Acquisition of a simple motor skill: task-dependent adaptation and long-term changes in the human soleus stretch reflex.

Changing the H reflex through operant conditioning leads to CNS multisite plasticity and can affect previously learned skills. To further understand the mechanisms of this plasticity, we operantly conditioned the initial component (M1) of the soleus stretch reflex. Unlike the H reflex, the stretch reflex is affected by fusimotor control, comprises several bursts of activity resulting from temporally dispersed afferent inputs, and may activate spinal motoneurons via several different spinal and supraspinal pathways. Neurologically normal participants completed 6 baseline sessions and 24 operant conditioning sessions in which they were encouraged to increase (M1up) or decrease (M1down) M1 size. Five of eight M1up participants significantly increased M1; the final M1 size of those five participants was 143 ± 15% (mean ± SE) of the baseline value. All eight M1down participants significantly decreased M1; their final M1 size was 62 ± 6% of baseline. Similar to the previous H-reflex conditioning studies, conditioned reflex change consisted of within-session task-dependent adaptation and across-session long-term change. Task-dependent adaptation was evident in conditioning session 1 with M1up and by session 4 with M1down. Long-term change was evident by session 10 with M1up and by session 16 with M1down. Task-dependent adaptation was greater with M1up than with the previous H-reflex upconditioning. This may reflect adaptive changes in muscle spindle sensitivity, which affects the stretch reflex but not the H reflex. Because the stretch reflex is related to motor function more directly than the H reflex, M1 conditioning may provide a valuable tool for exploring the functional impact of reflex conditioning and its potential therapeutic applications. NEW & NOTEWORTHY Since the activity of stretch reflex pathways contributes to locomotion, changing it through training may improve locomotor rehabilitation in people with CNS disorders. Here we show for the first time that people can change the size of the soleus spinal stretch reflex through operant conditioning. Conditioned stretch reflex change is the sum of task-dependent adaptation and long-term change, consistent with H-reflex conditioning yet different from it in the composition and amount of the two components.

Precision Measurement of the Radiative ß Decay of the Free Neutron.

The standard model predicts that, in addition to a proton, an electron, and an antineutrino, a continuous spectrum of photons is emitted in the ß decay of the free neutron. We report on the RDK II experiment which measured the photon spectrum using two different detector arrays. An annular array of bismuth germanium oxide scintillators detected photons from 14 to 782 keV. The spectral shape was consistent with theory, and we determined a branching ratio of 0.00335±0.00005[stat]±0.00015[syst]. A second detector array of large area avalanche photodiodes directly detected photons from 0.4 to 14 keV. For this array, the spectral shape was consistent with theory, and the branching ratio was determined to be 0.00582±0.00023[stat]±0.00062[syst]. We report the first precision test of the shape of the photon energy spectrum from neutron radiative decay and a substantially improved determination of the branching ratio over a broad range of photon energies.

Endothelial function and insulin sensitivity during acute non-esterified fatty acid elevation: Effects of fat composition and gender.

BACKGROUND AND AIMS: We have reported that adverse effects on flow-mediated dilation of an acute elevation of non-esterified fatty acids rich in saturated fat (SFA) are reversed following addition of long-chain (LC) n-3 polyunsaturated fatty acids (PUFA), and hypothesised that these effects may be mediated through alterations in insulin signalling pathways. In a subgroup, we explored the effects of raised NEFA enriched with SFA, with or without LC n-3 PUFA, on whole body insulin sensitivity (SI) and responsiveness of the endothelium to insulin infusion. METHODS AND RESULTS: Thirty adults (mean age 27.8 y, BMI 23.2 kg/m(2)) consumed oral fat loads on separate occasions with continuous heparin infusion to elevate NEFA between 60 and 390 min. For the final 150 min, a hyperinsulinaemic-euglycaemic clamp was performed, whilst FMD and circulating markers of endothelial function were measured at baseline, pre-clamp (240 min) and post-clamp (390 min). NEFA elevation during the SFA-rich drinks was associated with impaired FMD (P = 0.027) whilst SFA + LC n-3 PUFA improved FMD at 240 min (P = 0.003). In males, insulin infusion attenuated the increase in FMD with SFA + LC n-3 PUFA (P = 0.049), with SI 10% greater with SFA + LC n-3 PUFA than SFA (P = 0.041). CONCLUSION: This study provides evidence that NEFA composition during acute elevation influences both FMD and SI, with some indication of a difference by gender. However our findings are not consistent with the hypothesis that the effects of fatty acids on endothelial function and SI operate through a common pathway. This trial was registered at clinical trials.gov as NCT01351324 on 6th May 2011.

