Long-term risk factors of recurrent stroke, myocardial infarction and death in patients leaving hospital with a diagnosis of ischemic stroke or TIA.

Objectives. The prevalence of patients with prior stroke is increasing globally. Accordingly, there is a need for up-to-date evidence of patient-related prognostic factors for stroke recurrence, post stroke myocardial infarction (MI) and death based on long-term follow-up of stroke survivors. For this purpose, the RIALTO study was established in 2004. Design. A prospective cohort study in which patients diagnosed with ischemic stroke (IS) or transient ischemic attack (TIA) in three Copenhagen hospitals were included. Data were collected from medical records and by structured interview. Data on first stroke recurrence, first MI and all-cause death were extracted from the Danish National Patient Registry and the Danish Civil Registration System. Results. We included 1215 patients discharged after IS or TIA who were followed up by register data from April 2004 to end of 2018 giving a median follow-up of 3.5-6.9 years depending on the outcome. At the end of follow-up 406 (33%) patients had been admitted with a recurrent stroke, 100 (8%) had a MI and 822 (68%) had died. Long-term prognostic predictors included body mass index, diabetes, antihypertensive and lipid lowering treatment, smoking, a sedentary lifestyle as well as poor self-rated health and psychosocial problems. Conclusions. Long-term risk of recurrent stroke and MI remain high in patients discharged with IS or TIA despite substantial improvements in tertiary preventive care in recent decades. Continued attention to the patient risk profile among patients surviving the early phase of stroke, including comorbidities, lifestyle, and psychosocial challenges, is warranted.

Are self-reported and self-monitored adherence good proxies for reaching relevant plasma concentrations?: Experiences from a study of anti-depressants in healthy volunteers.

BACKGROUND: The use of electronic-based devices to measure and to improve adherence of subjects in clinical trials is increasing. AiCure has developed a mobile technology that is claimed to provide visual confirmation of drug ingestion. While there is evidence suggesting that including such self-monitoring device in a study increases adherence, the quality of the data produced by the device may be questionable. Can the mobile technology reliably distinguish whether a subject takes the study drug or not? METHODS: Adherence was calculated based on exposure, self-reporting and self-monitoring for subjects randomized to an anti-depressant. Levels of adherence and agreement between the three approaches were investigated based on calculation of proportions, two-way tables and receiver operating curves. RESULTS: A total of 214 subjects had measured concentrations of study drug at all three time points (end of weeks 3, 4 and 5), along with adherence data to define proportion of days adherent based on self-reporting and the self-monitoring instrument developed by AiCure. Self-reported adherence proportions were higher than self-monitored adherence proportions, although both were high (>90%). Neither self-reported and self-monitored adherence agreed with exposure-based adherence. CONCLUSION: Both self-reported and self-monitored adherence overestimated adherence. Neither the self-reported nor the self-monitored adherence measure reflected subjects' actual adherence. This prompts for cautiousness when interpreting either of them, and it underlines the need for thorough validation of electronic devices and software that claims to measure adherence. The AiCure instrument may not be able to reliably determine whether the subjects swallow the study medication.

Rainfall manipulation experiments as simulated by terrestrial biosphere models: Where do we stand?

