EBV T-cell immunotherapy generated by peptide selection has enhanced effector functionality compared to LCL stimulation.

Adoptive immunotherapy with Epstein-Barr virus (EBV)-specific T cells is an effective treatment for relapsed or refractory EBV-induced post-transplant lymphoproliferative disorders (PTLD) with overall survival rates of up to 69%. EBV-specific T cells have been conventionally made by repeated stimulation with EBV-transformed lymphoblastoid cell lines (LCL), which act as antigen-presenting cells. However, this process is expensive, takes many months, and has practical risks associated with live virus. We have developed a peptide-based, virus-free, serum-free closed system to manufacture a bank of virus-specific T cells (VST) for clinical use. We compared these with standard LCL-derived VST using comprehensive characterization and potency assays to determine differences that might influence clinical benefits. Multi-parameter flow cytometry revealed that peptide-derived VST had an expanded central memory population and less exhaustion marker expression than LCL-derived VST. A quantitative HLA-matched allogeneic cytotoxicity assay demonstrated similar specific killing of EBV-infected targets, though peptide-derived EBV T cells had a significantly higher expression of antiviral cytokines and degranulation markers after antigen recall. High-throughput T cell receptor-beta (TCRß) sequencing demonstrated oligoclonal repertoires, with more matches to known EBV-binding complementary determining region 3 (CDR3) sequences in peptide-derived EBV T cells. Peptide-derived products showed broader and enhanced specificities to EBV nuclear antigens (EBNAs) in both CD8 and CD4 compartments, which may improve the targeting of highly expressed latency antigens in PTLD. Importantly, peptide-based isolation and expansion allows rapid manufacture and significantly increased product yield over conventional LCL-based approaches.

Cognitive and Noncognitive Factors Influencing Nursing Students' Academic Success: Structural Equation Model Analysis.

AIM: The study aim was to identify and explore relationships among cognitive and noncognitive factors that may contribute to prelicensure baccalaureate nursing students' academic success across their program of study. BACKGROUND: Nurse educators are challenged to improve students' academic success. With limited evidence, cognitive and noncognitive factors have been identified in the literature as potential factors that influence academic success and may support students' readiness for practice as new graduate nurses. METHOD: Data sets from 1,937 BSN students at multiple campuses were analyzed using an exploratory design and structural equation modeling. CONCLUSION: Six factors were conceptualized as contributing equally to the initial cognitive model. The final noncognitive model, with deletion of two factors, yielded the best fit for the four-factor model. Cognitive and noncognitive factors were not significantly correlated. This study provides a beginning understanding of cognitive and noncognitive factors associated with academic success that may support readiness for practice.

The Importance of Meaningful Faculty Recognition in Creating a Healthy Academic Work Environment: A Mixed-Methods Study.

AIM: The purpose of this study was to understand nursing faculty's perceptions of meaningful recognition and how it contributes to a caring academic climate. BACKGROUND: A supportive, healthy work environment is critical in recruiting and retaining nursing faculty. Research on caring for faculty through meaningful recognition and the impact on the workplace climate is limited. METHOD: The study employed a parallel mixed-methods design in which quantitative and qualitative findings were integrated into synthesized conclusions. A total of 193 full-time faculty participated in the survey portion of the study; 15 full- and part-time faculty participated in video-conferenced focus groups. RESULTS: Results of this study demonstrated that meaningful recognition contributes to a caring workplace, motivates faculty work performance, and impacts faculty roles in positive ways. CONCLUSION: For recognition to be meaningful, it must be genuine, aligned with faculty's perceptions of performance, commensurate with level of effort, and relevant to individuals.

Developing a Social Determinants of Learning™ Framework: A Case Study.

