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Background Lithium-associated hypercalcemia (LAH) is an ill-defined endocrinopathy. The aim of the present study was to determine the prevalence of hypercalcemia in a cohort of bipolar patients (BP) with and without concomitant lithium treatment and to study surgical outcomes for lithium-associated hyperparathyroidism. Methods Retrospective data, including laboratory results, surgical outcomes and medications, were collected from 313 BP treated with lithium from two psychiatric outpatient units in central Sweden. In addition, data were collected from 148 BP without lithium and a randomly selected control population of 102 individuals. Logistic regression was used to compare odds of hypercalcemia in these respective populations. Results The prevalence of lithium-associated hypercalcemia was 26%. Mild hypercalcemia was detected in 87 out of 563 study participants. The odds of hypercalcemia were significantly higher in BP with lithium treatment compared with BP unexposed to lithium (adjusted OR 13.45; 95% CI 3.09, 58.55; p = 0.001). No significant difference was detected between BP without lithium and control population (adjusted OR 2.40; 95% CI 0.38, 15.41; p = 0.355). Seven BP with lithium underwent surgery where an average of two parathyroid glands was removed. Parathyroid hyperplasia was present in four patients (57%) at the initial operation. One patient had persistent disease after the initial operation, and six patients had recurrent disease at follow-up time which was on average 10 years. Conclusion The high prevalence of LAH justifies the regular monitoring of calcium homeostasis, particularly in high-risk groups. If surgery is necessary, bilateral neck exploration should be considered in patients on chronic lithium treatment. Prospective studies are needed.

Physiological processes of terrestrial plants regulate the land-atmosphere exchange of carbon, water, and energy, yet few studies have explored the acclimation responses of mature boreal conifer trees to climate change. Here we explored the acclimation responses of photosynthesis, respiration, and stomatal conductance to elevated temperature and/or CO2 concentration ([CO2]) in a 3-year field experiment with mature boreal Norway spruce. We found that elevated [CO2] decreased photosynthetic carboxylation capacity (-23% at 25 °C) and increased shoot respiration (+64% at 15 °C), while warming had no significant effects. Shoot respiration, but not photosynthetic capacity, exhibited seasonal acclimation. Stomatal conductance at light saturation and a vapour pressure deficit of 1 kPa was unaffected by elevated [CO2] but significantly decreased (-27%) by warming, and the ratio of intercellular to ambient [CO2] was enhanced (+17%) by elevated [CO2] and decreased (-12%) by warming. Many of these responses differ from those typically observed in temperate tree species. Our results show that long-term physiological acclimation dampens the initial stimulation of plant net carbon assimilation to elevated [CO2], and of plant water use to warming. Models that do not account for these responses may thus overestimate the impacts of climate change on future boreal vegetation-atmosphere interactions. (Less)

Background Little is known about the long-term side-effects of different treatments for hyperthyroidism. The few studies previously published on the subject either included only women or focused mainly on cancer outcomes. This register study compared the impact of surgery versus radioiodine on all-cause and cause-specific mortality in a cohort of men and women. Methods Healthcare registers were used to find hyperthyroid patients over 35 years of age who were treated with radioiodine or surgery between 1976 and 2000. Comparisons between treatments were made to assess all-cause and cause-specific deaths to 2013. Three different statistical methods were applied: Cox regression, propensity score matching and inverse probability weighting. Results Of the 10 992 patients included, 10 250 had been treated with radioiodine (mean age 65·1 years; 8668 women, 84·6 per cent) and 742 had been treated surgically (mean age 44·1 years; 633 women, 85·3 per cent). Mean duration of follow-up varied between 16·3 and 22·3 years, depending on the statistical method used. All-cause mortality was significantly lower among surgically treated patients, with a hazard ratio of 0·82 in the regression analysis, 0·80 in propensity score matching and 0·85 in inverse probability weighting. This was due mainly to lower cardiovascular mortality in the surgical group. Men in particular seemed to benefit from surgery compared with radioiodine treatment. Conclusion Compared with treatment with radioiodine, surgery for hyperthyroidism is associated with a lower risk of all-cause and cardiovascular mortality in the long term. This finding was more evident among men.

Previous research has suggested an increased risk of death and cardiovascular disease in patients treated for hyperthyroidism. However, studies on this subject are heterogeneous, often based on old data, or have not considered the impact that treatment for hyperthyroidism might have on cardiovascular risk. It is also unclear whether long-term prognosis differs between Graves' disease and toxic nodular goiter. The aim of this study was to use a very large cohort built on recent data to assess whether improvements in cardiovascular care might have changed the prognosis over time. The study also investigated the impact of different etiologies of hyperthyroidism.This was an observational register study for the period 1976-2012, with subjects followed for a median period of 18.4 years. Study patients were Stockholm residents treated for Graves' disease or toxic nodular goiter with either radioactive iodine or surgery (N = 12,239). This group was compared to Stockholm residents treated for nontoxic goiter (N = 3685), with adjustments made for age, sex, comorbidities, and time of treatment. Comparisons were also made to the general population of Stockholm. Outcomes were assessed in terms of all-cause and cardiovascular mortality as well as cardiovascular morbidity.The hazard ratios (HR) for all-cause mortality and for cardiovascular mortality were 1.27 [confidence interval (CI) 1.20-1.35] and 1.29 [CI 1.17-1.42], respectively, for hyperthyroid patients compared to those with nontoxic goiter. For cardiovascular morbidity, the HR was 1.12 [CI 1.06-1.18]. Patients aged ≥45 years who were treated for toxic nodular goiter were generally at greater risk than others, and those included from the year 1990 and onwards were at greater risk than those included earlier. Increased all-cause mortality, as well as cardiovascular mortality and morbidity, were also seen in comparisons with the general population.This is the first large study to indicate that the long-term risk of death and cardiovascular disease in hyperthyroid subjects is due to the hyperthyroidism itself and not an effect of confounding introduced by its treatment. Much of the excess risk is confined to individuals treated for toxic nodular goiter. Despite advances in cardiovascular care during recent decades, hyperthyroidism is still a diagnosis associated with increased cardiovascular morbidity and mortality.

Background Approximately half of trauma patients develop post-traumatic depression. It is suggested that beta-blockade impairs trauma memory recollection, reducing depressive symptoms. This study investigates the effect of early beta-blockade on depression following severe traumatic injuries in patients without significant brain injury. Methods Patients were identified by retrospectively reviewing the trauma registry at an urban university hospital between 2007 and 2011. Severe extracranial injuries were defined as extracranial injuries with Abbreviated Injury Scale score ≥3, intracranial Abbreviated Injury Scale score

Stomatal CO2 responsiveness and photosynthetic capacity vary greatly among plant species, but the factors controlling these physiological leaf traits are often poorly understood. To explore if these traits are linked to taxonomic group identity and/or to other plant functional traits, we investigated the short-term stomatal CO2 responses and the maximum rates of photosynthetic carboxylation (V cmax) and electron transport (J max) in an evolutionary broad range of tropical woody plant species. The study included 21 species representing four major seed plant taxa: gymnosperms, monocots, rosids and asterids. We found that stomatal closure responses to increased CO2 were stronger in angiosperms than in gymnosperms, and in monocots compared to dicots. Stomatal CO2 responsiveness was not significantly related to any of the other functional traits investigated, while a parameter describing the relationship between photosynthesis and stomatal conductance in combined leaf gas exchange models (g 1) was related to leaf area-specific plant hydraulic conductance. For photosynthesis, we found that the interspecific variation in V cmax and J max was related to within leaf nitrogen (N) allocation rather than to area-based total leaf N content. Within-leaf N allocation and water use were strongly co-ordinated (r 2 = 0.67), such that species with high fractional N investments into compounds maximizing photosynthetic capacity also had high stomatal conductance. We conclude that while stomatal CO2 responsiveness of tropical woody species seems poorly related to other plant functional traits, photosynthetic capacity is linked to fractional within-leaf N allocation rather than total leaf N content and is closely co-ordinated with leaf water use.

