Acceleration of Electrons by Whistler-Mode Hiss Waves at Saturn.

Plasmaspheric hiss waves at the Earth are well known for causing losses of electrons from the radiation belts through wave particle interactions. At Saturn, however, we show that the different plasma density environment leads to acceleration of the electrons rather than loss. The ratio of plasma frequency to electron gyrofrequency frequently falls below one creating conditions for hiss to accelerate electrons. The location of hiss at high latitudes (>25°) coincides very well with this region of very low density. The interaction between electrons and hiss only occurs at these higher latitudes, therefore the acceleration is limited to mid to low pitch angles leading to butterfly pitch angle distributions. The hiss is typically an order of magnitude stronger than chorus at Saturn and the resulting acceleration is rapid, approaching steady state in one day at 0.4 MeV at L = 7 and the effect is stronger with increasing L-shell.

Vaccine hesitancy among working-age adults with/without disability in the UK.

OBJECTIVES: To estimate levels of COVID-19 vaccine hesitancy among working-age adults with disabilities in the United Kingdom. STUDY DESIGN: Cross-sectional survey. METHODS: Secondary analysis of data collected on a nationally representative sample of 10,114 respondents aged 16-64 years. RESULTS: The adjusted relative risk for hesitancy among respondents with a disability was 0.92 (95% CI 0.67-1.27). There were stronger associations between gender and hesitancy and ethnic status and hesitancy among participants with a disability. The most common reasons cited by people with disabilities who were hesitant were: concern about the future effects of the vaccine, not trusting vaccines and concern about the side effects of vaccination. CONCLUSIONS: The higher rates of vaccine hesitancy among women with disabilities and among people from minority ethnic groups with disabilities are concerning.

How do employment conditions and psychosocial workplace exposures impact the mental health of young workers? A systematic review.

PURPOSE: To assess the quality of the research about how employment conditions and psychosocial workplace exposures impact the mental health of young workers, and to summarize the available evidence. METHODS: We undertook a systematic search of three databases using a tiered search strategy. Studies were included if they: (a) assessed employment conditions such as working hours, precarious employment, contract type, insecurity, and flexible work, or psychosocial workplace exposures such as violence, harassment and bullying, social support, job demand and control, effort-reward imbalance, and organizational justice; (b) included a validated mental health measure; and (c) presented results specific to young people aged ≤ 30 years or were stratified by age group to provide an estimate for young people aged ≤ 30 years. The quality of included studies was assessed using the Risk of Bias in Non-randomized Studies of Exposures (ROBINS-E) tool. RESULTS: Nine studies were included in the review. Four were related to employment conditions, capturing contract type and working hours. Five studies captured concepts relevant to psychosocial workplace exposures including workplace sexual harassment, psychosocial job quality, work stressors, and job control. The quality of the included studies was generally low, with six of the nine at serious risk of bias. Three studies at moderate risk of bias were included in the qualitative synthesis, and results of these showed contemporaneous exposure to sexual harassment and poor psychosocial job quality was associated with poorer mental health outcomes among young workers. Longitudinal evidence showed that exposure to low job control was associated with incident depression diagnosis among young workers. CONCLUSIONS: The findings of this review illustrate that even better studies are at moderate risk of bias. Addressing issues related to confounding, selection of participants, measurement of exposures and outcomes, and missing data will improve the quality of future research in this area and lead to a clearer understanding of how employment conditions and psychosocial workplace exposures impact the mental health of young people. Generating high-quality evidence is particularly critical given the disproportionate impact of COVID-19 on young people's employment. In preparing for a post-pandemic world where poor-quality employment conditions and exposure to psychosocial workplace exposures may become more prevalent, rigorous research must exist to inform policy to protect the mental health of young workers.

Gendered experiences of unemployment, suicide and self-harm: a population-level record linkage study.

