

    PubMed

    Oneda, Beatrice; Steindl, Katharina; Masood, Rahim; Reshetnikova, Irina; Krejci, Pavel; Baldinger, Rosa; Reissmann, Regina; Taralczak, Malgorzata; Guetg, Adriano; Wisser, Josef; Fauchère, Jean-Claude; Rauch, Anita

    2016-05-01

    Non-invasive prenatal testing (NIPT) is increasingly being used in prenatal aneuploidy screening. The objective of this study was to assess the positive predictive value in our cohort of 68 cases with positive NIPT result. In addition, we wondered if the use of NIPT in cases with ultrasound abnormalities is appropriate, given the limited number of chromosomes investigated. We performed confirmative invasive testing using karyotyping, fluorescence in situ hybridization (FISH) and/or high-resolution chromosomal microarray analysis. In line with the published data, the positive NIPT result was confirmed in 64.7% of cases. Inconclusive and negative NIPT results followed by cytogenetically pathologic findings were encountered in three and in five cases, respectively. Four of the five fetuses with negative NIPT but pathologic cytogenetic findings were born with several malformations and diagnosed right after birth with severe genetic conditions. Of note, in all of those four cases, NIPT was offered despite the finding of major fetal ultrasound abnormalities and despite the fact that the family would not have opposed invasive testing or pregnancy termination. More education of health care providers and caution in counseling and interpretation of test results are needed in order to meet the challenges that this new test, which enriches our diagnostic options in prenatal testing, poses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. [Non-invasive ventilation].

    PubMed

    Gallardo Romero, Jose Manuel; García, Teresa Gómez; Sancho Chust, José Norberto; González Martínez, Mónica

    2010-10-01

    The advent of non-invasive mechanical ventilation (NIMV) has radically changed the management of acute and chronic respiratory failure. Over the last few years, the number of possible applications of NIMV has progressively increased, both in the hospital and extrahospital setting. NIMV is now used in all hospitals and resident physicians currently receive specific training -nonexistent until a few years ago- in this modality. It falls to all of us to push forward the clinical and scientific advances represented by the development of NIMV, by promoting the events that accompany better knowledge of the physiopathological bases of ventilation and of its continuous applications in daily clinical practice and by perfecting the elements required for the correct application of this technique. The present review aims to provide a broad overview of NIMV, from the most theoretical knowledge (the physiopathology of NIMV) to the most practical skills (recognition of patient-ventilator asynchrony). Through this progression from the complex to the most basic, or from the basics to the most complex, depending on the perspective taken, we aim to provide deeper knowledge of the concepts required to understand the technical functioning of the ventilator, describing its distinct modes and parameters and the abilities that must be developed for the correct indication, use and monitoring of the technique. We provide a final reflection on other forms of respiratory support that can be offered to patients with ventilatory failure. Copyright © 2010 Sociedad Española de Neumología y Cirugía Torácica. Published by Elsevier Espana. All rights reserved.

  17. Prenatal testing for hemolytic disease of the newborn and fetal neonatal alloimmune thrombocytopenia - current status.

    PubMed

    Avent, Neil D

    2014-12-01

    Incompatibility of red cell and platelet antigens can lead to maternal alloimmunization causing hemolytic disease of the fetus & newborn and fetal neonatal alloimmune thrombocytopenia respectively. As the molecular background of these polymorphisms emerged, prenatal testing using initially fetal DNA obtained from invasively obtained amniotic fluid or chorionic villus was implemented. This evolved into testing using maternal plasma as source of fetal DNA, and this is in routine use as a safe non-invasive diagnostic that has no risk to the fetus of alloimmunization or spontaneous miscarriage. These tests were initially applied to high risk pregnancies, but has been applied on a mass scale, to screen fetuses in D-negative pregnant populations as national screening programs. Fetal neonatal alloimmune thrombocytopenia management has had comparatively small take up in non-invasive testing for causative fetal platelet alleles (e.g., HPA-1A), but mass scale genotyping of mothers to identify at risk HPA-1b1b pregnancies and their treatment with prophylactic anti-HPA-1A is being considered in at least one country (Norway).

  18. Communicating risk in prenatal genetic testing.

    PubMed

    Gates, Elena A

    2004-01-01

    Prenatal testing for Down syndrome and neural tube defects has become routine, and testing for other genetic conditions is becoming commonplace. Counseling about these tests involves a discussion of risk information, so pregnant women and their partners can use the information effectively when they make choices about testing. Discussing risk can be challenging, as many individuals, particularly those of lower literacy, have a poor understanding of the numerical concept of risk. Furthermore, whether risk is comprehended accurately or not, it is interpreted by patients in light of their existing knowledge and past experiences. Strategies available to optimize understanding of risk include communication of risk figures as frequencies rather than as probabilities or percentages and explicit discussion of a woman's preconceptions about her risk and about the condition being tested for.

  19. Interest of non-invasive and semi-invasive testings in asymptomatic children with pre-excitation syndrome.

    PubMed

    Brembilla-Perrot, B; Chometon, F; Groben, L; Ammar, S; Bertrand, J; Marcha, C; Cloez, J L; Tisserand, A; Huttin, O; Tatar, C; Duhoux, F; Yangni N'da, O; Beurrier, D; Terrier de Chaise, A; Zhang, N; Abbas, M; Cedano, J; Marçon, F

    2007-09-01

    To determine the feasibility and the results of exercise testing (ET) and electrophysiological study (EPS) in outpatient asymptomatic children with a Wolff-Parkinson-White (WPW) syndrome. Exercise testing and transesophageal EPS were performed in 55 outpatient asymptomatic children aged 6 to 19 years old (14 +/- 3) with WPW. Wolff-Parkinson-White persisted during maximal exercise. Isoproterenol was not required in five children younger than 10 years old, because they developed a catecholaminergic sinus tachycardia. Maximal rate conducted through accessory pathway (AP) was higher in children younger than 16 years old than in teenagers (P < 0.05). Atrioventricular re-entrant tachycardia (AVRT) was induced in six children; atrial fibrillation (AF) in 12 children. The induction of tachycardias and the dangerous forms (18%) were not influenced by age. After 5 +/- 1 years, one child, 12 year old with inducible rapid AF, had a sudden cardiac arrest; two children became symptomatic after ablation. Transesophageal EPS was required to determine the prognosis of asymptomatic WPW in children. The maximal rate conducted in AP was higher in children younger than 16 years old than in teenagers; other data did not differ. AVRT was rare; 71% of children had no inducible arrhythmia and were authorized to resume physical activities.

  20. Design and testing of an MRI-compatible cycle ergometer for non-invasive cardiac assessments during exercise

    PubMed Central

    2012-01-01

    Background Magnetic resonance imaging (MRI) is an important tool for cardiac research, and it is frequently used for resting cardiac assessments. However, research into non-pharmacological stress cardiac evaluation is limited. Methods We aimed to design a portable and relatively inexpensive MRI cycle ergometer capable of continuously measuring pedalling workload while patients exercise to maintain target heart rates. Results We constructed and tested an MRI-compatible cycle ergometer for a 1.5 T MRI scanner. Resting and sub-maximal exercise images (at 110 beats per minute) were successfully obtained in 8 healthy adults. Conclusions The MRI-compatible cycle ergometer constructed by our research group enabled cardiac assessments at fixed heart rates, while continuously recording power output by directly measuring pedal force and crank rotation. PMID:22423637

  1. Concordance of non-invasive mechanical and serum tests for liver fibrosis evaluation in chronic hepatitis C

    PubMed Central

    Paranaguá-Vezozzo, Denise C; Andrade, Adriana; Mazo, Daniel F C; Nunes, Vinicius; Guedes, Ana L; Ragazzo, Taisa G; Moutinho, Renata; Nacif, Lucas S; Ono, Suzane K; Alves, Venâncio A F; Carrilho, Flair J

    2017-01-01

    AIM To determine the sensitivity and specificity of liver stiffness measurement (LSM) and serum markers (SM) for liver fibrosis evaluation in chronic hepatitis C. METHODS Between 2012 and 2014, 81 consecutive hepatitis C virus (HCV) patients had METAVIR score from liver biopsy compared with concurrent results from LSM [transient elastography (TE) [FibroScan®/ARFI technology (Virtual Touch®)] and SM [FIB-4/aspartate aminotransferase-to-platelet ratio index (APRI)]. The diagnostic performance of these tests was assessed using receiver operating characteristic curves. The optimal cut-off levels of each test were chosen to define fibrosis stages F ≥ 2, F ≥ 3 and F = 4. The Kappa index set the concordance analysis. RESULTS Fifty point six percent were female and the median age was 51 years (30-78). Fifty-six patients (70%) were treatment-naïve. The optimal cut-off values for predicting F ≥ 2 stage fibrosis assessed by TE were 6.6 kPa, for acoustic radiation force impulse (ARFI) 1.22 m/s, for APRI 0.75 and for FIB-4 1.47. For F ≥ 3 TE was 8.9 kPa, ARFI was 1.48 m/s, APRI was 0.75, and FIB-4 was 2. For F = 4, TE was 12.2 kPa, ARFI was 1.77 m/s, APRI was 1.46, and FIB-4 was 3.91. The APRI could not distinguish between F2 and F3, P = 0.92. The negative predictive value for F = 4 for TE and ARFI was 100%. Kappa index values for F ≥ 3 METAVIR score for TE, ARFI and FIB-4 were 0.687, 0.606 and 0.654, respectively. This demonstrates strong concordance between all three screening methods, and moderate to strong concordance between them and APRI (Kappa index = 0.507). CONCLUSION Given the costs and accessibility of LSM methods, and the similarity with the outcomes of SM, we suggest that FIB-4 as well as TE and ARFI may be useful indicators of the degree of liver fibrosis. This is of particular importance to developing countries. PMID:28357031

  2. Prognostic impact of coronary microcirculation abnormalities in systemic sclerosis: a prospective study to evaluate the role of non-invasive tests

    PubMed Central

    2013-01-01

    Introduction Microcirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome. Methods Forty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7- ± 3.5-year follow-up. Results Nineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r = -0.57, P <0.0001) was observed; in addition, CFR was significantly reduced (2.21 ± 0.38) in patients with WMA as compared to those without (2.94 ± 0.60) (P <0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7- ± 3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests. Conclusions A-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases. PMID:23302110

  3. The UroCuff test: a non-invasive alternative to pressure flow studies in adult males with lower urinary tract symptoms secondary to bladder outlet obstruction.

    PubMed

    Matulewicz, Richard S; Hairston, John C

    2015-08-01

    To assure that patients with lower urinary tract symptoms (LUTS) benefit from interventions, urologists must practice careful selection of surgical candidates. Currently, 15%-30% of men do not benefit optimally from these invasive and potentially morbid procedures. Success rates following transurethral resection of the prostate (TURP) are higher if bladder outlet obstruction (BOO) is confirmed prior to the procedure by invasive pressure flow studies (PFS). However, PFS may not be performed because of many reasons. We report a study of a non-invasive method of assessing BOO. The UroCuff test was compared to invasive urodynamic studies in adult males with lower urinary tract symptoms. Patients undergoing PFS for LUTS presumed to be due to BOO were recruited from a single site to perform a penile cuff test (UroCuff) at the same time as PFS. Standard PFS were performed followed immediately by a penile cuff test in the same test setting. The results were compared using basic statistical analysis. A total of 19 men were evaluated by both PFS and UroCuff evaluation. Using PFS as the gold standard, the positive predictive value of the UroCuff penile cuff test to diagnose BOO was found to be 92%. The sensitivity of the UroCuff test for detecting BOO was 75%. When compared to PFS, patients preferred the UroCuff 100% of the time. The UroCuff test is accurate in predicting BOO when compared to conventional invasive pressure flow studies in men with LUTS. It is well tolerated and preferred over invasive pressure flow studies.

  4. NSGC practice guideline: prenatal screening and diagnostic testing options for chromosome aneuploidy.

    PubMed

    Wilson, K L; Czerwinski, J L; Hoskovec, J M; Noblin, S J; Sullivan, C M; Harbison, A; Campion, M W; Devary, K; Devers, P; Singletary, C N

    2013-02-01

    The BUN and FASTER studies, two prospective multicenter trials in the United States, validated the accuracy and detection rates of first and second trimester screening previously reported abroad. These studies, coupled with the 2007 release of the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin that endorsed first trimester screening as an alternative to traditional second trimester multiple marker screening, led to an explosion of screening options available to pregnant women. ACOG also recommended that invasive diagnostic testing for chromosome aneuploidy be made available to all women regardless of maternal age. More recently, another option known as Non-invasive Prenatal Testing (NIPT) became available to screen for chromosome aneuploidy. While screening and testing options may be limited due to a variety of factors, healthcare providers need to be aware of the options in their area in order to provide their patients with accurate and reliable information. If not presented clearly, patients may feel overwhelmed at the number of choices available. The following guideline includes recommendations for healthcare providers regarding which screening or diagnostic test should be offered based on availability, insurance coverage, and timing of a patient's entry into prenatal care, as well as a triage assessment so that a general process can be adapted to unique situations.

  5. The non-invasive 13C-methionine breath test detects hepatic mitochondrial dysfunction as a marker of disease activity in non-alcoholic steatohepatitis

    PubMed Central

    2011-01-01

    Introduction Mitochondrial dysfunction plays a central role in the general pathogenesis of non-alcoholic fatty liver disease (NAFLD), increasing the risk of developing steatosis and subsequent hepatocellular inflammation. We aimed to assess hepatic mitochondrial function by a non-invasive 13C-methionine breath test (MeBT) in patients with histologically proven NAFLD. Methods 118 NAFLD-patients and 18 healthy controls were examined by MeBT. Liver biopsy specimens were evaluated according to the NASH scoring system. Results Higher grades of NASH activity and fibrosis were independently associated with a significant decrease in cumulative 13C-exhalation (expressed as cPDR(%)). cPDR1.5h was markedly declined in patients with NASH and NASH cirrhosis compared to patients with simple steatosis or borderline diagnosis (cPDR1.5h: 3.24 ± 1.12% and 1.32 ± 0.94% vs. 6.36 ± 0.56% and 4.80 ± 0.88% respectively; p < 0.001). 13C-exhalation further declined in the presence of advanced fibrosis which was correlated with NASH activity (r = 0.36). The area under the ROC curve (AUROC) for NASH diagnosis was estimated to be 0.87 in the total cohort and 0.83 in patients with no or mild fibrosis (F0-1). Conclusion The 13C-methionine breath test indicates mitochondrial dysfunction in non-alcoholic fatty liver disease and predicts higher stages of disease activity. It may, therefore, be a valuable diagnostic addition for longitudinal monitoring of hepatic (mitochondrial) function in non-alcoholic fatty liver disease. PMID:21810560

  6. Comparing four non-invasive methods to determine the ventilatory anaerobic threshold during cardiopulmonary exercise testing in children with congenital heart or lung disease.

    PubMed

    Visschers, Naomi C A; Hulzebos, Erik H; van Brussel, Marco; Takken, Tim

    2015-11-01

    The ventilatory anaerobic threshold (VAT) is an important method to assess the aerobic fitness in patients with cardiopulmonary disease. Several methods exist to determine the VAT; however, there is no consensus which of these methods is the most accurate. To compare four different non-invasive methods for the determination of the VAT via respiratory gas exchange analysis during a cardiopulmonary exercise test (CPET). A secondary objective is to determine the interobserver reliability of the VAT. CPET data of 30 children diagnosed with either cystic fibrosis (CF; N = 15) or with a surgically corrected dextro-transposition of the great arteries (asoTGA; N = 15) were included. No significant differences were found between conditions or among testers. The RER = 1 method differed the most compared to the other methods, showing significant higher results in all six variables. The PET-O2 method differed significantly on five of six and four of six exercise variables with the V-slope method and the VentEq method, respectively. The V-slope and the VentEq method differed significantly on one of six exercise variables. Ten of thirteen ICCs that were >0.80 had a 95% CI > 0.70. The RER = 1 method and the V-slope method had the highest number of significant ICCs and 95% CIs. The V-slope method, the ventilatory equivalent method and the PET-O2 method are comparable and reliable methods to determine the VAT during CPET in children with CF or asoTGA. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  7. Lactate is an ideal non-invasive marker for evaluating temporal alterations in cell stress and toxicity in repeat dose testing regimes.

    PubMed

    Limonciel, Alice; Aschauer, Lydia; Wilmes, Anja; Prajczer, Sinikka; Leonard, Martin O; Pfaller, Walter; Jennings, Paul

    2011-12-01

    Technological developments are driving in vitro methods towards integrated "omic" strategies. However, there is still an over reliance on classical viability assays for dose range finding. Such assays are not readily suited to the investigation of subtle alterations in cell function and most require termination of the experiment, which makes it difficult to monitor temporal alterations in repeat-dose long term exposure experiments. To this end, we investigated the use of lactate production as a marker of cell stress in long term repeat dose experiments. We conducted daily exposures to eight compounds at five concentrations for 14 days on human renal proximal tubular cells (RPTEC/TERT1), human hepatoma cells (HepaRG) and mouse fibroblasts (BALB-3T3) cells. Compounds were chosen from a training set used in the 7th EU Framework project Predict-IV and consisted of amiodarone, diclofenac, troglitazone, cadmium chloride, cephaloridine, cidofovir, cyclosporine A and buflomedil. At days 1, 3, 7 and 14, lactate was measured in the supernatant medium. At day 14, cells were assayed for resazurin reduction capability and subsequently lysed in methanol for ATP determination. Compound-induced loss of viability was comparable across all cell lines. For all cell types, when cell viability was compromised at day 14, lactate production was induced during the treatment period. In some situations, lactate also fell below control values, indicating cell death. Thus, temporal alterations in supernatant lactate provides information on the time and concentration of stress induction and the time and concentration where cell death becomes the dominant factor. Supernatant lactate production is a simple, cheap and non-invasive parameter. Since many molecular pathways converge on the glycolytic pathway, enhanced lactate production may be considered as a global marker of sub-lethal injury and thus an ideal marker for investigating temporal alterations in long term repeat dose testing in vitro

  8. 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

  9. The scale epithelium as a novel, non-invasive tool for environmental assessment in fish: Testing exposure to linear alkylbenzene sulfonate.

    PubMed

    Alves, R M S; Pereira, B F; Ribeiro, R G L G; Pitol, D L; Ciamarro, C M; Valim, J R T; Caetano, F H

    2016-07-01

    Increasing pollution levels have turned our attention to assessing lethal and sublethal effects of toxic agents using the most informative techniques possible. We must seek non-invasive or non-lethal sampling methods that represent an attractive alternative to traditional techniques of environmental assessment in fish. Detergents are amongst the most common contaminants of water bodies, and LAS (Linear Alkylbenzene Sulfonate) is one of the most used anionic surfactant on the market. Our study analyzed morphological alterations (histological and histochemical) of the scale epithelium of Prochilodus lineatus under exposure to two concentrations of LAS, 3.6mg/L and 0.36mg/L, for a period of 30 days and evaluated at 14, 21 and 30 days. In order to establish morphological analysis of the scale epithelium as a new non-lethal environmental assessment tool that is reliable and comparable to classic methods, the relative sensibility of this technique was compared to a commonly used method of environmental assessment in fish, the estimation of the effects of pollutants upon branchial morphology. Two experiments were carried out, testing animals in tanks, and in individual aquariums. Results of analyses on gill tissue show that exposure to 3.6mg/L of surfactant caused severe damage, including hyperplasia, hypertrophy and fusion at 14 days, with aneurisms at 21 and 30 days; while exposure to 0.36mg/L had lighter effects on the organ, mainly lower incidence of fusion and hyperplasia. Aditionally, scale morphology was altered severely in response to 3.6mg/L of LAS, consistently showing increased mucous and club cell production. Epithelial thickness was the most variable parameter measured. Scale epithelium sensibility has the potential to be a reliable environmental marker for fish species since it has the advantage of being less invasive when compared to traditional methods. However, more studies are required to increase the robustness of the technique before it can be

  10. Ambiguous genitalia: what prenatal genetic testing is practical?

    PubMed

    Adam, Margaret P; Fechner, Patricia Y; Ramsdell, Linda A; Badaru, Angela; Grady, Richard E; Pagon, Roberta A; McCauley, Elizabeth; Cheng, Edith Y; Parisi, Melissa A; Shnorhavorian, Margarett

    2012-06-01

    Concern for ambiguous genitalia or chromosome-phenotype discordance detected in a prenatal setting has increased over the last two decades. Practitioners faced with this prenatal finding have a variety of genetic tests available to them; however, it is unclear to what extent prenatal testing for disorders of sex development (DSD) is useful or practical. We undertook a retrospective review of the medical records of 140 individuals evaluated through the DSD clinic at Seattle Children's Hospital with birthdates from 01/01/1994 through 08/16/2011 to determine the rate of prenatal detection of ambiguous genitalia in individuals with DSD, what prenatal diagnostic workup was undertaken, and the postnatal outcome, including whether a postnatal genetic diagnosis was confirmed. Of all 140 subjects, 34 (24%) were identified prenatally. The most common postnatal diagnoses were penoscrotal hypospadias with transposition of the scrotum with no known genetic cause (24/140; 17%) and 21-hydroxylase deficiency (20/140; 14%). Apart from these, no single diagnosis comprised more than a few cases. Prenatal diagnostic testing varied widely, from no tests to multiple molecular tests with amniotic fluid hormone concentrations. In the absence of other fetal anomalies or growth retardation on ultrasound, prenatal karyotype with fluorescence in situ hybridization for the SRY gene is the most useful test when ambiguous genitalia is suspected. Further prenatal testing for Smith-Lemli-Opitz syndrome in 46,XY individuals and congenital adrenal hyperplasia in 46,XX individuals may be considered. However, targeted molecular testing for rare DSD conditions in the absence of a family history of DSD has a low yield. Copyright © 2012 Wiley Periodicals, Inc.

  11. Second-generation non-invasive high-throughput DNA sequencing technology in the screening of Down's syndrome in advanced maternal age women

    PubMed Central

    ZHANG, JIAO; ZHANG, BIN

    2016-01-01

    The aim of the present study was to evaluate the efficacy of using non-invasive DNA testing technology in screening Down's syndrome among women of advanced maternal age (AMA) and to provide evidence for prenatal screening of Down's syndrome. With a double-blind design, 8 ml of peripheral venous blood samples were collected from 87 women aged ≥35 years after 12 weeks of pregnancy. All cases were recorded with unique identification cards with clinical details and followed up until delivery. All the non-invasive prenatal testing results were confirmed by amniotic fluid fetal karyotyping (the gold standard of aneuploidy test), follow-up examination by neonatologists or neonatal blood karyotyping. The sensitivity, specificity and other indicators of non-invasive DNA testing technology were calculated based on the data of 87 women of AMA. Among the 87 women of AMA, 5 were cases with abnormal numbers of chromosomes (3 cases of trisomy 21, 1 case of trisomy 18 and 1 case of 47, XXX). The sensitivity and specificity reached 100% for trisomy 21, trisomy 18 and 47, XXX. The present study supports that non-invasive DNA testing is a useful method of AMA screening of Down's syndrome with 100% accuracy. Therefore, it can be used as an important alternative screening method for Down's syndrome in women of AMA. PMID:27313855

  12. A national perspective on prenatal testing for mitochondrial disease.

    PubMed

    Nesbitt, Victoria; Alston, Charlotte L; Blakely, Emma L; Fratter, Carl; Feeney, Catherine L; Poulton, Joanna; Brown, Garry K; Turnbull, Doug M; Taylor, Robert W; McFarland, Robert

    2014-11-01

    Mitochondrial diseases affect >1 in 7500 live births and may be due to mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Genetic counselling for families with mitochondrial diseases, especially those due to mtDNA mutations, provides unique and difficult challenges particularly in relation to disease transmission and prevention. We have experienced an increasing demand for prenatal diagnostic testing from families affected by mitochondrial disease since we first offered this service in 2007. We review the diagnostic records of the 62 prenatal samples (17 mtDNA and 45 nDNA) analysed since 2007, the reasons for testing, mutation investigated and the clinical outcome. Our findings indicate that prenatal testing for mitochondrial disease is reliable and informative for the nuclear and selected mtDNA mutations we have tested. Where available, the results of mtDNA heteroplasmy analyses from other family members are helpful in interpreting the prenatal mtDNA test result. This is particularly important when the mutation is rare or the mtDNA heteroplasmy is observed at intermediate levels. At least 11 cases of mitochondrial disease were prevented following prenatal testing, 3 of which were mtDNA disease. On the basis of our results, we believe that prenatal testing for mitochondrial disease is an important option for couples where appropriate genetic analyses and pre/post-test counselling can be provided.

  13. Prenatal and pre-implantation genetic diagnosis.

    PubMed

    Vermeesch, Joris Robert; Voet, Thierry; Devriendt, Koenraad

    2016-09-15

    The past decade has seen the development of technologies that have revolutionized prenatal genetic testing; that is, genetic testing from conception until birth. Genome-wide single-cell arrays and high-throughput sequencing analyses are dramatically increasing our ability to detect embryonic and fetal genetic lesions, and have substantially improved embryo selection for in vitro fertilization (IVF). Moreover, both invasive and non-invasive mutation scanning of the genome are helping to identify the genetic causes of prenatal developmental disorders. These advances are changing clinical practice and pose novel challenges for genetic counselling and prenatal care.

  14. Commercial landscape of noninvasive prenatal testing in the United States.

    PubMed

    Agarwal, Ashwin; Sayres, Lauren C; Cho, Mildred K; Cook-Deegan, Robert; Chandrasekharan, Subhashini

    2013-06-01

    Cell-free fetal DNA-based noninvasive prenatal testing (NIPT) could significantly change the paradigm of prenatal testing and screening. Intellectual property (IP) and commercialization promise to be important components of the emerging debate about clinical implementation of these technologies. We have assembled information about types of testing, prices, turnaround times, and reimbursement of recently launched commercial tests in the United States from the trade press, news articles, and scientific, legal, and business publications. We also describe the patenting and licensing landscape of technologies underlying these tests and ongoing patent litigation in the United States. Finally, we discuss how IP issues may affect clinical translation of NIPT and their potential implications for stakeholders. Fetal medicine professionals (clinicians and researchers), genetic counselors, insurers, regulators, test developers, and patients may be able to use this information to make informed decisions about clinical implementation of current and emerging noninvasive prenatal tests. © 2013 John Wiley & Sons, Ltd.

  15. Women's experiences receiving abnormal prenatal chromosomal microarray testing results.

    PubMed

    Bernhardt, Barbara A; Soucier, Danielle; Hanson, Karen; Savage, Melissa S; Jackson, Laird; Wapner, Ronald J

    2013-02-01

    Genomic microarrays can detect copy-number variants not detectable by conventional cytogenetics. This technology is diffusing rapidly into prenatal settings even though the clinical implications of many copy-number variants are currently unknown. We conducted a qualitative pilot study to explore the experiences of women receiving abnormal results from prenatal microarray testing performed in a research setting. Participants were a subset of women participating in a multicenter prospective study "Prenatal Cytogenetic Diagnosis by Array-based Copy Number Analysis." Telephone interviews were conducted with 23 women receiving abnormal prenatal microarray results. We found that five key elements dominated the experiences of women who had received abnormal prenatal microarray results: an offer too good to pass up, blindsided by the results, uncertainty and unquantifiable risks, need for support, and toxic knowledge. As prenatal microarray testing is increasingly used, uncertain findings will be common, resulting in greater need for careful pre- and posttest counseling, and more education of and resources for providers so they can adequately support the women who are undergoing testing.

  16. 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

  17. Non-invasive neural stimulation

    NASA Astrophysics Data System (ADS)

    Tyler, William J.; Sanguinetti, Joseph L.; Fini, Maria; Hool, Nicholas

    2017-05-01

    Neurotechnologies for non-invasively interfacing with neural circuits have been evolving from those capable of sensing neural activity to those capable of restoring and enhancing human brain function. Generally referred to as non-invasive neural stimulation (NINS) methods, these neuromodulation approaches rely on electrical, magnetic, photonic, and acoustic or ultrasonic energy to influence nervous system activity, brain function, and behavior. Evidence that has been surmounting for decades shows that advanced neural engineering of NINS technologies will indeed transform the way humans treat diseases, interact with information, communicate, and learn. The physics underlying the ability of various NINS methods to modulate nervous system activity can be quite different from one another depending on the energy modality used as we briefly discuss. For members of commercial and defense industry sectors that have not traditionally engaged in neuroscience research and development, the science, engineering and technology required to advance NINS methods beyond the state-of-the-art presents tremendous opportunities. Within the past few years alone there have been large increases in global investments made by federal agencies, foundations, private investors and multinational corporations to develop advanced applications of NINS technologies. Driven by these efforts NINS methods and devices have recently been introduced to mass markets via the consumer electronics industry. Further, NINS continues to be explored in a growing number of defense applications focused on enhancing human dimensions. The present paper provides a brief introduction to the field of non-invasive neural stimulation by highlighting some of the more common methods in use or under current development today.

  18. Considering medical risk information and communicating values: A mixed-method study of women's choice in prenatal testing.

    PubMed

    Chen, An; Tenhunen, Henni; Torkki, Paulus; Heinonen, Seppo; Lillrank, Paul; Stefanovic, Vedran

    2017-01-01

    Nowadays, an important decision for pregnant women is whether to undergo prenatal testing for aneuploidies and which tests to uptake. We investigate the factors influencing women's choices between non-invasive prenatal testing (NIPT) and invasive prenatal tests in pregnancies with elevated a priori risk of fetal aneuploidies. This is a mixed-method study. We used medical data (1st Jan 2015-31st Dec 2015) about women participating in further testing at Fetomaternal Medical Center at Helsinki University Hospital and employed Chi-square tests and ANOVA to compare the groups of women choosing different methods. Multinomial logistic regressions revealed the significant clinical factors influencing women's choice. We explored the underlying values, beliefs, attitudes and other psychosocial factors that affect women's choice by interviewing women with the Theory of Planned Behavior framework. The semi-structured interview data were processed by thematic analysis. Statistical data indicated that gestational age and counseling day were strong factors influencing women's choice. Interview data revealed that women's values and moral principles on pregnancy and childbirth chiefly determined the choices. Behavioral beliefs (e.g. safety and accuracy) and perceived choice control (e.g. easiness, rapidness and convenience) were also important and the major trade-offs happened between these constructs. Values are the determinants of women's choice. Service availability and convenience are strong factors. Medical risk status in this choice context is not highly influential. Choice aids can be developed by helping women to identify their leading values in prenatal testing and by providing lists of value-matching test options and attributes.

  19. Considering medical risk information and communicating values: A mixed-method study of women’s choice in prenatal testing

    PubMed Central

    Tenhunen, Henni; Torkki, Paulus; Heinonen, Seppo; Lillrank, Paul; Stefanovic, Vedran

    2017-01-01

    Introduction Nowadays, an important decision for pregnant women is whether to undergo prenatal testing for aneuploidies and which tests to uptake. We investigate the factors influencing women’s choices between non-invasive prenatal testing (NIPT) and invasive prenatal tests in pregnancies with elevated a priori risk of fetal aneuploidies. Methodology This is a mixed-method study. We used medical data (1st Jan 2015-31st Dec 2015) about women participating in further testing at Fetomaternal Medical Center at Helsinki University Hospital and employed Chi-square tests and ANOVA to compare the groups of women choosing different methods. Multinomial logistic regressions revealed the significant clinical factors influencing women’s choice. We explored the underlying values, beliefs, attitudes and other psychosocial factors that affect women’s choice by interviewing women with the Theory of Planned Behavior framework. The semi-structured interview data were processed by thematic analysis. Results Statistical data indicated that gestational age and counseling day were strong factors influencing women’s choice. Interview data revealed that women’s values and moral principles on pregnancy and childbirth chiefly determined the choices. Behavioral beliefs (e.g. safety and accuracy) and perceived choice control (e.g. easiness, rapidness and convenience) were also important and the major trade-offs happened between these constructs. Discussion Values are the determinants of women’s choice. Service availability and convenience are strong factors. Medical risk status in this choice context is not highly influential. Choice aids can be developed by helping women to identify their leading values in prenatal testing and by providing lists of value-matching test options and attributes. PMID:28355226

  20. Maternal Plasma DNA and RNA Sequencing for Prenatal Testing.

    PubMed

    Tamminga, Saskia; van Maarle, Merel; Henneman, Lidewij; Oudejans, Cees B M; Cornel, Martina C; Sistermans, Erik A

    2016-01-01

    Cell-free DNA (cfDNA) testing has recently become indispensable in diagnostic testing and screening. In the prenatal setting, this type of testing is often called noninvasive prenatal testing (NIPT). With a number of techniques, using either next-generation sequencing or single nucleotide polymorphism-based approaches, fetal cfDNA in maternal plasma can be analyzed to screen for rhesus D genotype, common chromosomal aneuploidies, and increasingly for testing other conditions, including monogenic disorders. With regard to screening for common aneuploidies, challenges arise when implementing NIPT in current prenatal settings. Depending on the method used (targeted or nontargeted), chromosomal anomalies other than trisomy 21, 18, or 13 can be detected, either of fetal or maternal origin, also referred to as unsolicited or incidental findings. For various biological reasons, there is a small chance of having either a false-positive or false-negative NIPT result, or no result, also referred to as a "no-call." Both pre- and posttest counseling for NIPT should include discussing potential discrepancies. Since NIPT remains a screening test, a positive NIPT result should be confirmed by invasive diagnostic testing (either by chorionic villus biopsy or by amniocentesis). As the scope of NIPT is widening, professional guidelines need to discuss the ethics of what to offer and how to offer. In this review, we discuss the current biochemical, clinical, and ethical challenges of cfDNA testing in the prenatal setting and its future perspectives including novel applications that target RNA instead of DNA.

  1. Analysis of theory utilization among prenatal HIV-testing research.

    PubMed

    Delissaint, Dieula; McKyer, E Lisako J

    2008-01-01

    To ascertain extent and quality of theory utilization among published empirical studies specific to prenatal HIV testing. Systematic literature search for peer-reviewed articles was performed. Articles with "perceived barriers" construct to prenatal HIV testing from perspective of potential testees were sought. Most studies mention constructs, but not specific theory. Few studies clearly reported how operationalized constructs were used within their studies. Paucity of theory utilization points to a breach of the "science" in the scientific process. Researchers either failed to adequately use theory or did so but failed to describe how.

  2. Non-invasive glucose monitor

    NASA Technical Reports Server (NTRS)

    Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)

    2001-01-01

    A non-invasive method for determining blood level of an analyte of interest, such as glucose, comprises: generating an excitation laser beam (e.g., at a wavelength of 700 to 900 nanometers); focusing the excitation laser beam into the anterior chamber of an eye of the subject so that aqueous humor in the anterior chamber is illuminated; detecting (preferably confocally detecting) a Raman spectrum from the illuminated aqueous humor; and then determining the blood glucose level (or the level of another analyte of interest) for the subject from the Raman spectrum. Preferably, the detecting step is followed by the step of subtracting a confounding fluorescence spectrum from the Raman spectrum to produce a difference spectrum; and determining the blood level of the analyte of interest for the subject from that difference spectrum, preferably using linear or nonlinear multivariate analysis such as partial least squares analysis. Apparatus for carrying out the foregoing method is also disclosed.

  3. Non-invasive Evaluation for Epilepsy Surgery

    PubMed Central

    IWASAKI, Masaki; JIN, Kazutaka; NAKASATO, Nobukazu; TOMINAGA, Teiji

    2016-01-01

    Epilepsy surgery is aimed to remove the brain tissues that are indispensable for generating patient’s epileptic seizures. There are two purposes in the pre-operative evaluation: localization of the epileptogenic zone and localization of function. Surgery is planned to remove possible epileptogenic zone while preserving functional area. Since no single diagnostic modality is superior to others in identifying and localizing the epileptogenic zone, multiple non-invasive evaluations are performed to estimate the location of the epileptogenic zone after concordance between evaluations. Essential components of non-invasive pre-surgical evaluation of epilepsy include detailed clinical history, long-term video-electroencephalography monitoring, epilepsy-protocol magnetic resonance imaging (MRI), and neuropsychological testing. However, a significant portion of drug-resistant epilepsy is associated with no or subtle MRI lesions or with ambiguous electro-clinical signs. Additional evaluations including fluoro-deoxy glucose positron emission tomography (FDG-PET), magnetoencephalography and ictal single photon emission computed tomography can play critical roles in planning surgery. FDG-PET should be registered on three-dimensional MRI for better detection of focal cortical dysplasia. All diagnostic tools are complementary to each other in defining the epileptogenic zone, so that it is always important to reassess the data based on other results to pick up or confirm subtle abnormalities. PMID:27627857

  4. Prenatal genetic testing kits sold at your local pharmacy: promoting autonomy or promoting confusion?

    PubMed

    Modra, Lucy

    2006-09-01

    Research groups around the world are developing non-invasive methods of prenatal genetic diagnosis, in which foetal cells are obtained by maternal blood test. Meanwhile, an increasing number of genetic tests are sold directly to the public. I extrapolate from these developments to consider a scenario in which PNGD self-testing kits are sold directly to the public. Given the opposition to over-the-counter genetic tests and the continuing controversy surrounding PNGD, it is reasonable to expect objections to PNGD self-testing kits. I focus on one potential objection, that PNGD self-testing kits would undermine the autonomy of potential test subjects. More specifically, that 'direct to the public' PNGD would fail to ensure that consumers exercise authority in the following PNGD-related choices: Should I use PNGD? Based on the results of the PNGD test, should I continue or terminate my pregnancy? Under the current system, PNGD is provided by health care practitioners, who are required to counsel women both before and after the test. In contrast, 'direct to the public' PNGD would allow women to make their PNGD-related decisions outside the context of the health care system. I compare these two decision-making contexts, arguing that the health care system is not unequivocally better at promoting the autonomy of potential test subjects. Therefore the promotion of autonomy does not constitute a strong argument against such test kits. Other objections may be more persuasive, so I do not offer an overall assessment of the acceptability of 'direct to the public' PNGD.

  5. Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-by-ligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells.

