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Although the literature on individual job crafting has proliferated over the past decade, research on the collaborative crafting efforts of organizational teams has lagged behind, which is surprising given the prominence of team-based arrangements in contemporary work and the importance of team proactivity in today's business environment. Drawing on proactive motivation theory and the literature on proactive performance in teams, this article presents a large-scale intervention study aimed at increasing team proactive motivation, including a pretest/posttest control group with 96 teams and 1,077 employees. We study the extent to which a team proactive motivation intervention is associated with changes in three dimensions of team crafting (task team crafting, relational team crafting, and cognitive team crafting) at both 6 months and 1 year after the intervention. We also examine the mediating role of change in the three team-level crafting dimensions in explaining the association between the intervention and change in team performance over time. Our results show that the intervention is positively associated with change in all three forms of team crafting. Furthermore, change in team crafting positively associates with change in team performance 6 months and 1 year after the intervention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Our study provides the most comprehensive dataset for high-precision radiogenic isotopes of lead (Pb) in blood for the western European population. It investigates their potential for elucidating the contribution of soil Pb to blood Pb using a human biomonitoring survey involving 81 adults and 4 children living in the urban area of Liège (Belgium). Soils in the area show moderate (median of 360 mg/kg) to high (95th percentile of 1000 mg/kg) Pb concentrations, due to former metal processing activities. Blood lead levels (BLL) measured in the study population are, on average, quantitatively consistent with a â¼ 20 % increase due to the exposure to Pb from soils, as estimated by a single-compartment biokinetic model. Consistently, its isotopic composition does not represent an endmember that fully accounts for the variability of Blood lead isotope (BLI) compositions measured in the study population. While some individuals show more thorogenic BLI ratios (relatively more enriched in 208Pb), which could be consistent with a greater exposure to local soils and/or by their country of birth, the BLI data mostly follow a trend roughly parallel to the European Standard Lead Pollution (ESLP) line, within the European leaded gasoline field, even two decades after the withdrawal of this source. Differences in BLI are probably associated with factors related to the presence of Pb in dwellings (pipes, paint) and drinking water distribution system, suggesting that the anthropogenic Pb in use, relevant to human exposure, may contain ore components of different origins, including the Australian Pb ore signature.
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Exposição Ambiental , Chumbo , Poluentes do Solo , Chumbo/sangue , Poluentes do Solo/análise , Poluentes do Solo/sangue , Humanos , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/análise , Bélgica , Criança , Adulto , Radioisótopos de Chumbo/análise , Monitoramento Ambiental/métodos , Solo/química , Monitoramento Biológico/métodosRESUMO
OBJECTIVE: Previous studies evaluating interdisciplinary multimodal interventions for chronic spinal pain often excluded patients with comorbid mental disorders. This study aims to assess the effectiveness of an outpatient secondary care interdisciplinary multimodal integrative healthcare program for individuals experiencing co-occurring chronic spinal pain and mental disorders. METHODS: Participants were 944 patients with chronic spinal pain and comorbid mental disorders. Primary outcomes were health-related quality of life, assessed using the Research and Development-36 (RAND-36), and pain-related disability, assessed using the Quebec Back Pain Disability Scale (QBPDS). Secondary outcomes included pain intensity, pain catastrophizing, kinesiophobia, fatigue, lumbar mobility, and isometric strength. Data were collected during the healthcare program at four time points: pretreatment (T0), midway through 20-week treatment (T1), end of 20-week treatment (T2), and at completion of 12-month relapse prevention program (T3). Multilevel regression analyses were conducted to examine the effects of the healthcare program on primary outcomes over time. RESULTS: The 20-week treatment period yielded significant improvements in both mental ( B = 0.44, t (943) = 19.42, p < .001) and physical component summary scores ( B = 0.45, t (943) = 18.24, p < .001) of the RAND-36, as well as in QBPDS total score ( B = -0.77, t (943) = -26.16 p < .001). Pretreatment scores indicated the presence of problematic fatigue, kinesiophobia, and clinical levels of pain catastrophizing, all of which resolved by the end of the 12-month relapse prevention program. CONCLUSIONS: An interdisciplinary multimodal integrative healthcare program seems effective for patients with chronic spinal pain and comorbid mental disorders.
