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Objectives The prevalence of precarious employment is increasing, particularly among young adults where less is known about the long-term health consequences. The present study aims to test if being precariously employed in young adulthood is associated with an increased risk of alcohol-related morbidity later in life. Methods A register-based cohort study was conducted in Sweden. The Swedish Work, Illness, and Labor-market Participation (SWIP) cohort was used to identify individuals who were aged 27 years between 2000 and 2003 (n=339 403). Information on labour market position (precarious employment, long-term unemployment, substandard employment and standard employment relations) was collected for young people 3 years after graduation from school using nationwide registers. Details about alcohol-related morbidity during a 28-year follow-up period were collected from the National Hospital Discharge Register. Data on sex, age, country of birth, education and previous poor health were also obtained from the registers. Results Young adults in precarious employment had an increased risk of alcohol-related morbidity compared with individuals of the same age in standard employment (HR 1.43, 95% CI 1.32 to 1.55), after adjusting for several important covariates. A stronger association was found among young men who were precariously employed compared with young women. Conclusion This nationwide register-based study conducted in Sweden with a long-term follow-up suggests that being precariously employed in young adulthood is associated with an increased risk of alcohol-related morbidity later in life.

Background: The workplace can be affected negatively by hazardous alcohol use, and intervening at an early stage remains a challenge. Recently, a multi-component alcohol prevention program, Alcohol Policy and Managers’ skills Training (hereafter, ‘APMaT’), was delivered at the organizational level. In a previous outcome evaluation, APMaT appeared to be effective at the managerial level. The current study takes a step further by aiming to evaluate the effectiveness of APMaT in decreasing the alcohol risk level among employees. Methods: Data from 853 employees (control: n = 586; intervention: n = 267) were gathered through a cluster-randomized study. To analyze changes in the odds of hazardous alcohol use among employees, multilevel logistic regression was applied using group (control vs. intervention), time (baseline vs. 12-month follow-up), and the multiplicative interaction term (group × time) as the main predictors. The intervention effect was further adjusted for sociodemographic characteristics and policy awareness. Results: No statistically significant difference was observed in the odds of hazardous alcohol use, although employees in the intervention group showed a larger decrease compared to the control group. This remained even after adjusting for several factors, including the sociodemographic factors and policy awareness. Conclusions: The findings are insufficient to determine the effectiveness of APMaT at the employee level at the current stage of the evaluation. Future studies should strive to identify issues with implementation processes in workplace-based alcohol interventions., Open access funding provided by Stockholm University. The funding for this project was provided by the Public Health Agency of Sweden (grant no: 02781 − 2017; 03333 − 2018; 03843 − 2019).

Background: Alcohol interventions targeting the adult population are often conducted in healthcare settings, while preventive interventions often target adolescents or young adults. The general working population is often overlooked. A workplace-based intervention, consisting of development and implementation of an organizational alcohol policy, and skills development training for managers (APMaT) was carried out in order to prevent and reduce alcohol-related harms by identifying hazardous consumers at an early stage. Objective: This study aims to evaluate APMaT by focusing on managers’ inclination to initiate early alcohol intervention. Methods: In a cluster randomized design, data were obtained from 187 managers (control: n = 70; intervention: n = 117). Inclination to initiate early alcohol intervention was measured using three items on a 5-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). Changes in managers’ inclination to intervene were analyzed by applying multilevel ordered logistic regression. Predictors included in the model were group (control vs. intervention), time (baseline vs. 12-month follow-up), and the multiplicative interaction term (group × time). Results: Significant increase in inclination to intervene against hazardous alcohol consumption among managers in the intervention group compared to managers in the control group was observed. Specifically, a 50% increase of confidence to initiate an intervention was observed among managers in the intervention group. Conclusions: APMaT seems effective to increase managers’ inclination to intervene early against hazardous consumption in the workplace. The effectiveness of APMaT at the employee level should be explored in prospective studies.

Purpose - An alcohol prevention programme, consisting of the implementation of an organisational alcohol policy and skills development training for managers, was delivered in Swedish workplaces. Previous findings revealed challenges in policy implementation because of the lack of dissemination amongst managers. This study aims to describe perceived dissemination barriers of the organisational alcohol policy by managers. Design/methodology/approach - A cross-sectional survey (n = 193 managers) was performed to identify common dissemination barriers in the workplace and complementary case illustrations derived from semi-structured interviews (n = 18 managers) were used to understand the dissemination barriers of the organisational alcohol policy. Frequency distributions were presented to describe common perceived barriers. Findings - Sixty-five per cent of managers reported that their workplace had not changed their approach to addressing alcohol-related issues compared to their usual practice before programme delivery. Various organisational factors, such as deprioritisation of programme dissemination, lack of communication and inadequate strategies were some of the common barriers perceived by managers. Moreover, managers reported uncertainties regarding any changes concerning the workplace's approach for addressing alcohol-related issues. Increased efforts in disseminating the organisational alcohol policy can reduce uncertainties among managers. Practical implications - A thorough process evaluation to understand processes in programme delivery and implementation is necessary to ensure the uptake of the intervention. Originality/value - This study highlighted the complexity of disseminating an alcohol policy in a dynamic setting, such as the workplace, and provided the importance of addressing organisational obstacles.