AIM: The aim of the study was to propose a framework, social determinants of learning™ (SDOL™), an actionable model to address learning disparities and expand learning opportunities to support nursing student diversity, equity, and inclusion. BACKGROUND: There is significant growth in the racial and ethnic diversity across students at all levels of higher education, mirroring the growing diversity of the US population. Yet, lower rates of persistence and higher attrition rates among these student groups continue. METHOD: The authors established six socially imposed forces, causative domains, as foundational to the SDOL framework. Key attributes of each domain were identified through a literature search. A case study illustrates an initial study of interventions targeting specific domains of the framework aimed toward student success. CONCLUSION: Equitable education for all has far-reaching implications across nursing education and higher education in general. Further development and testing of the SDOL framework will support the goal of equitable education for all.

Role of information and communication technology in promoting oral health at residential aged care facilities.

Information and communication technology (ICT) can provide knowledge and clinical support to those working in residential aged care facilities (RACFs). This paper aims to: (1) review literature on ICT targeted at residents, staff and external providers in RACFs including general practitioners, dental and allied health professionals on improving residents' oral health; (2) identify barriers and enablers to using ICT in promoting oral health at RACFs; and (3) investigate evidence of effectiveness of these approaches in promoting oral health. Findings from this narrative literature review indicate that ICT is not widely used in RACFs, with barriers to usage identified as limited training for staff, difficulties accessing the Internet, limited computer literacy particularly in older staff, cost and competing work demands. Residents also faced barriers including impaired cognitive and psychosocial functioning, limited computer literacy and Internet use. Findings suggest that more education and training in ICT to upskill staff and residents is needed to effectively promote oral health through this medium.

Culturally and linguistically diverse (CALD) carers' perceptions of oral care in residential aged care settings in Perth, Western Australia.

OBJECTIVE: The aims of the study were twofold: to explore African migrant carers' perceptions of oral health who worked in residential aged care and to investigate their perspectives of oral care for aged care residents. BACKGROUND: Culturally and linguistically diverse (CALD) carers are strongly represented in Australian residential aged care facilities. METHODS: Exploratory qualitative research targeted carers from African backgrounds working in residential aged care facilities in Perth, Western Australia. Fifteen African carers were recruited through community networks and participated in semistructured interviews. Data were analysed for key themes related to the study's aims noting similarities and differences between participants. RESULTS: All participants considered oral health important to individual well-being and quality of life. Most had limited knowledge of prevention and early detection of oral disease resulting from regular dental check-ups with the majority visiting dental professionals only for dental pain. Yet participants considered oral health care for residents needed improvement. Suggestions included dental professionals on staff and training and professional development for all staff not just in oral health care but also in working respectfully and sensitively with residents and staff from CALD backgrounds. CONCLUSION: Our findings suggest that, to ensure residents receive high quality oral health care, ongoing professional development is required, not only for CALD carers in oral health but also for non-CALD staff in care that is respectful of cultural differences.

Does residential aged care need dental professionals? A qualitative study on dental professionals' perceptions in Australia.

OBJECTIVE: Adults in residential aged care often retain their own teeth following restorative dental procedures during their lives. They may also have physical and psychological comorbidities impacting on oral health including side effects from medications. residents' poor oral hygiene, dental caries and periodontal disease raise questions about the quality of oral health care in aged care facilities. This paper presents findings from a study investigating dental professionals' perceptions of barriers and enablers to providing oral care to residents in such settings. MATERIAL AND METHODS: Following university ethics approval, semi-structured interviews were conducted with 17 dental professionals [five dentists, three oral health therapists (OHTs) and nine dental hygienists] across Australia to address the issue. Interviews were transcribed and analysed for key themes, noting similarities and differences within and between groups that were compared to existing evidence. RESULTS: Key themes emerging from interviews included individual and organisational difficulties dental professionals experience when meeting residents' oral health needs; poor access to dental resources; limited oral health education for aged care staff; and lack of interprofessional collaboration. Suggested enablers to oral health included interprofessional education and practice, reflecting broader trends in health care that positively impact on health outcomes. CONCLUSION: Improving residents' oral health requires appropriate organisational commitment to support dental and non-dental health providers deliver high-quality oral care. This study highlights the need to critically review barriers and enablers to providing such care, particularly as Australia's ageing population increases and longer periods are spent in residential aged care.

