bluuebunny/crossref_metadata_2025 huggingface dataset:
MonkeySNP: a web portal for non-human primate single nucleotide polymorphisms
Authors: Khouangsathiene Samone , Pearson Carlo , Street Summer , Ferguson Betsy , Dubay Christopher
Published: September 2008

Summary: MonkeySNP is a web-based resource created by the Genetic Resource and Informatics Program at the Oregon National Primate Research Center to facilitate access to non-human primate (NHP) single nucleotide polymorphisms (SNP) data. MonkeySNP is a mirror of the NCBI dbSNP database and contains additional NHP subpopulation genotype data and visual genotype displays to support SNP review and selection.

Availability:  http://monkeysnp.ohsu.edu/snp/

Contact:  dubayc@ohsu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
A toolkit for capturing and sharing FuGE experiments
Authors: Belhajjame Khalid , Jones Andrew R. , Paton Norman W.
Published: September 2008

Motivation: The Functional Genomics Experiment Object Model (FuGE) supports modelling of experimental processes either directly or through extensions that specialize FuGE for use in specific contexts. FuGE applications commonly include components that capture, store and search experiment descriptions, where the requirements of different applications have much in common.

Results: We describe a toolkit that supports data capture, storage and web-based search of FuGE experiment models; the toolkit can be used directly on FuGE compliant models or configured for use with FuGE extensions. The toolkit is illustrated using a FuGE extension standardized by the proteomics standards initiative, namely GelML.

Availability: The toolkit and a demonstration are available at http://code.google.com/p/fugetoolkit

Contact:  khalid.belhajjame@manchester.ac.uk
Sediment-bound heavy metals as indicators of human influence and biological risk in coastal water bodies
Authors: Birch Gavin F. , Olmos Marco A.
Published: September 2008

Birch, G. F., and Olmos, M. A. 2008. Sediment-bound heavy metals as indicators of human influence and biological risk in coastal water bodies. – ICES Journal of Marine Science, 65: 1407–1413. Currently, many institutions are conducting or planning large, regional-scale ecosystem assessments of estuarine health. A full, integrated assessment of these environments requires a large suite of biological, physical, and chemical indicators, including sedimentary chemistry, ecotoxicology, benthic community structure, and bioaccumulation. This commitment is beyond the capacity of most organizations, and a simpler approach is required to accommodate limited financial resources. A case is made for the use of sedimentary heavy metals as an easy and inexpensive indicator. The advantages are that sediments identify the “pristine” condition and give baseline information against which future management strategies may be benchmarked, and that they differentiate solely human-induced change from natural variation. Sediment indicators in depositional environments are also less dynamic than those associated with water and biota. Our objective is to demonstrate that sediment-bound heavy metals data provide the spatial extent and magnitude of chemical change, as well as the risk of biological stress attributable to contamination in estuarine ecosystems. An assessment of this scheme involving seven New South Wales (Australia) estuaries suggests that sedimentary heavy-metal indicators used in a weight-of-evidence approach, with data collected during the recent Australian National Land and Water Resources Audit, enhances estuarine condition assessment.
Improving Hospital Preparedness for Radiological Terrorism: Perspectives From Emergency Department Physicians and Nurses
Authors: Becker Steven M. , Middleton Sarah A.
Published: September 2008

Background: Hospital emergency department (ED) clinicians will play a crucial role in responding to any terrorist incident involving radioactive materials. To date, however, there has been a paucity of research focusing specifically on ED clinicians’ perspectives regarding this threat.

Methods: At the request of the Centers for Disease Control and Prevention, researchers at the University of Alabama at Birmingham conducted a series of 10 focus groups (total participants, 77) with ED physicians and nurses at hospitals in 3 US regions. Participants considered a hypothetical “dirty bomb” scenario and discussed their perceptions, concerns, information needs, preferred information sources, and views of current guidance and informational materials.

Results: Study participants consistently expressed the view that neither EDs nor hospital facilities are sufficiently prepared for a terrorist event involving radioactive materials. Key clinician concerns included the possibility of the hospital being overwhelmed, safety of loved ones, potential staffing problems, readiness problems, and contamination and self-protection. Participants also expressed a need for additional information, strongly disagreed with aspects of current response guidance, and in some cases indicated they would not carry out current protocols.

Conclusions: This study is the first to examine the views, perceptions, and information needs of hospital ED clinicians regarding radiological terrorism. As such, the findings may be useful in informing current and future efforts to improve hospital preparedness. (Disaster Med Public Health Preparedness. 2008;2:174–184)
Fossil quality and naming dinosaurs
Authors: Benton Michael J
Published: September 2008

The intense interest in dinosaurs through the past 30 years might have led to an increase in poor practice in naming new species. A review of the data shows that the reverse is the case. For 130 years, from the 1820s to the 1950s, most new species of dinosaurs were based on scrappy and incomplete material. After 1960, the majority of new species have been based on complete skulls or skeletons, and sometimes on materials from several individuals. This switch in the quality of type specimens corresponds to the recent explosive renaissance of interest in dinosaurs, during which the number of new species named per year has risen, from three or four in the 1950s, to thirty or more today. The pattern of specimen quality varies by continent, with the highest proportion of new species based on good material in North America, then Asia, then South America, then Africa and finally Europe. This ranking reflects a complex pattern of perhaps overstudy in Europe, immensely rich reserves of new dinosaur materials in North America and Asia, and a relative paucity in South America and Africa.
Space versus phylogeny: disentangling phylogenetic and spatial signals in comparative data
Authors: Freckleton Robert P , Jetz Walter
Published: September 2008

