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BackgroundKnees undergoing revision anterior cruciate ligament reconstruction (rACLR) have a high prevalence of articular cartilage lesions.HypothesisThe prevalence of chondrosis at the time of rACLR is associated with meniscal status and lower extremity alignment.Study designCross-sectional study; Level of evidence, 3.MethodsData from the prospective Multicenter ACL Revision Study (MARS) cohort were reviewed to identify patients with preoperative lower extremity alignment films. Lower extremity alignment was defined by the weightbearing line (WBL) as a percentage of the tibial plateau width, while the chondral and meniscal status of each weightbearing compartment was recorded at the time of surgery. Multivariable proportional odds models were constructed and adjusted for relevant factors to examine which risk factors were independently associated with the degree of medial and lateral compartment chondrosis.ResultsThe cohort included 246 patients with lower extremity alignment films at the time of rACLR. Mean (±SD) patient age was 26.9 ± 9.5 years and body mass index (BMI) was 26.4 ± 4.6. The medial compartment had more chondrosis (grade 2/3, 42%; grade 4, 6.5%) than did the lateral compartment (grade 2/3, 26%; grade 4, 6.5%). Disruption of the meniscus was noted in 35% of patients on the medial side and 16% in the lateral side. The mean WBL was 0.43 ± 0.13. Medial compartment chondrosis was associated with BMI (P = .025), alignment (P = .002), and medial meniscal status (P = .001). None of the knees with the WBL lateral to 0.625 had grade 4 chondrosis in the medial compartment. Lateral compartment chondrosis was significantly associated with age (P = .013) and lateral meniscal status (P < .001). Subjects with "intact" menisci were found to decrease their odds of having chondrosis by 64% to 84%.ConclusionThe status of articular cartilage in the tibiofemoral compartments at the time of rACLR is related to meniscal status. Lower extremity alignment and BMI are associated with medial compartment chondrosis.

BackgroundAnterior cruciate ligament (ACL) reconstruction failure occurs in up to 10% of cases. Technical errors are considered the most common cause of graft failure despite the absence of validated studies. Limited data are available regarding the agreement among orthopaedic surgeons regarding the causes of primary ACL reconstruction failure and accuracy of graft tunnel placement.HypothesisExperienced knee surgeons have a high level of interobserver reliability in the agreement about the causes of primary ACL reconstruction failure, anatomic graft characteristics, and tunnel placement.Study designCohort study (diagnosis); Level of evidence, 3.MethodsTwenty cases of revision ACL reconstruction were randomly selected from the Multicenter ACL Revision Study (MARS) database. Each case included the patient's history, standardized radiographs, and a concise 30-second arthroscopic video taken at the time of revision demonstrating the graft remnant and location of the tunnel apertures. All 20 cases were reviewed by 10 MARS surgeons not involved with the primary surgery. Each surgeon completed a 2-part questionnaire dealing with each surgeon's training and practice, as well as the placement of the femoral and tibial tunnels, condition of the primary graft, and the surgeon's opinion as to the causes of graft failure. Interrater agreement was determined for each question with the kappa coefficient and the prevalence-adjusted, bias-adjusted kappa (PABAK).ResultsThe 10 reviewers have been in practice an average of 14 years and have performed at least 25 ACL reconstructions per year, and 9 were fellowship trained in sports medicine. There was wide variability in agreement among knee experts as to the specific causes of ACL graft failure. When participants were specifically asked about technical error as the cause for failure, interobserver agreement was only slight (PABAK = 0.26). There was fair overall agreement on ideal femoral tunnel placement (PABAK = 0.55) but only slight agreement on whether a femoral tunnel was too anterior (PABAK = 0.24) and fair agreement on whether it was too vertical (PABAK = 0.46). There was poor overall agreement for ideal tibial tunnel placement (PABAK = 0.17).ConclusionThis study suggests that more objective criteria are needed to accurately determine the causes of primary ACL graft failure as well as the ideal femoral and tibial tunnel placement in patients undergoing revision ACL reconstruction.

