Predicting selection for antimicrobial resistance in UK wastewater and aquatic environments: Ciprofloxacin poses a significant risk.

This is the final version. Available from Elsevier via the DOI in this record. Data access statement: The research data supporting this publication are provided within this paper and the supplementary information accompanying this publication.Antimicrobial resistance (AMR) is a threat to human and animal health, with the environment increasingly recognised as playing an important role in AMR evolution, dissemination, and transmission. Antibiotics can select for AMR at very low concentrations, similar to those in the environment, yet their release into the environment, e.g., from wastewater treatment plants, is not currently regulated. Understanding the selection risk antibiotics pose in wastewater and receiving waters is key to understanding if environmental regulation of antibiotics is required. We investigated the risk of selection occurring in UK wastewater and receiving waters by determining where measured environmental concentration data (n = 8187) for four antibiotics (ciprofloxacin, azithromycin, clarithromycin, and erythromycin) collected in England and Wales 2015-2018 (sites n = 67) exceeded selective concentration thresholds derived from complex microbial community evolution experiments undertaken previously. We show that selection for AMR by ciprofloxacin is likely to have occurred routinely in England and Wales wastewater during the 2015-2018 period, with some seasonal and regional trends. Wastewater treatment reduces the selection risk posed by ciprofloxacin significantly, but not completely, and predicted risk in surface waters remains high in several cases. Conversely, the potential risks posed by the macrolides (azithromycin, clarithromycin, and erythromycin) were lower than those posed by ciprofloxacin. Our data demonstrate further action is needed to prevent selection for AMR in wastewater, with environmental quality standards for some antibiotics required in the future, and that selection risk is not solely a concern in low/middle income countries.FRESH CDT/AstraZenecaBBSRC/ AstraZenecaNatural Environment Research CouncilNatural Environment Research Counci

Prominence eruption observed in He II 304 Å up to >6 R⊙ by EUI/FSI aboard Solar Orbiter⋆

Aims. We report observations of a unique, large prominence eruption that was observed in the He II 304 Å passband of the Extreme Ultraviolet Imager/Full Sun Imager telescope aboard Solar Orbiter on 15–16 February 2022. Methods. Observations from several vantage points – Solar Orbiter, the Solar-Terrestrial Relations Observatory, the Solar and Heliospheric Observatory, and Earth-orbiting satellites – were used to measure the kinematics of the erupting prominence and the associated coronal mass ejection. Three-dimensional reconstruction was used to calculate the deprojected positions and speeds of different parts of the prominence. Observations in several passbands allowed us to analyse the radiative properties of the erupting prominence. Results. The leading parts of the erupting prominence and the leading edge of the corresponding coronal mass ejection propagate at speeds of around 1700 km s−1 and 2200 km s−1, respectively, while the trailing parts of the prominence are significantly slower (around 500 km s−1). Parts of the prominence are tracked up to heights of over 6 R⊙. The He II emission is probably produced via collisional excitation rather than scattering. Surprisingly, the brightness of a trailing feature increases with height. Conclusions. The reported prominence is the first observed in He II 304 Å emission at such a great height (above 6 R⊙)

Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342

INTRODUCTION: The response to paclitaxel varies widely in metastatic breast cancer. We analyzed data from CALGB 9342, which tested three doses of paclitaxel in women with advanced disease, to determine whether response and outcomes differed according to HER2, hormone receptor, and p53 status. METHODS: Among 474 women randomly assigned to paclitaxel at a dose of 175, 210, or 250 mg/m(2), adequate primary tumor tissue was available from 175. Immunohistochemistry with two antibodies and fluorescence in situ hybridization were performed to evaluate HER2 status; p53 status was determined by immunohistochemistry and sequencing. Hormone receptor status was obtained from pathology reports. RESULTS: Objective response rate was not associated with HER2 or p53 status. There was a trend toward a shorter median time to treatment failure among women with HER2-positive tumors (2.3 versus 4.2 months; P = 0.067). HER2 status was not related to overall survival (OS). Hormone receptor expression was not associated with differences in response but was associated with longer OS (P = 0.003). In contrast, women with p53 over-expression had significantly shorter OS than those without p53 over-expression (11.5 versus 14.4 months; P = 0.002). In addition, triple negative tumors were more frequent in African-American than in Caucasian patients, and were associated with a significant reduction in OS (8.7 versus 12.9 months; P = 0.008). CONCLUSION: None of the biomarkers was predictive of treatment response in women with metastatic breast cancer; however, survival differed according to hormone receptor and p53 status. Triple negative tumors were more frequent in African-American patients and were associated with a shorter survival

