The Impact of Race, Ethnicity, and Sex on Fairness in Artificial Intelligence for Glaucoma Prediction Models.

Objective: Despite advances in artificial intelligence (AI) in glaucoma prediction, most works lack multicenter focus and do not consider fairness concerning sex, race, or ethnicity. This study aims to examine the impact of these sensitive attributes on developing fair AI models that predict glaucoma progression to necessitating incisional glaucoma surgery. Design: Database study. Participants: Thirty-nine thousand ninety patients with glaucoma, as identified by International Classification of Disease codes from 7 academic eye centers participating in the Sight OUtcomes Research Collaborative. Methods: We developed XGBoost models using 3 approaches: (1) excluding sensitive attributes as input features, (2) including them explicitly as input features, and (3) training separate models for each group. Model input features included demographic details, diagnosis codes, medications, and clinical information (intraocular pressure, visual acuity, etc.), from electronic health records. The models were trained on patients from 5 sites (N = 27 999) and evaluated on a held-out internal test set (N = 3499) and 2 external test sets consisting of N = 1550 and N = 2542 patients. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUROC) and equalized odds on the test set and external sites. Results: Six thousand six hundred eighty-two (17.1%) of 39 090 patients underwent glaucoma surgery with a mean age of 70.1 (standard deviation 14.6) years, 54.5% female, 62.3% White, 22.1% Black, and 4.7% Latinx/Hispanic. We found that not including the sensitive attributes led to better classification performance (AUROC: 0.77-0.82) but worsened fairness when evaluated on the internal test set. However, on external test sites, the opposite was true: including sensitive attributes resulted in better classification performance (AUROC: external #1 - [0.73-0.81], external #2 - [0.67-0.70]), but varying degrees of fairness for sex and race as measured by equalized odds. Conclusions: Artificial intelligence models predicting whether patients with glaucoma progress to surgery demonstrated bias with respect to sex, race, and ethnicity. The effect of sensitive attribute inclusion and exclusion on fairness and performance varied based on internal versus external test sets. Prior to deployment, AI models should be evaluated for fairness on the target population. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Using Electronic Health Record Data to Determine the Safety of Aqueous Humor Liquid Biopsies for Molecular Analyses.

Purpose: Knowing the surgical safety of anterior chamber liquid biopsies will support the increased use of proteomics and other molecular analyses to better understand disease mechanisms and therapeutic responses in patients and clinical trials. Manual review of operative notes from different surgeons and procedures in electronic health records (EHRs) is cumbersome, but free-text software tools could facilitate efficient searches. Design: Retrospective case series. Participants: A total of 1418 aqueous humor liquid biopsies from patients undergoing intraocular surgery. Methods: Free-text EHR searches were performed using the Stanford Research Repository cohort discovery tool to identify complications associated with anterior chamber paracentesis and subsequent endophthalmitis. Complications of the surgery unrelated to the biopsy were not reviewed. Main Outcome Measures: Biopsy-associated intraoperative complications and endophthalmitis. Results: A total of 1418 aqueous humor liquid biopsies were performed by 17 experienced surgeons. EHR free-text searches were 100% error-free for surgical complications, >99% for endophthalmitis (<1% false positive), and >93.6% for anesthesia type, requiring manual review for only a limited number of cases. More than 85% of cases were performed under local anesthesia without ocular muscle akinesia. Although the most common indication was cataract (50.1%), other diagnoses included glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration, endophthalmitis, retinitis pigmentosa, and uveal melanoma. A 50- to 100-µL sample was collected in all cases using either a 30-gauge needle or a blunt cannula via a paracentesis. The median follow-up was >7 months. There was only one minor complication (0.07%) identified: a case of a small tear in Descemet membrane without long-term sequelae. No other complications occurred, including other corneal injuries, lens or iris trauma, hyphema, or suprachoroidal hemorrhage. There was no case of postoperative endophthalmitis. Conclusions: Anterior chamber liquid biopsy during intraocular surgery is a safe procedure and may be considered for large-scale collection of aqueous humor samples for molecular analyses. Free-text EHR searches are an efficient approach to reviewing intraoperative procedures. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Sociodemographic profile, health-related behaviours and experiences of healthcare access in Italian transgender and gender diverse adult population.

PURPOSE: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population. METHODS: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP). RESULTS: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity. CONCLUSIONS: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.

Frequency of deployed emergency donor panel use prior to implementation of the low titre group O whole blood program.

