Patient-Reported Outcomes Among Adults With Congenital Heart Disease in the Congenital Heart Initiative Registry.

Importance: In the US, there are more than 1.5 million adults living with congenital heart disease (CHD). The Congenital Heart Initiative (CHI) is a digital, online, patient-empowered registry that was created to advance multicenter research and improve clinical care by gathering patient-reported outcomes (PROs) in adults with CHD. Objective: To report the initial findings of the PROs for adults with CHD from the first 3 years of the CHI. Design, Setting, and Participants: The CHI was launched nationally on December 7, 2020, as an observational cohort (survey) study. Data were collected virtually through December 31, 2023, and stored on Health Insurance Portability and Accountability Act-compliant cloud-based servers with restricted access. Adults with CHD were recruited through email, social media, general advertising through advocacy organizations, and targeted outreach (telephone and in-clinic recruitment) by clinical centers. Main Outcomes and Measures: Demographics and validated survey tools on quality of life, mental health, physical activity, and health care utilization were collected at baseline and every 4 months. Descriptive statistics were used to understand the associations between various factors, including the complexity of heart defects, physical activity levels, mental health comorbidities, and socioeconomic and health care access variables. All categorical variables were analyzed using χ2 or Fischer exact test as appropriate. Results: By December 31, 2023, the CHI had enrolled 4558 participants (2530 female [56%]) with a mean (SD) age of 38.5 (13.9) years, representing all 50 states. Approximately 88% of participants (3998 participants) completed at least 1 electronic visit as of December 31, 2023. The most prevalent CHD anatomy included tetralogy of Fallot (883 participants [22%]), transposition of great arteries (452 participants [11%]), and coarctation of the aorta (429 participants [11%]). Approximately 88% of participants (3998 participants) reported at least 1 comorbidity, with arrhythmia (1300 participants [33%]) as the most common cardiac comorbidity and mood disorder (1326 participants [35%]) as the most common noncardiac comorbidity. Among female participants, 45% (1147 participants) reported having had a pregnancy, with 38% (967 participants) resulting in biological children. Participants with complex CHD were less likely than those with moderate CHD to meet recommended physical activity guidelines (χ22 = 15.9; n = 3320; P < .001), a factor that was more pronounced among female participants. Overall health-related quality of life was rated as good or better by 84% of participants who completed the quality of life PROs (2882 participants), with no difference by CHD complexity. Conclusions and Relevance: In this cohort study of adults living with CHD, many patients reported mood disorders, but most reported good health-related quality of life. The CHI, the largest registry of adults with CHD, is poised to facilitate multicenter research with the goal of improving clinical outcomes for all adults with CHD.

Personal air sampling for pesticides in the California San Joaquin Valley.

BACKGROUND: California is a leading agricultural state and with that, has significant applications of pesticides. Levels of exposure have been measured to be higher among residents in agricultural areas, but measures of personal inhalation exposure to a wide range of pesticides are lacking. Community members in the San Joaquin Valley have expressed concern over pesticide exposures. Working with community members, a wide range of pesticides in personal air samples were measured. METHODS: Adult and school-aged participants were recruited from small agricultural towns in the San Joaquin Valley. Participants wore a backpack sampler for 8-14 h on 1-3 days. Samples were collected on two tubes, one with Tenax-TA resin and the other with XAD-2 resin. In total, 21 pesticides were analyzed using both LC/MS and GC/MS methods. RESULTS: Thirty-one adult participants and 11 school aged participants were recruited, and sampling occurred on a total of 92 days. Seven adults, 22% of adult participants, and one school child had detectable levels of at least one pesticide. Pesticides detected above the limit of detection were 1,3-dichloropropene, chlorpyrifos, pyrimethanil, burprofezin and penthiopyrad. When these samples were collected, chlorpyrifos was not permitted to be used in California. IMPACT STATEMENT: California, a leading agricultural state, has significant pesticide use, leading to concern about exposures among community members. Thirty-one adult and 11 school aged participants wore personal air sampling backpacks from 1-3 days. Twenty-two percent of adult participants had detectable levels of at least one pesticide. Two pesticides with established toxicity, 1,3-dichloropropene and chlorpyrifos were detected, along with first time measurements of pyrimethanil, burprofezin and penthiopyrad in the United States, which all have potential indications of toxicity. This study suggests the need to expand which pesticides are measured in agricultural communities.

