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Social determinants of health (SDoH), including factors such as education level, housing, poverty, racism, and food insecurity and their impact on health outcomes have been well documented. The "Wayne Pediatrics Health and Nutrition Expo" held at Detroit's Eastern Market was an activity-based health and nutrition event addressing pediatric SDoH. Partnering with community organizations, the event had 10 stations addressing SDoH: access to a primary-care pediatrician; HIV-care and prevention; childhood literacy; clothing & winter coats; mental health and childhood development; nutrition; staying active; vaccination; and food insecurity. The free, public event featured a child-themed treasure hunt and map, music, giveaways, and live demonstrations, all in a family-friendly park atmosphere. While SDoH are considered "non-medical" factors that contribute to health and may be difficult to completely address for any individual child, our practice addressed several key SDoH at a single-day, hands-on, child-friendly community event based on the local needs of children., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: EM serves as an Associate Editor (voluntary) for both Clinical Pediatrics and Global Pediatric Health.

Background and Purpose: Current imaging techniques have difficulty differentiating treatment success and failure in spinal metastases undergoing radiation therapy. This study investigated the correlation between changes in dynamic contrast-enhanced MR imaging perfusion parameters and clinical outcomes following radiation therapy for spinal metastases. We hypothesized that perfusion parameters will outperform traditional size measurements in discriminating treatment success and failure., Materials and Methods: This retrospective study included 49 patients (mean age, 63 [SD, 13] years; 29 men) with metastatic lesions treated with radiation therapy who underwent dynamic contrast-enhanced MR imaging. The median time between radiation therapy and follow-up dynamic contrast-enhanced MR imaging was 62 days. We divided patients into 2 groups: clinical success ( n = 38) and failure ( n = 11). Failure was defined as PET recurrence ( n = 5), biopsy-proved ( n = 1) recurrence, or an increase in tumor size ( n = 7), while their absence defined clinical success. A Mann-Whitney U test was performed to assess differences between groups., Results: The reduction in plasma volume was greater in the success group than in the failure group (-57.3% versus +88.2%, respectively; P < .001). When we assessed the success of treatment, the sensitivity of plasma volume was 91% (10 of 11; 95% CI, 82%-97%) and the specificity was 87% (33 of 38; 95% CI, 73%-94%). The sensitivity of size measurements was 82% (9 of 11; 95% CI, 67%-90%) and the specificity was 47% (18 of 38; 95% CI, 37%-67%)., Conclusions: The specificity of plasma volume was higher than that of conventional size measurements, suggesting that dynamic contrast-enhanced MR imaging is a powerful tool to discriminate between treatment success and failure., (© 2023 by American Journal of Neuroradiology.)

Background: Discharge to acute rehabilitation is strongly correlated with functional recovery after traumatic injury, including spinal cord injury (SCI). However, services such as acute care rehabilitation and Skilled Nursing Facilities (SNF) are expensive. Our objective was to understand if high-cost, resource-intensive post-discharge rehabilitation or alternative care facilities are utilized at disparate rates across socioeconomic groups after SCI., Methods: We performed a cohort analysis using the National Trauma Data Bank® tabulated from 2012-2016. Eligible patients had a diagnosis of cervical or thoracic spine fracture with spinal cord injury (SCI) and were treated surgically. We evaluated associations of sociodemographic and psychosocial variables with non-home discharge (e.g., discharge to SNF, other healthcare facility, or intermediate care facility) via multivariable logistic regression while correcting for injury severity and hospital characteristics., Results: We identified 3933 eligible patients. Patients who were older, male (OR=1.29 95% Confidence Interval [1.07-1.56], p=.007), insured by Medicare (OR=1.45 [1.08-1.96], p=.015), diagnosed with a major psychiatric disorder (OR=1.40 [1.03-1.90], p=.034), had a higher Injury Severity Score (OR=5.21 [2.96-9.18], p<.001) or a lower Glasgow Coma Score (3-8 points, OR=2.78 [1.81-4.27], p<.001) had a higher chance of a non-home discharge. The only sociodemographic variable associated with lower likelihood of utilizing additional healthcare facilities following discharge was uninsured status (OR=0.47 [0.37-0.60], p<.001)., Conclusions: Uninsured patients are less likely to be discharged to acute rehabilitation or alternative healthcare facilities following surgical management of SCI. High out-of-pocket costs for uninsured patients in the United States may deter utilization of these services., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Introduction: Physicians are often required to make treatment decisions for patients with Crohn's disease on the basis of limited objective information about the state of the patient's gastrointestinal tissue while aiming to achieve mucosal healing. Tools to predict changes in mucosal health with treatment are needed. We evaluated a computational approach integrating a mechanistic model of Crohn's disease with a responder classifier to predict temporal changes in mucosal health., Methods: A hybrid mechanistic-statistical platform was developed to predict biomarker and tissue health time courses in patients with Crohn's disease. Eligible patients from the VERSIFY study (n = 69) were classified into archetypical response cohorts using a decision tree based on early treatment data and baseline characteristics. A virtual patient matching algorithm assigned a digital twin to each patient from their corresponding response cohort. The digital twin was used to forecast response to treatment using the mechanistic model., Results: The responder classifier predicted endoscopic remission and mucosal healing for treatment with vedolizumab over 26 weeks, with overall sensitivities of 80% and 75% and overall specificities of 69% and 70%, respectively. Predictions for changes in tissue damage over time in the validation set (n = 31), a measure of the overall performance of the platform, were considered good (at least 70% of data points matched), fair (at least 50%), and poor (less than 50%) for 71%, 23%, and 6% of patients, respectively., Conclusion: Hybrid computational tools including mechanistic components represent a promising form of decision support that can predict outcomes and patient progress in Crohn's disease., (© 2022. The Author(s).)

