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The Arctic region is experiencing notable warming as well as more lightning. Lightning is the dominant source of upper tropospheric nitrogen oxides (NOx), which are precursors for ozone and hydroxyl radicals. In this study, we combine the nitrogen dioxide (NO2) observations from the TROPOspheric Monitoring Instrument (TROPOMI) with Vaisala Global Lightning Dataset 360 to evaluate lightning NO2 (LNO2) production in the Arctic. By analyzing consecutive TROPOMI NO2 observations, we determine the lifetime and production efficiency of LNO2 during the summers of 2019-2021. Our results show that the LNO2 production efficiency over the ocean is ∼6 times higher than over continental regions. Additionally, we find that a higher LNO2 production efficiency is often correlated with lower lightning rates. The summertime lightning NOx emission in the Arctic (north of 70° N) is estimated to be 219 ± 116 Mg of N, which is equal to 5% of anthropogenic NOx emissions. However, for the span of a few hours, the Arctic LNO2 density can even be comparable to anthropogenic NO2 emissions in the region. These new findings suggest that LNO2 can play an important role in the upper-troposphere/lower-stratosphere atmospheric chemical processes in the Arctic, particularly during the summer.

Contains fulltext : 290880.pdf (Publisher’s version ) (Open Access) Objective: Workers with a lower socioeconomic position (SEP) often face problems on multiple life domains. This study evaluated an intervention to identify and solve problems on multiple life domains, called 'Grip on Health'. Methods: A mixed methods process evaluation was performed among occupational health professionals (OHPs) and lower SEP workers with problems on multiple life domains. Results: Thirteen OHPs delivered the intervention to 27 workers. For seven workers the supervisor was involved, and for two, stakeholders from outside the workplace. Agreements between OHPs with employers often affected implementation. OHPs were essential to help workers identify and solve problems. The intervention increased workers’ health awareness and self-control, and led to small and practical solutions. Conclusions: Grip on Health can support lower SEP workers with solving problems on multiple life domains. However, contextual factors make implementation difficult. 9 p.

SamenvattingAchtergrond:Momenteel is er nauwelijks sprake van arbocuratieve samenwerking tussen de eerstelijns- en bedrijfsgezondheidszorg. Waar eerdere initiatieven tot verbetering vooral gericht waren op de huis- en bedrijfsarts, onderzoeken we in deze bijdrage welke rol praktijkondersteuners van de huisarts (POH-ggz en POH-S) en van de bedrijfsarts (POB) voor zichzelf zien bij multiproblematiek. Tevens exploreren we welke belemmeringen er zijn voor arbocuratieve samenwerking door praktijkondersteuners bij multiproblematiek.Methode:We hebben drie focusgroepgesprekken uitgevoerd met zeven POH’s-ggz, elf POH’s‑S en acht POB’s – 26 praktijkondersteuners in totaal.Resultaten:De praktijkondersteuners in ons onderzoek komen tijdens hun werk in aanraking met multiproblematiek. POH’s en POB’s zien een rol voor zichzelf weggelegd bij het bespreken en het bieden van ondersteuning bij respectievelijk werk- en privégerelateerde klachten. Daarbij erkennen ze, waar nodig, het belang van arbocuratieve samenwerking om goede zorg te leveren. Op dit moment vindt er echter geen directe samenwerking plaats op het niveau van de praktijkondersteuner. Belemmeringen hiervoor blijken de formele regels rond taakdelegatie en rolopvatting van de POB, onbekendheid en vooroordelen bij vooral POH’s wat betreft de bedrijfsgezondheidszorg, en praktische barrières als de AVG-wetgeving en bereikbaarheid.Conclusie:POH’s en POB’s staan open voor arbocuratieve samenwerking, mits een oplossing gevonden wordt voor deze fundamentele en praktische belemmeringen.

