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Introduction Talking about illness experience can be challenging for adolescents and young adults (AYAs) with cancer. Visual tools, in addition to spoken language, might make this easier, such as rich pictures and photovoice. We aimed to obtain a comprehensive view of the cancer experience of AYAs by using rich pictures and photovoice. Methods AYAs (18–35 years old) who had any type of cancer, or were in remission from cancer, were eligible. AYAs drew rich pictures about their experience of living with cancer and explained these during subsequent interviews. Some of the AYAs also participated in photovoice and spent two days with a photographer to make photos about their illness experience. Rich pictures and photos were first analyzed separately, using open coding, after which the identified themes were compared. Results Twelve AYAs made rich pictures (RPs), of whom seven also participated in photovoice. The two most predominant themes emerging from the data were struggles related to the future and defining one’s identity. The AYAs expressed concerns for the future related to relationships, education, and employment. Relating to defining one’s identity, many AYAs expressed that the cancer had a negative impact on their body- and self-image. The main themes were visible in the RPs as well as in the photovoice; however, subtle differences in sub-themes were found. Conclusions We found that cancer has an effect on many aspects of AYAs’ lives. Further research on how the identified themes play a role in the lives of AYAs with cancer is needed.

PDF file - 732K, A. CLL cells were stimulated with CD40L for 72 hrs. After detachment, cells were incubated with 0.1 �M of ABT-737. Protein lysates were probed for Mcl-1, Bfl-1, Noxa and �-actin. B. Densitometric analysis of Mcl-1/ �-actin levels of fourteen CLL samples is shown. Bars represent the mean � SEM, *** P < .001.

Purpose: Chronic lymphocytic leukemia (CLL) cells in lymph nodes (LN), from which relapses are postulated to originate, display an antiapoptotic profile in contrast to CLL cells from peripheral blood (PB). The BH3 mimetic ABT-737 antagonizes the antiapoptotic proteins Bcl-XL and Bcl-2 but not Mcl-1 or Bfl-1. Previously, it was shown that CD40-stimulated CLL cells were resistant to ABT-737. We aimed to define which antiapoptotic proteins determine resistance to ABT-737 in CLL and whether combination of known antileukemia drugs and ABT-737 was able to induce apoptosis of CD40-stimulated CLL cells.Experimental Design: To mimic the LN microenvironment, PB lymphocytes of CLL patients were cultured on feeder cells expressing CD40L and treated with ABT-737 with or without various drugs. In addition, we carried out overexpression or knockdown of pro- and antiapoptotic proteins in immortalized primary B cells.Results: Upon CD40 stimulation patient-specific variations in ABT-737 sensitivity correlated with differences in levels of Mcl-1 and its antagonist Noxa. Knockdown of Noxa, as well as Mcl-1 overexpression, corroborated the importance of the Noxa/Mcl-1 ratio in determining the response to ABT-737. Inhibition of NF-κB resulted in increased Noxa levels and enhanced sensitivity to ABT-737. Interestingly, increasing the Noxa/Mcl-1 ratio, by decreasing Mcl-1 (dasatinib and roscovitine) or increasing Noxa levels (fludarabine and bortezomib), resulted in synergy with ABT-737.Conclusions: Thus, the Noxa/Mcl-1 balance determines sensitivity to ABT-737 in CD40-stimulated CLL cells. These data provide a rationale to investigate the combination of drugs which enhance the Noxa/Mcl-1 balance with ABT-737 to eradicate CLL in chemoresistant niches. Clin Cancer Res; 18(2); 487–98. ©2011 AACR.

PDF file - 866K, CLL cells were stimulated with CD40L for 48 hrs. After detachment, cells were incubated with 10 �M or 100 �M fludarabine � Q-VD (12,5 �M), � NAC (5mM). Protein lysates were probed for Noxa, Mcl-1 and �-actin.