Objectives: NutriCoviD30 is a longitudinal multicenter cohort study that aimed to provide nutritional objective data of inpatients during COVID-19 infection. The aims of this study were to describe the nutritional effects of COVID-19 infection on adult inpatients on the short- to mid-term (≤30 d after hospital discharge), using food intake and weight measurements and to identify factors associated with a decrease in food intake and weight., Methods: Food intake and weight trajectories, as well as clinical signs of the disease, preexisting chronic diseases, and nutritional strategies were collected and analyzed during the course of the disease. Their association was estimated using mixed-effect regression modeling. Patients were recruited from French university hospitals from May to July 2020. For the 403 included patients (mean 62.2  ± 14.2 y of age; 63% men), median (interquartile range [IQR]) hospital length of stay was 13 d (IQR = 8, 20), and 30% of patients were admitted to the intensive care unit., Results: Patients declared a median 70% food intake decrease in the acute phase, and the disease resulted in an average loss of 8% of predisease weight (corresponding to -6.5 kg). Although most patients recovered their usual food intake 1 month after hospital discharge, they only regained half of their weight loss, such that malnutrition, which affected 67% of patients during hospitalization, persisted in 41%. Patients with overweight, obesity, and diabetes reported an additional weight loss of >1.5% of their initial bodyweight during hospitalization and recovery phase., Conclusions: To prevent malnutrition and its long-term effects, mainly combined with a rapid weight loss predominantly affecting lean body mass, implementation of nutritional support is needed for COVID-19 inpatients. It should be started early in the course of the infection, and be extended up to the recovery phase., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Receptor internalization by endocytosis regulates diverse cellular processes, from the rate of nutrient uptake to the timescale of essential signaling events. The established view is that internalization is tightly controlled by specific protein-binding interactions. However, recent work suggests that physical aspects of receptors influence the process in ways that cannot be explained by biochemistry alone. Specifically, work from several groups suggests that increasing the steric bulk of receptors may inhibit their uptake by multiple types of trafficking vesicles. How do biochemical and biophysical factors work together to control internalization? Here, we show that receptor uptake is well described by a thermodynamic trade-off between receptor-vesicle binding energy and the entropic cost of confining receptors within endocytic vesicles. Specifically, using large ligands to acutely increase the size of engineered variants of the transferrin receptor, we demonstrate that an increase in the steric bulk of a receptor dramatically decreases its probability of uptake by clathrin-coated structures. Further, in agreement with a simple thermodynamic analysis, all data collapse onto a single trend relating fractional occupancy of the endocytic structure to fractional occupancy of the surrounding plasma membrane, independent of receptor size. This fundamental scaling law provides a simple tool for predicting the impact of receptor expression level, steric bulk, and the size of endocytic structures on receptor uptake. More broadly, this work suggests that bulky ligands could be used to drive the accumulation of specific receptors at the plasma membrane surface, providing a biophysical tool for targeted modulation of signaling and metabolism from outside the cell., (Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Transcription factor nuclear factor kappa B (NF-κB) shows cooperative switch-like activation followed by prolonged oscillatory nuclear translocation in response to extracellular stimuli. These dynamics are important for activation of the NF-κB transcriptional machinery, however, NF-κB activity regulated by coordinated actions of these dynamics has not been elucidated at the system level. Using a variety of B cells with artificially rewired NF-κB signaling networks, we show that oscillations and switch-like activation of NF-κB can be dissected and that, under some conditions, these two behaviors are separated upon antigen receptor activation. Comprehensive quantitative experiments and mathematical analysis showed that the functional role of switch activation in the NF-κB system is to overcome transient IKK (IκB kinase) activity to amplify nuclear translocation of NF-κB, thereby inducing the prolonged NF-κB oscillatory behavior necessary for target gene expression and B-cell activation., Competing Interests: The authors declare no conflict of interest.

Introduction: The objective of this study was to document the initiation of insulin therapy in patients with type 2 diabetes mellitus (T2DM) and its maintenance as a function of time after initiation in a French nationwide representative cohort., Methods: A retrospective cohort study was conducted on a random sample of ~600,000 beneficiaries registered in the French national health insurance database. Newly insulin treated T2DM patients were selected. Persistence was defined as remaining on insulin without discontinuation (defined over a 6 or a 12-month period)., Results: Among 1909 initiations identified in 2012/2013 (basal scheme: 61.8%, basal/rapid: 15%, other schemes: 23.2%) the average age (standard deviation) at initiation was, respectively, 67.5 (14.2), 61.8 (18.1) and 63.2 (18.4) years. Insulin was initiated by general practitioners in 39.3% and prescribed without other antidiabetic drugs in 32.0%. Persistence was studied in 1969 patients initiating insulin in 2011/2012. Among survivors, nearly 25% stopped insulin during the first year (18.4% for basal scheme). Patients discontinuing insulin were younger [64.7 years (18.5) vs 67.3 years (14.3) p = 0.0003] and less often male (45.8% vs 55.7%, p < 0.0001). A proportion of 20.2% did not receive any antidiabetic drug over 12 months after discontinuation. These high percentages were only partly explained by transient intensive insulin regimens in acutely ill patients identifiable in the database., Conclusion: We observed a high rate of early discontinuation of insulin in T2DM patients (but lower with basal insulin scheme). Further real world studies are warranted to identify factors associated with this poor persistence., Funding: This study was supported by Sanofi-France.

The magnitude, duration and oscillation of cellular signalling pathway responses are often limited by negative feedback loops, defined as an 'activator-induced inhibitor' regulatory motif. Within the NFκB signalling pathway, a key negative feedback regulator is IκBα. We show here that, contrary to current understanding, NFκB-inducible expression is not sufficient for providing effective negative feedback. We then employ computational simulations of NFκB signalling to identify IκBα molecular properties that are critical for proper negative feedback control and test the resulting predictions in biochemical and single-cell live-imaging studies. We identified nuclear import and nuclear export of IκBα and the IκBα-NFκB complex, as well as the free IκBα half-life, as key determinants of post-induction repression of NFκB and the potential for subsequent reactivation. Our work emphasizes that negative feedback is an emergent systems property determined by multiple molecular and biophysical properties in addition to the required 'activator-induced inhibitor' relationship., (© 2015 The Author(s).)

Development and function of the immune system depends on cells exchanging information between themselves and with their environment. This information is processed and integrated by complex signal transduction and gene regulatory networks with rich temporal dynamics. A growing body of evidence points to a combination of network topology and temporal dynamics as a fundamental link between stimulus and function. Recent findings also bring cellular variability and stochastic events to the forefront as additional determinants of cell population responses to immune cues. In this article, we review examples of how the trinity of network topology, temporal dynamics, and cellular variability together determine the immune function. In particular we focus on Nuclear Factor kappa-B and T-cell receptor signaling networks as they have proven fertile ground for studying how function arises from the combination of topology, dynamics, and variability in a context of great clinical importance., (© 2015 Wiley Periodicals, Inc.)

Objectives: Our goal is to study the correlations among gray-scale seven-joint ultrasound score (GS-US7), power Doppler seven-joint ultrasound score (PD-US7), disease activity score-28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in patients with and without fibromyalgia (FM)., Methods: A matched case-control study included all patients consecutively seen in the Rheumatoid Arthritis (RA) Clinic. Participants were allocated into one of two groups: RA with FM and RA without FM. Ultrasound (US) and clinical scoring were blinded for the presence of FM. Medians and proportions were compared by Mann-Whitney's test and McNemar's test, respectively. Spearman's rank correlation coefficients (rs) were calculated among clinical and US scores and differences were tested by r-to-z transformation test., Results: Seventy-two women were included, out of 247 RA patients, mostly white, with median (IQR) age of 57.5 (49.3-66.8) years, with RA symptoms for 13.0 (6.0-19.0) years and FM symptoms for 6.0 (2.0-15.0) years. Disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs and prednisone use was comparable between groups. Objective activity parameters were not different between groups. RA patients with FM had greater DAS28, SDAI and CDAI but similar GS-US7 and PD-US7. GS-US7 correlated with DAS28, SDAI and CDAI in patients with and without FM (rs = 0.36-0.57), while PD-US7 correlated with clinical scores only in patients without FM (rs = 0.35-0.38)., Conclusion: To our knowledge, this is the first study to demonstrate that ultrasound synovitis scores are not affected by FM in RA patients. PD-US7 performed better than GS-US7 in long-standing RA patients with DAS28, SDAI or CDAI allegedly overestimated due to FM. Since sonographic synovitis predicts erosion better than swollen joint count, C-reactive protein and erythrocyte sedimentation rate, US should be considered a promising treatment target in RA patients with FM.