    PubMed

    Faas, Brigitte H W; de Ligt, Joep; Janssen, Irene; Eggink, Alex J; Wijnberger, Lia D E; van Vugt, John M G; Vissers, Lisenka; Geurts van Kessel, Ad

    2012-06-01

    Blood plasma of pregnant women contains circulating cell-free fetal DNA (ccffDNA), originating from the placenta. The use of this DNA for non-invasive detection of fetal aneuploidies using massively parallel sequencing (MPS)-by-synthesis has been proven previously. Sequence performance may, however, depend on the MPS platform and therefore we have explored the possibility for multiplex MPS-by-ligation, using the Applied Biosystems SOLiD(™) 4 system. DNA isolated from plasma samples from 52 pregnant women, carrying normal or aneuploid fetuses, was sequenced in multiplex runs of 4, 8 or 16 samples simultaneously. The sequence reads were mapped to the human reference genome and quantified according to their genomic location. In case of a fetal aneuploidy, the number of reads of the aberrant chromosome is expected to be higher or lower than in normal reference samples. To statistically determine this, Z-scores per chromosome were calculated as described previously, with thresholds for aneuploidies set at > +3.0 and < -3.0 for chromosomal over- or underrepresentation, respectively. All samples from fetal aneuploidies yielded Z-scores outside the thresholds for the aberrant chromosomes, with no false negative or positive results. Full-blown fetal aneuploidies can thus be reliably detected in maternal plasma using a multiplex MPS-by-ligation approach. Furthermore, the results obtained with a sample from a pregnancy with 45,X in the cytotrophoblastic cell layer and 46,XX in the mesenchymal core cells show that ccffDNA originates from the cytotrophoblastic cell layer. Discrepancies between the genetic constitution of this cell layer and the fetus itself are well known, and therefore, care should be taken when translating results to the fetus itself.

  6. Optimizing blood collection, transport and storage conditions for cell free DNA increases access to prenatal testing.

    PubMed

    Wong, David; Moturi, Sharmili; Angkachatchai, Vach; Mueller, Reinhold; DeSantis, Grace; van den Boom, Dirk; Ehrich, Mathias

    2013-08-01

    Fetal mutations and fetal chromosomal abnormalities can be detected by molecular analysis of circulating cell free fetal DNA (ccffDNA) from maternal plasma. This comprehensive study was aimed to investigate and verify blood collection and blood shipping conditions that enable Noninvasive Prenatal Testing. Specifically, the impact of shipping and storage on the stability and concentration of circulating cell-free DNA (ccfDNA) in Streck® Cell-Free DNA™ Blood Collection Tubes (Streck BCTs, Streck, Omaha NE). These BCTs were designed to minimize cellular degradation, and thus effectively prevent dilution of fetal ccf DNA by maternal genomic DNA, was evaluated. Peripheral venous maternal blood was collected into Streck BCTs to investigate four aspects of handling and processing conditions: (1) time from blood draw to plasma processing; (2) storage temperature; (3) mechanical stress; and (4) lot-to-lot tube variations. Maternal blood stored in Streck BCTs for up to 7 days at ambient temperature provides stable concentrations of ccffDNA. The amount of fetal DNA did not change over a broad range of storage temperatures (4°C, 23°C, 37°C, 40°C), but the amount of total (largely maternal) DNA increased in samples stored at 23°C and above, indicating maternal cell degradation and genomic DNA release at elevated temperatures. Shipping maternal blood in Streck BCTs, did not affect sample quality. Maternal plasma DNA stabilized for 0 to 7 days in Streck BCTs can be used for non-invasive prenatal molecular applications, when temperatures are maintained within the broad parameters assessed in this study. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  7. 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.

  8. Cell-Free Fetal DNA Testing for Prenatal Diagnosis.

    PubMed

    Drury, S; Hill, M; Chitty, L S

    Prenatal diagnosis and screening have undergone rapid development in recent years, with advances in molecular technology driving the change. Noninvasive prenatal testing (NIPT) for Down syndrome as a highly sensitive screening test is now available worldwide through the commercial sector with many countries moving toward implementation into their publically funded maternity systems. Noninvasive prenatal diagnosis (NIPD) can now be performed for definitive diagnosis of some recessive and X-linked conditions, rather than just paternally inherited dominant and de novo conditions. NIPD/T offers pregnant couples greater choice during their pregnancy as these safer methods avoid the risk of miscarriage associated with invasive testing. As the cost of sequencing falls and technology develops further, there may well be potential for whole exome and whole genome sequencing of the unborn fetus using cell-free DNA in the maternal plasma. How such assays can or should be implemented into the clinical setting remain an area of significant debate, but it is clear that the progress made to date for safer prenatal testing has been welcomed by expectant couples and their healthcare professionals. © 2016 Elsevier Inc. All rights reserved.

  9. Trends in Invasive Prenatal Diagnosis: Effect of Sequential Screening and Noninvasive Prenatal Testing.

    PubMed

    Khalifeh, Adeeb; Weiner, Stuart; Berghella, Vincenzo; Donnenfeld, Alan

    2016-01-01

    To examine trends in the incidence and method of invasive prenatal diagnosis due to the impact of sequential screening and noninvasive prenatal testing. This is a retrospective review of all pregnancies that have undergone invasive prenatal diagnostic testing between June 2002 and June 2014, divided in 3 periods: period 1 from June 2002 to October 2006, period 2 from November 2006 to December 2011, and period 3 from January 2012 to June 2014. The main outcome measures were trends in the incidence and method of each procedure. There were 88,135 deliveries and 6,080 invasive procedures during the study period. In period 1, 2,755 (8.8%) procedures were carried out, in period 2 2,820 (7.3%), and in period 3 505 (2.5%; p < 0.01). In period 1, there were 1,990 (6.3%) cases of amniocentesis, 1,646 (4.3%) in period 2, and 254 (1.2%) in period 3 (p < 0.01). In addition, in 765 (2.5%) cases, chorionic villus sampling (CVS) was performed in period 1, compared to 1,174 (3.0%) cases in period 2 and 251 (1.3%) cases in period 3 (p < 0.01). Advanced maternal age as the sole indication for invasive procedures decreased significantly over time, while the indication of abnormal serum screening and abnormal ultrasound findings increased (p < 0.01). There was a significant decline in the incidence of invasive prenatal testing over the 12 years of the study. The decrease in amniocentesis was more marked than that in CVS. © 2015 S. Karger AG, Basel.

  10. Preferences regarding contemporary prenatal genetic tests among women desiring testing: implications for optimal testing strategies.

    PubMed

    Kuppermann, Miriam; Norton, Mary E; Thao, Kao; O'Leary, Allison; Nseyo, Onouwem; Cortez, Abigail; Kaimal, Anjali J

    2016-05-01

    To compare utilities for prenatal testing outcomes among women inclined to continue their pregnancy despite abnormal results versus those inclined to terminate and to analyze how differences affect optimal prenatal testing strategies. Time tradeoff utilities for 23 outcomes were elicited from 281 women. We compared utilities based on termination inclination and applied them to a decision-analytic framework. Of participants, 46.6% indicated that they would 'definitely' or 'probably' continue their pregnancy despite results indicating an intellectual disability. These women assigned higher utilities to abnormal testing results and having a child with an intellectual disability than women who would probably or definitely terminate. Primary cell-free DNA screening had the most quality-adjusted life years for women inclined to continue their pregnancy but yielded an incremental cost-effectiveness ratio (ICER) of $1 685 449. Multiple marker screening with either cell-free DNA or diagnostic testing as follow-up had an ICER of $9037. Primary diagnostic testing resulted in the most quality-adjusted life years for women inclined to terminate, with an ICER of $111 776. Women seeking testing vary in prenatal testing outcome preferences and termination inclinations in the context of results indicating an intellectual disability. How they envision utilizing prenatal testing information impacts their optimal testing strategy. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  11. Non-Invasive Glucose Measurement

    NASA Astrophysics Data System (ADS)

    Blakley, Daniel

    2010-10-01

    There are two little words, when taken together have great implications: ``What IF'' In the US alone, there are millions who are burdened with diabetes and who must maintain their glucose levels by taking blood samples and having it analyzed. Even though this procedure has improved over time, still it is very intrusive and is a burden to many that must live with it. What if it were not necessary? Although it is current practice to measure glucose levels invasively (using blood samples), it may be possible to measure glucose non-invasively. Although several companies around the world have invested millions of dollars to address this problem, none have been successful thus far. However, there are many methods that hold a potential and many approaches that have not yet been explored. We are working on a review of what has been approached thus far and are entertaining proposals for a combined interdisciplinary approach which combines expertise from bioengineering, physics, and biology. We hope to learn from the unsuccessful attempts of others whilst employing innovative new approaches to this problem.

  12. Quality of prenatal care questionnaire: instrument development and testing

    PubMed Central

    2014-01-01

    Background Utilization indices exist to measure quantity of prenatal care, but currently there is no published instrument to assess quality of prenatal care. The purpose of this study was to develop and test a new instrument, the Quality of Prenatal Care Questionnaire (QPCQ). Methods Data for this instrument development study were collected in five Canadian cities. Items for the QPCQ were generated through interviews with 40 pregnant women and 40 health care providers and a review of prenatal care guidelines, followed by assessment of content validity and rating of importance of items. The preliminary 100-item QPCQ was administered to 422 postpartum women to conduct item reduction using exploratory factor analysis. The final 46-item version of the QPCQ was then administered to another 422 postpartum women to establish its construct validity, and internal consistency and test-retest reliability. Results Exploratory factor analysis reduced the QPCQ to 46 items, factored into 6 subscales, which subsequently were validated by confirmatory factor analysis. Construct validity was also demonstrated using a hypothesis testing approach; there was a significant positive association between women’s ratings of the quality of prenatal care and their satisfaction with care (r = 0.81). Convergent validity was demonstrated by a significant positive correlation (r = 0.63) between the “Support and Respect” subscale of the QPCQ and the “Respectfulness/Emotional Support” subscale of the Prenatal Interpersonal Processes of Care instrument. The overall QPCQ had acceptable internal consistency reliability (Cronbach’s alpha = 0.96), as did each of the subscales. The test-retest reliability result (Intra-class correlation coefficient = 0.88) indicated stability of the instrument on repeat administration approximately one week later. Temporal stability testing confirmed that women’s ratings of their quality of prenatal care did not change as a result of giving

  13. Non-invasive Assessment of Liver Fibrosis with ElastPQ: Comparison with Transient Elastography and Serologic Fibrosis Marker Tests, and Correlation with Liver Pathology Results.

    PubMed

    Lee, Jeong Eun; Shin, Kyung Sook; Cho, June-Sik; You, Sun Kyoung; Min, Ji Hye; Kim, Kyung-Hee; Song, In Sang; Cheon, Kwang Sik

    2017-11-01

    We investigated the feasibility of using ultrasound shear wave elastography point quantification (ElastPQ) for liver fibrosis staging and compared it with other non-invasive tools with respect to efficacy in liver stiffness measurement. A total of 106 patients who underwent liver stiffness measurements, using ElastPQ and biochemical investigations, before parenchymal liver biopsy or surgery were included. Among these, 51 also underwent transient elastography (TE). Correlations of ElastPQ, TE and aspartate aminotransferase-to-platelet ratio index (APRI) with histopathological findings (as the reference standard) were determined using Spearman's correlation coefficient. The diagnostic performance of ElastPQ, TE and APRI was evaluated using receiver operating characteristic (ROC) curve analysis. ElastPQ had good diagnostic accuracy in identifying each liver fibrosis stage, with an area under the ROC curve (AUC) of 0.810 to 0.864. Stiffness values obtained using ElastPQ, TE and APRI were significantly positively correlated (r = 0.686, r = 0.732 and r = 0.454, respectively) with histologic fibrosis staging (p < 0.001). According to the AUC for the diagnosis of significant fibrosis (≥F2) and cirrhosis (=F4), ElastPQ had better diagnostic accuracy (AUC = 0.929 and 0.834, respectively) than APRI (AUC = 0.656 and 0.618, respectively) (p < 0.05), and was similar to TE (AUC = 0.915 and 0.879, respectively). ElastPQ is a promising ultrasound-based imaging technique for evaluation of liver fibrosis, with a diagnostic accuracy comparable to that of TE. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  14. Women's uptake of non-invasive DNA testing following a high-risk screening test for trisomy 21 within a publicly funded healthcare system: findings from a retrospective review.

    PubMed

    Chan, Yiu Man; Leung, Wing Cheong; Chan, Wan Pang; Leung, Tak Yeung; Cheng, Yvonne Kwun Yue; Sahota, Daljit Singh

    2015-04-01

    The objective of the study was to evaluate the uptake of non-invasive cell-free fetal DNA screening test (NIDT) after a high-risk screening result for trisomy 21 METHODS: Association between maternal and pregnancy characteristics on women's test choice was assessed after adjusting for confounding factors in Hong Kong Chinese women who had a high-risk (term risk ≥1:250) first-trimester or second-trimester screening test at three public hospitals. Main outcome measures were rate of declining further testing and obstetric and maternal factors impacting on patient's selection of testing options. Compared with the pre-NIDT period, the availability of NIDT resulted in a 45% (P < 0.001) reduction in the rate of refusal for further testing and a decrease from 92.2% to 66.7% in the use of invasive diagnostic test after a positive screening test. Nulliparous women with a spontaneous [adjusted odds ratio (aOR) = 2.18, 95% confidence interval (CI) 1.63-2.92] or assisted reproduction pregnancy (aOR = 3.95, 95% CI 1.6-9.32) were more likely to choose NIDT. Women with an adjusted risk of '>1:10' (aOR = 7.36, 95% CI 4.22-12.8) and '1:10 to 1:50' (aOR = 1.53, 95% CI 1.01-2.32) were more likely to opt for chorionic villi sampling or amniocentesis. NIDT reduced the refusal rate. Uptake of NIDT was highest in pregnancies of nulliparous women. © 2014 John Wiley & Sons, Ltd.

  15. Diagnostic performance and comparative cost-effectiveness of non-invasive imaging tests in patients presenting with chronic stable chest pain with suspected coronary artery disease: a systematic overview.

    PubMed

    van Waardhuizen, Claudia N; Langhout, Marieke; Ly, Felisia; Braun, Loes; Genders, Tessa S S; Petersen, Steffen E; Fleischmann, Kirsten E; Nieman, Koen; Hunink, M G Myriam

    2014-01-01

    Several non-invasive imaging techniques are currently in use for the diagnostic workup of adult patients with stable chest pain suspected of having coronary artery disease (CAD). In this paper, we present a systematic overview of the evidence on diagnostic performance and comparative cost-effectiveness of new modalities in comparison to established technologies. A literature search for English language studies from 2009 to 2013 was performed, and two investigators independently extracted data on patient and study characteristics. The reviewed published evidence on diagnostic performance and cost-effectiveness support a strategy of CTCA as a rule out (gatekeeper) test of CAD in low- to intermediate-risk patients since it has excellent diagnostic performance and as initial imaging test is cost-effective under different willingness-to-pay thresholds. More cost-effectiveness research is needed in order to define the role and choice of cardiac stress imaging tests.

  16. Prenatal testing in Huntington disease: after the test, choices recommence.

    PubMed

    Bouchghoul, Hanane; Clément, Stéphane-Françoise; Vauthier, Danièle; Cazeneuve, Cécile; Noel, Sandrine; Dommergues, Marc; Héron, Delphine; Nizard, Jacky; Gargiulo, Marcela; Durr, Alexandra

    2016-11-01

    The objective of this study was (1) to determine the impact of prenatal diagnosis (PND) for Huntington disease (HD) on subsequent reproductive choices and family structure; and (2) to assess whether children born after PND were informed of their genetic status. Out of 354 presymptomatic carriers of HD gene mutation, aged 18-45 years, 61 couples requested 101 PNDs. Fifty-four women, 29 female carriers and 25 spouses of male carriers, accepted to be interviewed (0.6-16.3 years after the last PND, median 6.5 years) on their obstetrical history and information given to children born after PND. Women were willing to undergo two or more PNDs with a final success rate of 75%. Reproductive decisions differed depending on the outcome of the first PND. If favourable, 62% couples decided against another pregnancy and 10% chose to have an untested child. If unfavourable, 83% decided for another pregnancy (P<0.01), and the majority (87%) re-entered the PND procedure. In contrast, after a second PND, only 37% asked for a PND and 30% chose to have an untested child. Thirty-three percent had both, tested and untested children. Among children born after PND, 10 years and older, 75% were informed of their genetic status. The decision to prevent transmission of the HD mutation is made anew with each pregnancy. Couples may need more psychological support after PND and pre-counselling sessions should take into account the effect of the outcome of a first PND on subsequent reproductive choices.

  17. Prenatal Testing: Is It Right for You?

    MedlinePlus

    ... back of a baby's neck (nuchal translucency). In Down syndrome and in certain other conditions, the nuchal translucency ... baby who has certain chromosomal conditions, such as Down syndrome. The test can also help detect neural tube ...

  18. Prenatal Testing - Multiple Languages: MedlinePlus

    MedlinePlus

    ... sharing features on this page, please enable JavaScript. Arabic (العربية) Chinese - Simplified (简体中文) Chinese - Traditional (繁體中文) French ( ... Soomaali) Spanish (español) Ukrainian (Українська) Vietnamese (Tiếng Việt) Arabic (العربية) Non-Stress Test in Pregnancy (Arabic) اختبار ...

  19. Non-invasive sensing for food reassurance.

    PubMed

    Xiaobo, Zou; Xiaowei, Huang; Povey, Malcolm

    2016-03-07

    Consumers and governments are increasingly interested in the safety, authenticity and quality of food commodities. This has driven attention towards non-invasive sensing techniques used for rapid analyzing these commodities. This paper provides an overview of the state of the art in, and available alternatives for, food assurance based on non-invasive sensing techniques. The main food quality traits of interest using non-invasive sensing techniques are sensory characteristics, chemical composition, physicochemical properties, health-protecting properties, nutritional characteristics and safety. A wide range of non-invasive sensing techniques, from optical, acoustical, electrical, to nuclear magnetic, X-ray, biosensor, microwave and terahertz, are organized according to physical principle. Some of these techniques are now in a period of transition between experimental and applied utilization and several sensors and instruments are reviewed. With continued innovation and attention to key challenges, such non-invasive sensors and biosensors are expected to open up new exciting avenues in the field of portable and wearable wireless sensing devices and connecting with mobile networks, thus finding considerable use in a wide range of food assurance applications. The need for an appropriate regulatory framework is emphasized which acts to exclude unwanted components in foods and includes needed components, with sensors as part of a reassurance framework supporting regulation and food chain management. The integration of these sensor modalities into a single technological and commercial platform offers an opportunity for a paradigm shift in food reassurance.

  20. Non-Invasive Pneumothorax Detector

    DTIC Science & Technology

    2010-08-01

    Transfer: The design was completed and transferred into an ISO 13485 certified manufacturing facility. A production run was completed for the...Initiated Military Testing for Air Worthiness Evaluation 6. Completed EN60601 Testing for ISO Certification and CE MARK 7. Initiated discussions

  1. (13)C isotopic abundances in natural nutrients: a newly formulated test meal for non-invasive diagnosis of type 2 diabetes.

    PubMed

    Ghosh, Chiranjit; Mandal, Santanu; Pal, Mithun; Mukhopadhyay, Prabuddha; Ghosh, Shibendu; Pradhan, Manik

    2017-06-01

    A new method to replace commercially prepared (13)C-labelled glucose with naturally available (13)C-enriched substrates could result in promotion of the clinical applicability of the isotopic breath test for detection of type 2 diabetes (T2D). Variation of the carbon-13 isotope in human breath depends on the (13)C enrichment in the diet taken by subjects. Here, we formulated a new test meal comprising naturally available (13)C-enriched foods and subsequently administered it to non-diabetic control (NDC) subjects and those with T2D. We found that the new test meal-derived (13)C enrichment of breath CO2 was significantly lower in T2D compared with NDC. Furthermore, from our observations T2D exhibited higher isotopic enrichment of oxygen-18 ((18)O) in breath CO2 compared with NDC following ingestion of the new meal. We determined the optimal diagnostic cut-off values of (13)C (i.e. δ (13)C‰ = 7.5‰) and (18)O (i.e. δ (18)O‰ = 3.5‰) isotopes in breath CO2 for precise classification of T2D and NDC. Our new method involving the administration of naturally (13)C-abundant nutrients showed a typical diagnostic sensitivity and specificity of about 95%, suggesting a valid and potentially robust global method devoid of any synthetically manufactured commercial (13)C-enriched glucose which thus may serve as an alternative diagnostic tool for routine clinical applications.

  2. Effects of straight alkyl chain, extra hydroxylated alkyl chain and branched chain amino acids on gastric emptying evaluated using a non-invasive breath test in conscious rats

    PubMed Central

    Uchida, Masayuki; Kobayashi, Orie; Iwasawa, Kaori; Shimizu, Kimiko

    2016-01-01

    Aim: Some amino acids been known to influence gastric emptying. Thus we have evaluated the effects of straight alkyl chain, extra hydroxylated alkyl chain and branched chain amino acids on gastric emptying. Materials and Methods: Gastric emptying was evaluated in rats after feeding with Racol (nutrient formulae) containing [1-13C] acetic acid. Using a breath test, the content of 13CO2 in their expired air was measured by infrared analyzers. Rats were orally administered with test amino acids, while control rats were administered orally with distilled water. Results: The expired 13CO2 content in the expired air increased with time, peaked after about 30 min and decreased thereafter. Among the amino acids having an alkyl chain, l-serine, l-alanine and l-glycine, significantly decreased the 13CO2 content and Cmax, and delayed Tmax, suggesting inhibition and delay of gastric emptying. AUC120 min values of l-alanine and l-glycine also decreased significantly. l-Threonine significantly decreased 13CO2 content and delayed Tmax, but had no influence on Cmax and AUC120 min values, suggesting a delay of gastric emptying. l-Isoleucine and l-leucine and l-valine significantly decreased 13CO2 content, suggesting inhibition of the gastric emptying, but Cmax, Tmax and AUC120 min values were not significantly affected. Conclusion: The results show that the amino acids used in the present study had different effects on gastric emptying. Moreover, it was found that inhibition and delay of gastric emptying were clearly classifiable by analyzing the change in 13CO2 content of the expired air and the Cmax, Tmax and AUC120 min values. PMID:27169776

  3. Attitudes among Danes toward prenatal testing and termination of pregnancy.

    PubMed

    Uldall, Sigurd W; Norup, Michael S

    2013-02-01

    Denmark offers public financed prenatal testing (PNT) to all pregnant women, but results are typically not available until after 12 weeks gestation, which is also the time limit for termination of pregnancy (TOP) on request. Committees decide on requests for later TOP. In a questionnaire survey, we investigated attitudes among Danes toward these issues. We also asked for opinions on two claims commonly found in the debate concerning women's right to decide on TOP in relation to PNT. One thousand people aged 18-45 years were drawn randomly from the national personal register. The response rate was 49%. Women and older respondents were overrepresented and may have caused a bias toward conservative attitudes. A majority supported the current PNT program and time limit for TOP on request, but only one-third supported committees deciding on all cases of late TOP. The implications of prenatal testing results becoming more accessible are discussed. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

  4. Intestinal permeability in Hymenolepis nana as reflected by non invasive lactulose/mannitol dual permeability test and its impaction on nutritional parameters of patients.

    PubMed

    Mohammad, Mahmoud A; Hegazi, Mai A

    2007-12-01

    Assessment of Hymenolepis nana infection among 102 children and adults of both sexes (5-16 years) residing 2 Welfare Institutes (Giza and Cairo) showed a prevalence of 22.33%. The effect of H. nana on intestinal permeability and on nutritional parameters of patients was studied. A total of 46 subjects were divided into 2 groups: GI (20 H. nana patients) and GII (26 parasite-free control). Both groups were subjected to lactulose/mannitol dual permeability test, anthropometric study, estimation of vitamin B12 and folate levels in plasma and estimation of haemoglobin (HB)%, RBCs and WBCs counts and haematocrite value (HCT%) for anaemia. The H. nana patients showed significant higher percent (P = 0.04) of altered intestinal permeability versus controls denoting intestinal leakage, significant means lower levels of vitamin B12 (P = 0.01) and folate (P < 0.04) in blood plasma versus control denoting liability to vitamin B12 & folate deficiencies. Means value of HB%, RBC & WBC counts and HCT% showed generalized decrease but without significant difference in H. nana patients and control denoting anaemia liability. The percent of stunting (HAZ < or =2) and of wasting (WAZ < or =2) were higher among H. nana patients versus controls but without significant difference (P = 0.19 & P = 0.47 respectively).

  5. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    PubMed

    Sumida, Yoshio; Nakajima, Atsushi; Itoh, Yoshito

    2014-01-14

    It is estimated that 30% of the adult population in Japan is affected by nonalcoholic fatty liver disease (NAFLD). Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography (US) and computed tomography (CT), but the sensitivity of these imaging techniques is low in cases of mild steatosis. Alanine aminotransferase levels may be normal in some of these patients, warranting the necessity to establish a set of parameters useful for detecting NAFLD, and the more severe form of the disease, nonalcoholic steatohepatitis (NASH). Although liver biopsy is currently the gold standard for diagnosing progressive NASH, it has many drawbacks, such as sampling error, cost, and risk of complications. Furthermore, it is not realistic to perform liver biopsies on all NAFLD patients. Diagnosis of NASH using various biomarkers, scoring systems and imaging methods, such as elastography, has recently been attempted. The NAFIC score, calculated from the levels of ferritin, fasting insulin, and type IV collagen 7S, is useful for the diagnosis of NASH, while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis. This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH.

  6. Prenatal Screening Methods for Aneuploidies

    PubMed Central

    Dey, Madhusudan; Sharma, Sumedha; Aggarwal, Sumita

    2013-01-01

    Aneuploidies are a major cause of perinatal morbidity and mortality. Therefore, it is the most common indication for invasive prenatal diagnosis. Initially, screening for aneuploidies started with maternal age risk estimation. Later on, serum testing for biochemical markers and ultrasound markers were added. Women detected to be at high-risk for aneuploidies were offered invasive testing. New research is now focusing on non-invasive prenatal testing using cell-free fetal DNA in maternal circulation. The advantage of this technique is the ability to reduce the risk of miscarriage associated with invasive diagnostic procedures. However, this new technique has its own set of technical limitations and ethical issues at present and careful consideration is required before broad implementation PMID:23626953

  7. Non-invasive monitoring of spreading depression.

    PubMed

    Bastany, Zoya J R; Askari, Shahbaz; Dumont, Guy A; Speckmann, Erwin-Josef; Gorji, Ali

    2016-10-01

    Spreading depression (SD), a slow propagating depolarization wave, plays an important role in pathophysiology of different neurological disorders. Yet, research into SD-related disorders has been hampered by the lack of non-invasive recording techniques of SD. Here we compared the manifestations of SD in continuous non-invasive electroencephalogram (EEG) recordings to invasive electrocorticographic (ECoG) recordings in order to obtain further insights into generator structures and electrogenic mechanisms of surface recording of SD. SD was induced by KCl application and simultaneous SD recordings were performed by scalp EEG as well as ECoG electrodes of somatosensory neocortex of rats using a novel homemade EEG amplifier, AgCl recording electrodes, and high chloride conductive gel. Different methods were used to analyze the data; including the spectrogram, bi-spectrogram, pattern distribution, relative spectrum power, and multivariable Gaussian fit analysis. The negative direct current (DC) shifts recorded by scalp electrodes exhibited a high homogeneity to those recorded by ECoG electrodes. Furthermore, this novel method of recording and analysis was able to separate SD recorded by scalp electrodes from non-neuronal DC shifts induced by other potential generators, such as the skin, muscles, arteries, dura, etc. These data suggest a novel application for continuous non-invasive monitoring of DC potential changes, such as SD. Non-invasive monitoring of SD would allow early intervention and improve outcome in SD-related neurological disorders. Copyright © 2016 IBRO. All rights reserved.

  8. Non invasive assessment of the human tear film dynamics.

    PubMed

    Ring, M H; Rabensteiner, D F; Horwath-Winter, J; Boldin, I; Schrödl, F; Reitsamer, H; Haslwanter, T

    2015-11-01

    Dry eye disease, or keratoconjunctivitis sicca, is a multifactorial syndrome with altered tear film homeostasis leading to ocular irritations. These alterations cause discomfort and stress for the patient, but only a few objective parameters allow for proper differential diagnosis into different subtypes of this condition. The mostly invasively performed standard assessment procedures for tear film diagnosis are manifold, but often correlate quite poorly with the subjectively reported symptoms. Due to the inherent limitations, e.g. the subjectivity of the commonly performed invasive tests, a number of devices have been developed to assess the human tear film non-invasively. Since the production, delivery, distribution and drainage of the tear film is a dynamic process, we have focused our review on non-invasive methods which are capable of continuous or repetitive observations of the tear film during an inter-blink interval. These dynamic methods include (1) Interferometry, (2) Pattern Projection, (3) Aberrometry, (4) Thermography; and (5) Evaporimetry. These techniques are discussed with respect to their diagnostic value, both for screening and differential diagnostic of Dry Eye Disease. Many of the parameters obtained from these tests have been shown to have the potential to reliably discriminate patients from healthy subjects, especially when the tests are performed automatically and objectively. The differentiation into subtypes based solely on a single, dynamic parameter may not be feasible, but the combination of non-invasively performed procedures may provide good discrimination results.

  9. 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.

  10. Fetal DNA in maternal plasma: application to non-invasive blood group genotyping of the fetus.

    PubMed

    Lo, Y M

    2001-06-01

    The non-invasive determination of fetal genetic characteristics, including blood group types, is a long-sought goal of modern genetics. Previous work on the use of fetal cells in maternal blood has been hampered by the rarity of such cells. The recent discovery of cell-tree fetal DNA in maternal blood has opened up new possibilities for non-invasive prenatal diagnosis. It is particularly useful that fetal DNA is present in relatively high concentrations in maternal plasma, making its robust detection possible using modern technology. Large-scale clinical trials and standardization of protocols still need to be carried out. However, there is optimism that the accurate and safe prenatal determination of fetal blood group types may be achieved in routine clinical practice in the near future.

  11. Karyotype analysis with amniotic fluid in 12365 pregnant women with indications for genetic amniocentesis and strategies of prenatal diagnosis.

    PubMed

    Xiao, H; Yang, Y L; Zhang, C Y; Liao, E J; Zhao, H R; Liao, S X

    2016-01-01

    We explored the strategies of prenatal diagnosis by foetal karyotype analysis in pregnant women with indications for genetic amniocentesis. Karyotype analysis of amniotic fluid was performed on 12365 pregnant women with indications for genetic amniocentesis. The detection rates and distributions of abnormal karyotypes were observed in a variety of indications for genetic amniocentesis. The detection rates of abnormal karyotype were 57.4% in either a mother or father with chromosomal abnormality, 8.5% in the pregnant women with pathological ultrasound finding (PUF), 2.79% in the pregnant women with advanced age (35 years and over) and 2.23% in the women with abnormal maternal serum screening (MSS) tests. Foetal abnormal karyotype was found in 86 pregnant women with PUF; of the 86 pregnant women, 42 had trisomy 13, 18 or 21. Of the 12365 pregnant women, foetal abnormal karyotype was found in 428 (3.46%); of the 428 foetuses, only 154 had trisomy 13, 18 or 21. In the pregnant women with abnormal MSS, 111 foetuses had abnormal karyotype, but only 36 foetuses had trisomy 13, 18 or 21. We conclude that (1) ultrasound is an important approach to prevent the birth of foetuses with chromosomal disease. (2) Non-invasive prenatal DNA detection cannot completely replace invasive prenatal diagnosis and MSS. (3) The strategies of prenatal diagnosis: Genetic amniocentesis is strongly recommended for the pregnant women with indications for genetic amniocentesis. For pregnant women who refuse invasive prenatal diagnosis, non-invasive prenatal DNA detection is first performed. If the results of non-invasive prenatal DNA detection are negative, the pregnant women are followed up by ultrasound; if the results of non-invasive prenatal DNA detection are positive, the pregnant women should undergo invasive prenatal diagnosis.

  12. Assessment of an Interactive Computer-Based Patient Prenatal Genetic Screening and Testing Education Tool

    ERIC Educational Resources Information Center

    Griffith, Jennifer M.; Sorenson, James R.; Bowling, J. Michael; Jennings-Grant, Tracey

    2005-01-01

    The Enhancing Patient Prenatal Education study tested the feasibility and educational impact of an interactive program for patient prenatal genetic screening and testing education. Patients at two private practices and one public health clinic participated (N = 207). The program collected knowledge and measures of anxiety before and after use of…

  13. Invasive and non-invasive assessment of portal hypertension.

    PubMed

    Leung, Jonathan Chung-Fai; Loong, Thomson Chi-Wang; Pang, James; Wei, Jeremy Lok; Wong, Vincent Wai-Sun

    2017-03-30

    Portal hypertension is the central driver of complications in patients with chronic liver diseases and cirrhosis. The diagnosis of portal hypertension has important prognostic and clinical implications. In particular, screening for varices in patients with portal hypertension can effectively reduce the morbidity and mortality of variceal bleeding. In this article, we review the invasive and non-invasive methods to assess portal hypertension. Hepatic venous pressure gradient remains the gold standard to measure portal pressure but is invasive and seldom performed outside expert centers and research settings. In recent years, a number of non-invasive tests of fibrosis have shown good correlation with liver histology. They also show promise in identifying patients with portal hypertension and large varices. As a result, the latest Baveno VI consensus guidelines endorse the use of liver stiffness measurement by transient elastography and platelet count as initial assessment to select patients for varices screening. On the other hand, the performance of non-invasive tests in assessing the response to non-selective beta-blockers or transjugular intrahepatic portosystemic shunting is either suboptimal or unclear.

  14. The VITRO Score (Von Willebrand Factor Antigen/Thrombocyte Ratio) as a New Marker for Clinically Significant Portal Hypertension in Comparison to Other Non-Invasive Parameters of Fibrosis Including ELF Test

    PubMed Central

    Hametner, Stephanie; Ferlitsch, Arnulf; Ferlitsch, Monika; Etschmaier, Alexandra; Schöfl, Rainer; Ziachehabi, Alexander; Maieron, Andreas

    2016-01-01

    Background Clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) ≥10 mmHg, causes major complications. HVPG is not always available, so a non-invasive tool to diagnose CSPH would be useful. VWF-Ag can be used to diagnose. Using the VITRO score (the VWF-Ag/platelet ratio) instead of VWF-Ag itself improves the diagnostic accuracy of detecting cirrhosis/ fibrosis in HCV patients. Aim This study tested the diagnostic accuracy of VITRO score detecting CSPH compared to HVPG measurement. Methods All patients underwent HVPG testing and were categorised as CSPH or no CSPH. The following patient data were determined: CPS, D’Amico stage, VITRO score, APRI and transient elastography (TE). Results The analysis included 236 patients; 170 (72%) were male, and the median age was 57.9 (35.2–76.3; 95% CI). Disease aetiology included ALD (39.4%), HCV (23.4%), NASH (12.3%), other (8.1%) and unknown (11.9%). The CPS showed 140 patients (59.3%) with CPS A; 56 (23.7%) with CPS B; and 18 (7.6%) with CPS C. 136 patients (57.6%) had compensated and 100 (42.4%) had decompensated cirrhosis; 83.9% had HVPG ≥10 mmHg. The VWF-Ag and the VITRO score increased significantly with worsening HVPG categories (P<0.0001). ROC analysis was performed for the detection of CSPH and showed AUC values of 0.92 for TE, 0.86 for VITRO score, 0.79 for VWF-Ag, 0.68 for ELF and 0.62 for APRI. Conclusion The VITRO score is an easy way to diagnose CSPH independently of CPS in routine clinical work and may improve the management of patients with cirrhosis. PMID:26895398

  15. Non-invasive diagnosis of advanced fibrosis and cirrhosis.

    PubMed

    Sharma, Suraj; Khalili, Korosh; Nguyen, Geoffrey Christopher

    2014-12-07

    Liver cirrhosis is a common and growing public health problem globally. The diagnosis of cirrhosis portends an increased risk of morbidity and mortality. Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis. However, despite its universal use, liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks. In order to overcome the limitations of liver biopsy, a number of non-invasive techniques have been investigated for the assessment of cirrhosis. This review will focus on currently available non-invasive markers of cirrhosis. The evidence behind the use of these markers will be highlighted, along with an assessment of diagnostic accuracy and performance characteristics of each test. Non-invasive markers of cirrhosis can be radiologic or serum-based. Radiologic techniques based on ultrasound, magnetic resonance imaging and elastography have been used to assess liver fibrosis. Serum-based biomarkers of cirrhosis have also been developed. These are broadly classified into indirect and direct markers. Indirect biomarkers reflect liver function, which may decline with the onset of cirrhosis. Direct biomarkers, reflect extracellular matrix turnover, and include molecules involved in hepatic fibrogenesis. On the whole, radiologic and serum markers of fibrosis correlate well with biopsy scores, especially when excluding cirrhosis or excluding fibrosis. This feature is certainly clinically useful, and avoids liver biopsy in many cases.

  16. [Non-invasive assessment of liver fibrosis].

    PubMed

    Cohen-Ezra, Oranit; Ben-Ari, Ziv

    2015-03-01

    Chronic liver diseases represent a major public health problem, accounting for significant morbidity and mortality worldwide. Prognosis and management of chronic liver diseases depend on the amount of liver fibrosis. Liver biopsy has long remained the gold standard for assessment of liver fibrosis. Liver biopsy is an invasive procedure with associated morbidity, it is rarely the cause for mortality, and has a few limitations. During the past two decades, in an attempt to overcome the limitations of liver biopsy, non-invasive methods for the evaluation of liver fibrosis have been developed, mainly in the field of viral hepatitis. This review will focus on different methods available for non-invasive evaluation of liver fibrosis including a biological approach which quantifies serum levels of biomarkers of fibrosis and physical techniques which measure liver stiffness by transient elastography, ultrasound or magnetic resonance based elastography, their accuracy, advantages and disadvantages.

  17. Ultrasonic non invasive techniques for microbiological instrumentation

    NASA Astrophysics Data System (ADS)

    Elvira, L.; Sierra, C.; Galán, B.; Resa, P.

    2010-01-01

    Non invasive techniques based on ultrasounds have advantageous features to study, characterize and monitor microbiological and enzymatic reactions. These processes may change the sound speed, viscosity or particle distribution size of the medium where they take place, which makes possible their analysis using ultrasonic techniques. In this work, two different systems for the analysis of microbiological liquid media based on ultrasounds are presented. In first place, an industrial application based on an ultrasonic monitoring technique for microbiological growth detection in milk is shown. Such a system may improve the quality control strategies in food production factories, being able to decrease the time required to detect possible contaminations in packed products. Secondly, a study about the growing of the Escherichia coli DH5 α in different conditions is presented. It is shown that the use of ultrasonic non invasive characterization techniques in combination with other conventional measurements like optical density provides complementary information about the metabolism of these bacteria.

