Universities, SMEs and innovation frameworks : think global, act local?

Universities are increasingly encouraged to take a leading role in economic development, particularly through innovation. Simultaneously, economic development policy itself is increasingly focused on small and medium-sized enterprises (SMEs), creating overlapping interactions in the roles of government policy, universities and SMEs and the processes of innovation creation and dissemination. This paper examines issues arising from these developments and relating to the key stakeholders (industry, government and universities in particular), the enabling mechanisms (network governance, relevant education, training and learning, and suitable structures), and local and cross-local links. The authors then use quantitative analysis of 450 SMEs in the UK to begin to evaluate the roles of universities and highlight areas for further theoretical development.

Network structure, knowledge governance, and firm performance : evidence from innovation networks and SMEs in the UK

It is increasingly understood that learning and thus innovation often occurs via highly interactive, iterative, network-based processes. Simultaneously, economic development policy is increasingly focused on small and medium-sized enterprises (SMEs) as a means of generating growth, creating a clear research issue in terms of the roles and interactions of government policy, universities, and other sources of knowledge, SMEs, and the creation and dissemination of innovation. This paper analyses the contribution of a range of actors in an SME innovation creation and dissemination framework, reviewing the role of various institutions therein, exploring the contribution of cross-locality networks, and identifying the mechanisms required to operationalise such a framework. Bivariate and multivariate (regression) techniques are employed to investigate both innovation and growth outcomes in relation to these structures; data are derived from the survey responses of over 450 SMEs in the UK. Results are complex and dependent upon the nature of institutions involved, the type of knowledge sought, and the spatial level of the linkages in place but overall highlight the value of cross-locality networks, network governance structures, and certain spillover effects from universities. In general, we find less support for the factors predicting SME growth outcomes than is the case for innovation. Finally, we outline an agenda for further research in the area.

Measuring urban form : a comparative analysis of South East Queensland and South Florida

At first glance the built environments of South Florida and South East Queensland appear very similar, particularly along the highly urbanized coast. However this apparent similarity belies some fundamental differences between the two regions in terms of context and the approach to regulating development. This paper describes some of these key differences, but focuses on two research questions: 1) do these differences affect the built environment; and 2) if so, how does the built form differ? There has been considerable research on how to best measure urban form, particularly as it relates to measuring urban sprawl (Schwarz 2010; Clifton et al. 2008). Some of the key questions identified by this research include: what are the best variables to use?; what scale should be used?; and what time period to use? We will assimilate this research in order to develop a methodology for measuring urban form and apply it to both case study regions. There are several potential outcomes from this research -- one is that the built form between the two regions is quite different; and the second is that it is similar. The first outcome is what might be expected given the differences in context and development regulation. However how might the second outcome be explained – major differences in context and development regulation resulting in minor differences in key measures of urban form? One explanation is that differences in the way development is regulated are not as important in determining the built form as are private market forces.

Low formalin concentrations induce fine-tuned responses that are sex and age-dependent : a developmental study

The formalin test is increasingly applied as a model of inflammatory pain using high formalin concentrations (5–15%). However, little is known about the effects of low formalin concentrations on related behavioural responses. To examine this, rat pups were subjected to various concentrations of formalin at four developmental stages: 7, 13, 22, and 82 days of age. At postnatal day (PND) 7, sex differences in flinching but not licking responses were observed with 0.5% formalin evoking higher flinching in males than in females. A dose response was evident in that 0.5% formalin also produced higher licking responses compared to 0.3% or 0.4% formalin. At PND 13, a concentration of 0.8% formalin evoked a biphasic response. At PND 22, a concentration of 1.1% evoked higher flinching and licking responses during the late phase (10–30 min) in both males and females. During the early phase (0–5 min), 1.1% evoked higher licking responses compared to 0.9% or 1% formalin. 1.1% formalin produced a biphasic response that was not evident with 0.9 or 1%. At PND 82, rats displayed a biphasic pattern in response to three formalin concentrations (1.25%, 1.75% and 2.25%) with the presence of an interphase for both 1.75% and 2.25% but not for 1.25%. These data suggest that low formalin concentrations induce fine-tuned responses that are not apparent with the high formalin concentration commonly used in the formalin test. These data also show that the developing nociceptive system is very sensitive to subtle changes in formalin concentrations.

