Estrogenic activity in drainage water : a field study on a Swiss cattle pasture

Background: Dairy cow manure applied to pastures is a significant potential source of estrogenic contamination in nearby streams. One possible pathway is through infiltration via preferential flow to drainage pipes, particularly after heavy rainfall events. In a period of 73 days in the spring of 2010, a drainage catchment in a cattle pasture in the Swiss lowlands was closely monitored. Manure was applied three times during the study, and part of the catchment was also subjected to grazing. During five field campaigns, water samples from two sampling locations were taken for 4–24 h in consecutive sampling intervals. 17β-estradiol equivalents (EEQ) were determined with the yeast estrogen screen (YES) and the ER-CALUX assay. Some water chemistry parameters, pH, conductivity, oxygen content and soil moisture tension were also monitored. Results: Washout of estrogenic activity was highest during or right after heavy rainfall events, shortly after manure spreading, when peak values of >10 ng/l EEQ were found in several samples. However, in two field campaigns, high EEQ values were also found 14 and 28 days, after the last manure application, in one case during a dry weather period. This indicates that estrogenic compounds are more stable in natural soils than what is expected from data gathered in lab studies. Conclusions: Streams in agricultural areas with a high proportion of drained land may be subject to numerous peaks of EEQ during the course of the year. This may have a negative effect on aquatic organisms, namely fish embryos, living in these streams

Robust Flows over Time: Models and Complexity Results

We study dynamic network flows with uncertain input data under a robust optimization perspective. In the dynamic maximum flow problem, the goal is to maximize the flow reaching the sink within a given time horizon $T$, while flow requires a certain travel time to traverse an edge. In our setting, we account for uncertain travel times of flow. We investigate maximum flows over time under the assumption that at most $\Gamma$ travel times may be prolonged simultaneously due to delay. We develop and study a mathematical model for this problem. As the dynamic robust flow problem generalizes the static version, it is NP-hard to compute an optimal flow. However, our dynamic version is considerably more complex than the static version. We show that it is NP-hard to verify feasibility of a given candidate solution. Furthermore, we investigate temporally repeated flows and show that in contrast to the non-robust case (that is, without uncertainties) they no longer provide optimal solutions for the robust problem, but rather yield a worst case optimality gap of at least $T$. We finally show that the optimality gap is at most $O(\eta k \log T)$, where $\eta$ and $k$ are newly introduced instance characteristics and provide a matching lower bound instance with optimality gap $\Omega(\log T)$ and $\eta = k = 1$. The results obtained in this paper yield a first step towards understanding robust dynamic flow problems with uncertain travel times

Recombinant hirudin for extended aortic surgery in patients with heparin-induced thrombocytopenia

AbstractJ Thorac Cardiovasc Surg 1999;118:191-

Microfluidics/CMOS orthogonal capabilities for cell biology

The study of individual cells and cellular networks can greatly benefit from the capabilities of microfabricated devices for the stimulation and the recording of electrical cellular events. In this contribution, we describe the development of a device, which combines capabilities for both electrical and pharmacological cell stimulation, and the subsequent recording of electrical cellular activity. The device combines the unique advantages of integrated circuitry (CMOS technology) for signal processing and microfluidics for drug delivery. Both techniques are ideally suited to study electrogenic mammalian cells, because feature sizes are of the same order as the cell diameter, ∼ 50 μm. Despite these attractive features, we observe a size mismatch between microfluidic devices, with bulky fluidic connections to the outside world, and highly miniaturized CMOS chips. To overcome this problem, we developed a microfluidic flow cell that accommodates a small CMOS chip. We simulated the performances of a flow cell based on a 3-D microfluidic system, and then fabricated the device to experimentally verify the nutrient delivery and localized drug delivery performance. The flow-cell has a constant nutrient flow, and six drug inlets that can individually deliver a drug to the cells. The experimental analysis of the nutrient and drug flow mass transfer properties in the flowcell are in good agreement with our simulations. For an experimental proof-of-principle, we successfully delivered, in a spatially resolved manner, a ‘drug' to a culture of HL-1 cardiac myocyte

Conserved structured domains in plant non-coding RNA enod40, their evolution and recruitment of sequences from transposable elements