Contains fulltext : 251275.pdf (Publisher’s version ) (Open Access) Objective: To evaluate a pilot implementation of an organizational-level intervention. The Participatory Approach (PA) was used to create a supportive work environment for employees with chronic conditions, with a key role for occupational physicians (OPs). Methods: 28 semi-structured interviews were conducted with OPs and stakeholders within their organizations. Furthermore, observational data and research notes were gathered. Data analysis occurred through content analysis. Results: Recruitment of organizations was challenging, with a reach of 25%. Dose delivered, dose received and fidelity differed across the three organizations. Organizations were positive about the PA as a method to improve support for employees with chronic conditions. Conclusions: The PA could be of added value for creating a supportive work environment. However, research is needed on activating organizations to improve support for employees with chronic conditions. 10 p.

Background: Multiple sclerosis (MS) can impact working life, sickness absence (SA) and disability pension (DP). Different types of occupations involve different demands, which may be associated with trajectories of SA/DP among people with MS (PwMS). Objectives: To explore, among PwMS and references, if SA/DP differ according to type of occupation. Furthermore, to examine how trajectories of SA/DP days are associated with type of occupation among PwMS. Methods: A longitudinal nationwide Swedish register-based cohort study was conducted, including 6100 individuals with prevalent MS and 38,641 matched references from the population. Trajectories of SA/DP were identified with group-based trajectory modelling. Multinomial logistic regressions were estimated for associations between identified trajectories and occupations. Results: Increase of SA/DP over time was observed in all occupational groups, in both PwMS and references, with higher levels of SA/DP among PwMS. The lowest levels of SA/DP were observed among managers. Three trajectory groups of SA/DP were identified: Persistently Low (55.2%), Moderate Increasing (31.9%) and High Increasing (12.8%). Managers and those working in Science & Technology, and Economics, Social & Cultural were more likely to belong to the Persistently Low group. Conclusion: Results suggest that type of occupation plays a role in the level and course of SA/DP.

XLSX file - 186K, Somatic mutation in PRCC2

XLS file, 27K, Deregulated genes known to promote carcinogenesis, tumor progression, or metastatic dissemination.

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Urothelial carcinoma of the renal pelvis is a deadly disease with an unclear tumorigenic mechanism. We conducted gene expression profiling on a set of human tumors of this type and identified a phosphatidylinositol 3-kinase (PI3K)/AKT activation expression signature in 76.9% (n = 13) of our samples. Sequence analysis found both activating mutations of PIK3CA (13.6%, n = 22) and loss of heterozygosity at the PTEN locus (25%, n = 8). In contrast, none of the other subtypes of kidney neoplasms (e.g., clear-cell renal cell carcinoma) harbored PIK3CA mutations (n = 87; P < 0.001). Immunohistochemical analysis of urothelial carcinoma samples found loss of PTEN protein expression (36.4%, n = 11) and elevation of phosphorylated mammalian target of rapamycin (mTOR; 63.6%, n = 11). To confirm the role of the PI3K/AKT pathway in urothelial carcinoma, we generated mice containing biallelic inactivation of Pten in the urogenital epithelia. These mice developed typical renal pelvic urothelial carcinomas, with an incidence of 57.1% in mice older than 1 year. Laser capture microdissection followed by PCR confirmed the deletion of Pten exons 4 and 5 in the animal tumor cells. Immunohistochemical analyses showed increased phospho-mTOR and phospho-S6K levels in the animal tumors. Renal lymph node metastases were found in 15.8% of the animals with urothelial carcinoma. In conclusion, we identified and confirmed an important role for the PI3K/AKT pathway in the development of urothelial carcinoma and suggested that inhibitors of this pathway (e.g., mTOR inhibitor) may serve as effective therapeutic agents. [Cancer Res 2009;69(21):8256–64]

PDF file, 251K, Supplemental Figure S1 (a) Gene expression profiling of 131 clinical specimens for which we have staging information shows that overexpression of PTTG1 correlates with high tumor stage. (b) Association of increased PTTG1 expression with decreased probability of survival for 5-years. Dashed lines indicate 95% confidence intervals (c) Similarly, ECT2 overexpression is most prominent in high stage ccRCC tumors. (d) PTTG1 and ECT2 are coordinately overexpressed in primarily high stage tumors. (e) Cells completely deficient of ECT2 acquire a highly-branched and spindle-shaped morphology.

