Environmental drivers of increased ecosystem respiration in a warming tundra.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5-7. This hampers the accuracy of global land carbon-climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

Traditional plant functional groups explain variation in economic but not size-related traits across the tundra biome.

AIM: Plant functional groups are widely used in community ecology and earth system modelling to describe trait variation within and across plant communities. However, this approach rests on the assumption that functional groups explain a large proportion of trait variation among species. We test whether four commonly used plant functional groups represent variation in six ecologically important plant traits. LOCATION: Tundra biome. TIME PERIOD: Data collected between 1964 and 2016. MAJOR TAXA STUDIED: 295 tundra vascular plant species. METHODS: We compiled a database of six plant traits (plant height, leaf area, specific leaf area, leaf dry matter content, leaf nitrogen, seed mass) for tundra species. We examined the variation in species-level trait expression explained by four traditional functional groups (evergreen shrubs, deciduous shrubs, graminoids, forbs), and whether variation explained was dependent upon the traits included in analysis. We further compared the explanatory power and species composition of functional groups to alternative classifications generated using post hoc clustering of species-level traits. RESULTS: Traditional functional groups explained significant differences in trait expression, particularly amongst traits associated with resource economics, which were consistent across sites and at the biome scale. However, functional groups explained 19% of overall trait variation and poorly represented differences in traits associated with plant size. Post hoc classification of species did not correspond well with traditional functional groups, and explained twice as much variation in species-level trait expression. MAIN CONCLUSIONS: Traditional functional groups only coarsely represent variation in well-measured traits within tundra plant communities, and better explain resource economic traits than size-related traits. We recommend caution when using functional group approaches to predict tundra vegetation change, or ecosystem functions relating to plant size, such as albedo or carbon storage. We argue that alternative classifications or direct use of specific plant traits could provide new insights for ecological prediction and modelling.

Creative, strengths-based approaches to knowledge translation within indigenous health research.

OBJECTIVES: Good knowledge translation efforts can lead to significant changes in health status and service delivery. Although there is growing literature around ways to conduct knowledge translation within policy and health service delivery sectors, literature around how to conduct dissemination within indigenous community-based contexts remains scant. STUDY DESIGN: Using creative, strengths-based approaches to not only return results but also to function as tools to address gaps in health knowledge as identified by participants and community members within intergenerational contexts was a central component applied to dissemination and knowledge translation. METHODS: We developed a series of seven key considerations that we applied to the creation of dissemination products from qualitative interviews and focus group discussions from two Manitoba, Canada-specific public health research projects with indigenous communities. RESULTS: Products created (activity sheets, board game, and non-fiction storybooks) considered principles of timeliness, literacy level, feasibility of reproduction, and meeting the stated needs of study participants. CONCLUSIONS: By creating products that seek not only to return study information but also to answer questions and address specific challenges identified by participants, it is possible to continue to engage in research that is meaningful and ethical and strengthens relationships with all stakeholders.

Application of objective clinical human reliability analysis (OCHRA) in assessment of technical performance in laparoscopic rectal cancer surgery.

BACKGROUND: Laparoscopic rectal resection is technically challenging, with outcomes dependent upon technical performance. No robust objective assessment tool exists for laparoscopic rectal resection surgery. This study aimed to investigate the application of the objective clinical human reliability analysis (OCHRA) technique for assessing technical performance of laparoscopic rectal surgery and explore the validity and reliability of this technique. METHODS: Laparoscopic rectal cancer resection operations were described in the format of a hierarchical task analysis. Potential technical errors were defined. The OCHRA technique was used to identify technical errors enacted in videos of twenty consecutive laparoscopic rectal cancer resection operations from a single site. The procedural task, spatial location, and circumstances of all identified errors were logged. Clinical validity was assessed through correlation with clinical outcomes; reliability was assessed by test-retest. RESULTS: A total of 335 execution errors identified, with a median 15 per operation. More errors were observed during pelvic tasks compared with abdominal tasks (p < 0.001). Within the pelvis, more errors were observed during dissection on the right side than the left (p = 0.03). Test-retest confirmed reliability (r = 0.97, p < 0.001). A significant correlation was observed between error frequency and mesorectal specimen quality (r s = 0.52, p = 0.02) and with blood loss (r s = 0.609, p = 0.004). CONCLUSIONS: OCHRA offers a valid and reliable method for evaluating technical performance of laparoscopic rectal surgery.

