Average Risk Research Articles

Management of Patients With a Negative Multiparametric Prostate MRI Examination: AJR Expert Panel Narrative Review.

Multiparametric MRI (mpMRI) of the prostate aids risk stratification of patients with elevated PSA levels. Although most clinically significant prostate cancers are detected by mpMRI, insignificant cancers are less evident. Thus, multiple international prostate cancer guidelines now endorse routine use of prostate MRI as a secondary screening test before prostate biopsy. Nonetheless, management of patients with negative mpMRI results (defined as PI-RADS category 1 or 2) remains unclear. This AJR Expert Panel Narrative Review summarizes the available literature on patients with an elevated screening PSA level and a negative prostate mpMRI result and provides guidance for these patients' management. Systematic biopsy should not be routinely performed after a negative mpMRI examination in patients at average risk but should be considered in patients at high risk. In patients who undergo PSA screening rather than systematic biopsy after negative mpMRI, clear triggers should be established for when to perform a repeat MRI examination. Patients with a negative MRI result followed by negative biopsy should follow their health care practitioners' preferred guidelines concerning subsequent PSA screening for the patient's risk level. Insufficient high-level data exist to support routine use of adjunctive serum or urine biomarkers, artificial intelligence, or PSMA PET to determine the need for prostate biopsy after a negative mpMRI examination.

Targeted-BEHRT: Deep Learning for Observational Causal Inference on Longitudinal Electronic Health Records.

Observational causal inference is useful for decision-making in medicine when randomized clinical trials (RCTs) are infeasible or nongeneralizable. However, traditional approaches do not always deliver unconfounded causal conclusions in practice. The rise of "doubly robust" nonparametric tools coupled with the growth of deep learning for capturing rich representations of multimodal data offers a unique opportunity to develop and test such models for causal inference on comprehensive electronic health records (EHRs). In this article, we investigate causal modeling of an RCT-established causal association: the effect of classes of antihypertensive on incident cancer risk. We develop a transformer-based model, targeted bidirectional EHR transformer (T-BEHRT) coupled with doubly robust estimation to estimate average risk ratio (RR). We compare our model to benchmark statistical and deep learning models for causal inference in multiple experiments on semi-synthetic derivations of our dataset with various types and intensities of confounding. In order to further test the reliability of our approach, we test our model on situations of limited data. We find that our model provides more accurate estimates of relative risk [least sum absolute error (SAE) from ground truth] compared with benchmark estimations. Finally, our model provides an estimate of class-wise antihypertensive effect on cancer risk that is consistent with results derived from RCTs.

Identifying the best cutoff value of the fecal occult blood immunochemical test in the detection of advanced and neoplastic colorectal lesions.

Screening is an effective tool for detecting colorectal lesions in asymptomatic subjects. There is a positive correlation between fecal immunochemical test (FIT) values and the size of tumors. Despite the efficacy of screening, the detection of colorectal cancer (CRC) remains low. The primary objective was to evaluate the best FIT cutoff value for detecting advanced adenomas and CRC among individuals at average risk in a country with a high incidence and morbidity from CRC. This observational and prospective study analyzed consecutive cases in 1461 asymptomatic subjects with a positive FIT (≥ 100 ng hemoglobin [Hb]/mL) referred for colonoscopy (2012-2015) at a tertiary center in Uruguay. Colorectal lesions were detected in 35.3% (516/1461) of cases, with a mean age of 62.8 ± 8.3 years. About 53.2% were men and 65.1% of the tumors were located in the left side of the colon. The size of the lesion and FIT values (p = 0.001) were positively correlated. Laterally spreading tumors predominated in the right colon (586 ng Hb/mL; 95% Confidence interval [CI] 443.4-760). One hundred and thirty-five (26%) lesions were advanced adenomas (15 ± 6.7 mm); 694.6 ng/mL; 95% CI 632.4-756.9). The highest diagnostic yield (0.5112) for advanced adenomas was at a FIT level of 400 ng Hb/mL (accuracy 88.6%). There were significant differences in FIT values early and advanced CRC (927 ng/mL; [95% CI: 637-1082] vs. 1453 [95% CI: 1352-1594; p = 0.001]). A FIT value of 400 ng Hb/mL was the best diagnostic yield to detect advanced adenomas and CRC. This value is useful during the COVID-19 pandemic as it allows prioritization of colonoscopy to those most at risk of significant disease, thus reducing risks to both patients and healthcare workers.