Purpose: There is limited information on hemorrhagic complications during invasive dental procedures in patients treated with double antiplatelet therapy. The objective of this study is to assess the frequency of hemorrhagic complications of patients taking dual antiplatelet medication undergoing dental extractions., Patients and Methods: An observational, multicenter, prospective, cohort study was performed in 11 oral and dental care units of primary care. The study sample was derived from the population of patients aged 18 years or older who were undergoing double antiplatelet therapy and presented to the oral and dental care units requiring dental extraction. Double antiplatelet therapy is the combination of 100 mg per day of acetylsalicylic acid and a second antiplatelet agent. The predictor variables were type of extraction performed, number of extracted teeth, number of extracted roots, and presence of inflammation. The primary outcome variable was intraoperative hemorrhage, and the secondary outcome variables were hemorrhage at 24 hours and hemorrhage at 10 days. First, a univariate analysis that considered all studied variables was performed. All variables with P < .25 in the univariate analysis were included in a multivariate analysis. The association between hemorrhage severity and its relevant factors was evaluated using logistic regression analysis., Results: The study included 181 patients. Light hemorrhage (<30 minutes) was observed in 165 patients (91.2%). Intraoperative hemorrhage lasted more than 30 minutes in 15 patients (8.3%) and more than 60 minutes in only 1 patient, whose hemorrhage was controlled by local hemostatic measures. The presence of inflammation and 3-root extractions increased the probability of hemorrhage persisting for more than 30 minutes by factors of 10 and 7.3, respectively., Conclusions: In 8.3% of patients treated with dual antiplatelet therapy, dental extractions cause hemorrhagic complications lasting more than 30 minutes are resolved using local hemostatic measures. The results of this study support the safety of dental extraction without withdrawal double antiplatelet therapy.

A switchlike response in nuclear factor-κB (NF-κB) activity implies the existence of a threshold in the NF-κB signaling module. We show that the CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor of NF-κB (IκB) kinase-β (IKKβ) module is a switch mechanism for NF-κB activation in B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed that IKK activity is regulated by positive feedback from IKKβ to TAK1, generating a steep dose response to BCR stimulation. Mutation of the scaffolding protein CARMA1 at serine-578, an IKKβ target, abrogated not only late TAK1 activity, but also the switchlike activation of NF-κB in single cells, suggesting that phosphorylation of this residue accounts for the feedback., (Copyright © 2014, American Association for the Advancement of Science.)

Ion-beam cancer therapy is a promising technique to treat deep-seated tumors; however, for an accurate treatment planning, the energy deposition by the ions must be well known both in soft and hard human tissues. Although the energy loss of ions in water and other organic and biological materials is fairly well known, scarce information is available for the hard tissues (i.e., bone), for which the current stopping power information relies on the application of simple additivity rules to atomic data. Especially, more knowledge is needed for the main constituent of human bone, calcium hydroxyapatite (HAp), which constitutes 58% of its mass composition. In this work the energy loss of H and He ion beams in HAp films has been obtained experimentally. The experiments have been performed using the Rutherford backscattering technique in an energy range of 450-2000 keV for H and 400-5000 keV for He ions. These measurements are used as a benchmark for theoretical calculations (stopping power and mean excitation energy) based on the dielectric formalism together with the MELF-GOS (Mermin energy loss function-generalized oscillator strength) method to describe the electronic excitation spectrum of HAp. The stopping power calculations are in good agreement with the experiments. Even though these experimental data are obtained for low projectile energies compared with the ones used in hadron therapy, they validate the mean excitation energy obtained theoretically, which is the fundamental quantity to accurately assess energy deposition and depth-dose curves of ion beams at clinically relevant high energies. The effect of the mean excitation energy choice on the depth-dose profile is discussed on the basis of detailed simulations. Finally, implications of the present work on the energy loss of charged particles in human cortical bone are remarked.

Highly networked signaling hubs are often associated with disease, but targeting them pharmacologically has largely been unsuccessful in the clinic because of their functional pleiotropy. Motivated by the hypothesis that a dynamic signaling code confers functional specificity, we investigated whether dynamic features may be targeted pharmacologically to achieve therapeutic specificity. With a virtual screen, we identified combinations of signaling hub topologies and dynamic signal profiles that are amenable to selective inhibition. Mathematical analysis revealed principles that may guide stimulus-specific inhibition of signaling hubs, even in the absence of detailed mathematical models. Using the NFκB signaling module as a test bed, we identified perturbations that selectively affect the response to cytokines or pathogen components. Together, our results demonstrate that the dynamics of signaling may serve as a pharmacological target, and we reveal principles that delineate the opportunities and constraints of developing stimulus-specific therapeutic agents aimed at pleiotropic signaling hubs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

NF-κB plays a vital role in cellular immune and inflammatory response, survival, and proliferation by regulating the transcription of various genes involved in these processes. To activate transcription, RelA (a prominent NF-κB family member) interacts with transcriptional co-activators like CREB-binding protein (CBP) and its paralog p300 in addition to its cognate κB sites on the promoter/enhancer regions of DNA. The RelA:CBP/p300 complex is comprised of two components--first, DNA binding domain of RelA interacts with the KIX domain of CBP/p300, and second, the transcriptional activation domain (TAD) of RelA binds to the TAZ1 domain of CBP/p300. A phosphorylation event of a well-conserved RelA(Ser276) is prerequisite for the former interaction to occur and is considered a decisive factor for the overall RelA:CBP/p300 interaction. The role of the latter interaction in the transcription of RelA-activated genes remains unclear. Here we provide the solution structure of the latter component of the RelA:CBP complex by NMR spectroscopy. The structure reveals the folding of RelA-TA2 (a section of TAD) upon binding to TAZ1 through its well-conserved hydrophobic sites in a series of grooves on the TAZ1 surface. The structural analysis coupled with the mechanistic studies by mutational and isothermal calorimetric analyses allowed the design of RelA-mutants that selectively abrogated the two distinct components of the RelA:CBP/p300 interaction. Detailed studies of these RelA mutants using cell-based techniques, mathematical modeling, and genome-wide gene expression analysis showed that a major set of the RelA-activated genes, larger than previously believed, is affected by this interaction. We further show how the RelA:CBP/p300 interaction controls the nuclear response of NF-κB through the negative feedback loop of NF-κB pathway. Additionally, chromatin analyses of RelA target gene promoters showed constitutive recruitment of CBP/p300, thus indicating a possible role of CBP/p300 in recruitment of RelA to its target promoter sites., Competing Interests: The authors have declared that no competing interests exist.

