Search

Patients with cancer have impaired kidney function and increased susceptibility to nephrotoxic agents. Cisplatin is a commonly used chemotherapeutic with nephrotoxicity as the dose-limiting side effect. Cisplatin nephrotoxicity is almost exclusively studied in mice without cancer. Our current preclinical models do not adequately represent the complexity of patients with cancer. This study demonstrates increased renal toxicity, injury, and fibrosis in mice with lung cancer, which is exacerbated with cisplatin treatment. These results highlight the necessity of using preclinical models that more accurately capture the altered physiology of patients with cancer treated with cisplatin.

Structural racism-the ways that institutional policies, practices, and other norms operate to create and sustain race-based inequities1-has historically been foundational to the operations of academic medical centers and research institutions. Since its inception, academic medicine has depended on the exploitation of vulnerable communities to achieve medical, educational, and research goals.2 Research practices have long ignored or taken advantage of the individuals purportedly benefiting from the research, a dynamic most manifestly true for Black, Indigenous, and People of Color (BIPOC) communities in the United States. Reflecting current practices in racial justice work, we intentionally use the term "BIPOC" to highlight shared experiences within racially and ethnically minoritized communities, given the history of white supremacy in the United States. We acknowledge limitations of this term, which collapses myriad unique communities and histories into 1 construct. Specifically, child and adolescent psychiatry has historically been driven by Eurocentric approaches, paradigms, and methodology. These nonparticipatory dominant research practices have contributed to a lack of culturally responsive interventions for BIPOC communities, a paucity of evidence-based practices with demonstrated effectiveness within BIPOC communities, and disparities in access and quality of care.3 Mental health research involving BIPOC communities has been replete with exploitation and inequality.2.

Access to accurate, up-to-date information about resources and services is essential if survivors are to recover following disasters. Emergency managers need information about community resources to effectively plan for the recovery phase. Long-term recovery committees and case managers rely on resource directories to design recovery plans with survivors. This article describes a replicable approach used to swiftly create and maintain an online resource directory for individuals with disabilities following Hurricane Harvey.

In November 2018, we screened 315 feral Horse mares via veterinary rectal palpation and trans-rectal ultrasound, approximately 1 mo after their capture and removal from the Warm Springs herd management area in Oregon. We documented a pregnancy rate (58.3%) in 2-y-old mares that was nearly 3 times higher than previously published results. For 1-y-old mares (10.8% pregnant), and for mares pooled over all ages (64.4% pregnant), pregnancy rates were within the range of pregnancy rates reported from other feral Horse populations. High pregnancy rates in 2-y-old mares could contribute to higher than expected herd growth rates in feral Horses.

The use of multiple medications is growing at an alarming rate with some reports documenting an average of 12 to 22 prescriptions being used by individuals ≥50 years of age. The indirect consequences of polypharmacy include exacerbation of drug-drug interactions, adverse drug reactions, increased likelihood of prescribing cascades, chronic dependence, and hospitalizations - all of which have significant health and economic burden. While many practical solutions for reducing polypharmacy have been proposed, they have been met with limited efficacy. This highlights the need for a new systematic approach for fine-tuning dispensing of medications. Pharmacogenetic testing provides an empirical and scientifically rigorous approach for guiding appropriate selection of medicines, with the potential to reduce unnecessary polypharmacy while improving clinical outcomes. The goal of this review article is to provide healthcare providers with an understanding of polypharmacy, its adverse effects on the healthcare system and highlight how pharmacogenetic information can be used to avoid polypharmacy in patients.

The current moment in history is marked by a sense of anxiety about the future of human rights as a global project. In many instances, human rights pessimism has eclipsed a larger empirical picture of human rights progress. In assessing this paradox of perception, I argue that human rights professionals themselves contribute to this sense of pessimism and crisis in ways that can become counterproductive and demobilizing. Promoting a more positive and balanced human rights vision reflecting both progress and challenges will require several shifts in emphasis over the coming years, beginning with some neglected conversations for the broader field of human rights. These conversations relate to (1) an assessment of the ways in which the prism of professional experience has shaped the messaging and world view of human rights advocates; (2) the role of human rights critics in promoting new thinking and reform; and (3) the need for advocates to go beyond what I call the ‘legalistic referee model’ in their attempts to promote positive change.