Mucopolysaccharidosis type I (MPS I) is an inherited α-L-iduronidase (IDUA, I) deficiency in which glycosaminoglycan (GAG) accumulation causes progressive multisystem organ dysfunction, neurological impairment, and death. Current MPS I mouse models, based on a NOD/SCID (NS) background, are short-lived, providing a very narrow window to assess the long-term efficacy of therapeutic interventions. They also develop thymic lymphomas, making the assessment of potential tumorigenicity of human stem cell transplantation problematic. We therefore developed a new MPS I model based on a NOD/SCID/Il2rγ (NSG) background. This model lives longer than 1 year and is tumor-free during that time. NSG MPS I (NSGI) mice exhibit the typical phenotypic features of MPS I including coarsened fur and facial features, reduced/abnormal gait, kyphosis, and corneal clouding. IDUA is undetectable in all tissues examined while GAG levels are dramatically higher in most tissues. NSGI brain shows a significant inflammatory response and prominent gliosis. Neurological MPS I manifestations are evidenced by impaired performance in behavioral tests. Human neural and hematopoietic stem cells were found to readily engraft, with human cells detectable for at least 1 year posttransplantation. This new MPS I model is thus suitable for preclinical testing of novel pluripotent stem cell-based therapy approaches.

The PRDM9 protein determines sites of meiotic recombination in humans by directing meiotic DNA double-strand breaks to specific loci. Targeting specificity is encoded by a long array of C2H2 zinc fingers that bind to DNA. This zinc finger array is hypervariable, and the resulting alleles each have a potentially different DNA binding preference. The assessment of PRDM9 diversity is important for understanding the complexity of human population genetics, inheritance linkage patterns, and predisposition to genetic disease. Due to the repetitive nature of the PRDM9 zinc finger array, the large-scale sequencing of human PRDM9 is challenging. We, therefore, developed a long-read sequencing strategy to infer the diploid PRDM9 zinc finger array genotype in a high-throughput manner. From an unbiased study of PRDM9 allelic diversity in 720 individuals from seven human populations, we detected 69 PRDM9 alleles. Several alleles differ in frequency among human populations, and 32 alleles had not been identified by previous studies, which were heavily biased to European populations. PRDM9 alleles are distinguished by their DNA binding site preferences and fall into two major categories related to the most common PRDM9-A and PRDM9-C alleles. We also found that it is likely that inter-conversion between allele types is rare. By mapping meiotic double-strand breaks (DSBs) in the testis, we found that small variations in PRDM9 can substantially alter the meiotic recombination landscape, demonstrating that minor PRDM9 variants may play an under-appreciated role in shaping patterns of human recombination. In summary, our data greatly expands knowledge of PRDM9 diversity in humans.

abstract: Children's environments - especially relationships with caregivers - sculpt not only developing brains but also multiple bio-behavioral systems that influence long-term cognitive and socioemotional outcomes, including the ability to empathize with others and interact in prosocial and peaceful ways. This speaks to the importance of investing resources in effective and timely programs that work to enhance early childhood development (ECD) and, by extension, reach communities at-scale. Given the limited resources currently devoted to ECD services, and the devastating impact of COVID-19 on children and communities, there is a clear need to spur government leaders and policymakers to further invest in ECD and related issues including gender and racial equity. This essay offers concrete examples of scholarly paradigms and leadership efforts that focus on child development to build a peaceful, equitable, just, and sustainable world. As scholars and practitioners, we need to continue to design, implement, assess, and revise high-quality child development programs that generate much-needed evidence for policy and programmatic changes. We must also invest in global partnerships to foster the next generation of scholars, practitioners, and advocates dedicated to advance our understanding of the bio-behavioral systems that underlie love, sociality, and peace across generations. Especially where supported by structural interventions, ECD programs can help create more peaceful, just, and socially equitable societies.

