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Evading cancer drugs by identity fraud Prostate cancer growth is fueled by male hormones called androgens. Drugs targeting the androgen receptor (AR) are initially efficacious, but most tumors eventually become resistant (see the Perspective by Kelly and Balk). Mu et al. found that prostate cancer cells escaped the effects of androgen deprivation therapy through a change in lineage identity. Functional loss of the tumor suppressors TP53 and RB1 promoted a shift from AR-dependent luminal epithelial cells to AR-independent basal-like cells. In related work, Ku et al. found that prostate cancer metastasis, lineage switching, and drug resistance were driven by the combined loss of the same tumor suppressors and were accompanied by increased expression of the epigenetic regulator Ezh2. Ezh2 inhibitors reversed the lineage switch and restored sensitivity to androgen deprivation therapy in experimental models. Science , this issue p. 84 , p. 78 ; see also p. 29

Metal phosphate compounds are considered promising candidates as positive electrode materials for Na-ion batteries because they offer higher cation-insertion potentials than analogous metal oxides. One such example is sodium iron fluorophosphate (Na2FePO4F), a compound that is typically synthesized by high-temperature solid-state routes. In this study, we prepare phase-pure Na2FePO4F using the polyol route, a low-temperature process that allows for the synthesis of nanoparticles (15–25 nm), a form that enhances Na-ion insertion kinetics and cycling stability. We then apply two methods to enhance the electronic conductivity of Na2FePO4F: (i) converting residual organic byproducts of the polyol synthesis to conductive carbon coatings; and (ii) preparing a nanocomposite with reduced graphene oxide. The resulting electrode materials are characterized in nonaqueous Na-ion electrolytes, assessing such metrics as specific capacity, rate capability, and cycling stability. A thorough electrochemical kinetics analysis is performed to deconvolve surface-vs.-bulk Na-ion insertion as a function of composite structure. Specific capacities between 60–110 mA h g−1 were achieved in galvanostatic charge–discharge tests when cycling in the range from 10C to C/10, respectively.

Objectives Patient satisfaction with having a left ventricular assist device (LVAD) as a bridge to transplantation (BTT) or destination therapy (DT) may change over time early after surgery, as patients adjust to life on a device. We examined satisfaction at 2 time points early after surgery. Methods We evaluated patient self-report data at 3 and 6 months (mos) post implant at 12 U.S. sites (2016-2020). Measures included Satisfaction with Treatment (10 items, [FACIT-TS-G, modified]), VAD Team Communication (6 items, 0 [worst] - 18 [best] communication as wanted, [FACIT-TS-PS, modified]), and Being Bothered by VAD Self-care and Limitations (17 items, 1 [not] - 5 [very much] bothered, [new items]). Bowker's symmetry test was used to compare change in satisfaction for the 10 satisfaction items. Mixed effects models were estimated to assess change in VAD team communication and bother, assuming a missing at random mechanism. Results Patients (n=115) were primarily male (77%) and non-Hispanic White (65%); mean age(SD)=55 ( 12.5) years; 50% had an implant strategy of DT. Overall, no differences were detected regarding satisfaction with having a VAD between 3 and 6 mos after implant. 61% of patients (n=71) were satisfied (for the most part or completely) at 3 mos; of these, 63 (89%) responded similarly at 6 mos. Satisfaction with VAD team communication was high (least-squares means at 3 and 6 mos: 12.3 and 12.8) and being bothered by VAD self-care and limitations was low to moderate (least-squares means at 3 and 6 mos: 2.3 and 2.4), with no change over time (p>0.40). BTT and DT patients reported similar bother (p=0.21), but BTT patient satisfaction with communication was marginally higher than DT patients (p=0.05). Conclusions Patients were quite satisfied with having a VAD early after implant. Patients were also satisfied with communication from the VAD team and reported moderate or fewer hassles with having a VAD, which did not differ by implant strategy. Understanding satisfaction with a VAD may guide patient support early post implant.

Purpose Dosing of Anti-thymocyte globulin therapy (ATG), used in the prevention and treatment of rejection, is optimally guided by CD3 levels. The purpose of this study was to establish the reliability of using Absolute Lymphocyte Count (ALC) as a substitute for CD3 given its ready availability and low cost. Methods A retrospective review was conducted of heart transplant recipients from 9/2014 to 2/2019 who received ATG and had a CD3 count with corresponding ALC. The Pearson correlation coefficient was used to examine the correlation between ALC and CD3. Validity tests and the Youden Index were performed to identify an appropriate range for an ALC cutoff that would provide the greatest degree of validity of ALC as an appropriate surrogate for a CD3 cutoff of 100 cells/mm3. Results 332 paired samples were collected. Analysis demonstrated correlation between ALC and CD3 count. The Pearson correlation coefficient was 0.45 (R-Square 0.23), p less than 0.0001. Validity testing of ALC of 200 cells/mm3 against CD3 counts 100 cells/mm3 showed sensitivity 0.635 (160/252), specificity 0.875 (70/80), positive predictive value (PV) 0.941 (160/170), and negative PV 0.432 (70/162). Based on the Youden index, the zone for the optimal cutoff points ranged from 100 to 200 cells (Figure 1). AUC for the ROC analysis was 0.81 (Figure 2). Conclusion This study suggests that ALC may have validity as a selective substitute for CD3 monitoring in patients receiving ATG. Further studies of this novel approach are warranted.

Fixed-tissue ChIP-seq for H3K27 acetylation (H3K27ac) profiling (FiTAc-seq) is an epigenetic method for profiling active enhancers and promoters in formalin-fixed, paraffin-embedded (FFPE) tissues. We previously developed a modified ChIP-seq protocol (FiT-seq) for chromatin profiling in FFPE. FiT-seq produces high-quality chromatin profiles particularly for methylated histone marks but is not optimized for H3K27ac profiling. FiTAc-seq is a modified protocol that replaces the proteinase K digestion applied in FiT-seq with extended heating at 65 °C in a higher concentration of detergent and a minimized sonication step, to produce robust genome-wide H3K27ac maps from clinical samples. FiTAc-seq generates high-quality enhancer landscapes and super-enhancer (SE) annotation in numerous archived FFPE samples from distinct tumor types. This approach will be of great interest for both basic and clinical researchers. The entire protocol from FFPE blocks to sequence-ready library can be accomplished within 4 d.

