Pre-treatment fertility preservation and post-treatment reproduction in long-term survivors of adolescent and young adult (AYA) cancer

Purpose: To describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young adult (AYA) (age, 18–39 years) cancer. Methods: This study included n = 1457 male and n = 2112 female long-term survivors (M age = 43–45 years; 5–22 years from diagnosis) who provided self-report. Clinical data were supplied by the Netherlands Cancer Registry.Results: Most male survivors (72.7%) recalled fertility-related consultations and 22.6% completed sperm cryopreservation. Younger age (OR = 2.8; 95%CI [2.2–3.6]), not having children (OR = 5.0; 95%CI [3.2–7.7]), testicular cancer or lymphoma/leukemia (OR = 2.8/2.5 relative to “others”), and more intense treatments (OR = 1.5; 95%CI [1.1–2.0]) were associated with higher cryopreservation rates. Time since diagnosis had no effect. Of men who cryopreserved, 12.1% utilized assisted reproductive technologies (ART). Most men (88.5%) felt their diagnosis did not affect their reproductive goals, but 7.6% wanted no (additional) children due to cancer. Half of female survivors (55.4%; n = 1171) recalled fertility-related consultations. Rates of cryopreservation were very low (3.6%), but increased after 2013 when oocyte cryopreservation became non-experimental. Of women who cryopreserved, 13.2% successfully utilized ART. Most women (74.8%) experienced no effects of cancer on reproductive goals, but 17.8% wanted no (additional) children due to cancer. Conclusions: Cryopreservation in men varied by patient/clinical factors and was very low in women, but data of more recently treated females are needed. Utilizing cryopreserved material through ART was rare, which questions its cost-effectiveness, but it may enhance survivors’ well-being. Implications for Cancer Survivors: The extent to which cryopreservation positively affects survivors’ well-being remains to be tested. Moreover, effects of cancer on reproductive goals require further attention, especially in women who refrain from having children due to cancer.</p

Long-Term Survival Associated with Direct Oral Feeding Following Minimally Invasive Esophagectomy:Results from a Randomized Controlled Trial (NUTRIENT II)

Advancements in perioperative care have improved postoperative morbidity and recovery after esophagectomy. The direct start of oral intake can also enhance short-term outcomes following minimally invasive Ivor Lewis esophagectomy (MIE-IL). Subsequently, short-term outcomes may affect long-term survival. This planned sub-study of the NUTRIENT II trial, a multicenter randomized controlled trial, investigated the long-term survival of direct versus delayed oral feeding following MIE-IL. The outcomes included 3- and 5-year overall survival (OS) and disease-free survival (DFS), and the influence of complications and caloric intake on OS. After excluding cases of 90-day mortality, 145 participants were analyzed. Of these, 63 patients (43.4%) received direct oral feeding. At 3 years, OS was significantly better in the direct oral feeding group (p = 0.027), but not at 5 years (p = 0.115). Moreover, 5-year DFS was significantly better in the direct oral feeding group (p = 0.047) and a trend towards improved DFS was shown at 3 years (p = 0.079). Postoperative complications and caloric intake on day 5 did not impact OS. The results of this study show a tendency of improved 3-year OS and 5-year DFS, suggesting a potential long-term survival benefit in patients receiving direct oral feeding after esophagectomy. However, the findings should be further explored in larger future trials.</p

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention in adolescent and young adult (AYA) cancer survivors:results from the SURVAYA study