  18. Prenatal Testing for Intellectual Disability: Misperceptions and Reality with Lessons from down Syndrome

    ERIC Educational Resources Information Center

    Acharya, Kruti

    2011-01-01

    Down syndrome is the most common cause of intellectual disability. In the United States, it is recommended that prenatal testing for Down syndrome be offered to all women. Because of this policy and consequent public perception, having Down syndrome has become a disadvantage in the prenatal period. However, in the postnatal period, there may be…

  19. Prenatal Testing for Intellectual Disability: Misperceptions and Reality with Lessons from down Syndrome

    ERIC Educational Resources Information Center

    Acharya, Kruti

    2011-01-01

    Down syndrome is the most common cause of intellectual disability. In the United States, it is recommended that prenatal testing for Down syndrome be offered to all women. Because of this policy and consequent public perception, having Down syndrome has become a disadvantage in the prenatal period. However, in the postnatal period, there may be…

  20. Unfair discrimination in prenatal aneuploidy screening using cell-free DNA?

    PubMed

    Rolfes, Vasilija; Schmitz, Dagmar

    2016-03-01

    Non-invasive prenatal testing on the basis of cell-free DNA of placental origin (NIPT) changed the landscape of prenatal care and is seen as superior to all other up to now implemented prenatal screening procedures - at least in the high-risk population. NIPT has spread almost worldwide commercially, but only in a few countries the costs of NIPT are covered by insurance companies. Such financial barriers in prenatal testing can lead to significant restrictions to the average range of opportunities of pregnant women and couples, which on an intersubjective level can be defined as unfair discrimination and on an individual level weakens reproductive autonomy. Given that enabling reproductive autonomy is the main ethical justification for offering prenatal (genetic) testing, these barriers are not only an issue of justice in health care, but are potentially counteracting the primary purpose of these testing procedures.

  1. Invasive prenatal diagnosis of fetal thalassemia.

    PubMed

    Li, Dong-Zhi; Yang, Yan-Dong

    2017-02-01

    Thalassemia is the most common monogenic inherited disease worldwide, affecting individuals originating from many countries to various extents. As the disease requires long-term care, prevention of the homozygous state presents a substantial global disease burden. The comprehensively preventive programs involve carrier detections, molecular diagnostics, genetic counseling, and prenatal diagnosis. Invasive prenatal diagnosis refers to obtaining fetal material by chorionic villus sampling (CVS) at the first trimester, and by amniocentesis or cordocentesis at the second trimester. Molecular diagnosis, which includes multiple techniques that are aimed at the detection of mutations in the α- or β-globin genes, facilitates prenatal diagnosis and definitive diagnosis of the fetus. These are valuable procedures for couples at risk, so that they can be offered options to have healthy offspring. According to local practices and legislation, genetic counseling should accompany the invasive diagnostic procedures, DNA testing, and disclosure of the results. The most critical issue in any type of prenatal molecular testing is maternal cell contamination (MCC), especially when a fetus is found to inherit a particular mutation from the mother. The best practice is to perform MCC studies on all prenatal samples. The recent successful studies of fetal DNA in maternal plasma may allow future prenatal testing that is non-invasive for the fetus and result in significant reduction of invasive diagnostic procedures.

  2. 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

  3. Survey of prenatal testing for genetic disorders in Japan: Recent report.

    PubMed

    Nobuzane, Takahiro; Yamada, Takahiro; Miura, Kiyonori; Sawai, Hideaki; Masuzaki, Hideaki; Kudo, Yoshiki

    2016-04-01

    In order to investigate the current status of prenatal testing for genetic disorders, we conducted a multicenter retrospective questionnaire survey. The questionnaire was sent to 105 facilities with genetic counseling systems. The questionnaire consisted of two parts: (i) the number of prenatal tests conducted for genetic disorders from January 2010 to December 2012, whether the laboratory was combined with the counseling facility or separate, the sampling procedure method, the testing results, and the outcomes of the affected fetus in addition to treatment; and (ii) a survey of personal comments regarding prenatal testing for genetic disorders. We received responses from 69 of the 105 facilities (65.7%), and genetic testing was performed at 26 of these facilities. Nucleic acid sequential testing was performed on 45 disorders and 252 cases during a three-year period. There were 67 cases of affected fetuses. Six cases continued pregnancy and were treated. The comment survey highlighted difficulties in locating a laboratory to assess prenatal samples, as well as inadequate counseling and preparation for genetic disorders. Our study revealed that a number of prenatal testing for genetic disorders are conducted in Japan; however, it is difficult for counselors to locate a laboratory capable of testing for specific genetic disorders. Inadequate counseling and healthcare providers' lack of knowledge is a current problem. A well-established system of prenatal testing for genetic disorders and the further education of general physicians is required. © 2016 Japan Society of Obstetrics and Gynecology.

  4. Prenatal toxicity test of Morinda citrifolia (noni) fruit.

    PubMed

    West, Brett J; Su, Chen X; Jensen, C Jarakae

    2008-12-01

    Morinda citrifolia (noni) fruit juice use has increased greatly within the past decade, with more than 80,000,000 liters being consumed world wide. With increasing widespread use and the potential use among pregnant women, a prenatal developmental toxicity test was conducted to further evaluate the safety of noni juice. Freeze-dried noni fruit puree from French Polynesia was administered daily by gastric intubation to separate dose groups (n = 12) of pregnant Sprague Dawley rats at 1.72, 3.43, and 6.86 g/kg body weight, with a control group receiving water in place of noni. The dose schedule was followed from the first day of gestation until one day prior to expected delivery, 21 days. There were no symptoms of toxicity in the pregnant dams. There was no difference between the control and any noni group in the number of live fetuses, resorptions, fetal weight and length, or skeletal abnormalities. No dead fetuses, gross external malformations, or internal organ defects were observed in any group. These findings do not indicate that toxicity from noni juice to developing embryos and fetuses is expected.

  5. Non-invasive methods for embryo selection

    PubMed Central

    Sallam, HN; Sallam, NH; Sallam, SH

    2016-01-01

    Abstract With the widespread use of assisted reproduction, a simple and practical method for embryo selection is needed to optimize the chances of pregnancy while diminishing the incidence of multiple pregnancy and its accompanying problems. Many non-invasive methods for embryo selection have been proposed and some are more promising than others. This review summarizes these methods and attempts to evaluate them in the light of the best currently available evidence and to find out whether any of them is ripe for replacing or supplementing the time-honored method of morphological assessment. PMID:27909565

  6. 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.

  7. Facilitating informed choice in prenatal testing: how well are we doing?

    PubMed

    Marteau, T M; Dormandy, E

    2001-01-01

    There is a consensus that prenatal testing services need to provide the information and support necessary for women to make informed choices about prenatal testing. Informed choices are those based on relevant information that reflect the decision-maker's values. To date, most research has focused on the information provided to women deciding whether to undergo tests. This has highlighted the poor quality of information provided to many women. There is agreement on the need to provide information on three key aspects of any test: the condition for which testing is being offered, characteristics of the test, and the implications of testing. Very little research has been conducted on decisions after the diagnosis of a fetal abnormality and how information and emotional and decisional support are and should be provided. Research is now needed in four key areas: first, on the optimal ways of organizing services to facilitate choices that are not only based on relevant information, but also reflect the decision-maker's values; second, on the most effective ways of framing information needed for the different decisions involved in prenatal testing; third, on the most effective media in which to deliver information; and, fourth, to identify aspects of counseling that facilitate informed choices following diagnoses of fetal abnormality. If we value women's ability to make informed choices about prenatal tests as highly as we value reliable laboratory tests, evidence-based quality standards need to be developed for the information and support women are given at all stages of the process of prenatal testing.

  8. [Introduction of rapid syphilis and HIV testing in prenatal care in Colombia: qualitative analysis].

    PubMed

    Ochoa-Manjarrés, María Teresa; Gaitán-Duarte, Hernando Guillermo; Caicedo, Sidia; Gómez, Berta; Pérez, Freddy

    2016-12-01

    Interpret perceptions of Colombian health professionals concerning factors that obstruct and facilitate the introduction of rapid syphilis and HIV testing in prenatal care services. A qualitative study based on semi-structured interviews was carried out. A convenience sample was selected with 37 participants, who included health professionals involved in prenatal care services, programs for pregnant women, clinical laboratories, and directors of health care units or centers, as well as representatives from regional departments and the Ministry of Health. Colombia does not do widespread screening with rapid syphilis and HIV tests in prenatal care. The professionals interviewed stated they did not have prior experience in the use of rapid tests-except for laboratory staff-or in the course of action in response to a positive result. The insurance system hinders access to timely diagnosis and treatment. Health authorities perceive a need to review existing standards, strengthen the first level of care, and promote comprehensive prenatal care starting with contracts between insurers and health service institutional providers. Participants recommended staff training and integration between health-policymaking and academic entities for updating training programs. The market approach and the characteristics of the Colombian health system constitute the main barriers to implementation of rapid testing as a strategy for elimination of mother-to-child transmission of syphilis and HIV. Measures identified include making changes in contracts between insurers and health service institutional providers, adapting the timing and duration of prenatal care procedures, and training physicians and nurses involved in prenatal care.

  9. Prenatal Marijuana Exposure and Intelligence Test Performance at Age 6

    ERIC Educational Resources Information Center

    Goldschmidt, Lidush; Richardson, Gale A.; Willford, Jennifer; Day, Nancy L.

    2008-01-01

    A study was conducted on lower income population women who were moderate users of marijuana to examine the effects of prenatal marijuana exposure on children's intellectual development at the age of six. Results concluded that the Cognitive deficits noticed at the age of six were specific to verbal and quantitative reasoning and short-term memory.

  10. Prenatal Marijuana Exposure and Intelligence Test Performance at Age 6

    ERIC Educational Resources Information Center

    Goldschmidt, Lidush; Richardson, Gale A.; Willford, Jennifer; Day, Nancy L.

    2008-01-01

    A study was conducted on lower income population women who were moderate users of marijuana to examine the effects of prenatal marijuana exposure on children's intellectual development at the age of six. Results concluded that the Cognitive deficits noticed at the age of six were specific to verbal and quantitative reasoning and short-term memory.

  11. The value of non-invasive ventilation.

    PubMed

    Hull, Jeremy

    2014-11-01

    Non-invasive ventilation (NIV) use has increased markedly over the last 10 years. Children being treated with NIV are now a common sight in most paediatric intensive care units and high dependency units and nearly all tertiary respiratory units will look after a cohort of children who use NIV at home. Although the published evidence base for use of NIV in acute and chronic respiratory failure is relatively weak, it is now very unlikely that there will be any more randomised controlled trials of this intervention. Effectiveness of NIV will need to be evaluated on each child as it used. It is important to define the purpose of using NIV in each child, and then determine whether it is effective. 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.

  12. Prevalence of syphilis in pregnancy and prenatal syphilis testing in Brazil: Birth in Brazil study

    PubMed Central

    Domingues, Rosa Maria Soares Madeira; Szwarcwald, Celia Landmann; Souza, Paulo Roberto Borges; Leal, Maria do Carmo

    2014-01-01

    OBJECTIVE Determine the coverage rate of syphilis testing during prenatal care and the prevalence of syphilis in pregnant women in Brazil. METHODS This is a national hospital-based cohort study conducted in Brazil with 23,894 postpartum women between 2011 and 2012. Data were obtained using interviews with postpartum women, hospital records, and prenatal care cards. All postpartum women with a reactive serological test result recorded in the prenatal care card or syphilis diagnosis during hospitalization for childbirth were considered cases of syphilis in pregnancy. The Chi-square test was used for determining the disease prevalence and testing coverage rate by region of residence, self-reported skin color, maternal age, and type of prenatal and child delivery care units. RESULTS Prenatal care covered 98.7% postpartum women. Syphilis testing coverage rate was 89.1% (one test) and 41.2% (two tests), and syphilis prevalence in pregnancy was 1.02% (95%CI 0.84;1.25). A lower prenatal coverage rate was observed among women in the North region, indigenous women, those with less education, and those who received prenatal care in public health care units. A lower testing coverage rate was observed among residents in the North, Northeast, and Midwest regions, among younger and non-white skin-color women, among those with lower education, and those who received prenatal care in public health care units. An increased prevalence of syphilis was observed among women with < 8 years of education (1.74%), who self-reported as black (1.8%) or mixed (1.2%), those who did not receive prenatal care (2.5%), and those attending public (1.37%) or mixed (0.93%) health care units. CONCLUSIONS The estimated prevalence of syphilis in pregnancy was similar to that reported in the last sentinel surveillance study conducted in 2006. There was an improvement in prenatal care and testing coverage rate, and the goals suggested by the World Health Organization were achieved in two regions. Regional

  13. Intrauterine transfusion and non-invasive treatment options for hemolytic disease of the fetus and newborn - review on current management and outcome.

    PubMed

    Zwiers, Carolien; van Kamp, Inge; Oepkes, Dick; Lopriore, Enrico

    2017-04-01

    Hemolytic disease of the fetus and newborn (HDFN) remains a serious pregnancy complication which can lead to severe fetal anemia, hydrops and perinatal death. Areas covered: This review focusses on the current prenatal management, treatment with intrauterine transfusion (IUT) and promising non-invasive treatment options for HDFN. Expert commentary: IUTs are the cornerstone in prenatal management of HDFN and have significantly improved perinatal outcome in the past decades. IUT is now a relatively safe procedure, however the risk of complications is still high when performed early in the second trimester. Non-invasive management using intravenous immunoglobulin may be a safe alternative and requires further investigation.

  14. 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.

  15. Non-invasive assessment of the liver using imaging

    NASA Astrophysics Data System (ADS)

    Thorling Thompson, Camilla; Wang, Haolu; Liu, Xin; Liang, Xiaowen; Crawford, Darrell H.; Roberts, Michael S.

    2016-12-01

    Chronic liver disease causes 2,000 deaths in Australia per year and early diagnosis is crucial to avoid progression to cirrhosis and end stage liver disease. There is no ideal method to evaluate liver function. Blood tests and liver biopsies provide spot examinations and are unable to track changes in function quickly. Therefore better techniques are needed. Non-invasive imaging has the potential to extract increased information over a large sampling area, continuously tracking dynamic changes in liver function. This project aimed to study the ability of three imaging techniques, multiphoton and fluorescence lifetime imaging microscopy, infrared thermography and photoacoustic imaging, in measuring liver function. Collagen deposition was obvious in multiphoton and fluorescence lifetime imaging in fibrosis and cirrhosis and comparable to conventional histology. Infrared thermography revealed a significantly increased liver temperature in hepatocellular carcinoma. In addition, multiphoton and fluorescence lifetime imaging and photoacoustic imaging could both track uptake and excretion of indocyanine green in rat liver. These results prove that non-invasive imaging can extract crucial information about the liver continuously over time and has the potential to be translated into clinic in the assessment of liver disease.

  16. Prenatal nutrition, epigenetics and schizophrenia risk: can we test causal effects?

    PubMed Central

    Kirkbride, James B; Susser, Ezra; Kundakovic, Marija; Kresovich, Jacob K; Smith, George Davey; Relton, Caroline L

    2014-01-01

    We posit that maternal prenatal nutrition can influence offspring schizophrenia risk via epigenetic effects. In this article, we consider evidence that prenatal nutrition is linked to epigenetic outcomes in offspring and schizophrenia in offspring, and that schizophrenia is associated with epigenetic changes. We focus upon one-carbon metabolism as a mediator of the pathway between perturbed prenatal nutrition and the subsequent risk of schizophrenia. Although post-mortem human studies demonstrate DNA methylation changes in brains of people with schizophrenia, such studies cannot establish causality. We suggest a testable hypothesis that utilizes a novel two-step Mendelian randomization approach, to test the component parts of the proposed causal pathway leading from prenatal nutritional exposure to schizophrenia. Applied here to a specific example, such an approach is applicable for wider use to strengthen causal inference of the mediating role of epigenetic factors linking exposures to health outcomes in population-based studies. PMID:22690666

  17. Prenatal nutrition, epigenetics and schizophrenia risk: can we test causal effects?

    PubMed

    Kirkbride, James B; Susser, Ezra; Kundakovic, Marija; Kresovich, Jacob K; Davey Smith, George; Relton, Caroline L

    2012-06-01

    We posit that maternal prenatal nutrition can influence offspring schizophrenia risk via epigenetic effects. In this article, we consider evidence that prenatal nutrition is linked to epigenetic outcomes in offspring and schizophrenia in offspring, and that schizophrenia is associated with epigenetic changes. We focus upon one-carbon metabolism as a mediator of the pathway between perturbed prenatal nutrition and the subsequent risk of schizophrenia. Although post-mortem human studies demonstrate DNA methylation changes in brains of people with schizophrenia, such studies cannot establish causality. We suggest a testable hypothesis that utilizes a novel two-step Mendelian randomization approach, to test the component parts of the proposed causal pathway leading from prenatal nutritional exposure to schizophrenia. Applied here to a specific example, such an approach is applicable for wider use to strengthen causal inference of the mediating role of epigenetic factors linking exposures to health outcomes in population-based studies.

  18. Identifying craniofacial features associated with prenatal exposure to androgens and testing their relationship with brain development.

    PubMed

    Marečková, Klára; Chakravarty, Mallar M; Lawrence, Claire; Leonard, Gabriel; Perusse, Daniel; Perron, Michel; Pike, Bruce G; Richer, Louis; Veillette, Suzanne; Pausova, Zdenka; Paus, Tomáš

    2015-11-01

    We used magnetic resonance (MR) images obtained in same-sex and opposite-sex dizygotic twins (n = 119, 8 years of age) to study possible effects of prenatal androgens on craniofacial features. Using a principal component analysis of 19 craniofacial landmarks placed on the MR images, we identified a principal component capturing craniofacial features that distinguished females with a presumed differential exposure to prenatal androgens by virtue of having a male (vs. a female) co-twin (Cohen's d = 0.76). Subsequently, we tested the possibility that this craniofacial "signature" of prenatal exposure to androgens predicts brain size, a known sexually dimorphic trait. In an independent sample of female adolescents (singletons; n = 462), we found that the facial signature predicts up to 8% of variance in brain size. These findings are consistent with the organizational effects of androgens on brain development and suggest that the facial signature derived in this study could complement other indirect measures of prenatal exposure to androgens.

  19. Systematic review: non-invasive methods of fibrosis analysis in chronic hepatitis C.

    PubMed

    Smith, J O; Sterling, R K

    2009-09-15

    Accurate determination of the presence and degree of liver fibrosis is essential for prognosis and for planning treatment of patients with chronic hepatitis C virus (HCV). Non-invasive methods of assessing fibrosis have been developed to reduce the need for biopsy. To perform a review of these non-invasive measures and their ability to replace biopsy for assessing hepatic fibrosis in patients with chronic HCV. A systematic review of PUBMED and EMBASE was performed through 2008 using the following search terms: HCV, liver, elastography, hepatitis, Fibroscan, SPECT, noninvasive liver fibrosis, ultrasonography, Doppler, MRI, Fibrotest, Fibrosure, Actitest, APRI, Forns and breath tests, alone or in combination. We identified 151 studies: 87 using biochemical, 57 imaging and seven breath tests either alone or in combination. Great strides are being made in the development of accurate non-invasive methods for determination of fibrosis. Although no single non-invasive test or model developed to date can match that information obtained from actual histology (i.e. inflammation, fibrosis, steatosis), combinations of two modalities of non-invasive methods can reliably differentiate between minimal and significant fibrosis, and thereby avoid liver biopsy in a significant percentage of patients.

  20. Long-term non-invasive ventilation in children.

    PubMed

    Amaddeo, Alessandro; Frapin, Annick; Fauroux, Brigitte

    2016-12-01

    Use of long-term non-invasive ventilation is increasing exponentially worldwide in children of all ages. The treatment entails delivery of ventilatory assistance through a non-invasive interface. Indications for use of non-invasive ventilation include conditions that affect normal respiratory balance (eg, those associated with dysfunction of the central drive or respiratory muscles) and disorders characterised by an increase in respiratory load (eg, obstructive airway or lung diseases). The type of non-invasive ventilation used depends on the pathophysiological features of the respiratory failure. For example, non-invasive ventilation will need to either replace central drive if the disorder is characterised by an abnormal central drive or substitute for the respiratory muscles if the condition is associated with respiratory muscle weakness. Non-invasive ventilation might also need to unload the respiratory muscles in case of an increase in respiratory load, as seen in upper airway obstruction and some lung diseases. Technical aspects are also important when choosing non-invasive ventilation-eg, appropriate interface and device. The great heterogeneity of disorders, age ranges of affected children, prognoses, and outcomes of patients needing long-term non-invasive ventilation underline the need for management by skilled multidisciplinary centres with technical competence in paediatric non-invasive ventilation and expertise in sleep studies and therapeutic education.

  1. Implementation of non-invasive brain physiological monitoring concepts.

    PubMed

    Ragauskas, Arminas; Daubaris, Gediminas; Ragaisis, Vytautas; Petkus, Vytautas

    2003-10-01

    The paper presents innovative methods and technology for non-invasive intracranial hemodynamics monitoring based on the measurement of brain parenchyma acoustic properties. The clinical investigation of new technology shows the similarity between the invasively recorded intracranial pressure (ICP) and non-invasively recorded intracranial blood volume (IBV) pulse waves, slow waves and slow trends under intensive care unit (ICU) conditions. Also, the applicability of the non-invasive IBV slow wave monitoring technique for cerebrovascular autoregulation non-invasive long-term monitoring is demonstrated by theoretical and experimental studies.

  2. Non-invasive diagnostic methods in dentistry

    NASA Astrophysics Data System (ADS)

    Todea, Carmen

    2016-03-01

    The paper, will present the most important non-invasive methods for diagnostic, in different fields of dentistry. Moreover, the laser-based methods will be emphasis. In orthodontics, 3D laser scanners are increasingly being used to establish database for normative population and cross-sectional growth changes but also to asses clinical outcomes in orthognatic surgical and non-surgical treatments. In prevention the main methods for diagnostic of demineralization and caries detection in early stages are represented by laser fluorescence - Quantitative Light Florescence (QLF); DiagnoDent-system-655nm; FOTI-Fiberoptic transillumination; DIFOTI-Digital Imaging Fiberoptic transillumination; and Optical Coherence Tomography (OCT). In odontology, Laser Doppler Flowmetry (LDF) is a noninvasive real time method used for determining the tooth vitality by monitoring the pulp microcirculation in traumatized teeth, fractured teeth, and teeth undergoing different conservative treatments. In periodontology, recently study shows the ability of LDF to evaluate the health of gingival tissue in periodontal tissue diseases but also after different periodontal treatments.

  3. Non-invasive coronary wave intensity analysis.

    PubMed

    Broyd, Christopher J; Rigo, Fausto; Davies, Justin

    2017-07-01

    Wave intensity analysis is calculated from simultaneously acquired measures of pressure and flow. Its mathematical computation produces a profile that provides quantitative information on the energy exchange driving blood flow acceleration and deceleration. Within the coronary circulation it has proven most useful in describing the wave that originates from the myocardium and that is responsible for driving the majority of coronary flow, labelled the backward decompression wave. Whilst this wave has demonstrated valuable insights into the pathogenic processes of a number of disease states, its measurement is hampered by its invasive necessity. However, recent work has used transthoracic echocardiography and an established measures of central aortic pressure to produce coronary flow velocity and pressure waveforms respectively. This has allowed a non-invasive measure of coronary wave intensity analysis, and in particular the backward decompression wave, to be calculated. It is anticipated that this will allow this tool to become more applicable and widespread, ultimately moving it from the research to the clinical domain.

  4. Non-invasive physiology in conscious mice.

    PubMed

    Kale, Ajit; Amende, Ivo; Piskorski, Katrina; Chu, Victor; Otero, Jose M; Mueller, Peter; Hampton, Thomas G

    2004-06-01

    Linking gene defect to disease phenotypes in mice has become an essential step in the development of new drugs. Yet, many in vitro and in vivo assays require anaesthetic and surgery or do not reflect physiologically relevant phenomena. The effects of genes or diseases may only become apparent with stressors. Here, we apply non-invasive ECG monitoring and gait imaging systems to describe changes in the electrocardiogram and in gait dynamics resulting from a doubling of the ambulatory speed of mice. We found that B6C3H mice (n = 5) take 3.6 +/- 0.1 strides/second to walk 18cm/second and have a heart rate of 750 +/- 2bpm after 1 minute of walking at this speed. These mice significantly increase stride frequency to 5.2 +/- 0.1 strides/second in order to increase their speed to 36cm/second. The heart rate increased significantly (814 +/- 9bpm, p < 0.05) after trotting at the higher speed for 90 seconds, and the QRS interval duration significantly decreased (9.4 +/- 0.3ms vs. 10.4 +/- 0.3ms, p < 0.05). We discuss the application of the ECG screening and gait imaging systems to mouse models of Duchenne muscular dystrophy, Down syndrome and amyotrophic lateral sclerosis, diseases in humans that are known to affect the heart and neuromuscular systems.

  5. Women's opinions of legal requirements for drug testing in prenatal care.

    PubMed

    Tucker Edmonds, Brownsyne; Mckenzie, Fatima; Austgen, MacKenzie B; Carroll, Aaron E; Meslin, Eric M

    2017-07-01

    To explore women's attitudes and perceptions regarding legal requirements for prenatal drug testing. Web-based survey of 500 US women (age 18-45) recruited from a market research survey panel. A 24-item questionnaire assessed their opinion of laws requiring doctors to routinely verbal screen and urine drug test patients during pregnancy; recommendations for consequences for positive drug tests during pregnancy; and opinion of laws requiring routine drug testing of newborns. Additional questions asked participants about the influence of such laws on their own care-seeking behaviors. Data were analyzed for associations between participant characteristics and survey responses using Pearson's chi-squared test. The majority of respondents (86%) stated they would support a law requiring verbal screening of all pregnant patients and 73% would support a law requiring universal urine drug testing in pregnancy. Fewer respondents were willing to support laws that required verbal screening or urine drug testing (68% and 61%, respectively) targeting only Medicaid recipients. Twenty-one percent of respondents indicated they would be offended if their doctors asked them about drug use and 14% indicated that mandatory drug testing would discourage prenatal care attendance. Women would be more supportive of policies requiring universal rather than targeted screening and testing for prenatal drug use. However, a noteworthy proportion of women would be discouraged from attending prenatal care - a reminder that drug testing policies may have detrimental effects on maternal child health.

  6. Moral Enhancement Using Non-invasive Brain Stimulation

    PubMed Central

    Darby, R. Ryan; Pascual-Leone, Alvaro

    2017-01-01

    Biomedical enhancement refers to the use of biomedical interventions to improve capacities beyond normal, rather than to treat deficiencies due to diseases. Enhancement can target physical or cognitive capacities, but also complex human behaviors such as morality. However, the complexity of normal moral behavior makes it unlikely that morality is a single capacity that can be deficient or enhanced. Instead, our central hypothesis will be that moral behavior results from multiple, interacting cognitive-affective networks in the brain. First, we will test this hypothesis by reviewing evidence for modulation of moral behavior using non-invasive brain stimulation. Next, we will discuss how this evidence affects ethical issues related to the use of moral enhancement. We end with the conclusion that while brain stimulation has the potential to alter moral behavior, such alteration is unlikely to improve moral behavior in all situations, and may even lead to less morally desirable behavior in some instances. PMID:28275345

  7. Moral Enhancement Using Non-invasive Brain Stimulation.

    PubMed

    Darby, R Ryan; Pascual-Leone, Alvaro

    2017-01-01

    Biomedical enhancement refers to the use of biomedical interventions to improve capacities beyond normal, rather than to treat deficiencies due to diseases. Enhancement can target physical or cognitive capacities, but also complex human behaviors such as morality. However, the complexity of normal moral behavior makes it unlikely that morality is a single capacity that can be deficient or enhanced. Instead, our central hypothesis will be that moral behavior results from multiple, interacting cognitive-affective networks in the brain. First, we will test this hypothesis by reviewing evidence for modulation of moral behavior using non-invasive brain stimulation. Next, we will discuss how this evidence affects ethical issues related to the use of moral enhancement. We end with the conclusion that while brain stimulation has the potential to alter moral behavior, such alteration is unlikely to improve moral behavior in all situations, and may even lead to less morally desirable behavior in some instances.

  8. Non-invasive diagnosis of alcoholic liver disease

    PubMed Central

    Mueller, Sebastian; Seitz, Helmut Karl; Rausch, Vanessa

    2014-01-01

    Alcoholic liver disease (ALD) is the most common liver disease in the Western world. For many reasons, it is underestimated and underdiagnosed. An early diagnosis is absolutely essential since it (1) helps to identify patients at genetic risk for ALD; (2) can trigger efficient abstinence namely in non-addicted patients; and (3) initiate screening programs to prevent life-threatening complications such as bleeding from varices, spontaneous bacterial peritonitis or hepatocellular cancer. The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis (AH). The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on a combination of laboratory, clinical and imaging findings. It is not widely conceived that conventional screening tools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca. 40% of manifest alcoholic liver cirrhosis. Non-invasive methods such as transient elastography (Fibroscan), acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholic cirrhosis. Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca. 95% of patients. The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels. Other non-invasive methods such as controlled attenuation parameter, serum levels of M30 or M65, susceptometry or breath tests are under current evaluation to assess the degree of steatosis, apoptosis and iron overload in these patients. Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH. PMID:25356026

  9. Non-invasive markers of gut wall integrity in health and disease.

    PubMed

    Derikx, Joep P M; Luyer, Misha D P; Heineman, Erik; Buurman, Wim A

    2010-11-14

    The intestinal mucosa is responsible for the absorption of nutrients from the lumen and for the separation of the potentially toxic luminal content (external environment) from the host (internal environment). Disruption of this delicate balance at the mucosal interface is the basis for numerous (intestinal) diseases. Experimental animal studies have shown that gut wall integrity loss is involved in the development of various inflammatory syndromes, including post-operative or post-traumatic systemic inflammatory response syndrome, sepsis, and multiple organ failure. Assessment of gut wall integrity in clinical practice is still a challenge, as it is difficult to evaluate the condition of the gut non-invasively with currently available diagnostic tools. Moreover, non-invasive, rapid diagnostic means to assess intestinal condition are needed to evaluate the effects of treatment of intestinal disorders. This review provides a survey of non-invasive tests and newly identified markers that can be used to assess gut wall integrity.

  10. From prenatal HIV testing of the mother to prevention of sexual HIV transmission within the couple.

    PubMed

    Desgrées-du-Loû, Annabel; Brou, Hermann; Traore, Annick Tijou; Djohan, Gerard; Becquet, Renaud; Leroy, Valeriane

    2009-09-01

    The first step in preventing mother-to-child HIV transmission (PMTCT) programmes is offering HIV counselling and testing to pregnant women. In developing countries where HIV testing remains rare, it represents a unique opportunity for many women to learn their HIV status. This prenatal HIV testing is not only the entry point to prevention of mother-to-child HIV transmission, but also an occasion for women to sensitize their male partner to sexual risks. Here we explore if these women, HIV-tested as mothers, apply the prevention recommendations they also receive as women. In the Ditrame Plus PMTCT program in Abidjan, Côte d'Ivoire, two cohorts of women (475 HIV-infected women and 400 HIV-negative women) were followed up two years after the pregnancy when they were offered prenatal HIV testing. In each cohort, we compared the proportion of women who communicated with their regular partner on sexual risks, prior to and after prenatal HIV testing. We analysed socio-demographic factors related to this communication. We measured two potential conjugal outcomes of women HIV testing: the level of condom use at sex resumption after delivery and the risk of union break-up. Prenatal HIV testing increased conjugal communication regarding sexual risks, whatever the woman's serostatus. This communication was less frequent for women in a polygamous union or not residing with their partner. Around 30% of women systematically used condoms at sex resumption. Among HIV infected ones, conjugal talk on sexual risks was related to improved condom use. After HIV testing, more HIV-infected women separated from their partners than HIV-uninfected women, despite very few negative reactions from the notified partners. In conclusion, offering prenatal HIV counselling and testing is an efficient tool for sensitizing women and their partners to HIV prevention. But sexual prevention in a conjugal context remains difficult and need to be specifically addressed.

  11. Non invasive sensing technologies for cultural heritage management and fruition

    NASA Astrophysics Data System (ADS)

    Soldovieri, Francesco; Masini, Nicola

    2016-04-01

    The relevance of the information produced by science and technology for the knowledge of the cultural heritage depends on the quality of the feedback and, consequently, on the "cultural" distance between scientists and end-users. In particular, the solution to this problem mainly resides in the capability of end-users' capability to assess and transform the knowledge produced by diagnostics with regard to: information on both cultural objects and sites (decay patterns, vulnerability, presence of buried archaeological remains); decision making (management plan, conservation project, and excavation plan). From our experience in the field of the cultural heritage and namely the conservation, of monuments, there is a significant gap of information between technologists (geophysicists/physicists/engineers) and end-users (conservators/historians/architects). This cultural gap is due to the difficulty to interpret "indirect data" produced by non invasive diagnostics (i.e. radargrams/thermal images/seismic tomography etc..) in order to provide information useful to improve the historical knowledge (e.g. the chronology of the different phases of a building), to characterise the state of conservation (e.g. detection of cracks in the masonry) and to monitor in time cultural heritage artifacts and sites. The possible answer to this difficulty is in the set-up of a knowledge chain regarding the following steps: - Integrated application of novel and robust data processing methods; - Augmented reality as a tool for making easier the interpretation of non invasive - investigations for the analysis of decay pathologies of masonry and architectural surfaces; - The comparison between direct data (carrots, visual inspection) and results from non-invasive tests, including geophysics, aims to improve the interpretation and the rendering of the monuments and even of the archaeological landscapes; - The use of specimens or test beds for the detection of archaeological features and

  12. The expressivist objection to prenatal testing: the experiences of families living with genetic disease.

    PubMed

    Boardman, Felicity Kate

    2014-04-01

    The expressivist objection to prenatal testing is acknowledged as a significant critique of prenatal testing practices most commonly advanced by disability rights supporters. Such writers argue that prenatal testing and selective termination practices are objectionable as they express disvalue not only of the foetus being tested, but also of disabled people as a whole, by focusing exclusively on the disabling trait. While the objection has been widely critiqued on the basis of its theoretical incoherence, this paper highlights the way in which it, nevertheless, is a significant mediator in decisions around the use of reproductive genetic technologies. By drawing on 41 in-depth qualitative interviews (drawn from a sample of 61) conducted in the UK between 2007 and 2009 with families and individuals living with a genetic disease, Spinal Muscular Atrophy (SMA), this paper highlights the ways in which expressivist objections feature prominently in the reproductive decisions of families living with SMA and the significant emotional burden they represent. While the literature on the expressivist objection has focused on the reproductive decisions of those undergoing prenatal testing for a condition of which they have little (or no) prior knowledge, the context of intimate familial relationships and extensive experience with the tested-for condition fundamentally alters the nature and impact of expressivist objections within families living with an inheritable condition. By focussing on the reproductive decisions of families living with SMA and their strategic management of the expressivist objection, this paper will address the call, made primarily by disability rights supporters, for 'experientially based' (as opposed to medical) information about the tested-for disability to be made available to would-be parents considering selective termination. It will be argued that parents' experiential knowledge of the tested-for disability can, in fact, amplify expressivist

  13. Validity and reliability testing of the Prenatal Psychosocial Profile.

    PubMed

    Curry, M A; Campbell, R A; Christian, M

    1994-04-01

    Two studies of low-income pregnant women (N = 179) were done to examine the validity and reliability of the Prenatal Psychosocial Profile (PPP). The PPP, a composite of the Rosenberg Self-Esteem Scale, the Support Behaviors Inventory, and a newly developed measure of stress, is a brief, comprehensive clinical assessment of psychosocial risk during pregnancy. Construct validity of the stress scale was supported by theoretically predicted negative correlations with self-esteem, partner support, and support from others (N = 91). Convergent validity of the stress scale was demonstrated by a correlation of .71 with the Difficult Life Circumstances Scale. Adequate levels of internal consistency were found. Interrelationships between the four subscales were consistent with the underlying conceptualization, and there was beginning evidence of the factorial independence of the subscales.

  14. Impact of Prenatal Cocaine Exposure on Attention and Response Inhibition as Assessed by Continuous Performance Tests

    PubMed Central

    Accornero, Veronica H.; Amado, Alfred J.; Morrow, Connie E.; Xue, Lihua; Anthony, James C.; Bandstra, Emmalee S.

    2009-01-01

    Objective This study examined the influence of prenatal cocaine exposure on attention and response inhibition measured by continuous performance tests (CPTs) at ages 5 and 7 years. Methods The baseline sample consisted of 253 cocaine-exposed and 223 non–cocaine-exposed children enrolled prospectively at birth and assessed comprehensively through age 7 years in the longitudinal Miami Prenatal Cocaine Study. This report includes a subsample of 415 children (219 cocaine-exposed, 196 non–cocaine-exposed) who completed at least one CPT assessment at ages 5 and/or 7 years. Prenatal cocaine exposure was measured by maternal self-report and maternal and infant bioassays. Deficits in attention and response inhibition are estimated in relation to prenatal cocaine exposure using generalized estimating equations within the general linear model. Results Results indicate cocaine-associated increases in omission errors at ages 5 and 7 as well as increases in response times for target tasks (i.e., slower reaction times) and decreased consistency in performance at age 7. There were no demonstrable cocaine-associated deficits in commission errors. Estimates did not change markedly with statistical adjustment for selected prenatal and postnatal covariates. Conclusion Evidence supports cocaine-associated deficits in attention processing through age 7 years. PMID:17565286

  15. Prenatal counseling for congenital anomaly tests: parental preferences and perceptions of midwife performance.

    PubMed

    Martin, L; Van Dulmen, S; Spelten, E; De Jonge, A; De Cock, P; Hutton, E

    2013-04-01

    Evidence-based instruments to evaluate the preferences and experiences of future parents regarding prenatal counseling for congenital anomaly tests are currently lacking. We developed the quality of care through clients' eyes prenatal questionnaire (QUOTE(prenatal) ), a client-centered instrument, and assessed its components. Furthermore, the QUOTE(prenatal) was used to provide insight into (1) clients' previsit preferences and (2) clients' postvisit experience, that is, perceived care provider performance regarding the counseling they received. In the questionnaire survey, a principal component analysis was used to gain insight into the underlying components of the questionnaire. Regression analysis was performed to examine differences between groups. In 17 Dutch midwifery practices, 941 pregnant women and their partners (response rate 79%) completed the 59-item QUOTE(prenatal) previsit and postvisit, measuring preferences and perceived performances, respectively. A principal component analysis revealed three counseling components: client-midwife relation, health education and decision-making support. Reponses showed that, previsit, most clients consider the client-midwife relationship and health education to be (very) important. One third of the clients consider decision-making support to be (very) important. Nulliparae had higher preferences for health education and decision-making support than multiparae. Clients perceive that their midwives perform well in building the client-midwife relationship and in giving health education. Improvement is needed in decision-making support. © 2013 John Wiley & Sons, Ltd.

