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ObjectivesThis paper assessed the impact of working in casual employment, compared with permanent employment, on eight health attributes that make up the 36-Item Short Form (SF-36) Health Survey, separately by sex. The mental health impacts of casual jobs with irregular hours over which the worker reports limited control were also investigated.MethodsLongitudinal data from the Household, Income and Labour Dynamics in Australia Survey, over the period 2001–2018, were used to investigate the relationship between the eight SF-36 subscales and workers’ employment contract type. Individual, household and job characteristic confounders were included in dynamic panel data regression models with correlated random effects.ResultsFor both men and women, health outcomes for casual workers were no worse than for permanent workers for any of the eight SF-36 health attributes. For some health attributes, scores for casual workers were higher (ie, better) than for permanent workers (role physical: men: β=1.15, 95% CI 0.09 to 2.20, women: β=1.79, 95% CI 0.79 to 2.80; bodily pain: women: β=0.90, 95% CI 0.25 to 1.54; vitality: women: β=0.65, 95% CI 0.13 to 1.18; social functioning: men: β=1.00, 95% CI 0.28 to 1.73); role emotional: men: β=1.81, 95% CI 0.73 to 2.89, women: β=1.24, 95% CI 0.24 to 2.24). Among women (but not men), mental health and role emotional scores were lower for irregular casual workers than for regular permanent workers but not statistically significantly so.ConclusionsThis study found no evidence that casual employment in Australia is detrimental to self-assessed worker health.

The distribution of relaxation times (DRT) analysis offers a model-free approach for a detailed investigation of electrochemical impedance spectra. Typically, the calculation of the distribution function is an ill-posed problem requiring regularization methods which are strongly parameter-dependent. Before statements on measurement data can be made, a process parameter study is crucial for analyzing the impact of the individual parameters on the distribution function. The optimal regularization parameter is determined together with the number of discrete time constants. Furthermore, the regularization term is investigated with respect to its mathematical background. It is revealed that the algorithm and its handling of constraints and the optimization function significantly determine the result of the DRT calculation. With optimized parameters, detailed information on the investigated system can be obtained. As an example of a complex impedance spectrum, a commercial Nickel–Manganese–Cobalt–Oxide (NMC) lithium-ion pouch cell is investigated. The DRT allows the investigation of the SOC dependency of the charge transfer reactions, solid electrolyte interphase (SEI) and the solid state diffusion of both anode and cathode. For the quantification of the single polarization contributions, a peak analysis algorithm based on Gaussian distribution curves is presented and applied.

Background There is agreement among educators and professional bodies that interprofessional education needs to be implemented at the pre-registration level. We performed a systematic review assessing interprofessional learning interventions, measuring attitudes towards interprofessional education and involving pre-registration medical students across all years of medical education. Methods A systematic literature review was performed using PubMed, PsycINFO, EThOS, EMBASE, PEDro and SCOPUS. Search terms were composed of interprofession*, interprofessional education, inter professional, inter professionally, IPE, and medical student. Inclusion criteria were 1) the use of a validated scale for assessment of attitudes towards IPE, and results for more than 35 medical students; 2) peer-reviewed articles in English and German, including medical students; and 3) results for IPE interventions published after the 2011 Interprofessional Education Collaborative (IPEC) report. We identified and screened 3995 articles. After elimination of duplicates or non-relevant topics, 278 articles remained as potentially relevant for full text assessment. We used a data extraction form including study designs, training methods, participant data, assessment measures, results, and medical year of participants for each study. A planned comprehensive meta-analysis was not possible. Results This systematic review included 23 articles with a pre-test-post-test design. Interventions varied in their type and topic. Duration of interventions varied from 25 min to 6 months, and interprofessional groups ranged from 2 to 25 students. Nine studies (39%) reported data from first-year medical students, five (22%) from second-year students, six (26%) from third-year students, two (9%) from fourth-year students and one (4%) from sixth-year students. There were no studies including fifth-year students. The most frequently used assessment method was the Readiness for Interprofessional Learning Scale (RIPLS) ( n  = 6, 26%). About half of study outcomes showed a significant increase in positive attitudes towards interprofessional education after interventions across all medical years. Conclusions This systematic review showed some evidence of a post-intervention change of attitudes towards IPE across different medical years studied. IPE was successfully introduced both in pre-clinical and clinical years of the medical curriculum. With respect to changes in attitudes to IPE, we could not demonstrate a difference between interventions delivered in early and later years of the curriculum. Trial registration PROSPERO registration number:  CRD42020160964 .

