bluuebunny/crossref_metadata_2025 huggingface dataset:
Engaging medical staff in clinical governance: introducing new technologies and clinical practice into public hospitals
Authors: Dwyer Alison J. , Becker Gavin , Hawkins Cindy , McKenzie Lisa , Wells Malcolm
Published: February 2012

Introduction.
To enhance patient care, medical staff at major tertiary teaching hospitals are encouraged to innovate through introducing new technologies and clinical practices. However, such introduction must be safe, efficient, effective and appropriate for patients and the organisation, and actively lead by engage medical staff.

Method.
This study outlines the development, implementation and evaluation of a framework for introducing new technologies and clinical practice to a major tertiary health service. Evaluation includes survey of medical Heads of Units (HOUs) for framework’s effectiveness, and comparison of level of medical staff engagement against a best-practice model.

Results.
Over 2-year period: 19 applications, 7 approved. Successful external funding of $1.993 million achieved. Survey of HOUs in June 2009: response rate 59% (25 of 42 HOUs), with 11 of 25 respondents utilised the committee. Of those 14 of 25 who had not utilised the committee, low awareness of the committee’s existence (2 respondents). Most elements of the best-practice model for engaging medical staff were achieved. Recommendations include improvements to committee process and raising profile with medical staff.

Discussion.
This study demonstrates an effective and successful clinical governance process for introducing new technologies and clinical practice into a major tertiary teaching hospital, supported by moderate levels of medical staff engagement.

What is known about the topic?
To enhance patient care in an innovative research and teaching environment, medical staff at major tertiary teaching hospitals are encouraged to innovate and introduce new technologies and clinical practices. However, such introduction needs to be safe, efficient, effective and appropriate for patients and the organisation, and actively engage medical staff in overseeing such responsibility.

What does this paper add?
This study demonstrates an effective and successful clinical governance process for introducing new technologies and clinical practice into a major tertiary teaching hospital, supported by moderate levels of medical staff engagement.

What are the implications for practitioners?
All health services or hospitals with a focus for medical research and innovation, that incorporate new technologies into their clinical practice, should ensure governance processes similar to those outlined, to ensure best-practice evidence-based clinical and corporate governance. Effective engagement of medical staff in such processes is essential.
Standardising practices improves clinical diabetic foot management: the Queensland Diabetic Foot Innovation Project, 2006 - 09
Authors: Lazzarini Peter A. , O'Rourke Sharon R. , Russell Anthony W. , Derhy Patrick H. , Kamp Maarten C.
Published: February 2012

Objective. The aim of this paper is to report the clinical practice changes resulting from strategies to standardise diabetic foot clinical management in three diverse ambulatory service sites in Queensland, Australia. Methods. Multifaceted strategies were implemented in 2008, including: multidisciplinary teams, clinical pathways, clinical training, clinical indicators, and telehealth support. Prior to the intervention, none of the aforementioned strategies were used, except one site had a basic multidisciplinary team. A retrospective audit of consecutive patient records from July 2006 to June 2007 determined baseline clinical activity (n = 101). A clinical pathway teleform was implemented as a clinical activity analyser in 2008 (n = 327) and followed up in 2009 (n = 406). Pre- and post-implementation data were analysed using Chi-square tests with a significance level set at P < 0.05. Results. There was an improvement in surveillance of the high risk population of 34% in 2008 and 19% in 2009, and treating according to risk of 15% in 2009 (P < 0.05). The documentation of all best-practice clinical activities performed improved 13–66% (P < 0.03). Conclusion. These findings support the use of multifaceted strategies to standardise practice and improve diabetic foot complications management in diverse ambulatory services. What is known about the topic? Diabetic foot complications are recognised as the most common reason for diabetes-related hospitalisation and lower extremity amputations. Approximately 20% of people with diabetes in Australia are at risk of developing a diabetic foot ulcer. Multifaceted strategies to reduce diabetic foot hospitalisation and amputation rates have been successful. However, most people with diabetic foot ulcers are managed in ambulatory settings where data availability is poor and studies limited. What does this paper add? This paper demonstrates that significant improvements in evidence-based diabetic foot complication management can be achieved in diverse Australian ambulatory care settings with multifaceted strategies. This paper contributes to the body of knowledge regarding diabetic foot clinical management in ambulatory settings. What are the implications for practitioners? Practical strategies are available to improve clinical management across a variety of ambulatory settings. Substantial literature suggests this should translate to reduced rates of hospitalisation and amputation for diabetic foot complications.
Effective clinical supervision for regional allied health professionals - the supervisee's perspective
Authors: Dawson Margaret , Phillips Bev , Leggat Sandra G.
Published: February 2012

Aim.
Clinical supervision (CS) for health professionals supports quality clinical practice. This study explored current CS effectiveness for allied health professionals (AHPs) at a regional health service from a supervisee perspective and identified improvements.

Method.
The Manchester Clinical Supervision Scale (MCSS) was completed by 30 supervisees to determine their perceptions of CS effectiveness.

