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Flashiness is a hydrologic signature used to describe the responsiveness of streamflow to precipitation. In practise, flashiness has most often been correlated with rainfall intensity and the presence of urban land cover or imperviousness. However, a number of watershed characteristics can influence flashiness, necessitating further investigation of how this particular watershed behaviour and its associated drivers vary at regional scales. We investigated how ten measurable watershed characteristics are empirically related to flashiness of 195 gauged streams in the Mid‐Atlantic region using linear regression analysis. The selected gauges had drainage areas ranging in size from 15 to 250 km2. To explore multiple quantifications of flashiness, we determined both the Richards‐Baker flashiness index, calculated from the continuous hydrograph, and number of peaks‐over‐threshold, for all watersheds for a 10‐year period. As found in other studies, the percentage of watershed development was strongly correlated with stream flashiness, though significant inverse relationships also existed for forest cover, water and wetlands and carbonate geology. Differences in flashiness values between rural and suburban watersheds were not significant, with a significant increase in flashiness (p < 0.01) occurring at 80% development or ~ 25% imperviousness. In addition, we found significant differences in relationships between watershed characteristics and flashiness when differentiated by physiographic regions. For the study area and each of its five physiographic sub‐regions, we identified the four most important predictors through multiple regression. The overall mid‐Atlantic model suggested that development, wetlands and compactness ratio as the most important predictors (adj R2 = 0.57). Significant predictors of stream flashiness varied among regions; however, wetlands served as a significant buffer of flashiness in four of five sub‐regions demonstrating the importance of wetlands in modulating flash‐flooding. In all physiographic regions, empirical models of flashiness values outperformed the Mid‐Atlantic regional model, underscoring the value of local landscape characteristics in augmenting or modulating flashy watershed responses. Our findings suggest the potential for improvements to operational flash‐flood forecasting using hydrologic characteristics of the landscape. [ABSTRACT FROM AUTHOR]

Fine particulate organic matter (FPOM) is an important basal resource in stream ecosystems for deposit- and filter-feeding macroinvertebrates (collectively 'particle feeders'). Microplastics (MP) share many characteristics with FPOM (e.g. size range, surface area to volume ratios) and are potentially consumed by particle feeders. Accordingly, MP contamination of natural FPOM pools might affect particle feeder growth and survival, particularly when background FPOM resource quality is low, or intraspecific competition is high. We conducted a microcosm experiment to evaluate how a realistic (1400 particles/kg sediment) polyethylene MP (ø = 45–53 µm) concentration interacts with FPOM (ø = 63–250 µm) resource quality (low versus high nutrient content) and consumer density (10 versus 20 individuals per microcosm) to affect growth and survival of larval Chironomus riparius (Diptera: Chironomidae), a model particle feeder. We additionally quantified community respiration, based on three hour measurements of oxygen consumption in the microcosms at the end of the experiment. MP exposure reduced larval body lengths by 26.7%, but only under the low consumer density treatment. MPs reduced community respiration by 26.2%, but only in the absence of chironomids, indicating an impact on microbial respiration. In comparison, low resource quality and high consumer density were associated with 53.5–70.2% reductions in community respiration, chironomid body length and/or body mass. These results suggest that effects of contamination of FPOM with MPs at environmentally realistic concentrations on the life histories of particle feeders such as C. riparius might be limited, especially relative to the effects of resource quality and consumer density. However, the reduction in microbial respiration when MPs were present highlights the need for further research addressing MP impacts on microbes, given their key roles in ecosystem functioning. [ABSTRACT FROM AUTHOR]