Disinfection Byproducts in Drinking Water from the Tap: Variability in Household Calculated Additive Toxicity (CAT).

Recent studies have implemented a calculated additive toxicity (CAT) approach that sums measured disinfection byproduct (DBP) concentrations weighted by their respective in vitro bioassay potencies to estimate their associated risk in disinfected waters. In this study, the CAT approach was used to systematically investigate 21 regulated and unregulated DBPs measured in drinking water at the household level. Water samples from the tap were collected from over 120 randomly selected participants supplied by eight public water systems using four distinct source water types, two types of disinfection processes, and across two seasons. The purpose of this study was to compare CAT using multiple biological end points, examine household variability, identify DBPs driving toxicity, and assess if current regulated DBPs are adequate predictors of unregulated DBPs. Our results support the significance of unregulated DBPs, particularly haloacetonitriles and iodoacetic acid, as drivers of toxicity. Simple linear models between regulated versus unregulated concentrations and CAT were overall weak with 67% considered poor (r 2 < 0.3). These results reveal that current regulatory monitoring approaches may not be adequately capturing true household exposure due to higher contribution of unregulated DBPs to CAT and poor predictability between regulated and unregulated DBP-mediated CAT.

Glioblastoma and radiotherapy: A multicenter AI study for Survival Predictions from MRI (GRASP study).

BACKGROUND: The aim was to predict survival of glioblastoma at 8 months after radiotherapy (a period allowing for completing a typical course of adjuvant temozolomide), by applying deep learning to the first brain MRI after radiotherapy completion. METHODS: Retrospective and prospective data were collected from 206 consecutive glioblastoma, isocitrate dehydrogenase -wildtype patients diagnosed between March 2014 and February 2022 across 11 UK centers. Models were trained on 158 retrospective patients from 3 centers. Holdout test sets were retrospective (n = 19; internal validation), and prospective (n = 29; external validation from 8 distinct centers). Neural network branches for T2-weighted and contrast-enhanced T1-weighted inputs were concatenated to predict survival. A nonimaging branch (demographics/MGMT/treatment data) was also combined with the imaging model. We investigated the influence of individual MR sequences; nonimaging features; and weighted dense blocks pretrained for abnormality detection. RESULTS: The imaging model outperformed the nonimaging model in all test sets (area under the receiver-operating characteristic curve, AUC P = .038) and performed similarly to a combined imaging/nonimaging model (P > .05). Imaging, nonimaging, and combined models applied to amalgamated test sets gave AUCs of 0.93, 0.79, and 0.91. Initializing the imaging model with pretrained weights from 10 000s of brain MRIs improved performance considerably (amalgamated test sets without pretraining 0.64; P = .003). CONCLUSIONS: A deep learning model using MRI images after radiotherapy reliably and accurately determined survival of glioblastoma. The model serves as a prognostic biomarker identifying patients who will not survive beyond a typical course of adjuvant temozolomide, thereby stratifying patients into those who might require early second-line or clinical trial treatment.

Spatial and temporal variability of micropollutants within a wastewater catchment system.

Treated wastewater effluent is a major contributor to concentrations of many anthropogenic chemicals in the environment. Examining patterns of these compounds measured from different catchment areas comprising the influent to a wastewater treatment plant, across many months, may reveal patterns in compound sources and seasonality helpful to management efforts. This study considers a wastewater catchment system that was sampled at six sub-catchment sites plus the treatment plant influent and effluent at seven time points spanning nine months. Wastewater samples were analyzed with LC-QTOF-MS using positive electrospray ionization and GC-QTOF-MS using negative chemical ionization and electron ionization. MS data were screened against spectral libraries to identify micropollutants. As expected, multiple classes of chemicals were represented, including pharmaceuticals, plasticizers, personal care products, and flame retardants. Patterns in the compounds seen at different sampling sites and dates reflect the varying uses and down-the-drain routes that influence micropollutant loading in sewer systems. Patterns in examined compounds revealed little spatial variation, and greater temporal variation. For example, the greatest loads of DEET were found to occur in the summer months. Additionally, groups of compounds exhibited strong correlation with each other, which could be indicative of similar down-the-drain routes (such as a group intercorrelated chemicals that are components of cleaning products) or the influence of similar physicochemical processes within the sewer system. This study contributes to the understanding of dynamics of micropollutants in sewer systems.

