Observations at the End of Days by Michael Hall

Systolic dysfunction in cardiac-specific ligand-inducible MerCreMer transgenic mice

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At one site the subjects were transported to and from the metabolic chamber by automobile under supervision. The energy and macronutrient composition for each day of both the BD and KD menus was verified by chemical analysis Covance Laboratories. Most of the food was prepared at the Pennington Biomedical Research Center metabolic kitchen, frozen, and shipped to the study sites, where fresh produce was added and the meals were prepared for consumption according to standardized procedures.

Both the BD and KD menus contained minimal quantities of processed food, and, despite the large differences in macronutrient composition and sugar content, the BD did not include large quantities of added or liquid sugars. In that regard, the BD may have differed somewhat from the customary diets of these subjects. Sample menus for 1 d of each diet are included in the Supplemental Materials. The energy intake was determined weekly for each subject during the initial BD period by using the average EE chamber for the previous week and rounding upward to the nearest 50 kcal.

Table 1 presents the 7-d average diet compositions during the isocaloric BD and KD periods. The macronutrient proportions determined by chemical analyses were consistent with the values calculated by the nutrient analysis software used to design the diets. All subjects were confined to the metabolic ward throughout the study with no access to outside food.

Subjects knew that it was imperative that they eat all of the food provided. If they were not able to eat a study food, they were instructed to notify the study dietitian immediately so that other arrangements could be considered. Dietitians and health technicians met with the subjects regularly to discuss the diet and assess compliance.

Meals were consumed in a common area under observation of the research staff, and participants were not allowed to leave the table during the meals. All meal trays were checked after consumption, and any food that was not consumed was weighed and subsequent meals were adjusted for previously uneaten food.

See the Supplemental Materials for a detailed derivation of the indirect calorimetry equations and their parameterization Supplemental Table 1 for both the BD and KD periods. Indirect calorimetry calculations are affected by the end products of protein oxidation Interestingly, unlike prolonged fasting, in which the ratio of nitrogen contained in urea plus creatinine to ammonia can decrease substantially from the standard ratio of During the KD period, the equations were adjusted as shown in Equation 2 to account for urinary ketone excretion, K excr:.

SEE was determined by the lowest EE over a continuous min period between the hours of and Other components of EE, including energy cost of cycling exercise at a clamped intensity EE exercise , EE when not moving EE sedentary , physical activity expenditure on days inside the metabolic chamber PAE chamber , spontaneous physical activity inside the metabolic chamber SPA , and awake and fed thermogenesis AFT , were defined as described in the Supplemental Materials and Supplemental Figures 1 and 2. The procedures used to adjust the primary EE data for measured changes in body weight and composition are also described in the Supplemental Materials.

An aliquot of the stock solution was saved for dilution to be analyzed along with each set of urine samples. The water was weighed to the nearest 0.

Why aren't those kids in class?

The prescribed dose was 1. Spot urine samples were collected daily. Isotopic enrichments of urine samples were measured by isotope ratio mass spectrometry. The average CO 2 production rate rCO 2 can be estimated from the rate constants describing the exponential disappearance of the labeled 18 O and D water isotopes k O and k D in repeated spot urine samples collected over several days and were corrected for previous isotope doses. We used the parameters of Racette et al. We quantified the physical activity EE on nonchamber days as shown in Equation Body weight and height were measured to the nearest 0.

See Supplemental Table 2 for the description of the methods and assay statistics for the various blood and urine measurements. Because acetoacetate could be lost from the urine as a result of non-enzymatic decarboxylation to acetone, it is possible that ketone excretion may have been underestimated because of acetone evaporation from the h urine collection containers. If a substantial amount of acetoacetate had been lost from the urine samples, then the acetoacetate fraction of total ketones would be decreased in urine compared with the blood.

This did not happen. Furthermore, the measured urinary ketone excretion was commensurate with the circulating ketone concentrations 15 , suggesting that the measured total ketone excretion was not severely affected by loss of acetoacetate. Statistical analyses were performed with the use of SAS version 9.

We also tested a first-order autoregressive covariance pattern, and the results were unchanged. Study site was not a significant determinant when included in the mixed model, and its inclusion had no significant effect on the primary endpoints. Data are therefore reported without adjusting for study site.

