Minimal Risk Research Articles

Advancing Lip Augmentation: State-of-the-Art 2D and 3D Analysis for Assessing Volume Enhancement and Lip Line Redefinition

Over the preceding five decades, there has been a noticeable surge in the pursuit of achieving voluminous and well-defined lips. This trend has prompted an escalating number of individuals to undergo lip augmentation procedures, aiming for a natural three-dimensional enhancement of lip volume and distinct vermilion borders. Despite the proliferation of lip augmentation techniques, there remains a dearth of comprehensive investigations into their precise effects on the three-dimensional structural integrity of the lips. This research endeavors to address this gap by employing stereophotogrammetry as a quantitative tool to scrutinize lip augmentation outcomes and to appraise the efficacy of lip plumpers. The study methodology involves a comparative analysis of lip dimensions among subjects treated with a commercial lip plumper using multi-spectral imaging for lip dimension assessment, coupled with markerless tracking technology and 3D interpolating surface methodology to analyze lip volume and shape. Additionally, the study evaluated lip youth state, including moisture level, softness, firmness, and tissue density. The demand for lip augmentation procedures is driven by perceived advantages such as quick recovery and minimal risk. Therefore, it is crucial to substantiate their efficacy with robust findings. The investigation suggests that both 3D and 2D stereophotogrammetry techniques are reliable for evaluating lip size before and after augmentation, whether through cosmetic or aesthetic approaches. Overall, the study provides a comprehensive analysis of a lip treatment aimed at enhancing volume and redesigning lip lines. It demonstrates that stereophotogrammetry is effective for assessing 3D lip dimensions and their correlation with internal lip structure. This research could be particularly valuable for evaluating the efficacy and duration of various lip enhancement techniques, including dermal fillers, implants, and topical cosmetic formulations, offering quantitative and reproducible assessments over time.

Abnormal Pathology Following Vaginal Hysterectomy for Pelvic Organ Prolapse Repair.

Objective: Uterine-sparing surgery for pelvic organ prolapse (POP) repair has shown good results, but the potential negative implications of leaving the uterus in place are yet to be fully defined. We aimed to assess the risk of unanticipated abnormal gynecological pathology at the time of reconstructive pelvic surgery. Methods: A retrospective consecutive case series including women who underwent vaginal hysterectomy for POP repair at a tertiary medical center in 2006-2020. All patients were offered a free Pap smear test at the age of 65 years as part of a national screening program. Transvaginal ultrasound was routinely performed preoperatively. Standard 3 pedicle hysterectomy was performed with/without bilateral salpingo-oophorectomy (BSO). Results: The study comprised 462 women of mean age 63 ± 9.3 years without previous known malignant or premalignant pathology. Benign pathology was observed in 286 patients (61.9%). Endometrial malignancy was found in three patients (0.7%) and significant premalignant pathology in 15 patients (3.2%), including cervical intraepithelial neoplasia stage 2-3 in seven patients (1.5%) and complex hyperplasia with atypia in eight patients (1.7%). All these pathologies were found in postmenopausal women. None had preoperative clinical symptoms or endometrial thickness of ≥5 mm on preoperative ultrasound. In the 35 patients after BSO, adnexal findings were normal (77.2%) or benign (22.8%). Conclusions: Premenopausal women with uterovaginal prolapse and normal preoperative evaluation have a minimal risk of significant abnormal uterine pathology. In postmenopausal women, the risk of unanticipated malignant uterine pathology is 0.7% and 3.2% for significant premalignancy.

Efficacy of automated insulin delivery in pregnant women with type 1 diabetes: a meta-analysis and trial sequential analysis of randomized controlled trials.