Rigid versus non-rigid fixation for bilateral mandibular angle fractures: a retrospective multicentre review.

BACKGROUND: Fractures involving the bilateral mandibular angle are an uncommon occurrence with limited evidence to inform the ideal fixation requirements for adequate treatment. The aim of this study was to evaluate the outcomes of managing bilateral mandibular angle fractures and determine if rigid fixation on one side improves outcomes compared to bilateral non-rigid fixation. METHODS: Patients with isolated bilateral mandibular angle fractures surgically treated at the Royal Brisbane and Women's Hospital, Princess Alexandra Hospital, Gold Coast University Hospital and Townsville University Hospital between January 1, 2010 and December 31, 2022 were retrospectively identified. Data collected included patient demographics, mechanism of injury, fixation scheme, postoperative occlusion and the occurrence of postoperative complications and subsequent management. RESULTS: Eighty-four patients met the inclusion criteria. Fifty-two patients had non-rigid fixation applied to both fractures, and thirty-two had rigid fixation placed on at least one side. All cases proceeded to union. There was no statistically significant difference between the groups for occlusal outcomes, wound dehiscence, infection or plate or screw loosening. CONCLUSION: Our results suggest that bilateral non-rigid fixation can be used to treat bilateral mandibular angle fractures in the appropriate clinical context.

Bifenthrin, a Ubiquitous Contaminant, Impairs the Development and Behavior of the Threatened Longfin Smelt during Early Life Stages.

The Longfin Smelt (Spirinchus thaleichthys) population in the San Franscisco Bay/Sacramento-San Joaquin Delta (Bay-Delta) has declined to ∼1% of its pre-1980s abundance and, as a result, is listed as threatened under the California Endangered Species Act. The reasons for this decline are multiple and complex, including the impacts of contaminants. Because the spawning and rearing seasons of Longfin Smelt coincide with the rainy season, during which concentrations of contaminants increase due to runoff, we hypothesized that early life stages may be particularly affected by those contaminants. Bifenthrin, a pyrethroid insecticide commonly used in agricultural and urban sectors, is of concern. Concentrations measured in the Bay-Delta have been shown to disrupt the behavior, development, and endocrine system of other fish species. The objective of the present work was to assess the impact of bifenthrin on the early developmental stages of Longfin Smelt. For this, embryos were exposed to 2, 10, 100, and 500 ng/L bifenthrin from fertilization to hatch, and larvae were exposed to 2, 10, and 100 ng/L bifenthrin from one day before to 3 days post-hatch. We assessed effects on size at hatch, yolk sac volume, locomotory behavior, and upper thermal susceptibility (via cardiac endpoints). Exposure to these environmentally relevant concentrations of bifenthrin did not significantly affect the cardiac function of larval Longfin Smelt; however, exposures altered their behavior and resulted in smaller hatchlings with reduced yolk sac volumes. This study shows that bifenthrin affects the fitness-determinant traits of Longfin Smelt early life stages and could contribute to the observed population decline.

Perspective-The Feasibility of Continuous Protein Monitoring in Interstitial Fluid.

Real-time continuous monitoring of proteins in-vivo holds great potential for personalized medical applications. Unfortunately, a prominent knowledge gap exists in the fundamental biology regarding protein transfer and correlation between interstitial fluid and blood. Additionally, technological sensing will require affinity-based platforms that cannot be robustly protected in-vivo and will therefore be challenged in sensitivity, longevity, and fouling over multi-day to week timelines. Here we use electrochemical aptamer sensors as a model system to discuss further research necessary to achieve continuous protein sensing.

