From neighborhood to household: connections between neighborhood vacant and abandoned property and family violence.

Rates of family violence, including intimate partner violence (IPV) and child maltreatment, remain high in the U.S. and contribute to substantial health and economic costs. How neighborhood environment may influence family violence remains poorly understood. We examine the association between neighborhood vacant and abandoned properties and family violence, and the role collective efficacy may play in that relationship. Data were used from a longitudinal cohort of 218 maternal-child dyads in a southern U.S. city known for elevated rates of violence. Women were matched on their propensity score, for living in a neighborhood with elevated vacant and cited properties. Analyses accounting for clustering in neighborhood and matched groups were conducted to examine the association between neighborhood vacant and abandoned property and family violence, and the potential mediating relationship of collective efficacy. The likelihood of experiencing child maltreatment at 12-months of age was more than twice as high for children living in neighborhoods with a high vacant and cited property rates compared to women living in neighborhoods with fewer vacant and cited properties (OR=2.11, 95% CI=1.03, 4.31). Women living in neighborhoods characterized by high levels of vacant and cited properties were also more than twice as likely to report IPV (OR=2.52, 95% CI=1.21, 5.25). Associations remained mostly stable after controlling for key covariates. Collective efficacy did not act as a mediator in the relationship between vacant and cited properties and family violence. Reducing neighborhood vacant and cited properties may be an important target for interventions focused on reducing family violence.

Arguments for a ban on pediatric intersex surgery: A dis/analogy with Jehovah witness blood transfusion.

This article argues for a ban on the performance of medically unnecessary genital normalizing surgeries as part of assigning a binary sex/gender to infants with intersex conditions on the basis of autonomy, regardless of etiology. It does this via a dis/analogy with the classic case in bioethics of Jehovah Witness (JW) parents' inability to refuse life-saving blood transfusions for their minor children. Both cases address ethical medical practice in situations where parents are making irreversible medical decisions on the basis of values strongly held, identity, and relationship-shaping values-such as religious beliefs or beliefs regarding the inherent value of binary sex/gender-amidst ethical pluralism. Furthermore, it takes seriously-as we must in the intersex case-that the restriction of parents' right to choose will likely result in serious harms to potentially large percentage of patients, their families, and their larger communities. I address the objection that parents' capacity to choose is restricted in the JW case on the basis of the harm principle or a duty to nonmaleficence, given that the result of parent choice would be death. I provide evidence that this is mistaken from how we treat epistemic uncertainty in the JW case and from cases in which clinicians are ethically obligated to restrict the autonomy of nonminor patients. I conclude that we restrict the parents' right to choose in the JW case-and should in the case of pediatric intersex surgery-to secure patient's future autonomy.

Interpregnancy interval and adverse birth outcomes: a population-based cohort study of twins.

BACKGROUND: To investigate associations between interpregnancy intervals (IPIs) and adverse birth outcomes in twin pregnancies. METHODS: This retrospective cohort study of 9,867 twin pregnancies in Western Australia from 1980-2015. Relative Risks (RRs) were estimated for the interval prior to the pregnancy (IPI) as the exposure and after the pregnancy as a negative control exposure for preterm birth (< 37 weeks), early preterm birth (< 34 weeks), small for gestational age (SGA: < 10th percentile of birth weight by sex and gestational age) and low birth weight (LBW: birthweight < 2,500 g). RESULTS: Relative to IPIs of 18-23 months, IPIs of < 6 months were associated with a higher risk of early preterm birth (aRR 1.41, 95% CI 1.08-1.83) and LBW for at least one twin (aRR 1.16, 95% CI 1.06-1.28). IPIs of 6-11 months were associated with a higher risk of SGA (aRR 1.24, 95% CI 1.01-1.54) and LBW for at least one twin (aRR 1.09, 95% CI 1.01-1.19). IPIs of 60-119 months and ≥ 120 months were associated with an increased risk of preterm birth (RR 1.12, 95% CI 1.03-1.22; and (aRR 1.25, 95% CI 1.10-1.41, respectively), and LBW for at least one twin (aRR 1.17, 95% CI 1.08-1.28; and aRR 1.20, 95% CI 1.05-1.36, respectively). IPIs of ≥ 120 months were also associated with an increased risk of early preterm birth (aRR 1.42, 95% CI 1.01-2.00). After negative control analysis, IPIs ≥ 120 months remained associated with early preterm birth and LBW. CONCLUSION: Evidence for adverse associations with twin birth outcomes was strongest for long IPIs.

