Aflatoxin B1 and Epstein-Barr virus-induced CCL22 expression stimulates B cell infection.

Epstein-Barr Virus (EBV) infects more than 90% of the adult population worldwide. EBV infection is associated with Burkitt lymphoma (BL) though alone is not sufficient to induce carcinogenesis implying the involvement of co-factors. BL is endemic in African regions faced with mycotoxins exposure. Exposure to mycotoxins and oncogenic viruses has been shown to increase cancer risks partly through the deregulation of the immune response. A recent transcriptome profiling of B cells exposed to aflatoxin B1 (AFB1) revealed an upregulation of the Chemokine ligand 22 (CCL22) expression although the underlying mechanisms were not investigated. Here, we tested whether mycotoxins and EBV exposure may together contribute to endemic BL (eBL) carcinogenesis via immunomodulatory mechanisms involving CCL22. Our results revealed that B cells exposure to AFB1 and EBV synergistically stimulated CCL22 secretion via the activation of Nuclear Factor-kappa B pathway. By expressing EBV latent genes in B cells, we revealed that elevated levels of CCL22 result not only from the expression of the latent membrane protein LMP1 as previously reported but also from the expression of other viral latent genes. Importantly, CCL22 overexpression resulting from AFB1-exposure in vitro increased EBV infection through the activation of phosphoinositide-3-kinase pathway. Moreover, inhibiting CCL22 in vitro and in humanized mice in vivo limited EBV infection and decreased viral genes expression, supporting the notion that CCL22 overexpression plays an important role in B cell infection. These findings unravel new mechanisms that may underpin eBL development and identify novel pathways that can be targeted in drug development.

MRD at the end of induction and EFS in T-cell lymphoblastic lymphoma: Children's Oncology Group trial AALL1231.

ABSTRACT: Defining prognostic variables in T-lymphoblastic lymphoma (T-LL) remains a challenge. AALL1231 was a Children's Oncology Group phase 3 clinical trial for newly diagnosed patients with T acute lymphoblastic leukemia or T-LL, randomizing children and young adults to a modified augmented Berlin-Frankfurt-Münster backbone to receive standard therapy (arm A) or with addition of bortezomib (arm B). Optional bone marrow samples to assess minimal residual disease (MRD) at the end of induction (EOI) were collected in T-LL analyzed to assess the correlation of MRD at the EOI to event-free survival (EFS). Eighty-six (41%) of the 209 patients with T-LL accrued to this trial submitted samples for MRD assessment. Patients with MRD <0.1% (n = 75) at EOI had a superior 4-year EFS vs those with MRD ≥0.1% (n = 11) (89.0% ± 4.4% vs 63.6% ± 17.2%; P = .025). Overall survival did not significantly differ between the 2 groups. Cox regression for EFS using arm A as a reference demonstrated that MRD EOI ≥0.1% was associated with a greater risk of inferior outcome (hazard ratio, 3.73; 95% confidence interval, 1.12-12.40; P = .032), which was independent of treatment arm assignment. Consideration to incorporate MRD at EOI into future trials will help establish its value in defining risk groups. CT# NCT02112916.

Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults.

Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with R/R cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms. We present the primary analysis of the standard-risk cohort. Data from the low-risk cohort are reported separately. Patients received 4 induction cycles with nivolumab plus BV; those without CMR (Deauville score >3, Lugano 2014) received BV plus bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (high-dose chemotherapy/auto-HCT per protocol). Primary end point was CMR any time before consolidation. Forty-four patients were treated. Median age was 16 years. At a minimum follow-up of 15.6 months, 43 patients received 4 induction cycles (1 discontinued), 11 of whom received intensification; 32 proceeded to consolidation. CMR rate was 59% after induction with nivolumab plus BV and 94% any time before consolidation (nivolumab plus BV ± BV plus bendamustine). One-year progression-free survival rate was 91%. During induction, 18% of patients experienced grade 3/4 treatment-related adverse events. This risk-stratified, response-adapted salvage strategy had high CMR rates with limited toxicities in CAYA with R/R cHL. Most patients did not require additional chemotherapy (bendamustine intensification). Additional follow-up is needed to confirm durability of disease control. This trial was registered at www.clinicaltrials.gov as #NCT02927769.