Long Interspersed Nuclear Element-1 (LINE-1) are DNAs that compromise 17% of our genome. LINE-1 expression is triggered by environmental stressors and accomplished through its demethylation leading to genomic instability. Expression of LINE-1 is regulated in adult somatic tissues through several endogenous defensive mechanisms, but is found to be associated with tumorigenesis in several cancers. This finding, has inspired the use of different indicators of LINE-1 activation, as biomarkers in cancer diagnostics and even therapeutic targets in recent years. The objective of this review is to provide a critical examination of LINE-1 elements as companion cancer diagnostic/prognostic biomarkers and anti-cancer drug targets. In our view, there's great potential for LINE-1 serving at both forefronts, but there is a need for more mechanistic studies in the clinic as well as on the bench research to validate LINE-1 activation elements as cancer biomarkers or therapeutic targets; in different cancer types and/or stages of the disease. In this context, development of minimally invasive, reliable and sensitive diagnostic tools for LINE-1 activation elements for clinical use, is of priority.

Background: κ and λ free light chains (FLCs) are monitored to aid in the diagnosis of plasma cell disorders. Our goal was to validate the Diazyme Human κ and λ assays on Beckman Coulter UniCel DxC 800 Synchron and compare to Freelite κ and λ assays on Roche Cobas Integra. Methods: Linearity verification, within- and between-run precision, method comparison, and reference range (RR) verification were conducted using CLSI guidelines. Statistical analysis was performed using EP Evaluator®. Mean, SD, CV, and bias were determined. Results: Diazyme κ FLC assay was linear within 0.00–191.00 mg/L. Diazyme λ FLC assay was linear within 0.00–205.30 mg/L. Diazyme κ FLC QC1 had a mean of 16.70 mg/L, CV of 7.0%. QC2 had a mean of 33.37 mg/L, CV of 2.6%. Diazyme λ FLC QC1 had a mean of 21.73 mg/L, CV of 2.3%. QC2 had a mean of 42.05 mg/L, CV of 1.5%. Bias of DxC-Diazyme FLCs compared to Integra-Freelite FLCs was −2.55 mg/L (κ FLC), and 4.54 mg/L (λ FLC). Qualitative comparison of κ FLC assays indicated 100% agreement for both normal and abnormal values. For λ FLC assay, agreement was 95% for normal values and 75% for abnormal values. For κ/λ ratio there was 50% agreement for normal values, and 100% for abnormal values. For RR verification, 1 sample was outside the Diazyme κ RR. For λ, all samples were within the manufacturer9s RR. Conclusions: Diazyme assays for FLCs have excellent precision and accuracy and are comparable to Freelite assays.

International audience; This paper reports the results of an international benchmark exercise on the measurement of fibre bed compaction behaviour. The aim was to identify aspects of the test method critical to obtain reliable results and to arrive at a recommended test procedure for fibre bed compaction measurements. A glass fibre 2/2 twill weave and a biaxial (±45°) glass fibre non-crimp fabric (NCF) were tested in dry and wet conditions. All participants used the same testing procedure but were allowed to use the testing frame, the fixture and sample geometry of their choice. The results showed a large scatter in the maximum compaction stress between participants at the given target thickness, with coefficients of variation ranging from 38 % to 58 %. Statistical analysis of data indicated that wetting of the specimen significantly affected the scatter in results for the woven fabric, but not for the NCF. This is related to the fibre mobility in the architectures in both fabrics. As isolating the effect of other test parameters on the results was not possible, no statistically significant effect of other test parameters could be proven. The high sensitivity of the recorded compaction pressure near the minimum specimen thickness to changes in specimen thickness suggests that small uncertainties in thickness can result in large variations in the maximum value of the compaction stress. Hence, it is suspected that the thickness measurement technique used may have an effect on the scatter.