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Dor Crônica , Comorbidade , Transtornos Mentais , Qualidade de Vida , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Dor Crônica/terapia , Dor Crônica/epidemiologia , Adulto , Transtornos Mentais/terapia , Transtornos Mentais/epidemiologia , Dor nas Costas/terapia , Dor nas Costas/epidemiologia , Terapia Combinada , Idoso , Equipe de Assistência ao Paciente , Medicina Integrativa/métodosRESUMO
Introduction: Nurses frequently innovate in response to operational failures, regulations, procedures, and/or other workflow barriers that prevent them from delivering high-quality patient care. Unfortunately, most nurse innovations do not diffuse to a broader audience, depriving other nurses from taking advantage of solutions that have already been developed elsewhere. This under-diffusion is problematic from a societal and welfare point of view. The goal of this paper is to understand how diffusion shortage of nurse innovations can be reduced. Methods: We develop a qualitative case study of a medical makerspace at the largest academic hospital in the Netherlands. This medical makerspace reported unusually high rates of nurse innovation diffusion. Our data collection includes on-site observations, archival data, secondary data, and fifteen in-depth interviews with key informants. Qualitative coding procedures and a combination of deductive and inductive reasoning are used to analyze the data. Results: Our data show that personal, organizational, regulatory, and market barriers prevent nurses from further developing and diffusion their innovations in an anticipatory manner. That is, because nurses expect that transforming an initial solution into an innovation that can be shared with others will be too time consuming and difficult they do not proceed with the further development. The medical makerspace that we investigated adequately addresses this problem by developing an innovation ecosystem that largely takes over the innovation and diffusion process. Discussion: We provide a concrete example of how a medical makerspace, and innovation support systems in a broader sense, can be designed to more adequately address the nurse innovation-diffusion gap. The two main elements of the practical solution that we identified are: (1) Support systems should facilitate that others may lead the development and diffusion of innovations and (2) The support system should promote that actors integrate their functional specializations within an innovation ecosystem. We make two theoretical contributions. First, we contribute to understanding barriers in the nurse innovation-diffusion process from a psychological point. Second, we identified that an ecosystem perspective is beneficial to develop innovation support systems in which diffusion occurs more often.
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Difusão de Inovações , Ecossistema , Humanos , Hospitais , Países Baixos , Resolução de ProblemasRESUMO
Objective: Although multimodal interventions are recommended in patients with severe depressive and/or anxiety disorders, available evidence is scarce. Therefore, the current study evaluates the effectiveness of an outpatient secondary care interdisciplinary multimodal integrative healthcare program, delivered within a transdiagnostic framework, for patients with (comorbid) depressive and/or anxiety disorders. Methods: Participants were 3,900 patients diagnosed with a depressive and/or anxiety disorder. The primary outcome was Health-Related Quality of Life (HRQoL) measured with the Research and Development-36 (RAND-36). Secondary outcomes included: (1) current psychological and physical symptoms measured with the Brief Symptom Inventory (BSI) and (2) symptoms of depression, anxiety, and stress measured with the Depression Anxiety Stress Scale (DASS). The healthcare program consisted of two active treatment phases: main 20-week program and a subsequent continuation-phase intervention (i.e., 12-month relapse prevention program). Mixed linear models were used to examine the effects of the healthcare program on primary/secondary outcomes over four time points: before start 20-week program (T0), halfway 20-week program (T1), end of 20-week program (T2) and end of 12-month relapse prevention program (T3). Results: Results showed significant improvements from T0 to T2 for the primary variable (i.e., RAND-36) and secondary variables (i.e., BSI/DASS). During the 12-month relapse prevention program, further significant improvements were mainly observed for secondary variables (i.e., BSI/DASS) and to a lesser extent for the primary variable (i.e., RAND-36). At the end of the relapse prevention program (i.e., T3), 63% of patients achieved remission of depressive symptoms (i.e., DASS depression score ≤ 9) and 67% of patients achieved remission of anxiety symptoms (i.e., DASS anxiety score ≤ 7). Conclusion: An interdisciplinary multimodal integrative healthcare program, delivered within a transdiagnostic framework, seems effective for patients suffering from depressive and/or anxiety disorders with regard to HRQoL and symptoms of psychopathology. As reimbursement and funding for interdisciplinary multimodal interventions in this patient group has been under pressure in recent years, this study could add important evidence by reporting on routinely collected outcome data from a large patient group. Future studies should further investigate the long-term stability of treatment outcomes after interdisciplinary multimodal interventions for patients suffering from depressive and/or anxiety disorders.
