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SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, although muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics.

Background: An earlier article in this journal provided a mapping of primary science teacher assessment practices in England using teacher reflections written for Round 4 of the Primary Science Quality Mark (PSQM). Purpose: In the intervening years, the National Curriculum and statutory assessment system of levels has been replaced with a system of age-related expectations and a call for schools to develop their own systems of assessment. The aim of this study is to find out whether schools have changed their practices and to consider the ongoing changes they are making to their systems of assessment. Sample: The previous analysis of 91 Round 4 schools in March 2013 was compared to teacher reflections from 200 schools from across England in the more recent PSQM Round 13, June 2017. Design and methods: Qualitative content analysis was used to code the reported assessment methods in PSQM Round 13. The frequency of assessment methods were compared to the Round 4 mapping. Results: Reported practice in summative assessment in Round 13 included more 'ongoing' assessment information, which could potentially support a more valid sampling of the construct, but there was a lack of clarity regarding the use of data tracking systems. In the PSQM year, subject leaders described starting or developing the use of a range of published and school developed resources to support assessment practices in formative and summative assessment. Conclusion: Changing statutory assessment processes instigates change in school practices, but without support for teacher assessment literacy, the implementation of new assessment systems may not lead to clear processes for assessment which support learning in primary science.

The emergence of SARS-CoV-2 variants of concern suggests viral adaptation to enhance human-to-human transmission1,2. Although much effort has focused on the characterization of changes in the spike protein in variants of concern, mutations outside of spike are likely to contribute to adaptation. Here, using unbiased abundance proteomics, phosphoproteomics, RNA sequencing and viral replication assays, we show that isolates of the Alpha (B.1.1.7) variant3 suppress innate immune responses in airway epithelial cells more effectively than first-wave isolates. We found that the Alpha variant has markedly increased subgenomic RNA and protein levels of the nucleocapsid protein (N), Orf9b and Orf6-all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein that is required for activation of the RNA-sensing adaptor MAVS. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful transmission of the Alpha variant, and may increase in vivo replication and duration of infection4. The importance of mutations outside the spike coding region in the adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the N and Orf9b regulatory regions of the Delta and Omicron variants.

Abstract Background Although it is known both patients’ and partners’ reactions to a prostate cancer diagnosis include fear, uncertainty, anxiety and depression with patients’ partners’ reactions mutually determining how they cope with and adjust to the illness, few psychosocial interventions target couples. Those that are available tend to be led by highly trained professionals, limiting their accessibility and long-term sustainability. In addition, it is recognised that patients who might benefit from conventional face-to-face psychosocial interventions do not access these, either by preference or because of geographical or mobility barriers. Self-directed interventions can overcome some of these limitations and have been shown to contribute to patient well-being. This study will examine the feasibility of a self-directed, coping skills intervention for couples affected by cancer, called Coping-Together, and begin to explore its potential impact on couples’ illness adjustment. The pilot version of Coping-Together includes a series of four booklets, a DVD, and a relaxation audio CD. Methods/design In this double-blind, two-group, parallel, randomized controlled trial, 70 couples will be recruited within 4 months of a prostate cancer diagnosis through urology private practices and randomized to: 1) Coping-Together or 2) a minimal ethical care condition. Minimal ethical care condition couples will be mailed information booklets available at the Cancer Council New South Wales and a brochure for the Cancer Council Helpline. The primary outcome (anxiety) and additional secondary outcomes (distress, depression, dyadic adjustment, quality of life, illness or caregiving appraisal, self-efficacy, and dyadic and individual coping) will be assessed at baseline (before receiving study material) and 2 months post-baseline. Intention-to-treat and per protocol analysis will be conducted. Discussion As partners’ distress rates exceed not only population norms, but also those reported by patients themselves, it is imperative that coping skills interventions target the couple as a unit and enhance both partners’ ability to overcome cancer challenges. This pilot study will examine the feasibility and potential efficacy of Coping-Together in optimising couples’ illness adjustment. This is one of the first feasibility studies to test this innovative coping intervention, which in turn will contribute to the larger literature advocating for psychosocial care of couples affected by prostate cancer. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12611000438954