Associations of Lifestyle Factors, Disease History and Awareness with Health-Related Quality of Life in a Thai Population

10.1371/journal.pone.0049921PLoS ONE711

Prognostic significance of bcl-2 expression in stage III breast cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy

BACKGROUND: Bcl-2 is positively regulated by hormonal receptor pathways in breast cancer. A study was conducted to assess the prognostic significances of clinico-pathologic variables and of ER, PR, p53, c-erbB2, bcl-2, or Ki-67 as markers of relapse in breast cancer patients who had received the identical adjuvant therapy at a single institution. METHODS: A cohort of 151 curatively resected stage III breast cancer patients (M:F = 3:148, median age 46 years) who had 4 or more positive lymph nodes and received doxorubicin and cyclophosphamide followed by paclitaxel (AC/T) as adjuvant chemotherapy was analyzed for clinico-pathologic characteristics including disease-free survival (DFS) and overall survival (OS). Patients with positive ER and/or PR expression received 5 years of tamoxifen following AC/T. The protein expressions of biomarkers were assessed immunohistochemically. RESULTS: The median follow-up duration was 36 months, and 37 patients (24.5%) experienced a recurrence. Univariate analyses indicated that the tumor size (P = 0.038) and the number of involved lymph nodes (P < 0.001) significantly affected the recurrences. However, the type of surgery, the histology, histologic grade, the presence of endolymphatic emboli, and a close resection margin did not. Moreover, ER positivity (P = 0.013), bcl-2 positivity (P = 0.002) and low p53 expression (P = 0.032) were found to be significantly associated with a prolonged DFS. Furthermore, multivariate analysis identified 10 or more involved lymph nodes (HR 7.366; P < 0.001), negative bcl-2 expression (HR 2.895; P = 0.030), and c-erbB2 over-expression (HR 3.535; P = 0.001) as independent indicators of poorer DFS. In addition, bcl-2 expression was found to be significantly correlated with the expressions of ER and PR, and inversely correlated with the expressions of p53, c-erbB2 and Ki-67. Patients with bcl-2 expression had a significantly longer DFS than those without, even in the ER (+) subgroup. Moreover, OS was significantly affected by ER, bcl-2 and c-erbB2. CONCLUSION: Bcl-2 is an independent prognostic factor of DFS in curatively resected stage III breast cancer patients and appears to be a useful prognostic factor in combination with c-erbB2 and the number of involved lymph nodes

Design of the EXercise Intervention after Stem cell Transplantation (EXIST) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of an individualized high intensity physical exercise program on fitness and fatigue in patients with multiple myeloma or (non-) Hodgkin's lymphoma treated with high dose chemotherapy and autologous stem cell transplantation

<p>Abstract</p> <p>Background</p> <p>The use of high-dose chemotherapy combined with autologous stem cell transplantation has improved the outcome of hematologic malignancies. Nevertheless, this treatment can cause persistent fatigue and a reduced global quality of life, role and physical function. Physical exercise interventions may be beneficial for physical fitness, fatigue and quality of life. However, the trials conducted so far to test the effects of physical exercise interventions in this group of patients were of poor to moderate methodological quality and economic evaluations are lacking. Hence there is need for a rigorous, appropriately controlled assessment of the effectiveness of exercise programs in these patients. The aims of the present study are (1) to determine the effectiveness of an individualized high intensity strength and interval training program with respect to physiological and psychological health status in patients with multiple myeloma or (non-)Hodgkin's lymphoma who have recently undergone high dose chemotherapy followed by autologous stem cell transplantation; and (2) to evaluate the cost-effectiveness of this program.</p> <p>Methods</p> <p>A multicenter, prospective, single blind randomized controlled trial will be performed. We aim to recruit 120 patients within an inclusion period of 2 years at 7 hospitals in the Netherlands. The patients will be randomly assigned to one of two groups: (1) intervention plus usual care; or (2) usual care. The intervention consists of an 18-week individualized supervised high-intensity exercise program and counselling. The primary outcomes (cardiorespiratory fitness, muscle strength and fatigue) and secondary outcomes are assessed at baseline, at completion of the intervention and at 12 months follow-up.</p> <p>Discussion</p> <p>The strengths of this study include the solid trial design with clearly defined research groups and standardized outcome measures, the inclusion of an economic evaluation and the inclusion of both resistance and endurance exercise in the intervention program.</p> <p>Trial registration</p> <p>This study is registered at the Netherlands Trial Register (NTR2341)</p