Neoplasia detection in FIT positive screening colonoscopies compared with an age-controlled symptomatic cohort: a retrospective review

Colonoscopy following a positive FIT test in an average risk population is effective in reducing CRC incidence and mortality. While lower gastrointestinal symptoms remain a common cause for referral for colonoscopy, symptoms are poor predictors of clinically significant disease. The study was performed to compare neoplasia detection FIT +ve individuals and age-matched symptomatic cohorts. A single centre retrospective observational study was performed including all index colonoscopies performed on patients aged 60-70 from January 2015 to September 2021. Diagnostic yield was reported as adenoma detection rate, SSL detection rate, detection of high risk finding or adenocarcinoma. 8,106 colonoscopies were performed on patients aged 60-70 years. 3,695 (45.6%) originated from screening (FIT +ve). With exclusion criteria applied, 2,640 (59.9%) for screening and 1,767 (40.1%) for symptomatic patients were included. Median age in screening was 65 years (IQR 62-67) and 64 years in the symptomatic group (IQR 62-68), with male predominance in both groups (n=1,536, 58.1%, n=944, 53.4%). There were significant differences in both the ADR (56% vs 26.3%, p<0.01) and the SSLDR (10.4% vs. 8.1%, p=0.05) in the screening cohort compared to the symptomatic group. High risk findings (21.3% vs. 7.5%, p<0.01) were significantly more prevalent in the screening group with a considerably higher colorectal cancer (4.7% vs. 0.9%, p=<0.001) detection rate. FIT based triage significantly outperforms symptom based investigation for individuals in the 60-70 age group. Patients should be preferentially referred to organised colorectal cancer screening. FIT can be performed on symptomatic patients, to identify low risk individuals.

Abstract A040: Improving specificity for ovarian cancer screening using a novel extracellular vesicle-based blood test

Abstract Introduction: The low incidence of ovarian cancer (OC) in average risk individuals dictates any OC screening method needs to be both highly sensitive and highly specific. Even using the multimodal OC screening strategy combining longitudinal serum CA125 and transvaginal ultrasound, 16% of OCs were not detected and false positives due to benign ovarian tumors, which are 5-10 times more prevalent than OC, remained high. Due to lack of mortality benefit, population screening is still not recommended. We hypothesized that detecting multiple colocalized protein or glycosylation epitopes (PGEs) on single tumor-derived extracellular vesicles (EVs) would increase specificity and sensitivity for detection of OC. Methods: The Mercy Halo™ OC test employs immunoaffinity capture and proximity-ligation qPCR to detect combinations of up to 3 PGE biomarkers to maximize specificity and measures multiple combinations to maximize sensitivity. We selected 3 PGE combinations to form a panel test to distinguish high-grade serous ovarian cancer (HGSC) from benign ovarian tumors and normal patients and compared performance of our test to CA125. We used a case-control training set from university-associated Canadian biobanks comprised of EDTA plasma from 124 healthy controls, 89 HGSC cases (17 Stage I, 35 Stage II, 37 Stage III)(10 BRCA+), and 192 benign adnexal masses to lock down the test, the data interpretation algorithm, and the cut-off between cancer and non-cancer. Performance was verified in an independent blinded diagnostic case-control set of 397 serum samples from 138 healthy controls, 111 benign adnexal masses, 20 borderlines, 66 HGSC and 62 non-HGSC from the UK Ovarian Cancer Population Study. For comparison, a CA125 ELISA was run for all samples in both studies. Results: Using the locked assay, algorithm, and cut-off established in the training cohort, our test showed a specificity in healthy controls of 92.8% (128/138; 95% CI: 0.87-0.96), a sensitivity in HGSC of 97.0% (64/66; 95% CI: 0.90-0.99), and an AUC of 0.92 (95% CI 0.89-0.95) in the verification cohort. We correctly identified 11/13 Stage I and all 54 Stage II/III/IV HGSC cases. Our test also detected 76.8% (63/82) of the borderline and non-HGSC histotypes. CA125 detected 92.4% (61/66) of the HGSC cases and 84.1% (69/82) of the borderlines and non-HGSC. The greatest improvement in test performance relative to CA125 was seen with benign adnexal masses. In the verification cohort 35.1% (39/111) of the benign samples were CA125 positive compared to 21.6% (24/111) with our test. This reduction in false positives was seen across 10 benign histotypes tested. Conclusions: These results demonstrate that our test using colocalized PGEs on EVs can detect OC, especially HGSC, in both plasma and serum with high sensitivity and specificity. The combinations of 5 biomarkers rather than CA125 alone also decreased benign false positives. The test performance suggests that our test may be useful in average and/or high-risk ovarian cancer screening. Future studies will explore this in asymptomatic populations. Citation Format: Emily S. Winn-Deen, Sanchari Banerjee, Daniel Gusenleitner, Laura T. Bortolin, Jonian Grosha, Kelly M. Biette, Karen Copeland, Christopher R. Sedlak, Bilal Hamzeh, Anthony D. Couvillon, Delaney M. Byrne, Peter A. Duff, Lauren T. Cuoco, MacKenzie S. King, Aleksandra Gentry-Maharaj, Sophia Apostolidou, Dawn R. Mattoon, Christine D. Berg, David F. Ransohoff, Steven J. Skates, Usha Menon. Improving specificity for ovarian cancer screening using a novel extracellular vesicle-based blood test [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A040.