Neonatal Drug Formularies-A Global Scope.

Neonatal drug information (DI) is essential for safe and effective pharmacotherapy in (pre)term neonates. Such information is usually absent from drug labels, making formularies a crucial part of the neonatal clinician's toolbox. Several formularies exist worldwide, but they have never been fully mapped or compared for content, structure and workflow. The objective of this review was to identify neonatal formularies, explore (dis)similarities, and raise awareness of their existence. Neonatal formularies were identified through self-acquaintance, experts and structured search. A questionnaire was sent to all identified formularies to provide details on formulary function. An original extraction tool was employed to collect DI from the formularies on the 10 most commonly used drugs in pre(term) neonates. Eight different neonatal formularies were identified worldwide (Europe, USA, Australia-New Zealand, Middle East). Six responded to the questionnaire and were compared for structure and content. Each formulary has its own workflow, monograph template and style, and update routine. Focus on certain aspects of DI also varies, as well as the type of initiative and funding. Clinicians should be aware of the various formularies available and their differences in characteristics and content to use them properly for the benefit of their patients.

UAV-Based Wildland Fire Air Toxics Data Collection and Analysis.

Smoke plumes emitted from wildland-urban interface (WUI) wildfires contain toxic chemical substances that are harmful to human health, mainly due to the burning of synthetic components. Accurate measurement of these air toxics is necessary for understanding their impacts on human health. However, air pollution is typically measured using ground-based sensors, manned airplanes, or satellites, which all provide low-resolution data. Unmanned Aerial Vehicles (UAVs) have the potential to provide high-resolution spatial and temporal data due to their ability to hover in specific locations and maneuver with precise trajectories in 3-D space. This study investigates the use of an octocopter UAV, equipped with a customized air quality sensor package and a volatile organic compound (VOC) air sampler, for the purposes of collecting and analyzing air toxics data from wildfire plumes. The UAV prototype developed has been successfully tested during several prescribed fires conducted by the California Department of Forestry and Fire Protection (CAL FIRE). Data from these experiments were analyzed with emphasis on the relationship between the air toxics measured and the different types of vegetation/fuel burnt. BTEX compounds were found to be more abundant for hardwood burning compared to grassland burning, as expected.

Sub-sewershed Monitoring to Elucidate Down-the-Drain Pesticide Sources.

Pesticides have been reported in treated wastewater effluent at concentrations that exceed aquatic toxicity thresholds, indicating that treatment may be insufficient to adequately address potential pesticide impacts on aquatic life. Gaining a better understanding of the relative contribution from specific use patterns, transport pathways, and flow characteristics is an essential first step to informing source control measures. The results of this study are the first of their kind, reporting pesticide concentrations at sub-sewershed sites within a single sewer catchment to provide information on the relative contribution from various urban sources. Seven monitoring events were collected from influent, effluent, and seven sub-sewershed sites to capture seasonal variability. In addition, samples were collected from sites with the potential for relatively large mass fluxes of pesticides (pet grooming operations, pest control operators, and laundromats). Fipronil and imidacloprid were detected in most samples (>70%). Pyrethroids were detected in >50% of all influent and lateral samples. There were significant removals of pyrethroids from the aqueous process stream within the facility to below reporting limits. Imidacloprid and fiproles were the only pesticides that were detected above reporting limits in effluent, highlighting the importance of source identification and control for the more hydrophilic compounds. Single source monitoring revealed large contributions of fipronil, imidacloprid, and permethrin originating from a pet groomer, with elevated levels of cypermethrin at a commercial laundry location. The results provide important information needed to prioritize future monitoring efforts, calibrate down-the-drain models, and identify potential mitigation strategies at the site of pesticide use to prevent introduction to sewersheds.

Airway emergency after dental extraction.