Results.
Supervision sessions typically occurred monthly (56.7%) and were one-to-one (86.2%). The mean total MCSS score was 142.83 (s.d. 15.73), greater than the reported threshold score of 136 for effective CS. The mean subscale scores of ‘trust/rapport’ and ‘improved care/skills’ were high, in contrast to the mean subscale scores for ‘finding time’ and ‘personal issues’, which were significantly lower than the other subscales (P < 0.001). Low scores for ‘finding time’ and ‘personal issues’ subscales may be associated with emotional exhaustion and depersonalisation.

Conclusions.
In this first study evaluating CS for AHPs using the MCSS, CS was reported as being valued and important. However, there is a need for improvement in addressing personal issues that affect work performance and for finding time for CS. As effective CS is an important component of clinical governance by supporting safe and effective healthcare provision, it is vital that CS processes are improved.

What is known about the topic?
There are reports on clinical supervision (CS) effectiveness for nurses, however, there is limited published information about CS for AHPs. Effective CS may enhance clinical skills, improve patient safety and support reflective practice and is a core component of clinical governance. The MCSS has been used to identify CS effectiveness in nurses; however, there have been no previous reports of its use with AHPs.

What does this paper add?
This is the first study to use the MCSS for AHPs and identifies areas for improvement in CS, including scheduling and the need to more effectively address personal issues that affect work performance.

What are the implications for practitioners?
Evaluating the effectiveness of CS in AHPs will lead to improved CS processes and therefore affect the quality of patient care. Effective CS may also affect the wellbeing and job satisfaction for AHPs.
Controlled clinical trial of a self-management program for people with mental illness in an adult mental health service - the Optimal Health Program (OHP)
Authors: Gilbert Monica M. , Chamberlain James A. , White Carolynne R. , Mayers Paul W. , Pawsey Brendan , Liew Danny , Musgrave Matthew , Crawford Kerry , Castle David J.
Published: February 2012

Objective. The objective of this study was to evaluate the effect and cost-effectiveness of a self-management intervention, delivered as part of routine care in an adult mental health service. Method. In a community mental health setting, routine care was compared with routine care plus a nine-session intervention (the Optimal Health Program) using a non-randomised controlled design. Adult (18–65 years) consumers of mental health services in the Australian Capital Territory were eligible for participation. Results. The Optimal Health Program was associated with significant improvements in health and social functioning as measured by the Health of the Nation Outcome Scale (average change relative to control: –3.17; 95% CI –4.49 to –1.84; P < 0.001). In addition, there was a reduction in hospital admissions in the treatment group (percentage of time in hospital reduced from 3.20 to 0.82; P = 0.07). This translated into a net cost saving of over AU$6000 per participant per year (uncertainty range AU$744 to AU$12 656). Conclusions. This study shows promising results for incorporating a self-management program into routine care to improve the health and social functioning of mental health consumers in a cost-effective manner. What is known about the topic? Current literature supports the efficacy of structured self-management programs for chronic conditions such as diabetes (type 1 and 2) and asthma, but there remains limited evidence that self-management programs improve outcomes for people with mental illness. What does this paper add? This study adds to the body of evidence supporting self-management as a cost-effective adjunct to routine care in mental health services. What are the implications for practitioners? Our study supports the feasibility of clinicians delivering cost-effective self-management programs as part of routine mental health service delivery.
How nurse practitioners implement their roles
Authors: Desborough Jane L.
Published: February 2012

Objective.
This is a report of a qualitative health research study examining how nurse practitioners construct and implement their roles.

Methods.
In-depth interviews and a focus group discussion were conducted to obtain narrative data from nurse practitioners from a variety of clinical backgrounds. Data were analysed utilising the principles of grounded theory.

Subjects.
Seven nurse practitioners participated in face-to-face interviews and six participated in a focus group discussion.

Results.
The central process of ‘developing legitimacy and credibility’ is achieved through the processes of: ‘developing Clinical Practice Guidelines’, ‘collaborating with the multidisciplinary team’, ‘communicating’, and ‘transitioning to practice’.

Conclusion.
Policy makers and those responsible for operationalising nurse practitioner roles need to support the central process of developing legitimacy and credibility vital for successful implementation. First, this involves enabling a supportive and informed process of Clinical Practice Guideline development. Second, key inter-disciplinary relationships need to be identified to facilitate collaboration and sources of mentorship for nurse practitioners. Finally, an identified period of transition will facilitate identification, development and implementation of the above processes.

What is known about the topic?
The contemporary role of the nurse practitioner was introduced to provide a flexible, innovative, integrated care strategy, providing increased continuity of nursing care at an advanced practice level. Implementation of the role of the nurse practitioner can be challenging and is influenced by several identified barriers and facilitators.

What does this paper add?
This paper adds an understanding of workplace relationships and processes, which are integral to the construction and implementation of nurse practitioner roles. The interplay of these processes and relationships support the central process of ‘developing legitimacy and credibility’.