BACKGROUND: Unemployment and being not in the labour force (NILF) are risk factors for suicide, but their association with self-harm is unclear, and there is continuing debate about the role of confounding by prior mental health conditions. We examine associations between employment status and self-harm and suicide in a prospective cohort, taking into account prior mental-health-related factors. METHODS: We used linked data from the New Zealand Integrated Data Infrastructure. The outcomes were chosen to be hospital presentation for self-harm and death by suicide. The exposure was employment status, defined as employed, unemployed, or NILF, measured at the 2013 Census. Confounders included demographic factors and mental health history (use of antidepressant medication, use of mental health services, and prior self-harm). Logistic regression was used to model effects. Analyses were stratified by gender. RESULTS: For males, unemployment was associated with an increased risk of suicide [odds ratio (OR): 1.48, 95% confidence interval (CI): 1.20-1.84] and self-harm (OR: 1.55, 95% CI: 1.45-1.68) after full adjustment for confounders. NILF was associated with an increased risk of self-harm (OR: 1.43, 95% CI: 1.32-1.55), but less of an association was seen with suicide (OR: 1.19, 95% CI: 0.94-1.49). For females, unemployment was associated with an increased risk of suicide (OR: 1.30, 95% CI: 0.93-1.80) and of self-harm (OR: 1.52, 95% CI: 1.43-1.62), and NILF was associated with a similar increase in risk for suicide (OR: 1.31, 95% CI: 0.98-1.75) and self-harm (OR: 1.32, 95% CI: 1.26-1.40). DISCUSSION: Exclusion from employment is associated with a considerably heightened risk of suicide and self-harm for both men and women, even among those without prior mental health problems.

Exposure to discrimination and subsequent changes in self-rated health: prospective evidence from the UK's Life Opportunities Survey.

OBJECTIVES: We sought to estimate risk of poor self-rated health (SRH) following exposure to disability-related and other forms of overt discrimination in a cohort of working age adults. STUDY DESIGN: The study design is a population-based cohort survey. METHODS: Secondary analysis of data collected in Waves 1 and 2 of the UK's Life Opportunities Survey which at Wave 2 involved the participation of 12,789 working age adults. Adjusted prevalence rate ratios were used to estimate the impact of exposure to disability and non-disability discrimination on two measures of SRH at Wave 2, controlling for SRH status at Wave 1. RESULTS: Exposure to disability discrimination in the previous year was reported by 3.9% of working age British adults. Other forms of discrimination were reported less frequently (age: 3.7%, ethnicity: 2.5%, gender: 1.6%, religion: 0.8%, sexual orientation: 0.4%). In all analyses, there were stronger associations between exposure to disability discrimination and poor SRH at Wave 2 when compared with exposure to other forms of discrimination. CONCLUSIONS: Disability discrimination represents a violation of human rights. It is also likely to be a major contributor to the health inequities experienced by working age adults with disability.

Seismic surveys reduce cetacean sightings across a large marine ecosystem.

Noise pollution is increasing globally, and as oceans are excellent conductors of sound, this is a major concern for marine species reliant on sound for key life functions. Loud, impulsive sounds from seismic surveys have been associated with impacts on many marine taxa including mammals, crustaceans, cephalopods, and fish. However, impacts across large spatial scales or multiple species are rarely considered. We modelled over 8,000 hours of cetacean survey data across a large marine ecosystem covering > 880,000 km2 to investigate the effect of seismic surveys on baleen and toothed whales. We found a significant effect of seismic activity across multiple species and habitats, with an 88% (82-92%) decrease in sightings of baleen whales, and a 53% (41-63%) decrease in sightings of toothed whales during active seismic surveys when compared to control surveys. Significantly fewer sightings of toothed whales also occurred during active versus inactive airgun periods of seismic surveys, although some species-specific response to noise was observed. This study provides strong evidence of multi-species impacts from seismic survey noise on cetaceans. Given the global proliferation of seismic surveys and large propagation distances of airgun noise, our results highlight the large-scale impacts that marine species are currently facing.

Disabling working environments and mental health: A commentary.

Employment is a fundamental Social Determinant of Health known to have large impacts on mental health and other health outcomes. Across many countries of the world, people with disabilities are much more likely to be unemployed and looking for work than those without disabilities. The deprivation of employment opportunities is likely to have notable impacts on the health of people with disabilities. In this commentary, we outline the concept of "disabling working environments," which are defined as the range of experiences that affect the likelihood of people with disabilities in obtaining and maintaining quality employment which may then affect a disabled person's health. Disabling working environments are comprised of the following three mutually reinforcing components: 1) Differential selection into work; 2) Selection into certain types of jobs and exposure to poor psychosocial working environments when in employment, and; 3) Differential selection out of work (e.g., leaving employment at an earlier age than those who do not have a disability). We argue that policy and intervention design should consider the life course effects of employment on the mental health of people with disabilities.

Built environment and cardio-metabolic health: systematic review and meta-analysis of longitudinal studies.