Abstract B051: Genome-wide association studies of 26,187 women without ovarian cancer identifies 12 genetic loci of blood CA125

Abstract Background: CA125 is elevated in women with ovarian cancer and is the single best ovarian cancer screening biomarker candidate to date, although two randomized screening trials showed no clinically significant difference in ovarian cancer mortality. Consideration of genetic variants that influence blood CA125 levels in healthy women could improve its performance as an ovarian cancer screening biomarker. Furthermore, while studies have suggested CA125 is associated with ovarian carcinogenesis and progression, its biological role remains unclear. Thus, we aimed to identify genetic variants of CA125 in women without ovarian cancer. Methods: We conducted a genome-wide association analysis to identify common genetic variants associated with CA125 using data on 26,187 women without ovarian cancer, leveraging existing blood CA125 data and genetic data from Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), European Prospective Investigation into Cancer and Nutrition (EPIC), Nurses’ Health Studies (NHS/NHSII), and New England Case Control Study (NEC). All genotype data were inputted using TOPMed. For blood CA125 measurement, PLCO, NHS/NHSII, and NEC used the CA125II assay and EPIC used the MSD assay. We used multivariable linear regression models adjusting for age, study, and population ancestry (top 4 principal components). Analyses were conducted separately by CA125 assay, genotyping platforms, and menopausal status at blood draw. Because epidemiological predictors of CA125 differ by menopausal status, we conducted analyses stratified by menopausal status. When we meta-analyzed these results, there were no significant heterogeneity by menopausal status in majority of the genome-wide significant SNPs. Therefore, we performed a fixed-effects meta-analysis to combine summary statistics across all the results. Results: We identified 12 independent loci associated with CA125 at a genome-wide significance level (p<5 × 10−8), of which one SNP (rs73005869) had been previously linked with CA125 and is located in the MUC16 gene. In our meta-analysis, 7 SNPs were associated with lower and 5 were associated with higher levels of CA125. We discovered SNPs on chromosome 16 in the TET2 gene that were significantly associated with increased CA125 levels. We also discovered SNPs in MSLN, a gene reported to be overexpressed in ovarian tumors that contributes to metastasis in the peritoneal microenvironment, were associated with lower CA125 levels. SNPs in the HIC1 gene on chromosome 17, a tumor suppressor gene whose aberrant methylation has been observed in ovarian tumors, was associated with lower CA125 levels. Conclusion: We identified 12 independent loci associated with blood CA125 levels in women without ovarian cancer, providing novel biological insights on the role of CA125. Accounting for these genetic factors that influence blood CA125 levels could improve the performance of CA125 as ovarian cancer screening biomarker in average risk women, substantially improving survival through earlier detection of this deadly disease. Citation Format: Naoko Sasamoto, Jihye Kim, Constance Turman, Shelley S. Tworoger, Rudolf Kaaks, Renée T. Fortner, Daniel W. Cramer, Kathryn L. Terry, Nicolas Wentzensen, Peter Kraft. Genome-wide association studies of 26,187 women without ovarian cancer identifies 12 genetic loci of blood CA125 [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B051.

