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Over the last several years and within the framework of the Sustainable Development Goals, there has been a need to improve the measurement and understanding of local geographic patterns to support more decentralized decision-making and more efficient program implementation. This requires more disaggregated data that are not currently available in a nationally representative household survey. This study explores the potential of model-based geostatistics methodology to model DHS survey indicators. We implement a stacked ensemble modeling approach that combines multiple model algorithmic methods to increase predictive validity relative to a single modeling. The approach captures potentially complex interactions and non-linear effects among the geospatial covariates. Three submodels are fitted to six DHS indicator survey data using the geospatial covariates as exploratory predictors. The model prediction surfaces generated from the submodels are used as covariates in the final Bayesian geostatistical model, which is implemented through a stochastic partial differential equation approach in the integrated nested Laplace approximations. The proposed approach can help to inform the allocation of resources and program implementation in areas that need more attention. Countries can use this approach to model other DHS survey indicators at much smaller spatial scales.

Background Chest radiation therapy (CRT) for malignant thoracic neoplasms is associated with development of valvular heart disease years later. As previous radiation exposure can complicate surgical treatment, transcatheter aortic valve replacement (TAVR) has emerged as an alternative. However, outcomes data are lacking for TAVR patients with a history of CRT. Methods We conducted a retrospective study of all patients who underwent a TAVR procedure at a single institution between September 2012 and November 2018. Among 1341 total patients, 50 had previous CRT. These were propensity-matched in a 1:2 ratio to 100 patients without history of CRT. Thirty-day adverse events were analyzed with generalized estimating equation models. Overall mortality was analyzed with stratified Cox regression modelling. Results Median clinical follow-up was 24 months (interquartile range [IQR], 12–44 months). There was no difference between CRT and non-CRT patients in overall mortality (hazard ratio [HR] 0.84 [0.37–1.90], P = 0.67), 30-day mortality (HR 3.1 [0.49–20.03], P = 0.23), or 30-day readmission rate (HR 1.0 [0.43–2.31], P = 1). There were no differences in the rates of most adverse events, but patients with CRT history had higher rates of postprocedural respiratory failure (HR 3.63 [1.32–10.02], P = 0.01) and permanent pacemaker implantation (HR 2.84 [1.15–7.01], P = 0.02). Conclusions For patients with aortic valve stenosis and previous CRT, TAVR is safe and effective, with outcomes similar to those in the general aortic stenosis population. Patients with history of CRT are more likely to have postprocedural respiratory failure and to require permanent pacemaker implantation.

Childhood cancer survivors (CCS) experience significant morbidity due to treatment- related late effects and benefit from late-effects surveillance. Adherence to screening recommendations is suboptimal. Survivorship care programs often struggle with resource limitations and may benefit from understanding institution-level financial outcomes associated with patient adherence to justify programmatic development and growth. The purpose of this study is to examine how CCS adherence to screening recommendations relates to the cost of care, insurance status, and institution-level financial outcomes. A retrospective chart review of 286 patients, followed in a structured survivorship program, assessed adherence to the Children’s Oncology Group follow-up guidelines by comparing recommended versus performed screening procedures for each patient. Procedure cost estimates were based on insurance status. Institutional profit margins and profit opportunity loss were calculated. Bivariate statistics tested adherent versus nonadherent subgroup differences on cost variables. A generalized linear model predicted the likelihood of adherence based on cost of recommended procedures, controlling for age, gender, race, and insurance. Adherence to recommended surveillance procedures was 50.2%. Nonadherence was associated with higher costs of recommended screening procedures compared to the adherent group estimates ($2,469.84 vs. $1,211.44). Failure to perform the recommended tests resulted in no difference in reimbursement to the health system between groups ($1,249.63 vs. $1,211.08). For the nonadherent group, this represented $1,055.13 in “lost profit opportunity” per visit for patients, which totaled $311,850 in lost profit opportunity due to nonadherence in this subgroup. In the final model, nonadherence was related to higher cost of recommended procedures (p < .0001), older age at visit (p = .04), Black race (p = .02), and government-sponsored insurance (p = .03). Understanding institutional financial outcomes related to patient adherence may help inform survivorship care programs and resource allocation. Potential financial burden to patients associated with complex care recommendations is also warranted.

