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Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a phenotypic shift in the tumor-associated macrophage population and increased the expression of MHC class II transcripts. We further demonstrated that ERK5 S496A knock-in mice, which are phosphorylation deficient at the S496 residue, mimicked the exercise effect when unexercised, yet when exercised, these mice displayed a reversal in the effect of exercise on tumor growth and macrophage polarization compared with wild-type mice. Taken together, our results reveal tumor-specific differences in the immune response to exercise and show that ERK5 signaling via the S496 residue plays a crucial role in exercise-induced tumor microenvironment changes. See related Spotlight by Betof Warner, p. 1158.

IntroductionAdolescent and young adult (AYA) survivors who have been treated for cancer during childhood and adolescence are at great risk of the physical, psychological, and social consequences of cancer and its associated treatments. However, compliance with long-term follow-up is low. One possible explanation is that follow-up care fails to meet the expectations of AYA survivors. This study explored the specific supportive care needs of AYA survivors of childhood and adolescent cancer five years post-diagnosis.MethodsSemi-structured interviews were conducted with 15 AYA aged 15 to 25 years old. Thematic analyses were conducted to establish categories of supportive care needs and classify them as being met or unmet.ResultsParticipants reported between 2 and 20 specific needs (M = 11), including needs concerning fertility issues and reassurance regarding relapse (each mentioned by 67% of AYA), followed by the need for locomotor care, follow-up coordination and multidisciplinary care (60% of AYA for each). Participants also reported needs regarding social relationships, administration and finance, and academic and professional domains. Most (69%) of these needs were reportedly unmet, including need of information about cancer repercussions and follow-up, support in managing fatigue and sleep problems, psychological assistance, and support from peers.DiscussionThe supportive care needs are still considerable and varied in AYA survivors of childhood and adolescent cancer 5 years post-diagnosis and are largely unmet. As unmet supportive care needs highlight the gap between available care in follow-up and the real needs of AYA survivors, a better understanding of their supportive care needs and unmet needs, thanks to systematic needs assessment, would enable long-term follow-up care to be adapted, thereby improving compliance and quality of life.

Abstract Though wind power predictions have been consistently improved in the last decade, persistent reasons for remaining uncertainties are sudden large changes in wind speed, so‐called ramps. Here, we analyse the occurrence of ramp events in a wind farm in Eastern Germany and the performance of a wind power prediction tool in forecasting these events for forecasting horizons of 15 and 30 min. Results on the seasonality of ramp events and their diurnal cycle are presented for multiple ramp definition thresholds. Ramps were found to be most frequent in March and April and least frequent in November and December. For the analysis, the wind power prediction tool is fed by different wind velocity forecast products, for example, numerical weather prediction (NWP) model and measurement data. It is shown that including observational wind speed data for very short‐term wind power forecasts improves the performance of the power prediction tool compared to the NWP reference, both in terms of ramp detection and in decreasing the mean absolute error between predicted and generated wind power. This improvement is enhanced during ramp events, highlighting the importance of wind observations for very short‐term wind power prediction.

We present the temperature-dependent reaction rate coefficients of CN ^− and C _3 N ^− with atomic hydrogen in the temperature range from 7 to 290 K, measured in a 16-pole radio-frequency ion trap. The rate of C _3 N ^− with H steadily increases toward lower temperatures, while the rate coefficients for the CN ^− + H system show a sudden change around 160 K. Fits to the data were performed to determine temperature-dependent reaction rate coefficients. The fits reveal a rate coefficient of $4.1{(3)\times {10}^{-10}(T/300)}^{-0.31(6)}$ cm ^3 s ^−1 for C _3 N ^− + H. For CN ^− , we determined a rate coefficient for the temperature regime below 160 K of $3.2{(4)\times {10}^{-10}(T/300)}^{-0.31(11)}$ cm ^3 s ^−1 . Given our present results, higher rate coefficients than previously reported must be assumed for the modeling of cold interstellar environments involving these H atom reactions.