Missing data were not imputed because the repeated-measures mixed-model procedure is robust to data missing at random Outlier data points were excluded from the analyses and treated as missing data. Seventeen men 10 black or African American, 5 white, 1 Asian, and 1 Hispanic successfully completed the screening phase of the study see Supplemental Figure 3 for the study flow diagram.

The diets were well tolerated, and all of the study food was consumed at each meal. Compliance with the daily prescribed cycling exercise was excellent in all but 3 subjects whose accelerometry data indicated that they sometimes failed to perform the exercise on non-chamber days. The subjects lost 0. Body composition and overall energy balance. Weight loss was accelerated during the first 2 wk of the KD, but the rate of body fat loss slowed during this period.

During the final 2 wk of the KD, both the rates of body weight and fat loss were similar to baseline. Introduction of the KD was followed by a rapid additional 1. Over the entire d KD period, the total weight lost was 2. All other data points from these subjects were retained in the analyses. This was not the same subject who was an outlier for the body fat mass changes described above. The data were analyzed by using a repeated-measures mixed model. AFT, awake and fed thermogenesis; BW adj, adjusted for measured changes in body weight; DXA adj, adjusted for measured changes in body composition; EE chamber , total daily energy expenditure measured during repeated stays in metabolic chambers; EE DLW , average energy expenditure measured by doubly labeled water; EE exercise , energy cost of cycling exercise at a clamped intensity; EE sedentary , energy expenditure when not moving; PAE chamber , physical activity expenditure on days inside the chamber; PAE nonchamber , physical activity expenditure on days outside the chamber; SEE, sleeping energy expenditure; SPA, spontaneous physical activity inside the metabolic chamber; h RQ, daily respiratory quotient.

Because EE is known to be proportional to body weight and even more strongly related to fat-free mass 19 , we adjusted EE chamber for the observed weight and body composition changes as described in the Supplemental Materials. Note that the statistical analyses presented in the main text and Table 2 used a repeated-measures mixed model rather than pairwise Bonferroni-adjusted comparisons with the final BD day. BD, high-carbohydrate baseline diet; EE chamber , total daily energy expenditure measured during repeated stays in metabolic chambers; KD, low-carbohydrate ketogenic diet; RQ, respiratory quotient; SEE, sleeping energy expenditure.

Table 2 and Figure 3C show that the h RQ decreased significantly from 0. The changes in h RQ were similar to the changes in daily food quotient calculated by chemical analysis of the diet. However, this difference in energy imbalance between diet periods calculated by DLW should be interpreted with caution since these exploratory endpoints were also subject to multiple comparisons with the DXA determined energy imbalances during both diet periods.

Urinary nitrogen excretion increased by 1. The time course of the changes in urinary nitrogen excretion showed that the increased protein utilization occurred within the first week of the KD and persisted until day 11 not shown. Excretion of both urea and ammonia significantly increased during the KD, whereas creatinine excretion was unchanged Table 3.

Figure 4 shows the changes in plasma ketones i. After the KD, there was an increased availability of circulating ketones and FFAs, a trend towards decreased triglycerides, no significant changes in circulating glucose or glycerol, and no significant change in overall circulating energy. Table 4 presents the overnight fasted plasma concentrations during the BD and KD periods. Fasting glucose was not significantly different between the diets, whereas glucagon significantly increased and C-peptide, insulin, and triglycerides significantly decreased during the KD.

Leptin was significantly decreased during the KD period.

Michael Hall (musician)

Thyroid-stimulating hormone and free thyroxine concentrations were significantly increased during the KD phase, whereas both free and total tri-iodothyronine were significantly decreased. Changes in circulating plasma fuel sources in the overnight fasted state. Plasma ketones calculated as the sum of acetoacetate and beta hydroxybutyrate A and FFAs B both significantly increased during the KD compared with those in the final BD day, whereas glucose C and glycerol D were unchanged from baseline.

Plasma triglycerides E tended to decrease during the KD, and the overall circulating energy F was unchanged. Note that the statistical analyses presented in the main text and Table 4 used a repeated-measures mixed-model rather than pairwise Bonferroni-adjusted comparisons with the final BD day.

Overnight fasted plasma concentrations measured during the BD and KD periods 1. Furthermore, the body weight and composition adjustments likely overestimated the EE changes during the KD because much of the weight loss was likely from water rather than loss of metabolically active tissues. Our study adds to the literature addressing the perennial question: A conventional view is that the proportion of carbohydrate to fat in the diet has a physiologically negligible effect on EE when dietary protein and energy intake are held constant 8.

