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Doctoral education, advanced practice and research are key elements that have shaped the advancement of nursing. Their impact is augmented when they are integrated and synergistic. To date, no publications have examined these elements holistically or through an international lens. Like a three-legged stool they are inter-reliant and interdependent. Research is integral to doctoral education and influential in informing best practice. This significance and originality of this discussion paper stem from an analysis of these three topics, their history, current status and associated challenges. It is undertaken by renowned leaders in 11 countries within the six World Health Organisation (WHO) regions: South Africa, Egypt, Finland, United Kingdom, Brazil, Canada, United States, India, Thailand, Australia, and the Republic of Korea. The first two authors used a purposive approach to identify nine recognized nurse leaders in each of the six WHO regions. These individuals have presented and published papers on one or more of the three topics. They have led, or currently lead, large strategic organisations in their countries or elsewhere. All these accomplished scholars agreed to collect relevant data and contribute to the analysis as co-authors. Doctoral education has played a pivotal role in advancing nurse scholarship. Many Doctor of Philosophy (PhD) prepared nurses become faculty who go on to educate and guide future nurse researchers. They generate the evidence base for nursing practice, which contributes to improved health outcomes. In this paper, the development of nursing doctoral programmes is examined. Furthermore, PhDs and professional doctorates, including the Doctor of Nursing Practice, are discussed, and trends, challenges and recommendations are presented. The increasing number of advanced practice nurses worldwide contributes to better health outcomes. Nonetheless, this paper shows that the role remains absent or underdeveloped in many countries. Moreover, role ambiguity and role confusion are commonplace and heterogeneity in definitions and titles, and regulatory and legislatorial inconsistencies limit the role's acceptance and adoption. Globally, nursing research studies continue to increase in number and quality, and nurse researchers are becoming partners and leaders in interdisciplinary investigations. Nonetheless, this paper highlights poor investment in nursing research and a lack of reliable data on the number and amount of funding obtained by nurse researchers. The recommendations offered in this paper aim to address the challenges identified. They have significant implications for policy makers, government legislators and nurse leaders.

Background: As global efforts to increase the nursing and midwifery workforce intensify to improve access and quality of healthcare, clinical nursing and midwifery research must increase concomitantly to provide a solid evidence base for these clinicians. To maximize research resources in resource-poor regions, the research team collaborated with regional experts in southern and eastern African countries to convene a Research Summit in Nairobi, Kenya. Objectives were to: build a network of midwifery and nurse scientists, identify regional gaps in knowledge and priorities for their research, develop strategies that address these gaps, and initiate a mentorship plan. Purpose: To review methods leading up to organizing and convening as well as the evaluation of the aforementioned Research Summit. Methods: A two-day regional Summit was convened; appropriate experts from 12 countries participated. In a year-long collaborative process, regional experts and research priorities were identified; during the Summit, a fluid agenda incorporated findings from workgroups. Summative evaluations were completed by participants and planners. Results: Through the Summit, a network of regional research experts was established; peer mentoring was initiated; research priorities were confirmed; regional action plans to address clinical nursing and midwifery research priorities were developed; and technical task forces and a steering committee were formed. Evaluations from participants, planners and core collaborators were collected. Follow up reports have been submitted by technical working groups. Conclusions: Evaluations provided favorable feedback regarding the process leading up to as well as the content of the Research Summit. While further long-term evaluations will be needed to determine the sustainability of this initiative, the Summit format afforded the opportunity for regional experts to meet, examine research priorities, and develop strategic action and mentorship plans. This paper describes a replicable method that could be utilized in other regions using available resources to minimize costs and modest grant funding.