INTRODUCTION: The US military has frequently used a 'walking blood bank', formally known as an 'emergency donor panel' (EDP) to obtain warm fresh whole blood (WFWB) which is then immediately transfused into the casualty. We describe the frequency of EDP activation by the US military. METHODS: We analysed data from 2007 to 2015 within the Department of Defense Trauma Registry for US, Coalition and US contractor casualties that received at least 1 unit of blood product within the first 24 hours and described the frequency of WFWB use. RESULTS: There were 3474 casualties that met inclusion, of which, 290 casualties (8%) required activation of the EDP. The highest proportion of EDP events was in 2014, whereas the highest number of EDP events was in 2011. Median injury severity scores were higher in the recipients, compared with non-EDP recipients (29 vs 20), as were proportions with serious injuries to the abdomen (43% vs 19%) and extremities (77% vs 65%). The median number of units of all blood products, except for packed red blood cells, was higher for WFWB recipients. Of the WFWB recipients, the median was 5 units (IQR 2-10) with a maximum documented 144 units. There were four documented cases of EDP recipients receiving >100 units of WFWB with only one surviving to hospital discharge. During the study period, there were a total of 3102 (3%) units of WFWB transfused among a total of 104 288 total units. CONCLUSIONS: We found nearly 1 in 11 casualties who received blood required activation of the EDP. Blood from the EDP accounted for 3% of all units transfused. These findings will enable future mission planning and medical training, especially for units with smaller, limited blood supplies. The lessons learned here can also enable mass casualty planning in civilian settings.

The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials.

Measurable residual disease (MRD) status in chronic lymphocytic leukemia (CLL), assessed on and after treatment, correlates with increased progression-free and overall survival benefit. More recently, MRD assessment has been included in large clinical trials as a primary outcome and is increasingly used in routine practice as a prognostic tool, a therapeutic goal, and potentially a trigger for early intervention. Modern therapy for CLL delivers prolonged remissions, causing readout of traditional trial outcomes such as progression-free and overall survival to be inherently delayed. This represents a barrier for the rapid incorporation of novel drugs to the overall therapeutic armamentarium. MRD offers a dynamic and robust platform for the assessment of treatment efficacy in CLL, complementing traditional outcome measures and accelerating access to novel drugs. Here, we provide a comprehensive review of recent major clinical trials of CLL therapy, focusing on small-molecule inhibitors and monoclonal antibody combinations that have recently emerged as the standard frontline and relapse treatment options. We explore the assessment and reporting of MRD (including novel techniques) and the challenges of standardization and provide a comprehensive review of the relevance and adequacy of MRD as a clinical trial endpoint. We further discuss the impact that MRD data have on clinical decision-making and how it can influence a patient's experience. Finally, we evaluate how upcoming trial design and clinical practice are evolving in the face of MRD-driven outcomes.

An app with brief behavioural support to promote physical activity after a cancer diagnosis (APPROACH): study protocol for a pilot randomised controlled trial.

BACKGROUND: There are multiple health benefits from participating in physical activity after a cancer diagnosis, but many people living with and beyond cancer (LWBC) are not meeting physical activity guidelines. App-based interventions offer a promising platform for intervention delivery. This trial aims to pilot a theory-driven, app-based intervention that promotes brisk walking among people living with and beyond cancer. The primary aim is to investigate the feasibility and acceptability of study procedures before conducting a larger randomised controlled trial (RCT). METHODS: This is an individually randomised, two-armed pilot RCT. Patients with localised or metastatic breast, prostate, or colorectal cancer, who are aged 16 years or over, will be recruited from a single hospital site in South Yorkshire in the UK. The intervention includes an app designed to encourage brisk walking (Active 10) supplemented with habit-based behavioural support in the form of two brief telephone/video calls, an information leaflet, and walking planners. The primary outcomes will be feasibility and acceptability of the study procedures. Demographic and medical characteristics will be collected at baseline, through self-report and hospital records. Secondary outcomes for the pilot (assessed at 0 and 3 months) will be accelerometer measured and self-reported physical activity, body mass index (BMI) and waist circumference, and patient-reported outcomes of quality of life, fatigue, sleep, anxiety, depression, self-efficacy, and habit strength for walking. Qualitative interviews will explore experiences of participating or reasons for declining to participate. Parameters for the intended primary outcome measure (accelerometer measured average daily minutes of brisk walking (≥ 100 steps/min)) will inform a sample size calculation for the future RCT and a preliminary economic evaluation will be conducted. DISCUSSION: This pilot study will inform the design of a larger RCT to investigate the efficacy and cost-effectiveness of this intervention in people LWBC. TRIAL REGISTRATION: ISRCTN registry, ISRCTN18063498 . Registered 16 April 2021.