Genome-scale clustered regularly interspaced short palindromic repeats screen identifies nucleotide metabolism as an actionable therapeutic vulnerability in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common malignancy that develops in patients with ataxia-telangiectasia, a cancer-predisposing inherited syndrome characterized by inactivating germline ATM mutations. ATM is also frequently mutated in sporadic DLBCL. To investigate lymphomagenic mechanisms and lymphoma-specific dependencies underlying defective ATM, we applied ribonucleic acid (RNA)-seq and genome-scale loss-offunction clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens to systematically interrogate B-cell lymphomas arising in a novel murine model (Atm-/-nu-/-) with constitutional Atm loss, thymic aplasia but residual T-cell populations. Atm-/-nu-/-lymphomas, which phenotypically resemble either activated B-cell-like or germinal center Bcell-like DLBCL, harbor a complex karyotype, and are characterized by MYC pathway activation. In Atm-/-nu-/-lymphomas, we discovered nucleotide biosynthesis as a MYCdependent cellular vulnerability that can be targeted through the synergistic nucleotidedepleting actions of mycophenolate mofetil (MMF) and the WEE1 inhibitor, adavosertib (AZD1775). The latter is mediated through a synthetically lethal interaction between RRM2 suppression and MYC dysregulation that results in replication stress overload in Atm-/-nu-/-lymphoma cells. Validation in cell line models of human DLBCL confirmed the broad applicability of nucleotide depletion as a therapeutic strategy for MYC-driven DLBCL independent of ATM mutation status. Our findings extend current understanding of lymphomagenic mechanisms underpinning ATM loss and highlight nucleotide metabolism as a targetable therapeutic vulnerability in MYC-driven DLBCL.

Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma.

The goal of therapy in pediatric Hodgkin lymphoma (HL) is to maximize overall survival while minimizing the morbidity of curative therapy. Key findings from recent Children's Oncology Group (COG) trials include: (i) superior event-free survival with the addition of brentuximab vedotin (Bv) in frontline regimens for high-risk disease, (ii) successful reduction in myeloablative regimens with demonstrated safety and efficacy of Bv and checkpoint inhibitor therapy in relapsed disease, and (ii) the potential to select a population that can be salvaged after relapse without receiving a stem cell transplant. The COG HL committee will lead a National cancer Institute National Clinical Trials Network phase 3 trial to evaluate the combination of Bv/nivolumab in early-stage disease. Ongoing advances in technology and blood biomarkers are increasing the ability to deliver biologically driven, personalized treatment for HL.

Posterior Reversible Encephalopathy Syndrome in the Setting of Asparaginase-associated Pancreatitis in 2 Pediatric Patients With Acute Leukemia.

Asparaginase, a critical component of current pediatric acute leukemia treatment protocols, is associated with a number of serious side effects, one of which is pancreatitis. Pancreatitis can result in significant morbidity and mortality from necrosis, pseudocyst formation, hemorrhage, systemic inflammation, intestinal perforation, and sepsis. Another rare complication of pancreatitis is posterior reversible encephalopathy syndrome, likely mediated by systemic inflammation secondary to pancreatic autodigestion and proinflammatory cytokine-mediated vascular endothelial damage. Here, we review this association in the literature and report 2 pediatric patients with leukemia who developed posterior reversible encephalopathy syndrome in the setting of asparaginase-associated pancreatitis.

Pediatric Donor Cell Acute Lymphoblastic Leukemia Following Bone Marrow Transplant for GATA2 Mutation.

Donor cell leukemia is a rare complication following hematopoietic stem cell transplant (HSCT). There are currently few reports in children and only rare, reported cases of donor-derived myelodysplastic syndrome/acute myeloid leukemia in patients with an underlying germline GATA2 mutation. Most reported cases are myeloid in origin and occur following related HSCT. We present a 3-year-old female who developed a donor-derived B-cell acute lymphoblastic leukemia 2 years post unrelated HSCT for GATA2 germline mutation.

Evaluation of the association of length of stay in hospital and outcomes.

