Blood–brain barrier water exchange measurements using contrast-enhanced ASL

A technique for quantifying regional blood–brain barrier (BBB) water exchange rates using contrast-enhanced arterial spin labelling (CE-ASL) is presented and evaluated in simulations and in vivo. The two-compartment ASL model describes the water exchange rate from blood to tissue, (Formula presented.), but to estimate (Formula presented.) in practice it is necessary to separate the intra- and extravascular signals. This is challenging in standard ASL data owing to the small difference in (Formula presented.) values. Here, a gadolinium-based contrast agent is used to increase this (Formula presented.) difference and enable the signal components to be disentangled. The optimal post-contrast blood (Formula presented.) ((Formula presented.)) at 3 T was determined in a sensitivity analysis, and the accuracy and precision of the method quantified using Monte Carlo simulations. Proof-of-concept data were acquired in six healthy volunteers (five female, age range 24–46 years). The sensitivity analysis identified the optimal (Formula presented.) at 3 T as 0.8 s. Simulations showed that (Formula presented.) could be estimated in individual cortical regions with a relative error (Formula presented.) % and coefficient of variation (Formula presented.) %; however, a high dependence on blood (Formula presented.) was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit time (Formula presented.) s, cerebral blood flow (Formula presented.) mL blood/min/100 mL tissue and water exchange rate (Formula presented.) s−1. CE-ASL can provide regional BBB water exchange rate estimates; however, the clinical utility of the technique is dependent on the achievable accuracy of measured (Formula presented.) values

Let me Google that for you:a time series analysis of seasonality in internet search trends for terms related to foot and ankle pain

BACKGROUND: The analysis of internet search traffic may present the opportunity to gain insights into general trends and patterns in information seeking behaviour related to medical conditions at a population level. For prevalent and widespread problems such as foot and ankle pain, this information has the potential to improve our understanding of seasonality and trends within these conditions and their treatments, and may act as a useful proxy for their true incidence/prevalence characteristics. This study aimed to explore seasonal effects, general trends and relative popularity of internet search terms related to foot and ankle pain over the past decade. METHODS: We used the Google Trends tool to obtain relative search engine traffic for terms relating to foot and ankle pain and common treatments from Google search and affiliated pages for major northern and southern hemisphere English speaking nations. Analysis of overall trends and seasonality including summer/winter differences was carried out on these terms. RESULTS: Searches relating to general foot pain were on average 3.4 times more common than those relating to ankle pain, and twice as common as searches relating to heel pain. Distinct seasonal effects were seen in the northern hemisphere, with large increases in search volumes in the summer months compared to winter for foot (p = 0.004, 95 % CI [22.2–32.1]), ankle (p = 0.0078, 95 % CI [20.9–35.5]), and heel pain (p = 0.004, 95 % CI [29.1–45.6]). These seasonal effects were reflected by data from Australia, with the exception of ankle pain. Annual seasonal effects for treatment options were limited to terms related to foot surgery and ankle orthoses (p = 0.031, 95 % CI [3.5–20.9]; p = 0.004, 95 % CI [7.6–25.2] respectively), again increasing in the summer months. CONCLUSIONS: A number of general trends and annual seasonal effects were found in time series internet search data for terms relating to foot and ankle pain. This data may provide insights into these conditions at population levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13047-015-0074-9) contains supplementary material, which is available to authorized users

Neoliberalisation and 'lad cultures' in higher education

This paper links HE neoliberalisation and ‘lad cultures’, drawing on interviews and focus groups with women students. We argue that retro-sexist ‘laddish’ forms of masculine competitiveness and misogyny have been reshaped by neoliberal rationalities to become modes of consumerist sexualised audit. We also suggest that neoliberal frameworks scaffold an individualistic and adversarial culture among young people that interacts with perceived threats to men’s privilege and intensifies attempts to put women in their place through misogyny and sexual harassment. Furthermore, ‘lad cultures’, sexism and sexual harassment in higher education may be invisibilised by institutions to preserve marketability in a neoliberal context. In response, we ask if we might foster dialogue and partnership between feminist and anti-marketisation politics

Small RNA analysis in Sindbis virus infected human HEK293 cells

In contrast to the defence mechanism of RNA interference (RNAi) in plants and invertebrates, its role in the innate response to virus infection of mammals is a matter of debate. Since RNAi has a well-established role in controlling infection of the alphavirus Sindbis virus (SINV) in insects, we have used this virus to investigate the role of RNAi in SINV infection of human cells