Online training resources to aid therapeutic radiographers in engaging in conversations about physical activity and diet: A mixed methods study.

INTRODUCTION: This study explored changes in therapeutic radiographers' (TRs) self-reported knowledge and skills to engage in conversations about physical activity and diet with people living with and beyond cancer following completion of publicly available online courses. METHODS: Participants were randomly assigned to two of five online courses that aim to support health professionals to engage in conversations about physical activity and diet in the oncology setting. Participants rated their agreement with 18 statements related to the COM-B (capability, opportunity and motivation-behaviour) model components following completion of an online course on healthy diet (n = 16) and physical activity (n = 21). Semi-structured telephone interviews (n = 21) were also conducted. Analysis of the interviews was guided by the Theoretical Domains Framework. RESULTS: Overall, the online courses were acceptable and the TRs in this study self-reported improved COM to deliver advice on physical activity and diet. The inclusion of the evidence and scientific rationale on the benefits of diet and physical activity, and also guidance on how to start conversations with patients were highlighted as important features of the courses. Suggestions for adaptations to the nutrition courses included the need for content that accounts for the side effects cancer patients experience while undergoing treatment. To support the implementation of training and the delivery of advice on these topics, multi-disciplinary working, organisational support and guidance around professional role boundaries were highlighted as important. CONCLUSION: Current publicly available online courses on physical activity and diet for oncology health professionals can reduce some barriers among TRs to providing advice to those living with and beyond cancer. IMPLICATIONS FOR PRACTICE: Existing online training courses could be used to support TRs to deliver physical activity and dietary advice in practice. Findings show that these courses can be disseminated within radiotherapy departments. The results also highlight a number of important considerations for the implementation of brief health behaviour advice and online training interventions on physical activity and diet within cancer care.

SIGIS-SIAMS-SIE position statement of gender affirming hormonal treatment in transgender and non-binary people.

PURPOSE: Gender Incongruence (GI) is a marked and persistent incongruence between an individual's experienced and the assigned gender at birth. In the recent years, there has been a considerable evolution and change in attitude as regards to gender nonconforming people. METHODS: According to the Italian Society of Gender, Identity and Health (SIGIS), the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Endocrinology (SIE) rules, a team of experts on the topic has been nominated by a SIGIS-SIAMS-SIE Guideline Board on the basis of their recognized clinical and research expertise in the field, and coordinated by a senior author, has prepared this Position statement. Later on, the present manuscript has been submitted to the Journal of Endocrinological Investigation for the normal process of international peer reviewing after a first internal revision process made by the SIGIS-SIAMS-SIE Guideline Board. RESULTS: In the present document by the SIGIS-SIAMS-SIE group, we propose experts opinions concerning the psychological functioning, gender affirming hormonal treatment, safety concerns, emerging issues in transgender healthcare (sexual health, fertility issues, elderly trans people), and an Italian law overview aimed to improve gender non-conforming people care. CONCLUSION: In this Position statement, we propose experts opinions concerning the psychological functioning of transgender people, the gender-affirming hormonal treatment (full/partial masculinization in assigned female at birth trans people, full/partial feminization and de-masculinization in assigned male at birth trans people), the emerging issues in transgender health care aimed to improve patient care. We have also included an overview of Italian law about gender affirming surgery and registry rectification.

Phase 2 study of anastrozole in rare cohorts of patients with estrogen receptor/progesterone receptor positive leiomyosarcomas and carcinosarcomas of the uterine corpus: The PARAGON trial (ANZGOG 0903).

