Conceptualizing Controlling Factors for PFAS Salting Out in Groundwater Discharge Zones Along Sandy Beaches.

Understanding fate and transport processes for per- and poly-fluoroalkyl substances (PFAS) is critical for managing impacted sites. "PFAS Salting Out" in groundwater, defined herein, is an understudied process where PFAS in fresh groundwater mixes with saline groundwater near marine shorelines, which increases sorption of PFAS to aquifer solids. While sorption reduces PFAS mass discharge to marine surface water, the fraction that sorbs to beach sediments may be mobilized under future salinity changes. The objective of this study was to conceptually explore the potential for PFAS Salting Out in sandy beach environments and to perform a preliminary broad-scale characterization of sandy shoreline areas in the continental U.S. While no site-specific PFAS data were collected, our conceptual approach involved developing a multivariate regression model that assessed how tidal amplitude and freshwater submarine groundwater discharge affect the mixing of fresh and saline groundwater in sandy coastal aquifers. We then applied this model to 143 U.S. shoreline areas with sandy beaches (21% of total beaches in the USA), indirectly mapping potential salinity increases in shallow freshwater PFAS plumes as low (<10 ppt), medium (10-20 ppt), or high (>20 ppt) along groundwater flow paths before reaching the ocean. Higher potential salinity increases were observed in West Coast bays and the North Atlantic coastline, due to the combination of moderate to large tides and large fresh groundwater discharge rates, while lower increases occurred along the Gulf of Mexico and the southern Florida Atlantic coast. The salinity increases were used to estimate potential perfluorooctane sulfonic acid (PFOS) sorption in groundwater due to salting out processes. Low-category shorelines may see a 1- to 2.5-fold increase in sorption of PFOS, medium-category a 2.0- to 6.4-fold increase, and high-category a 3.8- to 25-fold increase in PFOS sorption. The analysis presented provides a first critical step in developing a large-scale approach to classify the PFAS Salting Out potential along shorelines and the limitations of the approach adopted highlights important areas for further research.

The health and wellbeing of Australian social housing tenants compared to people living in other types of housing.

BACKGROUND: Although social housing provides access to safe and affordable housing, recent studies have found that social housing tenants consistently have lower levels of health and well-being compared to other people. Given this, there is a need to examine multimorbidity for social housing tenants. METHODS: Secondary data analysis of the 2017-18 Australian National Health Survey (n = 14,327) compared the health of adults residing in social housing compared to people in other housing types (private rentals, homeowners, and homeowners/mortgagees). RESULTS: Most health factors examined were more prevalent in social housing tenants compared to those living in other housing types. Individual health problems identified as more highly prevalent in social housing tenants compared to all other housing types included mental health issues (43%), arthritis (36%), back problems (32%), hypertension (25%), asthma (22%) and COPD (11%). 24% of social housing tenants reported five or more health factors compared to 3-6% of people in other housing types. CONCLUSIONS: Although these findings are not unexpected, they provide more detailed evidence that social housing providers and policy makers should consider when planning future initiatives.

How Does the Health Literacy of Adults Residing in Social Housing Compare with That of Those Living in Other Housing Tenures in Australia? A Secondary Analysis of the Australian National Health Survey 2017-2018 Dataset.

BACKGROUND: Social housing tenants have poorer health outcomes than homeowners or those renting privately. Health literacy is associated with access to care and health outcomes. This study aimed to examine the health literacy of Australian adults residing in social housing compared with that of people living in other housing types. METHODS: A secondary analysis of the Australian National Health Survey 2017-2018 dataset was undertaken. A total of 5275 respondents were included in the sample and completed the Health Literacy Questionnaire (HLQ). Respondents were categorised according to their housing tenure: 163 (3.1%) respondents were living in social housing, 873 (17%) were living in private rentals, 2085 (40%) were homeowners, and 2154 (41%) were homeowners/mortgages. Mean scores were calculated for each of the nine health literacy domains in the HLQ and compared across housing tenure using linear regression models. RESULTS: Social housing tenants had lower mean domain scores than either homeowners, owner mortgagees, or private renters on six of the nine health literacy domains. This included 'having sufficient information to manage my health', 'social support for health', 'ability to engage with healthcare providers', 'navigating the healthcare system' 'ability to find good health information', and being able to 'understand health information enough to know what to do'. However, the differences in mean scores were small. CONCLUSIONS: Increasing health literacy may be an important part of multicomponent interventions seeking to improve the health and wellbeing of social housing tenants.