Life-threatening airway emergencies and uncontrolled haemorrhage following dental extractions is rarely encountered. Inappropriate handling of dental luxators may lead to unexpected traumatic events resulting from penetrating or blunt trauma to the surrounding soft tissues and vascular damage. Bleeding during or after surgery usually resolves spontaneously or with local haemostatic interventions. Pseudoaneurysms are rare occurrences secondary to blunt or penetrating trauma usually produced by arterial injury leading to extravasation of blood. The rapidly enlarging haematoma with risk of spontaneous pseudoaneurysm rupture is an airway and surgical emergency necessitating urgent intervention. The following case highlights the importance of appreciating the potential complications associated with extractions in the maxilla, significant anatomical relationships and recognizing the clinical signs of a threatened airway.

Week-Long Operation of Electrochemical Aptamer Sensors: New Insights into Self-Assembled Monolayer Degradation Mechanisms and Solutions for Stability in Serum at Body Temperature.

Conventional wisdom suggests that widely utilized self-assembled alkylthiolate monolayers on gold are too unstable to last more than several days when exposed to complex fluids such as raw serum at body temperature. Demonstrated here is that these monolayers can not only last at least 1 week under such harsh conditions but that significant applied value can be captured for continuous electrochemical aptamer biosensors. Electrochemical aptamer biosensors provide an ideal tool to investigate monolayer degradation, as aptamer sensors require a tightly packed monolayer to preserve sensor signal vs background current and readily reveal fouling by albumin and other solutes when operating in biofluids. Week-long operation in serum at 37 °C is achieved by (1) increasing van der Waals interactions between adjacent monolayer molecules to increase the activation energy required for desorption, (2) optimizing electrochemical measurement to decrease both alkylthiolate oxidation and electric-field-induced desorption, and (3) mitigating fouling using protective zwitterionic membranes and zwitterion-based blocking layers with antifouling properties. This work further proposes origins and mechanisms of monolayer degradation in a logical stepwise manner that was previously unobservable over multiday time scales. Several of the observed results are surprising, revealing that short-term improvements to sensor longevity (i.e., hours) actually increase sensor degradation in the longer term (i.e., days). The results and underlying insights on mechanisms not only push forward fundamental understanding of stability for self-assembled monolayers but also demonstrate an important milestone for continuous electrochemical aptamer biosensors.

The provision of the baby box was associated with safe sleep practices in a low-resource community: a randomized control trial in Ecuador.

BACKGROUND: Sudden Unexpected Infant Deaths (SUID) can occur between 1 month and 1 year of age and are inequitably distributed with a greater burden in populations with numerous health disparities. Modifying the infant sleep environment to promote safe sleep is the most effective risk reduction strategy to reduce SUID. The provision of baby boxes with a mattress and infant supplies has been part of a larger anti-poverty social justice maternity package for decades in Finland. While infant mortality rates have generally improved after the maternity package was introduced, little is known about whether the provision of the baby box increased safe sleep practices. The purpose of the study was to evaluate whether the provision of a Finnish-style baby box reinforced safe infant sleep practice in the home in a low-resource community in Ecuador. METHODS: In this longitudinal randomized controlled trial all participants received the same safe sleep education in their third trimester of pregnancy (n = 100). This was followed by randomization into two groups; the control received a diaper bag and newborn gifts, and the intervention group received a baby box and the same gifts at each timepoint. Four infant sleep practices (room sharing, bed sharing/co-sleeping, position, and soft items in the sleep environment) were assessed at 1 month and 1 months post-delivery during a home visit where safe sleep education was also reinforced with both groups. RESULTS: Those in the baby box group were 2.5 times more likely to report safe sleep practices compared with mothers in the diaper bag group at 1 month (odds ratio [OR] = 2.45 and 95% confidence interval [CI]: 1.03-5.86; χ2 = 4.1, p = .043). The group difference was also present at 6-months post-birth: those in the baby box group were 2.9 times more likely to report safe sleep practices compared with those in the diaper bag group (OR = 2.86 and 95% CI: 1.16-7.05; χ2 = 5.2, p = .022). CONCLUSIONS: While not all participants used the box regularly, the mothers who received the box were more likely to practice safe sleep at 1 month and 6 months. This suggests the baby box may have served as an important prompt towards safer infant sleep practice. TRIAL REGISTRATION: (Clinical Trial Registry, per clinicaltrials.gov : not applicable under 42 CFR 11.22(b) as the study Facility Location was not in the United States (took place in Ecuador), does not involve FDA IND or IDE, and does not involve a drug, biological or device product that is manufactured in and exported from the US for study in another country. The University of San Francisco Quito, Research Ethics Committee in Human Beings approved the study, #2017- 127 M. The University of Kentucky Office of Research Integrity also approved the study, IRB # 42965).

