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.

Reduced prevalence of pain and distress during 4 years of screening with QUICATOUCH in Australian oncology patients.

While psychosocial screening has been recommended in oncology for some time, widespread adoption in clinical practice has lagged. The QUICATOUCH program is one example of sustained clinic-level screening, assessment and referral. We examined whether this program was associated with reductions in pain or distress. Oncology outpatients completed a brief, computerised assessment using Distress and Pain Thermometers. We describe population levels of pain and distress and model pain and distress scores over 4 years of the program. 9,133 patients were screened on 26,385 occasions over 48 months (October 2007-September 2011). Pain over threshold (1/10) reduced over time, from 33% in the first 3 months to 16% in the final quarter of the evaluation. Distress over threshold (4/10) reduced from 28% to 10%. A reduction was also observed when restricted to patients screened for the first time. Our analysis demonstrated this effect was not explained by measured potential confounders (gender, age, treatment status) and was unlikely to be attributable to regression to the mean. Observational studies cannot prove causation. However, the significant reduction in pain and distress levels in the 48 months following commencement of QUICATOUCH is consistent with a beneficial effect of the program.

Four steps to interpreting arterial blood gases.

This article examines acid-base balance and the interpretation of arterial blood gases (ABG). The article begins with a brief revision of related physiology, followed by a description of the primary disorders associated with acid-base imbalance. The normal ranges and the significance of abnormal ABG results are explored. The article concludes by providing an easy to follow four-step guide to ABG interpretation with practice examples presented in the CPD task section.

Who accesses complementary therapies and why?: An evaluation of a cancer care service.

INTRODUCTION: Advances in cancer diagnosis and treatment have resulted in longer survival, meaning patients are living with a chronic-type condition. Therefore the needs of such patients have changed placing greater emphasis on survivorship, such as impact on quality of life and sleep patterns. Evidence suggests complementary therapies positively impact not only on the cancer patient's quality of life but also on family members and friends. METHODOLOGY: This service evaluation examines self-reported benefits following a course of complementary therapy offered by a local cancer charity. RESULTS: Analysis of self-reported sleep scores and perceived quality of life experiences confirmed a number of trends relating to the demographics of people accessing the complementary therapy service. CONCLUSION: Results suggest the complementary therapies provided by Action Cancer significantly improved clients' quality of life. Based on these findings the authors make a number of recommendations in relation to the use of complementary therapies by cancer patients.

The principles and practice of interpreting cardiac rhythm strips: a seven-step model.

This open learning zone article examines the cardiac cycle and the interpretation of cardiac rhythm strips. The article begins with a brief revision of related physiology followed by a description of normal sinus rhythm and the main cardiac rhythm abnormalities. The article concludes by providing easy to follow steps for use in the interpretation of cardiac rhythm strips with practice examples presented in the continuing professional development (CPD) task section.

Type I IFN response to Papiine herpesvirus 2 (Herpesvirus papio 2; HVP2) determines neuropathogenicity in mice.

Isolates of baboon alpha-herpesvirus Papiine herpesvirus 2 (HVP2) exhibit one of two distinct phenotypes in mice: extremely neurovirulent or apathogenic. Previous studies implicated the type I interferon (IFN) response as being a major factor in controlling infection by apathogenic isolates. To further investigate the possibility that the host IFN-beta response underlies the pathogenicity of the two HVP2 subtypes, the susceptibility of mice lacking the IFN-beta receptor (IFNAR(-/-)) to infection was examined. Apathogenic isolates of HVP2 (HVP2ap) replicated in IFNAR(-/-) primary mouse dermal fibroblast (PMDF) cultures as well as neurovirulent (HVP2nv) isolates. IFNAR(-/-) mice were also susceptible to lethal infection by HVP2ap isolates. Unlike Balb/c or parental 129 mice, LD(50) and ID(50) values for HVP2ap were the same in IFNAR(-/-) mice indicating that in these mice infection always progressed to death. HVP2ap replicated in the skin at the site of inoculation and invaded dorsal root ganglia as efficiently as HVP2nv in IFNAR(-/-) mice. Since the virion host shutoff (vhs) protein encoded by the UL41 gene of herpes simplex virus has been implicated in circumventing the host IFN-beta response and the phenotype of UL41 deletion mutants of HSV is very similar to that of HVP2ap isolates, the UL41 gene was deleted from HVP2nv (Delta 41) and replaced with the UL41 ORF from HVP2ap (Delta 41C). Like the parental HVP2nv virus, the Delta 41C recombinant replicated efficiently in Balb/c PMDFs and did not induce a strong IFN-beta response. The neuropathogenicity of the Delta 41C recombinant was also the same as the parental HVP2nv virus in Balb/c mice, indicating that the vhs protein does not underlie the different neuropathogenic phenotype of HVP2ap and HVP2nv. In contrast, the Delta 41 deletion virus induced a strong IFN-beta response but was still able to undergo multiple rounds of replication in PMDF cultures, albeit at a slower pace than the parental HVP2nv. This was reflected in vivo as the Delta 41 mutant had an LD(50) equivalent to that of the parental HVP2nv virus although the time to death was longer. These results indicate that while the vhs protein is involved in preventing and/or suppressing an IFN-beta response, it is not responsible for the ability of HVP2nv to overcome IFN-beta induced resistance of uninfected cells and does not underlie the divergent pathogenicity of the two HVP2 subtypes in mice.

