Conclusion: Towards a new web of rules

In this concluding chapter, we draw together the various contributions presented in this volume, discuss the broader implications of our findings, and reflect on how this builds upon Willy Brown's work. The chapter examines how the patchwork of rules has been altered by new and emerging challenges, such as the COVID-19 pandemic, the rise of global supply chains and new forms of business. We return to the central objective of this volume of identifying and analysing the viability of various institutions for addressing these challenges and discuss how these might form the basis of a new web of rules for protecting labour standards in the future. © 2023 by Emerald Publishing Limited. All rights reserved.

‘Work not as usual': work and industrial relations in a post-COVID world

This article introduces the Labour & Industry special issue on ‘work not as usual', following the theme of the 2022 AIRAANZ Conference. In introducing the articles published in the special issue, it examines key themes regarding how work and industrial relations are changing in unusual ways. These relate to the impacts of COVID-19;how work and industrial relations are shifting in the public sector and in the care economy;and how workers and organisations are responding to changes at work through voice, control and resistance. Analysis of these developments in the articles published in this special issue suggest that organisations and labour markets will continue to be defined by ‘work not as usual' into the foreseeable future. © 2023 AIRAANZ.

Mechanisms by which cystic fibrosis transmembrane conductance regulator may influence SARS-CoV-2 infection

Background: People with cystic fibrosis (PwCF) have chronic, pronounced respiratory damage and have been considered among those at highest risk for serious harm from SARS-CoV-2. Numerous clinical studies have reported that individuals with CF in North America and Europe, although highly susceptible to COVID-19, do not have mortality levels that exceed those of the general population. Method(s): To understand features that might influence lethality of COVID- 19 in PwCF, we tested potential relationships between CFTR and viral pathogenesis. As one approach to evaluate impact of CF transmembrane conductance regulator (CFTR) on COVID-19 severity, independent sets of blood samples fromvirally infected individualswere genotyped. Bloodwas obtained from 424 U.S. patients hospitalized with severe COVID-19 and a much larger European cohort of 7147 healthy individuals and 2587 individuals with severe COVID-19. Deoxyribonucleic acid in both studies was probed for the F508del variant. In other experiments, we investigated the possibility that lack of CFTR might alter viral binding and propagation. We used human bronchial epithelial cell (HBEC) monolayers from individuals without functional CFTR for this purpose. Finally, we examined effects of CF airway secretions and features such as viscosity, pH, and protease/anti-protease imbalance during SARS-CoV-2 infection. Result(s): We found no evidence of a relationship between deficient CFTR function (based on carrier status for the severe F508del defect) and clinical outcomes from COVID-19. In addition, viral propagation studies using airway epithelial monolayers (a model that reproduces many aspects of in vivo tissue biology) were not influenced by homozygous absence of CFTR. We show that levels of angiotensin converting enzyme-2 receptor messenger ribonucleic acid (mRNA) appear normal in CF primary epithelium, whereas transmembrane serine protease 2 mRNA is variable but lower ( p < 0.001) in a manner that correlates with viral infectivity (R2 = 0.76). Dependence of viral proliferation on features of CF mucosal fluid-including pH (viral replication optimum at pH 7-7.5), viscosity (diminished propagation in highly viscous apical media), and protease/ anti-protease imbalancewere identified as likely contributors to efficiency of SARS-CoV-2 replication and pathogenesis. Conclusion(s): These findings using patient data, CF and non-CF primary airway epithelia, and CF airway secretions fail to demonstrate a causal relationship between loss of CFTR and susceptibility to severe COVID-19. Notwithstanding the caveat that addition of virus in small buffer volumes disrupts airway surface liquid depth and composition, our findings also argue against a role for CFTR during acute infection of airway cells in vitro. On the other hand, chronic disruption of periciliary liquid, diminished pH, altered protease/anti-protease homeostasis, and increased fluid viscosity (sequelae that occur in CF lungs) were implicated as contributors to impaired SARS-CoV-2 propagation. Such studies provide a basis for future work to test relationships between CFTR and severity of COVID-19. Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Utility of Virtual New-Patient Clinics in Women Under 30

