Banff 2022 pancreas transplantation multidisciplinary report: Refinement of guidelines for T cell-mediated rejection, antibody-mediated rejection and islet pathology. Assessment of duodenal cuff biopsies and noninvasive diagnostic methods.

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training.

Estimated Therapy Costs and Downstream Cost Consequences of iBASIS-Video Interaction to Promote Positive Parenting Intervention vs Usual Care Among Children Displaying Early Behavioral Signs of Autism in Australia.

Importance: The growing global prevalence of autism spectrum disorder (ASD) is associated with increasing costs for support services. Ascertaining the effects of a successful preemptive intervention for infants showing early behavioral signs of autism on human services budgets is highly policy relevant. Objective: To estimate the net cost impact of the iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP) intervention on the Australian government. Design, Setting, and Participants: Infants (aged 12 months) showing early behavioral indicators of autism were recruited through community settings into the multicenter Australian iBASIS-VIPP randomized clinical trial (RCT), a 5- to 6-month preemptive parent-mediated intervention, between June 9, 2016, and March 30, 2018, and were followed up for 18 months to age 3 years. This economic evaluation, including cost analysis (intervention and cost consequences) and cost-effectiveness analyses of iBASIS-VIPP compared with usual care (treatment as usual [TAU]), modeled outcomes observed at age 3 through to 12 years (13th birthday) and was conducted from April 1, 2021, to January 30, 2023. Data analysis was conducted from July 1, 2021, to January 29, 2023. Exposures: iBASIS-VIPP intervention. Main Outcomes and Measures: To project the diagnostic trajectory and associated disability support costs drawing on the Australian National Disability Insurance Scheme (NDIS), the main outcome was the differential treatment cost of iBASIS-VIPP plus TAU vs TAU and disability-related government costs modeled to age 12 years, using a clinical diagnosis of ASD and developmental delay (with autism traits) at 3 years. Costs were calculated in Australian dollars and converted to US dollars. Economic performance was measured through the following: (1) differential net present value (NPV) cost (iBASIS-VIPP less TAU), (2) investment return (dollars saved for each dollar invested, taking a third-party payer perspective), (3) break-even age when treatment cost was offset by downstream cost savings, and (4) cost-effectiveness in terms of the differential treatment cost per differential ASD diagnosis at age 3 years. Alternate values of key parameters were modeled in 1-way and probabilistic sensitivity analysis, the latter identifying the likelihood of an NPV cost savings. Results: Of the 103 infants enrolled in the iBASIS-VIPP RCT, 70 (68.0%) were boys. Follow-up data at age 3 years were available for 89 children who received TAU (44 [49.4%]) or iBASIS-VIPP (45 [50.6%]) and were included in this analysis. The estimated mean differential treatment cost was A $5131 (US $3607) per child for iBASIS-VIPP less TAU. The best estimate of NPV cost savings was A $10 695 (US $7519) per child (discounted at 3% per annum). For each dollar invested in treatment, a savings of A $3.08 (US $3.08) was estimated; the break-even cost occurred at age 5.3 years (approximately 4 years after intervention delivery). The mean differential treatment cost per lower incident case of ASD was A $37 181 (US $26 138). We estimated that there was an 88.9% chance that iBASIS-VIPP would deliver a cost savings for the NDIS, the dominant third-party payer. Conclusions and Relevance: The results of this study suggest that iBASIS-VIPP represents a likely good-value societal investment for supporting neurodivergent children. The estimated net cost savings were considered conservative, as they covered only third-party payer costs incurred by the NDIS and outcomes were modeled to just age 12 years. These findings further suggest that preemptive interventions may be a feasible, effective, and efficient new clinical pathway for ASD, reducing disability and the costs of support services. Long-term follow-up of children receiving preemptive intervention is needed to confirm the modeled results.

Financial, policy, and ethical barriers to the expansion of living donor liver transplant: Meeting report from a living donor liver transplant consensus conference.

