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BACKGROUND: In the 90s, digital human manikins (DHMs) were introduced in planning of workstations, by static or semi-static simulations. Modern DHMs can simulate dynamic work and offer a rapid way for a virtual pre-production ergonomic evaluation. Work-related musculoskeletal disorders may affect surgical performance and patient safety. A prototype of an open console, which is contrary to the conventional closed consoles and may be seen as a representative for a new generation, has been designed to reduce workload for robotic surgery surgeons. OBJECTIVE: The aim of this project was to test a new DHM tool with improved usability to evaluate the ergonomics of a console of a robotic surgical system in a pre-production stage. METHODS: The DHM tool IMMA was used together with a 3D model of the prototype console. Twelve manikins who represented females and males from two national populations were introduced. Manikin-console distances, after console adjustments per manikin, were compared with a US checklist and Swedish standard for VDU work. RESULTS: The DHM tool was useful for this case, but the distances of the checklist and the standard were needed to be obtained “manually”. The automatic functions of the DHM worked smoothly but were not optimized for VDU work. The prototype fulfilled most, but not all, of the ergonomic criteria of the checklist and the standard. CONCLUSIONS: There is room for improvements of the adjustable ranges of the console prototype. DHMs may facilitate rapid pre-production evaluation of workstations for static work; if ergonomic assessment models for VDU work are built-in, there may be a revival of DHMs in static work situations.

The use of cryoablation, a minimally-invasive image-guided technique to target and kill cancer cells, continues to gain traction within the medical field and with patients. This includes the use of cryoablation for the treatment of small breast cancers and focal sites of metastatic disease. In comparison to open surgical approaches, length of hospital stay and recovery time are decreased with the use of cryoablation. Research studies have also found that cryoablation may actually enhance tumor susceptibility to immunotherapy agents. Immunotherapy enhances a person’s own immune system to identify and attack cancer cells. It is proposed that after cryoablation there is increased expression of tumor specific antigens which the body can recognize as foreign invaders and with the combination of immunotherapy, result in an even more robust and efficient attack on the cancer cells. In this review we aim to highlight some of the recent advances in cryoablation which support the potential for cryoablation to induce these tumor-specific immune responses and thus supporting the use of combining cryoablation and immunotherapy for the treatment of breast cancer.

Working families commonly struggle with reconciling work and family demands. While the Nordic welfare states have been regarded as forerunners in family-friendly policies, worldwide trends threaten work–family reconciliation also in this context. Therefore, this study aimed to examine the associations between family interference with work (FIW)/work interference with family (WIF) and selected psychosocial risk and support factors in the work and family settings of Finnish working families. Data from the Finnish Quality of Work Life Survey 2018 collected by Statistics Finland were utilized to conduct binary logistic regression analyses (N = 1431). Risk factors in the work setting emerged as key covariates as all of them showed statistically significant associations with WIF or both WIF and FIW. Another key finding was that occasional conflicts within the family were beneficial in the context of both WIF and FIW. To conclude, both distinct and mutual psychosocial risk and support factors of FIW and WIF were identified, at the same time as two socio-demographic factors as well as one workplace factor were identified as covariates specifically of FIW. This study showed that work–family reconciliation is a considerable challenge among Finnish working families, and especially to women.

The aim of this study was to investigate physical fitness, football-specific skills and their association with injury risk in youth football. Altogether 447 male and female players aged 9 to 14 years (median 12 years) participated in performance tests and prospective follow-up. The physical fitness tests included five-jump test for distance, 30-m sprint, football-specific figure of eight agility, countermovement jump, and Yo-Yo intermittent endurance test level 1. The football-specific skill tests included dribbling and passing tests. Injuries and exposure were registered during the 20-week follow-up. Our candidate risk factors were low/high level of physical fitness measured with a composite score of physical fitness tests and low/high level of football-specific skills measured with a composite score of dribbling and passing tests. Secondarily, we investigated performance in individual tests and their association with injury risk. During the follow-up, players reported 565 injuries (264 acute and 301 overuse injuries). High level of physical fitness was associated with increased rate of all injuries (age-, sex- and mean team exposure - adjusted IRR 1.28, 95% CI 1.04–1.58). The level of football-specific skills had no influence on the overall injury rate. Burden of overuse injuries, but not acute injuries was significantly higher in most fit players compared with the players in the reference group (IRR 2.09, 95 % CI 1.04–4.24). In conclusion, most fit players were at greater risk of sustaining injuries in youth competitive football. peerReviewed

Objectives: Numerous studies investigate the advantages of rapid molecular drug susceptibility testing (DST) in comparison to phenotypic DST, but the clinical impact on treating multi/extensively drug resistant TB(M/XDR-TB) is less studied. Therefore, we examined how molecular DST testing may improve MDR-TB treatment management and outcome in Chinese settings. Methods: We performed a comparative study of patient cohorts before and after the implementation of molecular DST diagnosis with Genotype MTBDRsl/MTBDRplus assay in two Chinese hospitals. We collected clinical information including time to sputum culture conversion and final treatment outcome. Results: In total, 242 MDR-TB patients were studied including 114 before (pre-implementation group) and 128 after the implementation (post-implementation group) of molecular DST. Time to MDR-TB diagnosis was significantly reduced for patients in the post-implementation group, as compared to the pre-implementation group (median,16 vs 62 days; P < 0.001). Patients with early available molecular DST results had a more rapid culture conversion (aHR1.94 95% CI: 1.37-2.73; median,12 vs 24 months, respectively; P < 0.001) and higher rate of treatment success (68% vs 47%, P < 0.01). Conclusions: The use of molecular DST in routine care for MDR-TB diagnosis as compared to phenotypic DST was associated with a decreased time to culture conversion and improved treatment outcome, highlighting its important clinical value.

Aim: To describe and study the association between registered nurses' self-rated research utilization and their perception of their work climate. Background: Research utilization is an important part of evidence-based nursing, and registered nurses value a work climate that supports the possibility to work evidence-based. Method: This cross-sectional study was conducted using the Creative Climate Questionnaire together with three questions measuring instrumental, conceptual and persuasive research utilization. The analysis was done using variable- and pattern-oriented approaches. Results: An association was found between research utilization and experience of dynamism/liveliness. Women reported higher use of conceptual research utilization. Regarding work climate, younger registered nurses and registered nurses with less work experience gave higher scores for playfulness/humour and conflicts. The results showed an association between having a Bachelor's or Master's degree and higher instrumental research utilization. Discussion: Research utilization was higher in registered nurses with higher academic education. Low users of research tended to experience a lack of dynamism and liveliness, which indicates the importance of improving the work climate by creating a climate that allows opinions and initiate discussions. Conclusion: The findings support the importance of creating a work climate that encourages reflection and discussion among registered nurses, and to promote academic education for nurses plus an optimal work-place staffing-mix. Summary statement: What is already known about this topic? Research utilization is an important part of evidence-based nursing. Registered nurses value a work climate that supports the possibility to work evidence-based. Little is known about the association between how nurses use research in clinical work and how they perceive their work climate. What this paper adds? Low research users tended to experience low dynamism and liveliness in their work climate, showing the importance of improving the work climate in health care organizations to support clinical nurses' ability to express opinions and initiate discussions. The association between work climate and the use of research among nurses needs further investigation. Our findings support previous research showing that a higher academic level is associated with increased research among registered nurses working clinically, and therefore benefits patient outcomes. The implications of this paper: The association between low research utilization and experience of low dynamism and liveliness indicates the importance of improving the work climate by creating an atmosphere where nurses can express their opinions and initiate discussions. There is a need to support clinical registered nurses to maintain their research utilization throughout their working career. The health care sector and the individual workplace should support registered nurses in furthering their academic level.