The objective of this study was to explore and describe the factors that influence the decision by pregnant women to be tested for HIV. This was achieved through a qualitative research study that was exploratory, descriptive and contextual in nature. A sample of 13 pregnant women participated. Data obtained from semi-structured interviews was analysed according to a protocol based on a combination of methods of analysis. The three main themes, namely factors that contribute to the decision by pregnant women to be tested for HIV, factors that contribute to the decision by pregnant women not to be tested for HIV and organisational factors that influence the decision by pregnant women to be tested for HIV, were divided into nine subthemes. Conclusions and recommendations to promote counselling to pregnant women being tested for HIV are provided. Opsomming Die doel van die studie was om die faktore wat die besluit van swanger vroue om vir MIV getoets te word, te verken en beskryf. Dit is gedoen deur middel van verkennende, beskrywende, kontekstuele kwalitatiewe navorsing. ’n Steekproef van 13 swanger vroue het deelgeneem. Inligting is verkry deur middel van semi-gestruktureerde onderhoude. Hierdie inligting is ontleed aan die hand van ’n protokol gebaseer op ’n kombinasie van ontledingsmetodes. Die drie hooftemas, naamlik faktore wat bydra tot swanger vroue se besluit om vir MIV getoets te word, faktore wat bydra tot swanger vroue se besluit om nie vir MIV getoets te word nie en organisatoriese faktore wat swanger vroue se besluit beïnvloed om vir MIV getoets te word, is in nege subtemas onderverdeel. Gevolgtrekkings en aanbevelings ter bevordering van berading van swanger vroue vir MIV-toetsing, word verskaf.

Background: International health systems research confirms the critical role that nurses play in ensuring the delivery of high quality patient care and subsequent patient safety. It is therefore important that the education of nurses should prepare them for the provision of safe care of a high quality. The South African healthcare system is made up of public and private hospitals that employ various categories of nurses. The perceptions of the various categories of nurses with reference to quality of care and patient safety are unknown in South Africa (SA). Objective: To determine the relationship between the educational background of nurses and their perceptions of quality of care and patient safety in private surgical units in SA. Methods: A descriptive correlational design was used. A questionnaire was used for data collection, after which hierarchical linear modelling was utilised to determine the relationships amongst the variables. Results: Both the registered- and enrolled nurses seemed satisfied with the quality of care and patient safety in the units were they work. Enrolled nurses (ENs) indicated that current efforts to prevent errors are adequate, whilst the registered nurses (RNs) obtained high scores in reporting incidents in surgical wards. Conclusion: From the results it was evident that perceptions of RNs and ENs related to the quality of care and patient safety differed. There seemed to be a statistically-significant difference between RNs and ENs perceptions of the prevention of errors in the unit, losing patient information between shifts and patient incidents related to medication errors, pressure ulcers and falls with injury.

The aim of this research study was to describe guidelines for more effective management of a distance education institution at a residential university. Opsomming Die doel van hierdie navorsingstudie was tweeledig van aard. Eerstens, om die belewenis van onderwysstudente te verken en te beskryf wat studeer aan 'n afstandsonderrig instansie van 'n residensiele universiteit. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.

In the last two decades, the zebrafish has emerged as an important model species for heart regeneration studies. Various approaches to model loss of cardiac myocytes and myocardial infarction in the zebrafish have been devised, and have included resection, genetic ablation, and cryoinjury. However, to date, the response of the zebrafish ventricle to cautery injury has not been reported. Here, we describe a simple and reproducible method using cautery injury via a modified nichrome inoculating needle as a probe to model myocardial infarction in the zebrafish ventricle. Using light and electron microscopy, we show that cardiac cautery injury is attended by significant inflammatory cell infiltration, accumulation of collagen in the injured area, and the reconstitution of the ventricular myocardium. Additionally, we document the ablation of cardiac nerve fibers, and report that the re-innervation of the injured zebrafish ventricle is protracted, compared to other repair processes that accompany the regeneration of the cauterized ventricle. Taken together, our study demonstrates that cautery injury is a simple and effective means for generating necrotic tissue and eliciting a remodeling and regenerative response in the zebrafish heart. This approach may serve as an important tool in the methods toolbox for regeneration studies in the zebrafish.