C57BL/6 mice are one of the most commonly used mouse strains in research, especially in kidney injury studies. However, C57BL/6 mice are resistant to chronic kidney disease-associated pathologies, particularly the development of glomerulosclerosis and interstitial fibrosis. Our laboratory and others developed a more clinically relevant dosing regimen of cisplatin (7 mg/kg cisplatin once a week for 4 wk and mice euthanized at day 24) that leads to the development of progressive kidney fibrosis in FVB/n mice. However, we found that treating C57BL/6 mice with this same dosing regimen does not result in kidney fibrosis. In this study, we demonstrated that increasing the dose of cisplatin to 9 mg/kg once a week for 4 wk is sufficient to consistently induce fibrosis in C57BL/6 mice while maintaining animal survival. In addition, we present that cohorts of C57BL/6 mice purchased from Jackson 1 yr apart and mice bred in-house display variability in renal outcomes following repeated low-dose cisplatin treatment. Indepth analyses of this intra-animal variability revealed C-C motif chemokine ligand 2 as a marker of cisplatin-induced kidney injury through correlation studies. In addition, significant immune cell infiltration was observed in the kidney after four doses of 9 mg/kg cisplatin, contrary to what has been previously reported. These results indicate that multiple strains of mice can be used with our repeated low-dose cisplatin model with dose optimization. Results also indicate that littermate control mice should be used with this model to account for population variability.

Background For many laboratories, autoimmune encephalopathy (AE) panels are send-out tests. These tests are expensive, and ordering patterns vary greatly. There is also a lack of consensus on which panel to order and poor understanding of the clinical utility of these panels. These challenges were presented to our newly formed, multidisciplinary, diagnostic stewardship committee (DSC). Through this collaboration, we developed an algorithm for ordering AE panels; combining diagnostic criteria with practice guidelines. Methods We analyzed test-ordering patterns in 2018 and calculated a true-positive rate based on clinical presentation and panel interpretation. An evidence-based approach was combined with input from the Department of Neurology to synthesize our algorithm. Efficacy of the algorithm (number of panels ordered, cost, and true positives) was assessed before and after implementation. Results In 2018, 77 AE-related panels were ordered, costing $137 510. The true-positive rate was 10%, although ordering multiple, similar panels for the same patient was common. Before implementing the algorithm (January 1–July 31, 2019), 55 panels were ordered, costing $105 120. The total true-positive rate was 3.6%. After implementation, 23 tests were ordered in a 5-month period, totaling $50 220. The true-positive rate was 13%. Conclusion With the DSC-directed mandate, we developed an algorithm for ordering AE panels. Comparison of pre- and postimplementation data showed a higher true-positive rate, indicating that our algorithm was able to successfully identify the at-risk population for AE disorders. This was met with a 43% decrease in the number of tests ordered, with total cost savings of $25 000 over 5 months.

Transitional justice has been said to be in a state of crisis for over a decade now, giving rise to a number of alternative visions for justice-making thought to hold out the possibility of greater legitimacy and effectiveness going forward. One such alternative vision is that of transformative justice. While in many ways a welcome response to the blindspots of mainstream transitional justice, I argue that transformative justice is unlikely to resolve the crises and tensions at the heart of the field for several reasons. At its core, transformative justice does not so much transcend liberalism as it does take sides in a long-running contest between competing and irreconcilable liberal values. There is therefore a danger of simply displacing faith in one set of liberal values and political preferences for another without adequate examination of the tradeoffs involved. At a more operational level, the dilemmas that have stymied mainstream transitional justice arising out of the challenges of the law, of elites, and the global are likely to be re-encountered in another guise. Transformative justice will loosen old knots, only to succeed in tying new ones. Going forward, I call for a “both/and” stance to the complex realities of the post-conflict context, one that embraces the messy, hybrid, and essentially contested nature of peace and justice work.

