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Nitrogen dioxide (NO 2 ) is a major air pollutant causing significant environmental 1,2 and health problems 3,4 . We report reversible adsorption of NO 2 in a robust metal-organic framework. Under ambient conditions, MFM-300(Al) exhibits a reversible NO 2 isotherm uptake of 14.1 mmol g -1 , and, more importantly, exceptional selective removal of low-concentration NO 2 (5,000 to <1 ppm) from gas mixtures. Complementary experiments reveal five types of supramolecular interaction that cooperatively bind both NO 2 and N 2 O 4 molecules within MFM-300(Al). We find that the in situ equilibrium 2NO 2  ↔ N 2 O 4 within the pores is pressure-independent, whereas ex situ this equilibrium is an exemplary pressure-dependent first-order process. The coexistence of helical monomer-dimer chains of NO 2 in MFM-300(Al) could provide a foundation for the fundamental understanding of the chemical properties of guest molecules within porous hosts. This work may pave the way for the development of future capture and conversion technologies.

Background: Heart failure (HF) is a common, costly condition with an increasing burden on Australian health care system resources. Knowledge of the burden of HF on patients and on the health system is important for resource allocation. This study is the first systematic review to estimate the mortality and readmission rates after hospitalisation for HF in the Australian population., Methods: We searched for studies of HF hospitalisation in Australia published between January 1990 and May 2016, using a systematic search of PubMed, Medline, Scopus, Web of Science, EMBASE and Cochrane Library databases. Studies reporting 30-day and/or 1-year outcomes for mortality or readmission following hospitalisation were eligible and included in this study., Results: Out of 2889 articles matching the initial search criteria, a total of 13 studies representing 67,255 patients were included in the final analysis. The pooled mean age of heart failure patients was 76.3 years and 51% were male (n=34,271). The pooled estimated 30-day and 1-year all-cause mortality were 8% and 25% respectively. The pooled estimated 30-day and 1-year all-cause readmission rates were 20% and 56% respectively. There is a high prevalence of comorbidities in heart failure patients. There were limited data on readmission and mortality in rural patients and Indigenous people., Conclusions: Heart failure hospitalisations in Australia are followed by substantial readmission and mortality rates., (Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Australian guidelines advocate primary percutaneous coronary intervention (PPCI) as the reperfusion strategy of choice for ST elevation myocardial infarction (STEMI) in patients in whom it can be performed within 90 minutes of first medical contact; otherwise, fibrinolytic therapy is preferred. In a large health district, the reperfusion strategy is often chosen in the prehospital setting. We sought to identify a distance from a PCI centre, which made it unlikely first medical contact to balloon time (FMCTB) of less than 90 minutes could be achieved in the Hunter New England health district and to identify causes of delay in patients who were triaged to a PPCI strategy., Methods and Results: We studied 116 patients presenting via the ambulance service with STEMI from January 2016 to December 2016. In patients who were taken directly to the cardiac catheterisation lab, a maximum distance of 50 km from hospital resulted in 75% of patients receiving PCI within 90 minutes and approximately 95% of patients receiving PCI within 120 minutes. Patients who bypassed the emergency department (ED) were significantly more likely to have FMCTB of less than 90 minutes ( p < 0.001) despite having a longer travel distance (28.5 km versus 17.4 km, p < 0.001). Patients transiting via the ED were significantly more likely to present out of hours (60 versus 24.2% p < 0.001)., Conclusions: Patients who do not bypass the ED have a longer FMCTB across all spectrum of distances from the PCI centre; therefore, bypassing the ED is key to achieving target FMCTB times. Using a cutoff distance of 50 km may reduce human error in estimating travel time to our PCI centre and thereby identifying patients who should receive prehospital thrombolysis.

We report magnetic quantum oscillations measured using torque magnetisation in the Kondo insulator YbB 12 and discuss the potential origin of the underlying Fermi surface. Observed quantum oscillations as well as complementary quantities such as a finite linear specific heat capacity in YbB 12 exhibit similarities with the Kondo insulator SmB 6 , yet also crucial differences. Small heavy Fermi sections are observed in YbB 12 with similarities to the neighbouring heavy fermion semimetallic Fermi surface, in contrast to large light Fermi surface sections in SmB 6 which are more similar to the conduction electron Fermi surface. A rich spectrum of theoretical models is suggested to explain the origin across different Kondo insulating families of a bulk Fermi surface potentially from novel itinerant quasiparticles that couple to magnetic fields, yet do not couple to weak DC electric fields.

Aims: The aim of the current study is to examine 10 year trends in mortality and readmission following heart failure (HF) hospitalization in metropolitan and regional Australian settings., Methods and Results: We identified all index HF hospitalizations in the Hunter New England region from 2005 to 2014, using a 10 year 'look back' period. The primary endpoint was a composite of all-cause mortality or all-cause readmission at 1 year. Secondary endpoints included all-cause mortality, all-cause readmission, and HF readmission at 30 days and 1 year. We used logistic regression to explore the predictors of the composite outcome of either all-cause death or readmission at 1 year. There were 12 114 patients admitted with a first episode of HF between 2005 and 2014, followed up until death or the end of 2015. The mean age was 78 ± 12 years and 49% (n = 5906) were male. A total of 4831 (40%) resided in regional areas and the remainder in metropolitan areas. One hundred sixty-eight patients (1.4%) were Aboriginal. Approximately 69% of patients had either died or been readmitted for any cause within 12 months of their index event. The 30 day and 1 year all-cause mortality rates were 13% and 32%, respectively, with no change in the trend over the study period. Age, socio-economic disadvantage, ischaemic heart disease, renal failure, and chronic lower respiratory disease were predictors of the primary endpoint., Conclusions: Heart failure hospitalizations are followed by high rates of death or readmission. There was no change in this composite endpoint over the 10 year study period., (© 2017 The Authors ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Checkpoint inhibitor medications have revolutionized oncology practice, but frequently induce immune-related adverse events. During autoimmune neurology practice over 20 months, we prospectively identified four patients with likely antibody-mediated neurological diseases after checkpoint inhibitors: longitudinally extensive transverse myelitis, Guillain-Barré syndrome, and myasthenia gravis. All patients shared three characteristics: symptoms commenced 4 weeks after drug administration, responses to conventional immunotherapies were excellent, and autoantibodies traditionally associated with their syndrome were absent. However, serum immunoglobulins from the myelitis and Guillain-Barré syndrome patients showed novel patterns of tissue reactivity. Vigilance is required for antibody-mediated neurology after checkpoint inhibitor administration. This phenomenon may inform the immunobiology of antibody-mediated diseases.

Left ventricular end-diastolic pressure (LVEDP) is an easily obtained, physiologically integrative measure of total LV function. LVEDP may be a useful prognostic measure in patients with acute myocardial infarction and utilised to guide medical therapy and assess risk for post myocardial infarction heart failure. To assess the utility of LVEDP as a prognostic measure in patients presenting with acute myocardial infarction. We performed an unrestricted search of electronic databases (1946 to March 2017) using a predefined search strategy. Publications were included if patients had an acute coronary syndrome and LVEDP was measured by cardiac catheterisation and included outcome data specifying major adverse cardiac events. Two reviewers performed independent study selection, data abstraction and quality assessment by using the Cochrane tool for randomised trials and the ROBINS-I tool for non-randomised studies. Our search identified 8637 patients in seven studies. In patients with elevated LVEDP and STEMI, there was a significantly increased risk of 30-day death (three studies, 5372 participants; RR 1.9; 95% CI 1.4-2.7; p < 0.001; I 2  = 35.3%) and heart failure (two studies, 2574 participants; RR 2.9; 95% CI 1.9-4.5; p = < 0.001; I 2  = 0.0%). There was no significant increase in risk of 30 day reinfarction (RR 1.25; 95% CI 0.77-2.1; p = 0.37; I 2  = 41.3%). Elevated LVEDP measured during cardiac catheterisation for acute myocardial infarction appears to be a predictor of heart failure and mortality.