Reference materials (RMs) are vital tools in the validation of methods used to detect environmental pollutants. Microplastics, a relatively new environmental pollutant, require a variety of complex approaches to address their presence in environmental samples. Both interlaboratory comparison (ILC) studies and RMs are essential to support the validation of methods used in microplastic analysis. Presented here are results of quality assurance and quality control (QA/QC) performed on two types of candidate microplastic RMs: dissolvable gelatin capsules and soda tablets. These RMs have been used to support numerous international ILC studies in recent years (2019–2022). Dissolvable capsules containing polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyethylene (PE), and polystyrene (PS), in different size fractions from 50 to 1000 µm, were produced for one ILC study, obtaining relative standard deviation (RSD) from 0 to 24%. The larger size fraction allowed for manual addition of particles to the capsules, yielding 0% error and 100% recovery during QA/QC. Dissolvable capsules were replaced by soda tablets in subsequent ILC studies and recovery test exercises because they were found to be a more reliable carrier for microplastic RMs. Batches of soda tablets were produced containing different single and multiple polymer mixtures, i.e., PE, PET, PS, PVC, polypropylene (PP), and polycarbonate (PC), with RSD ranging from 8 to 21%. Lastly, soda tablets consisting of a mixture of PE, PVC, and PS (125–355 µm) were produced and used for recovery testing during pretreatment of environmental samples. These had an RSD of 9%. Results showed that soda tablets and capsules containing microplastics >50 µm could be produced with sufficient precision for internal recovery tests and external ILC studies. Further work is required to optimize this method for smaller microplastics (< 50 µm) because variation was found to be too large during QA/QC. Nevertheless, this approach represents a valuable solution addressing many of the challenges associated with validating microplastic analytical methods. [ABSTRACT FROM AUTHOR]

Improper handling of plastic waste and related chemical pollution has garnered much attention in recent years owing to the associated detrimental impacts on human health and the environment. This article reports an overview of the main interlinkages between persistent organic pollutants (POPs) and plastic in the waste management system of India. Both plastics and POPs share certain common traits such as persistence, resistance to biological degradation, and the ability to get transported over long distances. Throughout the processes of production, consumption, and disposal, plastics interact with and accumulate POPs through several mechanisms and end up co-existing in the environment. Plastic waste can undergo long-range transport through rivers and the oceans, break down into microplastics and get transported through the air, or remain locked in waste dump yards and landfills. Over time, environmental processes lead to the leaching and release of accumulated POPs from these plastic wastes. Plastic recycling in the Indian informal sector including smelting, scrubbing, and shredding of plastic waste, is also a potential major POPs source that demands further investigation. The presence of POPs in plastic waste and their fate in the plastic recycling process have not yet been elucidated. By enhancing our understanding of these processes, this paper may aid policy decisions to combat the release of POPs from different waste types and processes in India. [ABSTRACT FROM AUTHOR]

Microplastics have been detected in lake environments globally, including in remote regions. Agricultural and populated areas are known to congregate several inputs and release pathways for microplastic. This study investigated microplastic (50–5000 µm) contamination in five Danish freshwater lakes with catchments dominated by arable land use. The concentrations in sediments (n = 3/site) and the zebra mussel, Dreissena polymorpha (n = 30/site), were calculated and compared with catchment characteristics and environmental parameters. Microplastic concentrations in sediment were relatively low (average 0.028 ± 0.017 items/g dry weight sediment) whilst only a single microplastic was found in the mussels (average 0.067 ± 0.249 items/10 individual). Hence, no relationship between the number of observed microplastics in sediment and mussels could be identified, nor could a relationship between concentration in sediment and environmental parameters. As all lakes studied received their water from moderate to heavily anthropogenically impacted catchments, it was expected that they would be sinks for microplastic with high bioavailability. Based on the results of the present study, D. polymorpha were found to not be contaminated by microplastics in the five study lakes. Thus, our results suggest that these mussels do not interact with microplastics at low concentrations. We speculate that the results on sediment and biota could be explained by several factors related to regional differences in plastic use, species characteristics, sampling size, and the fact that finding no microplastic is not always reported in the scientific literature. Thus, the paper provides insight into the dynamics between the catchment, lake, and biota in systems with low microplastic concentration. [ABSTRACT FROM AUTHOR]