Automated insulin delivery (AID) devices have shown to be a promising treatment to improve glycemic control in patients with type 1 diabetes mellitus (T1DM). However, its efficacy in pregnant women with T1DM remains uncertain. PubMed, Scopus, Cochrane Central and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) comparing AID to standard care (SC), defined as use of sensor-augmented pump and multiple daily insulin injections. Outcomes included time in range (TIR), nocturnal TIR, time in hypoglycemic and hyperglycemic ranges, among others. Sensitivity and trial sequential analyses (TSA) were performed. CRD42023474398. We included five RCTs with a total of 236 pregnant women, of whom 117 (50.6%) received AID. There was a significant increase in nocturnal TIR (mean difference [MD] 12.69%; 95% CI 8.74-16.64; p < 0.01; I2 = 0%) and a decrease in glucose variability (standard deviation of glucose; MD -2.91; 95% CI -5.13 to -0.69; p = 0.01; I2 = 0%). No significant differences were observed for TIR, HBGI, LGBI, mean glucose and time spent in hyperglycemia and hypoglycemia. Regarding TSA, the statistical significance obtained in nocturnal TIR was conclusive and with minimal risk of a type I error. Our findings suggest that AID systems can significantly improve nocturnal glycemic control and potentially reduce glycemic variability in pregnant women with T1DM, with no effect in the risk of hypoglycemia and hyperglycemia compared with current insulin treatments.

ENHANCING ELECTIVE SURGERY MANAGEMENT WITH OPENPREDICTOR: VALIDATION OF A CLINICAL DECISION AID FOR OPTIMIZING ELECTIVE PATHWAYS

OpenPredictor, a machine learning-enabled clinical decision aid, has been developed to manage backlogs in elective surgeries. It aims to optimise the use of high volume, low complexity surgical pathways by accurately stratifying patient risk, thereby facilitating the allocation of patients to the most suitable surgical sites. The tool augments elective surgical pathways by providing automated secondary opinions for perioperative risk assessments, enhancing decision-making. Its primary application is in elective sites utilising lighter pre-assessment methods, identifying patients with minimal complication risks and those high-risk individuals who may benefit from early pre-assessment.The Phase 1 clinical evaluation of OpenPredictor entailed a prospective analysis of 156 patient records from elective hip and knee joint replacement surgeries. Using a polynomial logistic regression model, patients were categorised into high, moderate, and low-risk groups. This categorisation incorporated data from various sources, including patient demographics, co-morbidities, blood tests, and overall health status.In identifying patients at risk of postoperative complications, OpenPredictor demonstrated parity with consultant-led preoperative assessments. It accurately flagged 70% of patients who later experienced complications as moderate or high risk. The tool's efficiency in risk prediction was evidenced by its balanced accuracy (75.6%), sensitivity (70% with a 95% confidence interval of 62.05% to 76.91%), and a high negative predictive value (96.7%).OpenPredictor presents a scalable and consistent solution for managing elective surgery pathways, comparable in performance to secondary consultant opinions. Its integration into pre-assessment workflows assists in efficient patient categorisation, reduces late surgery cancellations, and optimises resource allocation. The Phase 1 evaluation of OpenPredictor underscores its potential for broader clinical application and highlights the need for ongoing data refinement and system integration to enhance its performance.

Pharmacokinetic and Environmental Risk Assessment of Prime-2-CoV, a Non-Replicating Orf Virus-Based Vaccine against SARS-CoV-2.

Viral vector vaccines represent a substantial advancement in immunization technology, offering numerous benefits over traditional vaccine modalities. The Orf virus (ORFV) strain D1701-VrV is a particularly promising candidate for vaccine development due to its distinctive attributes, such as a good safety profile, the ability to elicit both humoral and cellular immunity, and its favorable genetic and thermal stability. Despite ORFV's theoretical safety advantages, such as its narrow host range and limited systemic spread post-inoculation, a critical gap persists between these theoretical benefits and the empirical evidence regarding its in vivo safety profile. This discrepancy underscores the need for comprehensive preclinical validations to bridge this knowledge gap, especially considering ORFV's use in humans. Our research introduces Prime-2-CoV, an innovative ORFV-based vaccine candidate against COVID-19, designed to elicit a robust immune response by expressing SARS-CoV-2 Nucleocapsid and Spike proteins. Currently under clinical trials, Prime-2-CoV marks the inaugural application of ORFV in human subjects. Addressing the aforementioned safety concerns, our extensive preclinical evaluation, including an environmental risk assessment (ERA) and detailed pharmacokinetic studies in rats and immunocompromised NOG mice, demonstrates Prime-2-CoV's favorable pharmacokinetic profile, negligible environmental impact, and minimal ERA risks. These findings not only affirm the vaccine's safety and efficacy but also pioneer the use of ORFV-based therapeutics, highlighting its potential for wider therapeutic applications.