Solitary metastasis to the skull as the first sign of hepatocellular carcinoma in a patient in long-term remission.

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with a 5-year survival rate of 10%, presenting with extrahepatic metastases in 15-17% of patients. HCC-bone metastases represent approximately one-quarter of all HCC metastases, most frequently in the spine, pelvis, ribs, or femur. HCC-skull metastases, however, make up 0.4-1.6% of all HCC- bone metastases. Furthermore, solitary HCC-skull metastasis without known active primary HCC is an unusual presentation warranting further review and consideration. Case Description: Here, the authors report a unique case of a solitary HCC-skull metastasis in a patient without known active cancer but in long-term remission for HCC. The patient is a 69-year-old male with past HCC who presented with a nontender skull mass. A computed tomography scan showed a heterogeneously enhancing mass centered in the high left parietal bone with intracranial extension. There was a noted mass effect on the left posterior frontoparietal region without worrisome midline shift. Pathology ultimately revealed the mass to be metastatic HCC. To aid in the understanding and clinical management of this rare presentation, we reviewed the literature regarding clinical presentation, radiological features, pathology, and outcome. Conclusion: Ultimately, early detection of the primary source of cancer is pivotal to successful treatment and prognosis, and skull lesions such as these must include HCC in the differential diagnosis.

Modeling a well-characterized perfluorooctane sulfonate (PFOS) source and plume using the REMChlor-MD model to account for matrix diffusion.

Two of the most important retention processes for per- and polyfluoroalkyl substances (PFAS) in groundwater likely are sorption and matrix diffusion. The objective of this study was to model concentration and mass discharge of one PFAS, perfluorooctane sulfonate (PFOS), with matrix diffusion processes incorporated using data from a highly chemically- and geologically-characterized site. When matrix diffusion is incorporated into the REMChlor-MD model for PFOS at this research site, it easily reproduces the field data for three key metrics (concentration, mass discharge, and total mass). However, the no-matrix diffusion model produced a much poorer match. Additionally, after about 40 years of groundwater transport, field data and the REMChlor-MD model both showed the majority (80%) of the measured PFOS mass that exited the source zones was located in downgradient low permeability zones due to matrix diffusion. As such, most of the PFOS mass is not available to immediately migrate downgradient via advection in the more permeable sands at this site, which has important implications for monitored natural attenuation (MNA). Plume expansion over the next 50 years is forecasted to be limited, from a 350-m plume length in 2017 to 550 m in 2070, as matrix diffusion will attenuate groundwater plumes by slowing their expansion. This phenomenon is important for constituents that do not degrade, such as PFOS, compared to those susceptible to degradation. Overall, this work shows that matrix diffusion is a relevant process in environmental PFAS persistence and slows the rate of plume expansion over time.

The wellbeing needs of social housing tenants in Australia: an exploratory study.