Tissue engineering is primarily associated with medical disciplines, and research has thus focused on mammalian cells. For applications where clinical relevance is not a constraint, it is useful to evaluate the potential of alternative cell sources to form tissues in vitro. Specifically, skeletal muscle tissue engineering for bioactuation and cultured foods could benefit from the incorporation of invertebrate cells, due to their less stringent growth requirements and other versatile features. Here, we used a Drosophila muscle cell line to demonstrate the benefits of insect cells relative to those derived from vertebrates. The cells were adapted to serum-free media, transitioned between adherent and suspension cultures, and manipulated with hormones. Furthermore, we analyzed scaffolds to support cell adhesion and assayed cellular protein and minerals to evaluate nutrition potential. The insect muscle cells exhibited advantageous growth patterns and hold unique functionality for tissue engineering applications beyond the medical realm., This document is the Authors Accepted Manuscript (or "postprint") and may have minor differences from the Version of Record due to final copyedits.

Peer support has begun to gain traction as a mechanism for improving well-being in medicine. In this paper, we share our experience building, training, and piloting a peer support team based on a "critical incident stress management" model. The HOPES team (Helping Our Peers Endure Stress) is dedicated to, and composed entirely of, members of our division of pediatric hematology/oncology. Peer support will not solve all the well-being problems afflicting medicine. It is, however, a very good place to start.

Background In vitro meat production has been proposed as a solution to environmental and animal welfare issues associated with animal agriculture. While most academic work on cell-cultured meat has focused on innovations for scalable muscle tissue culture, fat production is an important and often neglected component of this technology. Developing suitable biomanufacturing strategies for adipose tissue from agriculturally relevant animal species may be particularly beneficial due to the potential use of cell-cultured fat as a novel food ingredient. Scope and Approach Here we review the relevant studies from areas of meat science, cell biology, tissue engineering, and bioprocess engineering to provide a foundation for the development of in vitro fat production systems. We provide an overview of adipose tissue biology and functionality with respect to meat products, then explore cell lines, bioreactors, and tissue engineering strategies of potential utility for in vitro adipose tissue production for food. Regulation and consumer acceptance are also discussed. Key Findings and Conclusions Existing strategies and paradigms are insufficient to meet the full set of unique needs for a cell-cultured fat manufacturing platform, as tradeoffs are often present between simplicity, scalability, stability, and projected cost. Identification and validation of appropriate cell lines, bioprocess strategies, and tissue engineering techniques must therefore be an iterative process as a deeper understanding of the needs and opportunities for cell-cultured fat develops., Note: This document is the Authors Accepted Manuscript (or "postprint") and may have minor differences from the Version of Record due to final copyedits. The final published version can be accessed at https://doi.org/10.1016/j.tifs.2020.02.005.

Over 80% of children diagnosed with cancer are now cured. The burgeoning population of survivors of childhood cancer experiences high rates of morbidity and mortality due to 'late-effects' of treatment. These can be defined as any consequence of treatment that persists beyond or develops after the completion of cancer therapy. Awareness of late-effects is critically important for pediatricians and adult providers alike, as late-effects impact children in proximity to cancer treatment, as well as adults many decades removed. This review presents the importance of lifelong follow-up care for survivors, highlights existing screening guidelines, and reviews various models of survivor care.National and international guidelines have been developed to standardize screening for survivors, and multiple models of survivorship care exist. The optimal model likely depends on individual factors, including the survivor's needs and preferences, as well as local resources. Key strategies for the successful care of survivors include accurate risk-stratification for specific late-effects, individualized screening plans, education of survivors and professionals, clear communication between providers, and well coordinated transition of care across services.Early identification and management of late-effects are important for survivors of childhood cancer. Providers should be familiar with the risks for specific late-effects and have access to screening guidelines. The strengths and weaknesses of care models, along with individual circumstances, should be considered in designing the optimal approach to care for each survivor.