Background: There is currently little patient information on bronchiectasis, a chronic lung disease with rising prevalence. Previous work shows that patients and their families want more information, which could potentially improve their understanding and self-management. Using interviews and focus groups, we have co-developed a novel patient and carer information resource, aiming to meet their identified needs. The aims and objectives are: 1. To assess the potential impact of the information resource 2. To evaluate and refine the intervention 3. To establish the feasibility of carrying out a multi-centre randomised controlled trial to determine its effect on understanding, self-management and health outcomes, Methods/design: This is a feasibility study, with a single-centre, randomised controlled trial design, comparing use of a novel patient information resource to usual care in bronchiectasis. Additionally, patients and carers will be invited to focus groups to discuss their views on both the intervention itself and the trial process. The study duration for each participant will be 3 months from the study entry date. A total of 70 patients will be recruited to the study, and a minimum of 30 will be randomised to each arm. Ten participants (and their carers if applicable) will be invited to attend focus groups on completion of the study visits. Participants will be adults with bronchiectasis diagnosed as per national bronchiectasis guidelines. Once consented, participants will be randomised to the intervention or control arm using random permuted blocks to ensure treatment group numbers are evenly balanced. Randomisation will be web-based. Those randomised to the intervention will receive the information resource (website and booklet) and instructions on its use. Outcome measures (resource satisfaction, resource use and alternative information seeking, quality of life questionnaires, unscheduled healthcare visits, exacerbation frequency, bronchiectasis knowledge questionnaire and lung function tests) will be recorded at baseline, 2 weeks and 3 months., Discussion: All outcome measures will be used in assessing feasibility and acceptability of a future definitive trial. Feasibility outcomes include recruitment, retention and study scale form completion rates. Focus groups will strengthen qualitative data for resource refinement and to identify participant views on the trial process, which will also inform feasibility assessments. Questionnaires will also be used to evaluate and refine the resource., Trial Registration: ISRCTN84229105.

Background: The hallmark of non-cystic fibrosis bronchiectasis is recurrent bronchial infection, yet there are significant gaps in our understanding of pathogen persistence, resistance and exacerbation frequencies. Pseudomonas aeruginosa is a key pathogen thought to be a marker of disease severity and progression, yet little is known if the infection risk is seen in those with milder disease or if there is any potential for eradication. These data are important in determining risk stratification and follow up., Methods and Patient Cohort: A retrospective review of consecutive adult patients attending a specialist UK bronchiectasis clinic over a two-year recruitment period between July 2007 and June 2009 was performed. Analysis of our primary outcome, longitudinal microbiological status, was recorded based on routine clinical follow-up through to data capture point or date of death. Patients were stratified by lung function and infecting organism., Results: 155 patients (mean (SD) age 62.2 (12.4) years; 60.1% female) were identified from clinic records with microbiological data for a median (IQR) follow up duration of 46 (35-62) months. Baseline mean FEV1% predicted was 60.6% (24.8) with mean exacerbation frequency of 4.42/year; 73.6% reported 3 or more exacerbations/year. Haemophilus influenzae was isolated in 90 (58.1%) patients and P. aeruginosa in 78 (50.3%) patients with persistent infection in 51 (56.7%) H. influenzae and 47 (60.3%) P. aeruginosa, respectively. Of the P. aeruginosa colonised patients, 16 (34%) became culture negative on follow-up with a mean of 5.2 negative sputum cultures/patient. P. aeruginosa was isolated from 5 out of 39 patients (12.8%) with minimal airflow limitation as compared to 18 out of 38 patients (47.4%) with severe airflow limitation. Although hospital admissions were significantly higher in the P. aeruginosa infected group (1.3 vs. 0.7 admissions per annum, p = 0.035), overall exacerbation rates were the same (4.6 vs. 4.3, p = 0.58). Independent predictors of P. aeruginosa colonisation were low FEV1% predicted (OR 2.46; 95% CI 1.27-4.77) and polymicrobial colonisation (OR 4.07; 95% CI 1.56-10.58). 17 (11%) patients were infected with multi-resistant strains; however, none were pan-resistant., Conclusions: P. aeruginosa is associated with greater persistent infection rates and more hospital admissions than H. influenzae. Exacerbation rates, however, were similar; therefore H. influenzae causes significant out-patient morbidity. P. aeruginosa infection occurs across all strata of lung function impairment but is infrequently multi-resistant in bronchiectasis. Careful microbiology follow up is required even in those with well-preserved lung function., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background and Objective: Neutrophils are consistently found in inflamed and infected airways in idiopathic bronchiectasis, but relatively little is known about the function of blood neutrophils in this condition. We hypothesized that peripheral blood neutrophil (PBN) phagocytosis and superoxide generation are impaired in bronchiectasis, and that granulocyte-macrophage colony-stimulating factor (GM-CSF) is capable of improving neutrophil function., Methods: Neutrophils were isolated from the peripheral blood of patients with idiopathic bronchiectasis who were free of exacerbation, and from healthy controls of similar age (n = 21 in both groups). Ingestion of serum-opsonized zymosan by neutrophils was used to quantify phagocytic capacity. Superoxide generation in neutrophils was measured in response to addition of platelet activating factor and formyl-methionyl-leucyl-phenylalanine. Experiments were performed in the presence or absence of GM-CSF., Results: No differences were observed in either phagocytic capacity (P = 0.99) or superoxide generation (P = 0.81) when comparing patients and controls. However, a significant increase in phagocytic capacity above baseline levels in both patients (P < 0.005) and controls (P < 0.005) was induced by GM-CSF. Similarly, the superoxide generation in patients (P < 0.005) and controls (P = 0.001) was significantly increased by GM-CSF., Conclusions: PBN function was preserved in idiopathic bronchiectasis. Enhancement of neutrophil phagocytosis and superoxide generation by GM-CSF requires further study., (© 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.)