Extracellular vesicle-based liquid biopsy biomarkers and their application in precision immuno-oncology.

While the field of precision oncology is rapidly expanding and more targeted options are revolutionizing cancer treatment paradigms, therapeutic resistance particularly to immunotherapy remains a pressing challenge. This can be largely attributed to the dynamic tumor-stroma interactions that continuously alter the microenvironment. While to date most advancements have been made through examining the clinical utility of tissue-based biomarkers, their invasive nature and lack of a holistic representation of the evolving disease in a real-time manner could result in suboptimal treatment decisions. Thus, using minimally-invasive approaches to identify biomarkers that predict and monitor treatment response as well as alert to the emergence of recurrences is of a critical need. Currently, research efforts are shifting towards developing liquid biopsy-based biomarkers obtained from patients over the course of disease. Liquid biopsy represents a unique opportunity to monitor intercellular communication within the tumor microenvironment which could occur through the exchange of extracellular vesicles (EVs). EVs are lipid bilayer membrane nanoscale vesicles which transfer a plethora of biomolecules that mediate intercellular crosstalk, shape the tumor microenvironment, and modify drug response. The capture of EVs using innovative approaches, such as microfluidics, magnetic beads, and aptamers, allow their analysis via high throughput multi-omics techniques and facilitate their use for biomarker discovery. Artificial intelligence, using machine and deep learning algorithms, is advancing multi-omics analyses to uncover candidate biomarkers and predictive signatures that are key for translation into clinical trials. With the increasing recognition of the role of EVs in mediating immune evasion and as a valuable biomarker source, these real-time snapshots of cellular communication are promising to become an important tool in the field of precision oncology and spur the recognition of strategies to block resistance to immunotherapy. In this review, we discuss the emerging role of EVs in biomarker research describing current advances in their isolation and analysis techniques as well as their function as mediators in the tumor microenvironment. We also highlight recent lung cancer and melanoma studies that point towards their application as predictive biomarkers for immunotherapy and their potential clinical use in precision immuno-oncology.

Exploring treatment of inflammatory bowel disease with infliximab in the Middle East and Northern Africa: An analysis of the HARIR observational cohort study.

Background: In 2017, inflammatory bowel disease, including Crohn's disease (CD) and ulcerative colitis (UC) affected more than 6.8 million people worldwide, with increased incidence in newly industrialized countries. Although treatment options were previously limited to symptom reduction, current approaches benefit from disease-modifying biologics. In this study, we aimed to explore disease characteristics, treatment, and outcomes of patients with CD or UC treated with infliximab or golimumab in routine clinical practice in the Middle East and Northern Africa. Methods: HARIR was a prospective, observational, multicenter study (NCT03006198), in patients who were treatment naïve or who received two or fewer biologic agents. Observed data from routine clinical practice were presented descriptively. Results: Data from 86 patients enrolled from five countries (Algeria, Egypt, Kuwait, Qatar, and Saudi Arabia) were analyzed, 62 with CD and 24 with UC. All patients received infliximab. Clinically meaningful efficacy data were observed only for the CD group (up to Month 3) due to limited patient numbers. Crohn's Disease Activity Index (CDAI) scores at Month 3 indicated a positive response to treatment (reduced score of ≥70 and ≥25% compared with baseline) for 14/48 (29.2%) patients; notably, 28/52 (53.8%) patients had CDAI score <150 at baseline. Rates of serious and severe adverse events (AEs) were low in both groups. The most common AEs were gastrointestinal disorders. Conclusion: Infliximab treatment was well tolerated in this Middle Eastern and Northern African population, and a clinical response was observed for 29.2% of CD patients. Limited accessibility to biologics and concomitant treatments restricted study conduct.

How do DEI initiatives impact STEMM, and why do we still need them?

The number of diversity, equity, and inclusion (DEI) initiatives in science, technology, engineering, mathematics, and medicine (STEMM) have grown over the last few years. We asked several Black scientists what impact they have and why STEMM still needs them. They answer these questions and describe how DEI initiatives should evolve.

Autocrine activation of MAPK signaling mediates intrinsic tolerance to androgen deprivation in LY6D prostate cancer cells.