Background: Globally, women constitute 30% of researchers. Despite an increasing proportion of women in research, they are still less likely to have international collaborations. Literature on barriers to knowledge transfer and exchange (KTE) between men and women remains limited. This study aimed to assess perceived gender barriers to KTE activities in vaccination-related research in low-, middle- and high-income countries. Methods: This was a cross-sectional data assessment from a self-administered questionnaire distributed to researchers in the field of vaccination research. The administered questionnaire was developed and validated by WHO and McMaster University. Descriptive statistics were carried out. Structural factors of KTE were assessed using 12 statements measured with a five-point Likert scale, ranging from 1 (strongly disagree) to 5 (strongly agree). An index ranging from 12 to 60 points was created to assess structural factors of KTE, with higher score indicating fewer perceived barriers. Multivariable linear regression modelling was applied to examine the association between KTE barriers and gender. Results: A total of 158 researchers were included in the analysis. Regardless of gender and country of affiliation, researchers experienced challenges with respect to KTE activities; particularly factors related to the availability of human and financial resources and level of technical expertise among their target audience. We were also able to identify perceived facilitators among men and women, such as the presence of structures that link researchers and target audiences, the investment of target audiences in KTE efforts and the presence of stable contacts among target audiences. Our linear regression analysis showed that women perceived more barriers than men (R-2 = 0.014; B = -1.069; 95% CI -4.035; 1.897). Conclusions: Men and women shared common perspectives on barriers to KTE. KTE activities could be strengthened by improving structural efforts to r

Purpose - Individual factors associated with managers' organisational alcohol policy knowledge and inclination to initiate early alcohol interventions have been understudied. This study aims to examine differences in managers' policy knowledge and inclination across a range of socio-demographic, work-related and health characteristics, and it aims to examine the association between policy knowledge and inclination to intervene, net of these characteristics. Design/methodology/approach - Questionnaire data were collected from 430 managers. Organisational alcohol policy knowledge and inclination to intervene were measured using a 5-point Likert scale ranging from 1 (very low) to 5 (very high). Socio-demographic, work-related and health characteristics included gender, age, education, managerial responsibility, years in current position, self-rated health and alcohol consumption. Associations were examined using multilevel ordinal regression analysis. Findings - Managers with a greater number of employees demonstrated the highest level of organisational alcohol policy knowledge and were more inclined to initiate early alcohol interventions. Alcohol policy knowledge was associated with inclination to intervene, net of individual characteristics. Practical implications - Considering how managers' characteristics might influence efforts to decrease hazardous alcohol consumption is potentially important when designing future workplace alcohol prevention programmes. Originality/value - Several individual factors related to managers' organisational alcohol policy knowledge and inclination to initiate early alcohol interventions were identified, particularly managerial responsibility. However, the association between policy knowledge and inclination to intervene remained strong after accounting for these individual factors. Future studies should explore alternative explanations at the individual and organisational levels., This study was funded by the Public Health Agency of Sweden.

Item does not contain fulltext, To generate doxorubicin (Dox) specifically at the tumor site, the chemotherapeutic agent was incorporated into a prodrug by linkage to a peptide specifically recognized by plasmin, which is overproduced in many cancers. ST-9905, which contains an elongated self-elimination spacer, is activated more rapidly in vitro by plasmin than is ST-9802. Prodrug activation in vitro depended on the level of urokinase produced by tumor cells and was inhibited by aprotinin, a plasmin inhibitor. Comparison of equimolar concentrations of ST-9905, ST-9802, and Dox in EF43.fgf-4 and MCF7 models revealed that both prodrugs, in sharp contrast to Dox, displayed antiproliferative and antiangiogenic activities without discernible toxicity. Although MCF7 cells are poor urokinase producers in vitro, prodrug efficacy in this model may be explained by production of plasmin by tumor-infiltrating host cells. Mice treated with equitoxic concentrations (maximum tolerated doses) of prodrugs showed 100% survival and negligible body weight loss, in contrast to results after Dox treatment. ST-9905 was substantially more effective than ST9802 and induced similar tumor growth inhibition as Dox but without apparent toxicity. This finding may be explained by the elongated spacer, which facilitates enzymatic prodrug activation. These data validate both the use of elongated spacers in vivo and the concept of targeting anticancer prodrugs to tumor-associated plasmin.