Abstract A049: Fallopian tubes of BRCA carriers are characterized by an alteration of epithelial differentiation

Abstract Patients with a germline mutation in BRCA1/2 are at high risk of developing ovarian cancer, the deadliest gynecologic cancer leading to over 207,000 deaths per year in the world. Although the ovarian surface epithelium was long thought to be the origin of this cancer, it is now widely appreciated that the fallopian tube epithelium harbors the cell-of-origin for high-grade serous “ovarian” cancers (HGSC). Nonetheless the earliest stages of carcinogenesis remain poorly characterized. Our study aims to better understand why patients with highly penetrant inherited mutations in BRCA1/2 are at greater risk of HGSC using state-of-the art single cell genomics and spatial profiling of fallopian tubes removed during prophylactically risk-reducing salpingo-oophorectomies (RRSOs). Fallopian tubes from patients with BRCA1/2 mutations are fully embedded in paraffin for careful pathologic examination, limiting the technologies that can be applied to study the molecular profiles of the cancer-prone epithelium. The first aim of our study was to determine whether the samples of cells from fimbria of fallopian tubes obtained through an exfoliative cytology following RRSO are comparable to histologic preparation at the transcriptomic level. We performed single cell RNA sequencing of brushings from 14 fimbriae removed during RRSOs from high-risk mutation carriers, brushings of 3 non-carriers and 12 tissues from non-carriers. As expected, fimbrial brushing mainly consisted of epithelial cells and immune cells and were depleted of fibroblasts and endothelial cells relative to enzymatically dissociated tissue specimens. Fallopian tubes from high-risk mutation carriers were associated with signatures of altered epithelial differentiation suggesting that altered epithelial differentiation processes proceed and may even be required for cancer development. The immune compartment was also markedly different in mutation carriers compared to matched controls. We have recently described how in mutation carriers the myeloid cell compartment shifts from monocyte-enriched in normal Fallopian tubes to macrophage-enriched in HGSCs (Brand et al). In Fallopian tubes of high-risk mutation carriers, we discovered a novel subset of cancer-free patients with signatures similar to advanced tumors, suggesting myeloid compartment remodeling is a prerequisite for, although not sufficient for, tumor formation. BRCA1/2 carriers with higher macrophages also have features of dysfunctional natural killer and T cells. Ongoing spatial transcriptomic profiling of high and average risk fallopian tubes are enabling dissection of the altered cell-cell communications occurring concomitantly with disordered epithelial differentiation. Together these data are expected to advance our understanding of the cellular and molecular signatures of early stage HGSC. Leveraging this insight could lead to the development of new diagnostic tools for early detection of this cancer, an essential prerequisite for improving the chances of survival for patients. Citation Format: Quentin Chartreux, Marcela Haro, Joshua Brand, Andrew Li, Bobbie J. Rimel, Simon Gayther, Huy Dinh, Fabiola Medeiros, Kate Lawrenson. Fallopian tubes of BRCA carriers are characterized by an alteration of epithelial differentiation [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A049.

Compassion fatigue in people who care for animals: An investigation of risk and protective factors.

Compassion fatigue (CF), comprising secondary traumatic stress (STS) and burnout (BO), can adversely affect caring professions. This study explored CF risk levels among paid and volunteer animal-care professionals (N = 559) and identified the extent to which job demands predict CF. Potential moderators were also investigated. Participants reported average risk levels for CF. No significant differences in CF risk levels were found between paid and volunteer animal carers. Hierarchical multiple regression revealed job demands predicted 18% and 17% of the variance in STS and BO, respectively, after controlling for age, involvement with euthanasia, and hours spent in the animal-care role. Significant relationships were identified among STS, BO, and the hypothesized moderators. Moderation analyses showed these did not significantly moderate the relationship. It was concluded that job demands are an important risk factor for CF in animal carers. Reducing job demands may be an effective intervention for employers seeking to promote the well-being of animal-care professionals.

Performance of the Asia-Pacific Colorectal Screening score in stratifying the risk of advanced colorectal neoplasia: A meta-analysis and systematic review.

This study systematically reviewed and meta-analyzed the performance of the Asia-Pacific Colorectal Screening (APCS) score and its incorporation with the fecal immunochemical test (FIT) in stratifying the risk of advanced colorectal neoplasia (ACN). We systematically searched for relevant articles in 12 electronic databases and registers on October 20, 2021, and updated the search to September 1, 2023. Random-effect models were used to obtain the pooled performance statistics of the APCS score for ACN risk. From the 101 records screened, 13 eligible studies in the Asia-Pacific region involving 69762 subjects who had undergone colonoscopy were enrolled. The pooled prevalences of ACN in the average-risk (AR) tier (APCS 0-1), moderate-risk (MR) tier (APCS 2-3), and high-risk (HR) tier (APCS≥4) groups were 0.9%, 3.1%, and 8.1%, respectively. Compared with the combined AR-MR group, the HR group was significantly associated with a higher ACN risk (pooled diagnostic odds ratio: 2.84, 95% confidence interval [CI]: 2.35-3.45, P<0.001). The APCS score showed a sensitivity of 0.42 (95% CI: 0.40-0.44) and a specificity of 0.86 (95% CI: 0.85-0.86) for predicting the ACN risk, with a weighted area under the curve of 0.642 (95% CI: 0.610-0.657). The combination of the APCS score and FIT substantially improved ACN risk identification, demonstrating pooled diagnostic odds ratios of 4.02 (95% CI: 2.50-6.49) in the AR-MR groups and 5.44 (95% CI: 1.89-15.63) in the MR-HR groups. The APCS score could effectively stratify the ACN risk in the Asia-Pacific population. Incorporating FIT further improves its performance in identifying high-risk subjects who should be prioritized for colonoscopy screenings.