Changes in rainfall amounts and patterns have been observed and are expected to continue in the near future with potentially significant ecological and societal consequences. Modelling vegetation responses to changes in rainfall is thus crucial to project water and carbon cycles in the future. In this study, we present the results of a new model-data intercomparison project, where we tested the ability of 10 terrestrial biosphere models to reproduce the observed sensitivity of ecosystem productivity to rainfall changes at 10 sites across the globe, in nine of which, rainfall exclusion and/or irrigation experiments had been performed. The key results are as follows: (a) Inter-model variation is generally large and model agreement varies with timescales. In severely water-limited sites, models only agree on the interannual variability of evapotranspiration and to a smaller extent on gross primary productivity. In more mesic sites, model agreement for both water and carbon fluxes is typically higher on fine (daily-monthly) timescales and reduces on longer (seasonal-annual) scales. (b) Models on average overestimate the relationship between ecosystem productivity and mean rainfall amounts across sites (in space) and have a low capacity in reproducing the temporal (interannual) sensitivity of vegetation productivity to annual rainfall at a given site, even though observation uncertainty is comparable to inter-model variability. (c) Most models reproduced the sign of the observed patterns in productivity changes in rainfall manipulation experiments but had a low capacity in reproducing the observed magnitude of productivity changes. Models better reproduced the observed productivity responses due to rainfall exclusion than addition. (d) All models attribute ecosystem productivity changes to the intensity of vegetation stress and peak leaf area, whereas the impact of the change in growing season length is negligible. The relative contribution of the peak leaf area and vegetation stress intensity was highly variable among models.

Bronchoscopic mucosal cryobiopsies as a method for studying airway disease.

BACKGROUND: Investigating disease mechanisms and treatment responses in obstructive airway diseases with invasive sampling are hampered by the small size and mechanical artefacts that conventional forceps biopsies suffer from. Endoscopic cryobiopsies are larger and more intact and are being increasingly used. However, the technique has not yet been explored for obtaining mucosa biopsies. OBJECTIVE: To investigate differences in size and quality of endobronchial mucosal biopsies obtained with cryotechnique and forceps. Further, to check for eligibility of cryobiopsies to be evaluated with immunohistochemistry and in situ hybridization and to investigate tolerability and safety of the technique. METHODS: Endobronchial mucosal biopsies were obtained with cryotechnique and forceps from patients with haemoptysis undergoing bronchoscopy and evaluated by quantitative morphometry, automated immunohistochemistry and in situ hybridization. RESULTS: A total of 40 biopsies were obtained from 10 patients. Cross-sectional areas were threefold larger in cryobiopsies (median: 3.08 mm2 (IQR: 1.79) vs 1.03 mm2 (IQR: 1.10), P < 0.001). Stretches of intact epithelium were 8-fold longer (median: 4.61 mm (IQR: 4.50) vs 0.55 mm (IQR: 1.23), P = 0.001). Content of glands (median: 0.095 mm2 (IQR: 0.30) vs 0.00 mm2 (IQR: 0.01), P = 0.002) and airway smooth muscle (median: 0.25 mm2 (IQR: 0.30) vs 0.060 mm2 (IQR: 0.11), P = 0.02) was higher in the cryobiopsies compared with forceps biopsies. Further, the cryobiopsies had well-preserved protein antigens and mRNA. Mild to moderate bleeding was the only complication observed. CONCLUSION AND CLINICAL RELEVANCE: By yielding significantly larger and more intact biopsies, the cryotechnique represents a valuable new research tool to explore the bronchi in airway disease. Ultimately with the potential to create better understanding of underlying disease mechanisms and improvement of treatments.

Accumulation of soil carbon under elevated CO2 unaffected by warming and drought.

Elevated atmospheric CO2 concentration and climate change may substantially alter soil carbon (C) dynamics, which in turn may impact future climate through feedback cycles. However, only very few field experiments worldwide have combined elevated CO2 (eCO2 ) with both warming and changes in precipitation in order to study the potential combined effects of changes in these fundamental drivers of C cycling in ecosystems. We exposed a temperate heath/grassland to eCO2 , warming, and drought, in all combinations for 8 years. At the end of the study, soil C stocks were on average 0.927 kg C/m2 higher across all treatment combinations with eCO2 compared to ambient CO2 treatments (equal to an increase of 0.120 ± 0.043 kg C m-2  year-1 ), and showed no sign of slowed accumulation over time. However, if observed pretreatment differences in soil C are taken into account, the annual rate of increase caused by eCO2 may be as high as 0.177 ± 0.070 kg C m-2  year-1 . Furthermore, the response to eCO2 was not affected by simultaneous exposure to warming and drought. The robust increase in soil C under eCO2 observed here, even when combined with other climate change factors, suggests that there is continued and strong potential for enhanced soil carbon sequestration in some ecosystems to mitigate increasing atmospheric CO2 concentrations under future climate conditions. The feedback between land C and climate remains one of the largest sources of uncertainty in future climate projections, yet experimental data under simulated future climate, and especially including combined changes, are still scarce. Globally coordinated and distributed experiments with long-term measurements of changes in soil C in response to the three major climate change-related global changes, eCO2 , warming, and changes in precipitation patterns, are, therefore, urgently needed.

