bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of cell‐free protein synthesis for the crystallization of membrane proteins – a case study on a member of the glutamate transporter family from Staphylothermus marinus
Authors: Jaehme Michael , Michel Hartmut
Published: December 2012

Cell‐free in vitro synthesis of proteins using coupled transcription/translation is considered to be a powerful alternative to the use of traditional cell‐based expression systems. Recently, promising developments have been reported applying cell‐free production to membrane proteins for structural biology and in particular for NMR spectroscopy. However, the general applicability of this system to produce large amounts of stable, functional and homogeneous membrane proteins as required for X‐ray crystallography remains to be determined. Here, we present a systematic study comparing structural and functional properties of membrane proteins produced using Escherichia coli derived in vitro and in vivo expression systems. The function of the target membrane protein, a previously uncharacterized bacterial glutamate transporter homolog from Staphylothermus marinus, was analyzed using ligand binding and transport assays. In addition, the protein structure was investigated with respect to its overall fold and oligomeric state in different detergents. We found that the protein synthesized in vitro is highly stable and monodisperse. However, in contrast to the protein produced using an in vivo system, it was not able to assemble into the native trimeric state nor to bind substrate. We thus conclude that cell‐free expression systems can compromise folding and function of such complex secondary active transporters. The expression product has to be carefully characterized prior to biophysical investigations like crystallography of membrane proteins.

Structured digital abstract

GltSM and GltSM bind by molecular sieving (View interaction)

GltSM and GltSM bind by cross-linking study (View interaction)
Unraveling the function of the two Entner–Doudoroff branches in the thermoacidophilic Crenarchaeon Sulfolobus solfataricus P2
Authors: Kouril Theresa , Wieloch Patricia , Reimann Julia , Wagner Michaela , Zaparty Melanie , Albers Sonja‐Verena , Schomburg Dietmar , Ruoff Peter , Siebers Bettina
Published: December 2012

Sulfolobus solfataricus P2 is a thermoacidophilic archaeon that metabolizes glucose and galactose via an unusual branched Entner–Doudoroff (ED) pathway, which is characterized by a non‐phosphorylative (np) and a semi‐phosphorylative (sp) branch. However, so far the physiological significance of the two pathway branches is unknown. In order to address these questions two key enzymes of the branched ED pathway, the class II glycerate kinase (GK) of the np‐ED branch and the 2‐keto‐3‐deoxygluconate kinase (KDGK) of the sp‐ED branch in S. solfataricus, were investigated. GK was recombinantly purified and characterized with respect to its kinetic properties. Mg2+ dependent Sso‐GK (glycerate + ATP → 2‐phosphoglycerate + ADP) showed unusual regulatory properties, i.e. substrate inhibition and cooperativity by d‐glycerate and ATP, and a substrate‐inhibition model was established fitting closely to the experimental data. Furthermore, deletion of the sp‐ED key enzyme KDGK in S. solfataricus PBL2025 resulted in a similar growth phenotype on glucose as substrate compared with the wild‐type. In contrast, the mutant showed strongly increased concentrations of np‐ED intermediates whereas the hexose and pentose phosphates as well as trehalose were decreased. Together the results indicate (a) that the np‐ED pathway is able to compensate for the missing sp‐ED branch in glucose catabolism, (b) that in addition to its catabolic function the sp‐ED pathway has an additional although not essential role in providing sugar phosphates for anabolism/gluconeogenesis and (c) that GK, with its unusual regulatory properties, seems to play a major role in controlling the flux between the glycolytic np‐ED and the glycolytic/gluconeogenetic sp‐ED pathway.

Database

The amino acid sequence data of GK of S. solfataricus P2 is available in the UniProt Protein Database under the accession number Q7LXP1 (http://www.uniprot.org/uniprot/Q7LXP1).
Detecting nonlinear response of spring phenology to climate change by Bayesian analysis
Authors: Pope Katherine S. , Dose Volker , Da Silva David , Brown Patrick H. , Leslie Charles A. , DeJong Theodore M.
Published: December 2012

The impact of climate change on the advancement of plant phenological events has been heavily studied in the last decade. Although the majority of spring plant phenological events have been trending earlier, this is not universally true. Recent work has suggested that species that are not advancing in their spring phenological behavior are responding more to lack of winter chill than increased spring heat. One way to test this hypothesis is by evaluating the behavior of a species known to have a moderate to high chilling requirement and examining how it is responding to increased warming. This study used a 60‐year data set for timing of leaf‐out and male flowering of walnut (Juglans regia) cultivar ‘Payne’ to examine this issue. The spring phenological behavior of ‘Payne’ walnut differed depending on bud type. The vegetative buds, which have a higher chilling requirement, trended toward earlier leaf‐out until about 1994, when they shifted to later leaf‐out. The date of male bud pollen shedding advanced over the course of the whole record. Our findings suggest that many species which have exhibited earlier bud break are responding to warmer spring temperatures, but may shift into responding more to winter temperatures (lack of adequate chilling) as warming continues.
Synchrotron XRF and XANES investigation of uranium speciation and element distribution in fluid inclusions from unconformity‐related uranium deposits
Authors: Richard A. , Cauzid J. , Cathelineau M. , Boiron M.‐C. , Mercadier J. , Cuney M.
Published: December 2012

