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Optimal stomatal theory predicts that stomata operate to maximise photosynthesis (Anet) and minimise transpirational water loss to achieve optimal intrinsic water-use efficiency (iWUE). We tested whether this theory can predict stomatal responses to elevated atmospheric CO2 (eCO2), and whether it can capture differences in responsiveness among woody plant functional types (PFTs). We conducted a meta-analysis of tree studies of the effect of eCO2 on iWUE and its components Anet and stomatal conductance (gs). We compared three PFTs, using the unified stomatal optimisation (USO) model to account for confounding effects of leaf–air vapour pressure difference (D). We expected smaller gs, but greater Anet, responses to eCO2 in gymnosperms compared with angiosperm PFTs. We found that iWUE increased in proportion to increasing eCO2 in all PFTs, and that increases in Anet had stronger effects than reductions in gs. The USO model correctly captured stomatal behaviour with eCO2 across most datasets. The chief difference among PFTs was a lower stomatal slope parameter (g1) for the gymnosperm, compared with angiosperm, species. Land surface models can use the USO model to describe stomatal behaviour under changing atmospheric CO2 conditions. AG gratefully acknowledges a studentship provided by the John Horseman Trust and the University of Birmingham. The BIFoR FACE facility is supported by the JABBS Foundation, the University of Birmingham and the John Horseman Trust. ARMK acknowledges support from the UK Natural Environment Research Council through grant NE/S015833/1. MJ and BEM acknowledge funding from the Australian Research Council (DE210101654, FL190100003).

Tropical montane forests are among the most productive ecosystems within the tropical region and store a significant amount of carbon in live biomass. With ongoing global climate warming, tropical climates are also getting warmer. The productivity and climate feedbacks of future tropical montane forests depend on the ability of trees to acclimate their photosynthetic metabolism to these new, warmer conditions. However, knowledge of acclimation ability of photosynthesis and its underlying biochemical processes to warming in trees grown under natural field conditions is currently limited due to data scarcity. To reduce this knowledge gap, we used two separate field experiments located in Colombia (with 15 species) and Rwanda (16 species), and for each experiment, tree species were grown at three different sites along an elevation gradient differing in ambient air temperature. At all three sites, we measured the responses of net CO2 assimilation at different CO2 concentration (50 to 2000 ppm) and at different leaf temperatures (15 to 40 °C) in ≈ 3 years old trees. We used these data to derive key photosynthetic biochemical parameters (maximum Rubisco carboxylation capacity - Vcmax and maximum electron transport rate - Jmax) and their temperature sensitivity, as well as the thermal optimum of net photosynthesis (ToptA). We show that tropical montane tree species from the two continents are generally able to acclimate their ToptA by increasing in trees grown in warmer conditions, but the magnitude of change in ToptA differs among species from different successional groups (early- versus late succession) and climate of origin (lowland versus montane). Shifts in ToptA are largely driven by concomitant changes in thermal sensitivity parameters of underlying biochemical processes of photosynthesis (Vcmax and Jmax) with warming. We also show that, at a standard temperature of 25 °C, Vcmax is largely constant, while Jmax decreases with warming. Our findings indicate tropical montane tree species from Latin America and Africa can thermally acclimate their photosynthetic physiology, but that this thermal acclimation ability is related to species successional group and their climate of origin.

Current estimates of temperature effects on plants are usually based on air temperature (Tair), although it is well known that leaf temperature (Tleaf) can deviate considerably from Tair. In some studies, to overcome the problem of Tair often being a poor proxy of Tleaf, measurements of canopy temperature (Tcan) have been used instead. However, Tcan data do not capture the spatial variation in Tleaf among leaves with different thermoregulatory traits. This may be particularly problematic for highly diverse and heterogeneous tropical forest canopies. In this study, we used infrared thermometers to study Tleaf and Tcan in multispecies tropical tree plantations established at three sites along an elevation gradient from 2,400 m a.s.l. (17.1°C mean daytime temperature) to 1,300 m a.s.l. (24.0°C) in Rwanda. Measurements of chlorophyll fluorescence were also conducted to study the photosynthetic heat tolerance of these species. Our results showed high Tleaf (up to ~50°C) and leaf-to-air temperature differences (ΔTleaf; on average 8-10°C and up to 24°C) of sun-exposed leaves. Both leaf size and stomatal conductance were important traits in controlling Tleaf. The Tleaf (and thus ΔTleaf) of sun-exposed leaves greatly exceeded the simultaneously measured values of Tcan (and ΔTcan). Photosynthetic heat tolerance partially acclimated to increased growth temperature; on average 0.31°C increase in heat tolerance per 1°C increase in growth temperature. Consequently, thermal safety margins were narrower for species at the warmer, lower-elevation sites. Our findings highlight the importance of leaf traits for leaf thermoregulation and show that monitoring of canopy temperature is not enough to capture the peak temperatures and heat stress experienced by individual leaves in diverse tropical forest canopies. They also suggest that tropical trees have limited abilities to thermally acclimate to increasing temperatures.Keywords: Canopy temperature, elevation gradient, fluorescence, heat tolerance, leaf area, leaf temperature, stomatal conductance, thermoregulation, tropical forest.

The responses of tropical forests to climate change depends on the ability of trees to acclimate to warming, as well as how interspecific variation in these responses affect tree community composition. In a unique tropical elevation gradient experiment in Rwanda, Rwanda TREE, we examine the sensitivity of tropical trees and forest stands to warming and altered water supply. Mixed multi-species plantations (20 tree species, 1800 trees per site) have been established at three sites with large variation in elevation (1300-2400 m) and climate (17-24 °C mean daytime temperature), with additional water and nutrient manipulation treatments being applied at each site. Here we present an overview of results obtained this far regarding: (1) leaf gas exchange physiology; (2) photosynthetic heat tolerance; (3) water-use traits; (4) tree growth and mortality; (5) stand-level tree community composition. We also discuss the potential implications of our findings for the biodiversity and carbon storage of tropical forests in a changing climate.