INTRODUCTION: In October 2021, the American Society of Transplantation (AST) hosted a virtual consensus conference aimed at identifying and addressing barriers to the broader, safe expansion of living donor liver transplantation (LDLT) throughout the United States (US). METHODS: A multidisciplinary group of LDLT experts convened to address issues related to financial implications on the donor, transplant center crisis management, regulatory and oversight policies, and ethical considerations by assessing the relative significance of issues in preventing LDLT growth, with proposed strategies to overcome barriers. RESULTS: Living liver donors endure multiple obstacles including financial instability, loss of job security, and potential morbidity. These concerns, along with other center, state, and federal specific policies can be perceived as significant barriers to expanding LDLT. Donor safety is of paramount importance to the transplant community; however, regulatory and oversight policies aimed at ensuring donor safety can be viewed as ambiguous and complicated leading to time-consuming evaluations that may deter donor motivation and program expansion. CONCLUSION: Transplant programs need to establish appropriate crisis management plans to mitigate potential negative donor outcomes and ensure program viability and stability. Finally, ethical aspects, including informed consent for high-risk recipients and use of non-directed donors, can be perceived as additional barriers to expanding LDLT.

Effect of socioeconomic status on patients undergoing elective abdominal aortic aneurysm repair in a publicly funded health care system.

BACKGROUND: The association between socioeconomic status (SES) and outcomes after abdominal aortic aneurysm (AAA) repair in publicly funded health care systems is poorly described. The purpose of this study was to determine the effect of SES on postoperative outcomes in patients who underwent AAA repair in Nova Scotia, Canada. METHODS: We performed a retrospective analysis of all elective AAA repairs in Nova Scotia between November 2005 and March 2015 using administrative data sources. We compared postoperative 30-day outcomes and long-term survival across socio-economic quintiles, defined as the Pampalon Material Deprivation Index (MDI) and Social Deprivation Index (SDI). We also compared the relation between baseline characteristics, MDI quintile, SDI quintile and 30-day mortality. We used multivariable logistic regression and survival analysis to calculate adjusted 30-day mortality and long-term survival, respectively. RESULTS: A total of 1913 patients underwent AAA repair during the study period. The overall 30-day mortality rate was 2.6% (50 patients). Thirty-day outcomes including death (p = 0.8), stroke (p = 0.7), myocardial infarction (p = 0.06), length of stay (p = 0.3) and discharge disposition other than home (p = 0.8) were similar across MDI quintiles. Similarly, there was no statistically significant association between SDI quintile and postoperative outcomes. Multivariable analysis showed that age greater than 70 years (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.55-6.06) and open repair (OR 3.22, 95% CI 1.59-6.52) but not MDI quintile (p = NS) or SDI quintile (p = NS) were associated with increased 30-day mortality. There was no effect of MDI or SDI quintile on long-term survival on univariable or multivariable analysis. CONCLUSION: Socioeconomic status does not appear to affect short- or long-term mortality after AAA repair in a publicly funded health care system. Further research is needed to address any existing gaps in screening and referral before repair.

Disparities in Air Pollutants Across Racial, Ethnic, and Poverty Groups at US Public Schools.

We investigate socioeconomic disparities in air quality at public schools in the contiguous US using high resolution estimates of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) concentrations. We find that schools with higher proportions of people of color (POC) and students eligible for the federal free or reduced lunch program, a proxy for poverty level, are associated with higher pollutant concentrations. For example, we find that the median annual NO2 concentration for White students, nationally, was 7.7 ppbv, compared to 9.2 ppbv for Black and African American students. Statewide and regional disparities in pollutant concentrations across racial, ethnic, and poverty groups are consistent with nationwide results, where elevated NO2 concentrations were associated with schools with higher proportions of POC and higher levels of poverty. Similar, though smaller, differences were found in PM2.5 across racial and ethnic groups in most states. Racial, ethnic, and economic segregation across the rural-urban divide is likely an important factor in pollution disparities at US public schools. We identify distinct regional patterns of disparities, highlighting differences between California, New York, and Florida. Finally, we highlight that disparities exist not only across urban and non-urban lines but also within urban environments.