We determine criteria for the prime spectrum of an ambiskew polynomial algebra $R$ over an algebraically closed field $K$ to be akin to those of two of the principal examples of such an algebra, namely the universal enveloping algebra $U(sl_2)$ (in characteristic $0$) and its quantization $U_q(sl_2)$ (when $q$ is not a root of unity). More precisely, we aim to determine when the prime spectrum of $R$ consists of $0$, the ideals $(z-\lambda)R$ for some central element $z$ of $R$ and all $\lambda\in K$, and, for some positive integer $d$ and each positive integer $m$, $d$ height two prime ideals with Goldie rank $m$. New applications are to certain ambiskew polynomial rings over coordinate rings of quantum tori which arise, as localizations of connected quantized Weyl algebras., Comment: Corrections and amendments following referee's comments

Following the discovery of a fetal hepatic tumor, labor was induced at 38 weeks, and a phenotypically normal female was delivered vaginally. A serum alpha-fetoprotein level at birth was 373,170 ng/mL. Postnatal magnetic resonance imaging confirmed a mass in the right lobe of the liver, and a percutaneous core biopsy revealed an epithelial type hepatoblastoma with predominantly embryonal histology. Methylation testing revealed hypomethylation at imprinting center 2, consistent with a diagnosis of Beckwith-Wiedemann syndrome. This case suggests that Beckwith-Wiedemann syndrome testing should be considered in all patients with hepatoblastoma, even in the absence of other phenotypic stigmata.

Due to significant environmental concerns associated with industrial livestock farming, it is vital to accelerate the development of sustainable production methods for foods. Cellular agriculture presents an option, by using cell culture, as opposed to whole animals, to generate foods, including meats, eggs, and dairy products. The cost-effective scale-up of such cultured products requires addressing key constraints in core research areas: (1) cell sources, (2) growth media, (3) scaffolding biomaterials and (4) bioreactor design. Here we summarize work in the area of insect cell cultures as a promising avenue to address some of the needs in the field. Properties unique to invertebrate cells from insects allow for convenient and efficient tissue production and have already been exploited for various applications, such as industrial recombinant protein production. Insect muscle has also been employed in the field of tissue engineering for bioactuator applications. Compared to mammalian or avian cultures, invertebrate cell cultures require fewer resources and are more resilient to changes in environmental conditions, as they can thrive in a wide range of temperature, pH and osmolarity conditions. Alterations necessary for large-scale production are relatively simple to achieve with insect cells, including immortalization, serum-free media adaptation and suspension culture. Additional benefits include ease of transfection, nutrient density, and relevance to seafood organisms. To advance insect-based tissue engineering for food purposes, it is necessary to develop methods to regulate the differentiation of insect cells into relevant cell types, characterize cell interactions with biomaterials with an eye towards 3D culture, design supportive bioreactor systems and quantify nutritional profiles of cultured biomass.

Multicystic dysplastic kidney is a rare urinary anomaly characterized by multiple non-communicating cysts resulting in a non-functional kidney. In addition to association with hypertension and contralateral renal anomalies, children with multicystic dysplastic kidney have an increased risk of Wilms tumor. Cohort studies and systematic reviews are hampered in estimating the true risk of this association due to the rarity and infrequent reporting of the condition. We present a case of a 2-year-old male child with an antenatal diagnosis of multicystic dysplastic kidney undergoing surveillance ultrasonography who presented with a symptomatic Wilms tumor. Level of evidence: Not applicable for this multicentre audit.

Background Childhood cancer survivors (CCSs) are at high risk of morbidity and mortality from long-term complications of their cancer treatment. The Children's Oncology Group developed screening guidelines to enable the early identification of and intervention for late effects of cancer treatment. There is a paucity of data on the adherence of CCSs to screening recommendations. Procedure A retrospective analysis of medical records to evaluate the rate of adherence of CCSs to the personalized, risk-based recommendations provided to them in the context of a structured long-term follow-up program over a 3-year period. Results Two hundred eighty-six CCSs visited the survivorship clinic 542 times during the 3-year study period. The overall rate of adherence to recommended screening was 74.2%. Using a univariate model and greater age at diagnosis and at screening recommendation were associated with decreased screening adherence. Gender, cancer diagnosis, radiation therapy, anthracycline exposure, and hematopoietic stem cell transplant were not significantly associated with adherence. In a multivariate model, age over 18 years at the time of the visit was significantly associated with decreased adherence (P < 0.0329) (odds ratio: 1.53, 95% confidence interval: 1.04–2.25). Conclusions Adherence to recommended screening tests is suboptimal among CCSs, with lower rates of adherence in CCSs older than 18 years of age compared with those younger than 18 years of age. Given the morbidity and mortality from the late effects of therapy among young adult CCSs, it is critically important to identify and remove barriers to late-effects screening among CCSs.