Aim: Virtual consultations (VC) in breast surgery have been successfully utilised during the COVID pandemic and have potential to reduce the costs of outpatient clinics as well as increase patient satisfaction. We aimed to assess the utility and safety of VC in new patient clinics in women under 30, which are considered a low-risk subgroup. Method: Data was prospectively collected on 118 women aged under 30 who were referred from primary care to the breast clinic between December 2020 and April 2021. Clinicopathological data was collected on referrals, imaging and follow up. Results: Median age was 24 years (range 17-30). The commonest presenting symptoms were a lump (69%), breast pain (16%) and nipple symptoms (14%). The VC was performed via video in 63 (53%) patients and via telephone alone in 55 (47%). Nineteen patients (16%) were reassured and discharged directly from VC. Ninety-four patients (80%) underwent an outpatient ultrasound with a sonographer trained in clinical palpation. Twenty-six (27%) ultrasounds showed benign pathology with the remainder being normal. Six biopsies were performed, all of which were benign. Seventeen (14%) patients required a face-to-face appointment with a breast surgeon after ultrasound or biopsy. Ninety-four (79%) patients were discharged after VC + ultrasound alone. No patients required surgery. Conclusions: Utilising VC, the majority of new referrals in women under 30 did not require face-to-face appointments. VC have potential to reduce burden on new patient clinics whilst improving patient convenience. Early data suggest a low risk of compromising safety in this subgroup.

Dose Response of Bulky Tumors in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

This study sought to assess whether there is a radiotherapy (RT) dose response for bulky tumors in relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Patients with r/r DLBCL (age ≥18 years) treated with salvage- or palliative-intent RT (2008-2020) at a single institution were included. Course-level data were examined to assess in-field responses of index lesions. Courses used for either post-therapy consolidation, CNS or skin disease, and TBI conditioning were excluded. Index lesion size ≥7.5 cm was considered bulky. EQD2s (α/β = 10) were calculated to accurately compare biologic effective doses between conventional and hypofractionated (≥2.5 Gy/fraction) schemes. Post-treatment responses of index lesions were classified using Lugano Criteria. Objective response rates (ORR), defined as achieving either CR or PR, were compared between non-bulky and bulky tumors using Fisher's exact test. Freedom from local progression (FFLP) and overall survival (OS, patient-level data) from RT start date were recorded. Bulky disease impacts on FFLP and OS were assessed using Kaplan-Meier and multivariable-adjusted Cox proportional hazard regression analyzes. 151 r/r DLBCL patients underwent 183 RT courses (median follow-up time: 6 months, IQR: 2-17 months). Median age at RT was 67 years (IQR: 56-72 years) with a male/female ratio of 55%/45%. Non-bulky and bulky tumors were treated in 109 (60%) and 74 (40%) cases, respectively. Intent was classified as salvage or palliative in 68 (37%) and 115 (63%) cases, respectively. Median EQD2 was 33 Gy (IQR: 23-39 Gy) with hypofractionation used in 84 (46%) cases. Of those with post-RT imaging (n = 146, 80%), there was a trend towards lower ORR for bulky vs. non-bulky tumors (50% vs. 65%, p = 0.087;CR: 21% vs. 42%, PR: 29% vs. 23%, SD: 28% vs. 14%, PD: 22% vs. 22%). For bulky tumors, RT regimens with EQD2s >30 Gy were associated with better ORR (≤30 Gy vs. >30 Gy: 27% vs. 64%, p = 0.014), whereas a lower EQD2 cut-off was sufficient for non-bulky tumors (<20 Gy vs. ≥20 Gy: 38% vs. 73%, p = 0.0076). In all courses, bulky tumors were significantly associated with shorter FFLP (median: 5.6 months vs. not reached, HR = 2.30, 95% CI: 1.24-4.26, p = 0.0079) and OS (median: 3.7 vs. 10.1 months, HR = 1.66, 95% CI: 1.06-2.58, p = 0.025). Amongst bulky tumors, there was a trend towards improved FFLP with RT regimens with higher EQD2s (20-30 Gy vs. <20 Gy - median: 4.2 vs. 2.3 months, HR = 0.38, 95% CI: 0.09-1.62, p = 0.19;>30 Gy vs. <20 Gy - median: not reached vs. 2.3 months, HR = 0.34, 95% CI: 0.11-1.01, p = 0.053). In this study, bulky r/r DLBCL tumors were associated with less favorable outcomes in salvage and palliative settings. If durable local control of bulky tumors is needed, RT regimens using higher EQD2s (>30 Gy) should be considered, including cases where shortened, hypofractionated courses are opted for such as during the SARS-CoV-2 pandemic, bridging to CAR-T cell infusion, or prior to allogeneic stem cell transplantation. [ FROM AUTHOR] Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

THE USE OF INPATIENT VIRTUAL SHARED MEDICAL APPOINTMENTS FOR PATIENTS WITH ACUTE CEREBROVASCULAR PATHOLOGIES AND THEIR CAREGIVERS: A PILOT STUDY TO IMPROVE HEALTH LITERACY, PATIENT SELF-EFFICACY AND REDUCE PROVIDER BURNOUT

