Quantitative Proteomics of the Cancer Cell Line Encyclopedia.

Proteins are essential agents of biological processes. To date, large-scale profiling of cell line collections including the Cancer Cell Line Encyclopedia (CCLE) has focused primarily on genetic information whereas deep interrogation of the proteome has remained out of reach. Here, we expand the CCLE through quantitative profiling of thousands of proteins by mass spectrometry across 375 cell lines from diverse lineages to reveal information undiscovered by DNA and RNA methods. We observe unexpected correlations within and between pathways that are largely absent from RNA. An analysis of microsatellite instable (MSI) cell lines reveals the dysregulation of specific protein complexes associated with surveillance of mutation and translation. These and other protein complexes were associated with sensitivity to knockdown of several different genes. These data in conjunction with the wider CCLE are a broad resource to explore cellular behavior and facilitate cancer research.

Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening.

Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the discovery of therapeutic targets for counteracting tumor suppressor gene loss is needed. To identify vulnerabilities relevant to specific cancer subtypes, we conducted a large-scale RNAi screen in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines. We describe findings of this screen, outlining the classes of cancer dependency genes and their relationships to genetic, expression, and lineage features. In addition, we describe robust gene-interaction networks recapitulating both protein complexes and functional cooperation among complexes and pathways. This dataset along with a web portal is provided to the community to assist in the discovery and translation of new therapeutic approaches for cancer.

Next-generation characterization of the Cancer Cell Line Encyclopedia.

Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers. Together, this dataset and an accompanying public data portal provide a resource for the acceleration of cancer research using model cancer cell lines.

Bioavailability of vitamin D biofortified pork meat: results of an acute human crossover study in healthy adults.

Vitamin D intakes are concerningly low. Food-based strategies are urgently warranted to increase vitamin D intakes and subsequently improve 25-hydroxyvitamin D (25(OH)D) concentrations. This acute randomised three-way crossover study investigated the efficacy of vitamin D biofortified pork derived from pigs exposed to UVB light to increase serum 25(OH)D3 concentrations, compared to a dose-matched vitamin D3 supplement and control pork in adults (n = 14). Blood samples were obtained at baseline and then 1.5, 3, 6, 9 and 24 h postprandially. There was a significant effect of time (p < 0.01) and a significant treatment*time interaction (p < 0.05). UV pork and supplement significantly increased within-group serum 25(OH)D3 concentrations over timepoints (p < 0.05) (max. change 0.9 nmol/L (2.2%) UV pork, 1.5 nmol/L (3.5%) supplement, 0.7 nmol/L (1.9%) control). Vitamin D biofortified pork modestly increased 25(OH)D3 concentrations and produced a similar response pattern as a dose-matched vitamin D supplement, but biofortification protocols should be further optimised to ensure differentiation from standard pork.

A highly multiplexed quantitative phosphosite assay for biology and preclinical studies.

Reliable methods to quantify dynamic signaling changes across diverse pathways are needed to better understand the effects of disease and drug treatment in cells and tissues but are presently lacking. Here, we present SigPath, a targeted mass spectrometry (MS) assay that measures 284 phosphosites in 200 phosphoproteins of biological interest. SigPath probes a broad swath of signaling biology with high throughput and quantitative precision. We applied the assay to investigate changes in phospho-signaling in drug-treated cancer cell lines, breast cancer preclinical models, and human medulloblastoma tumors. In addition to validating previous findings, SigPath detected and quantified a large number of differentially regulated phosphosites newly associated with disease models and human tumors at baseline or with drug perturbation. Our results highlight the potential of SigPath to monitor phosphoproteomic signaling events and to nominate mechanistic hypotheses regarding oncogenesis, response, and resistance to therapy.

Iron transport across the human placenta is regulated by hepcidin.