Vectors and methods for hairpin RNA and artificial microRNA-mediated gene silencing in plants

In plant cells, DICER-LIKE4 processes perfectly double-stranded RNA (dsRNA) into short interfering (si) RNAs, and DICER-LIKE1 generates micro (mi) RNAs from primary miRNA transcripts (pri-miRNA) that form fold-back structures of imperfectly dsRNA. Both si and miRNAs direct the endogenous endonuclease, ARGONAUTE1 to cleave complementary target single-stranded RNAs and either small RNA (sRNA)-directed pathway can be harnessed to silence genes in plants. A routine way of inducing and directing RNA silencing by siRNAs is to express self-complementary single-stranded hairpin RNA (hpRNA), in which the duplexed region has the same sequence as part of the target gene's mRNA. Artificial miRNA (amiRNA)-mediated silencing uses an endogenous pri-miRNA, in which the original miRNA/miRNA* sequence has been replaced with a sequence complementary to the new target gene. In this chapter, we describe the plasmid vector systems routinely used by our research group for the generation of either hpRNA-derived siRNAs or amiRNAs.

Watermemories : a swimming club for people with dementia

The purpose of this article is to describe the conceptual model and implementation strategies of an evidence-based, aquatic exercise program specifically targeting individuals with dementia—The Watermemories Swimming Club (WSC). Physical exercise not only improves the functional capacity of people with dementia but also has significant effects on other aspects of quality of life such as sleep, appetite, behavioral and psychological symptoms, depression, and falls. Additionally, exercise can improve a person’s overall sense of well-being and positively enhance their sociability. The WSC was designed to increase physical exercise while being easy to implement, safe, and pleasurable. Many challenges were faced along the way, and we discuss how these were overcome. Implications for nurses are also provided.

The Watermemories Swimming Club

This pilot project aimed to try something different - rekindle positive memories of swimming in people with dementia who enjoyed swimming throughout their lives, and involve them in active swimming again using a swimming club intervention. Club members were recruited from two residential aged care facilities in Queensland, Australia (n=25 recruited, n=18 commenced, n=11 (median age=88.4, IQR=12.3; 1 male) completed the intervention). The 12 week program consisted of two, 45 minute sessions per week held at a municipal pool, using a trained instructor and assistants. Measures, taken at baseline, Week 6, Week 9 and post intervention included psychosocial and physical assessments such as the Revised Memory and Behavior Problems Checklist, Psychological Well-Being in Cognitively Impaired Persons, Seniors Physical Performance Battery and bioelectric impedance analysis. Stakeholder focus groups determined the barriers and facilitators for the club. Three outcomes have been achieved: 1) the development of a dementia specific, evidence-based, aquatic exercise program. This valuable resource will ensure that the benefits will be maximized with tailored exercises for strength, agility, flexibility, balance, relaxation and stress reduction, 2) improved quality of life for members, with statistically significant improvements in psychological wellbeing (χ2 =8.66, p<0.05), BPSD expression (χ2=16.91, p=0.001) and staff distress (χ2=16.86, p=0.001) and 3) an informative website with instructional video clips and a manual to assist others in implementing and maintaining a Watermemories Swimming Club. This pilot project has provided strong evidence that aquatic exercise can produce positive physical, psychosocial and behavioral outcomes for people with dementia.

Aha! The return of Alan Partridge

Throughout a long and occasionally distinguished career first as a television sports correspondent, then chat show host (dramatically ended by the accidental homicide of a guest live on air), then rebirth as a radio presenter at North Norfolk Digital, Alan Partridge has navigated the stormy waters of the British media landscape, now achieving mainstream success on the big screen with a starring role in Steve Coogan’s Alpha Papa (Declan Lowney, 2013). A man who in his desperation for a television series of his own once sank so low as to pitch a show called Monkey Tennis to the BBC finally finds his inner hero in a film which, while presenting mainly as comedy, also contains a biting critique of trends in the British media with which all journalists and media practitioners in general will be familiar. Alpha Papa is a nostalgic, elegiac riff on the pleasures and values of local radio the way it used to be, exemplified by North Norfolk Digital’s stable of flawed, but endearing jocks – Wally Banter, Bruno Brooks, Dave Clifton (who in one scene recounts the depths to which he sank as an alcoholic, drug addicted wreck—“I woke up in a skip with someone else’s underpants in my mouth. I can laugh about it now …”), and Pat Farrell. 50- something Pat is sacked by the new owners of North Norfolk Digital, who in their efforts to transform the station into a “multiplatform content provider” going by the more Gen Yfriendly name of Shape (“the way you want it to be”), wish to replace him with a younger, brattish model lacking in taste and manners. Out go records by the likes of Glen Campbell and Neil Diamond (“You can keep Jesus Christ”, observes Partridge after playing Diamond’s Sweet Caroline in a demonstration of the crackling radio repartee for which he is by now renowned, “that was the king of the Jews”), in comes Roachford. Pat, grieving his dead wife Molly, finally snaps and turns the glitzy media launch of Shape into a hostage siege. Only Alan Partridge, it seems, can step in and talk Pat out of a looming catastrophe.