New limit on time-reversal violation in beta decay.

We report the results of an improved determination of the triple correlation DP·(p(e)×p(v)) that can be used to limit possible time-reversal invariance in the beta decay of polarized neutrons and constrain extensions to the standard model. Our result is D=[-0.96±1.89(stat)±1.01(sys)]×10(-4). The corresponding phase between gA and gV is ϕAV=180.013°±0.028° (68% confidence level). This result represents the most sensitive measurement of D in nuclear ß decay.

Trans fatty acids, insulin resistance and diabetes.

The possible relationship between consumption of trans fatty acids (TFAs) and risk of insulin resistance or development of diabetes mellitus type II has been considered by a number of human and animal studies over the past decade. This review evaluates the evidence, and concludes that there is limited evidence for a weak association at high TFA intakes, but very little convincing evidence that habitual exposure as part of a standard western diet has a significant contribution to risk of diabetes or insulin resistance. The possibility of increased risk for individuals with particular genotypes (such as the FABP2 Thr54 allele) is of interest, but further work would be required to provide sufficient evidence of any association.

Trans fatty acids and weight gain.

Increasing rates of obesity have stimulated research into possible contributing factors, including specific dietary components such as trans fatty acids (TFAs). This review considers the evidence for an association between TFA intake and weight gain. It concludes that there is limited but consistent evidence from epidemiological studies, and from a primate model, that increased TFA consumption may result in a small additional weight gain. Data from a long-term study in a primate model suggest that TFA may have a greater adipogenic effect than cis monounsaturated fatty acids; however, there are currently inadequate mechanistic data to provide a comprehensive and plausible explanation for any such metabolic differences between the types of fatty acids.

Invited article: development of high-field superconducting Ioffe magnetic traps.

We describe the design, construction, and performance of three generations of superconducting Ioffe magnetic traps. The first two are low current traps, built from four racetrack shaped quadrupole coils and two solenoid assemblies. Coils are wet wound with multifilament NbTi superconducting wires embedded in epoxy matrices. The magnet bore diameters are 51 and 105 mm with identical trap depths of 1.0 T at their operating currents and at 4.2 K. A third trap uses a high current accelerator-type quadrupole magnet and two low current solenoids. This trap has a bore diameter of 140 mm and tested trap depth of 2.8 T. Both low current traps show signs of excessive training. The high current hybrid trap, on the other hand, exhibits good training behavior and is amenable to quench protection.

Preparation of liposomes from milk fat globule membrane phospholipids using a microfluidizer.

The isolation of milk fat globule membrane (MFGM) material from buttermilk on a commercial scale has provided a new ingredient rich in phospholipids and sphingolipids. An MFGM-derived phospholipid fraction was used to produce liposomes via a high-pressure homogenizer (Microfluidizer). This technique does not require the use of solvents or detergents, and is suitable for use in the food industry. The liposome dispersion had an average hydrodynamic diameter of 95 nm, with a broad particle-size distribution. Increasing the number of passes through the Microfluidizer, increasing the pressure, or reducing the phospholipid concentration all resulted in a smaller average liposome diameter. Changing these variables did not have a significant effect on the polydispersity of the dispersion. Electron microscopy showed that the dispersions formed had a range of structures, including unilamellar, multilamellar, and multivesicular liposomes. The composition of the MFGM phospholipid material is different from that of the phospholipids usually used for liposome production in the pharmaceutical and cosmetic industries. The MFGM-derived fraction comprises approximately 25% sphingomyelin, and the fatty acids are primarily saturated and monounsaturated. These differences are likely to affect the properties of the liposomes produced from the phospholipid material, and it may be possible to exploit the unique composition of the MFGM phospholipid fraction in the delivery of bioactive ingredients in functional foods.

The Fundamental Neutron Physics Facilities at NIST.