The management of forests to store carbon and mitigate climate change has received significant inter- national attention during the last decade. Using in situ data from a 2008–2009 forest inventory field campaign in Sri Lanka, this study describes the structural characteristics and carbon stocks of six natural forest types. This paper has a dual scope: i) to highlight the variation in carbon stored in aboveground biomass within and between forest types and ii) to determine the implications of the allometric equa- tions chosen to calculate biomass carbon stocks. This study concerns work related to climate change interventions, such as Reducing Emissions from Deforestation and Forest Degradation (REDD+) and other forest-related, performance-based initiatives that require proper monitoring, reporting, and verification of carbon stocks, sinks and emissions. The results revealed that forests are heterogeneous in terms of tree density and height–diameter relationships, both between and within the six forest types investigated. The mean aboveground carbon stock in the different forest types ranged from 22 to 181 Mg C ha−1 , and there were statistically significant differences in the carbon stocks of the six forest types in 7 of 15 cases. The estimated carbon stock depended heavily on the allometric equation used for the calculations, the variables, and its application to the specific life zone. Due to the diversity of forest structures, these results suggest that caution should be taken when applying default values to estimate forest carbon stocks and emission values in reporting and accounting schemes. The results also indicated the need for allometric equations that are context-specific for different forest types. Therefore, new field investigations and mea- surements are needed to determine these specific allometric equations, as well as the potential variation in forest carbon stocks in tropical natural forests.

Introduction Prevalence studies demonstrate that a significant proportion of lithium-treated patients develop hypercalcaemia (3–30%). Lithium-associated hyperparathyroidism (LHPT) is poorly defined, and calcium homeostasis may be affected in a more complicated fashion than purely by elevated PTH secretion. The current study aims to examine in detail calcium homeostasis principally with regard to lithium duration. Methods Medical records of 297 lithium-treated patients (193 women, 104 men; median age 58 years) were examined, and information on gender, age, lithium treatment duration and calcium homeostasis was obtained. The median treatment duration with lithium was 16 (1.5–45) years. Results A total of 8504 calcium values were retrieved. Before initiation of lithium treatment, serum calcium was on average 2.33 mmol/l (2.02–2.60). During the treatment period, 178 patients (60%) remained normocalcaemic, 102 (34%) developed hypercalcaemia or were strongly suspected of LHPT, 17 (6%) had 3 or more intermittent episodes of hypocalcaemia. Forty-one per cent of patients with suspected or confirmed LHPT had low ( Conclusions The prevalence of hypercalcaemia during lithium treatment is very high. In addition, hypocalcaemic episodes appear to occur frequently, possibly reflecting a more complicated parathyroid dysfunction than previously known. Long-term surgical results are unsatisfactory. LHPT biochemical profile is different from that of primary hyperparathyroidism and is in some ways similar to familial hypocalciuric hypercalcaemia.

Background: The treatment efficacy of antithyroid drug (ATD) therapy, radioactive iodine (131I), or surgery for Graves' hyperthyroidism is well described. However, there are a few reports on the lo...

International audience; The temperature response of photosynthesis is one of the key factors determining predicted responses to warming in global vegetation models (GVMs). The response may vary geographically, owing to genetic adaptation to climate, and temporally, as a result of acclimation to changes in ambient temperature. Our goal was to develop a robust quantitative global model representing acclimation and adaptation of photosynthetic temperature responses. We quantified and modelled key mechanisms responsible for photosynthetic temperature acclimation and adaptation using a global dataset of photosynthetic CO2 response curves, including data from 141 C3 species from tropical rainforest to Arctic tundra. We separated temperature acclimation and adaptation processes by considering seasonal and common‐garden datasets, respectively. The observed global variation in the temperature optimum of photosynthesis was primarily explained by biochemical limitations to photosynthesis, rather than stomatal conductance or respiration. We found acclimation to growth temperature to be a stronger driver of this variation than adaptation to temperature at climate of origin. We developed a summary model to represent photosynthetic temperature responses and showed that it predicted the observed global variation in optimal temperatures with high accuracy. This novel algorithm should enable improved prediction of the function of global ecosystems in a warming climate.

Hyperthyroidism is known to have a significant impact on quality of life (QoL), at least in the short term. The purpose of the present study was to assess QoL in patients 6-10 years after treatment for Graves' disease (GD) with radioiodine (RAI) compared to those treated with thyroidectomy or antithyroid drugs (ATD) as assessed with both thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) questionnaire and general (36-item Short Form Health Status) QoL survey.The study evaluated 1186 GD patients in a sub-cohort from an incidence study 2003-2005 who had been treated according to routine clinical practice at seven participating centers. Patients were included if they had returned the ThyPRO (n = 975) and/or the 36-item Short Form Health Status survey questionnaire (n = 964) and informed consent at follow-up. Scores from ThyPRO were compared to scores from a general population sample (n = 712) using multiple linear regression adjusting for age and sex as well as multiple testing. Treatment-related QoL outcome for ATD, RAI, and surgery were compared, including adjustment for the number of treatments received, sex, age, and comorbidity.Regardless of treatment modality, patients with GD had worse thyroid-related QoL 6-10 years after diagnosis compared to the general population. Patients treated with RAI had worse thyroid-related and general QoL than patients treated with ATD or thyroidectomy on the majority of QoL scales. Sensitivity analyses supported the relative negative comparative effects of RAI treatment on QoL in patients with hyperthyroidism.GD is associated with a lower QoL many years after treatment compared to the general population. In a previous small randomized controlled trial, no difference was found in patient satisfaction years after ATD, RAI, or surgery. Now, it is reported that in a large non-randomized cohort, patients who received RAI had adverse scores on ThyPRO and 36-item Short Form Health Status survey. These findings in a Swedish population are limited by comparison to normative data from Denmark, older age, and possibly a more prolonged course in those patients who received RAI, and a lack of information regarding thyroid status at the time of evaluation. The way RAI may adversely affect QoL is unknown, but since the results may be important for future considerations regarding treatment options for GD, they need to be substantiated in further studies.