Physical and functional implications of aquatic exercise for nursing home residents with dementia

Exercise has reported benefits for those with dementia. In the current study we investigated the feasibility of delivery and the physical and functional benefits of an innovative aquatic exercise program for adults with moderate to severe dementia living in a nursing home aged care facility. Ten adults (88.4 years, inter quartile range 12.3) participated twice weekly for 12 weeks. Anthropometric and grip strength data, and measures of physical function and balance were collected at baseline and post-intervention. Feasibility was assessed by attendance, participation, enjoyment and recruitment. Following exercise, participant's left hand grip strength had improved significantly (p = .017). Small to moderate effect sizes were observed for other measures. A number of delivery challenges emerged, but participant enjoyment, benefits and attendance suggest feasibility. Aquatic exercise shows promise as an intervention among those with dementia who live in a nursing home aged care facility. Greater program investigation is warranted.

Whole exome sequencing is an efficient and sensitive method for detection of germline mutations in patients with phaeochromcytomas and paragangliomas

Background Genetic testing is recommended when the probability of a disease-associated germline mutation exceeds 10%. Germline mutations are found in approximately 25% of individuals with phaeochromcytoma (PCC) or paraganglioma (PGL); however, genetic heterogeneity for PCC/PGL means many genes may require sequencing. A phenotype-directed iterative approach may limit costs but may also delay diagnosis, and will not detect mutations in genes not previously associated with PCC/PGL. Objective To assess whether whole exome sequencing (WES) was efficient and sensitive for mutation detection in PCC/PGL. Methods Whole exome sequencing was performed on blinded samples from eleven individuals with PCC/PGL and known mutations. Illumina TruSeq™ (Illumina Inc, San Diego, CA, USA) was used for exome capture of seven samples, and NimbleGen SeqCap EZ v3.0 (Roche NimbleGen Inc, Basel, Switzerland) for five samples (one sample was repeated). Massive parallel sequencing was performed on multiplexed samples. Sequencing data were called using Genome Analysis Toolkit and annotated using annovar. Data were assessed for coding variants in RET, NF1, VHL, SDHD, SDHB, SDHC, SDHA, SDHAF2, KIF1B, TMEM127, EGLN1 and MAX. Target capture of five exome capture platforms was compared. Results Six of seven mutations were detected using Illumina TruSeq™ exome capture. All five mutations were detected using NimbleGen SeqCap EZ v3.0 platform, including the mutation missed using Illumina TruSeq™ capture. Target capture for exons in known PCC/PGL genes differs substantially between platforms. Exome sequencing was inexpensive (<$A800 per sample for reagents) and rapid (results <5 weeks from sample reception). Conclusion Whole exome sequencing is sensitive, rapid and efficient for detection of PCC/PGL germline mutations. However, capture platform selection is critical to maximize sensitivity.

Altered formalin-induced pain and Fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure

Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process

Altered nociceptive, endocrine, and dorsal horn neuron responses in rats following a neonatal immune challenge

Summary The neonatal period is characterized by significant plasticity where the immune, endocrine, and nociceptive systems undergo fine-tuning and maturation. Painful experiences during this period can result in long-term alterations in the neurocircuitry underlying nociception, including increased sensitivity to mechanical or thermal stimuli. Less is known about the impact of neonatal exposure to mild inflammatory stimuli, such as lipopolysaccharide (LPS), on subsequent inflammatory pain responses. Here we examine the impact of neonatal LPS exposure on inflammatory pain sensitivity and HPA axis activity during the first three postnatal weeks. Wistar rats were injected with LPS (0.05 mg/kg IP, Salmonella enteritidis) or saline on postnatal days (PNDs) 3 and 5 and later subjected to the formalin test at PNDs 7, 13, and 22. One hour after formalin injection, blood was collected to assess corticosterone responses. Transverse spinal cord slices were also prepared for whole-cell patch clamp recording from lumbar superficial dorsal horn neurons (SDH). Brains were obtained at PND 22 and the hypothalamus was isolated to measure glucocorticoid (GR) and mineralocorticoid receptor (MR) transcript expression using qRT-PCR. Behavioural analyses indicate that at PND 7, no significant differences were observed between saline- or LPS-challenged rats. At PND 13, LPS-challenged rats exhibited enhanced licking (p < .01), and at PND 22, increased flinching in response to formalin injection (p < .05). LPS-challenged rats also displayed increased plasma corticosterone at PND 7 and PND 22 (p < .001) but not at PND 13 following formalin administration. Furthermore, at PND 22 neonatal LPS exposure induced decreased levels of GR mRNA and increased levels of MR mRNA in the hypothalamus. The intrinsic properties of SDH neurons were similar at PND 7 and PND 13. However, at PND 22, ipsilateral SDH neurons in LPS-challenged rats had a lower input resistance compared to their saline-challenged counterparts (p < .05). These data suggest neonatal LPS exposure produces developmentally regulated changes in formalin-induced behavioural responses, corticosterone levels, and dorsal horn neuron properties following noxious stimulation later in life. These findings highlight the importance of immune activation during the neonatal period in shaping pain sensitivity later in life. This programming involves both spinal cord neurons and the HPA axis.