Fluid inclusions from two quartz samples of the McArthur River and Rabbit Lake unconformity‐related uranium deposits (Athabasca Basin, Canada) were analysed by synchrotron X‐ray fluorescence (SXRF) and X‐ray absorption near‐edge spectroscopy (XANES) to shed light on (i) the detailed chemistry of the fluids having transported the uranium and (ii) the speciation of uranium in these fluids. The analysed samples contain variable proportions of NaCl‐rich or CaCl2‐rich (25–35 wt% salts) fluid inclusions that homogenise into the liquid phase between 120 and 200°C. For unknown reason, all of the CaCl2‐rich fluid inclusions decrepitate under X‐ray beam after a few seconds, precluding any SXRF or XANES measurement. SXRF on 12 homogenised NaCl‐rich fluid inclusions from the Rabbit Lake sample shows that the fluid inclusions contain appreciable amounts of Br, Fe, Sr, transition metals (Mn, Ni, Cu, Zn), Pb, U and rare earth elements (REE) (La, Ce), with concentrations being relatively homogeneous among fluid inclusions. Within the complex McArthur River sample (numerous fluid inclusions + randomly distributed solids), statistical analyses of hyperspectral SXRF images were performed using the non‐negative matrix approximation (NNMA) method. This strategy allows distinguishing the three domains contributing to the overall signal: (i) the quartz matrix, which notably contains significant amounts of Cr, Cu and Pb; (ii) the fluid inclusions characterised by high amounts of Br, Fe, Sr and transition metals; and (iii) La‐Ce ± Fe solids. Part of the U and REE are spatially associated with distinct optically invisible solids within the quartz matrix. XANES on four McArthur River sample fluid inclusions at room temperature and at 150°C (fluid inclusion trapping temperature) as well as in solid and liquid U(IV) and U(VI) standards, respectively, shows that the uranium has remained in the form of U(VI) from trapping to present in the fluid inclusion.
Modelling fault reactivation and fluid flow around a fault restraining step‐over structure in the Laverton gold region, Yilgarn Craton, Western Australia
Authors: Zhang Y. , Schaubs P. M. , Sheldon H. A. , Poulet T. , Karrech A.
Published: December 2012

Laverton is an important region in the Yilgarn Craton for gold mineralization. Previous studies suggested that the premineralization structure was dominated by a fault restraining step‐over structure with the Wallaby fault and Sunrise Shear Zone as the key fault splays hosting the world‐class Wallaby and Sunrise Dam gold deposits, respectively. Two major gold mineralization phases occurred during two of a series of tectonic events with different far‐field stress orientations. 3D coupled deformation and fluid flow modelling was used to investigate the effects of varying far‐field stress orientations on reactivation of the fault structure in the region. The results show that structural reactivation is sensitive to regional shortening directions. Two shortening directions are identified to be favourable for reactivation of the Wallaby fault and Sunrise Shear Zone: (i) NW–SE shortening and (ii) ENE–WSW to E–W shortening. The reactivated segments exhibited localization of shear strain and dilation as well as fluid focusing at locations corresponding to the Wallaby and Sunrise Dam deposits. This is in contrast to the models with shortening direction between NNW–SSE and NE–SW, which showed little fault reactivation at both locations. These results support previous independent interpretations of the controls on gold mineralization at Laverton. The two shortening directions favourable for structural reactivation inferred from the models are consistent with the kinematics of the two main gold mineralization events in the region. Our results suggest that strain localization, dilation and fluid focusing during structural reactivation could be some of the key factors governing gold mineralization at Laverton.
Impact of single‐session motivational interviewing on clinical outcomes following periodontal maintenance therapy
Authors: Brand VS , Bray KK , MacNeill S , Catley D , Williams K
Published: December 2012

Objectives

Patient engagement in effective oral hygiene following periodontal therapy is essential to long‐term success. Motivational interviewing (MI) is a behavioural counselling approach documented to positively influence behaviour change related to smoking, diabetes control and medication adherence. Emerging evidence suggests utility of MI to improve oral health. The objective of this study was to evaluate whether the use of brief motivational interviewing (BMI) is effective in improving internal motivation for oral hygiene behaviour.

Methods

A convenience sample of fifty‐six previously treated periodontal patients who were in maintenance yet presented with signs of clinical inflammation were recruited to participate in this single blind, randomized controlled trial. Patients were randomly assigned to receive either BMI in conjunction with traditional oral health education (TOHE), (n = 29) or TOHE alone (n = 27). Bleeding on probing scores (BOP), plaque index (PI), pocket depths (PD), motivation (M), autonomous regulation (AR) controlled regulation (CR) and oral health knowledge (K) were assessed at baseline, 6 weeks and 12 weeks.

Results

Statistically significant decreases were found over time for BOP (P = 0.001), PI (P = 0.001) and PD 4–6 mm (P = 0.001) for both groups. Differences in clinical parameters between groups were not evident at either 6 or 12 weeks.

Conclusion

Results show that a one‐time MI session is insufficient for improving oral hygiene in long‐standing maintenance patients.
In vivo evaluation of the iPex and Root ZX electronic apex locators using various irrigants
Authors: Duran‐Sindreu F. , Gomes S. , Stöber E. , Mercadé M. , Jané L. , Roig M.
Published: December 2012

Aim

To evaluate in vivo the performance of the iPex and Root ZX electronic apex locators (EALs) in the presence of several irrigant solutions: 2.5% sodium hypochlorite (NaOCl) and 2% chlorhexidine (CHX).