Objective Admission to the hospital for an acute cerebrovascular condition such as stroke or brain hemorrhage can be a traumatic and disorienting experience for patients and their family members. The COVID-19 pandemic has further intensified this experience in addition to exacerbating clinician and resident burnout. To ameliorate some of these concerns, a team of resident and medical student trainees implemented a virtual shared medical appointment (vSMA) program for inpatients with acute cerebrovascular disorders and their caregivers. This study hypothesized that an early intervention vSMA improves patient and caregiver health literacy and preparedness, simultaneously educates trainees on effective communication skills, and reduces clinician burnout. Methods Patients and caregivers of admitted patients were screened through the neurosurgery, neurocritical care, and neurology electronic medical record census. A weekly 60- minute secure virtual session consisted of introductions, a 10- minute standardized presentation on cerebrovascular disease management, followed by participant-guided discussion. Participants completed pre- and post-surveys. We report data on this feasibility study and present challenges, both expected and unforeseen. Results A total of 170 patients were screened;13 patients and 26 caregivers participated in at least 1 session. A total of 6 different healthcare providers facilitated sessions. The vSMA program received overwhelmingly positive feedback from caregivers. Surveys demonstrated 96.4% of caregivers and 75% of patients were satisfied with the session. 96.4% of caregivers and 87.5% of patients would recommend this type of appointment to a friend or family member. 88.8% of providers felt validated by conducting the session. The participant group had a 20% greater percentage of patients discharged home without home needs compared to the non-participant group. The primary obstacle encountered included technological frustrations with the consent process and the sessions themselves. Conclusions Implementation of a vSMA program at a tertiary care center during a pandemic was feasible. Themes caregivers expressed on the post-survey included better understanding of caring for a stroke patient, and coping with the unpredictability of a patient's prognosis. The pandemic has precipitated shifts towards telehealth, but our study highlights the importance of avoiding marginalization of the elderly and less technologically inclined populations (Table Presented).

Relationship Between Challenges With the Use of Telehealth and Psychologists' Response During the Coronavirus Pandemic

Public Significance Statement This study is among the first in examining the relationship between challenges with the use of telehealth and psychologists' response during the coronavirus pandemic, highlighting the need to address both provider and patient barriers to telehealth that influence provider well-being. Allowing flexibility in policies, regulations, and format of service delivery and making telehealth training opportunities and resources available are key to ensure a healthy behavioral workforce and the continued delivery of health care services. The coronavirus pandemic drastically altered the landscape of mental health care delivery as psychologists pivoted to telehealth and grappled with increasing population mental health care needs. Despite the rapid shift to telehealth, many challenges on both the provider and patient sides remain. The purpose of this study is to examine the relationship between challenges with the use of telehealth and psychologists' response during the pandemic. The study used survey data from 1,679 doctoral-level licensed psychologists who provided services via telehealth during September-October 2020. Results from ordered logistic and ordinary least squares regressions suggest that the degree of telehealth challenge psychologists experienced was not statistically associated with workload, patient load, or ability to meet patient demand during the pandemic. However, the degree of telehealth challenge patients experienced was significantly associated with these outcomes. The fewer patients who experienced telehealth challenges, the more psychologists were able to maintain or increase their workload and patient load and meet patient demand. Telehealth challenges experienced by both psychologists and their patients were associated with psychologists' mental health. Psychologists experiencing fewer telehealth challenges, and having fewer patients experiencing telehealth challenges, were more likely to report lower stress levels, be able to practice self-care and maintain positive work-life balance, and less likely to experience burnout. Findings of this study have clear policy implications to encourage continued telehealth after the public health emergency ends and address barriers to effectively utilize telehealth. These measures are critical to supporting the health service psychologist workforce and maintaining the continuity of mental health care.

Utility of virtual new-patient clinics in women under 30

Aim: Virtual consultations (VC) in breast surgery have been successfully utilised during the COVID pandemic and have potential to reduce the costs of outpatient clinics as well as increase patient satisfaction. We aimed to assess the utility and safety of VC in new patient clinics in women under 30, which is considered a low-risk subgroup. Methods: Data was prospectively collected on 118 women aged under 30 who were referred from primary care to the breast clinic between December 2020 and April 2021. Clinicopathological data was collected on referrals, imaging and follow up. Results: Median age was 24 years (range 17-30). The commonest presenting symptoms were a lump (69%), breast pain (16%) and nipple symptoms (14%). The VC was performed via video in 63 (53%) patients and via telephone alone in 55 (47%). Nineteen patients (16%) were reassured and discharged directly from VC. Ninety-four patients (80%) underwent an outpatient ultrasound with a sonographer trained in clinical palpation. Twenty-six (27%) ultrasounds showed benign pathology with the remainder being normal. Six biopsies were performed, all of which were benign. Seventeen (14%) patients required a face-to-face appointment with a breast surgeon after ultrasound or biopsy. Ninety-four (79%) patients were discharged after VC + ultrasound alone. No patients required surgery. Conclusion: Utilising VC, the majority of new referrals in women under 30 did not require face-to-face appointments. VC have potential to reduce burden on new patient clinics whilst improving patient convenience. Early data suggest a low risk of compromising safety in this subgroup.