PDF file - 986K, A. ABT-737 resistant CLL cells were stimulated with CD40L for 72 hours (n=4). The black line shows apoptosis levels from CLL cells detached from the feeder layer and subsequently treated with different concentrations of ABT-737 (0.001-10 �M). CLL cells treated with ABT-737 in the presence of CD40-expressing feeder cells are depicted in gray. B. ABT-737 sensitive CD40-stimulated CLL cells treated with ABT-737 after detachment from feeder cells (black line) and while continuously in contact with CD40-expressing feeder cells (gray line) (n=5).

PDF file - 620K, CLL cells were stimulated with CD40L for the indicated time (24, 48 and 72 hrs). Western blots of Bfl-1 were quantified with Odyssey software in both ABT-737 sensitive (n=4) and ABT-737 resistant (n=4) CD40-stimulated CLL cells. Bars represent the mean � SEM.

PDF file - 793K, Nucleofection with Noxa siRNA or control siRNA was performed on CLL cells in the presence or absence of the proteasoom inhibitor GSI. Protein lysates were probed for Mcl-1, Noxa and �-actin. As a control, lysates of untransfected CLL cells in the presence or absence of GSI are shown.

Terrace-sized, single-orientation graphene can be grown on top of a carbon buffer layer on silicon carbide by thermal decomposition. Despite its homogeneous appearance, a surprisingly large variation in electron transport properties is observed. Here, we employ Aberration-Corrected Low-Energy Electron Microscopy (AC-LEEM) to study a possible cause of this variability. We characterize the morphology of stacking domains between the graphene and the buffer layer of high-quality samples. Similar to the case of twisted bilayer graphene, the lattice mismatch between the graphene layer and the buffer layer at the growth temperature causes a moir\'e pattern with domain boundaries between AB and BA stackings. We analyze this moir\'e pattern to characterize the relative strain and to count the number of edge dislocations. Furthermore, we show that epitaxial graphene on silicon carbide is close to a phase transition, causing intrinsic disorder in the form of co-existence of anisotropic stripe domains and isotropic trigonal domains. Using adaptive geometric phase analysis, we determine the precise relative strain variation caused by these domains. We observe that the step edges of the SiC substrate influence the orientation of the domains and we discuss which aspects of the growth process influence these effects by comparing samples from different sources.

In van der Waals (vdW) materials, the electron mean free path (MFP) is largely influenced by the discrete states in the unoccupied band structure. So far, the influence of these states has only been measured in graphene, while all measurements on other vdW materials lack energy resolution. Here, we present reflection and transmission spectra of freestanding, few-layered molybdenum disulfide (MoS2) samples in the 0-55 eV electron range. Our measurements reveal states of enhanced electron transmissivity above the vacuum level, that correspond to the (unoccupied) density of states. We also show a full quantum-mechanical calculation that confirms a good understanding of the elastic scattering in MoS2. A model is developed to extract the inelastic MFP spectrum, which is a measure of the inelastic scattering cross section. As MoS2 is a complicated system of different atomic planes, we expect that our methods generalize well to other van der Waals materials and heterostacks thereof.

The current review provides a literature overview of studies assessing the oncological and fertility outcomes of treatment with neo-adjuvant chemotherapy followed by fertility-sparing surgery in patients with cervical cancer >2 cm. Six cohort studies were included showing severe heterogeneity regarding patient selection, chemotherapy regimen, and surgical approach. In total, 111 patients were studied, with overall favorable characteristics. Patients were on average 29 years old, had a tumor of 36 mm, no lymph node metastasis, and response to chemotherapy. In approximately 5-year follow-up, the recurrence rate was 13% (0%-21%) and overall death rate 2.7% (0%-10%). Three patients were alive with recurrent disease (2.7% and 0%-11%). Of the 111 patients, 90 underwent successful fertility-sparing treatment (83%). Roughly one-third conceived and one-fourth had a healthy live-born child. More research is essential to determine proper selection criteria for fertility-sparing treatment of cervical cancer >2 cm and the optimal treatment management.