Surgical timing after chemoradiotherapy for rectal cancer, analysis of technique (STARRCAT): results of a feasibility multi-centre randomized controlled trial.

BACKGROUND: The optimal time of rectal resection after long-course chemoradiotherapy (CRT) remains unclear. A feasibility study was undertaken for a multi-centre randomized controlled trial evaluating the impact of the interval after chemoradiotherapy on the technical complexity of surgery. METHODS: Patients with rectal cancer were randomized to either a 6- or 12-week interval between CRT and surgery between June 2012 and May 2014 (ISRCTN registration number: 88843062). For blinded technical complexity assessment, the Observational Clinical Human Reliability Analysis technique was used to quantify technical errors enacted within video recordings of operations. Other measured outcomes included resection completeness, specimen quality, radiological down-staging, tumour cell density down-staging and surgeon-reported technical complexity. RESULTS: Thirty-one patients were enrolled: 15 were randomized to 6 and 16-12 weeks across 7 centres. Fewer eligible patients were identified than had been predicted. Of 23 patients who underwent resection, mean 12.3 errors were observed per case at 6 weeks vs. 10.7 at 12 weeks (p = 0.401). Other measured outcomes were similar between groups. CONCLUSIONS: The feasibility of measurement of operative performance of rectal cancer surgery as an endpoint was confirmed in this exploratory study. Recruitment of sufficient numbers of patients represented a challenge, and a proportion of patients did not proceed to resection surgery. These results suggest that interval after CRT may not substantially impact upon surgical technical performance.

Developing model-based public health policy through knowledge translation: the need for a 'Communities of Practice'.

OBJECTIVES: The 2009 influenza A (H1N1) pandemic prompted public health agencies worldwide to respond in a context of substantial uncertainty. While many lessons around successful management strategies were learned during the influenza A (H1N1) pandemic, the usefulness and impact of mathematical models to optimize policy decisions in protecting public health were poorly realized. The authors explored the experiences of modellers and public health practitioners in trying to develop model-based public health policies in the management of the 2009 influenza A (H1N1) pandemic in Canada. STUDY DESIGN: A qualitative case study design based on interviews and other textual data was used. METHODS: Individual interviews were conducted with mathematical modellers and public health professionals from academia and government health departments during the second wave of the 2009 influenza A (H1N1) pandemic (both prior to and following the vaccine roll-out), using a convergent interviewing process. Interviews were supplemented with discussions held during three separate workshops involving representatives from these groups on the role of modelling in pandemic preparedness and responses. NVivo9™ was used to analyse interview data and associated notes. RESULTS: Mathematical models were underutilized during the response phase of the 2009 influenza A (H1N1) pandemic, largely because many public health professionals were unaware of modelling infrastructure in Canada. Challenges were reflected in three ways: 1) the relevance of models to public health priorities; 2) the need for clear communication and plain language around modelling and its contributions and limitations; and 3) the need for increased trust and collaboration to develop strong working relationships. CONCLUSIONS: Developing a 'Communities of Practice' between public health professionals and mathematical modellers during inter-pandemic periods based on common targeted goals, using plain language, and where relationships between individuals and organizations are developed early, could be an effective strategy to assist the process of public health policy decision-making, particularly when characterized by high levels of uncertainty.

Global plant trait relationships extend to the climatic extremes of the tundra biome.

The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world.

Differential effects of glucose on agonist-induced relaxations in human mesenteric and subcutaneous arteries.

BACKGROUND AND PURPOSE: Acute periods of hyperglycaemia are strongly associated with vascular disorder, yet the specific effects of high glucose on human blood vessel function are not fully understood. In this study we (1) characterized the endothelial-dependent relaxation of two similarly sized but anatomically distinct human arteries to two different agonists and (2) determined how these responses are modified by acute exposure to high glucose. EXPERIMENTAL APPROACH: Ring segments of human mesenteric and subcutaneous arteries were mounted in a wire myograph. Relaxations to acetylcholine and bradykinin were determined in a control (5 mM) and high glucose (20 mM) environment over a 2 and 6 h incubation period. KEY RESULTS: Bradykinin-induced relaxation in both sets of vessels was mediated entirely by EDHF whilst that generated by acetylcholine, though principally generated by EDHF, also had contribution from prostacyclin and possibly nitric oxide in mesenteric and subcutaneous vessels, respectively. A 2-h incubation of high glucose impaired bradykinin-induced relaxation of subcutaneous vessels whilst, in contrast, the relaxation generated by bradykinin in mesenteric vessels was enhanced at the same time point. High glucose significantly augmented the relaxation generated by acetylcholine in mesenteric and subcutaneous vessels at a 2 and 6 h incubation point, respectively. CONCLUSIONS AND IMPLICATIONS: Short periods of high glucose exert a variable influence on endothelial function in human isolated blood vessels that is dependent on factors of time, agonist-used and vessel studied. This has implications for how we view the effects of acute hyperglycaemia found in patients with diabetes mellitus as well as other conditions.