Temperature response of soil respiration largely unaltered with experimental warming.

The respiratory release of carbon dioxide (CO2) from soil is a major yet poorly understood flux in the global carbon cycle. Climatic warming is hypothesized to increase rates of soil respiration, potentially fueling further increases in global temperatures. However, despite considerable scientific attention in recent decades, the overall response of soil respiration to anticipated climatic warming remains unclear. We synthesize the largest global dataset to date of soil respiration, moisture, and temperature measurements, totaling >3,800 observations representing 27 temperature manipulation studies, spanning nine biomes and over 2 decades of warming. Our analysis reveals no significant differences in the temperature sensitivity of soil respiration between control and warmed plots in all biomes, with the exception of deserts and boreal forests. Thus, our data provide limited evidence of acclimation of soil respiration to experimental warming in several major biome types, contrary to the results from multiple single-site studies. Moreover, across all nondesert biomes, respiration rates with and without experimental warming follow a Gaussian response, increasing with soil temperature up to a threshold of ∼25 °C, above which respiration rates decrease with further increases in temperature. This consistent decrease in temperature sensitivity at higher temperatures demonstrates that rising global temperatures may result in regionally variable responses in soil respiration, with colder climates being considerably more responsive to increased ambient temperatures compared with warmer regions. Our analysis adds a unique cross-biome perspective on the temperature response of soil respiration, information critical to improving our mechanistic understanding of how soil carbon dynamics change with climatic warming.

To replicate, or not to replicate - that is the question: how to tackle nonlinear responses in ecological experiments.

A fundamental challenge in experimental ecology is to capture nonlinearities of ecological responses to interacting environmental drivers. Here, we demonstrate that gradient designs outperform replicated designs for detecting and quantifying nonlinear responses. We report the results of (1) multiple computer simulations and (2) two purpose-designed empirical experiments. The findings consistently revealed that unreplicated sampling at a maximum number of sampling locations maximised prediction success (i.e. the R² to the known truth) irrespective of the amount of stochasticity and the underlying response surfaces, including combinations of two linear, unimodal or saturating drivers. For the two empirical experiments, the same pattern was found, with gradient designs outperforming replicated designs in revealing the response surfaces of underlying drivers. Our findings suggest that a move to gradient designs in ecological experiments could be a major step towards unravelling underlying response patterns to continuous and interacting environmental drivers in a feasible and statistically powerful way.

A Network Meta-Analysis Comparing Effects of Various Antidepressant Classes on the Digit Symbol Substitution Test (DSST) as a Measure of Cognitive Dysfunction in Patients with Major Depressive Disorder.

Background: Major depressive disorder is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis were carried out to assess the relative effect of antidepressants on cognitive dysfunction in major depressive disorder. Methods: MEDLINE, Embase, Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant conference abstracts were searched for randomized controlled trials assessing the effects of antidepressants/placebo on cognition. A network meta-analysis comparing antidepressants was conducted using a random effects model. Results: The database search retrieved 11337 citations, of which 72 randomized controlled trials from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test, which targets multiple domains of cognition and is recognized as being sensitive to change, was the only test that was used across 12 of the included randomized controlled trials and that allowed the construction of a stable network suitable for the network meta-analysis. The interventions assessed included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the Digit Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI = 0.120; 0.529, P=.009}. Compared with other antidepressants, vortioxetine was statistically more efficacious on the Digit Symbol Substitution Test vs escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and tricyclic antidepressant classes. Conclusions: This study highlighted the large variability in measures used to assess cognitive functioning. The findings on the Digit Symbol Substitution Test indicate differential effects of various antidepressants on improving cognitive function in patients with major depressive disorder.