BACKGROUND: Aromatase inhibitors have been used empirically to treat a subset of patients with hormone receptor positive uterine leiomyosarcomas(LMS) and carcinosarcomas (UCS) mainly supported by retrospective data. We evaluated the activity of anastrozole in two rare cohorts; patients with recurrent/metastatic LMS and UCS enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER+)/progesterone receptor positive (PR+) gynecological cancers. METHOD: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER &/or PR + ve LMS or UCS with measurable disease, treated until progression or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. RESULTS: 39 eligible patients were enrolled, 32 with LMS and 7 with UCS. For the LMS cohort CBR at 3 months was 35% (95% CI: 21-53%) with a median duration of clinical benefit of 5.8 months. Best response was a partial response in one patient. Two patients remained on treatment for more than one year. The median progression-free survival was 2.8 months (95% CI: 2.6-4.9). For the UCS cohort CBR at 3 months was 43% (95% CI: 16-75%) with a median duration of clinical benefit of 5.6 months. Stable disease was seen in 3 patients but no objective responses were seen. The median progression-free survival was 2.7 months (95% CI, 1.1-8.2). Safety was acceptable with 5/39 evaluable patients showing grade 3 toxicities. CONCLUSION: Whilst objective response rates with anastrozole are low, the clinical benefit rate and good tolerance suggests that aromatase inhibitor therapy may have a role in a subset of patients with metastatic LMS and UCS.

The impact of the COVID-19 pandemic on mental health and well-being of people living with a long-term physical health condition: a qualitative study.

BACKGROUND: The COVID-19 pandemic and associated restrictions caused major global disruption. Individuals with long-term physical health conditions (LTCs) are at higher risk of severe illness and often subject to the strictest pandemic guidance, so may be disproportionally affected. The aim of this study was to qualitatively explore how living with a LTC during the COVID-19 pandemic affected people's mental health and wellbeing. METHODS: Participants were people living with LTCs who participated in telephone/video call interviews based on a semi-structured topic guide. Key themes and subthemes were determined using deductive and inductive thematic analysis. RESULTS: The sample included 32 participants with LTCs (most commonly cancer, respiratory conditions or cardiovascular diseases), mean age 57 (SD 13) years, 66% female and 72% white British. There were four overarching themes specific to living with a LTC. These were 1) high levels of fear and anxiety related to perceived consequences of catching COVID-19, 2) impact of shielding/isolation on mental health and wellbeing, 3) experience of healthcare during the pandemic and 4) anxiety created by uncertainty about the future. Fourteen subthemes were identified, including concerns about accessing essential supplies and the importance of social support. Individuals who lived alone and were advised to shield could be profoundly negatively affected. CONCLUSIONS: This study found that there were a number of aspects of living with a LTC during the pandemic that had a significant impact on mental health and well-being. There should be focus on how best to provide practical and social support to people with LTCs during a pandemic, particularly if they have to shield or isolate.

Implicit Bias and the Association of Redaction of Identifiers With Residency Application Screening Scores.

IMPORTANCE: Diversity in the ophthalmology profession is important when providing care for an increasingly diverse patient population. However, implicit bias may inadvertently disadvantage underrepresented applicants during resident recruitment and selection. OBJECTIVE: To evaluate the association of the redaction of applicant identifiers with the review scores on ophthalmology residency applications as an intervention to address implicit bias. DESIGN, SETTING, AND PARTICIPANTS: In this quality improvement study, 46 faculty members reviewed randomized sets of 462 redacted and unredacted applications from a single academic institution during the 2019-2020 ophthalmology residency application cycle. INTERVENTIONS: Applications electronically redacted for applicant identifiers, including name, sex or gender, race and ethnicity, and related terms. MAIN OUTCOMES AND MEASURES: The main outcome was the distribution of scores on redacted and unredacted applications, stratified by applicant's sex, underrepresentation in medicine (URiM; traditionally comprising American Indian or Alaskan Native, Black, and Hispanic individuals) status, and international medical graduate (IMG) status; the application score ß coefficients for redaction and the applicant and reviewer characteristics were calculated. Applications were scored on a scale of 1 to 9, where 1 was the best score and 9 was the worst score. Scores were evaluated for a significant difference based on redaction among female, URiM, and IMG applicants. Linear regression was used to evaluate the adjusted association of redaction, self-reported applicant characteristics, and reviewer characteristics with scores on ophthalmology residency applications. RESULTS: In this study, 277 applicants (60.0%) were male and 71 (15.4%) had URiM status; 32 faculty reviewers (69.6%) were male and 2 (0.4%) had URiM status. The distribution of scores was similar for redacted vs unredacted applications, with no difference based on sex, URiM status, or IMG status. Applicant's sex, URiM status, and IMG status had no association with scores in multivariable analysis (sex, ß = -0.08; 95% CI, -0.32 to 0.15; P = .26; URiM status, ß = -0.03; (95% CI, -0.36 to 0.30; P = .94; and IMG status, ß = 0.39; 95% CI, -0.24 to 1.02; P = .35). In adjusted regression, redaction was not associated with differences in scores (ß = -0.06 points on a 1-9 scale; 95% CI, -0.22 to 0.10 points; P = .48). Factors most associated with better scores were attending a top 20 medical school (ß = -1.06; 95% CI, -1.37 to -0.76; P < .001), holding an additional advanced degree (ß = -0.86; 95% CI, -1.22 to -0.50; P < .001), and having a higher United States Medical Licensing Examination Step 1 score (ß = -0.35 per 10-point increase; 95% CI, -0.45 to -0.26; P < .001). CONCLUSIONS AND RELEVANCE: This quality improvement study did not detect an association between the redaction of applicant characteristics on ophthalmology residency applications and the application review scores among underrepresented candidates at this institution. Although the study may not have been powered adequately to find a difference, these findings suggest that the association of redaction with application review scores may be preempted by additional approaches to enhance diversity, including pipeline programs, implicit bias training, diversity-centered culture and priorities, and targeted applicant outreach. Programs may adapt this study design to probe their own application screening biases and track over time before-and-after bias-related interventions.