Oxygen tension and normalisation pressure modulate nifedipine-sensitive relaxation of human placental chorionic plate arteries.

Fetoplacental blood vessel constriction in response to reduced oxygenation has been demonstrated in placenta perfused in vitro. In pulmonary vessels, hypoxic vasoconstriction involves Ca2+ influx into smooth muscle through membrane ion channels including voltage-gated Ca2+ channels (VGCCs). We hypothesised that VGCCs are involved in agonist-induced constriction of fetoplacental resistance vessels and that their contribution is modulated by oxygen. Chorionic plate small arteries were studied using wire myography. Arteries were normalised at high (0.9 of L(13.3 kPa)) or low (0.9 of L(5.1 kPa)) stretch and experiments performed at 156, 38 or 15 mmHg oxygen. At low stretch, U46619 (thromboxane-mimetic) or KCl (smooth muscle depolarisation) constriction was greater at 38 than 156 or 15 mmHg oxygen. An L-type VGCC blocker nifedipine, inhibited KCl constriction by >85% but was less effective in U46619 constrictions (43-67%). At high stretch, nifedipine inhibition of KCl- and U46619-induced constriction was less at 15 than 38 or 156 mmHg oxygen. Oxygen did not affect constriction to U46619 or nifedipine-induced relaxation when vessels were normalised at high stretch. In conclusion, oxygen modulates chorionic plate arterial constriction at low stretch but regulation is lost at high stretch. U46619 constriction is underlain by VGCCs and nifedipine-insensitive processes; their relative contribution is influenced by oxygen.

Freeze-thaw cycles have minimal effect on the mineralisation of low molecular weight, dissolved organic carbon in Arctic soils.

Warmer winters in Arctic regions may melt insulating snow cover and subject soils to more freeze-thaw cycles. The effect of freeze-thaw cycles on the microbial use of low molecular weight, dissolved organic carbon (LMW-DOC) is poorly understood. In this study, soils from the Arctic heath tundra, Arctic meadow tundra and a temperate grassland were frozen to -7.5 °C and thawed once and three times. Subsequently, the mineralisation of 3 LMW-DOC substrates types (sugars, amino acids and peptides) was measured over an 8-day period and compared to controls which had not been frozen. This allowed the comparison of freeze-thaw effects between Arctic and temperate soil and between different substrates. The results showed that freeze-thaw cycles had no significant effect on C mineralisation in the Arctic tundra soils. In contrast, for the same intensity freeze-thaw cycles, a significant effect on C mineralisation was observed for all substrate types in the temperate soil although the response was substrate specific. Peptide and amino acid mineralisation were similarly affected by FT, whilst glucose had a different response. Further work is required to fully understand microbial use of LMW-DOC after freeze-thaw, yet these results suggest that relatively short freeze-thaw cycles have little effect on microbial use of LMW-DOC in Arctic tundra soils after thaw.

Distribution of [3H]MK-801 binding in the turtle retina: an autoradiographical study.

Frozen sections (15 microns) of the turtle (Pseudemys scripta elegans) retina were incubated in 1.6 nM [3H]MK-801. Autoradiograms were generated using dry autoradiographical techniques. A band of [3H]MK-801 labelling was observed in the outer plexiform layer and cells were occasionally labelled in the inner nuclear and ganglion cell layers. This pattern of labelling was enhanced by preincubation in 1.0 mM glycine but not affected by pre-incubation in 3.0 mM N-methyl-D-aspartate (NMDA). We did not observe labelling associated with somata of bipolar cells and photoreceptors, or in the inner plexiform layer. The distribution of label suggests that [3H]MK-801 was bound to horizontal cells and occasional ganglion and/or amacrine cells. We have previously reported that exposure of L-type horizontal cells to MK-801 irreversibly altered the intracellular response of the cell to exogenous NMDA. The present finding strongly suggests that these physiological effects of MK-801 were due to specific binding of MK-801 to the NMDA receptor complex on the horizontal cell membrane.