Methodology

Thirty‐two single‐rooted human teeth that were scheduled for extraction were selected. Teeth with metallic restorations, fractures, root resorption, pulp necrosis or open apices were not included The working length (WL) was determined electronically for the root canals with the iPex and Root ZX EALs in the presence of two different irrigant solutions, 2.5% NaOCl and 2% CHX. After the teeth had been extracted, a size 10 K‐file was used to determine the reference working length (RWL), which was established at 0.5 mm short of the major foramen. In each case, the RWL was subtracted from the electronic measurements. Positive values indicated electronic measurements that exceeded the RWL (long measurements), whereas negative values indicated measurements that were short of the RWL. The values obtained with the different irrigants and EALs were compared using the paired t‐test. Significance was set at P < 0.05.

Results

The accuracy of the iPex nor Root ZX EAL was not affected by 2.5% NaOCl or 2% CHX (P > 0.05). However, significant differences were observed between the readings of the iPex and Root ZX, irrespective of whether 2.5% NaOCl or 2% CHX was used as the irrigant (P < 0.05). The iPex was less accurate than the Root ZX in determining the RWL.

Conclusions

The accuracy of neither the iPex nor Root ZX EAL was affected by the irrigant used. However, the iPex was less accurate than the Root ZX in determining the RWL both for 2.5% NaOCl and for 2% CHX.
Understanding the Self‐initiated Expatriate: A Review and Directions for Future Research
Authors: Doherty Noeleen
Published: December 2012

The study of self‐initiated expatriates (SIEs) has gained pace in the last decade, focusing on these individuals, their motivations, their behaviours and their relevance to the global workforce. Published works produced between 1996 and 2011 are reviewed. A thematic analysis indicates that key topics of focus in current research cover: characteristics of the self‐initiated and their work‐related experiences and management; comparative studies of company‐backed versus self‐initiated expatriation and the self‐initiated as global talent flow. This paper identifies a need for clarification of the construct ofSIEs, expands on the theoretical perspectives used to examineSIEsand offers a framework to facilitate coherence in the direction of future research and the application of knowledge to practice in this field of study.
When Should Rehabilitation Begin after Stroke?
Authors: Bernhardt Julie , Indredavik Bent , Langhorne Peter
Published: December 2012

Early rehabilitation is widely regarded as an important feature of effective stroke care. But what is ‘early’, and what kinds of therapies should, or can, we begin soon after stroke onset? In this commentary, some of the barriers and drivers for early rehabilitation research and practice are explored.
US Remittances to the Caribbean, Jamaica and Trinidad & Tobago
Authors: Sampson Samuel S. , Branch‐Vital Angela
Published: December 2012

A remittance is part of an employee's wages or salary that is sent back home. Remittances not only help the workers' family members, but also help the home countries to strengthen their balance of payments. Remittances are remuneration to employees from the economy in which they work, and thus they contribute to both the gross domestic product (GDP) and the gross national income (GNI) of that economy. Because of their stability and dependability, remittances have become a permanent fixture of governments' financial revenues. The primary objective of this research is to determine whether foreign nationals make a significant contribution to the level of remittances and what some of the determinants are. We utilize three models to test whether the categories of foreign nationals – immigrants admitted; persons naturalized; and non‐immigrants admitted as temporary workers, exchange visitors and intra‐company transferees – send significant amounts of remittances. In this work, we look at the flow of remittances during the 1982–2001 period from the United States to the Caribbean region, Jamaica, and Trinidad and Tobago. The results indicate that the number of “immigrants admitted”, “persons naturalized” and “non‐immigrants admitted as temporary workers, exchange visitors and intra‐company transferees”, together with the “exchange rate”, the “Hispanic unemployment rate” and the “median income of Hispanic families”, are significant determinants in the size of remittances. When the results are extrapolated, the number of “immigrants admitted” produces the maximum remittance flow to Jamaica. The number of persons naturalized is important to the total remittances for the overall Caribbean region. The non‐immigrant temporary worker group is the largest single source of remittances. This group may potentially send US$15 billion to Trinidad and Tobago.
Here or There? Shifting Meanings and Practices in Mother–Child Relationships across Time and Space
Authors: Bonizzoni Paola
Published: December 2012

In this paper, I analyse the changes that mothers and children experience in their relationship due to the physical separations and reunions entailed by the international migration process. I argue that the different geographical configurations that migrant families take over time are the outcome of a negotiation of care responsibility and desired geographies of family life, and are accompanied by changing meanings and practices in intimate relationships: the location of care relationships is influenced by the relatives' capacity both to take part in family negotiations as well as to overcome the constraints imposed by policies. Time is relevant because it leads to shifting meanings and practices of transnational family life, as well as to the changing role of children in the family.
The Impact of Migration on Children's Psychological and Academic Functioning in the Republic of Moldova
Authors: Robila Mihaela
Published: December 2012