  16. Exploring informed choice in the context of prenatal testing: findings from a qualitative study

    PubMed Central

    Potter, Beth K.; O’Reilly, Natasha; Etchegary, Holly; Howley, Heather; Graham, Ian D.; Walker, Mark; Coyle, Doug; Chorny, Yelena; Cappelli, Mario; Boland, Isabelle; Wilson, Brenda J.

    2008-01-01

    Abstract Purpose  This study explored whether and how a sample of women made informed choices about prenatal testing for foetal anomalies; its aim was to provide insights for future health policy and service provision. Methods  We conducted semi‐structured interviews with 38 mothers in Ottawa, Ontario, all of whom had been offered prenatal tests in at least one pregnancy. Using the Multi‐dimensional Measure of Informed Choice as a general guide to analysis, we explored themes relevant to informed choice, including values and knowledge, and interactions with health professionals. Results  Many, but not all, participants seemed to have made informed decisions about prenatal testing. Values and knowledge were interrelated and important components of informed choice, but the way they were discussed differed from the way they have been presented in scientific literature. In particular, ‘values’ related to expressions of women’s moral views or ideas about ‘how life should be lived’ and ‘knowledge’ related to the ways in which women prioritized and interpreted factual information, through their own and others’ experiences and in ‘thinking through’ the personal implications of testing. While some women described non‐directive discussions with health professionals, others perceived testing as routine or felt pressured to accept it. Conclusions  Our findings suggest a need for maternity care providers to be vigilant in promoting active decision making about prenatal testing, particularly around the consideration of personal implications. Further development of measures of informed choice may be necessary to fully evaluate decision support tools and to determine whether prenatal testing programmes are meeting their objectives. PMID:18798759

  17. Inspiring Change: a report on acute non-invasive ventilation.

    PubMed

    Juniper, M C; Ellis, G; Protopapa, K L; Smith, Nce

    2017-09-02

    The British Thoracic Society audit of non-invasive ventilation has shown that mortality rates are higher than expected and increasing. The National Confidential Enquiry into Patient Outcome and Death undertook a detailed analysis of data from 432 patients treated with acute non-invasive ventilation to identify how clinical aspects of non-invasive ventilation treatment could be improved. The study 'Inspiring Change' was published in July 2017. This review summarizes some of the important findings and associated recommendations that will improve treatment of patients and help to reduce mortality rates.

  18. 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.

  19. Prenatal Exposure to an Environmental Toxin: A Test of the Multiple Effects Model.

    ERIC Educational Resources Information Center

    Jacobson, Joseph L.; And Others

    1984-01-01

    Tests 242 newborns exposed prenatally to low levels of polychlorinated biphenyls from maternal consumption of contaminated lake fish. The Brazelton Neonate Scale was used to assess behavioral outcomes. Contaminated fish consumption predicted motoric immaturity, poorer labeling of states, a greater amount of startle, and abnormally weak…

  20. Prenatal Exposure to an Environmental Toxin: A Test of the Multiple Effects Model.

    ERIC Educational Resources Information Center

    Jacobson, Joseph L.; And Others

    1984-01-01

    Tests 242 newborns exposed prenatally to low levels of polychlorinated biphenyls from maternal consumption of contaminated lake fish. The Brazelton Neonate Scale was used to assess behavioral outcomes. Contaminated fish consumption predicted motoric immaturity, poorer labeling of states, a greater amount of startle, and abnormally weak…

  1. Reactions to Prenatal Testing: Reflection of Religiosity and Attitudes toward Abortion and People with Disabilities.

    ERIC Educational Resources Information Center

    Bell, Martie; Stoneman, Zolinda

    2000-01-01

    A study asked 166 undergraduates what they would do if through prenatal testing they discovered that they (or their partner) were carrying a fetus with disabilities. Respondents were more uncertain about whether to continue the pregnancy when the fetus was diagnosed with Down syndrome than with spina bifida or hemophilia. (Contains references.)…

  2. Diagnostic test for prenatal identification of Down's syndrome and mental retardation and gene therapy therefor

    DOEpatents

    Smith, Desmond J.; Rubin, Edward M.

    2000-01-01

    A a diagnostic test useful for prenatal identification of Down syndrome and mental retardation. A method for gene therapy for correction and treatment of Down syndrome. DYRK gene involved in the ability to learn. A method for diagnosing Down's syndrome and mental retardation and an assay therefor. A pharmaceutical composition for treatment of Down's syndrome mental retardation.

  3. Reactions to Prenatal Testing: Reflection of Religiosity and Attitudes toward Abortion and People with Disabilities.

    ERIC Educational Resources Information Center

    Bell, Martie; Stoneman, Zolinda

    2000-01-01

    A study asked 166 undergraduates what they would do if through prenatal testing they discovered that they (or their partner) were carrying a fetus with disabilities. Respondents were more uncertain about whether to continue the pregnancy when the fetus was diagnosed with Down syndrome than with spina bifida or hemophilia. (Contains references.)…

  4. Improving non-invasive ventilation documentation.

    PubMed

    Smith, Matthew; Elkheir, Natalie

    2014-01-01

    Record keeping for patients on non-invasive ventilation (NIV) at St. Georges Hospital is poor. The initial NIV prescription is often not recorded, and changes to the NIV prescription or the rationale for the changes (ABG results) are also poorly documented. This leads to confusion for nurses/doctors as to what the correct settings are, meaning patients could receive ineffective ventilation. The use of NIV is also poorly recorded by nursing staff meaning that doctors are unsure if the prescribed NIV is being achieved. This can lead to treatment being escalated unnecessarily in the event of treatment failure. Non-invasive ventilation (NIV) is the provision of ventilatory support in the form of positive pressure via the patient's upper airway using a mask or similar device. NIV is indicated for treatment of acute hypercapnic respiratory failure, of which there are many causes, though COPD is the indication in up to 70% of cases.[1] British Thoracic Society (BTS) guidelines for NIV suggest that the rationale for commencing a patient on NIV and the proposed settings should be clearly documented.[2] Clinicians cannot effectively tailor changes to the patients NIV settings if this information is not clearly recorded, which could lead to increased time requiring NIV or NIV failure. Three main areas were considered important to measure for this project. The initial prescription of the NIV, changes to the NIV settings, and nursing documentation surrounding NIV. A baseline measurement of NIV documentation for two weeks found NIV documentation to globally very poor. NIV was formally prescribed 29% of the time, full detail of intended settings were documented 57% of the time, the decision to commence NIV was discussed with the respiratory consultant/SpR just 29% of the time and on no occasion was a decision regarding escalation of treatment recorded. Eighteen changes were made to the NIV settings. These were formally prescribed 22% of the time and detail of the intended

  5. Increasing rates of prenatal testing among Jewish and Arab women in Israel over one decade.

    PubMed

    Romano-Zelekha, Orly; Ostrovsky, Jenny; Shohat, Tamy

    2014-01-01

    BACKGROUND/AIMS/OBJECTIVE: This study compared data on the use of prenatal tests offered to pregnant women in Israel as reported in a national survey conducted by the Israel Center for Disease Control in 2001 to data from 2010. Mothers of newborns were interviewed 8-72 h after delivery in 29 maternity wards in Israel on May 31, 2010. A total of 768 women were interviewed, 569 (72.3%) were Jewish and 197 (25.7%) were Arabs. Nuchal translucency screening and early ultrasound level 2 were significantly more frequently done in both Jewish and Arab women in 2010 than in 2001. The use of the biochemical triple marker test and amniocentesis did not change. The increased rate of nuchal translucency screening and early ultrasound level 2 was significantly higher among the Jewish women compared to the Arabs (21.5 and 28.0% vs. 2.9 and 13.7% in 2001; 62.0 and 65.6% vs. 30.1 and 30.9% in 2010, respectively). The rates of amniocentesis in the Jewish women aged ≥35 years were 47.6 and 47.5% in 2001 and 2010, respectively; they are significantly higher than among the Arabs (18.5 and 28.5%, respectively). The factors associated with making more use of different prenatal tests were: secularity, a higher income, and supplementary medical insurance for the Jewish women, and supplementary medical insurance and printed information on prenatal testing for the Arabs. The prenatal testing rates have risen over the last decade in both population groups, but there are still significant gaps. We suggest that public funding of additional prenatal tests may increase their use in both population groups. © 2014 S. Karger AG, Basel.

  6. Non-invasive screening for colorectal cancer in Asia.

    PubMed

    Chiu, Han-Mo; Chang, Li-Chun; Hsu, Wen-Feng; Chou, Chu-Kuang; Wu, Ming-Shiang

    2015-12-01

    There is an increasing trend of colorectal cancer incidence in Asia and nearly 45% of CRC cases worldwide occur in Asia therefore screening for CRC becomes an urgent task. Stool-based tests, including guaiac fecal occult blood test (gFOBT) and fecal immunochemical test (FIT), can select subjects at risk of significant colorectal neoplasms from the large target population thus are currently the most commonly used non-invasive screening tool in large population screening programs. FIT has the advantage over gFOBT in terms of higher sensitivity for early neoplasms, the ability to provide high-throughput automatic analysis, and better public acceptance thus greater effectiveness on reducing CRC mortality and incidence is expected. Owing to the large target population and constrained endoscopic capacity and manpower, FIT is nowadays the most popular CRC screening test in Asia. Some Asian countries have launched nationwide screening program in the past one or two decades but also encountered some challenges such as low screening participation rate, low verification rate after positive stool tests, low public awareness, and insufficient manpower. In addition, some controversial or potential future research issues are also addressed in this review.

  7. Modified Breastfeeding Attrition Prediction Tool: Prenatal and Postpartum Tests

    PubMed Central

    Evans, Marilyn L.; Dick, Margaret J.; Lewallen, Lynne P.; Jeffrey, Cynthia

    2004-01-01

    In earlier studies, the Breastfeeding Attrition Prediction Tool (BAPT) demonstrated predictive validity in the postpartum period. The purpose of this study was to compare the effectiveness of a modified version of the BAPT when given in the last trimester (BAPT1) and following delivery (BAPT2) in predicting breastfeeding attrition among 117 women who planned to breastfeed for at least 8 weeks. Subjects completed the BAPT during a prenatal breastfeeding class and again at delivery, and they received a phone call at 8 weeks to determine breastfeeding status. In this study, neither of the two administrations of the BAPT was predictive of breastfeeding status at 8 weeks. Findings here may differ because subjects in the current study were all committed enough to attend breastfeeding class and, thus, varied less on commitment than women in earlier studies. Significant associations were found with level of education and having a close relative who breastfed. To assist the perinatal educator in identifying women most at risk for early cessation of breastfeeding, the use of three questions regarding level of education, family support, and breastfeeding preparation is suggested. PMID:17273370

  8. Modified breastfeeding attrition prediction tool: prenatal and postpartum tests.

    PubMed

    Evans, Marilyn L; Dick, Margaret J; Lewallen, Lynne P; Jeffrey, Cynthia

    2004-01-01

    In earlier studies, the Breastfeeding Attrition Prediction Tool (BAPT) demonstrated predictive validity in the postpartum period. The purpose of this study was to compare the effectiveness of a modified version of the BAPT when given in the last trimester (BAPT1) and following delivery (BAPT2) in predicting breastfeeding attrition among 117 women who planned to breastfeed for at least 8 weeks. Subjects completed the BAPT during a prenatal breastfeeding class and again at delivery, and they received a phone call at 8 weeks to determine breastfeeding status. In this study, neither of the two administrations of the BAPT was predictive of breastfeeding status at 8 weeks. Findings here may differ because subjects in the current study were all committed enough to attend breastfeeding class and, thus, varied less on commitment than women in earlier studies. Significant associations were found with level of education and having a close relative who breastfed. To assist the perinatal educator in identifying women most at risk for early cessation of breastfeeding, the use of three questions regarding level of education, family support, and breastfeeding preparation is suggested.

  9. No. 261-Prenatal Screening for Fetal Aneuploidy in Singleton Pregnancies.

    PubMed

    Chitayat, David; Langlois, Sylvie; Wilson, R Douglas

    2017-09-01

    To develop a Canadian consensus document on maternal screening for fetal aneuploidy (e.g., Down syndrome and trisomy 18) in singleton pregnancies. Pregnancy screening for fetal aneuploidy started in the mid 1960s, using maternal age as the screening test. New developments in maternal serum and ultrasound screening have made it possible to offer all pregnant patients a non-invasive screening test to assess their risk of having a fetus with aneuploidy to determine whether invasive prenatal diagnostic testing is necessary. This document reviews the options available for non-invasive screening and makes recommendations for Canadian patients and health care workers. To offer non-invasive screening for fetal aneuploidy (trisomy 13, 18, 21) to all pregnant women. Invasive prenatal diagnosis would be offered to women who screen above a set risk cut-off level on non-invasive screening or to pregnant women whose personal, obstetrical, or family history places them at increased risk. Currently available non-invasive screening options include maternal age combined with one of the following: (1) first trimester screening (nuchal translucency, maternal age, and maternal serum biochemical markers), (2) second trimester serum screening (maternal age and maternal serum biochemical markers), or (3) 2-step integrated screening, which includes first and second trimester serum screening with or without nuchal translucency (integrated prenatal screen, serum integrated prenatal screening, contingent, and sequential). These options are reviewed, and recommendations are made. Studies published between 1982 and 2009 were retrieved through searches of PubMed or Medline and CINAHL and the Cochrane Library, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational

  10. Modern non-invasive mechanical ventilation turns 25.

    PubMed

    Díaz Lobato, Salvador; Mayoralas Alises, Sagrario

    2013-11-01

    The history of non-invasive mechanical ventilation goes back more than 100 years, but it was not until 1987 when what we could call "modern" non-invasive mechanical ventilation was developed. The description of Delaubier and Rideau of a patient with Duchenne's disease who had been effectively ventilated through a nasal mask marked the start of a new era in the history of non-invasive mechanical ventilation. Over these last 25years, we have witnessed exponential growth in its use, field of activity and technological advances on an exciting fast-paced track. We believe that it is time to review the main milestones that have marked the development of non-invasive mechanical ventilation to date, while paying homage to this therapeutic method that has contributed so much to the advancement of respiratory medicine in the last 25years.

  11. Communication with patients during the prenatal testing procedure: an explorative qualitative study.

    PubMed

    van Zwieten, Myra; Willems, Dick; Knegt, Lia; Leschot, Nico

    2006-10-01

    While generally two phases of prenatal genetic counseling are distinguished, i.e. pre- and post-test counseling, we revealed a third form of communication during the testing procedure. The content of this intermediate communication was explored. A secondary analysis was performed on data obtained in another observational study, which was focussed on how indefinite testing results are clarified. Thirteen testing trajectories in which communication with parents took place during the testing procedure were further analysed. In the majority of cases the content of intermediate communication was similar to the content of pre-test counseling. In four cases the content was different, because the communication involved the parents in decision-making about a testing result, which was still being processed. Communication in (prenatal) genetic testing is not always restricted to separate phases, but can be an ongoing process occurring parallel to, and sometimes even intertwined with, the testing process. The advocated model of shared decision-making might work better once it is determined if the decision concerns the area wherein the provider is the expert, or the patient. Further research into the process of continuing decision-making could clarify how providers' and patients' responsibilities regarding the diagnostic process are distributed. Meanwhile, the possible occurrence of continuous decision-making should be mentioned in (prenatal) genetic counseling.

  12. Prenatal genetic testing: content of discussions between obstetric providers and pregnant women.

    PubMed

    Bernhardt, B A; Geller, G; Doksum, T; Larson, S M; Roter, D; Holtzman, N A

    1998-05-01

    To document the content and accuracy of discussions about prenatal genetic testing between obstetric providers and pregnant women. The first prenatal visits of 169 pregnant women with 21 obstetricians and 19 certified nurse-midwives were audiotaped and analyzed for whether a discussion of family history or genetic testing took place and if so, its length, content, and accuracy. Family history was discussed in 60% of visits, maternal serum marker screening in 60%, second-trimester ultrasonography for fetal anomalies in 34%, and for women at least 35 years old, amniocentesis or chorionic villus sampling (CVS) in 98%. The length of discussions of genetic testing averaged 2.5 minutes for women younger than 35 years of age and 6.9 minutes for older women. Topics discussed most often were the practical details of testing, the purpose of testing, and the fact that testing is voluntary. Discussions seldom were comprehensive. Obstetricians were more likely to make a recommendation about testing than were nurse-midwives and were less likely to indicate that testing is voluntary. Most women were satisfied with the amount of information, and the majority of women of advanced maternal age had made a decision about amniocentesis or CVS by the end of the visit. The information about genetic testing provided in the first prenatal visit is inadequate for ensuring informed autonomous decision-making. Guidelines addressing the content of these discussions should be developed with input from obstetricians, nurse-midwives, genetic counselors, and pregnant women.

  13. The role of attitudes towards the targets of behaviour in predicting and informing prenatal testing choices.

    PubMed

    Bryant, Louise D; Green, Josephine M; Hewison, Jenny

    2010-12-01

    Research considering the role of attitudes in prenatal testing choices has commonly focused on the relationship between the attitude towards undergoing testing and actual testing behaviour. In contrast, this study focused on the relationship between testing behaviour and attitudes towards the targets of the behaviour (in this case people with Down syndrome (DS) and having a baby with DS). A cross-sectional, prospective survey of 197 pregnant women measured attitudes towards the targets of prenatal testing along with intentions to use screening and diagnostic testing, and the termination of an affected pregnancy. Screening uptake was established via patient records. Although attitudes towards DS and having a baby with DS were significantly associated with screening uptake and testing and termination intentions, unfavourable attitudes were better than favourable ones at predicting these outcomes. For example, in the quartile of women with the 'most favourable' attitude towards people with DS 67% used screening although only 8% said they would terminate an affected pregnancy. Qualitative data suggested that not all women considered personal attitudes towards DS to be relevant to their screening decisions. This finding has implications for the way in which informed choice is currently understood and measured in the prenatal testing context.

  14. [Prenatal genetic test and clinical guidance for 213 hereditary deaf families].

    PubMed

    Han, Ming-yu; Lu, Yan-ping; Bian, Xu-ming; Wang, Long-xia; Huang, Sha-sha; Wang, Guo-jian; Wang, Yi; Kang, Dong-yang; Zhang, Xin; Dai, Pu

    2012-02-01

    To summarize the workflow, strategy and experience of prenatal genetic test for deafness based on the 6-year clinical practice. There were 213 families who received prenatal test from 2005 to 2011. Among the 213 families, 205 families had had one deaf child, including 204 couples with normal hearing and one couple of the deaf husband and normal wife, 8 families including 6 couples with normal hearing and 2 deaf couples, had no child before test. Genomic and mitochondrial DNA of each subject was extracted from whole blood. The etiology and recurrent risks in 212 families were confirmed by means of the genetic test of GJB2, SLC26A4 and mtDNA 12sRNA, but one family carried POU3F4 c.647G > A heterozygous mutation causing X-linked hereditary hearing impairment confirmed by pedigree study. The prenatal test was carried out during the pregnancy of all mothers from 11 to 30 weeks, and the following genetic information and counseling were supplied based on the results. The recurrent risk was 25% in 209 families, including 204 families with one deaf child and 5 families without child, among which all couples were GJB2 or SLC26A4 mutation carriers and deaf children were caused by homozygous or compound GJB2/SLC26A4 mutations; The recurrent risk was 50% in 3 families, the father and his child in one family had compound SLC26A4 mutations and the mother with heterozygous SLC26A4 mutation, the wife had POU3F4 c.647G > A heterozygous mutation in another one family, and the husband with compound SLC26A4 mutations and the wife with mtDNA A1555G mutation and heterozygous SLC26A4 mutation simultaneously happened in the rest one family; The recurrent risk was 100% in one family of the deaf couple who were both found to carry homozygous or compound GJB2 mutations, and the deaf wife got pregnant by artificial insemination with the sperm from the local Human Sperm Bank. 226 times of prenatal test were applied in all 213 families that 11 families of them received prenatal test twice, and

  15. A meta-analysis of trait differences between invasive and non-invasive plant species.

    PubMed

    van Kleunen, Mark; Weber, Ewald; Fischer, Markus

    2010-02-01

    A major aim in ecology is identifying determinants of invasiveness. We performed a meta-analysis of 117 field or experimental-garden studies that measured pair-wise trait differences of a total of 125 invasive and 196 non-invasive plant species in the invasive range of the invasive species. We tested whether invasiveness is associated with performance-related traits (physiology, leaf-area allocation, shoot allocation, growth rate, size and fitness), and whether such associations depend on type of study and on biogeographical or biological factors. Overall, invasive species had significantly higher values than non-invasive species for all six trait categories. More trait differences were significant for invasive vs. native comparisons than for invasive vs. non-invasive alien comparisons. Moreover, for comparisons between invasive species and native species that themselves are invasive elsewhere, no trait differences were significant. Differences in physiology and growth rate were larger in tropical regions than in temperate regions. Trait differences did not depend on whether the invasive alien species originates from Europe, nor did they depend on the test environment. We conclude that invasive alien species had higher values for those traits related to performance than non-invasive species. This suggests that it might become possible to predict future plant invasions from species traits.

  16. The Down Syndrome Information Act: Balancing the Advances of Prenatal Testing Through Public Policy.

    PubMed

    Leach, Mark W

    2016-04-01

    Since the dawn of prenatal testing in the 1970s, concerns have been raised over its administration to respect a mother's autonomy as well as the expressive critique against those with the tested-for condition. Advances in prenatal testing have made it such that more mothers than ever are given a test result of Down syndrome, yet are not provided the rest of the information recommended by professional guidelines. In response, first federal legislation and then, increasingly, state legislation is requiring that this information be provided to expectant mothers. Though receiving broad bipartisan support in passage, some of the statutes have received criticism. These public policy measures will be surveyed and evaluated as to their relative merits and limitations.

  17. Clinical outcome of subchromosomal events detected by whole‐genome noninvasive prenatal testing

    PubMed Central

    Helgeson, J.; Wardrop, J.; Boomer, T.; Almasri, E.; Paxton, W. B.; Saldivar, J. S.; Dharajiya, N.; Monroe, T. J.; Farkas, D. H.; Grosu, D. S.

    2015-01-01

    Abstract Objective A novel algorithm to identify fetal microdeletion events in maternal plasma has been developed and used in clinical laboratory‐based noninvasive prenatal testing. We used this approach to identify the subchromosomal events 5pdel, 22q11del, 15qdel, 1p36del, 4pdel, 11qdel, and 8qdel in routine testing. We describe the clinical outcomes of those samples identified with these subchromosomal events. Methods Blood samples from high‐risk pregnant women submitted for noninvasive prenatal testing were analyzed using low coverage whole genome massively parallel sequencing. Sequencing data were analyzed using a novel algorithm to detect trisomies and microdeletions. Results In testing 175 393 samples, 55 subchromosomal deletions were reported. The overall positive predictive value for each subchromosomal aberration ranged from 60% to 100% for cases with diagnostic and clinical follow‐up information. The total false positive rate was 0.0017% for confirmed false positives results; false negative rate and sensitivity were not conclusively determined. Conclusion Noninvasive testing can be expanded into the detection of subchromosomal copy number variations, while maintaining overall high test specificity. In the current setting, our results demonstrate high positive predictive values for testing of rare subchromosomal deletions. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. PMID:26088833

  18. Mucositis and non-invasive markers of small intestinal function.

    PubMed

    Tooley, Katie L; Howarth, Gordon S; Butler, Ross N

    2009-05-01

    Mucositis is a common and debilitating side effect of chemotherapy that manifests due to the inability of chemotherapy agents to discriminate between normal and neoplastic cells. This results in ulcerating lesions lining the gastrointestinal tract. Moreover, the development of efficacious treatments for small intestinal mucositis has been hindered as the pathobiology of mucositis is still not fully understood. The small intestine is an extensive organ which is largely inaccessible by conventional means. Non-invasive biomarkers such as small intestinal permeability, H(2) breath tests, serum citrulline tests and the (13)C-sucrose breath test (SBT) have emerged as potential markers of small intestinal function. The SBT is emerging as the more appropriate biomarker to assess chemotherapy-induced mucositis in cancer patients and animal models, where it measures the decrease in sucrase activity associated with villus blunting and crypt disruption. The SBT has been successfully applied to detect mucositis induced by different classes of chemotherapy agents and has been used successfully to monitor small intestinal function with a range of candidate anti-mucositis treatments. We propose the SBT a superior biomarker of small intestinal function that could be successfully applied in clinical practice for monitoring the development of mucositis in cancer patients undergoing chemotherapy.

  19. Other non-invasive markers of liver fibrosis.

    PubMed

    Leroy, V

    2008-09-01

    An intensive research effort in the field of non-invasive evaluation of liver fibrosis has recently permitted the description and validation of several serum markers of fibrosis, mainly in chronic hepatitis C patients. In addition to the commonly used tests such as FibroTest or FibroMeters, other either indirect (aspartate aminotransferase, prothrombin time, platelets) or direct (PIIINP, hyaluronic acid, metalloproteinases) markers, usually used in combination, have been evaluated. Simple scores such as APRI or FIB-4 have also been widely studied and have revealed interesting, albeit non-comprehensive, data on liver fibrosis, especially in terms of significant, extensive fibrosis or cirrhosis. These simple scores may be proposed as a first-line investigation, bearing in mind their limitations and comparing them with more accurate methods for evaluating liver fibrosis if necessary. Other scores, including direct serum markers, which can be difficult to assess, have given disappointing results that, in general, were either similar to, or only slightly better than, the results of the simpler tests. Further studies are needed to identify new markers that are more accurate and, above all, able to predict the outcome of liver fibrosis.

  20. Prenatal testing for Huntington's disease in the Netherlands from 1998 to 2008.

    PubMed

    van Rij, M C; de Koning Gans, P A M; Aalfs, C M; Elting, M; Ippel, P F; Maat-Kievit, J A; Vermeer, S; Verschuuren-Bemelmans, C C; van Belzen, M J; Belfroid, R D M; Losekoot, M; Geraedts, J P M; Roos, R A C; Tibben, A; de Die-Smulders, C E M; Bijlsma, E K

    2014-01-01

    This study aims to give an overview of the number of prenatal tests for Huntington's disease (HD), test results, and pregnancy outcomes in the Netherlands between 1998 and 2008 and to compare them with available data from the period 1987 to 1997. A total of 126 couples underwent prenatal diagnosis (PND) on 216 foetuses: 185 (86%) direct tests and 31 (14%) exclusion tests. In 9% of direct tests the risk for the foetus was 25%. Four at-risk parents (4%) carried intermediate alleles. Ninety-one foetuses had CAG expansions ≥36% or 50% risk haplotypes: 75 (82%) were terminated for HD, 12 (13%) were carried to term; four pregnancies were miscarried, terminated for other reasons or lost to follow-up. Unaffected pregnancies (122 foetuses) resulted in the birth of 112 children. The estimated uptake of PND was 22% of CAG expansion carriers (≥36 repeats) at reproductive age. PND was used by two new subgroups: carriers of intermediate alleles and 50% at-risk persons opting for a direct prenatal test of the foetus. A significant number of HD expansion or 50% risk pregnancies were continued. Speculations were made on causative factors contributing to these continuations. Further research on these couples' motives is needed.

  1. Fasting plasma glucose test at the first prenatal visit as a screen for gestational diabetes.

    PubMed

    Sacks, David A; Chen, Wansu; Wolde-Tsadik, Girma; Buchanan, Thomas A

    2003-06-01

    To determine whether the fasting plasma glucose test administered at the first prenatal visit could serve as an efficient screen for gestational diabetes. A total of 5557 women not known to have diabetes were offered a fasting plasma glucose test at their first prenatal visit. Results less than 100 mg/dL were blinded. A glucose tolerance test was requested immediately of those whose screening test result was 100-125 mg/dL and of all women not identified as having diabetes by their 23rd gestational week. A total of 4507 women (81%) complied with the protocol. Of the 302 women found to have gestational diabetes, 46 (15%) were detected before 24 weeks. A false-positive rate of 57% was found at a threshold fasting glucose concentration giving a sensitivity of 80% for the detection of gestational diabetes. The fasting plasma glucose screening test at the first prenatal visit has good patient compliance. However, its poor specificity (high false-positive rate) makes it an inefficient screening test for gestational diabetes.

  2. Cost-Effectiveness of Rapid Syphilis Screening in Prenatal HIV Testing Programs in Haiti

    PubMed Central

    Schackman, Bruce R; Neukermans, Christopher P; Fontain, Sandy N. Nerette; Nolte, Claudine; Joseph, Patrice; Pape, Jean W; Fitzgerald, Daniel W

    2007-01-01

    Background New rapid syphilis tests permit simple and immediate diagnosis and treatment at a single clinic visit. We compared the cost-effectiveness, projected health outcomes, and annual cost of screening pregnant women using a rapid syphilis test as part of scaled-up prenatal testing to prevent mother-to-child HIV transmission in Haiti. Methods and Findings A decision analytic model simulated health outcomes and costs separately for pregnant women in rural and urban areas. We compared syphilis syndromic surveillance (rural standard of care), rapid plasma reagin test with results and treatment at 1-wk follow-up (urban standard of care), and a new rapid test with immediate results and treatment. Test performance data were from a World Health Organization–Special Programme for Research and Training in Tropical Diseases field trial conducted at the GHESKIO Center Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes in Port-au-Prince. Health outcomes were projected using historical data on prenatal syphilis treatment efficacy and included disability-adjusted life years (DALYs) of newborns, congenital syphilis cases, neonatal deaths, and stillbirths. Cost-effectiveness ratios are in US dollars/DALY from a societal perspective; annual costs are in US dollars from a payer perspective. Rapid testing with immediate treatment has a cost-effectiveness ratio of $6.83/DALY in rural settings and $9.95/DALY in urban settings. Results are sensitive to regional syphilis prevalence, rapid test sensitivity, and the return rate for follow-up visits. Integrating rapid syphilis testing into a scaled-up national HIV testing and prenatal care program would prevent 1,125 congenital syphilis cases and 1,223 stillbirths or neonatal deaths annually at a cost of $525,000. Conclusions In Haiti, integrating a new rapid syphilis test into prenatal care and HIV testing would prevent congenital syphilis cases and stillbirths, and is cost-effective. A similar approach may

  3. Criminality and the 2D:4D ratio: testing the prenatal androgen hypothesis.

    PubMed

    Ellis, Lee; Hoskin, Anthony W

    2015-03-01

    A decade old theory hypothesizes that brain exposure to androgens promotes involvement in criminal behavior. General support for this hypothesis has been provided by studies of postpubertal circulating levels of testosterone, at least among males. However, the theory also predicts that for both genders, prenatal androgens will be positively correlated with persistent offending, an idea for which no evidence currently exists. The present study used an indirect measure of prenatal androgen exposure-the relative length of the second and fourth fingers of the right hand (r2D:4D)-to test the hypothesis that elevated prenatal androgens promote criminal tendencies later in life for males and females. Questionnaires were administered to 2,059 college students in Malaysia and 1,291 college students in the United States. Respondents reported their r2D:4D relative finger lengths along with involvement in 13 categories of delinquent and criminal acts. Statistically significant correlations between the commission of most types of offenses and r2D:4D ratios were found for males and females even after controlling for age. It is concluded that high exposure to androgens during prenatal development contributes to most forms of offending following the onset of puberty.

  4. [Non-invasive electrical markers in patients with the Brugada syndrome].

    PubMed

    Alvarez-Gómez, Juan Antonio; Dorantes Sánchez, Margarita; Stanley, Jeanice; Stusser Beltranena, Rodolfo; Castro Hevia, Jesús; Barrera Sarduy, Darío; Rivas Estany, Eduardo; Dorticós Balea, Francisco

    2006-01-01

    Throughout the 13 years of recognizing the Brugada syndrome as a separate entity, there has been a search for invasive and non-invasive markers for detecting risk of life-threatening arrhythmic events, particularly for asymptomatic individuals in whom the first manifestation may be sudden cardiac death. Hence, the preclinical diagnosis is pivotal for adequate and timely preventive measures. The objective of this study was to compare various non-invasive markers to characterize and stratify patients at risk. Late potentials, QT interval, QT dispersion, and heart variability were analyzed over a two-year period, in 20 patients (17 men and 3 women) with the Brugada syndrome (symptomatic and asymptomatic) and compared with 20 normal individuals similar in age and gender (control group). Late potentials were present in 80% of patients versus 5% in the control group (p < 0.0001); all of these with recurrent episodes had late potentials. In conclusion, this is the most important non-invasive marker for risk stratification, recurrences and inducibility of malignant arrhythmias during electrophysiological testing. Markers, invasive and non-invasive, should be considered integrally, for a better diagnostic and prognostic approach to reality.

  5. Updates on the use of non-invasive brain stimulation in physical and rehabilitation medicine.

    PubMed

    Williams, Julie A; Imamura, Marta; Fregni, Felipe

    2009-04-01

    Brain stimulation for the treatment of neuropsychiatric diseases has been used for more than 50 years. Although its development has been slow, current advances in the techniques of brain stimulation have improved its clinical efficacy. The use of non-invasive brain stimulation has significant advantages, such as not involving surgical procedures and having relatively mild adverse effects. In this paper we briefly review the use of 2 non-invasive brain stimulation techniques, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), as therapeutic approaches in physical and rehabilitation medicine. We also compare the effects of non-invasive central nervous system stimulation with techniques of non-invasive peripheral electrical stimulation, in order to provide new insights for future developments. Although the outcomes of these initial trials include some conflicting results, the evidence supports that rTMS and tDCS might have a therapeutic value in different neurological conditions. Studies published within the last year have examined new approaches of stimulation, such as longer intensities of stimulation, new electrode sizes for tDCS, novel coils for stimulation of deeper areas, and new frequencies of stimulation for rTMS. These new approaches need to be tested in larger clinical trials in order to determine whether they offer significant clinical effects.

  6. Qualifying choice: ethical reflection on the scope of prenatal screening.

    PubMed

    Stapleton, Greg

    2017-06-01

    In the near future developments in non-invasive prenatal testing (NIPT) may soon provide couples with the opportunity to test for and diagnose a much broader range of heritable and congenital conditions than has previously been possible. Inevitably, this has prompted much ethical debate on the possible implications of NIPT for providing couples with opportunities for reproductive choice by way of routine prenatal screening. In view of the possibility to test for a significantly broader range of genetic conditions with NIPT, the European Society of Human Genetics (ESHG) and American Society of Human Genetics (ASHG) recommend that, pending further debate, prenatal screening for reproductive choice should only be offered where concerning serious congenital conditions and childhood disorders. In support of this recommendation, the ESHG and ASHG discuss a number of ethical issues on which they prompt further debate: the informational privacy of the future child, the trivialization of abortion, the risk of information overload, and issues of distributive justice. This paper responds to this call with further reflection on each ethical issue and how it relates to the moral justification of providing couples with opportunities for meaningful reproductive choice. The paper concludes that whilst there may be good reasons for qualifying the scope of any unsolicited prenatal screening offer to serious congenital conditions and childhood disorders, if prenatal screening is justified for providing couples with opportunities for meaningful reproductive choice, then health services may have obligations to empower couples with the same opportunity where concerning other conditions.

  7. Do prenatally methamphetamine-exposed adult male rats display general predisposition to drug abuse in the conditioned place preference test?

    PubMed

    Šlamberová, R; Pometlová, M; Schutová, B; Hrubá, L; Macúchová, E; Nová, E; Rokyta, R

    2012-01-01

    Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.

  8. Cell-free fetal DNA testing for fetal aneuploidy and beyond: clinical integration challenges in the US context

    PubMed Central

    Allyse, Megan; Sayres, Lauren C.; King, Jaime S.; Norton, Mary E.; Cho, Mildred K.

    2012-01-01

    The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field. Ongoing research portends the arrival of a wide range of cffDNA tests. However, it is not yet clear how these tests will be integrated into well-established prenatal testing strategies in the USA, as the timing of such testing and the degree to which new non-invasive tests will supplement or replace existing screening and diagnostic tools remain uncertain. We argue that there is an urgent need for policy-makers, regulators and professional societies to provide guidance on the most efficient and ethical manner for such tests to be introduced into clinical practice in the USA. PMID:22863603

  9. Tissue Damage Characterization Using Non-invasive Optical Modalities

    NASA Astrophysics Data System (ADS)

    Diaz, David

    The ability to determine the degree of cutaneous and subcutaneous tissue damage is essential for proper wound assessment and a significant factor for determining patient treatment and morbidity. Accurate characterization of tissue damage is critical for a number of medical applications including surgical removal of nonviable tissue, severity assessment of subcutaneous ulcers, and depth assessment of visually open wounds. The main objective of this research was to develop a non-invasive method for identifying the extent of tissue damage underneath intact skin that is not apparent upon visual examination. This work investigated the relationship between tissue optical properties, blood flow, and tissue viability by testing the hypotheses that (a) changes in tissue oxygenation and/or microcirculatory blood flow measurable by Diffuse Near Infrared Spectroscopy (DNIRS) and Diffuse Correlation Spectroscopy (DCS) differ between healthy and damaged tissue and (b) the magnitude of those changes differs for different degrees of tissue damage. This was accomplished by developing and validating a procedure for measuring microcirculatory blood flow and tissue oxygenation dynamics at multiple depths (up to 1 centimeter) using non-invasive DCS and DNIRS technologies. Due to the lack of pressure ulcer animal models that are compatible with our optical systems, a proof of concept was conducted in a porcine burn model prior to conducting clinical trials in order to assess the efficacy of the system in-vivo. A reduction in total hemoglobin was observed for superficial (5%) and deep burns (35%) along with a statistically significant difference between the optical properties of superficial and deep burns (p < 0.05). Burn depth and viable vessel density were estimated via histological samples. 42% of vessels in the dermal layer were viable for superficial burns, compared to 25% for deep burns. The differences detected in optical properties and hemoglobin content by optical measurements

  10. Non-invasive photo acoustic approach for human bone diagnosis.

    PubMed

    Thella, Ashok Kumar; Rizkalla, James; Helmy, Ahdy; Suryadevara, Vinay Kumar; Salama, Paul; Rizkalla, Maher

    2016-12-01

    The existing modalities of bone diagnosis including X-ray and ultrasound may cite drawback in some cases related to health issues and penetration depth, while the ultrasound modality may lack image quality. Photo acoustic approach however, provides light energy to the acoustic wave, enabling it to activate and respond according to the propagating media (which is type of bones in this case). At the same time, a differential temperature change may result in the bio heat response, resulting from the heat absorbed across the multiple materials under study. In this work, we have demonstrated the features of using photo acoustic modality in order to non-invasively diagnose the type of human bones based on their electrical, thermal, and acoustic properties that differentiate the output response of each type. COMSOL software was utilized to combine both acoustic equations and bio heat equations, in order to study both the thermal and acoustic responses through which the differential diagnosis can be obtained. In this study, we solved both the acoustic equation and bio heat equations for four types of bones, bone (cancellous), bone (cortical), bone marrow (red), and bone marrow (yellow). 1 MHz acoustic source frequency was chosen and 10(5) W/m(2) power source was used in the simulation. The simulation tested the dynamic response of the wave over a distance of 5 cm from each side for the source. Near 2.4 cm was detected from simulation from each side of the source with a temperature change of within 0.5 K for various types of bones, citing a promising technique for a practical model to detect the type of bones via the differential temperature as well as the acoustic was response via the multiple materials associated with the human bones (skin and blood). The simulation results suggest that the PA technique may be applied to non-invasive diagnosis for the different types of bones, including cancerous bones. A practical model for detecting both the temperature change via

  11. Tumor LOH analysis provides reliable linkage information for prenatal genetic testing of sporadic NF1 patients.

    PubMed

    Serra, Eduard; Pros, Eva; García, Carles; López, Eva; Gili, M Lluïsa; Gómez, Carolina; Ravella, Anna; Capellá, Gabriel; Blanco, Ignacio; Lázaro, Conxi

    2007-09-01

    The neurofibromatosis type 1 gene has one of the highest mutation rates in humans: about 50% of NF1 patients are de novo cases. Although direct mutation characterization has greatly improved over the past decade, in the context of clinical genetics services worldwide, there is still a significant number of patients for which, while fulfilling NF1 clinical criteria, no constitutive mutation is found at a desired time. This is particularly critical for prenatal genetic testing of sporadic cases. Here we describe the use of loss of heterozygosity information in neurofibromas to obtain linkage information on the affected NF1 haplotype, which may be applied for prenatal testing in sporadic patients. However, proper genetic counseling should be provided regarding the possibility of somatic mosaicism.