The transcription factor NFκB, a key component of the immune system, shows intricate stimulus-specific temporal dynamics. Those dynamics are thought to play a role in controlling the physiological response to cytokines and pathogens. Biochemical evidence suggests that the NFκB inducing kinase, IKK, a signaling hub onto which many signaling pathways converge, is regulated via a regulatory cycle comprising a poised, an active, and an inactive state. We hypothesize that it operates as a modulator of signal dynamics, actively reshaping the signals generated at the receptor proximal level. Here we show that a regulatory cycle can function in at least three dynamical regimes, tunable by regulating a single kinetic parameter. In particular, the simplest three-state regulatory cycle can generate signals with two well-defined phases, each with distinct coding capabilities in terms of the information they can carry about the stimulus. We also demonstrate that such a kinase cycle can function as a signal categorizer classifying diverse incoming signals into outputs with a limited set of temporal activity profiles. Finally, we discuss the extension of the results to other regulatory motifs that could be understood in terms of the regimes of the three-state cycle., (Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Introduction: sick-leave in the course of pregnancy play a role under estimated according to several studies.They bring to light the existence of risk factors concerning the physical load for contractions, sick-leave, hospitalizations and prematurity.The data obtained on the totality of the wage earners of the AP-HP allow to avoid all the possible bias and to determine the potential impact of a policy of reduction of the physical load, Method: The data of four years could be analyzed.The used database is PILOT RH, intranet application restoring information extracted from GIPSIE who was until 2008 the institutional software of management of the careers of all the workers of the AP-HP., Results: In 2008,3 937 women having had a maternity leave (ML) accumulated 132 360 days of ordinary sick-leave (OL) (that is 33,6 days on average) without inclusion of the 15 days accepted for "pathological pregnancy" (PP) and "post pregnancy leave". Ordinary sick-leave of all the 53 132 women amounts to 11.5 days by agent. But, the set apart of the women having had a ML reduces the number of days of sick-leave to 9,7 days This difference weighs for 15.6 % of the total of the absenteeism OL. The results are similar on the four years. The analysis by occupational catégory, for 2008, shows that the average number of days of sick-leave, after exclusion of women having had a ML, decreases with the physical load of the posts estimated by the study PRESST-NEXT :ancillary staff 19.9 days, nursing aids 13.7 days, registered nurses 8.2 days, specialized nurses 7.7 days, medico - technical workers 5.7 days and head nurses 5.1 days. For the women having had a ML, the average number of days of ordinary sick-leave, is the most raised for nursing aids (41.9 days) followed by the ancillary staff (36 days) and the registered nurses (36 days) and slightly less for the specialized nurses (28.3 days). On the other hand, in the professions having least physical load the women have less than 25 days of ordinary sick-leave the year of their pregnancy :medico-technical workers 21.3 days, head nurses 23.1 days and administration staff 23.7 days.The results are similar on the four years. For the nurses, it is 25.5% of total ordinary sick-leave that are attributable to the women having had a pregnancy, and 34.4 % if we add OL and 15 days of official "pathological pregnancy"., Discussion: An intervention to reduce the physical load in test hospitals could be led.The reduction of sick-leave in the course of pregnancy can be a fast indicator of evaluation of the efficiency of the investments. The improvements will benefit to all the agents, in the medium term, with a reduction of the risks of musculoskeletal disorders. Such an action also allows to maintain the employability of the older employees and to integrate) persons into situation of handicap in a work which has for them a strong sense and which they do not want to give up.

Besides activating NFκB by phosphorylating IκBs, IKKα/IKKβ kinases are also involved in regulating metabolic insulin signaling, the mTOR pathway, Wnt signaling, and autophagy. How IKKβ enzymatic activity is targeted to stimulus-specific substrates has remained unclear. We show here that NEMO, known to be essential for IKKβ activation by inflammatory stimuli, is also a specificity factor that directs IKKβ activity toward IκBα. Physical interaction and functional competition studies with mutant NEMO and IκB proteins indicate that NEMO functions as a scaffold to recruit IκBα to IKKβ. Interestingly, expression of NEMO mutants that allow for IKKβ activation by the cytokine IL-1, but fail to recruit IκBs, results in hyperphosphorylation of alternative IKKβ substrates. Furthermore IKK's function in autophagy, which is independent of NFκB, is significantly enhanced without NEMO as IκB scaffold. Our work establishes a role for scaffolds such as NEMO in determining stimulus-specific signal transduction via the pleiotropic signaling hub IKK., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Mathematical modeling has proved to be a critically important approach in the study of many complex networks and dynamic systems in physics, engineering, chemistry, and biology. The nuclear factor κB (NF-κB) system consists of more than 50 proteins and protein complexes and is both a highly networked and dynamic system. To date, mathematical modeling has only addressed a small fraction of the molecular species and their regulation, but when employed in conjunction with experimental analysis has already led to important insights. Here, we provide a personal account of studying how the NF-κB signaling system functions using mathematical descriptions of the molecular mechanisms. We focus on the insights gained about some of the key regulatory components: the control of the steady state, the signaling dynamics, and signaling crosstalk. We also discuss the biological relevance of these regulatory systems properties., (© 2012 John Wiley & Sons A/S.)

The maintenance and detection of signaling gradients are critical for proper development and cell migration. In single-cell organisms, gradient detection allows cells to orient toward a distant mating partner or nutrient source. Budding yeast expand their growth toward mating pheromone gradients through a process known as chemotropic growth. MATα cells secrete α-factor pheromone that stimulates chemotropism and mating differentiation in MATa cells and vice versa. Paradoxically, MATa cells secrete Bar1, a protease that degrades α-factor and that attenuates the mating response, yet is also required for efficient mating. We observed that MATa cells avoid each other during chemotropic growth. To explore this behavior, we developed a computational platform to simulate chemotropic growth. Our simulations indicated that the release of Bar1 enabled individual MATa cells to act as α-factor sinks. The simulations suggested that the resultant local reshaping of pheromone concentration created gradients that were directed away from neighboring MATa cells (self-avoidance) and that were increasingly amplified toward partners of the opposite sex during elongation. The behavior of Bar1-deficient cells in gradient chambers and mating assays supported these predictions from the simulations. Thus, budding yeast dynamically remodel their environment to ensure productive responses to an external stimulus and avoid nonproductive cell-cell interactions.

Knowing the metal extraction capacity of a digestion method is crucial for a better environmental interpretation of metal concentrations determined in sediments. One of the main problems at the present is the lack of harmonization of information obtained by two of the most popular sediment partial digestion methods: ISO 11466.3 (aqua regia) and EPA 3050B (HNO₃--H₂O₂--HCl). In the present work, the amount of Cu, Ni and Pb leached by using both methods was compared with the total content of those elements in marine sediments collected, as an example, from the Cienfuegos Bay, Cuba. Similar amounts of Cu were extracted by both methods; while leaching of Ni and Pb were different. Generally, the EPA method extracted more Ni than the ISO method. In contrast, Pb was extracted in a larger amount by the ISO method. Some explanations are given for the observed results. X-ray Diffraction, X-ray Fluorescence, Particle Induced X-ray Emission Spectrometry and Energy Dispersive X-ray coupled to Scanning Electron Microscopy were employed for this purpose. On the other hand, none of the methods studied extracted simultaneously the fraction of all the metals, probably provided by human activity (Theoretical Anthropogenic Fraction) in both sediments studied. The use of ISO 11466.3 or EPA 3050B is recommended since the analytical performance parameters of both, in combination with Flame Atomic Absorption Spectrometry, are adequate. For a better environmental interpretation of the analytical results, information on the extraction efficiency of the selected method for specific elements and sediments under study should also be provided, together with the determined concentrations., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The French Federation of Nursing Student (FNESI) conducted a study in nursing studies institutions from 6 administrative Regions in order to understand risk factors linked with stress or satisfaction of students. Conducted from september 2008 to june 2009, the response rate was 71.2%. Bivariate analysis were conducted on a sample selected by random of 1450 students, to determine potentials risk factors linked with poorer estimated general health and stress. Students declare more and more frequently stress or poor general health in second and third year of nursing studies. Their life habits are inadequate and do not improve when their knowledge increases: lack of sport practice, tobacco smoke, alcohol consumption, other addictive substances ... Among students who declare a too much supported rhythm of training or a poor quality of training, the majority qualify their health of bad. Practical training is considered by a quarter of first year student and 44% of second and third year students. Existence of "speech groups" and free discussion groups have a major influence on satisfaction or stress and poor general health declaration. This study demonstrated the major influence of good mentorship quality by trained nurses and that this nurse in a tutorial position has to be the same all along the training in each department. These aspects have to be improved in order to attract and retain motivated students.