BACKGROUND: There exist wide variations in healthcare quality within the National Health Service (NHS). A shorter hospital length of stay (LOS) has been implicated as premature discharge, that may in turn lead to adverse consequences. We tested the hypothesis that a short LOS might be associated with increased risk of readmissions within 28 days of hospital discharge and also post-discharge mortality. METHODS: We conducted a single-centred study of 32 270 (46.1% men) consecutive alive-discharge episodes (mean age = 64.0 years, standard deviation = 20.5, range = 18-107 years), collected between 01/04/2017 and 31/03/2019. Associations of LOS tertiles (middle tertile as a reference) with readmissions and mortality were assessed using observed/expected ratios, and logistic and Cox regressions to estimate odds (OR) and hazard ratios (HR) (adjusted for age, sex, patients' severity of underlying health status and index admissions), with 95% confidence intervals (CIs). RESULTS: The observed numbers of readmissions within 28 days of hospital discharge or post-discharge mortality were lower than expected (observed: expected ratio < 1) in patients in the bottom tertile (<1.2 days) and middle tertile (1.2-4.3 days) of LOS, whilst higher than expected (observed: expected ratio > 1) in patients in the top tertile (>4.3 days), amongst all ages. Patients in the top tertile of LOS had increased risks for one readmission: OR = 2.32 (95% CI = 1.86-2.88) or ≥2 readmissions: OR = 6.17 (95% CI = 5.11-7.45), death within 30 days: OR = 2.87 (95% CI = 2.34-3.51), and within six months of discharge: OR = 2.52 (95% CI = 2.23-2.85), and death over a two-year period: HR = 2.25 (95% CI = 2.05-2.47). The LOS explained 7.4% and 15.9% of the total variance (r2) in one readmission and ≥2 readmissions, and 9.1% and 10.0% of the total variance in mortality with 30 days and within six months of hospital discharge, respectively. Within the bottom, middle and top tertiles of the initial LOS, the median duration from hospital discharge to death progressively shortened from 136, 126 to 80 days, whilst LOS during readmission lengthened from 0.4, 0.9 to 2.8 days, respectively. CONCLUSION: Short LOS in hospital was associated with favourable post-discharge outcomes such as early readmission and mortality, and with a delay in time interval from discharge to death and shorter LOS in hospital during readmission. These findings indicate that timely discharge from our hospital meets the aims of the NHS-generated national improvement programme, Getting It Right First Time.

An etiological role for the Epstein-Barr virus in the pathogenesis of classical Hodgkin lymphoma.

Although a pathogenic role for the Epstein-Barr virus (EBV) is largely undisputed for tumors that are consistently EBV genome positive (eg, nasopharyngeal carcinoma, endemic Burkitt lymphoma), this is not the case for classical Hodgkin lymphoma (cHL), a tumor with only a variable EBV association. In light of recent developments in immunotherapeutics and small molecules targeting EBV, we believe it is now timely to reevaluate the role of EBV in cHL pathogenesis.

Changes in cortisol levels by continuous positive airway pressure in patients with obstructive sleep apnoea: Meta-analysis of 637 individuals.

BACKGROUND: Obesity, obstructive sleep apnoea (OSA) and hypertension frequently coexist and are associated with elevated cortisol levels. Identification and treatment of such patients is important when investigating for suspected Cushing's syndrome and hypertension. Studies of the impact of continuous positive airway pressure (CPAP) on cortisol and blood pressure are limited by the small sample size and show conflicting findings. We conducted a meta-analysis to document changes in the levels of cortisol and blood pressure in response to CPAP treatment of OSA. METHODS: Meta-analysis was conducted using RevMan (v5.3) and expressed in standardized mean difference (SMD) for catecholamines and mean difference for systolic (SBP) and diastolic blood pressure (DBP). The quality of the studies was evaluated using standard tools for assessing the risk of bias. RESULTS: A total of 22 studies met our search criteria; they consisted of 16 prospective cohort studies (PCS) that recruited 385 participants and six randomized control trials (RCT) totalling 252 participants. The range of mean age was 41-62 years and BMI 27.2-35.1 kg/m2 . CPAP treatment reduced plasma cortisol levels in PCS: SMD = -0.28 [95% confidence interval (95% CI) = -0.45 to -0.12], I2 = 0%, p = .79 and in RCT: SMD = -0.39 (95% CI = -0.75 to -0.03), I2 = 28.3%, p = .25. CPAP treatment reduced SBP by 5.4 mmHg (95% CI = 1.7-9.1) and DBP by 3.3 mmHg (95% CI = 1.0-5.7). Interstudy heterogeneity was low for all studies. Bias in most RCT arose from the lack of blinding of participants and personnel. CONCLUSION: CPAP treatment in individuals with OSA reduces cortisol levels and blood pressure.

The human lymph node microenvironment unilaterally regulates T-cell activation and differentiation.