Abstract A joint pre‐ and post‐equalization scheme is proposed for an optical intensity modulation and direct detection (IM/DD) system. At the transmitter, a linear feed‐forward pre‐equalizer with just two, three, or four filter taps is suggested to limit the transmitter's complexity and to allow the use of multi‐level modulation. Finally, this concept is combined with a zero‐forcing post‐equalizer at the receiver. By utilizing numerical optimization to design the multi‐level signals, the intersymbol‐interference originating from the channel is mitigated pre‐equalizer taps, a reduction of 3 % in received power compared to a conventional zero‐forcing design is achieved. The equalization scheme is tailored for an optical IM/DD system. Therefore, the specific power constraints of such a setup are taken into account in the equalizer design process. In contrast to existing research, the approach is tested for a multi‐mode fiber system, which is affected by increased inter‐symbol interference due to modal dispersion. The simulation results show that by shifting a small portion of the equalization complexity to the transmitter side, the required optical power to reach a bit‐error rate of 10−3$10^{-3}$ is reduced by 7.3% for zero‐forcing and 6.8% for minimum mean square error post‐equalizers. the noise increase by the post‐equalizer is reduced by 6.9 % when including the pre‐equalizer with just two filter taps. Compared to an equalization scheme that solely relies on a zero‐forcing post‐equalizer, the suggested joint pre‐ and post‐equalization scheme is able to improve the bit‐error rate performance by an average of 7.15 %. A testbed experiment with a 250 m multi‐mode fiber channel and a data rate of 2.5 Gbps operating at 1550 nm confirms these simulation results.

Drastic events such as pandemics, earthquakes or other disasters not only threaten the immediate living conditions of people but also indirect circumstances such as energy supply, infrastructure and food production. To ensure that damage and failures in these areas do not lead to a disaster, special requirements are placed on this critical infrastructure. In this context resilience, which is defined as the resistance of a system to external effects, is required. A field that is indeed part of the critical infrastructure, but which has not been considered as intensively as the energy sector, is food production.The investigation focuses on how fundamental principles of thermodynamics, system theory and reliability theory can be applied to the modelling of food production processes to obtain a measure of resilience. Using known state and process variables from thermodynamics and electrical power engineering, analogous variables are derived for the food industry. These variables serve as an evaluation standard for a quality measure Q. In addition to system-theoretical considerations, it is investigated how existing evaluation criteria of power engineering, such as System Average Interruption Duration Index (SAIDI) and Customer Average Interruption Duration Index (CAIDI), can be transferred to food production.Design: The investigation focuses on how fundamental principles of thermodynamics, system theory and reliability theory can be applied to the modelling of food production processes to obtain a measure of resilience. Using known state and process variables from thermodynamics and electrical power engineering, analogous variables are derived for the food industry.Purpose: Drastic events such as pandemics, earthquakes or other disasters not only threaten the immediate living conditions of people but also indirect circumstances such as energy supply, infrastructure and food production. To ensure that damage and failures in these areas do not lead to a disaster, special requirements are placed on this critical infrastructure. In this context resilience is required.Findings: The aforementioned state and process variables serve as an evaluation standard for a quality measure Q. In addition to system-theoretical considerations, it is investigated how existing evaluation criteria of power engineering, such as SAIDI and CAIDI, can be transferred to food production.Originality: This paper fulfils an identified need to study a part of the critical infrastructure that has not been as extensively looked at as the energy sector, namely food production.