After the fall of communism, many Eastern Europeans sought work abroad, leaving their children with relatives. Eastern European migrants represent a target group with unstudied immigration patterns. The goal of this study was to examine how parental migration and economic pressure impact children outcomes in the Republic of Moldova. I examined a model of the impact of parental migration on children (13–15 years old), using a survey with 388 children who have migrant and non‐migrant parents. The conceptual model of migration, economic pressure, family relations and child outcomes integrated within the family stress perspective allows these pathways to be incorporated within a broader Moldovan context. I conducted quantitative data analysis using structural equation modelling. The results indicated that higher economic pressure was associated with children's lower psychological functioning, academic achievement and satisfaction with life. Parenting behaviours, especially parental support and monitoring, mediated the impact of satisfaction with migration and economic pressure on children's outcomes. I underline the importance of using a family perspective in the migration policymaking process, and provide specific recommendations for migration policies and programmes.
Recent advances in the management of transient ischaemic attack: a clinical review
Authors: Phan T. G. , Sanders L. , Srikanth V.
Published: December 2012

Transient ischaemic attack (TIA) if untreated carries a high risk of early stroke and is associated with poorer long‐term survival. There have been recent advances in the understanding of TIA, its investigations, management and organisation of services for patient care. Clinically, patients are diagnosed TIA if they have transient sudden‐onset focal neurological symptoms which usually completely and rapidly resolve by presentation. Patients with residual symptoms should be evaluated as potentially having stroke, if they present within 4.5 h of onset, should be urgently evaluated for their potential eligibility for thrombolysis. TIA patients should receive rapid attention with essential investigations, including brain imaging, electrocardiograph and carotid ultrasound. Immediate administration of an antiplatelet agent is recommended after brain imaging, with subsequent attention to preventing or treating other mechanistic factors. There is emerging evidence that TIA patients can be managed safely in the outpatient setting after initial rapid management in emergency departments as part of a structured clinical pathway supervised by stroke specialists. Clinical systems of management may require approaches individualised to the healthcare setting, while adopting the central aspects of rapid management.
Local perspective on a rare brain tumour: adult medulloblastoma
Authors: Wong S. F. , Mak G. , Rosenthal M. A. , Cher L. , Gan H. K.
Published: December 2012

Background

Little contemporary data are available regarding Australian patterns of care in adult medulloblastoma. It is unclear whether treatment, extrapolated from paediatric protocols despite known differences between the two groups, results in comparable efficacy.

Aim

To perform a retrospective review of patterns of care in adult medulloblastoma, especially with respect to adjuvant chemotherapy, in Australian patients.

Methods

All medulloblastoma patients aged 15 years or older at two neuro‐oncology institutions were identified from January 1995–May 2011. Patients with supratentorial or peripheral tumours were excluded. Standardised data were extracted from each institution regarding symptoms, disease staging, treatments received, toxicities and survival outcomes.

Results

Seventeen eligible patients were identified. Median age was 37 years (range 20–67 years). All had good performance status (Eastern Cooperative Oncology Group 0–1). There were 11 standard‐risk de novo patients, three high‐risk de novo patients and three patients with recurrent disease. Median overall survival (OS) had not been reached for standard‐risk patients with median follow up of 58 months. The median OS for high‐risk de novo patients was 21 months, while the median OS was 15 months for patients with recurrent disease. Treatment was well tolerated, with haematological toxicities being most common.

Conclusions

Combined modality therapy (surgery followed by postoperative radiotherapy and adjuvant chemotherapy) was well tolerated and associated with good outcomes in standard‐risk de novo patients. High‐risk and recurrent disease patients do extremely poorly regardless of treatment and better treatment strategies are needed in these patients.
Emergency demand and repeat attendances by older patients
Authors: Lowthian J. , Curtis A. , Stoelwinder J. , McNeil J. , Cameron P.
Published: December 2012

Background

Population ageing is projected to impact on health services utilisation including Emergency Departments (ED), with older patients reportedly having a high rate of return visits. We describe and compare patterns in ED utilisation between older and younger adults, and quantify the proportion and rate of return visits.

Methods

Population‐based retrospective analysis of metropolitan Melbourne public hospital ED data, 1999/2000 to 2008/2009. Numbers of patients, presentations, re‐presentations and rates per 1000 population were calculated, with comparison of older (aged ≥70 years) and younger (15–69 years) attendances.

Results

Population growth in each age group was similar over the study period, yet ED presentations rose by 72% for older adults compared with a 59% increase for younger adults. Rates per 1000 population rose with increasing age. Of the population aged ≥70 years, 39% presented to ED compared with 17% of the population aged 15–69 years in 2008/2009. Twenty‐seven per cent of the increase in older adult presentations was driven by a cohort who attended ≥4 times in 2008/2009. The number of older patients presenting ≥4 times doubled over the decade, contributing to 23% of all older presentations in 2008/2009. ED length of stay rose with increasing age; 69% of older adults remained in ED for ≥4 h compared with 39% of younger adults in 2008/2009. The number of older adult ED hospital admissions doubled over the decade.

Conclusions

Older patients are disproportionately represented among ED attendances. They also have an increasing propensity to re‐present to ED, indicating a need to identify the clinical, social and health system‐related risk factors for re‐attendance by specific patients.
Hyperuricaemia and gout in New Zealand rural and urban Māori and non‐Māori communities
Authors: Stamp L. K. , Wells J. E. , Pitama S. , Faatoese A. , Doughty R. N. , Whalley G. , Richards A. M. , Cameron V. A.
Published: December 2012

Background

There are few current data on the prevalence of hyperuricaemia and gout in New Zealand, particularly among the indigenous Māori population.