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Item does not contain fulltext, To generate doxorubicin (Dox) specifically at the tumor site, the chemotherapeutic agent was incorporated into a prodrug by linkage to a peptide specifically recognized by plasmin, which is overproduced in many cancers. ST-9905, which contains an elongated self-elimination spacer, is activated more rapidly in vitro by plasmin than is ST-9802. Prodrug activation in vitro depended on the level of urokinase produced by tumor cells and was inhibited by aprotinin, a plasmin inhibitor. Comparison of equimolar concentrations of ST-9905, ST-9802, and Dox in EF43.fgf-4 and MCF7 models revealed that both prodrugs, in sharp contrast to Dox, displayed antiproliferative and antiangiogenic activities without discernible toxicity. Although MCF7 cells are poor urokinase producers in vitro, prodrug efficacy in this model may be explained by production of plasmin by tumor-infiltrating host cells. Mice treated with equitoxic concentrations (maximum tolerated doses) of prodrugs showed 100% survival and negligible body weight loss, in contrast to results after Dox treatment. ST-9905 was substantially more effective than ST9802 and induced similar tumor growth inhibition as Dox but without apparent toxicity. This finding may be explained by the elongated spacer, which facilitates enzymatic prodrug activation. These data validate both the use of elongated spacers in vivo and the concept of targeting anticancer prodrugs to tumor-associated plasmin.

Item does not contain fulltext

Membrane type 1 metalloprotease (MT1-MMP) is a transmembrane metalloprotease that plays a major role in the extracellular matrix remodeling, directly by degrading several of its components and indirectly by activating pro-MMP2. We investigated the effects of MT1-MMP overexpression on in vitro and in vivo properties of human breast adenocarcinoma MCF7 cells, which do not express MT1-MMP or MMP-2. MT1-MMP and MMP-2 cDNAs were either transfected alone or cotransfected. All clones overexpressing MT1-MMP 1) were able to activate endogenous or exogenous pro-MMP-2, 2) displayed an enhanced in vitro invasiveness through matrigel-coated filters independent of MMP-2 transfection, 3) induced the rapid development of highly vascularized tumors when injected subcutanously in nude mice, and 4) promoted blood vessels sprouting in the rat aortic ring assay. These effects were observed in all clones overexpressing MT1-MMP regardless of MMP-2 expression levels, suggesting that the production of MMP-2 by tumor cells themselves does not play a critical role in these events. The angiogenic phenotype of MT1-MMP-producing cells was associated with an up-regulation of VEGF expression. These results emphasize the importance of MT1-MMP during tumor angiogenesis and open new opportunities for the development of antiangiogenic strategies combining inhibitors of MT1-MMP and VEGF antagonists. - Sounni, N. E., Devy, L., Hajitou, A., Frankenne, F., Munaut, C., Gilles, C., Deroanne, C., Thompson, E. W., Foidart, J. M., Noel, A. MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression.

Purpose: An alcohol prevention programme, consisting of the implementation of an organisational alcohol policy and skills development training for managers, was delivered in Swedish workplaces. Previous findings revealed challenges in policy implementation due to the lack of dissemination amongst managers. This study aims to describe perceived dissemination barriers of the organisational alcohol policy by managers. Methodology: A cross-sectional survey (n=193 managers) was performed to identify common dissemination barriers in the workplace and complementary case illustrations derived from semi-structured interviews (n=18 managers) were used to understand the dissemination barriers of the organisational alcohol policy. Frequency distributions were presented to describe common perceived barriers. Findings: Sixty-five percent of managers reported that their workplace had not changed their approach to addressing alcohol-related issues compared to their usual practice before programme delivery. Various organisational factors, such as deprioritisation of programme dissemination, lack of communication, and inadequate strategies were some of the common barriers perceived by managers. Moreover, managers reported uncertainties regarding any changes concerning the workplace’s approach for addressing alcohol-related issues. Increased efforts in disseminating the organisational alcohol policy can reduce uncertainties among managers. Practical implications: A thorough process evaluation to understand processes in programme delivery and implementation is necessary to ensure the uptake of the intervention. Originality/value: The study highlighted the complexity of disseminating an alcohol policy in a dynamic setting, such as the workplace, and provided the importance of addressing organisational obstacles.

Background: The workplace can be affected negatively by hazardous alcohol use, and intervening at an early stage remains a challenge. Recently, a multi-component alcohol prevention program, Alcohol Policy and Managers’ skills Training (hereafter, ‘APMaT’), was delivered at the organizational level. In a previous outcome evaluation, APMaT appeared to be effective at the managerial level. The current study takes a step further by aiming to evaluate the effectiveness of APMaT in decreasing the alcohol risk level among employees. Methods: Data from 853 employees (control: n = 586; intervention: n = 267) were gathered through a cluster-randomized study. To analyze changes in the odds of hazardous alcohol use among employees, multilevel logistic regression was applied using group (control vs intervention), time (baseline vs 12-month follow-up), and the multiplicative interaction term (group × time) as the main predictors. The intervention effect was further adjusted for sociodemographic characteristics and policy awareness. Results: Employees in the intervention group showed a larger decrease in the odds of hazardous alcohol use compared to the control group. However, this difference was not statistically significant, even after adjusting for several factors, including the sociodemographic factors and policy awareness. Conclusions: The findings are insufficient to determine the effectiveness of APMaT at the employee level at the current stage of the evaluation. Future studies should strive to identify issues with implementation processes in workplace-based alcohol interventions. Trial registration: ISCRTN: ISRCTN17250048.