What are the implications for practitioners?
This paper provides a clear guide for policy makers and those responsible for operationalising nurse practitioner roles in regard to the requirements underpinning successful role development and implementation.
Chemically Specific Imaging Through Stimulated Raman Photoexcitation and Ultrasound Detection: Minireview
Authors: Yakovlev Vladislav V. , Petrov Georgi I. , Zhang Hao F. , Noojin Gary D. , Thomas Patrick A. , Denton Michael L. , Rockwell Benjamin A. , Thomas Robert J.
Published: February 2012

A powerful combination of chemically specific Raman excitation and deep tissue ultrasound imaging holds the promise to attain spatially resolved distribution of chemical compounds inside the scattering medium. In this report, an attempt is made to evaluate the recent achievements and possible challenges with an eye on potential clinical applications.
Highly Monodispersed PEG-stabilized Ni Nanoparticles: Proficient Catalyst for the Synthesis of Biologically Important Spiropyrans
Authors: Khurana Jitender M. , Yadav Sneha
Published: February 2012

A convenient and efficient synthesis of biologically and pharmacologically important spiropyrans from the condensation of malononitrile, 1,3-dicarbonyl compounds and ninhydrin/acenaphthequinone/isatin has been reported using recyclable heterogeneous polyethylene glycol (PEG)-stabilized Ni nanoparticles in ethylene glycol. This new protocol affords products in high yields and less reaction time.
Development of spermatogenesis in captive-bred Spix's yellow-toothed cavy (Galea spixii)
Authors: Santos P. R. S. , Oliveira M. F. , Silva A. R. , Neto A. C. Assis
Published: February 2012

The aim of this study was to evaluate the phases of sexual development and spermatogenesis of Spix’s yellow-toothed cavy (Galea spixii) based on analyses of the structural components of the testes. The testes of animals from 0 to 150 days of age were collected by orchiectomy, weighed, and processed for analysis by light microscopy. At 45 days of age, spermatozoa were seen in the tubular lumen. Spermatogenesis was not established in animals from 45 to 150 days of age. The stages of sexual development may be classified into the following phases: from birth to the age of 15 days (immature); 30 days of age (prepubertal); 45–105 days of age (pubertal); and 120 and 150 days of age (postpubertal). This is the first study to address the male reproductive biology of Spix’s yellow-toothed cavy.
Monitoring water transport between pores and voids in aerated gypsum using two-dimensional nuclear magnetic resonance exchange measurements
Authors: Song Kyung-Min , Mitchell Jonathan , Jaffel Hamouda , Gladden Lynn F
Published: February 2012

We investigate the connectivity between aeration voids (radius 200–300 µm) and pores (radius 20 µm) in aerated gypsum plaster using two-dimensional (2D) nuclear magnetic resonance T
2–T
2 relaxation time exchange experiments. These measurements provide an estimate of diffusive exchange rates for water molecules moving between environments differentiated by relaxation time. Aerated gypsum is a lightweight material manufactured by the inclusion of voids to reduce the bulk density. Such materials exhibit a multi-modal distribution of pore and void sizes and are associated with novel water imbibition processes. Here, we use T
2–T
2 exchange experiments to characterize the extent of fluid communication between the voids and pores to better understand the structure–transport relationships in these systems. In turn, this will aid the design of gypsum plasters with improved physical and mechanical properties. Utilizing an analytical model based on diffusion-driven exchange, we extract exchange times and hence diffusive length-scales, which are equivalent to the pore diameter. Overall, we conclude that the voids and pores are well connected. This confirms our previous hypothesis that water uptake occurs via capillary-driven imbibition through a continuum of voids and pores in aerated gypsum.
Study on the light leakage mechanism of a blue phase liquid crystal cell with oblique interfaces
Authors: Yoon Sukin , Yang Gyu Hyung , Nayek Prasenjit , Jeong Heon , Lee Seung Hee , Hong Seung Ho , Lee Hyeok Jin , Shin Sung-Tae
Published: February 2012

The mechanism of light leakage in the dark state of a blue phase liquid crystal display cell which has protruded electrodes was investigated. We have performed a hybrid numerical simulation by combining the geometrical optics with the extended Jones matrix method. The light leakage in the cell was caused by changes in the polarization state which has been explained by the asymmetric amplitude change of transverse electric and transverse magnetic fields at the oblique interface and the change in an effective angle between crossed polarizers by the light path refraction. Based on our analysis, light leakage can be suppressed by the matching of the refractive indices of adjacent materials to the interface of the protruded electrodes whose surfaces are not parallel to the substrate.
Phenomenology and Mathematical Practice
Authors: Leng Mary
Published: February 2012

A phenomenological approach to mathematical practice is sketched out, and some problems with this sort of approach are considered. The approach outlined takes mathematical practices as its data, and seeks to provide an empirically adequate philosophy of mathematics based on observation of these practices. Some observations are presented, based on two case studies of some research into the classification of C*-algebras. It is suggested that an anti-realist account of mathematics could be developed on the basis of these and other studies, locating the substance of mathematics in the various informal argument methods used by mathematicians.
Brouwer and Weyl: The Phenomenology and Mathematics of the Intuitive Continuum
Authors: VAN ATTEN MARK , VAN DALEN DIRK , TIESZEN RICHARD
Published: February 2012