The microenvironment of lymphoid organs can aid healthy immune function through provision of both structural and molecular support. In mice, fibroblastic reticular cells (FRCs) create an essential T-cell support structure within lymph nodes, while human FRCs are largely unstudied. Here, we show that FRCs create a regulatory checkpoint in human peripheral T-cell activation through 4 mechanisms simultaneously utilised. Human tonsil and lymph node-derived FRCs constrained the proliferation of both naïve and pre-activated T cells, skewing their differentiation away from a central memory T-cell phenotype. FRCs acted unilaterally without requiring T-cell feedback, imposing suppression via indoleamine-2,3-dioxygenase, adenosine 2A Receptor, prostaglandin E2, and transforming growth factor beta receptor (TGFßR). Each mechanistic pathway was druggable, and a cocktail of inhibitors, targeting all 4 mechanisms, entirely reversed the suppressive effect of FRCs. T cells were not permanently anergised by FRCs, and studies using chimeric antigen receptor (CAR) T cells showed that immunotherapeutic T cells retained effector functions in the presence of FRCs. Since mice were not suitable as a proof-of-concept model, we instead developed a novel human tissue-based in situ assay. Human T cells stimulated using standard methods within fresh tonsil slices did not proliferate except in the presence of inhibitors described above. Collectively, we define a 4-part molecular mechanism by which FRCs regulate the T-cell response to strongly activating events in secondary lymphoid organs while permitting activated and CAR T cells to utilise effector functions. Our results define 4 feasible strategies, used alone or in combinations, to boost primary T-cell responses to infection or cancer by pharmacologically targeting FRCs.

LACE index predicts age-specific unplanned readmissions and mortality after hospital discharge.

BACKGROUND: The LACE index scoring tool (Length of stay, Acuity of admission, Co-morbidities and Emergency department visits) has been designed to predict hospital readmissions. We evaluated the ability of the LACE index to predict age-specific frequent admissions and mortality. METHODS: Analysis of prospectively collected data of alive-discharge episodes between 01/04/2017 and 31/03/2019 in an NHS hospital. Data on 14,878 men and 17,392 women of mean age 64.0 years, SD = 20.5, range 18.0-106.7 years were analysed. The association of the LACE index with frequency of all-cause readmissions within 28 days of discharge and over a 2-year period, and with all-cause mortality within 30 days or within 6 months after discharge from hospital were evaluated. RESULTS: Within LACE index scores of 0-4, 5-9 or ≥ 10, the proportions of readmission ≥ 2 times within 28 days of discharge were 0.1, 1.3 and 9.2% (χ2 = 3070, p < 0.001) and over a 2-year period were 1.7, 4.8 and 19.1% (χ2 = 3364, p < 0.001). Compared with a LACE index score of 0-4, a score ≥ 10 increased the risk (adjusted for age, sex and frequency of admissions) of death within 6 months of discharge by 6.8-fold (5.1-9.0, p < 0.001) among all ages, and most strongly in youngest individuals (18.0-49.9 years): adjusted odds ratio = 16.1 (5.7-45.8, p < 0.001). For those aged 50-59.9, 60-69.9, 70-79.9 and ≥ 80 years, odds ratios reduced progressively to 9.6, 7.7, 5.1 and 2.3, respectively. Similar patterns were observed for the association of LACE index with mortality within 30 days of hospital discharge. CONCLUSIONS: The LACE index predicts short-term and long-term frequent admissions and short-term and medium-term mortality, most pronounced among younger individuals, after hospital discharge.

Novel Therapies Potentially Available for Pediatric B-Cell Non-Hodgkin Lymphoma.

Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma are the most common aggressive pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs). Despite excellent survival with current chemotherapy regimens, therapy for Burkitt lymphoma and DLBCL has a high incidence of short- and long-term toxicities. Patients who experience relapse generally have a very poor prognosis. Therefore, novel approaches using targeted therapies to reduce toxicities and improve outcomes in the relapse setting are needed. The addition of rituximab, a monoclonal antibody against CD20, to upfront therapy has improved survival outcomes for high-risk patients and may allow decreased total chemotherapy in those with low-risk disease. Antibody-drug conjugates have been combined with chemotherapy in relapsed/refractory (R/R) NHL, and multiple antibody-drug conjugates are in development. Additionally, bispecific T-cell-engaging antibody constructs and autologous CAR T-cells have been successful in the treatment of R/R acute leukemias and are now being applied to R/R B-NHL with some successes. PD-L1 and PD-L2 on tumor cells can be targeted with checkpoint inhibitors, which restore T-cell-mediated immunity and antitumor responses and can be added to conventional chemotherapy and immune-directed therapies to augment responses. Lastly, trials of small molecule inhibitors targeting cell signaling pathways in NHL subtypes are underway. This article reviews many of the targeted therapies under development that could be considered for future trials in R/R pediatric mature B-NHL.