Objective Combined computed tomography (CT) occurs when one anatomical area is simultaneously imaged both without and with contrast, or two overlapping anatomical areas are imaged concurrently. While this has been studied in a Traditional Medicare population, it has not been studied in other populations subject to prior authorization. This study explores between-facility variation in ordering and receiving orders to render combined CT in a mixed commercial and Medicare Advantage population. Methods Orders for CT abdomen (without/with contrast), CT thorax (without/with contrast), and concurrent CT brain and sinus authorized by a prior authorization company from 2013–2017, pertaining to patients with commercial or Medicare Advantage health plans from one national insurer, were extracted. Orders were issued and rendered by both hospitals and nonhospitals. The analysis was performed separately for each anatomical area in two ways: orders were grouped by ordering facility, and by designated rendering facility. For each facility, the ratio of combined to total orders was calculated, and analysis of variance was used to determine whether there were significant differences in this rate by year. The association between health plan type and combined imaging rates was assessed. Results Combined rates [ratio±standard deviation] for abdomen, thorax, and brain/sinus were 0.306±0.246, 0.089±0.142, and 0.002±0.01 respectively when the analysis was conducted according to ordering facility, and 0.311±0.178, 0.096±0.113, and 0.001±0.006 when the analysis was conducted according to designated rendering facility. Combined CT abdomen and CT thorax rates decreased monotonically from 2013 to 2017, decreases that were significant (P < .01) regardless of whether orders were grouped by ordering or rendering facility. Combined CT abdomen and CT thorax rates significantly differed between orders pertaining to people with commercial and Medicare Advantage plans. Discussion Variability was greater when orders were grouped by ordering facility, rather than rendering facility. Health plan type may influence whether a patient receives combined CT.

Key Points Question What is the association between mortality and increasing treatment coverage for eating disorders, taking into account individual-level eating disorder disease dynamics? Findings In this decision analytical model study, the estimated lifetime prevalence of eating disorders is high, with nearly 1 in 7 male individuals (14.3%) and 1 in 5 female individuals (19.7%) experiencing an eating disorder by age 40 years. Increasing treatment coverage for all eating disorder cases could avert 70.5 deaths per 100 000 individuals by age 40 years. Meaning The findings suggest that increasing treatment coverage for eating disorders could substantially reduce the mortality associated with these common psychiatric disorders., This decision analytical model study uses a virtual cohort of 100 000 individuals modeled from birth to age 40 years for 4 eating disorder diagnoses to examine whether increasing treatment coverage could reduce the mortality associated with eating disorders., Importance Eating disorders (EDs) are common psychiatric disorders associated with high mortality. However, data on ED disease dynamics and treatment coverage are sparse. Objectives To model the individual-level disease dynamics of ED from birth to age 40 years and to estimate the association of increased treatment coverage with ED-related mortality. Design, Setting, and Participants In this decision analytical model study, an individual-level Markov state transition model was empirically calibrated in April 2019 using a Bayesian approach to synthesize available clinical and epidemiologic ED data. The simulation model was calibrated to nationally representative US survey data from 2007 and 2011. A virtual cohort of 100 000 individuals (50 000 [50%] male) was modeled from birth to age 40 years for 4 ED diagnoses: anorexia nervosa, bulimia nervosa, binge eating disorder, and other specified feeding and eating disorders. Exposures Age-specific ED incidence and mortality rates and background (all-cause) mortality. Main Outcomes and Measures The main outcomes were age-specific 12-month and lifetime ED prevalence and number of deaths per 100 000 general population individuals by age 40 years. The mean and 95% uncertainty intervals (UIs) of 1000 simulations, accounting for stochastic and parameter uncertainty, are reported. Results The highest estimated mean annual prevalence of ED occurred at approximately age 21 years for both male individuals (7.4%; 95% UI, 3.5%-11.5%) and female individuals (10.3%; 95% UI, 7.0%-14.2%), with lifetime mean prevalence estimates increasing to 14.3% (95% UI, 9.7%-19.0%) for male individuals and 19.7% (95% UI, 15.8%-23.9%) for female individuals by age 40 years. Ninety-five percent of first-time cases occurred by age 25 years. Current treatment coverage averts an estimated mean of 41.7 deaths per 100 000 people (95% UI, 13.0-82.0 deaths per 100 000 people) by age 40 years, whereas increasing treatment coverage for all patients with ED could avert an estimated mean of 70.5 deaths per 100 000 people by age 40 years (95% UI, 26.0-143.0 deaths per 100 000 people). Conclusions and Relevance In this simulation modeling study, the estimated lifetime prevalence of ED was high, with approximately 1 in 7 male and 1 in 5 female individuals having an ED by age 40 years. The initial onset of EDs was highly concentrated during adolescence and young adulthood, suggesting that this is a critical period for prevention efforts. However, the high estimated prevalence of recurring ED later in life highlights the importance of identification and treatment of ED at older ages as well. These findings suggest that increasing treatment coverage could substantially reduce ED-related mortality.

Background: The extracellular matrix (ECM) provides structural and functional support for the myocardium, but myocardial infarction (MI) changes the composition of the ECM. One of the chief components of the ECM, hyaluronan (HA), is elevated after MI; however, specific biological actions of HA—particularly at the level of infiltrating immune cells and implications of such interactions on ventricular remodeling—have not been explored. Goals: Because upregulation of HA coincides with macrophage infiltration after MI, we determined whether hyaluronan interacts with macrophages and investigated the implication of such interactions on macrophage function. Methods: WT mice were subjected to non-reperfused MI to determine changes in hyaluronan synthases (HAS), hyaluronidases (HYAL), and HA levels in the heart. Interaction of HA with macrophages was studied by polarizing bone marrow derived macrophages and analyzing cells by flow cytometry. Next, we characterized the ability of macrophages to metabolize HA by profiling polarized macrophages for HA-metabolizing enzymes, HA receptors, HA-binding proteins, hyaluronidase activity, and phagocytosis. Results: Compared to Sham hearts, MI (n=5/group) augmented the expression of HAS-2 (10-fold, p=0.002) and HYAL-2 (2 to 4-fold, p=0.0004) in the infarct and remote regions of the heart at 5 d post-MI. HA levels (n=8/group) were elevated in the infarct (1 to 2-fold, p=0.0200) and remote (2 to 3-fold, p=0.0007) regions of the heart compared to sham hearts. Polarizing macrophages (n=3/group) in the presence fluorescein-conjugated HA (HA-FL) showed that naïve (M0), pro-inflammatory (M1), and pro-resolving (M2) macrophages interact with HA-FL; M1 showed the highest FITC intensity. Interestingly, exposing macrophages (n=5/group) to HA provoked an inflammatory phenotype, as reflected by enhanced expression of TNFα (4-fold, p=0.0001) and IL-1β (7-fold, p=0.0094) mRNA; HA also enhanced macrophage phagocytosis (0.5-fold, p= 0.0476). Conclusion: Hyaluronan is elevated following MI and can influence macrophage function. Because of the accumulation of hyaluronan and macrophages in the post-MI heart, macrophage-hyaluronan interactions may be a nexus regulating ventricular remodeling.