The program in fundamental neutron physics at the National Institute of Standards and Technology (NIST) began nearly two decades ago. The Neutron Interactions and Dosimetry Group currently maintains four neutron beam lines dedicated to studies of fundamental neutron interactions. The neutrons are provided by the NIST Center for Neutron Research, a national user facility for studies that include condensed matter physics, materials science, nuclear chemistry, and biological science. The beam lines for fundamental physics experiments include a high-intensity polychromatic beam, a 0.496 nm monochromatic beam, a 0.89 nm monochromatic beam, and a neutron interferometer and optics facility. This paper discusses some of the parameters of the beam lines along with brief presentations of some of the experiments performed at the facilities.

Determination of the Neutron Lifetime Using Magnetically Trapped Neutrons.

We report progress on an experiment to measure the neutron lifetime using magnetically trapped neutrons. Neutrons are loaded into a 1.1 T deep superconducting Ioffe-type trap by scattering 0.89 nm neutrons in isotopically pure superfluid (4)He. Neutron decays are detected in real time using the scintillation light produced in the helium by the beta-decay electrons. The measured trap lifetime at a helium temperature of 300 mK and with no ameliorative magnetic ramping is substantially shorter than the free neutron lifetime. This is attributed to the presence of neutrons with energies higher than the magnetic potential of the trap. Magnetic field ramping is implemented to eliminate these neutrons, resulting in an [Formula: see text] trap lifetime, consistent with the currently accepted value of the free neutron lifetime.

Proposed Measurement of the Beta-Neutrino Correlation in Neutron Decay.

Currently, the beta-neutrino asymmetry has the largest uncertainty (4 %) of the neutron decay angular correlations. Without requiring polarimetry this decay parameter can be used to measure λ (ga/gv ), test Cabibbo-Kobayashi-Maskawa (CKM) unitarity limit scalar and tensor currents, and search for Charged Vector Current (CVC) violation. We propose to measure the beta-neutrino asymmetry coeffcient, a, using time-of-flight for the recoil protons. We hope to achieve a systematic uncertainty of σa / a ≈ 1.0 %. After tests at Indiana University's Low Energy Neutron Source (LENS), the apparatus will be moved to the National Institute of Standards and Technology (NIST) where the measurement can achieve a statistical uncertainty of 1 % to 2 % in about 200 beam days.

Detecting the Radiative Decay Mode of the Neutron.

Beta decay of the neutron into a proton, electron, and electron antineutrino is occasionally accompanied by the emission of a photon. Despite decades of detailed experimental studies of neutron beta-decay, this rare branch of a fundamental weak decay has never been observed. An experiment to study the radiative beta-decay of the neutron is currently being developed for the NG-6 fundamental physics endstation at the National Institute of Standards and Technology (NIST) Center for Neutron Research (NCNR). The experiment will make use of the existing apparatus for the NIST proton-trap lifetime experiment, which can provide substantial background reduction by providing an electron-proton coincidence trigger. Tests and design of a detector for gamma-rays in the 10 keV to 200 keV range are under development. The need for a large solid-angle gamma-ray detector that can operate in a strong magnetic field and at low temperature has led us to consider scintillating crystals in conjunction with avalanche photodiodes. The motivation and experimental technique will be discussed.

A Backscatter Suppressed Electron Detector for the Measurement of "a".

A new method of measuring the electron-antineutrino angular correlation coefficient, little "a", from neutron decay-to be performed at the National Institute of Standards and Technology-will require an electron spectrometer that strongly suppresses backscattered electrons. A prototype consisting of six trapezoidal veto detectors arranged around a plastic scintillator has been tested with an electron beam produced by a Van de Graaff accelerator. The results of this test and its implications for the little "a" measurement are discussed.

Can the standard gamble and rating scale be used to measure quality of life in rhinoconjunctivitis? Comparison with the RQLQ and SF-36.