Regulation of S1PR2 by the EBV oncogene LMP1 in aggressive ABC-subtype diffuse large B-cell lymphoma.

The Epstein-Barr virus (EBV) is found almost exclusively in the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), yet its contribution to this tumour remains poorly understood. We have focused on the EBV-encoded latent membrane protein-1 (LMP1), a constitutively activated CD40 homologue expressed in almost all EBV-positive DLBCLs and which can disrupt germinal centre (GC) formation and drive lymphomagenesis in mice. Comparison of the transcriptional changes that follow LMP1 expression with those that follow transient CD40 signalling in human GC B cells enabled us to define pathogenic targets of LMP1 aberrantly expressed in ABC-DLBCL. These included the down-regulation of S1PR2, a sphingosine-1-phosphate (S1P) receptor that is transcriptionally down-regulated in ABC-DLBCL, and when genetically ablated leads to DLBCL in mice. Consistent with this, we found that LMP1-expressing primary ABC-DLBCLs were significantly more likely to lack S1PR2 expression than were LMP1-negative tumours. Furthermore, we showed that the down-regulation of S1PR2 by LMP1 drives a signalling loop leading to constitutive activation of the phosphatidylinositol-3-kinase (PI3-K) pathway. Finally, core LMP1-PI3-K targets were enriched for lymphoma-related transcription factors and genes associated with shorter overall survival in patients with ABC-DLBCL. Our data identify a novel function for LMP1 in aggressive DLBCL. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Compact multispectral pushframe camera for nanosatellites.

In this paper we present an evolution of the single-pixel camera architecture, called "pushframe," which addresses the limitations of pushbroom cameras in space-based applications. In particular, it is well-suited to observing fast-moving scenes while retaining high spatial resolution and sensitivity. We show that the system is capable of producing color images with good fidelity and scalable resolution performance. The principle of our design broadens the choice of spectral ranges that can be captured, making it suitable for wide spectral ranges of infrared imaging.

Low-cost hyper-spectral imaging system using a linear variable bandpass filter for agritech applications.

Hyperspectral imaging for agricultural applications provides a solution for non-destructive, large-area crop monitoring. However, current products are bulky and expensive due to complicated optics and electronics. A linear variable filter was developed for implementation into a prototype hyperspectral imaging camera that demonstrates good spectral performance between 450 and 900 nm. Equipped with a feature extraction and classification algorithm, the proposed system can be used to determine potato plant health with ∼88% accuracy. This algorithm was also capable of species identification and is demonstrated as being capable of differentiating between rocket, lettuce, and spinach. Results are promising for an entry-level, low-cost hyperspectral imaging solution for agriculture applications.

Advanced Symptom Management System for Patients with Malignant Pleural Mesothelioma (ASyMSmeso): Mixed Methods Study.

BACKGROUND: Patients with malignant pleural mesothelioma (MPM) have a life-limiting illness and short prognosis and experience many debilitating symptoms from early in the illness. Innovations such as remote symptom monitoring are needed to enable patients to maintain wellbeing and manage symptoms in a proactive and timely manner. The Advanced Symptom Management System (ASyMS) has been successfully used to monitor symptoms associated with cancer. OBJECTIVE: This study aimed to determine the feasibility and acceptability of using an ASyMS adapted for use by patients with MPM, called ASyMSmeso, enabling the remote monitoring of symptoms using a smartphone. METHODS: This was a convergent mixed methods study using patient-reported outcome measures (PROMs) at key time points over a period of 2-3 months with 18 patients. The Sheffield Profile for Assessment and Referral for Care (SPARC), Technology Acceptance Model (TAM) measure for eHealth, and Lung Cancer Symptom Scale-Mesothelioma (LCSS-Meso) were the PROMs used in the study. Patients were also asked to complete a daily symptom questionnaire on a smartphone throughout the study. At the end of the study, semistructured interviews with 11 health professionals, 8 patients, and 3 carers were conducted to collect their experience with using ASyMSmeso. RESULTS: Eighteen patients with MPM agreed to participate in the study (33.3% response rate). The completion rates of study PROMs were high (97.2%-100%), and completion rates of the daily symptom questionnaire were also high, at 88.5%. There were no significant changes in quality of life, as measured by LCSS-Meso. There were statistically significant improvements in the SPARC psychological need domain (P=.049) and in the "Usefulness" domain of the TAM (P=.022). End-of-study interviews identified that both patients and clinicians found the system quick and easy to use. For patients, in particular, the system provided reassurance about symptom experience and the feeling of being listened to. The clinicians largely viewed the system as feasible and acceptable, and areas that were mentioned included the early management of symptoms and connectivity between patients and clinicians, leading to enhanced communication. CONCLUSIONS: This study demonstrates that remote monitoring and management of symptoms of people with MPM using a mobile phone are feasible and acceptable. The evidence supports future trials using remote symptom monitoring to support patients with MPM at home.