Description of total population hospital admissions for cleft lip and/or palate in Australia.

BACKGROUND: Orofacial clefts are a group of frequently observed congenital malformations often requiring multiple hospital admissions over the lifespan of affected individuals. The aim of this study was to describe the total-population hospital admissions with principal diagnosis of cleft lip and/or palate in Australia over a 10 year period. METHODS: Data for admissions to hospitals were obtained from the Australian Institute of Health and Welfare National Hospital Morbidity Database (July 2000 to June 2010). The outcome variable was a hospital separation with the principal diagnosis of cleft palate, cleft lip or cleft lip and palate (ICD-10-AM diagnosis codes Q35-Q37 respectively). Trends in rates of admission and length of stay by age, gender and cleft type were investigated. RESULTS: A total of 11, 618 admissions were identified; cleft palate (4,454; 0.22 per 10,000 people per year), cleft lip (2,251; 0.11) and cleft lip and palate (4,913; 0.25). Admission age ranged from birth to 79 years with males more frequently admitted. Most admissions occurred prior to adolescence in cleft palate and cleft lip and through to late teens in cleft lip and palate, declining for all groups after 25 years. CONCLUSIONS: This study identified population level trends in hospital separations for orofacial cleft diagnosis in Australia.

Critical role for p53-serine 15 phosphorylation in stimulating transactivation at p53-responsive promoters.

The p53 tumour suppressor is induced by various stress stimuli and coordinates an adaptive gene expression programme leading to growth arrest or cell death. Some stimuli, such as DNA damage, lead to rapid and substantial multisite phosphorylation of p53, nucleated initially through phosphorylation of serine 15. Other stimuli, such as hyper-proliferation, do not stimulate p53-phosphorylation, raising questions regarding the physiological role for phosphorylation. Here, we show that a basal level of Ser15 phosphorylation occurs in both unstimulated cells and cells stimulated pharmacologically to induce p53. p53 in which Ser15 is substituted by alanine (S15A) fails to mediate p53-dependent transcription or growth arrest but can be rescued by substitution with aspartate (S15D: a phospho-mimic). Chromatin immunoprecipitation (ChIP) analyses show that, while wt- and S15A-p53 are detectable on the CDKN1A (p21) promoter (as a representative p53-responsive promoter), S15A-p53 does not stimulate histone acetylation (a measure of chromatin relaxation), nor is its recruitment stimulated, in response to a DNA damage or pharmacological stimulus. These data demonstrate that Ser15 phosphorylation is required for p53 function in the physiological context of p53-responsive promoters and suggest a key and possibly universal role even for low levels of this modification in promoting p53-transcription function.

Dental hospital admissions in the children of mothers with an alcohol-related diagnosis: a population-based, data-linkage study.

OBJECTIVE: To investigate the relationship between maternal alcohol-use disorder and dental hospital admissions in children up to 5 years of age. STUDY DESIGN: Mothers with an International Classification of Diseases, 9th revision/10th revision alcohol-related diagnosis, a proxy for alcohol-use disorder, were identified through the Western Australian data-linkage system. Exposed mothers were frequency-matched by maternal age, Aboriginal status, and child's birth year to randomly selected comparison mothers without an alcohol diagnosis. Linkage with the Midwives Notification System (1983-2002) identified all births of these mothers; "exposed" (non-Aboriginal, n = 11,171; Aboriginal, n = 8145) and comparison cohorts (non-Aboriginal, n = 32,508; Aboriginal, n = 16,719). Dental hospital admissions were identified through linkage with Hospital Morbidity Data (1983-2007) (3.2% exposed; 3.0% comparison) and cases of fetal alcohol syndrome (n = 84) through linkage with the Western Australian Register of Developmental Anomalies. ORs and 95% CIs for having a dental admission (International Classification of Diseases, 9th revision: 520-529; International Classification of Diseases, 10th revision: K0-K14.9) were generated by the use of generalized estimating equations, which we adjusted for potential confounding factors (aOR). RESULTS: Children of mothers with an alcohol-related diagnosis had increased adjusted odds of gingivitis and periodontal diseases (aOR 1.67; 95% CI 1.12-2.51) and "other" diseases of the lip and oral mucosa (aOR 1.56; 95% CI 1.21-2.01). Diseases of the salivary glands were increased only in Aboriginal children of mothers with an alcohol-related diagnosis (aOR 2.65; 95% CI 1.09-6.44). Children diagnosed with fetal alcohol syndrome had increased ORs of any dental admission (aOR 2.58; 95% CI 1.30-5.11). CONCLUSIONS: Maternal alcohol-use disorder was associated with dental admissions related to disorders of the soft tissues, but questions remain regarding perinatal influences on dental admissions and disease.