BACKGROUND: With interest in health economics growing, it is important to know whether utilities may be used to measure health-related quality of life in patients with rhinoconjunctivitis. The objective was to compare the validity and measurement properties of disease-specific versions of the standard gamble and rating scale with those of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the Short-Form 36 (SF-36). METHODS: One hundred adults with symptomatic rhinoconjunctivitis participated in a 5 week observational study, completing the standard gamble, rating scale, RQLQ and SF-36 at baseline and after 1 and 5 weeks. Symptom diaries were completed for 1 week before each follow-up visit. RESULTS: Reliability was highest for the RQLQ (intraclass correlation coefficient = 0.97), followed by the rating scale (0.75), the SF-36 physical (0.75), the SF-36 mental (0.74) and the standard gamble (0.12). The responsiveness index was highest for the RQLQ (0.76), followed by the rating scale (0.56) and the SF-36 mental (0.28). Both cross-sectional and longitudinal validity were strongest for the RQLQ and the rating scale. CONCLUSIONS: Both the rating scale and the RQLQ have strong evaluative and discriminative properties. The SF-36 has acceptable discriminative properties but its evaluative properties are poor. All measurement properties for the standard gamble are inadequate. Poor correlation between the standard gamble and the rating scale indicates that utilities cannot be derived from rating scale data.

Compressing Spin-Polarized (3)He With a Modified Diaphragm Pump.

Nuclear spin-polarized (3)He gas at pressures on the order of 100 kPa (1 bar) are required for several applications, such as neutron spin filters and magnetic resonance imaging. The metastability-exchange optical pumping (MEOP) method for polarizing (3)He gas can rapidly produce highly polarized gas, but the best results are obtained at much lower pressure (~0.1 kPa). We describe a compact compression apparatus for polarized gas that is based on a modified commercial diaphragm pump. The gas is polarized by MEOP at a typical pressure of 0.25 kPa (2.5 mbar), and compressed into a storage cell at a typical pressure of 100 kPa. In the storage cell, we have obtained 20 % to 35 % (3)He polarization using pure (3)He gas and 35 % to 50 % (3)He polarization using (3)He-(4)He mixtures. By maintaining the storage cell at liquid nitrogen temperature during compression, the density has been increased by a factor of four.

Quality of life in patients with allergic rhinitis.

LEARNING OBJECTIVES: Reading this article will familiarize the practitioner with ongoing efforts to measure the effects of allergic rhinitis symptoms and its treatments on the health-related quality of life (HRQOL) of patients. The reader will learn about instruments used to collect HRQOL data, results of studies showing the burden of illness and the effects of treatments on HRQOL, and efforts to interpret the clinical relevance of changes in HRQOL status. DATA SOURCES: Information was gleaned from articles listed in MEDLINE regarding HRQOL in allergic rhinitis between 1966 and 2000 (English language only), and from the personal experiences of the authors. STUDY SELECTION: Questionnaire validation studies and representative controlled trials employing measures to assess the effects of allergic rhinitis symptoms and its treatments on HRQOL are described. RESULTS FROM THIS REVIEW: Allergic rhinitis symptoms can have detrimental effects on the physical, psychologic, and social aspects of patients' lives. Clinical trial data suggest a variety of pharmacologic therapies can significantly improve HRQOL in patients with allergic rhinitis. Validated questionnaires are now available that can easily be used in clinical practice to measure the effects of interventions on HRQOL for individual patients. CONCLUSIONS: Evaluating the effects of interventions on HRQOL may be particularly important in a non-life-threatening condition such as rhinitis. Health-related quality of life measures can be used to indicate the risk/benefit and the cost/benefit ratios of competing treatment options. Clinicians and policy makers are already using HRQOL data to evaluate results of medical interventions to guide patient management and reimbursement decisions.

Effect of 60 mg twice-daily fexofenadine HCl on quality of life, work and classroom productivity, and regular activity in patients with chronic idiopathic urticaria.

The effect of 60 mg twice-daily fexofenadine HCl on health-related quality of life and productivity at work, in the classroom, and during daily activities in patients with moderate to severe chronic idiopathic urticaria symptoms was studied in two identical, 4-week, placebo-controlled, multicenter clinical trials. Patients self-administered the Dermatology Life Quality Index (score, 0-30) and the Work Productivity and Activity Impairment instrument (0%-100%). In both trials, improvements in Dermatology Life Quality Index scores in fexofenadine-treated patients (N = 169) were statistically significant compared with placebo (P < or =.0002). Similarly, improvements in productivity scores with fexofenadine 60 mg twice daily were statistically superior to placebo at work (n = 120, P < or =.0152) and in performance of daily activities (n = 166, P < or =.0002). There was a trend toward improved classroom productivity (n = 26) with fexofenadine. We conclude fexofenadine 60 mg twice daily improves health-related quality of life, increases work productivity, and improves performance of daily activities in patients with moderate to severe chronic idiopathic urticaria.