Radiation treatment of thoracic malignancies is linked with development of valvular disease years after exposure. Given the challenges to surgical treatment related to previous radiation exposure, TAVR has emerged as an alternative. However, outcomes data for patients with history of mediastinal

An 18-year-old girl is diagnosed with Ewing sarcoma. The treatment of her cancer will include 8.4 g/m2 of cyclophosphamide and 63 g/m2 of ifosfamide. She has questions about the impact the treatment may have on her future fertility and what options are available to preserve her fertility. Available fertility preservation techniques are discussed, including embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation.

Background Cardiovascular disease is prevalent among childhood cancer survivors (CCS). Arterial stiffness measured by pulse wave velocity (PWV) may be predictive of cardiovascular morbidity. Increased PWV has been seen in adults following chemotherapy. Purpose To evaluate PWV in a cohort of CCS and healthy controls. Patients and Methods All participants were >6 years old. CCS were >12 months off-therapy and free of cardiac disease, diabetes, and kidney dysfunction. Height, weight, blood pressure (BP), medications, cancer diagnosis, age at diagnosis, time off therapy, chemotherapy, and radiation exposures were recorded. PWV was measured on all participants. Results Sixty-eight CCS (mean 17.3 ± 6 years, 52.9% male), and 51 controls (mean 18.4 ± 5.5 years, 37.3% male) were evaluated. Among CCS, 34% had lymphoma, 44% leukemia, and 22% solid tumors, and 49% were exposed to radiation. CCS were off therapy 7 ± 4.2 years. Both groups were statistically similar in age, BMI, and BP. CCS ≥18 years old had significantly higher PWV compared to controls ≥18 years old (6.37 ± 0.89 vs. 5.76 ± 0.88 m/sec, P = 0.012). The relationship persisted in a regression model adjusted for age, sex, and BMI z-score (β = 0.52, 95%CI 0.051–0.979, P = 0.03). Seventy percent of CCS ≥18 had elevated PWV compared to established norms. Radiation therapy, anthracycline dose, and chemotherapy exposures were not predictive of increased PWV in CCS. Conclusions CCS ≥18 demonstrated prematurely elevated PVW. Further studies are needed to determine the predictive value of PWV in this population and its utility as a screening modality. Pediatr Blood Cancer 2015;62:1832–1837. © 2015 Wiley Periodicals, Inc.

Background Childhood sarcomas are rare and require complex interdisciplinary care including surgery, chemotherapy, and radiation. The goal of this study was to determine if racial or ethnic disparities exist for pediatric sarcoma patients in the United States. Methods The United States' National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify patients aged 0-21 diagnosed with primary sarcomas from 1973 to 2012. Patients were considered by race and ethnicity. Survival curves were computed using the Kaplan-Meier method and the log-rank test. Results A total of 11,502 patients were included in this study. When stratified by race, non-Hispanic black and Hispanic patients were significantly more likely to present with advanced stage disease than white patients. White patients were more likely to receive radiation therapy than black and Hispanic patients (P = 0.01). There was no significant difference between patients who underwent surgery (P = 0.21). Overall survival was better for white patients than black or Hispanic ones. Despite the overall 5-year survival improvement during the study period (56.2%-70.3%), survival disparities between race and ethnicity have grown. Conclusions Racial and ethnic disparities do exist with respect to stage, treatment, and survival of these rare tumors. Black and Hispanic patients are presenting at more advanced stage and have overall worse survival. This survival disparity has widened over the past 4 decades.