Supplementary Figure 1 from Activation of the PI3K/AKT Pathway Induces Urothelial Carcinoma of the Renal Pelvis: Identification in Human Tumors and Confirmation in Animal Models

Supplementary Table 1 from Activation of the PI3K/AKT Pathway Induces Urothelial Carcinoma of the Renal Pelvis: Identification in Human Tumors and Confirmation in Animal Models

Supplementary Figures C1-C2 from A Molecular Classification of Papillary Renal Cell Carcinoma

Supplementary Table 1 from A Molecular Classification of Papillary Renal Cell Carcinoma

PDF file, 646K, Supplemental Figure S2. (a) SiRNA targeting PTTG1 achieved complete suppression of PTTG1 expression for at least 72 hours. (b) Immunofluorescent staining revealed abundant nuclear and cytoplasmic localization of PTTG1 in 786-O cells and suppression of PTTG1 expression upon treatment with targeted siRNA. (c) A 2-dimensional colony formation assay demonstrated that PTTG1 knockdown had little effect on anchorage-dependent growth rate. Crystal violet staining and microscopic imaging of these colonies further revealed that 786-O cells exhibit no major morphological differences following PTTG1 knockdown.

Supplementary Figure Legend from Activation of the PI3K/AKT Pathway Induces Urothelial Carcinoma of the Renal Pelvis: Identification in Human Tumors and Confirmation in Animal Models

PDF file - 772K, Knowledge-guided strategy of driver mutation discovery for NRF2 activation in sporadic PRCC2

XLSX file - 613K, Genes significantly downregulated in samples with either CUL3 or NRF2 mutations

Sustained activation of the stress-regulated transcription factor NRF2 (NFE2L2) is a prominent feature of many types of cancer, implying that mutations driving NRF2 may be important to tumor progression. In hereditary type 2 papillary renal cell carcinoma (PRCC2, also known as hereditary leiomyomatosis and renal cell cancer), NRF2 activation is a direct consequence of the accumulation of intracellular fumarate, a result of fumarate hydratase (FH) inactivation, but it is not clear how NRF2 may be activated in sporadic forms of PRCC2. Here we show that somatic mutations in NRF2, CUL3, and SIRT1 are responsible for driving the NRF2 activation phenotype in sporadic PRCC2. Transcriptome sequencing revealed the expression pattern of mutant alleles of NRF2, CUL3, and SIRT1 and also confirmed NRF2 activation in clinical specimens. Our results show a convergence in somatic mutations in sporadic PRCC2 with FH mutation in hereditary PRCC2. Cancer Res; 73(7); 2044–51. ©2013 AACR.

PDF file - 614K, Cycloheximide chase assay results indicate that the NRF2-E82G and the NRF2-V36del are more stable than the wild-type NRF2 (NRF2-WT)

Supplementary Table 2 from Activation of the PI3K/AKT Pathway Induces Urothelial Carcinoma of the Renal Pelvis: Identification in Human Tumors and Confirmation in Animal Models

XLSX file - 5963K, Genes that are significantly deregulated (fdr < 0.1) in tumor tissue from Case-337 in relative to pooled normal kidney tissues

PDF file - 727K, Dideoxynucleotide sequencing confirmed the presence of NRF2, CUL3, and SIRT1 mutations in case samples

PDF file, 278K, Supplemental Figure S3. Direct targeting of ECT2 by siRNA results in a dose-dependent inhibition of ccRCC cell growth. (a) MTS proliferation assays showed a dose-dependent reduction in 786-O cell growth upon treatment with siRNA's targeting ECT2. (b) Depletion of ECT2 results in an accumulation of cells in G2/M phase. (c) Cells unable to complete cell division acquired a multinucleate phenotype, indicative of cytokinesis defects upon ECT2 knockdown.

PDF file, 27K, FISH Samples: Clinical Features and Maximum PTTG1 Copy Number. Interphase FISH analysis of ccRCC tumor touch preparations. FISH probe locations are shown in Figure 1a.

