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Discusses the abstract of the study 'A Survey of Genetic Counseling and Testing of Early Onset Breast Cancer Survivors,' presented at the 21st Annual Education Conference of the National Society of Genetic Counselors held in Phoenix, Arizona in November 2002.

Abstract Background In April 2004, an incentive based contract was introduced to UK primary care. An important element of the new contract is the ability to exclude individuals from quality indicators for a variety of reasons (known as 'exception reporting'). Exception of patients with stroke or TIA from the recording and achievement of quality indicators may have important consequences in terms of stroke recurrence and mortality. Methods A cross-sectional retrospective analysis of anonymised patient data was performed using 312 Scottish primary care practices. Results Patients recorded as unsuitable for inclusion in the contract were more likely to be female (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.36–1.68), older (>75 years:OR 3.15, 95%CI 2.69–3.69), and have dementia (OR 4.40, 95%CI 3.57–5.43) when compared to those patients without such a code. Patients were less likely to be older (>75 years:OR 0.70, 95%CI 0.56–0.87) and were more likely to be from the most deprived areas of Scotland (Quintile 5: OR 2.02, 95%CI 1.50–2.70) if they refused to attend for review or did not reply to letters asking for attendance at primary care clinics. Patients with multiple co-morbidities were more likely to have exclusions for achieving diagnostic clinical targets such as cholesterol control (3 or more co-morbidities: OR 3.37, 95%CI 2.50–4.50). Conclusion Scottish practices have appeared to use exception reporting appropriately by excluding patients who are older or have dementia. However, younger or more socio-economically deprived patients were more likely to be recorded as having refused to attend for review or not replying to letters asking for attendance at primary care clinics. It is important for primary care practices to identify and monitor these individuals so that all patients fully benefit from the implementation of an incentive based contract and receive appropriate clinical care to prevent stroke recurrence, further disability and mortality.

Introduction and Objectives The "Run-In" study is an on-going longitudinal, observational study of CF patients assessing outcome measures for a future gene therapy trial. Spirometry is performed at each visit and volumes are converted to % predicted values according to published reference equations; historically these were separate for adults and children. Here, we describe the issues arising from this approach, and highlight the benefit of using a reference source which bridges the transition from child to adulthood. Methods CF subjects (=10 years; FEV1=40% predicted) were recruited from three sites in London and Edinburgh. Visits were undertaken during periods of stability every 3-6 months; data presented here are from the first four visits. Spirometry was performed on an Easyone spirometer. Volumes were converted to % predicted values according to Rosenthal (<18 years) and Quanjer (=18 years) reference equations. The FEV1 raw data were subsequently re-analysed using Stanojevic reference equations, which span all age ranges. Comparisons were made using paired t-tests. Results 191 patients attended visit 1 (mean age 22.7 years, 55% male; 91 patients <18 years). Rosenthal and Quanjer FEV1% predicted values were significantly higher than the Stanojevic values: mean differences 2.8 (95% CI 1.9 to 3.7) for children with Rosenthal equations (p<0.0001), and 2.4 (95% CI 2.1 to 2.8) for adults using Quanjer equations (p<0.0001). 10 patients transitioned between paediatric and adult reference ranges during the study period; the slope of change in their FEV1% over visits 1-4 was significantly greater with Rosenthal/Quanjer references than with Stanojevic (p=0.001) largely due to an artefactual drop when switching from Rosenthal to Quanjer values. As an example, a female patient aged 17.8 years at visit 1 had a drop in absolute FEV1% predicted between visits 1 and 2 of 11% when Rosenthal/Quanjer were used but only 3% with Stanojevic reference values. Conclusions Our results highlight issues raised when separate adult and paediatric spirometry reference ranges are used in longitudinal study. The UK CF Gene Therapy Consortium has adopted the Stanojevic reference source for all spirometry analysis in its ongoing Clinical Programme. [ABSTRACT FROM AUTHOR]

Presents the abstract of the article "Structure and Quality of UK Molecular Genetic Testing From International Surveys," by Rob Elles and colleagues.

Presents a response by M.B.H. Smith and M.C. McGovern to a letter to the editor about their article "Causes of apparent life threatening events in infants: A systematic review," in the 2004 issue of the journal "Archives of Diseases in Children."

Background: Perinatal anxiety is common: up to 40% of pregnant women and new mothers experience high levels of anxiety. Given its prevalence, interventions that are low-intensity, highly accessible and cost-efficient, and target modifiable risk factors for anxiety are needed. Repetitive negative thinking (RNT)-such as worrying about ways things will go wrong in the future or ruminating about past negative events-is a risk factor for the development of anxiety. RNT is maintained by the tendency to generate negative interpretations of ambiguous situations., Methods: A parallel two-arm randomised controlled trial will assess the efficacy of adding interpretation training (RELAX) to usual maternity care. Participants (N = 268) will be randomised to (i) 12 sessions of online interpretation training (RELAX) plus usual care, or (ii) usual care alone. We will assess anxiety, depression, RNT, and work and social adjustment at baseline, plus 4, 8 and 36 weeks later., Discussion: Should the intervention result in lower levels of anxiety than usual care, it could be an accessible, cost-effective way to help women who are vulnerable to experiencing anxiety in the perinatal period., Trial Registration: ISRCTN 12754931. Registered 25th May 2023, prior to recruitment., (© 2024. The Author(s).)

The opioid overdose epidemic is a growing and evolving public health crisis fueled by the widespread presence of fentanyl and fentanyl analogues (F/FAs) in both street mixtures and counterfeit pills. To expand current treatment options, drug-targeting monoclonal antibodies (mAbs) offer a viable therapeutic for both pre- and postexposure clinical scenarios. This study reports the isolation, in vitro characterization, and in vivo efficacy of two murine mAb families targeting fentanyl, carfentanil, or both. Because humanization of the mAbs by CDR grafting negatively impacted affinity for both fentanyl and carfentanil, crystal structures of mAbs in complex with fentanyl or carfentanil were analyzed to identify key residues involved in ligand binding in murine versus humanized structures, and site-directed mutagenesis was used to verify their functional importance. The structural analysis identified a framework residue, Tyr36, present in the murine germline sequence of two mAbs, which was critical for binding to fentanyl and carfentanil. These studies emphasize the importance of structural considerations in mAb engineering to optimize mAbs targeting small molecules including opioids and other drugs of public health interest., Competing Interests: The authors declare the following competing financial interest(s): Authors M.Pa., J.R., M.M., Y.Z., P.S.O., B.H., and S.D. declare no competing interests. M.Pr., C.B., and D.H. are co-inventors of patent applications describing mAbs against fentanyl and carfentanil included in this manuscript. M.Pr. is the founder and shareholder of CounterX Therapeutics, Inc., (© 2024 The Authors. Published by American Chemical Society.)

