Behavioural variability, physical activity, rumination time, and milk characteristics of dairy cattle in response to regrouping

We gratefully thank the farm staff and the Lely Farm Management Support Ireland and UK manager, Mr Bas Van Santen, for technical assistance and data retrieval from the Lely T4C software database and Dr Sharon Mitchell for assistance with the laboratory analyses. This work has already been published as part of a PhD thesis (Marumo et al. (2021a)).Peer reviewe

The personalized advantage index: Translating research on prediction into individualized treatment recommendations. A demonstration

Background: Advances in personalized medicine require the identification of variables that predict differential response to treatments as well as the development and refinement of methods to transform predictive information into actionable recommendations. Objective: To illustrate and test a new method for integrating predictive information to aid in treatment selection, using data from a randomized treatment comparison. Method: Data from a trial of antidepressant medications (N = 104) versus cognitive behavioral therapy (N = 50) for Major Depressive Disorder were used to produce predictions of post-treatment scores on the Hamilton Rating Scale for Depression (HRSD) in each of the two treatments for each of the 154 patients. The patient's own data were not used in the models that yielded these predictions. Five pre-randomization variables that predicted differential response (marital status, employment status, life events, comorbid personality disorder, and prior medication trials) were included in regression models, permitting the calculation of each patient's Personalized Advantage Index (PAI), in HRSD units. Results: For 60% of the sample a clinically meaningful advantage (PAI≥3) was predicted for one of the treatments, relative to the other. When these patients were divided into those randomly assigned to their "Optimal" treatment versus those assigned to their "Non-optimal" treatment, outcomes in the former group were superior (d = 0.58, 95% CI .17-1.01). Conclusions: This approach to treatment selection, implemented in the context of two equally effective treatments, yielded effects that, if obtained prospectively, would rival those routinely observed in comparisons of active versus control treatments. © 2014 DeRubeis et al

Hsa-miRNA-765 as a key mediator for inhibiting growth, migration and invasion in fulvestrant-treated prostate cancer

Fulvestrant (ICI-182,780) has recently been shown to effectively suppress prostate cancer cell growth in vitro and in vivo. But it is unclear whether microRNAs play a role in regulating oncogene expression in fulvestrant-treated prostate cancer. Here, this study reports hsa-miR-765 as the first fulvestrant-driven, ERβ-regulated miRNA exhibiting significant tumor suppressor activities like fulvestrant, against prostate cancer cell growth via blockage of cell-cycle progression at the G2/M transition, and cell migration and invasion possibly via reduction of filopodia/intense stress-fiber formation. Fulvestrant was shown to upregulate hsa-miR-765 expression through recruitment of ERβ to the 5′-regulatory-region of hsa-miR-765. HMGA1, an oncogenic protein in prostate cancer, was identified as a downstream target of hsa-miR-765 and fulvestrant in cell-based experiments and a clinical study. Both the antiestrogen and the hsa-miR-765 mimic suppressed HMGA1 protein expression. In a neo-adjuvant study, levels of hsa-miR-765 were increased and HMGA1 expression was almost completely lost in prostate cancer specimens from patients treated with a single dose (250 mg) of fulvestrant 28 days before prostatectomy. These findings reveal a novel fulvestrant signaling cascade involving ERβ-mediated transcriptional upregulation of hsa-miR-765 that suppresses HMGA1 protein expression as part of the mechanism underlying the tumor suppressor action of fulvestrant in prostate cancer. © 2014 Leung et al

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

<p>Abstract</p> <p>Background</p> <p>In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence.</p> <p>Method</p> <p>The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at <url>http://www.seleblat.org.</url> Patients are randomly assigned to selenium yeast (200 μg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study.</p> <p>Design</p> <p>The SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial.</p> <p>Discussion</p> <p>This is the first report on a selenium randomized trial in bladder cancer patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00729287">NCT00729287</a></p

Ethical issues in autologous stem cell transplantation (ASCT) in advanced breast cancer: A systematic literature review

BACKGROUND: An effectiveness assessment on ASCT in locally advanced and metastatic breast cancer identified serious ethical issues associated with this intervention. Our objective was to systematically review these aspects by means of a literature analysis. METHODS: We chose the reflexive Socratic approach as the review method using Hofmann's question list, conducted a comprehensive literature search in biomedical, psychological and ethics bibliographic databases and screened the resulting hits in a 2-step selection process. Relevant arguments were assembled from the included articles, and were assessed and assigned to the question list. Hofmann's questions were addressed by synthesizing these arguments. RESULTS: Of the identified 879 documents 102 included arguments related to one or more questions from Hofmann's question list. The most important ethical issues were the implementation of ASCT in clinical practice on the basis of phase-II trials in the 1990s and the publication of falsified data in the first randomized controlled trials (Bezwoda fraud), which caused significant negative effects on recruiting patients for further clinical trials and the doctor-patient relationship. Recent meta-analyses report a marginal effect in prolonging disease-free survival, accompanied by severe harms, including death. ASCT in breast cancer remains a stigmatized technology. Reported health-related-quality-of-life data are often at high risk of bias in favor of the survivors. Furthermore little attention has been paid to those patients who were dying. CONCLUSIONS: The questions were addressed in different degrees of completeness. All arguments were assignable to the questions. The central ethical dimensions of ASCT could be discussed by reviewing the published literature

Behavioural variability, physical activity, rumination time, and milk characteristics of dairy cattle in response to regrouping

In the commercial dairy industry worldwide, it is common practice to periodically regroup cows as part of their management strategy within housed systems. While this animal husbandry practice is intended to improve management efficiency, cows may experience social stress as a result of the social environment changes, which may have an impact on their behavioural patterns, performance, and welfare. We investigated whether regrouping altered dairy cows’ behaviour and impacted their cortisol concentration (a physiological marker of stress), oxytocin, milk yield, and quality in a robotic milking system. Fifty-two lactating cows (17 primiparous; 35 multiparous) were moved in groups of 3–5 individuals into established pens of approximately 100 cows. Behaviour of the regrouped cows was directly observed continuously for 4 h/day across 4-time blocks (day-prior (d-1), day-of regrouping (d0), day-after (d + 1), and 6-days after (d + 6) regrouping). Cows were categorised as being with others, alone, or feeding every 2.5 min prior to the assessment of behavioural dynamics. Milk yield (MY) and composition, total daily activity, and rumination time (RUM) data were extracted from the Lely T4C management program (Lely Industries, Maassluis, the Netherlands), and milk samples were collected for cortisol and oxytocin concentration analyses; data were analysed using linear mixed-effect modelling. Primiparous cows were less likely to be interacting with others on d + 1 than d-1 compared with multiparous. However, average bout duration (minutes) between being alone and feeding activity states were similar on d-1, d + 1, and d + 6, for both primiparous and multiparous cows. A reduction in the average alone and feeding bout duration was observed on d0. Multiparous cows spent significantly more total time being alone on d0 compared to d-1. Neither regrouping nor parity statistically influenced milk DM content, energy, or cortisol concentration. Primiparous cows produced 3.80 ± 2.42 kg (12.2%) less MY on d + 1 compared to their d-1, whereas multiparous cows did not change MY. A significant decrease of 0.2% fat was found in both parity groups following regrouping and remained low up to d + 6. Daily activity in both parity groups increased significantly and RUM reduced after regrouping. A significant decrease in oxytocin concentration was observed in all cows on d + 1. The results, specifically for primiparous cows, indicated a negative impact of regrouping on social interactions, due to changes in the social environment which may lead to short-term social instability. Multiparous cows may benefit from previous regrouping experiences