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

Evaluating the importance of metamorphism in the foundering of continental crust

The metamorphic conditions and mechanisms required to induce foundering in deep arc crust are assessed using an example of representative lower crust in SW New Zealand. Composite plutons of Cretaceous monzodiorite and gabbro were emplaced at ~1.2 and 1.8 GPa are parts of the Western Fiordland Orthogneiss (WFO); examples of the plutons are tectonically juxtaposed along a structure that excised ~25 km of crust. The 1.8 GPa Breaksea Orthogneiss includes suitably dense minor components (e.g. eclogite) capable of foundering at peak conditions. As the eclogite facies boundary has a positive dP/dT, cooling from supra-solidus conditions (T > 950 ºC) at high-P should be accompanied by omphacite and garnet growth. However, a high monzodioritic proportion and inefficient metamorphism in the Breaksea Orthogneiss resulted in its positive buoyancy and preservation. Metamorphic inefficiency and compositional relationships in the 1.2 GPa Malaspina Pluton meant it was never likely to have developed densities sufficiently high to founder. These relationships suggest that the deep arc crust must have primarily involved significant igneous accumulation of garnet–clinopyroxene (in proportions >75%). Crustal dismemberment with or without the development of extensional shear zones is proposed to have induced foundering of excised cumulate material at P > 1.2 GPa

Pimecrolimus 1% cream for anogenital lichen sclerosus in childhood

BACKGROUND: Lichen sclerosus is a chronic inflammatory disease with a predilection of the anogenital region. Because of the potential side effects of repeated local application of potent glucocorticosteroids, equally-effective, safer therapeutic options are required, especially in the treatment of children. CASE PRESENTATIONS: We report on the efficacy of twice-daily application of pimecrolimus 1% cream in four prepubertal girls (range of age: 4 to 9 years) who suffered from anogenital lichen sclerosus. After three to four-month treatment, all patients had almost complete clinical remission including relief from itch, pain and inflammation. Only minor improvement was observed for the white sclerotic lesions. No significant side effects have been observed. CONCLUSIONS: Topical pimecrolimus appears to be an effective and safe treatment for children with anogenital lichen sclerosus. The clinical benefits observed in the four patient presented particularly include relief of pruritus, pain and inflammation. Vehicle-controlled studies on a larger number of patients are now warranted to substantiate our promising findings, and to investigate long-term efficacy and safety of topical pimecrolimus in anogenital lichen sclerosus

Comparison of embedded and added motor imagery training in patients after stroke: Study protocol of a randomised controlled pilot trial using a mixed methods approach

Copyright @ 2009 Schuster et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Two different approaches have been adopted when applying motor imagery (MI) to stroke patients. MI can be conducted either added to conventional physiotherapy or integrated within therapy sessions. The proposed study aims to compare the efficacy of embedded MI to an added MI intervention. Evidence from pilot studies reported in the literature suggests that both approaches can improve performance of a complex motor skill involving whole body movements, however, it remains to be demonstrated, which is the more effective one.Methods/Design: A single blinded, randomised controlled trial (RCT) with a pre-post intervention design will be carried out. The study design includes two experimental groups and a control group (CG). Both experimental groups (EG1, EG2) will receive physical practice of a clinical relevant motor task ('Going down, laying on the floor, and getting up again') over a two week intervention period: EG1 with embedded MI training, EG2 with MI training added after physiotherapy. The CG will receive standard physiotherapy intervention and an additional control intervention not related to MI.The primary study outcome is the time difference to perform the task from pre to post-intervention. Secondary outcomes include level of help needed, stages of motor task completion, degree of motor impairment, balance ability, fear of falling measure, motivation score, and motor imagery ability score. Four data collection points are proposed: twice during baseline phase, once following the intervention period, and once after a two week follow up. A nested qualitative part should add an important insight into patients' experience and attitudes towards MI. Semi-structured interviews of six to ten patients, who participate in the RCT, will be conducted to investigate patients' previous experience with MI and their expectations towards the MI intervention in the study. Patients will be interviewed prior and after the intervention period.Discussion: Results will determine whether embedded MI is superior to added MI. Findings of the semi-structured interviews will help to integrate patient's expectations of MI interventions in the design of research studies to improve practical applicability using MI as an adjunct therapy technique