BACKGROUND: Transport of iron across the placenta is critical for appropriate development of the fetus. Iron deficiency during pregnancy remains a major public health concern, particularly in low- and middle-income countries, often exacerbated by infectious diseases leading to altered iron trafficking via inflammatory responses. Herein, we investigate the role of hepcidin, a master regulator of iron homeostasis, on regulation of iron transport across trophoblast cells. METHODS: We utilized the Jeg-3 choriocarcinoma cell line for analysis of the expression of transferrin receptor, ferritin, and ferroportin as well as the export of 59Fe in the presence of hepcidin. Placental tissue from human term pregnancies was utilized for immunohistochemistry. RESULTS: Hepcidin treatment of Jeg-3 cells decreased the expression of ferroportin and transferrin receptor (TfR) and reduced the cellular export of iron. Lower expression of TfR on the syncytiotrophoblast was associated with the highest levels of hepcidin in maternal circulation, and ferroportin expression was positively associated with placental TfR. Placentas from small-for-gestational-age newborns had significantly lower levels of ferroportin and ferritin gene expression at delivery. CONCLUSIONS: Our data suggest that hepcidin plays an important role in the regulation of iron transport across the placenta, making it a critical link in movement of iron into fetal circulation. IMPACT: Hepcidin has a direct impact on iron transport across the human placenta. This study provides the first evidence of direct regulation of iron efflux from human trophoblast cells by hepcidin. These data extend our understanding of iron transport across the maternal-fetal interface, a process critical for fetal health and development.

Systematic Review of the Impact on Return to Work of Return-to-Work Coordinators.

Purpose We conducted a systematic review to understand the impact that return-to-work coordinators (RTWCs) have on return to work (RTW) outcomes for sick/injured workers. Methods MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, and ABI Inform were searched from January 1, 2000 to September 16, 2020. Of 2,927 retrieved and screened citations, 14 quantitative articles fulfilled the eligibility and quality criteria. Quality assessment, data extraction, and evidence synthesis followed article screening. Results We focused on the impact of RTWCs for outcomes of work absence, RTW rates, quality of life, and cost-benefit. Our final synthesis included 14 articles. We found strong evidence that work absence duration was reduced when workers had face-to-face contact with a RTWC. As well, there was strong evidence linking face-to-face RTWC interventions with higher RTW rates and moderate evidence that this reduced intervention costs. RTWC interventions involving the identification of barriers and facilitators to RTW also showed promising results. However, only limited evidence was found that RTWCs improved quality of life for workers. Conclusions Our synthesis identifies key features of RTW interventions that improve RTW outcomes. Future high-quality research should measure long-term outcomes of RTWC interventions to evaluate sustainability and consider the nature of work. They should also focus on RTWC impact on worker quality of life assessments and for older workers and workers with chronic health conditions.

Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease-associated psychological morbidity.

BACKGROUND: Alopecia areata (AA) is a common autoimmune disease, causing patchy hair loss that can progress to involve the entire scalp (totalis) or body (universalis). CD8+ NKG2D+ T cells dominate hair follicle pathogenesis, but the specific mechanisms driving hair loss are not fully understood. OBJECTIVES: To provide a detailed insight into the systemic cytokine signature associated with AA, and to assess the association between cytokines and depression. METHODS: We conducted multiplex analysis of plasma cytokines from patients with AA, patients with psoriatic arthritis (PsA) and healthy controls. We used the Hospital Anxiety and Depression Scale (HADS) to assess the occurrence of depression and anxiety in our cohort. RESULTS: Our analysis identified a systemic inflammatory signature associated with AA, characterized by elevated levels of interleukin (IL)-17A, IL-17F, IL-21 and IL-23 indicative of a type 17 immune response. Circulating levels of the type 2 cytokines IL-33, IL-31 and IL-17E (IL-25) were also significantly increased in AA. In comparison with PsA, AA was associated with higher levels of IL-17F, IL-17E and IL-23. We hypothesized that circulating inflammatory cytokines may contribute to wider comorbidities associated with AA. Our assessment of psychiatric comorbidity in AA using HADS scores showed that 18% and 51% of people with AA experienced symptoms of depression and anxiety, respectively. Using linear regression modelling, we identified that levels of IL-22 and IL-17E are positively and significantly associated with depression. CONCLUSIONS: Our data highlight changes in both type 17 and type 2 cytokines among people with AA, suggesting that complex systemic cytokine profiles may contribute both to the pathogenesis of AA and to the associated depression. What's already known about this topic? NKG2D+ CD8+ T cells cause hair loss in alopecia areata (AA) but the immunological mechanisms underlying the disease are not fully understood. AA is associated with changes in levels of interleukin (IL)-6, tumour necrosis factor-α, IL-1ß and type 17 cytokines. Psychiatric comorbidity is common among people with AA. What does this study add? People with AA have increased plasma levels of the type 2 cytokines IL-33, IL-31 and IL-17E (IL-25), in addition to the type 17 cytokines IL-17A, IL-21, IL-23 and IL-17F. Levels of IL-17E and IL-22 positively predict depression score. What is the translational message? AA is associated with increased levels of multiple inflammatory cytokines, implicating both type 17- and type 2 immune pathways. Our data indicate that therapeutic strategies for treating AA may need to address the underlying type 17- and type 2 immune dysregulation, rather than focusing narrowly on the CD8+ T-cell response. An immunological mechanism might contribute directly to the depression observed in people with AA.