Background To reduce the prevalence of anemia, the Indian government recommends daily iron and folic acid supplements (iron supplements) for pregnant women and weekly iron supplements for adolescents and all women of reproductive age. The government has distributed free iron supplements to adolescents and pregnant women for over four decades. However, initial uptake and adherence remain inadequate and non-pregnant women of reproductive age are largely ignored. The aim of this study is to examine the multilevel barriers to iron supplement use and to subsequently identify promising areas to intervene. Methods We conducted a qualitative study in the state of Odisha, India. Data collection included key informant interviews, focus group discussions with women, husbands, and mothers-in-law, and direct observations in health centers, pharmacies and village health and nutrition days. Results We found that at the individual level, participants knew that iron supplements prevent anemia but underestimated anemia prevalence and risk in their community. Participants also believed that taking too many iron supplements during pregnancy would “make your baby big” causing a painful birth and a costly cesarean section. At the interpersonal level, mothers-in-law were not supportive of their daughters-in-law taking regular iron supplements during pregnancy but husbands were more supportive. At the community level, participants reported that only pregnant women and adolescents are taking iron supplements, ignoring non-pregnant women altogether. Unequal gender norms are also an upstream barrier for non-pregnant women to prioritize their health to obtain iron supplements. At the policy level, frontline health workers distribute iron supplements to pregnant women only and do not follow up on adherence. Conclusions Interventions should address multiple barriers to iron supplement use along the socio-ecological model. They should also be tailored to a woman’s reproductive life course stage: adolescents, pregnancy, and non-pregnant women of reproductive age because social norms and available services differ between the subpopulations.

Summary Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumorigenesis, and yet their mechanistic roles remain challenging to characterize. Here, we integrate functional proteomics with lncRNA-interactome profiling to characterize Urothelial Cancer Associated 1 (UCA1), a candidate driver of ovarian cancer development. Reverse phase protein array (RPPA) analysis indicates that UCA1 activates transcription coactivator YAP and its target genes. In vivo RNA antisense purification (iRAP) of UCA1 interacting proteins identified angiomotin (AMOT), a known YAP regulator, as a direct binding partner. Loss-of-function experiments show that AMOT mediates YAP activation by UCA1, as UCA1 enhances the AMOT-YAP interaction to promote YAP dephosphorylation and nuclear translocation. Together, we characterize UCA1 as a lncRNA regulator of Hippo-YAP signaling and highlight the UCA1-AMOT-YAP signaling axis in ovarian cancer development., Graphical Abstract, Highlights • A super-enhancer drives the expression of lncRNA UCA1 in EOC • Inactivation of UCA1 impairs tumor growth in vivo • UCA1 activates transcription coactivator YAP and its target genes • UCA1 promotes YAP dephosphorylation and nuclear translocation via AMOTp130, Cancer Systems Biology; Omics; Proteomics; Systems Biology

Web cameras are transforming coastal environmental monitoring. Improvements in camera technology and image processing capabilities, paired with decreases in cost, enable widespread use of camera systems by researchers, managers and first responders for a growing range of environmental monitoring applications. Applications are related to transportation and commerce, preparedness, risk reduction and response, and stewardship of coastal resources. While web cameras are seemingly ubiquitous, operators often follow unique installation procedures and collect, store, and process imagery data in various ways. These inconsistencies significantly limit the ability for imagery data to be shared and utilized across research and operational disciplines. Similar to the early days of other remote sensing networks like High Frequency Radar, the benefits and downstream application of coastal imagery data can be greatly enhanced through centralized data access and standardization of data collection, analysis and dissemination. The NOAA National Ocean Service Web Camera Applications Testbed (WebCAT) was launched in 2017 in partnership with SECOORA, as a public-private partnership to address this coastal ocean observing standardization need. WebCAT is a pilot project relying on the private sector expertise of Surfline, Inc., to install and operate several web cameras capable of meeting the short-term needs of diverse users including NOAA, USGS, state health agencies, academia and others. The project aims to determine operational imagery collection, storage, processing, access, and archival requirements that will foster collaboration across research and operational user communities. Seven web cameras have been installed at six locations along the southeast United States coast (from Florida to North Carolina) for purposes including: counting animals on the beach and migrating right whales, identifying rip currents, validating wave runup models, and understanding human use of natural resources. Here we present a review of the state of coastal imagery data and an overview of the WebCAT project. Goals of an upcoming community workshop will also be presented along with our vision for how WebCAT can motivate a future sustained operational web camera network.

Several post-translational modifications figure prominently in ventricular remodeling. The beta-O-linkage of N-acetylglucosamine (O-GlcNAc) to proteins has emerged as an important signal in the cardiovascular system. Although there are limited insights about the regulation of the biosynthetic pathway that gives rise to the O-GlcNAc post-translational modification, much remains to be elucidated regarding the enzymes, such as O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which regulate the presence/absence of O-GlcNAcylation. Recently, we showed that the transcription factor, E2F1, could negatively regulate OGT and OGA expression in vitro. The present study sought to determine whether E2f1 deletion would improve post-infarct ventricular function by de-repressing expression of OGT and OGA. Male and female mice were subjected to non-reperfused myocardial infarction (MI) and followed for 1 or 4 week. MI significantly increased E2F1 expression. Deletion of E2f1 alone was not sufficient to alter OGT or OGA expression in a naïve setting. Cardiac dysfunction was significantly attenuated at 1-week post-MI in E2f1-ablated mice. During chronic heart failure, E2f1 deletion also attenuated cardiac dysfunction. Despite the improvement in function, OGT and OGA expression was not normalized and protein O-GlcNAcyltion was not changed at 1-week post-MI. OGA expression was significantly upregulated at 4-week post-MI but overall protein O-GlcNAcylation was not changed. As an alternative explanation, we also performed guided transcriptional profiling of predicted targets of E2F1, which indicated potential differences in cardiac metabolism, angiogenesis, and apoptosis. E2f1 ablation increased heart size and preserved remote zone capillary density at 1-week post-MI. During chronic heart failure, cardiomyocytes in the remote zone of E2f1-deleted hearts were larger than wildtype. These data indicate that, overall, E2f1 exerts a deleterious effect on ventricular remodeling. Thus, E2f1 deletion improves ventricular remodeling with limited impact on enzymes regulating O-GlcNAcylation.