Background. The statutory requirement for continuing professional development (CPD) for all health professionals registered with the Health Professions Council of South Africa (HPCSA) has been in place since 2007. The HPCSA intends to implement maintenance of licensure (MoL). Objectives. To determine practitioners’ perceptions and experiences of engaging with CPD to inform the development of the MoL system. Methods. A cross-sectional survey of practitioners registered with the HPCSA was conducted. The self-administered 30-item electronic questionnaire covered practitioner demographics and patterns of CPD practice and was completed by 11 307 respondents. Results. Methods used to determine learning needs included self-assessment (56.8%) and audit of own practice (53.2%). Selection of CPD activities was based on interest (80.2%) and expertise (72.8%) and less so on gaps in knowledge (66.1%) and skills (61.8%). The most frequent learning activities were primarily didactic (workshops (58%), lectures (53%) and conferences (51%)). Barriers included cost and location of CPD activities, especially for women and rural practitioners ( p

e18125 Background: The 2010 Dependent Coverage Provision (DCP) of the Affordable Care Act (ACA) allowed young adults to remain on their parents' health insurance until age 26 years (y), whereas pre-DCP the cut-off varied, but was most often 18 y. Our objective was to compare rates of insurance disenrollment among patients with cancer who were DCP-eligible compared to those who were not. Methods: A retrospective cohort from the OptumLabs Data Warehouse, which includes claims data for privately insured enrollees in a large US health plan, was used. Patients born between 1982-93 diagnosed with cancer between 2000-15 were included. In the Recent Cohort, patients who turned 19 in 2010-12 (who were always eligible to stay on parents’ insurance) were matched to patients who turned 19 in 2007-09 (who were not protected by the DCP when they turned 19). Sensitivity analyses paired patients in an Earlier Cohort, who turned 19 (in 2001-03 and 2004-06), none of whom were eligible for the DCP when they turned 19. Patients were matched on cancer type, diagnosis date, and additional clinical characteristics. Using a time to loss of coverage analysis (defined as > 90 d interruption in insurance enrollment), hazard ratios (HR) were calculated using Cox proportional hazards models. Difference-in-difference between pairs from the Recent and Earlier cohorts was evaluated. Results: Of the 3,013 patients who turned 19 in 2010-12, 2,829 were matched. Median time to disenrollment was 26 months (m) compared to 22 m among patients who turned 19 in 2007-09 (HR 0.88, 95% CI 0.81-0.95, p = 0.0009). In the 4,489 pairs of patients who turned 19 between 2001-06, median time to disenrollment was 20 m among both the younger and older patients in the pair (p = 0.047). In grouped analyses, the difference-in-difference between the Recent and Earlier sets of pairs displayed a 14% reduction in the hazard for losing coverage (p < 0.0001), favoring those who turned 19 after DCP became available. Conclusions: In pediatric cancer patients and survivors, a vulnerable population that needs continuous insurance coverage, these data suggest that the DCP of the ACA lowers the insurance drop-out rate.

Purpose – The purpose of this paper is to describe synchronous, remote tutoring for the Deaf STEM Community Alliance's virtual academic community (VAC). The alliance addresses critical barriers for students who are deaf or hard of hearing (D/HH) in postsecondary science, technology, engineering, and mathematics (STEM) majors. Design/methodology/approach – A mixed-method approach (qualitative content analysis and descriptive statistics) documents project activities. Findings – Google+ Hangouts was used for remote tutoring. Participants completed 57 tutoring sessions. Participants found tutoring beneficial, especially for its convenience. Technical assistance and feedback systems were created to support participants. Grade point averages (GPA) and retention remained stable. Research limitations/implications – Research on this project continues. Small sample size is a limitation of the study. Ongoing research investigates how remote technology and social media impact learning for students who are D/HH. Practical implications – Scholarship on social media for educational purposes is minimal. While specifics of particular social media platforms vary, recruitment, technical assistance, and establishing feedback mechanisms are common issues for VACs. Outcomes from this study will be used to improve this VAC and create documentation for replication. Social implications – The Deaf STEM Community Alliance provides supportive resources to underrepresented students in STEM majors. Improved GPA and retention in STEM majors will generate more individuals qualified for STEM careers. Research on VACs creates opportunities to understand how technology and networked communities change knowledge and learning. Originality/value – The Deaf STEM Community Alliance is a unique project for postsecondary students in STEM fields who are D/HH. The information is valuable to educators interested in using social media for instruction.