Anxious temperament, characterized by heightened behavioral and physiological reactivity to potential threat, is an early childhood risk factor for the later development of stress-related psychopathology. Using a well-validated nonhuman primate model, we tested the hypothesis that the prefrontal cortex (PFC) is critical in regulating the expression of primate anxiety-like behavior, as well as the function of subcortical components of the anxiety-related neural circuit. We performed aspiration lesions of a narrow ‘strip’ of the posterior orbitofrontal cortex (OFC) intended to disrupt both cortex and axons entering, exiting and coursing through the pOFC, particularly those of the uncinate fasciculus (UF), a white matter tract that courses adjacent to and through this region. The OFC is of particular interest as a potential regulatory region because of its extensive reciprocal connections with amygdala, other subcortical structures and other frontal lobe regions. We validated this lesion method by demonstrating marked lesion-induced decreases in the microstructural integrity of the UF, which contains most of the fibers that connect the ventral PFC with temporal lobe structures as well as with other frontal regions. While the lesions resulted in modest decreases in threat-related behavior, they substantially decreased metabolism in components of the circuit underlying threat processing. These findings provide evidence for the importance of structural connectivity between the PFC and key subcortical structures in regulating the functions of brain regions known to be involved in the adaptive and maladaptive expression of anxiety.

PURPOSE Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a contralateral TGCT (CTGCT). Although some studies suggest that prior treatment with platinum-based chemotherapy affects CTGCT risk, a relationship between CTGCT risk and platinum dose has not previously been assessed. We analyzed the association between the number of platinum-based chemotherapy cycles and CTGCT risk. PATIENTS AND METHODS The risk of developing a metachronous CTGCT was evaluated in a nationwide cohort of 4,755 patients diagnosed with primary TGCT in the Netherlands between 1989 and 2007. Standardized incidence ratios were computed to compare CTGCT incidence with expected TGCT on the basis of TGCT incidence in the general population. The cumulative incidence of CTGCT was estimated in the presence of death as competing risk. The effect of treatment with platinum-based chemotherapy on CTGCT risk was assessed using multivariable Cox proportional hazards regression models. RESULTS CTGCT was diagnosed in 136 patients (standardized incidence ratio, 14.6; 95% CI, 12.2 to 17.2). The cumulative incidence increased up to 20 years after primary diagnosis, reaching 3.4% (95% CI, 2.8% to 4.0%) after 20 years of follow up. The risk of developing a CTGCT decreased with age (hazard ratio [HR], 0.93; 95% CI, 0.90 to 0.96), was lower after nonseminomatous germ cell tumor (HR, 0.58; 95% CI, 0.35 to 0.96) and decreased with every additional cycle of chemotherapy (HRper cycle, 0.74; 95% CI, 0.64 to 0.85). CONCLUSION Approximately one in every 30 survivors of TGCT will develop a CTGCT, with CTGCT incidence increasing up to 20 years after a primary TGCT. Treatment with platinum-based chemotherapy shows a dose-dependent inverse association with CTGCT risk.

Stacking domain boundaries occur in Van der Waals heterostacks whenever there is a twist angle or lattice mismatch between subsequent layers. Not only can these domain boundaries host topological edge states, imaging them has been instrumental to determine local variations in twisted bilayer graphene. Here, we analyse the mechanisms causing stacking domain boundary contrast in Bright Field Low-Energy Electron Microscopy (BF-LEEM) for both graphene on SiC, where domain boundaries are caused by strain and for twisted few layer graphene. We show that when domain boundaries are between the top two graphene layers, BF-LEEM contrast is observed due to amplitude contrast and corresponds well to calculations of the contrast based purely on the local stacking in the domain boundary. Conversely, for deeper-lying domain boundaries, amplitude contrast only provides a weak distinction between the inequivalent stackings in the domains themselves. However, for small domains phase contrast, where electrons from different parts of the unit cell interfere causes a very strong contrast. We derive a general rule-of-thumb of expected BF-LEEM contrast for domain boundaries in Van der Waals materials.

