Acute phase reaction to LPS induced mastitis in early lactation dairy cows fed nitrogenic, glucogenic or lipogenic diets.

The availability of certain macronutrients is likely to influence the capacity of the immune system. Therefore, we investigated the acute phase response to intramammary (i.mam.) LPS in dairy cows fed either a nitrogenic diet (n = 10) high in crude protein, a glucogenic diet (n = 11) high in carbohydrates and glucogenic precursors, or a lipogenic diet (n = 11) high in lipids. Thirty-two dairy cows were fed one of the dietary concentrates directly after calving until the end of trial at 27 ± 3 DIM (mean ± SD). In wk 3 of lactation, 20 µg of LPS was i.mam. injected in one quarter, and sterile NaCl (0.9%) in the contralateral quarter. Milk samples of the LPS challenged and control quarter were taken hourly from before (0 h) until 9 h after LPS challenge, and analyzed for milk amyloid A (MAA), haptoglobin (Hp), and IL-8. In addition, blood samples were taken in the morning, and composite milk samples at morning and evening milkings from 1 d before until 3 d after LPS challenge, and again on d 9 to determine serum amyloid A (SAA) and Hp in blood, and MAA and Hp in milk. The mRNA abundance of various immunological and metabolic factors in blood leukocytes was quantified by RT-qPCR from samples taken at -18 h, -1 h, 6 h, 9 h and 23 h relative to LPS application. The dietary concentrates did not affect any of the parameters in blood, milk, and leukocytes. The IL-8 was increased from 2 h, Hp from 2 to 3 h, and MAA from 6 h relative to the LPS administration in the milk of the challenged quarter and remained elevated until 9 h. The MAA and Hp were also increased at 9 h after LPS challenge in whole udder composite milk, whereas Hp and SAA in blood were increased only after 23 h. All 4 parameters were decreased again on d 9. Similar for all groups, the mRNA abundance of Hp and the heat shock protein family A (HSP70) increased after the LPS challenge, while the mRNA expression of the tumor necrosis factor α (TNF) and the leukocyte integrin β 2 subunit (CD18) were decreased at 6 h after LPS challenge. The glucose transporter (GLUT)1 mRNA abundance decreased after LPS, whereas that of the GLUT3 increased, and that of the GLUT4 was not detectable. The mRNA abundance of GAPDH was increased at 9 h after LPS and remained elevated. The APP response was detected earlier in milk compared with blood indicating mammary production. However, immunological responses to LPS were not affected by the availability of specific macronutrients provided by the different diets

Effect of different dietary regimens at dry-off on performance, metabolism, and immune system in dairy cows.

Concentrate withdrawal and feed restriction are commonly used to reduce milk production and to facilitate dry-off, but may impair immune function in dairy cows. We investigated the effect of feed rations providing different amounts of nutrients in combination with feed restriction on performance, endocrine, and metabolic responses, as well as on leukocyte function before and after abrupt dry-off. Forty-three cows were studied from d 12 before until d 6 after dry-off (56 d before scheduled calving). Cows were fed experimental concentrates rich in crude protein (nitrogenic, n = 14), glucogenic precursors (glucogenic, n = 14), or lipids (lipogenic, n = 15). On d 3 before dry-off, total feed allowance was restricted to 50% in half of the animals of each dietary group, whereas feed allowance remained unchanged in the other animals. Performance parameters (milk yield, milk composition, and dry matter intake) were recorded, and daily blood and milk samples were taken and analyzed for various metabolic and endocrine parameters. Additionally, activity and mRNA abundance of several genes in leukocytes were measured at selected time points before and after feed restriction and dry-off, respectively. Feed restriction immediately resulted in a negative energy balance and decreased milk production. Concomitantly, concentrations of nonesterified fatty acids increased, whereas insulin, insulin-like growth factor-1, and glucagon decreased. After dry-off, energy balance turned positive and plasma nonesterified fatty acids decreased. Plasma glucose, insulin, and insulin-like growth factor-1 concentrations increased in all groups after dry-off. Glucose, insulin, and glucagon concentrations in plasma were higher in nonrestricted compared with restricted animals after dry-off. The experimental concentrate types marginally affected the investigated metabolic and endocrine factors, with the exception of elevated milk and plasma urea concentrations in cows fed the nitrogenic concentrate. Chemotactic and phagocytic activity of leukocytes were not affected by diets, feed restriction, or dry-off. Likewise, blood leukocyte mRNA abundance encoding for tumor necrosis factor α (TNF), heat shock protein family A (HSP70), and the glucose transporters (GLUT) 1 and 3 remained unchanged throughout the study period. Overall, the short-term negative energy balance induced by feed restriction was temporarily accompanied by metabolic adaptations, but did not alter the studied factors related to the immune system. Metabolic and endocrine adaptations supporting milk synthesis were continued during the first days after dry-off despite cessation of milking. Thus, the abrupt dry-off resulted in a short-term increase of glucose and triglyceride concentrations, with a delayed endocrine response to re-establish nutrient homeostasis in blood

Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study

Background: Relapsed or refractory diffuse large B-cell and mantle-cell lymphoma have a poor prognosis. The EPOCH regimen and rituximab monotherapy have demonstrated activity as salvage therapies. Because of their non-overlapping toxicity, we evaluated their combination as salvage therapy in a phase II study. Patients and methods: Patients with relapsed or refractory CD20-positive large B-cell and mantle-cell lymphoma were offered treatment with rituximab 375 mg/m2 intravenously (i.v.) on day 1, doxorubicin 15 mg/m2 as a continuous i.v. infusion on days 2-4, etoposide 65 mg/m2 as a continuous i.v. infusion on days 2-4, vincristine 0.5 mg as a continuous i.v. infusion on days 2-4, cyclophosphamide 750 mg/m2 i.v. on day 5 and prednisone 60 mg/m2 orally on days 1-14. Results: Fifty patients, with a median age of 56 years (range 23-72), entered the study. Twenty-five had primary diffuse large B-cell lymphoma, 18 transformed large B-cell lymphoma and seven mantle-cell lymphoma. The median number of prior chemotherapy regimens was 1.7 (range one to four). The median number of treatment cycles was four (range one to six). Possible treatment-related death occurred in two patients. Objective responses were obtained in 68% of patients (28% complete responses, 40% partial responses). Nineteen patients received consolidating high-dose chemotherapy with autologous stem-cell transplantation. The median follow-up was 33 months. Three patients developed a secondary myelodysplastic syndrome. The median overall survival was 17.9 months; the projected overall survival at 1, 2 and 3 years was 66, 42 and 35%, respectively. The median event-free survival was 11.8 months; the projected event-free survival at 1, 2 and 3 years was 50, 30 and 26%, respectively. Conclusion: The rituximab-EPOCH regimen is effective and well tolerated, even in extensively pretreated patients with relapsed or refractory large B-cell lymphoma and mantle-cell lymphom

Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma

Background: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. Patients and methods: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients. Results: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5). Conclusions: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distres

Analytic frameworks for assessing dialogic argumentation in online learning environments

Over the last decade, researchers have developed sophisticated online learning environments to support students engaging in argumentation. This review first considers the range of functionalities incorporated within these online environments. The review then presents five categories of analytic frameworks focusing on (1) formal argumentation structure, (2) normative quality, (3) nature and function of contributions within the dialog, (4) epistemic nature of reasoning, and (5) patterns and trajectories of participant interaction. Example analytic frameworks from each category are presented in detail rich enough to illustrate their nature and structure. This rich detail is intended to facilitate researchers’ identification of possible frameworks to draw upon in developing or adopting analytic methods for their own work. Each framework is applied to a shared segment of student dialog to facilitate this illustration and comparison process. Synthetic discussions of each category consider the frameworks in light of the underlying theoretical perspectives on argumentation, pedagogical goals, and online environmental structures. Ultimately the review underscores the diversity of perspectives represented in this research, the importance of clearly specifying theoretical and environmental commitments throughout the process of developing or adopting an analytic framework, and the role of analytic frameworks in the future development of online learning environments for argumentation