Built environment attributes may be related to cardio-metabolic diseases (e.g. type 2 diabetes, heart disease and stroke) and their risk factors, potentially by influencing residents' physical activity. However, existing literature reviews on the built environment and health for the most part focus on obesity as the outcome and rely on cross-sectional studies. This systematic review synthesized current evidence on longitudinal relationships between built environment attributes and cardio-metabolic health outcomes among adults and on the potential mediating role of physical inactivity. By searching eight databases for peer-reviewed journal articles published in the English language between January 2000 and July 2016, the review identified 36 articles. A meta-analysis method, weighted Z-test, was used to quantify the strength of evidence by incorporating the methodological quality of the studies. We found strong evidence for longitudinal relationships of walkability with obesity, type 2 diabetes and hypertension outcomes in the expected direction. There was strong evidence for the impact of urban sprawl on obesity outcomes. The evidence on potential mediation by physical activity was inconclusive. Further longitudinal studies are warranted to examine which specific built environment attributes influence residents' cardio-metabolic health outcomes and how physical inactivity may be involved in these relationships.

Gender, parental education, and experiences of bullying victimization by Australian adolescents with and without a disability.

BACKGROUND: This study sought to compare the prevalence of bullying victimization between adolescents with and without a disability and between adolescents with and without borderline intellectual functioning or intellectual disability (BIF/ID). We also sought to assess whether the relationships between either disability or BIF/ID and bullying victimization vary by gender and parental education. METHODS: The sample included 3,956 12- to 13-year-old adolescents who participated in Wave 5 of the Longitudinal Study of Australian Children. Three indicators of bullying were used: physical bullying victimization, social bullying victimization, and "any bullying victimization." We used Poisson regression to obtain the prevalence risk ratios (PRR) of bullying by disability status adjusting for potential confounders. RESULTS: In adjusted models, we found evidence that social bullying victimization was more prevalent among adolescents with a disability than those without a disability (PRR 1.29, 95% confidence interval [CI] 1.06-1.42) and between adolescents with BIF/ID than those without (PRR 1.24, 95% CI 1.07-1.44). Adolescents with BIF/ID were also more likely to experience "any bullying victimization"(PRR 1.10, 95% CI 1.00-1.22). Having a disability and living in a family with low parental education were associated with an elevated risk of social bullying victimization BIF/ID. CONCLUSIONS: Adolescents with disabilities and BIF/ID are at elevated risk of social bullying victimization. School-based antibullying initiatives should concentrate on enhancing the inclusion of adolescents with disabilities, with an emphasis on adolescents from disadvantaged backgrounds.

The Development of Technology for Effective Respiratory-Gated Irradiation Using an Image-Guided Small Animal Irradiator.

The development of image-guided small animal irradiators represents a significant improvement over standard irradiators by enabling preclinical studies to mimic radiotherapy in humans. The ability to deliver tightly collimated targeted beams, in conjunction with gantry or animal couch rotation, has the potential to maximize tumor dose while sparing normal tissues. However, the current commercial platforms do not incorporate respiratory gating, which is required for accurate and precise targeting in organs subject to respiration related motions that may be up to the order of 5 mm in mice. Therefore, a new treatment head assembly for the Xstrahl Small Animal Radiation Research Platform (SARRP) has been designed. This includes a fast X-ray shutter subsystem, a motorized beam hardening filter assembly, an integrated transmission ionization chamber to monitor beam delivery, a kinematically positioned removable beam collimator and a targeting laser exiting the center of the beam collimator. The X-ray shutter not only minimizes timing errors but also allows beam gating during imaging and treatment, with irradiation only taking place during the breathing cycle when tissue movement is minimal. The breathing related movement is monitored by measuring, using a synchronous detector/lock-in amplifier that processes diffuse reflectance light from a modulated light source. After thresholding of the resulting signal, delays are added around the inhalation/exhalation phases, enabling the "no movement" period to be isolated and to open the X-ray shutter. Irradiation can either be performed for a predetermined time of X-ray exposure, or through integration of a current from the transmission monitor ionization chamber (corrected locally for air density variations). The ability to successfully deliver respiratory-gated X-ray irradiations has been demonstrated by comparing movies obtained using planar X-ray imaging with and without respiratory gating, in addition to comparing dose profiles observed from a collimated beam on EBT3 radiochromic film mounted on the animal's chest. Altogether, the development of respiratory-gated irradiation facilitates improved dose delivery during animal movement and constitutes an important new tool for preclinical radiation studies. This approach is particularly well suited for irradiation of orthotopic tumors or other targets within the chest and abdomen where breathing related movement is significant.

Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study.

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression.

Perceptions of safety and exposure to violence in public places among working age adults with disabilities or long-term health conditions in the UK: cross sectional study.

OBJECTIVES: To examine perceptions of safety and exposure to violence in public places among working age adults with and without disabilities in the UK and to assess the extent to which any between-group differences may be moderated by gender and socio-economic situation. STUDY DESIGN: Cross-sectional study. METHODS: Secondary analysis of data collected in Wave 3 (2011-13) of Understanding Society. Data were extracted on a subsample of 5069 respondents aged 16 to 64 years (28% of whom had a disability/long-term health condition) who were administered a questionnaire module addressing experiences of harassment. Between-group comparisons were made on four self-reported indicators of safety. RESULTS: Respondents with disabilities/long-term health conditions were significantly more likely to have been attacked (adjusted OR 2.30, 95%CI 1.17-4.50, P < 0.05), insulted (adjusted OR 1.48, 95%CI 1.16-1.90, P < 0.01) and to feel unsafe in public places (adjusted OR 1.32, 95%CI 1.16-1.56, P < 0.01) over the previous 12 months. There were no statistically significant differences between groups with regard to self-reported avoidance of public places. These associations were moderated by both gender and poverty status, with the increased risk of exposure to violence among people with disabilities being greater for both women and people living in poverty. CONCLUSIONS: The data add further support to the growing evidence base suggesting that people with a disability/long-term health condition are at significantly increased risk of exposure to interpersonal violence, particularly if they are living in poverty or are women. As such, there is a clear need to develop interventions that are targeted to the particular circumstances and needs of these high risk groups.

Psychosocial job quality in a national sample of working Australians: A comparison of persons working with versus without disability.

OBJECTIVES: There is growing international policy interest in disability employment, yet there has been little investigation of job quality among people working with disability. This study uses Australian national data to compare the psychosocial job quality of people working with versus without disability. METHODS: We used 10 annual waves of data from a large representative Australian panel survey to estimate the proportion of the population experiencing poorer psychosocial job quality (overall and by individual 'adversities' of low job control, high demands, high insecurity, and low fairness of pay) by disability status and impairment type. We used logistic regression to examine the pooled cross-sectional associations between disability and job quality, adjusting for age, sex, education and job type. RESULTS: Those working with any disability showed approximately 25% higher odds of reporting one or more adversity at work (OR: 1.23, 95% CI: 1.15, 1.31), and this finding was consistent across impairment types with the exception of intellectual/developmental disability. Estimates were largely unchanged after adjustments. Similar results were found for reporting two or more adversities compared one or more. CONCLUSIONS: We observed that working people with a disability in Australia reported systematically poorer psychosocial job quality than those working without disability. These results suggest the need for further research to understand the reasons for these patterns, as well as policy and practice efforts to address this inequity.

Does disability status modify the association between psychosocial job quality and mental health? A longitudinal fixed-effects analysis.

BACKGROUND: People with disabilities have difficulties in obtaining work. However, evidence suggests that those with disabilities derive substantial mental health benefits from employment. This paper assesses how the relationship between work and mental health is influenced by psychosocial job quality for people working with a disability. METHODS: The study design was a longitudinal cohort with 13 annual waves of data collection, yielding a sample of 122,883 observations from 21,848 people. Fixed-effects within-person regression was used to control for time invariant confounding. The Mental Component Summary (MCS) of the Short Form 36 (SF-36) measure was used as the primary outcome measure. The main exposure was a six-category measure of psychosocial job quality and employment status (including 'not in the labour force' [NILF] and unemployment). Disability status ('no waves of disability reported' and 'all contributed waves with reported disability') was assessed as an effect modifier. We also conducted a secondary analysis on respondents contributing both disability and non-disability waves. RESULTS: For those with no disability, the greatest difference in mental health (compared to optimal employment) occurs when people have the poorest quality jobs (-2.12, 95% CI -2.48, -1.75, p < 0.001). The relative difference in mental health was less in relation to NILF and unemployment (-0.39 and -0.66 respectively). For those with consistent disability, the difference in mental health when employed in an optimal job was similar between the poorest quality jobs (-2.25, 95% CI -3.84, -0.65, p = 0.006), NILF (-2.84, 95% CI -4.49, -1.20, p = 0.001) or unemployment (-2.56, 95% CI -4.32, -0.80, p = 0.004). These results were confirmed by the secondary analysis. CONCLUSIONS: Efforts to improve psychosocial job quality may have significant mental health benefits for people with disabilities. This will contribute to the economic viability of disability employment insurance schemes in Australia and other high-income countries.

