Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis.

BACKGROUND: While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remains poorly understood. METHODS: Single-cell RNA sequencing data generated with SmartSeq2 (≈8000 genes/cell) in 16 588 single cells isolated during atherosclerosis progression in Ldlr-/-Apob100/100 mice with human-like plasma lipoproteins and from humans with asymptomatic and symptomatic carotid plaques was clustered into multiple subtypes. For clinical and pathophysiological context, the advanced-stage and symptomatic subtype clusters were integrated with 135 tissue-specific (atherosclerotic aortic wall, mammary artery, liver, skeletal muscle, and visceral and subcutaneous, fat) gene-regulatory networks (GRNs) inferred from 600 coronary artery disease patients in the STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) study. RESULTS: Advanced stages of atherosclerosis progression and symptomatic carotid plaques were largely characterized by 3 smooth muscle cells (SMCs), and 3 macrophage subtype clusters with extracellular matrix organization/osteogenic (SMC), and M1-type proinflammatory/Trem2-high lipid-associated (macrophage) phenotypes. Integrative analysis of these 6 clusters with STARNET revealed significant enrichments of 3 arterial wall GRNs: GRN33 (macrophage), GRN39 (SMC), and GRN122 (macrophage) with major contributions to coronary artery disease heritability and strong associations with clinical scores of coronary atherosclerosis severity. The presence and pathophysiological relevance of GRN39 were verified in 5 independent RNAseq data sets obtained from the human coronary and aortic artery, and primary SMCs and by targeting its top-key drivers, FRZB and ALCAM in cultured human coronary artery SMCs. CONCLUSIONS: By identifying and integrating the most gene-rich single-cell subclusters of atherosclerosis to date with a coronary artery disease framework of GRNs, GRN39 was identified and independently validated as being critical for the transformation of contractile SMCs into an osteogenic phenotype promoting advanced, symptomatic atherosclerosis.

Potential impact and cost-effectiveness of Shigella vaccination in 102 low-income and middle-income countries in children aged 5 years or younger: a modelling study.

BACKGROUND: Vaccine impact and cost-effectiveness models have mostly focused on acute burden. Shigella-attributable moderate-to-severe diarrhoea has been shown to be associated with childhood linear growth faltering. Evidence also links less severe diarrhoea to linear growth faltering. As Shigella vaccines are in late stages of clinical development, we aimed to estimate the potential impact and cost-effectiveness of vaccination against Shigella burden that includes stunting and the acute burden attributable to less severe diarrhoea and moderate-to-severe diarrhoea. METHODS: We used a simulation model to estimate Shigella burden and potential vaccination in children aged 5 years or younger from 102 low-income to middle-income countries from 2025 to 2044. Our model included stunting associated with Shigella-related moderate-to-severe diarrhoea and less severe diarrhoea and we explored vaccination impact on health and economic outcomes. FINDINGS: We estimate 109 million (95% uncertainty interval [UI] 39-204) Shigella-attributable stunting cases and 1·4 million (0·8-2·1) deaths in unvaccinated children over 20 years. We project that Shigella vaccination could avert 43 million (13-92) stunting cases and 590 000 (297 000-983 000) deaths over 20 years. The overall mean incremental cost-effectiveness ratio (ICER) was US$849 (95% uncertainty interval 423-1575; median $790 [IQR 635-1005]) per disability-adjusted life-year averted. Vaccination was most cost-effective in the WHO African region and in low-income countries. Including the burden of Shigella-related less severe diarrhoea improved mean ICERs by 47-48% for these groups and substantially improved ICERs for other regions. INTERPRETATION: Our model suggests that Shigella vaccination would be a cost-effective intervention, with a substantial impact in specific countries and regions. Other regions could potentially benefit upon the inclusion of the burden of Shigella-related stunting and less severe diarrhoea in the analysis. FUNDING: Bill & Melinda Gates Foundation and Wellcome Trust.

The carbon economics of vegetative phase change.