Mesophyll conductance (gm) is a critical variable for the use of stable carbon isotopes to infer photosynthetic water-use efficiency (WUE). Although gm is similar in magnitude to stomatal conductance (gs), it has been measured less often, especially under field conditions and at high temporal resolution. We mounted an isotopic CO2 analyser on a field photosynthetic gas exchange system to make continuous online measurements of gas exchange and photosynthetic 13C discrimination (Δ13C) on mature Pinus sylvestris trees. This allowed the calculation of gm, gs, net photosynthesis (Anet), and WUE. These measurements highlighted the asynchronous diurnal behaviour of gm and gs. While gs declined from around 10:00, Anet declined first after 12:00, and gm remained near its maximum until 16:00. We suggest that high gm played a role in supporting an extended Anet peak despite stomatal closure. Comparing three models to estimate WUE from ∆13C, we found that a simple model, assuming constant net fractionation during carboxylation (27‰), predicted WUE well, but only for about 75% of the day. A more comprehensive model, accounting explicitly for gm and the effects of daytime respiration and photorespiration, gave reliable estimates of WUE, even in the early morning hours when WUE was more variable. Considering constant, finite gm or gm/gs yielded similar WUE estimates on the diurnal scale, while assuming infinite gm led to overestimation of WUE. These results highlight the potential of high-resolution gm measurements to improve modelling of Anet and WUE and demonstrate that such gm data can be acquired, even under field conditions. Electronic supplementary material The online version of this article (10.1007/s11120-019-00645-6) contains supplementary material, which is available to authorized users.

Effective societal responses to rapid climate change in the Arctic rely on an accurate representation of region-specific ecosystem properties and processes. However, this is limited by the scarcity and patchy distribution of field measurements. Here, we use a comprehensive, geo-referenced database of primary field measurements in 1,840 published studies across the Arctic to identify statistically significant spatial biases in field sampling and study citation across this globally important region. We find that 31% of all study citations are derived from sites located within 50 km of just two research sites: Toolik Lake in the USA and Abisko in Sweden. Furthermore, relatively colder, more rapidly warming and sparsely vegetated sites are under-sampled and under-recognized in terms of citations, particularly among microbiology-related studies. The poorly sampled and cited areas, mainly in the Canadian high-Arctic archipelago and the Arctic coastline of Russia, constitute a large fraction of the Arctic ice-free land area. Our results suggest that the current pattern of sampling and citation may bias the scientific consensuses that underpin attempts to accurately predict and effectively mitigate climate change in the region. Further work is required to increase both the quality and quantity of sampling, and incorporate existing literature from poorly cited areas to generate a more representative picture of Arctic climate change and its environmental impacts.

1. The rising levels of atmospheric carbon dioxide concentration ([CO2]) and temperature have the potential to substantially affect the terrestrial water and energy balance by altering the stomatal ...

Previous leaf-scale studies of carbon assimilation describe short-term resource-use efficiency (RUE) trade-offs where high use efficiency of one resource requires low RUE of another. However, varying resource availabilities may cause long-term RUE trade-offs to differ from the short-term patterns. This may have important implications for understanding canopy-scale resource use and allocation. We used continuous gas exchange measurements collected at five levels within a Norway spruce, Picea abies (L.) karst., canopy over 3 years to assess seasonal differences in the interactions between shoot-scale resource availability (light, water and nitrogen), net photosynthesis (An ) and the use efficiencies of light (LUE), water (WUE) and nitrogen (NUE) for carbon assimilation. The continuous data set was used to develop and evaluate multiple regression models for predicting monthly shoot-scale An . These models showed that shoot-scale An was strongly dependent on light availability and was generally well described with simple one- or two-parameter models. WUE peaked in spring, NUE in summer and LUE in autumn. However, the relative importance of LUE for carbon assimilation increased with canopy depth at all times. Our results suggest that accounting for seasonal and within-canopy trade-offs may be important for RUE-based modelling of canopy carbon uptake.

Objective: This retrospective study determined the prevalence of lithium-associated hyperparathyroidism (LHPT) in 2 geographically defined, equivalent populations in Sweden, with no other selection ...

The sensitivity of photosynthetic metabolism to temperature has been identified as a key uncertainty for projecting the magnitude of the terrestrial feedback on future climate change. While temperature responses of photosynthetic capacities have been comparatively well investigated in temperate species, the responses of tropical tree species remain unexplored. We compared the responses of seedlings of native cold-adapted tropical montane rainforest tree species with those of exotic warm-adapted plantation species, all growing in an intermediate temperature common garden in Rwanda. Leaf gas exchange responses to carbon dioxide (CO2 ) at different temperatures (20-40°C) were used to assess the temperature responses of biochemical photosynthetic capacities. Analyses revealed a lower optimum temperature for photosynthetic electron transport rates than for Rubisco carboxylation rates, along with lower electron transport optima in the native cold-adapted than in the exotic warm-adapted species. The photosynthetic optimum temperatures were generally exceeded by daytime peak leaf temperatures, in particular in the native montane rainforest climax species. This study thus provides evidence of pronounced negative effects of high temperature in tropical trees and indicates high susceptibility of montane rainforest climax species to future global warming.

Physiological processes of terrestrial plants regulate the land-atmosphere exchange of carbon, water, and energy, yet few studies have explored the acclimation responses of mature boreal conifer trees to climate change. Here we explored the acclimation responses of photosynthesis, respiration, and stomatal conductance to elevated temperature and/or CO

Trees are able to reduce their carbon (C) losses by refixing some of the CO2 diffusing out of their stems through corticular photosynthesis. Previous studies have shown that under ideal conditions the outflowing CO2 can be completely assimilated in metabolically active, young stem and branch tissues. Fewer studies have, however, been carried out on the older stem sections of large trees and, accordingly, the importance of refixation is still unclear under natural environmental conditions. We investigated the spatial and temporal variation in refixation in ~90-year-old boreal Scots pine (Pinus sylvestris L.) trees by utilizing month-long continuous measurements of stem CO2 efflux (Ec) made at four heights along the bole. Refixation rates were found to vary considerably along the bole, leading to a 28% reduction in long-term Ec in the upper stem compared with a negligible reduction at breast height. This vertical pattern correlated with variation in light availability, bark chlorophyll content and bark type. Analysis of the vertical and diurnal patterns in Ec further suggested that the influence of sap flow on the observed daytime reduction in Ec was small. The areal rates of corticular photosynthesis were much lower than previous estimates of photosynthetic rates per unit leaf area from the same trees, implying that the impact of refixation on tree-scale C uptake was small. However, upscaling of refixation indicated that 23-27% of the potential Ec was refixed by the bole and the branches, thereby significantly reducing the woody tissue C losses. Thus, our results suggest that refixation needs to be considered when evaluating the aboveground C cycling of mature P. sylvestris stands and that breast-height estimates should not be extrapolated to the whole tree.