Appraisal of pollution levels and non-carcinogenic health risks associated with the emergence of heavy metals in Indonesian community water for sanitation, hygiene, and consumption

Excessive heavy metal concentrations in water can pose a threat to human health. The research analyzed 160 groundwater samples used for hygiene and sanitation, of which 62 were used for consumption, and 98 other types of drinking water were analyzed. The research findings indicate that 6% of groundwater for hygiene and sanitation and 13% of drinking water (7.8% groundwater, 5.2% refill water) were deemed unfit for use due to elevated concentrations of certain heavy metals surpassing the maximum limits. As, Cd, Co, Hg, Mn, and Pb were detected in several drinking water samples deemed unsuitable for consumption. Several heavy metals suspected to originate from natural sources are Co, Fe, Mn, As, and Zn, while Pb, Cd, Hg, and Co are suspected to have anthropogenic sources. Only arsenic exposure through the ingestion pathway posed a non-carcinogenic health risk to the local population. Children were found to be more susceptible than adult males and females. The estimated average non-carcinogenic risk levels based on the water sources were refill water > well water > rainwater > spring water. Therefore, it is essential to monitor raw water sources at refill water depots in the study area and implement policies related to the quality of raw water sources, technology maintenance processes, and the quality of processed water from refill water depots. Additionally, the community should be educated about household-scale water treatment to minimize health risks and consider using untreated well water and rainwater for consumption.

The impact of employment restriction on the risk of an accident at work in the mining industry in Poland

Abstract The European Union's energy policy has necessitated a reduction in coal mining, with significant consequences for occupational safety within the industry. This study investigates the correlation between employment reduction and accident risk within Poland's mining sector during 2006-2020, a period marked by over a 40% decrease in coal extraction and a corresponding 30% decrease in mining employment. An escalation in the relative risk (RR) of accidents was observed, increasing from 1.28 to 2.33. More critically, the RR of fatal accidents rose from 2.54 to 8.22 by 2019. Analysis revealed a critical employment threshold: a fall in mining employment below 140,000 is associated with a marked increase in accident risk, particularly fatal accidents. A linear model was developed to suggest that a reduction in the RR of accidents to 0.7 is requisite to achieve a national average risk for fatal accidents (RR = 1). The findings advocate for targeted safety interventions and propose a preventive strategy model. The implications are vital for policymakers and industry stakeholders aiming to improve worker safety in response to employment changes within the mining sector.

Would initiating colorectal cancer screening from age of 45 be cost-effective in Germany? An individual-level simulation analysis.

Colorectal cancer (CRC) screening has been shown to be effective and cost-saving. However, the trend of rising incidence of early-onset CRC challenges the current national screening program solely for people ≥50 years in Germany, where extending the screening to those 45-49 years might be justified. This study aims to evaluate the cost-effectiveness of CRC screening strategies starting at 45 years in Germany. DECAS, an individual-level simulation model accounting for both adenoma and serrated pathways of CRC development and validated with German CRC epidemiology and screening effects, was used for the cost-effectiveness analysis. Four CRC screening strategies starting at age 45, including 10-yearly colonoscopy (COL), annual/biennial fecal immunochemical test (FIT), or the combination of the two, were compared with the current screening offer starting at age 50 years in Germany. Three adherence scenarios were considered: perfect adherence, current adherence, and high screening adherence. For each strategy, a cohort of 100,000 individuals with average CRC risk was simulated from age 20 until 90 or death. Outcomes included CRC cases averted, prevented death, quality-adjusted life-years gained (QALYG), and total incremental costs considering both CRC treatment and screening costs. A 3% discount rate was applied and costs were in 2023 Euro. Initiating 10-yearly colonoscopy-only or combined FIT + COL strategies at age 45 resulted in incremental gains of 7-28 QALYs with incremental costs of €28,360-€71,759 per 1,000 individuals, compared to the current strategy. The ICER varied from €1,029 to €9,763 per QALYG, and the additional number needed for colonoscopy ranged from 129 to 885 per 1,000 individuals. Among the alternatives, a three times colonoscopy strategy starting at 45 years of age proves to be the most effective, while the FIT-only strategy was dominated by the currently implemented strategy. The findings remained consistent across probabilistic sensitivity analyses. The cost-effectiveness findings support initiating CRC screening at age 45 with either colonoscopy alone or combined with FIT, demonstrating substantial gains in quality-adjusted life-years with a modest increase in costs. Our findings emphasize the importance of implementing CRC screening 5 years earlier than the current practice to achieve more significant health and economic benefits.

