Using 3D image registration to maximize the reproducibility of longitudinal bone strength assessment by HR-pQCT and finite element analysis.

We developed and validated a finite element (FE) approach for longitudinal high-resolution peripheral quantitative computed tomography (HR-pQCT) studies using 3D image registration to account for misalignment between images. This reduced variability in longitudinal FE estimates and improved our ability to measure in vivo changes in HR-pQCT studies of bone strength. INTRODUCTION: We developed and validated a finite element (FE) approach for longitudinal high-resolution peripheral quantitative computed tomography (HR-pQCT) studies using 3D rigid-body registration (3DR) to maximize reproducibility by accounting for misalignment between images. METHODS: In our proposed approach, we used the full common bone volume defined by 3DR to estimate standard FE parameters. Using standard HR-pQCT imaging protocols, we validated the 3DR approach with ex vivo samples of the distal radius (n = 10, four repeat scans) by assessing whether 3DR can reduce measurement variability from repositioning error. We used in vivo data (n = 40, five longitudinal scans) to assess the sensitivity of 3DR to detect changes in bone strength at the distal radius by the standard deviation of the rate of change (σ), where the ideal value of σ is minimized to define true change. FE estimates by 3DR were compared to estimates by no registration (NR) and slice-matching (SM). RESULTS: Group-wise comparisons of ex vivo variation (CVRMS, %) found that FE measurement precision was improved by SM (CVRMS < 0.80%) and 3DR (CVRMS < 0.62%) compared to NR (CVRMS~2%), and 3DR was advantageous as repositioning error increased. Longitudinal in vivo reproducibility was minimized by 3DR for failure load estimates (σ = 0.008 kN/month). CONCLUSION: Although 3D registration cannot negate motion artifacts, it plays an important role in detecting and reducing variability in FE estimates for longitudinal HR-pQCT data and is well suited for estimating effects of interventions in in vivo longitudinal studies of bone strength.

Effect of high-dose vitamin D supplementation on peripheral arterial calcification: secondary analysis of a randomized controlled trial.

Although high-dose vitamin D supplementation is common, effects on arterial calcification remain unexplored. Tibial artery calcification was identified and quantified over 3 years in participants randomized to 400, 4000, or 10,000 IU vitamin D3 daily. High-dose vitamin D supplementation did not affect the development or progression of arterial calcification. INTRODUCTION: To determine whether vitamin D supplementation has a dose-dependent effect on development and progression of arterial calcification. METHODS: This was a secondary analysis of the Calgary Vitamin D Study, a 3-year, double-blind, randomized controlled trial conducted at a single-center in Calgary, Canada. Participants were community-dwelling adults aged 55-70 years with serum 25-hydroxyvitamin D 30-125 nmol/L. Participants were randomized 1:1:1 to receive vitamin D3 400, 4000, or 10,000 IU/day for 3 years. Tibial artery calcification was identified and quantified (in milligrams of hydroxyapatite, mgHA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6, 12, 24, and 36 months. Changes in calcification over time and treatment group interaction were evaluated using a constrained linear mixed effects model. RESULTS: Of 311 randomized participants, 302 (400: 105, 4000: 96, 10,000: 101) were eligible for analysis of arterial calcification (54% male, mean (SD) age 62 (4) years, mean (SD) 25-hydroxyvitamin D 78.9 (19.9) nmol/L). At baseline, 85 (28%) had tibial artery calcification, and mean (95% CI) calcification quantity was 2.8 mgHA (95% CI 1.7-3.9). In these 85 participants, calcification quantity increased linearly by 0.020 mgHA/month (95% CI 0.012-0.029) throughout the study, with no evidence of a treatment-group effect (p = 0.645 for interaction). No participants developed new arterial calcifications during the study. CONCLUSIONS: In this population of community-dwelling adults who were vitamin D replete at baseline, supplementation with vitamin D 400, 4000, or 10,000 IU/day did not have differential effects on the development or progression of arterial calcification over 3 years. TRIAL REGISTRATION: clinicaltrials.gov (NCT01900860).

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. V. Effects of time zone crossings.