Maternal smoking during pregnancy (SDP) has been linked to poorer offspring executive function across development, but SDP does not occur independent of other familial risk factors. As such, poor and inconsistent control for potential confounds, notably shared familial (i.e., genetic and environmental) confounds, preclude concluding causal effects of SDP on child outcomes. We examined the within-family association between SDP and one component of executive function, inhibitory control, in a sample of families (N = 173) specifically selected for sibling pairs discordant for exposure to SDP. Thus, the present study examines if the SDP-inhibitory control association withstands rigorous control for potential child and familial confounds. 79% of the variation in child inhibitory control was attributable to within-family differences and 21% was attributable to differences between families, indicating that the variability in inhibitory control was primarily a function of differences between siblings rather than differences across families. Further, the association between SDP and inhibitory control was fully attenuated when confounds were considered. These findings suggest that co-occurring vulnerabilities act as more salient risk factors for poorer child inhibitory control than SDP and may serve as effective targets of interventions seeking to improve children's inhibitory control in families with nicotine dependent mothers.

Objective: Although bullying is traditionally considered within the context of primary and secondary school, recent evidence suggests that bullying continues into college and workplace settings. Participants/Method: Latent class analysis (LCA) was employed to classify college bullying involvement typologies among 325 college students attending a northeastern university. Results: Four classes concerning bullying involvement were revealed: Non-involved (36%); Instructor victim (30%); Peer bully-victim (22%); and Peer bully-victim/ Instructor victim (12%). Conclusions: Findings from this study, which classified college bullying experiences by incorporating both peer and instructor (teacher and professor) bullying, add substantially to the literature by providing insight into patterns of relatively unexplored bullying behaviors.

Este trabalho tem como objetivo apresentar um panorama da produção acadêmica a respeito da temática “desinteresse escolar” a partir do mapeamento de teses e dissertações que abordam o assunto. Metodologicamente, realizou-se uma revisão de literatura sistemática no banco de teses e dissertações da Capes, com a qual foram localizados 46 estudos. A análise foi realizada por meio da leitura do título e do resumo dos trabalhos, com base nas seguintes categorias emergentes: (1) desinteresse pela educação escolar; (2) implicações do desinteresse do aluno na atividade docente; (3) desinteresse como uma construção sócio-histórica; ligado a aspectos sociais e (4) desinteresse associado à indisciplina, abandono, evasão e desempenho escolar. Dentre os resultados, destaca-se que apesar da escola ser entendida como um espaço significativo para adquirir conhecimentos e ser uma “promessa para um futuro melhor”, a falta de interesse dos estudantes é um fenômeno presente e que marca tanto a trajetória escolar destes, quanto afeta a saúde mental do corpo docente. Foi possível inferir, ainda, que o desinteresse envolve diferentes dimensões, podendo estar relacionado tanto a disciplinas específicas quanto ao processo de aprendizagem escolar de modo geral.

BackgroundBecause of the deceased donor organ shortage, more kidney patients are considering whether to receive kidneys from family and friends, a process called living donor kidney transplantation (LDKT). Although Blacks and Hispanics are 3.4 and 1.5 times more likely, respectively, to develop end stage renal disease (ESRD) than Whites, they are less likely to receive LDKTs. To address this disparity, a new randomized controlled trial (RCT) will assess whether Black, Hispanic, and White transplant patients' knowledge, readiness to pursue LDKT, and receipt of LDKTs can be increased when they participate in the Your Path to Transplant (YPT) computer-tailored intervention.Methods/designNine hundred Black, Hispanic, and White ESRD patients presenting for transplant evaluation at University of California, Los Angeles Kidney and Pancreas Transplant Program (UCLA-KPTP) will be randomly assigned to one of two education conditions, YPT or Usual Care Control Education (UC). As they undergo transplant evaluation, patients in the YPT condition will receive individually-tailored telephonic coaching sessions, feedback reports, video and print transplant education resources, and assistance with reducing any known socioeconomic barriers to LDKT. Patients receiving UC will only receive transplant education provided by UCLA-KPTP. Changes in transplant knowledge, readiness, pros and cons, and self-efficacy to pursue LDKT will be assessed prior to presenting at the transplant center (baseline), during transplant evaluation, and 4- and 8-months post-baseline, while completion of transplant evaluation and receipt of LDKTs will be assessed at 18-months post-baseline. The RCT will determine, compared to UC, whether Black, Hispanic, and White patients receiving YPT increase in their readiness to pursue LDKT and transplant knowledge, and become more likely to complete transplant medical evaluation and pursue LDKT. It will also examine how known patient, family, and healthcare system barriers to LDKT act alone and in combination with YPT to affect patients' transplant decision-making and behavior. Statistical analyses will be performed under an intent-to-treat approach.DiscussionAt the conclusion of the study, we will have assessed the effectiveness of an innovative and cost-effective YPT intervention that could be utilized to tailor LDKT discussion and education based on the needs of individual patients of different races in many healthcare settings.Trial registrationClinicalTrials.gov, number NCT02181114.