Abstract PO4-07-09: CONTRAST-ENHANCED MAMMOGRAPHY IN LOCAL STAGING OF SCREEN-DETECTED BREAST CANCER: ADDITIONAL LESIONS AND CHANGES TO CLINICAL MANAGEMENT

Abstract Background BreastScreen Australia, a mammographic population screening program, provides assessment of suspected breast cancer to the point of diagnosis using a combination of conventional imaging and percutaneous biopsy. Comprehensive local staging, not performed at BreastScreen, determines the extent of disease and may identify additional clinically significant breast abnormalities. Local staging options include completion of bilateral mammographic work-up, ultrasound, and/or contrast-based imaging (CBI) (magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM)), with biopsy as required. We introduced CBI for local staging after diagnosis of screen-detected cancer at our academic hospital breast service in Melbourne, Australia. We report diagnostic findings for otherwise occult disease and their impact on treatment decisions in women who underwent CEM for local staging. Material and methods Women with screen-detected breast cancer who underwent CEM for local staging between November 2018 to April 2022 were identified retrospectively. The reporting breast-specialised radiologist compared BreastScreen and CEM images to identify additional enhancing abnormalities. Additional abnormalities were further investigated with preoperative percutaneous biopsy, surgical biopsy, or problem-solving CBI. Additional CEM-detected abnormalities were documented, with invasive cancer or DCIS recorded as true positive (TP) and any other findings as false positive (FP). Impact on surgical decisions was assessed. Results 204 patients underwent CEM. 62/204 (30%) patients had 76 additional abnormalities, of which 36 (47%) were TP and 40 (53%) FP. CEM identified otherwise occult malignant lesions in 30/204 (15%) patients. TPs comprised 75% invasive cancers and 25% DCIS. 83% (30/36) of malignant abnormalities were ipsilateral to the index lesion, while 17% (6/36) were contralateral. The majority of additional invasive cancers were Grade 2 (20/27, 74.1%), followed by Grade 1 (4/27, 14.8%) then Grade 3 (3/27, 11.1%). All additional invasive cancers had the same phenotype as the patient’s index cancer (ER+/HER2-), except for one abnormality which was ER+/HER2+ where the index cancer was ER+/HER2-. The FP abnormalities consisted of normal breast tissue (20/40, 50%), benign lesions (16/40, 40%) and atypical proliferative lesions (4/40, 10%). Occult malignancies were more common for patients with higher background parenchymal enhancement (20% for moderate/marked vs 4% for minimal/mild, p=0.0023), with no statistically significant differences found by breast density (BIRADS A or B = 12%, vs BIRADS C or D = 20%, p=0.23) or by age (40-49=38%, 50-59=13%, 60-69=13%, ³70=19%, p=0.88). Additional abnormalities found on CEM resulted in surgical management change in 45/204 (22%) patients, including wider resection (24/45), conversion to mastectomy (8/45), contralateral breast surgery (6/45), additional ipsilateral excision (5/45), and bracketing (2/45). Conclusions The use of CEM for local staging of screen-detected breast cancers identified otherwise occult malignancy in 15% of patients. Age and mammographic density did not identify groups at minimal risk of additional findings. Pathology of additional malignancy suggests it is clinically significant. CEM may improve local staging and direct appropriate management of screen-detected breast cancers. Citation Format: Caroline MacCallum, Kenneth Elder, Carolyn Nickson, Kelly Ruecker, Allan Park, Bruce Mann. CONTRAST-ENHANCED MAMMOGRAPHY IN LOCAL STAGING OF SCREEN-DETECTED BREAST CANCER: ADDITIONAL LESIONS AND CHANGES TO CLINICAL MANAGEMENT [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-09.

Abstract PO4-19-02: Genetic risk estimation in breast cancer and assessing health disparities