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Gallium is a moderately volatile, moderately siderophile element with two stable isotopes: 69Ga and 71Ga. A general interest in Ga isotopes arose over the last few years, as its moderately volatile behavior potentially marks it as a useful tracer of various processes such as condensation and evaporation. Nevertheless, there is a lack of agreement between laboratories for consistent δ71Ga values in geological reference materials. In this work, we have developed and evaluated two methods for purification protocols leading to precise analysis of gallium (Ga) isotopic composition in silicate rock materials. The first method is a three-step column chemistry using the resins AG1-X8, HDEHP, and AG50W-X12 whereas the second method uses only two columns, AG1-X8 and AG50W-X8. The two methods were applied to a range of both synthetic (multi-element) solutions and geological samples. Both methods show comparable results with no isotope fractionation occurring during purification chemistry, allowing us to define the δ71Ga of selected USGS reference materials (BHVO-2, BCR-2, RGM-2). Similar to previously reported results, we also observe no Ga fractionation between distinct igneous terrestrial materials.
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OBJECTIVE: Although multimodal interventions are generally recommended in patients with long-term somatic symptom disorders (SSD), available evidence is limited. The current study evaluates the effectiveness of an outpatient secondary care interdisciplinary multimodal integrative healthcare program for patients with SSD and predominant (spinal) pain. METHOD: The healthcare program consisted of two active treatment phases: main 20-week program and a 12-month relapse prevention program. Participants were 4453 patients diagnosed with SSD. The primary outcome was health-related quality of life (HRQoL) assessed using the RAND-36 (i.e., mental/physical component summary) and secondary outcomes included physical and psychological symptoms assessed using the Brief Symptom Inventory (BSI) and RAND-36 subscales. Mixed linear models were used to examine the effects of the multimodal healthcare program on primary/secondary outcomes over four time points: before start 20-week program (T0), halfway 20-week program (T1), end of 20-week program (T2) and end of relapse prevention program (T3). RESULTS: Significant improvements were found from T0 to T2 for all primary variables (i.e., mental/physical component summary) and secondary variables (i.e., BSI/RAND-36 subscales), which were maintained until the end of the relapse prevention program (T3). CONCLUSION: An interdisciplinary multimodal integrative treatment for SSD is effective for improving HRQoL and reducing physical and psychological symptoms.
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Sintomas Inexplicáveis , Transtornos Mentais , Humanos , Qualidade de Vida , Dor , Atenção à SaúdeRESUMO
OBJECTIVE: Small fiber neuropathy (SFN) is characterized by chronic neuropathic pain and autonomic dysfunction. Currently, symptomatic pharmacological treatment is often insufficient and frequently causes side effects. SFN patients have a reduced quality of life. However, little is known regarding whether psycho-social variables influence the development and maintenance of SFN-related disability and complaints. Additional knowledge may have consequences for the treatment of SFN. For example, factors such as thinking, feeling, and behavior are known to play roles in other chronic pain conditions. The aim of this study was to obtain further in-depth information about the experience of living with SFN and related chronic pain. METHODS: Fifteen participants with idiopathic SFN participated in a prospective, semi-structured, qualitative, focus group interview study. The focus groups were audio-recorded, transcribed, and analyzed cyclically after each interview. RESULTS: The following main themes were identified: "pain appraisal", "coping", "social, work, and health environment", and "change in identity". Catastrophic thoughts and negative emotions were observed. Living with SFN resulted in daily limitations and reduced quality of life. CONCLUSIONS: Given the results, it can be concluded that an optimal treatment should include biological, psychological, and social components.