Bacterial infections represent an increasing problem in modern health care, in particular due to ageing populations and accumulating bacterial resistance to antibiotics. Diagnosis is rarely straightforward and consequently treatment is often delayed or indefinite. Therefore, novel tools that can be clinically implemented are urgently needed to accurately and swiftly diagnose infections. Especially, the direct imaging of infections is an attractive option. The challenge of specifically imaging bacterial infections in vivo can be met by targeting bacteria with an imaging agent. Here we review the current status of targeted imaging of bacterial infections, and we discuss advantages and disadvantages of the different approaches. Indeed, significant progress has been made in this field and the clinical implementation of targeted imaging of bacterial infections seems highly feasible. This was recently highlighted by the use of so-called smart activatable probes and a fluorescently labelled derivative of the antibiotic vancomycin. A major challenge remains the selection of the best imaging probes, and we therefore present a set of target selection criteria for clinical implementation of targeted bacterial imaging. Altogether, we conclude that the spectrum of potential applications for targeted bacterial imaging is enormous, ranging from fundamental research on infectious diseases to diagnostic and therapeutic applications. This review discusses recent advances in the targeted imaging of bacterial infections, a rapidly developing field of microbiological research that aims at distinguishing bacterial infections from sterile inflammation in vivo.

Triple-negative breast cancer (TNBC), characterized by the absence of ER, PR, and HER2 receptors, remains one of the most aggressive breast cancer subtypes, with limited therapeutic options and a high relapse rate. While immune checkpoint inhibitors (ICIs) have shown promise by leveraging TNBC’s immunogenic profile, their use is often accompanied by significant toxicity, necessitating the development of safer immunomodulatory strategies. Non-invasive physical plasma (NIPP), a novel low thermal plasma technology that can be generated using various gases, including argon, and producing reactive oxygen and nitrogen species (RONS), has emerged as a potential alternative. This study investigates the capacity of direct (argon plasma devitalization, APD) and indirect (plasma-treated solution, PTS) plasma modalities to induce cytotoxicity and activate immune signaling via the stimulator of interferon genes (STING) pathway in TNBC. Dose-dependent RONS generation by APD and PTS correlated with reduced viability and apoptosis induction in MDA-MB-231 TNBC cells. Both plasma modalities caused DNA damage and upregulated key proteins in the STING pathway, including γ-H2AX, p-STING, and p-TBK1, with sustained activation observed up to 24 hours post-treatment. Furthermore, STING-dependent transcription of IFN-β and interferon-stimulated genes (ISGs) confirmed the immunogenic potential of NIPP. Conditioned media from plasma-treated TNBC cells induced M1 polarization in THP-1-derived macrophages, an effect significantly reduced upon specific STING inhibition with H-151. The immunomodulatory effects of NIPP were validated in patient-derived TNBC organoids, where plasma treatment disrupted organoid structure, reduced viability, and promoted M1 macrophage polarization. Collectively, these findings highlight the dual cytotoxic and immunostimulatory potential of NIPP in TNBC through STING pathway activation, claiming it as a promising, low-toxicity component in combination with conventional immunotherapy.

The dynamics and phenotypes of intratumoral myeloid cells during tumor progression are poorly understood. Here we define myeloid cellular states in gliomas by longitudinal single-cell profiling and demonstrate their strict control by the tumor genotype: in isocitrate dehydrogenase (IDH)-mutant tumors, differentiation of infiltrating myeloid cells is blocked, resulting in an immature phenotype. In late-stage gliomas, monocyte-derived macrophages drive tolerogenic alignment of the microenvironment, thus preventing T cell response. We define the IDH-dependent tumor education of infiltrating macrophages to be causally related to a complex re-orchestration of tryptophan metabolism, resulting in activation of the aryl hydrocarbon receptor. We further show that the altered metabolism of IDH-mutant gliomas maintains this axis in bystander cells and that pharmacological inhibition of tryptophan metabolism can reverse immunosuppression. In conclusion, we provide evidence of a glioma genotype-dependent intratumoral network of resident and recruited myeloid cells and identify tryptophan metabolism as a target for immunotherapy of IDH-mutant tumors.

Background Mammographic screening alone will miss a certain fraction of malignancies, as evidenced by retrospective reviews of mammograms following a subsequent screening. Mammographic breast density is a marker for increased breast cancer risk and is associated with a higher risk of interval breast cancer, i.e. cancer detected between screening tests. The purpose of this review is to estimate risks and benefits of supplemental breast ultrasound in women with negative mammographic screening with dense breast tissue. Methods A systematic search and review of studies involving mammography and breast ultrasound for screening of breast cancer was conducted. The search was performed for the period 1/2000-8/2008 within the data source of PubMed, DARE, and Cochrane databases. Inclusion and exclusion criteria were determined prospectively, and the Oxford evidence classification system for diagnostic studies was used for evidence level. The parameters biopsy rate, positive predictive value (PPV) for biopsy, cancer yield for breast ultrasound alone, and carcinoma detection rate by breast density were extracted or constructed. Results The systematic search identified no randomized controlled trials or systematic reviews, six cohort studies of intermediate level of evidence (3b) were found. Only two of the studies included adequate follow-up of subjects with negative or benign findings. Supplemental breast ultrasound after negative mammographic screening permitted diagnosis of primarily invasive carcinomas in 0.32% of women in breast density type categories 2-4 of the American College of Radiology (ACR); mean tumor size for those identified was 9.9 mm, 90% with negative lymph node status. Most detected cancers occurred in mammographically dense breast ACR types 3 and 4. Biopsy rates were in the range 2.3%-4.7%, with PPV of 8.4-13.7% for those biopsied due to positive ultrasound, or about one third of the PPV of biopsies due to mammography. Limitations: The study populations included wide age ranges, and the application to women age 50-69 years as proposed for mammographic screening could result in less striking benefit. Further validation studies should employ a uniform assessment system such as BI-RADS and report not only PPV, but also negative predictive value, sensitivity and specificity. Conclusion Supplemental breast ultrasound in the population of women with mammographically dense breast tissue (ACR 3 and 4) permits detection of small, otherwise occult, breast cancers. Potential adverse impacts for women in this intermediate risk group are associated with an increased biopsy rate.