  12. Effective radiation doses associated with non-invasive versus invasive assessment of coronary anatomy and physiology.

    PubMed

    Toth, G G; Ntalianis, A; Ntarladimas, Y; de Booij, M; De Winter, O; Barbato, E; Pilet, B; Van Mieghem, C; Wijns, W; De Bruyne, B

    2015-06-01

    To compare the effective radiation dose (ERD) needed to obtain information on coronary anatomy and physiology by a non-invasive versus an invasive diagnostic strategy. Knowledge of anatomy and physiology is needed for management of patients with coronary artery disease (CAD). There is, however, a growing concern about detrimental long-term effects of radiation associated with diagnostic procedures. In a total of 671 patients with suspected CAD, we compared the ERD needed to obtain anatomical and physiological information through a non-invasive strategy or an invasive strategy. The non-invasive strategy consisted of coronary computed tomography angiography (CCTA) and single photon emission computed tomography (SPECT). The invasive strategy included coronary angiography (CA) and fractional flow reserve (FFR) measurement. In 464 patients, the data were acquired in Period 2009 and in 207 the data were acquired in Period 2011 (after each period, the CCTA- and the CA-equipment had been upgraded). For the Period 2009 total ERD of the non-invasive approach was significantly larger compared to the invasive approach (28.45 ± 5.37 mSv versus 15.79 ± 7.95 mSv, respectively; P < 0.0001). For Period 2011, despite the significant decrease in ERD for both groups (P<0.0001 for both), the ERD remained higher for the non-invasive approach compared to the invasive approach (16.67 ± 10.45 mSv vs. 10.36 ± 5.87 mSv, respectively; P < 0.0001). Simulation of various diagnostic scenarios showed cumulative radiation dose is the lowest when a first positive test is followed by an invasive strategy. To obtain anatomic and physiologic information in patients with suspected CAD, the combination of CA and FFR is associated with lower ERD than the combination of CCTA and SPECT. © 2014 Wiley Periodicals, Inc.

  13. Umbilical diagnosis as a non-invasive visual diagnostic aide.

    PubMed

    Shimotsuura, Yasuhiro; Nishimura, Mitsuhiro; Kawabata, Rikimaru; Ohki, Motomu; Kawashima, Hiroshi; Ichiki, Masato; Matsunobu, Takanori; Omura, Yoshiaki

    2003-01-01

    Using Bi-Digital O-Ring Test (Omura, Y. 1977-2002; BDORT), we have researched the abnormal shapes of the umbilicus and the surrounding areas of the umbilicus, and the relationship between diseased internal organs and abnormal shape and direction of the radial sulcus of the umbilicus for several years. In this report we have mapped the organ representation area of the umbilicus and its surrounding areas of a healthy person by using BDORT. Then the abnormal organs around the umbilicus of the patients with certain diseases were mapped by using BDORT. Also Oncogene C-fos Ab2 positive response network (specially relation between the radial sulcus and the disease) of the cancer response (Oncogene C-fos Ab2) positive person were examined all over the body. In many cases, the radial sulcus from the umbilicus and the organ representation area of abnormal organs at the umbilicus of diseased person mapped using BDORT were highly correlated. Abnormality observed in a specific organ with strong resonance by BDORT meridian network was connected to the umbilicus. Mapped chart of the organ representation area surrounding the umbilicus is clinically very useful for non-invasive visual umbilical diagnosis.

  14. Non-invasive diagnosis of mitral regurgitation by Doppler echocardiography.

    PubMed Central

    Blanchard, D; Diebold, B; Peronneau, P; Foult, J M; Nee, M; Guermonprez, J L; Maurice, P

    1981-01-01

    The value of Doppler echocardiography for the non-invasive diagnosis of mitral regurgitation was studied blindly in 161 consecutive invasively investigated adult patients. Regurgitation was graded from 0 to 3 at selective left ventricular angiography. The Doppler echocardiographic examination was considered to be positive when a disturbed systolic flow was found within the left atrium behind the aorta or the anterior leaflet of the mitral valve. The test was considered to be negative in the absence of a regurgitant jet. The level of the signal to noise ratio was checked by the recording of the ventricular filling flow. The study was performed in 131 cases from the left side of the sternum and in 101 cases from the apex. There were no false positives and thus the specificity was 100 per cent. The 20 false negatives were all in patients with grade 1 regurgitation. Thus only some (33%) instances of mild regurgitation were misdiagnosed, and the sensitivity for moderate to severe mitral regurgitation was 100 per cent. PMID:7236465

  15. Genotyping approach for non-invasive foetal RHD detection in an admixed population

    PubMed Central

    Boggione, Carolina Trucco; Luján Brajovich, Melina E.; Mattaloni, Stella M.; Di Mónaco, René A.; García Borrás, Silvia E.; Biondi, Claudia S.; Cotorruelo, Carlos M.

    2017-01-01

    Background Non-invasive foetal RHD genotyping can predict haemolytic disease of the foetus and the newborn in pregnancies with anti-D alloantibodies and also avoid antenatal anti-D prophylaxis in pregnant women carrying an RHD negative foetus. Considering that the Argentine genetic background is the result of generations of intermixing between several ethnic groups, we evaluated the diagnostic performance of a non-invasive foetal RHD determination strategy to guide targeted antenatal RhD immunoprophylaxis. This algorithm is based on the analysis of four regions of the RHD gene in cell-free foetal DNA in maternal plasma and maternal and paternal RHD genotyping. Materials and methods DNA from 298 serologically D negative pregnant women between 19–28 weeks gestation were RHD genotyped. Foetal RHD status was determined by real-time PCR in 296 maternal plasma samples. In particular cases, RHDΨ and RHD-CE-Ds alleles were investigated in paternal DNA. Umbilical cord blood was collected at birth, and serological and molecular studies were performed. Results Of the 298 maternal samples, 288 were D−/RHD− and 10 D−/RHD+ (2 RHD*DAR; 5 RHD-CE-Ds; 3 RHDΨ). Plasma from RHD*DAR carriers was not analysed. Real-time PCR showed 210 RHD+ and 78 RHD− foetuses and 8 inconclusive results. In this latter group, paternal molecular studies were useful to report a RHD negative status in 5 foetuses while only 3 remained inconclusive. All the results, except one false positive due to a silent allele (RHD[581insG]), agreed with the neonatal typing performed in cord blood. Discussion The protocol used for non-invasive prenatal RHD genotyping proved to be suitable to determine foetal RHD status in our admixed population. The knowledge of the genetic background of the population under study and maternal and paternal molecular analysis can reduce the number of inconclusive results when investigating foetal RHD status. PMID:27136427

  16. Midwives and information on prenatal testing with focus on Down syndrome.

    PubMed

    Ternby, Ellen; Ingvoldstad, Charlotta; Annerén, Göran; Axelsson, Ove

    2015-12-01

    To investigate midwives' knowledge of prenatal diagnosis especially Down syndrome, information given by midwives to parents, expectant parents' requests for information and how midwives perceive their own competence to give information. A cross-sectional, prospective study with a questionnaire was completed by 64 out of 70 midwives working in the outpatient antenatal care in Uppsala County, Sweden. The midwives had varying and in some areas low levels of knowledge about Down syndrome. Information about Down syndrome was most often given only when asked for or when there was an increased probability of a Down syndrome pregnancy. The most common questions from expectant parents concerned test methods and risk assessments while questions regarding symptoms of Down syndrome and consequences of having a child with Down syndrome were uncommon. The majority (83-89%) had insufficient or no education regarding different prenatal tests. Only two midwives (3%) had received education about Down syndrome, and 9% felt they had sufficient knowledge to inform about the syndrome. More education about prenatal tests and Down syndrome was desired by 94%. It is important to ensure that midwives in antenatal care have sufficient knowledge to inform expectant parents about the conditions screened for. © 2015 John Wiley & Sons, Ltd. © 2015 John Wiley & Sons, Ltd.

  17. Noninvasive Prenatal Paternity Testing (NIPAT) through Maternal Plasma DNA Sequencing: A Pilot Study

    PubMed Central

    Ge, Huijuan; Deng, Yongqiang; Mu, Haofang; Feng, Xiaoli; Yin, Lu; Du, Zhou; Chen, Fang; He, Nongyue

    2016-01-01

    Short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) have been already used to perform noninvasive prenatal paternity testing from maternal plasma DNA. The frequently used technologies were PCR followed by capillary electrophoresis and SNP typing array, respectively. Here, we developed a noninvasive prenatal paternity testing (NIPAT) based on SNP typing with maternal plasma DNA sequencing. We evaluated the influence factors (minor allele frequency (MAF), the number of total SNP, fetal fraction and effective sequencing depth) and designed three different selective SNP panels in order to verify the performance in clinical cases. Combining targeted deep sequencing of selective SNP and informative bioinformatics pipeline, we calculated the combined paternity index (CPI) of 17 cases to determine paternity. Sequencing-based NIPAT results fully agreed with invasive prenatal paternity test using STR multiplex system. Our study here proved that the maternal plasma DNA sequencing-based technology is feasible and accurate in determining paternity, which may provide an alternative in forensic application in the future. PMID:27631491

  18. Obstetrician and Gynecologist Utilization of the Noninvasive Prenatal Testing Expanded Option

    PubMed Central

    Mayes, Sarah; Hashmi, Syed; Turrentine, Mark A.; Darilek, Sandra; Friel, Lara A.; Czerwinski, Jennifer

    2015-01-01

    Objective Noninvasive prenatal testing (NIPT) enables the detection of common fetal aneuploidies such as trisomy 21, trisomy 18, trisomy 13, and sex chromosome abnormalities via analysis of cell-free fetal DNA circulating in maternal serum. In October 2013, the option to screen for additional trisomies and select microdeletion syndromes became clinically available. The complex testing methods, oftentimes unclear clinical utility of results, and lack of professional guidelines renders it challenging for clinicians to keep abreast of evolving prenatal screening options. We undertook a survey to assess physicians' awareness of, utilization of, and attitudes toward the expanded NIPT option. Study Design Obstetricians attending hospital service meetings in the Houston Texas Medical Center completed an anonymous survey regarding the utilization patterns of expanded NIPT. Results Overall, 85 obstetricians were surveyed. While all respondents indicated awareness of NIPT in its traditional form, 75% (64/85) were aware of the expanded testing option, and 14% (12/85) reported having ordered the expanded NIPT option. A total of 91% (77/85) expressed that practitioners need more information regarding the screening. Conclusion Based on these findings and the fluid landscape of prenatal screening, education, and reeducation of health care professionals is imperative to ensure responsible patient counseling, informed consent, and appropriate posttest management. PMID:26929864

  19. Do parental perceptions and motivations towards genetic testing and prenatal diagnosis for deafness vary in different cultures?

    PubMed

    Nahar, Risha; Puri, Ratna D; Saxena, Renu; Verma, Ishwar C

    2013-01-01

    Surveys of attitudes of individuals with deafness and their families towards genetic testing or prenatal diagnosis have mostly been carried out in the West. It is expected that the perceptions and attitudes would vary amongst persons of different cultures and economic background. There is little information on the prevailing attitudes for genetic testing and prenatal diagnosis for deafness in developing countries. Therefore, this study evaluates the motivations of Indian people with inherited hearing loss towards such testing. Twenty-eight families with history of congenital hearing loss (23 hearing parents with child/family member with deafness, 4 couples with both partners having deafness and 1 parent and child with deafness) participated in a semi-structured survey investigating their interest, attitudes, and intentions for using genetic and prenatal testing for deafness. Participants opinioned that proper management and care of individuals with deafness were handicapped by limited rehabilitation facilities with significant financial and social burden. Nineteen (68%) opted for genetic testing. Twenty-six (93%) expressed high interest in prenatal diagnosis, while 19 (73%) would consider termination of an affected fetus. Three hearing couples, in whom the causative mutations were identified, opted for prenatal diagnosis. On testing, all the three fetuses were affected and the hearing parents elected to terminate the pregnancies. This study provides an insight into the contrasting perceptions towards hearing disability in India and its influence on the desirability of genetic testing and prenatal diagnosis.

  20. 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

  1. Non-invasive femoropopliteal assessment: is that angiogram really necessary?

    PubMed Central

    Shearman, C P; Gwynn, B R; Curran, F; Gannon, M X; Simms, M H

    1986-01-01

    A method of non-invasive preoperative assessment of chronically ischaemic legs was developed that used clinical data and data derived from Doppler ultrasonography to produce a numerical score that could be compared with an angiographic score for stenosis of the popliteal artery trifurcation. The two scoring systems were applied retrospectively to 144 legs after femorodistal bypass. A close correlation was observed (r = 0.89, p less than 0.001), and both systems tended to predict the level of grafting undertaken. A prospective comparison was then made in 81 ischaemic legs that were examined by arteriography; the correlation between the two scoring systems remained close (r = 0.89, p less than 0.001), and the level of bypass was correctly predicted by the non-invasive assessment in 44 of 50 legs that were operated on. Use of the non-invasive assessment subsequently greatly reduced the indications for preoperative arteriography in patients requiring femorodistal vascular reconstruction. PMID:3094784

  2. Congenital anomalies: parents' anxiety and women's concerns before prenatal testing and women's opinions towards the risk factors.

    PubMed

    Sahin, Nevin Hotun; Gungor, Ilkay

    2008-03-01

    The aims of the study were to determine parents' anxiety and women's concerns before prenatal testing and women's opinions towards the risk factors for congenital anomalies. Undergoing prenatal screening or diagnostic tests cause potential distress and worry for parents. Little attention has been paid to the psychological aspect of such testing in clinical and research areas. This descriptive study was conducted in a prenatal diagnosis unit in a university hospital in Istanbul. The convenience sample of the study consisted of 200 women and 104 partners who applied for prenatal screening or diagnosis tests. Women were interviewed by the researcher before they underwent prenatal screening or diagnostic procedures. Data were gathered through interviews using an interview form that addressed women's evaluations for causes of fear and their opinions towards the risk factors for congenital anomalies. Spielberger State Anxiety Inventory was used to assess parents' anxiety before prenatal testing. Anxiety scores of women and their partners were higher in invasive tests group and suspicious findings group. The possibility of a malformation detected and of it being missed were major concerns of women. Receiving insufficient information about the procedure, undergoing this test for the first time, smoking and lower education was associated with increased anxiety scores in women. Although women knew about some certain risk factors for congenital anomalies like drug use, smoking and malnutrition, their knowledge about other risks were not sufficient. Prenatal tests, both routine screening and prenatal diagnosis, cause anxiety for parents. Understanding women's concerns and awareness of risk factors are important for providing care and counselling. Relevance to clinical practice. Nurses can provide appropriate information and support at each step in the screening and diagnosis process so that parents' psychological stress is minimised.

  3. An Acetone Nanosensor For Non-invasive Diabetes Detection

    NASA Astrophysics Data System (ADS)

    Wang, L.; Yun, X.; Stanacevic, M.; Gouma, P. I.

    2009-05-01

    Diabetes is a most common disease worldwide. Acetone in exhaled breath is a known biomarker of Type- 1 diabetes. An exhaled breath analyzer has been developed with the potential to diagnose diabetes as a non-invasive alternative of the currently used blood-based diagnostics. This device utilizes a chemiresistor based on ferroelectric tungsten oxide nanoparticles and detects acetone selectively in breath-simulated media. Real-time monitoring of the acetone concentration is feasible, potentially making this detector a revolutionary, non- invasive, diabetes diagnostic tool.

  4. Non-invasive high resolving power quantum microscope

    NASA Astrophysics Data System (ADS)

    Karmakar, Sanjit; Meyers, Ronald; Shih, Yanhua

    2013-09-01

    The development of a non-invasive high resolving power quantum microscope would further advance progress in research and development in biomedical and biosciences as well as the field of medical technology. Longer wavelengths, i.e visible or near-infrared, provide less invasive impact. On the other hand shorter wavelengths, i.e. UV, can provide better resolving power. That is why the development of a non-invasive high resolving power quantum microscope is critical. In this article, we propose such a microscope by using two-color entangled photon ghost imaging technology.

  5. Non-invasive brain stimulation in early rehabilitation after stroke.

    PubMed

    Blesneag, A V; Popa, L; Stan, A D

    2015-01-01

    The new tendency in rehabilitation involves non-invasive tools that, if applied early after stroke, promote neurorecovery. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation may correct the disruption of cortical excitability and effectively contribute to the restoration of movement and speech. The present paper analyses the results of non-invasive brain stimulation (NIBS) trials, highlighting different aspects related to the repetitive transcranial magnetic stimulation frequency, transcranial direct current stimulation polarity, the period and stimulation places in acute and subacute ischemic strokes. The risk of adverse events, the association with motor or language recovery specific training, and the cumulative positive effect evaluation are also discussed.

  6. A new microtomographic technique for non-invasive evaluation of the bone structure around implants.

    PubMed

    Sennerby, L; Wennerberg, A; Pasop, F

    2001-02-01

    A new X-ray microtomographic technique for non-invasive assessment of the structure of bone surrounding implants was tested. Three titanium microimplants retrieved directly (n = 2) or 6 months (n = 1) after insertion in 3 patients were used as test samples. Two samples were used dry and one was embedded in plastic resin prior to microtomography. The technique provided high-resolution consecutive cross-sectional X-ray images of the specimens with a slice-to-slice distance of 4.4 to 11.0 microns. The pictures could be imported into an image analysing software with which semiautomatic quantitative measurement of the bone area and three-dimensional images of the specimens could be made. It is suggested that the technique may be used for non-invasive assessment of the bone structure around implants. Further studies are needed to evaluate the accuracy of the technique, for instance by comparing tomographic sections with histologic ones.

  7. Non-invasive investigation of inflammatory bowel disease

    PubMed Central

    Tibble, JA; Bjarnason, I

    2001-01-01

    The assessment of inflammatory activity in intestinal disease in man can be done using a variety of different techniques. These range from the use of non-invasive acute phase inflammatory markers measured in plasma such as C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) (both of which give an indirect assessment of disease activity) to the direct assessment of disease activity by intestinal biopsy performed during endoscopy in association with endoscopic scoring systems. Both radiology and endoscopy are conventional for the diagnosis of inflammatory bowel disease (IBD). However these techniques have severe limitations when it comes to assessing functional components of the disease such as activity and prognosis. Here we briefly review the value of two emerging intestinal function tests. Intestinal permeability, although ideally suited for diagnostic screening for small bowel Crohn’s disease, appears to give reliable predictive data for imminent relapse of small bowel Crohn’s disease and it can be used to assess responses to treatment. More significantly it is now clear that single stool assay of neutrophil specific proteins (calprotectin, lactoferrin) give the same quantitative data on intestinal inflammation as the 4-day faecal excretion of 111Indium labelled white cells. Faecal calprotectin is shown to be increased in over 95% of patients with IBD and correlates with clinical disease activity. It reliably differentiates between patients with IBD and irritable bowel syndrome. More importantly, at a given faecal calprotectin concentration in patients with quiescent IBD, the test has a specificity and sensitivity in excess of 85% in predicting clinical relapse of disease. This suggests that relapse of IBD is closely related to the degree of intestinal inflammation and suggests that targeted treatment at an asymptomatic stage of the disease may be indicated. PMID:11819811

  8. "If it helps..." the use of microarray technology in prenatal testing: patient and partners reflections.

    PubMed

    Hillman, Sarah C; Skelton, John; Quinlan-Jones, Elizabeth; Wilson, Amie; Kilby, Mark D

    2013-07-01

    The objective was to gain insight into the experiences of women and their partners diagnosed with a fetal abnormality on prenatal ultrasound examination and receiving genetic testing including microarray. Twenty-five semi-structured interviews were performed with women +/- their partners after receiving the results of prenatal genetic testing. Framework analysis was performed to elicit themes and subthemes. Five main themes were recognized; diagnosis, genetic testing, family and support, reflections of the treatment received and emotions. Our results showed that women recall being told about QFPCR for trisomy 13, 18, and 21 but often no further testing. Women expected the conventional karyotype and microarray result would be normal following a normal QFPCR result. There were frequent misconceptions by couples regarding aspects of counseling/testing. Communication of variants of unknown (clinical) significance (VOUS) presents a particularly difficult challenge. Good clear communication by health care professionals is paramount. When counseling women and their partners for fetal chromosomal testing it should be reinforced that although the most common, trisomy 13, 18, and 21 only account for some of the chromosomal changes resulting in abnormal scan findings. Couples should have literature to take home summarizing scan anomalies and reinforcing information about genetic testing.

  9. Method for non-invasive detection of ocular melanoma

    DOEpatents

    Lambrecht, R.M.; Packer, S.

    1984-10-30

    An apparatus and method is disclosed for diagnosing ocular cancer that is both non-invasive and accurate. The apparatus comprises two radiation detectors positioned before each of the patient's eyes which will measure the radiation level produced in each eye after the administration of a tumor-localizing radiopharmaceutical such as gallium-67. 2 figs.

  10. Non-invasive method of measuring cerebral spinal fluid pressure

    NASA Technical Reports Server (NTRS)

    Borchert, Mark S. (Inventor); Lambert, James L. (Inventor)

    2000-01-01

    The invention provides a method of non-invasively determining intracranial pressure from measurements of an eye. A parameter of an optic nerve of the eye is determined, along with an intraocular pressure of the eye. The intracranial pressure may be determined from the intraocular pressure and the parameter.

  11. Eyeblink Conditioning: A Non-Invasive Biomarker for Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Reeb-Sutherland, Bethany C.; Fox, Nathan A.

    2015-01-01

    Eyeblink conditioning (EBC) is a classical conditioning paradigm typically used to study the underlying neural processes of learning and memory. EBC has a well-defined neural circuitry, is non-invasive, and can be employed in human infants shortly after birth making it an ideal tool to use in both developing and special populations. In addition,…

  12. [Non-invasive ventilation and acute cardiogenic pulmonary oedema].

    PubMed

    Golmard, Céline

    2015-11-01

    Non-invasive ventilation is an integral part of therapies used in patients presenting acute cardiogenic pulmonary oedema. In cardiac intensive care, these patients are treated by teams trained and practised in this technique. The nurses play a central role in the support and monitoring of the patients.

  13. Method for non-invasive detection of ocular melanoma

    DOEpatents

    Lambrecht, Richard M.; Packer, Samuel

    1984-01-01

    There is described an apparatus and method for diagnosing ocular cancer that is both non-invasive and accurate which comprises two radiation detectors positioned before each of the patient's eyes which will measure the radiation level produced in each eye after the administration of a tumor-localizing radiopharmaceutical such as gallium-67.

  14. Non-invasive treatment options for focal cortical dysplasia

    PubMed Central

    WANG, TING-TING; ZHOU, DONG

    2016-01-01

    Focal cortical dysplasia (FCD) presents a strong clinical challenge especially for the treatment of the associated epilepsy. Epilepsy in FCD is often treatment-resistant and constitutes 50% of treatment-resistant cases. Antiepileptic drugs (AEDs) have been widely used in the treatment of FCD. However, evidence to suggest their specific effect on the treatment of FCD remains to be established. In view of this resistance, several alternative treatments have been suggested. Although treatment currently involves surgical management, non-invasive treatments have been identified. The aim of the present review, was to assess non-invasive management strategies including, i) mammalian target of rapamycin (mTOR) inhibitors, ii) ketogenic diet (KD), and iii) vagus nerve stimulation (VNS). In addition, we discussed the literature available regarding the use of AEDs in FCD. Experiments conducted with mammals detailing rapamycin gene mutations in FCD have produced vital information for exploring treatment options using mTOR inhibitors. Of note is the importance of KD in children with FCD. This diet has been shown to modify disease progression by attenuating chromatin modification, a master regulator for gene expression and functional adaptation of the cell. FCD has also been studied widely with neurostimulation techniques. The outcomes of these techniques have been found to be variable. For widespread dysplasias, VNS has been shown to produce responder rates of >50%. Nevertheless, non-invasive cranial nerve stimulation techniques such as transcutaneous VNS and non-invasive VNS are gaining better patient compatibility, albeit their efficacy remains to be established. PMID:27168769

  15. Why SQUID experiments can rule out non-invasive measurability

    NASA Astrophysics Data System (ADS)

    Elby, Andrew; Foster, Sara

    1992-06-01

    From macrorealism and non-invasive measurability (NIM), Leggett and Garg derive inequalities that contradict QM's predictions for SQUIDs. We derive those inequalities from NIM and a “realism” assumption weaker than macrorealism. If Tesche's null-result measurements violate those inequalities, our derivation suggests that NIM is the “culprit” and must be renounced.

  16. Non-invasive Prediction of Pork Loin Tenderness

    USDA-ARS?s Scientific Manuscript database

    The present experiment was conducted to develop a non-invasive method to predict tenderness of pork loins. Boneless pork loins (n = 901) were evaluated either on line on the loin boning and trimming line of large-scale commercial plants (n = 465) or at the U.S. Meat Animal Research Center abattoir ...

  17. Eyeblink Conditioning: A Non-Invasive Biomarker for Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Reeb-Sutherland, Bethany C.; Fox, Nathan A.

    2015-01-01

    Eyeblink conditioning (EBC) is a classical conditioning paradigm typically used to study the underlying neural processes of learning and memory. EBC has a well-defined neural circuitry, is non-invasive, and can be employed in human infants shortly after birth making it an ideal tool to use in both developing and special populations. In addition,…

  18. Non-invasive in vivo measurement of macular carotenoids

    NASA Technical Reports Server (NTRS)

    Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)

    2009-01-01

    A non-invasive in vivo method for assessing macular carotenoids includes performing Optical Coherence Tomography (OCT) on a retina of a subject. A spatial representation of carotenoid levels in the macula based on data from the OCT of the retina can be generated.

  19. 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

  20. Non-invasive, non-radiological quantificationof anteroposterior knee joint ligamentous laxity: A study in cadavers.

    PubMed

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

    2013-01-01

    We performed in vitro validation of a non-invasive skin-mounted system that could allow quantification of anteroposterior (AP) laxity in the outpatient setting. 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. 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). 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.

  1. Non-invasive estimation of hyperthermia temperatures with ultrasound.

    PubMed

    Arthur, R M; Straube, W L; Trobaugh, J W; Moros, E G

    2005-09-01

    Ultrasound is an attractive modality for temperature monitoring because it is non-ionizing, convenient, inexpensive and has relatively simple signal processing requirements. This modality may be useful for temperature estimation if a temperature-dependent ultrasonic parameter can be identified, measured and calibrated. The most prominent methods for using ultrasound as a non-invasive thermometer exploit either (1) echo shifts due to changes in tissue thermal expansion and speed of sound (SOS), (2) variation in the attenuation coefficient or (3) change in backscattered energy from tissue inhomogeneities. The use of echo shifts has received the most attention in the last decade. By tracking scattering volumes and measuring the time shift of received echoes, investigators have been able to predict the temperature from a region of interest both theoretically and experimentally in phantoms, in isolated tissue regions in vitro and preliminary in vivo studies. A limitation of this method for general temperature monitoring is that prior knowledge of both SOS and thermal-expansion coefficients is necessary. Acoustic attenuation is dependent on temperature, but with significant changes occurring only at temperatures above 50 degrees C, which may lead to its use in thermal ablation therapies. Minimal change in attenuation, however, below this temperature range reduces its attractiveness for use in clinical hyperthermia. Models and measurements of the change in backscattered energy suggest that, over the clinical hyperthermia temperature range, changes in backscattered energy are dependent on the properties of individual scatterers or scattering regions. Calibration of the backscattered energy from different tissue regions is an important goal of this approach. All methods must be able to cope with motion of the image features on which temperature estimates are based. A crucial step in identifying a viable ultrasonic approach to temperature estimation is its performance during

  2. Non-Invasive Mouse Models of Post-Traumatic Osteoarthritis

    PubMed Central

    Christiansen, Blaine A.; Guilak, Farshid; Lockwood, Kevin A.; Olson, Steven A.; Pitsillides, Andrew A.; Sandell, Linda J.; Silva, Matthew J.; van der Meulen, Marjolein C. H.; Haudenschild, Dominik R.

    2015-01-01

    Animal models of osteoarthritis (OA) are essential tools for investigating the development of the disease on a more rapid timeline than human OA. Mice are particularly useful due to the plethora of genetically modified or inbred mouse strains available. The majority of available mouse models of OA use a joint injury or other acute insult to initiate joint degeneration, representing post-traumatic osteoarthritis (PTOA). However, no consensus exists on which injury methods are most translatable to human OA. Currently, surgical injury methods are most commonly used for studies of OA in mice; however, these methods may have confounding effects due to the surgical/invasive injury procedure itself, rather than the targeted joint injury. Non-invasive injury methods avoid this complication by mechanically inducing a joint injury externally, without breaking the skin or disrupting the joint. In this regard, non-invasive injury models may be crucial for investigating early adaptive processes initiated at the time of injury, and may be more representative of human OA in which injury is induced mechanically. A small number of non-invasive mouse models of PTOA have been described within the last few years, including intra-articular fracture of tibial subchondral bone, cyclic tibial compression loading of articular cartilage, and anterior cruciate ligament rupture via tibial compression overload. This review describes the methods used to induce joint injury in each of these non-invasive models, and presents the findings of studies utilizing these models. Altogether, these non-invasive mouse models represent a unique and important spectrum of animal models for studying different aspects of PTOA. PMID:26003950

  3. Prenatal screening: current practice, new developments, ethical challenges.

    PubMed

    de Jong, Antina; Maya, Idit; van Lith, Jan M M

    2015-01-01

    Prenatal screening pathways, as nowadays offered in most Western countries consist of similar tests. First, a risk-assessment test for major aneuploides is offered to pregnant women. In case of an increased risk, invasive diagnostic tests, entailing a miscarriage risk, are offered. For decades, only conventional karyotyping was used for final diagnosis. Moreover, several foetal ultrasound scans are offered to detect major congenital anomalies, but the same scans also provide relevant information for optimal support of the pregnancy and the delivery. Recent developments in prenatal screening include the application of microarrays that allow for identifying a much broader range of abnomalities than karyotyping, and non-invasive prenatal testing (NIPT) that enables reducing the number of invasive tests for aneuploidies considerably. In the future, broad NIPT may become possible and affordable. This article will briefly address the ethical issues raised by these technological developments. First, a safe NIPT may lead to routinisation and as such challenge the central issue of informed consent and the aim of prenatal screening: to offer opportunity for autonomous reproductive choice. Widening the scope of prenatal screening also raises the question to what extent 'reproductive autonomy' is meant to expand. Finally, if the same test is used for two different aims, namely detection of foetal anomalies and pregnancy-related problems, non-directive counselling can no longer be taken as a standard. Our broad outline of the ethical issues is meant as an introduction into the more detailed ethical discussions about prenatal screening in the other articles of this special issue.

  4. 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.

  5. Single core-shell nanoparticle probes for non-invasive magnetic force microscopy.

    PubMed

    Uhlig, Tino; Wiedwald, Ulf; Seidenstücker, Axel; Ziemann, Paul; Eng, Lukas M

    2014-06-27

    We present an easy, fast and reliable method for the preparation of magnetic force microscopy (MFM) probes based on single Co nanoparticles (NPs). Due to their dipolar character, these magnetic probes open up a new approach for quantitative and non-invasive MFM measurements on the nanometer length scale. To guarantee long-term stability of these tips under ambient conditions, an ultrathin protecting Au shell was grown around the Co NPs through photochemical deposition. Single magnetic particles were firmly attached to standard silicon AFM tips using bifunctional self-assembling molecules. Such probes were tested on longitudinal magnetic recording media and compared to the results as recorded with conventional thin-film MFM tips. Easy data interpretation of the magnetic nanoparticle probes in a point dipole model is shown. Our nanoparticle tips provide excellent endurance for MFM recording, enable non-invasive probing while maintaining a high sensitivity, resolution, and reproducibility.

  6. Increasing use of rapid HIV testing in labor and delivery among women with no prenatal care: a local initiative.

    PubMed

    Levison, Judy; Williams, Lena T; Moore, Anna; McFarlane, Jenny; Davila, Jessica A

    2011-08-01

    Pregnant women who do not receive prenatal care and may not be aware of their HIV status are at greatest risk of transmitting HIV to their newborn. A multi-component intervention was designed and implemented to increase the use of rapid HIV testing among pregnant women with no prenatal care at labor and delivery in two county hospitals in Houston/Harris County, Texas. The intervention involved establishing a local task force including representatives from each hospital, assessing each hospital's readiness to implement rapid testing, providing educational presentations and materials, and offering individualized follow-up. Outcomes data were obtained and included the number of patients presenting with no prenatal care who received rapid HIV testing on admission. Before the intervention, both hospitals had rapid test kits available but were not using them consistently. Following the intervention, we observed a significant increase in the use of rapid HIV testing at both institutions (P < 0.001). In the 3 months immediately following the intervention, use of rapid testing at Hospital 1 increased from 7.4 to 35.3% and at Hospital 2 from 27.4 to 41.5%. At 1 year, almost 100% of women with no prenatal care at both hospitals received rapid testing. Educating staff and clinicians and implementing system-wide changes may facilitate behavior change regarding prenatal HIV testing.

  7. Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing

    PubMed Central

    Yu, Stephanie C. Y.; Chan, K. C. Allen; Zheng, Yama W. L.; Jiang, Peiyong; Liao, Gary J. W.; Sun, Hao; Akolekar, Ranjit; Leung, Tak Y.; Go, Attie T. J. I.; van Vugt, John M. G.; Minekawa, Ryoko; Oudejans, Cees B. M.; Nicolaides, Kypros H.; Chiu, Rossa W. K.; Lo, Y. M. Dennis

    2014-01-01

    Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring. PMID:24843150

  8. Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing.

    PubMed

    Yu, Stephanie C Y; Chan, K C Allen; Zheng, Yama W L; Jiang, Peiyong; Liao, Gary J W; Sun, Hao; Akolekar, Ranjit; Leung, Tak Y; Go, Attie T J I; van Vugt, John M G; Minekawa, Ryoko; Oudejans, Cees B M; Nicolaides, Kypros H; Chiu, Rossa W K; Lo, Y M Dennis

    2014-06-10

    Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring.

  9. Optimized intravenous Flat Detector CT for non-invasive visualization of intracranial stents: first results.

    PubMed

    Struffert, Tobias; Kloska, Stephan; Engelhorn, Tobias; Deuerling-Zheng, Yu; Ott, Sabine; Doelken, Marc; Saake, Marc; Köhrmann, Martin; Doerfler, Arnd

    2011-02-01

    As stents for treating intracranial atherosclerotic stenosis may develop in-stent re-stenosis (ISR) in up to 30%, follow-up imaging is mandatory. Residual stenosis (RS) is not rare. We evaluated an optimised Flat Detector CT protocol with intravenous contrast material application (i.v. FD-CTA) for non-invasive follow-up. In 12 patients with intracranial stents, follow-up imaging was performed using i.v. FD-CTA. MPR, subtracted MIP and VRT reconstructions were used to correlate to intra-arterial angiography (DSA). Two neuroradiologists evaluated the images in anonymous consensus reading and calculated the ISR or RS. Correlation coefficients and a Wilcoxon test were used for statistical analysis. In 4 patients, no stenosis was detected. In 6 patients RS and in two cases ISR by intima hyperplasia perfectly visible on MPR reconstructions of i.v. FD-CTA were detected. Wilcoxon's test showed no significant differences between the methods (p > 0.05). We found a high correlation with coefficients of the pairs DSA/ FD-CT MIP r = 0.91, DSA/ FD-CT MPR r = 0.82 and FD-CT MIP/ FD-CT MPR r = 0.8. Intravenous FD-CTA could clearly visualise the stent and the lumen, allowing ISR or RS to be recognised. FD-CTA provides a non-invasive depiction of intracranial stents and might replace DSA for non-invasive follow-up imaging.

  10. Stress detection in bivalve mollusk using non-invasive bioelectric monitoring of myoneural behavior

    SciTech Connect

    Morgan, E.L.; Hardison, B.S.; Dawson, V.K.; Waller, D.; Waller, W.T.; Dickson, K.L.; Allen, H.J.