Brouwer and Weyl recognized that the intuitive continuum requires a mathematical analysis of a kind that set theory is not able to provide. As an alternative, Brouwer introduced choice sequences. We first describe the features of the intuitive continuum that prompted this development, focusing in particular on the flow of internal time as described in Husserl's phenomenology. Then we look at choice sequences and their logic. Finally, we investigate the differences between Brouwer and Weyl, and argue that Weyl's conception of choice sequences is defective on several counts.
Definitions of Pediatric Pancreatitis and Survey of Present Clinical Practices
Authors: Morinville Veronique D. , Husain Sohail Z. , Bai Harrison , Barth Bradley , Alhosh Rabea , Durie Peter R. , Freedman Steven D. , Himes Ryan , Lowe Mark E. , Pohl John , Werlin Steven , Wilschanski Michael , Uc Aliye ,   INSPPIRE Group
Published: February 2012

Objectives:

There is limited literature on acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP) in children. The International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE) consortium was formed to standardize definitions, develop diagnostic algorithms, investigate disease pathophysiology, and design prospective multicenter studies in pediatric pancreatitis.

Methods:

Subcommittees were formed to delineate definitions of pancreatitis, and a survey was conducted to analyze present practice.

Results:

AP was defined as requiring 2 of the following: abdominal pain compatible with AP, serum amylase and/or lipase values ≥3 times upper limits of normal, and imaging findings of AP. ARP was defined as ≥2 distinct episodes of AP with intervening return to baseline. CP was diagnosed in the presence of typical abdominal pain plus characteristic imaging findings, or exocrine insufficiency plus imaging findings, or endocrine insufficiency plus imaging findings. We found that children with pancreatitis were primarily managed by pediatric gastroenterologists. Unless the etiology was known, initial investigations included serum liver enzymes, triglycerides, calcium, and abdominal ultrasound. Further investigations (usually for ARP and CP) included magnetic resonance or other imaging, sweat chloride, and genetic testing. Respondents' future goals for INSPPIRE included determining natural history of pancreatitis, developing algorithms to evaluate and manage pancreatitis, and validating diagnostic criteria.

Conclusions:

INSPPIRE represents the first initiative to create a multicenter approach to systematically characterize pancreatitis in children. Future aims include creation of patient database and biologic sample repository.
Control of Gibbs free energy relationship between hen egg white lysozyme polymorphs under application of an external alternating current electric field
Authors: Tomita Y. , Koizumi H. , Uda S. , Fujiwara K. , Nozawa J.
Published: February 2012

The distribution of phases between bulk (tetragonal structure) and spherulitic crystals for hen egg white lysozyme was controlled under application of an external alternating current electric field. The distribution of phases differed depending on differences in the magnitude of the electrostatic energy contribution to the respective chemical potentials of the two solid phases. Therefore, the Gibbs free energy relationship between the two solid phases could be controlled by changing the frequency of the applied external electric field. Such a method of controlling the Gibbs free energy relationship among polymorphs would be adaptable to many kinds of protein.
Two isomorphous lanthanide crotonate complexes: di-μ-but-2-enoato-bis[diaquabis(but-2-enoato)dysprosium(III)] adenine monosolvate heptahydrate and the samarium(II) analogue
Authors: Atria Ana María , Garland Maria Teresa , Baggio Ricardo
Published: February 2012

The asymmetric unit of the title dimeric compounds, [Ln2(C4H5O2)6(H2O)4]·C5H5N5·7H2O, with Ln = Dy, (I), and Sm, (II), consists of an LnIIIcation, three crotonate (but-2-enoate) anions and two coordinated water molecules forming the neutral complex, cocrystallized with half of an external adenine molecule and 3.5 water molecules. The metal complex has crystallographic inversion symmetry. The LnO9coordination polyhedra are connected through the sharing of a single edge to form isolated dimeric units, with Ln...Ln separations of 4.1766 (12) Å for (I) and 4.2340 (12) Å for (II). The unbound adenine molecule and one of the solvent water molecules are disordered around an inversion centre into two overlapping, equally populated, units. The structure is sustained by a complex hydrogen-bonding scheme involving all possible O—H and N—H groups as donors, and crotonate and water O and adenine N atoms as acceptors. The system is compared with recently published related compounds.
Geometry and conformation of cyclopropane derivatives having σ-acceptor and σ-donor substituents: a theoretical and crystal structure database study
Authors: Cruz-Cabeza Aurora J. , Allen Frank H.
Published: February 2012

The structures of cyclopropane rings which carry σ-acceptor or σ-donor substituents have been studied using density-functional theory (DFT), and mean bond lengths and conformational parameters retrieved from the Cambridge Structural Database. It is confirmed that σ-acceptor substituents, e.g. halogens, generate positive ring bond-length asymmetry in which there is lengthening of the distal bond (opposite to the point of substitution), and shortening of the two vicinal bonds. This is due to withdrawal of electron density from the cyclopropane 1e′′ orbitals, which are bonding for the distal bond and antibonding for the vicinal bonds. For σ-donor substituents such as SiH3 or Si(CH3)3, the DFT and crystal structure data show negative ring bond-length asymmetry (distal bond shortened, vicinal bonds lengthened), owing to electron donation into the 4e′ ring orbital, which are also bonding for the distal bond and antibonding for the vicinal bonds. The results also show that —OH substituents induce weak positive asymmetry, but that the effects of methyl or amino substituents are either non-existent or extremely small, certainly too small to measure using crystal structure information.
Overnight glucose infusion suppresses renal ammoniagenesis and reduces hyperammonaemia induced by a simulated bleed in cirrhotic patients
Authors: Mpabanzi L. , Deutz N. , Hayes P. C , Dejong C. H. C. , Olde Damink S. W. M. , Jalan R.
Published: February 2012