Costs in the Year Following Deceased Donor Kidney Transplantation: Relationships With Renal Function and Graft Failure.

Relationships between renal function and medical costs for deceased donor kidney transplant recipients are not fully quantified post-transplant. We describe these relationships with renal function measured by estimated glomerular filtration rate (eGFR) and graft failure. The United States Renal Data System identified adults receiving single-organ deceased donor kidneys 2012-2015. Inpatient, outpatient, other facility costs and eGFRs at discharge, 6 and 12 months were included. A time-history of costs was constructed for graft failures and monthly costs in the first year post-transplant were compared to those without failure. The cohort of 24,021 deceased donor recipients had a 2.4% graft failure rate in the first year. Total medical costs exhibit strong trends with eGFR. Recipients with 6-month eGFRs of 30-59 ml/min/1.73m2 have total costs 48% lower than those <30 ml/min/1.73m2. For recipients with graft failure monthly costs begin to rise 3-4 months prior to failure, with incremental costs of over $38,000 during the month of failure. Mean annual total incremental costs of graft failure are over $150,000. Total costs post-transplant are strongly correlated with eGFR. Graft failure in the first year is an expensive, months-long process. Further reductions in early graft failures could yield significant human and economic benefits.

Towards a generic prototyping approach for therapeutically-relevant peptides and proteins in a cell-free translation system.

Advances in peptide and protein therapeutics increased the need for rapid and cost-effective polypeptide prototyping. While in vitro translation systems are well suited for fast and multiplexed polypeptide prototyping, they suffer from misfolding, aggregation and disulfide-bond scrambling of the translated products. Here we propose that efficient folding of in vitro produced disulfide-rich peptides and proteins can be achieved if performed in an aggregation-free and thermodynamically controlled folding environment. To this end, we modify an E. coli-based in vitro translation system to allow co-translational capture of translated products by affinity matrix. This process reduces protein aggregation and enables productive oxidative folding and recycling of misfolded states under thermodynamic control. In this study we show that the developed approach is likely to be generally applicable for prototyping of a wide variety of disulfide-constrained peptides, macrocyclic peptides with non-native bonds and antibody fragments in amounts sufficient for interaction analysis and biological activity assessment.

Disparities in Deceased Organ Donor Research Authorization: Experience at One Organ Procurement Organization and Call for National Conversations.

INTRODUCTION: Research with deceased donor organs can provide an important platform for studying interventions to improve organ use and outcomes after authorization from the next-of-kin (NOK) or before death by the decedent (i.e., first-person authorization [FPA]). To date, information on authorization rates across donor subgroups is lacking. METHODS: We performed a retrospective chart review of all 690 deceased organ donors from January 2017 to December 2019 at a midsized Midwestern organ procurement organization (OPO). Multivariable logistic regression was used to assess associations between donor factors and research decline (adjusted odds ratio [aOR], 95% confidence interval [CI]). RESULTS: Electronic records for all 690 deceased donors were reviewed. Of these, 659 (95.5%) yielded at least one transplanted organ. Overall, research was declined in 10.8% of donations. Compared to White donors, research decline was higher for Black (16.0% vs. 8.9%; aOR, 1.87; 95% CI, 1.03-3.40; P = 0.04) and other non-White donors (24.0% vs. 8.9%; aOR, 4.21; 95% CI, 1.02-17.39; P = 0.05). Unadjusted research decline trended higher for Hispanic donors versus non-Hispanic donors (23.1% vs. 10.5%; P = 0.14). Compared to donors age <40 years, research decline trended higher for donors age ≥65 years (16.7% vs. 11.8%; aOR, 4.87; 95% CI, 1.12-21.05; P = 0.03), whereas research decline was 55% lower when donors provided FPA (7.3% vs 15.0%; aOR, 0.45; 95% CI, 0.27-0.76; P = 0.003). CONCLUSIONS: Deceased donor research authorization decline is higher for Black, other non-White, and older donors, but lower when the descendent provides FPA. Identification of disparities in research authorization may stimulate educational strategies to reduce barriers to scientific investigations directed at optimizing the outcomes of organ donation.