Primary mouse dermal fibroblast cell cultures as an in vitro model system for the differential pathogenicity of cross-species herpesvirus papio 2 infections.

Infection of mice with herpesvirus papio 2 (HVP2) parallels zoonotic monkey B virus infections. A major benefit of the HVP2/mouse model is the existence of two HVP2 subtypes: HVP2nv rapidly invades and destroys the CNS while HVP2ap produces no clinical signs and mild histopathological lesions. However, in the natural baboon host, no difference in pathogenicity of HVP2 subtypes is evident. Primary dermal fibroblast cells were evaluated as a model system for defining virus-host interactions that influence the outcome of a cross-species infection. No differences in plaque formation or virus replication were observed between HVP2 subtypes in primary baboon dermal fibroblast cultures. In contrast, when primary mouse dermal fibroblasts (PMDF) were infected, HVP2nv replicated to higher titers and was more efficient at shutting down host-cell protein synthesis compared to HVP2ap. HVP2ap-infected PMDF cells produced more IFN-beta compared to HVP2nv, and IFN-beta pretreatment of PMDF cultures inhibited HVP2ap replication but did not affect HVP2nv. The differential pathogenicity of HVP2 subtypes in mice and the lack of such differences in the natural baboon host are recapitulated in the primary dermal fibroblast cell culture system. This model may prove useful in examining early, local, host responses that influence the outcome of cross-species infections.

Disruption of the Candida albicans CYB5 gene results in increased azole sensitivity.

Sterol synthesis in fungi is an aerobic process requiring molecular oxygen and, for several cytochrome-mediated reactions, aerobically synthesized heme. Cytochrome b(5) is required for sterol C5-6 desaturation and the encoding gene, CYB5, is nonessential in Saccharomyces cerevisiae. Cyb5p and Ncp1p (cytochrome P-450 reductase) appear to have overlapping functions in this organism, with disruptions of each alone being viable. The cytochrome P-450 reductase phenotype has also been shown to demonstrate increased sensitivity to azole antifungals. Based on this phenotype, the CYB5 gene in the human pathogen Candida albicans was investigated to determine whether the cyb5 genotype was viable and would also demonstrate azole sensitivity. Sequential disruption of the CYB5 alleles by direct transformation resulted in viability, presumably conferred by the presence of a third copy of the CYB5 gene. Subsequent disruption procedures with a pMAL2-CYB5 rescue cassette and a CYB5-URA3 blaster cassette resulted in viable cyb5 strains with no third copy. The C. albicans CYB5 gene is concluded to be nonessential. Thus, the essentiality of this gene and whether we observed two or three alleles was dependent upon the gene disruption protocol. The C. albicans cyb5 strains produced a sterol profile containing low ergosterol levels and sterol intermediates similar to that reported for the S. cerevisiae cyb5. The C. albicans cyb5 shows increased sensitivity to azoles and terbinafine, an inhibitor of squalene epoxidase, and, unexpectedly, increased resistance to morpholines, which inhibit the ERG2 and ERG24 gene products. These results indicate that an inhibitor of Cyb5p would not be lethal but would make the cell significantly more sensitive to azole treatment.

