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Embodied design ideation methods rely on subjective —first-person— experiences of the designer to bring new ways of designing into being. Shifting the embodied design ideation method to the body of the other, we propose a three-step process that makes the experiences of a dancer accessible to a designer for the ideation of remote intimacies. To support the access to the dancer’s experiences, we facilitate embodied, dialogical exchange over three phases: i) observation of embodied explorations between the dancer and a set of tangibles, ii) analysis of phase (i) visual documentation, and iii) a semi-structured interview with the dancer, using phase (ii) outcomes, incorporating drawing as a form of reflection. This reflexive process reveals the ways how incorporating tangibility, ambiguity, and care into a conversation with the body of the other allows us to open a space of possibilities.

BACKGROUND: Retrospective comparative studies suggest a survival benefit after complete local treatment of recurrence (LTR) in renal cell carcinoma (RCC), which may be largely due to an indication bias. OBJECTIVE: To determine the role of LTR in a homogeneous population characterised by limited and potentially resectable recurrence. DESIGN SETTING AND PARTICIPANTS: RECUR is a protocol-based multicentre European registry capturing patient and tumour characteristics, risk of recurrence (RoR), recurrence patterns, and survival of those curatively treated for nonmetastatic RCC from 2006 to 2011. Per-protocol resectable disease (RD) recurrence was defined as (1) solitary metastases, (2) oligometastases, or (3) renal fossa or renal recurrence after radical or partial nephrectomy, respectively. INTERVENTION: Local treatment of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) and cancer-specific survival was compared in the RD population that underwent LTR versus no LTR. We constructed a multivariate model to predict risk factors for overall mortality and analysed the effect of LTR across RoR groups. RESULTS AND LIMITATIONS: Of 3039 patients with localised RCC treated with curative intent, 505 presented with recurrence, including 176 with RD. Of these patients, 97 underwent LTR and 79 no LTR. Patients in the LTR group were younger (64.3 [40-80] vs 69.2 [45-87] yr; p = 0.001). The median OS was 70.3 mo (95% confidence interval [CI] 58-82.6) versus 27.4 mo (95% CI 23.6-31.15) in the LTR versus no-LTR group (p < 0.001). After a multivariate analysis, having LTR (hazard ratio [HR] 0.37 [95% CI 0.2-0.6]), having low- versus high-risk RoR (HR 0.42 [95% CI [0.20-0.83]), and not having extra-abdominal/thoracic metastasis (HR 1.96 [95% CI 1.02-3.77]) were prognostic factors of longer OS. The LTR effect on survival was consistent across risk groups. OS HR for high, intermediate, and low risks were 0.36 (0.2-0.64), 0.27 (0.11-0.65), and 0.26 (0.08-0.

BACKGROUND: Retrospective comparative studies suggest a survival benefit after complete local treatment of recurrence (LTR) in renal cell carcinoma (RCC), which may be largely due to an indication bias. OBJECTIVE: To determine the role of LTR in a homogeneous population characterised by limited and potentially resectable recurrence. DESIGN SETTING AND PARTICIPANTS: RECUR is a protocol-based multicentre European registry capturing patient and tumour characteristics, risk of recurrence (RoR), recurrence patterns, and survival of those curatively treated for nonmetastatic RCC from 2006 to 2011. Per-protocol resectable disease (RD) recurrence was defined as (1) solitary metastases, (2) oligometastases, or (3) renal fossa or renal recurrence after radical or partial nephrectomy, respectively. INTERVENTION: Local treatment of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) and cancer-specific survival was compared in the RD population that underwent LTR versus no LTR. We constructed a multivariate model to predict risk factors for overall mortality and analysed the effect of LTR across RoR groups. RESULTS AND LIMITATIONS: Of 3039 patients with localised RCC treated with curative intent, 505 presented with recurrence, including 176 with RD. Of these patients, 97 underwent LTR and 79 no LTR. Patients in the LTR group were younger (64.3 [40-80] vs 69.2 [45-87] yr; p = 0.001). The median OS was 70.3 mo (95% confidence interval [CI] 58-82.6) versus 27.4 mo (95% CI 23.6-31.15) in the LTR versus no-LTR group (p < 0.001). After a multivariate analysis, having LTR (hazard ratio [HR] 0.37 [95% CI 0.2-0.6]), having low- versus high-risk RoR (HR 0.42 [95% CI [0.20-0.83]), and not having extra-abdominal/thoracic metastasis (HR 1.96 [95% CI 1.02-3.77]) were prognostic factors of longer OS. The LTR effect on survival was consistent across risk groups. OS HR for high, intermediate, and low risks were 0.36 (0.2-0.64), 0.27 (0.11-0.65), and 0.26 (0.08-0.