Deficiency of mannose-binding lectin (MBL), a serum protein involved in killing and promoting phagocytosis of pathogens, is associated with respiratory infection and disease progression in a number of acute and chronic lung diseases, including cystic fibrosis (CF)- associated bronchiectasis. No such association has been studied in non-CF bronchiectasis (nCF-Br). One hundred and thirty-three adult patients with nCF-Br were studied. Serum MBL levels were measured and deficiency defined using two cut-off levels, i.e. MBL ≤100 ng/ml and ≤600 ng/ml. Parameters of severity included lung function impairment, annual exacerbation and hospital admission rates, breathlessness, and Pseudomonas aeruginosa and Haemophilus influenzae infection rates. The incidence of MBL deficiency using cut-off levels of 100 ng/ml and 600 ng/ml was 10% and 26% respectively, similar to rates seen in the general population. There was no significant difference in mean FEV(1)% predicted between MBL deficient and sufficient patients at both cut-off levels (≤100 ng/ml: 63.8% vs. 64.6%, P = 0.91; ≤ 600 ng/ml: 66.5% vs. 63.9%, P = 0.56). In addition, exacerbation/hospital admission rates, symptoms of breathlessness and isolation/colonisation rates with P. aeruginosa and H. influenzae were similar in both groups at both cut-off levels. In conclusion, MBL deficiency is not associated with markers of disease severity in patients with nCF-Br.

Background: Fatigue is a complex, disabling symptom in non-CF bronchiectasis (nCF-Br). Fatigue can be formally measured using the validated fatigue impact scale (FIS). The relationship between fatigue and clinically important factors such as airflow obstruction, breathlessness or Pseudomonas aeruginosa infection in nCF-Br is unclear., Aim: To measure the correlation between FIS scores and markers of disease severity in nCF-Br., Design: A prospective cohort study., Methods: Patients attending a specialist service were studied. Lung function (FEV(1)% predicted), Medical Research Council dyspnoea score (MRCD), sputum culture results and FIS were recorded. Patients were categorized according to sputum culture into three subgroups: Pseudomonas 'colonization', 'isolation' and neither., Results: One hundred and seventeen consecutive patients were included. Average FEV(1)% predicted was 64% (SD ±28%). Twelve (10%) patients had Pseudomonas aeruginosa isolation; 47 (40%) patients had P. aeruginosa colonization. Fatigue levels were similar in patients with and without colonization (median 38 versus 32, P = 0.155). Significant fatigue (FIS > 40) was similar in all three Pseudomonas subgroups (P = 0.31, chi-square). Fatigue correlated with MRCD score (r = 0.57, P < 0.001) and FEV(1)% predicted (r = -0.30, P = 0.001). FEV(1)% predicted was lower in patients who had ever isolated or been colonized with P. aeruginosa (P ≤ 0.001)., Conclusion: There are significant correlations between FIS score and MRCD score and FEV(1)% predicted in bronchiectasis. Pseudomonas aeruginosa infection appears to be associated with poorer lung function, and higher MRCD scores, yet there is no significant association between P. aeruginosa status and fatigue.