Wages, Travel, and Lodging Reimbursement by the National Kidney Registry: An Important Step Toward Financial Neutrality for Living Kidney Donors in the United States.

BACKGROUND: Since 2007, the National Living Donor Assistance Center has provided the most financial support to US living donors meeting specific income criteria by reimbursing travel, meal, and lodging expenses. In 2019, the National Kidney Registry started providing lost wages, travel, and lodging reimbursement via their Donor Shield program. Donor Shield is automatically provided to donors who participate in kidney paired donation through the National Kidney Registry or who donate at a Donor Shield Direct center, without any income restrictions. METHODS: The support donors across the United States received from the Donor Shield program between January 2019 and February 2020 was studied. RESULTS: During the study period, 326 (25.9%) of the 1260 donors covered by Donor Shield, from 46 programs received reimbursements amounting to a total of $647 384.45, with $472 389.97 (73.0%) covering lost wages. Median reimbursement per donor was $1813.80 (range, $44.0-$165.63). Eighty-one percent of 108 reimbursed donors who were surveyed reported that the lack of these reimbursements would have posed a financial hardship, and 4% said they would have been unable to donate without this support. CONCLUSIONS: Expansion of lost wages reimbursement programs to all donors in the United States would be an important step toward achieving financial neutrality for this unique population and could also help meet the growing demand for transplantable organs by increasing living donation rates.

Center-level Variation in HLA-incompatible Living Donor Kidney Transplantation Outcomes.

BACKGROUND: Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown. METHODS: We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes. RESULTS: After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSIONS: Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.

Maternal and Infant Health Care Costs Related to Preeclampsia.

OBJECTIVE: To provide U.S. case-based preeclampsia health care cost estimates for mothers and infants from a U.S. payer perspective, with comparisons with both uncomplicated and hypertensive pregnancies. METHODS: Electronic health record and billing data from a large regional integrated health care system in Pennsylvania were used to identify mother-singleton infant pairs with deliveries between 2010 and 2015. Data on clinical care and costs using actual payment amounts were compiled from 20 weeks of gestation to 6 weeks postdelivery for mothers and birth to 12 months for infants. Three defined pregnancy study cohorts, uncomplicated, hypertension and preeclampsia, were matched using a 1:1:1 ratio on the basis of maternal age, parity, body mass index, and comorbidities. Costs per pregnancy were calculated in 2015 dollars and preeclampsia incremental costs estimated by subtracting the average cost of the matched cohorts. RESULTS: The final study population included 712 matched mother-infant pairs in each cohort. The mean combined maternal and infant medical care costs in the preeclampsia cohort of $41,790 were significantly higher than those for the uncomplicated cohort of $13,187 (P<.001) and hypertension cohort of $24,182 (P<.001), and were largely driven by differences in the infant costs. The mean infant cost in the preeclampsia cohort were $28,898, in the uncomplicated cohort $3,669 and $12,648 in the hypertension cohort (P<.001). Mothers with preeclampsia delivered 3 weeks earlier (median 36.5 weeks of gestation) than women in the uncomplicated cohort and more than 2 weeks earlier than women in the hypertension cohort. A significantly larger percentage of women with preeclampsia and their infants experienced adverse events (13.9% for mothers and 14.6% for infants) compared with unaffected women (4.1% and 0.7%) and those with hypertension (9.4% and 4.8%), respectively (P<.001). CONCLUSION: The economic burden of preeclampsia health care is significant with the main cost drivers being infant health care costs associated with lower gestational age at birth and greater adverse outcomes. FUNDING SOURCE: This study is funded by Progenity, Inc.

Racial discrimination and the health and wellbeing of Aboriginal and Torres Strait Islander children: Does the timing of first exposure matter?