BACKGROUND: Social housing provides homes for some of the most vulnerable in society. Those in social housing often have complex issues that may require support. Limited research has examined the unmet needs of those living in social housing from the tenant perspective. This exploratory study aimed to embark on filling this gap. METHODS: A cross-sectional study survey of adult social housing tenants in New South Wales, Australia. Consenting tenants completed a survey asking about their support needs across five domains: transport, employment and financial stress; housing and safety; health and health behaviour; access to services; and control over one's life. Negative binomial regression analysis was used to examine associations between the mean number of support needs and characteristics. RESULTS: Of the 104 tenants invited, 101 agreed to participate (97%) of which 100 completed the survey. Paying unexpected bills' (43%), feeling sad or anxious (40%), feelings of anger or frustration (34%), and memory or concentration problems (33%) were the most prevalent reported needs. Other needs included antisocial behaviour from neighbours (31%) and having control in the direction your life is taking (27%). Seventy-five percent of tenants reported at least one need, with an average of seven needs across the sample (median 5.5, range 0-24). Tenants who identified as Aboriginal or Torres Strait Islander had a higher number of needs compared to other tenants (RR 1.87 95% CI 1.08 to 3.35). CONCLUSIONS: More research describing tenant wellbeing needs is required to guide initiatives improving tenant wellbeing. Development of a standardised tool to measure and prioritise tenant wellbeing needs would be beneficial. There is a need for well-controlled research to establish the potential effectiveness and cost effectiveness of initiatives implemented at the policy or housing provider level. Future research must consider the multifaceted needs of this population. Further, Aboriginal and Torres Strait Islander people are generally overrepresented in social housing in Australia, and in this study Aboriginal and Torres Strait Islander tenants reported a higher number of needs compared to non-Aboriginal and Torres Strait Islander tenants. Given this, future research should ensure measurement tools or strategy initiatives are culturally sensitive and appropriate, and are developed in collaboration with Aboriginal and Torres Strait Islander communities.

Evaluation of natural attenuation of 1,4-dioxane in groundwater using a 14C assay.

Monitored Natural Attenuation (MNA) is a preferred remedy for sites contaminated with 1,4-dioxane due to its low cost and limited environmental impacts compared to active remediation. Having a robust estimate of the rate at which biodegradation occurs is an essential component of assessing MNA. In this study, an assay was developed using 14C-labeled 1,4-dioxane to measure rate constants for biodegradation based on accumulation of 14C products. Purification of the 14C-1,4-dioxane stock solution lowered the level of 14C impurities to below 1% of the total 14C activity. This enabled determination of rate constants in groundwater as low as 0.0021 yr-1, equating to a half-life greater than 300 years. Of the 54 groundwater samples collected from 10 sites in the US, statistically significant rate constants were determined with the 14C assay for 24. The median rate constant was 0.0138 yr-1 (half-life = 50 yr); the maximum rate constant was 0.367 yr-1 (half-life = 1.9 yr). The results confirmed that biodegradation of 1,4-dioxane is occurring at 9 of the 10 sites sampled, albeit with considerable variability in the level of activity. The specificity of the assay was confirmed using acetylene and the absence of oxygen to inhibit monooxygenases.

Pituitary Incidentalomas in the United States: A National Database Estimate.

OBJECTIVE: Increasing use of imaging is associated with increasing diagnoses of pituitary incidentalomas (PIs), which often do not require surgical or medical treatment. In this study, we evaluate U.S. incidence, epidemiology, and trends of pituitary adenomas (PAs) and PIs from 2004 to 2018. METHODS: A total of 50,220 PAs were selected from the SEER (Surveillance Epidemiology and End Results) 2020 submission. PIs that do not initially require surgical or medical treatment were filtered from PAs if they were best diagnostically confirmed by radiography, not indicated as prolactinomas in physician reports, not recommended surgery initially, and reported a correct tumor size. Age-adjusted incidence rates, patient demographics, tumor characteristics, trends over time, and differences between PAs and PIs were explored. RESULTS: Between 2004 and 2018, the incidence rates of PAs and PIs were 4.28 ± 0.04 and 1.53 ± 0.02 per 100,000 population, respectively. When observing changes from 2004 to 2018, a nearly 3-fold increase from 0.73 ± 0.05 to 2.00 ± 0.09 per 100,000 was observed for PIs. The proportion of PIs significantly increased from 24.91% of all PA diagnoses in 2004 to 42.07% in 2018 (P < 0.001). When comparing non-PI PAs with PIs, PIs were more commonly diagnosed in females (64.72% vs. 54.27%; P < 0.001) with microadenomas (61.68% vs. 13.37%; P < 0.001). CONCLUSIONS: Reports of increasing PAs in the United States are likely caused by an increase in diagnosing PIs. This result parallels findings from other countries. This national PI estimate may serve as a point of comparison for future studies investigating imaging and PI rates at individual institutions.