Variation in traits across species or populations is the outcome of both environmental and historical factors. Trait variation is therefore a function of both the phylogenetic and spatial context of species. Here we introduce a method that, within a single framework, estimates the relative roles of spatial and phylogenetic variations in comparative data. The approach requires traits measured across phylogenetic units, e.g. species, the spatial occurrences of those units and a phylogeny connecting them. The method modifies the expected variance of phylogenetically independent contrasts to include both spatial and phylogenetic effects. We illustrate this approach by analysing cross-species variation in body mass, geographical range size and species-typical environmental temperature in three orders of mammals (carnivores, artiodactyls and primates). These species attributes contain highly disparate levels of phylogenetic and spatial signals, with the strongest phylogenetic autocorrelation in body size and spatial dependence in environmental temperatures and geographical range size showing mixed effects. The proposed method successfully captures these differences and in its simplest form estimates a single parameter that quantifies the relative effects of space and phylogeny. We discuss how the method may be extended to explore a range of models of evolution and spatial dependence.
When in doubt, chimpanzees rely on estimates of past reward amounts
Authors: Beran Michael J , Evans Theodore A , Harris Emily H
Published: September 2008

Many animals can repeatedly judge the larger of two sets of food items. However, it remains unclear as to what information might accrue regarding the relative rates of return from these repeated responses. Information about overall rates of return is, in fact, unnecessary to perform well at the task itself. However, if an uncertain situation arose, such as when the quantity in one set was unknown, that information would be useful in determining whether to select a known quantity or an unknown quantity. We gave chimpanzees this test. First, they made multiple judgements between two visible food sets that varied in the number of items across trials. Then, they were faced with the same combinations of set sizes, but only one set was revealed while the other remained unknown. Rather than using a specific quantity as a threshold for choosing the known or the unknown set, the chimpanzees' choice of the unknown set varied in relation to the rate of return from responses in the first phase (when both sets were known). This indicated that the chimpanzees' decisions in the face of uncertainty were guided by a sense of how well they were rewarded overall during the session.
Several deep-sea mussels and their associated symbionts are able to live both on wood and on whale falls
Authors: Lorion Julien , Duperron Sébastien , Gros Olivier , Cruaud Corinne , Samadi Sarah
Published: September 2008

Bathymodiolin mussels occur at hydrothermal vents and cold seeps, where they thrive thanks to symbiotic associations with chemotrophic bacteria. Closely related generaIdasandAdipicolaare associated with organic falls, ecosystems that have been suggested as potential evolutionary ‘stepping stones’ in the colonization of deeper and more sulphide-rich environments. Such a scenario should result from specializations to given environments from species with larger ecological niches. This study provides molecular-based evidence for the existence of two mussel species found both on sunken wood and bones. Each species specifically harbours one bacterial phylotype corresponding to thioautotrophic bacteria related to other bathymodiolin symbionts. Phylogenetic patterns between hosts and symbionts are partially congruent. However, active endocytosis and occurrences of minor symbiont lineages within species which are not their usual host suggest an environmental or horizontal rather than strictly vertical transmission of symbionts. Although the bacteria are close relatives, their localization is intracellular in one mussel species and extracellular in the other, suggesting that habitat choice is independent of the symbiont localization. The variation of bacterial densities in host tissues is related to the substrate on which specimens were sampled and could explain the abilities of host species to adapt to various substrates.
Theoretical and empirical evidence for the impact of inductive biases on cultural evolution
Authors: Griffiths Thomas L , Kalish Michael L , Lewandowsky Stephan
Published: September 2008

The question of how much the outcomes of cultural evolution are shaped by the cognitive capacities of human learners has been explored in several disciplines, including psychology, anthropology and linguistics. We address this question through a detailed investigation of transmission chains, in which each person passes information to another along a chain. We review mathematical and empirical evidence that shows that under general conditions, and across experimental paradigms, the information passed along transmission chains will be affected by the inductive biases of the people involved—the constraints on learning and memory, which influence conclusions from limited data. The mathematical analysis considers the case where each person is a rational Bayesian agent. The empirical work consists of behavioural experiments in which human participants are shown to operate in the manner predicted by the Bayesian framework. Specifically, in situations in which each person's response is used to determine the data seen by the next person, people converge on concepts consistent with their inductive biases irrespective of the information seen by the first member of the chain. We then relate the Bayesian analysis of transmission chains to models of biological evolution, clarifying how chains of individuals correspond to population-level models and how selective forces can be incorporated into our models. Taken together, these results indicate how laboratory studies of transmission chains can provide information about the dynamics of cultural evolution and illustrate that inductive biases can have a significant impact on these dynamics.
MATERNALLY EXPRESSED PAB C-TERMINAL, a Novel Imprinted Gene inArabidopsis, Encodes the Conserved C-Terminal Domain of Polyadenylate Binding Proteins
Authors: Tiwari Sushma , Schulz Reiner , Ikeda Yoko , Dytham Lindsay , Bravo Jaime , Mathers Lucille , Spielman Melissa , Guzmán Plinio , Oakey Rebecca J. , Kinoshita Tetsu , Scott Rod J.
Published: September 2008