Racial discrimination has been observed to negatively impact on the health of Aboriginal and Torres Strait Islander children, although evidence surrounding periods of greater vulnerability to the stressor of racism have not yet been explored in this population. We compared first exposure to interpersonal racism at either ages 4-5 years or 7 years with no exposure to examine the influence of sensitive periods of racism exposure on mental health and physiological outcomes during middle childhood (7-12 years). The study cohort comprised 1,759 Aboriginal and Torres Strait Islander children aged 4-12 years from waves 2-8 (2009-2015) of the Footprints in Time: 1The Longitudinal Study of Indigenous Children (LSIC) dataset. Multilevel logistic regression was used in all analysis. We observed a larger effect (OR: 2.8; 95% CI: 1.4-5.4) for negative mental health with first exposure at 4-5 years compared to 7 years (OR: 2.1; 95% CI: 1.2-3.6), referenced to children with no exposure. Effect sizes were similar in both exposure groups for the significantly increased risk of sleep difficulties, while a stronger adverse effect on behavioural issues was found at 7 years (OR: 2.2; 95% CI: 1.3-4.0) relative to 4-5 years (OR: 1.7; 95% CI: 0.8-3.7). No significant associations were found with general health, obesity or being underweight. This study generates new evidence surrounding sensitive periods of exposure to racism in Aboriginal and Torres Strait Islander children. A pattern of consistently greater adverse effects on mental and physiological health was not observed with first exposure at 4-5 compared to 7 years, although initial evidence indicates that first exposure to racism at these ages increases the likelihood of negative mental health relative to children without racism exposure. Longitudinal data extending from earlier to later developmental periods will allow further investigations into the presence of sensitive periods of exposure to racism in these children.

Birth Hospitalization Costs and Days of Care for Mothers and Neonates in California, 2009-2011.

OBJECTIVE: To provide population-based estimates of the hospital-related costs of maternal and newborn care, and how these vary by gestational age and birth weight. STUDY DESIGN: We conducted a retrospective analysis of 2009-2011 California in-hospital deliveries at nonfederal hospitals with the infant and maternal discharge data successfully (96%) linked to birth certificates. Cost-to-charge ratios were used to estimate costs from charges. Physician hospital payments were estimated by mean diagnosis related group-specific reimbursement and costs were adjusted for inflation to December 2017 values. After exclusions for incomplete or missing data, the final sample was 1 265 212. RESULTS: The mean maternal costs for all in-hospital deliveries was $8204, increasing to $13 154 for late preterm (32-36 weeks) and $22 702 for very preterm (<32 weeks) mothers. The mean cost for all newborns was $6389: $2433 for term infants, $22 102 for late preterm, $223 931 for very preterm infants, and $317 982 for extremely preterm infants (<28 weeks). Preterm infants were 8.1% of cases but incurred 60.9% of costs; for very preterm and extremely preterm infants, these shares were 1.0% and 36.5%, and 0.4% and 20.0%, respectively. Overall, mothers incurred 56% of the total costs during the delivery hospitalization. CONCLUSIONS: Both maternal and neonatal costs are skewed, with this being much more pronounced for infants. Preterm birth is much more expensive than term delivery, with the additional costs predominately incurred by the infants. The small share of infants who require extensive stays in neonatal intensive care incur a large share of neonatal costs and these costs have increased over time.

Leveraging a Landscape-Level Monitoring and Assessment Program for Developing Resilient Shorelines throughout the Laurentian Great Lakes.