Implementation of Hands-on, Home-based Laboratory for Two Electrical Engineering Courses (A Pilot Study)

Across the spectrum of higher education the delivery of instruction is changing. These changes are predominantly driven by the shrinking pool of traditional 18-22 year old students, the need for working adults to remotely have access to education, and most recently, the abrupt shift to online instruction secondary to the COVID-19 pandemic. Engineering education is not immune to these new dynamics, and institutions need to plan and prepare to embrace new modalities of instruction. Historically, electrical engineering courses have had lab requirements that have involved physical presence in a laboratory with several pieces of test equipment available for testing circuits. In recent years, computer-based laboratory equipment has become available that can provide the same robustness needed to facilitate learning for online electrical engineering courses. A pilot study was conducted at our institution using a home-based laboratory for two electrical engineering courses (Microcontrollers and Electric Circuit Analysis). Presented will be the development of the labs, implementation of the pilot study, description of the labs, and assessment. © American Society for Engineering Education, 2021

A phase 1 translational pharmacology study in healthy elderly volunteers evaluating the safety, tolerability, pharmacokinetics, and CNS Activity of IW-6463, a CNS-penetrant, soluble guanylate cyclase stimulator

Objective: To evaluate the safety, tolerability, pharmacokinetics, and central nervous system (CNS) activity of IW-6463, a CNS-penetrant soluble guanylate cyclase (sGC) stimulator in healthy elderly volunteers. Background: IW-6463 is being developed as a symptomatic and potentially disease-modifying therapy for serious CNS diseases. Nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) is a fundamental neurotransmitter system critical to basic neuronal function. Impaired signaling of this pathway is believed to play an important role in the pathogenesis of many neurodegenerative diseases. sGC stimulation by IW-6463 can amplify endogenous NO signaling by increasing cGMP production. Preclinically, IW-6463 improves neuronal function, cerebral blood flow, neuroinflammation, and cellular bioenergetics. Design/Methods: In this double-blind, placebo-controlled, crossover study, 24 healthy elderly (≥65 years) volunteers were randomized to receive study drug once daily across two 15-day dosing periods separated by a washout period. Due to COVID-related restrictions, a total of 24 participants completed period 1 and 12 participants completed period 2. Adverse events were recorded, standard safety assessments were performed, and samples of cerebral spinal fluid (CSF) and plasma were collected. Neuroimaging, electroencephalography (EEG), and cognitive performance measures were conducted at baseline and on Day 15 of each dosing period. Results: IW-6463 was well tolerated with no safety concerns and demonstrated blood-brainbarrier penetration at CSF concentrations predicted to be pharmacologically active based on preclinical studies. Although pharmacological effects were not measurable via neuroimaging, increases in posterior alpha power, trend increases in gamma power, and shortening of N200 auditory event-related potential (ERP) latencies were observed via EEG. Improvements in saccadic reaction time and saccadic peak velocity were also observed. Conclusions: IW-6463's favorable safety profile and impacts on biomarkers of CNS activity after 15 days of dosing in elderly individuals support further evaluation of IW-6463 in patients with serious CNS diseases, including Alzheimer's disease.

Regulatory affairs strategic planning: How to do it well

Strategy can be summarised as “choosing to perform activities differently than rivals do” and it makes a company unique and identifiable from its competitors. The overall strategic plan captures important aspects of the regulatory plan, but a departmental regulatory affairs strategic plan will contain further information concerning market entry (ie, including risks and mitigation, timing, route to market) and the requirements needed by health authorities (ie, data on safety, efficacy, quality). Business strategy toolkits provide a number of measures that can be used in defining strategic plans and strategic frameworks. They can be useful structured approaches for defining and refining the regulatory strategy. Various tools can be considered when analysing the strategy, for example, internal and external factors can be uncovered using a SWOT analysis. However, to be truly effective, strategic plans must be regularly monitored and measured in the workplace and considered a living document, as we are all learning during the current coronavirus pandemic, which has instilled its own strategic response. © 2020, TOPRA. All rights reserved.