The assembly of magnetic Janus particles in a quasi-two-dimensional environment with a dipole moment shifted from the center and oriented perpendicular to the Janus cap height is studied with optical microscopy and found to adhere to a general model accounting for the particle dipole strength, the particle Brownian dynamics, the initial concentration, and, most importantly, the magnetic dipole shift. The particle aggregates are treated as diffusing spherocylinders with length and width dependent on the magnetic dipole shift. Aggregation occurs irreversibly once particle aggregates enter within a distance at which Brownian and dipole forces are equal, defined as the capture distance. The capture distance model is expressed as a general Smoluchowski coagulation rate kernel for chains of an arbitrary length, dipole strength, and dipole shift, allowing for aggregation rate predictions for related systems.

As physicians strive to provide evidence-based care, challenges arise if different entities disseminate divergent Appropriate Use Criteria (AUC) or clinical guidelines on the same topic. To characterize these challenges in one field, this study reviews the literature on comparisons of clinical recommendations regarding medical imaging. The PubMed database was searched for the years 2013-2018 for studies describing discordance among clinical recommendations regarding the performance of imaging. Of the 406 articles identified, 15 met the selection criteria: 8 qualitative and 7 quantitative. Reasons for discordance varied, with lack of evidence often cited. Quantitative studies often found that different decisions would be reached depending on the clinical recommendation followed. Nonetheless, quantitative studies also tended not to consider one set of recommendations superior to another. The findings of this review might help clinicians seek guidance more thoughtfully and could inform use of guidelines and AUC for quality improvement and clinical decision support.

SUMMARY Androgen-receptor (AR) inhibitors, including enzalutamide, are used for treatment of all metastatic castration-resistant prostate cancers (mCRPCs). However, some patients develop resistance or never respond. We find that the transcription factor CREB5 confers enzalutamide resistance in an open reading frame (ORF) expression screen and in tumor xenografts. CREB5 overexpression is essential for an enzalutamide-resistant patient-derived organoid. In AR-expressing prostate cancer cells, CREB5 interactions enhance AR activity at a subset of promoters and enhancers upon enzalutamide treatment, including MYC and genes involved in the cell cycle. In mCRPC, we found recurrent amplification and overexpression of CREB5. Our observations identify CREB5 as one mechanism that drives resistance to AR antagonists in prostate cancers., In Brief Advanced prostate cancers develop resistance to androgen receptor (AR)-targeting therapies. Hwang et al. show that resistant prostate cancers overexpress or amplify CREB5, mediating resistance to AR inhibition. CREB5 suppression reduces the viability of therapy-resistant patient-derived models, suggesting that CREB5 is a target in prostate cancer patients with limited treatment options., Graphical Abstract

Eradicating tumor dormancy that develops following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of EGFR-mutant non-small cell lung cancer, is an attractive therapeutic strategy but the mechanisms governing this process are poorly understood. Blockade of ERK1/2 reactivation following EGFR TKI treatment by combined EGFR/MEK inhibition uncovers cells that survive by entering a senescence-like dormant state characterized by high YAP/TEAD activity. YAP/TEAD engage the epithelial-to-mesenchymal transition transcription factor SLUG to directly repress pro-apoptotic BMF, limiting drug-induced apoptosis. Pharmacological co-inhibition of YAP and TEAD, or genetic deletion of YAP1, all deplete dormant cells by enhancing EGFR/MEK inhibition-induced apoptosis. Enhancing the initial efficacy of targeted therapies could ultimately lead to prolonged treatment responses in cancer patients.

Study objective Primary care (PC) follow-up for discharged emergency department (ED) patients provides patients with further medical attention. We conducted a pilot randomized controlled trial to determine whether using a freely-available physician appointment-booking website results in higher self-reported PC follow-up. Methods We randomized discharged patients whom treating physicians determined PC follow-up was important and who possessed health insurance but had no PC provider to one of three groups: (1) a PC appointment booked through the booking website prior to ED discharge; (2) written information on how to use the booking website; or (3) usual care (i.e. standard follow-up instructions). We phoned subjects two weeks after the ED visit to determine whether they had completed a PC follow-up visit. We also asked subjects about their satisfaction with obtaining a PC appointment, satisfaction with the ED visit, symptom resolution and subsequent ED visits. The self-reported PCP follow-up rate was compared among the study groups by estimating the risk difference (RD) and 95% CI between usual care and each intervention group. Results 272 subjects were enrolled and randomized and 68% completed the two-week telephone follow-up interview. The self-reported PCP follow-up rate was higher (52%) among subjects whose appointment was booked on the website before ED discharge (RD = 16%; 95% CI -1%, 34%) and lower (25%) for subjects who received booking website information (RD = 13%; 95% CI -32%, 7%) compared to subjects (36%) in the usual care group. A higher percentage of subjects in the booking group were more likely to report being extremely or very satisfied with obtaining a PC appointment (78%) compared to those who received booking website information (54%) or usual care (40%). Conclusion Among ED patients that providers judged PC follow-up is important, using a booking website to schedule an appointment before ED discharge resulted in a higher but not statistically significant self-reported PC follow-up rate. This intervention warrants further investigation in a study with a larger sample size and objective follow-up visit data.

OBJECTIVES: To evaluate the association of the 2009 changes to the US Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) food package and childhood obesity trends. We hypothesized that the food package change reduced obesity among children participating in WIC, a population that has been especially vulnerable to the childhood obesity epidemic. METHODS: We used an interrupted time-series design with repeated cross-sectional measurements of state-specific obesity prevalence among WIC-participating 2- to 4-year-old children from 2000 to 2014. We used multilevel linear regression models to estimate the trend in obesity prevalence for states before the WIC package revision and to test whether the trend in obesity prevalence changed after the 2009 WIC package revision, adjusting for changes in demographics. In a secondary analysis, we adjusted for changes in macrosomia and high prepregnancy BMI. RESULTS: Before the 2009 WIC food package change, the prevalence of obesity across states among 2- to 4-year-old WIC participants was increasing by 0.23 percentage points annually (95% confidence interval: 0.17 to 0.29; P < .001). After 2009, the trend was reversed (−0.34 percentage points per year; 95% confidence interval: −0.42 to −0.25; P < .001). Changes in sociodemographic and other obesity risk factors did not account for this change in the trend in obesity prevalence. CONCLUSIONS: The 2009 WIC food package change may have helped to reverse the rapid increase in obesity prevalence among WIC participants observed before the food package change.