Whether hyperthyroidism influences the birth characteristics of children born several years after treatment is unknown.The objective of the study was to compare birth characteristics in singleton newborns delivered by women previously treated for Graves' disease (GD), toxic nodular goiter (TNG), or nontoxic goiter (NTG).This was a nested case-control design within a national cohort registry study from 1950 through 2006.The study was conducted at a university and a hospital center in collaboration.The birth characteristics of newborns (n = 3421) delivered in a cohort of 43 633 women treated for GD or toxic nodular goiter by radioiodine or surgery (exposed group) at least 1 year prior to pregnancy were compared with newborns (n = 2914) of 45 655 mothers, previously operated for NTG (unexposed group).The primary outcome was birth weight, length, and head circumference. The secondary outcome was malformations, gestational age, and type of hyperthyroidism.The birth weight of exposed children was 3431 ± 607 g (mean ± SD) compared with the unexposed, 3520 ± 641 g (P.001). The cumulative odds ratio (OR) for lower birth weight was 1.29 [95% confidence interval (CI) 1.16-1.43]. The average birth length for the exposed children was 50.0 ± 2.7 cm compared with the unexposed of 50.4 cm ± 2.6 cm (P.01) [cumulative OR 1.25 (95% CI 1.13-1.37)]. The head circumference was 34.5 ± 1.9 cm among exposed and 34.7 ± 1.8 cm, respectively (P.001), with an OR of 1.24 (95% CI 1.13-1.35). No differences in birth characteristics were observed between children born after maternal GD or toxic nodular goiter.Previous GD or TNG may influence the birth characteristics several years after radioiodine or surgical treatment.

Stem CO2 efflux is known to vary seasonally and vertically along tree stems. However, annual tree- and stand-scale efflux estimates are commonly based on measurements made only a few times a year, during daytime and at breast height. In this study, the effect of these simplifying assumptions on annual efflux estimates and their influence on the estimates of the importance of stems in stand-scale carbon cycling are evaluated. In order to assess the strength of seasonal, diurnal and along-stem variability in CO2 efflux, half-hourly measurements were carried out at three heights on three mature Norway spruce (Picea abies (L.) Karst.) trees over a period of 3 years. Making the common assumption of breast height efflux rates being representative of the entire stem was found to result in underestimations of 10-17% in the annual tree-scale CO2 efflux. Upscaling using only daytime measurements from breast height increased the underestimation to 15-20%. Furthermore, the results show that the strength of the vertical gradient varies seasonally, being strongest in the early summer and non-existent during the cool months. The observed seasonality in the vertical CO2 efflux gradient could not be explained by variation in stem temperature, temperature response of the CO2 efflux (Q(10)), outer-bark permeability, CO2 transport in the xylem or CO2 release from the phloem. However, the estimated CO2 concentration immediately beneath the bark was considerably higher in the upper stem during the main period of diameter growth, coinciding with the strongest vertical efflux gradient. These results suggest that higher growth rates in the upper stem are the main cause for the observed vertical variation in the stem CO2 effluxes. Furthermore, the results indicate that accounting for the vertical efflux variation is essential for assessments of the importance of stems in stand-scale carbon cycling.

The purpose of this study was to investigate the effect of preinjury β-blockade in patients experiencing isolated severe traumatic brain injury (TBI). We hypothesized that β-blockade before TBI is associated with improved survival.The trauma registry of an urban academic trauma center was queried to identify patients with an isolated severe TBI between January 2007 and December 2011. Isolated severe TBI was defined as an intracranial injury with an Abbreviated Injury Scale (AIS) score of 3 or greater excluding all extracranial injuries AIS score of 3 or greater. Patient demographics, clinical characteristics on admission, injury profile, Injury Severity Score (ISS), AIS score, in-hospital morbidity, and β-blocker exposure were abstracted for analysis. The primary outcome evaluated was in-hospital mortality stratified by preinjury β-blockade exposure.Overall, a total of 662 patients met the study criteria. Of these, 25% (n = 159) were exposed to β-blockade before their traumatic insult. When comparing the demographics and injury characteristics between the groups, the sole difference was age, with the β-blocked group being older (69 [12] years vs. 63 [13] years, p0.001). β-blocked patients had a higher rate of infectious complications (30% vs. 19%, p = 0.04), with no difference in cardiac or pulmonary complications between the cohorts. Patients exposed to β-blockade versus no β-blockade experienced 13% and 22% mortality, respectively (p = 0.01). Stepwise logistic regression predicted the absence of β-blockade exposure as a risk factor for mortality (odds ratio, 2.7; 95% confidence interval, 1.5-4.8; p = 0.002). After adjustment for significant differences between the groups, patients not exposed to β-blockade experienced twofold increased risk of mortality (adjusted odds ratio, 2.2; 95% confidence interval, 1.3-3.7; p = 0.004).Preinjury β-blockade improves survival following isolated severe TBI. The role of prophylactic β-blockade and the timing of initiation of such therapy after TBI warrant further investigations.Therapeutic study, level III; prognostic study, level II.

Afforestation has been proposed as a strategy to mitigate the often high greenhouse gas (GHG) emissions from agricultural soils with high organic matter content. However, the carbon dioxide (CO2) and nitrous oxide (N2O) fluxes after afforestation can be considerable, depending predominantly on site drainage and nutrient availability. Studies on the full GHG budget of afforested organic soils are scarce and hampered by the uncertainties associated with methodology. In this study we determined the GHG budget of a spruce-dominated forest on a drained organic soil with an agricultural history. Two different approaches for determining the net ecosystem CO2 exchange (NEE) were applied, for the year 2008, one direct (eddy covariance) and the other indirect (analyzing the different components of the GHG budget), so that uncertainties in each method could be evaluated. The annual tree production in 2008 was 8.3 ± 3.9 t C ha−1 yr−1 due to the high levels of soil nutrients, the favorable climatic conditions and the fact that the forest was probably in its phase of maximum C assimilation or shortly past it. The N2O fluxes were determined by the closed-chamber technique and amounted to 0.9 ± 0.8 t Ceq ha−1 yr−1. According to the direct measurements from the eddy covariance technique, the site acts as a minor GHG sink of −1.2 ± 0.8 t Ceq ha−1 yr−1. This contrasts with the NEE estimate derived from the indirect approach which suggests that the site is a net GHG emitter of 0.6 ± 4.5 t Ceq ha−1 yr−1. Irrespective of the approach applied, the soil CO2 effluxes counter large amounts of the C sequestration by trees. Due to accumulated uncertainties involved in the indirect approach, the direct approach is considered the more reliable tool. As the rate of C sequestration will likely decrease with forest age, the site will probably become a GHG source once again as the trees do not compensate for the soil C and N losses. Also forests in younger age stages have been shown to have lower C assimilation rates; thus, the overall GHG sink potential of this afforested nutrient-rich organic soil is probably limited to the short period of maximum C assimilation.

