A systematic review of biomarkers for disease progression in Parkinson's disease

This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0707-10124).BACKGROUND: Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true disease-modifying effects. A systematic review was undertaken to determine what biomarkers for disease progression in Parkinson's disease (PD) exist. METHODS: MEDLINE and EMBASE (1950-2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with idiopathic PD diagnosed by formal criteria or clearly described clinical means were included. We made no restriction on age, disease duration, drug treatment, or study design. We included studies which attempted to draw associations between any tests used to investigate disease progression and any clinical measures of disease progression. The electronic search was validated by hand-searching the two journals from which most included articles came. RESULTS: 183 studies were included: 163 (89%) cross-sectional, 20 (11%) longitudinal. The electronic search strategy had a sensitivity of 71.4% (95% CI 51.1-86.0) and a specificity of 97.1% (95% CI 96.5-97.7). In longitudinal studies median follow-up was 2.0 years (IQR 1.1-3.5). Included studies were generally poor quality--cross-sectional with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and simplistic statistical analyses. CONCLUSION: We found insufficient evidence to recommend the use of any biomarker for disease progression in PD clinical trials, which may simply reflect the poor quality of research in this area. We therefore present a provisional 'roadmap' for conducting future disease progression biomarker studies, and recommend new quality criteria by which future studies may be judged.Publisher PDFPeer reviewe

Hemisystems of small flock generalized quadrangles

In this paper, we describe a complete computer classification of the hemisystems in the two known flock generalized quadrangles of order $(5^2,5)$ and give numerous further examples of hemisystems in all the known flock generalized quadrangles of order $(s^2,s)$ for $s \le 11$. By analysing the computational data, we identify two possible new infinite families of hemisystems in the classical generalized quadrangle $H(3,q^2)$.Comment: slight revisions made following referee's reports, and included raw dat

A systematic review of biomarkers for disease progression in Parkinson's disease

Peer reviewedPublisher PD

Industrial relations in European hypermarkets: Home and host country influences

YesIn this article we examine the industrial relations practices of three large European food retailers when they transfer the hypermarket format to other countries. We ask, first, how industrial relations in hypermarkets differ from those in other food retailing outlets. Second, we examine how far the approach characteristic of each company’s country-of-origin (Germany, France and the UK) shapes the practices adopted elsewhere. Third, we ask how they respond to the specific industrial relations systems of each host country (Turkey, Poland, Ireland and Spain)

A novel disorder reveals clathrin heavy chain-22 is essential for human pain and touch development

Congenital inability to feel pain is very rare but the identification of causative genes has yielded significant insights into pain pathways and also novel targets for pain treatment. We report a novel recessive disorder characterized by congenital insensitivity to pain, inability to feel touch, and cognitive delay. Affected individuals harboured a homozygous missense mutation in CLTCL1 encoding the CHC22 clathrin heavy chain, p.E330K, which we demonstrate to have a functional effect on the protein. We found that CLTCL1 is significantly upregulated in the developing human brain, displaying an expression pattern suggestive of an early neurodevelopmental role. Guided by the disease phenotype, we investigated the role of CHC22 in two human neural crest differentiation systems; human induced pluripotent stem cell-derived nociceptors and TRKB-dependant SH-SY5Y cells. In both there was a significant downregulation of CHC22 upon the onset of neural differentiation. Furthermore, knockdown of CHC22 induced neurite outgrowth in neural precursor cells, which was rescued by stable overexpression of small interfering RNA-resistant CHC22, but not by mutant CHC22. Similarly, overexpression of wild-type, but not mutant, CHC22 blocked neurite outgrowth in cells treated with retinoic acid. These results reveal an essential and non-redundant role for CHC22 in neural crest development and in the genesis of pain and touch sensing neurons

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Impacts of biomass production at civil airports on grassland bird conservation and aviation strike risk

Growing concerns about climate change, foreign oil dependency, and environmental quality have fostered interest in perennial native grasses (e.g., switchgrass [Panicum virgatum]) for bioenergy production while also maintaining biodiversity and ecosystem function. However, biomass cultivation in marginal landscapes such as airport grasslands may have detrimental effects on aviation safety as well as conservation efforts for grassland birds. In 2011–2013, we investigated effects of vegetation composition and harvest frequency on seasonal species richness and habitat use of grassland birds and modeled relative abundance, aviation risk, and conservation value of birds associated with biomass crops. Avian relative abundance was greater in switchgrass monoculture plots during the winter months, whereas Native Warm-Season Grass (NWSG) mixed species plantings were favored by species during the breeding season. Conversely, treatment differences in aviation risk and conservation value were not biologically significant. Only 2.6% of observations included avian species of high hazard to aircraft, providing support for semi-natural grasslands as a feasible landcover option at civil airports. Additionally, varied harvest frequencies across a mosaic of switchgrass monocultures and NWSG plots allows for biomass production with multiple vegetation structure options for grassland birds to increase seasonal avian biodiversity and habitat use

Systematic review and economic modelling of the relative clinical benefit and cost-effectiveness of laparoscopic surgery and robotic surgery for removal of the prostate in men with localised prostate cancer

PMID: 23127367 [PubMed - indexed for MEDLINE] Free full text Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.Peer reviewedPublisher PD