Parental imprinting is important for seed development, but few imprinted genes have been identified in plants. The four known imprinted genes in Arabidopsis thaliana encode transcriptional regulators. Here, we describe a novel imprinted gene, MATERNALLY EXPRESSED PAB C-TERMINAL (MPC), which encodes the C-terminal domain of poly(A) binding proteins (PABPs). PABPs play roles in mRNA stability and translation. MPC interacts with proteins that also interact with the C-terminal domain of typical PABPs, suggesting that MPC may regulate translation by modulating PABP activity. In the endosperm, MPC is expressed only from the maternal allele. Reduction of MPC expression affects seed development. In dna methyltransferase1 (met1) mutants, MPC is ectopically expressed, and the paternal allele is active in the endosperm. CGs in the 5′ flanking region and gene body of MPC lose methylation in a met1 background. Both regions are required to confer imprinted reporter expression, suggesting that the gene body contains imprinting control region elements. In Arabidopsis, DEMETER (DME) activates expression of maternal alleles. MPC expression is reduced in flowers and seeds in a dme-4 mutant but only after fertilization in dme-1. We conclude that other factors along with DME promote MPC expression and that DME has indirect effects on imprinted gene expression in endosperm.
Characterization of the steric defense of the HIV‐1 gp41 N‐trimer region
Authors: Eckert Debra M. , Shi Yu , Kim Sunghwan , Welch Brett D. , Kang Eunchai , Poff Emily S. , Kay Michael S.
Published: September 2008

During viral entry, HIV gp41 adopts a transient conformation called the “prehairpin intermediate” in which a highly conserved therapeutic target, the N‐trimer, is exposed. Despite extensive discovery efforts, potent and broadly neutralizing antibodies that target the N‐trimer are elusive. We previously demonstrated the N‐trimer is protected by a steric block that prevents large proteins, such as antibodies, from accessing it. Here we further characterize the steric block and identify its source. To study the N‐trimer steric accessibility, we produced two sets of C‐peptide inhibitors (a potent inhibitor targeting the N‐trimer) fused to cargo proteins of increasing size facing either the virus or cell side of the prehairpin intermediate. Both bulky inhibitor sets show a steric block, but the effect is more pronounced with virus‐side cargo. Additionally, both sets maintain their potencies in a modified entry assay that removes possible sources of target cell steric hindrance. These results implicate a viral source, likely gp120, as the primary component of the steric block. In addition, we studied the steric accessibility of the “pocket” region of the N‐trimer, a highly attractive drug and vaccine target. We demonstrated a pocket‐specific antibody, D5, is more potent as an scFv than as a full‐length IgG, suggesting the N‐trimer steric restriction extends to the pocket. This characterization will facilitate the design of sterically restricted antigens that mimic the steric environment of the N‐trimer in the prehairpin intermediate and are capable of inducing potent and broadly neutralizing antibodies that circumvent the N‐trimer steric block.
Ethnic variation in lower oesophageal sphincter pressure and length
Authors: VEGA K. J. , LANGFORD‐LEGG T. , JAMAL M. M.
Published: September 2008

Background  Oesophageal manometry (OM) is used to diagnose oesophageal motor disorders. Normal values of OM among United States ethnic groups are only available for Hispanic Americans (HA).

Aim  To obtain normal values of OM in adult African American (AA) volunteers, compare these with those obtained in HA and non‐Hispanic white (nHw) volunteers to determine if ethnic variation in normal oesophageal motor function exists.

Methods  Healthy AA, HA and nHw were recruited from the Jacksonville metropolitan area. Ethnicity was self‐reported. Exclusion criteria were symptoms suggestive of oesophageal disease, medication use or concurrent illness affecting OM. All underwent OM using a solid‐state system with wet swallows. Resting lower oesophageal sphincter (LOS) pressure and LOS length were measured at mid‐expiration, while per cent peristaltic contractions, distal oesophageal contraction velocity, amplitude and duration were measured after 5 cc water swallows.

Results  Fifty‐six AA, 20 HA and 48 nHw were enrolled. All completed OM. AA had significantly higher resting LOS pressure, LOS length and distal oesophageal contraction duration than nHw (P < 0.05).

Conclusions  Significant ethnic exist in OM findings between AA and nHw. These underscore the need for ethnic specific reference values for OM to allow for correct diagnosis of oesophageal motor disorders in AA.
Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements
Authors: BJELAKOVIC G. , NIKOLOVA D. , SIMONETTI R. G. , GLUUD C.
Published: September 2008

Background  The evidence on whether antioxidant supplements prevent gastrointestinal cancers is contradictory.

Aim  To assess the beneficial and harmful effects of antioxidant supplements in preventing gastrointestinal cancers.

Methods  Using the Cochrane Collaboration methodology, we reviewed the randomized trials comparing antioxidant supplements with placebo or no intervention on the occurrence of gastrointestinal cancers. We searched electronic databases and reference lists until October, 2007. Our outcome measures were gastrointestinal cancers, overall mortality and adverse events. Outcomes were reported as relative risks (RR) with 95% confidence intervals (CI) based on random‐effects and fixed‐effect models meta‐analyses.