Abstract Background With the growing recognition that patients and partners react to a cancer diagnosis as an interdependent system and increasing evidence that psychosocial interventions can be beneficial to both patients and partners, there has been a recent increase in the attention given to interventions that target couples. The aim of this systematic review was to identify existing couple-based interventions for patients with cancer and their partners and explore the efficacy of these interventions (including whether there is added value to target the couple versus individuals), the content and delivery of couple-based interventions, and to identify the key elements of couple-based interventions that promote improvement in adjustment to cancer diagnosis. Method A systematic review of the cancer literature was performed to identify experimental and quasi-experimental couple-based interventions published between 1990 and 2011. To be considered for this review, studies had to test the efficacy of a psychosocial intervention for couples affected by cancer. Studies were excluded if they were published in a language other than English or French, focused on pharmacological, exercise, or dietary components combined with psychosocial components, or did not assess the impact of the intervention on psychological distress (e.g., depression, anxiety) or quality of life. Data were extracted using a standardised data collection form, and were analysed independently by three reviewers. Results Of the 709 articles screened, 23 were included in this review. Couple-based interventions were most efficacious in improving couple communication, psychological distress, and relationship functioning. Interventions had a limited impact on physical distress and social adjustment. Most interventions focused on improving communication and increasing understanding of the cancer diagnosis within couples. Interventions were most often delivered by masters-level nurses or clinical psychologists. Although most were delivered in person, few were telephone-based. No difference in efficacy was noted based on mode of delivery. Factors associated with uptake and completion included symptom severity, available time and willingness to travel. Conclusion Given effect sizes of couple-based interventions are similar to those reported in recent meta-analyses of patient-only and caregiver-only interventions (~d=.35-.45), it appears couple-based interventions for patients with cancer and their partners may be at least as efficacious as patient-only and caregiver-only interventions. Despite evidence that couple-based interventions enhance psycho-social adjustment for both patients and partners, these interventions have not yet been widely adopted. Although more work is needed to facilitate translation to routine practice, evidence reviewed is promising in reducing distress and improving coping and adjustment to a cancer diagnosis or to cancer symptoms.

Abstract Background Childhood obesity is a substantial public health problem. The extent to which health state preferences (utilities) are related to a child's weight status has not been reported. The aims of this study were (1) to use a generic health state classification system to measure health related quality of life and calculate health utilities in a convenience sample of children and adolescents and (2) to determine the extent to which these measures are associated with weight status and body mass index (BMI). Methods We enrolled 76 children 5-18 years of age from a primary care clinic and an obesity clinic in Boston MA. We administered the Health Utilities Index (HUI) and used the HUI Mark 3 single- and multi-attribute utility functions to calculate health utilities. We determined BMI percentile and weight status based on CDC references. We examined single-attribute and overall utilities in relation to weight status and BMI. Results Mean (range) age was 10.8 (5-18) years. Mean (SD) BMI percentile was 76 (26); 55% of children were overweight or obese. The mean (SD) overall utility was 0.79 (0.17) in the entire sample. For healthy-weight children, the mean overall utility was higher than for overweight or obese children (0.81 vs. 0.78), but the difference was not statistically significant (difference 0.04, 95% CI -0.04, 0.11). Conclusions Our results provide a quantitative estimate of the health utility associated with overweight and obesity in children, and will be helpful to researchers performing cost effectiveness analyses of interventions to prevent and/or treat childhood obesity.

Abstract Background Despite evidence that up to 35% of patients with cancer experience significant distress, access to effective psychosocial care is limited by lack of systematic approaches to assessment, a paucity of psychosocial services, and patient reluctance to accept treatment either because of perceived stigma or difficulties with access to specialist psycho-oncology services due to isolation or disease burden. This paper presents an overview of a randomised study to evaluate the effectiveness of a brief tailored psychosocial Intervention delivered by health professionals in cancer care who undergo focused training and participate in clinical supervision. Methods/design Health professionals from the disciplines of nursing, occupational therapy, speech pathology, dietetics, physiotherapy or radiation therapy will participate in training to deliver the psychosocial Intervention focusing on core concepts of supportive-expressive, cognitive and dignity-conserving care. Health professional training will consist of completion of a self-directed manual and participation in a skills development session. Participating health professionals will be supported through structured clinical supervision whilst delivering the Intervention. In the stepped wedge design each of the 5 participating clinical sites will be allocated in random order from Control condition to Training then delivery of the Intervention. A total of 600 patients will be recruited across all sites. Based on level of distress or risk factors eligible patients will receive up to 4 sessions, each of up to 30 minutes in length, delivered face-to-face or by telephone. Participants will be assessed at baseline and 10-week follow-up. Patient outcome measures include anxiety and depression, quality of life, unmet psychological and supportive care needs. Health professional measures include psychological morbidity, stress and burnout. Process evaluation will be conducted to assess perceptions of participation in the study and the factors that may promote translation of learning into practice. Discussion This study will provide important information about the effectiveness of a brief tailored psychological Intervention for patients with cancer and the potential to prevent development of significant distress in patients considered at risk. It will yield data about the feasibility of this model of care in routine clinical practice and identify enablers and barriers to its systematic implementation in cancer settings. Trial registration ACTRN12610000448044

