Techniques for evaluation of LAMP amplicons and their applications in molecular biology

Loop-mediated isothermal amplification (LAMP) developed by Notomi et al. (2000) has made it possible to amplify DNA with high specificity, efficiency and rapidity under isothermal conditions. The ultimate products of LAMP are stem-loop structures with several inverted repeats of the target sequence and cauliflower-like patterns with multiple loops shaped by annealing between every other inverted repeats of the amplified target in the similar strand. Because the amplification process in LAMP is achieved by using four to six distinct primers, it is expected to amplify the target region with high selectivity. However, evaluation of reaction accuracy or quantitative inspection make it necessary to append other procedures to scrutinize the amplified products. Hitherto, various techniques such as turbidity assessment in the reaction vessel, post-reaction agarose gel electrophoresis, use of intercalating fluorescent dyes, real-time turbidimetry, addition of cationic polymers to the reaction mixture, polyacrylamide gel-based microchambers, lateral flow dipsticks, fluorescence resonance energy transfer (FRET), enzyme-linked immunosorbent assays and nanoparticle-based colorimetric tests have been utilized for this purpose. In this paper, we reviewed the best-known techniques for evaluation of LAMP amplicons and their applications in molecular biology beside their advantages and deficiencies. Regarding the properties of each technique, the development of innovative prompt, cost-effective and precise molecular detection methods for application in the broad field of cancer research may be feasible

Comparison of surgical margin after breast cancer surgery between oncoplastic technique and conventional breast-conserving surgery

Background: Compared to other breast surgery methods, the accurate determination of pathologic margin in oncoplastic technique can affect its development and further employment of this technique. The current study aimed at evaluating positive pathologic margin after oncoplastic surgery and comparing it to that of the conventional breast-conserving surgery. Methods: The current cross sectional and prospective study enrolled patients with breast cancer referring to the surgical clinic of Tehran Cancer Institute from 2010 to 2013. In this study, patients with breast cancer were evaluated based on the type of surgery (oncoplastic or conventional breast-conserving) they had undergone. Accordingly, the positive or negative result of the margin surgery was compared between the groups. Results: In the current study, 317 patients with breast cancer underwent the surgery during the study period (154 patients in the oncoplastic and 163 patients in the conventional breast-conserving surgery groups). The highest frequency in the oncoplastic surgery belonged to Omega method (27.3). The pathological evaluations after surgery showed ductal breast carcinoma in most of the cases in both groups (oncoplastic surgery = 94.2; conventional breast-conserving surgery = 90.8; P = 0.053). Positive margin in oncoplastic surgery and conventional breast-conserving surgery groups were 10.4 and 18.4, respectively (P = 0.043). Among the 317 studied subjects, 14 relapse cases were observed; in 7 cases, mastectomy and in the rest, re-excision were conducted. Two out of 14 cases belonged to the positive margin group. Conclusions: Using oncoplastic surgery as a method for breast surgery may play an important role in reducing the prevalence of positive margins compared to the conventional breast-conserving surgery. © 2018, Cancer Research Center (CRC), Shahid Beheshti University of Medical Sciences

Comparison of surgical margin after breast cancer surgery between oncoplastic technique and conventional breast-conserving surgery

Background: Compared to other breast surgery methods, the accurate determination of pathologic margin in oncoplastic technique can affect its development and further employment of this technique. The current study aimed at evaluating positive pathologic margin after oncoplastic surgery and comparing it to that of the conventional breast-conserving surgery. Methods: The current cross sectional and prospective study enrolled patients with breast cancer referring to the surgical clinic of Tehran Cancer Institute from 2010 to 2013. In this study, patients with breast cancer were evaluated based on the type of surgery (oncoplastic or conventional breast-conserving) they had undergone. Accordingly, the positive or negative result of the margin surgery was compared between the groups. Results: In the current study, 317 patients with breast cancer underwent the surgery during the study period (154 patients in the oncoplastic and 163 patients in the conventional breast-conserving surgery groups). The highest frequency in the oncoplastic surgery belonged to Omega method (27.3). The pathological evaluations after surgery showed ductal breast carcinoma in most of the cases in both groups (oncoplastic surgery = 94.2; conventional breast-conserving surgery = 90.8; P = 0.053). Positive margin in oncoplastic surgery and conventional breast-conserving surgery groups were 10.4 and 18.4, respectively (P = 0.043). Among the 317 studied subjects, 14 relapse cases were observed; in 7 cases, mastectomy and in the rest, re-excision were conducted. Two out of 14 cases belonged to the positive margin group. Conclusions: Using oncoplastic surgery as a method for breast surgery may play an important role in reducing the prevalence of positive margins compared to the conventional breast-conserving surgery. © 2018, Cancer Research Center (CRC), Shahid Beheshti University of Medical Sciences

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions. Funding: Bill & Melinda Gates Foundation

Assessment of the Trustworthiness of Digital Records

Part 3: Short PapersInternational audienceIt is easy enough to assert the trustworthiness or otherwise of a digital record, but it is far more difficult to present an objective basis for that assertion. A number of recent research efforts have focused on the trustworthiness of a digital record while paying scant attention to the record’s evidential value as a measure of and a basis for the assessment of its trustworthiness. In this work, we study a model for the assessment of the trustworthiness of digital records based on their evidential values using the Dempster-Shafer (D-S) theory. The model is divided into three modules, (i) a knowledge-modelling module that models expert knowledge and consequent belief of evidence, (ii) an evidence-combination module that combines evidence from different sources in the face of uncertainty, and (iii) a trustworthiness assessment module that aggregates and integrates evidence, and assesses its trustworthiness. An example is presented to show how the model works