Association of FOXE1 Polyalanine Repeat Region with Papillary Thyroid Cancer

CONTEXT: Polyalanine tract variations in transcription factors have been identified for a wide spectrum of developmental disorders. The thyroid transcription factor forkhead factor E1 (FOXE1) contains a polymorphic polyalanine tract with 12-22 alanines. Single-nucleotide polymorphisms (SNP) close to this locus are associated with papillary thyroid cancer (PTC), and a strong linkage disequilibrium block extends across this region. OBJECTIVE: The objective of the study was to assess whether the FOXE1 polyalanine repeat region was associated with PTC and to assess the effect of polyalanine repeat region variants on protein expression, DNA binding, and transcriptional function on FOXE1-responsive promoters. DESIGN: This was a case-control study. SETTING: The study was conducted at a tertiary referral hospital. PATIENTS AND METHODS: The FOXE1 polyalanine repeat region and tag SNP were genotyped in 70 PTC, with a replication in a further 92 PTC, and compared with genotypes in 5767 healthy controls (including 5667 samples from the Wellcome Trust Case Control Consortium). In vitro studies were performed to examine the protein expression, DNA binding, and transcriptional function for FOXE1 variants of different polyalanine tract lengths. RESULTS: All the genotyped SNP were in tight linkage disequilibrium, including the FOXE1 polyalanine repeat region. We confirmed the strong association of rs1867277 with PTC (overall P = 1 × 10(-7), odds ratio 1.84, confidence interval 1.31-2.57). rs1867277 was in tight linkage disequilibrium with the FOXE1 polyalanine repeat region (r(2) = 0.95). FOXE1(16Ala) was associated with PTC with an odds ratio of 2.23 (confidence interval 1.42-3.50; P = 0.0005). Functional studies in vitro showed that FOXE1(16Ala) was transcriptionally impaired compared with FOXE1(14Ala), which was not due to differences in protein expression or DNA binding. CONCLUSIONS: We have confirmed the previous association of FOXE1 with PTC. Our data suggest that the coding polyalanine expansion in FOXE1 may be responsible for the observed association between FOXE1 and PTC.

Improving diagnosis of tumor-induced osteomalacia with gallium-68 DOTATATE PET/CT

Context: Tumor-induced osteomalacia (TIO) is a rarely diagnosed disorder presenting with bone pain, fractures, muscle weakness, and moderate-to-severe hypophosphatemia resulting from fibroblast growth factor 23-mediated renal phosphate wasting. Tumors secreting fibroblast growth factor 23 are often small and difficult to find with conventional imaging. Objective: We studied the utility of 68Ga-DOTA-octreotate (DOTATATE) somatostatin receptor positron emission tomography (PET)/computed tomography (CT) imaging in the diagnosis of TIO. Design and Setting: A multicenter case series was conducted at tertiary referral hospitals. Patients and Methods: Six patients with TIO diagnosed between 2003 and 2012 in Australia were referred for DOTATATE PET imaging. We reviewed the clinical history, biochemistry, imaging characteristics, histopathology, and clinical outcome of each patient. Results: Each case demonstrated delayed diagnosis despite severe symptoms. DOTATATE PET/CT imaging demonstrated high uptake and localized the tumor with confidence in each case. After surgical excision, there was resolution of clinical symptoms and serum phosphate, except in one patient who demonstrated residual disease on PET/CT. All tumors demonstrated high somatostatin receptor subtype 2 cell surface receptor expression using immunohistochemistry. Conclusions: In patients with TIO, DOTATATE PET/CT can successfully localize phosphaturic mesenchymal tumors and may be a practical first step in functional imaging for this disorder. Serum phosphate should be measured routinely in patients with unexplained muscle weakness, bone pain, or stress fractures to allow earlier diagnosis of TIO. - See more at: http://press.endocrine.org/doi/abs/10.1210/jc.2012-3642#sthash.eXD0CopL.dpuf