The productivity and climate feedbacks of tropical forests depend on tree physiological responses to warmer and, over large areas, seasonally drier conditions. However, knowledge regarding such responses is limited due to data scarcity. We studied the impact of growth temperature on net photosynthesis (An), maximum rates of Rubisco carboxylation at 25 °C (Vcmax25), stomatal conductance (gs) and the slope parameter of the stomatal conductance-photosynthesis model (g1), in 10 early successional (ES) and 8 late-successional (LS) tropical tree species grown at three sites along an elevation gradient in Rwanda, differing by 6.8 °C in daytime ambient air temperature. The effect of seasonal drought on An was also investigated. We found that warm climate decreased wet-season An in LS species, but not in ES species. Values of Vcmax25 were lower at the warmest site across both successional groups, and An and Vcmax25 were higher in ES compared with LS species. Stomatal conductance exhibited no significant site differences and g1 was similar across both sites and successional groups. Drought strongly reduced An at warmer sites but not at the coolest montane site and this response was similar in both ES and LS species. Our results suggest that warming has negative effects on leaf-level photosynthesis in LS species, while both LS and ES species suffer photosynthesis declines in a warmer climate with more pronounced droughts. The contrasting responses of An between successional groups may lead to shifts in species’ competitive balance in a warmer world, to the disadvantage of LS trees.

The response of tropical trees and tree communities to climate change is crucial for the carbon storage and biodiversity of the terrestrial biosphere. Trees in tropical montane rainforests (TMFs) are considered particularly vulnerable to climate change, but this hypothesis remains poorly evaluated due to data scarcity. To reduce the knowledge gap on the response of TMFs trees to warming, we established a field experiment along a 1300–2400 m elevation gradient in Rwanda. Twenty tree species native to montane forests in East and Central Africa were planted in multispecies plots at three sites along the gradient. They have overlapping distributions but primarily occur in either transitional rainforest (1600–2000 m a.s.l) or mid elevation TMF (2000–3000 m a.s.l.), with both early- (ES) and late-successional (LS) species represented in each elevation origin group. Tree growth (diameter and height) and survival were monitored regularly over two years. We found that ES species, especially from lower elevations, grew faster at warmer sites while several of the LS species, especially from higher elevations, did not respond or grew slower. Moreover, a warmer climate increased tree mortality in LS species, but not much in ES species. ES species with transitional rainforest origin strongly increased in proportion of stand basal area at warmer sites, while TMF species declined, suggesting that lower-elevation ES species will have an advantage over higher-elevation species in a warming climate. The risk of higher-elevation and LS species to become outcompeted by lower-elevation and ES species in a warmer climate has important implications for biodiversity and carbon storage of Afromontane forests.

Boreal forests undergo a strong seasonal photosynthetic cycle; however, the underlying processes remain incompletely characterised. Here, we present a novel analysis of the seasonal diffusional and biochemical limits to photosynthesis (Anet ) relative to temperature and light limitations in high-latitude mature Pinus sylvestris, including a high-resolution analysis of the seasonality of mesophyll conductance (gm ) and its effect on the estimation of carboxylation capacity (VCmax ). We used a custom-built gas-exchange system coupled to a carbon isotope analyser to obtain continuous measurements for the estimation of the relevant shoot gas-exchange parameters, and quantified the biochemical and diffusional controls alongside the environmental controls over Anet . The seasonality of Anet was strongly dependent on VCmax and the diffusional limitations. Stomatal limitation was low in spring and fall but increased to 31% in June. In contrast, mesophyll limitation was nearly constant (19%). We found that VCmax limited Anet in the spring, while daily temperatures and the gradual reduction of light availability limited Anet in the autumn, despite relatively high VCmax . We describe for the first time the role of mesophyll conductance in connection with seasonal trends in net photosynthesis of P. sylvestris, revealing a strong coordination between gm and Anet , but not between gm and gs .

Warming climate increases the risk for harmful leaf temperatures in terrestrial plants, causing heat stress and loss of productivity. The heat sensitivity may be particularly high in equatorial tropical tree species adapted to a thermally stable climate. Thermal thresholds of the photosynthetic system of sun-exposed leaves were investigated in three tropical montane tree species native to Rwanda with different growth and water use strategies (Harungana montana, Syzygium guineense and Entandrophragma exselsum). Measurements of chlorophyll fluorescence, leaf gas exchange, morphology, chemistry and temperature were made at three common gardens along an elevation/temperature gradient. Heat tolerance acclimated to maximum leaf temperature (Tleaf ) across the species. At the warmest sites, the thermal threshold for normal function of photosystem II was exceeded in the species with the highest Tleaf despite their higher heat tolerance. This was not the case in the species with the highest transpiration rates and lowest Tleaf . The results point to two differently effective strategies for managing thermal stress: tolerance through physiological adjustment of leaf osmolality and thylakoid membrane lipid composition, or avoidance through morphological adaptation and transpiratory cooling. More severe photosynthetic heat stress in low-transpiring montane climax species may result in a competitive disadvantage compared to high-transpiring pioneer species with more efficient leaf cooling.