Electronics assembly workers are reported to have a high prevalence of musculoskeletal disorders (MSDs). This study investigated the prevalence of cervical MSDs and the complex relationships between cervical MSDs and individual, physical, psychosocial factors among electronics assembly workers.In this cross-sectional survey, self-administered questionnaires from 700 workers in electronics manufacturing workshops were analysed. Information concerning musculoskeletal symptoms, personal and work-related factors was collected. Finally, the prevalence of cervical MSDs was computed for different subgroups, and the relationships with different factors were analyzed using logistic regression and structural equation modeling (SEM).The total 12 month prevalence of cervical MSDs among the survey population was 29.4%. Variables of gender, job tenure, twisting head frequently, neck flexion/extension for long time and work required to be done quickly showed significant associations with MSDs in a multivariate logistic regression (P 0.05). The SEM analysis showed moderate and significant correlations between postural load (γ = 0.279), gender (γ = 0.233) and cervical MSDs, while there were weak but significant correlations between vibration (γ = 0.024), work stress (γ = 0.126), job tenure (γ = 0.024) and cervical MSDs. Both work stress and vibration affected the MSDs indirectly through postural load.The logistic regression results support previous general epidemiological MSD studies, and indicates that individual, physical, and psychosocial factors are related to cervical MSDs. The SEM provides a better approximation of the complexity of the relationship between risk factors and cervical MSDs. Improving awkward postures may be effective ways to control the influence of occupational stressors or vibration on MSDs. Practical Applications: The study is to improve prevention of MSDs among electronics assembly workers and promote their occupational health.

AIMS: To propose new exposure targets for Bayesian dose optimisation suited for high‐dose rifampicin and to apply them using measured plasma concentrations coupled with a Bayesian forecasting algorithm allowing predictions of future doses, considering rifampicin's auto‐induction, saturable pharmacokinetics and high interoccasion variability. METHODS: Rifampicin exposure targets for Bayesian dose optimisation were defined based on literature data on safety and anti‐mycobacterial activity in relation to rifampicin's pharmacokinetics i.e. highest plasma concentration up to 24 hours and area under the plasma concentration–time curve up to 24 hours (AUC(0–24h)). Targets were suggested with and without considering minimum inhibitory concentration (MIC) information. Individual optimal doses were predicted for patients treated with rifampicin (10 mg/kg) using the targets with Bayesian forecasting together with sparse measurements of rifampicin plasma concentrations and baseline rifampicin MIC. RESULTS: The suggested exposure target for Bayesian dose optimisation was a steady state AUC(0–24h) of 181–214 h × mg/L. The observed MICs ranged from 0.016–0.125 mg/L (mode: 0.064 mg/L). The predicted optimal dose in patients using the suggested target ranged from 1200–3000 mg (20–50 mg/kg) with a mode of 1800 mg (30 mg/kg, n = 24). The predicted optimal doses when taking MIC into account were highly dependent on the known technical variability of measured individual MIC and the dose was substantially lower compared to when using the AUC(0–24h)‐only target. CONCLUSIONS: A new up‐to‐date exposure target for Bayesian dose optimisation suited for high‐dose rifampicin was derived. Using measured plasma concentrations coupled with Bayesian forecasting allowed prediction of the future dose whilst accounting for the auto‐induction, saturable pharmacokinetics and high between‐occasion variability of rifampicin.

To investigate the influence of adherence to psychotropic medications upon the risk of completed suicide by comparing person-level prescriptions and postmortem toxicological findings among complete-suicide cases and non-suicide controls in Sweden 2006–2013. Using national registries with full coverage on dispensed prescriptions, results of medico-legal autopsies, causes of death, and diagnoses from inpatient care, estimated continuous drug use for 30 commonly prescribed psychotropic medications was compared with forensic-toxicological findings. Subjects who had died by suicide (cases) were matched (1:2) with subjects who had died of other causes (controls) for age, sex, and year of death. Odds ratios were calculated using logistic regression to estimate the risk of completed suicide conferred by partial adherence and non-adherence to pharmacotherapy. Adjustments were made for previous inpatient care and the ratio of initiated and discontinued dispensed prescriptions, a measure of the continued need of treatment preceding death. In 5294 suicide cases and 9879 non-suicide controls, after adjusting for the dispensation ratio and other covariates, partial adherence and non-adherence to antipsychotics were associated with 6.7-fold and 12.4-fold risks of completed suicide, respectively, whereas corresponding risk estimates for antidepressant treatment were not statistically significant and corresponding risk increases for incomplete adherence to antidepressant treatment were lower (1.6-fold and 1.5-fold, respectively) and lacked statistical significance. After adjustment for the need of treatment, biochemically verified incomplete adherence to antipsychotic pharmacotherapy was associated with markedly increased risks of completed suicide.

Similar to bacteria, synthesis of mitochondrial DNA–encoded proteins requires an N-formylated methionine to initiate translation. Thus, the N-formylated methionine peptides originating from mitochondria should be recognized as danger signals. To date, only one such peptide, denoted as mitocryptide-2 (MCT-2), originating from the N-terminal of the mitochondrial cytochrome b, has been isolated from mammalian tissues. Human neutrophils express FPR1 and FPR2 that detect formyl peptides, and the precise structural determinants for receptor recognition remain to be elucidated. MCT-2 is known to activate neutrophils through FPR2 but not FPR1. The aim of this study was to elucidate the structural determinants of importance for receptor preference and human neutrophil activation in MCT-2 by generating a series of MCT-2 variants. We show that there is an absolute requirement for the N-formyl group and the side chain of Met1 at position 1 of MCT-2 but also the C terminus is of importance for MCT-2 activity. We also uncovered individual side chains that positively contribute to MCT-2 activity as well as those suppressed in the response. The MCT-2 peptide and its two polymorphic variants ([Thr7]MCT-2 and [Ser8]MCT-2) all activated neutrophils, but MCT-2 containing Ile7 and Asn8 was the most potent. We also show that some peptide variants displayed a biased FPR2-signaling property related to NADPH oxidase activation and β-arrestin recruitment, respectively. In conclusion, we disclose several critical elements in MCT-2 that are required for neutrophil activation and disclose structural insights into how FPR2 recognition of this mitochondrial DNA–derived peptide may increase our understanding of the role of FPR2 in aseptic inflammation.

A permanent alcohol interlock programme was introduced in Sweden in 2012. The programme is voluntary and allows drink driving offenders to keep their driving licenses if they install alcohol interlocks in their vehicles. The duration of the programme is one or two years, depending on the severity of the drink driving offence. This study aims to improve our knowledge of drink drivers' views of the programme, among both participants and those who chose not to participate. These views were collected through paper questionnaires mailed to the drink drivers' residences. Of 1550 questionnaires mailed to participants and 1492 to non-participants, 689 and 408 were completed, for response rates of 45% among participants and 28% among non-participants (excluding returns because of incorrect addresses or because the respondent was deceased). For participants who were employed or had their own business (n = 513), the main reasons for choosing the alcohol interlock were the need to operate a vehicle at work (69.6%, 95% CI: 65.6-73.6%) and to get to/from work (69.4%, 95% CI: 65.4-73.4%). For those not working (n = 153), the main reasons for participating were that the driving license was required to have a social life and meaningful leisure time (79.7%, 95% CI: 73.3-86.2%) and for shopping (65.4%, 95% CI: 57.7-73.0%). For non-participants, the main reasons for not applying were programme costs (64.4%, 95% CI: 59.5-69.3%), being afraid of being considered alcoholics (37.1%, 95% CI: 32.2-42.1%), and doing well without a license (26.5%, 95% CI: 22.0-31.0%). The results also indicate improved health after the drink driving offence. The largest improvement was found in participants in the two-year programme, in which the proportion of respondents who felt good or very good increased by 39.4% (95% CI: 34.2-44.5%) compared to before the drink driving offence.

Background Inhaled corticosteroids reduce inflammation in asthma but chronic use may cause adverse effects. AZD7594, an inhaled non-steroidal selective glucocorticoid receptor modulator, has the potential of an improved risk-benefit profile. We investigated the safety and efficacy of AZD7594 in asthma. Methods This phase 2a multi-center, randomized, double-blind, placebo-controlled crossover study enrolled adults with asthma aged 18 to 75 years. Patients were treated with budesonide 200 μg twice daily for 2–3 3 weeks (run in part one). If controlled, as demonstrated by an asthma control questionnaire-5 score of

OBJECTIVES: No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery.METHODS: This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015. Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery.RESULTS: 57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment.CONCLUSIONS: The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.