Photosynthesis is highly responsive to environmental and physiological variables, including phenology, foliage nitrogen (N) content, atmospheric CO2 concentration ([CO2]), irradiation (Q), air temperature (T) and vapour pressure deficit (D). Each of these responses is likely to be modified by long-term changes in climatic conditions such as rising air temperature and [CO2]. When modelling photosynthesis under climatic changes, which parameters are then most important to calibrate for future conditions? To assess this, we used measurements of shoot carbon assimilation rates and microclimate conditions collected at Flakaliden, northern Sweden. Twelve 40-year-old Norway spruce trees were enclosed in whole-tree chambers and exposed to elevated [CO2] and elevated air temperature, separately and in combination. The treatments imposed were elevated temperature, +2.8 °C in July/August and +5.6 °C in December above ambient, and [CO2] (ambient CO2 ∼370 μ mol mol(-1), elevated CO2 ∼700 μ mol mol(-1)). The relative importance of parameterization of Q, T and D responses for effects on the photosynthetic rate, expressed on a projected needle area, and the annual shoot carbon uptake was quantified using an empirical shoot photosynthesis model, which was developed and fitted to the measurements. The functional form of the response curves was established using an artificial neural network. The [CO2] treatment increased annual shoot carbon (C) uptake by 50%. Most important was effects on the light response curve, with a 67% increase in light-saturated photosynthetic rate, and a 52% increase in the initial slope of the light response curve. An interactive effect of light saturated photosynthetic rate was found with foliage N status, but no interactive effect for high temperature and high CO2. The air temperature treatment increased the annual shoot C uptake by 44%. The most important parameter was the seasonality, with an elongation of the growing season by almost 4 weeks. The temperature response curve was almost flat over much of the temperature range. A shift in temperature optimum had thus an insignificant effect on modelled annual shoot C uptake. The combined temperature and [CO2] treatment resulted in a 74% increase in annual shoot C uptake compared with ambient conditions, with no clear interactive effects on parameter values. (Less)

Quantifying the adjustments of leaf respiration in response to seasonal temperature variation and climate warming is crucial because carbon loss from vegetation is a large but uncertain part of the global carbon cycle. We grew fast-growing Eucalyptus globulus Labill. trees exposed to +3 °C warming and elevated CO2 in 10-m tall whole-tree chambers and measured the temperature responses of leaf mitochondrial respiration, both in light (RLight) and in darkness (RDark), over a 20-40 °C temperature range and during two different seasons. RLight was assessed using the Laisk method. Respiration rates measured at a standard temperature (25 °C - R25) were higher in warm-grown trees and in the warm season, related to higher total leaf nitrogen (N) investment with higher temperatures (both experimental and seasonal), indicating that leaf N concentrations modulated the respiratory capacity to changes in temperature. Once differences in leaf N were accounted for, there were no differences in R25 but the Q10 (i.e., short-term temperature sensitivity) was higher in late summer compared with early spring. The variation in RLight between experimental treatments and seasons was positively correlated with carboxylation capacity and photorespiration. RLight was less responsive to short-term changes in temperature than RDark, as shown by a lower Q10 in RLight compared with RDark. The overall light inhibition of R was ∼40%. Our results highlight the dynamic nature of leaf respiration to temperature variation and that the responses of RLight do not simply mirror those of RDark. Therefore, it is important not to assume that RLight is the same as RDark in ecosystem models, as doing so may lead to large errors in predicting plant CO2 release and productivity.

As a result of different types of disturbance, forests are a mixture of stands at different stages of ecological succession. Successional stage is likely to influence forest productivity and carbon storage, linking the degree of forest disturbance to the global carbon cycle and climate. Although tropical montane forests are an important part of tropical forest ecosystems (c. 8 %, elevation > 1000 m a.s.l.), there are still significant knowledge gaps regarding the carbon dynamics and stocks of these forests, and how these differ between early (ES) and late successional (LS) stages. This study examines the carbon (C) stock, relative growth rate (RGR), and net primary production (NPP) of ES and LS forest stands in an Afromontane tropical rainforest using data from inventories of quantitatively important ecosystem compartments in fifteen 0.5 ha plots in Nyungwe National Park in Rwanda. The total C stock was 35 % larger in LS compared to ES plots due to significantly larger above ground biomass (AGB; 185 and 76 Mg C ha−1 in LS and ES plots, respectively), while the soil and root C stock (down to 45 cm depth in the mineral soil) did not significantly differ between the two successional stages (178 and 204 Mg C ha−1 in LS and ES plots, respectively). The main reasons for the difference in AGB were that ES trees had significantly lower stature and wood density compared to LS trees. However, ES and LS stands had similar total NPP (canopy, wood and roots of all plots ~ 9.4 Mg C ha−1) due to counterbalancing effects of differences in AGB (higher in LS stands) and RGR (higher in ES stands). The AGB in the LS plots was considerably higher than the average value reported for old-growth tropical montane forest of Southeast Asia and central and South America at similar elevations and temperatures, and of the same magnitude as in tropical lowland forest of different regions. The results of this study highlight the importance of accounting for disturbance regimes and differences in wood density and allometry of tree species dominating at different successional stages in attempts to quantify the C stock and sink strength of tropical montane forests and how it may differ among continents.

Reply to comments From Dr Lozano, et al - Concerning the prevalence of lithium-associated hyperparathyroidism

According to well-known biochemical and biophysical mechanisms, the stimulation of C(3) photosynthesis by elevated atmospheric CO(2) concentration ([CO(2)]) is strongly modified by changes in temperature and radiation. In order to investigate whether a static parameterization of the commonly used Farquhar et al. model of photosynthesis (i.e., without CO(2)-induced seasonal or thermal acclimation of photosynthetic capacity) can accurately predict these interactions in mature boreal Norway spruce (Picea abies (L.) Karst.) during the frost-free part of the growing season, shoot gas exchange was continuously measured on trees during their second/third year of exposure to ambient or doubled [CO(2)] inside whole-tree chambers. The relative CO(2)-induced enhancement of net photosynthesis (A(n)) at a given temperature remained stable over the study period, but increased strongly with temperature and radiation, in agreement with predictions by the model. Light-saturated A(n) (+67% at 20 °C), dark respiration (+36%) and intercellular to ambient [CO(2)] ratio (c(i)/c(a); +27%) were significantly increased by CO(2) treatment. Stomatal conductance (g(s)) was not significantly affected. Our results demonstrate that the Farquhar et al. model of photosynthesis has the capability to predict interactions between [CO(2)] and seasonal weather variability on A(n) in Norway spruce during the non-frost growing season without accounting for CO(2)-induced seasonal and/or thermal photosynthetic acclimation. However, stomatal model assumptions of reduced g(s) and constant c(i)/c(a) under rising atmospheric [CO(2)] did not hold.

Background Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy of the thyroid gland. Patients at our institution are treated with external radiotherapy up to 46 Gray (Gy) and low-dose doxorubicin prior to surgery. We retrospectively evaluated the outcome of ATC patients over a 13-year period. Methods Clinical, histopathological, and follow-up data for 59 patients diagnosed between 1997 and 2010 were collected and analyzed. Results Median age at diagnosis was 77 years. Female-male ratio was 2.5:1. Median survival from time of diagnosis was 3.3 months. Thirty-six patients completed the treatment protocol (including surgery), of whom one succumbed due to local tumor growth. In multivariate analysis, the only factor significantly associated with longer survival among operated patients was absence of metastases at diagnosis (P = 0.031). No impact on survival time was found for gender, extent of surgical resection, and absence of extrathyroidal invasion. Conclusions Despite aggressive treatment, survival rates in ATC patients remain low. Locoregional control is feasible for most patients, underscoring the importance of an intense, multimodal treatment regimen. Further oncological intervention is of crucial importance to achieve a better prognosis for ATC patients. J. Surg. Oncol. 2012; 106: 981–986. © 2012 Wiley Periodicals, Inc.