Objective This study aimed to estimate the cost-effectiveness and impact on childhood obesity of installation of chilled water dispensers ("water jets") on school lunch lines and to compare water jets' cost, reach, and impact on water consumption with three additional strategies. Methods The Childhood Obesity Intervention Cost Effectiveness Study(CHOICES) microsimulation model estimated the cost-effectiveness of water jets on US childhood obesity cases prevented in 2025. Also estimated were the cost, number of children reached, and impact on water consumption of the installation of water jets and three other strategies. Results Installing water jets on school lunch lines was projected to reach 29.6 million children (95% uncertainty interval [UI]: 29.4 million-29.8 million), cost $4.25 (95% UI: $2.74-$5.69) per child, prevent 179,550 cases of childhood obesity in 2025 (95% UI: 101,970-257,870), and save $0.31 in health care costs per dollar invested (95% UI: $0.15-$0.55). In the secondary analysis, installing cup dispensers next to existing water fountains was the least costly but also had the lowest population reach. Conclusions Installating water jet dispensers on school lunch lines could also save almost half of the dollars needed for implementation via a reduction in obesity-related health care costs. School-based interventions to promote drinking water may be relatively inexpensive strategies for improving child health.

School telehealth is an alternative delivery model to increase student health-care access with minimal evaluation to aid decision makers in the adoption or expansion of programs. This systematic review assesses school-based telehealth programs using a dissemination and implementation (D&I) framework to inform practitioners and decision makers of the value of school telehealth. We assessed findings from 20 studies on telehealth published between January 2006 and June 2018 and summarized program evaluation on a range of D&I constructs. The sample population included children in school- or center-based early childhood education under age 22 and included parents, providers, and school personnel across urban and suburban locations. There is some evidence that school telehealth can reduce emergency department visits and improve health status for children with chronic and acute illnesses. Future research should report on barriers and facilitators of implementation of programs, including costs related to application of telehealth services and utilization rates.

Objective To investigate the characteristics and patterns of factors such as victims' information, injury tools and time of occurrence of intentional injury cases in southwest China. Methods One thousand three hundred and forty intentional injury cases from several places in southwest China from 2014 to 2016 assessed as minor injury level Ⅱ and above had been randomly selected. Data on victims' information, motives, injury tools, sites of occurrence, time of occurrence, injured parts and degrees of injury were classified and gathered, and then association analyses of motives and types of injury tools as well as degrees of injury and injury tools were made. Results Most of the victims were young adults between 20-50 years （65.2%）, male （82.3%）, rural household registration （62.8%）; the motives were mainly dispute （45.8%）. Injury tools were mostly blunt （54.6%） or sharp （36.0%）. Specifically, injuries were mostly made bare-handed （36.9%） and by cutting tools （33.2%）; the cases mainly occurred in public areas （59.0%）. Cases occurred more frequently in January （11.3%）, February （13.1%）, March （11.6%） and from 22：00 to 01：00 every night. Injuries mainly involved the craniofacial region. The wounds were mainly assessed as minor injury level Ⅱ （61.6%）. There was statistical significance in the difference of types of injury tools among cases with different motives （西南地区1 340例故意伤害案件的特征及相关因素分析.目的 探究我国西南地区故意伤害案件的伤者信息、致伤工具、发生时间等因素的特点及规律。 方法 随机抽取西南地区多地2014—2016年轻伤二级及以上故意伤害案件1 340例，分类汇总伤者信息、作案动机、致伤工具、发生场所、发生时间、损伤部位和损伤程度，并对作案动机与致伤工具类型，以及损伤程度与致伤工具作关联分析。 结果 所涉案件中，伤者多为20~50岁青壮年（65.2%）、男性（82.3%）、农村户籍（62.8%）；作案动机以纠纷为主（45.8%），致伤工具多为钝器（54.6%）和锐器（36.0%），尤以徒手（36.9%）和刀具（33.2%）多见；案件主要发生在公共场所（59.0%），1月（11.3%）、2月（13.1%）、3月（11.6%）及每天夜晚22：00~01：00（23.2%）是高发时期；损伤主要涉及颅面部，所致损伤程度以轻伤二级（61.6%）为主。不同作案动机中致伤工具的类型差异有统计学意义（法医学；创伤和损伤；回顾性研究；故意伤害；损伤程度；西南地区；案例分析.

Peripapillary choroidal neovascularisation (PPCNV) associated with optic disc drusen is a rare complication that can result in severe vision impairment in children. We report the first case of paediatric PPCNV secondary to optic disc drusen successfully treated with intravitreal aflibercept. A 6-year-old girl presented with a one week history of reduced vision in her right eye with best-corrected visual acuity of 20/500. Fundus examination revealed bilateral elevated discs with a peripapillary pigmentary lesion in the right eye. Optical coherence tomography of the right eye showed marked subfoveal fluid. Both B-scan ultrasonography and fundus autofluorescence demonstrated findings consistent with optic disc drusen. Diagnosis of PPCNV was further confirmed on fluorescein fundus angiography. The child received three intravitreal aflibercept injections with complete resolution of the subfoveal fluid. Her visual acuity improved to 20/25 with no recurrence at a 16-month follow-up. No adverse side effects were reported.

The primary purpose of this chapter is to examine how leadership connects to principled and international negotiation. International negotiation is conceptualized with an in-depth description of the process followed by a description of negotiation styles. A corollary purpose is to extend the discussion of negotiation by introducing and defining MAGNUS leadership and how it can translate into negotiation. The authors offer a few practical tips for beginning the journey of becoming MAGNUS. Recommendation for international MAGNUS negotiators are offered.