Introduction: France is facing a shortage of available physicians due to a greying population and the lack of a proportional increase in the formation of doctors. Emergency physicians are the medical system's first line of defence., Methods: The authors prepared a comprehensive questionnaire using established scales measuring various aspects of working conditions, satisfaction and health of salaried physicians and pharmacists. It was made available online, and the two major associations of emergency physicians promoted its use. 3196 physicians filled out the questionnaire. Among them were 538 emergency physicians. To avoid bias, 1924 physicians were randomly selected from the total database to match the demographic characteristics of France's physician population: 42.5% women, 57.5% men, 8.2% < 35 years old, 33.8% 35-44 years old, 34.5% 45-54 years old and 23.6% ≥ 55 years old. The distribution of physicians in the 23 administrative regions and by speciality was also precisely taken into account. This representative sample was used to compare subgroups of physicians by speciality., Results: The outcomes indicate that the intent to leave the profession (ITL) was quite prevalent across French physicians and even more so among emergency physicians (17.4% and 21.4% respectively), and burnout was highly prevalent (42.4% and 51.5%, respectively). Among the representative sample and among emergency physicians, work-family conflict (OR=4.47 and OR=6.14, respectively) and quality of teamwork (OR=2.21 and OR=5.44, respectively) were associated with burnout in a multivariate analysis, and these risk factors were more prevalent among emergency physicians than other types. A serious lack of quality of teamwork appears to be associated with a higher risk of ITL (OR=3.92 among the physicians in the representative sample and OR=4.35 among emergency physicians), and burnout doubled the risk of ITL in multivariate analysis., Conclusions: In order to prevent the premature departure of French doctors, it is important to improve work-family balance, working processes through collaboration, multidisciplinary teamwork and to develop team training approaches and ward design to facilitate teamwork.

Objective: France encounters difficulties attracting physicians to work in hospitals. Organisation at work and at home may be at the heart of the problem for female as well as for male physicians., Participants: A comprehensive questionnaire was filled out online by a representative sample of 1924 French hospital physicians., Methods: We conducted gender bivariate and multivariate analysis of the risk factors for burnout and intent to leave the profession(ITL)., Results: ITL was declared by 17.4% of physicians. According to 41.3% of female physicians (FP), their profession was an obstacle to having children (versus 19.3% for male physicians (MP)). Major factors linked with burnout were Effort/Reward imbalance (FP adjOR = 5.09, MP adjOR = 5.93), Work-family conflicts (FP adjOR = 2.97, MP adjOR = 3.04), and Low quality of teamwork (FP adjOR = 1.82, MP adjOR = 2.68). Major factors linked with ITL were Low quality of teamwork (FP adjOR = 4.49, MP adjOR = 3.03), Patient-related burnout (FP adjOR = 2.10, MP adjOR = 2.35) and General burnout (FP adjOR = 1.85, MP adjOR = 1.45)., Conclusions: Excessive job demands are linked with burnout and with work-family conflicts, conducting to difficulties in organising one's life in order to have and raise children. Potential solutions include facilitating teamwork in order to reduce departure, which increase workload on those who stay increasing their work family conflict.

Presst-Next, the European study carried out between 2004 and 2006, highlighted the importance of teamwork in reducing the frequency of professional exhaustion and the early departure of care staff. On the basis of these results, the Armand-Trousseau Hospital in Paris (AP-HP 75) has committed to a participative ergonomics approach at its paediatric emergency service.

The health of organisms and cells depends on appropriate responses to diverse internal and external cues, stimuli, or challenges, such as changes in hormone or cytokine levels, or exposure to a pathogen. Cellular responses must be tailored to the identity and intensity of the stimulus and therefore intra-cellular signals must carry information about both. However, signaling mediators often form intricate networks that react to multiple stimuli yet manage to produce stimulus-specific responses. The multi-functionality ('functional pleiotropism') of signaling nodes suggests that biological networks have evolved ways of passing physiologically relevant stimulus information through shared channels. Increasing evidence supports the notion that this is achieved in part through temporal regulation of signaling mediators' activities. The present challenge is to identify the features of temporal activity profile that represent information about a given stimulus and understand how cells read the temporal codes to control their responses., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: While many scholars have acknowledged the relationship between personal and work-related factors associated with job search and actual turnover, there is a lack of longitudinal designs that test this relationship empirically., Objectives: This longitudinal study examines specific determinant factors that differentiate between so-called 'stayers' and 'leavers' within the nursing profession, and identifies risk factors for premature leaving by comparing nurses who have left their job, or the nursing profession, with nurses who stay., Methods: This cross-national exploratory European survey included 34,587 nurses (baseline measurement) working in 623 hospitals, nursing homes, and home care institutions, and comprised two measurements with a one-year time interval. The final samples for the follow-up measurement included 14,016 stayers and 866 leavers. As regards the leavers, the participating nurses were asked to indicate to what extent personal and work-related factors had contributed to the decision to leave their health care institution., Results: Nurses' intent-to-leave scores were higher in the baseline measurement among those who left the organization during the following 12 months, than among those who stayed (24.0% versus 13.5%). A majority of nurses (86.8%) left their profession voluntarily. Involuntary departure occurred more often in Eastern European countries. Nurses indicated that the reasons for leaving were: working conditions (e.g., relationship problems, emotional difficulties,time pressure and quality of care, dissatisfaction with use of one's competence and lack of autonomy, work schedule difficulties, and dissatisfaction with pay) family reasons (e.g., caring for relatives). For a considerable number of nurses, health reasons and the desire for continuing education added to their decision to leave., Discussion: Health care organizations should pay attention to preventive measures in order to protect labor market potential. Recommendations are made for human resource development in health care organizations and for further empirical research to better understand to what extent different policy systems across the European countries explain variance in outcomes.