    1995-12-31

    Few studies have demonstrated cause-and-effect linkages between extrinsic environmental factors and intrinsic bioelectric action potentials of bivalve mollusk using non-invasive, non-destructive approaches. A non-invasive, external probe configuration and detection system, similar to one used previously with native unionids, was developed for continuously monitoring bioelectric activities of clams and mussels. Using remote probes and differential amplifiers, bioelectric activities were recorded for cardiac, adductor, siphon and foot responses using a computer equipped with integrating software. To test if remote, non-invasive probes would detect similar information to that recorded by invasive needle electrodes, two individuals of zebra mussel (Dreissenia polymorpha), and Asiatic clam (Corbicula fluminea) were each configured with two sets of probes. One set was inserted between the valves and along the inside surface of the shelf; the other set was positioned remotely about the outside margins of the valves. Signal validation was made by simultaneously recording bioelectric responses for the same animal from both sets of probes. In preliminary stress tests monitored bivalves were subjected to changes in temperatures over 2 to 3 hr intervals from ambient to potentially lethal levels (20 to 30 C for zebra, 25 C to 40 C for corbicula). Dramatic increases resulted in both number and amplitude of cardiac events as temperature increased. Planned studies will use this approach to evaluate bivalve myoneural behavior patterns in response to chemical and non-chemical stimuli.

  11. Haemodynamic effects of non-invasive ventilation in patients with obesity-hypoventilation syndrome.

    PubMed

    Castro-Añón, Olalla; Golpe, Rafael; Pérez-de-Llano, Luis A; López González, María Jesús; Escalona Velasquez, Edgar J; Pérez Fernández, Ruth; Testa Fernández, Ana; González Quintela, Arturo

    2012-11-01

    Although it has been reported that pulmonary hypertension is more frequent in patients with obesity-hypoventilation syndrome than in patients with 'pure' obstructive sleep apnoea syndrome, little is known about the haemodynamic repercussions of this entity. The aim was to describe the haemodynamic status, as assessed by echocardiography and 6-min walk test (6MWT), of patients with a newly diagnosed, most severe form of obesity-hypoventilation syndrome, and to evaluate the impact of non-invasive ventilation in these patients. A prospective, descriptive, and single-centre follow-up study was conducted. At baseline, patients underwent echocardiography, spirometry, static lung volume measurement, 6MWT, overnight pulse-oximetry and polygraphic recording. Changes in echocardiography and 6MWT were assessed after 6 months of non-invasive ventilation. Right ventricular overload was defined on the basis of right ventricular dilatation, hypokinesis, paradoxical septal motion and/or pulmonary hypertension. Thirty patients (20 women; mean age 69 ± 11) were tested. The percentage of patients with right ventricular overload did not change significantly after non-invasive ventilation (43.3-41.6%; P = 0.24). In patients with right ventricular overload at diagnosis, pulmonary artery systolic pressure decreased significantly at six months (58 ± 11 to 44 ± 12 mm Hg; P = 0.014), and mean distance on 6MWT increased from 350 ± 110 to 426 ± 78 m (P = 0.006), without significant changes in body mass index. Right ventricular overload is a frequent finding in patients with the most severe form of obesity-hypoventilation syndrome. Treatment with non-invasive ventilation is associated with a decrease in pulmonary artery systolic pressure at six months and an increase in the distance covered during the 6MWT. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

  12. 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.

  13. The Role of Invasive and Non-Invasive Procedures in Diagnosing Fever of Unknown Origin

    PubMed Central

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

    2012-01-01

    Background: 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. Objective: To determine the etiological distribution and role of non-invasive and invasive diagnostic tools in the diagnosis of fever of unknown origin. Materials & Methods: 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. Results: 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. Conclusion: 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. PMID:23091404

  14. Prenatal Tests

    MedlinePlus

    ... recommended only for certain women, especially those with high-risk pregnancies. These may include women who: are age 35 or older are adolescents have had a premature baby have had a baby with a ... high blood pressure , diabetes , lupus , heart disease, kidney problems, ...

  15. Prenatal Tests

    MedlinePlus

    ... in cells that holds genes. Genetic conditions include cystic fibrosis (also called CF), sickle cell disease and heart defects . A common ... condition. All women can have carrier screening for CF , spinal muscular atrophy (also called SMA), thalassemias and ...

  16. Fetal Sex Determination using Non-Invasive Method of Cell-free Fetal DNA in Maternal Plasma of Pregnant Women During 6th– 10th Weeks of Gestation

    PubMed Central

    Zargari, Maryam; Sadeghi, Mohammad Reza; Shahhosseiny, Mohammad Hassan; Kamali, Koroush; Saliminejad, Kyomars; Esmaeilzadeh, Ali; Khorshid, Hamid Reza Khorram

    2011-01-01

    In previous years, identification of fetal cells in maternal blood circulation has caused a new revolution in non-invasive method of prenatal diagnosis. Low number of fetal cells in maternal blood and long-term survival after pregnancy limited the use of fetal cells in diagnostic and clinical applications. With the discovery of cell-free fetal DNA (cffDNA) in plasma of pregnant women, access to genetic material of the fetus had become possible to determine early gender of a fetus in pregnancies at the risk of X-linked genetic conditions instead of applying invasive methods. Therefore in this study, the probability of detecting sequences on the Y chromosome in pregnant women has been evaluated to identify the gender of fetuses. Peripheral blood samples were obtained from 80 pregnant women at 6th to 10th weeks of gestation and then the fetal DNA was extracted from the plasma. Nested PCR was applied to detect the sequences of single copy SRY gene and multi copy DYS14 & DAZ genes on the Y chromosome of the male fetuses. At the end, all the obtained results were compared with the actual gender of the newborns. In 40 out of 42 born baby boys, the relevant gene sequences were identified and 95.2% sensitivity was obtained. Non-invasive early determination of fetal gender using cffDNA could be employed as a pre-test in the shortest possible time and with a high reliability to avoid applying invasive methods in cases where a fetus is at the risk of genetic diseases. PMID:23407464

  17. Novel Epigenetic Markers on Chromosome 21 for Noninvasive Prenatal Testing of Fetal Trisomy 21.

    PubMed

    Lee, Da Eun; Lim, Ji Hyae; Kim, Min Hyoung; Park, So Yeon; Ryu, Hyun Mee

    2016-05-01

    Until now, fetal placenta-specific epigenetic markers for noninvasive prenatal testing of fetal trisomy 21 (T21) have been identified based only on differences in tissue-specific epigenetic characteristics between placenta and maternal blood, but these characteristics have not been validated in T21 placenta. We aimed to discover novel epigenetic markers on chromosome 21 that show a hypermethylated pattern in fetal placenta compared with blood, regardless of the presence of T21. We performed a high-resolution tiling array analysis of chromosome 21 using the methylated-CpG binding domain protein-based method. We identified 93 epigenetic regions that showed fetal placenta-specific differential methylation patterns; among these, three regions showed fetal placenta-specific methylation patterns in T21 placenta samples. The methylation patterns of these three regions in the array were confirmed by bisulfite direct sequencing. The three regions were detectable in first-trimester maternal plasma. Moreover, a combination of their methylation ratio achieved high diagnostic accuracy for noninvasive prenatal testing of fetal T21 by further statistical analysis. These three novel regions with fetal placenta-specific differential methylation patterns on chromosome 21 were identified irrespective of the presence of T21. Our findings suggest that epigenetic characteristics of markers according to the presence or absence of T21 should be considered in the development of noninvasive prenatal testing of fetal T21 using fetal placenta-specific epigenetic markers. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  18. Genetic counselling and ethical issues with chromosome microarray analysis in prenatal testing.

    PubMed

    McGillivray, George; Rosenfeld, Jill A; McKinlay Gardner, R J; Gillam, Lynn H

    2012-04-01

    Molecular karyotyping using chromosome microarray analysis (CMA) detects more pathogenic chromosomal anomalies than classical karyotyping, making CMA likely to become a first tier test for prenatal diagnosis. Detecting copy number variants of uncertain clinical significance raises ethical considerations. We consider the risk of harm to a woman or her fetus following the detection of a copy number variant of uncertain significance, whether it is ethically justifiable to withhold any test result information from a woman, what constitutes an 'informed choice' when women are offered CMA in pregnancy and whether clinicians are morally responsible for 'unnecessary' termination of pregnancy. Although we are cognisant of the distress associated with uncertain prenatal results, we argue in favour of the autonomy of women and their right to information from genome-wide CMA in order to make informed choices about their pregnancies. We propose that information material to a woman's decision-making process, including uncertain information, should not be withheld, and that it would be paternalistic for clinicians to try to take responsibility for women's decisions to terminate pregnancies. Non-directive pre-test and post-test genetic counselling is central to the delivery of these ethical objectives.

  19. Changes within lipid fractions offer a new way to non-invasively monitor seed viability during storage

    USDA-ARS?s Scientific Manuscript database

    Monitoring seed viability using germination tests consumes large quantities of seeds and does not predict when seed viability will crash. Non-invasive tests that show the progress of seed aging would provide greater efficiency. This study investigates the changes in the chemical and physical propert...

  20. Noninvasive prenatal testing in routine clinical practice for a high-risk population

    PubMed Central

    Qi, Guijie; Yi, Jianping; Han, Baosheng; Liu, Heng; Guo, Wanru; Shi, Chong; Yin, Lirong

    2016-01-01

    Abstract This study aimed to summarize the effects of noninvasive prenatal testing (NIPT) on aneuploidy among high-risk participants in Tangshan Maternal and Children Health Hospital. NIPT or invasive prenatal diagnosis was recommended to patients with a high risk of fetal aneuploidy from February 2013 to February 2014. Patients who exhibited eligibility and applied for NIPT from January 2012 to January 2013 were included in a comparison group. The rates of patients who underwent invasive testing, declined to undergo further testing, and manifested trisomies 21, 18, and 13 were compared between two groups. Follow-up data were obtained from the participants who underwent NIPT from 2013 to 2014. A total of 7223 patients (3018 and 4205 individuals before and after NIPT) were eligible for analysis. After NIPT was introduced in 2013 to 2014, 727 patients (17.3%) underwent invasive testing, 2828 preferred NIPT (67.3%), and 650 declined to undergo further testing (15.5%). A total of 34 cases of trisomies 21, 18, and 13 (0.8%) were found. In 2012 to 2013, 565 patients (18.7%) underwent invasive testing and 2453 declined to undergo further testing (81.3%). A total of 7 cases of trisomies 21, 18, and 13 were documented (0.2%). Of these cases, 24 were found from NIPT and 10 cases were found from invasive testing. The number of participants who declined to undergo further testing significantly decreased after NIPT was introduced (81.3% vs. 15.5%, P < 0.001). The sensitivity and specificity of NIPT for trisomies 21, 18, and 13 were 100% and 99.9%, respectively. The detection rates of NIPT for trisomies 21, 18, and 13 also significantly increased (0.2% vs. 0.8%, P < 0.001). By contrast, the overall rates of invasive testing remained unchanged (18.7% vs. 17.3%, P = 0.12). The positive predictive values of NIPT for trisomies 21, 18, and 13 were 100%, 83.3%, and 50.0%, respectively. The false positive rates of NIPT were 0% and 0.04%. With NIPT implementation in clinical

  1. Non-invasive electric current stimulation for restoration of vision after unilateral occipital stroke.

    PubMed

    Gall, Carolin; Silvennoinen, Katri; Granata, Giuseppe; de Rossi, Francesca; Vecchio, Fabrizio; Brösel, Doreen; Bola, Michał; Sailer, Michael; Waleszczyk, Wioletta J; Rossini, Paolo M; Tatlisumak, Turgut; Sabel, Bernhard A

    2015-07-01

    Occipital stroke often leads to visual field loss, for which no effective treatment exists. Little is known about the potential of non-invasive electric current stimulation to ameliorate visual functions in patients suffering from unilateral occipital stroke. One reason is the traditional thinking that visual field loss after brain lesions is permanent. Since evidence is available documenting vision restoration by means of vision training or non-invasive electric current stimulation future studies should also consider investigating recovery processes after visual cortical strokes. Here, protocols of repetitive transorbital alternating current stimulation (rtACS) and transcranial direct current stimulation (tDCS) are presented and the European consortium for restoration of vision (REVIS) is introduced. Within the consortium different stimulation approaches will be applied to patients with unilateral occipital strokes resulting in homonymous hemianopic visual field defects. The aim of the study is to evaluate effects of current stimulation of the brain on vision parameters, vision-related quality of life, and physiological parameters that allow concluding about the mechanisms of vision restoration. These include EEG-spectra and coherence measures, and visual evoked potentials. The design of stimulation protocols involves an appropriate sham-stimulation condition and sufficient follow-up periods to test whether the effects are stable. This is the first application of non-invasive current stimulation for vision rehabilitation in stroke-related visual field deficits. Positive results of the trials could have far-reaching implications for clinical practice. The ability of non-invasive electrical current brain stimulation to modulate the activity of neuronal networks may have implications for stroke rehabilitation also in the visual domain. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Evaluation of non-invasive screening measures to identify individuals with prediabetes

    PubMed Central

    Vanderwood, Karl K; Kramer, Mary Kaye; Miller, Rachel G.; Arena, Vincent C.; Kriska, Andrea M.

    2016-01-01

    Aims Because blood-based screening to identify those with prediabetes to take part in Diabetes Prevention Program (DPP) translation efforts can be costly and time-consuming, non-invasive methods are needed. The aims of this paper are to evaluate the ability of the American Diabetes Association (ADA) risk test in identifying individuals with prediabetes, as well as the use of body composition measures for this purpose. In addition the utility of these alternate methods to ascertain the presence of the metabolic syndrome was assessed. Methods Potential participants were recruited from a worksite and three community centers to take part in a DPP translation study. Participants completed onsite screening where anthropometric measures, fasting lipids and glucose, and hemoglobin A1c were assessed. Those with a BMI ≥24kg/m2 and prediabetes and/or the metabolic syndrome were eligible to participate. Non-invasive screening methods were evaluated for their ability to identify those with prediabetes and the metabolic syndrome based on clinically measured values. Results All non-invasive methods were highly sensitive (68.9% to 98.5%) in the detection of prediabetes, but specificity was low (6.7% to 44.5%). None of the alternatives evaluated achieved acceptable discrimination levels in ROC analysis. Similar results were noted in identifying the metabolic syndrome. Conclusions The non-invasive methods evaluated in this study effectively identify participants with prediabetes, but would also allow for enrollment of a large number of individuals who do not have prediabetes. Deciding whether to use these alternatives, blood-based measures, or a combination of both will ultimately depend on the purpose of the program and the level of flexibility regarding participant eligibility. PMID:25441924

  3. Non-invasive blood glucose detection system based on conservation of energy method.

    PubMed

    Zhang, Yang; Zhu, Jian-Ming; Liang, Yong-Bo; Chen, Hong-Bo; Yin, Shi-Min; Chen, Zhen-Cheng

    2017-02-01

    The most common method used for minimizing the occurrence of diabetes complications is frequent glucose testing to adjust the insulin dose. However, using blood glucose (BG) meters presents a risk of infection. It is of great importance to develop non-invasive BG detection techniques. To realize high-accuracy, low-cost and continuous glucose monitoring, we have developed a non-invasive BG detection system using a mixed signal processor 430 (MSP430) microcontroller. This method is based on the combination of the conservation-of-energy method with a sensor integration module, which collects physiological parameters, such as the blood oxygen saturation (SPO2), blood flow velocity and heart rate. New methods to detect the basal metabolic rate (BMR) and BV are proposed, which combine the human body heat balance and characteristic signals of photoplethysmography as well dual elastic chambers theory. Four hundred clinical trials on real-time non-invasive BG monitoring under suitable experiment conditions were performed on different individuals, including diabetic patients, senior citizens and healthy adults. A multisensory information fusion model was applied to process these samples. The algorithm (we defined it as DCBPN algorithm) applied in the model combines a decision tree and back propagation neural network, which classifies the physiological and environmental parameters into three categories, and then establishes a corresponding prediction model for the three categories. The DCBPN algorithm provides an accuracy of 88.53% in predicting the BG of new samples. Thus, this system demonstrates a great potential to reliably detect BG values in a non-invasive setting.

  4. Non-invasive prediction of hemoglobin levels by principal component and back propagation artificial neural network

    PubMed Central

    Ding, Haiquan; Lu, Qipeng; Gao, Hongzhi; Peng, Zhongqi

    2014-01-01

    To facilitate non-invasive diagnosis of anemia, specific equipment was developed, and non-invasive hemoglobin (HB) detection method based on back propagation artificial neural network (BP-ANN) was studied. In this paper, we combined a broadband light source composed of 9 LEDs with grating spectrograph and Si photodiode array, and then developed a high-performance spectrophotometric system. By using this equipment, fingertip spectra of 109 volunteers were measured. In order to deduct the interference of redundant data, principal component analysis (PCA) was applied to reduce the dimensionality of collected spectra. Then the principal components of the spectra were taken as input of BP-ANN model. On this basis we obtained the optimal network structure, in which node numbers of input layer, hidden layer, and output layer was 9, 11, and 1. Calibration and correction sample sets were used for analyzing the accuracy of non-invasive hemoglobin measurement, and prediction sample set was used for testing the adaptability of the model. The correlation coefficient of network model established by this method is 0.94, standard error of calibration, correction, and prediction are 11.29g/L, 11.47g/L, and 11.01g/L respectively. The result proves that there exist good correlations between spectra of three sample sets and actual hemoglobin level, and the model has a good robustness. It is indicated that the developed spectrophotometric system has potential for the non-invasive detection of HB levels with the method of BP-ANN combined with PCA. PMID:24761296

  5. Non-invasive prediction of hematocrit levels by portable visible and near-infrared spectrophotometer.

    PubMed

    Sakudo, Akikazu; Kato, Yukiko Hakariya; Kuratsune, Hirohiko; Ikuta, Kazuyoshi

    2009-10-01

    After blood donation, in some individuals having polycythemia, dehydration causes anemia. Although the hematocrit (Ht) level is closely related to anemia, the current method of measuring Ht is performed after blood drawing. Furthermore, the monitoring of Ht levels contributes to a healthy life. Therefore, a non-invasive test for Ht is warranted for the safe donation of blood and good quality of life. A non-invasive procedure for the prediction of hematocrit levels was developed on the basis of a chemometric analysis of visible and near-infrared (Vis-NIR) spectra of the thumbs using portable spectrophotometer. Transmittance spectra in the 600- to 1100-nm region from thumbs of Japanese volunteers were subjected to a partial least squares regression (PLSR) analysis and leave-out cross-validation to develop chemometric models for predicting Ht levels. Ht levels of masked samples predicted by this model from Vis-NIR spectra provided a coefficient of determination in prediction of 0.6349 with a standard error of prediction of 3.704% and a detection limit in prediction of 17.14%, indicating that the model is applicable for normal and abnormal value in Ht level. These results suggest portable Vis-NIR spectrophotometer to have potential for the non-invasive measurement of Ht levels with a combination of PLSR analysis.

  6. Continuous non-invasive monitoring improves blood pressure stability in upright position: randomized controlled trial.

    PubMed

    Benes, Jan; Simanova, Alena; Tovarnicka, Tereza; Sevcikova, Silvie; Kletecka, Jakub; Zatloukal, Jan; Pradl, Richard; Chytra, Ivan; Kasal, Eduard

    2015-02-01

    Intermittent blood pressure (BP) monitoring is the standard-of-care during low and intermediate risk anaesthesia, yet it could lead to delayed recognition of BP fluctuations. Perioperative hypotension is known to be associated with postoperative complications. Continuous, non-invasive methods for BP monitoring have been developed recently. We have tested a novel non-invasive, continuous monitor (using the volume clamp method) to assist with maintaining BP in safe ranges for patients undergoing surgery in a beach chair position. Forty adult patients undergoing thyroid gland surgery in an upright position were included in this prospective randomised controlled trial. Patients were equally allocated to the group with continuous monitoring of BP using the CNAP® Monitor and to the control group managed using an intermittent oscillometric BP cuff. The absolute and proportional time spent outside the range of ±20% of the target BP along with other hemodynamic and clinical parameters were evaluated. The continuous monitoring decreased the anaesthesia time spent below -20% pressure range [absolute: 12 min (4-20) vs. 27 min (16-34); p=0.001; relative to procedure length: 14% (7-20) vs. 33.5% (17.5-53); p=0.003]. No significant differences were observed in postoperative morbidity or in hospital length of stay. Continuous non-invasive BP monitoring via the CNAP® Monitor allows for better BP management in patients undergoing surgery in a beach chair position. In our randomised trial the time spent in hypotension was significantly shorter using continuous monitoring.

  7. Prediction of oesophageal varices in patients with primary biliary cirrhosis by non-invasive markers

    PubMed Central

    Gao, Lili; Li, Hanwei; Han, Jun; Zhang, Weihui

    2017-01-01

    Introduction Preliminary data suggested that non-invasive methods could be useful to assess presence of oesophageal varices (OV) in liver cirrhosis. The primary objectives were to investigate non-invasive markers for diagnosing and grading OV in patients with primary biliary cirrhosis. Material and methods This study included a total of 106 consecutive treatment-naive patients with primary biliary cirrhosis (PBC). Results of physical examination, blood tests, and abdominal ultrasound scan (USS) were measured. Performance of non-invasive markers for OV was expressed as sensitivity, specificity, positive, and negative predictive values (PPV, NPV), accuracy, and area under the curve (AUC). Results Oesophageal varices were found in 54 (50.9%) and large OV in 28 of the 106 patients. Variables found to differ significantly between patients with any grade or large and without OV included increased spleen length, increased portal vein diameter, low platelet count, and low levels of albumin or low γ-glutamyltranspeptidase (γ-GTP) values. Area under the receiver operating characteristic curve showed that spleen length (cutoff = 156.0) had AUC 0.753 (95% CI: 0.657–0.849), and high NPV (82.1%) to exclude any grade OV. Large OV could be excluded with NPV 70.6% by spleen length. Conclusions Predictive risk factors that use readily available laboratory results and ultrasound scan results may reliably identify esophageal varices in patients with PBC. PMID:28261290

  8. Non-invasive, transient determination of the core temperature of a heat-generating solid body

    NASA Astrophysics Data System (ADS)

    Anthony, Dean; Sarkar, Daipayan; Jain, Ankur

    2016-11-01

    While temperature on the surface of a heat-generating solid body can be easily measured using a variety of methods, very few techniques exist for non-invasively measuring the temperature inside the solid body as a function of time. Measurement of internal temperature is very desirable since measurement of just the surface temperature gives no indication of temperature inside the body, and system performance and safety is governed primarily by the highest temperature, encountered usually at the core of the body. This paper presents a technique to non-invasively determine the internal temperature based on the theoretical relationship between the core temperature and surface temperature distribution on the outside of a heat-generating solid body as functions of time. Experiments using infrared thermography of the outside surface of a thermal test cell in a variety of heating and cooling conditions demonstrate good agreement of the predicted core temperature as a function of time with actual core temperature measurement using an embedded thermocouple. This paper demonstrates a capability to thermally probe inside solid bodies in a non-invasive fashion. This directly benefits the accurate performance prediction and control of a variety of engineering systems where the time-varying core temperature plays a key role.

  9. Non-invasive, transient determination of the core temperature of a heat-generating solid body.

    PubMed

    Anthony, Dean; Sarkar, Daipayan; Jain, Ankur

    2016-11-02

    While temperature on the surface of a heat-generating solid body can be easily measured using a variety of methods, very few techniques exist for non-invasively measuring the temperature inside the solid body as a function of time. Measurement of internal temperature is very desirable since measurement of just the surface temperature gives no indication of temperature inside the body, and system performance and safety is governed primarily by the highest temperature, encountered usually at the core of the body. This paper presents a technique to non-invasively determine the internal temperature based on the theoretical relationship between the core temperature and surface temperature distribution on the outside of a heat-generating solid body as functions of time. Experiments using infrared thermography of the outside surface of a thermal test cell in a variety of heating and cooling conditions demonstrate good agreement of the predicted core temperature as a function of time with actual core temperature measurement using an embedded thermocouple. This paper demonstrates a capability to thermally probe inside solid bodies in a non-invasive fashion. This directly benefits the accurate performance prediction and control of a variety of engineering systems where the time-varying core temperature plays a key role.

  10. Non-invasive, transient determination of the core temperature of a heat-generating solid body

    PubMed Central

    Anthony, Dean; Sarkar, Daipayan; Jain, Ankur

    2016-01-01

    While temperature on the surface of a heat-generating solid body can be easily measured using a variety of methods, very few techniques exist for non-invasively measuring the temperature inside the solid body as a function of time. Measurement of internal temperature is very desirable since measurement of just the surface temperature gives no indication of temperature inside the body, and system performance and safety is governed primarily by the highest temperature, encountered usually at the core of the body. This paper presents a technique to non-invasively determine the internal temperature based on the theoretical relationship between the core temperature and surface temperature distribution on the outside of a heat-generating solid body as functions of time. Experiments using infrared thermography of the outside surface of a thermal test cell in a variety of heating and cooling conditions demonstrate good agreement of the predicted core temperature as a function of time with actual core temperature measurement using an embedded thermocouple. This paper demonstrates a capability to thermally probe inside solid bodies in a non-invasive fashion. This directly benefits the accurate performance prediction and control of a variety of engineering systems where the time-varying core temperature plays a key role. PMID:27804981

  11. 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

  12. Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy?

    PubMed Central

    Chin, Jun L.; Pavlides, Michael; Moolla, Ahmad; Ryan, John D.

    2016-01-01

    Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care. PMID:27378924

  13. Research of transmissive near infrared spectroscopy for non-invasive blood glucose measurement

    NASA Astrophysics Data System (ADS)

    Yang, Wenming; Liao, Ningfang; Li, Yasheng; Shao, Liwei; Huang, Dehuang

    2016-10-01

    Near infrared (NIR) has prospectively applied in non-invasive blood glucose measurement due to glucose absorption among the 1.0-2.5m spectral bands. However, this significant technology is hard to be developed because of other blood components and low signal-to-noise ratio (SNR). In this work, we presented a non-invasive glucose measurement system using Fourier transform spectrometer which will work in fingertips or other human body tissues. A refrigerated InGaAs detector with high quantum efficiency performing well in the range of 1.0-1.7μm wavelength is used to acquire transmissive radiation. Preliminary experiment investigations were set up to test glucose levels of aqueous solutions with different concentrations. The analytical modeling of the interferogram data is based on arithmetic Fourier transform and supported by the curvilineal characterization. Experimental results show the variation of light intensity among different glucose concentrations and emphasize the obvious absorption of glucose in NIR wave-range. This study confirms the suitability that NIR can be developed in non-invasive glucose measurement.

  14. Prenatal diagnosis: choices women make about pursuing testing and acting on abnormal results.

    PubMed

    Pryde, P G; Drugan, A; Johnson, M P; Isada, N B; Evans, M I

    1993-09-01

    Liberalization of abortion laws in several US states (e.g., New York and California) coincided with the development of prenatal techniques, which diagnose chromosomal abnormalities and biochemical disorders. Increased use of prenatal diagnostic services has not been accompanied by adequate examination of the decision making process women undergo when contemplating prenatal diagnosis, pregnancy termination, or experimental fetal therapy. The limited literature exploring these issues indicates that many women do not know as much as possible about the health of their fetus. Women who are at risk of abnormal pregnancy tend to become distressed and willing to accept invasive testing, even when they know the significant, albeit low, risks of such testing. Women's perceptions of risk, which stem from complex psychologic-phenomena, are likely to be very inconsistent with objective reality. Neither counseling nor education can easily change these misperceptions. Nevertheless, counseling can at least alter misperceptions enough so they move closer to objective reality. On the other hand, counseling can sway perceptions and choices made based on these perceptions. Decision making is even more complex and emotional when women encounter abnormalities. Considerable social, moral, and psychologic factors influence this process, making this a very problematic area to study. Almost all women who carry an abnormal fetus with a very serious prognosis and a high degree of diagnostic certainty chose to terminate the pregnancy. The decision is much more difficult for women carrying a fetus with less diagnostic or prognostic certainty. Insufficient data exists to determine how they handle these management decisions. Women tend to opt for abortion in cases of chromosomal abnormalities, regardless of the severity or certainty of the outcome. Women carrying a fetus with anatomic disorders with prognostic uncertainty or less severity choose to abort at lower rates. More research is needed to

  15. Transmission ratio distortion in the spinal muscular atrophy locus: data from 314 prenatal tests.

    PubMed

    Botta, A; Tacconelli, A; Bagni, I; Giardina, E; Bonifazi, E; Pietropolli, A; Clementi, M; Novelli, G

    2005-11-22

    Spinal muscular atrophy (SMA) is a recessive neurodegenerative disorder characterized by the loss of alpha-motor neurons in the spinal cord and subsequent death of motor neuron cells. SMA occurs with a frequency of 1 in 6,000 live births, with a carrier frequency of 1 in 40, and is a leading genetic cause of infant mortality. SMA is caused by loss or mutation of the telomeric survival motor neuron gene (SMN1), which is deleted in almost 94% of SMA patients To analyze the transmission ratio at the SMA locus, examining the segregation of the SMN1-deleted alleles in 314 fetuses from carrier parents who requested prenatal testing for the disease. Prenatal diagnosis of SMA in families at 25% risk of the disease has been performed on chorionic villous sampling specimens, through direct detection of the SMN1 gene mutation and linkage analysis using microsatellite markers from the 5q13 region. Analysis of the genotypic/allelic frequencies of the SMN1 gene was performed using the chi2 test, assuming a recessive mendelian inheritance. Of 314 fetuses analyzed, 95 were homozygous for the wild-type allele (30.3%), 154 were carriers (49.0%), and the remaining 65 were homozygous for the mutated allele (20.7%). Statistical analysis demonstrated that proportion of fetuses predicted with SMA is lower than 25% expected for a recessive disorder, resulting in a transmission rate of the SMN1-deleted allele deviant from the 50% expected in a random the segregation of a mendelian tract (p = 0.016) This is the first study to evaluate the genotypic frequencies at the spinal muscular atrophy (SMA) locus based on data derived from prenatal analysis, which are not subject to ascertainment bias. The analysis showed a transmission ratio distortion at the SMA locus in favor of the SMN1 wild-type alleles.

  16. Novel circulating microRNA signature as a potential non-invasive multi-marker test in ER-positive early-stage breast cancer: a case control study.

    PubMed

    Kodahl, Annette R; Lyng, Maria B; Binder, Harald; Cold, Søren; Gravgaard, Karina; Knoop, Ann S; Ditzel, Henrik J

    2014-07-01

    There are currently no highly sensitive and specific minimally invasive biomarkers for detection of early-stage breast cancer. MicroRNAs (miRNAs) are present in the circulation and may be unique biomarkers for early diagnosis of human cancers. The aim of this study was to investigate the differential expression of miRNAs in the serum of breast cancer patients and healthy controls. Global miRNA analysis was performed on serum from 48 patients with ER-positive early-stage breast cancer obtained at diagnosis (24 lymph node-positive and 24 lymph node-negative) and 24 age-matched healthy controls using LNA-based quantitative real-time PCR (qRT-PCR). A signature of miRNAs was subsequently validated in an independent set of 111 serum samples from 60 patients with early-stage breast cancer and 51 healthy controls and further tested for reproducibility in 3 independent data sets from the GEO Database. A multivariable signature consisting of 9 miRNAs (miR-15a, miR-18a, miR-107, miR-133a, miR-139-5p, miR-143, miR-145, miR-365, miR-425) was identified that provided considerable discrimination between breast cancer patients and healthy controls. Further, the ability of the 9 miRNA signature to stratify samples from breast cancer patients and healthy controls was confirmed in the validation set (p = 0.012) with a corresponding AUC = 0.665 in the ROC-curve analysis. No association between miRNA expression and tumor grade, tumor size, menopausal- or lymph node status was observed. The signature was also successfully validated in a previously published independent data set of circulating miRNAs in early-stage breast cancer (p = 0.024). We present herein a 9 miRNA signature capable of discriminating between ER-positive breast cancer and healthy controls. Using a specific algorithm based on the 9 miRNA signature, the risk for future individuals can be predicted. Since microRNAs are highly stable in blood components, this signature might be useful in the development of a blood

  17. Simulation on how to customize glucose adjustment method for non-invasive blood glucose sensing by NIRS

    NASA Astrophysics Data System (ADS)

    Min, Xiaolin; Jiang, Jingying; Zou, Da; Liu, Rong; Xu, Kexin

    2013-02-01

    Previous studies have shown the limitations of taking OGTT (Oral Glucose Tolerance Test) as the glucose adjustment protocol for non-invasive blood glucose sensing. Previous studies built a mathematical model of glucose metabolism system-IMM (the Integrated Minimal Model) to probe other available adjustment methods. In this talk, a further study would be focused on more detailed combination options of different glucose input types for glucose adjustment projects in non-invasive blood glucose sensing. And predictive models of blood glucose concentration have been established by means of partial least squares (PLS) method, which could be used to evaluate the quality of different glucose adjustment options. Results of PLS modeling suggested that predictive models under combined glucose input types, compared with OGTT, show a great enhancement in the stability. This would finally improve the precision of non-invasive blood glucose sensing.

  18. Assessment of left anterior descending artery stenosis of intermediate severity by fractional flow reserve, instantaneous wave-free ratio and non-invasive coronary flow reserve.

    PubMed

    Meimoun, P; Clerc, J; Ardourel, D; Martis, S; Djou, U; Botoro, T; Boulanger, J; Elmkies, F; Zemir, H

    2016-11-01

    Assessment of the functional significance of left anterior descending coronary artery (LAD) stenosis of intermediate severity is challenging and often based on fractional flow reserve (FFR). The instantaneous wave-free ratio (IFR), a new vasodilator-free index of coronary stenosis severity, and non-invasive coronary flow reserve (CFR) by transthoracic Doppler echocardiography are also potentially useful. A direct comparison of FFR, IFR, and non-invasive CFR has never been performed. Our objective was to test the usefulness of non-invasive CFR by comparison to invasive FFR and IFR in patients with LAD stenosis of angiographic intermediate severity and stable coronary artery disease.

  19. Skin Rejuvenation with Non-Invasive Pulsed Electric Fields

    NASA Astrophysics Data System (ADS)

    Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm, Martin C., Jr.; Austen, William G., Jr.; Yarmush, Martin L.

    2015-05-01

    Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.

  20. Skin Rejuvenation with Non-Invasive Pulsed Electric Fields

    PubMed Central

    Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm Jr., Martin C.; Austen Jr., William G.; Yarmush, Martin L.

    2015-01-01

    Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases. PMID:25965851

  1. Hepatic steatosis and fibrosis: Non-invasive assessment

    PubMed Central

    Karanjia, Rustam N; Crossey, Mary M E; Cox, I Jane; Fye, Haddy K S; Njie, Ramou; Goldin, Robert D; Taylor-Robinson, Simon D

    2016-01-01

    Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and non-invasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy. PMID:28018096

  2. Non-invasive Imaging of Colitis using Multispectral Optoacoustic Tomography.

    PubMed

    Bhutiani, Neal; Grizzle, William E; Galandiuk, Susan; Otali, Denis; Dryden, Gerald W; Egilmez, Nejat K; McNally, Lacey R

    2016-12-01

    Currently, several non-invasive modalities, including MRI and PET, are being investigated to identify early intestinal inflammation, longitudinally monitor disease status, or detect dysplastic changes in patients with inflammatory bowel disease (IBD). Here, we assess the applicability and utility of multispectral optoacoustic tomography (MSOT) in evaluating the presence and severity of colitis. Mice with bacterial colitis demonstrated a temporally associated increase in mesenteric and colonic vascularity with an increase in mean signal intensity of oxygenated hemoglobin (p=0.004) by MSOT two days after inoculation. These findings were significantly more prominent 7 days after inoculation, with increased mean signal intensity of oxygenated hemoglobin (p=0.0002) and the development of punctate vascular lesions on the colonic surface, which corresponded to changes observed on colonoscopy as well as histology. With improvements in depth of tissue penetration, MSOT may hold potential as a sensitive, accurate, non-invasive imaging tool in evaluation of patients with IBD.

  3. Non-invasive microsensors for studying cell/tissue physiology

    NASA Astrophysics Data System (ADS)

    Vanegas, D. C.; Taguchi, M.; Chaturvedi, P.; Burrs, S.; McLamore, E. S.

    2013-05-01

    Non-invasive tools that allow real-time quantification of molecules relevant to metabolism, homeostasis, and cell signaling in cells and tissue are of great importance for studying physiology. Several microsensor technologies have been developed to monitor concentration of molecules such as ions, oxygen, electroactive molecules (e.g., nitric oxide, hydrogen peroxide), and biomolecules (e.g., sugars, hormones). The major challenges for microsensors are overcoming relatively low sensitivity and low signal-to-noise ratio. Modern approaches for enhancing microsensor performance focus on the incorporation of catalytic nanomaterials to increase sensitivity, reduce response time, and increase operating range. To improve signal-to-noise ratio, a non-invasive microsensor modality called self-referencing (SR) is being applied. The SR technique allows measurement of temporal and spatial transport dynamics at the cell, tissue, organ, and organismal level.

  4. Non-invasive assessments of adipose tissue metabolism in vitro

    PubMed Central

    Abbott, Rosalyn D.; Borowsky, Francis E.; Quinn, Kyle P.; Bernstein, David L.; Georgakoudi, Irene; Kaplan, David L.

    2015-01-01

    Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with noninvasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored. PMID:26399988

  5. Skin rejuvenation with non-invasive pulsed electric fields.

    PubMed

    Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P; Albadawi, Hassan; Felix Broelsch, G; Watkins, Michael T; Georgakoudi, Irene; Papisov, Mikhail; Mihm, Martin C; Austen, William G; Yarmush, Martin L

    2015-05-12

    Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.

  6. Expanding the phenotype of Triple X syndrome: A comparison of prenatal versus postnatal diagnosis.

    PubMed

    Wigby, Kristen; D'Epagnier, Cheryl; Howell, Susan; Reicks, Amy; Wilson, Rebecca; Cordeiro, Lisa; Tartaglia, Nicole

    2016-11-01

    Triple X syndrome (47, XXX) occurs in approximately 1:1,000 female births and has a variable phenotype of physical and psychological features. Prenatal diagnosis rates of 47, XXX are increasing due to non-invasive prenatal genetic testing. Previous studies suggest that prenatal diagnosed females have better neurodevelopmental outcomes. This cross-sectional study describes diagnosis, physical features, medical problems, and neurodevelopmental features in a large cohort of females with 47, XXX. Evaluation included review of medical and developmental history, physical exam, cognitive, and adaptive testing. Medical and developmental features were compared between the prenatal and postnatal diagnosis groups using rate calculations and Fisher's exact test. Cognitive and adaptive tests scores were compared using t-tests. Seventy-four females age 6 months-24 years (mean 8.3 years) participated. Forty-four (59.5%) females were in the prenatal diagnosis group. Mean age of postnatal diagnosis was 5.9 years; developmental delay was the most common indication for postnatal genetic testing. Common physical features included hypertelorism, epicanthal folds, clinodactyly, and hypotonia. Medical problems included dental disorders (44.4%), seizure disorders (16.2%), genitourinary malformations (12.2%). The prenatal diagnosis group had higher verbal (P < 0.001), general ability index (P = 0.004), and adaptive functioning scores (P < 0.001). Rates of ADHD (52.2% vs. 45.5%, P = 0.77) and learning disabilities (39.1% vs. 36.3%, P = 1.00) were similar between the two groups. These findings expand on the phenotypic features in females with Triple X syndrome and support that prenatally ascertained females have better cognitive and functional outcomes. However, prenatally diagnosed females are still at risk for neurodevelopmental disorders. Genetic counseling and treatment recommendations are summarized. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Non-invasive, investigative methods in skin aging.