Plant long noncoding RNA enod40 is involved in the regulation of symbiotic associations with bacteria, in particular, in nitrogen-fixing root nodules of legumes, and with fungi in phosphate-acquiring arbuscular mycorrhizae formed by various plants. The presence of enod40 genes in plants that do not form such symbioses indicates its other roles in cell physiology. The molecular mechanisms of enod40 RNA function are poorly understood. Enod40 RNAs form several structured domains, conserved to different extents. Due to relatively low sequence similarity, identification of enod40 sequences in plant genomes is not straightforward, and many enod40 genes remain unannotated even in complete genomes. Here, we used comparative structure analysis and sequence similarity searches in order to locate enod40 genes and determine enod40 RNA structures in nitrogen-fixing clade plants and in grasses. The structures combine conserved features with considerable diversity of structural elements, including insertions of structured domain modules originating from transposable elements. Remarkably, these insertions contain sequences similar to tandem repeats and several stem-loops are homologous to microRNA precursors.</p

Prognostic Significance of the Myelodysplastic Syndrome-Specific Comorbidity Index (MDS-CI) in Patients with Myelofibrosis: A Retrospective Study.

In myelofibrosis, comorbidities (CMs) add prognostic information independently from the Dynamic International Prognostic Scoring System (DIPSS). The Myelodysplastic Syndrome-Specific Comorbidity Index (MDS-CI) offers a simple tool for CM assessment as it is calculable after having performed a careful history and physical examination, a small routine chemistry panel (including creatinine and liver enzymes) and a limited set of functional diagnostics. To assess the prognostic impact of the MDS-CI in addition to the DIPSS and the Mutation-Enhanced International Prognostic Scoring System (MIPSS)-70, we performed a retrospective chart review of 70 MF patients who had not received allogeneic stem cell transplantation (primary MF, n = 51; secondary MF, n = 19; median follow-up, 40 months) diagnosed at our institution between 2000 and 2020. Cardiac diseases (23/70) and solid tumors (12/70) were the most common CMs observed at MF diagnosis. Overall survival (OS) was significantly influenced by the MDS-CI (median OS MDS-CI low (n = 38): 101 months; MDS-CI intermediate (n = 25): 50 months; and high (n = 7): 8 months; p < 0.001). The MDS-CI added prognostic information after inclusion as a categorical variable in a multivariate model together with the dichotomized DIPSS or the dichotomized MIPSS70: MDS-CI high HR 14.64 (95% CI 4.42; 48.48), p = 0.0002, and MDS-CI intermediate HR 1.97 (95% CI 0.96; 4.03), p = 0.065, and MDS-CI high HR 19.65 (95% CI 4.71; 81.95), p < 0.001, and MDS-CI intermediate HR 1.063 (95% CI 0.65; 4.06), p = 0.2961, respectively. The analysis of our small and retrospective MF cohort suggests that the MDS-CI represents a useful tool to identify MF patients with an increased vulnerability due to comorbidities. However, analyses of larger cohorts are necessary to define the value of the MDS-CI as a prognostic tool in comparison with other comorbidity indices

Vigorous Intermittent Lifestyle Physical Activity and Cancer Incidence Among Nonexercising Adults: The UK Biobank Accelerometry Study

IMPORTANCE: Vigorous physical activity (VPA) is a time-efficient way to achieve recommended physical activity (PA) for cancer prevention, although structured longer bouts of VPA (via traditional exercise) are unappealing or inaccessible to many individuals. OBJECTIVES: To evaluate the dose-response association of device-measured daily vigorous intermittent lifestyle physical activity (VILPA) with incident cancer, and to estimate the minimal dose required for a risk reduction of 50% of the maximum reduction. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort analysis of 22 398 self-reported nonexercising adults from the UK Biobank accelerometry subsample. Participants were followed up through October 30, 2021 (mortality and hospitalizations), or June 30, 2021 (cancer registrations). EXPOSURES: Daily VILPA of up to 1 and up to 2 minutes, assessed by accelerometers worn on participants' dominant wrist. MAIN OUTCOMES AND MEASURES: Incidence of total cancer and PA-related cancer (a composite outcome of 13 cancer sites associated with low PA levels). Hazard ratios and 95% CIs were estimated using cubic splines adjusted for age, sex, education level, smoking status, alcohol consumption, sleep duration, fruit and vegetable consumption, parental cancer history, light- and moderate-intensity PA, and VPA from bouts of more than 1 or 2 minute(s), as appropriate. RESULTS: The study sample comprised 22 398 participants (mean [SD] age, 62.0 [7.6] years; 10 122 [45.2%] men and 12 276 [54.8%] women; 21 509 [96.0%] White individuals). During a mean (SD) follow-up of 6.7 (1.2) years (149 650 person-years), 2356 total incident cancer events occurred, 1084 owing to PA-related cancer. Almost all (92.3%) of VILPA was accrued in bouts of up to 1 minute. Daily VILPA duration was associated with outcomes in a near-linear manner, with steeper dose-response curves for PA-related cancer than total cancer incidence. Compared with no VILPA, the median daily VILPA duration of bouts up to 1 minute (4.5 minutes per day) was associated with an HR of 0.80 (95% CI, 0.69-0.92) for total cancer and 0.69 (95% CI, 0.55-0.86) for PA-related cancer. The minimal dose was 3.4 minutes per day for total (HR, 0.83; 95% CI, 0.73-0.93) and 3.7 minutes for PA-related (HR, 0.72; 95% CI, 0.59-0.88) cancer incidence. Findings were similar for VILPA bout of up to 2 minutes. CONCLUSIONS AND RELEVANCE: The findings of this prospective cohort study indicate that small amounts of VILPA were associated with lower incident cancer risk. Daily VILPA may be a promising intervention for cancer prevention in populations not able or motivated to exercise in leisure time