Establishing the prevalence and relative rates of 1,4-dioxane biodegradation in groundwater to improve remedy evaluations.

Options for remediating 1,4-dioxane at groundwater sites are limited due to the physical-chemical properties of this compound. The relevance of natural attenuation processes for 1,4-dioxane was investigated through data from field, lab, and modeling efforts. The objectives were to use multiple lines of evidence for 1,4-dioxane biodegradation to understand the prevalence of this activity and evaluate convergence between lines of evidence. A 14C-1,4-dioxane assay confirmed 1,4-dioxane biodegradation at 9 of 10 sites (median rate constant of 0.0105 yr-1 across wells). Site-wide rate constants were established using a calibrated fate and transport model at 8 sites (median = 0.075 yr-1). The 14C assay constants are likely more conservative, and variability in rates suggested that biodegradation at sites may be localized. Stable isotope fractionation was observed at 7 of 10 sites and served as another direct line of evidence of in situ biodegradation of 1,4-dioxane. This includes sites where indirect lines of evidence, including geochemical conditions or genetic biomarkers for degradation, would not necessarily have been supportive. This highlights the importance of collecting multiple lines of evidence to document 1,4-dioxane natural attenuation, and the widespread prevalence of biodegradation suggests that this process should be part of long-term management decisions.

Can we rely on synthetic pharmacotherapy for the treatment of glioblastoma?

Introduction: Despite decades of clinical trials utilizing conventional and novel therapeutics, the effective treatment of glioblastoma remains one of the most formidable challenges in oncology. Current standard of care includes surgery and chemoradiation. Synthetic pharmacotherapies continue to be explored as potential therapeutic options for glioblastoma patients.Areas covered: This study reviews synthetic pharmacotherapies that are currently under investigation in phase I-III clinical trials. The authors of this study highlight the mechanisms of action of the synthetic pharmacotherapy agents under investigation, outline the available evidence for their utility based on the literature, and summarize the current landscape.Expert opinion: Although warranting further investigation, the studies generally highlighted here have not shown remarkable changes in clinical benefits beyond what has already been established with radiochemotherapy. As we develop more synthetics, we will likely need to combine them with other synthetics to target multiple separate molecular pathways. There is considerable potential when this treatment strategy is guided by molecular profiling approaches which seek to stratify patients based on treatments that would be most efficacious for them.

Perfluoroalkyl acids on suspended particles: Significant transport pathways in surface runoff, surface waters, and subsurface soils.

Eroded particles from the source zone could transport a high concentration of perfluoroalkyl acids (PFAAs) to sediments and water bodies. Yet, the contribution of suspended particles has not been systematically reviewed. Analyzing reported studies, we quantitatively demonstrate that suspended particles in surface water can contain significantly higher concentrations of PFAAs than the sediment below, indicating the source of suspended particles are not the sediment but particles eroded and carried from the source zone upstream. The affinity of PFAAs to particles depends on the particle composition, including organic carbon fraction and iron or aluminum oxide content. In soils, most PFAAs are retained within the top 5 m below the ground surface. The distribution of PFAAs in the subsurface varies based on site properties and local weather conditions. The depth corresponding to the maximum concentration of PFAA in soil decreases with an increase in soil organic carbon or rainfall amount received in the catchment areas. We attribute a greater accumulation of PFAAs near the upper layer of the subsurface to an increase in the accumulation of particles eroded from source zones upstream receiving heavy rainfall. Precursor transformation in the aerobic zone is significantly higher than in the anaerobic zone, thereby making the aerobic subsurface zone serve as a long-term source of groundwater pollution. Collectively, these results suggest that suspended particles, often an overlooked vector for PFAAs, can be a dominant pathway for the transport of PFAAs in environments.

Pituitary Adenomas: From Diagnosis to Therapeutics.