The emergence of castration-resistant prostate cancer remains an area of unmet clinical need. We recently identified a subpopulation of normal prostate progenitor cells, characterized by an intrinsic resistance to androgen deprivation and expression of LY6D. We here demonstrate that conditional deletion of PTEN in the murine prostate epithelium causes an expansion of transformed LY6D+ progenitor cells without impairing stem cell properties. Transcriptomic analyses of LY6D+ luminal cells identified an autocrine positive feedback loop, based on the secretion of amphiregulin (AREG)-mediated activation of mitogen-activated protein kinase (MAPK) signaling, increasing cellular fitness and organoid formation. Pharmacological interference with this pathway overcomes the castration-resistant properties of LY6D+ cells with a suppression of organoid formation and loss of LY6D+ cells in vivo. Notably, LY6D+ tumor cells are enriched in high-grade and androgen-resistant prostate cancer, providing clinical evidence for their contribution to advanced disease. Our data indicate that early interference with MAPK inhibitors can prevent progression of castration-resistant prostate cancer.

A Pleistocene assemblage of near-modern Papio hamadryas from the Middle Awash study area, Afar Rift, Ethiopia.

OBJECTIVES: The aim of this study is to assess a new assemblage of papionin fossils (n = 143) recovered from later Pleistocene sediments in the Middle Awash study area in the Afar Rift of Ethiopia. MATERIALS AND METHODS: We collected metric and qualitative data to compare the craniodental and postcranial anatomy of the papionin fossils with subspecies of modern Papio hamadryas and with Plio-Pleistocene African papionins. We also estimated sex and ontogenetic age. RESULTS: The new fossils fit well within the range of morphological variation observed for extant P. hamadryas, overlapping most closely in dental size and proportions with the P. h. cynocephalus individuals in our extant samples, and well within the ranges of P. h. anubis and P. h. hamadryas. The considerable overlap in craniodental anatomy with multiple subspecies precludes subspecific diagnosis. We therefore referred 143 individuals to P. hamadryas ssp. The majority of the individuals assessed for ontogenetic age fell into middle- and old-adult age categories based on the degree of dental wear. Males (26%) were better represented than females (12%) among individuals preserving the canine-premolar honing complex. DISCUSSION: These new near-modern P. hamadryas fossils provide a window into population-level variation in the later Pleistocene. Our findings echo previous suggestions from genomic studies that the papionin family tree may have included a ghost population and provide a basis for future testing of hypotheses regarding hybridization in the recent evolutionary history of this taxon.

Symptom experiences in hypertension: a mixed methods systematic review.

AIM: Understanding patients' hypertension (HTN) symptoms can assist healthcare professionals' awareness of individual, cultural, and behavioral responses and improve diagnostic accuracy to optimize treatment. The purpose of this review was to evaluate and synthesize current literature exploring HTN symptoms. METHODS: Databases searched included MEDLINE (PubMed), CINAHL (EBSCO), Scopus, and Web of Science from January 2010 to January 2022. The search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The McMaster critical review forms were used to determine the quality of both qualitative and quantitative articles. Synthesis of the data was guided by the Joanna Briggs Institute Convergent Integrated Approach to Mixed Study Systematic Reviews. RESULTS: In total, 41 articles were included, nine qualitative studies and 32 quantitative. The quality of the articles varied. Symptoms included commonly reported symptoms and some less prevalent, including some reporting absence of symptoms. Factors that affected symptoms included culture, beliefs, psychosocial factors, and knowledge. We also found that there may be a bidirectional relationship between symptoms and behaviors that may lead to self-management. CONCLUSION: HTN is common and symptoms are frequently reported. HTN management is related to multiple factors. Symptoms continue in a number of individuals after initial diagnosis. Evaluating symptoms after initial diagnosis may help to optimally manage and meet blood pressure guidelines.

The effects of birth spacing on early childhood development in high-income nations: A systematic review.

Objective: This study aimed to systematically review the literature on the associations between birth spacing and developmental outcomes in early childhood (3-10 years of age). Studies examining the associations between interpregnancy intervals and child development outcomes during and beyond the perinatal period have not been systematically reviewed. Methods: We searched Ovid/MEDLINE, Global Health, PsycINFO, EMBASE, CINAHL Plus, Educational Source, Research Starters, ERIC, Scopus, PubMed, Social Science Research Network database, and ProQuest's Social Sciences Databases for relevant articles published between 1 January 1989 and 25 June 2021. Studies published in English, conducted in populations residing in high-income countries with any measure of birth spacing, and child development outcomes among children aged <10 years were included. Two authors independently assessed the eligibility of studies and extracted data on the study design, setting and population, birth spacing, outcomes, and results. Results: The search yielded 1,556 records, of which seven studies met the inclusion criteria. Five of these seven studies used birth intervals as the exposure measure. Definitions of exposure differed between the studies. Three studies reported an association between short birth spacing and poorer child development outcomes, and two studies reported an association between long birth spacing and poorer child development outcomes. Conclusion: Currently, limited evidence suggests that the adverse effects of sub-optimal birth spacing are observable beyond infancy.