Background

A simulated upper gastrointestinal (UGI) bleed in cirrhotic patients has been shown to induce hyperammonaemia. The kidney was the site of this exaggerated ammoniagenesis with alanine as substrate. Administration of alanine to decompensated cirrhotic patients did not change hepatic gluconeogenesis, but resulted in increased ammoniagenesis. We hypothesise that reduced hepatic glycogen stores result in hyperglucagonaemia which may drive increased renal gluconeogenesis and therefore alanine uptake and renal ammoniagenesis.

Aim

To determine whether an overnight glucose infusion lowers renal ammoniagenesis by reducing hyperglucagonaemia and renal ammoniagenesis.

Methods

Patients with decompensated cirrhosis were studied in a cross‐over design. An UGI bleed was simulated via intragastric administration of an amino acids mixture mimicking the haemoglobin molecule after a 12‐h overnight fast (F‐group) or after a 12‐h treatment with 20% glucose solution (G‐group).

Results

Before the simulated bleed the glucagon levels were 21 (15–31) pmol/L in the F‐group and 15 (9–21) pmol/L in the G‐group (P < 0.01). After the simulated bleed, arterial ammonia levels increased in both groups [F‐group: 73–118 μmol/L (P = 0.01); G‐group 64–87 μmol/L (P = 0.01)]. The enhancement of hyperammonaemia was significantly higher in the F‐group (45 [19–71] μmol/L) compared with the G‐group (23 [13–39] μmol/L) (P = 0.01). The difference in renal ammoniagenesis during the simulated bleed in the F‐group was 399 (260–655) nmol/kg/bwt/min and was significantly higher than in the G‐group 313 (1–498) nmol/kg/bwt/min (P = 0.05).

Conclusions

Overnight glucose infusion results in reduced renal ammoniagenesis and attenuates ammonia levels. These observations have implications for the development of nutritional strategies in hyperammonaemic patients.
Cardiovascular outcomes associated with concomitant use of clopidogrel and proton pump inhibitors in patients with acute coronary syndrome in Taiwan
Authors: Lin Chen‐Fang , Shen Li‐Jiuan , Wu Fe‐Lin Lin , Bai Chyi‐Huey , Gau Churn‐Shiouh
Published: February 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Conflicting results have been reported regarding the increased risk of adverse outcomes in the concomitant use of clopidogrel and proton pump inhibitors (PPIs) compared with the use of clopidogrel alone.

WHAT THIS STUDY ADDS

• Our study indicated no statistically significant increase in the risk of rehospitalization for acute coronary syndrome due to concurrent use of clopidogrel and PPIs in an Asian population with higher prevalence of CYP2C19 intermediate and poor metabolizers. Among all PPIs, only omeprazole was found to be statistically significantly associated with an increased risk of rehospitalization for acute coronary syndrome.

AIMS Our study aimed to examine the impact of concomitant use of proton pump inhibitors (PPIs) with clopidogrel on the cardiovascular outcomes of patients with acute coronary syndrome (ACS). Furthermore, we sought to quantify the effects of five individual PPIs when used concomitantly with clopidogrel.

METHODS We conducted a retrospective cohort study of patients who were newly hospitalized for ACS between 1 January 2006 and 31 December 2007 retrieved from the Taiwan National Health Insurance Research Database (NHIRD) and who were prescribed clopidogrel (n= 37 099) during the follow‐up period. A propensity score technique was used to establish a matched cohort in 1:1 ratio (n= 5173 for each group). The primary clinical outcome was rehospitalization for ACS, while secondary outcomes were rehospitalization for percutaneous transluminal coronary angioplasty (PTCA) with stent, PTCA without stent and revascularization (PTCA or coronary artery bypass graft surgery) after the discharge date for the index ACS event.

RESULTS The adjusted hazard ratio of rehospitalization for ACS was 1.052 (95% confidence interval, 0.971–1.139; P= 0.214) in the propensity score matched cohort. Among all PPIs, only omeprazole was found to be statistically significantly associated with an increased risk of rehospitalization for ACS (adjusted hazard ratio, 1.226; 95% confidence interval, 1.066–1.410; P= 0.004). Concomitant use of esomeprazole, pantoprazole, rabeprazole and lansoprazole did not increase the risk.