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Dor Crônica , Neuropatia de Pequenas Fibras , Humanos , Neuropatia de Pequenas Fibras/diagnóstico , Neuropatia de Pequenas Fibras/etiologia , Grupos Focais , Qualidade de Vida , Estudos ProspectivosRESUMO
PURPOSE: While both perceived job autonomy and self-leadership are assumed to be important for optimal functioning of healthcare workers, their mutual relationship remains unclear. This cross-lagged study aims to theorize and test that perceived job autonomy and self-leadership have a reciprocal relationship, which is moderated by need for job autonomy. DESIGN/METHODOLOGY/APPROACH: Two-wave panel data were used to measure cross-lagged relationships over a time period of three months. Self-leadership is indicated by both self-leadership strategies and self-leadership behavior. The data were analyzed using hierarchical multiple regression (HMR). FINDINGS: Job autonomy was not causally nor reverse related to self-leadership strategies, but did relate to self-leadership behavior in both directions. Need for job autonomy did not influence the causal and reverse relationships between job autonomy and self-leadership (strategies and behavior). Instead, need for job autonomy discarded the influence of job autonomy on self-leadership behavior, and predicted self-leadership behavior over time. PRACTICAL IMPLICATIONS: For optimizing healthcare jobs, human resource management (HRM) policy makers need to consider other interventions such as training self-leadership, or developing an autonomy supportive work environment, since job autonomy does not lead to more use of self-leadership strategies. ORIGINALITY/VALUE: This study used a cross-lagged study design which gives the opportunity to investigate causal relationships between job autonomy and self-leadership. Both self-leadership strategies and self-leadership behavior are included.
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Liderança , Local de Trabalho , Pessoal de Saúde , Humanos , Satisfação no Emprego , Inquéritos e Questionários , Recursos HumanosRESUMO
In prostate cancer, androgen receptor (AR)-targeting agents are very effective in various disease stages. However, therapy resistance inevitably occurs, and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multiomics analyses on tissues isolated before and after 3 months of AR-targeting enzalutamide monotherapy from patients with high-risk prostate cancer enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors toward a neuroendocrine-like disease state. Additionally, epigenomic profiling revealed massive enzalutamide-induced reprogramming of pioneer factor FOXA1 from inactive chromatin sites toward active cis-regulatory elements that dictate prosurvival signals. Notably, treatment-induced FOXA1 sites were enriched for the circadian clock component ARNTL. Posttreatment ARNTL levels were associated with patients' clinical outcomes, and ARNTL knockout strongly decreased prostate cancer cell growth. Our data highlight a remarkable cistromic plasticity of FOXA1 following AR-targeted therapy and revealed an acquired dependency on the circadian regulator ARNTL, a novel candidate therapeutic target. SIGNIFICANCE: Understanding how prostate cancers adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenomic plasticity toward prosurvival signaling and uncovered the circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel lead for therapeutic development. See related commentary by Zhang et al., p. 2017. This article is highlighted in the In This Issue feature, p. 2007.
