Validation of the United Kingdom copy-number alteration classifier in 3239 children with B-cell precursor ALL

Genetic abnormalities provide vital diagnostic and prognostic information in pediatric acute lymphoblastic leukemia (ALL) and are increasingly used to assign patients to risk groups. We recently proposed a novel classifier based on the copy-number alteration (CNA) profile of the 8 most commonly deleted genes in B-cell precursor ALL. This classifier defined 3 CNA subgroups in consecutive UK trials and was able to discriminate patients with intermediate-risk cytogenetics. In this study, we sought to validate the United Kingdom ALL (UKALL)-CNA classifier and reevaluate the interaction with cytogenetic risk groups using individual patient data from 3239 cases collected from 12 groups within the International BFM Study Group. The classifier was validated and defined 3 risk groups with distinct event-free survival (EFS) rates: good (88%), intermediate (76%), and poor (68%) (P < .001). There was no evidence of heterogeneity, even within trials that used minimal residual disease to guide therapy. By integrating CNA and cytogenetic data, we replicated our original key observation that patients with intermediate-risk cytogenetics can be stratified into 2 prognostic subgroups. Group A had an EFS rate of 86% (similar to patients with good-risk cytogenetics), while group B patients had a significantly inferior rate (73%, P < .001). Finally, we revised the overall genetic classification by defining 4 risk groups with distinct EFS rates: very good (91%), good (81%), intermediate (73%), and poor (54%), P < .001. In conclusion, the UKALL-CNA classifier is a robust prognostic tool that can be deployed in different trial settings and used to refine established cytogenetic risk groups

Short water restriction episode in lactating Alpine and Saanen goats

This project aims to assess the effect of a short episode of water restriction on high producing lactating goats. Water was withheld from eight Saanen and eight Alpine goats after the afternoon milking and until the following morning, on two consecutive days. Water and feed intake, body weight and major blood parameters were assessed daily for one day before, during water restriction, and two days after. Milk production and composition was also measured on a daily basis. The results showed that the animals experienced some dehydration due to the treatment, although they were able to maintain a total water intake similar to the control values recorded on day 1. A drop in feed intake was observed on the days of water restriction although body weight was not affected. Several blood indicators also pointed to the state of dehydration the animals were experiencing namely the increase in albumin, urea, osmolality and Na+. The goats were able to maintain milk production although milk composition was altered; milk urea and lactose increased under water restriction thus keeping milk isotonic with the blood. The observed changes reflect the activated mechanisms that limit body water loss and prevent further dehydration. It was concluded that high producing goats were able to sustain two short consecutive cycles of dehydration and rehydration, as indicated by their maintained body weight and milk production, with only transient physiological and milk changes

Mild heat stress and short water restriction treatment in lactating Alpine and Saanen goats

Heat and water stress are rampant challenges in animal production as a result of climate change. Sixteen lactating goats of the Alpine and Saanen breeds were subjected to water restriction for 16 h on two consecutive days followed by rehydration, along with naturally rising temperature that culminated by the end of an experimental period of one week. Data were collected from the animals on four separate days representing their status under control conditions when temperature was still within their comfort zone, on the second day of the water restriction treatment, 24 h after rehydration and finally on the day when ambient temperature was above the normal average. Animals showed an increase in rectal temperature with time as ambient temperature increased. The heat stress was reflected by the decrease in pCO2 and HCO3 concentrations consistent with the onset of panting, while milk production was maintained but the concentration of major milk components decreased. Water stress, on the other hand, led to hemoconcentration with increased osmolality, Na+, urea, glucose and albumin concentrations and an increase in milk lactose. The changes in blood parameters were reversed 24 h after rehydration but were slightly lower than normal, indicating the need for more than 24 h to re-adjust water balance in these lactating animals. Finally, the latency between first feeding and the following drinking event after return from milking showed that the shortest latency was under the water restriction treatment indicating thirst, in addition, a trend for shorter latency before drinking over the experimental period was observed in response to the rise in temperature. This experiment showed the capacity of these highly productive breeds to withstand mild water and heat stress. However, subtle changes in physiology and milk composition warrant further research into their effect on milk quality and animal welfare