Traditionally, ecosystem monitoring, conservation, and restoration have been conducted in a piecemeal manner at the local scale without regional landscape context. However, scientifically driven conservation and restoration decisions benefit greatly when they are based on regionally determined benchmarks and goals. Unfortunately, required data sets rarely exist for regionally important ecosystems. Because of early recognition of the extreme ecological importance of Laurentian Great Lakes coastal wetlands, and the extensive degradation that had already occurred, significant investments in coastal wetland research, protection, and restoration have been made in recent decades and continue today. Continued and refined assessment of wetland condition and trends, and the evaluation of restoration practices are all essential to ensuring the success of these investments. To provide wetland managers and decision makers throughout the Laurentian Great Lakes basin with the optimal tools and data needed to make scientifically-based decisions, our regional team of Great Lakes wetland scientists developed standardized methods and indicators used for assessing wetland condition. From a landscape perspective, at the Laurentian Great Lakes ecosystem scale, we established a stratified random-site-selection process to monitor birds, anurans, fish, macroinvertebrates, vegetation, and physicochemical conditions of coastal wetlands in the US and Canada. Monitoring of approximately 200 wetlands per year began in 2011 as the Great Lakes Coastal Wetland Monitoring Program. In this paper, we describe the development, delivery, and expected results of this ongoing international, multi-disciplinary, multi-stakeholder, landscape-scale monitoring program as a case example of successful application of landscape conservation design.

The impact of racial discrimination on the health of Australian Indigenous children aged 5-10 years: analysis of national longitudinal data.

BACKGROUND: A growing body of literature highlights that racial discrimination has negative impacts on child health, although most studies have been limited to an examination of direct forms of racism using cross-sectional data. We aim to provide further insights on the impact of early exposure to racism on child health using longitudinal data among Indigenous children in Australia and multiple indicators of racial discrimination. METHODS: We used data on 1239 Indigenous children aged 5-10 years from Waves 1-6 (2008-2013) of Footprints in Time, a longitudinal study of Indigenous children across Australia. We examined associations between three dimensions of carer-reported racial discrimination (measuring the direct experiences of children and vicarious exposure by their primary carer and family) and a range of physical and mental health outcomes. Analysis was conducted using multivariate logistic regression within a multilevel framework. RESULTS: Two-fifths (40%) of primary carers, 45% of families and 14% of Indigenous children aged 5-10 years were reported to have experienced racial discrimination at some point in time, with 28-40% of these experiencing it persistently (reported at multiple time points). Primary carer and child experiences of racial discrimination were each associated with poor child mental health status (high risk of clinically significant emotional or behavioural difficulties), sleep difficulties, obesity and asthma, but not with child general health or injury. Children exposed to persistent vicarious racial discrimination were more likely to have sleep difficulties and asthma in multivariate models than those with a time-limited exposure. CONCLUSIONS: The findings indicate that direct and persistent vicarious racial discrimination are detrimental to the physical and mental health of Indigenous children in Australia, and suggest that prolonged and more frequent exposure to racial discrimination that starts in the early lifecourse can impact on multiple domains of health in later life. Tackling and reducing racism should be an integral part of policy and intervention aimed at improving the health of Australian Indigenous children and thereby reducing health disparities between Indigenous and non-Indigenous children.

Predictive Variables for Abnormal Comprehensive Metabolic Panel Testing and Potential Cost Savings in Children Receiving Pediatric Emergency Department Care.

OBJECTIVE: The aim of this study was to determine variables predictive of abnormal comprehensive metabolic panel (CMP) results in pediatric emergency department (PED) patients and the potential cost savings of a basic metabolic panel (BMP) versus a CMP. METHODS: This is a retrospective cross-sectional descriptive study of children (<18 y) at an urban academic PED (annual census, 22,000). Clinical data included 12 clinical variables: right upper quadrant pain, overdose, emesis, liver disorder, malignancy, heart disease, bleeding disorder, jaundice, right upper quadrant tenderness, hepatomegaly, ascites/peripheral edema and shock, and the liver function test (LFT) results not in a BMP (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total protein, and albumin). RESULTS: There were 207 children in the study population. The mean age was 8 years. There were 106 boys (51%).Variables significantly associated with abnormal LFT result were history of liver disease (P = 0.007), history of heart disease (P = 0.040), jaundice (P = 0.045), and hepatomegaly (P = 0.048). The false-negative rate was 16%. However, of the 10 patients for whom this false-negative rate remained true, the LFT values were marginally abnormal, and performance of further investigation of these results was minimal to none. There were 66 patients with no clinical variables and normal CMP results. With a cost difference of $21 between BMP and CMP, this gives a potential savings of $7125 if extrapolated for 1 year in our PED. CONCLUSIONS: Limiting testing to a BMP for patients with none of the 12 clinical variables has the potential annual cost savings of $7125.