Pituitary adenomas are tumors that arise in the anterior pituitary gland. They are the third most common cause of central nervous system (CNS) tumors among adults. Most adenomas are benign and exert their effect via excess hormone secretion or mass effect. Clinical presentation of pituitary adenoma varies based on their size and hormone secreted. Here, we review some of the most common types of pituitary adenomas, their clinical presentation, and current diagnostic and therapeutic strategies.

Trends in Academic Misrepresentation in Neurological Surgery Residency Applicants: A 2-Year Analysis.

OBJECTIVE: Academic misrepresentation is not an unknown phenomenon, with recent reports in neurosurgery detecting a 45% misrepresentation rate in prospective neurosurgical residents. The purpose of this study was to determine current rates of academic misrepresentation by prospective neurosurgical residents at a single institution across 2 distinct application cycles. METHODS: We retrospectively reviewed all Electronic Residency Application Service applications to 1 institution's neurosurgical residency program in the 2015 (n = 320) and 2020 (n = 355) application cycles. Reported academic works were verified through an extensive Web search of PubMed, Google Scholar, and the individual journal Web sites. Misrepresentation was defined in our study as listing work that does not exist, self-promotion to primary authorship, self-promotion (excluding primary authorship), incorrectly listing online-only publications, and listing non-peer-reviewed work as peer-reviewed. RESULTS: In 2015, 253 (79.1%) applicants reported a total of 2097 citations and 305 (85.9%) applicants reported a total of 3018 citations in 2020 (P < 0.05). Median peer-reviewed articles per applicant rose significantly in 2020 (3.0 vs. 4.0, P < 0.001). Misrepresentation rates decreased dramatically in 2020 to 18.4% from a previously reported misrepresentation rate of 45% in 2012 (P < 0.0001). Increased United States Medical Licensing Exam Step 2 scores were associated with a decreased likelihood of misrepresentation (odds ratio = 0.97, P < 0.001). CONCLUSIONS: Misrepresentation rates within neurosurgical residency candidates have significantly decreased despite an increase in reported citations. A variety of steps including education, modifying reporting methods, and increased screening may help even further decrease misrepresentation.

Current FDA-Approved Therapies for High-Grade Malignant Gliomas.

The standard of care (SOC) for high-grade gliomas (HGG) is maximally safe surgical resection, followed by concurrent radiation therapy (RT) and temozolomide (TMZ) for 6 weeks, then adjuvant TMZ for 6 months. Before this SOC was established, glioblastoma (GBM) patients typically lived for less than one year after diagnosis, and no adjuvant chemotherapy had demonstrated significant survival benefits compared with radiation alone. In 2005, the Stupp et al. randomized controlled trial (RCT) on newly diagnosed GBM patients concluded that RT plus TMZ compared to RT alone significantly improved overall survival (OS) (14.6 vs. 12.1 months) and progression-free survival (PFS) at 6 months (PFS6) (53.9% vs. 36.4%). Outside of TMZ, there are four drugs and one device FDA-approved for the treatment of HGGs: lomustine, intravenous carmustine, carmustine wafer implants, bevacizumab (BVZ), and tumor treatment fields (TTFields). These treatments are now mainly used to treat recurrent HGGs and symptoms. TTFields is the only treatment that has been shown to improve OS (20.5 vs. 15.6 months) and PFS6 (56% vs. 37%) in comparison to the current SOC. TTFields is the newest addition to this list of FDA-approved treatments, but has not been universally accepted yet as part of SOC.

Convection Enhanced Delivery in the Setting of High-Grade Gliomas.

Development of effective treatments for high-grade glioma (HGG) is hampered by (1) the blood-brain barrier (BBB), (2) an infiltrative growth pattern, (3) rapid development of therapeutic resistance, and, in many cases, (4) dose-limiting toxicity due to systemic exposure. Convection-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and increase therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

Clinically Explored Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma in Adults.

As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of the introduction of either wild-type or engineered viruses to the site of disease, where they exert an antitumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induces tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights the potential to integrate this therapeutic strategy into promising combinatory approaches.