Cisplatin is used to treat many solid cancers, but its dose-limiting side effect is nephrotoxicity, causing acute kidney injury in 30% of patients. Previously, we have developed a mouse model that better recapitulates the cisplatin dosing regimen humans receive and found that repeated dosing of cisplatin induces interstitial renal fibrosis. Chronic kidney disease is progressive and is characterized by chronic inflammation, worsening interstitial fibrosis, development of glomerulosclerosis, and endothelial dysfunction. To determine if damage caused by repeated cisplatin dosing results in bona fide chronic kidney disease, mice were treated with our repeated dosing regimen and then aged for 6 mo. These mice had progressive, chronic inflammation and worsened interstitial fibrosis compared with mice euthanized after day 24. Mice aged for 6 mo developed glomerular pathologies, and endothelial dysfunction was persistent. Mice treated with only two doses of cisplatin had little inflammation or kidney damage. Thus repeated dosing of cisplatin causes long-term effects that are characteristic of chronic kidney disease. This translational mouse model of cisplatin injury may better represent the 70% of patients that do not develop clinical acute kidney injury and can be used to identify both biomarkers for early injury, as well as novel therapeutic targets for the prevention of cisplatin-induced chronic kidney disease.

Tics occur in up to 20% of children and are a defining feature of Tourette syndrome (TS). When treatment is necessary, there are many options available. The purpose of this review is to present an overview of the standard, complementary/alternative medicine (CAM), and emerging treatments of tics and provide examples of the current evidence supporting these therapies. Behavioral therapy and conventional pharmacotherapy are the mainstays of treatment and have the strongest evidence to support their use. CAM is common, but there are few rigorous randomized, controlled trials evaluating the safety and efficacy of these modalities. Several novel pharmacological and nonpharmacological treatments targeting specific pathways thought to be involved in TS are currently being studied with the hope of expanding future treatment options. We conclude that there is an ongoing need for new evidence-based approaches for safe and effective treatment of tics.

Background Identification of newborns exposed to illicit drugs during pregnancy is important to assess families with substance abuse disorders requiring a close follow-up of the infant by both medical and social services. Drug screening and confirmation in newborns has been traditionally performed on meconium. In recent years, umbilical cord (UC) tissue has gained popularity as an alternative specimen. Here, we present two cases of paired meconium and UC drug testing leading to different outcomes. The objective of this report is to highlight the inconsistencies that may occur with paired testing, and how these results may be interpreted. Methods We report two cases of newborn drug screening of premature infants born to mothers with a history of drug abuse. The drug testing was performed on paired meconium, UC tissue and/or urine samples. UC tissue testing was referred to NMS laboratories (Horsham, PA) using HPLC-MS/MS followed by confirmation with the same method. Meconium samples were analyzed by LabCorp laboratories (Louisville, KY) using immunoassay followed by confirmation by HPLC-MS/MS. Urine drug screening was performed on both maternal and newborn samples at University of Louisville Hospital (ULH) using an immunoassay-based method. Confirmation of urine drug screening was confirmed with HPLC-MS/MS send-out to LabCorp. Each specimen was tested for amphetamine, methamphetamine, opiates, cocaine, cannabinoids and phencyclidine. Results Case I: An early term infant was born at 38 weeks and 3 days to a 35-year-old mother who has a history of drug abuse of amphetamines and opiates. Initially, the urine drug screens from both the mother and the baby were positive for amphetamine and/or methamphetamine. Meconium drug screening indicated the presence of amphetamine, methamphetamine, morphine, codeine, benzoylecgonine and m-OH-benzoylecgonine. In the UC, codeine was not detected, and fentanyl and norfentanyl gave positive results. Case II A preterm infant was born at approximately 36 weeks to a 33-year-old mother who had a history of drug abuse, stillbirth, and was diagnosed with hepatitis C. The mother had no prenatal care or ultrasounds for this pregnancy. Maternal urine drug screening was positive for amphetamine, methamphetamine and buprenorphine; the newborn’s urine sample was not available at that time. No confirmation was performed for UDS. LC-MS/MS toxicology testing on meconium revealed the presence of amphetamine, methamphetamine, buprenorphine and its metabolite norbuprenorphine. UC did not detect any buprenorphine or norbuprenorphine. Conclusion The two cases have revealed different sensitivities for drug detection in meconium and UC tissue. Meconium, to a significant extent, provides higher sensitivity, and is likely to remain the specimen of choice when sensitivity is of greatest importance. These results can help clinicians, laboratorians, and epidemiologists to (1) select the most appropriate test to confirm a suspected drug exposure and (2) interpret discordant results when testing is performed in multiple matrices.