Across plant species and biomes, a conserved set of leaf traits govern the economic strategy used to assimilate and invest carbon. As plants age, they face new challenges that may require shifts in this leaf economic strategy. In this study, we investigate the role of the developmental transition, vegetative phase change (VPC), in altering carbon economics as plants age. We used overexpression of microRNA 156 (miR156), the master regulator of VPC, to modulate the timing of VPC in Populus tremula x alba, Arabidopsis thaliana and Zea mays to understand the impact of this transition on leaf economic traits, including construction cost, payback time and return on investment. Here, we find that VPC causes a shift from a low-cost, quick return juvenile strategy to a high-cost, high-return adult strategy. The juvenile strategy is advantageous in light-limited conditions, whereas the adult strategy provides greater returns in high light. The transition between these strategies is correlated with the developmental decline in the level of miR156, suggesting that is regulated by the miR156/SPL pathway. Our results provide an ecophysiological explanation for the existence of juvenile and adult leaf types and suggest that natural selection for these alternative economic strategies could be an important factor in plant evolution.

Defining the relative utility of lumbar spine surgery: A systematic literature review of common surgical procedures and their impact on health states.

Degenerative lumbar spondylosis is a common indication for patients undergoing spine surgery. As healthcare costs rise, measuring quality of life (QOL) gains after surgical procedures is critical in assessing value. We set out to: 1) compare baseline and postoperative EuroQol-5D (EQ-5D) scores for lumbar spine surgery and common surgical procedures to obtain post-operative quality-adjusted life year (QALY) gain, and 2) establish the relative utility of lumbar spine surgery as compared to other commonly performed surgical procedures. A systematic literature review was conducted to identify all studies reporting preoperative/baseline and postoperative EQ-5D scores for common surgical procedures. For each study, the number of patients included and baseline/preoperative and follow-up mean EQ-5D scores were recorded, and mean QALY gained for each intervention was calculated. A total of 67 studies comprising 95,014 patients were identified. Patients with lumbar spondylosis had the worst reported QOL at baseline compared to other surgical cohorts. The greatest QALY gain was seen in patients undergoing hip arthroplasty (0.38), knee arthroplasty (0.35) and lumbar spine surgery (0.32), nearly 2.5-fold greater QALY gained than for all other procedures. The low preoperative QOL, coupled with the improvements offered with surgery, highlight the utility and value of lumbar spine surgery compared to other common surgical procedures.

Estimating and Evaluating Tuberculosis Incidence Rates Among People Experiencing Homelessness, United States, 2007-2016.

OBJECTIVES: Persons experiencing homelessness (PEH) are disproportionately affected by tuberculosis (TB). We estimate area-specific rates of TB among PEH and characterize the extent to which available data support recent transmission as an explanation of high TB incidence. METHODS: We estimated TB incidence among PEH using National Tuberculosis Surveillance System data and population estimates for the US Department of Housing and Urban Development's Continuums of Care areas. For areas with TB incidence higher than the national average among PEH, we estimated recent transmission using genotyping and a plausible source-case method. For cases with ≥1 plausible source case, we assessed with TB program partners whether available whole-genome sequencing and local epidemiologic data were consistent with recent transmission. RESULTS: During 2011-2016, 3164 TB patients reported experiencing homelessness. National incidence was 36 cases/100,000 PEH. Incidence estimates varied among 21 areas with ≥10,000 PEH (9-150 cases/100,000 PEH); 9 areas had higher than average incidence. Of the 2349 cases with Mycobacterium tuberculosis genotyping results, 874 (37%) had ≥1 plausible source identified. In the 9 areas, 23%-82% of cases had ≥1 plausible source. Of cases with ≥1 plausible source, 63% were consistent and 7% were inconsistent with recent transmission; 29% were inconclusive. CONCLUSIONS: Disparities in TB incidence for PEH persist; estimates of TB incidence and recent transmission vary by area. With a better understanding of the TB risk among PEH in their jurisdictions and the role of recent transmission as a driver, programs can make more informed decisions about prioritizing TB prevention strategies.

MicroRNA156-mediated changes in leaf composition lead to altered photosynthetic traits during vegetative phase change.