Demonstration of a compact compressor for application of metastability-exchange optical pumping of 3He to human lung imaging.

Hyperpolarized gas magnetic resonance imaging has recently emerged as a method to image lungs, sinuses, and the brain. The best lung images to date have been produced using hyperpolarized 3He, which is produced by either spin-exchange or metastability-exchange optical pumping. For hyperpolarized gas MRI, the metastable method has demonstrated higher polarization levels and higher polarizing rates, but it requires compression of the hyperpolarized gas. Prior to this work, compression of hyperpolarized gas had only been accomplished using a large, complex and expensive apparatus. Here, human lung ventilation images are presented that were obtained using a compact compressor that is relatively simple and inexpensive. For this test, 1.1 bar-L of 15% hyperpolarized 3He gas was produced at the National Institute of Standards and Technology using a modified commercial diaphragm pump. The hyperpolarized gas was transported to the University of Pennsylvania in a holding field provided by a portable solenoid.

Development and validation of the mini Rhinoconjunctivitis Quality of Life Questionnaire.

BACKGROUND: The 28-item Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) has strong measurement properties but for large clinical trials, surveys and practice monitoring, where high efficiency is important, a shorter questionnaire is needed. OBJECTIVE: To develop and validate an abbreviated version of the RQLQ. METHODS: Using five RQLQ databases, items with high item-item correlations were combined and then the highest scoring items were selected for the MiniRQLQ (14 questions). There are five domains: activity limitations (standardized), practical problems and nose symptoms, eye symptoms and other symptoms. The MiniRQLQ, which is self-administered, was tested in a 5-week observational study in 100 adults with symptomatic rhinoconjunctivitis. Patients completed the MiniRQLQ, the RQLQ, and other measures of health status at baseline, 1 and 5 weeks. RESULTS: In patients whose rhinoconjunctivitis was stable between clinic visits, reliability (reproducibility and ability to discriminate between patients of different impairment) was very acceptable for the MiniRQLQ (ICC = 0.93) but not quite as good as for the RQLQ (ICC = 0.97). Responsiveness to change in clinical status was better with the MiniRQLQ than the RQLQ (P = 0. 044). Construct validity (correlation with other indices of health status) was strong for both the MiniRQLQ and the RQLQ. Concordance between the two instruments was high (ICC = 0.87). CONCLUSIONS: The MiniRQLQ has strong measurement properties and measures the same construct as the original RQLQ. The choice of questionnaire should depend on the task at hand.

Once-daily fexofenadine HCl improves quality of life and reduces work and activity impairment in patients with seasonal allergic rhinitis.

BACKGROUND: Fexofenadine HCl (Allegra, Telfast) is approved in the US for twice-daily dosing for treatment of seasonal allergic rhinitis. OBJECTIVE: To determine the effect of once-daily fexofenadine HCl on patient-reported quality of life and impairment at work, in the classroom, and in daily activities due to seasonal allergic rhinitis symptoms. METHODS: This placebo-controlled, double-blind, randomized study included patients aged 12 to 65 years with moderate-to-severe seasonal allergic rhinitis symptoms. Outcomes were assessed using self-administered questionnaires at baseline, week 1, and week 2. Outcome measures included change from baseline in: overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score; individual RQLQ domain scores; work, classroom, and daily activity impairment measured using the Work Productivity and Activity Impairment (WPAI) instrument; and ratings in 3 generic health domains from the SF-36 Health Survey. RESULTS: Intent to treat efficacy analyses included 845 patients from 40 sites. Patients receiving either 120 or 180 mg QD fexofenadine HCl reported significantly greater improvement (P < or = .006) in overall RQLQ score than patients receiving placebo. Similarly, both fexofenadine treatment groups reported significantly greater reductions in overall work impairment and daily activity impairment compared with the placebo group (P < or = .004). There was a trend for improvement in classroom impairment with fexofenadine treatment, although differences from placebo were not statistically significant. Generic health measures demonstrated fexofenadine HCl treatment had a positive effect on general health. CONCLUSION: Once-daily fexofenadine HCl, 120 or 180 mg, significantly improved patient-reported quality of life and reduced performance impairment in work and daily activities due to seasonal allergic rhinitis symptoms compared with placebo.