Which SMEs seek external support? Business characteristics, management behaviour and external influences in a contingency approach

To improve SME growth and competitiveness, governments often encourage business owner-managers to make use of external sources of support. Whether they seek this depends on the degree to which they perceive themselves to need assistance. Additionally its use can be constrained by market failures. In this paper, we model whether SME owner-managers seek information and advice from formal sources, including public and private providers. In 2011, the researchers conducted a telephone survey of 1202 SMEs (1-249 employees) in England to assess the use and non-use of external support between 2008 and 2011. Using a contingency approach, we model various influences on the use and non-use of formal support and identify those owner-managers who face more concerns but have less confidence in their capabilities. We find the demand for support, especially from private providers, is fuelled by a firm’s objective to grow and a size threshold, although this is moderated by various concerns which increase the likelihood of using public sources. The willingness to take informal advice can act as a stepping stone to using formal sources. Whilst market failures affected less than a fifth of firms, those with women directors were particularly affected as were newly founded firms

The complete mitochondrial genome of Epomophorus gambianus (Chiroptera: Pteropodidae) and its phylogenetic analysis

The Gambian epauletted fruit bat, Epomophorus gambianus, is widely distributed across sub-Saharan Africa. Its assembled and annotated mitochondrial genome (GenBank accession no. KT963027) is 16,702 bases in length, containing 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and two non-coding regions: the control region (D-loop) and the origin of light-strand replication (OL). The average base composition is 32.2% A; 27.6% C; 14% G; and 26.1% T. The mitogenome presented a structural composition greatly conserved between members of the Pteropodidae family

Recent trends in cutaneous malignant melanoma in the Yorkshire region of England; incidence, mortality and survival in relation to stage of disease, 1993–2003

The aim of this study was to investigate recent trends in incidence, mortality and survival in patients diagnosed with malignant melanoma (MM) in relation to stage (Breslow thickness). Cases of primary invasive and in situ MM diagnosed between 1st January 1993 and 31st December 2003 in the former Yorkshire Health Authority were identified from cancer registry data. Over the study period, the incidence of invasive MM increased from 5.4 to 9.7 per 100 000 in male subjects and from 7.5 to 13.1 per 100 000 in female subjects. Most of this increase was seen in thin tumours (<1.5 mm). Thin tumours were more likely to be diagnosed in the younger age groups and be classified as superficial spreading melanoma. In situ melanoma rates increased only slightly. Over the same time period, mortality rates have been relatively constant in both male and female subjects. Five-year relative survival varied from 91.8% (95% CI 90.4–93.1) for patients with thin tumours to 41.5% (95% CI 36.7–46.3) for those with thick tumours. In multivariable analyses, Breslow thickness was the most important prognostic factor. Age, sex and level of deprivation were also identified as independent prognostic factors. The trends in incidence suggest that the increase is real, rather than an artefact of increased scrutiny, implying that primary prevention in the Yorkshire area of the UK has failed to control trends in incidence. Mortality, in contrast, appears to be levelling off, indicating that secondary prevention has been more effective

Melanoma-inhibiting activity (MIA) mRNA is not exclusively transcribed in melanoma cells: low levels of MIA mRNA are present in various cell types and in peripheral blood

The detection of minimal amounts of melanoma cells by tyrosinase reverse transcription polymerase chain reaction (RT-PCR) is seriously hampered by false negative reports in blood of melanoma patients with disseminated melanoma. Therefore, additional assays which make use of multiple melanoma markers are needed. It has been shown that introduction of multiple markers increases the sensitivity of detection. Melanoma inhibitory activity (MIA) is one such melanoma-specific candidate gene. To test the specificity of MIA PCR, we performed 30 and 60 cycles of PCR with two different sets of MIA specific primers on 19 melanoma and 16 non-melanoma cell lines. MIA mRNA was detected in 16 out of 19 melanoma cell lines and in seven out of 16 non-melanoma cell lines after 30 cycles of PCR. However, MIA mRNA could be detected in all cell lines after 60 cycles of PCR. Also, in 14 out of 14 blood samples of melanoma patients, five out of six blood samples of non-melanoma patients and in seven out of seven blood samples of healthy volunteers, MIA mRNA was detected after 60 cycles of PCR, whereas no MIA PCR product could be detected in any of the blood samples after 30 cycles of PCR. We conclude that low levels of MIA transcripts are present in various normal and neoplastic cell types. Therefore, MIA is not a suitable marker gene to facilitate the detection of minimal amounts of melanoma cells in blood or in target organs of the metastatic process. © 1999 Cancer Research Campaig

Stalking influenza by vaccination with pre-fusion headless HA mini-stem.

Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity

Suppression of HBV by Tenofovir in HBV/HIV coinfected patients : a systematic review and meta-analysis

Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

Approximating Optimal Behavioural Strategies Down to Rules-of-Thumb: Energy Reserve Changes in Pairs of Social Foragers

Functional explanations of behaviour often propose optimal strategies for organisms to follow. These ‘best’ strategies could be difficult to perform given biological constraints such as neural architecture and physiological constraints. Instead, simple heuristics or ‘rules-of-thumb’ that approximate these optimal strategies may instead be performed. From a modelling perspective, rules-of-thumb are also useful tools for considering how group behaviour is shaped by the behaviours of individuals. Using simple rules-of-thumb reduces the complexity of these models, but care needs to be taken to use rules that are biologically relevant. Here, we investigate the similarity between the outputs of a two-player dynamic foraging game (which generated optimal but complex solutions) and a computational simulation of the behaviours of the two members of a foraging pair, who instead followed a rule-of-thumb approximation of the game's output. The original game generated complex results, and we demonstrate here that the simulations following the much-simplified rules-of-thumb also generate complex results, suggesting that the rule-of-thumb was sufficient to make some of the model outcomes unpredictable. There was some agreement between both modelling techniques, but some differences arose – particularly when pair members were not identical in how they gained and lost energy. We argue that exploring how rules-of-thumb perform in comparison to their optimal counterparts is an important exercise for biologically validating the output of agent-based models of group behaviour

CT colonography with minimal bowel preparation: evaluation of tagging quality, patient acceptance and diagnostic accuracy in two iodine-based preparation schemes

PURPOSE: The aim of this study was to compare a 1-day with a 2-day iodine bowel preparation for CT colonography in a positive faecal occult blood test (FOBT) screening population. MATERIALS AND METHODS: One hundred consecutive patients underwent CT colonography and colonoscopy with segmental unblinding. The first 50 patients (group 1) ingested 7 50 ml iodinated contrast starting 2 days before CT colonography. The latter 50 patients (group 2) ingested 4 50 ml iodinated contrast starting 1 day before CT colonography. Per colonic segment measurements of residual stool attenuation and homogeneity were performed, and a subjective evaluation of tagging quality (grade 1-5) was done. Independently, two reviewers performed polyp and carcinoma detection. RESULTS: The tagging density was 638 and 618 HU (p = 0.458) and homogeneity 91 and 86 HU for groups 1 and 2, respectively (p = 0.145). The tagging quality was graded 5 (excellent) in 90% of all segments in group 1 and 91% in group 2 (p = 0.749). Mean per-polyp sensitivity for lesions >or=10 mm was 86% in group 1 and 97% in group 2 (p = 0.355). Patient burden from diarrhoea significantly decreased for patients in group 2. CONCLUSIONS: One-day preparation with meglumine ioxithalamate results in an improved patient acceptability compared with 2-day preparation and has a comparable, excellent image quality and good diagnostic performanc

A Sensitive Assay for Virus Discovery in Respiratory Clinical Samples

In 5–40% of respiratory infections in children, the diagnostics remain negative, suggesting that the patients might be infected with a yet unknown pathogen. Virus discovery cDNA-AFLP (VIDISCA) is a virus discovery method based on recognition of restriction enzyme cleavage sites, ligation of adaptors and subsequent amplification by PCR. However, direct discovery of unknown pathogens in nasopharyngeal swabs is difficult due to the high concentration of ribosomal RNA (rRNA) that acts as competitor. In the current study we optimized VIDISCA by adjusting the reverse transcription enzymes and decreasing rRNA amplification in the reverse transcription, using hexamer oligonucleotides that do not anneal to rRNA. Residual cDNA synthesis on rRNA templates was further reduced with oligonucleotides that anneal to rRNA but can not be extended due to 3′-dideoxy-C6-modification. With these modifications >90% reduction of rRNA amplification was established. Further improvement of the VIDISCA sensitivity was obtained by high throughput sequencing (VIDISCA-454). Eighteen nasopharyngeal swabs were analysed, all containing known respiratory viruses. We could identify the proper virus in the majority of samples tested (11/18). The median load in the VIDISCA-454 positive samples was 7.2 E5 viral genome copies/ml (ranging from 1.4 E3–7.7 E6). Our results show that optimization of VIDISCA and subsequent high-throughput-sequencing enhances sensitivity drastically and provides the opportunity to perform virus discovery directly in patient material

Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage in humans and mice

With molecular treatments coming into reach for spinocerebellar ataxia type 3 (SCA3), easily accessible, cross-species validated biomarkers for human and preclinical trials are warranted, particularly for the preataxic disease stage. We assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in ataxic and preataxic subjects of two independent multicentric SCA3 cohorts and in a SCA3 knock-in mouse model. Ataxic SCA3 subjects showed increased levels of both NfL and pNfH. In preataxic subjects, NfL levels increased with proximity to the individual expected onset of ataxia, with significant NfL elevations already 7.5 years before onset. Cross-sectional NfL levels correlated with both disease severity and longitudinal disease progression. Blood NfL and pNfH increases in human SCA3 were each paralleled by similar changes in SCA3 knock-in mice, here also starting already at the presymptomatic stage, closely following ataxin-3 aggregation and preceding Purkinje cell loss in the brain. Blood neurofilaments, particularly NfL, might thus provide easily accessible, cross-species validated biomarkers in both ataxic and preataxic SCA3, associated with earliest neuropathological changes, and serve as progression, proximity-to-onset and, potentially, treatment-response markers in both human and preclinical SCA3 trials