The effect of shoe material on the kinetics and kinematics of foot slip at impact on concrete.

Previous studies on shoeing have demonstrated that shoe material alters the time taken from foot impact to the foot stopping sliding (slip time) and the distance slid. These are assumed to reflect differences in the craniocaudal ground reaction force (GRF) between the shoe and the ground during foot slip. This study tested the hypothesis that the slip time and distance are reflected in the resistance to slippage of the foot after impact. The forefeet of 8 horses were shod in horseshoes constructed of steel, plastic and rubber. Each horse was trotted for 8 placements per forefoot in each shoe type over a concrete topped forceplate and simultaneous kinematic data recorded at 240 Hz. Slip distance and slip time were calculated from the kinematic data and craniocaudal (Fy), and vertical (Fz) GRFs determined during slip the averaged for each shoe type. The slip time and distance were variable between runs in all 3 shoe types, and there was no significant difference between the mean values for the 3 shoe types. Fy reached a value of 0.98 +/- 0.17 N/kg during slip in the plastic shoes which was significantly lower than the rubber shoes, at 1.13 +/- 0.17 N/kg, P = 0.02. The Fy/Fz ratio (a measure of dynamic friction) was significantly lower in the plastic shoes, 0.34 +/- 0.08, compared to the steel shoes, 0.46 +/- 0.04, P = 0.003. This study is being extended to investigate effects of shoe slippage at the end of the stance phase and the energy dissipation during foot slip in the different shoe types. Future investigations should aim to identify the optimum slip characteristics to modulate loading (magnitude and rate) during impact, with the aim of reducing the risk of injury.

Spiral codes and Goldberg representations of icosahedral fullerenes and octahedral analogues.

An icosahedral fullerene may be considered as a tessellation of the sphere specified by an ordered pair of integers, or as a tightly wound spiral of faces. Explicit analytical relations for interconverting the two representations are given, enabling the canonical spiral code to be constructed for an icosahedral fullerene of any size. Analogous relations hold for the octahedral square + hexagon polyhedra that have been mentioned as possible candidates for boron-nitride "fullerenes".

Audit in pain clinics: changing the management of low-back and nerve-damage pain.

This audit study took place in ten outpatient pain clinics and focused on the management of low back pain and nerve-damage pain. The objective was to identify and promote appropriate changes in management. An analysis of the treatment of 1236 patients with low back pain and/or nerve-damage pain highlighted wide variations in practice. Presentation of these data to the clinics was used as a means of promoting change. Data on a further 1791 patients were used to assess the extent of any changes in practice. Prior to the audit feedback, treatments were used often in some clinics, but only rarely in other clinics, for seemingly similar patients. During the feedback sessions three treatments were identified for more frequent use by several of the clinics: antidepressant and anticonvulsant drugs, and transcutaneous electrical nerve stimulation. Many changes in practice occurred after the audit intervention, with large increases in the utilisation of these three treatments. Since there is reasonable evidence to support the use of these treatments for chronic pain this represents an improvement in the process of care. The audit demonstrated that patient management can be improved by a combination of active feedback and discussions based around comparisons between centres.

Induction of an acute phase response in lambs causes an increase in plasma levels of GH and IGF-I.

GH and IGF-I plasma concentrations were measured in lambs during an acute phase response induced by an intrathoracic injection of yeast. The acute phase response was indicated by reduced feed intake, weight loss and an increase in plasma concentrations of the acute phase protein haptoglobin. Intensive blood sampling on day 1 revealed elevated basal concentrations of GH in the yeast-injected group compared with concentrations in pair weight and ad libitum fed control lambs. This suggests that at the beginning of an acute phase response there is an increase in either GH secretion or the half life of GH. No evidence of a specific GH-binding protein in sheep plasma could be detected. IGF-I concentrations in the yeast-injected group remained constant for 3 days then increased to a peak level at day 6. In contrast, plasma IGF-I concentrations were depressed from days 3 to 6 in the pair weight control group and they were unchanged in the ad libitum fed controls. When the IGF-I concentrations were elevated in the yeast-injected group, this group had a higher daily weight gain despite their lower feed intake compared with the ad libitum fed controls. These results suggest that IGF-I may be associated with the increase in weight in the late stage of an acute phase response during recovery from an infection or injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute phase protein response, food intake, liveweight change and lesions following intrathoracic injection of yeast in sheep.