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Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is a disproportionately limited understanding of its underlying genetic programs. There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials. A morphologic classification of PRCC into type 1 and 2 tumors has been recently proposed, but its biological relevance remains uncertain. We studied the gene expression profiles of 34 cases of PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both unsupervised and supervised analyses. Comparative genomic microarray analysis was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples with 15 independent tumors. We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histologic subtypes: type 1, low-grade type 2, and mixed type 1/low-grade type 2 tumors. The second class, with poor survival, corresponded to high-grade type 2 tumors (n = 11). Dysregulation of G1-S and G2-M checkpoint genes were found in class 1 and 2 tumors, respectively, alongside characteristic chromosomal aberrations. We identified a seven-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in class 1 tumors and of topoisomerase IIα in class 2 tumors. We report two molecular subclasses of PRCC, which are biologically and clinically distinct and may be readily distinguished in a clinical setting.

XLS file, 27K, Known Chromosome 5q Oncogenes.

PDF file - 197K, The pGL4luc2P-NRF2-ARE-Hygro construct (Promega)

Background With the worldwide rising obesity epidemic and the aging population, it is essential to deliver (cost-)effective care that results in enhanced societal participation among knee arthroplasty patients. The purpose of this study is to describe the development, content, and protocol of our (cost-)effectiveness study that assesses a perioperative integrated care program, including a personalized eHealth app, for knee arthroplasty patients aimed to enhance societal participation post-surgery compared to care as usual. Methods The intervention will be tested in a multicentre randomized controlled trial with eleven participating Dutch medical centers (i.e., hospitals and clinics). Working patients on the waiting-list for a total- or unicompartmental knee arthroplasty with the intention to return to work after surgery will be included. After pre-stratification on medical centre with or without eHealth as usual care, operation procedure (total- or unicompartmental knee arthroplasty) and recovery expectations regarding return to work, randomization will take place at the patient-level. A minimum of 138 patients will be included in both the intervention and control group, 276 in total. The control group will receive usual care. On top of care as usual, patients in the intervention group will receive an intervention consisting of three components: 1) a personalized eHealth intervention called ikHerstel (‘I Recover’) including an activity tracker, 2) goal setting using goal attainment scaling to improve rehabilitation and 3) a referral to a case-manager. Our main outcome is quality of life, based on patient-reported physical functioning (using PROMIS-PF). (Cost-)effectiveness will be assessed from a healthcare and societal perspective. Data collection has been started in 2020 and is expected to finish in 2024. Discussion Improving societal participation for knee arthroplasty is relevant for patients, health care providers, employers and society. This multicentre randomized controlled trial will evaluate the (cost-)effectiveness of a personalized integrated care program for knee arthroplasty patients, consisting of effective intervention components based on previous studies, compared to care as usual. Trial registration Trialsearch.who.int; reference no. NL8525, reference date version 1: 14–04-2020.

Additional file 3: Appendix 3. Participant information for participation in medical scientific research.

Additional file 1.

Additional file 2. ‘Health’ and ‘Social life’including sub-themes and main codes.

Additional file 1. Main theme ‘Work status’, including themes, sub-themes, and main codes.

Additional file 1: Appendix 1. SPIRIT checklist.

Purpose Health problems among employees with a lower socioeconomic position (SEP) often result from an interplay of problems on multiple life domains. Contextual factors greatly affect implementation of interventions that aim to solve these type of problems. The aim of this study was to gain insight into the organizational and socio-political context for implementation of preventive interventions that consider multiple life domains among employees with a lower SEP. Methods In total 16 semi-structured interviews were conducted with stakeholders at organizational level, occupational health service (OHS) level, and at socio-political macro level. Thematic analysis was performed to identify themes that describe the perceptions of stakeholders about the impact of contextual factors on implementation. Results The following themes were identified: (1) the importance of addressing problems on multiple life domains among employees with a lower SEP, (2) unclarity of responsibilities for solving problems on multiple life domains, (3) necessity of better collaboration between occupational and curative healthcare, (4) insufficient investments in prevention by employers, (5) difficulties in early identification of employees at risk for health problems, and (6) risk of conflicting role for supervisors in addressing problems on multiple life domains. Conclusions Implementation of preventive interventions considering multiple life domains among lower SEP employees is challenging, due to various contextual factors. To improve the feasibility, many different stakeholders both in- and outside occupational health practice need to be involved, collaborate, and need to be convinced of the added value to prevent problems on multiple life domains among employees with a lower SEP.