Return to Work for Mental Ill-Health: A Scoping Review Exploring the Impact and Role of Return-to-Work Coordinators.

Purpose This scoping review was completed to explore the role and impact of having a return-to-work (RTW) coordinator when dealing with individuals with common mental ill-health conditions. Methods Peer reviewed articles published in English between 2000 and 2018 were considered. Our research team reviewed all articles to determine if an analytic focus on RTW coordinator and mental ill-health was present; consensus on inclusion was reached for all articles. Data were extracted for all relevant articles and synthesized for outcomes of interest. Results Our search of six databases yielded 1798 unique articles; 5 articles were found to be relevant. The searched yielded only quantitative studies. Of those, we found that studies grouped mental ill-health conditions together, did not consider quality of life, and used different titles to describe RTW coordinators. Included articles described roles of RTW coordinators but did not include information on their strategies and actions. Included articles suggest that RTW interventions for mental ill-health that utilize a RTW coordinator may result in delayed time to RTW. Conclusions Our limited findings suggest that interventions for mental ill-health that employ RTW coordinators may be more time consuming than conventional approaches and may not increase RTW rate or worker's self-efficacy for RTW. Research on this topic with long-term outcomes and varied research designs (including qualitative) is needed, as well as studies that clearly define RTW coordinator roles and strategies, delineate results by mental health condition, and address the impact of RTW coordinators on workers' quality of life.

Correction of copy number induced false positives in CRISPR screens.

Cell autonomous cancer dependencies are now routinely identified using CRISPR loss-of-function viability screens. However, a bias exists that makes it difficult to assess the true essentiality of genes located in amplicons, since the entire amplified region can exhibit lethal scores. These false-positive hits can either be discarded from further analysis, which in cancer models can represent a significant number of hits, or methods can be developed to rescue the true-positives within amplified regions. We propose two methods to rescue true positive hits in amplified regions by correcting for this copy number artefact. The Local Drop Out (LDO) method uses the relative lethality scores within genomic regions to assess true essentiality and does not require additional orthogonal data (e.g. copy number value). LDO is meant to be used in screens covering a dense region of the genome (e.g. a whole chromosome or the whole genome). The General Additive Model (GAM) method models the screening data as a function of the known copy number values and removes the systematic effect from the measured lethality. GAM does not require the same density as LDO, but does require prior knowledge of the copy number values. Both methods have been developed with single sample experiments in mind so that the correction can be applied even in smaller screens. Here we demonstrate the efficacy of both methods at removing the copy number effect and rescuing hits from some of the amplified regions. We estimate a 70-80% decrease of false positive hits with either method in regions of high copy number compared to no correction.

Multistate outbreak of Salmonella Poona infections associated with imported cucumbers, 2015-2016.

We investigated a large multistate outbreak that occurred in the United States in 2015-2016. Epidemiologic, laboratory, and traceback studies were conducted to determine the source of the infections. We identified 907 case-patients from 40 states with illness onset dates ranging from July 3, 2015 to March 2, 2016. Sixty-three percent of case-patients reported consuming cucumbers in the week before illness onset. Ten illness sub-clusters linked to events or purchase locations were identified. All sub-clusters investigated received cucumbers from a single distributor which were sourced from a single grower in Mexico. Seventy-five cucumber samples were collected, 19 of which yielded the outbreak strain. Whole genome sequencing performed on 154 clinical isolates and 19 cucumber samples indicated that the sequenced isolates were closely related genetically to one another. This was the largest US foodborne disease outbreak in the last ten years and the third largest in the past 20 years. This was at least the fifth multistate outbreak caused by contaminated cucumbers since 2010. The outbreak is noteworthy because a recall was issued only 17 days after the outbreak was identified, which allowed for the removal of the contaminated cucumbers still available in commerce, unlike previous cucumber associated outbreaks. The rapid identification and response of multiple public health agencies resulted in preventing this from becoming an even larger outbreak.