Comparative response of the immature and mature ovine fetus to corticotrophin-releasing hormone (CRH).

The aim of this study was to address the possibility that the low concentrations of adrenocorticotrophin (ACTH) seen in the ovine fetus between 90 and 120 days of gestation could be attributed to an alteration in the sensitivity or responsiveness of the fetal pituitary to corticotrophin-releasing hormone (CRH), a key regulator of ACTH secretion. Chronically cannulated ovine fetuses at Days 104-108 (n = 11, representing fetuses from this 90-120-day period) and Days 138-142 (n = 6) of pregnancy received graded doses of ovine CRH (0.8, 1.6, 3.8 and 7.6 micrograms h-1 for 60 min each, given consecutively and in ascending order) or isotonic saline (n = 4 at both age groups studied). Arterial blood samples were taken concurrently for analysis of plasma immunoreactive CRH, ACTH and cortisol throughout the infusion to assess the pituitary-adrenal response. Regression lines describing the relationship between log.PCRH and log.PACTH were calculated for both age group studied. A significant (P < 0.001) rightward shift in the log.PCRH/log.PACTH regression line for the Day 104-108 group was found, suggesting that the ovine fetus at this age is less sensitive or responsive to exogenous oCRH than the mature Day 138-142 fetus. This decreased responsiveness could explain the low concentrations of endogenous ACTH seen during the 90-120-day period.

Radioimmunoassay for salivary carbonic anhydrase in human parotid saliva.

A specific radioimmunoassay for human carbonic anhydrase (CA) VI has been developed and used to determine the concentrations of the enzyme in saliva. The assay detected as little as 200 pg of CA VI and the antibody used did not cross-react with CA II or other salivary proteins. The method showed an intra-assay variation of 8.5% and an inter-assay variation of 16.9%. The concentration in parotid saliva varied over a wide range (from 9.7 micrograms/ml to 121 micrograms/ml) with an average value of 47.0 +/- 39.2 (SD) micrograms/ml (n = 50). The mean secretion rate of CA VI from the combined parotid glands was 42.8 +/- 37.9 micrograms/min. CA VI represented about 3% of the total protein in parotid saliva.

Wellness programs slow rising costs.

Actual cost-savings for company wellness programs may require several years, but such tangible savings as improved morale and decreased absenteeism are almost immediate.

Protein carboxyl methylase in asthenospermia.

Protein carboxyl methylase (PCM) activity was measured in human spermatozoa of 16 normal fertile men and 26 men with various forms of asthenospermia. PCM activities were in the range 14-635 pmol/min per 10(9) sperm. Six men with idiopathic asthenospermia had low PCM activity but the defect of sperm motility was not severe (sperm motility 25-50%). One man with zero sperm motility and sparse mitochondria in the midpiece spiral had high PCM activity. Two men, one with idiopathic asthenospermia and the other with asthenospermia following vasoepididymostomy, also had high PCM activities. PCM activity did not correlate with motility or motility index but there was a correlation between PCM activity and the proportion of immature forms in semen. Thus, the relationship between PCM activity and low motility of sperm is not simple and other cells also contribute to overall seminal PCM activity.

Seminal transferrin, an index of Sertoli cell function: is it of clinical value?

To determine the clinical value of seminal transferrin measurements, transferrin concentrations in seminal plasma were determined by single radial immunodiffusion. Men with various disorders of spermatogenesis had significantly lower mean values than those with normal semen (170 micrograms/ejaculate, s.e.m. = 18.4), oligospermia (40.5 micrograms, s.e.m. = 7.2) or azoospermia due to primary seminiferous tubule failure (65.9 micrograms, s.e.m. = 29.1). In these subjects with patent genital tracts, seminal transferrin was directly correlated with sperm concentration and indirectly correlated with serum FSH levels. Seminal transferrin increased following gonadotrophin treatment of men with gonadotrophin deficiency from 19.6 micrograms (s.e.m. = 5.5) to 108.6 micrograms (s.e.m. = 31.7). Patients with genital tract obstructions also had low levels; vasal agenesis (21.8 micrograms, s.e.m. = 5.6), vasectomy (48.5 micrograms, s.e.m. = 21.0), epididymal obstruction (46.6 micrograms, s.e.m. = 7.1). These results confirm that most seminal transferrin comes from the testes and reflects Sertoli cell function. However, there is a very wide range of transferrin levels in normal semen and a number of normospermic samples have low values similar to those seen with abnormal Sertoli cell function or obstruction. Thus, measurement of seminal transferrin is of limited diagnostic value.