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Androgênios , Neoplasias de Próstata Resistentes à Castração , Fatores de Transcrição ARNTL/genética , Androgênios/farmacologia , Androgênios/uso terapêutico , Linhagem Celular Tumoral , Ritmo Circadiano , Resistencia a Medicamentos Antineoplásicos/genética , Epigenômica , Humanos , Masculino , Nitrilas/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/genéticaRESUMO
The importance of DNA evidence for gaining investigative leads demands a fast workflow for forensic DNA profiling performed in large volumes. Therefore, we developed software solutions for automated DNA profile analysis, contamination check, major donor inference, DNA database (DDB) comparison and reporting of the conclusions. This represents the Fast DNA IDentification Line (FIDL) and this study describes its development, validation and implementation in criminal casework at the authors' institute. This first implementation regards single donor profiles and major contributors to mixtures. The validation included testing of the software components on their own and examination of the performance of different DDB search strategies. Furthermore, end-to-end testing was performed under three conditions: (1) testing of scenarios that can occur in DNA casework practice, (2) tests using three months of previous casework data, and (3) testing in a casework production environment in parallel to standard casework practices. The same DNA database candidates were retrieved by this automated line as by the manual workflow. The data flow was correct, results were reproducible and robust, results requiring manual analysis were correctly flagged, and reported results were as expected. Overall, we found FIDL valid for use in casework practice in our institute. The results from FIDL are automatically reported within three working days from receiving the trace sample. This includes the time needed for registration of the case, DNA extraction, quantification, polymerase chain reaction and capillary electrophoresis. FIDL itself takes less than two hours from intake of the raw CE data to reporting. Reported conclusions are one of five options: (1) candidate retrieved from DDB, (2) no candidate retrieved from DDB, (3) high evidential value with regards to reference within the case, (4) results require examination of expert, or (5) insufficient amount of DNA obtained to generate a DNA profile. In our current process, the automated report is sent within three working days and a complete report, with confirmation of the FIDL results, and signed by a reporting officer is sent at a later time. The signed report may include additional analyses regarding e.g. minor contributors. The automated report with first case results is quickly available to the police enabling them to act upon the DNA results prior to receiving the full DNA report. This line enables a uniform and efficient manner of handling large numbers of traces and cases and provides high value investigative leads in the early stages of the investigation.
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Impressões Digitais de DNA , DNA , DNA/genética , Impressões Digitais de DNA/métodos , Eletroforese Capilar , Humanos , Reação em Cadeia da Polimerase , SoftwareRESUMO
Atmospheric deposition is a key mode of iron (Fe) input to ocean regions where low concentrations of this micronutrient limit marine primary production. Various natural particles (e.g., mineral dust, volcanic ash) and anthropogenic particles (e.g., from industrial processes, biomass burning) can deliver Fe to the ocean, and assessment of their relative importance in supplying Fe to seawater requires knowledge of both their deposition flux and their Fe solubility (a proxy for Fe bioavailability). Iron isotope (54Fe, 56Fe, 57Fe, 58Fe) analysis is a potential tool for tracing natural and anthropogenic Fe inputs to the ocean. However, it remains uncertain how the distinct Fe isotopic signatures (δ56Fe) of these particles may be modified by physicochemical processes (e.g., acidification, photochemistry, condensation-evaporation cycles) that are known to enhance Fe solubility during atmospheric transport. In this experimental study, we measure changes over time in both Fe solubility and δ56Fe of a Tunisian soil dust and an Fe-Mn alloy factory industrial ash exposed under irradiation to a pH 2 solution containing oxalic acid, the most widespread organic complexing agent in cloud- and rainwater. The Fe released per unit surface area of the ash (â¼1460 µg Fe m-2) is â¼40 times higher than that released by the dust after 60 min in solution. Isotopic fractionation is also observed, to a greater extent in the dust than the ash, in parallel with dissolution of the solid particles and driven by preferential release of 54Fe into solution. After the initial release of 54Fe, the re-adsorption of A-type Fe-oxalate ternary complexes on the most stable surface sites of the solid particles seems to impair the release of the heavier Fe isotopes, maintaining a relative enrichment in the light Fe isotope in solution over time. These findings provide new insights on Fe mobilisation and isotopic fractionation in mineral dust and industrial ash during atmospheric processing, with potential implications for ultimately improving the tracing of natural versus anthropogenic contributions of soluble Fe to the ocean.