Risk classification for patients with renal cell carcinoma (RCC) is critical for clinical decision-making and ultimately for patient outcomes [1]. Staging is the single most informative piece of information for risk assessment in patients with cancer. Currently, the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM scheme is the most universally accepted staging system [2]. Since its first publication in 1977, the UICC/AJCC TNM staging system has changed while still retaining its characteristics of simplicity, reproducibility, and user-friendliness.

BACKGROUND: Retrospective comparative studies suggest a survival benefit after complete local treatment of recurrence (LTR) in renal cell carcinoma (RCC), which may be largely due to an indication bias. OBJECTIVE: To determine the role of LTR in a homogeneous population characterised by limited and potentially resectable recurrence. DESIGN SETTING AND PARTICIPANTS: RECUR is a protocol-based multicentre European registry capturing patient and tumour characteristics, risk of recurrence (RoR), recurrence patterns, and survival of those curatively treated for nonmetastatic RCC from 2006 to 2011. Per-protocol resectable disease (RD) recurrence was defined as (1) solitary metastases, (2) oligometastases, or (3) renal fossa or renal recurrence after radical or partial nephrectomy, respectively. INTERVENTION: Local treatment of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) and cancer-specific survival was compared in the RD population that underwent LTR versus no LTR. We constructed a multivariate model to predict risk factors for overall mortality and analysed the effect of LTR across RoR groups. RESULTS AND LIMITATIONS: Of 3039 patients with localised RCC treated with curative intent, 505 presented with recurrence, including 176 with RD. Of these patients, 97 underwent LTR and 79 no LTR. Patients in the LTR group were younger (64.3 [40-80] vs 69.2 [45-87] yr; p = 0.001). The median OS was 70.3 mo (95% confidence interval [CI] 58-82.6) versus 27.4 mo (95% CI 23.6-31.15) in the LTR versus no-LTR group (p < 0.001). After a multivariate analysis, having LTR (hazard ratio [HR] 0.37 [95% CI 0.2-0.6]), having low- versus high-risk RoR (HR 0.42 [95% CI [0.20-0.83]), and not having extra-abdominal/thoracic metastasis (HR 1.96 [95% CI 1.02-3.77]) were prognostic factors of longer OS. The LTR effect on survival was consistent across risk groups. OS HR for high, intermediate, and low risks were 0.36 (0.2-0.64), 0.27 (0.11-0.65), and 0.26 (0.08-0.

In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER). Owing to heterogeneity, a meta-analysis is not recommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to predict outcome are lacking. Uncertainty exists and overtreatment is occurring. Treatment decisions should be made with caution and with the involvement of each patient. Patient summary: New results from three trials of immunotherapy after surgery for kidney cancer to reduce the risk of recurrence showed no improvement with these treatments. These results are in contrast to an earlier study that showed that the antibody pembrolizumab did extend the time before kidney cancer recurrence, even though it is not yet clear if overall survival is longer. Thus, we cautiously recommend pembrolizumab as additional treatment in high-risk kidney cancer after surgery, but patient preference should be carefully considered and the risk of overtreatment should be discussed.

