Uniform electron gases

We show that the traditional concept of the uniform electron gas (UEG) --- a homogeneous system of finite density, consisting of an infinite number of electrons in an infinite volume --- is inadequate to model the UEGs that arise in finite systems. We argue that, in general, a UEG is characterized by at least two parameters, \textit{viz.} the usual one-electron density parameter $\rho$ and a new two-electron parameter $\eta$. We outline a systematic strategy to determine a new density functional $E(\rho,\eta)$ across the spectrum of possible $\rho$ and $\eta$ values.Comment: 8 pages, 2 figures, 5 table

The Emergence and Progression of Motor Dysfunction in Individuals at Risk of Parkinson's Disease

BACKGROUNDL: PREDICT-PD is a United Kingdom population-based study aiming to stratify individuals for future Parkinson's disease (PD) using a risk algorithm. METHODS: A randomly selected, representative sample of participants in PREDICT-PD were examined using several motor assessments, including the motor section of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-III, at baseline (2012) and after an average of 6 years of follow-up. We checked for new PD diagnoses in participants seen at baseline and examined the association between risk scores and incident sub-threshold parkinsonism, motor decline (increasing ≥5 points in MDS-UPDRS-III) and single motor domains in the MDS-UPDRS-III. We replicated analyses in two independent datasets (Bruneck and Parkinson's Progression Markers Initiative [PPMI]). RESULTS: After 6 years of follow-up, the PREDICT-PD higher-risk group (n = 33) had a greater motor decline compared with the lower-risk group (n = 95) (30% vs. 12.5%, P = 0.031). Two participants (both considered higher risk at baseline) were given a diagnosis of PD during follow-up, with motor signs emerging between 2 and 5 years before diagnosis. A meta-analysis of data from PREDICT-PD, Bruneck, and PPMI showed an association between PD risk estimates and incident sub-threshold parkinsonism (odds ratio [OR], 2.01 [95% confidence interval (CI), 1.55–2.61]), as well as new onset bradykinesia (OR, 1.69 [95% CI, 1.33–2.16]) and action tremor (OR, 1.61 [95% CI, 1.30–1.98]). CONCLUSIONS: Risk estimates using the PREDICT-PD algorithm were associated with the occurrence of sub-threshold parkinsonism, including bradykinesia and action tremor. The algorithm could also identify individuals whose motor examination experience a decline over time

The effect of sex, stature, and limb length on the preferred walk-to-run transition speed

Background The preferred walk-to-run transition speed (PTS) for healthy adults is approximately 2 m∙s-1, however, PTS is influenced by anthropometric factors. Yet despite known sex differences in anthropometrics, studies have reported no sex differences in PTS. Research question Do stature and limb length affect PTS in the same way for both male and female healthy adults? Methods Thirty-seven (19 female) non-injured adults volunteered for this study. Participants completed a walk-to-run transition protocol, where the treadmill speed was increased from 1.2 m∙s-1 to 2.2 m∙s-1, in increments of 0.1 m∙s-1 every two minutes. An independent t-test compared PTS between sexes. Multiple regression analysis determined the effect of sex and stature and sex and limb length on PTS. Results Female participants transitioned at a lower PTS than male participants (1.8 (0.2) m∙s-1 versus 1.9 (0.1) m∙s-1; p ≤ 0.026). Sex and stature explained 19% of the variance in PTS, while sex and limb length explained 21% of the variance. Including interactions increased the variance explained by 23% and 2% for sex and stature and sex and limb length, respectively. The significant interaction between sex and stature showed PTS was inversely proportional to stature for male participants but directly proportional for female participants. Significance These findings suggest that the extent to which stature and limb length influence the preferred transition speed may differ between sexes

A comparison of the illness beliefs of people with angina and their peers: a questionnaire study

BACKGROUND: What people believe about their illness may affect how they cope with it. It has been suggested that such beliefs stem from those commonly held within society . This study compared the beliefs held by people with angina, regarding causation and coping in angina, with the beliefs of their friends who do not suffer from angina. METHODS: Postal survey using the York Angina Beliefs Questionnaire (version 1), which elicits stress attributions and misconceived beliefs about causation and coping. This was administered to 164 people with angina and their non-cohabiting friends matched for age and sex. 132 people with angina and 94 friends completed the questionnaire. RESULTS: Peers are more likely than people with angina to believe that angina is caused by a worn out heart (p <0.01), angina is a small heart attack (p = 0.02), and that it causes permanent damage to the heart (p <0.001). Peers were also more likely to believe that people with angina should take life easy (p <0.01) and avoid exercise (p = 0.04) and excitement (p <0.01). CONCLUSIONS: The beliefs of the peer group about causation and coping in angina run counter to professional advice. Over time this may contribute to a reduction in patient concordance with risk factor reduction, and may help to create cardiac invalids

Dapagliflozin-lowered blood glucose reduces respiratory Pseudomonas aeruginosa infection in diabetic mice.

BACKGROUND AND PURPOSE: Hyperglycaemia increases glucose concentrations in airway surface liquid and increases the risk of pulmonary Pseudomonas aeruginosa infection. We determined whether reduction of blood and airway glucose concentrations by the anti-diabetic drug dapagliflozin could reduce P. aeruginosa growth/survival in the lungs of diabetic mice. EXPERIMENTAL APPROACH: The effect of dapagliflozin on blood and airway glucose concentration, the inflammatory response and infection were investigated in C57BL/6J (wild type, WT) or leptin receptor-deficient (db/db) mice, treated orally with dapagliflozin prior to intranasal dosing with LPS or inoculation with P. aeruginosa. Pulmonary glucose transport and fluid absorption were investigated in Wistar rats using the perfused fluid-filled lung technique. KEY RESULTS: Fasting blood, airway glucose and lactate concentrations were elevated in the db/db mouse lung. LPS challenge increased inflammatory cells in bronchoalveolar lavage fluid from WT and db/db mice with and without dapagliflozin treatment. P. aeruginosa colony-forming units (CFU) were increased in db/db lungs. Pretreatment with dapagliflozin reduced blood and bronchoalveolar lavage glucose concentrations and P. aeruginosa CFU in db/db mice towards those seen in WT. Dapagliflozin had no adverse effects on the inflammatory response in the mouse or pulmonary glucose transport or fluid absorption in the rat lung. CONCLUSION AND IMPLICATIONS: Pharmacological lowering of blood glucose with dapagliflozin effectively reduced P. aeruginosa infection in the lungs of diabetic mice and had no adverse pulmonary effects in the rat. Dapagliflozin has potential to reduce the use, or augment the effect, of antimicrobials in the prevention or treatment of pulmonary infection

Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using primary motor neuron cultures or motor neuron cell lines we demonstrated that expression of DAOR199W, promoted the formation of ubiquitinated protein aggregates, activated autophagy and increased apoptosis. The aim of this study was to characterise the effects of DAOR199W in vivo, using transgenic mice overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were evident in mice expressing DAOR199W, which were associated with a significant loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When separated by gender, this effect was greater in females (26%; p< 0.0132). In addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse model of ALS to determine whether the effects of SOD1G93A were potentiated in the double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not affected, onset of neurological signs was significantly earlier in female double transgenic animals than their female SOD1G93A littermates (125 days vs 131 days, P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor neuron function (i.e. kyphosis and loss of motor neurons) were detected which were most marked in females and could contribute to the earlier onset of neurological signs in double transgenic females compared to SOD1G93A littermates, highlighting the importance of recognizing gender effects present in animal models of ALS