Microplastic ingestion has been shown for various organisms, but knowledge of the potential adverse effects on freshwater invertebrates remains limited. We assessed the ingestion capacity and the associated effects of polyester fibers (26–5761 µm) and car tire particles (25–75 µm) on freshwater invertebrates under acute and chronic exposure conditions. A range of microplastic concentrations was tested on Daphnia magna, Hyalella azteca, Asellus aquaticus, and Lumbriculus variegatus using water only (up to 0.15 g/L) or spiked sediment (up to 2 g/kg dry wt), depending on the habitat of the species. Daphnia magna did not ingest any fibers, but low levels of fibers were ingested by all tested benthic invertebrate species. Car tire particle ingestion rose with increasing exposure concentration for all tested invertebrates and was highest in D. magna and L. variegatus. In most cases, no statistically significant effects on mobility, survival, or reproductive output were observed after acute and chronic exposure at the tested concentrations. However, fibers affected the reproduction and survival of D. magna (no‐observed‐effect concentration [NOEC]: 0.15 mg/L) due to entanglement and limited mobility under chronic conditions. Car tire particles affected the reproduction (NOEC: 1.5 mg/L) and survival (NOEC: 0.15 mg/L) of D. magna after chronic exposure at concentrations in the same order of magnitude as modeled river water concentrations, suggesting that refined exposure and effect studies should be performed with these microplastics. Our results confirm that microplastic ingestion by freshwater invertebrates depends on particle shape and size and that ingestion quantity depends on the exposure pathway and the feeding strategy of the test organism. Environ Toxicol Chem 2022;41:1555–1567. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Purpose: BRCA1 or BRCA2 mutated cancers (BRCAmut) have intrinsic sensitivity to PARP inhibitors due to deficiency in homologous recombination-mediated DNA repair. There are similarities between BRCAmut and BRCAwt ovarian and basal-like breast cancers. This phase I study determined the recommended phase II dose (RP2D) and preliminary efficacy of the PARP inhibitor, veliparib (ABT-888), in these patients. Patients and methods: Patients (n = 98) were dosed with veliparib 50–500 mg twice daily (BID). The BRCAmut cohort (n = 70) contained predominantly ovarian (53%) and breast (23%) cancers; the BRCAwt cohort (n = 28) consisted primarily of breast cancer (86%). The MTD, DLT, adverse events, PK, PD, and clinical response were assessed. Results: DLTs were grade 3 nausea/vomiting at 400 mg BID in a BRCAmut carrier, grade 2 seizure at 400 mg BID in a patient with BRCAwt cancer, and grade 2 seizure at 500 mg BID in a BRCAmut carrier. Common toxicities included nausea (65%), fatigue (45%), and lymphopenia (38%). Grade 3/4 toxicities were rare (highest lymphopenia at 15%). Overall response rate (ORR) was 23% (95% CI 13–35%) in BRCAmut overall, and 37% (95% CI 21–55%) at 400 mg BID and above. In BRCAwt, ORR was 8% (95% CI 1–26%), and clinical benefit rate was 16% (95% CI 4–36%), reflecting prolonged stable disease in some patients. PK was linear with dose and was correlated with response and nausea. Conclusions: Continuous veliparib is safe and tolerable. The RP2D was 400 mg BID. There is evidence of clinical activity of veliparib in patients with BRCAmut and BRCAwt cancers. [ABSTRACT FROM AUTHOR]

Repeated measures studies are frequently performed in patient-derived xenograft (PDX) models to evaluate drug activity or compare effectiveness of cancer treatment regimens. Linear mixed effects regression models were used to perform statistical modeling of tumor growth data. Biologically plausible structures for the covariation between repeated tumor burden measurements are explained. Graphical, tabular, and information criteria tools useful for choosing the mean model functional form and covariation structure are demonstrated in a Case Study of five PDX models comparing cancer treatments. Power calculations were performed via simulation. Linear mixed effects regression models applied to the natural log scale were shown to describe the observed data well. A straight growth function fit well for two PDX models. Three PDX models required quadratic or cubic polynomial (time squared or cubed) terms to describe delayed tumor regression or initial tumor growth followed by regression. Spatial(power), spatial(power) + RE, and RE covariance structures were found to be reasonable. Statistical power is shown as a function of sample size for different levels of variation. Linear mixed effects regression models provide a unified and flexible framework for analysis of PDX repeated measures data, use all available data, and allow estimation of tumor doubling time. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy is characterized by pain, numbness, and tingling in the hands and feet and by diminished quality of life. Multiple previous studies, mostly preclinical, suggest that poly (ADP-ribose) polymerase (PARP) inhibitors may help with these symptoms. Objective: To assess the relationship between PARP inhibition and prevention/palliation of peripheral neuropathy in a clinical setting. Design: Meta-analysis of placebo-controlled clinical trials with PARP inhibitors. Setting/Subjects: We conducted 9 literature searches that included PubMed and other sources to compile fully published placebo-controlled clinical trials that tested PARP inhibitors and that reported on peripheral neuropathy. Measurements: The relative risks for neuropathy of all grades based on PARP inhibition were calculated for each trial. Each trial was weighted by its respective sample size. A forest plot was constructed. Results: Five trials, inclusive of 843 patients, met this study's eligibility criteria. Four included a concomitant PARP inhibitor (either olaparib or veliparib) and paclitaxel, a neuropathy-causing chemotherapy agent; the remaining trial evaluated long-term monotherapy with olaparib. The pooled overall relative risk for the development of neuropathy with PARP inhibition was 1.06 (95% confidence interval: 1–1.4). Conclusions: PARP inhibition does not appear to reduce the risk of chemotherapy-induced peripheral neuropathy. Whether PARP inhibitors may palliate (rather than prevent) neuropathy remains an area in need of further investigation. [ABSTRACT FROM AUTHOR]