The prevalence of ALK rearrangement in pulmonary adenocarcinomas in an unselected Caucasian population from a defined catchment area: impact of smoking.

AIMS: To assess the prevalence of EML4-ALK rearrangement gene measured by immunohistochemistry in an unselected population-based consecutive cohort of patients with adenocarcinoma of the lung (ACL), and the correlation with smoking history, thyroid transcription factor 1 (TTF1), gender and age. METHODS AND RESULTS: All patients diagnosed in the population of the greater Copenhagen area were included, irrespective of gender, age, smoking habits, stage or type of available diagnostic material. Tumours were stained with immunohistochemistry (clone 5A4). Immunohistochemistry-positive tumours were tested by fluorescence in-situ hybridization (FISH). During a 16-month period, 760 patients in the population were diagnosed with ACL. In 2.6% there was insufficient material for ALK testing (20 of 760). Eleven per cent of the remaining 740 ACL patients were never smokers, 43% were ex-smokers smokers and 46% were current smokers. Fourteen patients [1.9%, 95% confidence interval (CI) = 1.1-3.2] were ALK-positive by immunohistochemistry. Nine of 82 never-smokers (11%, 95% CI = 5.9-19.6) and five of 652 ex- or current smokers (0.8%, 95% CI = 0.4-2.1) were ALK-positive. Only two ALK-positive patients were found among 586 heavy smokers (> 15 pack-years) (0.3%, 95% CI = 0.09-1.2). Thirteen of the 14 immunohistochemistry-positive patients were FISH-positive. All ALK-positive tumours were TTF1-positive. The number needed to test (NNT) to identify one ALK positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively. CONCLUSIONS: Immunohistochemical analysis of ALK rearrangement was possible in 97.4% of patients. ALK rearrangement was found primarily in never smokers. NNT to identify one ALK-positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively.

Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling.

RATIONALE: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. OBJECTIVES: Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. METHODS: A total of 4,104 participants aged 50-70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group). MEASUREMENTS AND MAIN RESULTS: Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66-1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, respectively; P < 0.001), particularly adenocarcinomas (58 vs. 18, respectively; P < 0.001). More early-stage cancers (stages I and II, 54 vs. 10, respectively; P < 0.001) and stage IIIa cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group. CONCLUSIONS: No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung Screening Trial. Clinical trial registered with www.clinicaltrials.gov (NCT00496977).

A replicated climate change field experiment reveals rapid evolutionary response in an ecologically important soil invertebrate.

Whether species can respond evolutionarily to current climate change is crucial for the persistence of many species. Yet, very few studies have examined genetic responses to climate change in manipulated experiments carried out in natural field conditions. We examined the evolutionary response to climate change in a common annelid worm using a controlled replicated experiment where climatic conditions were manipulated in a natural setting. Analyzing the transcribed genome of 15 local populations, we found that about 12% of the genetic polymorphisms exhibit differences in allele frequencies associated to changes in soil temperature and soil moisture. This shows an evolutionary response to realistic climate change happening over short-time scale, and calls for incorporating evolution into models predicting future response of species to climate change. It also shows that designed climate change experiments coupled with genome sequencing offer great potential to test for the occurrence (or lack) of an evolutionary response.

Few multiyear precipitation-reduction experiments find a shift in the productivity-precipitation relationship.

