What makes a successful SME in a rural location?

The study seeks to examine the different elements that contribute to the success of rural small and medium sized enterprises (SMEs) with an emphasis on firms in the North West of England. There has been growing literature to highlight the importance that SMEs have on the economy (BIS, 2015; Glover, 2012) alongside government initiatives to promote the expansion of rural firms (Love and Roper, 2015; Lord Young, 2013). The ability for SMEs to drive the economy and contribute to wealth creation is one of the many reasons why there has been increasing focus in the area of entrepreneurship and small business management. This research intends to explore and uncover the key issues and elements that enable and affect success in rural SMEs. Examining current literature around SME success revealed a number of factors that were prevalent such as firm growth, longevity, size and innovation. In addition to this, the position of the entrepreneur and their ability to affect success has also examined. These considerations were incorporated into a conceptual framework which aided in the development of the data collection instrument. The study applied a quantitative methodological approach utilising structured questionnaires in the data collection process. An accurate sampling frame of rural SMEs in the North West of England was drawn from the FAME database, where random sampling methods were then applied. Analysis of perceptual data revealed that the issues of growth, longevity, innovation and the entrepreneur are key factors that affect rural SME success. Ultimately, the study contributes to current knowledge by indicating vital areas for consideration in drive towards rural SME success, suggesting that focus should be placed upon SME size, longevity and innovation. Certain characteristics of the entrepreneur such as being from the local area and having parents that had previously owned a business were also found to be linked to rural SME success. Similarly, the research also suggests that financial measures of success should not be considered in singularity but rather in tandem with the direction of the firm. These conclusions provide some vital areas of consideration for rural SMEs as well as signposts where government initiatives and policies could be improved to facilitate their growth

Ethnic-specific suggestions for physical activity based on existing recreational physical activity preferences of New Zealand women

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Onasemnogene abeparvovec preserves bulbar function in infants with presymptomatic spinal muscular atrophy: a post-hoc analysis of the SPR1NT trial

Bulbar function in spinal muscular atrophy has been defined as the ability to meet nutritional needs by mouth while maintaining airway protection and communicate verbally. The effects of disease-modifying treatment on bulbar function are not clear. A multidisciplinary team conducted post-hoc analyses of phase 3 SPR1NT trial data to evaluate bulbar function of infants at risk for spinal muscular atrophy who received one-time gene replacement therapy (onasemnogene abeparvovec) before symptom onset. Three endpoints represented adequate bulbar function in SPR1NT: (1) absence of physiologic swallowing impairment, (2) full oral nutrition, and (3) absence of adverse events indicating pulmonary instability. Communication was not assessed in SPR1NT. We descriptively assessed numbers/percentages of children who achieved each endpoint and all three collectively. SPR1NT included infants <6 postnatal weeks with two (n = 14) or three (n = 15) copies of the survival motor neuron 2 gene. At study end (18 [two-copy cohort] or 24 [three-copy cohort] months of age), 100% (29/29) of patients swallowed normally, achieved full oral nutrition, maintained pulmonary stability, and achieved the composite endpoint. When administered to infants before clinical symptom onset, onasemnogene abeparvovec allowed children at risk for spinal muscular atrophy to achieve milestones within published normal ranges of development and preserve bulbar function

Changes in urinary metabolomic profile during relapsing renal vasculitis

Current biomarkers of renal disease in systemic vasculitis lack predictive value and are insensitive to early damage. To identify novel biomarkers of renal vasculitis flare, we analysed the longitudinal urinary metabolomic profile of a rat model of anti-neutrophil cytoplasmic antibody (ANCA) vasculitis. Wistar-Kyoto (WKY) rats were immunised with human myeloperoxidase (MPO). Urine was obtained at regular intervals for 181 days, after which relapse was induced by re-challenge with MPO. Urinary metabolites were assessed in an unbiased fashion using nuclear magnetic resonance (NMR) spectroscopy, and analysed using partial least squares discriminant analysis (PLS-DA) and partial least squares regression (PLS-R). At 56 days post-immunisation, we found that rats with vasculitis had a significantly different urinary metabolite profile than control animals; the observed PLS-DA clusters dissipated between 56 and 181 days, and re-emerged with relapse. The metabolites most altered in rats with active or relapsing vasculitis were trimethylamine N-oxide (TMAO), citrate and 2-oxoglutarate. Myo-inositol was also moderately predictive. The key urine metabolites identified in rats were confirmed in a large cohort of patients using liquid chromatography-mass spectrometry (LC-MS). Hypocitraturia and elevated urinary myo-inositol remained associated with active disease, with the urine myo-inositol:citrate ratio being tightly correlated with active renal vasculitis

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

Background Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. Methods A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Results Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Conclusions Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER

The Dawn of Open Access to Phylogenetic Data

The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

Effect of pre-milking teat preparation procedures on the microbial count on teats prior to cluster application

A study was carried out to investigate the effect of six pre-milking teat preparation procedures on lowering the staphylococal, streptococcal and coliform microbial count on teat skin prior to cluster application. The teat preparations included 'Iodine', 'Chlorhexidine' teat foam, 'Washing and drying' with paper, 'No preparation', 'Chlorine' teat foam, and disinfectant 'Wipes'. Teat preparations were applied for five days to 10 cows for each treatment during two herd management periods (indoors and outdoors). Teats were swabbed on day four and five before teat preparation and repeated after teat preparation. The swabs were plated on three selective agars: Baird Parker (Staphylococcus spp.), Edwards (Streptococcus spp.), and MacConkey (coliform). Following incubation, microbial counts for each pathogen type were manually counted and assigned to one of six categories depending on the microbial counts measured. The results were analysed by logistic regression using SAS [28]. The main analysis was conducted on binary improvement scores for the swabbing outcomes. There were no differences for staphylococcal, streptococcal and coliform bacterial counts between treatments, measured 'before' teat preparation. Treatments containing 'Chlorhexidine' teat foam (OR = 4.46) and 'Wipes' (OR = 4.46) resulted in a significant reduction (P < 0.01) in the staphylococcal count on teats compared to 'Washing and drying' or 'No preparation'. 'Chlorine' teat foam (OR = 3.45) and 'Wipes' (3.45) had the highest probability (P < 0.01) of reducing streptococcal counts compared to 'Washing and drying' or 'No preparation'. There was no statistical difference between any of the disinfectant treatments applied in reducing coliforms. Thus, the use of some disinfectant products for pre-milking teat preparation can have beneficial effects on reducing the levels of staphylococcal and streptococcal pathogens on teat skin

Identification of multiple root disease resistant wheat germplasm against cereal nematodes and dryland root rot and their validation in regions of economic importance

História da literatura portuguesa coordenada por Giulia Lanciani - primeiras páginas de um total pp. 7-108)História literária do século XVIII portuguêsGoverno de Portuga

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

Peer reviewedPublisher PD