Extreme ultraviolet (EUV) lithography (13.5 nm) is the newest technology that allows high-throughput fabrication of electronic circuitry in the sub-20 nm scale. It is commonly assumed that low-energy electrons (LEEs) generated in the resist materials by EUV photons are mostly responsible for the solubility switch that leads to nanopattern formation. Yet, reliable quantitative information on this electron-induced process is scarce. In this work, we combine LEE microscopy (LEEM), electron energy loss spectroscopy (EELS), and atomic force microscopy (AFM) to study changes induced by electrons in the 0–40 eV range in thin films of a state-of-the-art molecular organometallic EUV resist known as tin-oxo cage. LEEM–EELS uniquely allows to correct for surface charging and thus to accurately determine the electron landing energy. AFM postexposure analyses revealed that irradiation of the resist with LEEs leads to the densification of the resist layer because of carbon loss. Remarkably, electrons with energies as low as 1.2 eV can induce chemical reactions in the Sn-based resist. Electrons with higher energies are expected to cause electronic excitation or ionization, opening up more pathways to enhanced conversion. However, we do not observe a substantial increase of chemical conversion (densification) with the electron energy increase in the 2–40 eV range. Based on the dose-dependent thickness profiles, a simplified reaction model is proposed where the resist undergoes sequential chemical reactions, first yielding a sparsely cross-linked network and then a more densely cross-linked network. This model allows us to estimate a maximum reaction volume on the initial material of 0.15 nm3 per incident electron in the energy range studied, which means that about 10 LEEs per molecule on average are needed to turn the material insoluble and thus render a pattern. Our observations are consistent with the observed EUV sensitivity of tin-oxo cages.

Contains fulltext : 288341.pdf (Publisher’s version ) (Open Access) BACKGROUND: In all giant-cell-rich lesions (GCRL) occurring in bone, a common underlying excessive RANKL expression is held responsible for the osteolytic activity. Apart from giant cell tumour of bone (GCTB), systematic outcome analysis of RANKL inhibition in other GCRL is unavailable. The aim of this study is to assess the efficacy and safety of a 1-year denosumab protocol in giant cell lesions of the jaw (GCLJ). METHODS: A retrospective cohort study was conducted compromising patients treated with a 1-year protocol of monthly subcutaneously administered 120 mg denosumab. Objective tumour response based on histology and imaging was used to calculate objective tumour response rate, progression-free survival (PFS) and time to progression. Type, severity and frequency of adverse events were recorded in a standardised way to assess safety. RESULTS: Twenty patients, predominantly female (90%), were included. Fifty-five per cent of lesions were located in the mandible; most classified as aggressive lesions (90%). Thirty-five per cent (7/20) of cases were either recurrent after prior treatment or progressive, while on other drug treatment. Objective tumour response rate was 100% after 12 months of treatment. Median PFS was 50.4 months (95% CI 38.0-62.8) with a cumulative PFS rate of 22.6% (95% CI 1.8-43.4) at 5 years follow-up. Median time to progression was 38.4 months (95% CI 26.0-50.8). Treatment was well tolerated, and none of the patients had to interrupt therapy for toxicity. CONCLUSION: High-dose denosumab is effective and safe in achieving a complete response in GCLJ within 12 months. The high long-term relapse rate after treatment cessation is the main obstacle for denosumab to become standard treatment for GCLJ.

