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IMPORTANCE: Metastatic soft tissue sarcomas (STSs) have limited systemic therapy options, and immunomodulation has not yet meaningfully improved outcomes. Intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist glycopyranosyl lipid A in stable-emulsion formulation (GLA-SE) has been studied as immunotherapy in other contexts. OBJECTIVE: To evaluate the safety, efficacy, and immunomodulatory effects of IT GLA-SE with concurrent radiotherapy in patients with metastatic STS with injectable lesions. DESIGN, SETTING, AND PARTICIPANTS: This phase 1 nonrandomized controlled trial of patients with STS was performed at a single academic sarcoma specialty center from November 17, 2014, to March 16, 2016. Data analysis was performed from August 2016 to September 2022. INTERVENTIONS: Two doses of IT GLA-SE (5 μg and 10 μg for 8 weekly doses) were tested for safety in combination with concurrent radiotherapy of the injected lesion. MAIN OUTCOMES AND MEASURES: Primary end points were safety and tolerability. Secondary and exploratory end points included local response rates as well as measurement of antitumor immunity with immunohistochemistry and T-cell receptor (TCR) sequencing of tumor-infiltrating and circulating lymphocytes. RESULTS: Twelve patients (median [range] age, 65 [34-78] years; 8 [67%] female) were treated across the 2 dose cohorts. Intratumoral GLA-SE was well tolerated, with only 1 patient (8%) experiencing a grade 2 adverse event. All patients achieved local control of the injected lesion after 8 doses, with 1 patient having complete regression (mean regression, −25%; range, −100% to 4%). In patients with durable local response, there were detectable increases in tumor-infiltrating lymphocytes. In 1 patient (target lesion −39% at 259 days of follow-up), TCR sequencing revealed expansion of preexisting and de novo clonotypes, with convergence of numerous rearrangements coding for the same binding sequence (suggestive of clonal convergence to antitumor targets). Single-cell sequencing identified these same expanded TCR clones in peripheral blood after treatment; these T cells had markedly enhanced Tbet expression, suggesting TH1 phenotype. CONCLUSIONS AND RELEVANCE: In this nonrandomized controlled trial, IT GLA-SE with concurrent radiotherapy was well tolerated and provided more durable local control than radiotherapy alone. Patients with durable local response demonstrated enhanced IT T-cell clonal expansion, with matched expansion of these clonotypes in the circulation. Additional studies evaluating synergism of IT GLA-SE and radiotherapy with systemic immune modulation are warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02180698

This study examines the effects of four types of employee support on a sample of 231 junior accountants' organisational commitment, job involvement and intention to quit. The four types of support include organisational, supervisory, psycho‐social and career development support. Results of path analysis suggest that only organisational support and psycho‐social support influence organisational commitment which, in turn, increases job involvement and reduces intention to quit.

This paper reports the results of a survey of Australian auditors' perceptions of their time‐budget pressure, as well as whether they had exhibited “reduced audit quality” (RAQ) behaviours. Further questions examined why RAQ practices were used and what areas of the audit were likely to be subject to these practices. There appears to be a high level of time‐budget pressure on auditors, and many auditors have at some time performed RAQ practices, potentially having implications for the quality of the audit function. These results point to the importance of placing an appropriate value on the audit function to ensure that time budgets are adequate.

In March 1995, the APB in the UK issued its Statements of Auditing Standards 300 (SAS 300): «Accounting and Internal Control Systems and Audit Risk Assessment». The standard identifies inherent risk as one of the three components of audit risk; inherent risk being defined as «the susceptibility of an account balance or class of transactions to material mis-statement». If the inherent risk is low, less substantive testing is required, with possible resultant savings in staff time and audit costs. It is thus beneficial for audit firms (and clients) to assess adequately the inherent risk element of an audit assignment to ensure that audits are carried out as efficiently and effectively as possible. This research project focuses on inherent risk and using a questionnaire survey investigates 100 auditors' perceptions of the importance of certain factors which may determine inherent risk. The findings of the study suggest that the variables identified in the literature as being closely associated with inherent risk factors are regarded in a similar fashion by auditors; variables such as bonus schemes tied to management earnings, a high turnover rate in top management personnel, a company reputation for taking unusual business risks and a history of material errors are believed to be the major determinants of inherent risk. Perhaps unsurprisingly, the findings of this study suggest that auditors attach greater importance to high risk variables than to low risk variables in their evaluation of inherent risk. Finally, the evidence revealed that auditors had difficulty in distinguishing between inherent risk and control risk factors.