Batch correction methods for nontarget chemical analysis data: application to a municipal wastewater collection system.

Nontarget chemical analysis using high-resolution mass spectrometry has increasingly been used to discern spatial patterns and temporal trends in anthropogenic chemical abundance in natural and engineered systems. A critical experimental design consideration in such applications, especially those monitoring complex matrices over long time periods, is a choice between analyzing samples in multiple batches as they are collected, or in one batch after all samples have been processed. While datasets acquired in multiple analytical batches can include the effects of instrumental variability over time, datasets acquired in a single batch risk compound degradation during sample storage. To assess the influence of batch effects on the analysis and interpretation of nontarget data, this study examined a set of 56 samples collected from a municipal wastewater system over 7 months. Each month's samples included 6 from sites within the collection system, one combined influent, and one treated effluent sample. Samples were analyzed using liquid chromatography high-resolution mass spectrometry in positive electrospray ionization mode in multiple batches as the samples were collected and in a single batch at the conclusion of the study. Data were aligned and normalized using internal standard scaling and ComBat, an empirical Bayes method developed for estimating and removing batch effects in microarrays. As judged by multiple lines of evidence, including comparing principal variance component analysis between single and multi-batch datasets and through patterns in principal components and hierarchical clustering analyses, ComBat appeared to significantly reduce the influence of batch effects. For this reason, we recommend the use of more, small batches with an appropriate batch correction step rather than acquisition in one large batch.

A Single-Blind, Randomized, Placebo Controlled Study to Evaluate the Benefits and Safety of Endourage Targeted Wellness Formula C Sublingual +Drops in People with Post-Acute Coronavirus Disease 2019 Syndrome.

Introduction: Coronavirus Disease 2019 (COVID-19) causes a wide range of symptoms, including death. As persons recover, some continue to experience symptoms described as Post-Acute COVID-19 Syndrome (PACS). The objectives of this study were to measure the efficacy of Formula C™, a cannabidiol (CBD)-rich, whole-flower terpene-rich preparation in managing PACS symptoms. Materials and Methods: This randomized, placebo-controlled, single-blind, open-label crossover study was conducted in 2021. Informed consent was obtained from participants, and they were randomized to two treatment groups. Group 1 (n=15) received blinded active product for 28 days, and Group 2 (n=16) received blinded placebo for 28 days (Treatment Period 1). Both groups crossed over to open-label active product for 28 days (Treatment Period 2) with a safety assessment at day 70. Patient-Reported Outcomes Measurement Information System (PROMIS®) scores and the Patient Global Impression of Change (PGIC) score were used to assess primary and secondary objectives. Safety assessments were also done at each visit. Results: Twenty-four participants completed study, with 8 withdrawals, none related to study product. PGIC and PROMIS scores improved across both groups at day 28. This raised questions about the placebo. A reanalysis of the placebo confirmed absence of CBD and unexpected medical concentration of terpenes. The study continued despite no longer having a true placebo. The improved scores on outcome measures were maintained across the open label treatment period. There were no safety events reported throughout the study. Discussion: For persons with PACS who are nonresponsive to conventional therapies, this study demonstrated symptom improvement for participants utilizing Formula C. In addition, the benefits seen in Group 2 suggest the possibility that non-CBD formulations rich in antioxidants, omega-3, and omega-6 fatty acids, gamma-linoleic acid, and terpenes may also have contributed to the overall improvement of the partial active group through the study. Conclusion: Given that both groups demonstrated improvement, both formulations may be contributing to these findings. Limitations include the small number of participants, the lack of a true placebo, and limited time on study products. Additional studies are warranted to explore both CBD-rich hemp products and hempseed oil as treatment options for PACS. Trial Registration ClinicalTrials.gov Identifier: NCT04828668.