For an algebraically closed field $K$, we investigate a class of noncommutative $K$-algebras called connected quantized Weyl algebras. Such an algebra has a PBW basis for a set of generators $\{x_1,\dots,x_n\}$ such that each pair satisfies a relation of the form $x_ix_j=q_{ij}x_jx_i+r_{ij}$, where $q_{ij}\in K^*$ and $r_{ij}\in K$, with, in some sense, sufficiently many pairs for which $r_{ij}\neq 0$. We classify connected quantized Weyl algebras, showing that there are two types, linear and cyclic, each depending on a single parameter $q$. When $q$ is not a root of unity we determine the prime spectra for each type. In the linear case all prime ideals are completely prime but in the cyclic case, which can only occur if $n$ is odd, there are prime ideals for which the factors have arbitrarily large Goldie rank. We apply connected quantized Weyl algebras to obtain presentations of the quantum cluster algebras for two classes of quiver, namely, for $m$ even, the Dynkin quiver of type $A_m$ and the quiver $P_m^{(1)}$ identified by Fordy and Marsh in their analysis of periodic quiver mutation. We establish Poisson analogues of the results on prime ideals and quantum cluster algebras., Minor corrections to previous version, this version to appear in the Journal of Pure and Applied Algebra

Since the 1970s, outcomes for childhood cancer have shown remarkable and steady improvements. Five-year overall survival from childhood cancer now exceeds 80% and as many as 1 in 500 young American adults are survivors of childhood cancer. Despite these successes, nearly a quarter of survivors will have multiple severe, disabling or life-threatening conditions by age 50, over 90% have measurable end-organ damage and almost 20% will die within 30 years of diagnosis. The complications faced by survivors, and the care they require, are multisystem and complex. The most common complications include endocrine, cardiac, musculoskeletal and pulmonary complications, as well as treatment-related secondary neoplasms. Survivors also often face societal, emotional and psychological barriers, such as learning challenges, school difficulties, and problems obtaining insurance, and almost one in five suffer from stress-related mental disorders such as post-traumatic stress symptoms. Extensive, intricate, long-term medical and psychological follow-up is required to maintain survivors’ health and quality of life.

The efficient engraftment in immune-deficient mice achieved with both acute lymphoblastic leukemia (ALL) cell lines and primary samples has facilitated identification of the antileukemia activity of a wide variety of agents. Despite widespread usage, however, little is known about the early ALL localization and engraftment kinetics in this model, limiting experimental read-outs primarily to survival and endpoint analysis at high disease burden. In this study, we report that bioluminescent imaging can be reproducibly achieved with primary human ALL samples. This approach provides a noninvasive, longitudinal measure of leukemia burden and localization that enhances the sensitivity of treatment response detection and provides greater insight into the mechanism of action of antileukemia agents. In addition, this study reveals significant cell line– and species-related differences in leukemia migration, especially early in expansion, which may confound observations between various leukemia models. Overall, this study demonstrates that the use of bioluminescent primary ALL allows the detection and quantitation of treatment effects at earlier, previously unquantifiable disease burdens and thus provides the means to standardize and expedite the evaluation of anti-ALL activity in preclinical xenograft studies.

The last decade has brought increasing recognition that the wellness of health care providers has an impact on the quality of care, patient satisfaction, and health care economics. This review will describe models of burnout, discuss the impact of burnout on medicine with a focus on pediatric hematologists/oncologists, and present interventions that may help ameliorate physician burnout.