Assessment of disease extent on contrast-enhanced MRI in breast cancer detected at digital breast tomosynthesis versus digital mammography alone.

AIM: To compare the utility of breast magnetic resonance imaging (MRI) in determining the extent of disease in patients with newly diagnosed breast cancer detected on combination digital breast tomosynthesis (DBT) versus digital screening mammography (DM). MATERIALS AND METHODS: Review of 24,563 DBT-screened patients and 10,751 DM-screened patients was performed. Two hundred and thirty-five DBT patients underwent subsequent MRI examinations; 82 to determine extent of disease after newly diagnosed breast cancer. Eighty-three DM patients underwent subsequent MRI examinations; 23 to determine extent of disease. MRI examinations performed to assess disease extent were considered true positives if additional disease was discovered in the contralateral breast or >2 cm away from the index malignancy. Differences in cancer subtypes and MRI outcomes between the DM and DBT cohorts were compared using chi-squared tests and post-hoc Bonferroni-adjusted tests for equal proportions. RESULTS: No differences in cancer subtype findings were observed between the two cohorts; however, MRI outcomes were found to differ between the DBT and DM cohorts (p=0.024). Specifically, the DBT cohort had significantly (p=0.013) fewer true-positive findings (7/82, 8.5%) than did the DM cohort (7/23; 30%), whereas the false-positive rate was similar between the cohorts (not statistically significant). When stratifying by breast density, this difference in true-positive rates was primarily observed when evaluating women with non-dense breasts (p=0.001). CONCLUSION: In both the DM- and DBT-screened populations with new cancer diagnoses, MRI is able to detect additional cancer; however, in those patients who have DBT screen-detected cancers the positive impact of preoperative MRI is diminished, particularly in those women with non-dense breasts.

Frequency, severity and risk factors for urinary and faecal incontinence at 4 years postpartum: a prospective cohort.

OBJECTIVES: To investigate frequency, severity and risk factors for urinary incontinence and faecal incontinence 4 years after a first birth. DESIGN: Prospective pregnancy cohort study. SETTING: Melbourne, Australia. SAMPLE: A total of 1011 nulliparous women recruited in early pregnancy. METHODS: Participants were followed up at 32 weeks of gestation; then at 3, 6, 9 and 12 months and 4 years postpartum. MAIN OUTCOME MEASURES: Frequency and severity of urinary and faecal incontinence. RESULTS: At 4 years, 29.6% of women reported urinary incontinence and 7.1% reported faecal incontinence. Compared with women having only spontaneous vaginal births, women who delivered exclusively by caesarean section were less likely to have urinary incontinence at 4 years postpartum (adjusted odds ratio 0.4, 95% confidence interval 0.3-0.6). Women who reported urinary incontinence before or during the index pregnancy, and those experiencing symptoms in the first year postpartum had increased odds of incontinence at 4 years, with the highest odds (6-12 times higher) among women who had previously reported moderate or severe symptoms. The odds of reporting faecal incontinence at 4 years were two to six times higher for women experiencing symptoms in pregnancy, and around four to eight times higher for those with symptoms in the first year postpartum. CONCLUSION: Urinary and faecal incontinence are prevalent conditions 4 years after a first birth. Women reporting urinary or faecal incontinence during pregnancy had markedly higher odds of reporting symptoms at 4 years postpartum, suggesting a need for further investigation and elucidation of aetiological pathways involving nonbirth-related risk factors. TWEETABLE ABSTRACT: Moderate/severe incontinence prevalent 4 years after first birth in population cohort. Prior symptoms are biggest predictor.

Vulnerability to intimate partner violence and poor mental health in the first 4-year postpartum among mothers reporting childhood abuse: an Australian pregnancy cohort study.