Well-defined productivity-precipitation relationships of ecosystems are needed as benchmarks for the validation of land models used for future projections. The productivity-precipitation relationship may be studied in two ways: the spatial approach relates differences in productivity to those in precipitation among sites along a precipitation gradient (the spatial fit, with a steeper slope); the temporal approach relates interannual productivity changes to variation in precipitation within sites (the temporal fits, with flatter slopes). Precipitation-reduction experiments in natural ecosystems represent a complement to the fits, because they can reduce precipitation below the natural range and are thus well suited to study potential effects of climate drying. Here, we analyse the effects of dry treatments in eleven multiyear precipitation-manipulation experiments, focusing on changes in the temporal fit. We expected that structural changes in the dry treatments would occur in some experiments, thereby reducing the intercept of the temporal fit and displacing the productivity-precipitation relationship downward the spatial fit. The majority of experiments (72%) showed that dry treatments did not alter the temporal fit. This implies that current temporal fits are to be preferred over the spatial fit to benchmark land-model projections of productivity under future climate within the precipitation ranges covered by the experiments. Moreover, in two experiments, the intercept of the temporal fit unexpectedly increased due to mechanisms that reduced either water loss or nutrient loss. The expected decrease of the intercept was observed in only one experiment, and only when distinguishing between the late and the early phases of the experiment. This implies that we currently do not know at which precipitation-reduction level or at which experimental duration structural changes will start to alter ecosystem productivity. Our study highlights the need for experiments with multiple, including more extreme, dry treatments, to identify the precipitation boundaries within which the current temporal fits remain valid.

Simulator training for endobronchial ultrasound: a randomised controlled trial.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is very operator dependent and has a long learning curve. Simulation-based training might shorten the learning curve, and an assessment tool with solid validity evidence could ensure basic competency before unsupervised performance.A total of 16 respiratory physicians, without EBUS experience, were randomised to either virtual-reality simulator training or traditional apprenticeship training on patients, and then each physician performed EBUS-TBNA procedures on three patients. Three blinded, independent assessor assessed the video recordings of the procedures using a newly developed EBUS assessment tool (EBUSAT).The internal consistency was high (Cronbach's α=0.95); the generalisability coefficient was good (0.86), and the tool had discriminatory ability (p<0.001). Procedures performed by simulator-trained novices were rated higher than procedures performed by apprenticeship-trained novices: mean±sd are 24.2±7.9 points and 20.2±9.4 points, respectively; p=0.006. A pass/fail standard of 28.9 points was established using the contrasting groups method, resulting in 16 (67%) and 20 (83%) procedures performed by simulator-trained novices and apprenticeship-trained novices failing the test, respectively; p<0.001.The endobronchial ultrasound assessment tool could be used to provide reliable and valid assessment of competence in EBUS-TBNA, and act as an aid in certification. Virtual-reality simulator training was shown to be more effective than traditional apprenticeship training.

Perioperative rehabilitation in operation for lung cancer (PROLUCA) - rationale and design.

BACKGROUND: The purpose of the PROLUCA study is to investigate the efficacy of preoperative and early postoperative rehabilitation in a non-hospital setting in patients with operable lung cancer with special focus on exercise. METHODS: Using a 2 x 2 factorial design with continuous effect endpoint (Maximal Oxygen Uptake (VO2peak)), 380 patients with non-small cell lung cancer (NSCLC) stage I-IIIa referred for surgical resection will be randomly assigned to one of four groups: (1) preoperative and early postoperative rehabilitation (starting two weeks after surgery); (2) preoperative and late postoperative rehabilitation (starting six weeks after surgery); (3) early postoperative rehabilitation alone; (4) today's standard care which is postoperative rehabilitation initiated six weeks after surgery. The preoperative rehabilitation program consists of an individually designed, 30-minute home-based exercise program performed daily. The postoperative rehabilitation program consists of a supervised group exercise program comprising cardiovascular and resistance training two-hour weekly for 12 weeks combined with individual counseling. The primary study endpoint is VO2peak and secondary endpoints include: Six-minute walk distance (6MWD), one-repetition-maximum (1RM), pulmonary function, patient-reported outcomes (PROs) on health-related quality of life (HRQoL), symptoms and side effects of the cancer disease and the treatment of the disease, anxiety, depression, wellbeing, lifestyle, hospitalization time, sick leave, work status, postoperative complications (up to 30 days after surgery) and survival. Endpoints will be assessed at baseline, the day before surgery, pre-intervention, post-intervention, six months after surgery and one year after surgery. DISCUSSION: The results of the PROLUCA study may potentially contribute to the identification of the optimal perioperative rehabilitation for operable lung cancer patients focusing on exercise initiated immediately after diagnosis and rehabilitation shortly after surgery. TRIAL REGISTRATION: NCT01893580.