Abstract Background: Breast Cancer (BC) incidence and the distribution of BC risk factors vary between racial and ethnic groups within the United States. It has been demonstrated that providing education on individualized breast cancer risk will improve patient uptake to recommended BC screening and prevention strategies. Most clinical risk assessment tools, including the validated IBIS model were derived from data using non-Hispanic white women. Consortia have also now identified over 300 common genetic susceptibility loci for BC, summarized by the polygenic risk score (PRS). When combined with clinical risk assessment tools, such as the IBIS or BCRAT models, the PRS can further refine risk estimation for patients. To date, most studies on the use of PRS have been done in non-Hispanic white women. While these PRS still perform well in racial minorities, there has been a recognized need to improve racial and ethnic diversity in genomic research cohorts. Herein, we aim to combine clinical risk assessment models that are already used in routine clinical practice with information derived from PRS testing in women of racial minorities to determine if this can improve risk estimation, patient understanding, and uptake to recommended breast cancer screening and prevention strategies. Design: This is a minimal risk prospective study with a single arm incorporating the PRS into a standard breast cancer risk reduction consultation, followed by annual surveys over 10 years to determine if and how the information provided by the PRS influenced patient decisions regarding recommended BC screening and prevention. Patients will have IBIS and BCRAT risks calculated at baseline visit. A survey of patient perceptions/understanding of risk, intention to undergo screening, and use of preventive medicine is completed after baseline visit prior to receiving the PRS results. Blood sample is obtained at baseline and DNA samples are analyzed for approximately 300 SNPs on a custom-designed, targeted SNP panel from ThermoFisher Scientific by the Mayo Clinic Genomics Laboratory. This PRS result is then combined with the clinical risk assessments (IBIS and BCRAT scores) using the R package Individualized Coherent Absolute Risk Estimators (iCare) tool to provide a new estimate of breast cancer risk for 5year, 10year, and lifetime risk. Patients are seen for follow-up to review results and then complete a second survey to assess their understanding of the results, BC risk, and how the PRS impacted their decision to undergo screening/prevention strategies. Eligibility Criteria: Women who self-identify as African American/Black or Hispanic/Latinx between 30-75 years old with any of the following: 1.)IBIS score of ≥5% for the 10 year risk OR BCRAT score of ≥ 3 % for the 5 year risk. 2.) History of biopsy proven atypical hyperplasia 3.) History of biopsy proven lobular carcinoma in situ. Specific Aims: Aim 1: The primary aim of this study is to explore if the addition of PRS to the BCRAT and IBIS score will improve intentions to undergo recommended breast cancer screening strategies such as mammography, MRI, or molecular breast imaging in women of underserved racial minorities Aim 2: To explore if the addition of the PRS to the BCRAT and IBIS risk score will aid women of racial minorities in deciding whether to take preventative endocrine therapy. Aim 3: To understand how individualized risk assessment and information on PRS may alter perceived risk of breast cancer. Statistical Methods Analysis will be mostly descriptive. Continuous variables will be summarized as mean (standard deviation) or median (range) and categorical variables will be reported as frequency (percentage). Kaplan-Meier method will be used to estimate the long-term cumulative risk of cancer. Current Accrual: 3. Target Accrual: 50 Citation Format: Lauren Cornell, Sandhya Pruthi, Linda Hasadsri, Sarah McLaughlin. Genetic risk estimation in breast cancer and assessing health disparities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-02.

A Dialogues Summarization Algorithm Based on Multi-task Learning

With the continuous advancement of social information, the number of texts in the form of dialogue between individuals has exponentially increased. However, it is very challenging to review the previous dialogue content before initiating a new conversation. In view of the above background, a new dialogue summarization algorithm based on multi-task learning is first proposed in the paper. Specifically, Minimum Risk Training is used as the loss function to alleviate the problem of inconsistent goals between the training phase and the testing phase. Then, in order to deal with the problem that the model cannot effectively distinguish gender pronouns, a gender pronoun discrimination auxiliary task based on contrast learning is designed to help the model learn to distinguish different gender pronouns. Finally, an auxiliary task of reducing exposure bias is introduced, which involves incorporating the summary generated during inference into another round of training to reduce the difference between the decoder inputs during the training and testing stages. Experimental results show that our model outperforms strong baselines on three public dialogue summarization datasets: SAMSUM, DialogSum, and CSDS.

Perceptions About Marijuana Use in Pregnancy Among Pregnant Users and Nonusers in a State Without Legalized Recreational Cannabis [ID 2683513