Embodied design ideation methods rely on subjective —first-person— experiences of the designer to bring new ways of designing into being. Shifting the embodied design ideation method to the body of the other, we propose a three-step process that makes the experiences of a dancer accessible to a designer for the ideation of remote intimacies. To support the access to the dancer’s experiences, we facilitate embodied, dialogical exchange over three phases: i) observation of embodied explorations between the dancer and a set of tangibles, ii) analysis of phase (i) visual documentation, and iii) a semi-structured interview with the dancer, using phase (ii) outcomes, incorporating drawing as a form of reflection. This reflexive process reveals the ways how incorporating tangibility, ambiguity, and care into a conversation with the body of the other allows us to open a space of possibilities.

Embodied design ideation methods rely on subjective —first-person— experiences of the designer to bring new ways of designing into being. Shifting the embodied design ideation method to the body of the other, we propose a three-step process that makes the experiences of a dancer accessible to a designer for the ideation of remote intimacies. To support the access to the dancer’s experiences, we facilitate embodied, dialogical exchange over three phases: i) observation of embodied explorations between the dancer and a set of tangibles, ii) analysis of phase (i) visual documentation, and iii) a semi-structured interview with the dancer, using phase (ii) outcomes, incorporating drawing as a form of reflection. This reflexive process reveals the ways how incorporating tangibility, ambiguity, and care into a conversation with the body of the other allows us to open a space of possibilities.

Embodied design ideation methods rely on subjective —first-person— experiences of the designer to bring new ways of designing into being. Shifting the embodied design ideation method to the body of the other, we propose a three-step process that makes the experiences of a dancer accessible to a designer for the ideation of remote intimacies. To support the access to the dancer’s experiences, we facilitate embodied, dialogical exchange over three phases: i) observation of embodied explorations between the dancer and a set of tangibles, ii) analysis of phase (i) visual documentation, and iii) a semi-structured interview with the dancer, using phase (ii) outcomes, incorporating drawing as a form of reflection. This reflexive process reveals the ways how incorporating tangibility, ambiguity, and care into a conversation with the body of the other allows us to open a space of possibilities.

BACKGROUND: Retrospective comparative studies suggest a survival benefit after complete local treatment of recurrence (LTR) in renal cell carcinoma (RCC), which may be largely due to an indication bias. OBJECTIVE: To determine the role of LTR in a homogeneous population characterised by limited and potentially resectable recurrence. DESIGN SETTING AND PARTICIPANTS: RECUR is a protocol-based multicentre European registry capturing patient and tumour characteristics, risk of recurrence (RoR), recurrence patterns, and survival of those curatively treated for nonmetastatic RCC from 2006 to 2011. Per-protocol resectable disease (RD) recurrence was defined as (1) solitary metastases, (2) oligometastases, or (3) renal fossa or renal recurrence after radical or partial nephrectomy, respectively. INTERVENTION: Local treatment of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) and cancer-specific survival was compared in the RD population that underwent LTR versus no LTR. We constructed a multivariate model to predict risk factors for overall mortality and analysed the effect of LTR across RoR groups. RESULTS AND LIMITATIONS: Of 3039 patients with localised RCC treated with curative intent, 505 presented with recurrence, including 176 with RD. Of these patients, 97 underwent LTR and 79 no LTR. Patients in the LTR group were younger (64.3 [40-80] vs 69.2 [45-87] yr; p = 0.001). The median OS was 70.3 mo (95% confidence interval [CI] 58-82.6) versus 27.4 mo (95% CI 23.6-31.15) in the LTR versus no-LTR group (p < 0.001). After a multivariate analysis, having LTR (hazard ratio [HR] 0.37 [95% CI 0.2-0.6]), having low- versus high-risk RoR (HR 0.42 [95% CI [0.20-0.83]), and not having extra-abdominal/thoracic metastasis (HR 1.96 [95% CI 1.02-3.77]) were prognostic factors of longer OS. The LTR effect on survival was consistent across risk groups. OS HR for high, intermediate, and low risks were 0.36 (0.2-0.64), 0.27 (0.11-0.65), and 0.26 (0.08-0.