Intergenerational programming during the pandemic: Transformation during (constantly) changing times.

Intergenerational programs have long been employed to reduce ageism and optimize youth and older adult development. Most involve in-person meetings, which COVID-19 arrested. ​​Needs for safety and social contact were amplified during COVID-19, leading to modified programming that engaged generations remotely rather than eliminating it. Our collective case study incorporates four intergenerational programs in five US states prior to and during COVID-19. Each aims to reduce ageism, incorporating nutrition education, technology skills, or photography programming. Authors present case goals, participants, implementation methods, including responses to COVID-19, outcomes, and lessons learned. Technology afforded opportunities for intergenerational connections; non-technological methods also were employed. Across cases, programmatic foci were maintained through adaptive programming. Community partners' awareness of immediate needs facilitated responsive programming with universities, who leveraged unique resources. While new methods and partnerships will continue post-pandemic, authors concurred that virtual contact cannot fully substitute for in-person relationship-building. Remote programming maintained ties between groups ready to resume shared in-person programming as soon as possible; they now have tested means for responding to routine or novel cancellations of in-person programming. Able to implement in-person and remote intergenerational programming, communities can fight ageism and pursue diverse goals regardless of health, transportation, weather, or other restrictions.

Keeping 21st Century Paleontology Grounded: Quantitative Genetic Analyses and Ancestral State Reconstruction Re-Emphasize the Essentiality of Fossils.

Advances in genetics and developmental biology are revealing the relationship between genotype and dental phenotype (G:P), providing new approaches for how paleontologists assess dental variation in the fossil record. Our aim was to understand how the method of trait definition influences the ability to reconstruct phylogenetic relationships and evolutionary history in the Cercopithecidae, the Linnaean Family of monkeys currently living in Africa and Asia. We compared the two-dimensional assessment of molar size (calculated as the mesiodistal length of the crown multiplied by the buccolingual breadth) to a trait that reflects developmental influences on molar development (the inhibitory cascade, IC) and two traits that reflect the genetic architecture of postcanine tooth size variation (defined through quantitative genetic analyses: MMC and PMM). All traits were significantly influenced by the additive effects of genes and had similarly high heritability estimates. The proportion of covariate effects was greater for two-dimensional size compared to the G:P-defined traits. IC and MMC both showed evidence of selection, suggesting that they result from the same genetic architecture. When compared to the fossil record, Ancestral State Reconstruction using extant taxa consistently underestimated MMC and PMM values, highlighting the necessity of fossil data for understanding evolutionary patterns in these traits. Given that G:P-defined dental traits may provide insight to biological mechanisms that reach far beyond the dentition, this new approach to fossil morphology has the potential to open an entirely new window onto extinct paleobiologies. Without the fossil record, we would not be able to grasp the full range of variation in those biological mechanisms that have existed throughout evolution.

The acceptability of cognitive analytic therapy (CAT): Meta-analysis and benchmarking of treatment refusal and treatment dropout rates.

AIM: To estimate treatment refusal and treatment dropout rates for cognitive analytic therapy (CAT) and then benchmark these rates against other psychotherapies. METHOD: PROSPERO registration CRD4202017081. Systematic searches found CAT treatment studies reporting treatment refusal and dropout rates. Studies were narratively and quantitatively synthesised in a proportional random-effects meta-analysis and moderator analyses were performed. Secondary analyses compared refusal and dropout rates for CAT versus other psychotherapies via direct comparisons in the original studies and via benchmarking these rates against other acceptability meta-analyses for other psychotherapies. RESULTS: Thirty-four CAT studies were included in the review. The treatment refusal rate was 15.35% (k = 9, 95% CIs 8.78-23.21). The treatment dropout rate was 18.69% (k = 34, 95% CI's 15.02-22.62). CAT generated significantly lower dropout rates relative to treatment comparators in the original studies (OR = 0.67; 95% CI 0.48-0.93). Country and younger age were significant moderators of dropout rates. CAT had a comparable treatment refusal rate and was towards the lower end of the dropout range when benchmarked against other psychotherapies. CONCLUSIONS: CAT as a brief and integrative psychotherapy for individuals presenting with typically complex psychological disorders appears a relatively acceptable intervention to patients.

