Small business survey: linking 2006 and 2007 waves to the IDBR

This report describes work to link two waves of the Small Business Survey (SBS) to the Inter-Departmental Business Register (IDBR)1. The first is the Annual Small Business Survey 2006/07, hereafter SBS 2006; the second is the survey for 2007/8, hereafter SBS 2007. The linking work has been undertaken by Belmana and Middlesex University; IFF Research conducted both surveys and has overseen this work. The focus of this research was to understand the strengths and weaknesses of different methods of linking and then develop an approach for application to the 2006 and 2007 waves of the survey. A particular difficulty, as older waves of SBS are linked to the IDBR, is the changes to businesses that would have occurred since the survey. This work has taken steps to reduce the effect of the age of the survey on the quality of the data linking, by linking to historic vintages of the IDBR and the Companies House register. The report also reviews earlier work by the Office for National Statistics (ONS) linking the 2010 and 2012 SBS surveys to the IDBR. The project draws on insights from this, but introduces new linking methods that improve link rates. Various quality checks have been undertaken and, given the surveys were conducted almost a decade ago, the ability to link a higher proportion of respondents to the IDBR than achieved for the 2010 survey indicates the linking of SBS can be undertaken even for relatively old waves. Some preliminary analysis of the linked survey data suggests that there is potential for understanding the more long-term outcomes for businesses and correlating these with SBS responses

Upregulation of Mrps18a in breast cancer identified by selecting phage antibody libraries on breast tissue sections

Abstract Background One of the hallmarks of cancer is an altered energy metabolism, and here, mitochondria play a central role. Previous studies have indicated that some mitochondrial ribosomal proteins change their expression patterns upon transformation. Method In this study, we have used the selection of recombinant antibody libraries displayed on the surface of filamentous bacteriophage as a proteomics discovery tool for the identification of breast cancer biomarkers. A small subpopulation of breast cells expressing both cytokeratin 19 and cytokeratin 14 was targeted using a novel selection procedure. Results We identified the mitochondrial ribosomal protein s18a (Mrps18a) as a protein which is upregulated in breast cancer. However, Mrps18a was not homogeneously upregulated in all cancer cells, suggesting the existence of sub-populations within the tumor. The upregulation was not confined to cytokeratin 19 and cytokeratin 14 double positive cells. Conclusion This study illustrates how phage display can be applied towards the discovery of proteins which exhibit changes in their expression patterns. We identified the mitochondrial protein Mrps18a as being upregulated in human breast cancer cells compared to normal breast cells

Muscle velocity recovery cycles in myopathy.

OBJECTIVE To understand the pathophysiology of myopathies by using muscle velocity recovery cycles (MVRC) and frequency ramp (RAMP) methodologies. METHODS 42 patients with quantitative electromyography (qEMG) and biopsy or genetic verified myopathy and 42 healthy controls were examined with qEMG, MVRC and RAMP, all recorded from the anterior tibial muscle. RESULTS There were significant differences in the motor unit potential (MUP) duration, the early and late supernormalities of the MVRC and the RAMP latencies in myopathy patients compared to controls (p < 0.05 apart from muscle relatively refractory period (MRRP)). When dividing into subgroups, the above-mentioned changes in MVRC and RAMP parameters were increased for the patients with non-inflammatory myopathy, while there were no significant changes in the group of patients with inflammatory myopathy. CONCLUSIONS The MVRC and RAMP parameters can discriminate between healthy controls and myopathy patients, more significantly for non-inflammatory myopathy. MVRC differences with normal MRRP in myopathy differs from other conditions with membrane depolarisation. SIGNIFICANCE MVCR and RAMP may have a potential in understanding disease pathophysiology in myopathies. The pathogenesis in non-inflammatory myopathy does not seem to be caused by a depolarisation of the resting membrane potential but rather by the change in sodium channels of the muscle membrane

Demographic reconstruction from ancient DNA supports rapid extinction of the great auk

The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species’ geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation

Thule Inuit environmental impacts on Kangeq, southwest Greenland

The Leverhulme Trust is thanked for financial support for the project “Footsteps on the Edge of Thule” (Programme Grant F/00 152/Q), directed by Kevin Edwards (University of Aberdeen), Andy Dugmore, Eva Panagiotakopulu (both University of Edinburgh), and Ian Simpson (Stirling University). We are grateful to Andy McMullen, Kirsty Collinge and Ian Simpson for assistance with fieldwork and advice. Gordon Cook is thanked for the provision of radiocarbon dates. Jamie Bowie kindly assisted with the production of diagrams relating to palynological work. The maps and section were drawn by Anastasios Panagiotakopoulos, whose help is warmly acknowledged. Last but not least we are grateful for the helpful comments by the editor and three anonymous reviewers.Peer reviewedPostprin

Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma

Histamine inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). Two randomised phase II trials of IL-2 with or without histamine dihydrochloride (HDC) in patients with metastatic renal cell carcinoma (mRCC) were run in parallel. A total of 41 patients were included in Manchester, UK and 63 in Aarhus, Denmark. The self-administered, outpatient regimen included IL-2 as a fixed dose, 18 MIU s.c. once daily, 5 days per week for 3 weeks followed by 2 weeks rest. Histamine dihydrochloride was added twice daily, 1.0 mg s.c., concomitantly with IL-2. A maximum of four cycles were given. The Danish study showed a statistically significant 1-year survival benefit (76 vs 47%, P=0.03), a trend towards benefit in both median survival (18.3 vs 11.4 months, P=0.07), time to PD (4.5 vs 2.2 months, P=0.13) and clinical benefit (CR+PR+SD) (58 vs 37%, P=0.10) in favour of IL-2/HDC, whereas the UK study was negative for all end points. Only three patients had grade 4 toxicity; however, two were fatal. A randomised phase III trial is warranted to clarify the potential role of adding histamine to IL-2 in mRCC

Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues and organs. Clinical manifestations include severe airway obstruction, skeletal deformities, cardiomyopathy and, in most patients, neurological decline. Death usually occurs in the second decade of life, although some patients with less severe disease have survived into their fifth or sixth decade. Until recently, there has been no effective therapy for MPS II, and care has been palliative. Enzyme replacement therapy (ERT) with recombinant human iduronate-2-sulphatase (idursulfase), however, has now been introduced. Weekly intravenous infusions of idursulfase have been shown to improve many of the signs and symptoms and overall wellbeing in patients with MPS II. This paper provides an overview of the clinical manifestations, diagnosis and symptomatic management of patients with MPS II and provides recommendations for the use of ERT. The issue of treating very young patients and those with CNS involvement is also discussed. ERT with idursulfase has the potential to benefit many patients with MPS II, especially if started early in the course of the disease

Correlates of record linkage and estimating risks of non-linkage biases in business data sets

Researchers often utilize data sets that link information from multiple sources, but non‐linkage biases caused by linked and non‐linked subject differences are little understood, especially in business data sets. We address these knowledge gaps by studying biases in linkable 2010 UK Small Business Survey data sets. We identify correlates of business linkage propensity, and also for the first time its components: consent to linkage and register identifier appendability. As well, we take a novel approach to evaluating non‐linkage bias risks, by computing data set representativeness indicators (comparable, decomposable sample subset similarity measures). We find that the main impacts on linkage propensities and bias risks are due to consenter–non‐consenter differences explicable given business survey response processes, and differences between subjects with and without identifiers caused by register undercoverage of very small businesses. We then discuss consequences for the analysis of linked business data sets, and implications of the evaluation methods we introduce for linked data set producers and users