The autism spectrum disorders (ASDs) comprise a set of neurodevelopmental disorders that are, at best, poorly understood but are the fastest growing developmental disorders in the United States. Because animal models of polygenic disorders such as the ASDs are difficult to validate, the derivation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming offers an alternative strategy for identifying the cellular mechanisms contributing to ASDs and the development of new treatment options. Access to statistically relevant numbers of ASD patient cell lines, however, is still a limiting factor for the field. We describe a new resource with more than 200 cell lines (fibroblasts, iPSC clones, neural stem cells, glia) from unaffected volunteers and patients with a wide range of clinical ASD diagnoses, including fragile X syndrome. We have shown that both normal and ASD-specific iPSCs can be differentiated toward a neural stem cell phenotype and terminally differentiated into action-potential firing neurons and glia. The ability to evaluate and compare data from a number of different cell lines will facilitate greater insight into the cause or causes and biology of the ASDs and will be extremely useful for uncovering new therapeutic and diagnostic targets. Some drug treatments have already shown promise in reversing the neurobiological abnormalities in iPSC-based models of ASD-associated diseases. The ASD Stem Cell Resource at the Children's Hospital of Orange County will continue expanding its collection and make all lines available on request with the goal of advancing the use of ASD patient cells as disease models by the scientific community.

Common bean (Phaseolus vulgaris L.) is the most important grain legume for human consumption and has a role in sustainable agriculture owing to its ability to fix atmospheric nitrogen. We assembled 473 Mb of the 587-Mb genome and genetically anchored 98% of this sequence in 11 chromosome-scale pseudomolecules. We compared the genome for the common bean against the soybean genome to find changes in soybean resulting from polyploidy. Using resequencing of 60 wild individuals and 100 landraces from the genetically differentiated Mesoamerican and Andean gene pools, we confirmed 2 independent domestications from genetic pools that diverged before human colonization. Less than 10% of the 74 Mb of sequence putatively involved in domestication was shared by the two domestication events. We identified a set of genes linked with increased leaf and seed size and combined these results with quantitative trait locus data from Mesoamerican cultivars. Genes affected by domestication may be useful for genomics-enabled crop improvement.

Abstract Introduction The Role of Inflammation after Surgery for Elders study correlates novel inflammatory markers measured in blood, cerebrospinal fluid (CSF) assays, and [11C]‐PBR28 positron‐emission tomography imaging. Methods This study involved a prospective cohort design with patients who underwent elective hip and knee arthroplasty under spinal anesthesia. Sixty‐five adults participated with their family members. Inflammatory biomarker assays were measured preoperatively on day 1 and postoperatively at one month. Results On average, participants were 75 years old, and 72% were female. 54% underwent total knee arthroplasty, and 46% underwent total hip arthroplasty. The mean Modified Mini‐Mental State (3MS) Examination score was 89.3; four patients (6%) scored ≤77 points. Plasma assays were completed in 63 (97%) participants, cerebrospinal fluid assays in 61 (94%), and PET imaging in 44 (68%). Discussion This complex study presents an innovative effort to correlate peripheral and central inflammatory biomarkers before and after major surgery in older adults. Strengths include collecting concurrent blood, cerebrospinal fluid, and positron‐emission tomography with detailed clinical characterization of delirium, cognition, and functional status.