Peptide-Affinity Isolation of Extracellular Vesicles and Cell-Free DNA From Human Plasma.

Extracellular vesicles (EVs) are membrane-bound nanoparticles that carry DNA, RNA, and protein cargoes and are found in a variety of biofluids. EVs, along with cell-free DNA (cfDNA), have attracted interest as a source of biomarker material for liquid biopsy, a process in which a sample of body fluid is used for the detection or monitoring of disease. The Vn96 synthetic peptide facilitates the isolation of both EVs and cfDNA from multiple body fluids, including human plasma, placing it as a versatile tool for the capture of multiple biomarker materials for disease detection and/or treatment monitoring. In this chapter, we describe an optimized protocol for Vn96-mediated isolation of EVs and cfDNA from human plasma samples, as well as downstream methods for EV enumeration and DNA, RNA, and protein extraction from the material captured by Vn96 for use in biomarker discovery or detection.

Development and implementation of a national online application system for cross-jurisdictional linked data.

The Population Health Research Network (PHRN) is an Australian national data linkage infrastructure that links a wide range of health and human services data in privacy-preserving ways. The data linkage infrastructure enables researchers to apply for access to routinely collected, linked, administrative data from the six states and two territories which make up the Commonwealth of Australia, as well as data collected by the Australian Government. The PHRN is a distributed network where data is collected and managed at the respective jurisdictional and/or cross-jurisdictional levels. As a result, access to linked data from multiple jurisdictions requires complex approval processes. This paper describes Australia's approach to enabling access to linked data from multiple jurisdictions. It covers the identification of, and agreement to, a minimum set of data items to be included in a unified national application form, the development and implementation of a national online application system and the harmonisation of business processes for cross-jurisdictional research projects. Utilisation of the online application system and the ongoing challenges of data linkage across jurisdictions are discussed. Changes to the data custodian and ethics committee approval criteria were out of scope for this project.

Progressing to Objective Measures of Daily Mobility in Hospitalized Older Adults.

Accurate mobility assessment of hospitalized older adults is necessary to aid nurses in planning and providing appropriate mobility support; however, nurses cite lack of resources and time limitations as barriers. Accelerometry enables a detailed objective measurement of predominant hospital mobility activities in the older adult population, such as percent time sitting, and the sit-to-stand (STS) transition. The current exploratory study examined the use of a novel, unobtrusive accelerometry technique to obtain postural and STS metrics on 27 older adults during their hospital stay. Total device wear time in the hospital was 96.2%. Participants spent 60.3% time lying, 20.3% time sitting, 5.3% time standing, and 2% time stepping during hospitalization, and, on average, completed the STS transition 20 times (SD = 13) per 24-hour period. There were no participant complaints about wearing the device. Our exploratory study shows accelerometry provides automated, continuous data and may support accurate nursing assessment of patient mobility. [Journal of Gerontological Nursing, 48(5), 35-41.].

Small Molecule 20S Proteasome Enhancer Regulates MYC Protein Stability and Exhibits Antitumor Activity in Multiple Myeloma.

Despite the addition of several new agents to the armamentarium for the treatment of multiple myeloma (MM) in the last decade and improvements in outcomes, the refractory and relapsing disease continues to take a great toll, limiting overall survival. Therefore, additional novel approaches are needed to improve outcomes for MM patients. The oncogenic transcription factor MYC drives cell growth, differentiation and tumor development in many cancers. MYC protein levels are tightly regulated by the proteasome and an increase in MYC protein expression is found in more than 70% of all human cancers, including MM. In addition to the ubiquitin-dependent degradation of MYC by the 26S proteasome, MYC levels are also regulated in a ubiquitin-independent manner through the REGγ activation of the 20S proteasome. Here, we demonstrate that a small molecule activator of the 20S proteasome, TCH-165, decreases MYC protein levels, in a manner that parallels REGγ protein-mediated MYC degradation. TCH-165 enhances MYC degradation and reduces cancer cell growth in vitro and in vivo models of multiple myeloma by enhancing apoptotic signaling, as assessed by targeted gene expression analysis of cancer pathways. Furthermore, 20S proteasome enhancement is well tolerated in mice and dogs. These data support the therapeutic potential of small molecule-driven 20S proteasome activation for the treatments of MYC-driven cancers, especially MM.