Results  We identified 20 randomized trials (211 818 participants) assessing beta‐carotene, vitamin A, vitamin C, vitamin E, and selenium. The trial quality was generally high. The antioxidant supplements were without a significant effect on the occurrence of gastrointestinal cancers (RR 0.94, 95% CI 0.83–1.06, I2 = 54.0%). The heterogeneity seemed to be explained by bias risk (low‐bias risk trials RR 1.04, 95% CI 0.96–1.13 compared to high‐bias risk trials RR 0.59, 95% CI 0.43–0.80, test of interaction P < 0.0005) and type of antioxidant supplement (beta‐carotene potentially increasing and selenium potentially decreasing cancer risk). Antioxidant supplements had no significant effect on mortality in a random‐effects model meta‐analysis (RR 1.02, 95% CI 0.97–1.07, I2 = 53.5%) but significantly increased mortality in a fixed‐effect model meta‐analysis (RR 1.04, 95% CI 1.02–1.07).

Conclusions  We could not find evidence that the studied antioxidant supplements prevented gastrointestinal cancers. On the contrary, they seem to increase overall mortality.
Systematic review: nutritional support in acute pancreatitis
Authors: PETROV M. S. , PYLYPCHUK R. D. , EMELYANOV N. V.
Published: September 2008

Background  There has been controversy concerning the merits of enteral and parenteral nutrition compared with no supplementary nutrition in the management of patients with acute pancreatitis.

Aim  To perform a systematic review of the data from randomized controlled trials (RCTs) in acute pancreatitis that compares enteral nutrition with no supplementary nutrition, parenteral nutrition with no supplementary nutrition and enteral nutrition with parenteral nutrition.

Methods  A search was undertaken in the MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials.

Results  Fifteen RCTs were included. Enteral nutrition, when compared with no supplementary nutrition, was associated with no significant change in infectious complications: ratio of relative risks (RR) 0.56, 95% confidence interval (CI) 0.07–4.32, P = 0.58, but a significant reduction in mortality: ratio of RR 0.22, 95% CI 0.07–0.70, P = 0.01. Parenteral nutrition, when compared with no supplementary nutrition, was associated with no significant change in infectious complications: RR 1.36, 95% CI 0.18–10.40; P = 0.77, but a significant reduction in mortality: RR 0.36, 95% CI 0.13–0.97, P = 0.04. Enteral nutrition, when compared with parenteral nutrition, was associated with a significant reduction in infectious complications: RR 0.41, 95% CI 0.30–0.57, P < 0.001, but no significant change in mortality: RR 0.60, 95% CI 0.32–1.14, P = 0.12.

Conclusions  The use of either enteral or parenteral nutrition, in comparison with no supplementary nutrition, is associated with a lower risk of death in acute pancreatitis. Enteral nutrition is associated with a lower risk of infectious complications compared with parenteral nutrition.
Clinical trial: oral feeding with a soft diet compared with clear liquid diet as initial meal in mild acute pancreatitis
Authors: SATHIARAJ E. , MURTHY S. , MANSARD M. J. , RAO G. V. , MAHUKAR S. , REDDY D. N.
Published: September 2008

Background  In mild acute pancreatitis, traditional treatment has been initial fasting and oral refeeding with clear liquids to prevent adverse gastrointestinal events such as pain. The diet is gradually progressed to soft solids and hospital discharge is planned based on patients’ tolerance to a solid diet.

Aim  To determine the length of hospitalization and tolerance to oral refeeding when initiated on a soft diet as compared to a clear liquid diet.

Methods  One hundred and one patients with mild acute pancreatitis were randomized to receive either a clear liquid diet or soft diet when oral feeding was initiated. Frequency of pain, total and postrefeeding length of hospitalization, and dietary intake were monitored. Hospital discharge was decided by the medical team without input from the study coordinators.

Results  A statistically significant decrease in the length of hospitalization (total and postrefeeding) of a median of 2 days was seen in patients receiving a soft diet (P < 0.001). No significant difference in the need for cessation of diet because of pain was observed between the two groups. Patients initiated on a soft diet consumed significantly more calories and fats on study day 1 (P < 0.001).

Conclusion  Oral refeeding with a soft diet in patients with mild acute pancreatitis can be considered safe and can result in shorter length of hospitalization.
Clinical trial: a randomized trial of early endoscopy, Helicobacter pylori testing and empirical therapy for the management of dyspepsia in primary care
Authors: DUGGAN A. E. , ELLIOTT C. A. , MILLER P. , HAWKEY C. J. , LOGAN R. F. A.
Published: September 2008

Background  Early endoscopy, Helicobacter pylori eradication and empirical acid suppression are commonly used dyspepsia management strategies in primary care but have not been directly compared in a single trial.

Aim  To compare endoscopy, H. pylori test and refer, H. pylori test and treat and empirical acid suppression for dyspepsia in primary care.

Methods  Patients presenting to their general practitioner with dyspepsia were randomized to endoscopy, H. pylori‘test and treat’, H. pylori test and endoscope positives, or empirical therapy with symptoms, patient satisfaction, healthcare costs and cost effectiveness at 12 months being the outcomes.