CONCLUSIONS Our study indicated no statistically significant increase in the risk of rehospitalization for ACS due to concurrent use of clopidogrel and PPIs overall. Among individual PPIs, only omeprazole was found to be statistically significantly associated with increased risk of rehospitalization for ACS.
Hydroxycarbamide alters erythroid gene expression in children with sickle cell anaemia
Authors: Flanagan Jonathan M. , Steward Shirley , Howard Thad A. , Mortier Nicole A. , Kimble Amy C. , Aygun Banu , Hankins Jane S. , Neale Geoffrey A. , Ware Russell E.
Published: February 2012

Sickle cell anaemia (SCA) is a severe debilitating haematological disorder associated with a high degree of morbidity and mortality. The level of fetal haemoglobin (HbF) is well‐recognized as a critical laboratory parameter: lower HbF is associated with a higher risk of vaso‐occlusive complications, organ damage, and early death. Hydroxycarbamide treatment can induce HbF, improve laboratory parameters, and ameliorate clinical complications of SCA but its mechanisms of action remain incompletely defined and the HbF response is highly variable. To identify pathways of hydroxycarbamide activity, we performed microarray expression analyses of early reticulocyte RNA obtained from children with SCA enrolled in the HydroxyUrea Study of Long‐term Effects (NCT00305175) and examined the effects of hydroxycarbamide exposure in vivo. Hydroxycarbamide affected a large number of erythroid genes, with significant decreases in the expression of genes involved in translation, ribosome assembly and chromosome organization, presumably reflecting the daily cytotoxic pulses of hydroxycarbamide. Hydroxycarbamide also affected expression of numerous genes associated with HbF including BCL11A, a key regulator of baseline HbF levels. Together, these data indicate that hydroxycarbamide treatment for SCA leads to substantial changes in erythroid gene expression, including BCL11A and other potential signalling pathways associated with HbF induction.
Tissue factor‐positive monocytes in children with sickle cell disease: correlation with biomarkers of haemolysis
Authors: Setty B. N. Yamaja , Key Nigel S. , Rao A. Koneti , Gayen‐Betal Suhita , Krishnan Suba , Dampier Carlton D. , Stuart Marie J.
Published: February 2012

Tissue Factor (TF) initiates thrombin generation, and whole blood TF (WBTF) is elevated in sickle cell disease (SCD). We sought to identify the presence of TF‐positive monocytes in SCD and their relationship with the other coagulation markers including WBTF, microparticle‐associated TF, thrombin‐antithrombin (TAT) complexes and D‐dimer. Whether major SCD‐related pathobiological processes, including haemolysis, inflammation and endothelial activation, contribute to the coagulation abnormalities was also studied. The cohort comprised children with SCD (18 HbSS, 12 HbSC, mean age 3·6 years). We demonstrated elevated levels of TF‐positive monocytes in HbSS, which correlated with WBTF, TAT and D‐dimer (P = 0·02 to P = 0·0003). While TF‐positive monocytes, WBTF, TAT and D‐dimer correlated with several biomarkers of haemolysis, inflammation and endothelial activation in univariate analyses, in multiple regression models the haemolytic markers (reticulocytes and lactate dehydrogenase) contributed exclusively to the association with all four coagulant markers evaluated. The demonstration that haemolysis is the predominant operative pathology in the associated perturbations of coagulation in HbSS at a young age provides additional evidence for the early use of therapeutic agents, such as hydroxycarbamide to reduce the haemolytic component of this disease.
Terrestrial biosphere model performance for inter‐annual variability of land‐atmosphere CO2 exchange
Authors: Keenan T.F. , Baker Ian , Barr Alan , Ciais Philippe , Davis Ken , Dietze Michael , Dragoni Danillo , Gough Christopher M , Grant Robert , Hollinger David , Hufkens Koen , Poulter Ben , McCaughey Harry , Raczka Brett , Ryu Youngryel , Schaefer Kevin , Tian Hanqin , Verbeeck Hans , Zhao Maosheng , Richardson Andrew D.
Published: February 2012

Interannual variability in biosphere‐atmosphere exchange of CO2 is driven by a diverse range of biotic and abiotic factors. Replicating this variability thus represents the ‘acid test’ for terrestrial biosphere models. Although such models are commonly used to project responses to both normal and anomalous variability in climate, they are rarely tested explicitly against inter‐annual variability in observations. Herein, using standardized data from the North American Carbon Program, we assess the performance of 16 terrestrial biosphere models and 3 remote sensing products against long‐term measurements of biosphere‐atmosphere CO2 exchange made with eddy‐covariance flux towers at 11 forested sites in North America. Instead of focusing on model‐data agreement we take a systematic, variability‐oriented approach and show that although the models tend to reproduce the mean magnitude of the observed annual flux variability, they fail to reproduce the timing. Large biases in modeled annual means are evident for all models. Observed interannual variability is found to commonly be on the order of magnitude of the mean fluxes. None of the models consistently reproduce observed interannual variability within measurement uncertainty. Underrepresentation of variability in spring phenology, soil thaw and snowpack melting, and difficulties in reproducing the lagged response to extreme climatic events are identified as systematic errors, common to all models included in this study.
Foam stability of leaves from anthocyanidin‐accumulating Lc‐alfalfa and relation to molecular structures detected by fourier‐transformed infrared‐vibration spectroscopy
Authors: Jonker A. , Gruber M. Y. , Wang Y. , Coulman B. , McKinnon J. J. , Christensen D. A. , Yu P.
Published: February 2012