INTRODUCTION: Cannabis use in pregnancy is rising. The objective of this study is to compare attitudes regarding marijuana use among pregnant users and nonusers. METHODS: This was a prospective study (IRB #262700) in which a 35-question, anonymous survey was distributed to pregnant patients at outpatient prenatal visits across gestation. Questions included topics regarding marijuana use in pregnancy, perceived risks, and provider–patient education. RESULTS: 408/460 (88.7%) approached pregnant patients completed the survey. Self-reported rate of marijuana use during pregnancy: 11.8% (48/408). There were no ethnic differences in users and the most common age for use was 18–24 years (24/48). 79% (38/48) reported use two to three times weekly or greater. Average response score (Likert scale) for participants using marijuana compared to those who did not to the following statements were statistically significant and positive towards prenatal use: belief that pregnant patients should refrain from marijuana use: 2.31 versus 3.53 (&lt;.001); acceptability of medical marijuana: 3.68 versus 2.82 (&lt;.001); minimal health risk: 4.15 versus 2.96 (&lt;.001); support for legalization of recreational marijuana: 4.58 versus 3.51 (&lt;.001). Lack of counseling on cessation and risk of cannabis use in pregnancy were reported by 82% and 84% of participants with 74% of current users reporting lack of counseling. 54% of users desired more information regarding cannabis-related pregnancy complications. CONCLUSION: Higher-than-expected self-reported marijuana use during pregnancy. Lack of counseling on risks of marijuana use and importance of cessation highlight an important opportunity for counseling and intervention supporting current ACOG guidelines of SBIRT (screening, brief intervention, and treatment referral).

Neurologic Complication Rates in Obstetric Patients With Chiari Malformation Based on Mode of Delivery [ID 2683669

INTRODUCTION: Chiari malformation (CM) describes inferior displacement of hindbrain structures. Because of the theoretical effects of labor on cerebrospinal fluid dynamics, CM alone has historically been suggested as a sufficient indication for cesarean delivery because of concern for herniation. However, existing literature is limited and does not demonstrate increased adverse outcomes of vaginal delivery in this population. This novel work utilizes a national dataset to describe neurologic complication rates in CM parturients in relation to mode of delivery. METHODS: The 2016–2018 Nationwide Readmissions Datasets were queried for obstetric patients with and without documented CM. ICD-10 codes were used to identify parturients who experienced neurologic complications relevant to CM. Univariate and multivariate analyses were performed to assess associations between CM and mode of delivery. RESULTS: 11,021,188 parturients were identified, including 1,210 with preexisting CM. The primary cesarean rate was 50.7% (n=479) in CM parturients compared to 20% (n=1,823,650) in the general population and CM independently predicted cesarean delivery (OR 3.8, CI, 3.1–4.7). There was no significant difference (P=.87) in the rate of herniation based on delivery method in CM parturients. The incidence of stroke, myelopathy, and hydrocephalus was zero regardless of delivery method. CONCLUSION: There is no significant difference in neurological complication rates in CM patients based on delivery method, yet CM patients are more than twice as likely to undergo cesarean delivery. Data suggest that vaginal delivery carries minimal risk to CM patients and should be considered during clinical decision making. Future studies should stratify risk based on type and severity of CM.

The Prevalence of Prostate Cancer in Organ Donors With Increased Prostate-Specific Antigen

Elevated PSA levels were found in 139 kidney donors out of a total of 472 donors from our Transplant Centre tested between 2009 and 2022, representing 29,4%. We analyzed these kidney donors with elevated prostate specific antigen (PSA) levels, at mean age 47,3 years. PSA values ranged from 2.8 to 160.4 ng/ml, mean 13,9ng/ml), proper range <2.5 ng/ml. Prostate hist-pat examination was performed in 38/139 - 27% donors. 14 cases of prostate cancer (Pca) were found, Gleason 3+3 in 8 cases, 3+4 in four cases (one donor disqualification), one case Gleason 4+3 (donor disqualification), one case Gleason 4+5 (donor disqualification). There were 33 patients who met the criteria, age ≥50 years and PSA level > 10 mg/mL; of these, prostate hist-pat was performed in 24 cases, Pca was found in 10/42% cases. There were no difference between donors ≥ 50 years old, PSA>10 ng/ml with and without pathomorphological diagnosis of Pca in respect of age (mean 60,4 vs. 60,6 years), creatinine clearance according to the Cockroft-Gaulta formula (mean 101,6 vs. 94,8 ml/min) and PSA levels (mean 34,1 vs. 29,3 ng/ml). Among other donors with Pca three were <50 years with PSA >10 ng/ml and one was ≥ 50 years and PSA< 8 ng/ml. Kidneys from donors with prostate cancer were transplanted into 19 recipients, 10 men, nine women, follow-up time 1-10 years. There was no case of prostate cancer transmission. One of the recipients died of neoplasm – breast cancer. ConclusionsDonors ≥ 50 years old, PSA>10 ng/ml have higher risk of Pca. Accepting donors with Pca (Gleason 3+3, and 3+4) possesses minimal risk of transmission. All donors ≥ 50 years and also younger with increased PSA require further diagnostic procedure (e.g. DRE, USG, eventually histological examination).