Abstract Background The diagnosis and treatment of cancer is a major life stress such that approximately 35% of patients experience persistent clinically significant distress and carers often experience even higher distress than patients. This paper presents the design of a two arm randomised controlled trial with patients and carers who have elevated psychological distress comparing minimal contact self management vs. an individualised tele-based cognitive behavioural intervention. Methods/design 140 patients and 140 carers per condition (560 participants in total) will been recruited after being identified as high distress through caller screening at two community-based cancer helplines and randomised to 1) a single 30-minute telephone support and education session with a nurse counsellor with self management materials 2) a tele-based psychologist delivered five session individualised cognitive behavioural intervention. Session components will include stress reduction, problem-solving, cognitive challenging and enhancing relationship support and will be delivered weekly. Participants will be assessed at baseline and 3, 6 and 12 months after recruitment. Outcome measures include: anxiety and depression, cancer specific distress, unmet psychological supportive care needs, positive adjustment, overall Quality of life. Discussion The study will provide recommendations about the efficacy and potential economic value of minimal contact self management vs. tele-based psychologist delivered cognitive behavioural intervention to facilitate better psychosocial adjustment and mental health for people with cancer and their carers. Trial Registration ACTRN12609000301268.

Introduction: The Maternal Child Health (MCH) Bureau created MCH Leadership Competencies to support current and future leaders by defining the knowledge and skills necessary to lead in this field. The Michigan-LEND (MILEND) training program developed a 'LIFE. framework', an acronym that stands for Leadership, Interdisciplinary, Family-Professional Partnerships, and Equity, to codify the 12 MCH leadership competencies into an easy to remember and easy to apply structure. This manuscript addresses the question, Does the LIFE framework align with the 12 MCH Leadership Competencies? Our hypothesis is that MI-LEND trainees will demonstrate improvement in their self-assessment of the 12 MCH leadership competencies after completing the MI-LEND program which uses the LIFE framework. Methods: Data were collected from 24 MI-LEND long-term trainees (> 300 hours) who completed a 100-itemleadership self-assessment questionnaire based on the MCH Navigator at the beginning and the end of the training year. Non-parametric sign tests were used to test the median difference, item by item for each of the questions under each competency. Parametric paired-sample t-tests were used to analyze mean difference, competency by competency when the assumption of normality was met. Results: All basic and advanced-level competencies had a statistically significant improvement between the beginning and end of the training year. The greatest changes were seen in Family-Professional Partnerships, Policy, Interdisciplinary Team Building, MCH Knowledge Base and Critical Thinking - all areas emphasized in the L.I.F.E. framework. Discussion: While the LIFE framework may oversimplify MCH Leadership Competencies, it is an effective mnemonic tool to organize and articulate MCH leadership competencies and could foster consistency across MCH programs., Author(s): Sharon Milberger [sup.1] [sup.3] , Ke Zhang [sup.1] , Michael Bray [sup.1] , Jane Turner [sup.2] Author Affiliations: (1) grid.254444.7, 0000 0001 1456 7807, Wayne State University, , Detroit, [...]

Abstract Background The acetamidase of Mycobacterium smegmatis is a highly inducible enzyme. Expression of this enzyme is increased 100-fold when the substrate acetamide is present. The acetamidase gene is found immediately downstream of three open reading frames. Two of these are proposed to be involved in regulation. Results We constructed a deletion mutant in one of the upstream ORFs (amiA). This mutant (Mad1) showed a constitutively high level of acetamidase expression. We identified four promoters in the upstream region using a β-galactosidase reporter gene. One of these (P2) was inducible in the wild-type, but was constitutively active in Mad1. Conclusions These results demonstrate that amiA encodes a negative regulatory protein which interacts with P2. Since amiA has homology to DNA-binding proteins, it is likely that it exerts the regulatory effect by binding to the promoter to prevent transcription.