Quantifying Collaboration Quality in Face-to-Face Classroom Settings Using MMLA

Producción CientíficaThe estimation of collaboration quality using manual observation and coding is a tedious and difficult task. Researchers have proposed the automation of this process by estimation into few categories (e.g., high vs. low collaboration). However, such categorical estimation lacks in depth and actionability, which can be critical for practitioners. We present a case study that evaluates the feasibility of quantifying collaboration quality and its multiple sub-dimensions (e.g., collaboration flow) in an authentic classroom setting. We collected multimodal data (audio and logs) from two groups collaborating face-to-face and in a collaborative writing task. The paper describes our exploration of different machine learning models and compares their performance with that of human coders, in the task of estimating collaboration quality along a continuum. Our results show that it is feasible to quantitatively estimate collaboration quality and its sub-dimensions, even from simple features of audio and log data, using machine learning. These findings open possibilities for in-depth automated quantification of collaboration quality, and the use of more advanced features and algorithms to get their performance closer to that of human coders.European Union via the European Regional Development Fund and in the context of CEITER and Next-Lab (Horizon 2020 Research and Innovation Programme, grant agreements no. 669074 and 731685)Junta de Castilla y León (Project VA257P18)Ministerio de Ciencia, Innovación y Universidades (Project TIN2017-85179-C3-2-R

Cell-free DNA analysis in healthy individuals by next-generation sequencing: a proof of concept and technical validation study.

Pre-symptomatic screening of genetic alterations might help identify subpopulations of individuals that could enter into early access prevention programs. Since liquid biopsy is minimally invasive it can be used for longitudinal studies in healthy volunteers to monitor events of progression from normal tissue to pre-cancerous and cancerous condition. Yet, cell-free DNA (cfDNA) analysis in healthy individuals comes with substantial challenges such as the lack of large cohort studies addressing the impact of mutations in healthy individuals or the low abundance of cfDNA in plasma. In this study, we aimed to investigate the technical feasibility of cfDNA analysis in a collection of 114 clinically healthy individuals. We first addressed the impact of pre-analytical factors such as cfDNA yield and quality on sequencing performance and compared healthy to cancer donor samples. We then confirmed the validity of our testing strategy by evaluating the mutational status concordance in matched tissue and plasma specimens collected from cancer patients. Finally, we screened our group of healthy donors for genetic alterations, comparing individuals who did not develop any tumor to patients who developed either a benign neoplasm or cancer during 1-10 years of follow-up time. To conclude, we have established a rapid and reliable liquid biopsy workflow that allowed us to study genomic alterations with a limit of detection as low as 0.08% of variant allelic frequency in healthy individuals. We detected pathogenic cancer mutations in four healthy donors that later developed a benign neoplasm or invasive breast cancer up to 10 years after blood collection. Even though larger prospective studies are needed to address the specificity and sensitivity of liquid biopsy as a clinical tool for early cancer detection, systematic screening of healthy individuals will help understanding early events of tumor formation

Short-term memory for emotional faces in dysphoria

The study aimed to determine if the memory bias for negative faces previously demonstrated in depression and dysphoria generalises from long- to short-term memory. A total of 29 dysphoric (DP) and22 non-dysphoric (ND) participants were presented with a series of faces and asked to identify the emotion portrayed (happiness, sadness, anger, or neutral affect). Following a delay, four faces were presented (the original plus three distractors) and participants were asked to identify the target face. Half of the trials assessed memory for facial emotion, and the remaining trials examined memory for facial identity. At encoding, no group differences were apparent. At memory testing, relative to ND participants, DP participants exhibited impaired memory for all types of facial emotion and for facial identity when the faces featured happiness, anger, or neutral affect, but not sadness. DP participants exhibited impaired identity memory for happy faces relative to angry, sad, and neutral, whereas ND participants exhibited enhanced facial identity memory when faces were angry. In general, memory for faces was not related to performance at encoding. However, in DP participants only, memory for sad faces was related to sadness recognition at encoding. The results suggest that the negative memory bias for faces in dysphoria does not generalise from long- to short-term memory