Development and validation of a theoretical test in endosonography for pulmonary diseases.

BACKGROUND: Theoretical testing provides the necessary foundation to perform technical skills. Additionally, testing improves the retention of knowledge. OBJECTIVES: The aims of this study were to develop a multiple-choice test in endosonography for pulmonary diseases and to gather validity evidence for this test. METHODS: Initially, 78 questions were constructed after informal conversational interviews with 4 international experts in endosonography. The clarity and content validity of the questions were tested using a Delphi-like approach. Construct validity was explored by administering the test to 3 groups with different levels of endosonography experience: 27 medical students, 18 respiratory physicians with limited endosonography experience, and 14 experts in endosonography. RESULTS: Two Delphi iterations reduced the test to 52 questions. After item analysis, the final test consisted of 46 questions with a mean item discrimination of 0.47 and a mean item difficulty of 0.63. The internal consistency reliability was calculated at 0.91. The 3 groups performed significantly differently (ANOVA: p < 0.001), and post hoc tests were significant. The experts performed significantly more consistently than the novices (p = 0.037) and the intermediates (p < 0.001). CONCLUSIONS: This study provides a theoretical test in endosonography consisting of multiple-choice questions. Validity evidence was gathered, and the test demonstrated content and construct validity.

Long-term temporal patterns in ecosystem carbon flux components and overall balance in a heathland ecosystem.

Terrestrial ecosystems have strong feedback to atmospheric CO2 concentration and climate change. However, the long-term whole life cycle dynamics of ecosystem carbon (C) fluxes and overall balance in some ecosystem types, such as heathland ecosystems, have not been thoroughly explored. We studied the changes in ecosystem CO2 flux components and overall C balance over a full ecosystem lifecycle in stands of Calluna vulgaris (L.) Hull by using a chronosequence of 0, 12, 19 and 28 years after vegetation cutting. Overall, the ecosystem C balance was highly nonlinear over time and exhibited a sinusoidal-like curvature of C sink/source change over the three-decade timescale. After cutting, plant-related C flux components of gross photosynthesis (PG), aboveground autotrophic respiration (Raa) and belowground autotrophic respiration (Rba) were higher at the young age (12 years) than at middle (19 years) and old (28 years) ages. The young ecosystem was a C sink (12 years: -0.374 kg C m-2 year-1) while it became a C source with aging (19 years: 0.218 kg C m-2 year-1) and when dying (28 years: 0.089 kg C m-2 year-1). The post-cutting C compensation point was observed after four years, while the cumulative C loss in the period after cutting had been compensated by an equal amount of C uptake after seven years. Annual ecosystem C payback from the ecosystem to the atmosphere started after 16 years. This information may be used directly for optimizing vegetation management practices for maximal ecosystem C uptake capacity. Our study highlights that whole life cycle observational data of changes in C fluxes and balance in ecosystems are important and the ecosystem model needs to take the successional stage and vegetation age into account when projecting component C fluxes, ecosystem C balance, and overall feedback to climate change.

A case of bilateral pneumothorax following computer-tomography guided transthoracic biopsy in a woman with suspected pulmonary cancer.