Foam stability related to pasture bloat from alfalfa pastures might be reduced by introducing a gene that stimulates the accumulation of mono‐/polymeric‐anthocyanidin. The objective of this study was to determine the foam formation (at 0 min) and stability (at 150 min) from aqueous leaf extracts of three transgenic Lc‐alfalfa progeny (BeavLc1, RambLc3 and RangLc4), parental non‐transgenic (NT) alfalfa and AC Grazeland (bloat‐reduced cultivar) harvested at 07:00 or 18:00 h. Initial and final foam volumes at 07:00 h were lower for AC Grazeland compared with all other treatments and lower for RangLc4 compared with the other two Lc‐progeny at 0 min and NT‐alfalfa at 150 min. At 18:00 h, initial foam volume was larger for NT‐alfalfa and final foam volume was larger for RambLc3 compared with AC Grazeland, BeavLc1 and RangLc4. Spectroscopic vibration associated with carbohydrates increased initial foam volume and stability. More amide I relative to amide II, fewer α‐helices relative to β‐sheets and leaf extract ethanol‐film and protein content increased initial foam volume but did not stabilize it. Spectroscopic vibration associated with all carbohydrates other than structural carbohydrates was more important than vibration from protein structures for foam formation and stabilization. In conclusion, Lc‐alfalfa accumulated anthocyanidin and had reduced foaming properties compared with parental NT alfalfa but AC Grazeland and RangLc4 had the lowest foaming properties.
Modelling carcass disposal practices: implications for the management of an ecological service provided by vultures
Authors: Dupont Hélène , Mihoub Jean‐Baptiste , Bobbé Sophie , Sarrazin François
Published: February 2012

1. In many European countries, private companies are in charge of livestock carcass disposal. In agro‐pastoral systems, however, scavengers such as vultures provide an alternative ecological service for disposing of carcasses.

2. By combining interviews with farmers and ecological data from the Grands Causses region (southern France), we developed an agent‐based model to assess the environmental and economic consequences of various farmers’ carcass disposal strategies, involving private companies and/or vultures. The model includes ‘offering’ vulture feeding behaviour, as an ecological service, and farmer choices of carcass disposal system, representing the ‘demand’ for this service.

3. This ecological service can provide benefits through reducing monetary costs and carbon emissions associated with carcass disposal, but also represent a sanitary risk if vultures fail to remove carrion efficiently. Benefits and risks strongly depend on carcass disposal techniques and the wider strategy.

4. The most sustainable strategy to match the ‘demand’ and ‘offer’ for carcass disposal involves the adaptive use by farmers of both the ecological and the industrial services. This strategy enables the optimization of the ecological service benefits while minimizing sanitary risks by using a private company service, when carcass disposal by vultures is uncertain.

5. Synthesis and applications. In cases where there is a mismatch between the demand and the offer, negative feedback can occur for both humans and vultures. Preserving vulture populations and enhancing benefits from the sustainable service, they provide might henceforth be explicitly accounted for in legislation and carcass management guidance, in accordance with vulture food requirements. The agent‐based modelling approach described here offers a tool that can guide management strategies and policies and support coordination among stakeholders.
Upland deforestation triggered an ecosystem state‐shift in a kettle peatland
Authors: Ireland Alex W. , Booth Robert K.
Published: February 2012

1. European settlement of eastern North America resulted in dramatic changes to ecosystems, although the dynamics and underlying causes of these changes are not always obvious. For example, land clearance likely exposed soils to increased wind erosion, potentially impacting downwind ecosystems indirectly through subsequent enhancement of dust deposition. We hypothesized that otherwise undisturbed wetlands were altered through this indirect disturbance mechanism, increasing nutrient availability and initiating a cascade of ecosystem‐level changes.

2. We tested this hypothesis in a floating kettle peatland located in north‐western Pennsylvania, USA, using an interdisciplinary approach. A series of peat cores were collected along a transect oriented parallel to the dominant wind direction. Palaeoecological techniques were used to identify signatures of upland deforestation and mineral matter deposition within the peat profiles. Elemental analyses were used to reconstruct historic availability of major macronutrients, plant community dynamics were reconstructed using plant macrofossils and tree rings (Pinus strobus) and testate amoebae were used as a proxy for microbial community dynamics.

3. Strong correlations between the concentration of ragweed (Ambrosia) pollen and fine‐grained mineral matter linked upland deforestation to enhanced dust deposition on the peatland surface. Elemental analyses indicated that nitrogen, phosphorus and potassium concentrations increased coincident with dust deposition. Plant communities shifted from Sphagnum dominance to vascular‐plant dominance coincident with enhanced dust deposition, including increased recruitment of P. strobus onto the peatland. Testate amoeba communities shifted towards those adapted to highly variable microenvironmental conditions and likely reflect broader changes in microbial communities.