Aims

To determine the prevalence of gout and hyperuricaemia in rural and urban Māori and non‐Māori community samples and describe the treatment and comorbidities of participants with gout.

Methods

Participants aged 20–64 years were recruited by random selection from the electoral roll. Māori samples were selected from among those identified as being of Māori descent on the roll and who self‐identified as being of Māori ethnicity at interview. Personal medical history, blood pressure, anthropometrics, fasting lipids, glucose, HbA1c and urate were recorded.

Results

There were 751 participants. Mean serum urate (SU) was 0.30 mmol/L (0.06–0.69 mmol/L). Māori had a significantly higher prevalence of hyperuricaemia (SU > 0.40 mmol/L) compared with non‐Māori (17.0% vs 7.5%, P = 0.0003). A total of 57 participants had a history of gout, with a higher prevalence in Māori compared with non‐Māori (10.3% vs 2.3%, P < 0.0001). Of the participants, 18/57 (31.6%) with gout were receiving urate‐lowering therapy, but in 38.9%, SU was >0.36 mmol/L. Participants with gout were more likely to have metabolic syndrome, diabetes, cardiac disease or hypertension.

Conclusions

Gout and hyperuricaemia were more prevalent in Māori, and participants with gout were more likely to have comorbidities. There was not a higher overall adjusted cardiovascular disease risk in Māori participants with gout. Despite the high prevalence of gout, management remains suboptimal.
B‐type natriuretic peptide levels are decreased by reducing dietary salt intake in patients with compensated heart failure with preserved ejection fraction
Authors: Sadanaga T. , Ando K. , Hirota S. , Mitamura H. , Tsuchihashi T. , Kohsaka S. , Fukuda K. , Ogawa S.
Published: December 2012

Background

Dietary salt restriction is believed to be a mainstay in the management of patients with heart failure. However, the effect of salt intake on heart failure has not been well evaluated in outpatient medical practice.

Aims

The aim of the present study was to assess the hypothesis that B‐type natriuretic peptide (BNP) level, as an objective marker of heart failure, is associated with salt intake in patients with heart failure.

Methods

One hundred and thirteen consecutive patients with mild compensated heart failure (77 ± 10 years old, 51 female) were included. We estimated dietary salt intake by the concentration of sodium and creatinine in spot urine. We measured BNP at the time of urine sampling and assessed the relationship between the % changes in BNP levels (%ΔBNP) and the changes in the estimated daily salt excretion (ΔNaCl) during the follow‐up period.

Results

The baseline median BNP level was 150 (interquartile range: 83–263) pg/mL and the estimated daily salt excretion was 162 ± 45 mmol/day. There was a positive correlation between %ΔBNP and ΔNaCl (r = 0.61, P < 0.01). Multiple regression analysis revealed that %ΔBNP was associated with ΔNaCl (P < 0.01), but not with changes in systolic blood pressure and bodyweight.

Conclusions

Changes in BNP levels were associated with changes in the estimated daily salt excretion in outpatients with compensated heart failure. Salt restriction may be beneficial for the management of patients with heart failure.
Antifungal drug usage in haematologic patients during a 4‐year period in an Asian university teaching hospital
Authors: Chan T. S. Y. , Hwang Y.‐Y. , Gill H. , Cheung W. W. W. , Tse E. , Leung A. Y. H. , Chim C.‐S. , Lie A. K. W. , Kwong Y.‐L.
Published: December 2012

Background

Invasive fungal disease (IFD) is an important problem complicating the therapy of haematologic patients.

Aim

This study aimed to provide data on the epidemiology of IFD in an Asian teaching hospital, as well as the prescription practice of antifungal drugs.

Method

We conducted a retrospective review of 275 haematologic patients who were prescribed antifungal drugs in a 4‐year period (2007–2010), of whom 130 (47%) had undergone haematopoietic stem cell transplantation.

Results

Antifungal prophylaxis with either fluconazole or itraconazole was given in 214 patients (78%). There were 414 prescriptions of antifungal drugs (including liposomal amphotericin B, voriconazole, caspofungin, micafungin, anidulafungin), of which 361 prescriptions were empirical. There were 14 patients with proven IFD, 11 of whom had breakthrough infection while on itraconazole prophylaxis. Interestingly, seven of these cases were due to infection by itraconazole‐sensitive candida.

Conclusion

These results provide important epidemiologic data necessary for the formulation of strategies for prevention and treatment of IFD in Asian patients.
Relationship between in‐hospital location and outcomes of care in patients of a large general medical service
Authors: Perimal‐Lewis L. , Li J. Y. , Hakendorf P. H. , Ben‐Tovim D. I. , Qin S. , Thompson C. H.
Published: December 2012

Background

The discrepancy between the number of admissions and the allocation of hospital beds means that many patients admitted under the care of a general medical service can be placed in other departments' wards. These patients are called ‘outliers’, and their outcomes are unknown.

Aims

To examine the relation between the proportion of time each patient spent in their ‘home ward’ during an index admission and the outcomes of that hospital stay.

Methods

Data from Flinders Medical Centre's patient journey database were extracted and analysed. The analysis was carried out on the patient journeys of patients admitted under the general medicine units.