Recruitment of neutrophils from blood to tissues is a cardinal event in inflammation during which neutrophils switch from a resting, naive state to a preactivated, primed phenotype; the priming process is characterized by alterations in the composition of cell surface adhesins, for example, shedding of l-selectin and mobilization of granule-stored integrins to the cell surface. Ligation of chemotactic receptors and interactions with the endothelial lining are established triggers of neutrophil priming and in line with this, in vivo transmigrated neutrophils obtained from tissues are typically highly primed. We here characterize the priming of neutrophils brought about by in vivo recruitment from blood to inflamed joints by the analyses of synovial fluid and blood from patients with inflammatory arthritis. For comparisons, we used controlled in vivo models of neutrophil transmigration to skin of healthy subjects. In contrast to the residing view and in vivo transmigrated neutrophils from skin models, neutrophils from synovial fluid were often surprisingly resting and phenotypically very similar to naive cells isolated from peripheral blood; synovial fluid cells often retained l-selectin and had undergone minimal up-regulation of integrin receptors. In complete agreement with our in vivo findings, cell-free synovial fluid was potently chemotactic without triggering alteration of surface receptors also in vitro. We conclude that tissue recruitment of neutrophils does not by default trigger l-selectin shedding and granule mobilization, and the chemoattractant(s) guiding neutrophils to synovial fluid apparently operate without inducing cellular priming.

Background Breeding site choice constitutes an important part of the species niche. Nest predation affects breeding site choice, and has been suggested to drive niche segregation and local coexistence of species. Interspecific social information use may, in turn, result in copying or rejection of heterospecific niche characteristics and thus affect realized niche overlap between species. We tested experimentally whether a migratory bird, the pied flycatcher Ficedula hypoleuca, collects information about nest predation risk from indirect cues of predators visiting nests of heterospecific birds. Furthermore, we investigated whether the migratory birds can associate such information with a specific nest site characteristic and generalize the information to their own nest site choice. Results Our results demonstrate that flycatchers can use the fate of heterospecific nesting attempts in their own nest site choice, but do so selectively. Young flycatcher females, when making the decision quickly, associated the fate of an artificial nest with nest-site characteristics and avoided the characteristic associated with higher nest predation risk. Conclusions Copying nest site choices of successful heterospecifics, and avoiding choices which led to failed attempts, may amplify or counter effects of nest predation on niche overlap, with important consequences for between-species niche divergence-convergence dynamics, species coexistence and predator-prey interactions.

Background Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). Methods PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. Findings Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17 women, 745 [83 men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2 951.0-15.6) of 898 patients, with 66 (8.0 95.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9[SD 15.9]). Highly lipidic lesions (851 [24 of 3500 lesions, present in 520 [59 of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22 of 3629 lesions, present in 530 [59 of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.095.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.295.4-17.6). Interpretation Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes. Copyright (C) 2021 Elsevier Ltd. All rights reserved. BackgroundNear-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).MethodsPROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.FindingsBetween June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55–70] years). Median follow-up was 3·7 (IQR 3·0–4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0–15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2–10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25–4·13) and non-culprit lesion-specific MACEs (7·83, 4·12–14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0–10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4–17·6).InterpretationCombined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.FundingAbbott Vascular, Infraredx, and The Medicines Company.

Tularemia, a disease caused by the environmental bacterium Francisella tularensis, is characterized by acute febrile illness. F. tularensis is highly infectious: as few as 10 organisms can cause human disease. Tularemia is not known to be spread from person to person., Francisella tularensis, the causative agent of the zoonotic disease tularemia, can cause seasonal outbreaks of acute febrile illness in humans with disease peaks in late summer to autumn. Interestingly, its mechanisms for environmental persistence between outbreaks are poorly understood. One hypothesis is that F. tularensis forms biofilms in aquatic environments. We utilized two fully virulent wild-type strains: FSC200 (Francisella tularensis subsp. holarctica) and Schu S4 (Francisella tularensis subsp. tularensis) and three control strains, the attenuated live vaccine strain (LVS; F. tularensis subsp. holarctica), a Schu S4 ΔwbtI mutant that is documented to form biofilms, and the low-virulence strain U112 of the closely related species Francisella novicida. Strains were incubated in saline solution (0.9% NaCl) microcosms for 24 weeks at both 4°C and 20°C, whereupon viability and biofilm formation were measured. These temperatures were selected to approximate winter and summer temperatures of fresh water in Scandinavia, respectively. U112 and Schu S4 ΔwbtI formed biofilms, but F. tularensis strains FSC200 and Schu S4 and the LVS did not. All strains exhibited prolonged viability at 4°C compared to 20°C. U112 and FSC200 displayed remarkable long-term persistence at 4°C, with only 1- and 2-fold log reductions, respectively, of viable cells after 24 weeks. Schu S4 exhibited lower survival, yielding no viable cells by week 20. At 24 weeks, cells from FSC200, but not from Schu S4, were still fully virulent in mice. Taken together, these results demonstrate biofilm-independent, long-term survival of pathogenic F. tularensis subsp. holarctica in conditions that mimic overwinter survival in aquatic environments. IMPORTANCE Tularemia, a disease caused by the environmental bacterium Francisella tularensis, is characterized by acute febrile illness. F. tularensis is highly infectious: as few as 10 organisms can cause human disease. Tularemia is not known to be spread from person to person. Rather, all human infections are independently acquired from the environment via the bite of blood-feeding arthropods, ingestion of infected food or water, or inhalation of aerosolized bacteria. Despite the environmental origins of human disease events, the ecological factors governing the long-term persistence of F. tularensis in nature between seasonal human outbreaks are poorly understood. The significance of our research is in identifying conditions that promote long-term survival of fully virulent F. tularensis outside a mammalian host or insect vector. These conditions are similar to those found in natural aquatic environments in winter and provide important new insights on how F. tularensis may persist long-term in the environment.

Background: While becoming a parent can be challenging for all, it can particularly be challenging for those parents and children who are in a vulnerable situation—e.g., in families whose members have problems related to health, relationships, or socioeconomic status. It is essential for health care professionals to identify the more vulnerable families at an early stage. Home visits are one cost-effective way of identifying and supporting such families. This study describes the parental experiences of an intervention that involves professional support in the form of extended home visits. The aim of the study is to describe the parents' understanding of their experiences of receiving professional support through extended home visits both during pregnancy and the first 15 months of their child's life. Methods/Design: A phenomenographic approach was used. Semi-structured interviews were conducted with 12 parents who had received the intervention. The interviews were analyzed using the seven-step phenomenography model described by Sjöström and Dahlgren. Results: The following three descriptive categories emerged from the analysis: (1) conceptions concerning the meaning of the physical environment, (2) conceptions concerning extended home visits promoting feelings of self-confidence in the parental role, and (3) conceptions concerning extended home visits promoting parental participation and relations. Conclusion and Clinical Implications: Extended home visits as a form of professional support appear to promote parental self-confidence in parenting ability, giving parents a feeling of security that facilitates conversation with professionals. Children and their entire families had natural roles during home visits, which allowed the children to behave more characteristically. Furthermore, the home visits were understood to facilitate social support through social activities at the child health center as well as integration into Swedish society for migrant parents. Professional support should be adjusted to the unique individual needs of parents, which demands a variety of supportive interventions—for example, reorganizing one or two of the regular clinical visits currently being scheduled as home visits instead. CC BY 4.0© Copyright © 2021 Bäckström, Thorstensson, Pihlblad, Forsman and Larsson.This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)Correspondence: Caroline Bäckström caroline.backstrom@his.se

This population-based study evaluated motion and form perception in 71 children born extreme premature (EPT; < 27 gestational weeks), aged 6.5 years, as compared to a matched group of 79 control children born at term. Motion and form perception were evaluated by motion coherence and form coherence tests. The EPT group showed a poorer performance on both tasks as compared to the control group. However, after controlling for IQ and visual acuity, the EPT group showed only a significant deficit in motion perception. No association was found between motion perception accuracy and gestational age, previous retinopathy of prematurity, or previous intraventricular hemorrhage in the EPT group. The results highlight the long-term motion perception deficits in children born EPT.

Chimeric antigen receptor (CAR) T cell therapy has yielded unprecedented outcomes in some patients with hematological malignancies; however, inhibition by the tumor microenvironment has prevented the broader success of CART cell therapy. We used chronic lymphocytic leukemia (CLL) as a model to investigate the interactions between the tumor microenvironment and CART cells. CLL is characterized by an immunosuppressive microenvironment, an abundance of systemic extracellular vesicles (EVs), and a relatively lower durable response rate to CART cell therapy. In this study, we characterized plasma EVs from untreated CLL patients and identified their leukemic cell origin. CLL-derived EVs were able to induce a state of CART cell dysfunction characterized by phenotypical, functional, and transcriptional changes of exhaustion. We demonstrate that, specifically, PD-L1(+) CLL-derived EVs induce CART cell exhaustion. In conclusion, we identify an important mechanism of CART cell exhaustion induced by EVs from CLL patients.