Here are the starting lineups for Netherlands vs Argentina The Netherlands takes on Argentina today at 2 p.m. ET for a spot in the semifinals. Here are the starting squads for each team: The Netherlands Goalkeeper: Andries Noppert Defenders: Jurriën Timber, Virgil van Dijk, Nathan Aké Midfielders: Memphis Depay, Marten de Roon, Daley Blind, Denzel Dumfries, Frenkie de Jong Forward: Steven Bergwijn, Cody Gakpo ------- Argentina Goalkeeper: Damián Emiliano Martínez Defenders: Cristian Romero, Lisandro Martínez, Nicolás Otamendi Midfielders: Rodrigo De Paul, Marcos Acuña, Alexis Mac Allister, Enzo Fernández, Nahuel Molina Forwards: Julián Álvarez, Lionel Messi

The TROPOspheric Monitoring Instrument (TROPOMI) onboard the Sentinel-5 Precursor (S-5P) satellite, launched in 2017, measures the total column concentration of the trace gas Carbon Monoxide (CO) daily on a global scale and at a high spatial resolution of 7 x 7 km2, improved to 5.5 x 7 km2 in August 2019. The TROPOMI observations show plumes of CO due to localized CO emissions from industrial sources and biomass burning. In this paper, we quantify these CO emissions for biomass burning by an automated algorithm, APE, to detect plumes and quantify the CO emission rate using cross-sectional flux method. Furthermore, the influence of a constant and a varying plume height in downwind direction on emissions is investigated and algorithm uncertainties are quantified. The VIIRS active fire data in conjunction with the TROPOMI CO datasets is used to identify fires and the fire locations. Then, an automated plume detection algorithm using traditional image processing algorithms is developed and utilized to identify plumes. For these plumes, the emission rate is estimated by the cross-section flux method at three different plume heights. The first two are constant plume heights at a 100 m and an IS4FIRES injection height from Global Fire Assimilation System. And the last one is a varying plume height in downwind direction. A 3D Lagrangian model is used to simulate tracer particles where the source locations for the simulation are based on the VIIRS fire counts and IS4FIRES injection height. 3D velocities at 137 model levels (ERA5) are utilized to simulate tracer particles. We demonstrate the quality and validity of our automated approach by investigating biomass burning events and their emissions for Australia on Oct 2019 and the US on Sept 2020. A total of 110 and 31 individual fire plumes in Australia and the US, respectively were detected and their emissions estimated. The emissions were severely under-predicted and negative for 11 cases when based on constant plume height of 100 m compared to emissions based on varying plume height. Furthermore, the effect of the changing plume height in downwind direction on the emission estimate compared to emissions from constant IS4FIRES plume height was minor as 124 cases are found to have emission variation less than 10 %. However, we were able to identify several cases where the flux estimates become more reliable with varying plume height. Thus, the varying plume height in downwind direction is considered for the automated algorithm. The cross-section flux method is found to have an uncertainty of 38 % in one of the idealized cases. However, overall uncertainty of the algorithm is difficult to quantify as conditions for each fire are unique.

For employees with a work disability adequate daily guidance from supervisors is key for sustainable employability. Supervisors often lack expertise to guide this group of employees. Mentorwijs (literal translation: Mentorwise) is a training for supervisors to improve the guidance of employees with a work disability. The aim of this study was to investigate the experiences of employees with a work disability regarding: (1) the guidance from their supervisors (who followed the Mentorwijs training), (2) which differences they notice in the guidance due to the Mentorwijs training, and (3) what kind of aspects they consider important in their guidance to achieve sustainable employability.A qualitative study was performed with semi-structured (group) interviews among twenty-one employees with a work disability. Thematic analysis was performed to analyze the data.Themes that followed from the interviews were: (1) work tasks and conditions can facilitate or hinder sustainable employability: (2) relationships among employees and with supervisors can affect sustainable employability; (3) a desire for new opportunities and challenges; and (4) a need for supervisor skills to facilitate sustainable employability, i.e. appreciation, availability of help, dealing with problems, listening, attitude and communication. According to employees, changes were mainly noticed in supervisor skills.Employees with a work disability were very satisfied with the guidance of supervisors who followed the Mentorwijs training. To improve sustainable employability, training of supervisors should focus more on adequate work conditions, providing employees opportunities to learn new work tasks and improving supervisors' skills regarding appreciation, attitude and communication.