4. Synthesis. Upland deforestation by European settlers triggered a cascade of ecological changes on a nutrient‐poor peatland by enhancing dust deposition and nutrient delivery on the surface. These results demonstrate that indirect, unintended and often overlooked human disturbances can lead to dramatic structural and functional alterations of carbon‐rich wetland ecosystems, highlighting the potential vulnerability of these systems in human‐dominated landscapes.
Glycyrrhizin in patients who failed previous interferon alpha‐based therapies: biochemical and histological effects after 52 weeks
Authors: Manns M. P. , Wedemeyer H. , Singer A. , Khomutjanskaja N. , Dienes H. P. , Roskams T. , Goldin R. , Hehnke U. , Inoue H. ,   the European SNMC Study Group
Published: February 2012

Summary.  Chronic hepatitis C patients often fail to respond to interferon‐based therapies. This phase III study aimed at confirming the efficacy and safety of glycyrrhizin in interferon + ribavirin‐based therapy non‐responders. A randomised, double‐blind, placebo‐controlled, comparison of glycyrrhizin, administered intravenously 5×/or 3×/week, and 5×/week placebo for 12 weeks to 379 patients, was followed by a randomised, open comparison of glycyrrhizin i.v. 5×/versus 3×/week for 40 weeks. Primary endpoints were: (1) the proportion of patients with ≥50% ALT (alanine aminotransferase) reduction after 12 weeks double‐blind phase, and (2) the proportion of patients with improvement of necro‐inflammation after 52 weeks as compared with baseline. The proportion of patients with ALT reduction ≥50% after 12 weeks was significantly higher with 5×/week glycyrrhizin (28.7%, P < 0.0001) and 3×/week glycyrrhizin (29.0%, P < 0.0001) compared with placebo (7.0%). The proportion of patients with improvement in necro‐inflammation after 52 weeks was 44.9% with 5×/week and 46.0% with 3×/week, respectively. Glycyrrhizin exhibited a significantly higher ALT reduction compared to placebo after 12 weeks of therapy and an improvement of necro‐inflammation and fibrosis after 52‐weeks treatment. Generally, glycyrrhizin treatment was well tolerated.
Evidence for selection at cytokine loci in a natural population of field voles (Microtus agrestis)
Authors: TURNER ANDREW K. , BEGON MIKE , JACKSON JOSEPH A. , PATERSON STEVE
Published: February 2012

Individuals in natural populations are frequently exposed to a wide range of pathogens. Given the diverse profile of gene products involved in responses to different types of pathogen, this potentially results in complex pathogen‐specific selection pressures acting on a broad spectrum of immune system genes in wild animals. Thus far, studies into the evolution of immune genes in natural populations have focused almost exclusively on the Major Histocompatibility Complex (MHC). However, the MHC represents only a fraction of the immune system and there is a need to broaden research in wild species to include other immune genes. Here, we examine the evidence for natural selection in a range of non‐MHC genes in a natural population of field voles (Microtus agrestis). We concentrate primarily on genes encoding cytokines, signalling molecules critical in eliciting and mediating immune responses and identify signatures of natural selection acting on several of these genes. In particular, genetic diversity withinInterleukin 1 betaandInterleukin 2appears to have been maintained through balancing selection. Taken together with previous findings that polymorphism within these genes is associated with variation in resistance to multiple pathogens, this suggests that pathogen‐mediated selection may be an important force driving genetic diversity at cytokine loci in voles and other natural populations. These results also suggest that, along with the MHC, preservation of genetic variation within cytokine genes should be a priority for the conservation genetics of threatened wildlife populations.
Treatment outcome of dogs with meticillin‐resistant and meticillin‐susceptibleStaphylococcus pseudintermediuspyoderma
Authors: Bryan Jacqueline , Frank Linda A. , Rohrbach Barton W. , Burgette Laura J. , Cain Christine L. , Bemis David A.
Published: February 2012

Background – The prevalence of meticillin‐ and multidrug‐resistantStaphylococcus pseudintermedius(MRSP) in canine pyoderma has been increasing in recent years; thus, treatment of these cases has become challenging.

Hypothesis/Objectives – To compare treatment outcome (clinical resolution and treatment duration), adverse effects of medication, and concurrent diseases and medications in dogs with meticillin‐susceptibleS. pseudintermedius(MSSP) and MRSP pyoderma.

Animals/Methods – Medical records were reviewed retrospectively, and 123 MSSP and 93 MRSP clinical cases between January 2008 and April 2010 were included.

Results – In MSSP infections, cefalexin and cefpodoxime were the most commonly prescribed antimicrobials, accounting for 43.2 and 34.4% of cases, respectively. In MRSP infections, chloramphenicol and doxycycline were most commonly prescribed, accounting for 52.6 and 14.4% of cases, respectively. Adverse effects were reported in seven MSSP and 31 MRSP cases. The most commonly reported adverse effects were gastrointestinal, prompting antibiotic discontinuation in three MSSP and 20 MRSP cases. Chloramphenicol was associated with the highest incidence of adverse reactions (27 of 51 cases). Of 164 cases with follow up, 43 of 88 MSSP infections and 29 of 76 MRSP infections achieved complete clinical resolution at the first recheck examination. Three MSSP and seven MRSP cases failed to improve or resolve at subsequent visits assessed at 3–4 week intervals.

Conclusions and clinical importance – Results from this study showed that the majority of pyodermas resolved regardless of meticillin susceptibility. Although some cases of MRSP pyoderma took longer to treat, this is likely to be because of chronicity and not the organism. In addition, adverse effects were frequently associated with chloramphenicol administration.