Background: Although many scholars have acknowledged the relationship between personal and work-related factors associated with job search and actual turnover, there is a lack of longitudinal designs that test this relationship empirically., Objectives: This longitudinal study examines specific determinant factors that differentiate between so-called "stayers" and "leavers" within the nursing profession and identifies risk factors for premature leaving by comparing nurses who have left their job or the nursing profession with nurses who stay., Methods: This cross-national exploratory European survey included 34,587 nurses (baseline measurement) working in 623 hospitals, nursing homes, and home care institutions and was composed of two measurements with a 1-year time interval. The final samples for the follow-up measurement included 14,016 stayers and 866 leavers. As regards the leavers, the participating nurses were asked to indicate to what extent personal and work-related factors had contributed to the decision to leave their healthcare institution., Results: Nurses' intent-to-leave scores were higher in the baseline measurement among those who left the organization during the following 12 months than those among nurses who stayed (24.0% vs. 13.5%). A majority of nurses (86.8%) left their profession voluntarily. Involuntary departure occurred more often in Eastern European countries. Nurses indicated that the reasons for leaving were (a) working conditions (e.g., relationship problems, emotional difficulties, time pressure and quality of care, dissatisfaction with use of one's competence and lack of autonomy, work schedule difficulties, and dissatisfaction with pay) and (b) family reasons (e.g., caring for relatives). For a considerable number of nurses, health reasons and the desire for continuing education added to their decision to leave., Discussion: Healthcare organizations should pay attention to preventive measures to protect labor market potential. Recommendations are made for human resource development in healthcare organizations and for further empirical research to better understand to what extent different policy systems across the European countries explain variance in outcomes.

The cellular response elicited by an environmental cue typically varies with the strength of the stimulus. For example, in the yeast Saccharomyces cerevisiae, the concentration of mating pheromone determines whether cells undergo vegetative growth, chemotropic growth, or mating. This implies that the signaling pathways responsible for detecting the stimulus and initiating a response must transmit quantitative information about the intensity of the signal. Our previous experimental results suggest that yeast encode pheromone concentration as the duration of the transmitted signal. Here we use mathematical modeling to analyze possible biochemical mechanisms for performing this "dose-to-duration" conversion. We demonstrate that modulation of signal duration increases the range of stimulus concentrations for which dose-dependent responses are possible; this increased dynamic range produces the counterintuitive result of "signaling beyond saturation" in which dose-dependent responses are still possible after apparent saturation of the receptors. We propose a mechanism for dose-to-duration encoding in the yeast pheromone pathway that is consistent with current experimental observations. Most previous investigations of information processing by signaling pathways have focused on amplitude encoding without considering temporal aspects of signal transduction. Here we demonstrate that dose-to-duration encoding provides cells with an alternative mechanism for processing and transmitting quantitative information about their surrounding environment. The ability of signaling pathways to convert stimulus strength into signal duration results directly from the nonlinear nature of these systems and emphasizes the importance of considering the dynamic properties of signaling pathways when characterizing their behavior. Understanding how signaling pathways encode and transmit quantitative information about the external environment will not only deepen our understanding of these systems but also provide insight into how to reestablish proper function of pathways that have become dysregulated by disease.

Cell differentiation requires the ability to detect and respond appropriately to a variety of extracellular signals. Here we investigate a differentiation switch induced by changes in the concentration of a single stimulus. Yeast cells exposed to high doses of mating pheromone undergo cell division arrest. Cells at intermediate doses become elongated and divide in the direction of a pheromone gradient (chemotropic growth). Either of the pheromone-responsive MAP kinases, Fus3 and Kss1, promotes cell elongation, but only Fus3 promotes chemotropic growth. Whereas Kss1 is activated rapidly and with a graded dose-response profile, Fus3 is activated slowly and exhibits a steeper dose-response relationship (ultrasensitivity). Fus3 activity requires the scaffold protein Ste5; when binding to Ste5 is abrogated, Fus3 behaves like Kss1, and the cells no longer respond to a gradient or mate efficiently with distant partners. We propose that scaffold proteins serve to modulate the temporal and dose-response behavior of the MAP kinase.

Background: Recent research suggests that violence in health care is increasing and that it strongly influences the recruitment and retention of nurses as well as sick leave and burnout levels., Aims: To identify the prevalence of violence in nursing and to provide a basis for appropriate interventions., Methods: Nurses from 10 European countries answered to a questionnaire and to a follow-up assessment. Stepwise adjusted multiple logistic regression was used to assess the association between frequency of violence, factors related to teamwork and other work-related factors and outcomes, such as burnout, intention to leave nursing and intention to change institution., Results: A total of 39,894 nurses responded to the baseline questionnaire (51% response rate). After adjustment for age, gender and other risk factors, quality of teamwork appeared to be a major factor with odds ratio (OR) 1.35 (1.24-1.48) for medium quality and 1.52 (1.33-1.74) for low quality. Uncertainty regarding patients' treatments was linked with violence, with a clear gradient (OR 1.59, 1.47-1.72 for medium uncertainty and 2.13, 1.88-2.41 for high uncertainty). Working only night shift was at high risk (OR 2.17, 1.76-2.67). High levels of time pressure and physical load were associated with violence OR 1.45 (1.24-1.69) and 1.84 (1.66-2.04), respectively. High and medium frequency of violence was associated with higher levels of burnout, intent to leave nursing and intent to change institution. A 1-year follow-up assessment indicated stability in the relationships between outcomes., Conclusion: This study supports efforts aimed at improving teamwork-related factors as they are associated with a decrease in violence against nurses.

Background: Musculoskeletal disorders are a widespread affliction in the nursing profession. Back or neck-pain-related disability of nursing staff is mainly attributed to physical and psychosocial risk factors., Objectives: To investigate which-and to what extent-physical and psychosocial risk factors are associated with neck/back-pain-related disability in nursing, and to assess the role of the type of health care institution (hospitals, nursing homes and home care institutions) within different countries in this problem., Design: Cross-sectional secondary analysis of multinational data of nurses and auxiliary staff in hospitals (n=16,770), nursing homes (n=2140) and home care institutions (n=2606) in seven countries from the European NEXT-Study., Methods: Multinomial logistic regression analysis with raw models for each factor and mutually adjusted with all analysed variables., Results: Analysis of the pooled data revealed effort-reward imbalance as the predominant risk factor for disability in all settings (odds ratios for high disability by effort-reward ratio: hospital 5.05 [4.30-5.93]; nursing home 6.52 [4.04-10.52] and home care 6.4 [3.83-10.70] [after mutual adjustment of psychosocial and physical risk factors]). In contrast, physical exposure to lifting and bending showed only limited associations with odds ratios below 1.6; the availability and use of lifting aids was-after mutual adjustment-not or only marginally associated with disability. These findings were basically confirmed in separate analyses for all seven countries and types of institutions., Conclusions: The findings show a pronounced association between psychosocial factors and back or neck-pain-related disability. Further research should consider psychosocial factors and should take the setting where nurses work into account.