BACKGROUND: Retrospective comparative studies suggest a survival benefit after complete local treatment of recurrence (LTR) in renal cell carcinoma (RCC), which may be largely due to an indication bias. OBJECTIVE: To determine the role of LTR in a homogeneous population characterised by limited and potentially resectable recurrence. DESIGN SETTING AND PARTICIPANTS: RECUR is a protocol-based multicentre European registry capturing patient and tumour characteristics, risk of recurrence (RoR), recurrence patterns, and survival of those curatively treated for nonmetastatic RCC from 2006 to 2011. Per-protocol resectable disease (RD) recurrence was defined as (1) solitary metastases, (2) oligometastases, or (3) renal fossa or renal recurrence after radical or partial nephrectomy, respectively. INTERVENTION: Local treatment of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) and cancer-specific survival was compared in the RD population that underwent LTR versus no LTR. We constructed a multivariate model to predict risk factors for overall mortality and analysed the effect of LTR across RoR groups. RESULTS AND LIMITATIONS: Of 3039 patients with localised RCC treated with curative intent, 505 presented with recurrence, including 176 with RD. Of these patients, 97 underwent LTR and 79 no LTR. Patients in the LTR group were younger (64.3 [40-80] vs 69.2 [45-87] yr; p = 0.001). The median OS was 70.3 mo (95% confidence interval [CI] 58-82.6) versus 27.4 mo (95% CI 23.6-31.15) in the LTR versus no-LTR group (p < 0.001). After a multivariate analysis, having LTR (hazard ratio [HR] 0.37 [95% CI 0.2-0.6]), having low- versus high-risk RoR (HR 0.42 [95% CI [0.20-0.83]), and not having extra-abdominal/thoracic metastasis (HR 1.96 [95% CI 1.02-3.77]) were prognostic factors of longer OS. The LTR effect on survival was consistent across risk groups. OS HR for high, intermediate, and low risks were 0.36 (0.2-0.64), 0.27 (0.11-0.65), and 0.26 (0.08-0.

Context: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC. Objective: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC. Evidence acquisition: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines. Evidence synthesis: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence. Conclusions: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022. Patient summary: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer.

Context: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC. Objective: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC. Evidence acquisition: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines. Evidence synthesis: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence. Conclusions: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022. Patient summary: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer.

Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy. Patient summary: New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery.

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management.

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management.

Selective laser melting (SLM) based processing of Mo-based samples is challenging due to solidification cracking. We here demonstrate that the addition of 2 wt% MoS2 to the Mo feedstock markedly improves crack mitigation of SLM-processed Mo/MoS2/Mo2S3 composite micro-lattice structures (SLM-Mo/ Mo(x)S(x+1)). Crack inhibition is suggested to be a result of Mo2S3 formation, decreased lattice strain (0.04 4%), and a decrease in accumulated residual stresses. The increased values of polarization resistance from 42.3 and 19.2 kU cm2 to 437 and 78.2 kU cm2, respectively verified the hindering effect of the composition on stress corrosion cracking (SCC) and surface oxidation cracking. However, an increased corrosion current density, from 1.22 to 10.2 mA/cm2, and cathodic Tafel constant, from 175 to 260.5 mV, confirmed the decreased polarization resistance and occurrence of different types of corrosion such as SCC and pitting. The strategy to add 2 wt% MoS2 to the Mo feedstock enables the fabrication of hightemperature micro-lattice structure components with improved corrosion resistance properties applicable in e.g., electronic, power semiconductor heat sinks, offshore-, aerospace-, defense-, or particularly novel sodium-ion energy storage applications., QC 20230109

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management.

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management., Funding Agencies|Empros Pharma AB

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management.

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management., Funding Agencies|Empros Pharma AB

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management., Funding Agencies|Empros Pharma AB

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management.