Background Implementation of person-centred care (PCC) is a challenging undertaking. Thus, a call has been issued for a robust and generic instrument to measure and enable evaluation of PCC across settings and patient groups. This study aimed to develop a generic questionnaire measuring patients’ perceptions of PCC. Further aims were to evaluate its content and measurement properties using a mixed-methods approach entailing Rasch and qualitative content analyses. Methods The study was conducted in three iterative phases. Phase one included six key informants to gain a broad view of the concept. Phase two entailed a Delphi study involving two rounds with eight experts who generated ratings on relevance, readability, comprehensiveness and suggestions for revision. Data were analysed using the Item Content Validity Index in conjunction with qualitative comments to improve the questionnaire. Phase three was performed using a mixed-methods design. Quantitative data were collected from patients (n = 553) responding to the questionnaire who were recruited from six in- and outpatient care units in a health care region in Sweden. Data was analysed using the Rasch measurement model. Qualitative data were based on the respondents’ free-text comments, cognitive interviews (n = 10) and field notes, and then analysed with deductive content analysis. Results A questionnaire was developed and operationalised based on the information given by key informants in phase one and then validated for its content by experts in phase two. In phase three Rasch analyses revealed problems with targeting, thresholds and two misfitting items. These problems were corroborated by data from the qualitative analyses, which also revealed some issues of wording and interpretation of items. When thresholds were resolved and two items removed, the questionnaire met the assumptions of the Rasch model. Conclusions Experts gave the questionnaire content high ratings and it met measurement requirements assumed by the Rasch model after revisions. Those problems on targeting that remain need to be addressed in future studies. Meanwhile, we regard the questionnaire as of sufficient quality to be useful in benchmarking PCC.

Objective To determine whether a composite metric of arm elevation and trapezius activity (i.e. neck/shoulder load) is more strongly associated with the 2-year course of neck and shoulder pain intensity (NSPi) among construction and healthcare workers than each exposure separately. Methods Dominant arm elevation and upper trapezius muscle activity were estimated in construction and healthcare employees (n = 118) at baseline, using accelerometry and normalized surface electromyography (%MVE), respectively. At baseline and every 6 months for 2 years, workers reported NSPi (score 0–3). Compositions of working time were determined for arm elevation ( 60°), trapezius activity ( 7.0%MVE), and a composite metric “neck/shoulder load” (restitution, low, medium, and high load). Associations between each of these three compositions and the 2-year course of NSPi were determined using linear mixed models. Results Associations between exposure compositions and the course of NSPi were all weak and in general uncertain. Time spent in 0.5–7.0%MVE showed the largest and most certain association with changes in NSPi during follow-up (β = − 0.13; p = 0.037; corresponding to a −0.01 change in NPSi every 6 months). Among pain-free workers at baseline, medium (β = − 0.23; p = 0.039) and high (β = 0.15; p = 0.031) neck/shoulder load contributed the most to explaining changes in NSPi. Conclusion The composite metric of neck/shoulder load did not show a stronger association with the course of NSPi than arm elevation or trapezius activity alone in the entire population, while some indications of a stronger association were found among those who were pain-free at baseline.

Cognitive problems frequently accompany neurological manifestations of multiple sclerosis (MS). However, during screening of preclinical candidates, assessments of behaviour in mouse models of MS typically focus on locomotor activity. In the present study, we analysed cognitive behaviour of 9 to 10‐week‐old female C57Bl/6J mice orally administered with the toxin cuprizone that induces demyelination, a characteristic feature of MS. Animals received 400 mg/kg cuprizone daily for 2 or 4 weeks, and their performance was compared with that of vehicle‐treated mice. Cuprizone‐treated animals showed multiple deficits in short touchscreen‐based operant tasks: they responded more slowly to visual stimuli, rewards and made more errors in a simple rule‐learning task. In contextual/cued fear conditioning experiments, cuprizone‐treated mice showed significantly lower levels of contextual freezing than vehicle‐treated mice. Diffusion tensor imaging showed treatment‐dependent changes in fractional anisotropy as well as in axial and mean diffusivities in different white matter areas. Lower values of fractional anisotropy and axial diffusivity in cuprizone‐treated mice indicated developing demyelination and/or axonal damage. Several diffusion tensor imaging measurements correlated with learning parameters. Our results show that translational touchscreen operant tests and fear conditioning paradigms can reliably detect cognitive consequences of cuprizone treatment. The suggested experimental approach enables screening novel MS drug candidates in longitudinal experiments for their ability to improve pathological changes in brain structure and reverse cognitive deficits.

The use of social information for making decisions is common but can be constrained by behavioural traits via, for example, the ability to gather information. Such constrained information use has been described in foraging habitat selection; yet it remains unexplored in the breeding habitat selection context, despite potentially strong fitness consequences. We experimentally tested whether three behavioural traits (aggressiveness, boldness and neophobia) affected the use of heterospecific social information for nest site selection in wild collared flycatchers Ficedula albicollis . Flycatchers have previously been found to copy or reject an artificial apparent preference of tits (their main competitors) for a nest site feature: they preferred nest-boxes with the same or a different feature, depending on tit early reproductive investment. Here, we confirmed this result and showed that shy individuals and less aggressive old males (i.e. 2 years old or older) copied tit apparent preference, while more aggressive old males rejected the tit preference. Aggressiveness and boldness may allow males to access more information sources or affect males' interactions with dominant tits when selecting a nest site. Our study highlights the links between variation in behaviours and social information use for breeding habitat selection and calls for further work to explore underlying mechanisms.

BackgroundPrior research has shown that individuals with experience of out-of-home care (foster family care or residential care) in childhood are educationally disadvantaged compared to their peers. In order to be better equipped to design interventions aimed at improving the educational outcomes of children for whom society has assumed responsibility, this study seeks to further our understanding about which factors that contribute to the educational disparities throughout the life course.MethodsUsing longitudinal data from a cohort of more than 13,000 Swedes, of which around 7% have childhood experience of out-of-home care, Peters-Belson decomposition is utilized to quantify the extent to which the gap in educational achievement in school (age 16) and midlife educational attainment (age 50) captures differences in the prevalence of factors influencing educational outcomes, and differences in the impacts between these factors.ResultsWe find that the achievement and the attainment gap was around 13% and 9% respectively. These gaps were to a large extent explained by differences in the distribution of predictors. The major explanatory factor for placed children's lower achievement was a lower average cognitive ability. Yet there were some evidence that the rewards of cognitive ability in these children differed across the life course. While the lower returns of cognitive ability suggest that they were underperforming in compulsory school, the higher returns of cognitive ability on midlife attainment indicate that-given previous underperformance-their attainment at age 50 reflects their cognitive capacity more accurately than their achievement at age 16 do.ConclusionThe large influence of the unequal distribution of predictors suggests that policy efforts are needed to promote equity in the distribution of factors contributing to educational achievement and attainment. Since cognitive ability was found to be an important contributory factor, such efforts may include promoting cognitive and intellectual development among children in out-of-home care, preferably starting at a young age.

Treatment of multidrug-resistant tuberculosis (MDR-TB) is challenging due to high treatment failure rate and adverse drug events. This study aimed to develop and validate a simple LC-MS/MS method for simultaneous measurement of five TB drugs in human plasma and to facilitate therapeutic drug monitoring (TDM) in MDR-TB treatment to increase efficacy and reduce toxicity. Moxifloxacin, levofloxacin, prothionamide, pyrazinamide and ethambutol were prepared in blank plasma from healthy volunteers and extracted using protein precipitation reagent containing trichloroacetic acid. Separation was achieved on an Atlantis T3 column with gradient of 0.1% formic acid in water and acetonitrile. Drug concentrations were determined by dynamic multiple reaction monitoring in positive ion mode on a LC-MS/MS system. The method was validated according to the United States' Food and Drug Administration (FDA) guideline for bioanalytical method validation. The calibration curves for moxifloxacin, levofloxacin, prothionamide, pyrazinamide and ethambutol were linear, with the correlation coefficient values above 0.993, over a range of 0.1-5, 0.4-40, 0.2-10, 2-100 and 0.2-10 mg/L, respectively. Validation showed the method to be accurate and precise with bias from 6.5% to 18.3% for lower limit of quantification and -5.8% to 14.6% for LOW, medium (MED) and HIGH drug levels, and with coefficient of variations within 11.4% for all levels. Regarding dilution integrity, the bias was within 7.2% and the coefficient of variation was within 14.9%. Matrix effect (95.7%-112.5%) and recovery (91.4%-109.7%) for all drugs could be well compensated by their isotope-labelled internal standards. A benchtop stability test showed that the degradation of prothionamide was over 15% after placement at room temperature for 72 h. Clinical samples (n = 224) from a cohort study were analyzed and all concentrations were within the analytical range. The signal of prothionamide was suppressed in samples with hemolysis which was solved by sample dilution. As the method is robust and sample preparation is simple, it can easily be implemented to facilitate TDM in programmatic MDR-TB treatment.