Educational Outcomes of Childhood Survivors of Critical Illness-A Population-Based Linkage Study.

OBJECTIVES: Major postintensive care sequelae affect up to one in three adult survivors of critical illness. Large cohorts on educational outcomes after pediatric intensive care are lacking. We assessed primary school educational outcomes in a statewide cohort of children who survived PICU during childhood. DESIGN: Multicenter population-based study on children less than 5 years admitted to PICU. Using the National Assessment Program-Literacy and Numeracy database, the primary outcome was educational achievement below the National Minimum Standard (NMS) in year 3 of primary school. Cases were compared with controls matched for calendar year, grade, birth cohort, sex, socioeconomic status, Aboriginal and Torres Strait Islander status, and school. Multivariable logistic regression models to predict educational outcomes were derived. SETTING: Tertiary PICUs and mixed ICUs in Queensland, Australia. PATIENTS: Children less than 5 years admitted to PICU between 1998 and 2016. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Year 3 primary school data were available for 5,017 PICU survivors (median age, 8.0 mo at first PICU admission; interquartile range, 1.9-25.2). PICU survivors scored significantly lower than controls across each domain (p < 0.001); 14.03% of PICU survivors did not meet the NMS compared with 8.96% of matched controls (p < 0.001). In multivariate analyses, socioeconomic status (odds ratio, 2.14; 95% CI, 1.67-2.74), weight (0.94; 0.90-0.97), logit of Pediatric Index of Mortality-2 score (1.11; 1.03-1.19), presence of a syndrome (11.58; 8.87-15.11), prematurity (1.54; 1.09-2.19), chronic neurologic conditions (4.38; 3.27-5.87), chronic respiratory conditions (1.65; 1.24-2.19), and continuous renal replacement therapy (4.20; 1.40-12.55) were independently associated with a higher risk of not meeting the NMS. CONCLUSIONS: In this population-based study of childhood PICU survivors, 14.03% did not meet NMSs in the standardized primary school assessment. Socioeconomic status, underlying diseases, and severity on presentation allow risk-stratification to identify children most likely to benefit from individual follow-up and support.

Cryoablation for Chest Wall Trauma: A Brief Report.

Respiratory failure secondary to rib fractures is a major source of morbidity and mortality in trauma patients, particularly in older populations. Management of pain in these patients is complex due to the nature of the injuries. We present 3 patients who underwent a video-assisted thoracoscopic cryoablation of intercostal nerves for pain control after chest trauma. None of the patients developed post-operative complications related to poor respiratory status such as pneumonia or atelectasis. At one-month clinic follow-up, all patients reported no chest pain and were not using opiate analgesics. In patients for whom there is a contraindication to rib fixation in the setting of unstable rib fractures, cryoablation may be a method by which to improve respiratory status and decrease ventilator dependency due to pain. Cryoablation of intercostal nerves may provide a more durable and clinically feasible solution to aid in the healing process of these patients.

Renal protection during 177lutetium DOTATATE molecular radiotherapy in children: a proposal for safe amino acid infusional volume during peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues such as 177-lutetium DOTATATE is an effective treatment modality for neuroendocrine tumours, paragangliomas, and neuroblastomas. However, renal and haematopoietic toxicities are the major limitations of this therapeutic approach. The renal toxicity of PRRT is mediated by renal proximal tubular reabsorption and interstitial retention of the radiolabelled peptides resulting in excessive renal irradiation that can be dose-limiting. To protect the kidneys from PRRT-induced radiation nephropathy, basic amino acids are infused during PRRT as they competitively bind to the proximal tubular cells and prevent uptake of the radionuclide. In adults, 1 L of a basic amino acid solution consisting of arginine and lysine is infused over 4 h commencing 30 min prior to PRRT. However, this volume of amino acids infused over 4 h is excessive in small children and can result in hemodynamic overload. This is all the more relevant in paediatric oncology, as many of the children may have been heavily pretreated and so may have treatment-related renal and or cardiac impairment. We have therefore developed the following guidelines for safe paediatric dosing of renal protective amino acid infusions during PRRT. Our recommendations have been made taking into consideration the renal physiology in small children and the principles of safe fluid management in children.