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management., Funding Agencies|Empros Pharma AB

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management., Funding Agencies|Empros Pharma AB

Context: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC. Objective: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC. Evidence acquisition: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines. Evidence synthesis: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence. Conclusions: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022. Patient summary: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer.

Context: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC. Objective: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC. Evidence acquisition: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines. Evidence synthesis: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence. Conclusions: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022. Patient summary: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer.

Context: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC. Objective: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC. Evidence acquisition: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines. Evidence synthesis: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence. Conclusions: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022. Patient summary: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer.

Temes de Disseny #38 addresses the complex issue of health and human well-being. It explores how design and engineering can help by providing more meaningful, healthy and caring spaces, personal devices and interactions that promote well-being and, in turn, can make the world a better place. The issue looks at how design-related disciplines can promote care and well-being on different levels and encourages the establishment of connections between personal and planetary well-being while addressing technological, environmental, medical, ethical and behavioral-anthropological perspectives., https://www.librarystack.org/caring-through-design-from-personal-to-planetary-well-being/?ref=unknown

Temes de Disseny #38 addresses the complex issue of health and human well-being. It explores how design and engineering can help by providing more meaningful, healthy and caring spaces, personal devices and interactions that promote well-being and, in turn, can make the world a better place. The issue looks at how design-related disciplines can promote care and well-being on different levels and encourages the establishment of connections between personal and planetary well-being while addressing technological, environmental, medical, ethical and behavioral-anthropological perspectives., https://www.librarystack.org/caring-through-design-from-personal-to-planetary-well-being/?ref=unknown

Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk. PATIENT SUMMARY: New data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.

The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. Patient summary: New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.

Purpose: There is sparse evidence on outcomes of resected occult LN metastases at the time of nephrectomy (synchronous disease). We sought to analyse a large international cohort of patients and to identify clinico-pathological predictors of long-term survival. Materials and methods: We collected data of consecutive patients who underwent nephrectomy and LND for Tany cN0-1pN1 and cM0-1 RCC at 7 referral centres between 1988 and 2019. Patients were stratified into four clinico-pathological groups: (1) cN0cM0-pN1, (2) cN1cM0-pN1(limited, 1–3 positive nodes), (3) cN1cM0-pN1(extensive, > 3 positive nodes), and (4) cM1-pN1. Overall survival (OS) was estimated using the Kaplan–Meier method, and associations with all-cause mortality (ACM) were evaluated using Cox models with multiple imputations. Results: Of the 4370 patients with LND, 292 patients with pN1 disease were analysed. Median follow-up was 62 months, during which 171 patients died. Median OS was 21 months (95% CI 17–30 months) and the 5-year OS rate was 24% (95% CI 18–31%). Patients with cN0cM0-pN1 disease had a median OS of 57 months and a 5-year OS rate of 43%. 5-year OS (median OS) decreased to 29% (33 months) in cN1cM0-pN1(limited) and to 23% (23 months) in cN1cM0-pN1(extensive) patients. Those with cM1-pN1 disease had the worst prognosis, with a 5-year OS rate of 13% (9 months). On multivariable analysis, age (p = 0.034), tumour size (p = 0.02), grade (p = 0.02) and clinico-pathological group (p < 0.05) were significant predictors of ACM. Conclusion: Depending on clinico-pathological group, grade and tumour size, 5-year survival of patients with LN metastases varies from 13 to 43%. Patients with resected occult lymph node involvement (cN0/pN1 cM0) have the best prognosis with a considerable chance of long-term survival.