Objective: To evaluate the extent and plausible effects of blood transfusions given during cisplatin-based neoadjuvant chemotherapy (NAC) on overall survival in patients with muscle-invasive urothelial bladder cancer (MIBC) undergoing NAC and radical cystectomy (RC). Background: Several studies have demonstrated a decreased survival for MIBC patients receiving allogenic peri- and postoperative blood transfusions in conjunction with RC. No studies have previously investigated the effects of blood transfusions during NAC. Materials and methods: 120 patients with MIBC (cT2-T4aN0M0) undergoing NAC and RC between 2008 and 2014 at four Swedish cystectomy centers were retrospectively evaluated. Clinicopathological data were obtained, including data of allogenic blood administration. Survival data was analyzed by Kaplan–Meier plotting and Cox regression. Results: One third of the cohort received blood transfusions during the period of NAC. In univariate analysis, blood transfusions during NAC, nodal stage and advanced tumor stage (pT >2) were negative prognostic factors for survival. In multivariate analysis, only pNx and pT >2 remained significant negative prognostic factors. In a subgroup analysis consisting of patients with localized tumors without dissemination (n = 96), patients that received transfusions during NAC showed an 18.5% absolute risk increase of death at five years of observation, although without statistical significance (p = .197). Conclusions: This is the first time that the extent and plausible effects of allogenic blood transfusions during NAC is examined in MIBC. Data suggest that there may be an association between blood transfusion and poor pathological and oncological outcome. Firm conclusions are difficult to draw due to few study participants and the retrospective nature of the study.

International audience; Social information use for decision-making is common and affects ecological and evolutionary processes, including social aggrega-tion, species coexistence, and cultural evolution. Despite increasing ecological knowledge on social information use, very little is known about its genetic basis and therefore its evolutionary potential. Genetic variation in a trait affecting an individual's social and nonsocial environment may have important implications for population dynamics, interspecific interactions, and, for expression of other, environmentally plastic traits. We estimated repeatability, additive genetic variance, and heritability of the use of conspecific and heterospecific social cues (abundance and breeding success) for breeding site choice in a population of wild col-lared flycatchers Ficedula albicollis. Repeatability was found for two social cues: previous year conspecific breeding success and previous year heterospecific abundance. Yet, additive genetic variances for these two social cues, and thus heritabilities, were low. This suggests that most of the phenotypic variation in the use of social cues and resulting conspecific and heterospecific social environment experienced by individuals in this population stems from phenotypic plasticity. Given the important role of social information use on ecological and evolutionary processes, more studies on genetic versus environmental determinism of social information use are needed.

Aim: Claimed intake of alcohol after a traffic incident, called the hip-flask defence, can be objectively assessed by different methods. One of them is the use of two consecutive ethanol concentrations in urine and the ratio between ethanol concentrations in urine and blood. Another one is the concentrations of ethyl glucuronide (EtG) and ethyl sulphate (EtS) in blood and their ratio to ethanol. The experimental basis for both these models is from single dose studies only. The aim of this study was therefore to describe the kinetics of ethanol, EtG and EtS after ingestion of two repeated doses of ethanol and to investigate the usefulness of the different models for the assessment of the hip-flask defence. Methods: Thirty-five subjects ingested a first dose of 0.51 g of ethanol per kilo body weight, and two hours later a second dose (the hip-flask drink) of 0.25, 0.51 or 0.85 g of ethanol per kilo body weight. Ten urine and 17 blood samples were collected and analysed for ethanol, EtG and EtS using fully validated methods. It was investigated if all subjects fulfilled the criteria for recent drinking, according to the two different models, when using the samples collected 180-240 minutes after start of first dose drinking. According to the first model, increase in urinary ethanol concentrations and a ratio UAC/BAC below 1.3 indicated recent drinking. According to the second model, increase in blood EtG concentrations and a ratio ethanol (g/kg)/EtG (mg/L) above 1 indicated recent drinking. Results: All subjects in the high dose group fulfilled all criteria for recent drinking. One subject in the medium dose group and nine subjects in the low dose group failed to show increasing UAC and/or a UAC/ BAC ratio below 1.3. One subject in the low dose group failed to show increasing concentrations of blood EtG, but all subjects showed a ratio ethanol/EtG above 1. Conclusions: The present study showed, by the use of experimental data, that both two models used to investigate the hip-flask defence can be used, but only when the hip-flask dose is sufficiently high. (C) 2020 The Author(s). Published by Elsevier B.V.

Purpose: This study aimed to examine how participants aged 80 years old or over describe their mental well-being—exploring the suitability of the model of healthy ageing when outlining the mental well-being concept. Methods: Six structured focus group interviews with 28 participants were conducted in Western Finland in 2017. Qualitative content analysis was performed, where both manifest and latent content was considered in a process involving meaning condensation and coding, followed by categorization. Results: The healthy ageing model constituted a useful framework for the conceptualization of mental well-being, illustrating the links between these two constructs. The analysis resulted in a four-dimensional model of mental well-being in oldest old age, the key components being: Activities—enjoyment and fulfilment; Capability—functioning and independence; Orientation—awareness, shifted perspectives and values; and Connectedness—sense of belonging. Conclusions: Although functional status plays an important role for well-being in general, it is not the principal component of self-reported mental well-being within the heterogeneous group of the oldest old. Further, many persons in this age group do not view themselves as passive or dependent, on the contrary, they underline the importance of empowering attitudes, a positive mindset and actively creating circumstances which support their mental well-being.

While cycling is promoted as a clean, energy-efficient mode of transport generating physical activity, the number of injured cyclists must decrease to achieve traffic safety goals. The extent of the single bicycle crashes (SBCs) and crash causes are rather well studied. This study expands this knowledge by focusing on differences in injury severity. The aim of the study is to investigate the relationship between injury severity and characteristics of the crash and the cyclist with focus on SBCs. Furthermore, injury risk is calculated for different age classes and sexes, as well as for different purposes of the trip. The results are based on injured cyclists in Sweden (N = 105,836) registered in STRADA, 2010-2019, by both the police and accident and emergency departments (AEs), with a special focus on injury severity reported by the AEs. Binary logistic regression was applied to analyse how the odds of being severely injured differed for different cyclists and situations. Results from of the National Travel Survey, 2011-2016, were used to study differences in distance travelled with respect to sex, age group and purpose of the trip. Given that the cyclist is injured in an SBC, the results show a higher probability of being severely injured (maximal AIS 3 or more) for cyclists 45 years or older compared to younger cyclists, for males compared to females and for cyclists not wearing a helmet compared to cyclists wearing a helmet. A higher probability for severe injury was also found for crashes occurring during leisure trips compared to work/school trips, crashes occurring during weekdays compared to weekends and crashes at intersections and road stretches compared to pedestrian and cycle paths. Furthermore, the risk of being severely injured in an SBC per km travelled was higher for cyclists aged 45 and older and during a leisure trip.

ObjectiveTo survey the prevalence of lower extremity musculoskeletal disorders (MSDs) among Chinese manufacturing workers, and to identify the associated factors.DesignObservational study with cross-sectional design.SettingA self-administered questionnaire survey was conducted in four manufacturing factories in China.Participants7908 manufacturing workers were included in this study after excluding non-conforming personnel.Outcome measuresIndividual and work-related information, and MSDs in the whole leg and knee region were measured by the anonymous self-administered questionnaire. Individual and work-related factors associated with MSDs and their effects were identified through multivariate logistic regression.ResultsOf all respondents, 3241 (41.0%) reported having had lower extremity MSDs in the recent 12 months, and for the knees, ankles/feet and hips/thighs were 29.5%, 23.9% and 16.7%, respectively. After confounder-adjusted single-factor analysis, 22 variables (of 24) were significantly related to the disorders. Factors like always kneeling/squatting for long periods, always standing for long periods and often lifting in an uncomfortable position were shown to have higher risks, with ORs of 2.77 (95% CI: 2.33 to 3.30), 2.30 (1.96 to 2.69) and 2.25 (2.04 to 2.47). Comparable results were found on knee disorders. The final model included 15 variables of demography, biomechanics and work organisation. The following factors showed increased risks of lower extremity MSDs: being female, being older, longer working years, higher body mass index (BMI), keeping the same posture for a long time, awkward position, shift work and monotonous work. Whereas having enough breaks reduced the risk.ConclusionThe prevalence of lower extremity MSDs among Chinese manufacturing workers is high. The most commonly affected body regions were the knees and ankles/feet. Multiple factors were found associated with lower extremity MSDs including age, BMI, work experience, work organisations, physical ergonomics exposures, etc.