Results  At 2 months, the proportion of patients reporting no or minimal dyspeptic symptoms ranged from 74% for those having early endoscopy to 55% for those on empirical therapy (P = 0.009), but at 1 year, there was little difference among the four strategies. Early endoscopy was associated with fewer subsequent consultations for dyspepsia (P = 0.003). ‘Test and treat’ resulted in fewer endoscopies overall and was most cost‐effective over a range of cost assumptions. Empirical therapy resulted in the lowest initial costs, but the highest rate of subsequent endoscopy. Gastro‐oesophageal cancers were found in four patients randomized to the H. pylori testing strategies.

Conclusions  While early endoscopy offered some advantages ‘Test and treat’ was the most cost‐effective strategy. In older patients, early endoscopy may be an appropriate strategy in view of the greater risk of malignant disease.
The effect of mesalazine therapy on quality of life in patients with mildly and moderately active ulcerative colitis
Authors: IRVINE E. J. , YEH C.‐H. , RAMSEY D. , STIRLING A. L. , HIGGINS P. D. R.
Published: September 2008

Background  Ulcerative colitis (UC) has a major impact on the quality of life (QoL) of affected patients. Patient‐reported outcomes have not been thoroughly evaluated in patients with UC receiving oral mesalazine (mesalamine).

Aim  To examine the effect of mesalazine on QoL of patients with mildly and moderately active UC and assess the time course of change, baseline disease severity, mesalazine dose and responder status on QoL parameters.

Methods  Inflammatory Bowel Disease Questionnaire (IBDQ) data were combined from two double‐blind, randomized, multicentre, active‐controlled trials assessing 2.4 and 4.8 g/day oral delayed‐release mesalazine in 687 patients. Mean score changes from baseline were compared at 3 and 6 weeks and effects of baseline severity, mesalazine dose and response to therapy were examined.

Results  Mesalazine significantly improved IBDQ scores at 3 and 6 weeks (mean increase, 29.6 and 39.7 points, respectively; P < 0.0001 for both). Improvement was greater for patients with moderate disease. Greater week 6 changes occurred in clinical responders than nonresponders (50.1 vs. 23.6 points, respectively; P < 0.0001).

Conclusions  Delayed‐release oral mesalazine produces significant clinical and statistical improvements in QoL of patients with UC by 3 weeks, with further improvement at 6 weeks.
High frequency jet ventilation through the laryngeal mask airway in a critically obstructed airway
Authors: Williams A. , Patel A. , Ferguson C.
Published: September 2008

A 72 year‐old man with an anticipated difficult airway secondary to a large, obstructing supraglottic tumour was scheduled for a panendoscopy. An elective pre‐induction transtracheal catheter was placed to allow oxygenation if airway maintenance proved difficult. Following induction of anaesthesia, tracheal intubation was impossible and ventilation via both a facepiece and a laryngeal mask airway became progressively more difficult. An emergency tracheostomy was attempted whilst oxygenation was maintained with transtracheal jet ventilation, but the position of the transtracheal catheter made tracheostomy impossible. The catheter was removed and high frequency jet ventilation was then used via the laryngeal mask airway to maintain oxygenation. To our knowledge, the use of high frequency jet ventilation through the laryngeal mask airway in a critically obstructed airway has not been described before.
4β‐Hydroxycholesterol as an endogenous marker for CYP3A4/5 activity. Stability and half‐life of elimination after induction with rifampicin
Authors: Diczfalusy Ulf , Kanebratt Kajsa P. , Bredberg Eva , Andersson Tommy B. , Böttiger Ylva , Bertilsson Leif
Published: September 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• We have suggested that 4β‐hydroxycholesterol may be used as an endogenous marker of CYP3A activity.

• Recently, we found unexpectedly that the plasma concentration of 4β‐hydroxycholesterol continued to increase for several weeks after complete induction of CYP3A4/5 by carbamazepine.

• In the present study we investigated the time course of elimination of 4β‐hydroxycholesterol from the circulation following CYP3A induction with rifampicin.

WHAT THIS STUDY ADDS

• 4β‐Hydroxycholesterol is eliminated very slowly from the circulation with an apparent half‐life of 17 days.

• The long half‐life results in a low variation in plasma concentration with time, but excludes 4β‐hydroxycholesterol as a marker for rapid changes in CYP3A activity.

AIMS

The oxysterol 4β‐hydroxycholesterol has been suggested as a marker for CYP3A4/5 activity. We have previously shown that plasma 4β‐hydroxycholesterol continues to increase for several weeks after maximal induction of CYP3A4/5 by carbamazepine at the dose given. In the present study we aimed to determine the time course of the decrease in plasma 4β‐hydroxycholesterol after termination of induction of CYP3A4/5 by rifampicin. An additional aim was to determine the variation in plasma level of 4β‐hydroxycholesterol with time in 12 untreated healthy volunteers.

METHODS

Twenty‐four healthy subjects were allocated into three study groups of equal sizes. The volunteers were treated with rifampicin (either 20 mg day–1, 100 mg day–1 or 500 mg day–1) for 2 weeks. Blood samples were taken before, during and after rifampicin treatment. In another group of 12 untreated volunteers blood samples were collected at different time points in order to determine the intraindividual variations in plasma 4β‐hydroxycholesterol concentrations. Plasma levels of 4β‐hydroxycholesterol were determined by isotope‐dilution gas chromatography–mass spectrometry.