Backbone torsional strain has been implicated as a cause of rate enhancement in a class of autoprocessing proteins performing proteolysis and protein splicing. In the autoproteolytic protein domain SEA, folding and proteolytic activity have experimentally been shown to be coupled with about 7 kcal/mol of folding free energy available for catalysis. Here, we have examined the catalytic strategy of SEA with molecular dynamics simulations, potential of mean force free energy profiles, and B3LYP/6-311G(d,p) density functional calculations. A quantitative estimate of the free energy stored as protein strain (about 8 kcal/mol), that is available for catalyzing the cleavage reaction, is obtained and found to be in excellent agreement with thermodynamic and kinetic data. It is further shown that there is strong coupling between folding and reaction coordinates leading to reactant state destabilization in the direction of folding and transition state stabilization along the reaction coordinate. This situation is different from the preorganized active site model in that the fully folded transition state stabilizing structure is not realized until the reaction barrier is surmounted.

A long-established theoretical result states that, for a given total canopy nitrogen (N) content, canopy photosynthesis is maximized when the within-canopy gradient in leaf N per unit area (N(a)) is equal to the light gradient. However, it is widely observed that N(a) declines less rapidly than light in real plant canopies. Here we show that this general observation can be explained by optimal leaf acclimation to light subject to a lower-bound constraint on the leaf mass per area (m(a)). Using a simple model of the carbon-nitrogen (C-N) balance of trees with a steady-state canopy, we implement this constraint within the framework of the MAXX optimization hypothesis that maximizes net canopy C export. Virtually all canopy traits predicted by MAXX (leaf N gradient, leaf N concentration, leaf photosynthetic capacity, canopy N content, leaf-area index) are in close agreement with the values observed in a mature stand of Norway spruce trees (Picea abies L. Karst.). An alternative upper-bound constraint on leaf photosynthetic capacity (A(sat)) does not reproduce the canopy traits of this stand. MAXX subject to a lower bound on m(a) is also qualitatively consistent with co-variations in leaf N gradient, m(a) and A(sat) observed across a range of temperate and tropical tree species. Our study highlights the key role of constraints in optimization models of plant function.

ObjectiveThyroid proteomics is a new direction in thyroid cancer research aiming at etiological understanding and biomarker identification for improved diagnosis.MethodsTwo-dimensional electrophoresis was applied to cytosolic protein extracts from frozen thyroid samples (ten follicular adenomas, nine follicular carcinomas, ten papillary carcinomas, and ten reference thyroids). Spots with differential expression were revealed by image and multivariate statistical analyses, and identified by mass spectrometry.ResultsA set of 25 protein spots significant for discriminating between the sample groups was identified. Proteins identified for nine of these spots were studied further including 14-3-3 protein beta/alpha, epsilon, and zeta/delta, peroxiredoxin 6, selenium-binding protein 1, protein disulfide-isomerase precursor, annexin A5 (ANXA5), tubulin alpha-1B chain, and α1-antitrypsin precursor. This subset of protein spots carried the same predictive power in differentiating between follicular carcinoma and adenoma or between follicular and papillary carcinoma, as compared with the larger set of 25 spots. Protein expression in the sample groups was demonstrated by western blot analyses. For ANXA5 and the 14-3-3 proteins, expression in tumor cell cytoplasm was demonstrated by immunohistochemistry both in the sample groups and an independent series of papillary thyroid carcinomas.ConclusionThe proteins identified confirm previous findings in thyroid proteomics, and suggest additional proteins as dysregulated in thyroid tumors.

IntroductionThe incidence of hyperthyroidism has been reported in various countries to be 23–93/100 000 inhabitants per year. This extended study has evaluated the incidence for ∼40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country.MethodsAll patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003–2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows: clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered.ResultsA total of 2916 patients were diagnosed withde novohyperthyroidism showing the total incidence of 27.6/100 000 inhabitants per year. The incidence of GD was 21.0/100 000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100 000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed.ConclusionThe incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.

The hERG potassium channel is of major pharmaceutical importance, and its blockade by various compounds, potentially causing serious cardiac side effects, is a major problem in drug development. Despite the large amounts of existing biochemical data on blockade of hERG by drugs and druglike compounds, relatively little is known regarding the structural basis of binding of blockers to the channel. Here, we have used a recently developed homology model of hERG to conduct molecular docking experiments with a series of channel blockers, followed by molecular dynamics simulations of the complexes and evaluation of binding free energies with the linear interaction energy method. The calculations yield a remarkably good agreement with experimental binding affinities and allow for a rationalization of three-dimensional structure-activity relationships in terms of a number of key interactions. Two main interaction regions of the channel are thus identified with implications for further mutagenesis experiments and design of new compounds.

ObjectiveThe objective of this study was to investigate quality of life (QoL) in patients with Graves' disease treated with radioiodine or antithyroid drugs.Design and methodsThe design of the study consists of an open, prospective, randomized multicenter trial between radioiodine and medical treatment. A total of 308 patients were included in the study group: 145 patients in the medical group and 163 patients in the radioiodine group. QoL was measured with a 36-item Short Form Health Status Survey questionnaire (SF-36) at six time points during the 48-month study period.ResultsPatient who developed or got worse of thyroid-associated ophthalmopathy (TAO) at any time point during the 4-year study period (TAO group) had lower QoL when no respect was paid to the mode of treatment.TAO occurred in 75 patients who had radioiodine treatment at some time point during the study period as compared with TAO in 40 medically treated patients (PComparisons between the group of patients who have had TAO versus the group without TAO, in relation to treatments and time, showed significantly decreased QoL scores for the TAO groups at several time points during the study.In patients without TAO, there were no differences in QoL related to mode of treatment.ConclusionsThe QoL in patients with Graves' ophthalmopathy was similar in radioiodine and medically treated patients, but patients who developed or had worsening of TAO had decreased QoL independent of mode of treatment. Furthermore, patients with TAO recovered physically within 1 year but it took twice as long for them to recover mentally.

Recent progress in elucidating the peptide bond formation process on the ribosome has led to notion of a proton shuttle mechanism where the 2'-hydroxyl group of the P-site tRNA plays a key role in mediating proton transfer between the nucleophile and leaving group, whereas ribosomal groups do not actively participate in the reaction. Despite these advances, the detailed nature of the transition state for peptidyl transfer and the role of several trapped water molecules in the peptidyl transferase center remain major open questions. Here, we employ high-level quantum chemical ab initio calculations to locate and characterize global transition states for the reaction, described by a molecular model encompassing all the key elements of the reaction center. The calculated activation enthalpy as well as structures are in excellent agreement with experimental data and point to feasibility of an eight-membered “double proton shuttle” mechanism in which an auxiliary water molecule, observed both in computer simulations and crystal structures, actively participates. A second conserved water molecule is found to be of key importance for stabilizing developing negative charge on the substrate oxyanion and its presence is catalytically favorable both in terms of activation enthalpy and entropy. Transition states calculated both for six- and eight-membered mechanisms are invariably late and do not involve significant charge development on the attacking amino group. Predicted kinetic isotope effects consistent with this picture are similar to those observed for uncatalyzed ester aminolysis reactions in solution.