Results

Outlier patients' length of stay was significantly shorter than that of the inlier patients (110.7 h cf 141.9 h; P < 0.001).They had a reduced risk of readmission within 28 days of discharge from hospital. Outlier patients' discharge summaries were less likely to be completed within a week (64.3% cf 78.0%; P < 0.001). Being an outlier patient increased the risk‐adjusted risk of in‐hospital mortality by over 40%. Fifty per cent of deaths in the outlier group occurred within 48 h of admission. Outlier patients had spent longer in the emergency department waiting for a bed (6.3 h cf 5.3 h; P < 0.001) but duration of emergency department stay was not an independent predictor of mortality risk.

Conclusion

Outlier patients had significantly shorter length of stay in hospital but significantly greater in‐patient death rates. Surviving outlier patients had lower rates of readmission but lower rates of discharge summary completion.
Comparing dose prediction software used to manage gentamicin dosing
Authors: Wong C. , Kumar S. S. , Graham G. G. , Begg E. J. , Chin P. K. L. , Brett J. , Ray J. E. , Marriott D. J. E. , Williams K. M. , Day R. O.
Published: December 2012

Background

Current Australian guidelines recommend initiating directed therapy of gentamicin if administration exceeds 48 h. Directed doses of gentamicin require the monitoring of plasma concentrations of gentamicin to determine the 24‐h area under the time course of plasma gentamicin concentrations (AUC) and a dosage prediction program, for example TCIWorks or Aladdin. However, doses calculated by such programs have not been compared with an established program.

Aim

To compare the directed dosage of gentamicin calculated by TCIWorks, Aladdin and an Excel‐based program, with an established program, Abbottbase.

Methods

Peak and trough plasma concentrations after the first and second administered doses of gentamicin were available from three patient groups (n = 20–23) with varying creatinine clearances (<40, 40–80, >80 mL/min). The directed dose needed to produce 24‐h AUC values of 80 mg.h/L was calculated using each program.

Results

There was a strong correlation between the directed doses predicted by each of the three programs compared with Abbottbase, following the first administered dose (r2 > 0.97, P < 0.0001). The mean ratio (90% confidence intervals) of these directed doses of the gentamicin were: TCIWorks/Abbottbase 106% (105–107%), Aladdin/Abbottbase 102% (101–103%) and Excel/Abbottbase 108% (106–109%). The correlations and dose ratios were also similar when comparisons were made following the second administered dose. For each of the three renal function groups, all programs yielded similar directed doses.

Conclusions

The four programs used in the calculation of directed doses of gentamicin yielded similar results. Any would be suitable for use in clinical practice.
Epidemiology of hepatitis B‐associated hepatocellular carcinoma in Victoria
Authors: Sinclair M. , Roberts S. , Kemp W. , Knight V. , Dev A. , Gow P. , Philpott H. , Kronborg I. , Arachchi N. J. , Bell S. , Lim L. , Gorelik A. , Nicoll A. ,   Melbourne Collaboration for the Study of Hepatocellular Carcinoma
Published: December 2012

Background

Chronic hepatitis B (HBV) and cirrhosis are major risk factors for hepatocellular carcinoma (HCC). The proportion and characteristics of cases with cirrhosis are not well documented.

Aim

Our aim was to compare demographic, viral and tumour characteristics of HBV‐associated HCC in an Australian cohort, in patients with and without cirrhosis.

Methods

Existing HCC databases at six Melbourne teaching hospitals were reviewed for cases associated with HBV. Patient demographics, HBV viral characteristics, presence of cirrhosis, serum alpha‐fetoprotein and tumour size were assessed. Mode of diagnosis was recorded through surveillance or symptoms, and treatment was either palliative, percutaneous or surgical.

Results

We identified 197 cases of HBV‐related HCC. The mean age was 57.9 ± 12.9 years; 83% were male, and 55.3% and 35.3% were of Asian and European descent respectively. Of 168 patient with available data, 146 (87%) had cirrhosis versus 22 (13%) without. Patients with cirrhosis tended to be older (median 60 vs 52 years, P = 0.078). Asian patients were more likely to have HCC without cirrhosis than Europeans (17% vs 6%, P = 0.04). There were no other differences identified between cirrhotic and non‐cirrhotic patients. Thirty‐four per cent of patients had tumours greater than 5 cm at diagnosis, and 47% were diagnosed after presenting with symptoms. Twelve patients with HBV‐HCC were outside current screening guidelines.

Conclusion

Most patients in Melbourne with HBV‐associated HCC have cirrhosis. HCC characteristics in non‐cirrhotic and cirrhotic patients were similar. The large number of patients detected through symptoms and with large tumours reinforces the need for vigilance in screening.
Building a pulmonary vascular service: the 12‐year experience and outcomes of the Auckland pulmonary arterial hypertension clinic
Authors: Wasywich C. A. , Cicovic A. , McWilliams T. , Coverdale H. A. , Stewart C. , Whyte K.
Published: December 2012

Background and Aims

Pulmonary arterial hypertension (PAH) is associated with significant morbidity and mortality. In New Zealand, access to PAH‐specific pharmacotherapy has been restricted for economic reasons. Since 2009, access to medication has been provided by a Special Authority scheme that ensures equity of access for all patients. Management of patients with PAH in this environment poses unique challenges. This study describes outcomes of patients managed in the Auckland PAH clinic over a 12‐year period.

Methods

The clinic database was interrogated. Patients were eligible for this study if they had PAH (World Health Organization (WHO) Class 1, 1′ and 4) and had been managed in the clinic from the year 2000.