Design of 2D Sparse Array Transducers for Anomaly Detection in Medical Phantoms.

Aperiodic sparse 2D ultrasonic array configurations, including random array, log spiral array, and sunflower array, have been considered for their potential as conformable transducers able to image within a focal range of 30-80 mm, at an operating frequency of 2 MHz. Optimisation of the imaging performance of potential array patterns has been undertaken based on their simulated far field directivity functions. Two evaluation criteria, peak sidelobe level (PSL) and integrated sidelobe ratio (ISLR), are used to access the performance of each array configuration. Subsequently, a log spiral array pattern with -19.33 dB PSL and 2.71 dB ISLR has been selected as the overall optimal design. Two prototype transducers with the selected log spiral array pattern have been fabricated and characterised, one using a fibre composite element composite array transducer (CECAT) structure, the other using a conventional 1-3 composite (C1-3) structure. The CECAT device demonstrates improved coupling coefficient (0.64 to 0.59), reduced mechanical cross-talk between neighbouring array elements (by 10 dB) and improved operational bandwidth (by 16.5%), while the C1-3 device performs better in terms of sensitivity (~50%). Image processing algorithms, such as Hough transform and morphological opening, have been implemented to automatically detect and dimension particles located within a fluid-filled tube structure, in a variety of experimental scenarios, including bespoke phantoms using tissue mimicking material. Experiments using the fabricated CECAT log spiral 2D array transducer demonstrated that this algorithmic approach was able to detect the walls of the tube structure and stationary anomalies within the tube with a precision of ~0.1 mm.

A water-cooled monochromator for the B16 Test beamline at the Diamond Light Source: capabilities and performance characterization.

Systematic studies of the performance of a water-cooled X-ray monochromator, designed and built for the B16 Test beamline at the Diamond Light Source, UK, are presented. A technical description of the monochromator is given and the results of commissioning measurements are discussed. Overall, the monochromator satisfies the original specifications well and meets all the major requirements of the versatile beamline. Following its successful implementation on B16, the basic monochromator design has been reproduced and adapted on other Diamond Light Source beamlines, including B18 and B21.

Mentors' perspectives on the successes and challenges of mentoring in the COG Young Investigator mentorship program: A report from the Children's Oncology Group.

BACKGROUND: Identification and development of young investigators (YI) is critical to the long-term success of research organizations. In 2004, the Children's Oncology Group (COG) created a mentorship program to foster the career development of YIs (faculty <10 years from initial appointment). This study sought to assess mentors' long-term assessment of this program. PROCEDURE: In 2018, 101 past or current mentors in the COG YI mentorship program completed an online survey. Statistical comparisons were made with the Kruskal-Walis test. RESULTS: The response rate was 74.2%. As some mentors had multiple mentees, we report on 138 total mentee-mentor pairs. Mentors were 57.4% male, and mentees were 39.1% male. Mentors rated being mentored as a YI as important with a median rating of 90 on a scale of 1-100, interquartile range (IQR) 80-100. Most mentors reported that being mentored themselves helped their own success within COG (78.2%) and with their overall career development (92.1%). Most mentors enjoyed serving in the program (72.3%) and the median success rating (on a scale of 1-100) across the mentor-mentee pairings was 75, IQR 39-90. Success ratings did not differ by mentor/mentee gender, but improved with increased frequency of mentor-mentee interactions (P < .001). Mentor-mentee pairs who set initial goals reported higher success ratings than those who did not (P < .001). Tangible successes included current mentee COG committee involvement (45.7%), ongoing mentor-mentee collaboration (53.6%), and co-authored manuscript publication (38.4%). CONCLUSION: These data indicate that mentorship is important for successful professional development. Long-term mentoring success improves when mentors and mentees set goals upfront and meet frequently.