Simple Summary: Adolescent and young adult (AYA) cancer survivors diagnosed with cancer between ages 18-39 years often experience negative body changes, such as scars, amputation, hair loss, disfigurement, body weight changes, skin buns, and physical movement limitations. A negative body image could have negative implications for the self-esteem, self-identity, and social relationships of AYAs. Despite the possible long-term effects of cancer on body image, within the AYA literature, limited studies focus on AYA cancer survivors in a quantitative way. Therefore, the aim of our population-based cross-sectional study was to examine the prevalence, and association of a negative body image with sociodemographic, clinical, and psychosocial factors, among AYA survivors 5-20 years after diagnosis. Raising awareness and integrating supportive care for those who experience a negative body image into standard AYA survivorship care is warranted. Future longitudinal research could help to identify when and how this support for AYA survivors can be best utilized. Adolescent and young adult (AYA) cancer survivors (18-39 years at diagnosis) often experience negative body changes such as scars, amputation, and disfigurement. Understanding which factors influence body image among AYA survivors can improve age-specific care in the future. Therefore, we aim to examine the prevalence, and association of a negative body image with sociodemographic, clinical, and psychosocial factors, among AYA cancer survivors (5-20 years after diagnosis). A population-based cross-sectional cohort study was conducted among AYA survivors (5-20 years after diagnosis) registered within the Netherlands Cancer Registry (NCR) (SURVAYA-study). Body image was examined via the EORTC QLQ-C30 and QLQ-SURV100. Multivariable logistic regression models were used. Among 3735 AYA survivors who responded, 14.5% (range: 2.6-44.2%), experienced a negative body image. Specifically, AYAs who are female, have a higher Body Mass Index (BMI) or tumor stage, diagnosed with breast cancer, cancer of the female genitalia, or germ cell tumors, treated with chemotherapy, using more maladaptive coping strategies, feeling sexually unattractive, and having lower scores of health-related Quality of Life (HRQoL), were more likely to experience a negative body image. Raising awareness and integrating supportive care for those who experience a negative body image into standard AYA survivorship care is warranted. Future research could help to identify when and how this support for AYA survivors can be best utilized.

(1) Background: Deep brain stimulation (DBS) and continuous intrajejunal levodopa infusion (CLI) are efficacious treatments of medication related motor response fluctuations in advanced Parkinson’s disease (PD). Literature regarding the use of both advanced treatments within one patient is scarce. (2) Methods: We present a retrospective single center case series and a review of the literature. Patients with PD who were treated with both DBS and CLI in our tertiary referral center between 2005 and 2020 were identified and medical records were assessed. Additionally, literature on patients treated with both therapies was systematically searched for in Medline and Embase. (3) Results: Nineteen patients were included. Medication related motor response fluctuations were a major indication for the second therapy in all but one. Of nine patients initially treated with DBS, five reported improvement with CLI. Seven of ten patients initially treated with CLI experienced benefits from DBS. The systematic literature search resulted in fifteen previous publications comprising 66 patients. Of the 59 patients, for whom the effect of the second treatment was known, 57 improved. (4) Conclusions: PD patients, who have persisting medication related motor response fluctuations, despite DBS or CLI treatment, may benefit from an additional or alternative treatment with either CLI or DBS.

The imaging of dynamical processes at interfaces and on the nanoscale is of great importance throughout science and technology. While light-optical imaging techniques often cannot provide the necessary spatial resolution, electron-optical techniques damage the specimen and cause dose-induced artifacts. Here, optical near-field electron microscopy (ONEM) is proposed, an imaging technique that combines noninvasive probing with light, with a high-spatial-resolution readout via electron optics. Close to the specimen, the optical near fields are converted into a spatially varying electron flux using a planar photocathode. The electron flux is imaged using low-energy electron microscopy, enabling label-free nanometric resolution without the need to scan a probe across the sample. The specimen is never exposed to damaging electrons.