Background: Pre-operative infection with organisms from the Burkholderia cepacia complex (BCC), particularly B cenocepacia, has been linked with a poorer prognosis after transplantation compared to patients with cystic fibrosis (CF) without this infection. Therefore, many transplant centers do not list these patients for transplantation., Methods: We report the early and long-term results of a cohort of lung transplant recipients with CF and pre-operative BCC infection. Patients with pre-transplantation BCC infection were identified by case-note review. BCC species status was assigned by polymerase chain reaction (PCR)-based techniques. Survival rates were compared to recipients with CF without BCC infection. Survival rates in BCC subgroups were also compared, and then further analyzed pre- and post-2001, when a new immunosuppressive and antibiotic regime was introduced for such patients., Results: Two hundred sixteen patients with CF underwent lung transplantation and 22 had confirmed pre-operative BCC infection, with 12 of these being B cenocepacia. Nine B cenocepacia-infected recipients died within the first year, and in 8 BCC sepsis was considered to be the cause of death. Despite instituting a tailored peri-operative immunosuppressive and microbiologic care approach for such patients, post-transplantation BCC septic deaths occurred frequently in those with pre-transplantation B cenocepacia infection. In contrast, recipients infected with other BCC species had significantly better outcomes, with post-transplantation survival comparable to other recipients with CF., Conclusions: Mortality in patients with B cenocepacia infection was unacceptably high and has led to our center no longer accepting patients with this condition onto the lung transplant waiting list. Long-term survival in the non-B cenocepacia BCC group was excellent, without high rates of acute rejection or bronchiolitis obliterans syndrome (BOS) longer term, and these patients continue to be considered for lung transplantation., (Copyright © 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Salmonella enterica serovar Typhimurium harbors five pathogenicity islands (SPI) required for infection in vertebrate hosts. Although the role of SPI1 in promoting epithelial invasion and proinflammatory cell death has been amply documented, SPI4 has only more recently been implicated in Salmonella virulence. SPI4 is a 24-kb pathogenicity island containing six open reading frames, siiA to siiF. Secretion of the 595-kDa SiiE protein requires a type I secretory system encoded by siiC, siiD, and siiF. An operon polarity suppressor (ops) sequence within the 5' untranslated region upstream of siiA is required for optimal SPI4 expression and predicted to bind the antiterminator RfaH. SiiE concentrations are decreased in a SPI1 mutant strain, suggesting that SPI1 and SPI4 may have common regulatory inputs. SPI1 gene expression is positively regulated by the transcriptional activators HilA, HilC, and HilD, encoded within SPI1, and negatively regulated by the regulators HilE and PhoP. Here, we show that mutations in hilA, hilC, or hilD similarly reduce expression of siiE, and mutations in hilE or phoP enhance siiE expression. Individual overexpression of HilA, HilC, or HilD in the absence of SPI1 cannot activate siiE expression, suggesting that these transcriptional regulators act in concert or in combination with additional SPI1-encoded regulatory loci to activate SPI4. HilA is no longer required for siiE expression in an hns mutant strain, suggesting that HilA promotes SPI4 expression by antagonizing the global transcriptional silencer H-NS. Coordinate regulation suggests that SPI1 and SPI4 play complementary roles in the interaction of S. enterica serovar Typhimurium with the host intestinal mucosa.

Oral glucocorticoids are widely used to treat exacerbations of asthma and COPD. A role for their use in treating exacerbations in Cystic Fibrosis (CF) is not proven. We describe the current practice, amongst UK adult CF physicians, of oral glucocorticoid use as an adjuvant to intravenous (IV) antibiotic treatment during CF pulmonary exacerbation (P EX). The survey also examined whether physicians thought a randomised controlled trial (RCT) was necessary and their willingness to participate patients in such a trial. Eighty one percent of physicians replied. All of them used corticosteroids with P EX. Most physicians supported the need for a RCT and would be willing to enroll consenting patients in the trial. This survey highlighted the need for a RCT which would examine the role of adjuvant corticosteroids to IV antibiotics in CF P EX.