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Poeira , Água , Poeira/análise , Isótopos de Ferro , Minerais , SolubilidadeRESUMO
Exposure in vivo (EXP) is an effective treatment to reduce pain-related fear and disability in chronic pain populations. Yet, it remains unclear how reductions in fear and pain relate to each other. This single-case experimental design study attempted to identify patterns in the individual responses to EXP and to unravel temporal trajectories of fear and pain. Daily diaries were completed before, during and after EXP. Multilevel modelling analyses were performed to evaluate the overall effect. Temporal effects were scrutinized by individual regression analyses and determination of the time to reach a minimal clinically important difference. Furthermore, individual graphs were visually inspected for potential patterns. Twenty patients with chronic low back pain and complex regional pain syndrome type I were included. On a group level, both fear and pain were reduced following EXP. Individually, fear was significantly reduced in 65% of the patients, while pain in only 20%. A decrease in fear was seen mostly in the first weeks, while pain levels reduced later or remained unchanged. Daily measurements provided rich data on temporal trajectories of reductions in fear and pain. Overall, reductions in fear preceded pain relief and seemed to be essential to achieve pain reductions.
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Comprehensive analysis of tumor infiltrating myeloid cells in the tumor microenvironment of penile squamous cell carcinoma (PSCC) is lacking. In this retrospective study, for the first time, PSCC resection specimens (N = 103) were annotated into the following compartments: intratumoral tumor (IT Tumor), intratumoral stroma (IT Stroma), peritumoral tumor (PT Tumor) and peritumoral stroma (PT Stroma) compartments. We then quantified CD14+, CD68+ and CD163+ myeloid cells within these compartments using an image analysis software and assessed their association with various clinical parameters, including high-risk human papillomavirus (hrHPV) status. In the total cohort, hrHPV status, grade of differentiation, age and tumor size were associated with myeloid cell densities. hrHPV+ tumors had higher infiltration rates of CD14+, CD68+ and CD163+ myeloid cells in the IT tumor compartment (p < 0.001, for all) compared to hrHPV- tumors. Furthermore, when examining the association between compartment-specific infiltration and differentiation grade, increased myeloid cell densities in the IT tumor compartment were associated with a more advanced histological grade (p < 0.001, for all). This association remained significant when the hrHPV- cohort (N = 60) was analyzed (CD14+ p = 0.001; CD68+ p < 0.001; CD163+ p = 0.004). Subgroup analysis in the hrHPV+ group (N = 43) showed that high infiltration rates of CD68+ and CD163+ cells in the PT tumor compartment were associated with lymph node (LN) metastasis (p = 0.031 and p = 0.026, respectively). Regarding the association between myeloid cell densities and disease-specific survival, the risk of death was found to decrease slightly as the number of myeloid cells in the IT tumor compartment increased (CD14+ p = 0.04; CD68+ p = 0.05; CD163+ p = 0.02). However, after adjusting for hrHPV, no independent association between myeloid densities and disease-specific survival were found. Altogether, these findings demonstrate the importance of assessing myeloid cell densities within the spatial context of the tumor. Further studies are needed to unravel the specific phenotype of myeloid cells residing in the different compartments, their effect on clinical parameters and the impact of hrHPV on the recruitment of myeloid cell populations in PSCC.
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Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Células Mieloides/patologia , Infecções por Papillomavirus/complicações , Neoplasias Penianas/etiologia , Neoplasias Penianas/patologia , Microambiente Tumoral , Biomarcadores , Biópsia , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Infecções por Papillomavirus/virologiaRESUMO
The present study aims to test the impact of a self-leadership intervention on the work engagement, performance, and health of health care workers. By integrating self-determination theory and self-leadership theory, we propose that when employees are trained how they can autonomously influence own cognitions and behaviour, this will impact their work engagement, perceived performance, and general health. To test the hypotheses, a longitudinal field experiment with three measurement waves was conducted (pre-intervention, immediately after the intervention, and 2 months after the intervention). Health care professionals (n = 195) from five different organizations participated on voluntary basis and were randomly assigned to the intervention or control group. Results show that a self-leadership training positively impacts work engagement and performance of health care workers. Furthermore, the improved work engagement also mediates the effects of the training on health and performance 2 months later. No direct effect was found on general health. Theoretical and practical implications are discussed. PRACTITIONERS POINTS: The self-leadership intervention facilitates healthcare workers to develop self-determination and autonomous motivation, which will positively impact their work engagement, health, and performanceParticipation in the self-leadership intervention needs to be based on volition as this will contribute to the intrinsic motivation for actual self-leadership development through training.