RESULTS

Rifampicin treatment increased plasma 4β‐hydroxycholesterol levels. After termination of rifampicin treatment plasma levels of 4β‐hydroxycholesterol decreased slowly with an apparent half‐life of 17 days. The intraindividual variation in plasma levels of 4β‐hydroxycholesterol in untreated subjects was low, with coefficients of variation of between 4.8 and 13.2% over a period of 3 months.

CONCLUSIONS

After termination of induction of CYP3A4/5, plasma 4β‐hydroxycholesterol levels decreased slowly during 8 weeks. The half‐life of elimination (17 days) resembled that of cholesterol rather than other oxysterols. The long half‐life results in stable plasma concentrations with time.
Reduction of dietary fat absorption by the novel gastrointestinal lipase inhibitor cetilistat in healthy volunteers
Authors: Bryson Andrew , De La Motte Stephan , Dunk Christopher
Published: September 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Obesity is a significant and growing problem for which many patients seek pharmacological intervention.

• Orlistat, a lipase inhibitor, is licensed for the treatment of obesity.

• In combination with diet, orlistat is an effective product, but is associated with a number of adverse gastrointestinal adverse events.

WHAT THIS STUDY ADDS

• This study demonstrates that cetilistat is an effective inhibitor of gastrointestinal lipases, substantially increasing the amount of faecal fat excreted at all doses studied.

• In addition, cetilistat is well tolerated, and a comparison with orlistat suggests an improved tolerability profile.

AIMS

To assess the efficacy, pharmacodynamics, safety and tolerability of a range of doses of cetilistat, a novel inhibitor of gastrointestinal lipases, in healthy volunteers.

METHODS

Three Phase I, randomized, placebo‐controlled, parallel‐group studies were conducted. Enrolled subjects in the three studies (n = 99) received a controlled calorie diet (total intake 2160 calories daily, 30% from fat). Twenty‐four subjects were randomized to placebo and 66 were randomized to the following cetilistat doses: 50 mg three times daily [t.i.d. (n = 7)], 60 mg t.i.d. (n = 9), 100 mg t.i.d. (n = 7), 120 mg t.i.d. (n = 9), 150 mg t.i.d. (n = 16), 240 mg t.i.d. (n = 9) and 300 mg t.i.d. (n = 9). Nine subjects received the approved orlistat dose (120 mg t.i.d.). Treatment was for 5 days, with a 2‐day run‐in period and 1‐day post‐treatment follow‐up. The primary outcome measure was daily faecal fat excretion. Secondary outcomes included plasma lipid levels, tolerability [gastrointestinal adverse events (AEs)] and safety.

RESULTS

Cetilistat increased faecal fat excretion relative to baseline at all doses. Cetilistat was well tolerated, with gastrointestinal AEs the most common (51%). Steatorrhoea (oily stool) was more frequent in the orlistat group (4.11 events per subject) than in any cetilistat dose group (0.14–1.81 events per subject). Most AEs (98%) were mild or moderate in intensity.

CONCLUSIONS

Cetilistat increased dietary fat excretion in healthy volunteers receiving a controlled calorie diet. Cetilistat was well tolerated at all doses examined and tolerability appeared to be improved relative to orlistat. Faecal fat excretion in the cetilistat groups was at least comparable to the orlistat 120 mg t.i.d. group.
Benthic metabolism in two turbid dryland rivers
Authors: FELLOWS CHRISTINE S. , BUNN STUART E. , SHELDON FRAN , BEARD NERIDA J.
Published: September 2008

1. Australian dryland rivers have among the most variable discharge of any rivers worldwide and are characterized by extended periods of no flow during which aquatic habitat contracts into isolated waterholes. Despite naturally high turbidity, benthic primary production is known to be the main source of carbon to waterhole food webs. The objective of this study was to quantify rates of benthic metabolism and identify factors influencing these rates in two Australian dryland rivers, the Cooper Creek and the Warrego River.

2. Both rivers have similar variable hydrology and high levels of turbidity (photic depths < 0.4 m), but fish abundance in Cooper Creek is 10 times than that of the Warrego River. Therefore, an additional aim of the study was to determine if fish abundances reflected underlying differences in benthic primary production.

3. Benthic gross primary production (GPP), benthic respiration, nutrient concentrations and light penetration were measured immediately after flow had ceased (‘post‐flow’) and after at least 2 months of zero flow (‘no‐flow’) in 15 waterholes from each river. A subset of four waterholes from each river was sampled on two additional occasions to determine if patterns were consistent over time.

4. Cooper Creek generally had higher rates of GPP and a more autotrophic benthic zone than the Warrego River. As a result, the expected positive relationship between fish abundance and GPP was generally observed at a broad catchment scale.

4. Light was the major control in benthic GPP in both rivers, as nutrient concentrations were high on all sampling occasions. However, for similar values of photic depth, GPP was greater in Cooper Creek than in the Warrego River. This suggests that more frequent disturbance of the littoral zone may inhibit biofilm development in waterholes of the Warrego River.