Ferritins are ubiquitous iron (Fe) storage proteins that play a fundamental role in cellular Fe homeostasis. The enteric pathogen Salmonella enterica serovar Typhimurium possesses four ferritins: bacterioferritin, ferritin A, ferritin B and Dps. The haem-containing bacterioferritin (Bfr) accounts for the majority of stored Fe, followed by ferritin A (FtnA). Inactivation of bfr elevates the intracellular free Fe concentration and enhances susceptibility to H2O2 stress. The DNA-binding Dps protein provides protection from oxidative damage without affecting the steady-state intracellular free Fe concentration. FtnB appears to be particularly important for the repair of oxidatively damaged Fe-sulphur clusters of aconitase and, in contrast to Bfr and FtnA, is required for Salmonella virulence in mice. Moreover, ftnB and dps are repressed by the Fe-responsive regulator Fur and induced under conditions of Fe limitation, whereas bfr and ftnA are maximally expressed when Fe is abundant. The absence of a conserved ferroxidase domain and the potentiation of oxidative stress by FtnB in some strains lacking Dps suggest that FtnB serves as a facile cellular reservoir of Fe2+.

Crc (catabolite repression control) protein of Pseudomonas aeruginosa has shown to be involved in carbon regulation of several pathways. In this study, the role of Crc in catabolite repression control has been studied in Pseudomonas putida. The bkd operons of P. putida and P. aeruginosa encode the inducible multienzyme complex branched-chain keto acid dehydrogenase, which is regulated in both species by catabolite repression. We report here that this effect is mediated in both species by Crc. A 13-kb cloned DNA fragment containing the P. putida crc gene region was sequenced. Crc regulates the expression of branched-chain keto acid dehydrogenase, glucose-6-phosphate dehydrogenase, and amidase in both species but not urocanase, although the carbon sources responsible for catabolite repression in the two species differ. Transposon mutants affected in their expression of BkdR, the transcriptional activator of the bkd operon, were isolated and identified as crc and vacB (rnr) mutants. These mutants suggested that catabolite repression in pseudomonads might, in part, involve control of BkdR levels.

The effect of growth in 2xYT medium on catabolite repression control in Pseudomonas putida has been investigated using the bkd operon, encoding branched-chain keto acid dehydrogenase. Crc (catabolite repression control protein) was shown to be responsible for repression of bkd operon transcription in 2xYT. BkdR levels were elevated in a P. putida crc mutant, but bkdR transcript levels were the same in both wild type and crc mutant. This suggests that the mechanism of catabolite repression control in rich media by Crc involves posttranscriptional regulation of the bkdR message.

Reinvestigation of the transcriptional start site of the bkd operon of Pseudomonas putida revealed that the transcriptional start site was located 86 nucleotides upstream of the translational start. There was a sigma 70 binding site 10 bp upstream of the transcriptional start site. The dissociation constants for BkdR, the transcriptional activator of the bkd operon, were 3.1 x 10(-7) M in the absence of L-valine and 8.9 x 10(-8) M in the presence of L-valine. Binding of BkdR to substrate DNA in the absence of L-valine imposed a bend angle of 92 degrees in the DNA. In the presence of L-valine, the angle was 76 degrees. BkdR did not bind to either of the two fragments of substrate DNA resulting from digestion with AgeI. Because AgeI attacks between three potential BkdR binding sites, this suggests that binding of BkdR is cooperative. P. putida JS110 and JS112, mutant strains which do not express any of the components of branched-chain keto acid dehydrogenase, were found to contain missense mutations in bkdR resulting in R40Q and T22I changes in the putative helix-turn-helix of BkdR. Addition of glucose to the medium repressed expression of lacZ from a chromosomal bkdR-lacZ fusion, suggesting that catabolite repression of the bkd operon was the result of reduced expression of bkdR. These data are used to present a model for the role of BkdR in transcriptional control of the bkd operon.