Tulane virus is one of many enteric caliciviruses that cause acute gastroenteritis and diarrheal disease. Globally, enteric caliciviruses affect both humans and animals and amass >65 billion dollars per year in treatment and health care-associated costs, thus imposing an enormous economic burden. Recent progress has resulted in several cultivation systems (B cells, enteroids, and zebrafish larvae) to study human noroviruses, but mechanistic insights into the viral factors and host pathways important for enteric calicivirus replication and infection are still largely lacking. Here, we used Tulane virus, a calicivirus that is biologically similar to human noroviruses and can be cultivated by conventional cell culture, to identify and functionally validate NS1-2 as an enteric calicivirus viroporin. Viroporin-mediated calcium signaling may be a broadly utilized pathway for enteric virus replication, and its existence within caliciviruses provides a novel approach to developing antivirals and comprehensive therapeutics for enteric calicivirus diarrheal disease outbreaks., Enteric viruses in the Caliciviridae family cause acute gastroenteritis in humans and animals, but the cellular processes needed for virus replication and disease remain unknown. A common strategy among enteric viruses, including rotaviruses and enteroviruses, is to encode a viral ion channel (i.e., viroporin) that is targeted to the endoplasmic reticulum (ER) and disrupts host calcium (Ca2+) homeostasis. Previous reports have demonstrated genetic and functional similarities between the nonstructural proteins of caliciviruses and enteroviruses, including the calicivirus NS1-2 protein and the 2B viroporin of enteroviruses. However, it is unknown whether caliciviruses alter Ca2+ homeostasis for virus replication or whether the NS1-2 protein has viroporin activity like its enterovirus counterpart. To address these questions, we used Tulane virus (TV), a rhesus enteric calicivirus, to examine Ca2+ signaling during infection and determine whether NS1-2 has viroporin activity that disrupts Ca2+ homeostasis. We found that TV increases Ca2+ signaling during infection and that increased cytoplasmic Ca2+ levels are important for efficient replication. Further, TV NS1-2 localizes to the endoplasmic reticulum, the predominant intracellular Ca2+ store, and the NS2 region has characteristics of a viroporin domain (VPD). NS1-2 had viroporin activity in a classic bacterial functional assay and caused aberrant Ca2+ signaling when expressed in mammalian cells, but truncation of the VPD abrogated these activities. Together, our data provide new mechanistic insights into the function of the NS2 region of NS1-2 and support the premise that enteric viruses, including those within Caliciviridae, exploit host Ca2+ signaling to facilitate their replication. IMPORTANCE Tulane virus is one of many enteric caliciviruses that cause acute gastroenteritis and diarrheal disease. Globally, enteric caliciviruses affect both humans and animals and amass >65 billion dollars per year in treatment and health care-associated costs, thus imposing an enormous economic burden. Recent progress has resulted in several cultivation systems (B cells, enteroids, and zebrafish larvae) to study human noroviruses, but mechanistic insights into the viral factors and host pathways important for enteric calicivirus replication and infection are still largely lacking. Here, we used Tulane virus, a calicivirus that is biologically similar to human noroviruses and can be cultivated by conventional cell culture, to identify and functionally validate NS1-2 as an enteric calicivirus viroporin. Viroporin-mediated calcium signaling may be a broadly utilized pathway for enteric virus replication, and its existence within caliciviruses provides a novel approach to developing antivirals and comprehensive therapeutics for enteric calicivirus diarrheal disease outbreaks.