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors: New Oral Medications for the Treatment of Type 2 Diabetes

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycaemia, insulin resistance at peripheral target tissues, and pancreatic β-cell dysfunction. It is a global health problem with epidemic proportions and a huge economic burden. The dipeptidyl peptidase (DPP-4) inhibitors are a new class of antihyperglycaemic agents that are developed for the treatment of T2D. Many clinical studies have suggested that DPP-4 inhibitors (gliptins) are safe from cardiovascular perspective, and may also possess cardioprotective effect. These are regulators of inflammation and metabolism, and also prevent the proteolytic breakdown. These reduce postprandial glucose with minimal risk of hypoglycaemia and gastrointestinal adverse effects. These increase biologically intact forms of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), both of which enhance glucose-induced insulin secretion from pancreatic β-cells. These medications become popular and are widely used worldwide for their efficacy, safety, weight neutrality, and tolerability. This article reviews basic studies of the DPP-4 inhibitors in briefly for the management of T2D.

Portuguese macroalgae and halophytes for human consumption: Minimal risk of norovirus and Salmonella infection

Information regarding microbiological hazards in edible macroalgae and halophytes is scarce, and standard methods for detecting norovirus in vegetables have not yet been validated for these types of food products. Accordingly, the suitability of the NF EN ISO 15216-2 standard method for macroalgae and halophytes was evaluated using 57 samples collected along the Western coast of mainland Portugal. The presence of Salmonella in 46 samples was also tested to confirm potential hazard. The viral extraction process was validated for 72% of the samples, with results showing that the standard method is suitable for green and red macroalgae, as well as for halophytes. For brown macroalgae, a process optimization should be considered. None of the samples revealed the presence of norovirus genomes, neither genogroups I nor II. Salmonella was detected in one of the samples analysed. The present study shows the great potential of Portuguese coastal areas for marine agriculture.

Leveraging open-source data to study solar-wind complementarity in the global perspective

Renewable energy sources, particularly solar and wind power, offer promising solutions for sustainable electricity generation. However, their inherent dependency on natural conditions and resulting intermittent generation pose challenges to the electricity grid.This study investigates the strategy of wind-solar complementarity to partly mitigate this issue, leveraging open-source data from the Slovak Republic. Our analysis reveals that combined solar and wind generation aligns more closely with real consumption compared to individual solar generation. We employ two quantitative methodologies, ordinary least squares (OLS) and least absolute deviations (LAD) regressions, to demonstrate the consistency of our findings. Additionally, we assess the prevalence of dunkelflaute events using real-generation data, finding them to be infrequent and posing a minimal risk in the context of Central Europe.We show that complementarity can be studied using open-source data for virtually any country in the world and thus quantitative methods can be used to advocate for renewable energy in general and balanced building of both wind and solar energy in particular. This research contributes to the broader understanding of renewable energy integration strategies and informs policymakers and stakeholders on optimizing energy systems for sustainability and cost-effectiveness.

An overview of heavy metals treatment & management for laboratory waste liquid (LWL)

The laboratory waste liquid (LWL) is the discarded liquid after the completion of analysis and is produced from the testing laboratories including regulatory institutions, colleges, universities and research organizations. This LWL is laden with a variety of heavy metals due to the use of heavy metal salts in analysis and the treatment and safe disposal of LWL is seldom given due consideration. Thus, the management of hazardous laboratory waste liquid (HLWL) containing heavy metals is essential at the source itself. Accordingly, this article presents systematic review of three processes for heavy metals removal viz. precipitation, adsorption, and membrane separation. The review covers various factors such as heavy metal removal efficiencies & concentration ranges, optimum pH, most frequently studied methods, less studied aspects, its commercial availability, operational ease, and the potential of risk minimization with due concern to toxic heavy metals. The concentrations of heavy metals in LWL is also presented. Based on the review, activated carbon (AC) adsorption appears to be the best option for LWL having heavy metals concentration of less than 10 mg/L. The heavy metals removal efficiency of more than 95% can be achieved at an AC dose of 0.2–1 g/L. The hydroxide precipitation was found to achieve more than 95% removal efficiencies at higher heavy metals concentrations. Thus, for concentrations higher than 10 mg/L up to 3000 mg/L, the hydroxide precipitation followed by activated carbon adsorption may prove beneficial.