Objectives: Scientific evidence provides a widened view of differences in immune response between male and female neonates. The X-chromosome codes for several genes important in the innate immune response and neonatal innate immune cells express receptors for, and are inhibited by, maternal sex hormones. We hypothesized that sex differences in innate immune responses may be present in the neonatal population which may contribute to the increased susceptibility of premature males to sepsis. We aimed to examine the in vitro effect of pro-inflammatory stimuli and hormones in neutrophils and monocytes of male and female neonates, to examine the expression of X-linked genes involved in innate immunity and the miRNA profiles in these populations., Methods: Preterm infants ( n  = 21) and term control ( n  = 19) infants were recruited from the Coombe Women and Infants University Hospital Dublin with ethical approval and explicit consent. The preterm neonates (eight female, 13 male) were recruited with a mean gestation at birth (mean ± SD) of 28 ± 2 weeks and corrected gestation at the time of sampling was 30 + 2.6 weeks. The mean birth weight of preterm neonates was 1084 ± 246 g. Peripheral blood samples were used to analyze immune cell phenotypes, miRNA human panel, and RNA profiles for inflammasome and inflammatory genes., Results: Dividing neutrophil results by sex showed no differences in baseline CD11b between sexes among either term or preterm neonates. Examining monocyte CD11b by sex shows, that at baseline, total and classical monocytes have higher CD11b in preterm females than preterm males. Neutrophil TLR2 did not differ between sexes at baseline or following lipopolysaccharide (LPS) exposure. CD11b expression was higher in preterm male non-classical monocytes following Pam3CSK treatment when compared to females, a finding which is unique to our study. Preterm neonates had higher TLR2 expression at baseline in total monocytes, classical monocytes and non-classical monocytes than term. A sex difference was evident between preterm females and term females in TLR2 expression only. Hormone treatment showed no sex differences and there was no detectable difference between males and females in X-linked gene expression. Two miRNAs, miR-212-3p and miR-218-2-3p had significantly higher expression in preterm female than preterm male neonates., Conclusions: This study examined immune cell phenotypes and x-linked gene expression in preterm neonates and stratified according to gender. Our findings suggest that the responses of females mature with advancing gestation, whereas male term and preterm neonates have very similar responses. Female preterm neonates have improved monocyte activation than males, which likely reflects improved innate immune function as reflected clinically by their lower risk of sepsis. Dividing results by sex showed changes in preterm and term infants at baseline and following LPS stimulation, a difference which is reflected clinically by infection susceptibility. The sex difference noted is novel and may be limited to the preterm or early neonatal population as TLR2 expression on monocytes of older children does not differ between males and females. The differences shown in female and male innate immune cells likely reflect a superior innate immune defense system in females with sex differences in immune cell maturation. Existing human studies on sex differences in miRNA expression do not include preterm patients, and most frequently use either adult blood or cord blood. Our findings suggest that miRNA profiles are similar in neonates of opposite sexes at term but require further investigation in the preterm population. Our findings, while novel, provide only very limited insights into sex differences in infection susceptibility in the preterm population leaving many areas that require further study. These represent important areas for ongoing clinical and laboratory study and our findings represent an important contribution to exiting literature.

