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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]

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]

The objective of this study is to investigate the effectiveness of a local wearable cooling solution in improving thermal comfort, emotional state, and cognitive performance. The study was conducted in an environmental room with air temperature of 31.5 ± 0.26 °C. Thirty participants performed six cognitive tasks while periodically assessing their thermal experience locally where the cooling (Embr wave) was applied and for the whole body, as well as emotional states. The same protocol was applied to another thirty participants as the control group without local cooling. We also measured mean skin temperature and local skin temperature beneath the cooling device during the whole session. The results showed a significant drop in thermal sensation right after the application of the local cooling. Based on the ASHRAE 7-point scale for the overall thermal sensation vote, the local sensation dropped from 0.8 to −0.4 and the whole-body thermal sensation from 1.34 to 0.87. Over the 60 min of local cooling application, the local thermal sensation dropped from 0.98 to 0.04 and the whole-body thermal sensation dropped from 1.37 to 1.12. Furthermore, the local cooling group showed a significant drop in negative emotions and an increase in positive emotions compared to the control group. For cognitive performance, local cooling groups showed to be more inclined for risk taking for more rewards compared to the control group. The performance of other cognitive tests showed no significant difference between the two groups, even though attention, working memory and creativity were enhanced slightly but insignificantly. [Display omitted] • Proposed a low-energy cooling strategy to improve thermal comfort, emotion, and cognition. • Significant drop in local and whole-body thermal sensation right after the cooling. • Positive emotions increased while negative emotions decreased. • Positive effect of local cooling on risky decision making. [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]

Microplastic contamination of the aquatic environment is a global issue. Microplastics can be ingested by organisms leading to negative physiological impacts. The ingestion of microplastics by freshwater invertebrates has not been reported outside the laboratory. Here we demonstrate the ingestion of microplastic particles by Tubifex tubifex from bottom sediments in a major urban waterbody fed by the River Irwell, Manchester, UK. The host sediments had microplastic concentrations ranging from 5(5 to 2543 pa* tides kg1. 87% of the Tub if ex-ingested microplastic particles were microfibers (55-4100 μτη in length), while the remaining 13% were microplastic fragments (50-4500 μχη in length). FT-1R analysis revealed ingestion of a range of polymers, including polyester and auylk fibers. While microbeads were present in the host sediment matrix, they were not detected in Tubifex worm tissue. The mean concentration of ingested microplastlcs was 12y ± 65.4 particles 1 tissue. Wc also chow that Tubifex worms retain microplastics for longer than they retain other particulate components uf Lhe ingested sediment matrix. Mixoplastic ingestion by Tubifex worms poses a significant risk for trophic transfer and biomagnification of microplastics up the aquatic food chain. [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]