Our data do not support EE increases of that magnitude. Several controlled feeding studies have demonstrated significant differences in EE between isocaloric diets with differences in dietary protein 23 — Unless accompanied by an increase in dietary protein 22 , 26 , carbohydrate restriction has not previously been observed to increase EE. Mathematical model simulations predicted that cutting dietary carbohydrates to very low amounts would reverse this trend and lead to slightly increased EE The rapid increase in SEE and EE chamber within the first week of the KD may have been caused by increased hepatic oxygen consumption proportional to the rate of ketogenesis The KD likely also increased the flux through the energy-requiring gluconeogenic pathway as well as the triglyceride fatty acid cycle, both of which would be expected to slightly increase EE 26 , EE may have decreased subsequently as gluconeogenesis declined with the brain shifting away from glucose toward ketone oxidation 15 , 41 , Decreased insulin secretion per se may also result in an adaptive suppression of EE Furthermore, the overall state of negative energy balance, decreased circulating concentrations of thyroid hormones, and decreased h catecholamine secretion all favor decreased EE.

The carbohydrate—insulin model predicts a greater rate of body fat loss during the KD period. Our data do not support this prediction because body fat loss slowed on transition to the KD, possibly because of augmented utilization of body protein, as indicated by the increased urinary nitrogen excretion that persisted until day 11 of the KD period.

The rate of fat loss during the final 2 wk of the KD was similar to that of the baseline period.

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These mechanistic questions deserve further study, but it is clear that regulation of adipose tissue fat storage is multifaceted and that insulin does not always play a predominant role A major limitation of our study is the unintentional weight loss. This occurred despite confining the subjects to metabolic wards and our best efforts to maintain constant activity levels by prescribing 90 min of fixed intensity stationary cycling exercise every day.

It seems to work. Certainly the Michael Hall pupils seem to be a supremely content, confident and articulate lot who say they are used to alarming people who don't expect them to be able to string whole sentences together without choking on the traditional teenage mix of bile and hormones. And how do people react when they discover that the youngsters are from the Steiner school? But the laughter is tinged with understanding. They are aware that their school is different. We don't wear uniforms. You're treated more like an individual in class, so if they know you've got a problem with something, they'll come up to you and ask, and then try to explain it in a different way," says Alistair.

Still, knowing that behind them are people who hold a fairly odd set of beliefs nags at me as I sit in on various classes. In America, there are those who view "the Steiners" as a cult and some campaign against federal funding for the schools as a violation of the separation of church and state.

Introduction

From the pained look on Gillman's and Van-Manen's faces, it's apparent that they have been confronted with the "cult" word before. Van-Manen, a former Steiner student himself in Holland, emphasises that anthroposophy informs a teacher's approach though it is not necessary to subscribe to everything Steiner said, and some staff do not , but is not taught as a subject at any of the schools.

No way would you find me part of anything like that, because the moment you say that, there's a feeling of dogma, of having to do certain things.

12 very Irish observations about President Michael D Higgins

The whole point of anthroposophy is the freedom. Not as in 'do what you like' but as in coming to your own conclusions, both as adults and as children. Gillman objects to the secrecy implied in the term. But there's nothing hidden or concealed about it. There's a picture of what educating a child is about, but I think that can be sustained completely independently [of anthroposophy].

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It's an open, objective thing and something you either choose or not. But teachers who believe in reincarnation and in children having astral bodies - can they see how that might be unsettling for the parent in the street? But it's just terminology. We might say among ourselves, 'astral body'. Well, another word is 'soul' and everybody uses the word soul. Or use 'psyche', if you're more comfortable with that.

But we do have these terms and I accept that it is very off-putting. Do you think it's such a bad thing that teachers who work with your child think that your child comes from somewhere, brings certain qualities and then goes off somewhere else? No, it's a good thing. It doesn't really matter whether you accept it. The point is that a child has certain qualities. We try to work with those, bring them out, and feel that those qualities will go out and have a life beyond.

The class of year-olds is clear on the issue of beliefs and religion in the school. It's history - makes you realise what people thought"; "I'm not religious"; "We do say a verse every morning, but it's much more about the spirit of God, which could be anything"; "Could be me!

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