Although good progress was made by two international benchmark exercises on in-plane permeability, existing methods have not yet been standardized. This paper presents the results of a third benchmark exercise using in-plane permeability measurement, based on systems applying the radial unsaturated injection method. 19 participants using 20 systems characterized a non-crimp and a woven fabric at three different fiber volume contents, using a commercially available silicone oil as impregnating fluid. They followed a detailed characterization procedure and also completed a questionnaire on their set-up and analysis methods. Excluding outliers (2 of 20), the average coefficient of variation (c v ) between the participant´s results was 32% and 44% (non-crimp and woven fabric), while the average c v for individual participants was 8% and 12%, respectively. This indicates statistically significant variations between the measurement systems. Cavity deformation was identified as a major influence, besides fluid pressure/viscosity measurement, textile variations, and data analysis. Fil: May, D.. Institut Für Verbundwerkstoffe Gmbh; Alemania Fil: Aktas, A.. National Physical Laboratory; Reino Unido Fil: Advani, S.G.. University Of Delaware; Estados Unidos Fil: Berg, D. C.. Technische Universität Clausthal; Alemania Fil: Endruweit, A.. University of Nottingham; Estados Unidos. Science and Technology Facilities Council of Nottingham. Rutherford Appleton Laboratory; Reino Unido Fil: Fauster, E.. Montanuniversitat Leoben; Austria Fil: Lomov, S. V.. Katholikie Universiteit Leuven; Bélgica Fil: Long, A.. University of Nottingham; Estados Unidos. Science and Technology Facilities Council of Nottingham. Rutherford Appleton Laboratory; Reino Unido Fil: Mitschang, P.. Institut Für Verbundwerkstoffe Gmbh; Alemania Fil: Abaimov, S.. Skolkovo Institute Of Science And Technology; Rusia Fil: Abliz, D.. Technische Universität Clausthal; Alemania Fil: Akhatov, I.. Skolkovo Institute Of Science And Technology; Rusia Fil: Ali, M. A.. Khalifa University Of Science And Technology; Emiratos Arabes Unidos Fil: Allen, T. D.. University of Auckland; Nueva Zelanda Fil: Bickerton, S.. University of Auckland; Nueva Zelanda Fil: Bodaghi, M.. Institute Of Science And Innovation In Mechanical And Industrial; Portugal Fil: Caglar, B.. Koç Üniversitesi; Turquía Fil: Caglar, H.. Koç Üniversitesi; Turquía Fil: Chiminelli, A.. Instituto Tecnologico de Aragon; España Fil: Correia, N.. Institute Of Science And Innovation In Mechanical And Industrial; Portugal Fil: Cosson, B.. Imt Lille Douai; Francia Fil: Danzi, M.. Eth Zürich; Suiza Fil: Dittmann, J.. Universität Stuttgart; Alemania Fil: Ermanni, P.. Eth Zürich; Suiza Fil: Francucci, Gaston Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina Fil: George, A.. University Brigham Young; Estados Unidos Fil: Grishaev, V.. Skolkovo Institute Of Science And Technology; Rusia Fil: Hancioglu, M.. Koç Üniversitesi; Turquía Fil: Kabachi, M. A.. Eth Zürich; Suiza Fil: Kind, K.. Universitat Technical Zu Munich; Alemania Fil: Deléglise Lagardère, M.. Imt Lille Douai; Francia Fil: Laspalas, M.. Instituto Tecnologico de Aragon; España Fil: Lebedev, O. V.. Skolkovo Institute Of Science And Technology; Rusia Fil: Lizaranzu, M.. Instituto Tecnologico de Aragon; España Fil: Liotier, P. J.. Université de Lyon; Francia Fil: Middendorf, P.. Universität Stuttgart; Alemania Fil: Morán, J.. Universidad Nacional de Mar del Plata; Argentina Fil: Park, C. H.. Imt Lille Douai; Francia Fil: Pipes, R. B.. Purdue University; Estados Unidos Fil: Pucci, M. F.. Université de Montpellier; Austria Fil: Raynal, J.. Groupe Institut de Soudure; Francia Fil: Rodriguez, E. S.. Universidad Nacional de Mar del Plata; Argentina Fil: Schledjewski, R.. Montanuniversitat Leoben; Austria Fil: Schubnel, R.. Groupe Institut de Soudure; Francia Fil: Sharp, N.. Purdue University; Estados Unidos Fil: Sims, G.. National Physical Laboratory; Reino Unido Fil: Sozer, E. M.. Koç Üniversitesi; Turquía Fil: Sousa, P.. Katholikie Universiteit Leuven; Bélgica Fil: Thomas, J.. Khalifa University Of Science And Technology; Emiratos Arabes Unidos Fil: Umer, R.. Khalifa University Of Science And Technology; Emiratos Arabes Unidos Fil: Wijaya, W.. University of Auckland; Nueva Zelanda Fil: Willenbacher, B.. Institut Für Verbundwerkstoffe Gmbh; Alemania Fil: Yong, A.. National Physical Laboratory; Reino Unido Fil: Zaremba, S.. Universitat Technical Zu Munich; Alemania Fil: Ziegmann, G.. Technische Universität Clausthal; Alemania