Background: Neonatal chest-Xray (CXR)s are commonly performed as a first line investigation for the evaluation of respiratory complications. Although lung area derived from CXRs correlates well with functional assessments of the neonatal lung, it is not currently utilised in clinical practice, partly due to the lack of reference ranges for CXR-derived lung area in healthy neonates. Advanced MR techniques now enable direct evaluation of both fetal pulmonary volume and area. This study therefore aims to generate reference ranges for pulmonary volume and area in uncomplicated pregnancies, evaluate the correlation between prenatal pulmonary volume and area, as well as to assess the agreement between antenatal MRI-derived and neonatal CXR-derived pulmonary area in a cohort of fetuses that delivered shortly after the antenatal MRI investigation., Methods: Fetal MRI datasets were retrospectively analysed from uncomplicated term pregnancies and a preterm cohort that delivered within 72 h of the fetal MRI. All examinations included T2 weighted single-shot turbo spin echo images in multiple planes. In-house pipelines were applied to correct for fetal motion using deformable slice-to-volume reconstruction. An MRI-derived lung area was manually segmented from the average intensity projection (AIP) images generated. Postnatal lung area in the preterm cohort was measured from neonatal CXRs within 24 h of delivery. Pearson correlation coefficient was used to correlate MRI-derived lung volume and area. A two-way absolute agreement was performed between the MRI-derived AIP lung area and CXR-derived lung area., Results: Datasets from 180 controls and 10 preterm fetuses were suitable for analysis. Mean gestational age at MRI was 28.6 ± 4.2 weeks for controls and 28.7 ± 2.7 weeks for preterm neonates. MRI-derived lung area correlated strongly with lung volumes (p < 0.001). MRI-derived lung area had good agreement with the neonatal CXR-derived lung area in the preterm cohort [both lungs = 0.982]., Conclusion: MRI-derived pulmonary area correlates well with absolute pulmonary volume and there is good correlation between MRI-derived pulmonary area and postnatal CXR-derived lung area when delivery occurs within a few days of the MRI examination. This may indicate that fetal MRI derived lung area may prove to be useful reference ranges for pulmonary areas derived from CXRs obtained in the perinatal period., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: There is strong evidence that genetic factors influence retinopathy of prematurity (ROP), a neovascular eye disease. It has been previously suggested that polymorphisms in the genes involved in β-adrenergic receptor (ADRβ) pathways could protect against ROP. Antagonists for the ADRβ are actively tested in clinical trials for ROP treatment, but not without controversy and safety concerns. This study was designed to assess whether genetic variations in components of the ADRβ signaling pathways associate with risk of developing ROP., Design: An observational case-control targeted genetic analysis., Methods: A study was carried out in premature participants with (n = 30) or without (n = 34) ROP and full-term controls (n = 20), who were divided into a discovery cohort and a validation cohort. ROP was defined using International Classification of Retinopathy of Prematurity criteria (ICROP). Targeted sequencing of 20 genes in the ADRβ pathways was performed in the discovery cohort. Polymerase chain reaction (PCR)/restriction enzyme analysis for some of the discovered ROP-associated variants was performed for validation of the results using the validation cohort., Results: The discovery cohort revealed 543 bi-allelic variants within 20 genes of the ADRβ pathways. Ten single-nucleotide variants (SNVs) in 5 genes including protein kinase A regulatory subunit 1α (PRKAR1A), rap guanine exchange factor 3 (RAPGEF3), adenylyl cyclase 4 (ADCY4), ADCY7, and ADCY9 were associated with ROP (P < .05). The most significant SNV was found in PRKAR1A (P = .001). Multiple variants located in the 3'-untranslated region (3'UTR) of RAPGEF3 were also associated with ROP (P < .05). PCR/restriction enzyme analysis of the 3'UTR of RAPGEF3 methodologically validated these findings., Conclusion: SNVs in PRKAR1A may represent protective factors whereas SNVs in RAPGEF3 may represent risk factors for ROP. PRKAR1α has previously been implicated in retinal vascular development whereas the RAPGEF3 product has a role in the maintenance of vascular barrier function, 2 processes important in ROP. Multicenter validation of these newly discovered risk factors could lead to valuable tools for predicting and preventing the development of severe ROP., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Despite being a debilitating, costly, and potentially life-threatening condition, depression is often underdiagnosed and undertreated. Previsit Patient Health Questionnaire-9 (PHQ-9) may help primary care health systems identify symptoms of severe depression and prevent suicide through early intervention. Little is known about the impact of previsit web-based PHQ-9 on patient care and safety., Objective: We aimed to investigate differences among patient characteristics and provider clinical responses for patients who complete a web-based (asynchronous) versus in-clinic (synchronous) PHQ-9., Methods: This quality improvement study was conducted at 33 clinic sites across 2 health systems in Northern California from November 1, 2020, to May 31, 2021, and evaluated 1683 (0.9% of total PHQs completed) records of patients endorsing thoughts that they would be better off dead or of self-harm (question 9 in the PHQ-9) following the implementation of a depression screening program that included automated electronic previsit PHQ-9 distribution. Patient demographics and providers' clinical response (suicide risk assessment, triage nurse connection, medication management, electronic consultation with psychiatrist, and referral to social worker or psychiatrist) were compared for patients with asynchronous versus synchronous PHQ-9 completion., Results: Of the 1683 patients (female: n=1071, 63.7%; non-Hispanic: n=1293, 76.8%; White: n=831, 49.4%), Hispanic and Latino patients were 40% less likely to complete a PHQ-9 asynchronously (odds ratio [OR] 0.6, 95% CI 0.45-0.8; P<.001). Patients with Medicare insurance were 36% (OR 0.64, 95% CI 0.51-0.79) less likely to complete a PHQ-9 asynchronously than patients with private insurance. Those with moderate to severe depression were 1.61 times more likely (95% CI 1.21-2.15; P=.001) to complete a PHQ-9 asynchronously than those with no or mild symptoms. Patients who completed a PHQ-9 asynchronously were twice as likely to complete a Columbia-Suicide Severity Rating Scale (OR 2.41, 95% CI 1.89-3.06; P<.001) and 77% less likely to receive a referral to psychiatry (OR 0.23, 95% CI 0.16-0.34; P<.001). Those who endorsed question 9 "more than half the days" (OR 1.62, 95% CI 1.06-2.48) and "nearly every day" (OR 2.38, 95% CI 1.38-4.12) were more likely to receive a referral to psychiatry than those who endorsed question 9 "several days" (P=.002)., Conclusions: Shifting depression screening from in-clinic to previsit led to a dramatic increase in PHQ-9 completion without sacrificing patient safety. Asynchronous PHQ-9 can decrease workload on frontline clinical team members, increase patient self-reporting, and elicit more intentional clinical responses from providers. Observed disparities will inform future improvement efforts., (© Amelia Sattler, Julia Dunn, Marleni Albarran, Charlotte Berger, Ana Calugar, John Carper, Lalitha Chirravuri, Nadine Jawad, Mira Zein, Mark McGovern. Originally published in JMIR Mental Health (https://mental.jmir.org).)

Background: Although methamphetamine use associated heart failure (MU-HF) is increasing, data on its clinical course are limited due to a preponderance of single center studies and significant heterogeneity in the definition of MU-HF in the published literature. Our objective was to evaluate left ventricular ejection fraction (LVEF) distribution, methamphetamine use treatment engagement and postdischarge healthcare utilization among Veterans with heart failure hospitalization in the department of Veterans Affairs (VA) medical centers for MU-HF versus HF not associated with methamphetamine use (other-HF)., Methods: Observational study including a cohort of Veterans with a first heart failure hospitalization during 2007 - 2020 using data in the VA Corporate Data Warehouse. MU-HF was identified based on the presence of an ICD-code for methamphetmaine use or positive toxicology results within 1-year of heart failure hospitalization. LVEF values entered in the medical record were identified using a validated natural language processing algorithm. Healthcare utilization data was obtained using clinic stop-codes and hosptilaization records., Results: Of 203,005 first-time heart failure hospitlaizations, 4080 were categorized as MU-HF. Median (interquartile range) of LVEF was 30 (20-45) % for MU-HF versus 40 (25-55)% for other-HF (P < .0001). Eighteen percent of MU-HF had LVEF ≥ 50% compared to 28% in other-HF. Discharge against medical advice was higher in MU-HF (8% vs 2%). Among Veterans with MU-HF, post hospital discharge methamphetamine use treatment engagement was low (18% at 30 days post discharge), with higher follow-up in primary care (76% at 30 days). Post discharge emergency department visits (33% versus 22% at 30 days) and rehospitalizations (24% versus 18% at 30 days) were higher in MU-HF compared to other-HF., Conclusions: While the majority of MU-HF hospitalizations are HFrEF, a sizeable minority have HFpEF. This finding has implications for accurate MU-HF classification, treatment, and prognosis. Patients with MU-HF have low addiction treatment receipt and high postdischarge unplanned healthcare utilization. Increasing substance use disorder treatment in this population must be a priority to improve health outcomes. Care-coordination and linkage interventions are urgently needed to increase post-hospitalization addiction treatment and follow-up in an effort to increase evidence-base care and mitigate unplanned healthcare utilization., (Published by Elsevier Inc.)