Purpose The aim of this study was to assess the feasibility and safety of a novel IPOM procedure with peritoneal bridging (IPOM-pb) for laparoscopic ventral hernia repair, and to compare the outcomes of this procedure with IPOM with- (IPOM-plus) and IPOM without (sIPOM) defect closure. Method A single-centre retrospective study comparing a novel IPOM technique with peritoneal bridging (IPOM-pb) with the two commonly used IPOM techniques, IPOM with defect closure (IPOM-plus) and without defect closure (sIPOM). The intraoperative and postoperative data of patients who underwent laparoscopic IPOM ventral hernia repair were reviewed. Preoperative data, recurrence, and postoperative seroma, surgical site infection, and pain, were compared. Results From January 2017 to June 2020, a total of 213 patients underwent laparoscopic ventral and incisional hernia repair with IPOM technique. The mean length and width of the ventral hernia was 4.4 ± 1.8 cm and 3.6 ± 1.4 cm, respectively, and the mean BMI was 30.1 ± 5.2 kg/m2. The mean operating time was 67 ± 28 min and was longer for IPOM-pb (71 ± 27 min), less for IPOM-plus (63 ± 28 min), and least for sIPOM (61 ± 26 min). The incidence of early postoperative seroma was least in IPOM-pb (1/98, 1%), and similar in the IPOM-plus (4/94, 4%) and sIPOM (1/21, 5%) group. Late postoperative seroma was found only in IPOM-plus (2, 2%). The incidence of early and late postoperative pain was relatively higher in sIPOM (3, 14%; 1, 5%, respectively) compared to IPOM-pb and IPOM-plus in the early (5, 5% and 6, 6%) and late (2, 2% and 1, 1%) postoperative period, respectively. Surgical site infection was higher in sIPOM group (3, 14%), compared to IPOM-pb (1, 1%), and IPOM-plus (3, 3%). Recurrence rates were similar in IPOM-pb group (3/98, 3%) and IPOM-plus (3/94, 3%), and none in sIPOM (0/21). Conclusion IPOM with peritoneal bridging is as feasible and safe as conventional IPOM with defect closure and simple non-defect closure. However, a large randomised controlled trial is required to confirm this finding.

Optimal stomatal theory predicts that stomata operate to maximise photosynthesis (A

Summary Tropical climates are getting warmer, with pronounced dry periods in large areas. The productivity and climate feedbacks of future tropical forests depend on the ability of trees to acclimate their physiological processes, such as leaf dark respiration (R d), to these new conditions. However, knowledge on this is currently limited due to data scarcity.We studied the impact of growth temperature on R d and its dependency on net photosynthesis (A n), leaf nitrogen (N) and phosphorus (P) contents, and leaf mass per unit area (LMA) in 16 early‐successional (ES) and late‐successional (LS) tropical tree species in multispecies plantations along an elevation gradient (Rwanda TREE project). Moreover, we explored the effect of drought on R d in one ES and one LS species.Leaf R d at 20°C decreased at warmer sites, regardless if it was expressed per unit leaf area, mass, N or P. This acclimation resulted in an 8% and a 28% decrease in R d at prevailing nighttime temperatures in trees at the intermediate and warmest sites, respectively. Moreover, drought reduced R d, particularly in the ES species and at the coolest site.Thermal acclimation of R d is complete or overcompensatory and independent of changes in leaf nutrients or LMA in African tropical trees.

Interpreting phloem carbohydrate or xylem tissue carbon isotopic composition as measures of water-use efficiency or past tree productivity requires in-depth knowledge of the factors altering the isotopic composition within the pathway from ambient air to phloem contents and tree ring. One of least understood of these factors is mesophyll conductance (g(m)). We formulated a dynamic model describing the leaf photosynthetic pathway including seven alternative g(m) descriptions and a simple transport of sugars from foliage down the trunk. We parameterised the model for a boreal Scots pine stand and compared simulated g(m) responses with weather variations. We further compared the simulated delta C-13 of new photosynthates among the different g(m) descriptions and against measured phloem sugar delta C-13. Simulated g(m) estimates of the seven descriptions varied according to weather conditions, resulting in varying estimates of phloem delta C-13 during cold/moist and warm/dry periods. The model succeeded in predicting a drought response and a postdrought release in phloem sugar delta C-13 indicating suitability of the model for inverse prediction of leaf processes from phloem isotopic composition. We suggest short-interval phloem sampling during and after extreme weather conditions to distinguish between mesophyll conductance drivers for future model development.

Background Many patients develop seroma after laparoscopic ventral hernia repair. It was hypothesized that leaving the hernial sac in situ may cause this complication. Methods In this patient‐ and outcome assessor‐blinded, parallel‐design single‐centre trial, patients undergoing laparoscopic intraperitoneal onlay mesh ventral hernia repair were randomized (1 : 1) to either conventional fascial closure or peritoneal bridging. The primary endpoint was the incidence of seroma 12 months after index surgery detected by CT, evaluated in an intention‐to‐treat analysis. Results Between September 2017 and May 2018, 62 patients were assessed for eligibility, of whom 25 were randomized to conventional closure and 25 to peritoneal bridging. At 3 months, one patient was lost to follow‐up in the conventional and peritoneal bridging groups respectively. No seroma was detected at 6 or 12 months in either group. The prevalence of clinical seroma was four of 25 (16 (95 per cent c.i. 2 to 30) per cent) versus none of 25 patients in the conventional fascial closure and peritoneal bridging groups respectively at 1 month after surgery (P = 0·110), and two of 24 (8 (0 to 19) per cent) versus none of 25 at 3 months (P = 0·235). There were no significant differences between the groups in other postoperative complications (one of 25 versus 0 of 25), rate of recurrent hernia within 1 year (none in either group) or postoperative pain. Conclusion Conventional fascial closure and peritoneal bridging did not differ with regard to seroma formation after laparoscopic ventral hernia repair. Trial registration: ClinicalTrials.gov (NCT03344575)., Fifty patients were enrolled and randomized to laparoscopic hernia repair with conventional fascial closure or a peritoneal bridging approach. Follow‐up by CT at 12 months (primary endpoint) revealed no seroma in either group, but seroma was detected clinically in the early postoperative period after 1 month (4 of 25 versus 0 of 25 patients in fascial closure and peritoneal bridging groups respectively) and 3 months (2 of 24 versus 0 of 25). The results suggest that peritoneal bridging is a safe and feasible alternative to conventional fascial closure, although larger studies are required to confirm this. No difference in seroma formation, complications or rate of recurrent hernia.