Since the 1950s, the overall survival (OS) of children with cancer has gone from almost zero to approaching 80%. While there have been notable successes in treating solid tumors such as Wilms tumor, some childhood solid tumors, exemplified by diseases like high-risk neuroblastoma and metastatic sarcomas, have continued to elude effective therapy[1]. With the use of megatherapy techniques such as tandem transplantation, dose-escalation has been pushed to the edge of dose-limiting toxicities, and any further improvements in event-free survival (EFS) will have to be achieved through novel therapeutic approaches. In this chapter, we will review the status of autologous and allogeneic hematopoietic stem cell transplantation (HSCT) for many pediatric solid tumor types. The vast majority of the clinical experience in transplant for pediatric solid tumors is in the autologous setting, so we will review some general principles of autologous HSCT, followed by an examination of HSCT for diseases such as Hodgkin disease, Ewing sarcoma, and neuroblastoma. Finally, we will look to the future of cell-based therapies by considering some experimental approaches to effector cell therapies. (1) Principles of autologous HSCT Prior to the introduction of high-dose chemotherapy (HDC) with autologous stem cell rescue (also called autologous HSCT), marrow tolerance was the limiting factor in the escalation of chemotherapy for the treatment of malignancies. With the ability to safely harvest, store and re-infuse a patient’s own hematopoietic stem cells, doses of cytotoxic therapies for cancer could safely proceed beyond marrow tolerance, thereby allowing more intense treatment of certain malignancies. Two approaches to the use of HDC with stem cell rescue include: (1) myeloablative regimens, meaning that no hematopoietic recovery can occur without the stored HSCs; and (2) sub-myeloablative HDC regimens in which stem cell rescue is used to speed recovery, decrease toxicity and decrease the interval between courses of chemotherapy, although it is not absolutely required for engraftment[2–3]. Although the increased treatment intensity may improve disease-free survival for patients with some malignancies, this must be balanced with the increased treatment-related mortality associated with the higher doses of cytotoxic agents, as well as the potential late effects of more intense cytotoxic treatments and radiotherapeutic regimens in young children. Criteria that may help define circumstances in which HDC with stem cell rescue would be most beneficial include: (1) a tumor with good response to induction chemotherapy, but a poor 3 or 5-year EFS; and (2) a HDC regimen that can utilize multiple agents active against the disease, especially if the agents differ from those used during induction therapy. Although the use of HDC with stem cell rescue is controversial in most diseases, diseases such as Hodgkin disease and high-risk neuroblastoma (discussed below) meet the design criteria listed above and have demonstrated improved outcomes in clinical trials.

Over recent years there have been substantial efforts to record and interpret the post-nesting movements of leatherback turtles ( Dermochelys coriacea ) breeding in tropical regions. Less well documented are the movements undertaken by individual turtles during the breeding season itself, or more specifically between sequential nesting events. Such movements are of interest for two reasons: (1) gravid female leatherbacks may range extensively into the territorial waters and nesting beaches of neighbouring countries, raising questions for conservationists and population ecologists; and (2) the magnitude of movements themselves help elucidate underlying reproductive strategies (e.g. whether to rest near to the nesting or forage extensively). Here, satellite relay data loggers are used (SRDLs) to detail the movements and behaviour of two female leatherback turtles throughout three consecutive inter-nesting intervals in the Commonwealth of Dominica, West Indies. Both near-shore residence and extensive inter-nesting movements were recorded, contrasting previous studies, with movements away from the nesting beach increasing towards the end of the nesting season. Using this behavioural study as a backdrop, the suitability of attaching satellite transmitters directly to the carapace was additionally explored as an alternative approach to conventional harness deployments. Specifically, the principal aims were to (1) gather empirical data on speed of travel and (2) assess dive performance (aerobic dive limit) to enable comparisons with turtles previously fitted with harnesses elsewhere in the Caribbean ( n = 6 turtles; Grenada, WI). This produced mixed results with animals bearing directly attached transmitters travelling significantly faster (55.21 km day − 1 ; SD 6.68) than harnessed individuals (39.80 km day − 1 ; SD 6.19); whilst no discernable difference in dive performance could be found between the two groups of study animals.

Genetic mutations of proteins regulating nuclear factor of kappa-light polypeptide gene enhancer in B lymphocyte (NF-kappaB) activation result in heritable diseases of development and immunity. Hypomorphic, X-linked mutations in the IKBKG gene (NF-kappaB essential modulator (NEMO) protein), and hypermorphic, autosomal dominant mutations in the IKBA gene (inhibitor of NF-kappaB (IkappaB)-alpha protein), are associated with a phenotype of immune deficiency and often ectodermal dysplasia (ED-ID). ED-ID predisposes patients to recurrent and life-threatening infections and is typically fatal within the first few years of life. Allogeneic hematopoietic SCT (HSCT) may correct the immune deficiency associated with NEMO or IkappaBalpha mutations, but there is very little published data. We gathered clinical data on three ED-ID patients that had undergone HSCT. Conditioning regimens were variable, as were the stem cell sources. All three patients experienced engraftment difficulties as well as post transplant complications. These cases suggest that patients with immune deficiencies caused by NEMO or IkappaBalpha mutations may have intrinsic barriers to successful engraftment, which require further investigation.