Daily diary records of sleep and activity, and 4-h measurements of body temperature, performance and subjective alertness were collected on board ship from 15 watchkeepers on the 4-on/8-off system, and from 28 dayworkers, on both westward and eastward transatlantic voyages. The data from a balanced sample of the subjects were analysed over selected 8-d periods of the voyages where four or five time zones were crossed. During these periods the average amount of daily sleep obtained by dayworkers on the eastward voyage was more than 1 h less than that on the westward voyage, and its quality was rated lower. Watchkeepers' main sleep was also shorter when travelling eastward, but this reduction was partially compensated for by a slightly longer secondary sleep. With the exception of subjective alertness on the eastward voyage, the basic phase of the circadian rhythms in the measured variables adjusted appropriately to the clock changes associated with the time zone crossings. The normal shape of the average daily curves was, however, altered differentially in the two directions of travel; as a result, morning levels of all variables were lower on the eastward voyage than on the westward, but evening levels were higher. These distortions of rhythm waveforms, which probably arose from a combination of endogenous and exogenous factors, add another dimension to the basic problem caused by the effects of circadian rhythms on operational efficiency in the shipboard situation. This problem can only be solved by the development of alternative watchkeeping systems which take full account of these rhythms.

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. VI. A sea trial of an alternative watchkeeping system for the merchant marine.

A trial of an alternative to the traditional 4-on/8-off watchkeeping system was made on a container ship during a round trip from Europe to the Far East. The three navigating officers on the ship operated the new system, which involved "compressed" working hours with a long unbroken period of rest, during two sections of the voyage, one of which included six stops at ports. Despite unforeseen problems arising mainly from these stops, questionnaire responses concerning the new system were not altogether unfavourable to it, and daily records kept by the officers gave some support to the hypothesis that sleep would be better than under the traditional system. However, a number of difficulties were encountered; these are discussed in relation to the design of future studies of alternative watchkeeping systems.

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. I. Watchkeeping on board ships: a methodological approach.

The safety of a ship depends substantially on its bridge watchkeepers, whose alertness and efficiency must be maintained at all hours of the day and night. Fatigue, circadian rhythms, and sleep disruption occasioned by the unusual working hours of these personnel may all affect their performance. A methodology for assessing the magnitude of this problem is proposed. The application of this methodology in a large-scale shipboard study of merchant mariners on extended voyages is then described, and details given of the techniques used to measure sleep and activity, and temporal variations in a range of physiological und psychological parameters. A summary of the data collected in the study is provided as a reference point for the reports on the different aspects of the results that follow in subsequent articles.

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. III. Rhythms in physiological functions.

Oral and rectal temperature, urinary excretion of adrenaline and noradrenaline, and heart rate were measured in 28 watchkeepers working a "4-on/8-off" routine, and in 25 dayworkers, on board ships. Readings of oral temperature were taken over 4-hourly periods of up to two weeks; the rectal temperature, urine, and heart rate data were collected on selected days within these periods. Analysis of watchkeepers' temperatures and unconjugated catecholamine excretions showed slight signs of an interactive adaptation to time of day and hours of work, but it was clear that full phase adjustment of the circadian rhythms to shifted hours of work did not occur. The "split" pattern of sleep imposed by the watch system may be a major factor in preventing complete adaptation of physiological rhythms to shift work in the shipboard situation; this problem could be overcome by devising a system that allows sleep to be taken in a single uninterrupted block each day.

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. IV. Rhythms in performance and alertness.

Performance scores on both a simple detection task and a complex visual judgment task, together with subjective alertness ratings, were collected 4-hourly from 19 watchkeepers working a "4-on/8-off" routine, and from 20 dayworkers, over consecutive days of voyages on merchant ships. Adaptation of the circadian rhythms in the measures to the shifted hours of work of the three sections of the watchkeeping crews was at best only partial. These rhythms resulted in a depression of the levels of most measures during the night hours, which was exacerbated by the effects of recent awakening from sleep. It is suggested that these unwanted variations in operational effectiveness could be largely removed by replacing the 4-on/8-off watchkeeping system, with its associated "split" sleep pattern, by one which allows a single full length sleep each day. Such a system would encourage better adaptation of the rhythms; effects of recent awakening could be avoided by the provision of an adequate "waking up" period before duty begins.

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. II. Sleep duration, and subjective ratings of sleep quality.

Sleep length and sleep quality scores were collected on board ships over periods of up to two weeks from 38 watchkeepers working a '4-on/8-off routine' and 29 dayworkers. All watchkeepers exhibited fragmented sleeping patterns, which indicated a lack of adaptation of the sleep/wakefulness cycle to the hours of work. There were only slight differences in total sleep length between watchkeepers and dayworkers, however, both groups did not obtain an adequate amount of sleep. Within the watchkeeping crews the 3rd Officers had by far the shortest sleep length. Concerning sleep quality, daytime sleep was generally given the lowest ratings, whereas sleep starting before midnight was on average evaluated as the best, both by watchkeepers and dayworkers. Watchkeeping personnel do not normally have any "days off" during a voyage so that missed sleep might even amount to a sleep deficit. A solution for this problem could perhaps be a new, stabilized system that allows a single uninterrupted sleep, which is required for full recuperation, to be taken each day.