The purpose of this study was to investigate intergenerational patterns of abuse and trauma and the health consequences for women in the early childbearing years. A prospective pregnancy cohort of 1507 nulliparous women (≦24 weeks gestation) were recruited in Melbourne, Australia, 2003-2005. Follow-up was scheduled in late pregnancy, 3-, 6- and 12-month and 4-year postpartum. Childhood abuse was retrospectively reported at 4-year postpartum using the Child Maltreatment History Self Report. Intimate partner violence (IPV) was assessed at 1- and 4-year postpartum with the Composite Abuse Scale. Maternal depressive symptoms were assessed in all follow-ups using the Edinburgh Postnatal Depression Scale. Multivariable logistic regression was used to examine associations between childhood abuse, maternal mental health and IPV. Childhood abuse was reported by 41.1 % of women. In the 4 years after having their first child, 28.2 % of women reported IPV, 25.2 % depression and 31.6 % anxiety. Childhood abuse was associated with odds of depression or anxiety 1.5-2.6 times greater and 1.8-3.2 times greater for IPV. Childhood physical abuse remained significantly associated with depression and anxiety in pregnancy and postpartum after adjusting for IPV and stressful life events, while sexual abuse remained significantly associated only with anxiety. Women who begin childbearing with a history of childhood abuse are more vulnerable to IPV and poor mental health. All health care services and agencies in contact with children, young people and families should have adequate training to identify trauma associated with abuse and IPV and provide first line supportive care and referral.

Consultation about urinary and faecal incontinence in the year after childbirth: a cohort study.

OBJECTIVE: To investigate the extent to which primary-care practitioners routinely inquire about postpartum urinary and faecal incontinence, and assess the proportion of women who disclose symptoms. DESIGN: Prospective pregnancy cohort study of nulliparous women. SETTING: Melbourne, Australia. SAMPLE: A total of 1507 nulliparous women recruited in early pregnancy. METHOD: Women were recruited from six public maternity hospitals, with follow up at 3, 6, 9 and 12 months postpartum. MAIN OUTCOME MEASURES: Standardised measures of urinary and bowel symptoms, and measures of health service use. RESULTS: In the first 12 months postpartum, the period prevalence of urinary incontinence was 47%, and of faecal incontinence was 17%. In all, 86% of women visited a primary health-care practitioner at least once to discuss their own health in the first year after childbirth. However, only around a quarter were asked about urinary incontinence, and fewer than one in five women were asked about faecal incontinence. Discussion of symptoms with health professionals was most likely to occur in the first 3 months postpartum, and happened only rarely during the remainder of the first postnatal year. Over 70% of women reporting severe urinary incontinence and/or faecal incontinence had not discussed symptoms with a health professional. CONCLUSION: The findings provide robust evidence that many women experiencing postpartum urinary and faecal incontinence­including women with moderate and severe symptoms­do not receive adequate primary-care follow up in the first 12 months postpartum. Systems of maternal health surveillance need to include routine inquiry about urinary and faecal incontinence to overcome women's reluctance to seek help.

Dyspareunia and childbirth: a prospective cohort study.

OBJECTIVE: To investigate the relationship between mode of delivery, perineal trauma and dyspareunia. DESIGN: Prospective cohort study. SETTING: Six maternity hospitals in Melbourne, Australia. SAMPLE: A total of 1507 nulliparous women recruited in the first and second trimesters of pregnancy. METHOD: Data from baseline and postnatal questionnaires (3, 6, 12 and 18 months) were analysed using univariable and multivariable logistic regression. MAIN OUTCOME MEASURE: Study-designed self-report measure of dyspareunia at 18 months postpartum. RESULTS: In all, 1244/1507 (83%) women completed the baseline and all four postpartum questionnaires; 1211/1237 (98%) had resumed vaginal intercourse by 18 months postpartum, with 289/1211 (24%) women reporting dyspareunia. Compared with women who had a spontaneous vaginal delivery with an intact perineum or unsutured tear, women who had an emergency caesarean section (adjusted odds ratio [aOR] 2.41, 95% confidence interval [95% CI] 1.4-4.0; P = 0.001), vacuum extraction (aOR 2.28, 95% CI 1.3-4.1; P = 0.005) or elective caesarean section (aOR 1.71, 95% CI 0.9-3.2; P = 0.087) had increased odds of reporting dyspareunia at 18 months postpartum, adjusting for maternal age and other potential confounders. CONCLUSIONS: Obstetric intervention is associated with persisting dyspareunia. Greater recognition and increased understanding of the roles of mode of delivery and perineal trauma in contributing to postpartum maternal morbidities, and ways to prevent postpartum dyspareunia where possible, are warranted.