Climate change is altering patterns of precipitation, cryosphere thaw, and land-ocean influxes, affecting understudied Arctic estuarine tidal flats. These transitional zones between terrestrial and marine systems are hotspots for biogeochemical cycling, often driven by microbial processes. We investigated surface sediment bacterial community composition and function from May to September along a river-intertidal-subtidal-fjord gradient. We paired metabarcoding of in situ communities with in vitro carbon-source utilization assays. Bacterial communities differed in space and time, alongside varying environmental conditions driven by local seasonal processes and riverine inputs, with salinity emerging as the dominant structuring factor. Terrestrial and riverine taxa were found throughout the system, likely transported with runoff. In vitro assays revealed sediment bacteria utilized a broader range of organic matter substrates when incubated in fresh and brackish water compared to marine water. These results highlight the importance of salinity for ecosystem processes in these dynamic tidal flats, with the highest potential for utilization of terrestrially derived organic matter likely limited to tidal flat areas (and times) where sediments are permeated by freshwater. Our results demonstrate that intertidal flats must be included in future studies on impacts of increased riverine discharge and transport of terrestrial organic matter on coastal carbon cycling in a warming Arctic., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

Climate change driven increases in permafrost thaw and terrestrial runoff are expected to facilitate the mobilization and transport of mercury (Hg) from catchment soils to coastal areas in the Arctic, potentially increasing Hg exposure of marine food webs. The main aim of this study was to determine the impacts of seasonal riverine inputs on land-ocean Hg transport, zooplankton diet and Hg bioaccumulation in an Arctic estuary (Adventfjorden, Svalbard). The Adventelva River was a source of dissolved and particulate Hg to Adventfjorden, especially in June and July during the river's main discharge period. Stable isotope and fatty acid analyses suggest that zooplankton diet varied seasonally with diatoms dominating during the spring phytoplankton bloom in May and with increasing contributions of dinoflagellates in the summer months. In addition, there was evidence of increased terrestrial carbon utilization by zooplankton in June and July, when terrestrial particles contributed substantially to the particulate organic matter pool. Total (TotHg) and methyl Hg (MeHg) concentrations in zooplankton increased from April to August related to increased exposure to riverine inputs, and to shifts in zooplankton diet and community structure. Longer and warmer summer seasons will probably increase riverine runoff and thus Hg exposure to Arctic zooplankton., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures The authors have no conflicts of interests.

Purpose: Patient outcomes can improve when primary care and behavioral health providers use a collaborative system of care, but integrating these services is difficult. We tested the effectiveness of a practice intervention for improving patient outcomes by enhancing integrated behavioral health (IBH) activities., Methods: We conducted a pragmatic, cluster randomized controlled trial. The intervention combined practice redesign, quality improvement coaching, provider and staff education, and collaborative learning. At baseline and 2 years, staff at 42 primary care practices completed the Practice Integration Profile (PIP) as a measure of IBH. Adult patients with multiple chronic medical and behavioral conditions completed the Patient-Reported Outcomes Measurement Information System (PROMIS-29) survey. Primary outcomes were the change in 8 PROMIS-29 domain scores. Secondary outcomes included change in level of integration., Results: Intervention assignment had no effect on change in outcomes reported by 2,426 patients who completed both baseline and 2-year surveys. Practices assigned to the intervention improved PIP workflow scores but not PIP total scores. Baseline PIP total score was significantly associated with patient-reported function, independent of intervention. Active practices that completed intervention workbooks (n = 13) improved patient-reported outcomes and practice integration ( P ≤ .05) compared with other active practices (n = 7)., Conclusion: Intervention assignment had no effect on change in patient outcomes; however, we did observe improved patient outcomes among practices that entered the study with greater IBH. We also observed more improvement of integration and patient outcomes among active practices that completed the intervention compared to active practices that did not. Additional research is needed to understand how implementation efforts to enhance IBH can best reach patients., (© 2023 Annals of Family Medicine, Inc.)

Importance: Rates of alcohol-associated deaths increased over the past 20 years, markedly between 2019 and 2020. The highest rates are among individuals aged 55 to 64 years, primarily attributable to alcoholic liver disease and psychiatric disorders due to use of alcohol. This study investigates potential geographic disparities in documentation of alcohol-related problems in primary care electronic health records, which could lead to undertreatment of alcohol use disorder., Objective: To identify disparities in documentation of alcohol-related problems by practice-level social deprivation., Design, Setting, and Participants: A cross-sectional study using secondary data from the Integrating Behavioral Health and Primary Care clinical trial (September 21, 2017, to January 8, 2021) was performed. A national sample of 44 primary care practices with co-located behavioral health services was included in the analysis. Patients with 2 primary care visits within 2 years and at least 1 chronic medical condition and 1 behavioral health condition or at least 3 chronic medical conditions were included., Exposure: The primary exposure was practice-level Social Deprivation Index (SDI), a composite measure based on county income, educational level, employment, housing, single-parent households, and access to transportation (scores range from 0 to 100; 0 indicates affluent counties and 100 indicates disadvantaged counties)., Main Outcomes and Measures: Documentation of an alcohol-related problem in the electronic health record was determined by International Classification of Diseases, 9th Revision, Clinical Modification and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification codes or use of medications for alcohol use disorder in past 2 years. Multivariable models adjusted for alcohol consumption, screening for a substance use disorder, urban residence, age, sex, race and ethnicity, income, educational level, and number of chronic health conditions., Results: A total of 3105 participants (mean [SD] age, 63.7 [13.0] years; 64.1% female; 11.5% Black, 7.0% Hispanic, 76.7% White, and 11.9% other race or chose not to disclose; 47.8% household income <$30 000; and 80.7% urban residence). Participants had a mean (SD) of 4.0 (1.7) chronic conditions, 9.1% reported higher-risk alcohol consumption, 4% screened positive for substance use disorder, and 6% had a documented alcohol-related problem in the electronic health record. Mean (SD) practice-level SDI score was 45.1 (20.9). In analyses adjusted for individual-level alcohol use, demographic characteristics, and health status, practice-level SDI was inversely associated with the odds of documentation (odds ratio for each 10-unit increase in SDI, 0.89; 95% CI, 0.80 to 0.99; P = .03)., Conclusions and Relevance: In this study, higher practice-level SDI was associated with lower odds of documentation of alcohol-related problems, after adjusting for individual-level covariates. These findings reinforce the need to address primary care practice-level barriers to diagnosis and documentation of alcohol-related problems. Practices located in high need areas may require more specialized training, resources, and practical evidence-based tools that are useful in settings where time is especially limited and patients are complex.