Aged care staff perspectives on oral care for residents: Western Australia.

OBJECTIVE: To determine manager and staff perceptions of oral health and dental service issues for residents in aged care facilities in the Perth Metropolitan Area, Western Australia. DESIGN: Focus groups and face-to-face semi-structured interviews with aged care facility managers and staff. SETTING AND SUBJECTS: Personnel at 12 facilities (high-level and low-level care) located in the Perth Metropolitan Area participated in the study. Interviews were conducted with 14 facility managers. Focus groups and face-to-face interviews were conducted with 40 facility staff. RESULTS: Managers and staff had similar views regarding most issues. While resident oral health was considered important, regular oral care programmes were limited or lacking. In general, high care facility residents did not have regular dental checkups, while those in low-level care facilities usually visited their own dentist for checkups or treatment. Barriers to maintaining regular oral care included: resident noncompliance; financial concerns; lack of co-operation from family; mobility issues; and lack of interest from dental professionals. Suggested improvements to current services included regular on-site visits, staff education and specialised dental professionals. CONCLUSION: Residents face many barriers to maintenance of adequate oral health care, particularly those who are functionally dependent and cognitively impaired. There is an urgent need for appropriate oral care programmes for aged care residents, which include dentists with aged care experience and continuing education for facility staff. Any major programmes should be evaluated carefully.

Understanding the use of breast cancer screening services by women with intellectual disabilities.

OBJECTIVES: The uptake of mammography for breast cancer screening is considerably lower among women with intellectual disability than for women in the general population. The purpose of the present study was to investigate carer perceptions of barriers and enablers to mammography use by these women. METHODS: To determine the reasons why women with intellectual disability are not utilising screening services, a series of focus groups were held with social trainers working in accommodation provided for people with intellectual disability. RESULTS: The major themes identified included the need for a medical referral or invitation from the mammography service to motivate people to attend; the belief that many women with intellectual disability would not understand the procedure or why it needs to be done and therefore would experience fear and anxiety to a greater extent than women in the general population; and that physical disabilities comorbid in many of the women would limit their ability to be adequately accommodated by the machines used to take a mammogram. CONCLUSIONS: The social trainers agreed that many of the barriers to screening would be difficult to overcome and supported alternative strategies to mammography, such as clinical breast examination.

Experience of respiratory and allergic illness in children attending childcare.

OBJECTIVES: To describe previous illness for children attending two types of formal childcare (130 family daycare homes and 11 child daycare centres). DESIGN: A questionnaire was completed by the parents of 846 children, which provided information about previous illness and associated factors. The questionnaire was conducted in Perth, Western Australia. RESULTS: Of all children, 39% had experienced otitis media, 11% glue ear and 26% allergies; 18% had been diagnosed with asthma; 10% had been admitted to hospital with respiratory illness, and 9% had experienced more than six respiratory conditions in the previous year. Attending centre daycare compared with family daycare was more likely to be associated with some of the previous illness outcomes (more than six respiratory illnesses in the past year, asthma, otitis media and glue ear) but, for all children, the major predisposing factors associated with these illnesses were a family history of atopy or bronchitis. CONCLUSIONS: Children with a history of respiratory illness or otitis media are more likely to be attending centre than family daycare, but family history of respiratory illness is an important risk factor for all children in childcare.