Leaf morphological traits vary along climate gradients, but it is currently unclear to what extent this results from acclimation rather than adaptation. Knowing so is important for predicting the functioning of long-lived organisms, such as trees, in a rapidly changing climate. We investigated the leaf morphological warming responses of 18 tropical tree species with early (ES) abd late (LS) successional strategies, planted at three sites along an elevation gradient from 2400 m a.s.l. (15.2 °C mean temperature) to 1300 m a.s.l. (20.6 °C mean temperature) in Rwanda. Leaf size expressed as leaf area (LA) and leaf mass per area (LMA) decreased, while leaf width-to-length ratio (W/L) increased with warming, but only for one third to half of the species. While LA decreased in ES species, but mostly not in LS species, changes in LMA and leaf W/L were common in both successional groups. ES species had lower LMA and higher LA and leaf W/L compared to LS species. Values of LMA and LA of juvenile trees in this study were mostly similar to corresponding data on four mature tree species in another elevation-gradient study in Rwanda, indicating that our results are applicable also to mature forest trees. We conclude that leaf morphological responses to warming differ greatly between both successional groups and individual species, with potential consequences for species competitiveness and community composition in a warmer climate.

Simple Summary Virchow's node metastasis (VM) refers to the involvement of the left supraclavicular lymph nodes at the junction of the thoracic duct and the left subclavian vein. Generally, VM is considered by clinicians to be a strong indicator of metastatic abdominal malignancy, and its dismal prognostic significance has previously been described in patients with metastatic gastric and ovarian cancer. To date, comprehensive descriptions of patients with small intestinal neuroendocrine tumors (SI-NETs) and rare metastatic manifestations, including that of VM, are sparse. In the present study from two tertiary referral centers, the prevalence of the VM secondary to SI-NET primaries was found to be 3.9%. VM was more often encountered in patients with higher-grade tumors and established disseminated disease to distant para-aortic lymph nodes. However, the presence of VM did not yield any negative prognostic impact in patient outcomes when compared to age- and sex-matched patients of similar grade with distant metastases confined in the abdomen Small intestinal neuroendocrine tumors (SI-NETs) may rarely metastasize to the left supraclavicular lymph nodes, also known as Virchow's node metastasis (VM). Data on prevalence, prognostic significance, and clinical course of disease for SI-NET patients with VM is limited. In this retrospective analysis of 230 SI-NET patients treated at two tertiary referral centers, we found nine patients with VM (prevalence 3.9%). Among those, there were 5 females and median age at SI-NET and VM diagnosis was 61 and 65 years, respectively. Two patients had G1 tumors and five G2, while two tumors were of unspecified grade (median Ki67: 7%, range 2-15%). Four patients presented with synchronous VM, whereas five developed metachronous VM after a median of twenty-four months (range: 4.8-117.6 months). Hepatic metastases were present in seven patients, extrahepatic metastases (EM) in eight (six para-aortic distant lymph node metastases, one lung and one pancreatic metastasis), whereas peritoneal carcinomatosis (PC) in two patients. We used a control group of 18 age- and sex-matched SI-NET patients from the same cohort with stage IV disease but no extra-abdominal metastases. There was no difference in best-recorded response to first line treatment according to RECIST 1.1 as well as progression-free survival (PFS) between patients with VM and those in the control group (Chi-square test p = 0.516; PFS 71.7 vs. 106.9 months [95% CI 38.1-175.8]; log-rank p = 0.855). In addition, median overall survival (OS) of SI-NET patients with VM did not differ from those in the control group (138.6 [95% CI 17.2-260] vs. 109.9 [95% CI 91.7-128] months; log-rank p = 0.533). In conclusion, VM, although relatively rare in patients with SI-NETs, is more often encountered in patients with G2 tumors and established distant para-aortic lymph node metastases. The presence of VM in SI-NET patients does not seem to impact patients' survival outcomes and treatment responses, when compared to age- and sex-matched SI-NET patients with stage IV disease confined in the abdomen.

Introduction The treatment strategies for a 42‐year‐old female index patient with moderate Graves’ disease (GD) vary according to several international surveys. The important question whether surveys of treatment preferences in theoretical patient cases also match how real patients are treated has not yet been addressed. Materials and Methods From a Swedish cohort of 1186 GD patients (TT‐12 cohort), 27 women were identified using the same criteria as from the index patient surveys from the European and American Thyroid Associations. This ‘index patient cohort’ was age 40–45, otherwise healthy female, with two children and uncomplicated GD. The applied first‐line treatment of the patients in the index cohort, together with its variations, was compared with the treatment preferences according to international surveys. A comparison with the TT‐12 cohort was also performed. Results In the ‘Index cohort’, 77.8% were treated with antithyroid drugs (ATD), and 22.2% were treated with radioiodine (131I). This preference for ATD is in line with most countries/regions, with the exception of USA and the Middle East/North Africa, where 131I was preferred. The distribution of treatment in the TT‐12 cohort did not significantly differ from the index cohort. ATD was the preferred treatment in male and young (age 19–22) patients, as was RAI in old (age 69–73) patients. The age‐related, but not the gender‐related, cases differed significantly from the entire TT‐12 cohort. Conclusion The treatment choice in an index patient in Sweden seems in line with European practice, where ATD is the preferred first choice. This differs compared to US and North African survey intentions, where 131I is more often used. Age more than gender influences the treatment choice of GD patients. This is, to our best knowledge, the first time an index patient from ‘real life’ has been presented and compared to treatment preferences of international thyroid association surveys., According to several international surveys, the treatment strategies for a 42‐year‐old female index patient with moderate Graves’ disease vary considerably. In this study, the correlation of treatment strategies between patients from the Swedish thyrotoxicosis 2012 study cohort, who met the criteria for the index patient and its variations, and the theoretical index patient in international surveys is examined and compared. This is in order to allow a reasonable comparison with and, if possible, to validate the international surveys.