Plant morphology and physiology change with growth and development. Some of these changes are due to change in plant size and some are the result of genetically programmed developmental transitions. In this study we investigate the role of the developmental transition, vegetative phase change (VPC), on morphological and photosynthetic changes. We used overexpression of microRNA156, the master regulator of VPC, to modulate the timing of VPC in Populus tremula × alba, Zea mays, and Arabidopsis thaliana to determine its role in trait variation independent of changes in size and overall age. Here, we find that juvenile and adult leaves in all three species photosynthesize at different rates and that these differences are due to phase-dependent changes in specific leaf area (SLA) and leaf N but not photosynthetic biochemistry. Further, we found juvenile leaves with high SLA were associated with better photosynthetic performance at low light levels. This study establishes a role for VPC in leaf composition and photosynthetic performance across diverse species and environments. Variation in leaf traits due to VPC are likely to provide distinct benefits under specific environments; as a result, selection on the timing of this transition could be a mechanism for environmental adaptation.

Risk-based Vaccines and the Need for Risk-based Subnational Vaccination Strategies for Introduction.

BACKGROUND: Most vaccines in the Expanded Program on Immunization are universal childhood vaccines (eg, measles and rotavirus vaccines). Other vaccines such as typhoid conjugate (TCV) and Japanese encephalitis vaccines are risk based and only used in countries where populations are at risk of these diseases. However, strategies to introduce risk-based vaccines are becoming complex due to increasing intracountry variability in disease incidence. There is a need to assess whether subnational vaccine strategies are appropriate. CRITERIA, CHALLENGES, AND BENEFITS: Subnational strategies consider intracountry heterogeneous risk and prioritize vaccination only in those areas that are at risk; there is no intent to introduce the vaccine nationally. The following variables should be considered to determine appropriateness of subnational strategies: disease burden, outbreak potential, treatment availability and costs, cost-effectiveness, and availability of other preventive interventions. We propose criteria for each variable and use a hypothetical country considering TCV introduction to show how criteria are applied to determine if a subnational strategy is appropriate. Challenges include granularity of disease-burden data, political challenges of vaccinating only a portion of a population, and potentially higher costs of introduction. Benefits include targeted reduction of disease burden, increased equity for marginalized populations, and progress on development goals. CONCLUSIONS: In the absence of perfect information at the national level, adopting a subnational vaccine strategy can provide country decision makers with an alternative to national vaccine introduction. Given the changing nature of communicable disease burden, subnational vaccination may be a tool to effectively avert mortality and morbidity while maximizing the use of available health and financial resources.

Dual Mobility for Monoblock Metal-on-Metal Revision-Is It Safe?

BACKGROUND: Revision of monoblock metal-on-metal (MoM) total hip arthroplasty (THA) is associated with high complication rates. Limited revision by conversion to a dual mobility (DM) without acetabular component extraction may mitigate these complications. However, the concern for polyethylene wear and osteolysis remains unsettled. This study investigates the results of DM conversion of monoblock MoM THA compared to formal acetabular revision. METHODS: One hundred forty-three revisions of monoblock MoM THA were reviewed. Twenty-nine were revisions to a DM construct, and 114 were complete revisions of the acetabular component. Mean patient age was 61, 54% were women. Components used, acetabular cup position, radiographic outcomes, serum metal ion levels, and HOOS Jr clinical outcome scores were investigated. RESULTS: At 3.9 years of follow-up (range 2-5), there were 2 revisions (6.9%) in the DM cohort, 1 for instability and another for periprosthetic fracture. Among the formal acetabular revision group there was a 20% major complication rate (23/114) and 16% underwent revision surgery (18/114) for aseptic loosening of the acetabular component (6%), deep infection (6%), dislocation (4%), acetabular fracture (3%), or delayed wound healing (6%). In the DM cohort, there were no radiographic signs of aseptic loosening, component migration, or polyethylene wear. One DM patient had a small posterior metadiaphyseal femur lesion that will require close monitoring. There were no other radiographic signs of osteolysis. There were no clinically significant elevations of serum metal ion levels. HOOS Jr scores were favorable. CONCLUSION: Limited revision with conversion to DM is a viable treatment option for failed monoblock MoM THA with lower complication rates than formal revision. Limited revision to DM appears to be a safe option for revision of monoblock MoM THA with a cup in good position and an internal geometry free of sharp edges or articular surface damage. Longer follow-up is needed to demonstrate any potential wear implications of these articulations.