Acute phase protein concentrations in blood, food intake and liveweight changes were compared in 10 sheep given intrathoracic injections of yeast and 10 control sheep over a period of 61 days. The yeast injections caused acute pleuritis and limited necrotising lung lesions which progressed to fibrous pleural adhesions and walled-off abscesses. The responses of ceruloplasmin, fibrinogen and haptoglobin were closely correlated (r = 0.87 to 0.91) in the yeast-injected sheep with peaks on days 5 or 7 after treatment (4, 4.6 and over 130 times control, respectively). Albumin concentration fell to a nadir of 89 per cent of control on day 12 after treatment. Depression of food intake was temporally related to the 'positive' acute phase protein responses with a nadir on day 5 after treatment (30 per cent of control). Liveweight showed a pronounced fall to five days after treatment and thereafter remained depressed relative to the controls for most of the experimental period. The data suggest that the 'positive' acute phase proteins may be useful indicators of production losses due to inflammatory diseases in sheep.

Topics in clinical pharmacology: filgrastim, a myeloid colony stimulating factor.

Filgrastim (granulocyte colony stimulating factor) recently became commercially available for the treatment of chemotherapy-induced neutropenia. Studies have shown that filgrastim induces a dose-dependent granulocytosis in humans, thereby shortening the period of neutropenia in patients treated conventionally with submarrow ablative doses of chemotherapy, as well as with marrow ablative therapy given in the bone marrow transplant setting. By reducing the incidence and severity of infections and mucositis in patients treated with chemotherapy, it has a significant economic impact since it shortens the duration of antibiotic administration and hospitalization. Adverse reactions reported are limited to mild to moderate bone pain. Several other potential applications are being investigated for filgrastim, including treatment of patients with myelodysplastic syndrome and congenital neutropenia.

Factors affecting MSA levels in normal women and women with breast cancer.

Blood from 1497 women who were either non-pregnant, pregnant at all stages of gestation, lactating after parturition, postmenopausal, or who had benign breast lumps, primary breast cancer or advanced breast cancer were tested for their peripheral blood mammary serum antigen (MSA), using the 3E1.2 monoclonal antibody (MoAb) in an inhibition enzyme linked immunosorbent assay test system. The study aimed to establish normal ranges for comparison with MSA levels in breast cancer and benign breast disease. Compared with normal premenopausal women, which included women measured 8-10 times throughout their menstrual cycle, circulating MSA levels were significantly elevated throughout pregnancy (P less than 0.0001), in postmenopausal women (P less than 0.05), in women with primary breast cancer (P less than 0.05) and women with advanced (metastatic) breast cancer (P less than 0.0001). As a group, the 30 women with benign breast disease did not demonstrate significantly different MSA level from normal. However, 3% of the group did have levels above the 'cut off' for normal (400 IU/mL). Analysis of the normal premenopausal women according to age, parity and stage of the menstrual cycle and during lactation showed that these parameters did not affect MSA levels. It is concluded that the test is potentially valuable in the detection of metastatic but not primary breast cancer, and the effects of pregnancy and postmenopausal status on the circulating MSA levels need to be considered in the interpretation of MSA measurements.

Acute phase response of sheep: changes in the concentrations of ceruloplasmin, fibrinogen, haptoglobin and the major blood cell types associated with pulmonary damage.

The concentrations of plasma ceruloplasmin, plasma fibrinogen, serum haptoglobin and the major cell types in blood together with liveweight changes were monitored during the acute phase response in sheep. Five control sheep, five sheep that underwent sham bronchial obstruction, and five sheep that developed pneumonia after bronchial obstruction were examined. Blood samples were taken and liveweights were recorded from four to six days before until 14 days after the surgical operations (sham and bronchial obstruction). The operations led to an acute phase response in the sheep and the development of pneumonia increased and sustained the response or led to a secondary response. Statistically significant changes observed in the blood of the sheep during the acute phase response included increased concentrations of plasma ceruloplasmin and plasma fibrinogen, depression of erythrocyte numbers and elevation of neutrophil numbers (means on day of maximum change as percentage of pretreatment values; 250 per cent, 400 per cent, 80 per cent and 200 per cent, respectively). Serum haptoglobin showed a pronounced and significant increase in concentration (over 6000 per cent of pretreatment values in some sheep). All three groups of sheep showed significant depression of liveweight after overnight confinement in the surgery but this was sustained for the period of the experiment only in the bronchial obstruction group. The results indicated that measurement of the concentrations of the three plasma proteins may be more useful in the diagnosis of tissue injury and infectious disease than the number of circulating neutrophils in sheep.