Background Individual Placement and Support (IPS) is an evidence-based, effective approach to help people with severe mental illness (SMI) obtain and maintain competitive employment. The aim of the present study was to examine employment outcomes and associations with an organizational and a financial factor in people with SMI who participated in Individual Placement and Support using a multifaceted implementation strategy (IPS + MIS). The goal of this strategy was to improve IPS implementation by enhancing collaboration among mental health care and vocational rehabilitation stakeholders, and realizing secured IPS funding. Methods An observational cohort study including 103 participants was conducted, with a 30-month follow-up. Descriptive analyses were used to examine employment outcomes. Multivariable logistic and linear regression analyses were performed to study associations with an organizational and a financial factor: the level of experience of mental health agencies with providing IPS + MIS and the type of IPS funding (i.e. municipality funding (reference group) and the Dutch Social Security Institute: the Institute for Employee Benefits Schemes (UWV) funding). Results Forty-six percent of the participants were competitively employed at any time during the 30-month follow-up; the median number of days until competitive job obtainment and in competitive jobs was 201 and 265, respectively. The majority of all jobs obtained (81%) were categorized as ‘elementary occupations’, ‘clerical support workers’, and ‘service and sales workers’. A higher level of experience of the mental health agencies with providing IPS + MIS was found to be positively associated with job obtainment (OR = 3.83, 95% CI 1.42–10.30, p = 0.01) and the number of days worked in competitive jobs (B = 1.21, 95% CI 0.36–2.07, p = 0.01). UWV funding was found to be negatively associated with job obtainment (OR = 0.30, 95% CI 0.11–0.77, p = 0.01). No association was found for the type of IPS funding and the number of days worked in competitive jobs (B = -0.73, 95% CI -1.48–0.02, p = 0.06). Conclusions This study shows that almost half of the people who participate in IPS + MIS obtain a competitive job within 30 months. The results further suggest that both the level of experience of mental health agencies with providing IPS + MIS, and funding may play a role in employment outcomes.

Graphical abstract Despite the initial successful weight loss after bariatric surgery, a significant amount of patients experience weight loss failure and weight regain. Several factors are known to contribute to this, though the impact of employment status is unknown. The objective of this systematic review was to examine the impact of employment status on post-surgical weight loss outcomes. Eight studies were included with a follow-up ranging between 2 and 10 years. Employed patients seemed to present more weight loss (9.0–11.0% EWL, 1.3–1.6% BMI loss) compared to unemployed patients, but none of these numbers were statistically significant. Moreover, there were contrasting findings in terms of weight regain. This review may highlight the importance of working status after bariatric surgery and warrants further investigation on this topic. Supplementary Information The online version contains supplementary material available at 10.1007/s11695-021-05388-9.

The progress of plasmon-based technologies relies on an understanding of the properties of the enhanced electromagnetic fields generated by the coupling nanostrucutres1–6. Plasmon-enhanced applications include advanced spectroscopies7–10, optomechanics11, optomagnetics12 and biosensing13–17. However, precise determination of plasmon field intensity distribution within a nanogap remains challenging. Here, we demonstrate a molecular ruler made from a set of viologen-based, self-assembly monolayers with which we precisely measures field distribution within a plasmon nanocavity with ~2-A spatial resolution. We observed an unusually large plasmon field intensity inhomogeneity that we attribute to the formation of a plasmonic comb in the nanocavity. As a consequence, we posit that the generally adopted continuous media approximation for molecular monolayers should be used carefully. The strength of the plasmonic field between a plasmonic particle and a Au surface can be measured at ~2-A resolution by following the Raman peaks of a suitably labelled self-assembly monolayer.