Introduction: Methadone maintenance therapy (MMT) has been a pillar of opioid addiction treatment. Opioid treatment programs (OTPs) have been faced with an escalating threat of stimulant use and related overdose deaths among patients. We know little about how providers currently address stimulant use while maintaining treatment for opioid use disorder., Methods: We conducted 5 focus groups with 36 providers (n = 11 prescribers; 25 behavioral health staff), and collected an additional 46 surveys (n = 7 prescribers; 12 administrators; 27 behavioral health staff). Questions focused on perceptions of patient stimulant use and interventions. We applied inductive analysis to identify themes relevant to identification of stimulant use, use trends, intervention approaches, and perceived needs to improve care., Results: Providers indicated a trend of rising stimulant use among patients, especially those experiencing homelessness or comorbid health conditions. They reported a range of approaches to patient screening and intervention, including medication and harm reduction, improving treatment engagement, increasing level of care, and providing incentives. Providers expressed less agreement as to which of these interventions were effective, and though providers saw stimulant use as a common and severe problem, they reported little problem recognition and interest in treatment from their patients. A particular concern of providers was the prevalence and danger of synthetic opioids, such as fentanyl. They sought more research and resources to identify effective interventions and medications to address these issues. Also notable was an interest in contingency management (CM) and use of reinforcements/rewards to encourage stimulant use reduction., Conclusion: Providers face challenges in treating patients who use both opioids and stimulants. Although methadone is available to treat opioid use, no such "silver bullet" exists for stimulant use disorder. The rise in stimulant and synthetic opioid (e.g., fentanyl) combination products is presenting an extraordinary challenge for providers whose patients are at unprecedented risk for overdose. Providing OTPs with more resources to address polysubstance use is critical. Existing research indicates strong support for CM in OTPs, but providers reported regulatory and financial barriers to implementation. Further research should develop effective interventions that are accessible to providers in OTPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Servicewomen enhance the U.S. Military fighting force by bringing diverse perspectives, collaborative and creative problem-solving skills for global peace and security, and innovative, adaptive talent as leaders. Despite servicewomen integrating into combat units over the past decade, a number of barriers remain related to inclusion, promotion, and quality of life, particularly for marginalized women. To eliminate inequities experienced by servicewomen, leaders across all levels of the military play a key role in supporting the successful integration of servicewomen, cultivating an environment of belonging, and guarding against toxicity, which will result in optimized performance and readiness for all servicemembers in defense of the Nation. Herein, we review the original gaps related to leadership and peer behaviors identified by the 2014 Women in Combat Symposium, provide updates in the literature, address the topics that arose at the 2021 Women in Combat Symposium, and finally, outline the remaining barriers and challenges to the successful integration of female servicemembers., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Oncogenic virus infections are estimated to cause ~15% of all cancers. Two prevalent human oncogenic viruses are members of the gammaherpesvirus family: Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV). We use murine herpesvirus 68 (MHV-68), which shares significant homology with KSHV and EBV, as a model system to study gammaherpesvirus lytic replication. Viruses implement distinct metabolic programs to support their life cycle, such as increasing the supply of lipids, amino acids, and nucleotide materials necessary to replicate. Our data define the global changes in the host cell metabolome and lipidome during gammaherpesvirus lytic replication. Our metabolomics analysis found that MHV-68 lytic infection induces glycolysis, glutaminolysis, lipid metabolism, and nucleotide metabolism. We additionally observed an increase in glutamine consumption and glutamine dehydrogenase protein expression. While both glucose and glutamine starvation of host cells decreased viral titers, glutamine starvation led to a greater loss in virion production. Our lipidomics analysis revealed a peak in triacylglycerides early during infection and an increase in free fatty acids and diacylglyceride later in the viral life cycle. Furthermore, we observed an increase in the protein expression of multiple lipogenic enzymes during infection. Interestingly, pharmacological inhibitors of glycolysis or lipogenesis resulted in decreased infectious virus production. Taken together, these results illustrate the global alterations in host cell metabolism during lytic gammaherpesvirus infection, establish essential pathways for viral production, and recommend targeted mechanisms to block viral spread and treat viral induced tumors. IMPORTANCE Viruses are intracellular parasites which lack their own metabolism, so they must hijack host cell metabolic machinery in order to increase the production of energy, proteins, fats, and genetic material necessary to replicate. Using murine herpesvirus 68 (MHV-68) as a model system to understand how similar human gammaherpesviruses cause cancer, we profiled the metabolic changes that occur during lytic MHV-68 infection and replication. We found that MHV-68 infection of host cells increases glucose, glutamine, lipid, and nucleotide metabolic pathways. We also showed inhibition or starvation of glucose, glutamine, or lipid metabolic pathways results in an inhibition of virus production. Ultimately, targeting changes in host cell metabolism due to viral infection can be used to treat gammaherpesvirus-induced cancers and infections in humans., Competing Interests: The authors declare no conflict of interest.