We have previously demonstrated that mTOR inhibitors (MTIs) are active in preclinical models of acute lymphoblastic leukemia (ALL). MTIs may increase degradation of cyclin D1, a protein involved in dihydrofolate reductase (DHFR) synthesis. Because resistance to methotrexate may correlate with high DHFR expression, we hypothesized MTIs may increase sensitivity of ALL to methotrexate through decreasing DHFR by increasing turn-over of cyclin D1. We tested this hypothesis using multiple ALL cell lines and nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenografted with human ALL. We found MTIs and methotrexate were synergistic in combination in vitro and in vivo. Mice treated with both drugs went into a complete and durable remission whereas single agent treatment caused an initial partial response that ultimately progressed. ALL cells treated with MTIs had markedly decreased expression of DHFR and cyclin D1, providing a novel mechanistic explanation for a combined effect. We found methotrexate and MTIs are an effective and potentially synergistic combination in ALL.

An annotated list of the aquatic invertebrates inhabiting water impounded in the leaf axils of Florida’s native epiphytic bromeliads is provided. Of the 22 species reported, 9 are yet undescribed. Of the 13 described species, 10 are believed to be native. Five of the native species and perhaps all of the undescribed species are precinctive (“endemic”). These invertebrate animals and their bromeliad host plants are at risk of extinction due to destruction of the host plants by Metamasius callizona (Chevrolat) (Coleoptera: Dryophthoridae), an invasive weevil.

Understanding the pathogenesis of leukemia in the context of lymphopoiesis may reveal novel therapeutic targets. Previously, we have shown that mTOR inhibitors (MTI) show activity in vitro and in preclinical models of both human and murine precursor B acute lymphoblastic leukemia (pre-B ALL), inhibiting cell proliferation and inducing apoptosis. These MTI-mediated effects can be reversed by interleukin-7 (IL-7), an important regulator of early B-cell development. This observation led us to examine the contribution of signaling via the IL-7Rα chain, which is shared by the receptor complexes of IL-7 and thymic stromal-derived lymphopoietin (TSLP). TSLP is closely related to IL-7 and active in lymphopoiesis, but an effect of TSLP on leukemia cells has not been described. We examined the effect of TSLP on pre-B ALL cells and their response to MTIs. Here, we show that TSLP stimulates proliferation of pre-B ALL cell lines. TSLP also partially reverses the effects of MTI on proliferation, apoptosis, and ribosomal protein S6 and 4E-BP1 phosphorylation in cell lines, with similar biological effects seen in some primary human lymphoblast samples. These data show that TSLP can promote survival of pre-B ALL cells and antagonize the effects of MTIs. These findings suggest that IL-7Rα chain is responsible for transducing the survival signal that overcomes MTI-mediated growth inhibition in pre-B ALL. Thus, further exploration of the IL-7Rα pathway may identify potential therapeutic targets in the treatment of ALL. Our data illustrate that growth-factor–mediated signaling may provide one mechanism of MTI resistance. [Cancer Res 2007;67(20):9963–70]

Lateral sinus thrombosis (LST), a rare complication of otitis media, is managed by antibiotics, surgery and anticoagulation. Traditionally, post-operative anticoagulation has been achieved by intravenous unfractionated heparin followed by oral warfarin. Fractionated, or low-molecular weight heparin derivatives (LMWH) have been introduced recently. There has been minimal literature to date regarding their use for the management of LST. We present use of the LMWH enoxaparin (Lovenox) for otogenic LST in two children, both of whom experienced hemorrhagic complications. On this basis and in the context of a literature review, we urge caution when using LMWH for pediatric otogenic LST.