Results

One hundred and twenty‐six patients (75% female, mean age at diagnosis 50) were included. Most had idiopathic PAH (37%) or PAH because of connective tissue disease (29%). At diagnosis, patients had advanced disease (median WHO Class III, 6‐min walk distance 367 m and pulmonary vascular resistance of 10.6 Wood Units). Initial therapy was sildenafil in most cases. PAH‐specific therapy was associated with improved WHO class and longer 6‐min walk distance (P < 0.01 for both). Thirty per cent of patients were escalated to combination therapy. Survival was 91% at 1 year and 67% at 5 years.

Conclusions

Despite historic difficulties with access to PAH‐specific therapy, these data confirm benefits of therapy (primarily sildenafil as first‐line treatment) for patients with PAH managed within the Auckland PAH clinic. Survival data are comparable with other reported cohorts.
Asian ethnicity in systemic lupus erythematosus: an Australian perspective
Authors: Connelly K. , Morand E. F. , Hoi A. Y.
Published: December 2012

Ethnic differences in both disease susceptibility and expression have been noted in systemic lupus erythematosus (SLE). This review focuses on the evidence of disparities between SLE patients of Asian and Caucasian descent, the two predominant ethnic groups affected by SLE in the Australian context. While epidemiological studies suggest higher rates of SLE among Asian patients, multi‐ethnic cohort studies have allowed direct comparison of disease characteristics between different ethnic groups. Such studies suggest that Asians are affected by more severe SLE across several disease parameters, including increased renal involvement, autoantibody positivity, disease activity and damage accumulation. As delineation of these disparities becomes clearer, uncovering the biological basis of such differences poses a significant opportunity to progress understanding of SLE pathogenesis. Understanding ethnic variation in disease provides a platform for an individualised approach to risk assessment, monitoring and management of SLE.
Total length of stay, costs and outcomes at final discharge for admitted patients with hip fracture: linked episode data for Australian veterans and war widows
Authors: Ireland A. W. , Kelly P. J.
Published: December 2012

Background and Aim

To identify the total duration of hospital stay, total hospital costs and outcomes at final discharge for a series of Australian patients with hip fracture.

Methods

The study type was retrospective cohort study using episode linkage within and between administrative databases. Study population is 2552 Australian veterans and war widows with primary diagnosis of hip fracture (International Classification of Diseases 10th revision, S72.0–S72.2) and hospital separation dates between 1 July 2008 and 30 June 2009. The unique identifying number within Department of Veterans' Affairs health service databases was used to link records for relevant hospital episodes as defined. Additional linkages were made with data for residential care admissions and date of death.

Results

Mean length of stay (LOS) for unlinked acute episodes was 11.1 days, and cost of hospitalisation was A$13 095. Fifty‐one per cent of these episodes ended with transfer to ongoing hospital care, 9.5% were discharged to residential aged care (RAC), in‐hospital mortality was 6.5%, and 23% were discharged to ‘usual residence’. When data for all continuous episodes following hip fracture were combined, mean LOS was 30.8 days, costs were A$26 023 and in‐hospital mortality was 11.1%. Additional linkage with RAC records identified 38% of final discharges to RAC facilities with 44% of patients returning to independent living.

Conclusion

For complex conditions such as hip fracture, a process of patient‐specific episode linkage is required to identify accurately hospital LOS, costs and patient outcomes.
Ragweed pollen extract intensifies lipopolysaccharide‐induced priming of NLRP3 inflammasome in human macrophages
Authors: Varga Aliz , Budai Marietta M. , Milesz Sándor , Bácsi Attila , Tőzsér József , Benkő Szilvia
Published: December 2012

Ragweed pollen extract (RWE) possesses intrinsic NADPH oxidase activity that induces oxidative stress by initiating the production of intracellular reactive oxygen species (ROS). The ROS are important contributors to the manifestation of allergic inflammation; furthermore, concomitant exposure to an allergen and an endotoxin trigger a stronger inflammatory response. One of the main pro‐inflammatory cytokines produced in inflammatory responses is interleukin‐1β (IL‐1β), and its production is associated with caspase‐1‐containing inflammasome complexes. Intracellular ROS have been implicated in NLRP3 inflammasome‐mediated IL‐1β production, therefore, we aimed to study whether RWE influences the function of NLRP3 inflammasome. Here we describe that, in the presence of NADPH, RWE significantly elevates lipopolysaccharide‐induced IL‐1β production of THP‐1 cells as well as human primary macrophages and dendritic cells. We also demonstrate that increased IL‐1β production is mediated through NLRP3 inflammasome in THP‐1 macrophages. We provide evidence that RWE elevates cytosolic ROS level in these cells, and ROS inhibitors abolish IL‐1β production. Furthermore, we show that RWE enhances lipopolysaccharide‐induced gene transcription/expression of pro‐IL‐1β and key components of the inflammasome via a ROS‐dependent mechanism.
Adenosine and cAMP signalling skew human dendritic cell differentiation towards a tolerogenic phenotype with defective CD8+ T‐cell priming capacity
Authors: Challier John , Bruniquel Denis , Sewell Andrew K. , Laugel Bruno
Published: December 2012