Lipid and fatty acid digestibility is presumably high in Channel Catfish, but data is lacking. We determined the lipid and fatty acid digestibility of traditional and alternative dietary lipids in Channel Catfish to inform lipid choice for commercial diets. Six diets contained 4% of different lipids: soybean oil (SBO), soybean oil containing conjugated linoleic acids (CLA-SBO), catfish offal oil (COO), flaxseed oil (FXO), menhaden fish oil (MFO) and poultry fat (PF). Diets were fed to Channel Catfish (150–200 g) maintained at 26.5 °C in each of six 110 L aquaria. Six hours post-prandial, feces were collected for analysis. Total lipid, crude protein and fatty acids of lyophilized feces were analyzed, and apparent digestibility coefficients (ADCs) were calculated. ADCs of lipid, saturated and monounsaturated fatty acids, linoleic acid and protein digestibility were similar among diets. CLA isomers (cis-9, trans-11 (84.1%) and trans-10, cis-12 (90%)) in the CLA-SBO diet were highly digestible. Oleic acid digestibility was highest in the PF diet. ADC was high for α-linolenic acid in the FXO diet, and for arachidonic acid and n-3 LC-PUFA in the MFO diet. Overall, total lipid digestibility was high, but ADCs of individual fatty acids differed by source.

Grazing intensity in integrated crop-livestock systems (ICLS) can affect soil aggregation and C stabilization and, consequently, the soil condition and agricultural sustainability. This study evaluate the influence of 13 years of different grazing intensities on (i) soil aggregation, (ii) C content in different aggregate size, and (iii) C and N content in different fractions of soil organic matter (SOM), in a no-tilled with integrated soybean-beef production system on a subtropical Oxisol. Treatments consisted of four steers grazing intensities defined by sward height of 10, 20, 30 and 40 cm on mixed black oat and Italian ryegrass pasture in the winter under continuous stocking, plus an ungrazed treatment, in a randomized complete block design with three replicates. Soil aggregation was not affected by grazing intensities. There was no effect of the grazing intensities on organic C content in all aggregate-size fractions and in all soil layers evaluated, being lower in microaggregates than in large and small macroaggregates. The macroaggregates were predominant, representing 97% of the soil mass, of which 74% were large macroaggregates (>2 mm). The high macroaggregates stability contributed to the lack of difference in the C and N content on free light fraction and the light occlusal fraction of SOM. Most of C and N were observed heavy fraction of SOM (53–68%), with greater stock in the no grazing compared to the grazed treatments. Even with the animal trampling in the grazed systems, the soil maintained high stability of aggregates and consequently the labile forms of SOM.

Abstract Background Mindfulness- Based Cognitive Therapy (MBCT) could be a promising psychosocial intervention for people with bipolar disorder (BD). However, little is known about the feasibility of MBCT for people with BD. In this study we explore the facilitators and barriers people with BD experience of an adapted MBCT program. Method This qualitative study is part of a large, multicenter randomized controlled trial on MBCT for BD (trial registration number: NCT03507647). The present study included 16 participants with BD who participated in an 8-week adapted MBCT program. Semi- structured interviews exploring the feasibility, with a particular focus on the bipolar symptoms, were recorded verbatim, transcribed and analyzed. For reasons of triangulation, teachers were interviewed as well. Results Participants reported different barriers and facilitators of MBCT, both generally as well as with regard to their bipolar disorder. Four key themes arose: the training itself, psychosocial factors, personal characteristics and the bipolar disorder. Themes were further divided in subthemes. Conclusion The adapted MBCT program seemed to be feasible for people with BD. Depressive symptoms often acted as a barrier for participating in MBCT, suggesting that participants might need additional support when depressed. Manic symptoms could act both as a barrier and facilitator, suggesting that the occurrence of (hypo)mania does not necessarily have to be an exclusion criterion for participation. Further clinical and research implications are suggested. Trial registration: ClinicalTrials.gov, NCT03507647. Registered 25th of April 2018, https://clinicaltrials.gov/ct2/show/NCT03507647 .

