The role of corticosterone in human hypothalamic– pituitary–adrenal axis feedback

Objective  In humans, the glucocorticoid corticosterone circulates in blood at 10–20-fold lower levels than cortisol, but is found in higher relative amounts in postmortem brain samples. Access of cortisol and corticosterone to the central nervous system may not be equal. Additionally, the relative affinities for the glucocorticoid and mineralocorticoid receptors differ, such that corticosterone may play a significant role in human brain function. Design  We measured cortisol and corticosterone levels in paired plasma and cerebrospinal fluid (CSF) samples. To test the relative potency of cortisol vs. corticosterone on hypothalamic–pituitary–adrenal (HPA) feedback, subjects underwent a three-phase, single-blind, randomized study assessing the postmetyrapone ACTH response over 3 h to an intravenous bolus of vehicle, cortisol or corticosterone (0·15 mg/kg and 0·04 mg/kg). Participants  Outpatients undergoing diagnostic lumbar puncture who were subsequently deemed to be free of disease. Feedback was tested in healthy male volunteers. Measurements  Plasma and CSF corticosterone to cortisol ratio was calculated and the ACTH response over time after the bolus glucocorticoid measured. Results  Plasma corticosterone : cortisol was 0·069 ± 0·007; CSF corticosterone : cortisol was 0·387 ± 0·050 ( P <  0·001). Cortisol and corticosterone (0·15 mg/kg) suppressed ACTH vs. vehicle ( P =  0·002); there was no difference between corticosterone and cortisol. The 0·04 mg/kg dose had no effect on ACTH despite supraphysiological plasma corticosterone levels. Conclusions  Corticosterone contributes almost 40% of total active glucocorticoids (cortisol and corticosterone) in the CSF. Significant effects on HPA axis suppression were only seen with supraphysiological levels of corticosterone, suggesting that corticosterone is not important in this model of nonstress-induced ACTH hypersecretion, in which the effect of cortisol predominates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72329/1/j.1365-2265.2006.02540.x.pd

A glassy contribution to the heat capacity of hcp 4^4He solids

We model the low-temperature specific heat of solid $^4$He in the hexagonal closed packed structure by invoking two-level tunneling states in addition to the usual phonon contribution of a Debye crystal for temperatures far below the Debye temperature, $T < \Theta_D/50$. By introducing a cutoff energy in the two-level tunneling density of states, we can describe the excess specific heat observed in solid hcp $^4$He, as well as the low-temperature linear term in the specific heat. Agreement is found with recent measurements of the temperature behavior of both specific heat and pressure. These results suggest the presence of a very small fraction, at the parts-per-million (ppm) level, of two-level tunneling systems in solid $^4$He, irrespective of the existence of supersolidity.Comment: 11 pages, 4 figure

The effects of exercise on pain, fatigue, insomnia, and health perceptions in patients with operable advanced stage rectal cancer prior to surgery: a pilot trial

Background: Promoting quality of life (QoL) is a key priority in cancer care. We investigated the hypothesis that, in comparison to usual care, exercise post-neoadjuvant chemoradiation therapy/prior to surgical resection will reduce pain, fatigue, and insomnia, and will improve physical and mental health perceptions in patients with locally advanced stage rectal cancer. Methods: In this non-randomized controlled pilot trial, patients in the supervised exercise group (EG; Mage = 64 years; 64% male) and in the control group (CG; Mage = 72 years; 69% male) completed the European Organization for Research and Treatment of Cancer core Quality of Life questionnaire and the RAND 36-Item Health Survey three times: pre-neoadjuvant chemoradiation therapy (Time 1; nEC = 24; nCG = 11), post-neoadjuvant chemoradiation therapy/pre-exercise intervention (Time 2; nEC = 23; nCG = 10), and post-exercise intervention (Time 3; nEC = 22; nCG = 10). The 6-week exercise intervention was delivered in hospital and comprised of interval aerobic training. Patients trained in pairs three times per week for 30 to 40 minutes. Data were analyzed by Mann-Whitney tests and by Wilcoxon matched-pairs signed rank tests. Results: No significant between-group differences in change were found for any of the outcomes. In both groups, fatigue levels decreased and physical health perceptions increased from pre- to post-exercise intervention. Pain levels also decreased from pre- to post-exercise intervention, albeit not significantly. Conclusions: The findings from this study can be used to guide a more definitive trial as they provide preliminary evidence regarding the potential effects of pre-operative exercise on self-reported pain, fatigue, insomnia, and health perceptions in patients with locally advanced rectal cancer. Trial registration: This study has been registered with clinicaltrials.gov (NCT01325909; March 29, 2011)