Multiple endogenous mechanisms that regulate immune and inflammatory processes contribute to the maintenance of peripheral tolerance and prevent chronic inflammation in mammals. Yet pathogens and tumours are able to exploit these homeostatic pathways to foster immunosuppressive microenvironments and evade immune surveillance. The release of adenosine in the extracellular space contributes to these phenomena by exerting a broad range of immunomodulatory effects. Here we document the influence of adenosine receptor triggering on human dendritic cell differentiation and functions. We show that the expression of several immunomodulatory proteins and myeloid/monocytic lineage markers was affected by adenosine receptors and the cAMP pathway. These changes were reminiscent of the phenotype associated with tolerogenic dendritic cells and, functionally, translated into a defective capacity to prime CD8+ T‐cells with a common tumour antigen in vitro. These results establish a novel mechanism by which adenosine hampers CD8+ T‐cell immunity via dendritic cells that may contribute to peripheral tolerance as well as to the establishment of immunosuppressive microenvironments relevant to tumour biology.
CD2‐mediated regulation of peripheral CD4+ CD25+ regulatory T‐cell apoptosis accompanied by down‐regulation of Bim
Authors: Kashiwakura Yuji , Sakurai Daisuke , Kanno Yumiko , Hashiguchi Masaaki , Kobayashi Ayano , Kurosu Akira , Tokudome Shogo , Kobata Tetsuji , Kojima Hidefumi
Published: December 2012

Extensive studies on CD4+ CD25+ regulatory T (Treg) cells suggest that they are important in regulating immune responses. However, mechanisms of peripheral Treg cell homeostasis are unknown. We found that stromal cells isolated from secondary lymphoid organs such as spleen and lymph nodes could support the survival of Treg cells. This was dependent on CD2 engagement and a direct interaction between Treg cells and stromal cells. In the presence of stromal cells, Bim, a pro‐apoptotic factor, was partially decreased in Treg cells. This effect could be inhibited by anti‐CD2 blocking antibodies, indicating that stimulation through CD2 on Treg cells regulates Bim expression, which may be relevant to Treg cell apoptosis. Therefore, Treg cell interactions with stromal cells through CD2 may be essential for Treg cell survival. Surprisingly, the expression of CD2 ligands on stromal cells was not detected. Hence, it is not clear how CD2 on Treg cells contributes to a direct interaction with the stromal cells and participates in survival support for Treg cells. Taken together, CD2 stimuli were mandatory for Treg cell survival with reduced Bim expression, but CD2 may not function as a direct receptor for molecules on stromal cells.
Mental Health Nurse Incentive Program: Facilitating physical health care for people with mental illness?
Authors: Happell Brenda , Platania‐Phung Chris , Scott David
Published: December 2012

People with serious mental illness have increased rates of physical ill‐health and reduced contact with primary care services. In Australia, the Mental Health Nurse Incentive Program (MHNIP) was developed to facilitate access to mental health services. However, as a primary care service, the contribution to physical health care is worthy of consideration. Thirty‐eight nurses who were part of the MHNIP participated in a national survey of nurses working in mental health about physical health care. The survey invited nurses to report their views on the physical health of consumers and the regularity of physical health care they provide. Physical health‐care provision in collaboration with general practitioners (GPs) and other health‐care professionals was reported as common. The findings suggest that the MHNIP provides integrated care, where nurses and GPs work in collaboration, allowing enough time to discuss physical health or share physical health activities. Consumers of this service appeared to have good access to physical and mental health services, and nurses had access to primary care professionals to discuss consumers’ physical health and develop their clinical skills in the physical domain. The MHNIP has an important role in addressing physical health concerns, in addition to the mental health issues of people accessing this service.
Description of physical activity in outpatients with schizophrenia spectrum disorders
Authors: Beebe Lora Humphrey , Harris Robin Faust
Published: December 2012

This study describes physical activity level in outpatients with schizophrenia spectrum disorders (SSD) using extended‐wear pedometers. Demographic data, body fat and body mass index (BMI) measures were obtained from 24 outpatients. Participants were provided extended‐wear pedometers and instructed to wear them during waking hours for 1 week. More than 79% of subjects met Centres for Disease Control (CDC) obesity criteria. Participants wore pedometers, on average, 6 days during the week. Men walked more steps, walked longer distances, and burned more calories each day; differences were statistically significant for steps and distance on days 3 (t = 2.12, P = 0.045) and 5 (t = 2.19, P = 0.04). Higher percent body fat and BMI were significantly associated with fewer steps walked on most days. Extended‐wear pedometers are an easy‐to‐use, cost‐effective way to document physical activity and evaluate efforts to help this vulnerable group achieve activity‐related health improvements.
Parenteral fluids do not affect pulmonary immune responses to influenza or susceptibility to secondary bacterial pneumonia in mice
Authors: Sanders Robert D. , Godlee Alexandra , Goulding John C. , Ma Daqing , Maze Mervyn , Hussell Tracy
Published: December 2012

Animal models of viral respiratory disease often use weight loss as a marker of disease severity; however, this may relate to dehydration and malnutrition that would be corrected clinically. We tested whether parenteral fluid therapy improved weight loss from influenza infection. BALB/c and C57BL/6 mice were infected with A/X31 (H3N2) influenza and randomized to intraperitoneal fluid therapy. Blood glucose was also measured post‐viral infection on day 3 and 6 in BALB/c mice and on day 6 in C57BL/6 mice. Parenteral fluids did not alter weight loss or the immunological response to infection, and glucose levels were not abnormal.