Incorporating DNA Sequencing into Current Prenatal Screening Practice for Down's Syndrome

PMCID: PMC3604109This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Multi-marker risk-based screening for prostate cancer.

OBJECTIVE: To determine prostate cancer screening performance using prostate specific antigen (PSA) along with other markers, expressing markers in age-specific multiples of the median (MoM), and age. METHODS: A prospective nested case-control study used stored serum from 571 men who died of, or with history of, prostate cancer (cases), and 2169 matched controls. Total, free and intact PSA, human kallikrein-related peptidase 2 (hK2), and microseminoprotein were measured and converted into MoM values. Screening marker distribution parameters were estimated in cases and controls. Monte Carlo simulation used these in a risk-based algorithm to estimate screening performance (detection rates [DRs] and false-positive rates [FPRs]). RESULTS: Almost all (99%) cases occurred aged ≥55. Marker values were similar in cases who did and did not die of prostate cancer. Combining age, total PSA and hK2 MoM values (other markers added little or no discrimination) yielded a 1.2% FPR (95% CI 0.2-4.8%) for a 90% DR (59-98%) in men who died of or with a prostate cancer diagnosis within 5 years of blood collection (risk cut-off 1 in 20), two-thirds less than the 4.5% FPR using total PSA alone measured in ng/ml for the same 90% DR (cut-off 3.1 ng/ml). Screening performance over 10 years yielded a 33% (22-46%) FPR for a 90% DR. CONCLUSION: Screening performed up to every 5 years from age 55 using the multi-marker risk-based screening algorithm for future prostate cancer achieves a high DR and a much lower FPR than using PSA alone, resulting in reductions in overdiagnosis and overtreatment

The dose-response relationship between cigarette consumption, biochemical markers and risk of lung cancer.

The relationship between the number of cigarettes smoked per day and the incidence of lung cancer is linear but, from the multistage model of carcinogenesis, it should be quadratic (upwards curving). We investigated this anomaly in a study of 11,403 male never smokers and current smokers in whom carboxyhaemoglobin (COHb) was measured in all and serum cotinine in 1175. The relationship between the biochemical markers and the reported number of cigarettes per day was approximately linear up to 20 cigarettes per day as expected. But above 20 cigarettes per day the marker levels increased less steeply and were 35% lower than expected in men who smoked more than 40 cigarettes per day. Less smoke is inhaled from each cigarette by men with high daily cigarette consumption than by men with lower consumption. Allowance for this transforms the observed linear dose-response relationship into one consistent with the expected quadratic relationship. The anomaly is explained by the observation that heavier smokers inhale less smoke from each cigarette

Rapid testing versus karyotyping in Down's syndrome screening: cost-effectiveness and detection of clinically significant chromosome abnormalities

In all, 80% of antenatal karyotypes are generated by Down's syndrome screening programmes (DSSP). After a positive screening, women are offered prenatal foetus karyotyping, the gold standard. Reliable molecular methods for rapid aneuploidy diagnosis (RAD: fluorescence in situ hybridization (FISH) and quantitative fluorescence PCR (QF-PCR)) can detect common aneuploidies, and are faster and less expensive than karyotyping

Isolated and dynamical horizons and their applications

Over the past three decades, black holes have played an important role in quantum gravity, mathematical physics, numerical relativity and gravitational wave phenomenology. However, conceptual settings and mathematical models used to discuss them have varied considerably from one area to another. Over the last five years a new, quasi-local framework was introduced to analyze diverse facets of black holes in a unified manner. In this framework, evolving black holes are modeled by dynamical horizons and black holes in equilibrium by isolated horizons. We review basic properties of these horizons and summarize applications to mathematical physics, numerical relativity and quantum gravity. This paradigm has led to significant generalizations of several results in black hole physics. Specifically, it has introduced a more physical setting for black hole thermodynamics and for black hole entropy calculations in quantum gravity; suggested a phenomenological model for hairy black holes; provided novel techniques to extract physics from numerical simulations; and led to new laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte

UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening.

BACKGROUND: Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial. METHODS: The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction. RESULTS: 247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569). CONCLUSIONS: The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction. TRIAL REGISTRATION: ISRCTN 78513845

Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis.

Background: The NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial. Methods: From October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50-75) had a risk score (LLPv2) ≥ 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence. Findings: 1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1-7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41-1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76-0.92) from nine eligible trials. Interpretation: The UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups. Funding: NIHR Health Technology Assessment programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation

Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis

Background: The NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial. Methods: From October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50-75) had a risk score (LLPv2) ≥ 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence. Findings: 1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1-7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41-1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76-0.92) from nine eligible trials. Interpretation: The UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups. Funding: NIHR Health Technology Assessment programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation

Study of knowledge, perception and attitude of adolescent girls towards STIs/HIV, safer sex and sex education: (A cross sectional survey of urban adolescent school girls in South Delhi, India)

<p>Abstract</p> <p>Background</p> <p>Sexually Transmitted Infections (STI's), including HIV (Human Immunodeficiency Virus) mainly affects sexually active young people. Young adults aged 15–29 years, account for 32% of AIDS (Acquired Immunodeficiency Syndrome) cases reported in India and the number of young women living with HIV/AIDS is twice that of young men. The aim of the study was to evaluate adolescent school girls' knowledge, perceptions and attitudes towards STIs/HIV and safer sex practice and sex education and to explore their current sexual behaviour in India.</p> <p>Methods</p> <p>A cross sectional study was carried out in 2007 in South Delhi, India to investigate the perception, knowledge and attitude of adolescent urban schoolgirls towards sexually transmitted Infections (STIs), HIV/AIDS, safer sex practice and sex education. the self-administered questionnaire was completed by 251 female students from two senior secondary schools.</p> <p>Results</p> <p>More than one third of students in this study had no accurate understanding about the signs and symptoms of STIs other than HIV/AIDS. About 30% of respondents considered HIV/AIDS could be cured, 49% felt that condoms should not be available to youth, 41% were confused about whether the contraceptive pill could protect against HIV infection and 32% thought it should only be taken by married women.</p> <p>Conclusion</p> <p>Though controversial, there is an immense need to implement gender-based sex education regarding STIs, safe sex options and contraceptives in schools in India</p