Metal pollution in the topsoil of lands adjacent to Sahiwal Coal Fired Power Plant (SCFPP) in Sahiwal, Pakistan.

Coal fly ash from a coal fired power plant is a significant anthropogenic source of various heavy metals in surrounding soils. In this study, heavy metal contamination in topsoil around Sahiwal coal fired power plant (SCFPP) was investigated. Within distance of 0-10, 11-20, 21-30 and 31-40 km of SCFPP, total 56 soil samples were taken, 14 replicate from each distance along with a background subsurface soil sample beyond 60 km. Soil samples were subjected to heavy metals analysis including Fe, Cu and Pb by Atomic Absorption Spectrophotometer (AAS). Composite samples for each distance were analyzed for Al, As, Ba, Cd, Co, Cr, Mn, Mo, Ni, Se, Sr, Zn by Inductively Coupled Plasma (ICP). Pollution indices of exposed soil including Enrichment Factor (EF), Contamination Factor (CF), Geoaccumulation Index (Igeo), and Pollution Load Index (PLI) were calculated. Ecological risk index ([Formula: see text]) of individual metals and the Potential Ecological Risk Index (PERI) for all metals were determined. Soil samples within 40 km of SCFPP were significantly polluted with Pb (mean 2.81 ppm), Cu (mean 0.93 ppm), and Fe (mean 7.93 ppm) compared to their background values (Pb 0.45, Cu 0.3, and Fe 4.9 ppm). Some individual replicates were highly contaminated where Pb, Fe, and Cu values were as high as 6.10, 35.4 and 2.51 ppm respectively. PLI, Igeo, CF, and EF for metals classified the soil around CFPP as "moderate to high degree of pollution", "uncontaminated to moderately contaminated", "moderate to very high contamination", and "moderate to significant enrichment" respectively with average values for Cu as 2.75, 0.82, 3.09, 4.01; Pb 4.79, 1.56, 6.16, 7.76, and for Fe as 1.20, 0.40, 1.62, 3.35 respectively. Average Ecological Risk Index ([Formula: see text]) of each metal and Potential Ecological Risk Index (PERI) for all metals classified the soils as "low risk soils" in all distances. However, ([Formula: see text]) of Pb at a number of sites in all distances have shown "moderate risk". The linear correlation of physico-chemical parameter (EC, pH, Saturation %) and metals have recorded several differential correlations, however, their collective impact on Pb in 0-10 km, has recorded statistically significant correlation (p-value 0.01). This mix of correlations indicates complex interplay of many factors influencing metal concentrations at different sampling sites. The concentration of As, Cr, Co, Cd, and Zn was found within satisfactory limits and lower than in many parts of the world. Although the topsoil around SCFPP is largely recorded at low risk, for complete assessment of its ecological health, further research considering comprehensive environmental parameters, all important trace metals and variety of input pathways is suggested.

Screening and prevention of ovarian cancer.