Background Work-related pain and discomfort experienced by surgeons is widely reported in the literature. A survey was, therefore, conducted to explore this issue among members of the European Association for Endoscopic Surgery (EAES). Methods The survey was emailed to 2980 EAES members in 2017 enquiring about their working practice, musculoskeletal (MSK) pain and burnout. Results A total of 569 (19%) surgeons responded, of whom 556 were practicing surgeons; 86% were consultants, 84% were male, and 94% were right-handed. Respondents operated on average 3.3 days/week with 27% of their procedures lasting longer than 3 h. The 386 endoscopists surveyed reported performing an average of 5.3 procedures/day with 83% performing endoscopy at least once per week. Over half of practicing surgeons (62%) reported their worst pain score was 3 or higher (10-point scale) in the past 7 working days, encompassing 71% of their open, 72% laparoscopic, 48% robot-assisted cases and 52% of their endoscopies. Of the 120 surgeons who had ever sought medical help for aches, pain or discomfort, 38% were currently in pain and 16% had considered leaving surgery due to their MSK pain, 26% had reported work-related pain to their employer, 26% had been on short-term disability during their career and 4% long-term disability due to MSK disorders. A significant proportion of the respondents (49%) felt their physical discomfort would influence the ability to perform or assist with surgical procedures in the future. These surgeons reported significantly lower satisfaction from their work (p = 0.024), higher burnout (p = 0.005) and significantly higher callousness toward people (p

The present study aimed to identify whether or not an increase in ciliary-muscle contraction force, when the eye-lens is adjusted for viewing at a near distance, results in an increase in trapezius muscle activity, while performing a natural work task. Twelve participants, ranging in age from 21 to 32 years, performed a computer-mouse work task during free gaze conditions. A moving visual target was tracked with a computer mouse on a screen placed at two different distances from the eyes, 25 cm and 50 cm. Tracking performance, eye accommodation, and bilateral trapezius muscle activity were measured continuously. Ciliary-muscle contraction force was computed according to a formula which takes into account the age-dependent, non-linear relationship between the contraction force of the ciliary muscle and the produced level of eye accommodation. Generalized estimating equations analyses were performed. On the dominant hand side and for the nearest screen distance, there was a significant effect of ciliary-muscle contraction force on the trapezius muscle activity (p 0.05). The results support the hypothesis that high visual demands, during computer mouse work, increase ciliary muscle contraction force and contribute to a raise of the sustained level of trapezius muscle activity. The current study specifically clarifies the validity of the relationship between ciliary-muscle contraction force and trapezius muscle activity and demonstrates that this relationship is not due to a general personality trait. We conclude that a high level of ciliary muscle contraction force can contribute to a development of musculoskeletal complaints in the neck–shoulder area.

Objective: The objective of this study was to investigate odds ratios of overweight/obesity in children with ADHD and to compare the change in body mass index (BMI) after initiation of methylphenidate treatment in normal versus overweight/obese children. Method: This population-based study included 724 children (

Therapeutic drug monitoring (TDM) could improve current TB treatment, but few studies have reported pharmacokinetic data together with MICs.To investigate plasma concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol along with MICs.Drug concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol were analysed pre-dose and 2, 4 and 6 h after drug intake at week 2 in 31 TB patients and MICs in BACTEC 960 MGIT were determined at baseline. The highest plasma concentrations at 2, 4 and 6 h post-dose (Chigh) were determined, as well as estimates of Chigh/MIC and area under the concentration-time curve (AUC0-6)/MIC including the corresponding ratios based on calculated free-drug concentrations. This trial was registered at www.clinicaltrials.gov (NCT02042261).After 2 weeks of treatment, the median Chigh values for rifampicin, isoniazid, pyrazinamide and ethambutol were 10.0, 5.3, 41.1 and 3.3 mg/L respectively. Lower than recommended drug concentrations were detected in 42% of the patients for rifampicin (8 mg/L), 19% for isoniazid (3 mg/L), 27% for pyrazinamide (35 mg/L) and 16% for ethambutol (2 mg/L). The median Chigh/MIC values for rifampicin, isoniazid, pyrazinamide and ethambutol were 164, 128, 1.3 and 2.5, respectively, whereas the AUC0-6/MIC was 636 (range 156-2759) for rifampicin and 351 (range 72-895) for isoniazid.We report low levels of first-line TB drugs in 16%-42% of patients, in particular for rifampicin. There was a wide distribution of the ratios between drug exposures and MICs. The future use of MIC determinations in TDM is dependent on the development of a reference method and clinically validated pharmacokinetic/pharmacodynamic targets.

Regarding prevention of neck and shoulder pain (NSP), unsupported arm elevation is one factor that should be taken into account when performing work risk assessment. Triaxial accelerometers can be used to measure arm elevation over several days but it is not possible to differentiate between supported and unsupported arm elevation from accelerometers only. Supported arm elevation is more likely to exist during sitting than standing. The aim of the study was to evaluate the use of whole workday measurements of arm elevation with accelerometers to assess potentially harmful work exposure of arm elevation, by comparing arm elevation at work with arm elevation during leisure, in a population with diverse work tasks, and to assess how the exposure parameters were modified when upper arm elevation during sitting time was excluded. The participants, 197 workers belonging to 12 occupational groups with diverse work tasks, wore triaxial accelerometers on the dominant arm, hip, and back for 1–4 days to measure arm elevation and periods of sitting. None of the groups were found to have higher exposure to arm elevation during work compared to leisure. Even though some occupations where known to have work tasks that forced them to work with elevated arms to a large extent. A high proportion of arm elevation derived from sitting time, especially so during leisure. When arm elevation during sitting time was excluded from the analysis, arm elevation was significantly higher at work than during leisure among construction workers, garbage collectors, manufacturing workers, and domestic cleaners. Together this illustrates that it is not suitable to use whole workday measurments of arm elevation with accelerometer as a sole information source when assessing the risk for NSP due to arm elevation. Information on body posture can provide relevant contextual information in exposure assessments when it is known that the potential harmful exposure is performed in standing or walking.

BACKGROUND: Wrist disorders are common in force demanding industrial repetitive work. Visual assessment of force demands have a low reliability, instead surface electromyography (EMG) may be used as part of a risk assessment for work-related wrist disorders. For normalization of EMG recordings, a power grip (hand grip) is often used as maximal voluntary contraction (MVC) of the forearm extensor muscles. However, the test-retest reproducibility is poor and EMG amplitudes exceeding 100% have occasionally been recorded during work. An alternative MVC is resisted wrist extension, which may be more reliable. OBJECTIVE: To compare hand grip and resisted wrist extension MVCs, in terms of amplitude and reproducibility, and to examine the effect of electrode positioning. METHODS: Twelve subjects participated. EMG from right forearm extensors, from four electrode pairs, was recorded during MVCs, on three separate occasions. RESULTS: The group mean EMG amplitudes for resisted wrist extension were 1.2-1.7 times greater than those for hand grip. Resisted wrist extension showed better reproducibility than hand grip. CONCLUSIONS: The results indicate that the use of resisted wrist extension is a more accurate measurement of maximal effort of wrist extensor contractions than using hand grip and should increase the precision in EMG recordings from forearm extensor muscles, which in turn will increase the quality of risk assessments that are based on these. (Less)

We asked whether ambient temperatures can affect morph frequencies within a subarctic population of the polymorphic leaf beetle Chrysomela lapponica through thermal melanism and/or developmental plasticity. Body temperature increased faster in beetles of dark morph than in beetles of light morph under exposure to artificial irradiation. Dark males ran faster than light males in both field and laboratory experiments, and this difference decreased with increasing ambient air temperature, from significant at 10 °C to non-significant at 20 °C and 26 °C. On cold days (6–14 °C), significantly more dark males than light males were found on their host plants in copula (40.8% and 27.3% respectively); on warm days (15–22 °C) this difference disappeared. Light females produced twice as many eggs as dark females; this difference did not depend on the ambient temperature. The proportion of dark morphs in the progenies of pairs with one dark parent was twice as high as that in the progenies of pairs in which both parents were light, and this proportion was greater when larvae developed at low (10 and 15 °C) than at high (20 and 25 °C) temperatures. We conclude that low temperatures may increase the frequencies of dark morphs in C. lapponica populations due to both the mating advantages of dark males over light males and developmental plasticity. Variation in frequencies of low-fecund dark morphs in the population, caused by among-year differences in temperature together with density-dependent selection, may contribute to the evolutionary dynamics of the colour polymorphism and may influence abundance fluctuations in these leaf beetle populations.