∞ In recent years, a distinct critical turn in transitional justice scholarship has emerged, seeking to question the naturalness and inevitability of mainstream transitional justice theory and practice and to envision a broader and more holistic project. While in many ways a positive development, this newfound critical enthusiasm risks producing an unwarranted sense of pessimism and failure. This points to the need to better manage expectations as to what ‘success’ looks like even as we try to reimagine what transitional justice could become. To these ends, I draw upon and propose revisions to Robert Cox’s famous distinction between problem-solving and critical theory. To better maintain balance and perspective, I argue for the adoption of an ‘integrated’ approach to transitional justice critique that does more to engage with the difficult tradeoffs, policy choices and contextual realities that would inevitably be associated with efforts to implement an alternative vision of transitional justice.

Although there appears to be a growing interest in exploring the crossroads between spirituality and social change, spirituality remains a relatively obscure topic within mainstream international human rights. This article will explore what a more spiritual grounding for human rights might look like and how it might change perspectives and practices from the comparatively conventional and mainstream. I argue that viewing conventional human rights thinking, policy, and practice through the lens of spirituality can facilitate a better and more balanced reading of the human rights corpus, and ultimately, better and more sustainable human rights practice. While no panacea, spiritual perspectives that enhance a sense of interconnectedness and inclusionary identity may be one way of re-invigorating the human rights project at a time when it is said to be in a state of crisis.

Cisplatin, a chemotherapeutic used for the treatment of solid cancers, has nephrotoxic side effects leading to acute kidney injury (AKI). Cisplatin cannot be given to patients that have comorbidities that predispose them to an increased risk for AKI. Even without these comorbidities, 30% of patients administered cisplatin will develop kidney injury, requiring the oncologist to withhold or reduce the next dose, leading to a less effective therapeutic regimen. Although recovery can occur after one episode of cisplatin-induced AKI, longitudinal studies have indicated that multiple episodes of AKI lead to the development of chronic kidney disease, an irreversible disease with no current treatment. The standard mouse model of cisplatin-induced AKI consists of one high dose of cisplatin (>20 mg/kg) that is lethal to the animal 3 days later. This model does not accurately reflect the dosing regimen patients receive nor does it allow for the long-term study of kidney function and biology. We have developed a repeated dosing model whereby cisplatin is given once a week for 4 wk. Comparison of the repeated dosing model with the standard dosing model demonstrated that inflammatory cytokines and chemokines were induced in the repeated dosing model, but levels of cell death were lower in the repeated dosing model. The repeated dosing model had increased levels of fibrotic markers (fibronectin, transforming growth factor-β, and α-smooth muscle actin) and interstitial fibrosis. These data indicate that the repeated dosing model can be used to study the AKI to chronic kidney disease progression as well as the mechanisms of this progression.