Abiotrophia defectiva bacterial endocarditis complicated by an infective intracranial mycotic aneurysm - The need for aggressive odontogenic source control.

Abiotrophia defectiva or nutritionally variant streptococci (NVS) was first described in 1961 as a rare cause of infectious endocarditis (IE). It is distinct to the Streptococcus genus, pleomorphic, and demonstrates variable Gram-staining characteristics due to poor growth in culture media requiring extended incubation or 16S rRNA sequencing in culture negative situations.1 NVS has also been implicated in the pathogenesis of culture-negative endocarditis. In comparison with other causes of endocarditis, it has the ability to secrete exopolysaccharide and adheres to fibronectin in the extracellular matrix of endovascular structures.2 NVS is associated with significant morbidity and mortality, higher rates of multisystem complications ranging from pancreatic abscess, intracranial aneurysms, osteomyelitis, and valvular destruction, despite sensitivity to antibiotics.

In Silico Structure Predictions for Non-targeted Analysis: From Physicochemical Properties to Molecular Structures.

While important advances have been made in high-resolution mass spectrometry (HRMS) and its applications in non-targeted analysis (NTA), the number of identified compounds in biological and environmental samples often does not exceed 5% of the detected chemical features. Our aim was to develop a computational pipeline that leverages data from HRMS but also incorporates physicochemical properties (equilibrium partition ratios between organic solvents and water; Ksolvent-water) and can propose molecular structures for detected chemical features. As these physicochemical properties are often sufficiently different across isomers, when put together, they can form a unique profile for each isomer, which we describe as the "physicochemical fingerprint". In our study, we used a comprehensive database of compounds that have been previously reported in human blood and collected their Ksolvent-water values for 129 partitioning systems. We used RDKit to calculate the number of RDKit fragments and the number of RDKit bits per molecule. We then developed and trained an artificial neural network, which used as an input the physicochemical fingerprint of a chemical feature and predicted the number and types of RDKit fragments and RDKit bits present in that structure. These were then used to search the database and propose chemical structures. The average success rate of predicting the right chemical structure ranged from 60 to 86% for the training set and from 48 to 81% for the testing set. These observations suggest that physicochemical fingerprints can assist in the identification of compounds with NTA and substantially improve the number of identified compounds.

Do social protection programmes have a causal effect on suicide mortality? A protocol for a systematic review and meta-analysis.

INTRODUCTION: Recent international and national strategies to reduce suicide mortality have suggested that social protection programmes may be an effective multisectoral response given the link between material deprivation and suicides in observational studies. However, there is a lack of evidence on the causal relationship between social protection programmes and suicide, which may hinder substantial national budget reallocations necessary to implement these policies. Social protection programmes are government interventions that ensure adequate income now and in the future, through changes to earned income (eg, minimum wage increase) or social security (via cash transfers or cash equivalents). Our review aims to evaluate the existing evidence on a causal relationship between social protection programmes and suicide mortality by examining all relevant experimental and quasi-experimental studies between January 1980 and November 2021. METHODS AND ANALYSIS: The review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We will search references published between 1 January 1980 and 30 November 2021 in 10 electronic databases, including MEDLINE (PubMed), PsycINFO, EMBASE and Applied Social Sciences Index Abstracts. Seven reviewers will independently participate in screening studies from titles, abstracts and full texts across all the stages. Experimental (ie, randomised controlled trials) and quasi-experimental studies (ie, non-randomised interventional studies) written in English, French, Spanish, German, Chinese, Korean and Japanese examining the impact of income security programmes on suicide mortality were included. Meta-analyses will be conducted if there are at least three studies with similar income security programmes. ETHICS AND DISSEMINATION: Our proposed review does not require ethical approval. In collaboration with our community partners, we will develop a policy brief for stakeholders to support efforts to implement social protection programmes to help prevent suicides. Our findings will be presented at conferences, published in a peer-reviewer journal and promoted on social media platforms. PROSPERO REGISTRATION NUMBER: CRD42021252235.