X-ray absorption of cold gas: Simulating interstellar molecular clouds in the laboratory.

Galactic and extragalactic sources produce x-rays that are often absorbed by molecules and atoms in giant molecular clouds (GMCs), which provides valuable information about their composition and physical state. We mimic this phenomenon with a laboratory Z-pinch x-ray source, which is impinged on neutral molecular gas. This technique produces a soft x-ray pseudocontinuum using a pulsed-current generator. The absorbing gas is injected from a 1-cm-long planar gas-puff without any window or vessel along the line of sight. An x-ray spectrometer with a resolving power of λ/Δλ∼420, comparable to that of astrophysical space instruments, records the absorbed spectra. This resolution clearly resolves the molecular lines from the atomic lines, thus motivating the search for a molecular signature in astrophysical x-ray spectra. The experimental setup enables different gas compositions and column densities. K-shell spectra of CO_{2}, N_{2}, and O_{2} reveal a plethora of absorption lines and photoelectric edges measured at molecular column densities between ∼10^{16} and 10^{18} cm^{-2} typical of GMCs. We find that the population of excited states, contributing to the edge, increases with gas density.

Fracture-induced pain-like behaviours in a femoral fracture mouse model.

This study is the first comprehensive characterisation of the pain phenotype after fracture using both evoked and naturalistic behaviours in adult male and ovariectomised female mice. It also shows that an anti-nerve growth factor (NGF) therapy could be considered to reduce pain after fracture surgery. INTRODUCTION: Bone fractures are common due to the ageing population and very painful even after healing. The phenotype of this pain is still poorly understood. We aimed to characterise it in a femoral fracture model in mice. METHODS: We employed both adult male, and female ovariectomised (OVX) mice to mimic osteoporotic fractures. Mice underwent a unilateral femoral fracture maintained by an external fixator or a sham surgery. Pain behaviours, including mechanical and thermal sensitivity, weight bearing and LABORAS, were measured from baseline to 6 weeks after fracture. The effect on pain of an antibody against nerve growth factor (anti-NGF) was assessed. Changes in nerve density at the fracture callus were analysed by immunohistochemistry. RESULTS: Following surgery, all groups exhibited high levels of invoked nociception. Mechanical and thermal hyperalgesia were observed from 1 week after surgery, with nociceptive sensitization in the fracture group maintained for the 6 weeks, whereas it resolved in the sham group after 3 weeks. OVX induced reduction in pain thresholds, which was maintained after fracture. The frequency of naturalistic behaviours did not change between groups. Anti-NGF administered before and weekly after surgery alleviated fracture-induced mechanical nociception. The density of nerve fibres in the fracture callus was similar in all groups 6 weeks after surgery. CONCLUSIONS: Fractures in rodent models are highly painful in both sexes. This pain-like phenotype is prolonged and should be routinely considered in fracture healing studies as it can affect the study outcome. The anti-NGF alleviates fracture-induced mechanical pain.

Young adult cancer survivors' experience of taking part in a 12-week exercise referral programme: a qualitative study of the Trekstock RENEW initiative.