Ovarian cancer remains the most lethal gynaecological malignancy with 314 000 cases and 207 000 deaths annually worldwide. Ovarian cancer cases and deaths are predicted to increase in Australia by 42% and 55% respectively by 2040. Earlier detection and significant downstaging of ovarian cancer have been demonstrated with multimodal screening in the largest randomised controlled trial of ovarian cancer screening in women at average population risk. However, none of the randomised trials have demonstrated a mortality benefit. Therefore, ovarian cancer screening is not currently recommended in women at average population risk. More frequent surveillance for ovarian cancer every three to four months in women at high risk has shown good performance characteristics and significant downstaging, but there is no available information on a survival benefit. Population testing offers an emerging novel strategy to identify women at high risk who can benefit from ovarian cancer prevention. Novel multicancer early detection biomarker, longitudinal multiple marker strategies, and new biomarkers are being investigated and evaluated for ovarian cancer screening. Risk-reducing salpingo-oophorectomy (RRSO) decreases ovarian cancer incidence and mortality and is recommended for women at over a 4-5% lifetime risk of ovarian cancer. Pre-menopausal women without contraindications to hormone replacement therapy (HRT) undergoing RRSO should be offered HRT until 51 years of age to minimise the detrimental consequences of premature menopause. Currently risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) should only be offered to women at increased risk of ovarian cancer within the context of a research trial. Pre-menopausal early salpingectomy is associated with fewer menopausal symptoms and better sexual function than bilateral salpingo-oophorectomy. A Sectioning and Extensively Examining the Fimbria (SEE-FIM) protocol should be used for histopathological assessment in women at high risk of ovarian cancer who are undergoing surgical prevention. Opportunistic salpingectomy may be offered at routine gynaecological surgery to all women who have completed their family. Long term prospective opportunistic salpingectomy studies are needed to determine the effect size of ovarian cancer risk reduction and the impact on menopause.

Release characteristics of volatile organic compounds at residential garbage collection points: a case study of Hangzhou, China.

With the implementation of garbage classification, perishable waste has become increasingly concentrated. This has led to a significant change in the VOC release characteristics at residential garbage collection points, posing a potential risk with unknown characteristics. This study investigated the release characteristics, odor pollution, and health risks of VOCs at garbage collection points under different classification effectiveness, seasons, garbage drop-off periods, and garbage collection point types. The results showed that the average concentration of VOCs released from the garbage sorting collection points (SPs) was 341.43 ± 261.16 μg/m3, and oxygenated compounds (e.g., ethyl acetate and acetone) were the main VOC components. The VOC concentration increased as the community classification effectiveness improved, and it was higher in summer (followed by spring, autumn, and winter). Moreover, the VOC concentrations were higher in the evenings than in the mornings and at centralized garbage collection points (CPs) than at SPs. Further, odor activity value (OAV) assessments indicated that acrolein, styrene, and ethyl acetate were the critical odorous components, with an average OAV of 0.87 ± 0.85, implying marginal odor pollution in some communities. Health risk assessments further revealed that trichloroethylene, benzene, and chlorotoluene were the critical health risk substances, with an average carcinogenic risk (CR) value of 10-6-10-4, and a non-carcinogenic risk (HI) value < 1. These results indicated that HIs were acceptable, but potential CRs existed in the communities. Therefore, VOC pollution prevention and control measures should be urgently strengthened at the garbage collection points in high pollution risk scenarios.

Opportunistic Salpingectomy: A New Scope of Preventing a Deadly Disease

Background: Symptoms of ovarian cancer are non-specific and often do not arise until the cancer is in a late stage. Such late onset of symptoms and the lack of an effective screening test result in diagnosis at an advanced-stage for most patients of ovarian cancer. The fimbrial end of the fallopian tube has recently been suggested as the site of origin for epithelial ovarian cancers (EOC). Therefore, a change in practice with opportunistic salpingectomy (OS) at the time of hysterectomy has been advocated for prevention of ovarian cancer. Different gynaecological societies have published statements in favour of opportunistic salpingectomy in women at average population risk for ovarian cancer prevention. In recent years, salpingectomy has been increasingly performed for tubal sterilization also. We have gone through the available scientific publications and international guidelines in preparing this brief review in an attempt tobe familiar with the recent updated views regarding this issue. Delta Med Col J. Jan 2021;9(1):37-57

Inhalation exposure to toxic heavy metals in nail salon technicians and health risk assessment using Monte Carlo simulation

Objective Nail salons offer a developing and diverse occupation for many women, especially the new generation. Due to the increasing apprehension surrounding heavy metals in dust caused by filing nails containing dried nail polish, the present study was designed aimed to health risk assessment of heavy metals in breathing zone of nail salon technicians (NSTs). Methods This is a cross-sectional study that was conducted in NSTs. The concentration of Cadmium (Cd), Lead (Pb), Nickel (Ni), Chromium (Cr) and Manganese (Mn)in breathing zone of 20 NSTs was determined using ICP-OES. Results The metal concentrations were in the following order: Mn > Pb > Ni > Cr > Cd with corresponding arithmetic mean values of0.008, 0.0023, 0.0021, 0.001 and 0.0006 mg m−3, respectively, which are exceeded the recommended levels stated in the indoor air guidelines. The average lifetime carcinogenic risk (LCR) for Cr, Cd, Ni and Pb was calculated 0.0084, 0.00054, 0.00026 and 1.44 E − 05, respectively. The LCR values of all metals (except Pb) exceeded the acceptable level set by the USEPA. The mean of Hazard quotients (HQ) for Mn, Cd, Cr, Ni and Pb were calculated to be23.7, 4.74, 2.19, 0.51 and 0.0.24, respectively. The sensitivity analysis showed that, the exposure frequency (EF) for Cr and Ni had the strong effects on generation of both LCR and HQ. Furthermore, the concentrations of Mn, Cd and Pb had strong impacts on the HQ generation and the concentration of Cd and Pb had main effects on LCR generation. Conclusion To effectively reduce pollutant concentration, it is recommended to install a ventilation system near nail salon work tables and conduct continuous monitoring and quality control of nail products.