Background: The occurrence of workplace violence is rather frequent within the nursing profession, with well-known consequences on the psychological health of victims., Objectives: This study is aimed at assessing the relationships between relevant individual, organizational, and psychosocial factors, and the frequency of several types of workplace violence; the direct as well as the interactive impact of violence and psychosocial factors on organizational commitment and perceived health., Design: Questionnaire-based cross-sectional and longitudinal survey designs were employed for the two study objectives, respectively., Setting: Five hundred and sixty-five healthcare institutions from eight European countries participated in the Nurses' Early Exit Study., Participants: The 34,107 participants were nursing staff holding different qualifications. The response rate was 55.1% in the cross-sectional part and 40.5% in the follow-up phase. At baseline, the respondents were mostly female (89.3%), in the age group 30-44 years (52.9%), registered or specialized nurses (67.0%), working mainly in medico-surgical wards (36.3%), and employed full-time (72.8%)., Methods: In the cross-sectional analysis, the relationship between the predictor variables and frequency of violence was assessed by means of a hierarchical multiple linear regression. In the longitudinal analysis, main direct and interactive effects of violence and psychosocial factors on perceived health and organizational commitment were assessed by means of hierarchical multiple linear regression analyses with interaction terms., Results: Higher levels of adverse work-related factors were significantly associated with higher frequency of the distinguished types of violence. Significant interactions were found between psychosocial factors and violence only in predicting organizational commitment, even if effect sizes were very low. No interactions were observed for perceived health. The prevalence of the distinguished types of violence varied across the participating countries according to the presence of adverse work- and non-work-related factors., Conclusions: These findings suggest the necessity of interventions both over working conditions conducive to violence and violent behaviours themselves.

Intracellular signaling pathways that share common components often elicit distinct physiological responses. In most cases, the biochemical mechanisms responsible for this signal specificity remain poorly understood. Protein scaffolds and cross-inhibition have been proposed as strategies to prevent unwanted cross-talk. Here, we report a mechanism for signal specificity termed "kinetic insulation." In this approach signals are selectively transmitted through the appropriate pathway based on their temporal profile. In particular, we demonstrate how pathway architectures downstream of a common component can be designed to efficiently separate transient signals from signals that increase slowly over time. Furthermore, we demonstrate that upstream signaling proteins can generate the appropriate input to the common pathway component regardless of the temporal profile of the external stimulus. Our results suggest that multilevel signaling cascades may have evolved to modulate the temporal profile of pathway activity so that stimulus information can be efficiently encoded and transmitted while ensuring signal specificity.

We perform a systematic analysis of mechanisms of feedback regulation that underlie short-term adaptation in intracellular signaling systems. Upon receiving an external cue, these systems generate a transient response that quickly returns to basal levels even if the stimulus persists. Signaling pathways capable of short-term adaptation are found in systems as diverse as the high osmolarity response of yeast, gradient sensing in Dictyostelium, and the cytokine response in vertebrates. Using mathematical analysis and computational experiments, we compare different feedback architectures in terms of response amplitude and duration, ability to adapt, and response to variable stimulus levels. Our analysis reveals three important features of these systems: 1), multiple step signaling cascades improve sensitivity to low doses by an effect distinct from signal amplification; 2), some feedback architectures act as signal transducers converting stimulus strength into response duration; and 3), feedback deactivation acts as a dose-dependent switch between transient and sustained responses. Finally, we present characteristic features for each form of feedback regulation that can aid in their identification.

Approximately a third of all drugs act by binding directly to cell surface receptors coupled to G proteins. Other drugs act indirectly on these same pathways, for example, by inhibiting neurotransmitter reuptake or by blocking the inactivation of intracellular second messengers. These drugs have revolutionized the treatment of human disease. However, the complexity of G protein signaling mechanisms has significantly hampered our ability to identify additional new drug targets. Moreover, today's molecular pharmacologists are accustomed to working on narrowly focused problems centered on a single protein or enzymatic process. Here we describe emerging efforts in yeast aimed at identifying proteins and processes that modulate the function of receptors, G proteins and MAP kinase effectors. The scope of these efforts is far more systematic, comprehensive and quantitative than anything attempted previously, and includes integrated approaches in genetics, proteomics and computational biology.

Background: A common property of signal transduction systems is that they rapidly lose their ability to respond to a given stimulus. For instance in yeast, the mitogen-activated protein (MAP) kinase Hog1 is activated and inactivated within minutes, even when the osmotic-stress stimulus is sustained., Results: Here, we used a combination of experimental and computational analyses to investigate the dynamic behavior of Hog1 activation in vivo. Computational modeling suggested that a negative-feedback loop operates early in the pathway and leads to rapid attenuation of Hog1 signaling. Experimental analysis revealed that the membrane-bound osmosensor Sho1 is phosphorylated by Hog1 and that phosphorylation occurs on Ser-166. Moreover, Sho1 exists in a homo-oligomeric complex, and phosphorylation by Hog1 promotes a transition from the oligomeric to monomeric state. A phosphorylation-site mutation (Sho1(S166E)) diminishes the formation of Sho1-oligomers, dampens activation of the Hog1 kinase, and impairs growth in high-salt or sorbitol conditions., Conclusions: These findings reveal a novel phosphorylation-dependent feedback loop leading to diminished cellular responses to an osmotic-stress stimulus.

Aim: This paper reports a study exploring nurses' perceptions of the shift handover and the possible reasons for reported dissatisfaction in 10 European countries., Background: The nursing handover fulfils a number of purposes and has important consequences for the continuity of patient care and nurses' satisfaction with the quality of care they are able to provide. However, the performance and function of shift handovers in health care is a widely neglected topic in practice and research., Method: The Nurses' Early Exit Study (http://www.next-study.net) investigates the working conditions of nurses and variables influencing nursing retention. The data for this analysis were collected between 2002 and 2003 by self-report questionnaires in 10 European countries., Findings: The percentage of nurses dissatisfied with shift handovers ranged from 22% in England to 61% in France. In most countries the main reason for dissatisfaction with shift handovers was 'too many disturbances', followed by 'lack of time'. Most countries showed similar associations of dissatisfaction with qualification level and occupational seniority, but not with position and type of shift. 'Poor quality of leadership' and 'poor support from colleagues', were strongly associated with dissatisfaction., Conclusions: In several (but not all) European countries, shift handovers may be a frequent cause for nurses' irritation. The underlying causes appear to be of an organizational nature. The findings have implications for solutions. Further debate and research should clarify the different purposes of shift handovers and relate them to handover style and to the quality of patient care.

Introduction: The respective roles of medical specialties and work organization on violent events against healthcare workers (HCW) in different countries was examined., Methods: Using the results of the Presst-Next study, we analyzed data from 27134 HCW in 7 European countries. Multivariate logistic analyses were conducted with SPSS 12 software., Results: After adjustment for age, gender and other occupational risk factors, the factors indicating insufficient team work were highly associated with an increased risk of violent events. Dissatisfaction with shift change (OR=1.35; 95%CI 1.23-1.47), uncertainty about treatment (OR=1.57; 95%CI 1 .44-1.71), and frequent interruptions (OR=2.04; 95%CI 1.81-2.31) were linked to violent events, up to twice the number among HCW reporting better team work. Contradictory orders, dissatisfaction with psychological support, and harassment by superiors were all significantly associated with increased reporting of frequent violent events. We observed a positive gradient between violent events and job demand (time pressure) (OR=1.25 for an intermediate score and OR=1.55 for a high score, compared with a low score). Loneliness at work, certain work schedules, and physical load increased the risk. Nurses' aides were exposed to violent events more often (OR=1.57; 95%CI 1.38-1.79) than head nurses. Older HCW and those with more experience were less exposed. The highest risks were associated with working in psychiatric (OR=4.89; 95%CI 3.82-6.25) and emergency (OR=2.68; 95%CI 2.10-3.44) departments, compared with home care and day care. The excess risk was an additional 30% in geriatrics and long-stay departments. Significantly less risk was observed in pediatrics, obstetrics and gynecology departments (OR=0.70; 95%CI 0.56-0.88)., Conclusion: Team building requires time, and shift change is a key period. This time is far from nonproductive. Rather, its effective use reduces treatment errors, enhances quality of care, and reduces the frequency of violent events. It is crucial in every department.