Background: Acid Sphingomyelinase Deficiency (ASMD) is a rare autosomal recessive disorder caused by mutations in the SMPD1 gene. This rarity contributes to misdiagnosis, delayed diagnosis and barriers to good care. There are no published national or international consensus guidelines for the diagnosis and management of patients with ASMD. For these reasons, we have developed clinical guidelines that defines standard of care for ASMD patients., Methods: The information contained in these guidelines was obtained through a systematic literature review and the experiences of the authors in their care of patients with ASMD. We adopted the Appraisal of Guidelines for Research and Evaluation (AGREE II) system as method of choice for the guideline development process., Results: The clinical spectrum of ASMD, although a continuum, varies substantially with subtypes ranging from a fatal infantile neurovisceral disorder to an adult-onset chronic visceral disease. We produced 39 conclusive statements and scored them according to level of evidence, strengths of recommendations and expert opinions. In addition, these guidelines have identified knowledge gaps that must be filled by future research., Conclusion: These guidelines can inform care providers, care funders, patients and their carers about best clinical practice and leads to a step change in the quality of care for patients with ASMD with or without enzyme replacement therapy (ERT)., (© 2023. The Author(s).)

Tumor hypoxia drives resistance to many cancer therapies, including radiotherapy and chemotherapy. Methods that increase tumor oxygen pressures, such as hyperbaric oxygen therapy and microbubble infusion, are utilized to improve the responses to current standard-of-care therapies. However, key obstacles remain, in particular delivery of oxygen at the appropriate dose and with optimal pharmacokinetics. Toward overcoming these hurdles, gas-entrapping materials (GeMs) that are capable of tunable oxygen release are formulated. It is shown that injection or implantation of these materials into tumors can mitigate tumor hypoxia by delivering oxygen locally and that these GeMs enhance responsiveness to radiation and chemotherapy in multiple tumor types. This paper also demonstrates, by comparing an oxygen (O 2 )-GeM to a sham GeM, that the former generates an antitumorigenic and immunogenic tumor microenvironment in malignant peripheral nerve sheath tumors. Collectively the results indicate that the use of O 2 -GeMs is promising as an adjunctive strategy for the treatment of solid tumors., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Improving access to grant funding is a critical aspect of strengthening research capacity outside of higher income settings, particularly in HIV/AIDS where randomized control trials (RCTs) that require substantial resources are common. In this article, we assessed recent RCTs to examine variation in how studies were funded, depending on study location and the countries where publication authors were based. We conducted a PubMed literature review to identify RCTs with HIV status or viral load endpoints published in 2019 and 2020, then analyzed cross-tabulations of funding sources by study characteristics. One hundred sixteen publications met the inclusion criteria. Research in higher income countries was most likely to be funded by biotech/pharmaceutical companies, whereas research in lower- and middle-income countries was most likely to be funded by U.S. government sources. Overall, we found the distribution of funding sources differed significantly by study and author location ( χ 2  = 23, p  < .001). Published RCTs with HIV status or viral load endpoints are financed differently based on where studies take place and where the authors are based. As part of future research, understanding why this variation exists is critical for assessing how funding contributes to global imbalances in scientific resources.

Objective: To conduct a systematic review of observational studies on methamphetamine-associated heart failure (MethHF) ., Methods: Six databases were searched for original publications on the topic. Title/abstract and included full-text publications were reviewed in duplicate. Data extraction and critical appraisal for risk of bias were performed in duplicate., Results: Twenty-one studies are included in the final analysis. Results could not be combined because of heterogeneity in study design, population, comparator, and outcome assessment. Overall risk of bias is moderate due to the presence of confounders, selection bias and poor matching; overall certainty in the evidence is very low. MethHF is increasing in prevalence, affects diverse racial/ethnic/sociodemographic groups with a male predominance; up to 44% have preserved left-ventricular ejection fraction. MethHF is associated with significant morbidity including worse heart failure symptoms compared with non-methamphetamine related heart failure. Female sex, methamphetamine abstinence and guideline-directed heart failure therapy are associated with improved outcomes. Chamber dimensions on echocardiography and fibrosis on biopsy predict the extent of recovery after abstinence., Conclusions: The increasing prevalence of MethHF with associated morbidity underscores the urgent need for well designed prospective studies of people who use methamphetamine to accurately assess the epidemiology, clinical features, disease trajectory and outcomes of MethHF. Methamphetamine abstinence is an integral part of MethHF treatment; increased availability of effective non-pharmacological interventions for treatment of methamphetamine addiction is an essential first step. Availability of effective pharmacological treatment for methamphetamine addiction will further support MethHF treatment. Using harm reduction principles in an integrated addiction/HF treatment programme will bolster efforts to stem the increasing tide of MethHF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aims to compare primary care providers and medical assistants in degrees of comfort, confidence, and consistency when addressing behavioral health concerns with patients before and after the implementation of a model of integrated behavioral health in primary care (IBHPC), and evaluate whether these perceptions differ based on increased access to behavioral health clinicians., Methods: This longitudinal study was conducted at 2 primary care clinics in Northern California while implementing an IBHPC model. The Integrated Behavioral Health Staff Perceptions Survey was administered to assess the comfort, confidence, and consistency of behavioral health practices. Confidential online surveys were distributed to primary care faculty and staff members before and post-implementation. Responses from providers and medical assistants were compared between pre- and post-implementation with linear regression analyses. The relationships between accessibility to behavioral health clinicians and a change in comfort, confidence, and consistency of behavioral health practices were explored using a linear mixed-effects model., Results: A total of 35 providers and medical assistants completed the survey both before and post-implementation of IBHPC. Over time, there were increasingly positive perceptions about the consistency of behavioral health screening ( P  = .03) and overall confidence in addressing behavioral health concerns ( P  = .005). Comfort in addressing behavioral health concerns did not significantly change for either providers or staff over time. Medical assistants were initially more confident and comfortable addressing behavioral health concerns than providers, but providers' attitudes increased post-IBHPC implementation. Improved access to behavioral health clinicians was associated with greater consistency of screening and referral to specialty mental health care ( P  < .001)., Conclusion: The present study is the first to explore differences in provider and medical assistant perceptions during the course of an IBHPC implementation. Findings underscore the importance of integrating medical assistants, along with providers, into all phases of the implementation process.