Spatial Trends of Anionic, Zwitterionic, and Cationic PFASs at an AFFF-Impacted Site.

Soil and groundwater from an aqueous film-forming foam (AFFF)-impacted site were sampled at high resolution (n = 105 for soil, n = 58 for groundwater) and analyzed for an extensive list of anionic, zwitterionic, and cationic poly- and perfluoroalkyl substances (PFASs). Spatial trends for perfluoroalkyl acids and many precursors enabled a better understanding of PFAS composition, transport, and transformation. All PFASs without analytical standards were semi-quantified. Summed PFAS and individual PFAS concentrations were often higher at depth than near the surface in soil and groundwater. Zwitterionic and cationic compounds composed a majority of the total PFAS mass (up to 97%) in firefighter training area (FTA) soil. Composition of PFAS class, chain length, and structural isomers changed with depth and distance from the FTA, suggesting in situ transformation and differential transport. The percentage of branched perfluorooctane sulfonate increased with depth, consistent with differential isomeric transport. However, linear perfluorooctanoic acid (PFOA) was enriched, suggesting fluorotelomer precursor transformation to linear PFOA. Perfluorohexane sulfonamide, a potential transformation product of sulfonamide-based PFASs, was present at high concentrations (maximum 448 ng/g in soil, 3.4 mg/L in groundwater). Precursor compounds may create long-term sources of perfluoroalkyl acids, although many pathways remain unknown; precursor analysis is critical for PFAS fate and transport understanding.

Mass-Based, Field-Scale Demonstration of PFAS Retention within AFFF-Associated Source Areas.

Transport of poly- and perfluoroalkyl substances (PFAS) at aqueous film-forming foam (AFFF)-impacted sites is limited by various processes that can retain PFAS mass within the source area. This study used concentration data obtained via a high-resolution sampling and analytical protocol to estimate the PFAS mass distribution in source and downgradient areas of a former firefighter training area. The total PFAS mass present at the site was approximately 222 kg, with 106 kg as perfluoroalkyl acids (PFAAs) and 116 kg as polyfluorinated precursors. Zwitterionic and cationic PFAS represented 83% of the total precursor mass and were found primarily in the source and up/side-gradient areas (75%), likely due to preferential hydrophobic partitioning, electrostatic interactions, and diffusion into lower-permeability soils. Based on the release history and the high percentage of total PFAS mass represented by precursors (primarily electrochemical fluorination-derived compounds), the estimated conversion rate of precursors to PFAAs was less than 2% annually. Eighty-two percent of the total PFAS mass was encountered in lower-permeability soils, which limited the potential for advection and transformation. This contributed to a 99% decrease in the mass discharge rate at the far-downgradient plume (0.048 kg/yr compared to the near-source area (3.6 kg/yr)). The results provide field-scale evidence of the importance of these PFAS retention processes at sites where AFFF has been released.

Emerging and investigational targeted chemotherapy and immunotherapy agents for metastatic brain tumors.

INTRODUCTION: Metastases to the central nervous system are the most common cause of malignant intracranial tumors in adults. Current standard of care includes surgery and radiation, but overall survival remains poor. A range of systemic therapies are emerging as promising treatment options for these patients. AREAS COVERED: This study reviews novel drug regimens that are under investigation in phase 1 and 2 clinical trials. To identify relevant therapies under clinical investigation, a search was performed on http://clinicaltrials.gov and Pubmed with the keywords brain metastasis, Phase I clinical trial, and Phase II clinical trial from 2016 to 2020. The authors detail the mechanisms of action of all trial agents, outline evidence for their utility, and summarize the current state of the field. EXPERT OPINION: Current advancements in the medical management of brain metastases can be categorized into targeted therapies, methods of overcoming treatment resistance, novel combinations of therapies, and modulation of the tumor microenvironment with a specific focus on immunotherapy. Each of these realms holds great promise for the field going forward. A more streamlined structure for enrollment into clinical trials will be a crucial step in accelerating progress in this area.