ABSTRACT Objective Methods Results Conclusions Integrating Patient‐Reported Outcome Measures (PROMs) into clinical practice is increasing, with research showing benefits in patient outcomes. However, evidence regarding patient's acceptance of PROMs is limited. Sydney Cancer Survivorship Centre (SCSC) clinic is a multidisciplinary clinic where clinicians use PROMs to guide patient consultation. This study explored SCSC patient acceptability of PROMs in clinical care by evaluating PROMs' completion rates.This retrospective audit of PROMs completion rates evaluates two periods: 1) September 2013–November 2019 (pre‐coronavirus disease 2019) and 2) October 2020–September 2023, following the implementation of electronic PROMs. Overall, 866 new patients attended SCSC during the two audit periods, with 822 (95%) giving consent for data to be included. Descriptive statistical methods were used to analyse completion rates.Between September 2013 and November 2019 (audit period 1), 656 new survivors attended the SCSC clinic; 622 (95%) consented to data use. The highest completion rate for paper‐based PROMs was the food questionnaire (92%); with 91% for distress thermometer, symptoms, and exercise‐related PROMs; 85% for quality of life; 77% for self‐rated performance status, and 55.5% for a 3‐day food diary. From October 2020 to September 2023 (period 2), the response rate for PROMs was 99% (n = 198/200) for initial clinic attendees; and 92% for electronic PROMs (n = 169/184).Using comprehensive PROMs in clinical care is feasible. The completion rate was high; similar between paper‐based and electronic PROMs. Comprehensive PROMs can guide clinical consultations. PROMs may improve communication between survivors and clinicians and enhance the quality of care. [ABSTRACT FROM AUTHOR]

BackgroundDespite advances in cancer diagnosis and treatment have significantly improved survival rates, patients post-treatment-related health needs are often not adequately addressed by current health services. The aim of the Women's Wellness after Cancer Program (WWACP), which is a digitised multimodal lifestyle intervention, is to enhance health-related quality of life in women previously treated for blood, breast and gynaecological cancers.MethodsA single-blinded, multi-centre randomized controlled trial recruited a total of 351 women within 24 months of completion of chemotherapy (primary or adjuvant) and/or radiotherapy. Women were randomly assigned to either usual care or intervention using computer-generated permuted-block randomisation. The intervention comprises an evidence-based interactive iBook and journal, web interface, and virtual health consultations by an experienced cancer nurse trained in the delivery of the WWACP. The 12 week intervention focuses on evidence-based health education and health promotion after a cancer diagnosis. Components are drawn from the American Cancer Research Institute and the World Cancer Research Fund Guidelines (2010), incorporating promotion of physical activity, good diet, smoking cessation, reduction of alcohol intake, plus strategies for sleep and stress management. The program is based on Bandura's social cognitive theoretical framework. The primary outcome is health-related quality of life, as measured by the Functional Assessment of Cancer Therapy-General (FACT-G). Secondary outcomes are menopausal symptoms as assessed by Greene Climacteric Scale; physical activity elicited with the Physical Activity Questionnaire Short Form (IPAQ-SF); sleep measured by the Pittsburgh Sleep Quality Index; habitual dietary intake monitored with the Food Frequency Questionnaire (FFQ); alcohol intake and tobacco use measured by the Australian Health Survey and anthropometric measures including height, weight and waist-to-hip ratio. All participants were assessed with these measures at baseline (at the start of the intervention), 12 weeks (at completion of the intervention), and 24 weeks (to determine the level of sustained behaviour change). Further, a simultaneous cost-effectiveness evaluation will consider if the WWACP provides value for money and will be reported separately.DiscussionWomen treated for blood, breast and gynaecological cancers demonstrate increasingly good survival rates. However, they experience residual health problems that are potentially modifiable through behavioural lifestyle interventions such as the WWACP.Trial registrationThe protocol for this study was registered with the Australian and New Zealand Clinical Trials Registry, Trial ID: ACTRN12614000800628 , July 28, 2014.