The effect of temperature change on leaf physiology has been extensively studied in temperate trees and to some extent in boreal and tropical tree species. While increased temperature typically stimulates leaf CO2 assimilation and tree growth in high-altitude ecosystems, tropical species are often negatively affected. These trees may operate close to their temperature optima and have a limited thermal acclimation capacity due to low seasonal and historical variation in temperature. To test this hypothesis, we studied the extent to which the temperature sensitivities of leaf photosynthesis and respiration acclimate to growth temperature in four common African tropical tree species. Tree seedlings native to different altitudes and therefore adapted to different growth temperatures were cultivated at three different temperatures in climate-controlled chambers. We estimated the acclimation capacity of the temperature sensitivities of light-saturated net photosynthesis, the maximum rates of Rubisco carboxylation (Vcmax) and thylakoid electron transport (J), and dark respiration. Leaf thylakoid membrane lipid composition, nitrogen content and leaf mass per area were also analyzed. Our results showed that photosynthesis in tropical tree species acclimated to higher growth temperatures, but that this was weakest in the species originating from the coolest climate. The temperature optimum of J acclimated significantly in three species and variation in J was linked to changes in the thylakoid membrane lipid composition. For Vcmax, there was only evidence of significant acclimation of optimal temperature in the lowest elevation species. Respiration acclimated to maintain homeostasis at growth temperature in all four species. Our results suggest that the lowest elevation species is better physiologically adapted to acclimate to high growth temperatures than the highest elevation species, indicating a potential shift in competitive balance and tree community composition to the disadvantage of montane tree species in a warmer world.

Objective Rupture of abdominal aortic aneurysm (rAAA) with a contained retroperitoneal hematoma is potentially fatal. Physiological studies are difficult to perform in patients suffering from life-threatening conditions such as rAAA. A translational model of the condition is therefore needed. The aim was to develop and validate an endovascular animal model for retroperitoneal bleeding of the abdominal aorta with contained hematoma. Methods In anesthetized pigs, a puncture hole was made in the posterolateral portion of the infrarenal aorta by an Outback re-entry catheter device. The hole was gradually enlarged using angioplasty balloons to a specific diameter of either 4 mm ( n = 6), 6 mm ( n = 7), or 8 mm ( n = 6). Onset of bleeding was verified by angiography and macroscopically examined on completion of the experiments. Survival up to 180 min was the primary outcome. Hemodynamic and metabolic markers in arterial blood were secondary outcomes. Results Aortic injury with a contained retroperitoneal hematoma was achieved in all animals. Survival rate at 180 min after onset of bleeding was higher in the 4 mm group compared to the 6 mm ( P = 0.021) and 8 mm groups ( P = 0.002), but not when comparing the 6 mm and 8 mm groups. Systemic hypotension, arterial acidosis, and lactatemia were provoked in the 6 mm and 8 mm groups but not in the 4 mm group. Conclusions A porcine model for a controlled contained left posterolateral retroperitoneal bleeding was created using endovascular methods and validated. This model makes it possible to study the pathophysiology of a retroperitoneal hematoma.

The growing detection of papillary thyroid microcarcinomas (PTMCs) is paralleled by an increase in surgical procedures. Due to the frequent indolent nature, cost, and risk of surgery, active surveillance (AS) and ultrasound-guided minimally invasive treatments (MITs) are in suitable cases of incidental PTMC proposed as alternatives to thyroidectomy. Surgery and radioiodine are the established treatments for relapsing cervical differentiated thyroid carcinoma (DTC) metastases. But radioiodine refractoriness, risk of surgical complications, adverse influence on quality of life, or declining repeat surgery have led to AS and MIT being considered as alternatives for slow-growing DTC nodal metastases. Also, for distant radioiodine-refractory metastases not amenable to surgery, MIT is proposed as part of a multimodality therapeutic approach. The European Thyroid Association and the Cardiovascular and Interventional Radiological Society of Europe commissioned these guidelines for the appropriate use of MIT. Based on a systematic PubMed search, an evidence-based approach was applied, and both knowledge and practical experience of the panelists were incorporated to develop the manuscript and the specific recommendations. We recommend that when weighing between surgery, radioiodine, AS, or MIT for DTC, a multidisciplinary team including members with expertise in interventional radiology assess the demographic, clinical, histological, and imaging characteristics for appropriate selection of patients eligible for MIT. Consider TA in low-risk PTMC patients who are at surgical risk, have short life expectancy, relevant comorbidities, or are unwilling to undergo surgery or AS. As laser ablation, radiofrequency ablation, and microwave ablation are similarly safe and effective thermal ablation (TA) techniques, the choice should be based on the specific competences and resources of the centers. Use of ethanol ablation and high-intensity focused ultrasound is not recommended for PTMC treatment. Consider MIT as an alternative to surgical neck dissection in patients with radioiodine refractory cervical recurrences who are at surgical risk or decline further surgery. Factors that favor MIT are previous neck dissection, presence of surgical complications, small size metastases, and

Rates of net photosynthesis were measured on Norway spruce, Picea abies (L.) Karst. exposed to three different concentrations of ozone for three seasons (1985-7) in open-top chambers. The treatments were non-filtered air + ozone (NF +), non-filtered air (NF) and charcoal-filtered air (CF). Ozone was added daily between 11.00-18.00 local time. The study was performed during September and October, 1987. The rate of net photosynthesis was determined using an infrared gas analyser (IRGA) connected to a small cuvette, which was equipped with an artificial light source for unilateral illumination. The measurements were made on shoots of three different age classes: current year, 1 year old and 2 years old. Measurements took place at saturating light intensity (1150 μmol m1 s1 ), at a temperature of 16.6 ±0.7°C, and at a relative humidity of 67.5 ± 5.3%. In current-year shoots the rate of net photosynthesis expressed on a needle-area basis was lowest in the CF treatment and highest in the NF treatment. In 1- and 2-year-old shoots, a decreased rate of the net photosynthetic assimilation rate, expressed on a needle area basis, was observed in trees from the NF and NF+ treatment compared with that of trees from the CF treatment. The effect increased with increasing ozone concentration and shoot age. A significant increase in the rate of respiration, expressed on a dry-weight basis, was observed in current year shoots from trees exposed to NF+. A significant decrease of the leaf conductance to carbon dioxide was obtained in 2-year-old shoots exposed to NF and NF+. A decrease in the content of chlorophyll was observed in 1- and 2-year-old needles from trees exposed to NF+.