Vigorous Intermittent Lifestyle Physical Activity and Cancer Incidence Among Nonexercising Adults: The UK Biobank Accelerometry Study

IMPORTANCE Vigorous physical activity (VPA) is a time-efficient way to achieve recommended physical activity (PA) for cancer prevention, although structured longer bouts of VPA (via traditional exercise) are unappealing or inaccessible to many individuals. OBJECTIVES To evaluate the dose-response association of device-measured daily vigorous intermittent lifestyle physical activity (VILPA) with incident cancer, and to estimate the minimal dose required for a risk reduction of 50% of the maximum reduction. DESIGN, SETTING, AND PARTICIPANTS This was a prospective cohort analysis of 22 398 self-reported nonexercising adults from the UK Biobank accelerometry subsample. Participants were followed up through October 30, 2021 (mortality and hospitalizations), or June 30, 2021 (cancer registrations). EXPOSURES Daily VILPA of up to 1 and up to 2 minutes, assessed by accelerometers worn on participants’ dominant wrist. MAIN OUTCOMES AND MEASURES Incidence of total cancer and PA-related cancer (a composite outcome of 13 cancer sites associated with low PA levels). Hazard ratios and 95% CIs were estimated using cubic splines adjusted for age, sex, education level, smoking status, alcohol consumption, sleep duration, fruit and vegetable consumption, parental cancer history, light- and moderate-intensity PA, and VPA from bouts of more than 1 or 2 minute(s), as appropriate. RESULTS The study sample comprised 22 398 participants (mean [SD] age, 62.0 [7.6] years; 10 122 [45.2%] men and 12 276 [54.8%] women; 21 509 [96.0%] White individuals). During a mean (SD) follow-up of 6.7 (1.2) years (149 650 person-years), 2356 total incident cancer events occurred, 1084 owing to PA-related cancer. Almost all (92.3%) of VILPA was accrued in bouts of up to 1 minute. Daily VILPA duration was associated with outcomes in a near-linear manner, with steeper dose-response curves for PA-related cancer than total cancer incidence. Compared with no VILPA, the median daily VILPA duration of bouts up to 1 minute (4.5 minutes per day) was associated with an HR of 0.80 (95% CI, 0.69-0.92) for total cancer and 0.69 (95% CI, 0.55-0.86) for PA-related cancer. The minimal dose was 3.4 minutes per day for total (HR, 0.83; 95% CI, 0.73-0.93) and 3.7 minutes for PA-related (HR, 0.72; 95% CI, 0.59-0.88) cancer incidence. Findings were similar for VILPA bout of up to 2 minutes. CONCLUSIONS AND RELEVANCE The findings of this prospective cohort study indicate that small amounts of VILPA were associated with lower incident cancer risk. Daily VILPA may be a promising intervention for cancer prevention in populations not able or motivated to exercise in leisure time.publishedVersio

2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery

Authors/Task Force Members: Christa Boer (EACTA Chairperson)(Netherlands), Michael I. Meesters (Netherlands), Milan Milojevic (Netherlands), Umberto Benedetto (UK), Daniel Bolliger (Switzerland), Christian von Heymann (Germany), Anders Jeppsson (Sweden), Andreas Koster (Germany), Ruben L. Osnabrugge (Netherlands), Marco Ranucci (Italy), Hanne Berg Ravn (Denmark), Alexander B.A. Vonk (Netherlands), Alexander Wahba (Norway), Domenico Pagano (EACTS Chairperson)(UK),. Document Reviewers: Moritz W.V. Wyler von Ballmoos (USA), Mate Petricevic (Croatia), Arie Pieter Kappetein (Netherlands), Miguel Sousa-Uva (Portugal), Georg Trummer (Germany), Peter M. Rosseel (Netherlands), Michael Sander (Germany), Pascal Colson (France), Adrian Bauer (Germany)