Normal tissue exposure and second malignancy risk in vertebral-body-sparing craniospinal irradiation.

The purpose of this study was to compare dose to anterior organs at risk (OARs) and quantify the risk of developing secondary malignancy (SMN) in pediatric patients treated with vertebral-body-sparing (VBS) vs vertebral body (VB) pencil beam scanning proton craniospinal irradiation (CSI). Comparative plans of VBS and VB CSI were created for 10 previously treated patients. Dose-volume histograms were used to evaluate dose to OARs. Absolute excess risk of SMN was calculated according to the organ-specific, radiation-induced cancer incidence based on the organ equivalent dose. OAR dosimetric parameters and absolute excess risk of SMN were compared for VBS and VB plans using the Kruskal-Wallis H test (α = 0.05). VBS CSI leads to significantly lower radiation dose to the heart, esophagus, kidney, liver and bowel. Excluding the vertebral body also significantly decreases the absolute excess risk of SMN for liver, esophagus and bowel. For these reasons, implementation of VBS pencil beam scanning proton CSI should be considered.

A Donders' Like Law for Arm Movements: The Signal not the Noise.

Experiments were done to determine whether the starting position of the arm influences its final configuration (posture) when pointing to, or grasping, targets located within the common workspace of the arm. Subjects were asked to point to, or grasp, each of six targets from five, or seven, widely spaced starting positions. We found that the variability (standard deviation) of the arm's configuration, measured as the angle of inclination of the plane delimited by the arm and forearm, averaged about 4° for comfortable speed pointing movements and was only slightly higher for fast pointing movements. Comfortable speed reaches to grasp the targets were associated with slightly lower variability (3.5°) in final arm configuration. The average variability of repeated movements to a given target from a single start position (3.5°) was comparable to that of movements from different start positions to the same target (4.2°). A small difference in final arm inclination angle, averaged across all subjects and targets, of 3° was found between two pairs of starting positions. This small and possibly idiosyncratic effect is within the "noise" of final arm orientation variability for repeated movements (i.e., 3.5°). Thus, the variability of final posture is not for the most part due to different start positions, it is inherent to movement per se. Our results reconcile conflicting previous studies and are consistent with past works suggesting that a Donders' like law is indeed largely upheld for unconstrained visually guided arm movements. In summary, considering movements within a typical work space, when the hand is moved voluntarily to a given spatial location the posture of the arm is nearly the same regardless of its starting position. Importantly, variability is inherent to the rule.

Chronic hindlimb suspension unloading markedly decreases turnover rates of skeletal and cardiac muscle proteins and adipose tissue triglycerides.

We previously showed that a single bolus of "doubly-labeled" water ((2)H2 (18)O) can be used to simultaneously determine energy expenditure and turnover rates (synthesis and degradation) of tissue-specific lipids and proteins by modeling labeling patterns of protein-bound alanine and triglyceride-bound glycerol (Bederman IR, Dufner DA, Alexander JC, Previs SF. Am J Physiol Endocrinol Metab 290: E1048-E1056, 2006). Using this novel method, we quantified changes in the whole body and tissue-specific energy balance in a rat model of simulated "microgravity" induced by hindlimb suspension unloading (HSU). After chronic HSU (3 wk), rats exhibited marked atrophy of skeletal and cardiac muscles and significant decrease in adipose tissue mass. For example, soleus muscle mass progressively decreased 11, 43, and 52%. We found similar energy expenditure between control (90 ± 3 kcal · kg(-1)· day(-1)) and hindlimb suspended (81 ± 6 kcal/kg day) animals. By comparing food intake (∼ 112 kcal · kg(-1) · day(-1)) and expenditure, we found that animals maintained positive calorie balance proportional to their body weight. From multicompartmental fitting of (2)H-labeling patterns, we found significantly (P < 0.005) decreased rates of synthesis (percent decrease from control: cardiac, 25.5%; soleus, 70.3%; extensor digitorum longus, 44.9%; gastrocnemius, 52.5%; and adipose tissue, 39.5%) and rates of degradation (muscles: cardiac, 9.7%; soleus, 52.0%; extensor digitorum longus, 27.8%; gastrocnemius, 37.4%; and adipose tissue, 50.2%). Overall, HSU affected growth of young rats by decreasing the turnover rates of proteins in skeletal and cardiac muscles and adipose tissue triglycerides. Specifically, we found that synthesis rates of skeletal and cardiac muscle proteins were affected to a much greater degree compared with the decrease in degradation rates, resulting in large negative balance and significant tissue loss. In contrast, we found a small decrease in adipose tissue triglyceride synthesis paired with a large decrease in degradation, resulting in smaller negative energy balance and loss of fat mass. We conclude that HSU in rats differentially affects turnover of muscle proteins vs. adipose tissue triglycerides.