Background The alternative prey hypothesis describes the mechanism for apparent competition whereby the mortality of the secondary prey species increases (and population size decreases decreases) by the increased predation by the shared predator if the population size of the primary prey decreases. Apparent competition is a process where the abundance of two co-existing prey species are negatively associated because they share a mutual predator, which negatively affects the abundance of both prey Here, we examined whether alternative prey and/or apparent competition hypothesis can explain the population dynamics and reproductive output of the secondary prey, wild forest reindeer (Rangifer tarandus fennicus) in Finland, in a predator-prey community in which moose (Alces alces) is the primary prey and the wolf (Canis lupus) is the generalist predator. Methods We examined a 22-year time series (1996–2017) to determine how the population size and the calf/female ratio of wild forest reindeer in Eastern Finland were related to the abundances of wolf and moose. Only moose population size was regulated by hunting. Summer predation of wolves on reindeer focuses on calves. We used least squares regression (GLS) models (for handling autocorrelated error structures and resulting pseudo-R2s) and generalized linear mixed (GLMs) models (for avoidance of negative predictions) to determine the relationships between abundances. We performed linear and general linear models for the calf/female ratio of reindeer. Results and synthesis The trends in reindeer population size and moose abundance were almost identical: an increase during the first years and then a decrease until the last years of our study period. Wolf population size in turn did not show long-term trends. Change in reindeer population size between consecutive winters was related positively to the calf/female ratio. The calf/female ratio was negatively related to wolf population size, but the reindeer population size was related to the wolf population only when moose abundance was entered as another independent variable. The wolf population was not related to moose abundance even though it is likely to consist the majority of the prey biomass. Because reindeer and moose populations were positively associated, our results seemed to support the alternative prey hypothesis more than the apparent competition hypothesis. However, these two hypotheses are not mutually exclusive and the primary mechanism is difficult to distinguish as the system is heavily managed by moose hunting. The recovery of wild forest reindeer in eastern Finland probably requires ecosystem management involving both habitat restoration and control of species abundances.

Objective We aimed to assess the extent to which adherence to, and recreational use of, psychotropic medications influence the risk of homicide offending and victimization. Methods We conducted a population-based case-control study by way of linking a nationwide registry of dispensed prescriptions with a forensic-toxicological database. Homicide victims (n = 200) and offenders (n = 105) were identified for the years 2007-2009 and vehicle-accident controls (n = 1,643) for the years 2006-2013. The occurrence of congruence and incongruence between dispensed prescriptions and toxicology was used as a measure of adherence and recreational use. Results For antidepressants, incongruence-but not congruence-between dispensed prescriptions and toxicology was associated with a significantly increased risk of homicide offending (odds ratio adjusted for age and sex [aOR] = 6.2; 95% confidence interval [CI], 3.3-11.6) but not homicide victimization (aOR = 0.8; 95% CI, 0.3-2.0). For antipsychotics and mood stabilizers, a significantly increased risk of homicide offending was associated with incongruence between prescriptions and toxicology (aOR = 7.0; 95% CI, 2.8-17.7), whereas risk estimates for congruence were not significantly elevated for either homicide offending or victimization. For GABAergic hypnotics, congruence and incongruence were significantly associated with increased risks of both homicide offending (aOR = 5.4; 95% CI, 2.6-11.0 and aOR = 4.9; 95% CI, 2.6-9.3, respectively) and homicide victimization (aOR = 2.1; 95% CI, 1.1-4.2 and aOR = 3.2; 95% CI, 1.7-6.1, respectively). Sensitivity analyses with a subset of controls yielded similar estimates. Conclusions Nonadherence to medications used to treat affective and psychotic disorders appears to elevate the risk of homicide offending. Both medicinal and recreational use of GABAergic hypnotics appears to elevate the risk of homicide offending and victimization. In summary, vigilance regarding adherence to medications prescribed for mood disorders and psychosis, as well as restrictiveness regarding licit and illicit access to addictive hypnotics, might contribute to a reduction of homicidal violence.

Aims and objectives: To describe what nursing and rehabilitation staff know and do with regard to urinary incontinence and risk of urinary incontinence in patients 65 years or older undergoing hip surgery. Background: Urinary incontinence is a common but often neglected issue for older people. Despite the existence of evidence-based guidelines on how to assess, manage and prevent urinary incontinence, there are indications that these guidelines are not applied in hospital care. Design: A qualitative study with descriptive design was conducted in two orthopaedic units. Methods: Forty-six interviews and 36 observations of care were conducted from January-October 2014 and analysed with qualitative content analysis. Results: Enrolled nurses performed most of the care related to bladder function, with focus on urinary catheterisation and preventing urinary tract infection and urinary retention. Registered nurses' role in urinary matters mainly comprised documentation, while the rehabilitation staff focused on making it possible for the patient to be independent in toileting. The nursing staff considered urinary incontinence a common condition for older people and that it was convenient for the patients to have an indwelling catheter or incontinence pad/pant, although they acknowledged some of the risks associated with these procedures. Conclusions: Urinary incontinence is not a priority in orthopaedic care, and urinary incontinence guidelines are not applied. Further, attitudes and actions are mainly characterised by a lack of urinary incontinence knowledge and the nursing and rehabilitation staff do not take a team approach to preventing and managing urinary incontinence. Relevance to clinical practice: An increased focus on knowledge on urinary incontinence and evidence-based guidelines is needed. To secure evidence-based practice, the team of nursing and rehabilitation staff and managers must be aligned and work actively together, also including the patient in the team.

Animals must balance various costs and benefits when deciding when to breed. The costs and benefits of breeding at different times have received much attention, but most studies have been limited to investigating short-term season-to-season fitness effects. However, breeding early, versus late, in a season may influence lifetime fitness over many years, trading off in complex ways across the breeder’s lifespan. In this study, we examined the complete life histories of 867 female tree swallows (Tachycineta bicolor) breeding in Ithaca, New York, between 2002 and 2016. Earlier breeders outperformed later breeders in short-term measures of reproductive output and offspring quality. Though there were weak indications that females paid long-term future survival costs for breeding early, lifetime fledgling output was markedly higher overall in early-breeding birds. Importantly, older females breeding later in the season did not experience compensating life history advantages that suggested an alternative equal-fitness breeding strategy. Rather, most or all of the swallows appear to be breeding as early as they can, and differences in lay dates appear to be determined primarily by differences in individual quality or condition. Lay date had a significant repeatability across breeding attempts by the same female, and the first lay date of females fledged in our population was strongly influenced by the first lay date of their mothers, indicating the potential for ongoing selection on lay date. By examining performance over the entire lifespan of a large number of individuals, we were able to clarify the relationship between timing of breeding and fitness and gain new insight into the sources of variability in this important life history trait.

Background In the wake of climate change many environments will be exposed to increased and more variable temperatures. Knowledge about how species and populations respond to altered temperature regimes is therefore important to improve projections of how ecosystems will be affected by global warming, and to aid management. We conducted a common garden, split-brood temperature gradient (4.5 °C, 9.7 °C and 12.3 °C) experiment to study the effects of temperature in two populations (10 families from each population) of anadromous pike (Esox lucius) that normally experience different temperatures during spawning. Four offspring performance measures (hatching success, day degrees until hatching, fry survival, and fry body length) were compared between populations and among families. Results Temperature affected all performance measures in a population-specific manner. Low temperature had a positive effect on the Harfjärden population and a negative effect on the Lervik population. Further, the effects of temperature differed among families within populations. Conclusions The population-specific responses to temperature indicate genetic differentiation in developmental plasticity between populations, and may reflect an adaptation to low temperature during early fry development in Harfjärden, where the stream leading up to the wetland dries out relatively early in the spring, forcing individuals to spawn early. The family-specific responses to temperature treatment indicate presence of genetic variation for developmental plasticity (G x E) within both populations. Protecting between- and within-population genetic variation for developmental plasticity and high temperature-related adaptive potential of early life history traits will be key to long-term viability and persistence in the face of continued climate change. Electronic supplementary material The online version of this article (10.1186/s12862-019-1475-3) contains supplementary material, which is available to authorized users.