5. Although flow variability in dryland rivers is extreme compared with other rivers worldwide, cycles of expansion and contraction of aquatic habitat in these two rivers were associated with a shift in the dominance of regional scale (subcatchments contributing to river flow) versus local scale (waterhole morphology) influences on ecosystem functioning, similar to floodplain rivers in tropical and temperate regions.
Ripening stage influenced the expression of polyphenol oxidase, peroxidase, pectin methylesterase and polygalacturonase in two melon cultivars
Authors: Chisari Marco , Silveira Ana C. , Barbagallo Riccardo N. , Spagna Giovanni , Artés Francisco
Published: September 2008

The changes in degradative enzymatic activities (polyphenol oxidase, peroxidase, pectin methylesterase and polygalacturonase) as well as in the main physical and chemical attributes during ripening of two melon types (C. melo var. cantalupensis‘Galia’ cv. and inodorus‘Piel de sapo’ cv.), harvested at three ripening stages were studied. A general decrease of enzymatic activities during ripening of both melon types was found. A high correlation between cell wall degrading activities and melon softening was established. In particular, an increase of PG/firmness ratio in both melon types (r2 coefficients of 0.99 and 0.83 for ‘Galia’ and ‘Piel de sapo’, respectively) was found. Results obtained confirm the role of PG in ripening‐associated cell wall disassembly, in contrast with previous attempts to demonstrate that ripening‐associated pectin degradation in melon is PG independent. As far as we know, the PPO changes during melons ripening have not previously reported. It was remarkable that in ‘Galia’ cv. PPO activity showed a very high correlation with colour changes and the PME/firmness ratio highly correlated with the ripening stage. However in ‘Piel de sapo’ cv. any of these correlations was found.
Systematic review and meta‐analysis of the efficacy of tuina for cervical spondylosis
Authors: Wang Mei‐Yeh , Tsai Pei‐Shan , Lee Pi‐Hsia , Chang Wen‐Yin , Yang Che‐Ming
Published: September 2008

Aims and objectives.  This study performed a meta‐analysis of seven parallel‐group comparison studies evaluating the efficacy of tuina in treating cervical spondylosis.

Background.  Tuina is a form of Chinese manipulative therapy. It has been used as a modality for the treatment of symptoms associated with such a musculoskeletal condition as cervical spondylosis. However, evidence regarding the efficacy of tuina for cervical spondylosis has yet to be determined.

Design.  Systematic review.

Methods.  Cochrane library, Pubmed, MEDLINE, EBM review, ProQuest Medical Bundle and SCOPUS databases were searched using the following medical subject headings or key words: tuina, tuinaology, manual medicine, massotherapy, cervical spondylopathy, cervical spondylosis and cervical vertebrae. Chinese research papers were searched through the Chinese electronic periodical services and Wangfane database. The publication date was limited from 1996–2007. Studies were selected if they were written in English or Chinese, used tuina as a stand‐alone modality, used a parallel‐group comparison design and explicated raw data regarding symptoms relief. Two independent reviewers reviewed the selected studies based on the evidence rating system of the US Preventive Services Task Force. Studies with an evidence rating of II‐2 fair or above were included in this review.

Results.  The direction of the effect size for the improvement of blood flow velocity of vertebral artery and basilar artery was not consistent across studies. Moreover, the pooled effect size was negligible. No evidence supported that tuina could improve headache and vertigo. A small effect of tuina on the viscosity of blood and plasma was found.

Conclusion.  Based on the results of this systematic review, a definitive conclusion regarding the effects of tuina on cervical spondylosis remains to be determined.

Relevance to clinical practice.  The efficacy of tuina is not supported by parallel‐group comparison studies.
Reporting a research project on the potential of aged care nurse practitioners in the Australian Capital Territory
Authors: Arbon Paul , Bail Kasia , Eggert Marlene , Gardner Anne , Hogan Sonia , Phillips Christine , Van Dieman Nicole , Waddington Gordon
Published: September 2008

Aim.  This paper reports a project investigating the potential role of the nurse practitioner in aged care across residential, community and acute care venues in the Australian Capital Territory.

Background.  Australia, like many other countries, faces unprecedented challenges in the provision of health care. Escalating health care costs, an ageing population, increasing prevalence of comorbidities and chronic illnesses, inefficient health care delivery, changing models of health care and shifting professional role boundaries are factors that have contributed to the development of advanced practice roles for nursing.

Design.  This was a mixed methods study using multiple data sources.

Methods.  Student aged care nurse practitioners were examined across the continuum of care in the acute, community and residential aged care settings. The potential role of the nurse practitioner in these areas was evaluated qualitatively and quantitatively to identify a model of care to enhance the delivery of efficient and effective health care.

Results.  The project findings have demonstrated that there is potential for significant improvement in client outcomes arising from a transboundary aged care nurse practitioner model. The improved outcomes are associated with a decrease in acute hospital admissions for residential care clients, timely intervention for a range of common conditions and strengthened multidisciplinary approaches to care provision for older people.

Conclusions.  Overall the project findings strongly support the potential of a transboundary aged care nurse practitioner role. This role would focus on skilled assessment, timely assessment and intervention, brokering around access to care and clinical leadership and education for nurses.