The dissertation aims to advance our understanding about the role of local industry structure in regional economic development. More specifically, it investigates how relatedness between local industries (i.e. similarities in what kind of knowledge industries use) contributes to and constrains regional economic development. Empirically, the dissertation investigates Swedish regional development in 1991-2010.Inter-industry relatedness is a key concept in evolutionary economic geography and has a prominent role in narratives explaining the evolution of regional economies. The diversity of local industries and relatedness between them serve as sources of feedback and path dependencies that mould regional development trajectories. It is widely accepted that firms benefit from the local presence of other firms in related industries and such local related variety increases regional employment growth. Often these growth benefits are assumed to be ‘in the air’ or in local ‘buzz’ taking the form of pure knowledge spillovers via unintended interactions between individuals. The dissertation argues that the role of market-mediated knowledge flow channels like labour mobility is underestimated.Economic diversification is a major source of dynamics in regions. Researchers and policymakers increasingly recognise that existing industrial structure and local capabilities condition which new activities will be feasible to develop in regions. This is supported by empirical studies showing that regions tend to diversify into activities that are related to their current industry mix. For example, regions manufacturing cars are more likely to start producing motorcycles than tennis rackets. The dissertation demonstrates that regions’ potential for such related diversification has an inverted U-shaped relationship with regional size. The highest potential is in large and medium-sized regions, while core regions have few related diversification opportunities since they already host most in

The interaction between the adapter protein 14-3-3σ and transcription factor p53 is important for preserving the tumor-suppressor functions of p53 in the cell. A phosphorylated motif within the C-terminal domain (CTD) of p53 is key for binding to the amphipathic groove of 14-3-3. This motif is unique among 14-3-3 binding partners, and the precise dynamics of the interaction is not yet fully understood. Here, we investigate this interaction at the molecular level by analyzing the binding of different length p53 CTD peptides to 14-3-3σ using ITC, SPR, NMR, and MD simulations. We observed that the propensity of the p53 peptide to adopt turn-like conformation plays an important role in the binding to the 14-3-3σ protein. Our study contributes to elucidate the molecular mechanism of the 14-3-3-p53 binding and provides useful insight into how conformation properties of a ligand influence protein binding.

INTRODUCTION AND OBJECTIVE: Adjuvant studies with checkpoint inhibitors have attracted new interest in accurate pathological lymph node (LN) staging in renal cell carcinoma. Sentinel lymph node (SN) studies in cN0 patients revealed the pattern of lymphatic radiotracer drainage from renal tumors. The aim of this study was to describe the location of single- or oligometastatic LN and analyze if the topography of these first landing sites matches the drainage pattern observed in SN studies of renal tumors. MATERIALS AND METHODS: We collected data from 8 referral centers from 1990 to 2018 of all patients with pT1-4 cN0 or cN1 M0 renal cell carcinoma with pathologically confirmed single- or oligometastases in locoregional LN. The location of LN metastases, number, size of metastatic LN, and survival were analyzed using descriptive statistics with SPSS version 22 (IBM, Chicago, IL). RESULTS: From 3,794 patients with histologically confirmed pN1, a total of 76 patients (2%) with single- or oligometastatic pN1 were identified, of whom 24 (31.6%) and 52 (68.4%) were cN0 and cN1, respectively. On the left side, LN metastases were predominantly located in the para-aortal (48.0%; 95% confidence interval [CI] 29.22-63.12%) and hilar (31.42%; 95% CI 17.4-49.4%) area. On the right side, metastases located in retrocaval (26.82%; 95% CI 14.7-43.2%), hilar (26.82%; 95% CI 14.7-43.2%), interaortocaval (26.82%; 95% CI 14.7-43.2%), and paracaval (17.07%; 95% CI 7.6-32.6%) LNs. These landing sites exactly matched the lymphatic drainage pattern of intratumorally injected radiotracer reported in SN studies for both sides. CONCLUSIONS: Single- or oligometastatic LNs in renal cancer are mainly located in the hilar, retro-, para, and interaortocaval region on the right side and para-aortal region on the left side. These first landing sites match the drainage pattern reported in SN trials.