Abstract Background Use of food to soothe infant distress has been linked to greater weight in observational studies. We used ecological momentary assessment to capture detailed patterns of food to soothe and evaluate if a responsive parenting intervention reduced parents’ use of food to soothe. Methods Primiparous mother-newborn dyads were randomized to a responsive parenting intervention designed for obesity prevention or a safety control group. Responsive parenting curriculum included guidance on using alternative soothing strategies (e.g., swaddling), rather than feeding, as the first response to infant fussiness. After the initial intervention visit 3 weeks after delivery, mothers (n = 157) were surveyed for two 5–8 day bursts at infant ages 3 and 8 weeks. Surveys were sent via text message every 4 h between 10:00 AM-10:00 PM, with 2 surveys sent at 8:00 AM asking about nighttime hours. Infant fusses and feeds were reported for each 4-h interval. Food to soothe was defined as “Fed First” and “Not Fed First” in response to a fussy event. Use of food to soothe was modeled using random-intercept logistic regression. Results The control group had greater odds of having Fed First, compared to the responsive parenting group at ages 3 and 8 weeks (3 weeks: OR = 1.9; 95% CI = 1.4–2.7; p

Meiotic DSB formation, repair and recombination occur in a continuum of substages termed leptonema, zygonema, pachynema, and diplonema. Here, authors develop a method for isolating pure sub-populations of nuclei that allows for detailed study of meiotic substages.

Developing and raising replacement heifers requires a large capital investment for producers. Therefore, it is imperative to discover traits and management practices to eliminate subfertile heifers prior to breeding and pregnancy determination. In this study, four years of data was analyzed from a centralized beef heifer development yard in the Midwest of the United States. The objective of this study was to analyze various heifer physical characteristics and management practices in order to quantify their impact on pregnancy and date of conception. Logistic regression models were built to investigate risk factors associated with conception to artificial insemination (AI), pregnancy by natural service after AI exposure, and pregnancy in the first 21-days of the breeding season. Age at entry, average daily gain from entry to breeding, pelvic width, and year were associated with AI pregnancy (p < 0.05). On the second model, average daily gain from entry to yearling weight, weight at breeding, weight at pregnancy diagnosis, and age at AI were significantly associated with pregnancy. There were no associations with reproductive tract score with any of the response variables analyzed. These results indicate there are physical measurements that can be used to improve the ability to select and develop heifers for improved reproductive performance.

Education programs have been central to reestablishing social norms, rebuilding public educational institutions, and addressing public attitudes toward mental illness in Liberia following a protracted civil war and the Ebola epidemic. The aim of this study was to determine if a program combining an understanding of neuroscience with mental health literacy content could increase teachers’ awareness of students’ mental health issues and produce changes in teacher attitudes and classroom practices. A tiered Training-of-Trainers approach was employed. The first workshop trained 24 Liberian secondary science teachers in the neurobiology of learning, memory, emotions, stress and adolescent brain development. A Leadership Team formed from eight of the Tier I participants then adapted the curriculum, added in more mental health literacy content and led four Tier II workshops and four follow-up Refresher sessions. Participants completed a neuroscience knowledge test and surveys assessing stigma, general perceptions of people with mental illness, and burnout. A subset of Tier II teachers participated in a structured interview at the Refresher time point. Teachers in both tiers acquired basic neuroscience knowledge. Tier I, but not Tier II teachers significantly improved their surveyed attitudes toward people with mental illness. No changes were found in overall teacher burnout. Despite these survey results, the interviewed Tier II teachers self-reported behavioral changes in how they approached their teaching and students in their classrooms. Interviewees described how they now understood social and emotional challenges students might be experiencing and recognized abnormal behaviors as having a biopsychosocial basis. Teachers reported reduced use of verbal and corporal punishment and increased positive rewards systems, such as social and emotional support for students through building relationships. Refresher discussions concurred with the interviewees. In contrast to previous teacher mental health literacy programs which did not bring about a change in helping behaviors, this pilot program may have been successful in changing teacher knowledge and self-reported behaviors, improving teacher–student relationships and decreasing harsh discipline. The combination of basic neuroscience concepts with training on how to recognize mental health issues and refer students should be investigated further as a strategy to promote teacher mental health literacy.