Relevance to clinical practice.  This paper offers further evidence of support for the role of nurse practitioners in complementing existing health services and improving delivery of care.
The constitution of ‘lavender families’: a LGB perspective
Authors: Neville Stephen , Henrickson Mark
Published: September 2008

Aim. To explore and describe lesbian, gay and bisexual people’s families of origin and families of choice.

Background. As a family group lesbian, gay and bisexual people engage with nurses when they interface with any health care service. All health practitioners need to be aware of the existence and constitution of lesbian, gay and bisexual families to provide appropriate health care, including health promotion and education.

Design. Survey.

Method. From April to July 2004 a national survey of lesbian, gay and bisexual persons was carried out. Participants were recruited through mainstream and lesbian, gay and bisexual media and venues. A total of 2269 participants completed the survey instrument either electronically or via hard copy. The 133‐item instrument included a range of closed‐response questions in a variety of domains of interest. The article reports on results from the family and relationships domain.

Results. Findings identified that lesbian, gay and bisexual families present with a variety of both constructed and biological kinship ties and relationships. These relationships vary from supported to estranged in terms of biological family and exclusivity through to non‐exclusivity with regard to partners. Variations also exist in relation to the presence or absence of children and whether these were born before or after ‘coming out’.

Conclusions. Lesbian, gay and bisexual families bring with them to health care services a wide array of life experiences. Therefore it is vital that when interacting with this group of people nurses avoid making assumptions about how gay, lesbian and bisexual people construct their identities and relationships. Furthermore, it may be difficult to ascertain a person’s sexual identity when meeting them for the first time.

Relevance to clinical practice. Nurses need to ensure that they do not assume families seeking healthcare are heterosexual. Providing lesbian, gay and bisexual families with opportunities to disclose sexual identity without fear of disapproval or prejudice is integral to providing a quality and appropriate health service.
GadX/GadW‐dependent regulation of the Escherichia coli acid fitness island: transcriptional control at the gadY–gadW divergent promoters and identification of four novel 42 bp GadX/GadW‐specific binding sites
Authors: Tramonti Angela , De Canio Michele , De Biase Daniela
Published: September 2008

Escherichia coli has the remarkable ability to resist severe acid stress for several hours. With the notable exception of the gadBC operon, the most important genes involved in acid resistance are present within the acid fitness island (AFI), a 15 kb H‐NS‐repressed and RpoS‐controlled genome region. The AraC/XylS‐like transcriptional regulators GadX and GadW are also encoded within this region. In this article, we show that gadW transcription occurs from two native promoters, which are affected by the transcription of the divergently transcribed and GadX‐dependent gadY small RNA, and from the gadX promoter. The gadXW dicistronic transcript is subjected to post‐transcriptional processing in which GadY is involved. In contrast, gadW transcription negatively affects gadY transcription. By aligning the GadX/GadW binding site on the gadY promoter with the GadX/GadW binding sites previously identified in the gadA and gadBC 5′ regulatory regions, we generated a 42 bp GadX/GadW consensus sequence. DNase I footprinting analyses confirmed that a 42 bp GadX/GadW binding site, which matched the consensus sequence 5′‐WANDNCTDWTWKTRAYATWAWMATG KCTGATNTTTWYNTYAK‐3′, is also present in the regulatory region of the slp‐yhiF, hdeAB and gadE‐mtdEF operons, all of which belong to the AFI. The presence of five GadX/GadW‐specific binding sites in the AFI suggests that GadX and GadW may act as H‐NS counter‐silencers.
Abundant extracellular myelin in the meninges of patients with multiple sclerosis
Authors: Kooi E.‐J. , Van Horssen J. , Witte M. E. , Amor S. , Bø L. , Dijkstra C. D. , Van Der Valk P. , Geurts J. J. G.
Published: September 2008

Background: In multiple sclerosis (MS) myelin debris has been observed within MS lesions, in cerebrospinal fluid and cervical lymph nodes, but the route of myelin transport out of the brain is unknown. Drainage of interstitial fluid from the brain parenchyma involves the perivascular spaces and leptomeninges, but the presence of myelin debris in these compartments has not been described. Aims: To determine whether myelin products are present in the meninges and perivascular spaces of MS patients. Methods: Formalin‐fixed brain tissue containing meninges from 29 MS patients, 9 non‐neurological controls, 6 Alzheimer's disease, 5 stroke, 5 meningitis and 7 leucodystrophy patients was investigated, and immunohistochemically stained for several myelin proteins [proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNPase)]. On brain material from MS patients and (non)neurological controls, PLP immunostaining was used to systematically investigate the presence of myelin debris in the meninges, using a semiquantitative scale. Results: Extensive extracellular presence of myelin particles, positive for PLP, MBP, MOG and CNPase in the leptomeninges of MS patients, was observed. Myelin particles were also observed in perivascular spaces of MS patients. Immunohistochemical double‐labelling for macrophage and dendritic cell markers and PLP confirmed that the vast majority of myelin particles were located extracellularly. Extracellular myelin particles were virtually absent in meningeal tissue of non‐neurological controls, Alzheimer's disease, stroke, meningitis and leucodystrophy cases. Conclusions: In MS leptomeninges and perivascular spaces, abundant extracellular myelin can be found, whereas this is not the case for controls and other neurological disease. This may be relevant for understanding sustained immunogenicity or, alternatively, tolerogenicity in MS.