Purpose: For adolescent and young adult (AYA) cancer survivors with a good prognosis, having a healthy lifestyle prevents morbidity and mortality after treatment. The aim of this study was to investigate the prevalence of (un)healthy lifestyle behaviors and related determinants in AYA cancer survivors. Methods: A population-based, cross-sectional study was performed among long-term (5–20 years) AYA cancer survivors (18–39 years old at diagnosis) registered within the Netherlands Cancer Registry. Self-reported questionnaires data about health behaviors were used to calculate the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) adherence score. Associations between the score and clinical/sociodemographic determinants of (un)healthy behaviors were investigated using logistic regression models. Results: The mean WCRF/AICR score was low to moderate, 3.8 ± 1.2 (0.5–7.0) (n = 3668). Sixty-one percent adhered to “limit the consumption of sugar sweetened drinks,” 28% to “be a healthy weight,” 25% to “fruit and vegetable consumption,” and 31% to “limit alcohol consumption.” Moderate and high adherence were associated with being a woman (ORmoderate = 1.46, 95% CI = 1.14–1.85, and ORhigh = 1.87, 95% CI = 1.46–2.4) and highly educated (ORmoderate = 1.54, 95% CI = 1.30–1.83, and ORhigh = 1.87, 95% CI = 1.46–2.4). Low adherence was associated with smoking (ORmoderate = 0.68, 95% CI = 0.50–0.92, and ORhigh = 0.30, 95% CI = 0.21–0.44) and diagnosis of germ cell tumor (ORmoderate = 0.58, 95% CI = 0.39–0.86, and ORhigh = 0.45, 95% CI = 0.30–0.69). Conclusions: Adherence to the 2018 WCRF/AICR lifestyle recommendations was low to moderate, especially regarding body weight, fruit, vegetables, and alcohol consumption. Men, current smokers, lower-educated participants, and/or those diagnosed with germ cell tumors were less likely to have a healthy lifestyle. Implications for Cancer Survivors: Health-promotion programs (e.g., age-specific tools) are needed, focusing on high-risk groups.</p

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention in adolescent and young adult (AYA) cancer survivors:results from the SURVAYA study

Purpose: For adolescent and young adult (AYA) cancer survivors with a good prognosis, having a healthy lifestyle prevents morbidity and mortality after treatment. The aim of this study was to investigate the prevalence of (un)healthy lifestyle behaviors and related determinants in AYA cancer survivors. Methods: A population-based, cross-sectional study was performed among long-term (5–20 years) AYA cancer survivors (18–39 years old at diagnosis) registered within the Netherlands Cancer Registry. Self-reported questionnaires data about health behaviors were used to calculate the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) adherence score. Associations between the score and clinical/sociodemographic determinants of (un)healthy behaviors were investigated using logistic regression models. Results: The mean WCRF/AICR score was low to moderate, 3.8 ± 1.2 (0.5–7.0) (n = 3668). Sixty-one percent adhered to “limit the consumption of sugar sweetened drinks,” 28% to “be a healthy weight,” 25% to “fruit and vegetable consumption,” and 31% to “limit alcohol consumption.” Moderate and high adherence were associated with being a woman (ORmoderate = 1.46, 95% CI = 1.14–1.85, and ORhigh = 1.87, 95% CI = 1.46–2.4) and highly educated (ORmoderate = 1.54, 95% CI = 1.30–1.83, and ORhigh = 1.87, 95% CI = 1.46–2.4). Low adherence was associated with smoking (ORmoderate = 0.68, 95% CI = 0.50–0.92, and ORhigh = 0.30, 95% CI = 0.21–0.44) and diagnosis of germ cell tumor (ORmoderate = 0.58, 95% CI = 0.39–0.86, and ORhigh = 0.45, 95% CI = 0.30–0.69). Conclusions: Adherence to the 2018 WCRF/AICR lifestyle recommendations was low to moderate, especially regarding body weight, fruit, vegetables, and alcohol consumption. Men, current smokers, lower-educated participants, and/or those diagnosed with germ cell tumors were less likely to have a healthy lifestyle. Implications for Cancer Survivors: Health-promotion programs (e.g., age-specific tools) are needed, focusing on high-risk groups.</p

Oscillations of the magnetic polarization in a Kondo impurity at finite magnetic fields

The electronic properties of a Kondo impurity are investigated in a magnetic field using linear response theory. The distribution of electrical charge and magnetic polarization are calculated in real space. The (small) magnetic field does not change the charge distribution. However, it unmasks the Kondo cloud. The (equal) weight of the d-electron components with their magnetic moment up and down is shifted and the compensating s-electron clouds don't cancel any longer (a requirement for an experimental detection of the Kondo cloud). In addition to the net magnetic polarization of the conduction electrons an oscillating magnetic polarization with a period of half the Fermi wave length is observed. However, this oscillating magnetic polarization does not show the long range behavior of Rudermann-Kittel-Kasuya-Yosida oscillations because the oscillations don't extend beyond the Kondo radius. They represent an internal electronic structure of the Kondo impurity in a magnetic field. PACS: 75.20.Hr, 71.23.An, 71.27.+

Chronic kidney disease ten years after pediatric allogeneic hematopoietic stem cell transplantation