To identify clusters based on graduating nursing students' self-reported professional competence and their achievement on a national examination. Furthermore, to describe and compare the identified clusters regarding sample characteristics, students' perceptions of overall quality of the nursing programme, and students' general self-efficacy (GSE).A cross-sectional study combining survey data and results from a national examination.Data were collected at two universities and one university college in Sweden in January 2017, including 179 students in the final term of the nursing programme. The study was based on the Nurse Professional Competence Scale, the GSE scale, and results from the National Clinical Final Examination. A two-step cluster analysis was used to identify competence profiles, followed by comparative analyses between clusters.Three clusters were identified illustrating students' different competence profiles. Students in Clusters 1 and 2 passed the examination, but differed in their self-assessments of competence, rating themselves under and above the overall median value, respectively. Students in Cluster 3 failed the examination but rated themselves at the overall median level or higher.The study illustrates how nursing students' self-assessed competence might differ from competency assessed by examination, which is challenging for nursing education. Self-evaluation is a key learning outcome and is, in the long run, essential to patient safety.The study has identified clusters of students where some overestimate and others underestimate their competence. Students who assessed their competence low but passed the exam assessed their GSE lower than other students. The findings illuminate the need for student-centred strategies in nursing education, including elements of self-assessment in relation to examination to make the students more aware of their clinical competence.目的: 此研究旨在根据应届护理专业学生自我报告的专业能力及其在全国考试中的成绩来确定类别。此外还需对样本特征、学生对护理专业课程总体质量的看法以及学生的一般自我效能感(GSE)的已确定特征进行描述和比较。 设计: 一项结合了调查数据和国家考试结果的横断面研究。 方法: 2017年1月,我们收集了瑞典的两所大学和一所大学学院的数据,其中包括179名护理专业课程的应届毕业生。此项研究基于护士专业能力量表、一般自我效能感(GSE)量表以及国家临床期末考试。我们使用两步聚类分析法以确定能力性质,随后进行类别之间的比较分析。 结果: 此项研究最终确定了三个类别,分别说明学生的不同能力性质。类别1和类别2的学生通过了考试,但他们的自我能力评估有所不同,他们分别将自己评定为总体中位值以下和以上。类别3的学生未能通过考试,但他们认为自己处于总体中位水平或更高。 结论: 此项研究探讨了护理学生的自我能力评估可能与考试评定的能力可能存在怎样的差异,这对护理教育来说是一个挑战。自我评估是关键的学习成果,并且从长远来看,对患者安全至关重要。 影响: 此项研究确定了学生类别,其中部分学生高估了自己的能力,部分学生低估了自己的能力。自我评估能力较低但通过考试的学生所评定的一般自我效能感(GSE)要比其他学生低。研究结果表明需要在护理教育中使用以学生为中心的策略,包括与考试相关的自我评估要素,从而使得学生更清楚认识到自己的临床能力。.

BACKGROUND: In human body fluids, microRNA (miRNA) can be found as circulating cell-free miRNA (cfmiRNA), as well as secreted into extracellular vesicles (EVmiRNA). miRNAs are being intensively evaluated as minimally invasive liquid biopsy biomarkers in patients with cancer. The growing interest in developing clinical assays for circulating miRNA necessitates careful consideration of confounding effects of preanalytical and analytical parameters. METHODS: By using reverse transcription quantitative real-time PCR and next-generation sequencing (NGS), we compared extraction efficiencies of 5 different protocols for cfmiRNA and 2 protocols for EVmiRNA isolation in a multicentric manner. The efficiency of the different extraction methods was evaluated by measuring exogenously spiked cel-miR-39 and 6 targeted miRNAs in plasma from 20 healthy individuals. RESULTS: There were significant differences between the tested methods. Although column-based extraction methods were highly effective for the isolation of endogenous miRNA, phenol extraction combined with column-based miRNA purification and ultracentrifugation resulted in lower quality and quantity of isolated miRNA. Among all extraction methods, the ubiquitously expressed miR-16 was represented with high abundance when compared with other targeted miRNAs. In addition, the use of miR-16 as an endogenous control for normalization of quantification cycle values resulted in a decreased variability of column-based cfmiRNA extraction methods. Cluster analysis of normalized NGS counts clearly indicated a method-dependent bias. CONCLUSIONS: The choice of plasma miRNA extraction methods affects the selection of potential miRNA marker candidates and mechanistic interpretation of results, which should be done with caution, particularly across studies using different protocols.

Work metabolism (WM) can be accurately estimated by oxygen consumption (VO2), which is commonly assessed by heart rate (HR) in field studies. However, the VO2-HR relationship is influenced by individual capacity and activity characteristics. The purpose of this study was to evaluate three models for estimating WM compared with indirect calorimetry, during simulated work activities. The techniques were: the HR-Flex model; HR branched model, combining HR with hip-worn accelerometers (ACC); and HR + arm-leg ACC model, combining HR with wrist- and thigh-worn ACC. Twelve participants performed five simulated work activities and three submaximal tests. The HR + arm-leg ACC model had the overall best performance with limits of agreement (LoA) of -3.94 and 2.00 mL/min/kg, while the HR-Flex model had -5.01 and 5.36 mL/min/kg and the branched model, -6.71 and 1.52 mL/min/kg. In conclusion, the HR + arm-leg ACC model should, when feasible, be preferred in wearable systems for WM estimation. Practitioner Summary: Work with high energy demand can impair employees' health and life quality. Three models were evaluated for estimating work metabolism during simulated tasks. The model combining heart rate, wrist- and thigh-worn accelerometers showed the best accuracy. This is, when feasible, suggested for wearable systems to assess work metabolism. Mätning av det dagliga aktivitetsmönstret

Objective: In Sweden, cyclists, pedestrians, and moped riders share the space on combined pedestrian and cycle paths, and their speeds may differ greatly. Both actual speed and speed differences can potentially influence the number of accidents on the shared paths. As a starting point, this article studies the speed component and how cyclists’ speed varies at pedestrian and cycle paths depending on the day, week, and year; road user composition; and road design. Methods: Three data sources were used: Existing measurements of cycle speed and flow in 3 different Swedish municipalities, Eskilstuna (1 site, January–December 2015), Linköping (6 sites, 4 weeks in September–October 2015), and Stockholm (10 sites, 1–5 days in August–September 2015); complementary measurements of cycle speed and flow in Linköping (4 sites, 1–10 days in August–September 2016) and Stockholm (1 site, only part of 2 days in August 2016) were also conducted within the project, in addition to roadside observations of bicycle types at the 5 new sites. Results: The average speed of cyclists on the paths varied between 12.5 and 26.5 km/h. As expected, the lower average speeds were found in uphill directions, near intersections, and on paths with high pedestrian flows. The higher speeds were found in downhill directions and on commuter routes. In all, 70%–95% of road users observed on pedestrian and cycle paths were cyclists, and 5%–30% were pedestrians. The most common type of bicycle was a comfort bike, followed by a trekking bike. Electric-assisted bicycles and racer bikes occurred at all sites, with proportions of 1%–10% and 1%–15%, respectively. The 2 sites with the highest proportion of electric-assisted bicycles and racer bicycles also had the highest average speeds. The differences in average speed throughout the day, week, and year could only be assessed at one of the sites. Only small differences were found, with the most noticeable being that the average speed was lower in January and February (13.8 km/h) compared to the rest of the year (15.3–16.1 km/h). The average speed was also lower during daytime (14.7 km/h) than during other parts of the day (15.4–15.8 km/h). Conclusions: The relationship between bicycle type and measured speed was not entirely clear, but the results suggest that paths with higher proportions of electric and racer bicycles have higher average speeds. There also appears to be a connection between average speed and the width of the distribution; that is, the higher the average speed, the wider the speed distribution. More research is needed on how speed levels and speed variance affect accident risk.