The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel performed a protocol-driven systematic review (SR) on thermal ablation (TA) compared with partial nephrectomy (PN) for T1N0M0 renal masses, in order to provide evidence to support its recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed, and only comparative studies published between 2000 and 2019 were included. Twenty-six nonrandomised comparative studies were included, recruiting a total of 167 80 patients. Risk of bias (RoB) assessment revealed high or uncertain RoB across all studies, with the vast majority being retrospective, observational studies with poorly matched controls and short follow-up. Limited data showed TA to be safe, but its long-term oncological effectiveness compared with PN remains uncertain. A quality assessment of pre-existing SRs (n = 11) on the topic, using AMSTAR, revealed that all SRs had low confidence rating, with all but two SRs being rated critically low. In conclusion, the current data are inadequate to make any strong and clear conclusions regarding the clinical effectiveness of TA for treating T1N0M0 renal masses compared with PN. Therefore, TA may be cautiously considered an alternative to PN for T1N0M0 renal masses, but patients must be counselled carefully regarding the prevailing uncertainties. We recommend specific steps to improve the evidence base based on robust primary and secondary studies. Patient summary: In this report, we looked at the literature to determine the effectiveness of thermoablation (TA) in the treatment of small kidney tumours compared with surgical removal. We found that TA could cautiously be offered as an option due to many remaining uncertainties regarding its effectiveness.

Context: Little is known about the natural history of sporadic angiomyolipomas (AMLs); there is uncertainty regarding the indications of treatment and treatment options. Objective: To evaluate the indications, effectiveness, harms, and follow-up of different management modalities for sporadic AML to provide guidance for clinical practice. Evidence acquisition: A systematic review of the literature was undertaken, incorporating Medline, Embase, and the Cochrane Library (from 1 January 1990 to 30 June 2017), in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. No restriction on study design was imposed. Patients with sporadic AML were included. The main interventions included active surveillance, surgery (nephron-sparing surgery and radical nephrectomy), selective arterial embolisation, and percutaneous or laparoscopic thermal ablations (radiofrequency, microwaves, or cryoablation). The outcomes included indications for active treatment, AML growth rate, AML recurrence rate, risk of bleeding, post-treatment renal function, adverse events of treatments, and modalities of followup. Risk of bias assessment was performed using standard Cochrane methods. Evidence synthesis: Among 2704 articles identified, 43 were eligible for inclusion (zero randomised controlled trials, nine nonrandomised comparative retrospective studies, and 34 single-arm case series). Most studies were retrospective and uncontrolled, and had a moderate to high risk of bias. Conclusions: In active surveillance series, spontaneous bleeding was reported in 2% of patients and active treatment was undertaken in 5%. Active surveillance is the most chosen option in 48% of the cases, followed by surgery in 31% and selective arterial embolisation in 17% of the cases. Selective arterial embolisation appeared to reduce AML volume but required secondary treatment in 30% of the cases. Surgery (particularly nephron-sparing surgery) was the most effective treatment in term

We present the results from Verification of Reference Irradiance and Radiance Sources Laboratory Calibration Experiment Campaign. Ten international laboratories took part in the measurements. The spectral irradiance comparison included the measurements of the 1000 W tungsten halogen filament lamps in the spectral range of 350 nm–900 nm in the pilot laboratory. The radiance comparison took a form of round robin where each participant in turn received two transfer radiometers and did the radiance calibration in their own laboratory. The transfer radiometers have seven spectral bands covering the wavelength range from 400 nm–700 nm. The irradiance comparison results showed an agreement between all lamps within ±1.5%. The radiance comparison results presented higher than expected discrepancies at the level of ±4%. Additional investigation to determine the causes for these discrepancies identified them as a combination of the size-of-source effect and instrument effective field of view that affected some of the results.