A smartphone app to communicate child passenger safety: an application of theory to practice.

Child passenger safety remains an important public health problem because motor vehicle crashes are the leading cause of death for children, and the majority of children ride improperly restrained. Using a mobile app to communicate with parents about injury prevention offers promise but little information is available on how to create such a tool. The purpose of this article is to illustrate a theory-based approach to developing a tailored, smartphone app for communicating child passenger safety information to parents. The theoretical basis for the tailoring is the elaboration likelihood model, and we utilized the precaution adoption process model (PAPM) to reflect the stage-based nature of behavior change. We created assessment items (written at ≤6th grade reading level) to determine the child's proper type of car seat, the parent's PAPM stage and beliefs on selected constructs designed to facilitate stage movement according to the theory. A message library and template were created to provide a uniform structure for the tailored feedback. We demonstrate how messages derived in this way can be delivered through new m-health technology and conclude with recommendations for the utility of the methods used here for other m-health, patient education interventions.

Risk factors for TB and HIV coinfection in Scotland, 2001 to 2010.

The number of patients with tuberculosis (TB) increased steadily in Scotland between 2005 and 2010. Human immunodeficiency virus (HIV) infection has been a contributory factor to increases in TB in a number of comparable industrialised countries. This study investigated the extent of, and risk factors for, TB and HIV coinfection in Scotland from 2001 to 2010. Patients with TB in the national TB database were linked to those in the national HIV database using probabilistic data linkage. Patient records were anonymised to maintain confidentiality. From 2001 to 2010, 106/4, 097 (2.6%, 95% CI: 2.1 to 3.1) TB patients matched with HIV patients, equating to a 10-year incidence of 2.1 cases per million population. Patients with both TB and HIV were more often born outside the United Kingdom,were of black African ethnicity, had refugee status and had extra-thoracic lymph node involvement or cryptic/disseminated TB disease. Individuals with TB and HIV coinfection were younger and symptomatic for a shorter time before their diagnosis of TB, compared with TB patients without HIV. TB and HIV coinfection was relatively uncommon in Scotland in the study period. Clinicians should recognise the potential for HIV infection among TB patients and the importance of offering an HIV test to all TB patients.

Current management of relapsing-remitting multiple sclerosis.

Multiple sclerosis was without effective disease-modifying therapy for many years. The introduction of the injectable therapies (interferon and glatiramer acetate) some 20 years ago was considered a major advance. Recent years have heralded a revolution in treatment options with the introduction of intravenous natalizumab and, even more recently, three oral agents. We are currently in a period of determining the best use of these therapies to ensure prevention of disease progression while maintaining patient safety. Despite these new treatments, there are still many patients living with disability as a result of multiple sclerosis and significant attention must be given to symptomatic management.

Potential impact of the 2023 Lahaina wildfire on the marine environment: Modeling the transport of ash-laden benzo[a]pyrene and pentachlorophenol.

The Lahaina urban/wildland fire event is considered the deadliest wildfire in the past century of U.S. history. This fire resulted in over 2200 building structures destroyed or damaged, approximately 4000 automobiles were incinerated and between 450 and 878 ha of grassland burned in areas adjoining the town of Lahaina, Maui County, State of Hawaii, U.S.A. One of the most abundant contaminants of both wildland and urban fires is the incomplete combustion product, benzo[a]pyrene. Pentachlorophenol from burned and unburned utility poles/residential burn sites enter into navigable waters, thus posing a serious risk to the water quality of coastal waters. The Risk Quotient Plumes for benzo[a]pyrene and pentachlorophenol, mobilized from Lahaina into coastal waters were calculated based on a hydrodynamic analysis and an integrated ecological risk assessment. This plume was simulated using rainfall events in November 2022 as a proxy for the first major rainfall event expected in Lahaina in 2024. The models indicated that the estimated levels of benzo[a]pyrene and pentachlorophenol posed a risk to near shore habitants within 2 km of Lahaina. The levels of pentachlorophenol were more widespread than benzo[a]pyrene and were predicted to pose a hazard to marine life as far away as Molokini Shoal Marine Life Conservation District and 'Ahihi-Kina'u Natural Area Reserve. Fisheries species captured near these areas should be tested for consumption safety.