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Metastatic renal cell carcinoma (RCC) has a poor prognosis. Recent advances have shown beneficial responses to immune checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies. As only a subset of RCC patients respond, alternative strategies should be explored. Patients refractory to anti-PD-1 therapy may benefit from autologous tumor-infiltrating lymphocyte (TIL) therapy. Even though efficient TIL expansion was reported from RCC lesions, it is not well established how many RCC TIL products are tumor-reactive, how well they produce pro-inflammatory cytokines in response to autologous tumors, and whether their response correlates with the presence of specific immune cells in the tumor lesions. We here compared the immune infiltrate composition of RCC lesions with that of autologous kidney tissue of 18 RCC patients. Tcell infiltrates were increased in the tumor lesions, and CD8+ Tcell infiltrates were primarily of effector memory phenotype. Nine out of 16 (56%) tested TIL products we generated were tumor-reactive, as defined by CD137 upregulation after exposure to autologous tumor digest. Tumor reactivity was found in particular in TIL products originating from tumors with ahigh percentage of infiltrated Tcells compared to autologous kidney, and increased CD25 expression on CD8+ Tcells. Importantly, although TIL products had the capacity to produce the key effector cytokines IFN-γ, TNF-α or IL-2, they failed to produce significant amounts in response to autologous tumor digests. In conclusion, TIL products from RCC lesions contain tumor-reactive Tcells. Their restricted tumor-specific cytokine production requires further investigation of immunosuppressive factors in RCC and subsequent optimization of RCC-derived TIL culture conditions.
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Carcinoma de Células Renais , Neoplasias Renais , Linfócitos T CD8-Positivos , Citotoxicidade Imunológica , Humanos , Interleucina-2 , Linfócitos do Interstício Tumoral , Membro 9 da Superfamília de Receptores de Fatores de Necrose TumoralRESUMO
Background: A subset of patients with chronic pain who receive exposure in vivo (EXP) treatment experience clinically relevant relief of pain intensity. Although pain relief is not an explicit therapeutic target, it is important to understand how and why this concomitant effect occurs in some patients but not others. This longitudinal study therefore aimed to characterize brain plasticity as well as to explore pretreatment factors related to pain relief. Methods: Resting-state functional magnetic resonance imaging data were acquired in 30 patients with chronic pain. Twenty-three patients completed EXP, and 6-month follow-up data were available in 20 patients (magnetic resonance imaging data in 17 patients). Pain-free control data were acquired at two time points (n = 29, n = 21). Seed-based resting-state functional connectivity (rsFC) analyses were performed, with seeds in the amygdala, hippocampus, and nucleus accumbens. Results: Pain relief after EXP was highly variable, with 60% of patients reporting a clinically relevant improvement. Amygdala rsFC with the middle frontal gyrus decreased significantly over time in patients but was not associated with pain relief. In contrast, greater pain relief was associated with greater decreases over time in hippocampus rsFC with the precuneus, which was related to reductions in catastrophizing (EXP therapeutic target) as well. Greater pain relief was also associated with lower pretreatment rsFC between nucleus accumbens and postcentral gyrus. Conclusions: While changes in hippocampus rsFC were associated with pain relief after EXP, pretreatment nucleus accumbens rsFC showed potential prognostic value. Our findings further support the importance of corticolimbic circuitry in chronic pain, emphasizing its relation to pain relief and identifying potential underlying mechanisms and prognostic factors, warranting further testing in independent samples.