Previous randomized trials have suggested an association between radioiodine treatment for Graves' hyperthyroidism and thyroid-associated ophthalmopathy (TAO).The aim of the study was to compare the occurrence of worsening or development of TAO in patients who were treated with radioiodine or antithyroid drugs.We conducted a randomized trial (TT 96) with a follow-up of 4 yr. PATIENTS, SETTING, AND INTERVENTION: Patients with a recent diagnosis of Graves' hyperthyroidism were randomized to treatment with iodine-131 (163 patients) or 18 months of medical treatment (150 patients). Early substitution with T(4) was given in both groups.Worsening or development of TAO was significantly more common in the iodine-131 treatment group (63 patients; 38.7%) compared with the medical treatment group (32 patients; 21.3%) (P0.001).The risk for de novo development of TAO was greater in patients treated with iodine-131 (53 patients) than with medical treatment (23 patients). However, worsening of TAO in the 41 patients who had ophthalmopathy already before the start of treatment was not more common in the radioiodine group (10 patients) than in the medical group (nine patients). Smoking was shown to influence the risk of worsening or development of TAO, and smokers treated with radioiodine had the overall highest risk for TAO. However, in the group of smokers, worsening or development of TAO was not significantly associated with the choice of treatment for hyperthyroidism.Radioiodine treatment is a significant risk factor for development of TAO in Graves' hyperthyroidism. Smokers run the highest risk for worsening or development of TAO irrespective of treatment modality.

The linear interaction energy method (LIE), which combines force field based molecular dynamics (MD) simulations and linear response theory, has previously been shown to give fast and reliable estimates of ligand binding free energies, suggesting that this type of technique could be used also in a high-throughput fashion. However, a limiting step in such applications is the assignment of atomic charges for compounds that have not been parametrized within the given force field, in this case OPLS-AA. In order to reach an automatable solution to this problem, we have examined the performance of nine different ab initio and semiempirical charge methods, together with estimates of solvent induced polarization. A test set of ten HIV-1 reverse transcriptase inhibitors was selected, and LIE estimates of their relative binding free energies were calculated using the resulting 23 different charge variants. Over 800 ns of MD simulation show that the LIE method provides excellent estimates with several different charge methods and that the semiempirically derived CM1A charges, in particular, emerge as a fast and reliable alternative for fully automated LIE based virtual screens with the OPLS-AA force field. Our conclusions regarding different charge models are also expected to be valid for other types of force field based binding free energy calculations, such as free energy perturbation and thermodynamic integration simulations.

Acyl lipids and pigments were analyzed in young plants of garden pea, spring wheat and spinach exposed to < 5 or 65 nl l−1 ozone 12 h per day for 6 days. In one set of experiments, the plants were exposed to 14CO2 for 2 h 3 days prior to ozone exposure. The plants responded differently to the moderately enhanced level of ozone used Spinach was not at all sensitive while in both pea and wheat, leaves of different ages differed in ozone sensitivity. In pea, ozone sensitivity increased with leaf age. In the second and third oldest leaves, the amounts of galactolipids per leaf area and the proportions of 18:3 of the total lipid extract and of phosphatidylglycerol decreased. In the second oldest leaf, ozone also caused a decreased proportion of 18:3 of monogalactosyldiacylglycerol. In the fourth oldest leaf, lipid composition and galactolipid unsaturation was unaffected, but ozone caused decreased leaf expansion resulting in increased acyl lipid content per leaf area. In both the first and second leaves of wheat, ozone fumigation caused a marked decrease in the content of monogalactosyldiacylglycerol and in the first leaf, the contents of phosphatidylcholine and phosphatidylethanolamine increased. The proportion of 18:3 in phosphatidylcholine was larger in ozone-fumigated than in control plants, while the reverse applied for phosphatidylglycerol. In the oldest sampled leaves of pea and wheat, ozone caused an increase in the radioactivity associated with β-carotene, indicating increased turnover. Thus, while spinach was unaffected, in both pea and wheat ozone caused a decrease in the proportion of chloroplast membrane lipids to non-chloroplast membrane lipids in older leaves while younger leaves were less sensitive.

Anaplastic thyroid cancer (ATC) is a rare but highly aggressive disease with largely unexplained etiology and molecular pathogenesis. In this study, we analyzed genome-wide copy number changes, BRAF (V-raf sarcoma viral oncogene homolog B1) mutations, and p16 and cyclin D1 expressions in a panel of ATC primary tumors. Three ATCs harbored the common BRAF mutation V600E. Using array-comparative genomic hybridisation (array-CGH), several distinct recurrent copy number alterations were revealed including gains in 16p11.2, 20q11.2, and 20q13.12. Subsequent fluorescence in situ hybridization revealed recurrent locus gain of UBCH10 in 20q13.12 and Cyclin D1 (CCND1) in 11q13. The detection of a homozygous loss encompassing the CDKN2A locus in 9p21.3 motivated the examination of p16 protein expression, which was undetectable in 24/27 ATCs (89%). Based on the frequent gain in 11q13 (41%; n=11), the role of CCND1 was further investigated. Expression of cyclin D1 protein was observed at varying levels in 18/27 ATCs (67%). The effect of CCND1 on thyroid cell proliferation was assessed in vitro in ATC cells by means of siRNA and in thyroid cells after CCND1 transfection. In summary, the recurrent chromosomal copy number changes and molecular alterations identified in this study may provide an insight into the pathogenesis and development of ATC.

The diagnosis of follicular thyroid carcinoma (FTC) in the absence of metastasis can only be established postoperatively. Moreover, high-risk FTCs are often not identifiable at the time of diagnosis. In this study, we aimed to identify transcriptional markers of malignancy and high-risk disease in follicular thyroid tumors. The expression levels of 26 potential markers of malignancy were determined in a panel of 75 follicular thyroid tumors by a TaqMan quantitative RT-PCR approach. Logistic regression analysis (LRA) was used for gene selection and generation of diagnostic and prognostic algorithms. An algorithm based on the expression levels of five genes (TERT, TFF3, PPARγ, CITED1, and EGR2) could effectively predict high-risk disease with a specificity of 98.5%. The metastatic potential could be predicted in all four cases with apparently benign or minimally invasive (MI) disease at the time of diagnosis, but poor long-term outcome. In addition, a second model was produced by implementing two genes (TERT and TFF3), which was able to distinguish adenomas from de facto carcinomas. When this model was tested in an independent series of atypical adenomas (AFTA) and MI-FTCs, 16 out of 17 AFTAs were classified as ‘benign’, while MI-FTCs with vascular invasion (sometimes referred to as ‘moderately invasive’) and/or large tumor size tended to classify in the ‘malignant’ group. The reported models can be the foundation for the development of reliable preoperative diagnostic and prognostic tests that can guide the therapeutic approach of follicular thyroid neoplasms with indeterminate cytology.

Background and Aims: In patients with primary hyperparathyroidism (PHPT), parathyroid imaging is nowadays routinely used for the purpose to perform a focused unilateral minimally invasive operation. The outcome of this new strategy has, however, not been established in randomised trials. Material and Methods: Patients were randomised to either preoperative localisation with sestamibi scintigraphy and ultrasonography (group I) or no preoperative localisation (group II). In group I, a minimally invasive parathyroidectomy was performed in patients in whom both localisation studies were consistent with a single pathological gland, whereas a conventional bilateral neck exploration was performed in cases with negative localisation findings. In group II all patients underwent conventional bilateral neck exploration. Primary outcome measure was normocalcaemia at 6 months postoperatively. Results: In the preoperative localisation group (group I) 23/50 (46%) of the patients could be operated on with the focused operation whereas 26/50 (52%) were operated on by bilateral neck exploration. All patients in the no localisation group (group II; n=50) were operated on with the intended bilateral neck operation. Normocalcaemia was obtained in 96% and 94% in group I and II, respectively. Total (localisation and operative) costs were 21% higher in group I. Conclusions: Routine preoperative localisation, with the intention to perform minimally invasive parathyroidectomy, is not cost effective if concordant results of scintigraphy and ultrasonography are a prerequisite for the focused operation. Less than half of the patients were successfully managed with this strategy, at a higher cost and without obtaining a more favourable clinical outcome.