Prenatal Exposure to Valproic Acid Across Various Indications for Use.

Teratogenic outcomes associated with valproic acid use represent a substantial concern for persons of childbearing age. Regulatory agencies worldwide have enhanced warnings or implemented risk minimization programs to reduce exposure during pregnancy. To determine pregnancy rates during valproic acid use and concomitant contraception use across indications. This retrospective cohort study used data from the Merative MarketScan commercial claims databases from January 1, 2005, to December 31, 2020, to identify female patients aged 12 to 44 years who initiated valproic acid treatment and had continuous insurance enrollment 6 months before initiation and 9 months after treatment end. A treatment episode included consecutive prescription fills that occurred within 7 days from the end of the days' supply of the previous dispensing. Data were analyzed from March 1 to September 10, 2023. Treatment episodes were categorized by inferred indication using diagnoses preceding treatment initiation, including epilepsy, migraine or headache, mood disorders, and unknown or off-label uses. Pregnancy incidence rate ratios (IRRs) were calculated and were adjusted for age and calendar year. Contraceptive use (prescription contraceptives, intrauterine devices, and implants) during treatment was examined. The cohort included 165 772 valproic acid treatment episodes among 69 390 women (mean [SD] age, 29.8 [10.0] years). Mood disorders (42.5%) were the most common indication, followed by migraine or headache (20.1%), with epilepsy playing a minor role (14.9%). Pregnancy incidence rates during valproic acid use remained unchanged, with a rate of 1.74 (95% CI, 1.14-2.53) per 100 person-years in 2005 and a rate of 1.90 (95% CI, 1.16-3.12) per 100 person-years in 2019. Compared with epilepsy, pregnancy rates were more than double for mood disorder (IRR, 2.16 [95% CI, 1.93-2.42]) and migraine or headache (IRR, 2.01 [95% CI, 1.92-2.09]). Few treatment episodes coincided with contraceptive use (37 012 [22.3%]), and oral dosage forms were the most common (27 069 [73.1%]). In this cohort study of patients of childbearing age who used valproic acid, pregnancy rates during valproic acid use did not decrease despite enhanced US Food and Drug Administration safety communications, and contraception use remained low. Patients with migraine and mood disorders accounted for the largest proportion of valproic acid use and had the highest pregnancy rates, while patients with epilepsy had the lowest. These findings suggest a need to enhance efforts to mitigate prenatal exposure to valproic acid, especially for indications where the risk of use during pregnancy outweighs the benefit.

Quantification of the Heat-Related Risk and Burden of Hospitalizations for Cause-Specific Injuries and Contribution of Human-Induced Climate Change: A Time-Stratified Case-Crossover Study in China.

Although ambient temperature has been linked with injury incidence, there have been few nationwide studies to quantify the temperature-related risk and burden of cause-specific injury hospitalizations. Additionally, the impact of human-induced climate change to injury burden remains unknown. Our objectives are to examine the associations between ambient temperature and injury hospitalizations from various causes and to quantify the contribution of human-induced warming to the heat-related burden. We collected injury hospitalization data from a nationwide hospital-based registry in China during 2000-2019. Using a time-stratified case-crossover design, we investigated the associations between daily mean temperature (°C) and cause-specific injury hospitalizations. We also quantified the burden of heat-related injuries under the scenarios with and without anthropogenic forcing, using the Detection and Attribution Model Intercomparison Project to assess the contribution of human-induced warming. Our study included a total of 988,087 patients with hospitalization records for injuries. Overall, compared to the temperature at minimum risk of hospitalization (), the relative risk of hospitalization at extreme hot temperature (30.8°C, 97.5th percentile) was 1.18 [95% confidence interval (CI): 1.14, 1.22], with an approximately linear association between temperature and hospitalization. Vulnerability to heat-related injuries was more pronounced among males, young ( years of age) or middle-aged (45-64 years of age) individuals, and those living in the North. The heat-related attributable fraction increased from 23.2% in the 2000s to 23.6% in the 2010s, with a corresponding increase in the contribution of human-induced change over time. In the 2010s, the heat-related attributable fractions for specific causes of injury ranged from 12.4% to 54.4%, with human-induced change accounting for 6.7% to 10.6% of the burden. This nationwide study presents new evidence of significant associations between temperature and cause-specific injury hospitalizations in China and highlights the increasing contribution of human-induced warming to the injury burden. https://doi.org/10.1289/EHP14057.