The morphology of matrix vesicles produced in experimental arterial aneurysms of rabbits.

The morphology and possible modes of matrix vesicle production in the walls of experimental rabbit aneurysms were investigated at an ultrastructural level. The abundant matrix vesicles were mostly circular or oval, and in 95% the largest dimension measured 25 to 130nm. Many had been formed by the disintegration of whole smooth muscle cells or portions thereof but more frequently they were related to and even embedded in the thickened, dystrophic basement membranes of viable smooth muscle cells. Budding was an infrequent feature. Many matrix vesicles were associated with fragments of plasma membrane in the matrix and areas which were possibly interruptions of the plasma membranes. Phagocytosis was seen, but more often the matrix vesicles underwent calcification, and groups of larger closely packed, electron translucent vesicles (80-500nm) indicated lipid accumulation. Experimental aneurysms provide a rich source of matrix vesicles for future investigations.

The effect of haemodynamic stress on the glycosaminoglycan content of blood vessel walls of experimental aneurysms and arteriovenous fistulae.

The glycosaminoglycan content of experimental saccular aneurysms and arteriovenous fistulae of sheep has been measured. In the experimental aneurysm hyaluronic acid, heparan sulphate, dermatan sulphate, chondroitin sulphate and total glycosaminoglycans were all elevated above control tissue levels with increases most striking for dermatan sulphate and chondroitin sulphate. In the anastomosed vein of the arteriovenous fistulae, total glycosaminoglycans were also significantly raised but which individual glycosaminoglycans were responsible was not clearly established. In the arteries feeding the fistulae, increased chondroitin sulphate in the proximal arterial segment was the only significant change observed. The changes were attributed to altered haemodynamic stresses and are similar to those reported for animal models of hypertension and early human atherosclerosis.

X-ray microanalysis of mineralized matrix vesicles of experimental saccular aneurysms.

An energy dispersive X-ray microanalytical study was designed to examine the mineral deposits in matrix vesicles found in the walls of experimental aneurysms from two rabbits (103 and 1071 days postoperatively) and two sheep aneurysms (234 and 1202 days postoperatively). The freeze-substitution technique was adopted for use to retain inorganic ions in situ. Numerous, various sized extracellular electron-dense structures, believed to be matrix vesicles were observed. Size histograms for the mineralized vesicles showed that the proportion of smaller vesicles was higher in the older animals. A total of 370 vesicles were analyzed. Calcium and phosphorus with small amounts of magnesium were identified. No particular calcium phosphate mineral was dominant with the mean Ca/P molar ratio for all animals falling in the 1.1-1.2 range. Correlation coefficients for interrelationships between calcium, phosphorus, magnesium, and size were weak except for calcium vs phosphorus which was close to one, consistent with some type of calcium phosphate being the major constituent of the mineralized vesicles. Smaller electron-dense particles, probably mitochondrial granules were seen in some smooth muscle cells; a small number were analyzed and contained calcium and phosphorus (mean Ca/P molar ratio of 0.86) but no magnesium.

Treatment of intractable neurogenic pain with carbamazepine.

Sixteen patients with previously intractable neurogenic pain were treated with carbamazepine (CBZ) for a period of six weeks. CBZ initial daily dosage of 400 mg was increased by a similar amount every second week to a maximum of 1,200 mg. Single dose kinetic studies prior to initiating CBZ therapy showed that these patients metabolised the drug similarly to healthy controls. Side effects, including rash (3) and ataxia (3), necessitated discontinuation of treatment in six patients. A further three patients withdrew because of lack of effect. Of the seven patients who completed the protocol, five showed a significant fall in pain score at all dosage increments with a maximum effect at the highest dose (p less than 0.01). In the seven patients for whom data was available at all three CBZ dosages, there was a significant correlation between sedation scores and CBZ concentrations (p less than 0.005). CBZ may be of value in the management of chronic neurogenic pain. Further controlled studies are indicated.