Despite tremendous progress in deciphering breast cancer at the genomic level, the pronounced intra- and intertumoral heterogeneity remains a major obstacle to the advancement of novel and more effective treatment approaches. Frequent treatment failure and the development of treatment resistance highlight the need for patient-derived tumor models that reflect the individual tumors of breast cancer patients and allow a comprehensive analyses and parallel functional validation of individualized and therapeutically targetable vulnerabilities in protein signal transduction pathways. Here, we introduce the generation and application of breast cancer patient-derived 3D microtumors (BC-PDMs). Residual fresh tumor tissue specimens were collected from n  = 102 patients diagnosed with breast cancer and subjected to BC-PDM isolation. BC-PDMs retained histopathological characteristics, and extracellular matrix (ECM) components together with key protein signaling pathway signatures of the corresponding primary tumor tissue. Accordingly, BC-PDMs reflect the inter- and intratumoral heterogeneity of breast cancer and its key signal transduction properties. DigiWest®-based protein expression profiling of identified treatment responder and non-responder BC-PDMs enabled the identification of potential resistance and sensitivity markers of individual drug treatments, including markers previously associated with treatment response and yet undescribed proteins. The combination of individualized drug testing with comprehensive protein profiling analyses of BC-PDMs may provide a valuable complement for personalized treatment stratification and response prediction for breast cancer.

One in eight women is diagnosed with breast cancer in the course of their life. As systematic palliative treatment has only a limited effect on survival rates, the concept of health-related quality of life (HRQoL) was developed for measurement of patient-centered outcomes. Various studies have already demonstrated the reliability of paper-based patient-reported outcome (pPRO) and electronic patient-reported outcome (ePRO) surveys and that the 2 means of assessment are equally valid. The aim of this study was to analyze the acceptance and evaluation of a tablet-based ePRO app for breast cancer patients and to examine its suitability, effort, and difficulty in the context of HRQoL and sociodemographic factors. Overall, 106 women with adjuvant or advanced breast cancer were included in a 2-center study at 2 major university hospitals in Germany. Patients were asked to answer HRQoL and PRO questionnaires both on a tablet on-site using a specific eHealth assessment website and on paper. The suitability, effort, and difficulty of the app and self-reported technical skills were also assessed. Only the results of the electronically acquired data are presented here. The results of the reliability of the pPRO data have already been published elsewhere. Patients regarded the ePRO assessment as more suitable (80/106, 75.5%), less stressful (73/106, 68.9%), and less difficult (69/106, 65.1%) than pPRO. The majority of patients stated that ePRO assessment improves health care in hospitals (87/106, 82.1%). However, evaluation of ePROs depended on the level of education (P=.003) in the dimensions of effort and difficulty (regression analysis). The app was rated highly in all categories. HRQoL data and therapy setting did not show significant correlations with the app's evaluation parameters. The results indicate that ePRO surveys are feasible for measuring HRQoL in breast cancer patients and that those patients prefer ePRO assessment to pPRO assessment. It can also be seen that patients consider ePRO assessment to improve hospital health care. However, studies with larger numbers of patients are needed to develop apps that address the needs of patients with lower levels of education and technical skills.

Atkinson et al. (J. Econ. Lit. 49( 1 ):3–71, 2011) survey an important new literature using income-tax-based data to measure the share of income held by top income groups. But changes in tax legislation that expand the tax base to include income sources (e.g. capital gains, dividends, etc.) disproportionately held by these groups will conflate such an expansion with an increase in the share of income they hold. We provide a cautionary tale from Australia of how comprehensive tax reform legislation in 1985 substantially altered Australian top income series, especially those that do not separate taxable realized capital gains from other taxable income. Drawing on the Household, Income and Labour Dynamics in Australia (HILDA) Survey we then estimate the size and distribution (across income groups) of taxable realized capital gains in 2006 and 2009, and compare these results with those using accrued capital gains, finding substantially different distributions. More importantly, we find substantial differences across our measures in how capital gains changed between 2006 and 2009. Our results suggest that yearly taxable realized capital gains, often included in studies of top incomes, might be a poor proxy for the theoretically more appropriate yearly accrued capital gains.