PURPOSE: There is emerging evidence that physical activity interventions have the potential to improve the physical function and psychosocial well-being of young adult cancer survivors. However, most existing interventions for young adult cancer survivors have been delivered in an in-patient hospital setting. The purpose of this study is to explore young adult cancer survivors' (YACS) experiences of the RENEW programme, a 12-week community-based exercise referral scheme delivered by Trekstock, a UK-based cancer charity. METHODS: Sixteen semi-structured interviews were conducted with YACS (mean age, 33 years; 87.5% female) who participated in the RENEW exercise referral programme. Each interview followed the same semi-structured interview guide which asked participants about their experiences of the RENEW programme and their ideas for the future development of the scheme. Data was audio-recorded, transcribed full verbatim and analysed using framework analysis. RESULTS: YACs predominantly chose to take part in the RENEW programme as a means to improve their health and overcome cancer related impairments (e.g. fatigue, loss of strength, low body confidence). The offer of one-to-one tailored support and unlimited gym access was often cited as a factor which motivated enrolment. Overall, YACS experience of the programme was positive with many describing improvements in physical function and general well-being. Barriers to participating in the programme included sign-off from clinicians prior to enrolment, travelling to the gym and fear of exercising alone. CONCLUSIONS: Exercise referral schemes are acceptable to YACS and provide a promising opportunity for young people with cancer to improve their physical and psychosocial health through physical activity.

Microarray analysis of primary epithelial and fibroblast cells in chronic rhinosinusitis without nasal polyps.

BACKGROUND: Chronic rhinosinusitis is an inflammatory condition with an as yet unknown pathophysiology. We aimed to detect clusters of differentially regulated genes in the epithelial and fibroblast cells of patients with Chronic Rhinosinusitis without nasal polyposis (CRSsNP) and healthy controls. METHODOLOGY: Carefully phenotyped CRSsNP and healthy control participants were recruited. Primary cultures of isolated epithelial and fibroblast cells were established. Whole transcriptome analysis of the cells was performed using microarrays and replicated with quantitative RT-PCR and immunohistochemistry. RESULTS: Fibroblast cells from CRSsNP patients showed a significant upregulation (more than 2x) of the transcription factor NFE2L3 when compared to healthy controls by microarray with multiple hypothesis testing correction, qRT-PCR and immunohistochemistry. CONCLUSIONS: Here we have utilized microarray analysis to search for differentially expressed genes in isolated patient derived epithelial and fibroblast cells. The transcription factor NFE2L3 has been shown to be upregulated in fibroblast cells consistent with increasing evidence that fibroblasts play a key role in tissue specific inflammation within the paranasal sinuses.

Trekstock RENEW: evaluation of a 12-week exercise referral programme for young adult cancer survivors delivered by a cancer charity.

PURPOSE: To evaluate the uptake and effect of RENEW, a 12-week exercise referral programme for young adult cancer survivors delivered by Trekstock, a UK-based cancer charity. METHODS: The RENEW programme provides one-to-one individually tailored support from a level-4 cancer-rehabilitation-qualified gym instructor, free gym membership and access to information resources online. Objective and self-report data on cardiorespiratory function, strength, body composition, fatigue, sleep quality and general health-related quality of life (HRQoL) was collected from participants before the programme (week 0), immediately after (week 12) and 1 month later (week 16). RESULTS: Forty-eight young adults (83% female; mean age, 29 years) with a history of cancer took part within the 12-week programme and completed the evaluation measures. Physical activity (PA) levels significantly increased following the programme and remained raised at follow-up. Improvements in physical function were significant: peak expiratory flow (mean change, 30.96, p = 0.003), sit-and-reach test (mean change, 6.55 ± 4.54, p < 0.0001), and 6-mine-walk test (mean change, 0.12 ± 0.04, p < 0.0001). No significant changes in BMI, weight or muscle mass were observed. Improvements in fatigue, sleep and HRQoL were observed across the programme and at follow-up (mean change, weeks 0-16; 8.04 ± 1.49 p < 0.01; 1.05 ± 0.49 p < 0.05; and - 0.9 ± 0.46 p = 0.051, respectively). Changes in self-efficacy to exercise and motivations to exercise were not observed at 12 weeks or at follow-up. CONCLUSIONS: Results suggest that the RENEW exercise referral programme has a positive impact upon some domains of physical function and well-being among young adult cancer survivors. IMPLICATION FOR CANCER SURVIVORS: Exercise referral programmes delivered by charity organisations are one means by which PA behaviour change support may be widely disseminated to young adult cancer survivors. Health professionals and charitable bodies specialising in the care of young adults with cancer should look to address factors which prevent engagement and uptake of 'real-world' PA interventions such as the RENEW programme.