Este artigo analisa o processo de planejamento de um projeto comunitário realizado no âmbito dos estágios do curso de licenciatura em Educação do Campo da Universidade Federal de Santa Catarina. Se trata do projeto comunitário com o título ‘Não quero continuar aqui, porque na Volta Grande não tem nada’. Tal projeto parte de um longo e sucessivo processo de investigação da realidade, propiciada pelo regime de alternância do referido curso. Ele foi planejado com a participação dos jovens e a partir de inspirações na perspectiva freireana, principalmente das ideias de investigação temática (FREIRE, 2019), falas significativas (SILVA, 2004) e três momentos pedagógicos (DELIZOICOV, ANGOTTI, PERNAMBUCO, 2002), que também estruturam a análise realizada neste trabalho. Dentre os resultados destacamos alguns desafios em colocar em prática processos dialógicos. Desafios como: ouvir os jovens, propiciando a ruptura do silêncio e a participação desses jovens como protagonistas do projeto e da sua realidade; realizar planejamento de interações dialógicas; até a consciência de que esse processo é permanente e não se esgota quando o programa está momentaneamente pronto.

After acquiring knowledge of the neuroscience of learning, memory, stress and emotions, teachers incorporate more cognitive engagement and student-centered practices into their lessons. However, the role understanding neuroscience plays in teachers own affective and motivational competencies has not yet been investigated. The goal of this study was to investigate how learning neuroscience effected teachers’ self-efficacy, beliefs in their ability to teach effectively, self-responsibility and other components of teacher motivation. A pilot training-of-trainers program was designed and delivered in Liberia combining basic neuroscience with information on social, emotional, behavioral and mental health issues faced by students. Tier I of the professional development was a 2 weeks workshop led by a visiting neuroscientist. A subset of the 24 Tier I secondary science teachers formed a Leadership Team who adapted the content to the Liberian context and subsequently led additional workshops and follow-up sessions for the Tier II secondary science teachers. Science teachers in both tiers completed the affective-motivational scales from the internationally vetted, multiscale Innovative Teaching for Effective Learning Teacher Knowledge Survey from the OECD. Tier II teachers completed the survey in a pre-post-delayed post design. Tier I teachers completed the survey after the workshop with their attitudes at that time and separately with retrospective projections of their pre-workshop attitudes. Ten of the 92 Tier II teachers participated in structured interviews at follow-up. Statistical analysis of survey data demonstrated improved teacher self-efficacy, self-responsibility for student outcomes, and motivation to teach. Qualitatively, teachers expressed more confidence in their ability to motivate students, engage them through active learning, and manage the class through positive rather than negative reinforcement. Teachers’ own self-regulation improved as they made efforts to build supporting relationships with students. Together, these results demonstrated that (i) teacher affective-motivational attitudes can be altered with professional development, (ii) basic neuroscience, as knowledge of how students learn, can improve teacher competency, and (iii) a training-of-trainers model can be effective in a low and middle income country for disseminating neuroscience knowledge, increasing teachers’ knowledge of students’ social and emotional needs, and promoting educational improvement.

Abstract Endurance athletes are frequently exposed to environmental heat stress during training. We investigated whether exposure to 33°C during training would improve endurance performance in temperate conditions and stimulate mitochondrial adaptations. Seventeen endurance‐trained males were randomly assigned to perform a 3‐week training intervention in 18°C (TEMP) or 33°C (HEAT). An incremental test and 30‐min time‐trial preceded by 2‐h low‐intensity cycling were performed in 18°C pre‐ and post‐intervention, along with a resting vastus lateralis microbiopsy. Training was matched for relative cardiovascular demand using heart rates measured at the first and second ventilatory thresholds, along with a weekly “best‐effort” interval session. Perceived training load was similar between‐groups, despite lower power outputs during training in HEAT versus TEMP (p

Summary: Vertebrates have evolved three paralogs, termed LUC7L, LUC7L2, and LUC7L3, of the essential yeast U1 small nuclear RNA (snRNA)-associated splicing factor Luc7p. We investigated the mechanistic and regulatory functions of these putative splicing factors, of which one (LUC7L2) is mutated or deleted in myeloid neoplasms. Protein interaction data show that all three proteins bind similar core but distinct regulatory splicing factors, probably mediated through their divergent arginine-serine-rich domains, which are not present in Luc7p. Knockdown of each factor reveals mostly unique sets of significantly dysregulated alternative splicing events dependent on their binding locations, which are largely non-overlapping. Notably, knockdown of LUC7L2 alone significantly upregulates the expression of multiple spliceosomal factors and downregulates glycolysis genes, possibly contributing to disease pathogenesis. RNA binding studies reveal that LUC7L2 and LUC7L3 crosslink to weak 5′ splice sites and to the 5′ end of U1 snRNA, establishing an evolutionarily conserved role in 5′ splice site selection.