Simple Summary Functional imaging with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has evolved into a major clinical tool in cancer diagnosis and management for many malignancies in diverse clinical settings, providing valuable information on tumor behavior and aggressiveness. In the field of neuroendocrine tumors (NETs), recent advances in molecular imaging and targeted treatments with novel theranostic agents favor a more patient-tailored approach. Although peptide receptor radionuclide therapy (PRRT) has recently become an established therapy for progressive NETs, the role of 18F-FDG PET prior to PRRT in patients with NETs of different origins and grades remains to be determined. Herein, we provide a comprehensive summary of available evidence in contemporary literature by means of a systematic review and meta-analysis, demonstrating that dual-functional imaging with 68Ga-DOTA-peptides and 18F-FDG prior to PRRT appears to be a useful tool in NET management by delineating tumor somatostatin receptor expression and glycolytic metabolic activity, and predicting tumor response and survival outcomes. Abstract The role of 18F-FDG PET in patients with variable grades of neuroendocrine tumors (NETs) prior to peptide receptor radionuclide therapy (PRRT) has not been adequately elucidated. We aimed to evaluate the impact of 18F-FDG PET status on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in neuroendocrine tumor (NET) patients receiving PRRT. We searched the MEDLINE, Embase, Cochrane Library, and Web of Science databases up to July 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5091 articles were screened. In 12 studies, 1492 unique patients with NETs of different origins were included. The DCR for patients with negative 18F-FDG PET status prior to PRRT initiation was 91.9%, compared to 74.2% in patients with positive 18F-FDG PET status (random effects odds ratio (OR): 4.85; 95% CI: 2.27–10.36). Adjusted analysis of pooled hazard ratios (HRs) confirmed longer PFS and OS in NET patients receiving PRRT with negative 18F-FDG PET (random effects HR:2.45; 95%CIs: 1.48–4.04 and HR:2.25; 95% CIs:1.55–3.28, respectively). In conclusion, 18F-FDG PET imaging prior to PRRT administration appears to be a useful tool in NET patients to predict tumor response and survival outcomes and a negative FDG uptake of the tumor is associated with prolonged PFS and OS.

Boreal regions are undergoing rapid climate change but our understanding of the long-term consequences for forest processes is hampered by limited knowledge of how trees acclimate to rising atmospheric CO2 concentrations and temperature. This study used the detailed canopy flux model MAESTRA to simulate the effects of elevated CO2 (eCO2) and warming on net photosynthesis (An) and transpiration (E) of mature boreal Norway spruce, investigating how these effects are influenced by the observed acclimation of photosynthetic capacity, respiration, stomatal behavior, and phenology. Without any type of acclimation, eCO2 increased shoot and crown An during the non-frost growing season by 23-44%, while warming only had a minor effect (±2%). Photosynthetic downregulation greatly decreased the positive effect under eCO2. Under warming, both stomatal and phenological acclimation had substantial effects on An but in opposite directions. Transpiration at shoot and crown level was greatly decreased (23-50%) by eCO2 and increased by warming (27-42%) in the absence of acclimation. However, both these effects were largely cancelled by stomatal acclimation. Effects of eCO2 on An were generally smaller at entire crown compared to shoot level, as a result of photosynthetic stimulation being smaller in shaded canopy positions. In addition, upregulation of respiration in eCO2 had a considerably larger negative effect on An at crown compared to shoot level. Overall, tree physiological acclimation generally acted to dampen non-acclimated responses. We conclude that photosynthetic and respiratory acclimation greatly reduce the positive effect of eCO2 on tree CO2 assimilation, while stomatal and phenological acclimation are crucial for annual water consumption under warming. These results highlight the critical need to account for acclimation in models.

Background: Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs. Methods: At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques. Results: Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake. Conclusion: This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.

The temperature sensitivity of physiological processes and growth of tropical trees remains a key uncertainty in predicting how tropical forests will adjust to future climates. In particular, our knowledge regarding warming responses of photosynthesis, and its underlying biochemical mechanisms, is very limited. We grew seedlings of two tropical montane rainforest tree species, the early-successional species Harungana montana and the late-successional species Syzygium guineense, at three different sites along an elevation gradient, differing by 6.8℃ in daytime ambient air temperature. Their physiological and growth performance was investigated at each site. The optimum temperature of net photosynthesis (ToptA ) did not significantly increase in warm-grown trees in either species. Similarly, the thermal optima (ToptV and ToptJ ) and activation energies (EaV and EaJ ) of maximum Rubisco carboxylation capacity (Vcmax ) and maximum electron transport rate (Jmax ) were largely unaffected by warming. However, Vcmax , Jmax and foliar dark respiration (Rd ) at 25℃ were significantly reduced by warming in both species, and this decline was partly associated with concomitant reduction in total leaf nitrogen content. The ratio of Jmax /Vcmax decreased with increasing leaf temperature for both species, but the ratio at 25℃ was constant across sites. Furthermore, in H. montana, stomatal conductance at 25℃ remained constant across the different temperature treatments, while in S. guineense it increased with warming. Total dry biomass increased with warming in H. montana but remained constant in S. guineense. The biomass allocated to roots, stem and leaves was not affected by warming in H. montana, whereas the biomass allocated to roots significantly increased in S. guineense. Overall, our findings show that in these two tropical montane rainforest tree species, the capacity to acclimate the thermal optimum of photosynthesis is limited while warming-induced reductions in respiration and photosynthetic capacity rates are tightly coupled and linked to responses of leaf nitrogen.