Objective: In a 14–21 year follow-up of health-related quality of life (HRQL) outcome of 179 patients after randomized treatment of Graves’ disease (GD) with surgical, medical or radioiodine, we found no differences. The HRQL for Graves’ patients, however, was lower compared with a large age- and sex-matched Swedish reference population. We have now studied whether the reported HRQL-scores by Medical Outcome Study 36-item Short-Form Health Status Survey (SF36) and quality of life 2004 (QoL2004) answers were related to the thyroid hormone state of the patient. Methods: This report comprises 91 of the original patients in which both the results of SF36 and QoL2004 questionnaire as well as serum thyroid hormones and current use of l-thyroxine treatment were available. Results: A large number of the patients had low or undetectable serum TSH concentrations. SF36 scores and answers to QoL2004 questionnaires were not correlated to TSH levels or associated with suppressed TSH. A low free triiodothyronine was weakly associated with a low GH score (P < 0.02) and elevated thyrotropin receptor antibody with a low physical component summary (P < 0.02). Conclusion: HRQL do not seem to be influenced by the thyroid hormone state of the patient including subclinical thyrotoxicosis. It is possible that the personality of GD patients as such may have resulted both in the development of GD and lower HQRL scores later on in life. Alternatively, the generic SF36 may not be a proper instrument to detect relevant differences in HRQL related to the thyroid state.

Stomatal CO2 responsiveness and photosynthetic capacity vary greatly among plant species, but the factors controlling these physiological leaf traits are often poorly understood. To explore if these traits are linked to taxonomic group identity and/or to other plant functional traits, we investigated the short-term stomatal CO2 responses and the maximum rates of photosynthetic carboxylation (V cmax) and electron transport (J max) in an evolutionary broad range of tropical woody plant species. The study included 21 species representing four major seed plant taxa: gymnosperms, monocots, rosids and asterids. We found that stomatal closure responses to increased CO2 were stronger in angiosperms than in gymnosperms, and in monocots compared to dicots. Stomatal CO2 responsiveness was not significantly related to any of the other functional traits investigated, while a parameter describing the relationship between photosynthesis and stomatal conductance in combined leaf gas exchange models (g 1) was related to leaf area-specific plant hydraulic conductance. For photosynthesis, we found that the interspecific variation in V cmax and J max was related to within leaf nitrogen (N) allocation rather than to area-based total leaf N content. Within-leaf N allocation and water use were strongly co-ordinated (r 2 = 0.67), such that species with high fractional N investments into compounds maximizing photosynthetic capacity also had high stomatal conductance. We conclude that while stomatal CO2 responsiveness of tropical woody species seems poorly related to other plant functional traits, photosynthetic capacity is linked to fractional within-leaf N allocation rather than total leaf N content and is closely co-ordinated with leaf water use. Electronic supplementary material The online version of this article (doi:10.1007/s00442-017-3829-0) contains supplementary material, which is available to authorized users.

Yan-Shih Lin [et al.].- Received 16 August 2014, Accepted 16 January 2015, Published online 02 March 2015, Stomatal conductance (gs) is a key land-surface attribute as it links transpiration, the dominant component of global land evapotranspiration, and photosynthesis, the driving force of the global carbon cycle. Despite the pivotal role of gs in predictions of global water and carbon cycle changes, a global-scale database and an associated globally applicable model of gs that allow predictions of stomatal behaviour are lacking. Here, we present a database of globally distributed gs obtained in the field for a wide range of plant functional types (PFTs) and biomes. We find that stomatal behaviour differs among PFTs according to their marginal carbon cost of water use, as predicted by the theory underpinning the optimal stomatal model1 and the leaf and wood economics spectrum2, 3. We also demonstrate a global relationship with climate. These findings provide a robust theoretical framework for understanding and predicting the behaviour of gs across biomes and across PFTs that can be applied to regional, continental and global-scale modelling of ecosystem productivity, energy balance and ecohydrological processes in a future changing climate.

Scandinavian Quality Register for Thyroid and Parathyroid Surgery is an on-line web-based database with the aim to improve the quality of thyroid and parathyroid surgery. Preliminary data from surgery for primary hyperparathyroidism are reported here.Fifteen departments registered 806 operations, with 639 women (79.7%) and 167 men. The median age of the patients was 62 years.Approximately 95.4% of the patients had sporadic disease and first time operation was performed in 93.8% of the patients. Localization examinations were performed in 524 patients (65%); sestamibi scintigraphy in 413 patients, with a true positive adenoma localization in 64.4% and ultrasound in 293 patients with adenoma localization in 61.1%. Bilateral neck exploration was performed in 66.8%, unilateral exploration in 16.1%, and focused minimal invasive surgery in 17.1%. In 301 patients planned for limited parathyroid exploration, conversion to bilateral neck surgery occurred in 11%. The cure rate, based on short follow-up, was 91.9%. Postoperative hypocalcemia occurred in 11.4% of the patients, and was associated with reoperation, concomitant thyroid operation, and the weight of excised parathyroid tissue.Localization examinations are performed in 2/3 of the patients, but limited neck exploration was performed in only approximately 1/3 of the operations. The cure rate was lower and postoperative hypocalcemia was more frequent than expected.

Aim of the study To evaluate prognostic factors with respect to the outcome in a consecutive series of patients with papillary thyroid carcinoma (PTC) treated at the same institution during a 20-year-period, and to evaluate further the predictive ability of outcome of the pTNM, AMES and MACIS prognostic systems in these patients. Materials and methods Two hundred and twenty consecutive patients operated on for primary PTC at the Karolinska Hospital between 1980 and 1999 were examined retrospectively. Patient and tumour characteristics at the time of surgery were compared to the patients' outcomes. Univariate and multiple logistic regression analyses were used to identify independently significant prognostic factors with respect to the outcome. In addition, the classification of the patients according to the pTNM, AMES and MACIS prognostic systems were compared to the outcomes. Results At the end of the follow-up period 201 patients were still alive without disease, 6.5% had died from PTC and 2.5% were alive with persisting disease. In 16 patients, radical surgery could not be performed due to extensive tumour growth and/or distant metastases. Recurrences were detected in 14% of the patients considered as radically operated. The strongest independent predictors for local or distant recurrences and poor clinical outcome were the lack of radical surgery and increasing tumour size. In this investigation MACIS appeared to be the better system, regarding efficacy in predicting the outcome of PTC. Conclusion Removal of all tumour tissue appears most important to a favorable outcome and in our patients MACIS appears the most useful prognostic system taking completeness of resection into account.