Employment status and mental health among persons with and without a disability: evidence from an Australian cohort study.

BACKGROUND: Unemployment and economic inactivity are associated with worse mental health in the general population, but there is limited understanding of whether these relationships are different for those persons with mental or physical disabilities. The aim of this study was to assess whether there were differences in mental health by labour force status among persons with and without disabilities. METHOD: Over eight annual waves of the Household, Income and Labour Dynamics in Australia (HILDA) survey, a total of 2379 people with disabilities and 11 417 people without disabilities were identified. Mental health using the Mental Component Summary (MCS) from the Short Form 36 was modelled as a function of labour force status using fixed-effects regression models to control for time invariant confounding. Differences between those with and without disabilities were assessed by including an interaction term in regression models. RESULTS: After finding evidence of effect modification, regression models were stratified by disability status. After adjustment, unemployment and economic inactivity were associated with a -1.85 (95% CI -2.96 to -0.73, p=0.001) and -2.66 (95% CI -3.46 to -1.86, p<0.001) reduction in scores of the MCS among those with a disability. For those without a disability, there were smaller declines associated with unemployment (-0.57, 95% CI -1.02 to -0.12, p=0.013) and economic inactivity (-0.34, 95% CI -0.64 to 0.05, p=0.022). CONCLUSIONS: These results suggest a greater reduction in mental health for those persons with disabilities who were unemployed or economically inactive than those who were employed. This highlights the value of employment for people with disabilities.

Comparison of a semiautomated hand-held device to test minimal erythema dose before narrowband ultraviolet B phototherapy with the conventional method using matched doses.

BACKGROUND: A semiautomated hand-held device has been introduced in some phototherapy centres to establish the minimal erythema dose (MED) before treatment with narrowband ultraviolet (NBUV) B. OBJECTIVES: To compare the semiautomated hand-held device with the conventional method of MED testing (a UV-opaque template and a panel of UVB fluorescent tubes), using the same series of incremented doses. METHODS: Twenty-four patients referred for treatment with NBUVB phototherapy were included. Each patient had MED testing with the conventional method and the semiautomated hand-held device at the same level of the left and right back. The results were read by four investigators each time. RESULTS: The semiautomated hand-held device was a significant estimator of the MED using the conventional panel method (P < 0.001; r = 0.97). The average ratio of the hand-held MED to the conventional MED was 67%. The mean difference between the methods was 165 mJ/cm(2) . The interobserver test showed very high agreement for both methods of MED testing (Cronbach α coefficient 0.97 for the hand-held MED tester vs. 0.93 for the conventional method). CONCLUSIONS: The semiautomated hand-held device MED results were lower than that of the conventional panel method and may prolong the treatment course by 2-3 treatments. The hand-held tester is a fast and reproducible method, and may allow more phototherapy units, limited by staff and time, to do MED testing.

Psychosocial working conditions in a representative sample of working Australians 2001-2008: an analysis of changes in inequalities over time.

BACKGROUND: A number of widely prevalent job stressors have been identified as modifiable risk factors for common mental and physical illnesses such as depression and cardiovascular disease, yet there has been relatively little study of population trends in exposure to job stressors over time. The aims of this paper were to assess: (1) overall time trends in job control and security and (2) whether disparities by sex, age, skill level and employment arrangement were changing over time in the Australian working population. METHODS: Job control and security were measured in eight annual waves (2000-2008) from the Australian nationally-representative Household Income and Labour Dynamics of Australia panel survey (n=13 188 unique individuals for control and n=13 182 for security). Observed and model-predicted time trends were generated. Models were generated using population-averaged longitudinal linear regression, with year fitted categorically. Changes in disparities over time by sex, age group, skill level and employment arrangement were tested as interactions between each of these stratifying variables and time. RESULTS: While significant disparities persisted for disadvantaged compared with advantaged groups, results suggested that inequalities in job control narrowed among young workers compared with older groups and for casual, fixed-term and self-employed compared with permanent workers. A slight narrowing of disparities over time in job security was noted for gender, age, employment arrangement and occupational skill level. CONCLUSIONS: Despite the favourable findings of small reductions in disparities in job control and security, significant cross-sectional disparities persist. Policy and practice intervention to improve psychosocial working conditions for disadvantaged groups could reduce these persisting disparities and associated illness burdens.