Anomalous left main coronary artery is rare. We present four cases where anomalous left main coronary artery was diagnosed during emergent cardiac catheterization for ST elevation myocardial infarction. Procedural characteristics, technical challenges, and relevant literature are discussed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Little information is available to surgeons regarding how the lateral structures prevent instability in the replaced knee. The aim of this study was to quantify the lateral soft-tissue contributions to stability following cruciate-retaining total knee arthroplasty (CR TKA). Nine cadaveric knees were tested in a robotic system at full extension, 30°, 60°, and 90° flexion angles. In both native and CR implanted states, ±90 N anterior-posterior force, ±8 Nm varus-valgus, and ±5 Nm internal-external torque were applied. The anterolateral structures (ALS, including the iliotibial band), the lateral collateral ligament (LCL), the popliteus tendon complex (Pop T), and the posterior cruciate ligament (PCL) were transected and their relative contributions to stabilizing the applied loads were quantified. The LCL was found to be the primary restraint to varus laxity (an average 56% across all flexion angles), and was significant in internal-external rotational stability (28% and 26%, respectively) and anterior drawer (16%). The ALS restrained 25% of internal rotation, while the PCL was significant in posterior drawer only at 60° and 90° flexion. The Pop T was not found to be significant in any tests. Therefore, the LCL was confirmed as the major lateral structure in CR TKA stability throughout the arc of flexion and deficiency could present a complex rotational laxity that cannot be overcome by the other passive lateral structures or the PCL. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1902-1909, 2017., (© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Rationale: Carbonate clumped isotope thermometry examines the thermodynamic preference of 13 C- 18 O bonds to form within the carbonate crystal lattice. The 13 C 18 O 16 O isotopologue in analyte CO 2 has a natural abundance of 44.4 ppm necessitating stringent purification procedures to remove contaminant molecules that may produce significant isobaric effects within range of the mass 47 isotopologue. Strict purifications of analyte CO 2 are thus required as well as reliable contamination indicators., Methods: CO 2 purification was carried out by vacuum cryogenic purification through a static trap packed with Porapak™ Q (PPQ). The correlation between mass excesses on m/z 47, 48 and 49 in CO 2 produced by acid digestion of 12 natural samples was measured by isotope ratio mass spectrometry (IRMS). CO 2 from two contaminated carbonate samples was then purified at PPQ trap temperatures between -25 and -65°C and measured by IRMS to determine changes in mass excesses on m/z 47, 48 and 49. Finally carbonate standards, Carrara marble (CM) and ETH3, were purified at PPQ trap temperatures of -35 and -60°C to identify isotopic fractionation associated with lowering trap temperature., Results: The correlation between mass excesses on m/z 47, 48 and 49 is determined to be sample dependent. Lowering the PPQ trap temperature to -60°C has a 78% success rate in decreasing Δ 48offset , a measure of sample contamination, to within an acceptable range (<1.5 ‰). Lowering the PPQ temperature in purification of CM and ETH3 is associated with decreases in the δ 13 C and δ 18 O values as a result of isotopic fractionation . We demonstrate that we can correct for fractionation at a trap temperature of -60°C., Conclusions: Lowering the temperature of the Porapak Q trap to -60°C results in improved sample cleaning. It is possible to correct for fractionation in δ 13 C and δ 18 O values at lower PPQ trap temperatures using identically prepared standards. This result has important connotations for laboratories using similar sample preparation methods., (Copyright © 2017 John Wiley & Sons, Ltd.)

Purpose: The aim of this study was to quantify the medial soft tissue contributions to stability following constrained condylar (CC) total knee arthroplasty (TKA) and determine whether a medial reconstruction could restore stability to a soft tissue-deficient, CC-TKA knee., Methods: Eight cadaveric knees were mounted in a robotic system and tested at 0°, 30°, 60°, and 90° of flexion with ±50 N anterior-posterior force, ±8 Nm varus-valgus, and ±5 Nm internal-external torque. The deep and superficial medial collateral ligaments (dMCL, sMCL) and posteromedial capsule (PMC) were transected and their relative contributions to stabilising the applied loads were quantified. After complete medial soft tissue transection, a reconstruction using a semitendinosus tendon graft was performed, and the effect on kinematic behaviour under equivocal conditions was measured., Results: In the CC-TKA knee, the sMCL was the major medial restraint in anterior drawer, internal-external, and valgus rotation. No significant differences were found between the rotational laxities of the reconstructed knee to the pre-deficient state for the arc of motion examined. The relative contribution of the reconstruction was higher in valgus rotation at 60° than the sMCL; otherwise, the contribution of the reconstruction was similar to that of the sMCL., Conclusion: There is contention whether a CC-TKA can function with medial deficiency or more constraint is required. This work has shown that a CC-TKA may not provide enough stability with an absent sMCL. However, in such cases, combining the CC-TKA with a medial soft tissue reconstruction may be considered as an alternative to a hinged implant.

Background: Heart failure carries a major burden on our health system, mainly related to the high rate of hospital admission. An understanding of the recent trends in heart failure hospitalisation is essential to the future allocation of health resources. Our aim is to analyse the temporal trends in heart failure hospitalisation., Methods: We extracted all separations in the Hunter New England Local Health District between 2005-2014 (n=40,119) with an ICD 10 code for heart failure (I-50) in the first four diagnoses on discharge. The numbers of hospitalisations were age-standardised to the 2001 Australian population and compared based on gender and remoteness., Results: There was a decline in the age-standardised hospitalisation. However, there was a clear inflection point between 2009-2010, after which the decline levelled off. The absolute number of hospitalisations increased between 2010 and 2014. Heart failure hospitalisation was higher in males compared to females and rural compared to metropolitan inhabitants., Conclusion: The gains in heart failure treatment noted in recent years seem to have come to an end. Patients aged 75 years and older are contributing the majority of age-standardised hospitalisations., (Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Trends in the incidence of acute myocardial infarction (AMI) provide important information for healthcare providers and can allow for accurate planning of future health needs and targeted interventions in areas with an excess burden of cardiovascular disease., Aim: To investigate the regional variations in AMI incidence in the Hunter region., Methods: Incident cases of AMI identified between 1996 and 2013 from the Hunter New England Health Cardiac and Stroke Outcomes Unit were prospectively collected for this study. We calculated crude and age-adjusted incidence of AMI over an 18-year period and explored differences in remoteness, age, sex and indigenous status., Results: During 1996-2013, a total of 15 480 cases of AMI were identified. There was a significantly higher incidence of AMI in patients from regional areas compared to patients from metropolitan areas. More importantly, while rates of AMI declined by 28% in metropolitan patients, they increased by 8% in regional patients. Males had higher rates of AMI throughout the study period than females, however there was trend over time towards a reduction in AMI incidence in males that was not seen in females. The age-adjusted incidence of AMI for indigenous patients increased by 48% from 2007 to 2013, compared to a 23% decrease in non-indigenous patients., Conclusion: Between 1996 and 2013 in the Hunter region, the adjusted incidence of AMI increased for regional patients compared to metropolitan patients with a trend towards a higher adjusted incidence of AMI in the indigenous population., (© 2017 Royal Australasian College of Physicians.)

Introduction and Aims: The use of 'poppers' (volatile alkyl nitrites) has been associated with the development of visual symptoms secondary to the development of maculopathy. There are currently no data regarding the prevalence of this condition among poppers users. The aim of this study was to quantify the presence of visual symptoms among poppers users from a global cohort., Design and Methods: The Global Drug Survey (GDS) conducts annual anonymous online surveys of drug and alcohol use. Within the 2012 GDS, questions were inserted regarding the presence of visual symptoms in poppers users., Results: The GDS received a total of 21 575 valid responses, with a total of 17 479 from the UK, Australia, USA and Eurozone. Within these areas, 5152 (29.5%) had used poppers within their lifetime and 1322 (7.6%) within the previous year. Of the 'last year' users, when asked the question: 'Do you think poppers use has affected your eyesight?', 29 (2.2%) people responded 'yes', 130 (10.0%) responded 'maybe' and 1146 (87.8%) responded 'no (17 people did not answer). Both multiple choice and free-text responses regarding the nature of visual symptoms correlated with the central visual disturbance that would be expected from maculopathy. There was significant increased symptom prevalence with age (likelihood ratio (χ 2 )=19.0; p<0.001)., Discussion and Conclusions: This study demonstrates that a small, yet significant from a public health perspective, proportion of poppers users have visual symptoms. Clinical correlation is required to determine whether these reported symptoms are due to poppers associated maculopathy, or an alternative cause., Competing Interests: Competing interests: ARW is the owner and founder of Global Drug Survey (GDS) and has previously provided expert opinion on the use, risk and potential for health harms to the legal team that represented Perpol (the biggest supplier of Isopropyl nitrite In Europe).

Gamma-aminobutyric acid (GABA) depolarizes dorsal root ganglia (DRG) primary afferent neurons through activation of Cl - permeable GABA A receptors but the physiologic role of GABA A receptors in the peripheral terminals of DRG neurons remains unclear. In this study, we investigated the role of peripheral GABA A receptors in nociception using a mouse model of acute inflammation. In vivo, peripheral administration of the selective GABA A receptor agonist muscimol evoked spontaneous licking behavior, as well as spinal wide dynamic range (WDR) neuron firing, after pre-conditioning with formalin but had no effect in saline-treated mice. GABA A receptor-mediated pain behavior after acute formalin treatment was abolished by the GABA A receptor blocker picrotoxin and cyclooxygenase inhibitor indomethacin. In addition, treatment with prostaglandin E2 (PGE 2 ) was sufficient to reveal muscimol-induced licking behavior. In vitro, GABA induced sub-threshold depolarization in DRG neurons through GABA A receptor activation. Both formalin and PGE 2 potentiated GABA-induced Ca 2+ transients and membrane depolarization in capsaicin-sensitive nociceptive DRG neurons; these effects were blocked by the prostaglandin E2 receptor 4 (EP4) antagonist AH23848 (10  μ mol/L). Furthermore, potentiation of GABA responses by PGE 2 was prevented by the selective Na v 1.8 antagonist A887826 (100 nmol/L). Although the function of the Na + -K + -2Cl - co-transporter NKCC1 was required to maintain the Cl - ion gradient in isolated DRG neurons, NKCC1 was not required for GABA A receptor-mediated nociceptive behavior after acute inflammation. Taken together, these results demonstrate that GABA A receptors may contribute to the excitation of peripheral sensory neurons in inflammation through a combined effect involving PGE 2 -EP4 signaling and Na + channel sensitization., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Xenograft tendons have been used in few human studies, with variable results. With the advent of novel tissue processing techniques, which may mitigate against an immune-mediated rejection response without adversely affecting mechanical properties, there may now be a clinical role for xenograft tendons, particularly in knee ligament reconstruction. We hypothesize that 'BioCleanse®' processed bovine extensor digitorum medialis (EDM) tendons exhibit favorable time-zero pre-implantation biomechanical characteristics when compared to both unprocessed bovine EDM tendons and BioCleanse® processed human cadaveric allograft tibialis anterior tendons. In this in vitro case controlled laboratory study, three groups of tendons underwent a 5-stage static loading test protocol: 15 BioCleanse ® bovine (BCB), 15 fresh frozen unprocessed bovine (FFB), and 12 BioCleanse ® human allograft (BCA) tendons. Cross-sectional area of the grafts was measured using an alginate molding technique, and tendons were mounted within an Instron ® 5565 Materials Testing System using cryogenic clamps. BCB tendons displayed a higher ultimate tensile stress (p<0.05), with equivalent ultimate failure load, creep, and modulus of elasticity when compared to the FFB tendons (p>0.05). BCB tendons had an equivalent cross-sectional area to the BCA tendons (p>0.05) whilst exhibiting a greater failure load, ultimate tensile stress, less creep and a higher modulus of elasticity (p<0.05). The BioCleanse ® process did not adversely affect the time-zero biomechanical properties of bovine xenograft EDM tendons. BioCleanse ® processed bovine xenograft EDM tendons exhibited superior biomechanical characteristics when compared with BioCleanse ® processed allograft tibialis anterior tendons. These findings support further investigation of xenograft tendons in orthopedic soft tissue reconstructive surgery., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expression of Wnt signalling related proteins using quantitative immunohistochemical techniques on tissue arrays. We constructed tissue arrays with 58 individual replicate tissue samples. We tested for the expression of four key Wnt/ß-catenin transcription targets, namely Cyclin D1 (CCND1 or CD1), FRA1, c-Myc and MMP7. All antibodies showed cross reactivity in feline tissue except MMP7. Quantitative immunohistochemical analysis of single proteins (expressed as area fraction / amount of tissue for normal vs tumor, mean ± SE) showed that the expression of CD1 (3.9 ± 0.5 vs 12.2 ± 0.9), FRA1 (5.5 ± 0.6 vs 16.8 ± 1.1) and c-Myc (5.4 ± 0.5 vs 12.5 ± 0.9) was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls (p<0.0001). By using a multilabel, quantitative fluorophore technique we further investigated if the co-localization of these proteins (all transcription factors) with each other and in the nucleus (stained with 4',6-diamidino-2-phenylindole, DAPI) was altered in FOSCC compared to normal tissue. The global intersection coefficients, a measure of the proximity of two fluorophore labeled entities, showed that there was a significant change (p < 0.01) in the co-localization for all permutations (e.g. CD1/FRA1 etc), except for the nuclear localization of CD1. Our results show that putative targets of Wnt signalling transcription are up-regulated in FOSCC with alterations in the co-localization of these proteins and could serve as a useful marker for the disease., Competing Interests: Competing Interests: The authors of this manuscript have the following competing interests: AA (principal inventor) and CT and JRM (co-inventors) have filed for a patent through UCL Business for targeting Wnt signaling pathway for ß-catenin related disorders (New British Patent Application no. 1318659.8). AA is an associate editor of PLOS ONE. This do not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. One co-author (Jenny McKay) works for a commercial organization called IDEXX; another co-author (Malcolm Weetman) works for a commercial organization Independent Vetcare. The corresponding author declares, categorically, that none of the issues stated in these statements alter the authors' adherence to all policies of PLOS ONE.

We report on the growth and formation of single-layer boron nitride dome-shaped nanostructures mediated by small iron clusters located on flakes of hexagonal boron nitride. The nanostructures were synthesized in situ at high temperature inside a transmission electron microscope while the e-beam was blanked. The formation process, typically originating at defective step-edges on the boron nitride support, was investigated using a combination of transmission electron microscopy, electron energy loss spectroscopy and computational modelling. Computational modelling showed that the domes exhibit a nanotube-like structure with flat circular caps and that their stability was comparable to that of a single boron nitride layer.

Objective: The system of care in the Hunter New England Local Health District for patients with ST-segment elevation myocardial infarction (STEMI) foresees pre-hospital thrombolysis (PHT) administered by paramedics to patients more than 60 minutes from the cardiac catheterisation laboratory (CCL), and primary percutaneous coronary intervention (PCI) at the CCL for others. We assessed the safety and effectiveness of the pre-hospital diagnosis strategy, which allocates patients to PHT or primary PCI according to travel time to the CCL., Design, Setting and Participants: Prospective, non-randomised, consecutive, single-centre case series of STEMI patients diagnosed on the basis of a pre-hospital electrocardiogram (ECG), from August 2008 to August 2013. All patients were treated at the tertiary referral hospital (John Hunter Hospital, Newcastle)., Main Outcome Measures: The primary efficacy endpoint was all-cause mortality at 12 months; the primary safety endpoint was bleeding., Results: STEMI was diagnosed in 484 patients on the basis of pre-hospital ECG; 150 were administered PHT and 334 underwent primary PCI. The median time from first medical contact (FMC) to PHT was 35 minutes (IQR, 28-43 min) and to balloon inflation 130 minutes (IQR, 100-150 min). In the PHT group, 37 patients (27%) needed rescue PCI (median time, 4 h; IQR, 3-5 h). The 12-month all-cause mortality rate was 7.0% (PHT, 6.7%; PCI, 7.2%). The incidence of major bleeding (TIMI criteria) in the PHT group was 1.3%; no patients in the primary PCI group experienced major bleeding., Conclusion: PHT can be delivered safely by paramedical staff in regional and rural Australia with good clinical outcomes.

Purpose: The aim of this study was to quantify the contributions of medial soft tissues to stability following cruciate-retaining (CR) or posterior-stabilised (PS) total knee arthroplasty (TKA)., Methods: Using a robotic system, eight cadaveric knees were subjected to ±90-N anterior-posterior force, ±5-Nm internal-external and ±8-Nm varus-valgus torques at various flexion angles. The knees were tested intact and then with CR and PS implants, and successive cuts of the deep and superficial medial collateral ligaments (dMCL, sMCL) and posteromedial capsule (PMC) quantified the percentage contributions of each structure to restraining the applied loads., Results: In implanted knees, the sMCL restrained valgus rotation (62 % across flexion angles), anterior-posterior drawer (24 and 10 %, respectively) and internal-external rotation (22 and 37 %). Changing from CR TKA to PS TKA increased the load on the sMCL when resisting valgus loads. The dMCL restrained 11 % of external and 13 % of valgus rotations, and the PMC was significant at low flexion angles., Conclusions: This work has shown that medial release in the varus knee should be minimised, as it may inadvertently result in a combined laxity pattern. There is increasing interest in preserving constitutional varus in TKA, and this work argues for preservation of the sMCL to afford the surgeon consistent restraint and maintain a balanced knee for the patient.

Unlabelled: We report a phase II study to evaluate the efficacy and toxicity of abbreviated immunochemotherapy followed by (90) Y Ibritumomab tiuxetan ((90) Y-IT) in patients with recurrent follicular lymphoma. Of the 52 patients enrolled, 50 were treated with three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisolone), followed by (90) Y-IT regimen (15 MBq/kg, maximum 1200 MBq) preceded by two infusions of 250 mg/m(2) rituximab. The overall response rate was 98% with complete response (CR) 30% and partial response (PR) 68%. 18 patients with a PR following chemotherapy improved to a CR following (90) Y-IT: a conversion rate of 40%. Seven patients with PR following (90) Y-IT subsequently improved to a CR 12-18 months later, leading to an overall CR rate of 44%. With a median follow-up of 5 years, median progression-free survival was 23·1 months and overall survival was 77·5% at 5 years. High trough serum rituximab levels (median 112 μg/ml; range 52-241) were attained after four doses of rituximab, prior to (90) Y-IT; this was not found to influence response rates. The treatment was well tolerated with few (13·5%) grade 3 or 4 infective episodes and manageable haematological toxicity. Abbreviated immunochemotherapy followed by (90) Y-IT is an effective and well-tolerated treatment in recurrent follicular lymphoma patients previously exposed to rituximab., Trial Registration: clinicaltrials.gov identifier: NCT00637832., (© 2016 John Wiley & Sons Ltd.)

Background: Cryoballoon ablation is an established catheter-based approach to treating atrial fibrillation (AF). There is little data regarding the long-term efficacy of this approach., Methods: We enrolled 200 consecutive patients with symptomatic AF who had failed therapy with at least one anti-arrhythmic medication and followed them for five years. The primary efficacy endpoint was symptomatic recurrence of AF after a single cryoballoon ablation procedure., Results: Two hundred patients formed the study group. Median follow-up was 56 months. Following a single procedure, 46.7% of patients with paroxysmal AF remained free of symptomatic recurrence of AF compared to 35.6% of patients with persistent AF. When allowing for repeat ablations, at the end of the follow-up period 53.3% of patients in the paroxysmal group remained free of symptomatic AF compared to 47.5% in the persistent group. The rate of complications was low., Conclusions: Cryoballoon ablation is an effective catheter-based approach for treating symptomatic AF with a low risk of complications., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

The ability to estimate the speed of an object irrespective of size or texture is a crucial function of the visual system. However, previous studies have suggested that the neuronal coding of speed in the middle temporal area (MT, a key cortical area for motion analysis in primates) is ambiguous, with most neurons changing their speed tuning depending on the spatial frequency (SF) of a visual pattern. Here we demonstrate that the ability of MT neurons to encode speed is markedly improved when stimuli follow a trajectory across the visual field, prior to entering their receptive fields. We also show that this effect is much less marked in the primary visual area. These results indicate that MT neurons build up on computations performed at earlier levels of the visual system to provide accurate coding of speed in natural situations, and provide additional evidence that nonlinear pooling underlie motion processing.

Biogenic reefs are important for habitat provision and coastal protection. Long-term datasets on the distribution and abundance of Sabellaria alveolata (L.) are available from Britain. The aim of this study was to combine historical records and contemporary data to (1) describe spatiotemporal variation in winter temperatures, (2) document short-term and long-term changes in the distribution and abundance of S. alveolata and discuss these changes in relation to extreme weather events and recent warming, and (3) assess the potential for artificial coastal defense structures to function as habitat for S. alveolata. A semi-quantitative abundance scale (ACFOR) was used to compare broadscale, long-term and interannual abundance of S. alveolata near its range edge in NW Britain. S. alveolata disappeared from the North Wales and Wirral coastlines where it had been abundant prior to the cold winter of 1962/1963. Population declines were also observed following the recent cold winters of 2009/2010 and 2010/2011. Extensive surveys in 2004 and 2012 revealed that S. alveolata had recolonized locations from which it had previously disappeared. Furthermore, it had increased in abundance at many locations, possibly in response to recent warming. S. alveolata was recorded on the majority of artificial coastal defense structures surveyed, suggesting that the proliferation of artificial coastal defense structures along this stretch of coastline may have enabled S. alveolata to spread across stretches of unsuitable natural habitat. Long-term and broadscale contextual monitoring is essential for monitoring responses of organisms to climate change. Historical data and gray literature can be invaluable sources of information. Our results support the theory that Lusitanian species are responding positively to climate warming but also that short-term extreme weather events can have potentially devastating widespread and lasting effects on organisms. Furthermore, the proliferation of coastal defense structures has implications for phylogeography, population genetics, and connectivity of coastal populations.

Contingency plans are essential in guiding the response to marine oil spills. However, they are written before the pollution event occurs so must contain some degree of assumption and prediction and hence may be unsuitable for a real incident when it occurs. The use of Bayesian networks in ecology, environmental management, oil spill contingency planning and post-incident analysis is reviewed and analysed to establish their suitability for use as real-time environmental decision support systems during an oil spill response. It is demonstrated that Bayesian networks are appropriate for facilitating the re-assessment and re-validation of contingency plans following pollutant release, thus helping ensure that the optimum response strategy is adopted. This can minimise the possibility of sub-optimal response strategies causing additional environmental and socioeconomic damage beyond the original pollution event., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The photochemistry and photophysics of metal carbonyl compounds (W(CO)6, Cp*Rh(CO)2 (Cp* = η(5)-C5Me5), and fac-[Re(CO)3(4,4'-bpy)2Br] [bpy = bipyridine]) have been examined on the nanosecond timescale using a time-resolved infrared spectrometer with an external cavity quantum cascade laser (QCL) as the infrared source. We show the photochemistry of W(CO)6 in alkane solution is easily monitored, and very sensitive measurements are possible with this approach, meaning it can monitor small transients with absorbance changes less than 10(-6) ΔOD. The C-H activation of Cp*Rh(CO)(C6H12) to form Cp*Rh(CO)(C6H11)H occurs within the first few tens of nanoseconds following photolysis, and we demonstrate that kinetics obtained following deconvolution are in excellent agreement with those measured using an ultrafast laser-based spectrometer. We also show that the high flux and tunability of QCLs makes them suited for solid-state and time-resolved measurements.

A new haemogregarine species Hepatozoon affluomaloti sp. n. is described from erythrocytes in the peripheral blood of crag lizards Pseudocordylus melanotus (Smith) and Pseudocordylus subviridis (Smith) (Sauria: Cordylidae) from mountainous regions in the Eastern Free State, South Africa. This species can be distinguished from all other congeners based on its large size, staining properties and life cycle development in its vector, Culex (Afroculex) lineata (Theobald) (Diptera: Culicidae). Mature gamonts stain mostly uniformly pinkish-purple with Giemsa, sometimes containing darker azurophilic granules anterior and posterior to the nucleus. The reflexed posterior extremity of the gamont stage sometimes stains slightly deeper purple and the nucleus is dense and placed in the posterior third of the parasite body. Merogonic stages of this haemogregarine occur in the liver tissues of P. melanotus with dizoic meronts. Macromeronts contains 2-7 macromerozoites and micromeronts contains 9-24 micromerozoites. Sporogonic developmental stages found in the proposed final host and vector, C. lineata, include large oocysts, measuring 54 × 48 µm on average. Sporulating oocysts with 8 nuclei are present in mosquitoes 6-7 days post-feeding on infected lizards. Sporocysts with mature sporozoites measure 31.0 × 21.8 µm on average and each contains 2-8 large sporozoites. It is suggested that transmission of infective sporozoites is achieved through predation of lizards on mosquitoes.

A common cause for loss of a deep inferior epigastric perforator (DIEP) flap is venous congestion secondary to inadequate outflow via the deep perforating vessels. Further anastomosis of the superficial venous system provides effective outflow and salvage of the congested DIEP. Multiple methods have been described requiring dissection of additional recipient venous systems or around the perforating vessels in order to provide a vein onto which the superficial system may be anastomosed. These are potentially associated with increased morbidity and risk of damage to the pedicle. We describe an alternative technique of harvesting an additional length of deep inferior epigastric pedicle cranial to the perforator onto which an anastomosis may be performed. This avoids the need for additional dissection of recipient vessels or further handling of the perforator, its venae comitantes and the main pedicle of the flap thus reducing the risk of damage., (Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

The assessment of the biological activity of capsaicin, the compound responsible for the spicy flavor of chili pepper, produced controversial results, showing either carcinogenicity or cancer prevention. The innate immune system plays a pivotal role in cancer pathology and prevention; yet, the effect of capsaicin on natural killer (NK) cells, which function in cancer surveillance, is unclear. This study found that capsaicin inhibited NK cell-mediated cytotoxicity and cytokine production (interferon-γ and tumor necrosis factor-α). Capsaicin impaired the cytotoxicity of NK cells, thereby inhibiting lysis of standard target cells and gastric cancer cells by modulating calcium mobilization in NK cells. Capsaicin also induced apoptosis in gastric cancer cells, but that effect required higher concentrations and longer exposure times than those required to trigger NK cell dysfunction. Furthermore, capsaicin inhibited the cytotoxicity of isolated NK cells and of an NK cell line, suggesting a direct effect on NK cells. Antagonists of transient receptor potential vanilloid subfamily member 1 (TRPV1), a cognate capsaicin receptor, or deficiency in TRPV1 expression failed to prevent the defects induced by capsaicin in NK cells expressing functional TRPV1. Thus, the mechanism of action of capsaicin on NK cells is largely independent of TRPV1. Taken together, capsaicin may have chemotherapeutic potential but may impair NK cell function, which plays a central role in tumor surveillance., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

SUMMARY Research was undertaken to clarify the true taxonomic position of the terrestrial tortoise apicomplexan, Haemogregarina fitzsimonsi (Dias, 1953). Thin blood films were screened from 275 wild and captive South African tortoises of 6 genera and 10 species between 2009-2011. Apicomplexan parasites within films were identified, with a focus on H. fitzsimonsi. Ticks from wild tortoises, especially Amblyomma sylvaticum and Amblyomma marmoreum were also screened, and sporogonic stages were identified on dissection of adult ticks of both species taken from H. fitzsimonsi infected and apparently non-infected tortoises. Parasite DNA was extracted from fixed, Giemsa-stained tortoise blood films and from both fresh and fixed ticks, and PCR was undertaken with two primer sets, HEMO1/HEMO2, and HepF300/HepR900, to amplify parasite 18S rDNA. Results indicated that apicomplexan DNA extracted from tortoise blood films and both species of tick had been amplified by one or both primer sets. Haemogregarina  fitzsimonsi 18S rDNA sequences from tortoise blood aligned with those of species of Hepatozoon, rather than those of species of Haemogregarina or Hemolivia. It is recommended therefore that this haemogregarine be re-assigned to the genus Hepatozoon, making Hepatozoon fitzsimonsi (Dias, 1953) the only Hepatozoon known currently from any terrestrial chelonian. Ticks are its likely vectors.

Protein kinases C (PKCs) and extracellular signal-regulated kinases (ERKs) are evolutionary conserved cell signalling enzymes that coordinate cell function. Here we have employed biochemical approaches using 'smart' antibodies and functional screening to unravel the importance of these enzymes to Schistosoma mansoni physiology. Various PKC and ERK isotypes were detected, and were differentially phosphorylated (activated) throughout the various S. mansoni life stages, suggesting isotype-specific roles and differences in signalling complexity during parasite development. Functional kinase mapping in adult worms revealed that activated PKC and ERK were particularly associated with the adult male tegument, musculature and oesophagus and occasionally with the oesophageal gland; other structures possessing detectable activated PKC and/or ERK included the Mehlis' gland, ootype, lumen of the vitellaria, seminal receptacle and excretory ducts. Pharmacological modulation of PKC and ERK activity in adult worms using GF109203X, U0126, or PMA, resulted in significant physiological disturbance commensurate with these proteins occupying a central position in signalling pathways associated with schistosome muscular activity, neuromuscular coordination, reproductive function, attachment and pairing. Increased activation of ERK and PKC was also detected in worms following praziquantel treatment, with increased signalling associated with the tegument and excretory system and activated ERK localizing to previously unseen structures, including the cephalic ganglia. These findings support roles for PKC and ERK in S. mansoni homeostasis, and identify these kinase groups as potential targets for chemotherapeutic treatments against human schistosomiasis, a neglected tropical disease of enormous public health significance.

Regional scale habitat suitability models provide finer scale resolution and more focused predictions of where organisms may occur. Previous modelling approaches have focused primarily on local and/or global scales, while regional scale models have been relatively few. In this study, regional scale predictive habitat models are presented for deep-sea corals for the U.S. West Coast (California, Oregon and Washington). Model results are intended to aid in future research or mapping efforts and to assess potential coral habitat suitability both within and outside existing bottom trawl closures (i.e. Essential Fish Habitat (EFH)) and identify suitable habitat within U.S. National Marine Sanctuaries (NMS). Deep-sea coral habitat suitability was modelled at 500 m×500 m spatial resolution using a range of physical, chemical and environmental variables known or thought to influence the distribution of deep-sea corals. Using a spatial partitioning cross-validation approach, maximum entropy models identified slope, temperature, salinity and depth as important predictors for most deep-sea coral taxa. Large areas of highly suitable deep-sea coral habitat were predicted both within and outside of existing bottom trawl closures and NMS boundaries. Predicted habitat suitability over regional scales are not currently able to identify coral areas with pin point accuracy and probably overpredict actual coral distribution due to model limitations and unincorporated variables (i.e. data on distribution of hard substrate) that are known to limit their distribution. Predicted habitat results should be used in conjunction with multibeam bathymetry, geological mapping and other tools to guide future research efforts to areas with the highest probability of harboring deep-sea corals. Field validation of predicted habitat is needed to quantify model accuracy, particularly in areas that have not been sampled.

During its life cycle, the helminth parasite Schistosoma mansoni uses the freshwater snail Biomphalaria glabrata as an intermediate host to reproduce asexually generating cercariae for infection of the human definitive host. Following invasion of the snail, the parasite develops from a miracidium to a mother sporocyst and releases excretory-secretory products (ESPs) that likely influence the outcome of host infection. To better understand molecular interactions between these ESPs and the host snail defence system, we determined gene expression profiles of haemocytes from S. mansoni-resistant or -susceptible strains of B. glabrata exposed in vitro to S. mansoni ESPs (20 μg/ml) for 1 h, using a 5K B. glabrata cDNA microarray. Ninety-eight genes were found differentially expressed between haemocytes from the two snail strains, 57 resistant specific and 41 susceptible specific, 60 of which had no known homologue in GenBank. Known differentially expressed resistant-snail genes included the nuclear factor kappa B subunit Relish, elongation factor 1α, 40S ribosomal protein S9, and matrilin; known susceptible-snail specific genes included cathepsins D and L, and theromacin. Comparative analysis with other gene expression studies revealed 38 of the 98 identified genes to be uniquely differentially expressed in haemocytes in the presence of ESPs, thus identifying for the first time schistosome ESPs as important molecules that influence global snail host-defence cell gene expression profiles. Such immunomodulation may benefit the schistosome, enabling its survival and successful development in the snail host.

Background: Phosphatidylinositol-3-kinase delta (PI3Kδ) mediates B-cell receptor signaling and microenvironmental support signals that promote the growth and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an orally active selective PI3Kδ inhibitor, showed antitumor activity in patients with previously treated indolent non-Hodgkin's lymphomas., Methods: In this single-group, open-label, phase 2 study, 125 patients with indolent non-Hodgkin's lymphomas who had not had a response to rituximab and an alkylating agent or had had a relapse within 6 months after receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progressed or the patient withdrew from the study. The primary end point was the overall rate of response; secondary end points included the duration of response, progression-free survival, and safety., Results: The median age of the patients was 64 years (range, 33 to 87); patients had received a median of four prior therapies (range, 2 to 12). Subtypes of indolent non-Hodgkin's lymphoma included follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia (10). The response rate was 57% (71 of 125 patients), with 6% meeting the criteria for a complete response. The median time to a response was 1.9 months, the median duration of response was 12.5 months, and the median progression-free survival was 11 months. Similar response rates were observed across all subtypes of indolent non-Hodgkin's lymphoma, though the numbers were small for some categories. The most common adverse events of grade 3 or higher were neutropenia (in 27% of the patients), elevations in aminotransferase levels (in 13%), diarrhea (in 13%), and pneumonia (in 7%)., Conclusions: In this single-group study, idelalisib showed antitumor activity with an acceptable safety profile in patients with indolent non-Hodgkin's lymphoma who had received extensive prior treatment. (Funded by Gilead Sciences and others; ClinicalTrials.gov number, NCT01282424.).

Background: Tibiofemoral instability is a common reason for total knee arthroplasty failure, and may be attributed to soft tissue deficiency and incorrect ligament balancing. There are many different designs of implant with varying levels of constraint to overcome this instability; however there is little advice for surgeons to assess which is suitable for a specific patient, and soft tissue balance testing during arthroplasty is very subjective., Method: The current theories on primary and secondary soft tissue restraints to anterior/posterior, varus/valgus, and internal/external rotational motion of the knee are discussed. The paper reviews biomechanics literature to evaluate instability in the intact and implanted knee., Findings: The paper highlights important intra- and extra-capsular structures in the knee and describes the techniques used by clinicians to assess instability perioperatively. In vitro cadaveric studies were found to be a very useful tool in comparing different implants and contributions of different soft tissues., Interpretation: In vitro cadaveric studies can be utilised in helping less experienced surgeons with soft tissue releases and determining the correct implant. For this to happen, more biomechanical studies must be done to show the impact of release sequences on implanted cadavers, as well as determining if increasingly constrained implants restore the stability of the knee to pre-deficient conditions., (Copyright © 2013. Published by Elsevier Ltd.)

Background: Trypanosomes are ubiquitous blood parasites of marine and freshwater fishes, typically transmitted by aquatic leeches. Phylogenetic studies have been dominated by examples derived from freshwater fishes, with few marine representatives. Furthermore, life cycle studies on marine fish trypanosomes have focused on those of the northern hemisphere. In this investigation, we have examined the life cycle and molecular taxonomy of a marine fish trypanosome from South Africa., Methods: To locate trypanosome stages, leeches were removed from fishes captured on the west and south coasts of South Africa, and fish blood films and leech squashes were Giemsa-stained and screened; leeches were also examined histologically. To determine whether trypanosome stages in fishes and leeches were of the same genotype, DNA was extracted from Giemsa-stained fish blood films and leech squashes, and from fish whole blood. Fragments of the 18S rRNA gene were amplified by PCR using trypanosome-specific primers and sequenced. Resulting sequence data were compared with each other and with published trypanosome 18S rDNA sequences, and used for phylogenetic analysis., Results: Trypanosomes were detected in blood films from fishes of the families Clinidae, Blenniidae and Gobiidae. The flagellates ranged in size and staining properties within the films and across fish hosts. In squashes and histological sections of adult and juvenile leeches, identified as Zeylanicobdella arugamensis, trypanosome developmental stages were predominantly slender epimastigotes. Sequence data showed that trypanosomes derived from fishes were identical, irrespective of whether they were small or large forms; sequences derived largely from leech epimastigotes were also identical to those obtained from fish trypanosomes. Fish and leech trypanosome sequences fell into a marine fish aquatic clade, and aligned most closely with two trypanosome sequences from marine fishes off Norway., Conclusions: Combined morphological and molecular methods indicate that the trypanosomes examined here represent a single pleomorphic species, rather than the three species described originally. This species is identified as Trypanosoma nudigobii Fantham, 1919 with the leech Z. arugamensis as its vector, and T. capigobii Fantham, 1919 and T. blenniclini Fantham, 1930 are regarded as junior synonyms of the species. Phylogenetic analysis establishes its affinity with marine fish trypanosomes off Norway.

We recently demonstrated that pain-sensing neurons in the trigeminal system can be selectively anesthetized by co-application of QX-314 with the TRPV1 receptor agonist, capsaicin (QX cocktail). Here we examined whether this new anesthetic strategy can block the neuronal changes in the brainstem following molar tooth extraction in the rat. Adult male Sprague-Dawley rats received infiltration injection of anesthetic 10 min prior to lower molar tooth extraction. Neuronal activation was determined by immunohistochemistry for the proto-oncogene protein c-Fos in transverse sections of the trigeminal subnucleus caudalis (Sp5C). After tooth extraction, c-Fos-like immunoreactivity (Fos-LI) detected in the dorsomedial region of bilateral Sp5C was highest at 2 hrs (p < .01 vs. naïve ipsilateral) and declined to pre-injury levels by 8 hrs. Pre-administration of the QX cocktail significantly reduced to sham levels Fos-LI examined 2 hrs after tooth extraction; reduced Fos-LI was also observed with the conventional local anesthetic lidocaine. Pulpal anesthesia by infiltration injection was confirmed by inhibition of the jaw-opening reflex in response to electrical tooth pulp stimulation. Our results suggest that the QX cocktail anesthetic is effective in reducing neuronal activation following tooth extraction. Thus, a selective pain fiber 'nociceptive anesthetic' strategy may provide an effective local anesthetic option for dental patients in the clinic.

Old World frugivorous bats have been identified as natural hosts for emerging zoonotic viruses of significant public health concern, including henipaviruses (Nipah and Hendra virus), Ebola virus, and Marburg virus. Epidemiological studies of these viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. However, little is understood about bat immunology, including the duration of maternal antibodies in neonates. Understanding duration of maternally derived immunity is critical for characterizing viral dynamics in bat populations, which may help assess the risk of spillover to humans. We conducted two separate studies of pregnant Pteropus bat species and their offspring to measure the half-life and duration of antibodies to 1) canine distemper virus antigen in vaccinated captive Pteropus hypomelanus; and 2) Hendra virus in wild-caught, naturally infected Pteropus alecto. Both of these pteropid bat species are known reservoirs for henipaviruses. We found that in both species, antibodies were transferred from dam to pup. In P. hypomelanus pups, titers against CDV waned over a mean period of 228.6 days (95% CI: 185.4-271.8) and had a mean terminal phase half-life of 96.0 days (CI 95%: 30.7-299.7). In P. alecto pups, antibodies waned over 255.13 days (95% CI: 221.0-289.3) and had a mean terminal phase half-life of 52.24 days (CI 95%: 33.76-80.83). Each species showed a duration of transferred maternal immunity of between 7.5 and 8.5 months, which was longer than has been previously estimated. These data will allow for more accurate interpretation of age-related Henipavirus serological data collected from wild pteropid bats.

The trends in the publication of articles regarding knee arthroplasty and soft tissue surgery were analysed with regard to geographical authorship, institutional funding and number of authors. Over 7500 articles from relevant journals with the highest impact factors according to the Thomson Reuters Journal Citation Report (2010) were evaluated from 1995 to 2010. The rate of publication increased by 16.9 per year for arthroplasty articles and by 13.9 per year for soft tissue surgery articles. The relative supremacy of the USA has declined over the 16 years, its share dropping from 72.2% to 39.2% for arthroplasty articles and from 61.7% to 36.6% for soft tissue surgery articles. The UK, Japan, South Korea and smaller countries in Asia and South America have become increasingly prolific., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Porous NOTT-202a shows exceptionally high uptake of SO2, 13.6 mmol g(-1) (87.0 wt %) at 268 K and 1.0 bar, representing the highest value reported to date for a framework material. NOTT-202a undergoes a distinct irreversible framework phase transition upon SO2 uptake at 268-283 K to give NOTT-202b which has enhanced stability due to the formation of strong π···π interactions between interpenetrated networks.

Investigations to determine whether juvenile gnathiid isopods are vectors of haemogregarines between coral reef fishes were undertaken at Lizard Island, Australia. Haemogregarina balistapi parasitaemias in triggerfish, Rhinecanthus aculeatus, decreased under gnathiid-free, laboratory conditions, compared with those in tagged R. aculeatus returned to the reef. Gnathia aureamaculosa juveniles were common ectoparasites of reef R. aculeatus and laboratory reared specimens of this gnathiid were fed on R. aculeatus infected with H. balistapi. Subsequent squashes of this gnathiid contained haemogregarine gamonts similar to those seen in blood films of R. aculeatus, and haemogregarine developmental stages, including oocysts, sporozoites, meronts and merozoites. Biological transmission of H. balistapi and a second haemogregarine species, Haemogregarina bigemina, using laboratory reared gnathiids to several species of triggerfishes and surgeonfishes raised from larvae was then attempted. Investigations involved recipient fish ingesting, or being bitten by, G. aureamaculosa juveniles fed on donor fish with haemogregarines; control fish were exposed to gnathiids fed on uninfected donor fish. Subsequently, no haemogregarines were detected in recipient triggerfishes and controls were negative. However, a recipient surgeonfish, Acanthurus xanthopterus, which had ingested gnathiids likely infected with donor fish H. balistapi, carried H. bigemina-like stages. A second recipient surgeonfish, which had ingested gnathiids presumed to be infected with H. bigemina, also carried haemogregarine stages. Finally, a third surgeonfish apparently carried haemogregarines after gnathiids presumed to be infected with H. bigemina had bitten this fish, although not all gnathiids were recovered during the trials and the third infected surgeonfish may have also ingested gnathiids. The study provides strong evidence that G. aureamaculosa is the definitive host of H. balistapi, to our knowledge the first such observation from a coral reef environment. Although transmission of H. balistapi has not yet been demonstrated, laboratory trials tend to support the view that G. aureamaculosa is also a potential vector of H. bigemina between surgeonfish., (Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.)

Regulation of intracellular pH is critical for the maintenance of cell homeostasis in response to stress. We used yeast two-hybrid screening to identify novel interacting partners of the pH-regulating transporter NBCe1-B. We identified Hsp70-like stress 70 protein chaperone (STCH) as interacting with NBCe1-B at the N-terminal (amino acids 96-440) region. Co-injection of STCH and NBCe1-B cRNA into Xenopus oocytes significantly increased surface expression of NBCe1-B and enhanced bicarbonate conductance compared with NBCe1-B cRNA alone. STCH siRNA decreased the rate of Na(+)-dependent pHi recovery from NH4(+) pulse-induced acidification in an HSG (human submandibular gland ductal) cell line. We observed that in addition to NBCe1-B, Na(+)/H(+) exchanger (NHE)-dependent pHi recovery was also impaired by STCH siRNA and further confirmed the interaction of STCH with NHE1 but not plasma membrane Ca(2+) ATPase. Both NBCe1-B and NHE1 interactions were dependent on a specific 45-amino acid region of STCH. In conclusion, we identify a novel role of STCH in the regulation of pHi through site-specific interactions with NBCe1-B and NHE1 and subsequent modulation of membrane transporter expression. We propose STCH may play a role in pHi regulation at times of cellular stress by enhancing the recovery from intracellular acidification.

Two new haemogregarine species, Hepatozoon langii n. sp. and Hepatozoon vacuolatus n. sp., are described from the pe-ripheral blood of the high altitude crag lizard, Pseudocordylus langi, collected between October 2006 and April 2009 from the North Eastern Drakensberg, Eastern Free State. Hepatozoon langii n. sp. has maturing and mature gamonts that appear encapsulated and have narrow, curved tails. Their cytoplasm stains pinkish-purple with Giemsa, while their nuclei are pur-ple stained with stranded chromatin. Mature gamonts measure 19.1 ± 1.0 (15.4-28.1) μm long by 6.2 ± 1.1 (3.5-7.9) μm wide. Hepatozoon vacuolatus n. sp. gamonts are mostly broader at one pole than the other, have bluish-pink cytoplasm characterised by distinctive rounded and oval vacuoles, and demonstrate pink granules with Giemsa staining. Nuclei stain purple and are mainly coarsely granular. Mature gamonts measure 16.5 ± 1.0 (14.7 - 17.6) μm long by 5.9 ± 1.2 (4.0 - 7.7) μm wide. Both species parasitize erythroblasts, as well as erythrocytes and can dehaemoglobinize the cytoplasm of their host cells. Hepatozoon langii n. sp occurred in the absence of H. vacuolatus n. sp., but the latter haemogregarine always formed mixed infections with the former; no stages intermediate between the two haemogregarine types were observed.

Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A (PKA) is the major transducer of cAMP signalling in eukaryotic cells. Here, using laser scanning confocal microscopy and 'smart' anti-phospho PKA antibodies that exclusively detect activated PKA, we provide a detailed in situ analysis of PKA signalling in intact adult Schistosoma mansoni, a causative agent of debilitating human intestinal schistosomiasis. In both adult male and female worms, activated PKA was consistently found associated with the tegument, oral and ventral suckers, oesophagus and somatic musculature. In addition, the seminal vesicle and gynaecophoric canal muscles of the male displayed activated PKA whereas in female worms activated PKA localized to the ootype wall, the ovary, and the uterus particularly around eggs during expulsion. Exposure of live worms to the PKA activator forskolin (50 µM) resulted in striking PKA activation in the central and peripheral nervous system including at nerve endings at/near the tegument surface. Such neuronal PKA activation was also observed without forskolin treatment, but only in a single batch of worms. In addition, PKA activation within the central and peripheral nervous systems visibly increased within 15 min of worm-pair separation when compared to that observed in closely coupled worm pairs. Finally, exposure of adult worms to forskolin induced hyperkinesias in a time and dose dependent manner with 100 µM forskolin significantly increasing the frequency of gross worm movements to 5.3 times that of control worms (P≤0.001). Collectively these data are consistent with PKA playing a central part in motor activity and neuronal communication, and possibly interplay between these two systems in S. mansoni. This study, the first to localize a protein kinase when exclusively in an activated state in adult S. mansoni, provides valuable insight into the intricacies of functional protein kinase signalling in the context of whole schistosome physiology.

Histologic confirmation of axillary nodal metastases preoperatively avoids a sentinel node biopsy and enables a one step surgical procedure. The aim of this study was to establish the local positive predictive value of axillary ultrasound (AUS) and guided needle core biopsy (NCB) in axillary staging of breast cancer, and to identify factors influencing yield. A prospective audit of 142 consecutive patients (screening and symptomatic) presenting from 1st December 2008-31st May 2009 with breast lesions categorized R4-R5, who underwent a preoperative AUS, and proceeded to surgery was undertaken. Ultrasound-guided NCB was performed on nodes radiologically classified R3-R5. Lymph node size, number, and morphological features were documented. Yield was correlated with tumor size, grade, and histologic type. AUS/NCB was correlated with post surgical pathologic findings to determine sensitivity, specificity, positive and negative predictive value of AUS and NCB. A total of 142 patients underwent surgery, of whom 52 (37%) had lymph node metastases on histology. All had a preoperative AUS, 51 (36%) had abnormal ultrasound findings. 46 (90%) underwent axillary node NCB of which 24 (52%) were positive. The smallest tumor size associated with positive nodes at surgery was 11.5 mm. The sensitivity of AUS was 65%. Specificity was 81%, with a positive predictive value (PPV) of 67% and negative predictive (NPV) value of 80%. Sensitivity of U/S-guided NCB was 75%, with a specificity of 100%, PPV 100% and NPV 64%. Sensitivity of AUS for lobular carcinoma was 36% versus 76% for all other histologies. Sensitivity of NCB for lobular cancer was 33% versus 79% for all other histologies. The most significant factor producing discordance between preoperative AUS and definitive histologic evidence of lymph node metastasis was tumor type. Accurate preoperative lymph node staging was prejudiced by lobular histology (p < 0.0019)., (© 2012 Wiley Periodicals, Inc.)

The number of survivors having undergone high-dose therapy (HDT) followed by auto-SCT continues to increase, although some of the long-term sequelae remain incompletely understood. The immunological status and quality of life of 37 HDT/auto-SCT survivors with lymphoma in continuous remission of ≥3 years were assessed alongside 14 age-matched controls. At a median follow-up of 10.5 years (range 2.2-20.2) following HDT/auto-SCT, the proportion of CD4(+) cells remained significantly reduced in patients compared with controls (median 43.4% vs 62.5%, respectively; P = < 0.001), predominantly a result of sustained reduction in the naive CD4(+) component (P < 0.001). Naive CD8(+) lymphocytes (P = 0.014) and transitional B cells (P = 0.008) were also significantly reduced, but differences in other lymphocyte subsets were not observed. Uptake of revaccination following HDT/auto-SCT was sporadic; between 11% and 33% of patients had serological titres outside the protective ranges for five of six routinely used vaccines. In the main, patients were found to have a good quality of life, although their EORTC QLQ-C30 questionnaire scores were significantly lower for the physical and social functioning domains compared with controls. Ten years after HDT/auto-SCT immunological deficits persist; to avoid excess risk of preventable disease, serological immunity should be assessed post HDT/auto-SCT followed by appropriate revaccination.