Computer-tomography-guided needle biopsies are useful for diagnosing, staging, and classification of peripheral pulmonary nodules. However, the procedure carries a risk of iatrogenic pneumothorax. This report describes a patient-case where a woman had undergone a computer-tomography guided biopsy. Approximately 4 hours following discharge the patient was admitted to the emergency ward with severe chest pain and dyspnea. Chest x-ray revealed bilateral pneumothorax and subcutaneous emphysema at the biopsy site. Pleural drainage was administered on the patient's right side. Another chest x-ray following drainage showed regression of pneumothorax on both sides thus indicating communicating pleural cavities. Medical history revealed that the patient had been thymectomized 2 years earlier and a computer tomography visualized that the patient lacked mediastinal separation of the two pleural cavities. It is possible that patients with a history of mediastinal or thoracic surgery should be observed longer following procedures carrying risk of iatrogenic pneumothorax.

Higher sensitivity of gross primary productivity than ecosystem respiration to experimental drought and warming across six European shrubland ecosystems.

Shrubland ecosystems across Europe face a range of threats including the potential impacts of climate change. Within the INCREASE project, six shrubland ecosystems along a European climatic gradient were exposed to ecosystem-level year-round experimental nighttime warming and long-term, repeated growing season droughts. We quantified the ecosystem level CO2 fluxes, i.e. gross primary productivity (GPP), ecosystem respiration (Reco) and net ecosystem exchange (NEE), in control and treatment plots and compared the treatment effects along the Gaussen aridity index. In general, GPP exhibited higher sensitivity to drought and warming than Reco and was found to be the dominant contributor to changes in overall NEE. Across the climate gradient, northern sites were more likely to have neutral to positive responses of NEE, i.e. increased CO2 uptake, to drought and warming partly due to seasonal rewetting. While an earlier investigation across the same sites showed a good cross-site relationship between soil respiration responses to climate over the Gaussen aridity index, the responses of GPP, Reco and NEE showed a more complex response pattern suggesting that site-specific ecosystem traits, such as different growing season periods and plant species composition, affected the overall response pattern of the ecosystem-level CO2 fluxes. We found that the observed response patterns of GPP and Reco rates at the six sites could be explained well by the hypothesized position of each site on site-specific soil moisture response curves of GPP/Reco fluxes. Such relatively simple, site-specific analyses could help improve our ability to explain observed CO2 flux patterns in larger meta-analyses as well as in larger-scale model upscaling exercises and thereby help improve our ability to project changes in ecosystem CO2 fluxes in response to future climate change.

Assessment of patient life engagement in major depressive disorder using items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR).

BACKGROUND: Patient-reported outcomes can measure domains that are personally meaningful, such as life engagement, which reflects motivation, pleasure, and well-being. This study explored whether certain items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR) can capture patient life engagement in major depressive disorder (MDD). METHODS: IDS-SR life engagement items were identified by a) a panel of expert psychiatrists (n = 4), b) patient interviews (n = 20), and c) a principal component analysis (PCA) to explore clustering of items. Psychometric analyses were performed on potential subscales, and a minimal clinically important difference (MCID) was estimated by anchor- and distribution-based methods. IDS-SR data were obtained from three randomized controlled trials of adjunctive brexpiprazole in MDD. RESULTS: Expert psychiatrists selected 10 items by consensus from the IDS-SR that might capture patient life engagement (Cronbach's alpha, 0.82; item-total correlations, 0.36-0.58). Patient interviews identified 13 items as moderately to very relevant to life engagement (Cronbach's alpha, 0.85; item-total correlations, 0.35-0.61). The PCA revealed a cluster that included all 10 items selected by psychiatrists and 11 items identified by patients. Expert psychiatrists intentionally distinguished life engagement and core depressive symptoms, although patient insights and the PCA indicated that these aspects of MDD are strongly linked. The 10-item IDS-SR life engagement subscale had an MCID of 3-5 points. CONCLUSIONS: Different approaches consistently identified a subset of 10 IDS-SR items that can measure life engagement in MDD, which may be suitable to group into an IDS-SR life engagement subscale.