Crystalline films of pentacene molecules, two to four monolayers in thickness, are grown via in situ sublimation on silicon substrates in the ultrahigh vacuum chamber of a low-energy electron microscope. It is observed that the diffraction pattern of the pentacene layers fades upon irradiation with low-energy electrons. The damage cross section is found to increase by more than an order of magnitude for electron energies from 0 to 10 eV and by another order of magnitude from 10 to 40 eV. Close to 0 eV, damage is virtually nil. Creation of chemically reactive atomic centers after electron attachment or impact ionization is thought to trigger chemical reactions between neighboring molecules that gradually transform the layer into a disordered carbon nanomembrane. Additionally, diminishing spectroscopic features related to the unoccupied band structure of the layers, accompanied by loss of definition in real-space images, and an increase in the background intensity of diffraction images during irradiation point to chemical changes and formation of a disordered layer.

Transmission electron microscopy at very low energy is a promising way to avoid damaging delicate biological samples with the incident electrons, a known problem in conventional transmission electron microscopy. For imaging in the 0-30 eV range, we added a second electron source to a low energy electron microscopy (LEEM) setup, enabling imaging and spectroscopy in both transmission and reflection mode at nanometer (nm) resolution. The latter is experimentally demonstrated for free-standing graphene. Exemplary eV-TEM micrographs of gold nanoparticles suspended on graphene and of DNA origami rectangles on graphene oxide further establish the capabilities of the technique. The long and short axes of the DNA origami rectangles are discernable even after an hour of illumination with low energy electrons. In combination with recent developments in 2D membranes, allowing for versatile sample preparation, eV-TEM is paving the way to damage-free imaging of biological samples at nm resolution.

INTRODUCTION AND OBJECTIVE:Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a metachronous contralateral testicular germ cell tumor (CTGCT). It is unclear whether...

In a lot of systems, charge transport is governed by local features rather than being a global property as suggested by extracting a single resistance value. Consequently, techniques that resolve local structure in the electronic potential are crucial for a detailed understanding of electronic transport in realistic devices. Recently, we have introduced a new potentiometry method based on low-energy electron microscopy (LEEM) that utilizes characteristic features in the reflectivity spectra of layered materials [1]. Performing potentiometry experiments in LEEM has the advantage of being fast, offering a large field of view and the option to zoom in and out easily, and of being non-invasive compared to scanning-probe methods. However, not all materials show clear features in their reflectivity spectra. Here we, therefore, focus on a different version of low-energy electron potentiometry (LEEP) that uses the mirror mode transition, i.e. the drop in electron reflectivity around zero electron landing energy when they start to interact with the sample rather than being reflected in front of it. This transition is universal and sensitive to the local electrostatic surface potential (either workfunction or applied potential). It can consequently be used to perform LEEP experiments on a broader range of material compared to the method described in Ref [1] . We provide a detailed description of the experimental setup and demonstrate LEEP on workfunction-related intrinsic potential variations on the Si(111) surface and for a metal-semiconductor-metal junction with external bias applied. In the latter, we visualize the Schottky effect at the metal-semiconductor interface. Finally, we compare how robust the two LEEP techniques discussed above are against image distortions due to sample inhomogeneities or contamination.

The effects of space charge, aberrations and relativity on temporal compression are investigated for a compact spherical electrostatic capacitor (α-SDA). By employing the three-dimensional (3D) field simulation and the 3D space charge model based on numerical General Particle Tracer and SIMION, we map the compression efficiency for a wide range of initial beam size and single-pulse electron number and determine the optimum conditions of electron pulses for the most effective compression. The results demonstrate that both space charge effects and aberrations prevent the compression of electron pulses into the sub-ps region if the electron number and the beam size are not properly optimized. Our results suggest that α-SDA is an effective compression approach for electron pulses under the optimum conditions. It may serve as a potential key component in designing future time-resolved electron sources for electron diffraction and spectroscopy experiments.

Di-iron dithiolate hydrogenase model complexes are promising systems for electrocatalytic production of dihydrogen and have therefore been spectroscopically and theoretically investigated in this study. The direct effect of ligand substitution on the redox activity of the complex is examined. In order to understand and eventually optimize such systems, we characterised both metal and ligand in detail, using element specific X-ray absorption Fe- and S-K edge XAS. The (electronic) structure of three different [Fe