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IntroductionAtrial fibrillation (AF) affects approximately 2.5% of the UK population, with a risk of 1 in 3–5 individuals after the age of 45 years. The global prevalence has risen sharply in the past two decades, from 33.3 million to 59 million individuals living with AF, and is associated with stroke, heart failure and mortality. Catheter ablation is commonly used for symptomatic patients to restore normal rhythm. A recent Cochrane review of randomised clinical trials (RCTs) has demonstrated that exercise training may induce positive effects on AF burden, AF severity, exercise capacity, and quality of life. The aim was therefore to investigate the feasibility of delivering exercise-based cardiac rehabilitation for patients with AF receiving catheter ablation within usual care in the UK.Methods and analysisA two-armed feasibility RCT with embedded process evaluation will be undertaken as a phased programme of work. Patients on a waiting list for catheter ablation will be offered a referral to cardiac rehabilitation. The intervention consists of supervised exercise sessions run by a clinical exercise physiologist and psychoeducation sessions. The trial (n=60) will involve one National Health Service (NHS) research site enrolling patients to assess intervention and study design processes. Primary outcomes are recruitment rate, adherence to exercise-based cardiac rehabilitation and loss to follow-up. Semistructured interviews and focus groups with patients and clinicians will be used to gather data on the acceptability of the intervention and study procedures. Secondary outcome measures will be taken at baseline (pre-intervention), post-intervention and at 6-month follow-up and will consist of AF burden, AF recurrence, quality of life, exercise capacity measured by peak oxygen consumption and echocardiographic parameters.Ethics and disseminationThe trial was approved in the UK by the Northwest-Preston Research Ethics Committee (24/NW/0061; IRAS project ID: 330155). Results will be published in peer-reviewed journals and presented at national and international scientific meetings, and summaries will be communicated to participants.Trial registration numberClinicaltrials.gov identifier: NCT06401148.

Human beings are an active component of every terrestrial ecosystem on Earth. Although our local impact on the evolution of these ecosystems has been undeniable and extensively documented, it remains unclear precisely how our activities are altering them, in part because ecosystems are dynamic systems structured by complex, non-linear feedback processes and cascading effects. We argue that it is only by studying human–environment interactions over timescales that greatly exceed the lifespan of any individual human (i.e., the deep past or longue durée), we can hope to fully understand such processes and their implications. In this article, we identify some of the key challenges faced in integrating long-term datasets with those of other areas of sustainability science, and suggest some useful ways forward. Specifically, we (a) highlight the potential of the historical sciences for sustainability science, (b) stress the need to integrate theoretical frameworks wherein humans are seen as inherently entangled with the environment, and (c) propose formal computational modelling as the ideal platform to overcome the challenges of transdisciplinary work across large, and multiple, geographical and temporal scales. Our goal is to provide a manifesto for an integrated scientific approach to the study of socio-ecological systems over the long term.

Myeloablative conditioning regimens given prior to hematopoietic stem cell transplantation (HSCT) frequently cause permanent sterility in men. In patients with sickle cell disease (SCD) we use a nonmyeloablative regimen with sirolimus, alemtuzumab, and low-dose total-body irradiation (300 centigrays) with gonadal shielding preceding allogeneic HSCT. We report here the restoration of azoospermia in a patient with SCD after allogeneic HSCT. We discuss the impact of our patient's underlying chronic medical conditions and the therapies he had received (frequent blood transfusions, iron chelating drugs, ribavirin, hydroxyurea, opioids), as well as the impact of the nonmyeloablative conditioning regimen on male gonadal function, and we review the literature on this topic. We determined the patient's reproductive hormonal values and his semen parameters before, during, and after HSCT and infertility treatment. In addition, we routinely measured his serum laboratory parameters pertinent to SCD and infertility, such as iron and ferritin levels. A karyotype analysis was performed to assess the potential presence of Klinefelter syndrome. Finally, imaging studies of the patient's brain and testes were done to rule out further underlying pathology. A 42-year-old man with SCD, transfusional iron overload, and hepatitis C underwent a nonmyeloablative allogeneic HSCT. One year later he desired to father a child but was found to be azoospermic in the context of hypogonadotropic hypogonadism. Restoration of fertility was attempted with human chorionic gonadotropin (2,000 IU) plus human menopausal gonadotropin (75 IU follicle-stimulating hormone) injected subcutaneously 3 times weekly. Within 6 months of treatment, the patient's serum calculated free testosterone value normalized, and his sperm count and sperm motility improved. After 10 months, he successfully initiated a pregnancy through intercourse. The pregnancy was uncomplicated, and a healthy daughter was delivered naturally at term. Despite exposure to several gonadotoxins, transfusional iron overload and nonmyeloablative conditioning with radiation causing severe testicular atrophy suggesting extensive damage to seminiferous tubules and possibly Leydig cells, gonadotropins were efficacious in restoring our patient's reproductive capability.

Human beings are an active component of every terrestrial ecosystem on Earth. Although our local impact on the evolution of these ecosystems has been undeniable and extensively documented, it remains unclear precisely how our activities are altering them, in part because ecosystems are dynamic systems structured by complex, non-linear feedback processes and cascading effects. We argue that it is only by studying human–environment interactions over timescales that greatly exceed the lifespan of any individual human (i.e., the deep past or longue durée), we can hope to fully understand such processes and their implications. In this article, we identify some of the key challenges faced in integrating long-term datasets with those of other areas of sustainability science, and suggest some useful ways forward. Specifically, we (a) highlight the potential of the historical sciences for sustainability science, (b) stress the need to integrate theoretical frameworks wherein humans are seen as inherently entangled with the environment, and (c) propose formal computational modelling as the ideal platform to overcome the challenges of transdisciplinary work across large, and multiple, geographical and temporal scales. Our goal is to provide a manifesto for an integrated scientific approach to the study of socio-ecological systems over the long term.