The health behaviour status of teenage and young adult cancer patients and survivors in the United Kingdom.

PURPOSE: The primary aim of this study was to investigate the health behaviour status of teenage and young adult (TYA) cancer patients and survivors; the secondary aim was to determine if TYA cancer patients and survivors health behaviour differs to general population controls. METHODS: Two hundred sixty-seven young people with cancer (n =83 cancer patients receiving active treatment: n =174 cancer survivors, 57.1% >1 year since treatment completion) and 321 controls completed a health and lifestyle questionnaire which included validated measures of physical activity (PA) (Godin Leisure Time Exercise Questionnaire), diet (Dietary Instrument for Nutrition Education, DINE), smoking status, and alcohol consumption (AUDIT-C). RESULTS: General population controls and cancer survivors were more likely to meet current (PA) recommendations (p <0.001) than TYA cancer patients undergoing treatment (54.8% vs 52.3% vs 30.1%, respectively). Less than 40% of young people with cancer and controls met fat intake, sugar intake, fibre intake or current fruit and vegetable recommendations. TYA cancer survivors were more likely to report binge drinking than controls (OR=3.26, 95% CI 2.12-5.02, p <0.001). Very few young people with in the study were current smokers. The majority of TYA cancer patients and survivors reported a desire to make positive changes to their health behaviour. CONCLUSION: Consideration should be given to whether existing health behaviour change interventions which have demonstrated positive effects among the general TYA population could be adapted for young people with cancer.

Potential use of stem cells for fertility preservation.

BACKGROUND: Infertility and gonadal dysfunction can result from gonadotoxic therapies, environmental exposures, aging, or genetic conditions. In men, non-obstructive azoospermia (NOA) results from defects in the spermatogenic process that can be attributed to spermatogonial stem cells (SSC) or their niche, or both. While assisted reproductive technologies and sperm banking can enable fertility preservation (FP) in men of reproductive age who are at risk for infertility, FP for pre-pubertal patients remains experimental. Therapeutic options for NOA are limited. The rapid advance of stem cell research and of gene editing technologies could enable new FP options for these patients. Induced pluripotent stem cells (iPSC), SSC, and testicular niche cells, as well as mesenchymal stromal cells (aka medicinal signaling cells, MSCs), have been investigated for their potential use in male FP strategies. OBJECTIVE: Here, we review the benefits and challenges for three types of stem cell-based approaches under investigation for male FP, focusing on the role that promising sources of MSC derived from human umbilical cord, specifically human umbilical cord perivascular cells (HUCPVC), could fulfill. These approaches are as follows: 1. isolation and ex vivo expansion of autologous SSC for in vivo transplantation or in vitro spermatogenesis; 2. in vitro differentiation toward germ cell and testicular somatic cell lineages using autologous SSC, or stem cells such iPSC or MSC; and 3. protection or regeneration of the spermatogenic niche after gonadotoxic insults in vivo. CONCLUSION: Our studies suggest that HUCPVC are promising sources of cells that could be utilized in multiple aspects of male FP strategies.

Sexual orientation in transgender individuals: results from the longitudinal ENIGI study.

Transgender people and their next-of-kin may request information on sexual orientation and preferred partners during hormonal affirming process. Although previous research on sexual orientation in transgender people is extensive, this literature may already be outdated and/or the methodology of studies assessing sexual orientation may fall short. This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Gender role and preferred partner in sexual fantasies, sexual orientation and gender of current sexual partner were assessed at baseline (initiation of HT) and every follow-up visit. Data from 469 transgender women (TW) and 433 transgender men (TM) were analyzed cross-sectionally and prospectively. At baseline, more than half reported having no partner (35% of TW, 47% of TM). After 12 months, more than half reported having a partner (59% of TW, 56% of TM), with no changes between one and three years of HT. The majority of TM preferred a female partner, TW preferred male and female partners. The sexual identity of their partner matched their sexual orientation in >80%. Sexual orientation did not change over time. We did not observe associations with serum levels of sex steroids or gender-affirming surgery (chest or genital surgery). Sexual orientation did not change during hormonal transition and was not associated with sex steroids or surgery. Also, preferences matched the partner's sexual identity. We do not assume that changing serum levels of sex steroids is directly associated with changes in partner choice. The number of people with a current partner increased, possibly due to the indirect effects of gender-affirming care.