    PubMed

    Longo, C; Ciardo, S; Pellacani, G

    2015-12-01

    A precise and noninvasive quantification of aging is of outmost importance for in vivo assessment of the skin aging "stage", and thus acts to minimize it. Several bioengineering methods have been proposed to objectively, precisely, and non-invasively measure skin aging, and to detect early skin damage, that is sub-clinically observable. In this review we have described the most relevant methods that have emerged from recently introduced technologies, aiming at quantitatively assessing the effects of aging on the skin.

  8. Invasive versus non-invasive diagnosis of renal bone disease.

    PubMed

    Fournier, A; Oprisiu, R; Said, S; Sechet, A; Ghazali, A; Marié, A; el Esper, I; Brazier, M; Achard, J M; Morinière, P

    1997-07-01

    At present, bone histomorphometry remains the gold standard for the diagnosis of the various types of renal bone disease. In the search for a non-invasive method of diagnosis, biochemical serum markers of bone remodelling, in addition to serum intact parathyroid hormone and aluminium determinations, have been proposed as the most reliable tools and are at present widely used in clinical practice. Their respective diagnostic values, as separate items and in combined analysis, are thoroughly discussed in the present review.

  9. SQUID magnetometry applied as non-invasive electroanalytic chemical technique

    SciTech Connect

    Jette, B.D.; MacVicar, M.L.A. )

    1991-03-01

    This paper reports on a SQUID magnetometer, employed as a highly sensitive ammeter, used to perform standard electroanalytic chemical measurements non- invasively. Specifically, the magnetic fields generated by the net ionic movement in the solution of a driven electrochemical system is detected by the gradiometer coils. The SQUID signal can then be compared to conventional current measurements. One such standard measurement investigated is Cyclic Voltametry (CV) which determines the I-V characteristics of an electrochemical system yielding critical kinetic parameters.

  10. The Feasibility Study of Non-Invasive Fetal Trisomy 18 and 21 Detection with Semiconductor Sequencing Platform

    PubMed Central

    Guo, Qiwei; Chen, Jinchun; Quan, Shengmao; Zhang, Ahong; Zheng, Hailing; Zhu, Xingqiang; Lin, Jin; Xu, Huan; Wu, Ayang; Park, Sin-Gi; Kim, Byung Chul; Joo, Hee Jae; Chen, Hongliang; Bhak, Jong

    2014-01-01

    Objective Recent non-invasive prenatal testing (NIPT) technologies are based on next-generation sequencing (NGS). NGS allows rapid and effective clinical diagnoses to be determined with two common sequencing systems: Illumina and Ion Torrent platforms. The majority of NIPT technology is associated with Illumina platform. We investigated whether fetal trisomy 18 and 21 were sensitively and specifically detectable by semiconductor sequencer: Ion Proton. Methods From March 2012 to October 2013, we enrolled 155 pregnant women with fetuses who were diagnosed as high risk of fetal defects at Xiamen Maternal & Child Health Care Hospital (Xiamen, Fujian, China). Adapter-ligated DNA libraries were analyzed by the Ion Proton™ System (Life Technologies, Grand Island, NY, USA) with an average 0.3× sequencing coverage per nucleotide. Average total raw reads per sample was 6.5 million and mean rate of uniquely mapped reads was 59.0%. The results of this study were derived from BWA mapping. Z-score was used for fetal trisomy 18 and 21 detection. Results Interactive dot diagrams showed the minimal z-score values to discriminate negative versus positive cases of fetal trisomy 18 and 21. For fetal trisomy 18, the minimal z-score value of 2.459 showed 100% positive predictive and negative predictive values. The minimal z-score of 2.566 was used to classify negative versus positive cases of fetal trisomy 21. Conclusion These results provide the evidence that fetal trisomy 18 and 21 detection can be performed with semiconductor sequencer. Our data also suggest that a prospective study should be performed with a larger cohort of clinically diverse obstetrics patients. PMID:25329639

  11. The feasibility study of non-invasive fetal trisomy 18 and 21 detection with semiconductor sequencing platform.

    PubMed

    Jeon, Young Joo; Zhou, Yulin; Li, Yihan; Guo, Qiwei; Chen, Jinchun; Quan, Shengmao; Zhang, Ahong; Zheng, Hailing; Zhu, Xingqiang; Lin, Jin; Xu, Huan; Wu, Ayang; Park, Sin-Gi; Kim, Byung Chul; Joo, Hee Jae; Chen, Hongliang; Bhak, Jong

    2014-01-01

    Recent non-invasive prenatal testing (NIPT) technologies are based on next-generation sequencing (NGS). NGS allows rapid and effective clinical diagnoses to be determined with two common sequencing systems: Illumina and Ion Torrent platforms. The majority of NIPT technology is associated with Illumina platform. We investigated whether fetal trisomy 18 and 21 were sensitively and specifically detectable by semiconductor sequencer: Ion Proton. From March 2012 to October 2013, we enrolled 155 pregnant women with fetuses who were diagnosed as high risk of fetal defects at Xiamen Maternal & Child Health Care Hospital (Xiamen, Fujian, China). Adapter-ligated DNA libraries were analyzed by the Ion Proton™ System (Life Technologies, Grand Island, NY, USA) with an average 0.3× sequencing coverage per nucleotide. Average total raw reads per sample was 6.5 million and mean rate of uniquely mapped reads was 59.0%. The results of this study were derived from BWA mapping. Z-score was used for fetal trisomy 18 and 21 detection. Interactive dot diagrams showed the minimal z-score values to discriminate negative versus positive cases of fetal trisomy 18 and 21. For fetal trisomy 18, the minimal z-score value of 2.459 showed 100% positive predictive and negative predictive values. The minimal z-score of 2.566 was used to classify negative versus positive cases of fetal trisomy 21. These results provide the evidence that fetal trisomy 18 and 21 detection can be performed with semiconductor sequencer. Our data also suggest that a prospective study should be performed with a larger cohort of clinically diverse obstetrics patients.

  12. Non-invasive imaging through opaque scattering layers.

    PubMed

    Bertolotti, Jacopo; van Putten, Elbert G; Blum, Christian; Lagendijk, Ad; Vos, Willem L; Mosk, Allard P

    2012-11-08

    Non-invasive optical imaging techniques, such as optical coherence tomography, are essential diagnostic tools in many disciplines, from the life sciences to nanotechnology. However, present methods are not able to image through opaque layers that scatter all the incident light. Even a very thin layer of a scattering material can appear opaque and hide any objects behind it. Although great progress has been made recently with methods such as ghost imaging and wavefront shaping, present procedures are still invasive because they require either a detector or a nonlinear material to be placed behind the scattering layer. Here we report an optical method that allows non-invasive imaging of a fluorescent object that is completely hidden behind an opaque scattering layer. We illuminate the object with laser light that has passed through the scattering layer. We scan the angle of incidence of the laser beam and detect the total fluorescence of the object from the front. From the detected signal, we obtain the image of the hidden object using an iterative algorithm. As a proof of concept, we retrieve a detailed image of a fluorescent object, comparable in size (50 micrometres) to a typical human cell, hidden 6 millimetres behind an opaque optical diffuser, and an image of a complex biological sample enclosed between two opaque screens. This approach to non-invasive imaging through strongly scattering media can be generalized to other contrast mechanisms and geometries.

  13. Non-invasive wearable electrochemical sensors: a review.

    PubMed

    Bandodkar, Amay J; Wang, Joseph

    2014-07-01

    Wearable sensors have garnered considerable recent interest owing to their tremendous promise for a plethora of applications. Yet the absence of reliable non-invasive chemical sensors has greatly hindered progress in the area of on-body sensing. Electrochemical sensors offer considerable promise as wearable chemical sensors that are suitable for diverse applications owing to their high performance, inherent miniaturization, and low cost. A wide range of wearable electrochemical sensors and biosensors has been developed for real-time non-invasive monitoring of electrolytes and metabolites in sweat, tears, or saliva as indicators of a wearer's health status. With continued innovation and attention to key challenges, such non-invasive electrochemical sensors and biosensors are expected to open up new exciting avenues in the field of wearable wireless sensing devices and body-sensor networks, and thus find considerable use in a wide range of personal health-care monitoring applications, as well as in sport and military applications. Published by Elsevier Ltd.

  14. Method for non-invasively recording electrocardiograms in conscious mice

    PubMed Central

    Chu, Victor; Otero, Jose M; Lopez, Orlando; Morgan, James P; Amende, Ivo; Hampton, Thomas G

    2001-01-01

    Background The rapid increase in the development of mouse models is resulting in a growing demand for non-invasive physiological monitoring of large quantities of mice. Accordingly, we developed a new system for recording electrocardiograms (ECGs) in conscious mice without anesthesia or implants, and created Internet-accessible software for analyzing murine ECG signals. The system includes paw-sized conductive electrodes embedded in a platform configured to record ECGs when 3 single electrodes contact 3 paws. Results With this technique we demonstrated significantly reduced heart rate variability in neonates compared to adult mice. We also demonstrated that female mice exhibit significant ECG differences in comparison to age-matched males, both at baseline and in response to β-adrenergic stimulation. Conclusions The technology we developed enables non-invasive screening of large numbers of mice for ECG changes resulting from genetic, pharmacological, or pathophysiological alterations. Data we obtained non-invasively are not only consistent with what have been reported using invasive and expensive methods, but also demonstrate new findings regarding gender-dependent and age-dependent variations in ECGs in mice. PMID:11476671

  15. Uptake of prenatal diagnostic testing for retinoblastoma compared to other hereditary cancer syndromes in the Netherlands.

    PubMed

    Dommering, Charlotte J; Henneman, Lidewij; van der Hout, Annemarie H; Jonker, Marianne A; Tops, Carli M J; van den Ouweland, Ans M W; van der Luijt, Rob B; Mensenkamp, Arjen R; Hogervorst, Frans B L; Redeker, Egbert J W; de Die-Smulders, Christine E M; Moll, Annette C; Meijers-Heijboer, Hanne

    2017-04-01

    Since the 1980s the genetic cause of many hereditary tumor syndromes has been elucidated. As a consequence, carriers of a deleterious mutation in these genes may opt for prenatal diagnoses (PND). We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the Netherlands. Uptake for retinoblastoma (Rb) was compared with uptake for Von Hippel-Lindau disease (VHL), Li-Fraumeni syndrome (LFS), familial adenomatous polyposis (FAP), and hereditary breast ovarian cancer (HBOC). A questionnaire was completed by all nine DNA-diagnostic laboratories assessing the number of independent mutation-positive families identified from the start of diagnostic testing until May 2013, and the number of PNDs performed for these syndromes within these families. Of 187 families with a known Rb-gene mutation, 22 had performed PND (11.8%), this was significantly higher than uptake for FAP (1.6%) and HBOC (<0.2%). For VHL (6.5%) and LFS (4.9%) the difference was not statistically significant. PND for Rb started 3 years after introduction of diagnostic DNA testing and remained stable over the years. For the other cancer syndromes PND started 10-15 years after the introduction and uptake for PND showed an increase after 2009. We conclude that uptake of PND for Rb was significantly higher than for FAP and HBOC, but not different from VHL and LFS. Early onset, high penetrance, lack of preventive surgery and perceived burden of disease may explain these differences.

  16. Expanding the scope of noninvasive prenatal testing: detection of fetal microdeletion syndromes.

    PubMed

    Wapner, Ronald J; Babiarz, Joshua E; Levy, Brynn; Stosic, Melissa; Zimmermann, Bernhard; Sigurjonsson, Styrmir; Wayham, Nicholas; Ryan, Allison; Banjevic, Milena; Lacroute, Phil; Hu, Jing; Hall, Megan P; Demko, Zachary; Siddiqui, Asim; Rabinowitz, Matthew; Gross, Susan J; Hill, Matthew; Benn, Peter

    2015-03-01

    The purpose of this study was to estimate the performance of a single-nucleotide polymorphism (SNP)-based noninvasive prenatal test for 5 microdeletion syndromes. Four hundred sixty-nine samples (358 plasma samples from pregnant women, 111 artificial plasma mixtures) were amplified with the use of a massively multiplexed polymerase chain reaction, sequenced, and analyzed with the use of the Next-generation Aneuploidy Test Using SNPs algorithm for the presence or absence of deletions of 22q11.2, 1p36, distal 5p, and the Prader-Willi/Angelman region. Detection rates were 97.8% for a 22q11.2 deletion (45/46) and 100% for Prader-Willi (15/15), Angelman (21/21), 1p36 deletion (1/1), and cri-du-chat syndromes (24/24). False-positive rates were 0.76% for 22q11.2 deletion syndrome (3/397) and 0.24% for cri-du-chat syndrome (1/419). No false positives occurred for Prader-Willi (0/428), Angelman (0/442), or 1p36 deletion syndromes (0/422). SNP-based noninvasive prenatal microdeletion screening is highly accurate. Because clinically relevant microdeletions and duplications occur in >1% of pregnancies, regardless of maternal age, noninvasive screening for the general pregnant population should be considered. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Women's Attitudes Regarding Prenatal Testing for a Range of Congenital Disorders of Varying Severity.

    PubMed

    Norton, Mary E; Nakagawa, Sanae; Kuppermann, Miriam

    2014-01-21

    Little is known about women's comparative attitudes towards prenatal testing for different categories of genetic disorders. We interviewed women who delivered healthy infants within the past year and assessed attitudes towards prenatal screening and diagnostic testing, as well as pregnancy termination, for Down syndrome (DS), fragile X (FraX), cystic fibrosis (CF), spinal muscular atrophy (SMA), phenylketonuria (PKU) and congenital heart defects (CHD). Ninety-five women aged 21 to 48 years participated, of whom 60% were Caucasian, 23% Asian, 10% Latina and 7% African American; 82% were college graduates. Ninety-five to ninety-eight percent indicated that they would have screening for each condition, and the majority would have amniocentesis (64% for PKU to 72% for SMA). Inclinations regarding pregnancy termination varied by condition: Whereas only 10% reported they would probably or definitely terminate a pregnancy for CHD, 41% indicated they would do so for DS and 62% for SMA. Most women in this cohort reported that they would undergo screening for all six conditions presented, the majority without the intent to terminate an affected pregnancy. These women were least inclined to terminate treatable disorders (PKU, CHD) versus those associated with intellectual disability (DS, FraX) and were most likely to terminate for SMA, typically lethal in childhood.

  18. Non-invasive optical detection of glucose in cell culture nutrient medium

    NASA Technical Reports Server (NTRS)

    Cote, Gerald L.

    1993-01-01

    The objective of the proposed research was to begin the development of a non-invasive optical sensor for measuring glucose concentration in the output medium of cell cultures grown in a unique NASA bioreactor referred to as an integrated rotating-wall vessel (IRWV). The input, a bovine serum based nutrient media, has a known glucose concentration. The cells within the bioreactor digest a portion of the glucose. Thus, the non-invasive optical sensor is needed to monitor the decrease in glucose due to cellular consumption since the critical parameters for sustained cellular productivity are glucose and pH. Previous glucose sensing techniques have used chemical reactions to quantify the glucose concentration. Chemical reactions, however, cannot provide for continuous, real time, non-invasive measurement as is required in this application. Our effort while in the fellowship program was focused on the design, optical setup, and testing of one bench top prototype non-invasive optical sensor using a mid-infrared absorption spectroscopy technique. Glucose has a fundamental vibrational absorption peak in the mid-infrared wavelength range at 9.6 micron. Preliminary absorption data using a CO2 laser were collected at this wavelength for water based glucose solutions at different concentrations and one bovine serum based nutrient medium (GTSF) with added glucose. The results showed near linear absorption responses for the glucose-in-water data with resolutions as high at 108 mg/dl and as low as 10 mg/dl. The nutrient medium had a resolution of 291 mg/dl. The variability of the results was due mainly to thermal and polarization drifts of the laser while the decrease in sensitivity to glucose in the nutrient medium was expected due to the increase in the number of confounders present in the nutrient medium. A multispectral approach needs to be used to compensate for these confounders. The CO2 laser used for these studies was wavelength tunable (9.2 to 10.8 micrometers), however

  19. [Application of droplet digital PCR technology for genetic testing and prenatal diagnosis of spinal muscular atrophy].

    PubMed

    Zou, Yang; Xu, Peiwen; Li, Jie; Huang, Sexin; Gao, Ming; Kang, Ranran; Gao, Xuan; Gao, Yuan

    2016-10-01

    To explore the clinical application of droplet digital PCR (ddPCR) for genetic testing and prenatal diagnosis of spinal muscular atrophy (SMA) with deletion of SMN1 gene exon 7. A total of 138 clinical samples, including 121 peripheral blood, 13 amniotic fluid, 2 umbilical cord blood and 2 chorionic villi from 56 SMA families, were tested by both ddPCR and multiplex ligation-dependent probe amplification (MLPA). Results of the two approaches were analyzed with commercial software QuantaSoft (ddPCR) and Coffalyser (MLPA), respectively. Among the 138 cases, 25 had two copies, 84 had one copy, and 29 had null copy of exon 7 of the SMN1 gene. The results of ddPCR and MLPA were completely consistent. As a rapid, precise and economically efficient method, ddPCR will provide a new choice for genetic testing of SMA.

  20. Non-invasive computer-assisted measurement of knee alignment.

    PubMed

    Clarke, Jon V; Riches, Philip E; Picard, Frederic; Deakin, Angela H

    2012-01-01

    The quantification of knee alignment is a routine part of orthopaedic practice and is important for monitoring disease progression, planning interventional strategies, and follow-up of patients. Currently available technologies such as radiographic measurements have a number of drawbacks. The aim of this study was to validate a potentially improved technique for measuring knee alignment under different conditions. An image-free navigation system was adapted for non-invasive use through the development of external infrared tracker mountings. Stability was assessed by comparing the variance (F-test) of repeated mechanical femoro-tibial (MFT) angle measurements for a volunteer and a leg model. MFT angles were then measured supine, standing and with varus-valgus stress in asymptomatic volunteers who each underwent two separate registrations and repeated measurements for each condition. The mean difference and 95% limits of agreement were used to assess intra-registration and inter-registration repeatability. For multiple registrations the range of measurements for the external mountings was 1° larger than for the rigid model with statistically similar variance (p=0.34). Thirty volunteers were assessed (19 males, 11 females) with a mean age of 41 years (range: 20-65) and a mean BMI of 26 (range: 19-34). For intra-registration repeatability, consecutive coronal alignment readings agreed to almost ±1°, with up to ±0.5° loss of repeatability for coronal alignment measured before and after stress maneuvers, and a ±0.2° loss following stance trials. Sagittal alignment measurements were less repeatable overall by an approximate factor of two. Inter-registration agreement limits for coronal and sagittal supine MFT angles were ±1.6° and ±2.3°, respectively. Varus and valgus stress measurements agreed to within ±1.3° and ±1.1°, respectively. Agreement limits for standing MFT angles were ±2.9° (coronal) and ±5.0° (sagittal), which may have reflected a variation

  1. Barriers and facilitators for men to attend prenatal care and obtain HIV voluntary counseling and testing in Brazil

    PubMed Central

    Simon, Mariana; Mindry, Deborah; Nielsen-Saines, Karin; Chaves, Maria Cristina; Santos, Breno; Melo, Marineide; Mendoza, Brenna; Gorbach, Pamina

    2017-01-01

    Background Providing HIV voluntary counseling and testing (VCT) to men who attend their partner's prenatal care is an intervention with potential to reduce HIV transmission to women and infants during the vulnerable period of pregnancy. Little is known about the acceptability of this intervention in global settings outside of Africa. Methods We conducted in-depth qualitative interviews to evaluate potential barriers and facilitators to prenatal care attendance for HIV VCT with 20 men who did and 15 men who did not attend prenatal care with their partners at Hospital Conceiçao in Porto Alegre, Brazil. Men were recruited at the labor and delivery unit at Hospital Conceiçao via a scripted invitation while visiting their newborn infant. Interviews lasted from 35–55 minutes and were conducted in Portuguese by a local resident trained extensively in qualitative methods. All interviews were transcribed verbatim, translated, and then analyzed using Atlast.ti software. An analysis of themes was then conducted using direct quotes and statements. We applied and adapted the AIDS Risk Reduction Theoretical Model and HIV Testing Decisions Model to the qualitative data to identify themes in the 35 interviews. Results If offered HIV testing during prenatal care, all men in both groups stated they would accept this intervention. Yet, individual, relationship and systemic factors were identified that affect these Brazilian men's decision to attend prenatal care, informing our final conceptual model. The men interviewed had a general understanding of the value of HIV prevention of mother to child transmission. They also described open and communicative relationships with their significant others and displayed a high level of enthusiasm towards optimizing the health of their expanding family. The major barriers to attending prenatal care included perceived stigma against HIV infected individuals, men’s lack of involvement in planning of the pregnancy as well as inconvenient

  2. Barriers and facilitators for men to attend prenatal care and obtain HIV voluntary counseling and testing in Brazil.

    PubMed

    Yeganeh, Nava; Simon, Mariana; Mindry, Deborah; Nielsen-Saines, Karin; Chaves, Maria Cristina; Santos, Breno; Melo, Marineide; Mendoza, Brenna; Gorbach, Pamina

    2017-01-01

    Providing HIV voluntary counseling and testing (VCT) to men who attend their partner's prenatal care is an intervention with potential to reduce HIV transmission to women and infants during the vulnerable period of pregnancy. Little is known about the acceptability of this intervention in global settings outside of Africa. We conducted in-depth qualitative interviews to evaluate potential barriers and facilitators to prenatal care attendance for HIV VCT with 20 men who did and 15 men who did not attend prenatal care with their partners at Hospital Conceiçao in Porto Alegre, Brazil. Men were recruited at the labor and delivery unit at Hospital Conceiçao via a scripted invitation while visiting their newborn infant. Interviews lasted from 35-55 minutes and were conducted in Portuguese by a local resident trained extensively in qualitative methods. All interviews were transcribed verbatim, translated, and then analyzed using Atlast.ti software. An analysis of themes was then conducted using direct quotes and statements. We applied and adapted the AIDS Risk Reduction Theoretical Model and HIV Testing Decisions Model to the qualitative data to identify themes in the 35 interviews. If offered HIV testing during prenatal care, all men in both groups stated they would accept this intervention. Yet, individual, relationship and systemic factors were identified that affect these Brazilian men's decision to attend prenatal care, informing our final conceptual model. The men interviewed had a general understanding of the value of HIV prevention of mother to child transmission. They also described open and communicative relationships with their significant others and displayed a high level of enthusiasm towards optimizing the health of their expanding family. The major barriers to attending prenatal care included perceived stigma against HIV infected individuals, men's lack of involvement in planning of the pregnancy as well as inconvenient scheduling of prenatal care, due to

  3. Medical records and women's self-report are not reliable sources for determining whether prenatal HIV testing was done.

    PubMed

    Yudin, Mark H; Barbara, Angela M; Guenter, Dale; Shaul, Randi Zlotnik; Remis, Robert S; King, Susan M

    2006-10-01

    To determine whether medical records and the self-report of a postpartum patient provide reliable information about whether or not prenatal HIV testing has been done. Women on the postpartum wards at three Toronto teaching hospitals who gave informed consent were included in the study. The presence or absence of prenatal HIV testing was determined by interviews with postpartum women, review of hospital charts, and search of the Public Health Provincial Laboratory and Prenatal Testing databases. Two hundred ninety-nine women were enrolled. All had had at least one prenatal visit, and 92% had copies of prenatal records in their hospital charts. Health records and patient reports were both unreliable for determining who had and who had not had HIV testing. HIV status was documented on 55% of the charts; on 46% it was noted that testing was performed, and on 46% there was documentation of pre& or post&test counselling. In interviews, 73% of the women reported having an HIV test during this pregnancy. Using the laboratory databases as the gold standard of whether testing had truly been done, medical record sensitivity and specificity were 65% and 62% respectively, and self-report sensitivity and specificity were 87% and 52% respectively. Using medical records resulted in an underestimation and self-reports an overestimation of the number of women who had been tested. Both medical records and patient self-report are unreliable at the time of labour and delivery for determining whether or not a woman has been tested for HIV in pregnancy. Clinical and public health decisions may therefore be compromised by a lack of accurate testing information at the bedside.

  4. Non-Invasive Methods to Diagnose Fungal Infections in Pediatric Patients with Hematologic Disorders

    PubMed Central

    Badiee, Parisa; Hashemizadeh, Zahra; Ramzi, Mani; Karimi, Mohammad; Mohammadi, Rasoul

    2016-01-01

    Background Invasive fungal infection (IFIs) is a major infectious complication in immunocompromised patients. Early diagnosis and initiation of antifungal therapy is important to achieve the best outcome. Objectives The current study aimed to investigate the incidence of IFIs and evaluate the diagnostic performance of non-invasive laboratory tests: serologic (β-D-glucan, galactomannan) and molecular (nested polymerase chain reaction) tests to diagnose fungal infections in hematologic pediatric patients. Patients and Methods In a cross-sectional study from October 2014 to January 2015, 321 blood samples of 62 pediatric patients with hematologic disorders and at high risk for fungal infections were analyzed. Non-invasive tests including the Platelia Aspergillus enzyme immunoassay (EIA) to detect galactomannan antigen, Glucatell for β–D–glucan and nested PCR to detect Candida and Aspergillus species-specific DNA were used in a weekly screening strategy. Results Twenty six patients (42%) were considered as proven and probable IFIs, including 3 (5%) proven and 23 (37%) probable cases. Eighteen patients (29%) were considered as possible cases. The sensitivity, specificity, positive and negative predictive values for galactomannan test in 26 patients with proven and probable fungal infections were 94.4%, 100%, 100% and 94.7%; for β-D-glucan test 92.3%, 77.7%, 85%, 87.5% and for nested-PCR were 84.6%, 88.8%, 91.7% and 80%, respectively. Conclusions The rate of IFIs in pediatric patients with hematologic disorders is high, and sample collection from the sterile sites cannot be performed in immunocompromised patients. Detection of circulating fungal cell wall components and DNA in the blood using non-invasive methods can offer diagnostic help in patients with suspected IFIs. Their results should be interpreted in combination with clinical, radiological and microbiological findings. PMID:28138379

  5. Choosing offspring: prenatal genetic testing for thalassaemia and the production of a 'saviour sibling' in China.

    PubMed

    Sui, Suli; Sleeboom-Faulkner, Margaret

    2010-02-01

    This paper focuses on the pre-natal genetic testing and reproductive decision-making around thalassaemia in China. Findings are based on fieldwork conducted in hospitals and research institutions, interviews with families with thalassaemia-affected children, interviews with geneticists and genetic researchers and a literature review conducted between September and November 2007. The paper aims to provide insight into the ways in which those who carry thalassaemia decide to have a test for the condition and the choices available to prospective parents. The paper also analyses factors affecting reproductive choices and the decision to produce a 'saviour sibling', including financial implications, state family planning policy, images and information conveyed through the media and propaganda, advice and counselling from doctors, psychological pressure from the community and social discrimination. The paper concludes with a discussion on the issues involved in the creation of saviour siblings, some of which are particular to China.

  6. Bioinformatics Approaches for Fetal DNA Fraction Estimation in Noninvasive Prenatal Testing

    PubMed Central

    Peng, Xianlu Laura; Jiang, Peiyong

    2017-01-01

    The discovery of cell-free fetal DNA molecules in plasma of pregnant women has created a paradigm shift in noninvasive prenatal testing (NIPT). Circulating cell-free DNA in maternal plasma has been increasingly recognized as an important proxy to detect fetal abnormalities in a noninvasive manner. A variety of approaches for NIPT using next-generation sequencing have been developed, which have been rapidly transforming clinical practices nowadays. In such approaches, the fetal DNA fraction is a pivotal parameter governing the overall performance and guaranteeing the proper clinical interpretation of testing results. In this review, we describe the current bioinformatics approaches developed for estimating the fetal DNA fraction and discuss their pros and cons. PMID:28230760

  7. Bioinformatics Approaches for Fetal DNA Fraction Estimation in Noninvasive Prenatal Testing.

    PubMed

    Peng, Xianlu Laura; Jiang, Peiyong

    2017-02-20

    The discovery of cell-free fetal DNA molecules in plasma of pregnant women has created a paradigm shift in noninvasive prenatal testing (NIPT). Circulating cell-free DNA in maternal plasma has been increasingly recognized as an important proxy to detect fetal abnormalities in a noninvasive manner. A variety of approaches for NIPT using next-generation sequencing have been developed, which have been rapidly transforming clinical practices nowadays. In such approaches, the fetal DNA fraction is a pivotal parameter governing the overall performance and guaranteeing the proper clinical interpretation of testing results. In this review, we describe the current bioinformatics approaches developed for estimating the fetal DNA fraction and discuss their pros and cons.

  8. Predictive, pre-natal and diagnostic genetic testing for Huntington's disease: the experience in Canada from 1987 to 2000.

    PubMed

    Creighton, S; Almqvist, E W; MacGregor, D; Fernandez, B; Hogg, H; Beis, J; Welch, J P; Riddell, C; Lokkesmoe, R; Khalifa, M; MacKenzie, J; Sajoo, A; Farrell, S; Robert, F; Shugar, A; Summers, A; Meschino, W; Allingham-Hawkins, D; Chiu, T; Hunter, A; Allanson, J; Hare, H; Schween, J; Collins, L; Sanders, S; Greenberg, C; Cardwell, S; Lemire, E; MacLeod, P; Hayden, M R

    2003-06-01

    Predictive and pre-natal testing for Huntington's Disease (HD) has been available since 1987. Initially this was offered by linkage analysis, which was surpassed by the advent of the direct mutation test for HD in 1993. Direct mutation analysis provided an accurate test that not only enhanced predictive and pre-natal testing, but also permitted the diagnostic testing of symptomatic individuals. The objective of this study was to investigate the uptake, utilization, and outcome of predictive, pre-natal and diagnostic testing in Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian medical genetics centres and their affiliated laboratories offering genetic testing for HD were invited to participate. A total of 15 of 22 centres (68.2%), currently offering or ever having offered genetic testing for HD, responded, providing data on test results, demographics, and clinical history. A total of 1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were performed. The uptake for predictive testing was approximately 18% of the estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to 20.7% in British Columbia. There appears to have been a decline in the rate of testing in recent years. Of the predictive tests, 45.0% of individuals were found to have an increased risk, and a preponderance of females (60.2%) sought testing. A greater proportion of those at < or = 25% risk sought predictive testing once direct CAG mutation analysis had become available (10.9% after mutation analysis vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in termination of pregnancy in all but one. Diagnostic testing identified 68.5% of individuals to be positive by mutation analysis, while 31.5% of those with HD-like symptoms were not found to have the HD mutation. The positive diagnostic tests included 24.5% of individuals with no known

  9. 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

  10. The Psychological Challenges of Replacing Conventional Karyotyping with Genomic SNP Array Analysis in Prenatal Testing.

    PubMed

    Riedijk, Sam; Diderich, Karin E M; van der Steen, Sanne L; Govaerts, Lutgarde C P; Joosten, Marieke; Knapen, Maarten F C M; de Vries, Femke A T; van Opstal, Diane; Tibben, Aad; Galjaard, Robert-Jan H

    2014-07-03

    Pregnant couples tend to prefer a maximum of information about the health of their fetus. Therefore, we implemented whole genome microarray instead of conventional karyotyping (CK) for all indications for prenatal diagnosis (PND). The array detects more clinically relevant anomalies, including early onset disorders, not related to the indication and more genetic anomalies of yet unquantifiable risk, so-called susceptibility loci (SL) for mainly neurodevelopmental disorders. This manuscript highlights the psychological challenges in prenatal genetic counselling when using the array and provides counselling suggestions. First, we suggest that pre-test decision counselling should emphasize deliberation about what pregnant couples wish to learn about the future health of their fetus more than information about possible outcomes. Second, pregnant couples need support in dealing with SL. Therefore, in order to consider the SL in a proportionate perspective, the presence of phenotypes associated with SL in the family, the incidence of a particular SL in control populations and in postnatally ascertained patients needs highlighting during post-test genetic counselling. Finally, the decision that couples need to make about the course of their pregnancy is more complicated when the expected phenotype is variable and not quantifiable. Therefore, during post-test psychological counseling, couples should concretize the options of continuing and ending their pregnancy; all underlying feelings and thoughts should be made explicit, as well as the couple's resources, in order to attain adequate decision-making. As such, pre- and post-test counselling aids pregnant couples in handling the uncertainties that may accompany offering a broader scope of genetic PND using the array.

  11. The Psychological Challenges of Replacing Conventional Karyotyping with Genomic SNP Array Analysis in Prenatal Testing

    PubMed Central

    Riedijk, Sam; Diderich, Karin E. M.; van der Steen, Sanne L.; Govaerts, Lutgarde C. P.; Joosten, Marieke; Knapen, Maarten F. C. M.; de Vries, Femke A. T.; van Opstal, Diane; Tibben, Aad; Galjaard, Robert-Jan H.

    2014-01-01

    Pregnant couples tend to prefer a maximum of information about the health of their fetus. Therefore, we implemented whole genome microarray instead of conventional karyotyping (CK) for all indications for prenatal diagnosis (PND). The array detects more clinically relevant anomalies, including early onset disorders, not related to the indication and more genetic anomalies of yet unquantifiable risk, so-called susceptibility loci (SL) for mainly neurodevelopmental disorders. This manuscript highlights the psychological challenges in prenatal genetic counselling when using the array and provides counselling suggestions. First, we suggest that pre-test decision counselling should emphasize deliberation about what pregnant couples wish to learn about the future health of their fetus more than information about possible outcomes. Second, pregnant couples need support in dealing with SL. Therefore, in order to consider the SL in a proportionate perspective, the presence of phenotypes associated with SL in the family, the incidence of a particular SL in control populations and in postnatally ascertained patients needs highlighting during post-test genetic counselling. Finally, the decision that couples need to make about the course of their pregnancy is more complicated when the expected phenotype is variable and not quantifiable. Therefore, during post-test psychological counseling, couples should concretize the options of continuing and ending their pregnancy; all underlying feelings and thoughts should be made explicit, as well as the couple’s resources, in order to attain adequate decision-making. As such, pre- and post-test counselling aids pregnant couples in handling the uncertainties that may accompany offering a broader scope of genetic PND using the array. PMID:26237473

  12. [Prediction of serum albumin levels by non-invasive factors among elderly female patients].

    PubMed

    Kinoshita, Miki; Tokudome, Yuko; Takagi, Kenji; Kato, Shinji; Hotta, Yoshihiro

    2011-01-01

    To apply nutrition care management to elderly female patients, we predicted serum albumin (s-Alb) levels by non-invasive factors. After excluding patients with lesions/diseases which were directly related to s-Alb levels, we investigated 147 elderly women aged 75-years or over who were taking meals orally and were hospitalized from April 2008 to April 2009 at a hospital in Toyota. The patients were classified into 2 groups, one of patients with s-Alb levels of 3.5 g/dl or below (n=80), and the other of those with s-Alb levels of over 3.5 g/dl (n=67). Between the 2 groups, we examined differences in age, body mass index (BMI), living arrangements, necessary nursing care level (NNCL), bed confinement level (BCL), OH scale level (OHSL), and dietary intake either by the Student t-test, Mann-Whitney U test or chi-square test. Pearson correlation coefficients were calculated among s-Alb levels and selected variables. Taking into account the correlation coefficients, we conducted multiple regression analysis adopting the s-Alb level as a dependent variable and non-invasive factors as independent variables. For all the performed tests and analyses, a p value of less than 0.05 (on two-tailed analysis) was assumed to represent a statistically significant difference. S-Alb level was significantly associated with variables, including age, BMI, NNCL, BCL, OHSL, and percentage of protein intake (PPI). Multiple regression analysis revealed 4 significant variables: age, BCL, OHSL, and PPI. The multiple regression equation was y=4.977-(0.098×OHSL)-(0.080×BCL)-(0.016×age)+(0.003×PPI), and the multiple correlation coefficient R(2) was 0.398 (p <0.001). S-Alb levels among elderly female patients may be predicted by 4 non-invasive variables: age, BCL, OHSL, and PPI.

  13. Estimating Trabecular Bone Mechanical Properties From Non-Invasive Imaging

    NASA Technical Reports Server (NTRS)

    Hogan, Harry A.; Webster, Laurie

    1997-01-01

    An important component in developing countermeasures for maintaining musculoskeletal integrity during long-term space flight is an effective and meaningful method of monitoring skeletal condition. Magnetic resonance imaging (MRI) is an attractive non-invasive approach because it avoids the exposure to radiation associated with X-ray based imaging and also provides measures related to bone microstructure rather than just density. The purpose of the research for the 1996 Summer Faculty Fellowship period was to extend the usefulness of the MRI data to estimate the mechanical properties of trabecular bone. The main mechanical properties of interest are the elastic modulus and ultimate strength. Correlations are being investigated between these and fractal analysis parameters, MRI relaxation times, apparent densities, and bone mineral densities. Bone specimens from both human and equine donors have been studied initially to ensure high-quality MR images. Specimens were prepared and scanned from human proximal tibia bones as well as the equine distal radius. The quality of the images from the human bone appeared compromised due to freezing artifact, so only equine bone was included in subsequent procedures since these specimens could be acquired and imaged fresh before being frozen. MRI scans were made spanning a 3.6 cm length on each of 5 equine distal radius specimens. The images were then sent to Dr. Raj Acharya of the State University of New York at Buffalo for fractal analysis. Each piece was cut into 3 slabs approximately 1.2 cm thick and high-resolution contact radiographs were made to provide images for comparing fractal analysis with MR images. Dual energy X-ray absorptiometry (DEXA) scans were also made of each slab for subsequent bone mineral density determination. Slabs were cut into cubes for mechanical using a slow-speed diamond blade wafering saw (Buehler Isomet). The dimensions and wet weights of each cube specimen were measured and recorded. Wet weights

  14. Instrumentation for Non-Invasive Assessment of Cardiovascular Regulation

    NASA Technical Reports Server (NTRS)

    Cohen, Richard J.