This study assessed growth, feed conversion efficiency, and fatty acid composition of three size classes of northern largemouth bass Micropterus salmoides salmoides (80 g, 105 g, and 137 g) subjected to a 35 °C water temperature for 28 days. A completely randomized design was conducted, with ten fish per tank and treatments triplicated. The trial was conducted in 180-L tanks in a recirculating system. Fish were fed a commercial diet formulated for largemouth bass consisting of 48% protein and 18% lipid at approximately 0800 and 1500 h daily. The experimental period lasted for 28 days. Water temperature was a significant contributor to the feeding and growth results observed in this study. While the 137 g group did experience some growth, the observed growth was not biologically significant during this study. The percent body weight consumed by all treatment groups was less than 0.21% day −1. Feed conversion was best for the 137 g group at 4.0 ± 0.44 compared to 5.5 ± 2.57 and 5.8 ± 2.77 for the 80 g and 105 g groups, respectively. Fatty acid profiles of the groups remained similar except eicosapentaenoic acid, which was lower in the 80 g fish. This study was the first to examine the growth of northern largemouth bass at temperatures exceeding 32 °C and suggest extended periods of exposure to 35 °C or higher water temperatures resulted in thermal stress and the inability of these fish to grow at the rates necessary to make them profitable for commercial producers.

Four commercial protein blends—Elite 60™, Elite 65™, Elite 70™, and Pro-Cision™ (HJ Baker & Bros., Inc., Tuscola, Texas, USA)—were evaluated in hybrid striped bass (HSB) for nutrient digestibility and fishmeal (FM) replacement value. A control diet was formulated like a commercial HSB feed containing 17% FM that met or exceeded the nutritional requirements of HSB. Commercial blends replaced FM in the control diets on an ideal protein basis by supplementing the first-three limiting amino acids (methionine, lysine, threonine). Diets were formulated on a digestible protein basis (38% digestible protein), isolipidic (16%), and contained 10% lipid from marine fish sources. Fish fed the control diet generally exhibited better growth and nutrient utilization responses than the other diets. Responses to the Elite™ products were intermediate, while Pro-Cision™ lagged in both digestibility and growth responses. Digestibility of gross nutrients in each of the test products did not differ significantly from those of FM, but protein was significantly more digestible in Elite 70™ compared to that of FM and Pro-Cision™. Availabilities of leucine, phenylalanine, tyrosine, and valine in Pro-Cision™ were significantly less (92.2%, 91.3%, 91.0%, and 91.5%, respectively) than those in FM (96.1%, 96.8%, 94.6%, and 94.5%, respectively). Fish fed the Pro-Cision™ diet exhibited significantly lower cumulative feed intake, average weight, and muscle ratio compared to fish fed all other diets. Elite 60™, Elite 65™, and Elite 70™ fish did not differ in intraperitoneal fat or muscle ratio compared to fish fed the control diet. Fish fed all three Elite™ diets had significantly lower average weight (52.5–57.9 g) compared to fish fed the control diet (73.2 g). There were no differences in arginine and histidine whole-body nutrient retention among dietary treatments, while other nutrient retention efficiencies did differ across treatments. Nutrient retention of the averaged essential amino acids was not significantly different in fish fed Elite 70™ compared to fish fed the control diet. There were no significant differences in lysozyme activity and mean corpuscular hemoglobin concentration among treatments. It appears that Pro-Cision™ is not an attractive alternative to FM in HSB diets considering total feed intake, growth, and nutrient and energy retentions. However, Elite 65™ and Elite 70™ may be potential FM alternatives in HSB diets despite differences in growth performance after 13-weeks.

The multiple-input and multiple-output (MIMO) technology is a promising area of research to cope up with the demands of higher data rates and capacity. In the optical communication domain, the combination of space-division multiplexing (SDM) with higher-order modulation (HOM) formats over an optical MIMO system actively addresses these challenges. By allowing multi-level signaling with limited increment in the transmitter’s complexity, a jointly designed pre- and post-equalization (PPE) for an optical MIMO system with a multi-mode fiber (MMF) link is proposed. Cost-effectiveness of the system is incorporated by utilizing intensity modulation/direct detection (IM/DD) with HOM formats such as pulse-amplitude modulation (PAM) schemes. With the aid of a numerical optimization algorithm, the proposed joint-PPE filter coefficients are optimized with respect to the MMF channel and the transmit power constraint. In contrast to existing research on the single-mode fiber (SMF) based optical systems, the effectiveness of the proposed joint-PPE filter is analyzed on an MMF link, which is considerably degraded by the modal dispersion. In the analyzed experimental scenario, the proposed joint-PPE scheme confirms to be beneficial as compared to the post-equalization only (PE-only) in terms of bit-error rate (BER) performance. Furthermore, the required average received optical power to reach a BER 10−4 by the joint-PPE scheme is improved by 2 dB with comparison to the minimum mean-squared error (MMSE) PE-only.