An Ergonomic Risk Assessment of Ophthalmology Residents Using the Rapid Entire Body Assessment (REBA) Scale.

The healthcare industry has one of the highest rates of work-related injuries. Ophthalmologists are at particularly high risk for developing musculoskeletal disorders (MSDs), which are often the result of repetitive movements, such as performing slit lamp examinations. Previous studies used the Rapid Entire Body Assessment (REBA) scale to determine the ergonomic risk of a particular task.Higher REBA scores correlate with increased risk of injury, which ranges from negligible risk (1) to very high risk (11+). Given the long-term implications of repetitive examinations by ophthalmologists, this study aims to describe the average ergonomic risk posed to residents using the REBA scale. This descriptive case study assessed four ophthalmology residents performing slit lamp examinations between September 2022 and February 2023. Photographs were taken of residents performing slit lamp examinations. Total REBA scores, Score A, Score B, and the REBA scores for each participant were calculated and compared. The average REBA score across all participants was 4.59 (SD±0.89). The highest score was 7.00 and the lowest was 3.00. The average Score A, representing posture for the head, leg, and trunk, was 3.54 (SD±0.74) and the average Score B, representing posture for the upper arm, lower arm, and wrist, was 3.18 (SD±1.22). Our study found that residents are at increased risk for developing MSDs. Furthermore, variation in REBA scores between residents indicates that not all residents are at equal ergonomic risk. This highlights an opportunity for ophthalmology residency programs to implement ergonomics training into their curriculum.

Tracking IUCN extinction risk at sub-regional scale: lessons from comparing Italian Red List assessments for cartilaginous species within a decade (2013–2022)

This brief research report presents the 2022 updated IUCN Red List for the cartilaginous fish fauna (76 species) recorded in the Italian seas and compares it with the 2013 assessment. Overall, the number of Data Deficient (DD) species decreased in favor of both threatened and unthreatened categories. Out of five DD species in the 2013 assessment, three acquired the status of threatened species (Vulnerable or higher) and two an unthreatened (Least Concern or higher) status in the 2022 assessment. Additionally, the classification for one species changed from Least Concern in 2013 to DD in 2022. The comparison between assessments showed no significant change in the average extinction risk status of cartilaginous fish populations of the Italian seas. Even though 2013-DD species decreased in number, the latter still remains high in the updated Italian IUCN Red List assessment.

Genetic testing for familial melanoma.

While the average lifetime risk of melanoma worldwide is approximately 3%, those with inherited high-penetrance mutations face an increased lifetime risk of 52-84%. In countries of low melanoma incidence, such as in Southern Europe, familial melanoma genetic testing may be warranted when there are two first degree relatives with a melanoma diagnosis. Testing criteria for high incidence countries such as USA, or with very-high incidence, such as Australia and New Zealand, would require a threshold of 3 to 4 affected family members. A mutation in the most common gene associated with familial melanoma, CDKN2A, is identified in approximately 10-40% of those meeting testing criteria. However, the use of multi-gene panels covering additional less common risk genes can significantly increase the diagnostic yield. Currently, genetic testing for familial melanoma is typically conducted by qualified genetic counsellors, however with increasing demand on testing services and high incidence rate in certain countries, a mainstream model should be considered. With appropriate training, dermatologists are well placed to identify high risk individuals and offer melanoma genetic test in dermatology clinics. Genetic testing should be given in conjunction with pre- and post-test consultation. Informed patient consent should cover possible results, the limitations and implications of testing including inconclusive results, and potential for genetic discrimination. Previous studies reporting on participant outcomes of genetic testing for familial melanoma have found significant improvements in both sun protective behavior and screening frequency in mutation carriers.