A field intercomparison was conducted at the Acqua Alta Oceanographic Tower (AAOT) in the northern Adriatic Sea, from 9 to 19 July 2018 to assess differences in the accuracy of in- and above-water radiometer measurements used for the validation of ocean colour products. Ten measurement systems were compared. Prior to the intercomparison, the absolute radiometric calibration of all sensors was carried out using the same standards and methods at the same reference laboratory. Measurements were performed under clear sky conditions, relatively low sun zenith angles, moderately low sea state and on the same deployment platform and frame (except in-water systems). The weighted average of five above-water measurements was used as baseline reference for comparisons. For downwelling irradiance (), there was generally good agreement between sensors with differences of <6% for most of the sensors over the spectral range 400 nm–665 nm. One sensor exhibited a systematic bias, of up to 11%, due to poor cosine response. For sky radiance () the spectrally averaged difference between optical systems was <2.5% with a root mean square error (RMS) <0.01 mWm−2 nm−1 sr−1. For total above-water upwelling radiance (), the difference was <3.5% with an RMS <0.009 mWm−2 nm−1 sr−1. For remote-sensing reflectance (), the differences between above-water TriOS RAMSES were <3.5% and <2.5% at 443 and 560 nm, respectively, and were <7.5% for some systems at 665 nm. Seabird HyperSAS sensors were on average within 3.5% at 443 nm, 1% at 560 nm, and 3% at 665 nm. The differences between the weighted mean of the above-water and in-water systems was <15.8% across visible bands. A sensitivity analysis showed that accounted for the largest fraction of the variance in , which suggests that minimizing the errors arising from this measurement is the most important variable in reducing the inter-group differences in . The differences may also be due, in part, to using five of the above-water systems as a refere

The European Copernicus programme ensures long-term delivery of high-quality, global satellite ocean colour radiometry (OCR) observations from its Sentinel-3 (S3) satellite series carrying the ocean and land colour instrument (OLCI). In particular, the S3/OLCI provides marine water leaving reflectance and derived products to the Copernicus marine environment monitoring service, CMEMS, for which data quality is of paramount importance. This is why OCR system vicarious calibration (OC-SVC), which allows uncertainties of these products to stay within required specifications, is crucial. The European organisation for the exploitation of meteorological satellites (EUMETSAT) operates the S3/OLCI marine ground segment, and envisions having an SVC infrastructure deployed and operated for the long-term. This paper describes a design for such an SVC infrastructure, named radiometry for ocean colour satellites calibration and community engagement (ROSACE), which has been submitted to Copernicus by a consortium made of three European research institutions, a National Metrology Institute, and two small- to medium-sized enterprises (SMEs). ROSACE proposes a 2-site infrastructure deployed in the Eastern and Western Mediterranean Seas, capable of delivering up to about 80 high quality matchups per year for OC-SVC of the S3/OLCI missions.

Stabilization of protein-protein interactions (PPIs) holds great potential for therapeutic agents, as illustrated by the successful drugs rapamycin and lenalidomide. However, how such interface-binding molecules can be created in a rational, bottom-up manner is a largely unanswered question. We report here how a fragment-based approach can be used to identify chemical starting points for the development of small-molecule stabilizers that differentiate between two different PPI interfaces of the adapter protein 14-3-3. The fragments discriminately bind to the interface of 14-3-3 with the recognition motif of either the tumor suppressor protein p53 or the oncogenic transcription factor TAZ. This X-ray crystallography driven study shows that the rim of the interface of individual 14-3-3 complexes can be targeted in a differential manner with fragments that represent promising starting points for the development of specific 14-3-3 PPI stabilizers.

The purpose of this essay is to understand how individuals who are carriers of two cultures feel they are being perceived by other groups in society. We also seek answers to our research question about how individuals who have a belonging to two different cultural backgrounds experienced their identity through the meeting of different groups in society. The respondents are young people born in Sweden and have parents from another country. All the respondents live in Angered, a suburb in Gothenburg. The essay contains material collected from eight semi-structured life- world interviews where we interpret the empiricism through hermeneutic approach. The theory we are using is based on theories from Richard Jenkins, Anthony Giddens and Vanessa May, who with their work declare to explain in what way the adolescents identity is effected by various groups. Our analysis shows that young people who have a belonging to two different cultural backgrounds find themselves in a special situation, as their identity is affected by the differences of society and parents implementing the traditions of origin. Our results show that adolescents who have a belonging to two different cultural backgrounds are adapting to surroundings where differences between them and others becomes evident.