As the northern Largemouth bass (LMB) (Micropterus nigricans) industry shifts toward fingerling production, implementing practical feeding strategies to ensure efficient growth during high water temperatures is paramount. Twenty (12.7 ± 0.2 g) (Trial 1) and fifteen (7.2 ± 0.1 g) (Trial 2) LMB fingerlings were stocked in two recirculating systems (each containing nine tanks), acclimated to 30 °C, with one system fed daily rations of 3, 5 and 7% body weight (Trial 1), and the second system fed to satiation daily, every second day, or every third day (Trial 2), for 28 days each. All treatments were triplicated. Multiple growth metrics and lipid composition were analyzed. The 3% treatment yielded the lowest final average weight (36.05 g) and FCR (0.83), with no difference in final biomass in Trial 1 treatments. Fish fed to satiation daily and every second day produced FCRs and biomasses of 0.83 and 356.78 g, and 0.93 and 272.26 g, respectively. There were no differences in total lipid concentration, however, fatty acid profiles differed significantly between all treatments within their respective trials. Feeding LMB fingerlings 3% of total body weight or feeding daily to satiation allows for efficient growth at 30 °C and implements cost-effective feeding strategies.

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P

Introduction: Adolescent and young adult (AYA) survivors who have been treated for cancer during childhood and adolescence are at great risk of the physical, psychological, and social consequences of cancer and its associated treatments. However, compliance with long-term follow-up is low. One possible explanation is that follow-up care fails to meet the expectations of AYA survivors. This study explored the specific supportive care needs of AYA survivors of childhood and adolescent cancer five years post-diagnosis. Methods: Semi-structured interviews were conducted with 15 AYA aged 15 to 25 years old. Thematic analyses were conducted to establish categories of supportive care needs and classify them as being met or unmet. Results: Participants reported between 2 and 20 specific needs (M = 11), including needs concerning fertility issues and reassurance regarding relapse (each mentioned by 67% of AYA), followed by the need for locomotor care, follow-up coordination and multidisciplinary care (60% of AYA for each). Participants also reported needs regarding social relationships, administration and finance, and academic and professional domains. Most (69%) of these needs were reportedly unmet, including need of information about cancer repercussions and follow-up, support in managing fatigue and sleep problems, psychological assistance, and support from peers. Discussion: The supportive care needs are still considerable and varied in AYA survivors of childhood and adolescent cancer 5 years post-diagnosis and are largely unmet. As unmet supportive care needs highlight the gap between available care in follow-up and the real needs of AYA survivors, a better understanding of their supportive care needs and unmet needs, thanks to systematic needs assessment, would enable long-term follow-up care to be adapted, thereby improving compliance and quality of life. [ABSTRACT FROM AUTHOR]