Chronic kidney disease (CKD) is an important sequela of hematopoietic stem cell transplantation (HSCT), but data regarding CKD after pediatric HSCT are limited. In this single center cohort study, we evaluated the estimated glomerular filtration rate (eGFR) dynamics, proteinuria and hypertension in the first decade after HSCT and assessed risk factors for CKD in 216 pediatric HSCT survivors, transplanted 2002-2012. The eGFR decreased from a median of 148 to 116 ml/min/1.73 m(2) between pre-HSCT to ten years post-HSCT. CKD (KDIGO stages G2 or A2 or more; eGFR under 90 ml/min/1.73 m(2) and/or albuminuria) occurred in 17% of patients. In multivariate analysis, severe prolonged stage 2 or more acute kidney injury (AKI), with an eGFR under 60ml/min/1.73 m(2) and duration of 28 days or more, was the main risk factor for CKD (hazard ratio 9.5, 95% confidence interval 3.4-27). Stage 2 or more AKI with an eGFR of 60ml/min/1.73 m(2) or more and KDIGO stage 2 or more AKI with eGFR under 60ml/min/1.73 m(2) but recovery within 28 days were not associated with CKD. Furthermore, hematological malignancy as HSCT indication was an independent risk factor for CKD. One third of patients had both CKD criteria, one third had isolated eGFR reduction and one third only had albuminuria. Hypertension occurred in 27% of patients with CKD compared to 4.4% of patients without. Tubular proteinuria was present in 7% of a subgroup of 71 patients with available beta 2-microglobulinuria. Thus, a significant proportion of pediatric HSCT recipients developed CKD within ten years. Our data stress the importance of structural long-term monitoring of eGFR, urine and blood pressure after HSCT to identify patients with incipient CKD who can benefit from nephroprotective interventions.Diabetes mellitus: pathophysiological changes and therap

Large-amplitude driving of a superconducting artificial atom: Interferometry, cooling, and amplitude spectroscopy

Superconducting persistent-current qubits are quantum-coherent artificial atoms with multiple, tunable energy levels. In the presence of large-amplitude harmonic excitation, the qubit state can be driven through one or more of the constituent energy-level avoided crossings. The resulting Landau-Zener-Stueckelberg (LZS) transitions mediate a rich array of quantum-coherent phenomena. We review here three experimental works based on LZS transitions: Mach-Zehnder-type interferometry between repeated LZS transitions, microwave-induced cooling, and amplitude spectroscopy. These experiments exhibit a remarkable agreement with theory, and are extensible to other solid-state and atomic qubit modalities. We anticipate they will find application to qubit state-preparation and control methods for quantum information science and technology.Comment: 13 pages, 5 figure

The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histologic progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neoangiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution toward an IDHwt-like phenotype.</p

Dense Stellar Populations: Initial Conditions

This chapter is based on four lectures given at the Cambridge N-body school "Cambody". The material covered includes the IMF, the 6D structure of dense clusters, residual gas expulsion and the initial binary population. It is aimed at those needing to initialise stellar populations for a variety of purposes (N-body experiments, stellar population synthesis).Comment: 85 pages. To appear in The Cambridge N-body Lectures, Sverre Aarseth, Christopher Tout, Rosemary Mardling (eds), Lecture Notes in Physics Series, Springer Verla

The long-term survival chances of young massive star clusters

We review the long-term survival chances of young massive star clusters (YMCs), hallmarks of intense starburst episodes often associated with violent galaxy interactions. We address the key question as to whether at least some of these YMCs can be considered proto-globular clusters (GCs), in which case these would be expected to evolve into counterparts of the ubiquitous old GCs believed to be among the oldest galactic building blocks. In the absence of significant external perturbations, the key factor determining a cluster's long-term survival chances is the shape of its stellar initial mass function (IMF). It is, however, not straightforward to assess the IMF shape in unresolved extragalactic YMCs. We discuss in detail the promise of using high-resolution spectroscopy to make progress towards this goal, as well as the numerous pitfalls associated with this approach. We also discuss the latest progress in worldwide efforts to better understand the evolution of entire cluster systems, the disruption processes they are affected by, and whether we can use recently gained insights to determine the nature of at least some of the YMCs observed in extragalactic starbursts as proto-GCs. We conclude that there is an increasing body of evidence that GC formation appears to be continuing until today; their long-term evolution crucially depends on their environmental conditions, however.Comment: invited refereed review article; ChJA&A, in press; 33 pages LaTeX (2 postscript figures); requires chjaa.cls style fil