The treatment of central nervous system (CNS) tumors is complicated by high rates of recurrence and treatment resistance that contribute to high morbidity and mortality (Nat Rev Neurol. 2022;18:221-36. doi: 10.1038/s41582-022-00621-0). One of the challenges of treating these tumors is the limited permeability of the blood brain barrier (BBB). Early pharmacologic treatments worked to overcome the BBB by targeting vulnerabilities in the tumor cell replication process directly through alkylating agents like temozolomide. However, as advancements have been made options have expanded to include immunologic targets through the use of monoclonal antibodies. In the future, treatment will likely continue to focus on the use of immunotherapies, as well as emerging technology like the use of low-intensity focused ultrasound (LIFU). Ultimately, this paper serves as an introductory overview of current therapeutic options for post-resection primary brain tumors, as well as a look towards future work and emerging treatment options., Competing Interests: The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Uniformed Services University of the Health Sciences, the Department of Defense, or the U.S. Government., (© The Author(s) 2023.)

Introduction: The opioid epidemic has evolved into a combined stimulant epidemic, with escalating stimulant and fentanyl-related overdose deaths. Primary care providers are on the frontlines grappling with patients' methamphetamine use. Although effective models exist for treating opioid use disorder in primary care, little is known about current clinical practices for methamphetamine use., Methods: Six semistructured group interviews were conducted with 38 primary care providers. Interviews focused on provider perceptions of patients with methamphetamine use problems and their care. Data were analyzed using inductive and thematic analysis and summarized along the following dimensions: (1) problem identification, (2) clinical management, (3) barriers and facilitators to care, and (4) perceived needs to improve services., Results: Primary care providers varied in their approach to identifying and treating patient methamphetamine use. Unlike opioid use disorders, providers reported lacking standardized screening measures and evidence-based treatments, particularly medications, to address methamphetamine use. They seek more standardized screening tools, Food and Drug Administration-approved medications, reliable connections to addiction medicine specialists, and more training. Interest in novel behavioral health interventions suitable for primary care settings was also noteworthy., Conclusions: The findings from this qualitative analysis revealed that primary care providers are using a wide range of tools to screen and treat methamphetamine use, but with little perceived effectiveness. Primary care faces multiple challenges in effectively addressing methamphetamine use among patients singularly or comorbid with opioid use disorders, including the lack of Food and Drug Administration-approved medications, limited patient retention, referral opportunities, funding, and training for methamphetamine use. Focusing on patients' medical issues using a harm reduction, motivational interviewing approach, and linkage with addiction medicine specialists may be the most reasonable options to support primary care in compassionately and effectively managing patients who use methamphetamines., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Addiction Medicine.)

Personalized polygenic risk information may be used to guide risk-based melanoma prevention and early detection at a population scale, but research on communicating this information is limited. This mixed-methods study aimed to assess the acceptability of a genetic counselor (GC) phone call in communicating polygenic risk information in the Melanoma Genomics Managing Your Risk randomized controlled trial. Participants ( n = 509) received personalized melanoma polygenic risk information, an educational booklet on melanoma prevention, and a GC phone call, which was audio-recorded. Participants completed the Genetic Counseling Satisfaction Survey 1-month after receiving their risk information ( n = 346). A subgroup took part in a qualitative interview post-study completion ( n = 20). Survey data were analyzed descriptively using SPSS, and thematic analysis of the qualitative data was conducted using NVivo 12.0 software. The survey showed a high level of acceptability for the GC phone call (mean satisfaction score overall: 4.3 out of 5, standard deviation (SD): 0.6) with differences according to gender (mean score for women: 4.4, SD: 0.6 vs. men: 4.2, SD: 0.7; p = 0.005), health literacy (lower literacy: 4.1, SD: 0.8; average: 4.3, SD: 0.6; higher: 4.4, SD: 0.6: p = 0.02) and polygenic risk group (low risk: 4.5, SD: 0.5, SD: average: 4.3, SD: 0.7, high: 4.3, SD: 0.7; p = 0.03). During the GC phone calls, the discussion predominately related to the impact of past sun exposure on personal melanoma risk. Together our findings point to the importance of further exploring educational and support needs and preferences for communicating personalized melanoma risk among population subgroups, including diverse literacy levels.

Neurosurgery has benefited from innovations as a result of military conflict. The volume and complexity of injuries sustained on the battlefield require medical teams to triage, innovate, and practice beyond their capabilities in order to treat wartime injuries. The neurosurgeons who practiced in the Pacific Command (PACOM) during World War II, the Korean War, and the War in Vietnam built upon field operating room knowledge and influenced the logistics of treating battle-injured patients in far-forward environments. Modern-day battles are held on new terrain, and the military neurosurgeon must adapt. War in the PACOM uniquely presented significant obstacles due to geographic isolation, ultimately accelerating the growth and adaptability of military neurosurgery and medical evacuation. The advancements in infrastructure and resource mobilization made during PACOM conflicts continue to inform modern-day practices and provide insight for future conflicts. In this historical article, the authors review the development and evolution of neurosurgical care, forward surgical teams, and mobile field hospitals with surgical capabilities through US conflicts in the PACOM.

Despite recent changes to mental health policy in Australia and overseas, physical restraint continues to be widely employed in mental health services. While mental health nurses have a critical role to play in supporting initiatives designed to reduce restraint, it is unclear how they feel about moves to restrict the use of prone restraint. In this qualitative study, focus group interviews were conducted with mental health nursing staff and lived experience workers (LEWs) to gain their perspectives on the use of physical restraint in general and the restrictions being placed on prone ('face down') restraint. Five themes emerged: justifying the need for restraint, reliance on the prone position, the position is not the issue, time limits, and the psychological impact. Although mental health nurses were concerned about the risks associated with physical restraint, they provided strong justification for continued use of the prone position. LEWs raised concerns about the psychological impact of prone restraint and noted the need for a greater emphasis on de-escalation and other restraint avoidance strategies. The findings highlight the complexities and challenges to be considered when developing initiatives to reduce reliance on the use of restraint in general, and prone in particular., (© 2022 John Wiley & Sons Australia, Ltd.)