Abstract Background Despite multiple pharmacological interventions, many people with bipolar disorder (BD) experience substantial residual mood symptoms, even in the absence of severe mood episodes, which have a negative impact on the course of illness and quality of life. Limited data are available on how to optimize treatment for BD, especially for those who suffer from persistent and residual depressive symptoms. Preliminary evidence suggests Mindfulness-Based Cognitive Therapy (MBCT) as a psychological treatment option for BD. This study aims to investigate whether adding MBCT to treatment as usual (TAU) will result in symptomatic and functional improvements in adults with BD compared to TAU alone. Methods/design This study is a prospective, evaluator blinded, multicenter, randomized controlled trial of MBCT + TAU and TAU alone in 160 adults with bipolar type I and type II. Assessments will be conducted at baseline (T0), mid-treatment (Tmid), and at 3 (T1), 6 (T2), 9 (T3), 12 (T4), and 15 (T5) months follow-up. Primary outcome is post-treatment severity of depressive symptoms (Inventory of Depressive Symptomatology- Clinician administered). Secondary outcomes are severity of (hypo) manic symptoms, anxiety, relapse rates, overall functioning, positive mental health, and cost-effectiveness. As possible mediators will be assessed rumination of negative affect, dampening and rumination of positive affect, mindfulness skills, and self-compassion. Discussion This study will provide valuable insight into the (cost-)effectiveness of MBCT on clinician- and self-rated symptoms of BD, relapse rates, positive mental health, and overall functioning. Trial registration NCT03507647. Registered 25th of April 2018.

Metronidazole belongs to the class of nitroimidazole molecules and has been considered as a potential radiosensitizer for radiation therapy. During the irradiation of biological tissue, secondary electrons are released that may interact with molecules of the surrounding environment. Here, we present a study of electron attachment to metronidazole that aims to investigate possible reactions in the molecule upon anion formation. Another purpose is to elucidate the effect of microhydration on electron-induced reactions in metronidazole. We use two crossed electron/molecular beam devices with the mass-spectrometric analysis of formed anions. The experiments are supported by quantum chemical calculations on thermodynamic properties such as electron affinities and thresholds of anion formation. For the single molecule, as well as the microhydrated condition, we observe the parent radical anion as the most abundant product anion upon electron attachment. A variety of fragment anions are observed for the isolated molecule, with NO2− as the most abundant fragment species. NO2− and all other fragment anions except weakly abundant OH− are quenched upon microhydration. The relative abundances suggest the parent radical anion of metronidazole as a biologically relevant species after the physicochemical stage of radiation damage. We also conclude from the present results that metronidazole is highly susceptible to low-energy electrons.

Iron overload is a significant water quality issue in many parts of the world. Therefore, we evaluated the potential toxic effects of waterborne elevated iron on largemouth bass (Micropterus salmoides), a highly valued sport and aquaculture fish species. First, a 96 h-LC50 toxicity assay was performed to understand the tolerance limit of this species to iron; and was determined to be 22.07 mg/L (as Fe3+). Thereafter, to get a better insight on the fish survival during long-term exposure to high environmental iron (HEI) (5.52 mg/L, 25% of the determined 96 h-LC50 value), a suite of physio-biochemical, nitrogenous metabolic and ion-regulatory compensatory responses were examined at 7, 14, 21 and 28 days. Results showed that oxygen consumption dropped significantly at 21 and 28 days of HEI exposure. Ammonia excretion rate (Jamm) was significantly inhibited from day 14 and remained suppressed until the last exposure period. The transcript concentration of Rhesus glycoproteins Rhcg2 declined; likely diminishing ammonia efflux out of gills. These changes were also reflected by a parallel increment in plasma ammonia levels. Under HEI exposure, ion-balance was negatively affected, manifested by reduced plasma [Na+] and parallel inhibition in branchial Na+/K+-ATPase activity. Muscle water content was elevated in HEI-exposed fish, signifying an osmo-regulatory compromise. HEI exposure also increased iron burden in plasma and gills. The iron accumulation pattern in gills was significantly correlated with a suppression of Jamm, branchial Rhcg2 expression and Na+/K+-ATPase activity. There was also a decline in the glycogen, protein and lipid reserves in the hepatic tissue from 14 days, 28 days and 21 days, respectively. Overall, we conclude that sub-lethal chronic iron exposure can impair normal physio-biochemical and ion-regulatory functions in largemouth bass. Moreover, this data set can be applied in assessing the environmental risk posed by a waterborne iron overload on aquatic life.