Defects and glassy dynamics in solid He-4: Perspectives and current status

We review the anomalous behavior of solid He-4 at low temperatures with particular attention to the role of structural defects present in solid. The discussion centers around the possible role of two level systems and structural glassy components for inducing the observed anomalies. We propose that the origin of glassy behavior is due to the dynamics of defects like dislocations formed in He-4. Within the developed framework of glassy components in a solid, we give a summary of the results and predictions for the effects that cover the mechanical, thermodynamic, viscoelastic, and electro-elastic contributions of the glassy response of solid He-4. Our proposed glass model for solid He-4 has several implications: (1) The anomalous properties of He-4 can be accounted for by allowing defects to freeze out at lowest temperatures. The dynamics of solid He-4 is governed by glasslike (glassy) relaxation processes and the distribution of relaxation times varies significantly between different torsional oscillator, shear modulus, and dielectric function experiments. (2) Any defect freeze-out will be accompanied by thermodynamic signatures consistent with entropy contributions from defects. It follows that such entropy contribution is much smaller than the required superfluid fraction, yet it is sufficient to account for excess entropy at lowest temperatures. (3) We predict a Cole-Cole type relation between the real and imaginary part of the response functions for rotational and planar shear that is occurring due to the dynamics of defects. Similar results apply for other response functions. (4) Using the framework of glassy dynamics, we predict low-frequency yet to be measured electro-elastic features in defect rich He-4 crystals. These predictions allow one to directly test the ideas and very presence of glassy contributions in He-4.Comment: 33 pages, 13 figure

The effects of cancer therapies on physical fitness before oesophagogastric cancer surgery: a prospective, blinded, multi-centre, observational, cohort study [version 1; peer review: 2 approved]

Background: Neoadjuvant cancer treatment is associated with improved survival following major oesophagogastric cancer surgery. The impact of neoadjuvant chemo/chemoradiotherapy on physical fitness and operative outcomes is however unclear. This study aims to investigate the impact of neoadjuvant chemo/chemoradiotherapy on fitness and post-operative mortality. Methods: Patients with oesophagogastric cancer scheduled for chemo/chemoradiotherapy and surgery were recruited to a prospective, blinded, multi-centre, observational cohort study. Primary outcomes were changes in fitness with chemo/chemoradiotherapy, measured using cardiopulmonary exercise testing and its association with mortality one-year after surgery. Patients were followed up for re-admission at 30-days, in-hospital morbidity and quality of life (exploratory outcomes). Results: In total, 384 patients were screened, 217 met the inclusion criteria, 160 consented and 159 were included (72% male, mean age 65 years). A total of 132 patients (83%) underwent chemo/chemoradiotherapy, 109 (71%) underwent chemo/chemoradiotherapy and two exercise tests, 100 (63%) completed surgery and follow-up. A significant decline in oxygen uptake at anaerobic threshold and oxygen uptake peak was observed following chemo/chemoradiotherapy: -1.25ml.kg-1.min-1 (-1.80 to -0.69) and -3.02ml.kg-1.min-1 (-3.85 to -2.20); p<0.0001).  Baseline chemo/chemoradiotherapy anaerobic threshold and peak were associated with one-year mortality (HR=0.72, 95%CI 0.59 to 0.88; p=0.001 and HR=0.85, 0.76 to 0.95; p=0.005). The change in physical fitness was not associated with one-year mortality. Conclusion: Chemo/chemoradiotherapy prior to oesophagogastric cancer surgery reduced physical fitness. Lower baseline fitness was associated with reduced overall survival at one-year. Careful consideration of fitness prior to chemo/chemoradiotherapy and surgery is urgently needed

Linear temperature dependence of conductivity in the "insulating" regime of dilute two-dimensional holes in GaAs

The conductivity of extremely high mobility dilute two-dimensional holes in GaAs changes linearly with temperature in the insulating side of the metal-insulator transition. Hopping conduction, characterized by an exponentially decreasing conductivity with decreasing temperature, is not observed when the conductivity is smaller than $e^{2}/h$. We suggest that strong interactions in a regime close to the Wigner crystallization must be playing a role in the unusual transport.Comment: 3 pages, 2 figure

Tunnelling defect nanoclusters in hcp 4He crystals: alternative to supersolidity

A simple model based on the concept of resonant tunnelling clusters of lattice defects is used to explain the low temperature anomalies of hcp 4He crystals (mass decoupling from a torsional oscillator, shear modulus anomaly, dissipation peaks, heat capacity peak). Mass decoupling is a result of an internal Josephson effect: mass supercurrent inside phase coherent tunnelling clusters. Quantitative results are in reasonable agreement with experiments.Comment: 13 pages, 5 figure

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR