A bioavailable strontium (87Sr/86Sr) isoscape for Aotearoa New Zealand: Implications for food forensics and biosecurity.

As people, animals and materials are transported across increasingly large distances in a globalized world, threats to our biosecurity and food security are rising. Aotearoa New Zealand is an island nation with many endemic species, a strong local agricultural industry, and a need to protect these from pest threats, as well as the economy from fraudulent commodities. Mitigation of such threats is much more effective if their origins and pathways for entry are understood. We propose that this may be addressed in Aotearoa using strontium isotope analysis of both pests and products. Bioavailable radiogenic isotopes of strontium are ubiquitous markers of provenance that are increasingly used to trace the origin of animals and plants as well as products, but currently a baseline map across Aotearoa is lacking, preventing use of this technique. Here, we have improved an existing methodology to develop a regional bioavailable strontium isoscape using the best available geospatial datasets for Aotearoa. The isoscape explains 53% of the variation (R2 = 0.53 and RMSE = 0.00098) across the region, for which the primary drivers are the underlying geology, soil pH, and aerosol deposition (dust and sea salt). We tested the potential of this model to determine the origin of cow milk produced across Aotearoa. Predictions for cow milk (n = 33) highlighted all potential origin locations that share similar 87Sr/86Sr values, with the closest predictions averaging 7.05 km away from their true place of origin. These results demonstrate that this bioavailable strontium isoscape is effective for tracing locally produced agricultural products in Aotearoa. Accordingly, it could be used to certify the origin of Aotearoa's products, while also helping to determine if new pest detections were of locally breeding populations or not, or to raise awareness of imported illegal agricultural products.

A unique case of acute embolus in a renal transplant with salvage by catheter-directed thrombolysis.

INTRODUCTION: Acute renal transplant emboli can be disastrous and result in loss of the renal transplant. This case was successfully treated with thrombolysis. CASE PRESENTATION: A 66-year-old female underwent a right-sided deceased heart-beating donor renal transplant. She had excellent transplant function but presented acutely three years later with pain in the transplanted kidney, an acute rise in serum creatinine and new onset atrial fibrillation. Bedside ultrasound scan demonstrated absent transplant perfusion. Emergency angiogram confirmed acute emboli in the transplant renal artery with some kidney perfusion. Thrombolysis with alteplase and anticoagulation with heparin was commenced. Serial imaging at 24 and 36 h demonstrated significant improvement in transplant perfusion. Following a period of supportive therapy, her transplant function recovered, although not to pre-morbid baseline levels. CONCLUSION: Consider acute embolus in a renal transplant patient with acute kidney injury, transplant tenderness and cardiac arrhythmia. Early thrombolysis may salvage renal transplants and good transplant function may be regained.

Perceptions of supported and unsupported prone-restraint positions.

WHAT IS KNOWN ON THE SUBJECT?: Although the use of prone restraint should be avoided, it may remain a last resort emergency intervention for violent behaviour in psychiatric settings. However, when used as a last resort, concerns remain about the ability of staff to maintain the dignity, welfare and safety of the patient and minimize the potential adverse outcomes associated with restraint. This study builds on existing research regarding the risks of prone restraint by focusing on the psychological perceptions of individuals held in this position. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Individuals, who were asked to rate the psychological impact of two different prone-restraint positions (Supported and Unsupported Prone Positions) reported that the Supported Prone Position was more comfortable, less anxiety inducing and less limiting to breathing. Although no individual found prone restraint a positive experience, it shows that individuals found the psychological impact of the Supported Prone Position was less than the Unsupported Prone Position. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health professionals have a clear responsibility to maintain the dignity, safety and wellbeing of individuals subject to prone restraint as a short-term emergency procedure for the management of violent behaviour. Reducing both the physiological and psychological impact of prone restraint will help to reduce any adverse impact on individuals subject to such interventions. The findings will help influence current practice and promote the removal of the USPP as a specific prone-restraint intervention. ABSTRACT: Aim Restraint-related deaths are multi-factorial with prone restraint remaining a concern due to the physiological and psychological risks. This study builds on evidence presented by (Barnett et al. Medicine, Science and the Law (2012b): 1) that the Supported Prone Position (SPP) reduces physiological risks, by examining if the SPP also reduces the psychological impact of prone restraint. Methods Twenty participants ran to near maximal exertion before being held in two prone-restraint positions: SPP and Unsupported Prone Position (USPP). Perceptions of comfort, anxiety and breathing limitation were measured using Visual Analogue Scales. Results Results showed that (1) comfort was 23% greater in the SPP; (2) anxiety was 55% less in the SPP; and (3) perception of breathing limitation was 32% less in the SPP when compared with the USPP. Negative perceptions expressed for the USPP included feeling trapped, vulnerable and concern over heart rate. Discussion In addition to reducing physiological risks, this study shows that the SPP reduced the psychological impact of prone restraint compared to USPP. Implications for Practice Settings where prone restraint cannot be avoided should remove the USPP as an emergency procedure in favour of the SPP as a way of maintaining safety and reducing the psychological impact of prone restraint.

The effect of piezoelectric ultrasonic instrumentation on titanium discs: a microscopy and trace elemental analysis in vitro study.

AIM: To evaluate in vitro topographical and composition changes by piezoelectric ultrasonic instrumentation with metallic and plastic tips on machined and moderately roughened titanium surfaces. METHODS: Twenty machined and moderately roughened laser-marked titanium discs were ultrasonically instrumented with metallic and plastic tips. Surface instrumentation was carried out with controlled pressure for 20 and 30 seconds at two power settings. For each time and power setting, instrumentation was repeated four times with one instrumentation per disc quadrant. Surface topography analysis was performed using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Surface roughness measurements were compared between instrumented and non-instrumented surfaces. Surface element composition and rinsing solutions were evaluated using energy-dispersive spectroscopy (EDS) and trace elemental analysis using inductively coupled plasma mass spectrometry (ICPMS), respectively. RESULTS: SEM photomicrographs and CLSM 3D surface plot images of instrumented machined and moderately roughened surfaces demonstrated severe surface topographical alterations with metallic tips and mild to moderate changes for plastic tip instrumented sites. ICPMS analysis of the rinsing solutions identified titanium and other metal traces with the use of metallic tips, and mainly titanium and carbon when plastic tips were used. Surface EDS analysis showed elemental traces of the ultrasonic tips. CONCLUSION: Ultrasonic instrumentation with metallic or plastic tips created surface topographical and compositional changes. Different changes in surface topography were noted between the surfaces, as the roughness of the machined surfaces increased while the extent of roughness of the moderately roughened surfaces decreased. The clinical relevance of these changes is yet to be determined.

Vaccination of dogs with Duramune DAPPi+LC protects against pathogenic canine parvovirus type 2c challenge.

In this study, we determined whether vaccination with Duramune DAPPi+LC containing canine parvovirus (CPV) type 2b protects against challenge with virulent CPV antigenic type 2c. Seven healthy dogs, seronegative for CPV2, were enrolled into two treatment groups; five were vaccinated twice, 21 days apart, with minimum titre vaccine, and two were given saline. Dogs were challenged with CPV 2c three weeks later. Clinical observations, body weight and rectal temperature measurements, blood samples for serology and white blood cell counts and faecal samples for virus excretion were collected. Control dogs remained seronegative until challenge; vaccinated dogs seroconverted and were positive for antibodies to CPV2 from day 21. Four days after challenge, clinical signs associated with parvovirus infection (vomiting, paroxysmal shivering, depression, loose stools) were observed in the control dogs. Both animals were withdrawn from the study for welfare reasons one day later. On day 47, leucopenia was observed in controls, with white blood cell counts less than 50 per cent prechallenge values. No specific clinical sign of parvovirus infection were observed in the vaccinated dogs, nor was (detectable) challenge virus shed in faeces suggesting that antibodies generated contributed sterilising immunity. We conclude that vaccination of dogs with Duramune DAPPi+LC protects against challenge with a virulent field strain of CPV 2c.

Validation of the Global Rating Scale for endoscopy.

The Global Rating Scale for endoscopy is a web-based tool that can be used to assess and improve the quality of an endoscopy service. It was developed by asking endoscopy health professionals what they would want from the service for themselves or their relatives if they were undergoing an endoscopic procedure. To date, the Global Rating Scale has not been validated by patients themselves. We used focus groups in order to access the views and opinions of patients who had recently had experience of endoscopy services. Six focus groups were undertaken in five different Health Board areas across Scotland; in total 26 people participated. The results indicated that from the patients' perspective the 12 items of the GRS covered all areas of the endoscopy experience. There were no specific concerns identified that were not already covered within the Global Rating Scale. We conclude that the Global Rating Scale does address quality issues that matter to patients undergoing endoscopy, and validates the use of the GRS as a quality assessment tool for endoscopy services.

Does the trace element composition of brown trout Salmo trutta eggs remain unchanged in spawning redds?

The temporal stability of trace element concentrations in fertilized, artificially incubated anadromous brown trout Salmo trutta eggs and newly hatched fry was investigated. The anadromous status of the parental fish was confirmed using strontium isotopic analysis of otoliths. Whilst manganese concentrations in eggs varied over time, concentrations of aluminium, potassium, magnesium, strontium, barium and calcium were all unchanged 1 week and 6 weeks post-fertilization as well as in recently hatched larvae. The results clearly suggest that the distinctive trace element signature present in the eggs and newly hatched larvae of anadromous S. trutta (typically characterized by high strontium, low barium) is stable over time. Therefore analysis of the trace element composition of eggs is concluded to be a cost-effective and reliable method for determining the spatial and temporal extent of upstream spawning migration by anadromous salmonids. The temporal variability of at least one element in this study suggests the stability of untested multi-element signatures cannot automatically be assumed.

Consistency as tool to support in vitro batch potency testing in GMP production.

There is great interest in the veterinary vaccine field to move away from in vivo release tests for vaccines to reduce cost and testing time, improve consistency and of course the 3Rs (reduce, refine, replace). A brief overview of Good Manufacturing Practice (GMP) and the consistency approach is discussed below and an overview of how manufacturers can use the consistency approach and GMP controls along with statistical analysis of processes at each stage of the production process (starting materials, antigen and finished product) to build in quality and reduce the need for in vivo finished product tests. A final summary and outline of some challenges we will face in moving this approach forward is covered in conclusion.

Severe statin-induced rhabdomyolysis mimicking Guillain-Barré syndrome in four patients with diabetes mellitus treated with fusidic acid.

BACKGROUND: An interaction between fusidic acid and HMG coenzyme A reductase inhibitors (statins), resulting in rhabdomyolysis, has been described. Pain and mild weakness are common presenting symptoms. CASE REPORT: We report four patients with Type 2 diabetes prescribed long-term statin treatment who, following treatment with fusidic acid, presented atypically with painless, severe flaccid paralysis suggestive of Guillain-Barré syndrome. This, together with nerve conduction studies consistent with Guillain-Barré syndrome, resulted in the delayed recognition of rhabdomyolysis in these cases. CONCLUSIONS: The addition of fusidic acid can precipitate rhabdomyolysis in patients with diabetes already taking a statin. This can present with rapidly progressive weakness resembling Guillain-Barré syndrome. We recommend that creatine kinase is checked in patients with diabetes on statin therapy who present with profound weakness and routinely in those commenced on prolonged courses of fusidic acid.

Anaemia is common and predicts mortality in diabetic nephropathy.

BACKGROUND: Diabetes is the single largest cause of chronic renal failure, accounting for 18% of patients on renal replacement therapy in the UK. AIM: To investigate the chronic kidney disease stage at which patients with diabetic nephropathy are referred to renal services, determine the prevalence of anaemia in patients with diabetic nephropathy, examine patient outcome and identity prognostic factors. DESIGN: Retrospective review. METHODS: Patients with diabetic nephropathy referred to our renal services between 1989 and 2004 were identified from electronic records. Estimated glomerular filtration rate (calculated using the MDRD formula) and haemoglobin at referral were collected. Times to renal replacement therapy and death were noted. RESULTS: We identified 508 patients. At referral, mean eGFR was 34 ml/min/1.73 m(2) and 48% of patients were at CKD stages 4 and 5. Mean haemoglobin was 11.7 g/dl; 21% had a haemoglobin <10 g/dl at referral. Median survival was 37.9 months (95%CI 33.2-42.6); median survival independent of renal replacement therapy (RRT) was 21 months (95%CI 17.8-24.6). Of patients starting RRT, 38% did so within 1 year of referral. Older age (RR 1.02, 95%CI 1.01-1.04) and lower haemoglobin (RR 0.9, 95%CI 0.85-0.99) at referral predicted death on multivariate analysis. DISCUSSION: At referral to renal services, almost 50% of patients with diabetic nephropathy were at CKD stages 4 and 5. Anaemia was common and predicted mortality. All diabetic patients from CKD stage 3 should be screened for anaemia. We believe that patients with diabetic nephropathy should be discussed with renal services when they reach CKD stage 3 with evidence of progression of renal disease.

Vascular access in haemodialysis patients: a modifiable risk factor for bacteraemia and death.

BACKGROUND: Bacteraemia and the development of sepsis syndrome is second only to cardiovascular disease as the leading cause of death in patients on renal replacement therapy. AIM: To determine the contributions of laboratory and clinical variables to the risk of bacteraemia and death in haemodialysis patients. DESIGN: Retrospective analysis. METHODS: We analysed all patients receiving haemodialysis in our renal unit at the beginning of January 2004 (n=263), recording clinical and laboratory variables for each patient at study entry. Bacteraemia and mortality were recorded for the subsequent 18-month period. Multivariate analysis using a Cox proportional hazards model was used to test for independent associations between variables and outcomes. RESULTS: During the study period, 45 patients (17.1%) developed bacteraemia and 65 (24.7%) died. Under multivariate analysis, use of dialysis catheters at study entry was a major factor in the development of bacteraemia and death with hazard ratios (HR) of 5.4 (p<0.001) and 2.8 (p=0.012), respectively, for tunnelled central venous catheters vs. arteriovenous fistulas (AVFs) and 3.1 (p=0.01) and 3.4 (p=0.001), respectively, for non-tunnelled central venous catheters vs. AVFs. Elevated CRP at study entry was independently associated with bacteraemia (HR 1.5 per unit log-CRP, p=0.006). Low serum albumin (HR 0.92, p=0.005) was independently associated with death. DISCUSSION: Use of synthetic vascular access catheters and heightened inflammatory state both have strong independent associations with subsequent bacteraemia and death. Bacteraemia surveillance strategies should be developed, with consideration of vascular access type and baseline inflammatory state as key components.

Efficacy of particle-based DNA delivery for vaccination of sheep against FMDV.

As an alternative strategy to classical inactivated viral vaccine against FMDV, naked DNA vaccine is attractive because of safety, flexibility and low cost. However DNA vaccination is usually poorly efficient in target species. Indeed we found that naked DNA plasmids encoding for P1-2A3C3D and GM-CSF proteins did not induce any detectable immunity against FMDV in sheep. Interestingly, we demonstrate herein that formulations of DNA on poly(D,L-lactide-co-glycolide) (PLG) or in lipofectin triggered divergent types of immune responses: PLG stimulated a T cell response and could elicit significant neutralising antibody titers, whereas lipofectin generated even higher antibody titers but no significant T cell response. The DNA/PLG regimen used in five sheep protected against clinical symptoms and viraemia and prevented the carrier state in four of them. Thus formulated DNA can be remarkably efficient against FMDV in a ruminant species that is usually refractory to DNA vaccination.

Porcine gammadelta T cells: possible roles on the innate and adaptive immune responses following virus infection.

gammadelta T cells recognise different types of antigen in alternative ways to alphabeta T cells, and thus appear to play a complementary role in the immune response. However, unlike alphabeta T cells, the role or function of gammadelta T cells is still unclear. As pigs possess a high proportion of circulating gammadelta T cells, they are suitable large animal model to study gammadelta T cell functions. This as yet has not been fully exploited, leaving porcine gammadelta T cell biology and its role in immunity in its infancy. Foot-and-mouth disease (FMD) high potency "emergency" vaccines are able to induce early protection from challenge and it has been suggested that, in part, there is some involvement of innate immune responses. The antigen component of the vaccine is able to stimulate purified naive pig gammadelta T cells and induce the mRNA of various cytokines and chemokines. This observation suggests that gammadelta T cells probably contribute to the early phase of the immune responses to FMD vaccination, and perhaps infection. A subset of these circulating gammadelta T cells display a phenotype similar to professional antigen presenting cells and are able to take up and present soluble antigen to CD4(+) T cells in a direct cell-cell interaction via MHC class II. This direct interaction between gammadelta T cells and CD4(+) T cells is likely to have a significant influence on the out come of the adaptive immune response.

Treatment and outcome of adult patients with primary focal segmental glomerulosclerosis in five UK renal units.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is the least studied of the causes of idiopathic nephrotic syndrome, and there are few specific guidelines for treatment. AIM: To review data from five UK renal units to investigate whether adult patients with FSGS were treated uniformly, and to examine the effect of treatment on proteinuria and survival. DESIGN: Retrospective record review. METHODS: We examined electronic records of patients with idiopathic FSGS for information on baseline clinical parameters, treatment regimens and outcomes. RESULTS: Of 136 patients with primary FSGS and nephrotic range proteinuria, 76 (56%) were treated with prednisolone and of this group, 59% were treated with additional immunosuppression. Among the treated patients, the total remission rate (complete and partial) was 67%, and one hospital achieved a remission rate of 80%. Treated patients had a significantly higher remission rate than those who were not treated. Remission was associated with a 5-year survival off dialysis of 94%, compared with 53% if remission was not achieved. Baseline serum creatinine and remission were independently associated with survival off dialysis in a multivariate Cox proportional hazards model. DISCUSSION: Patients with primary FSGS and nephrotic range proteinuria, who are treated with corticosteroids, are more likely to enter remission than those who are not treated. Remission rates of up to 80% can be achieved with prolonged treatment, and remission is an independent predictor of survival off dialysis. Patients who do not achieve remission have a poor prognosis. Further clarification of optimal treatment regimens requires additional, prospective studies.

The effect of high dose atorvastatin therapy on lipids and lipoprotein subfractions in overweight patients with type 2 diabetes.

Few data are available on the effects of high dose statin therapy on lipoprotein subfractions in type 2 diabetes. In a double blind randomised placebo-controlled trial we have studied the effects of 80 mg atorvastatin over 8 weeks on LDL, VLDL and HDL subfractions in 40 overweight type 2 diabetes patients. VLDL and LDL subfractions were prepared by density gradient ultracentrifugation. Triglycerides, cholesterol, total protein and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. Atorvastatin 80 mg produced significant falls in LDL subfractions (LDL(1) 66.2 mg/dl:36.6 mg/dl, LDL(2) 118:56.6 mg/dl, LDL(3) 36.9:19.9 mg/dl all P < 0.01 relative to placebo) and VLDL subfractions (VLDL(1) 55:22.1 mg/dl, VLDL(2) 40.1:19.1 mg/dl, VLDL(3) 52.6:30 mg/dl all P < 0.01 relative to placebo). There was no change in the proportion of LDL present as LDL(3). There was a reduction in the proportion of VLDL as VLDL(1) and a reciprocal increase in the proportion as VLDL(3). Changes in VLDL subfractions were associated with changes in lipid composition, particularly a reduction in cholesterol ester and a reduction in the cholesterol ester/triglyceride ratio. Effects on HDL subfractions were largely neutral. High dose atorvastatin produces favourable effects on lipoprotein subfractions in type 2 diabetes which may enhance antiatherogenic potential.

Growth, photosynthetic performance and shade adaptation of rubber (Hevea brasiliensis) grown in natural shade.

We compared growth, photosynthetic performance and shade adaptation of rubber (Hevea brasiliensis Muell. Arg.) plants growing in natural shade (33, 55 and 77% reduction in incoming radiation) to control plants growing in full sunlight. Stem diameter and plant height, measured over a 15-month period, were greatest in plants grown in full sunlight, and both parameters decreased with increasing shade. At 7 and 14 months after planting (MAP), total plant dry mass was highest in control plants and lowest in plants in 77% shade. Expansion of the fourth leaf whorl, monitored at 5-6 MAP, was slowest in plants in 77% shade and fastest in unshaded plants, which had more leaves and higher leaf areas and inter-whorl shoot lengths. In response to increasing shade, specific leaf area increased, whereas leaf weight ratio and relative growth rate decreased. Chlorophyll a/b ratio decreased with increasing shade, indicating shade-induced partitioning of chlorophyll into light-harvesting complexes. Compared to the response in unshaded plants, CO2 assimilation saturated at lower photosynthetic photon flux densities in plants in 77% shade, with a lower upper-asymptote to the light response curve. Chlorophyll fluorescence revealed no evidence of sustained photoinhibitory damage in unshaded plants. Dynamic photoinhibition decreased with increasing shade, with the greatest depression in the ratio of variable to maximal fluorescence around midday. We conclude that shade adaptation and shade-induced reductions in dynamic photoinhibition account for the enhanced early growth of rubber in light shade.

Diarrhoea, vomiting and ACE inhibitors:--an important cause of acute renal failure.

The occurrence of severe acute renal failure in 3 patients who developed diarrhoea while taking angiotensin converting enzyme (ACE) inhibitors led us to undertake a retrospective cohort survey to determine the frequency with which diarrhoea and vomiting are associated with acute renal failure in patients taking this class of drug. Serum creatinine was measured as part of the diagnostic workup of 2398 consecutive admissions to an acute medical receiving unit in a district general hospital. Outcome measures were the presence of diarrhoea and/or vomiting, and whether taking an ACE inhibitor, NSAID or diuretic at the time of admission, also previous, initial and follow up serum creatinine concentrations. Peak serum creatinine in the 3 cases was 1159, 989 and 765 micromol/l. None of the 3 required dialysis and all recovered renal function completely after receiving large volumes of intravenous fluid. In the cohort study, 89 of 2398(3.7%) admissions had serum creatinine >/=200 micromol/l. Nine were regular dialysis patients. Of the remaining patients, 30 (37.5%) were taking an ACE inhibitor. Six of 30 (20%) gave a history of diarrhoea and/or vomiting. Median creatinine concentration in this group was 135 (range 111-209) micromol/l before admission, 292 (216-724) micromol/l when first seen in hospital, and 134 (94-219) micromol/l following the withdrawal of drug therapy and fluid replacement. In conclusion, volume depletion causing acute renal failure in patients taking ACE inhibitors is not uncommon. Such patients and their general practitioners should be aware that reversible renal impairment may occur during intercurrent illnesses, particularly if characterised by diarrhoea and/or vomiting.

Ssh1p determines the translocation and dislocation capacities of the yeast endoplasmic reticulum.

Sec61p is required both for protein translocation and dislocation across the membrane of the endoplasmic reticulum (ER). However, the cellular role of the Sec61p homolog Ssh1p has not been clearly defined. We show that deltassh1 mutant cells have strong defects in both SRP-dependent and -independent translocation. Moreover, these cells were also found to be induced for the unfolded protein response and to be defective in dislocation of a misfolded ER protein. In addition, deltassh1 mutant cells rapidly became respiratory deficient. The other defects discussed above were suppressed in the respiratory-deficient state or under conditions where the rate of polypeptide translation was artificially reduced. These data identify Ssh1p as a component of a second, functionally distinct translocon in the yeast ER membrane.