The Fridays for Future strikes involve students striking for increased action on climate change, and this movement has spread to 185 countries and received widespread media attention. This exploratory study investigates motives for participating or not in the climate strikes and future participation among students in Switzerland. In a sample of N = 638 university students, we found that trust in climate scientists, low trust in governments, response efficacy, protest enjoyment and the perceived success of the strikes predicted participation. Contrary to statements in the public media but consistent with the literature, students who participated in the climate strikes reported consuming less meat, flying less and taking more steps to compensate the CO2 emissions from flights compared to students who did not participate. We discuss how the insights from this study help reveal the determinants of youth collective action on climate change.

Robust strategies for developing patient-specific, human, induced pluripotent stem cell (iPSC)-based therapies of the brain require an ability to derive large numbers of highly defined neural cells. Recent progress in iPSC culture techniques includes partial-to-complete elimination of feeder layers, use of defined media, and single-cell passaging. However, these techniques still require embryoid body formation or coculture for differentiation into neural stem cells (NSCs). In addition, none of the published methodologies has employed all of the advances in a single culture system. Here we describe a reliable method for long-term, single-cell passaging of PSCs using a feeder-free, defined culture system that produces confluent, adherent PSCs that can be differentiated into NSCs. To provide a basis for robust quality control, we have devised a system of cellular nomenclature that describes an accurate genotype and phenotype of the cells at specific stages in the process. We demonstrate that this protocol allows for the efficient, large-scale, cGMP-compliant production of transplantable NSCs from all lines tested. We also show that NSCs generated from iPSCs produced with the process described are capable of forming both glia defined by their expression of S100β and neurons that fire repetitive action potentials.

BackgroundThe factors that lead to patients failing multiple anterior cruciate ligament (ACL) reconstructions are not well understood.HypothesisMultiple-revision ACL reconstruction will have different characteristics than first-time revision in terms of previous and current graft selection, mode of failure, chondral/meniscal injuries, and surgical charactieristics.Study designCase-control study; Level of evidence, 3.MethodsA prospective multicenter ACL revision database was utilized for the time period from March 2006 to June 2011. Patients were divided into those who underwent a single-revision ACL reconstruction and those who underwent multiple-revision ACL reconstructions. The primary outcome variable was Marx activity level. Primary data analyses between the groups included a comparison of graft type, perceived mechanism of failure, associated injury (meniscus, ligament, and cartilage), reconstruction type, and tunnel position. Data were compared by analysis of variance with a post hoc Tukey test.ResultsA total of 1200 patients (58% men; median age, 26 years) were enrolled, with 1049 (87%) patients having a primary revision and 151 (13%) patients having a second or subsequent revision. Marx activity levels were significantly higher (9.77) in the primary-revision group than in those patients with multiple revisions (6.74). The most common cause of reruptures was a traumatic, noncontact ACL graft injury in 55% of primary-revision patients; 25% of patients had a nontraumatic, gradual-onset recurrent injury, and 11% had a traumatic, contact injury. In the multiple-revision group, a nontraumatic, gradual-onset injury was the most common cause of recurrence (47%), followed by traumatic noncontact (35%) and nontraumatic sudden onset (11%) (P < .01 between groups). Chondral injuries in the medial compartment were significantly more common in the multiple-revision group than in the single-revision group, as were chondral injuries in the patellofemoral compartment.ConclusionPatients with multiple-revision ACL reconstructions had lower activity levels, were more likely to have chondral injuries in the medial and patellofemoral compartments, and had a high rate of a nontraumatic, recurrent injury of their graft.