Aim: This paper reports a study exploring nurses' perceived work ability and its associations with age and intention to leave nursing in a representative sample of registered nurses in 10 european countries., Background: Throughout Europe, there is now a substantial shortage of Registered Nurses and unless steps are taken to reverse this trend, numbers are likely to decline further. A study exploring nurses' perceived work ability will provide baseline evidence, which may lead to improved working conditions and increased nursing retention., Methods: A cross-sectional study design was employed. Questionnaire data were collected from 25,976 nurses in 10 member states of the European Union between October 2002 and June 2003. The response rate was 52.9% for the total investigation and varied between countries from 32.4% to 76.9%. Perceived work ability was assessed using the Work Ability Index. Intention to leave was measured by asking nurses how often they thought about leaving nursing. Data were examined using analysis of covariance and adjusted logistic regression., Results: In all 10 European countries, scores on the Work Ability Index were significantly lower (P < 0.01) among older nurses (>or=45 years). Work ability varied among countries and differences between younger and older nurses were more pronounced in some countries. In all countries, there was a significant association between low Work Ability Index and intention to leave nursing (odds ratios between 1.98 and 21.46), especially among younger nurses. The association between work ability and intention to leave was most marked for those items on the Work Ability Index which explored subjective rather than objective aspects of work ability., Conclusion: Attempts to redress nursing shortages could include institutional policies to sustain work ability through better working conditions, improving quality of the working environment and finding suitable alternative nursing work for those no longer able to cope in their current post. These approaches should include nurses in all age categories.

Objectives: The objective of the NEXT (Nurses' Early Exit) study was to identify the organizational and health factors in the 10 participating countries associated with job satisfaction of nurses and nurses' aides or with their desire to change occupation or stop working prematurely., Methods: Questions about health were somewhat more detailed in the French version of the questionnaire and allowed us to determine health behaviors of this representative sample of French caregivers (PRESST: Promotion of Health and Job Satisfaction of European Healthcare Workers [www.next-study.net; www.presst-next.fr])., Results: Of the 6980 (796 men and 6184 women) nurses and nurses' aides studied in late 2002 and early 2003, 32.6% reported that they smoked at least occasionally and 24.3% regularly. Only 24.4% of the staff in our sample exercised at least weekly. Overweight was observed in 27,6% of the sample, mostly women (42% of men and 24.7% of women), and obesity affected 6,4% of men and 7% of women. Overweight was slightly less frequent than among the general adult population of France, 39.8% according to the CREDES SPS survey in 2002, but these healthcare workers were younger. On the whole, burnout was higher among French caregivers than among those from other European nations in the Next study., Conclusion: This study demonstrates the need to conduct and assess interventions for the dual purpose of (1) reducing the morbidity and mortality associated with the conditions most sensitive to these risk factors in healthcare personnel and (2) improving their knowledge, motivations and credibility in providing health education to patients.

Background: The organization of French medical institutions is changing, and the nursing personnel can encounter difficulties of adaption to these changes. The results of 2 questionnaires of the PRESST/NEXT study relative to working conditions (respectively, the questionnaires "Q0" and "Q12"), sent in a year interval to a sample of nurses were compared., Methods: Three samples were made up: a sample of 5376 nurses having answered the initial questionnaire (Q0); a sample of 2627 nurses having answered the questionnaire sent one year after (Q12), and working in the same establishment; a group of 208 nurses having answered the questionnaire "Qex", specific to nurses who left their establishment., Results: Among nurses who answered the "Qex", approximately 1/5 of nurses chose to leave the profession definitively or temporarily before the retirement age; of these, almost 13% began a new work not in the healthcare sector. Seven factors are significantly related to the intention of leaving the profession: Dissatisfaction regarding professional prospects (Q0: OR = 3.1 and Q12: OR = 2.82); Difficulties assuming the family responsabilities (Q0: OR = 1.36 and Q12: OR = 2.10); Mental health disorders for nurses not followed medically (Q0: OR = 1.76 and Q12: OR = 1.47), and for nurses receiving care for this (Q0 : OR = 1.90 and Q12: OR = 1.77); Dissatisfaction concerning the psychological support available at work (Q0: OR = 1.57 and Q12: OR = 1.87); Tiredness (Q0 : OR = 1.40 and Q12: OR = 1.6); Musculo-skeletal disorders diagnosed by doctor (Q0: OR = 1.32 and Q12: OR = 1.61); Dissatisfaction concerning the use of competences (Q0: OR = 1.27 and Q12: OR = 1.97)., Conclusion: These results raise questions as to the benefits of new management which promotes flexibility in work and schedules, and which reduces the possibilities of support within the nursing teams. This type of management implies uncertainty for nurses as far as the technical aspects of their work are concerned, and a lack of time for the education and follow-up of patients.

Background and Objectives: In many industrialised countries the number of workers with low health is expected to increase in the nursing profession. This will have implications for occupational health work in health care. The European NEXT-Study (www. next-study. net, funded by EU) investigates working conditions of nurses in ten European countries and provides the opportunity to evaluate the role of health with respect to age and the consideration of leaving nursing., Methods: 26,263 female registered nurses from Belgium, Germany, Finland, France, England, Italy, Netherlands, Poland and Slovakia were eligible for analysis., Results: In most countries, older nurses considered leaving the profession more frequently than younger nurses. 'Health' was--next to 'professional opportunities' and 'work organisational factors'--strongly associated with the consideration of leaving nursing. However, more than half of all nurses with low health wanted to remain in the profession. This group reported rather positive psychosocial working conditions--but also the highest fear for unemployment., Conclusions: The findings indicate that 'the nurse with low health' is reality in many health care settings. Both positive supporting working conditions but also lack of occupational alternatives and fear of unemployment may contribute to this. Current economic, political and demographic trends implicate that the number of active nurses with low health will increase. Occupational health surveillance will be challenged by this. But NEXT findings implicate that prevention also will have to regard work organisational factors if the aim is to sustain nurses' health and to enable nurses to remain healthy in their profession until retirement age.

It is important to know whether working time schemes offer, following the adoption of the 1990 ILO Night Work Convention, a better use of the actual knowledge in moderating the adverse effects of shiftwork for both sexes. The last two national studies on a representative sample, about working conditions in France (1991, 1998), show an increase of night work among female nursing staff. Long hours of work are becoming more common for nurses. The percentage of women health care workers not working the same number of days every week increased, with work weeks of 7 days or more. Few positive aspects exist such as a reduction in the proportion of those having to work 17 Sundays or more and a reduction of shifts beginning before 7 a.m. for female nurses. New negotiations, starting in 2001, should be an opportunity for improvements.