MotivationThe chromatin profile measured by ATAC-seq, ChIP-seq, or DNase-seq experiments can identify genomic regions critical in regulating gene expression and provide insights on biological processes such as diseases and development. However, quality control and processing chromatin profiling data involve many steps, and different bioinformatics tools are used at each step. It can be challenging to manage the analysis.ResultsWe developed a Snakemake pipeline called CHIPS (CHromatin enrichment Processor) to streamline the processing of ChIP-seq, ATAC-seq, and DNase-seq data. The pipeline supports single- and paired-end data and is flexible to start with FASTQ or BAM files. It includes basic steps such as read trimming, mapping, and peak calling. In addition, it calculates quality control metrics such as contamination profiles, PCR bottleneck coefficient, the fraction of reads in peaks, percentage of peaks overlapping with the union of public DNaseI hypersensitivity sites, and conservation profile of the peaks. For downstream analysis, it carries out peak annotations, motif finding, and regulatory potential calculation for all genes. The pipeline ensures that the processing is robust and reproducible.AvailabilityCHIPS is available at https://github.com/liulab-dfci/CHIPS

BackgroundMore than half of women of reproductive age in India have anemia. Over the last decade, India has made some progress towards reducing anemia in pregnant women, but non-pregnant women, who make up the largest sub group of people with anemia, are largely disregarded.ObjectivesThe objective of this paper is to examine intentions to take iron supplements and factors associated with intentions to inform a social norms-based behavioral intervention to increase uptake of iron supplements and reduce anemia in Odisha, India.MethodsWe collected data from 3,914 randomly sampled non-pregnant women of reproductive age in 81 villages. We conducted a survey and took hemocue (anemia level) readings from each participant. We analyzed data using linear regression models beginning with demographics and social norms and adding other factors such as self-efficacy to take iron supplements, anemia risk perception, and knowledge about anemia in a subsequent model.Results63% of women in our sample were anemic but less than 5% knew they were anemic. Despite national guidelines that all women of reproductive age should take weekly iron supplements to prevent anemia, less than 3% of women in our sample were currently taking them. While actual use was low, intentions were rather high. On a five point Likert scale where higher numbers meant more intentions to take supplements, average intentions were above the midpoint (M= 3.48,SD= 1.27) and intentions and iron supplement use were significantly correlated (r= .10,p< .001). Both injunctive norms and collective norms were associated with intentions to take iron supplements but descriptive norms were not. Other significant factors included age, breastfeeding, knowledge, self-efficacy, and outcome expectations. The final model accounted for 74% of the variance in iron supplement intentions.ConclusionsIn this context, where the actual behavior is low but intentions to enact the behavior are high, starting an intervention with injunctive norms messaging (expectations around the behavior) and self-efficacy to enact the behavior is the step we recommend based on our results. As an intervention unfolds and iron supplement use increases, descriptive norms messaging (that people are indeed taking iron supplements) may add value.

Rapidly colonizing species often thrive in a wide-range of conditions due to a high degree of phenotypic plasticity that results in populations of “general purpose” genotypes. Alternatively, species with high genetic variation could rapidly respond to forces of selection such that a local population evolves traits that provide an advantage in its local environment. We tested this generalist versus local adaptation paradigm in a widely distributed, recently introduced riparian tree / shrub, Tamarix spp. Using an eighty-day, mid-summer common garden drought experiment, we tested three inter-related hypotheses: 1) stomatal sensitivity to soil water depletion is lower in genotypes from a low-elevation, ephemerally flowing river than genotypes from a low-elevation, perennially flowing river, indicative of local adaptation to hydrological conditions, 2) stomatal sensitivity to soil water depletion is lower in genotypes from high-elevations with regular freeze-thaw exposure than genotypes sourced from locations with no freeze-thaw exposure, indicative of local adaptation to temperature conditions, and 3) differences among genotypes in drought sensitivity are correlated with differences in fine root area to leaf area ratios (Ar:Al). For the most part, results did not support hypothesis 1, but largely supported hypotheses 2 and 3. Specifically, sap-flux scaled canopy transpiration (El) declined 14 days earlier in the low-elevation populations after drought initiation compared to El of the highest elevation population with the highest freeze-thaw exposure. Root area to leaf area ratios of the two low-elevation populations were also only 42% and 55% of Ar:Al in the highest elevation population. Results indicate that the high degree of reported Tamarix hybridization since its introduction to North America has largely produced a swarm of “generalist” genotypes in terms of drought sensitivity. Nevertheless, rapid changes in ecohydrologic conditions may result in some Tamarix populations becoming maladapted sooner to reductions in available water than others in the western US.

The Community Eligibility Provision (CEP) of the Healthy, Hunger-Free Kids Act of 2010 allows the provision of universal free meals (UFMs) in high-poverty school areas. Participation in UFM programs, including through CEP, could reduce meal costs due to economies of scale and a lower administrative burden. We analyzed the School Nutrition and Meal Cost Study (SNMCS) data from 508 UFM-eligible schools (103 UFMs) to evaluate whether meal costs varied by UFM status. We used school-level data to address the non-random selection to UFMs with inverse probability of treatment weighting (IPTW). We estimated a generalized linear model with a log link and gamma distribution to predict meal costs by UFM status and school size. Full costs among medium and large schools were marginally lower in UFM schools for lunch (−$0.673, 95% CI: −1.395, 0.0499, p = 0.068) and significantly lower for breakfast (−$0.575, 95% CI: −1.077, −0.074, p = 0.025). UFM was not associated with meal costs among smaller schools. Healthy Eating Index scores did not vary significantly by UFMs, suggesting that lower costs could be achieved without an adverse effect on nutritional quality. This analysis is limited by the lack of identified student percentage (ISP) data needed to definitively identify CEP eligibility, although results were robust to sensitivity analyses addressing the lack of ISP data. The potential policy impact of these findings emphasizes the need for future studies that assess ISP and cost with more recent data and longitudinal designs.

Electrical power can be generated from the controlled mixing of salinity gradients when solutions of differing salt concentration bathe opposing electrodes in a flow-cell configuration. The power density of such salinity-gradient cells is enhanced by moving beyond the double-layer capacitance of high-surface-area carbons to electrode materials that store charge via pseudocapacitance (e.g., manganese oxides; MnOx). We investigate the effects of MnOx loading on salinity-gradient power production, using anodic electrodeposition to coat carbon cloth (CC) electrodes with nanostructured Akhtenskite-type MnOx at controlled incremental mass loadings. Uniform MnOx deposition at exposed CC surfaces is confirmed by scanning electron microscopy with elemental mapping. Power-density measurements with the resulting MnOx@CC electrodes in a salinity-gradient cell fed by low (0.02 M NaCl) and high (0.5 M NaCl) concentration solutions show a positive correlation with MnOx loading, reaching a competitive peak average power density of 0.221 ± 0.001 mW cm–2 at 1.90 mg cm–2 MnOx. By comparing flow-cell data with results from half-cell electroanalytical characterization of individual electrodes, we show that salinity-gradient performance is ultimately limited by resistive losses in the modestly conductive MnOx coating at higher mass loading/thickness.