Association between fast food purchasing and the local food environment.

OBJECTIVE: In this study, an instrument was created to measure the healthy and unhealthy characteristics of food environments and investigate associations between the whole of the food environment and fast food consumption. DESIGN AND SUBJECTS: In consultation with other academic researchers in this field, food stores were categorised to either healthy or unhealthy and weighted (between +10 and -10) by their likely contribution to healthy/unhealthy eating practices. A healthy and unhealthy food environment score (FES) was created using these weightings. Using a cross-sectional study design, multilevel multinomial regression was used to estimate the effects of the whole food environment on the fast food purchasing habits of 2547 individuals. RESULTS: Respondents in areas with the highest tertile of the healthy FES had a lower likelihood of purchasing fast food both infrequently and frequently compared with respondents who never purchased, however only infrequent purchasing remained significant when simultaneously modelled with the unhealthy FES (odds ratio (OR) 0.52; 95% confidence interval (CI) 0.32-0.83). Although a lower likelihood of frequent fast food purchasing was also associated with living in the highest tertile of the unhealthy FES, no association remained once the healthy FES was included in the models. In our binary models, respondents living in areas with a higher unhealthy FES than healthy FES were more likely to purchase fast food infrequently (OR 1.35; 95% CI 1.00-1.82) however no association was found for frequent purchasing. CONCLUSION: Our study provides some evidence to suggest that healthier food environments may discourage fast food purchasing.

Combining advanced radiotherapy technologies to maximize safety and tumor control probability in stage III non-small cell lung cancer.

BACKGROUND: The goal of the current study was to investigate the tumor control probability (TCP) of advanced radiotherapy technologies for stage III non-small cell lung cancer (NSCLC) and to evaluate potential interplay effects between their applications. MATERIALS AND METHODS: Three-dimensional conformal radiotherapy (3D-CRT) with conventionally fractionated doses of 66 Gy served as reference for 13 patients with stage III NSCLC. Isotoxic dose escalation relative to the corresponding 3D-CRT plans was performed for three technologies and their combinations: intensity-modulated radiotherapy (IMRT), IMRT with a simultaneous integrated boost (IMRT-SIB) of 10% to the gross tumor volume (GTV), and adaptive re-planning twice during the treatment course (ART). All analyses were based on accumulated dose distributions using deformable image registration of CT images, which were acquired weekly during the treatment course. RESULTS: IMRT reduced the mean lung dose (MLD) by 5.6% ± 3.8% compared to 3D-CRT. ART resulted in lung sparing of 7.9% ± 4.8% and 9.2% ± 3.9% in 3D-CRT and IMRT planning, respectively. IMRT and ART escalated the irradiation dose by 6.6% ± 3.2% and 8.8% ± 6.3%, respectively, which was not statistically different. For the 7 patients with the largest GTVs, IMRT-SIB was superior to IMRT and ART with dose escalation of 11.9% ± 3.7%. The combination of ART, IMRT, and SIB achieved maximum dose escalation in all 13 patients by 17.1% ± 5.4% on average, which increased TCP from 19.9% ± 7.0 to 37.1% ± 10.1%. Adaptive re-planning was required to continuously conform the escalated and hypofractionated SIB doses to the shrinking tumor. CONCLUSION: Combining advanced radiotherapy technologies is considered as a safe and effective strategy to maximize local tumor control probability in stage III NSCLC.

CCL3 induced migration occurs independently of intracellular calcium release.

The molecular signalling pathway of cell migration and whether it can occur independently of the release of intracellular calcium is still not completely understood. Therefore we investigated here the molecular mechanisms of CCL3 induced cell migration and the importance of intracellular calcium for chemotaxis in more detail. We show that CCL3 induced cell migration is dependent on activation of PLC. Several PKC inhibitors block the release of intracellular calcium independently of CCL3 activation and do not affect cell migration. This confirms that the release of intracellular calcium is not necessary for chemotaxis towards CCL3 and that PKC inhibitors should be used with caution in calcium release assays.