Effects of a naturally occurring neurosteroid on GABAA IPSCs during development in rat hippocampal or cerebellar slices.

1. The effects of the naturally occurring neurosteroid tetrahydrodeoxycorticosterone (THDOC) on GABAA receptor-mediated miniature, spontaneous and evoked IPSCs was tested using patch-clamp techniques in slices of hippocampus and cerebellum from rats at two developmental stages ( approximately 10 and approximately 20 days postnatal). The cells studied were hippocampal granule cells and cerebellar Purkinje and granule cells. 2. Most miniature GABAergic currents (mIPSCs) decayed with two exponentials and neurosteroids caused a approximately 4-fold increase in the decay time constant of the second exponential at the highest concentration used (2 microM). Similar effects were seen at high concentrations of THDOC (1-2 microM) in all cell groups tested. No effects were seen on amplitude or rise time of mIPSCs. 3. The effects of THDOC (1 microM) were shown to be stereoselective and rapidly reversible, indicating that the neurosteroid binds to the GABAA receptor, rather than acting genomically. 4. At concentrations of THDOC likely to occur physiologically (50-100 nM), the decay time of IPSCs was also enhanced (25-50 %) in all cerebellar cell groups tested. In contrast, at 100 nM THDOC, seven of 11 hippocampal granule cells were sensitive from the 10 day group but the 20 day hippocampal granule cells showed no significant enhancement in the presence of these lower concentrations of THDOC. 5. The differences in sensitivity of hippocampal and cerebellar cells to THDOC are compared to data reported in the literature on regional development of expression of different receptor subunits in the brain and it is suggested that the progressive relative insensitivity of the 20 day hippocampal cells may depend on increasing expression of the delta subunit of the GABAA receptor and possibly an increase in the alpha4 subunit.

A comparison of bathwater and oral delivery of 8-methoxypsoralen in PUVA therapy for plaque psoriasis.

Bath-PUVA is an alternative to oral-PUVA for the treatment of psoriasis. This study compares the effectiveness of the two methods in two groups, each consisting of 17 patients with plaque psoriasis. Three patients who failed to improve with oral-PUVA were transferred to bath-PUVA and subsequently cleared. Another seven patients who returned with a further episode of psoriasis received the alternative treatment; this gave a group of 10 patients in whom a cross-over comparison was possible. In both comparisons bath-PUVA was as effective as, or more effective than, oral-PUVA and required, overall, less than 50% of the total UVA, although this saving was not as great as in previous reports. Bath-PUVA caused fewer immediate problems and was preferred by many patients. It is suitable for those taking other systemic medications and we recommend it as a valuable therapeutic option that should be available at all treatment centres.

Amelanotic malignant melanoma following cryosurgery for atypical lentigo maligna.

Cryosurgery is an alternative treatment option to surgical excision for lentigo maligna. Clinical evidence of recurrence is usually characterized by repigmentation at the treated site. We report two patients who developed amelanotic malignant melanoma following cryosurgery for a pigmented lentigo maligna. These cases illustrate the potential risk of treating lentigo maligna with cryosurgery.

Cutaneous malignant melanoma. Publicity, screening clinics and survival--the Edinburgh experience 1982-90.

The incidence of cutaneous malignant melanoma has increased considerably in south-east Scotland over recent years. In 1987 the Cancer Research Campaign launched a project to aid the early detection, diagnosis and treatment of malignant melanoma. Edinburgh, chosen as one of seven centres in the U.K. to participate in the study, was provided with funding for a direct access pigmented lesion clinic from 1987 to 1989. The changes in the pattern of cutaneous malignant melanoma before, during and after the publicity campaign have been examined; between 1982 and 1990. The incidence of malignant melanoma doubled from 5.7 to 11.4/100,000 per annum. The percentage of thin tumours (Breslow thickness < or = 1.5 mm) increased steadily and significantly (from 43% in 1982 to 68% in 1990), but the number of thick tumours (Breslow thickness > 3.0 mm) remained constant over the same period (22 +/- 3.8). The influence of publicity was assessed using a questionnaire. Those who were influenced by publicity were significantly younger and had more thin tumours (Breslow < or = 1.5 mm) than those who were uninfluenced by publicity. Five-year survival has significantly increased from 70% in the 1982-84 cohort to 84% in the 1987-89 cohort. The effect of the publicity campaign has been beneficial, but the impact on mortality cannot yet be assessed.