Soil nutrient maps of Sub-Saharan Africa: assessment of soil nutrient content at 250 m spatial resolution using machine learning.

Spatial predictions of soil macro and micro-nutrient content across Sub-Saharan Africa at 250 m spatial resolution and for 0-30 cm depth interval are presented. Predictions were produced for 15 target nutrients: organic carbon (C) and total (organic) nitrogen (N), total phosphorus (P), and extractable-phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), sulfur (S), sodium (Na), iron (Fe), manganese (Mn), zinc (Zn), copper (Cu), aluminum (Al) and boron (B). Model training was performed using soil samples from ca. 59,000 locations (a compilation of soil samples from the AfSIS, EthioSIS, One Acre Fund, VitalSigns and legacy soil data) and an extensive stack of remote sensing covariates in addition to landform, lithologic and land cover maps. An ensemble model was then created for each nutrient from two machine learning algorithms- random forest and gradient boosting, as implemented in R packages ranger and xgboost-and then used to generate predictions in a fully-optimized computing system. Cross-validation revealed that apart from S, P and B, significant models can be produced for most targeted nutrients (R-square between 40-85%). Further comparison with OFRA field trial database shows that soil nutrients are indeed critical for agricultural development, with Mn, Zn, Al, B and Na, appearing as the most important nutrients for predicting crop yield. A limiting factor for mapping nutrients using the existing point data in Africa appears to be (1) the high spatial clustering of sampling locations, and (2) missing more detailed parent material/geological maps. Logical steps towards improving prediction accuracies include: further collection of input (training) point samples, further harmonization of measurement methods, addition of more detailed covariates specific to Africa, and implementation of a full spatiotemporal statistical modeling framework.

Unraveling the Sikasso Paradox: Agricultural Change and Malnutrition in Sikasso, Mali.

When cash cropping leads to agricultural and livelihood changes in the Global South, concern about food security is common among policy makers. This is indeed the case in the Sikasso region of Mali, where many have suggested that the ubiquitous cash crop cotton is a cause of the unexpectedly high rates of malnutrition in the region. Using household and forest surveys, we found little evidence that cotton cultivation is associated with malnutrition or decreased food security at a household level, but we did find evidence of a coassociation between cotton cultivation, loss of natural capital, and malnutrition at the village level.

Natural product and natural product derived drugs in clinical trials.

There are a significant number of natural product (NP) drugs in development. We review the 100 NP and NP-derived compounds and 33 Antibody Drug Conjugates (ADCs) with a NP-derived cytotoxic component being evaluated in clinical trials or in registration at the end of 2013. 38 of these compounds and 33 ADCs are being investigated as potential oncology treatments, 26 as anti-infectives, 19 for the treatment of cardiovascular and metabolic diseases, 11 for inflammatory and related diseases and 6 for neurology. There was a spread of the NP and NP-derived compounds through the different development phases (17 in phase I, 52 in phase II, 23 in phase III and 8 NDA and/or MAA filed), while there were 23 ADCs in phase I and 10 in phase II. 50 of these 100 compounds were either NPs or semi-synthetic (SS) NPs, which indicated the original NP still plays an important role. NP and NP-derived compounds for which clinical trials have been halted or discontinued since 2008 are listed in the Supplementary Information. The 25 NP and NP-derived drugs launched since 2008 are also reviewed, and late stage development candidates and new NP drug pharmacophores analysed. The short term prospect for new NP and NP-derived drug approvals is bright, with 31 compounds in phase III or in registration, which should ensure a steady stream of approvals for at least the next five years. However, there could be future issues for new drug types as only five new drug pharmacophores discovered in the last 15 years are currently being evaluated in clinical trials. The next few years will be critical for NP-driven lead discovery, and a concerted effort is required to identify new biologically active pharmacophores and to progress these and existing compounds through pre-clinical drug development into clinical trials.