The efficacy of real versus sham external Trigeminal Nerve Stimulation (eTNS) in youth with Attention-Deficit/Hyperactivity Disorder (ADHD) over 4 weeks: a protocol for a multi-centre, double-blind, randomized, parallel-group, phase IIb study (ATTENS)

BackgroundAttention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action.MethodsA confirmatory, sham-controlled, double-blind, parallel-arm, multi-centre phase IIb RCT of 4 weeks of eTNS in 150 youth with ADHD, recruited in London, Portsmouth, and Southampton, UK. Youth with ADHD will be randomized to either real or sham eTNS, applied nightly for 4 weeks. Primary outcome is the change in the investigator-administered parent rated ADHD rating scale. Secondary outcomes are other clinical and cognitive measures, objective hyperactivity and pupillometry measures, side effects, and maintenance of effects over 6 months. The mechanisms of action will be tested in a subgroup of 56 participants using magnetic resonance imaging (MRI) before and after the 4-week treatment.DiscussionThis multi-centre phase IIb RCT will confirm whether eTNS is effective in a larger age range of children and adolescents with ADHD, whether it improves cognition and other clinical measures, whether efficacy persists at 6 months and it will test underlying brain mechanisms. The results will establish whether eTNS is effective and safe as a novel non-pharmacological treatment for ADHD.Trial registration: ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325.

Current state of the problem of voice correction, taking into account potential complications (literature review)

The discrepancy between the sound of the voice and the gender and appearance to which a person refers to himself leads to depression, the inability to socialize and carry out professional activities. To solve this problem, various ways of correcting vocal function have been proposed: hormone therapy, surgical interventions, phonopedic rehabilitation. The presented review is aimed at generalizing and systematizing the literature data on voice change, showing the possibilities of a rational approach to the management of patients with a mismatch in voice pitch to their gender and physique – both conservative and surgical methods – taking into account potential complications.The purpose of this study is to evaluate the possibilities of various methods of voice correction in patients wishing to change the pitch of their voice, and their likely complications according to the literature.There are a large number of operations to increase the pitch of the voice, which conditionally pursue three goals: reducing the length, total mass of the vocal folds or increasing their tension; they can be performed both openly and endoscopically – using classical instruments and a CO2 laser. In the postoperative period, dysphonia, decreased voice intensity, suture divergence, lack of increase in the fundamental frequency of the voice and even its decrease are often observed. In addition to granulomas, the need for revision with insufficient/asymmetric tension of the vocal folds, life-threatening complications in the form of infection, edema and an increase in signs of laryngeal stenosis are possible.Hormone therapy under medical supervision eliminates the risk of complications, however, uncontrolled testosterone intake leads to an increase in systolic blood pressure, an increase in hemoglobin, hematocrit, etc. The most characteristic complications of taking estrogens are a significant increase in thrombotic and cardiovascular risks, hyperprolactinemia. Phonopedia has a minimal risk of complications, it is possible before and after surgery to increase the fundamental frequency and improve other voice characteristics.Literature search was conducted in domestic (CyberLeninka, Google Academy) and international (PubMed) databases in Russian and English.

On the convergence of gradient descent for robust functional linear regression

Functional data analysis offers a set of statistical methods concerned with extracting insights from intrinsically infinite-dimensional data and has attracted considerable amount of attentions in the past few decades. In this paper, we study robust functional linear regression model with a scalar response and a functional predictor in the framework of reproducing kernel Hilbert spaces. A gradient descent algorithm with early stopping is introduced to solve the corresponding empirical risk minimization problem associated with robust loss functions. By appropriately selecting the early stopping rule and the scaling parameter of the robust losses, the convergence of the proposed algorithm is established when the response variable is bounded or satisfies a moment condition. Explicit learning rates with respect to both estimation and prediction error are provided in terms of regularity of the regression function and eigenvalue decay rate of the integral operator induced by the reproducing kernel and covariance function.