The prediction of wave runup, as well as its components, time-averaged setup and the time-varying swash, is a key element of coastal storm hazard assessments, as wave runup controls the transitions between morphodynamic response types such as dune erosion and overwash, and the potential for flooding by wave overtopping. While theoretically able to simulate the dominant low-frequency swash, previous studies using the infragravity-wave–resolving model XBeach (XBSB) have shown an underestimation of the observed swash variance and wave runup, which was in part related to the absence of incident-band swash motions in the model. Here, we use an incident-band wave-resolving, non-hydrostatic version of the XBeach model (XBNH) to simulate wave runup observed during the SandyDuck '97 experiment on an intermediate–reflective sandy beach. The results show that the XBNH model describes wave runup and the individual setup and swash components well. We subsequently examine differences in wave runup prediction between the XBSB and XBNH models and find that the XBNH model is a better predictor of wave runup than XBSB for this beach, which is due to better predictions of both the incident-band and infragravity-band swash. For a range of beach states from reflective to dissipative it is shown that incident-band swash is underestimated by XBSB relative to XBNH, in particular for reflective conditions. Infragravity-band swash is shown to be lower in XBSB than XBNH for most conditions, including dissipative conditions for which the mean difference is 16% of the deep water wave height. The difference in infragravity-band swash in XBNH relative to XBSB is shown to mainly be the result of processes occurring outside the swash zone, but approximately 15% of the difference is caused by explicitly resolving incident-band wave motions within the swash zone, such as swash-swash interactions, which inherently cannot be simulated by wave-averaged models.

STUDY DESIGN Retrospective cohort. OBJECTIVE To compare time to discharge for anterior cervical discectomy and fusions (ACDF) when performed as either a first case versus later surgical start times. SUMMARY OF BACKGROUND DATA ACDF is a commonly performed spinal procedure that typically has a short acute recovery period. With an increasing focus on reducing hospital costs and a shift toward outpatient surgical practices, early patient discharge has become a priority for hospitals and physicians alike. However, the impact of surgery start time on the ability for same-day discharge has not been explored in spine surgery. METHODS A surgical database of patients who underwent ACDF from 2013 to 2015 was reviewed. Patients were stratified into two cohorts: those whose surgery was the first of the day (early cohort), and those who underwent later surgeries. Baseline patient characteristics and perioperative variables were compared between cohorts using Student t test and χ test. Same-day discharge was tested for association with surgical start time using Poisson regression with robust error variance controlling for preoperative variables. RESULTS A total of 106 patients, divided into early and late cohorts of 60 and 46 patients, respectively, were included in the analysis. There were no significant differences in pre- or perioperative characteristics between cohorts (). Same-day discharge was achieved in 36.8% (n = 39) of all ACDF patients. The later cohort was significantly more likely to require an overnight stay compared with the early cohort (RR = 1.61 ± 0.30; P = 0.010).(Table is included in full-text article.)CONCLUSION.: Patients undergoing ACDF later in the day are at a higher risk for staying overnight than those who have the first surgery of the day. These results may influence operative scheduling, as performing ACDFs early in the day may result in a greater likelihood of same-day discharge, eliminating the increased resource utilization associated with an overnight hospital stay. LEVEL OF EVIDENCE 4.

Wildfire can damage headwater wetlands, yet the value of post-fire restoration treatments in channels has been contested. Staff from the White Mountain Apache Tribe, students from the local Cibecue Community School, and researchers from the U.S. Forest Service collaboratively recorded channel responses over 13 years at two headwater wetlands lying within watersheds that were severely burned by the Rodeo-Chediski wildfire (Arizona, U.S.) in 2002. One site, Turkey Spring, was left largely untreated for 11 years following the fire, while the second site, Swamp Spring, was treated in 2005 by placing large rock riffle formations and vegetation transplants to prevent further incision and stimulate wetland development. The treatment was soon followed by cessation of channel incision and reestablishment of native wetland vegetation, while headcutting caused extensive erosion at the untreated site for eight years. Radio-carbon dating indicated that the eroding soils at Turkey Spring were over 8,000 years old. This study demonstrates that headwater wetlands in this region are vulnerable to extreme incision events following high severity wildfires, but that such impacts can be partially and gradually reversed. Targeted treatments of incising channels may be warranted to conserve wetlands, soils and associated values that have established over thousands of years.

In human motor learning, it is thought that the more information we have about our errors, the faster we learn. Here, we show that additional error information can lead to improved motor performance without any concomitant improvement in learning. We studied split-belt treadmill walking that drives people to learn a new gait pattern using sensory prediction errors detected by proprioceptive feedback. When we also provided visual error feedback, participants acquired the new walking pattern far more rapidly and showed accelerated restoration of the normal walking pattern during washout. However, when the visual error feedback was removed during either learning or washout, errors reappeared with performance immediately returning to the level expected based on proprioceptive learning alone. These findings support a model with two mechanisms: a dual-rate adaptation process that learns invariantly from sensory prediction error detected by proprioception and a visual-feedback-dependent process that monitors learning and corrects residual errors but shows no learning itself. We show that our voluntary correction model accurately predicted behavior in multiple situations where visual feedback was used to change acquisition of new walking patterns while the underlying learning was unaffected. The computational and behavioral framework proposed here suggests that parallel learning and error correction systems allow us to rapidly satisfy task demands without necessarily committing to learning, as the relative permanence of learning may be inappropriate or inefficient when facing environments that are liable to change.

STUDY DESIGN Retrospective cohort analysis. OBJECTIVE The aim of the study was to identify medications that may potentially contribute to developing postoperative urinary retention (POUR) after lumbar spinal fusion procedures. SUMMARY OF BACKGROUND DATA POUR is a concerning event that may occur after routine orthopedic surgery. The relation between intraoperative medications and POUR after lumbar spine surgery has not been well characterized. METHODS A prospectively maintained database of patients who underwent a primary single-level, minimally invasive transforaminal lumbar interbody fusion between 2009 and 2013 was reviewed. POUR was defined as a bladder scan of 300 mL or higher, the postoperative necessity of a straight catheterization, or a urology consult for urinary retention. The use and dose-response of intraoperative medications between patients with and without POUR were compared. Potential risk factors for developing POUR were analyzed using multivariate analysis. RESULTS A total of 205 patients were included in the study, 17% of whom experienced POUR (n = 34). Administration of phenylephrine and neostigmine was associated with POUR (phenylephrine: 32.3% vs. 13.8%, P = 0.017; neostigmine: 19.5% vs. 6.5%, P = 0.042). Parametric analysis demonstrated an association of increasing dose of neostigmine with POUR (4.66 vs. 4.22 mg, P = 0.023). Similarly, a nonparametric analysis demonstrated an association of increasing doses of both neostigmine and phenylephrine with POUR (neostigmine: 4.25 vs. 3.16 mg, P = 0.02; phenylephrine: 105.88 vs. 40.64 mg, P = 0.008). CONCLUSION Approximately 20% of patients may develop POUR after routine lumbar spine surgery. The use of certain intraoperative anesthetics such as phenylephrine and neostigmine is strongly associated with the development of POUR postoperatively. This finding suggests that there may be modifiable anesthetic risk factors to prevent the development of POUR in patients undergoing lumbar spine surgery. Future prospective, controlled studies specifically addressing these findings could lead to improved patient care and decreased healthcare costs. LEVEL OF EVIDENCE 4.