On December 26, 2015 (Boxing Day), an exceptional flood event occurred in the Irwell catchment, United Kingdom, when the neighbouring Mersey catchment experienced a much more typical winter run‐off event. This provided an opportunity to examine the influence of high‐magnitude hydrological processes on the behaviour of fine‐grained metal‐contaminated bed sediments. Forty sites across the two catchments were sampled for channel bed fine sediment storage and sediment‐associated metal(loid) concentrations prior to, and following, the flooding. Sediments were analysed for total As, Cr, Cu, Pb, and Zn and then subjected to a five‐step sequential extraction procedure. Despite a significant reorganisation of fine‐grained (<63 μm) sediment storage, metal(loid) concentrations demonstrated markedly conservative behaviour with no significant difference observed between pre‐flooding and post‐flooding values across both catchments. Estimates of the channel bed storage of sediment‐associated metal(loid)s also showed minimal change as a result of the flooding. The metal partitioning data reveal only minor changes in the mobility of bed sediment‐associated metal(loid)s, indicating that such flood events do not increase the availability of sorbed contaminants in these catchments. Post‐flooding bed sediment metal(loid) loadings remain high, indicating persistent and long‐lasting sources of contamination within the Irwell and upper Mersey fluvial network. [ABSTRACT FROM AUTHOR]

Purpose: Manchester is often heralded as the first industrial city. Large volumes of physical and liquid contaminants were released into its river network throughout the industrial period up to the latter part of the twentieth century. Water quality has improved dramatically in recent decades, but, given their environmental significance, it is important to ascertain the extent to which a legacy of contamination persists in the modern bed sediments. Materials and methods: Fine-grained bed sediments were sampled at 40 sites in the Mersey and Irwell catchments. Sediments were wet sieved to isolate the <63-μm grain size fraction. Metal concentrations were determined using XRF. Particle size characteristics were also measured. Sediments were subjected to a five-step sequential extraction procedure to ascertain the environmental significance of metal concentrations. Alongside archival research of past industry, enrichment factors, multivariate statistical techniques and conditional inferences trees were used to identify sources of heavy metals. Results and discussion: Bed sediment-associated heavy metal(loid) concentrations were as follows: As (9.89-110 mg kg), Cr (76.5-413 mg kg), Cu (53.1-383 mg kg), Pb (80.4-442 mg kg) and Zn (282-1020 mg kg). Enrichment factors ranged from moderate to extremely severe, with Pb showing the greatest enrichment across the catchments. Chemical mobility was generally low, but metal(loid) partitioning identified the influence of anthropogenic sources. Statistical analysis highlighted a number of point sources associated with former industrial sites that operated during the industrial period. Conditional inference trees highlighted the role of the textile industry on Cu concentrations in addition to indicating the complexity of sources, fluxes and stores of sediment-associated contamination throughout the system. Conclusions: Fine-grained sediment-associated metal(loid)s in the Mersey and Irwell catchments are anthropogenically enriched. Concentrations also exceed sediment quality guidelines. A lack of distinct spatial patterning points to a complex network of contaminant inputs across the catchments, even in the headwaters. Whilst potential modern urban sources are likely to be important, spatial patterns and multivariate/data mining techniques also highlighted the importance of releases from former industrial sites as well as the reworking of historically contaminated floodplains and soils. [ABSTRACT FROM AUTHOR]

Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H2O2 and menadione/FeCl3 exposure, respectively. Several proteins were detected with altered abundance in response to H2O2, but not menadione/FeCl3 (i.e., valosin-containing protein), indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM) enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen. [ABSTRACT FROM AUTHOR]

Key Clinical Message The differential diagnosis of a large breast mass in a post-menopausal woman can include both benign and malignant etiologies. Although rare, diagnosis of giant intraductal papilloma must be considered in the differential. Furthermore, although benign, papillomas presenting as a large breast mass affecting the skin require extensive breast surgical treatment. [ABSTRACT FROM AUTHOR]

Poly(ADP-ribose) polymerase 1 (PARP1) is an important component of the base excision repair (BER) pathway as well as a regulator of homologous recombination (HR) and nonhomologous end-joining (NHEJ). Previous studies have demonstrated that treatment of HR-deficient cells with PARP inhibitors results in stalled and collapsed replication forks. Consequently, HR-deficient cells are extremely sensitive to PARP inhibitors. Several explanations have been advanced to explain this so-called synthetic lethality between HR deficiency and PARP inhibition: (i) reduction of BER activity leading to enhanced DNA double-strand breaks, which accumulate in the absence of HR; (ii) trapping of inhibited PARP1 at sites of DNA damage, which prevents access of other repair proteins; (iii) failure to initiate HR by poly(ADP-ribose) polymer-dependent BRCA1 recruitment; and (iv) activation of the NHEJ pathway, which selectively induces error-prone repair in HR-deficient cells. Here we review evidence regarding these various explanations for the ability of PARP inhibitors to selectively kill HR-deficient cancer cells and discuss their potential implications. [ABSTRACT FROM AUTHOR]

Simple Summary: Studies in tissue culture cell lines have indicated that silencing of the mitotic regulator CHFR is associated with increased paclitaxel sensitivity. More recently, it has been suggested that a UBC13-DNMT1-CHFR pathway also modulates sensitivity of ovarian cancer to paclitaxel in the clinic. Here we have credentialed an anti-CHFR monoclonal antibody for immunohistochemistry and directly examined the association of CHFR expression with outcome of paclitaxel-containing ovarian cancer therapy. While CHFR levels were higher in high grade, high stage ovarian cancer, after correction for stage and debulking status there was no association between CHFR levels and progression-free survival in high grade serous ovarian cancer treated with surgery followed by platinum/taxane therapy. Moreover, there was no association between CHFR expression and response of patient-derived ovarian cancer xenografts treated with paclitaxel monotherapy. These studies indicate that CHFR varies among ovarian cancers but is unlikely to be an independent biomarker for poor response to taxanes. The poly(ADP-ribose) binding protein CHFR regulates cellular responses to mitotic stress. The deubiquitinase UBC13, which regulates CHFR levels, has been associated with better overall survival in paclitaxel-treated ovarian cancer. Despite the extensive use of taxanes in the treatment of ovarian cancer, little is known about expression of CHFR itself in this disease. In the present study, tissue microarrays containing ovarian carcinoma samples from 417 women who underwent initial surgical debulking were stained with anti-CHFR antibody and scored in a blinded fashion. CHFR levels, expressed as a modified H-score, were examined for association with histology, grade, time to progression (TTP) and overall survival (OS). In addition, patient-derived xenografts from 69 ovarian carcinoma patients were examined for CHFR expression and sensitivity to paclitaxel monotherapy. In clinical ovarian cancer specimens, CHFR expression was positively associated with serous histology (p = 0.0048), higher grade (p = 0.000014) and higher stage (p = 0.016). After correction for stage and debulking, there was no significant association between CHFR staining and overall survival (p = 0.62) or time to progression (p = 0.91) in patients with high grade serous cancers treated with platinum/taxane chemotherapy (N = 249). Likewise, no association between CHFR expression and paclitaxel sensitivity was observed in ovarian cancer PDXs treated with paclitaxel monotherapy. Accordingly, differences in CHFR expression are unlikely to play a major role in paclitaxel sensitivity of high grade serous ovarian cancer. [ABSTRACT FROM AUTHOR]