Our aim was to investigate the clinical utility of serum 5HIAA for disease surveillance and diagnostic purposes in a cohort of patients with well-differentiated neuroendocrine neoplasms (WD-NENs). Forty-eight patients with WD-NENs and concurrent serum and urinary 5HIAA testing, as well as CT/MRI imaging, were included. Analysis of matching-pairs did not reveal any association between RECIST 1.1 responses and changes in serum 5HIAA levels (p = 0.673). In addition, no correlation was evident between RECIST 1.1 responses and &gt, 10%, &gt, 25% or &gt, 50% changes in serum 5HIAA levels (Fisher&rsquo, s exact test p = 0.380, p &gt, 0.999, and p &gt, 0.999, respectively). The presence of liver metastases and extensive liver tumor involvement were associated with higher serum 5HIAA levels (p = 0.045 and p = 0.041, respectively). We also confirmed a strong linear correlation between the measurements of serum and urine 5HIAA (n = 24, r = 0.791, p &lt, 0.0001). The concordance rate of serum and urinary 5HIAA positivity at standardized laboratory cut-offs was 75%. In patients with normal renal function tests, the concordance between the two methods was as high as 89%, and a sensitivity and specificity of 80% and 88.9%, respectively, was evident (Cohen&rsquo, s kappa coefficient = 0.685). In conclusion, serum 5HIAA performs well compared to urinary testing for diagnostic purposes, mainly in advanced disease stages, and corresponds well to liver tumor burden. However, it is not adequate to predict tumor progression.

International audience; Differences in photosynthetic capacity among tree species and tree functional types are currently assumed to be largely driven by variation in leaf nutrient content, particularly nitrogen (N). However, recent studies indicate that leaf N content is often a poor predictor of variation in photosynthetic capacity in tropical trees. In this study, we explored the relative importance of area-based total leaf N content (N tot) and within-leaf N allocation to photosynthetic capacity versus light-harvesting in controlling the variation in photosynthetic capacity (i.e. V cmax , J max) among mature trees of 12 species belonging to either early (ES) or late successional (LS) groups growing in a tropical montane rainforest in Rwanda, Central Africa. Photosynthetic capacity at a common leaf temperature of 25˚C (i.e. maximum rates of Rubisco carboxylation, V cmax25 and of electron transport, J max25) was higher in ES than in LS species (+ 58% and 68% for V cmax25 and J max25 , respectively). While N tot did not significantly differ between successional groups, the photosynthetic dependency on N tot was markedly different. In ES species, V cmax25 was strongly and positively related to N tot but this was not the case in LS species. However, there was no significant trade-off between relative leaf N investments in compounds maximizing photosynthetic capacity versus compounds maximizing light harvesting. Both leaf dark respiration at 25˚C (+ 33%) and, more surprisingly, apparent photosynthetic quantum yield (+ 35%) was higher in ES than in LS species. Moreover, R d25 was positively related to N tot for both ES and LS species. Our results imply that efforts to quantify carbon fluxes of tropical montane rainforests would be improved if they considered contrasting within-leaf N allocation and photosynthetic N tot dependencies between species with different successional strategies.

ObjectiveColon cancer surgery remains associated with substantial postoperative morbidity and mortality despite advances in surgical techniques and care. The trauma of surgery triggers adrenergic hyperactivation which drives adverse stress responses. We hypothesised that outcome benefits are gained by reducing the effects of hyperadrenergic activity with beta-blocker therapy in patients undergoing colon cancer surgery. This study aims to test this hypothesis.DesignRetrospective cohort study.Setting and participantsThis is a nationwide study which includes all adult patients undergoing elective colon cancer surgery in Sweden over 10 years. Patient data were collected from the Swedish Colorectal Cancer Registry. The national drugs registry was used to obtain information about beta-blocker use. Patients were subdivided into exposed and unexposed groups. The association between beta-blockade, short-term and long-term mortality was evaluated using Poisson regression, Kaplan-Meier curves and Cox regression.Primary and secondary outcomesPrimary outcome of interest was 1-year all-cause mortality. Secondary outcomes included 90-day all-cause and 5-year cancer-specific mortality.ResultsThe study included 22 337 patients of whom 36.1% were prescribed preoperative beta-blockers. Survival was higher in patients on beta-blockers up to 1 year after surgery despite this group being significantly older and of higher comorbidity. Regression analysis demonstrated significant reductions in 90-day deaths (IRR 0.29, 95% CI 0.24 to 0.35, pConclusionPreoperative beta-blockade is associated with significant reductions in postoperative short-term and long-term mortality following elective colon cancer surgery. Its potential prophylactic effect warrants further interventional studies to determine whether beta-blockade can be used as a way of improving outcomes for this patient group.

Mesenteric fibrosis (MF) constitutes an underrecognized sequela in patients with small intestinal neuroendocrine neoplasms (SI-NENs), often complicating the disease clinical course. The aim of the present systematic review, carried out by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, is to provide an update in evolving aspects of MF pathogenesis and its clinical management in SI-NENs. Complex and dynamic interactions are present in the microenvironment of tumor deposits in the mesentery. Serotonin, as well as the signaling pathways of certain growth factors play a pivotal, yet not fully elucidated role in the pathogenesis of MF. Clinically, MF often results in significant morbidity by causing either acute complications, such as intestinal obstruction and/or acute ischemia or more chronic conditions involving abdominal pain, venous stasis, malabsorption and malnutrition. Surgical resection in patients with locoregional disease only or symptomatic distant stage disease, as well as palliative minimally invasive interventions in advanced inoperable cases seem clinically meaningful, whereas currently available systemic and/or targeted treatments do not unequivocally affect the development of MF in SI-NENs. Increased awareness and improved understanding of the molecular pathogenesis of MF in SI-NENs may provide better diagnostic and predictive tools for its timely recognition and intervention and also facilitates the development of agents targeting MF.