Increasing terrestrial run-off from melting glaciers and thawing permafrost to Arctic coastal areas is expected to facilitate re-mobilization of stored legacy persistent organic pollutants (POPs) and mercury (Hg), potentially increasing exposure to these contaminants for coastal benthic organisms. We quantified chlorinated POPs and Hg concentrations, lipid content and multiple dietary markers, in a littoral deposit-feeding amphipod Gammarus setosus and sediments during the melting period from April to August in Adventelva river estuary in Svalbard, a Norwegian Arctic Aarchipelago. There was an overall decrease in concentrations of ∑POPs from April to August (from 58 ± 23 to 13 ± 4 ng/g lipid weight; lw), Hg (from 5.6 ± 0.7 to 4.1 ± 0.5 ng/g dry weight; dw) and Methyl Hg (MeHg) (from 5 ± 1 to 0.8 ± 0.7 ng/g dw) in G. setosus. However, we observed a seasonal peak in penta- and hexachlorobenzene (PeCB and HCB) in May (2.44 ± 0.3 and 23.6 ± 1.7 ng/g lw). Sediment concentrations of POPs and Hg (dw) only partly correlated with the contaminant concentrations in G. setosus. Dietary markers, including fatty acids and carbon and nitrogen stable isotopes, indicated a diet of settled phytoplankton in May-July and a broader range of carbon sources after the spring bloom. Phytoplankton utilization and chlorobenzene concentrations in G. setosus exhibited similar seasonal patterns, suggesting a dietary uptake of chlorobenzenes that is delivered to the aquatic environment during spring snowmelt. The seasonal decrease in contaminant concentrations in G. setosus could be related to seasonal changes in dietary contaminant exposure and amphipod ecology. Furthermore, this decrease implies that terrestrial run-off is not a significant source of re-mobilized Hg and legacy POPs to littoral amphipods in the Adventelva river estuary during the melt season., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Classical galactosemia (CG) is a disorder of galactose metabolism which results from deficiency of the enzyme galactose-1-phosphate uridylyl transferase (GALT). Treatment consists of immediately eliminating galactose from the diet in the new-born and lifelong restriction of dietary galactose. The inclusion of a wider variety of foods for people with CG may provide many benefits, including improved nutritional adequacy and quality of life. Galactose plays an important role in glycosylation of glycoproteins and glycolipids. Moderate liberalization of galactose restriction has been shown to improve immunoglobulin G (IgG) glycosylation for some individuals with CG. Moreover, recent outcome research suggests that strict restriction of nondairy galactose may have more unfavorable outcomes than moderate liberalization in CG patients. In the current work, based on patient feedback, we have analyzed the lactose and galactose content of different foods available in Ireland. These include a range of cheeses, yogurts, pizzas, soups, biscuits, cakes, pastries, crackers, mayonnaises, salad creams, fat spreads, crisps, corn chips, salamis, and gravies. This work provides information to support the development of a practical food-based approach to facilitate analysis of dietary galactose intake and to possibly increase overall variety of food choices for people with CG., Competing Interests: All authors declare that they have no conflict of interest., (© 2022 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Decades of atmospheric and oceanic long-range transport from lower latitudes have resulted in deposition and storage of persistent organic pollutants (POPs) in Arctic regions. With increased temperatures, melting glaciers and thawing permafrost may serve as a secondary source of these stored POPs to freshwater and marine ecosystems. Here, we present concentrations and composition of legacy POPs in glacier- and permafrost-influenced rivers and coastal waters in the high Arctic Svalbard fjord Kongsfjorden. Targeted contaminants include polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs) and chlordane pesticides. Dissolved (defined as fraction filtered through 0.7 μm GF/F filter) and particulate samples were collected from rivers and near-shore fjord stations along a gradient from the heavily glaciated inner fjord to the tundra-dominated catchments at the outer fjord. There were no differences in contaminant concentration or pattern between glacier and tundra-dominated catchments, and the general contaminant pattern reflected snow melt with some evidence of pesticides released with glacial meltwater. Rivers were a small source of chlordane pesticides, DDTs and particulate HCB to the marine system and the particle-rich glacial meltwater contained higher concentrations of particle associated contaminants compared to the fjord. This study provides rare insight into the role of small Arctic rivers in transporting legacy contaminants from thawing catchments to coastal areas. Results indicate that the spring thaw is a source of contaminants to Kongsfjorden, and that expected increases in runoff on Svalbard and elsewhere in the Arctic could have implications for the contamination of Arctic coastal food-webs., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Climate change-driven increases in air and sea temperatures are rapidly thawing the Arctic cryosphere with potential for remobilization and accumulation of legacy persistent organic pollutants (POPs) in adjacent coastal food webs. Here, we present concentrations of selected POPs in zooplankton (spatially and seasonally), as well as zoobenthos and sculpin (spatially) from Isfjorden, Svalbard. Herbivorous zooplankton contaminant concentrations were highest in May [e.g., ∑polychlorinated biphenyls ( 8 PCB); 4.43, 95% CI: 2.72-6.3 ng/g lipid weight], coinciding with the final stages of the spring phytoplankton bloom, and lowest in August (∑ 8 PCB; 1.6, 95% CI: 1.29-1.92 ng/g lipid weight) when zooplankton lipid content was highest, and the fjord was heavily impacted by sediment-laden terrestrial inputs. Slightly increasing concentrations of α-hexachlorocyclohexane (α-HCH) in zooplankton from June (1.18, 95% CI: 1.06-1.29 ng/g lipid weight) to August (1.57, 95% CI: 1.44-1.71 ng/g lipid weight), alongside a higher percentage of α-HCH enantiomeric fractions closer to racemic ranges, indicate that glacial meltwater is a secondary source of α-HCH to fjord zooplankton in late summer. Except for α-HCH, terrestrial inputs were generally associated with reduced POP concentrations in zooplankton, suggesting that increased glacial melt is not likely to significantly increase exposure of legacy POPs in coastal fauna.