    1999-01-01

    It is critically important to be able to assess alterations in cardiovascular regulation during and after space flight. We propose to develop an instrument for the non-invasive assessment of such alterations that can be used on the ground and potentially during space flight. This instrumentation would be used by the Cardiovascular Alterations Team at multiple sites for the study of the effects of space flight on the cardiovascular system and the evaluation of countermeasures. In particular, the Cardiovascular Alterations Team will use this instrumentation in conjunction with ground-based human bed-rest studies and during application of acute stresses e.g., tilt, lower body negative pressure, and exercise. In future studies, the Cardiovascular Alterations Team anticipates using this instrumentation to study astronauts before and after space flight and ultimately, during space flight. The instrumentation may also be used by the Bone Demineralization/Calcium Metabolism Team, the Neurovestibular Team and the Human Performance Factors, Sleep and Chronobiology Team to measure changes in autonomic nervous function. The instrumentation will be based on a powerful new technology - cardiovascular system identification (CSI) - which has been developed in our laboratory. CSI provides a non-invasive approach for the study of alterations in cardiovascular regulation. This approach involves the analysis of second-to-second fluctuations in physiologic signals such as heart rate and non-invasively measured arterial blood pressure in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of multiple physiologic mechanisms, CSI provides a closed-loop model of the cardiovascular regulatory state in an individual subject.

  15. Instrumentation for Non-Invasive Assessment of Cardiovascular Regulation

    NASA Technical Reports Server (NTRS)

    Cohen, Richard J.

    1999-01-01

    It is critically important to be able to assess alterations in cardiovascular regulation during and after space flight. We propose to develop an instrument for the non-invasive assessment of such alterations that can be used on the ground and potentially during space flight. This instrumentation would be used by the Cardiovascular Alterations Team at multiple sites for the study of the effects of space flight on the cardiovascular system and the evaluation of countermeasures. In particular, the Cardiovascular Alterations Team will use this instrumentation in conjunction with ground-based human bed-rest studies and during application of acute stresses e.g., tilt, lower body negative pressure, and exercise. In future studies, the Cardiovascular Alterations Team anticipates using this instrumentation to study astronauts before and after space flight and ultimately, during space flight. The instrumentation may also be used by the Bone Demineralization/Calcium Metabolism Team, the Neurovestibular Team and the Human Performance Factors, Sleep and Chronobiology Team to measure changes in autonomic nervous function. The instrumentation will be based on a powerful new technology - cardiovascular system identification (CSI) - which has been developed in our laboratory. CSI provides a non-invasive approach for the study of alterations in cardiovascular regulation. This approach involves the analysis of second-to-second fluctuations in physiologic signals such as heart rate and non-invasively measured arterial blood pressure in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of multiple physiologic mechanisms, CSI provides a closed-loop model of the cardiovascular regulatory state in an individual subject.

  16. BACs-on-Beads Technology: A Reliable Test for Rapid Detection of Aneuploidies and Microdeletions in Prenatal Diagnosis

    PubMed Central

    Martínez-Conejero, José Antonio; Serra, Vicente; Olmo, Inés; Lara, Coral; Simón, Carlos

    2014-01-01

    The risk of fetal aneuploidies is usually estimated based on high resolution ultrasound combined with biochemical determination of criterion in maternal blood, with invasive procedures offered to the population at risk. The purpose of this study was to investigate the effectiveness of a new rapid aneuploidy screening test on amniotic fluid (AF) or chorionic villus (CV) samples based on BACs-on-Beads (BoBs) technology and to compare the results with classical karyotyping by Giemsa banding (G-banding) of cultured cells in metaphase as the gold standard technique. The prenatal-BoBs kit was used to study aneuploidies involving chromosomes 13, 18, 21, X, and Y as well as nine microdeletion syndromes in 321 AF and 43 CV samples. G-banding of metaphase cultured cells was performed concomitantly for all prenatal samples. A microarray-based comparative genomic hybridization (aCGH) was also carried out in a subset of samples. Prenatal-BoBs results were widely confirmed by classical karyotyping. Only six karyotype findings were not identified by Prenatal-BoBs, all of them due to the known limitations of the technique. In summary, the BACs-on-Beads technology was an accurate, robust, and efficient method for the rapid diagnosis of common aneuploidies and microdeletion syndromes in prenatal samples. PMID:24795887

  17. BACs-on-Beads technology: a reliable test for rapid detection of aneuploidies and microdeletions in prenatal diagnosis.

    PubMed

    García-Herrero, Sandra; Campos-Galindo, Inmaculada; Martínez-Conejero, José Antonio; Serra, Vicente; Olmo, Inés; Lara, Coral; Simón, Carlos; Rubio, Carmen

    2014-01-01

    The risk of fetal aneuploidies is usually estimated based on high resolution ultrasound combined with biochemical determination of criterion in maternal blood, with invasive procedures offered to the population at risk. The purpose of this study was to investigate the effectiveness of a new rapid aneuploidy screening test on amniotic fluid (AF) or chorionic villus (CV) samples based on BACs-on-Beads (BoBs) technology and to compare the results with classical karyotyping by Giemsa banding (G-banding) of cultured cells in metaphase as the gold standard technique. The prenatal-BoBs kit was used to study aneuploidies involving chromosomes 13, 18, 21, X, and Y as well as nine microdeletion syndromes in 321 AF and 43 CV samples. G-banding of metaphase cultured cells was performed concomitantly for all prenatal samples. A microarray-based comparative genomic hybridization (aCGH) was also carried out in a subset of samples. Prenatal-BoBs results were widely confirmed by classical karyotyping. Only six karyotype findings were not identified by Prenatal-BoBs, all of them due to the known limitations of the technique. In summary, the BACs-on-Beads technology was an accurate, robust, and efficient method for the rapid diagnosis of common aneuploidies and microdeletion syndromes in prenatal samples.

  18. Non-invasive techniques for determining musculoskeleton body composition

    SciTech Connect

    Cohn, S.H.

    1984-01-01

    In vivo neutron activation analysis, combined with gamma spectrometry, has ushered in a new era of clinical diagnosis and evaluation of therapies, as well as investigation into and modelling of body composition in both normal individuals and patients suffering from various diseases and dysfunctions. Body composition studies have provided baseline data on such vital constituents as nitrogen, potassium and calcium. The non-invasive measurement techniques are particularly suitable for study of the musculo-skeletal changes in body composition. Of particular relevance here is the measurement of calcium loss in astronauts during prolonged space flights.

  19. Towards a smart non-invasive fluid loss measurement system.

    PubMed

    Suryadevara, N K; Mukhopadhyay, S C; Barrack, L

    2015-04-01

    In this article, a smart wireless sensing non-invasive system for estimating the amount of fluid loss, a person experiences while physical activity is presented. The system measures three external body parameters, Heart Rate, Galvanic Skin Response (GSR, or skin conductance), and Skin Temperature. These three parameters are entered into an empirically derived formula along with the user's body mass index, and estimation for the amount of fluid lost is determined. The core benefit of the developed system is the affluence usage in combining with smart home monitoring systems to care elderly people in ambient assisted living environments as well in automobiles to monitor the body parameters of a motorist.

  20. The Non-Invasive Measurement of Regional Cerebral Blood Flow

    PubMed Central

    Wilson, Edwin M.; Wills, Edward L.

    1977-01-01

    The non-invasive, repeatable measurement of bilateral, regional cerebral blood flow in man is achieved through the application of the 133xenon inhalation method. The clinical utility of the methodology is enhanced by integrating the method into a computer system which combines on-line data acquisition with rapid data analysis and display. The subsequent statistical analysis of the results from specific patient categories and normal populations is facilitated by a computerized data base coupled with the primary computer system. ImagesFig. 2

  1. Advances in non-invasive imaging of intracranial vascular disease.

    PubMed Central

    Jäger, H. R.; Grieve, J. P.

    2000-01-01

    Intra-arterial catheter angiography has, in the past, been the mainstay for the investigation of intracranial vascular disease. It is, however, invasive, usually requires in-patients admission, and is associated with a rate of neurological complications between 1% and 3%. In recent years, magnetic resonance angiography (MRA) and CT angiography (CTA) have emerged as non-invasive alternatives for imaging blood vessels and have made a significant impact on neuroradiological investigations. It is the purpose of this article to explain the basic technical principles of these two methods and to give an overview of their current clinical applications. PMID:10700757

  2. [Prenatal medicine and prenatal diagnosis].

    PubMed

    Valero de Bernabé Martín de Eugenio, Javier

    2009-01-01

    Prenatal diagnosis universalization allows knowing the prognostic possibilities in a situation of limited therapeutical resources. Therefore, besides permitting the peace of a normal fetal development, in other circumstances it can provoke parent's requirement to interrupt pregnancy in cases of malformation or chromosomal alteration, situations that parents may conceive as difficult for child's life and family environment. Diagnostic tests reliability and risks, information given to the parents, conversion in an eugenic practice of prenatal diagnosis and OMS recommendations in relation to the optional and voluntary character that this diagnosis should have are analysed.

  3. Decision outcomes in women offered noninvasive prenatal test (NIPT) for positive Down screening results.

    PubMed

    Lo, Tsz-Kin; Chan, Kelvin Yuen-Kwong; Kan, Anita Sik-Yau; So, Po-Lam; Kong, Choi-Wah; Mak, Shui-Lam; Lee, Chung-Nin

    2017-09-19

    In this first Asian study, the decision outcomes (decision conflict, decision regret, and anxiety) of 262 pregnant women offered noninvasive prenatal test (NIPT) for high-risk Down screening results were assessed. Decision conflict was experienced by 3.5% and level of decisional regret low (mean score 15.7, 95%CI 13.2-18.3). All 13 cases of decisional regret were NIPT acceptors. Elevated anxiety was experienced by 55.9% at the time of decision making about NIPT and persistent in 30.3%. Insufficient knowledge about NIPT was associated with elevated anxiety at decision making (p = .011) and with decisional regret (p = .016). Decisional regret was associated with prolonged anxiety (p = .010).

  4. Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes: a challenge for molecular analysis and genetic counseling.

    PubMed

    Eggermann, Thomas; Brioude, Frédéric; Russo, Silvia; Lombardi, Maria P; Bliek, Jet; Maher, Eamonn R; Larizza, Lidia; Prawitt, Dirk; Netchine, Irène; Gonzales, Marie; Grønskov, Karen; Tümer, Zeynep; Monk, David; Mannens, Marcel; Chrzanowska, Krystyna; Walasek, Malgorzata K; Begemann, Matthias; Soellner, Lukas; Eggermann, Katja; Tenorio, Jair; Nevado, Julián; Moore, Gudrun E; Mackay, Deborah Jg; Temple, Karen; Gillessen-Kaesbach, Gabriele; Ogata, Tsutomu; Weksberg, Rosanna; Algar, Elizabeth; Lapunzina, Pablo

    2016-06-01

    Beckwith-Wiedemann and Silver-Russell syndromes (BWS/SRS) are two imprinting disorders (IDs) associated with disturbances of the 11p15.5 chromosomal region. In BWS, epimutations and genomic alterations within 11p15.5 are observed in >70% of patients, whereas in SRS they are observed in about 60% of the cases. In addition, 10% of the SRS patients carry a maternal uniparental disomy of chromosome 7 11p15.5. There is an increasing demand for prenatal testing of these disorders owing to family history, indicative prenatal ultrasound findings or aberrations involving chromosomes 7 and 11. The complex molecular findings underlying these disorders are a challenge not only for laboratories offering these tests but also for geneticists counseling affected families. The scope of counseling must consider the range of detectable disturbances and their origin, the lack of precise quantitative knowledge concerning the inheritance and recurrence risks for the epigenetic abnormalities, which are hallmarks of these developmental disorders. In this paper, experts in the field of BWS and SRS, including members of the European network of congenital IDs (EUCID.net; www.imprinting-disorders.eu), put together their experience and work in the field of 11p15.5-associated IDs with a focus on prenatal testing. Altogether, prenatal tests of 160 fetuses (122 referred for BWS, 38 for SRS testing) from 5 centers were analyzed and reviewed. We summarize the current knowledge on BWS and SRS with respect to diagnostic testing, the consequences for prenatal genetic testing and counseling and our cumulative experience in dealing with these disorders.

  5. Online estimation of respiratory mechanics in non-invasive pressure support ventilation: a bench model study.

    PubMed

    Mulqueeny, Qestra; Tassaux, Didier; Vignaux, Laurence; Jolliet, Philippe; Schindhelm, Klaus; Redmond, Stephen; Lovell, Nigel H

    2010-01-01

    An online algorithm for determining respiratory mechanics in patients using non-invasive ventilation (NIV) in pressure support mode was developed and embedded in a ventilator system. Based on multiple linear regression (MLR) of respiratory data, the algorithm was tested on a patient bench model under conditions with and without leak and simulating a variety of mechanics. Bland-Altman analysis indicates reliable measures of compliance across the clinical range of interest (± 11-18% limits of agreement). Resistance measures showed large quantitative errors (30-50%), however, it was still possible to qualitatively distinguish between normal and obstructive resistances. This outcome provides clinically significant information for ventilator titration and patient management.

  6. Post-and prenatal testing for FSHD: Diagnostic approach for sporadic and familial cases

    SciTech Connect

    Bakker, E.; Wielen, M.J.R. van der; Losekoot, M.

    1994-09-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder. A major locus for FSHD was localized at the distal part of chromosome 4q. More recently, a disease associated DNA rearrangement was detected with the polymorphic probe p13E-11 (D4F104S1). In most FSHD patients, a shortened (< 28 kb instead of 50-300 kb) allele was detected. In sporadic patients a de novo deletion was found to be associated with the occurrence of FSHD. Diagnostically there were a number of problems to overcome. (1) About 5% of families show no linkage to chromosome 4q35. (2) Some 10% normal individuals show a shortened p13E11 allele, which is located at chromosome 10q. Our diagnostic strategy is as follows: If in sporadic patients a shortened p13E-11 allele is detected and neither parent shows this allele, then a de novo deletion has occurred and FSHD is proven. If no shortened allele is detected FSHD is less likely. In case one of the parents shows a shortened allele then clinical investigations and linkage studies are performed for both chromosome 4 and 10 markers. In familial cases both p13E-11 and polymorphic markers are tested. A shortened p13E-11 allele and/or chromosome 4 haplotype segregating with FSHD can be used for presymptomatic and prenatal diagnosis. Up to now, 45 sporadic cases and 21 families were referred for diagnosis. In 22 sporadic cases a shortened allele was detected, 13 were proven de novo. The first prenatal test was recently performed. The index patient was a de novo case with a shortened allele; the fetus had inherited this allele.

  7. Difference and Choice: Exploring Prenatal Testing and the Use of Genetic Information with People with Learning Difficulties.

    ERIC Educational Resources Information Center

    Ward, Linda; Howarth, Joyce; Rodgers, Jackie

    2002-01-01

    This article describes two workshops that explained the use of prenatal testing and genetic information to inform choices in pregnancy to people with learning difficulties, explored the issues with them, and describe the contribution subsequently made by these people to a British national conference on this subject. (Contains references.)…

  8. Non-Invasive Assessment of Skeletal Muscle Myosin Heavy Chain Expression in Trained and Untrained Men.

    PubMed

    Fry, Andrew C; Housh, Terry J; Cramer, Joel B; Weir, Joseph P; Beck, Travis W; Schilling, Brian K; Miller, Jonathan D; Nicoll, Justin X

    2016-09-20

    Numerous conditions and types of physical activity (e.g., exercise, aging, muscle-related diseases) can influence muscle fiber types and the proteins expressed. To date, muscle fibers can only be characterized by actually obtaining a tissue sample using the invasive muscle biopsy procedure. Mechanomyography (MMG) is the assessment of the vibration properties of contracting skeletal muscle, and has been proposed as a possible non-invasive method for muscle fiber analysis. Therefore, the purpose of this project was to examine the feasibility of using MMG and muscle performance measures to non-invasively assess muscle fiber characteristics. Fifteen men (5 endurance-trained [End], 5 weight-trained [WT], and 5 sedentary [Sed]) provided muscle samples from their vastus lateralis muscle. These samples were analyzed for relative myosin heavy chain protein expression, which is highly correlated with % muscle fiber type areas. Additionally, each subject performed several muscle performance tests, and MMG of the quadriceps was assessed during a knee extension exercise. Multiple regression was used to develop prediction equations for determining relative muscle content of myosin heavy chain (MHC) types I, IIa, and IIx. A combination of MMG and knee extension performance variables estimated types I, IIa, and IIx MHC with approximately 80% accuracy. Although preliminary, these data suggest that muscle performance tests in addition to MMG assessments during a simple muscle performance task (knee extension) can be used to estimate muscle fiber type composition in a healthy male population. Such methods could ultimately be used to non-invasively monitor muscle health and fitness.

  9. Comparison of Non-Invasive Methods for the Detection of Coronary Atherosclerosis

    PubMed Central

    Bampi, Angela Bacelar Albuquerque; Rochitte, Carlos Eduardo; Favarato, Desiderio; Lemos, Pedro Alves; da Luz, Protásio Lemos

    2009-01-01

    BACKGROUND: Non-invasive detection of atherosclerosis is critical for its prevention. Objective: To correlate non-invasively detectable indicators of coronary atherosclerosis, or Coronary Artery Disease (i.e., classical risk factors, hs-CRP test results, carotid intima-media thickness, endothelial function, ankle-brachial index and calcium score by computed tomography) with the extent of coronary disease assessed by the Friesinger index from conventional coronary angiography. METHODS: We conducted a prospective study of 100 consecutive patients, mean age 55.1 ± 10.7 years, 55% men and 45% women. Patients with acute coronary syndrome, renal dialytic insufficiency, collagen disease and cancer were not included. All patients were subjected to clinical evaluation and laboratory tests. Endothelial function of the brachial artery and carotid artery were evaluated by high-resolution ultrasound; ankle-brachial index and computed tomography for coronary determination of calcium score were also performed, and non-HDL cholesterol and TG/HDL-c ratio were calculated. All patients were subjected to coronary angiography at the request of the assistant physician. We considered patients without an obstructive lesion (< 29% stenosis) demonstrated by coronary angiography to be normal. RESULTS: Univariate analysis showed that calcium score, HDL-c, TG/HDL ratio and IMT were significantly correlated with the Friesinger index. However, multivariate analysis indicated that only calcium score and low HDL-c levels correlated significantly with the extension of CAD. On the other hand, hs-CRP, LDL-c, flow-mediated dilation, and Framingham score did not correlate with the Friesinger index. ROC analysis showed that calcium score, HDL-c and TG-HDL ratio accurately predicted extensive CAD in a statistically significant manner. CONCLUSION: It is possible to approximately determine the presence and extent of CAD by non-invasive methods, especially by calcium score, HDL-c and TG/HDL-c ratio assays

  10. Non-invasive primate head restraint using thermoplastic masks.

    PubMed

    Drucker, Caroline B; Carlson, Monica L; Toda, Koji; DeWind, Nicholas K; Platt, Michael L

    2015-09-30

    The success of many neuroscientific studies depends upon adequate head fixation of awake, behaving animals. Typically, this is achieved by surgically affixing a head-restraint prosthesis to the skull. Here we report the use of thermoplastic masks to non-invasively restrain monkeys' heads. Mesh thermoplastic sheets become pliable when heated and can then be molded to an individual monkey's head. After cooling, the custom mask retains this shape indefinitely for day-to-day use. We successfully trained rhesus macaques (Macaca mulatta) to perform cognitive tasks while wearing thermoplastic masks. Using these masks, we achieved a level of head stability sufficient for high-resolution eye-tracking and intracranial electrophysiology. Compared with traditional head-posts, we find that thermoplastic masks perform at least as well during infrared eye-tracking and single-neuron recordings, allow for clearer magnetic resonance image acquisition, enable freer placement of a transcranial magnetic stimulation coil, and impose lower financial and time costs on the lab. We conclude that thermoplastic masks are a viable non-invasive form of primate head restraint that enable a wide range of neuroscientific experiments. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Non-invasive diagnosis of liver fibrosis and cirrhosis.

    PubMed

    Lurie, Yoav; Webb, Muriel; Cytter-Kuint, Ruth; Shteingart, Shimon; Lederkremer, Gerardo Z

    2015-11-07

    The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.

  12. Modulation of Untruthful Responses with Non-Invasive Brain Stimulation

    PubMed Central

    Fecteau, Shirley; Boggio, Paulo; Fregni, Felipe; Pascual-Leone, Alvaro

    2013-01-01

    Deceptive abilities have long been studied in relation to personality traits. More recently, studies explored the neural substrates associated with deceptive skills suggesting a critical role of the prefrontal cortex. Here we investigated whether non-invasive brain stimulation over the dorsolateral prefrontal cortex (DLPFC) could modulate generation of untruthful responses about subject’s personal life across contexts (i.e., deceiving on guilt-free questions on daily activities; generating previously memorized lies about past experience; and producing spontaneous lies about past experience), as well as across modality responses (verbal and motor responses). Results reveal that real, but not sham, transcranial direct current stimulation (tDCS) over the DLPFC can reduce response latency for untruthful over truthful answers across contexts and modality responses. Also, contexts of lies seem to incur a different hemispheric laterality. These findings add up to previous studies demonstrating that it is possible to modulate some processes involved in generation of untruthful answers by applying non-invasive brain stimulation over the DLPFC and extend these findings by showing a differential hemispheric contribution of DLPFCs according to contexts. PMID:23550273

  13. Non-invasive primate head restraint using thermoplastic masks

    PubMed Central

    Drucker, Caroline B.; Carlson, Monica L.; Toda, Koji; DeWind, Nicholas K.; Platt, Michael L.

    2015-01-01

    Background The success of many neuroscientific studies depends upon adequate head fixation of awake, behaving animals. Typically, this is achieved by surgically affixing a head-restraint prosthesis to the skull. New Method Here we report the use of thermoplastic masks to non-invasively restrain monkeys’ heads. Mesh thermoplastic sheets become pliable when heated and can then be molded to an individual monkey’s head. After cooling, the custom mask retains this shape indefinitely for day-to-day use. Results We successfully trained rhesus macaques (Macaca mulatta) to perform cognitive tasks while wearing thermoplastic masks. Using these masks, we achieved a level of head stability sufficient for high-resolution eye-tracking and intracranial electrophysiology. Comparison with Existing Method Compared with traditional head-posts, we find that thermoplastic masks perform at least as well during infrared eye-tracking and single-neuron recordings, allow for clearer magnetic resonance image acquisition, enable freer placement of a transcranial magnetic stimulation coil, and impose lower financial and time costs on the lab. Conclusions We conclude that thermoplastic masks are a viable non-invasive form of primate head restraint that enable a wide range of neuroscientific experiments. PMID:26112334

  14. Non-invasive diagnostic imaging of colorectal liver metastases

    PubMed Central

    Mainenti, Pier Paolo; Romano, Federica; Pizzuti, Laura; Segreto, Sabrina; Storto, Giovanni; Mannelli, Lorenzo; Imbriaco, Massimo; Camera, Luigi; Maurea, Simone

    2015-01-01

    Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs. PMID:26217455

  15. Non-invasive diagnostic imaging of colorectal liver metastases.

    PubMed

    Mainenti, Pier Paolo; Romano, Federica; Pizzuti, Laura; Segreto, Sabrina; Storto, Giovanni; Mannelli, Lorenzo; Imbriaco, Massimo; Camera, Luigi; Maurea, Simone

    2015-07-28

    Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs.

  16. Non-invasive methodology for diagnostics of bearing impacts

    NASA Astrophysics Data System (ADS)

    Chi, John N.

    2007-04-01

    Various events in reciprocating machinery, such as connecting rod or piston movement, and diesel combustion produce a series of highly transient forces within the machine. These events generate force transients of short duration and broad frequency content. Even though these events may be part of a machine cycle and therefore periodic, it is often more appropriate to treat them on an individual basis because more diagnostics information is available from a single waveform during a cycle than from averages over several cycles. However, it is very rare for one to have direct access to source waveforms because of the expense and reliability problems associated with the required instrumentation, and non-invasive techniques will have to be used. This paper explores the use of cepstral smoothing and minimum phase extraction technique for non-invasive diagnostics of bearing impacts in reciprocating machinery. The methodology is based on extracting diagnostic signals from vibration measurements taken at a "convenient" location such as the crankshaft casing or bearing end-cap, and consists of source identification, diagnostic signature recovery, and diagnostic system decision-making. A dynamic simulation with lumped mass model is developed to analyze bearing impacts for the big end bearings, experimental measurements from accelerometers, transfer functions of vibration, and the structural response are presented.

  17. Infrared thermography: A non-invasive window into thermal physiology.

    PubMed

    Tattersall, Glenn J

    2016-12-01

    Infrared thermography is a non-invasive technique that measures mid to long-wave infrared radiation emanating from all objects and converts this to temperature. As an imaging technique, the value of modern infrared thermography is its ability to produce a digitized image or high speed video rendering a thermal map of the scene in false colour. Since temperature is an important environmental parameter influencing animal physiology and metabolic heat production an energetically expensive process, measuring temperature and energy exchange in animals is critical to understanding physiology, especially under field conditions. As a non-contact approach, infrared thermography provides a non-invasive complement to physiological data gathering. One caveat, however, is that only surface temperatures are measured, which guides much research to those thermal events occurring at the skin and insulating regions of the body. As an imaging technique, infrared thermal imaging is also subject to certain uncertainties that require physical modelling, which is typically done via built-in software approaches. Infrared thermal imaging has enabled different insights into the comparative physiology of phenomena ranging from thermogenesis, peripheral blood flow adjustments, evaporative cooling, and to respiratory physiology. In this review, I provide background and guidelines for the use of thermal imaging, primarily aimed at field physiologists and biologists interested in thermal biology. I also discuss some of the better known approaches and discoveries revealed from using thermal imaging with the objective of encouraging more quantitative assessment.

  18. Influence of hemoglobin on non-invasive optical bilirubin sensing

    NASA Astrophysics Data System (ADS)

    Jiang, Jingying; Gong, Qiliang; Zou, Da; Xu, Kexin

    2012-03-01

    Since the abnormal metabolism of bilirubin could lead to diseases in the human body, especially the jaundice which is harmful to neonates. Traditional invasive measurements are difficult to be accepted by people because of pain and infection. Therefore, the real-time and non-invasive measurement of bilirubin is of great significance. However, the accuracy of currently transcutaneous bilirubinometry(TcB) is generally not high enough, and affected by many factors in the human skin, mostly by hemoglobin. In this talk, absorption spectra of hemoglobin and bilirubin have been collected and analyzed, then the Partial Least Squares (PLS) models have been built. By analyzing and comparing the Correlation and Root Mean Square Error of Prediction(RMSEP), the results show that the Correlation of bilirubin solution model is larger than that of the mixture solution added with hemoglobin, and its RMSEP value is smaller than that of mixture solution. Therefore, hemoglobin has influences on the non-invasive optical bilirubin sensing. In next step, it is necessary to investigate how to eliminate the influence.

  19. Clinical role of non-invasive assessment of portal hypertension

    PubMed Central

    Bolognesi, Massimo; Di Pascoli, Marco; Sacerdoti, David

    2017-01-01

    Measurement of portal pressure is pivotal in the evaluation of patients with liver cirrhosis. The measurement of the hepatic venous pressure gradient represents the reference method by which portal pressure is estimated. However, it is an invasive procedure that requires significant hospital resources, including experienced staff, and is associated with considerable cost. Non-invasive methods that can be reliably used to estimate the presence and the degree of portal hypertension are urgently needed in clinical practice. Biochemical and morphological parameters have been proposed for this purpose, but have shown disappointing results overall. Splanchnic Doppler ultrasonography and the analysis of microbubble contrast agent kinetics with contrast-enhanced ultrasonography have shown better accuracy for the evaluation of patients with portal hypertension. A key advancement in the non-invasive evaluation of portal hypertension has been the introduction in clinical practice of methods able to measure stiffness in the liver, as well as stiffness/congestion in the spleen. According to the data published to date, it appears to be possible to rule out clinically significant portal hypertension in patients with cirrhosis (i.e., hepatic venous pressure gradient ≥ 10 mmHg) with a level of clinically-acceptable accuracy by combining measurements of liver stiffness and spleen stiffness along with Doppler ultrasound evaluation. It is probable that the combination of these methods may also allow for the identification of patients with the most serious degree of portal hypertension, and ongoing research is helping to ensure progress in this field. PMID:28104976

  20. Evolving strategies for liver fibrosis staging: Non-invasive assessment

    PubMed Central

    Stasi, Cristina; Milani, Stefano

    2017-01-01

    Transient elastography and the acoustic radiation force impulse techniques may play a pivotal role in the study of liver fibrosis. Some studies have shown that elastography can detect both the progression and regression of fibrosis. Similarly, research results have been analysed and direct and indirect serum markers of hepatic fibrosis have shown high diagnostic accuracy for advanced fibrosis/cirrhosis. The prognosis of different stages of cirrhosis is well established and various staging systems have been proposed, largely based on clinical data. However, it is still unknown if either non-invasive markers of liver fibrosis or elastography may contribute to a more accurate staging of liver cirrhosis, in terms of prognosis and fibrosis regression after effective therapy. In fact, not enough studies have shown both the fibrosis regression in different cirrhosis stages and the point beyond which the prognosis does not change - even in the event of fibrosis regression. Therefore, future studies are needed to validate non-invasive methods in predicting the different phases of liver cirrhosis. PMID:28127192

  1. Non-invasive assessment of cardiac output in children.

    PubMed Central

    Richardson, J R; Ferguson, J; Hiscox, J; Rawles, J

    1998-01-01

    BACKGROUND: Stroke distance, the systolic velocity integral of aortic blood flow, is a linear analogue of stroke volume; its product with heart rate is minute distance, analogous to cardiac output. OBJECTIVE: To investigate the feasibility of assessing cardiac output in children with a simple non-invasive Doppler ultrasound technique, and to determine the normal range of values. METHODS: Peak aortic blood velocity, stroke distance, and minute distance were measured through the suprasternal window in 166 children (mean age 9.6 years, range 2-14) using a portable non-imaging Doppler ultrasound instrument. RESULTS: The technique was well tolerated by all the children participating. Mean peak aortic blood velocity was 138 cm/s and was independent of age. Mean stroke distance was 31.8 cm and showed a small but significant increase with age; mean minute distance was 2490 cm and fell with age, as did heart rate. CONCLUSIONS: Suprasternal Doppler ultrasound measurement of stroke distance is a convenient, well tolerated, non-invasive technique for the assessment of cardiac output in children. The normal range of values during childhood has been established. The technique has great potential for assessing hypovolaemia in children. Images p307-a PMID:9785155

  2. Non-invasive diagnosis of liver fibrosis and cirrhosis

    PubMed Central

    Lurie, Yoav; Webb, Muriel; Cytter-Kuint, Ruth; Shteingart, Shimon; Lederkremer, Gerardo Z

    2015-01-01

    The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this “gold-standard” is imperfect; even according to its proponents, it is only “the best” among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future. PMID:26556987

  3. Clinical role of non-invasive assessment of portal hypertension.

    PubMed

    Bolognesi, Massimo; Di Pascoli, Marco; Sacerdoti, David

    2017-01-07

    Measurement of portal pressure is pivotal in the evaluation of patients with liver cirrhosis. The measurement of the hepatic venous pressure gradient represents the reference method by which portal pressure is estimated. However, it is an invasive procedure that requires significant hospital resources, including experienced staff, and is associated with considerable cost. Non-invasive methods that can be reliably used to estimate the presence and the degree of portal hypertension are urgently needed in clinical practice. Biochemical and morphological parameters have been proposed for this purpose, but have shown disappointing results overall. Splanchnic Doppler ultrasonography and the analysis of microbubble contrast agent kinetics with contrast-enhanced ultrasonography have shown better accuracy for the evaluation of patients with portal hypertension. A key advancement in the non-invasive evaluation of portal hypertension has been the introduction in clinical practice of methods able to measure stiffness in the liver, as well as stiffness/congestion in the spleen. According to the data published to date, it appears to be possible to rule out clinically significant portal hypertension in patients with cirrhosis (i.e., hepatic venous pressure gradient ≥ 10 mmHg) with a level of clinically-acceptable accuracy by combining measurements of liver stiffness and spleen stiffness along with Doppler ultrasound evaluation. It is probable that the combination of these methods may also allow for the identification of patients with the most serious degree of portal hypertension, and ongoing research is helping to ensure progress in this field.

  4. Visual memory improved by non-invasive brain stimulation.

    PubMed

    Chi, Richard P; Fregni, Felipe; Snyder, Allan W

    2010-09-24

    Our visual memories are susceptible to errors, but less so in people who have a more literal cognitive style. This inspired us to attempt to improve visual memory with non-invasive brain stimulation. We applied 13 min of bilateral transcranial direct current stimulation (tDCS) to the anterior temporal lobes. Our stimulation protocol included 3 conditions, each with 12 neurotypical participants: (i) left cathodal stimulation together with right anodal stimulation, (ii) left anodal stimulation together with right cathodal stimulation, and (iii) sham (control) stimulation. Only participants who received left cathodal stimulation (decrease in excitability) together with right anodal stimulation (increase in excitability) showed an improvement in visual memory. This 110% improvement in visual memory was similar to the advantage people with autism, who are known to be more literal, show over normal people in the identical visual task. Importantly, participants receiving stimulation of the opposite polarity (left anodal together with right cathodal stimulation) failed to show any change in memory performance. This is the first demonstration that visual memory can be enhanced in healthy people using non-invasive brain stimulation.

  5. Near-Infrared Spectroscopy as a Novel Non-Invasive Tool to Assess Spiny Lobster Nutritional Condition.

    PubMed

    Simon, Cedric J; 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.

  6. 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

  7. Prenatal Testing for Adult-Onset Conditions: the Position of the National Society of Genetic Counselors.

    PubMed

    Hercher, Laura; Uhlmann, Wendy R; Hoffman, Erin P; Gustafson, Shanna; Chen, Kelly M

    2016-12-01

    Advances in genetic testing and the availability of such testing in pregnancy allows prospective parents to test their future child for adult-onset conditions. This ability raises several complex ethical issues. Prospective parents have reproductive rights to obtain information about their fetus. This information may or may not alter pregnancy management. These rights can be in conflict with the rights of the future individual, who will be denied the right to elect or decline testing. This paper highlights the complexity of these issues, details discussions that went into the National Society of Genetic Counselors (NSGC) Public Policy Task Force's development of the Prenatal testing for Adult-Onset Conditions position statement adopted in November 2014, and cites relevant literature on this topic through December 2015. Issues addressed include parental rights and autonomy, rights of the future child, the right not to know, possible adverse effects on childhood and the need for genetic counseling. This paper will serve as a reference to genetic counselors and healthcare professionals when faced with this situation in clinical practice.

  8. Non-invasive physical treatments for chronic/recurrent headache.

    PubMed

    Bronfort, G; Nilsson, N; Haas, M; Evans, R; Goldsmith, C H; Assendelft, W J J; Bouter, L M

    2004-01-01

    Non-invasive physical treatments are often used to treat common types of chronic/recurrent headache. To quantify and compare the magnitude of short- and long-term effects of non-invasive physical treatments for chronic/recurrent headaches. We searched the following databases from their inception to November 2002: MEDLINE, EMBASE, BIOSIS, CINAHL, Science Citation Index, Dissertation Abstracts, CENTRAL, and the Specialised Register of the Cochrane Pain, Palliative Care and Supportive Care review group. Selected complementary medicine reference systems were searched as well. We also performed citation tracking and hand searching of potentially relevant journals. We included randomized and quasi-randomized controlled trials comparing non-invasive physical treatments for chronic/recurrent headaches to any type of control. Two independent reviewers abstracted trial information and scored trials for methodological quality. Outcomes data were standardized into percentage point and effect size scores wherever possible. The strength of the evidence of effectiveness was assessed using pre-specified rules. Twenty-two studies with a total of 2628 patients (age 12 to 78 years) met the inclusion criteria. Five types of headache were studied: migraine, tension-type, cervicogenic, a mix of migraine and tension-type, and post-traumatic headache. Ten studies had methodological quality scores of 50 or more (out of a possible 100 points), but many limitations were identified. We were unable to pool data because of study heterogeneity. For the prophylactic treatment of migraine headache, there is evidence that spinal manipulation may be an effective treatment option with a short-term effect similar to that of a commonly used, effective drug (amitriptyline). Other possible treatment options with weaker evidence of effectiveness are pulsating electromagnetic fields and a combination of transcutaneous electrical nerve stimulation [TENS] and electrical neurotransmitter modulation. For the

  9. 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

  10. Non-invasive Ventilation as Airway Clearance Technique in Cystic Fibrosis.

    PubMed

    Rodriguez Hortal, Maria Cecilia; Nygren-Bonnier, Malin; Hjelte, Lena

    2017-07-01

    For patients with cystic fibrosis, chest physiotherapy is crucial for evacuating airway secretions. Because chest physiotherapy increases energy expenditure, fatigue and dyspnoea, non-invasive ventilation (NIV) could be beneficial for severely ill patients during airway clearance. The aim of the study is to evaluate and compare the effects between NIV and positive expiratory pressure (PEP) on airway clearance. Prospective, randomized trial compares PEP to NIV. Thirty-two subjects, mean age 31 years, mean forced expiratory volume in 1 second 47% (±14) and mean forced vital capacity 69% (±13), completed a 3-month randomized trial comparing NIV with standard PEP treatment as airway clearance technique. Lung functions testing, 6-minute walk test, blood gases, sputum culture and inflammatory parameters were measured before and after the treatment period. There was a significant reduction in lung clearance index (LCI) following NIV compared with PEP (p = 0.01). LCI is performed within the lung function testing. Non-invasive ventilation was shown to be a good alternative to PEP in chest physiotherapy for patients with cystic fibrosis who are severely ill. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Does non-invasive brain stimulation improve cognition in major depressive disorder? A systematic review.

    PubMed

    Tortella, Gabriel; Selingardi, Priscila M L; Moreno, Marina L; Veronezi, Beatriz P; Brunoni, Andre R

    2014-01-01

    Non-invasive brain stimulation (NIBS) techniques, such as repeated transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have been increasingly used in different contexts to improve cognitive performance and ameliorate depression symptoms. Considering that major depression is usually accompanied by cognitive deficits, NIBS technique could be also helpful to improve cognition in depressed patients. In this systematic review, w