Global models of photosynthesis commonly use photosynthetic capacity parameters (Vcmax, Jmax) that are estimated based on Ci, the intercellular CO2 concentration. The underlying assumption of these models is that mesophyll conductance (gm) is infinite and therefore the CO2 concentration at the site of carboxylation (Cc) is equal to Ci, despite a growing body of literature acknowledging that these assumptions are incorrect. Because relatively few studies on gm have been conducted under natural conditions and with high enough resolution, it is currently unclear how significant the assumption of infinite Cc is for the accuracy of long-term predictions by large-scale photosynthesis models. In this study we investigated this question with data collected in a mature Scots pine stand, one of the dominant species of the boreal region. We conducted high-resolution gas-exchange and online 13C discrimination measurements over a whole growing season (May-October), and analysed the relative contribution of diffusional and biochemical limitations to photosynthesis. We hypothesised that diffusional limitation will be significant in this species, as conifers typically have low stomatal and mesophyll conductance (gs and gm respectively). Accordingly, we found that diffusional limitations were similar or stronger than biochemical limitation during May-July, and that all limitations reached minima around the end of June when Anet values were highest. However, during August-October biochemical limitation became increasingly dominant, as the diffusional limitations were relatively small and stable. Over the whole period, both gm and the relative mesophyll limitation were similar in magnitude to gs and the stomatal limitation, respectively, resulting in a 40-100 ppm reduction in CO2 concentration between Ci and Cc. This meant that Vcmax was under-estimated by 20-40% when calculated from Cicompared to Cc, highlighting the importance of accounting for the finite gm when determining photosynthetic capacity and modelling photosynthesis under natural conditions.

Several studies have suggested that CO2 transport in the transpiration stream can considerably bias estimates of root and stem respiration in ring-porous and diffuse-porous tree species. Whether this also happens in species with tracheid xylem anatomy and lower sap flow rates, such as conifers, is currently unclear. We infused 13C-labelled solution into the xylem near the base of two 90-year-old Pinus sylvestris L. trees. A custom-built gas exchange system and an online isotopic analyser were used to sample the CO2 efflux and its isotopic composition continuously from four positions along the bole and one upper canopy shoot in each tree. Phloem and needle tissue 13C enrichment was also evaluated at these positions. Most of the 13C label was lost by diffusion within a few metres of the infusion point indicating rapid CO2 loss during vertical xylem transport. No 13C enrichment was detected in the upper bole needle tissues. Furthermore, mass balance calculations showed that c. 97% of the locally respired CO2 diffused radially to the atmosphere. Our results support the notion that xylem CO2 transport is of limited magnitude in conifers. This implies that the concerns that stem transport of CO2 derived from root respiration biases chamber-based estimates of forest carbon cycling may be unwarranted for mature conifer stands.

The role of primary tumor resection in patients with pancreatic neuroendocrine neoplasms (PanNENs) and unresectable distant metastases remains controversial. We aimed to evaluate the effect of palliative primary tumor resection (PPTR) on overall survival (OS) in this setting. We searched the MEDLINE, Embase, Cochrane Library, Web of Science and SCOPUS databases up to January 2020 and used the Newcastle–Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5661 articles were screened. In 10 studies, 5551 unique patients with stage IV PanNEN and unresectable metastases were included. The five-year OS for PanNEN patients undergoing PPTR in stage IV was 56.6% vs. 23.9% in the non-surgically treated patients (random effects relative risk (RR): 1.70; 95% CI: 1.53–1.89). Adjusted analysis of pooled hazard ratios (HR) confirmed longer OS in PanNEN patients undergoing PPTR (random effects HR: 2.67; 95% CI: 2.24–3.18). Cumulative OS analysis confirmed an attenuated survival benefit over time. The complication rate of PPTR was as high as 27%. In conclusion, PPTR may exert a survival benefit in stage IV PanNEN. However, the included studies were subject to selection bias, and special consideration should be given to PPTR anchored to a multimodal treatment strategy. Further longitudinal studies are warranted, with long-term follow-up addressing the survival outcomes associated with surgery in stage IV disease.

The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category. Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed. Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31–35 years (52.1%, 95% confidence interval (CI) 37.9–66.2%), aged 36–40 years (55.9%, 95% CI 39.2–72.6%) and aged 41–45 years (46.9%, 95% CI 33–60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males. These data demonstrate that Bethesda categories 1–4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.

Trees have the potential to improve urban air quality as leaves and needles capture air pollutants from the air, but further empirical data has been requested to quantify these effects. We measured the concentration of 32 poly-cyclic aromatic hydrocarbons (PAHs) in leaves of pin oak (Quercus palustris) and needles of black pine (Pinus nigra) in the City of Gothenburg, Sweden, during the summer of 2018. Oak leaves were collected twice (June, Sep-tember), while one-year-old (C + 1) and three-year-old (C + 3) pine needles were sampled in June to study the temporal development of leaf/needle PAH concentrations. Specific leaf area (SLA) was estimated, which permit-ted calculation of leaf/needle area-based PAH content that were compared with the mass-based concentration. In addition, the air concentration of PAHs and NO2 was measured using passive samplers. There was a strong correlation between air concentrations of PAH and NO2, indicating that the pollutants to a large degree originate from the same sources. In the oak leaves there was a significant decrease in low molecular mass PAHs (L-PAH, mainly gaseous) between June and September, but a significant increase in high molecular mass PAHs (H-PAH, mainly particle-bound). There was a strong correlation between L-PAH concentration in leaves and in air indicating an influence of equilibrium processes between ambient air and leaf. In the pine needles, there was a significant increase of both L-PAH and H-PAH in three-year-old needles compared to one-year-old needles. Pine was superior to oak in accumulating PAHs from the air, especially for L-PAHs when comparing area-based content. However, H-PAH concentrations were higher in oak leaves compared to pine needles on a leaf mass basis, emphasizing the importance of how concentrations are expressed. The results from this study can contribute to the development of urban planning strategies regarding the effect of vegetation on air quality. (C) 2021 The Authors. Published by Elsevier B.V.

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)