BACKGROUND/OBJECTIVES: State-specific obesity prevalence data are critical to public health efforts to address the childhood obesity epidemic. However, few states administer objectively-measured BMI surveillance programs. This study reports state-specific childhood obesity prevalence by age and sex correcting for parent-reported child height and weight bias. SUBJECTS/METHODS: As part of the Childhood Obesity Intervention Cost Effectiveness Study (CHOICES), we developed childhood obesity prevalence estimates for states for the period 2005–2010 using data from the 2010 U.S. Census and American Community Survey (ACS), 2003–2004 and 2007–2008 National Survey of Children’s Health (NSCH) (n=133,213), and 2005–2010 National Health and Nutrition Examination Surveys (NHANES) (n=9,377; ages 2–17). Measured height and weight data from NHANES were used to correct parent-report bias in NSCH using a non-parametric statistical matching algorithm. Model estimates were validated against surveillance data from five states (AR, FL, MA, PA, and TN) that conduct censuses of children across a range of grades. RESULTS: Parent-reported height and weight resulted in the largest overestimation of childhood obesity in males ages 2–5 years (NSCH: 42.36% vs. NHANES: 11.44%). The CHOICES model estimates for this group (12.81%) and for all age and sex categories were not statistically different from NHANES. Our modeled obesity prevalence aligned closely with measured data from five validation states, with a 0.64 percentage point mean difference (range: 0.23–1.39) and a high correlation coefficient (r=0.96, p=0.009). Estimated state-specific childhood obesity prevalence ranged from 11.0% to 20.4%. CONCLUSION: Uncorrected estimates of childhood obesity prevalence from NSCH vary widely from measured national data, from a 278% overestimate among males aged 2–5 years to a 44% underestimate among females aged 14–17 years. This study demonstrates the validity of the CHOICES matching methods to correct the bias of parent-reported BMI data and highlights the need for public release of more recent data from the 2011–2012 NSCH.

Nickel–iron oxides and oxyhydroxides are among the most active oxygen-evolution reaction (OER) catalysts in alkaline electrolytes. Compositions rich in Ni are reported to show superior activity, but the establishment of competitive OER activity with lower cost, Fe-rich analogues is more desirable for metal–air batteries and other devices that will see large-scale production. Herein, we demonstrate that by controlling pore–solid architecture and the degree of crystallinity, we achieve a single-phase, Fe-rich NiFe2Ox catalyst that matches the OER performance metrics previously demonstrated for compositions with higher Ni-to-Fe ratios. We also show that OER activity linearly tracks increases in the catalyst surface area, whereas the degree of ex situ surface hydroxylation does not play a significant role. To prepare the pore–solid structured forms, NiFe2Ox gels were synthesized by using an epoxide-initiated sol–gel method and subsequently processed to aerogels or xerogels. The activities of these two sol–gel-derived nanostructures were compared with a nanoparticulate analogue with lower specific surface area, prepared by using conventional precipitation methods. The higher surface area and larger pore volume expressed by the NiFe2Ox formed as an aerogel result in a performance-competitive OER overpotential of 356 mV at a current density of 10 mA cm−2, with an approximately 140 mV improvement relative to the low-surface-area, precipitated analogue.

Policies targeted at high-crime neighbourhoods may have unintended consequences in the presence of organized crime. Whilst they reduce the incentive to commit crime at the margin, those who still choose to join the criminal organization have relatively high criminal propensities. Large organizations take advantage of this, substituting away from membership size towards increased individual criminal activity. Aggregate crime may rise. However, as more would-be recruits move into the formal labour market, falling revenue causes a reversal of this effect. Thereafter, the policy reduces both size and individual activity simultaneously.

STUDY DESIGN Retrospective analysis of a prospectively maintained surgical registry. OBJECTIVE To compare postoperative narcotic consumption between multimodal analgesia (MMA) and patient-controlled analgesia (PCA) after an anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA Studies suggest that a multimodal approach to pain management leads to decreased pain and morphine consumption after total joint arthroplasty and lumbar spinal procedures. Patients and surgeons would benefit from knowing whether a multimodal approach to pain management is superior to PCA for ACDF. METHODS A retrospective cohort study of ACDF patients receiving either MMA or PCA was conducted. Inpatient narcotic consumption, pain scores, nausea/vomiting, hospital length of stay, and narcotic dependence during the months after surgery were compared between MMA and PCA. RESULTS A total of 239 patients met inclusion criteria. Of these, 55 (23.0%) received MMA and 184 (77.0%) received PCA. Patients who received MMA had a lower rate of inpatient narcotic consumption (2.5 OME/h vs. 5.8 OME/h, P

Movements can be learned implicitly in response to new environmental demands or explicitly through instruction and strategy. The former is often studied in an environment that perturbs movement so that people learn to correct the errors and store a new motor pattern. Here, we demonstrate in human walking that implicit learning of foot placement occurs even when an explicit strategy is used to block changes in foot placement during the learning process. We studied people learning a new walking pattern on a split-belt treadmill with and without an explicit strategy through instruction on where to step. When there is no instruction, subjects implicitly learn to place one foot in front of the other to minimize step-length asymmetry during split-belt walking, and the learned pattern is maintained when the belts are returned to the same speed, i.e., postlearning. When instruction is provided, we block expression of the new foot-placement pattern that would otherwise naturally develop from adaptation. Despite this appearance of no learning in foot placement, subjects show similar postlearning effects as those who were not given any instruction. Thus locomotor adaptation is not dependent on a change in action during learning but instead can be driven entirely by an unexpressed internal recalibration of the desired movement.