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Cerium is the most abundant rare earth element (REE) in the solar photosphere, CI chondrites, and the Earth. It has four main stable isotopes (masses: 136,138,140, and 142), with 138Ce being the most studied species, used in geochronology and petrogenesis. In addition, more abundant 140Ce and 142Ce are suggested to be potentially applicable in geochemical investigations. In this work, we developed a modified four-step ion chromatography procedure for Ce chemical separation. Using a MC-ICPMS, we designed a cup configuration to measure 142Ce/140Ce ratio of the samples with an optimized Nd correction equation. A 0.03 (2SD) reproducibility was obtained for Ce Ames metal standard. We analyzed ten different igneous and one sedimentary geochemical reference materials. Mean δ142Ce range from -0.07 to 0.32. Most of the samples show a heavier Ce isotopic composition than the Ce Ames standard. The majority of rocks have a homogenous δ142Ce. The δ142Ce does not show any correlation with rock chemical composition including their Ce content or rock types. A carbonatite (SARM 40) has a mean δ142Ce of -0.07 ± 0.13 (2SD), lower than the other rocks, suggesting the possibility of a pronounced isotopic fractionation. Our work demonstrates the applicability of the developed methodology and the potential of Ce stable isotopes for future geochemical studies. Production of a larger database of δ142Ce values is required to obtain a clearer view on the similarities and differences between different geological material and explaining Ce stable isotope dynamics.
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The androgen receptor (AR) is the master regulator of prostate cancer (PCa) development, and inhibition of AR signalling is the most effective PCa treatment. AR is expressed in PCa cells and also in the PCa-associated stroma, including infiltrating macrophages. Macrophages have a decisive function in PCa initiation and progression, but the role of AR in macrophages remains largely unexplored. Here, we show that AR signalling in the macrophage-like THP-1 cell line supports PCa cell line migration and invasion in culture via increased Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) signalling and expression of its downstream cytokines. Moreover, AR signalling in THP-1 and monocyte-derived macrophages upregulates IL-10 and markers of tissue residency. In conclusion, our data suggest that AR signalling in macrophages may support PCa invasiveness, and blocking this process may constitute one mechanism of anti-androgen therapy.
Assuntos
Macrófagos/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Idoso , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Anilidas/farmacologia , Anilidas/uso terapêutico , Biópsia , Buffy Coat/citologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Quimioterapia Adjuvante , Técnicas de Cocultura , Intervalo Livre de Doença , Humanos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/prevenção & controle , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Intervalo Livre de Progressão , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Procedimentos Cirúrgicos Robóticos , Transdução de Sinais/imunologia , Análise de Célula Única , Células THP-1 , Compostos de Tosil/farmacologia , Compostos de Tosil/uso terapêuticoRESUMO
Due to the high workload, working within the healthcare industry can be quite demanding. This often results in high rates of absenteeism, unfulfilled vacancies, and voluntary turnover among healthcare workers. We expect that job autonomy is an important resource for work engagement and health of healthcare workers because it satisfies the basic need for autonomy. However, we propose that this relationship between job autonomy and work engagement and health can be explained by self-leadership. Self-leading individuals take initiative and responsibility and are assumed to use self-influencing strategies (e.g., goal setting, self-observation, creating natural rewards) as a way to improve motivation and general well-being. Employees from two healthcare organizations (N = 224 and N = 113) completed a questionnaire containing measures of job autonomy, work engagement, general health, and self-leadership. The hypothesized model was tested using a series of regressions, and the results confirmed the indirect relationships between job autonomy and work engagement and general health, respectively, through natural rewards strategies. The behavior-focused and cognitive self-leadership strategies were, as mediator, marginally significant: positively for work engagement and negatively for general health. Self-leadership behavior was not related with work engagement and general health. Implications of the findings for theory and practice on healthy healthcare workers are discussed.