Temporal correlation of elevated PRMT1 gene expression with mushroom body neurogenesis during bumblebee brain development.

Neural development depends on the controlled proliferation and differentiation of neural precursors. In holometabolous insects, these processes must be coordinated during larval and pupal development. Recently, protein arginine methylation has come into focus as an important mechanism of controlling neural stem cell proliferation and differentiation in mammals. Whether a similar mechanism is at work in insects is unknown. We investigated this possibility by determining the expression pattern of three protein arginine methyltransferase mRNAs (PRMT1, 4 and 5) in the developing brain of bumblebees by in situ hybridisation. We detected expression in neural precursors and neurons in functionally important brain areas throughout development. We found markedly higher expression of PRMT1, but not PRMT4 and PRMT5, in regions of mushroom bodies containing dividing cells during pupal stages at the time of active neurogenesis within this brain area. At later stages of development, PRMT1 expression levels were found to be uniform and did not correlate with actively dividing cells. Our study suggests a role for PRMT1 in regulating neural precursor divisions in the mushroom bodies of bumblebees during the period of neurogenesis.

Harmonic radar tracking reveals random dispersal pattern of bumblebee (Bombus terrestris) queens after hibernation.

The dispersal of animals from their birth place has profound effects on the immediate survival and longer-term persistence of populations. Molecular studies have estimated that bumblebee colonies can be established many kilometers from their queens' natal nest site. However, little is known about when and how queens disperse during their lifespan. One possible life stage when dispersal may occur, is directly after emerging from hibernation. Here, harmonic radar tracking of artificially over-wintered Bombus terrestris queens shows that they spend most of their time resting on the ground with intermittent very short flights (duration and distance). We corroborate these behaviors with observations of wild queen bees, which show similar prolonged resting periods between short flights, indicating that the behavior of our radar-monitored bees was not due to the attachment of transponders nor an artifact of the bees being commercially reared. Radar-monitored flights were not continuously directed away from the origin, suggesting that bees were not intentionally trying to disperse from their artificial emergence site. Flights did not loop back to the origin suggesting bees were not trying to remember or get back to the original release site. Most individuals dispersed from the range of the harmonic radar within less than two days and did not return. Flight directions were not different from a uniform distribution and flight lengths followed an exponential distribution, both suggesting random dispersal. A random walk model based on our observed data estimates a positive net dispersal from the origin over many flights, indicating a biased random dispersal, and estimates the net displacement of queens to be within the range of those estimated in genetic studies. We suggest that a distinct post-hibernation life history stage consisting mostly of rest with intermittent short flights and infrequent foraging fulfils the dual purpose of ovary development and dispersal prior to nest searching.

How foresight might support the behavioral flexibility of arthropods.

The small brains of insects and other invertebrates are often thought to constrain these animals to live entirely 'in the moment'. In this view, each one of their many seemingly hard-wired behavioral routines is triggered by a precisely defined environmental stimulus configuration, but there is no mental appreciation of the possible outcomes of one's actions, and therefore little flexibility. However, many studies show problem-solving behavior in various arthropod species that falls outside the range of fixed behavior routines. We propose that a basic form of foresight, the ability to predict the outcomes of one's own actions, is at the heart of such behavioral flexibility, and that the evolutionary roots of such outcome expectation are found in the need to disentangle sensory input that is predictable from self-generated motion versus input generated by changes in the outside world. Based on this, locusts, grasshoppers, dragonflies and flies seem to use internal models of the surrounding world to tailor their actions adaptively to predict the imminent future. Honeybees and orb-weaving spiders appear to act towards a desired outcome of their respective constructions, and the genetically pre-programmed routines that govern these constructions are subordinate to achieving the desired goal. Jumping spiders seem to preplan their route to prey suggesting they recognize the spatial challenge and actions necessary to obtain prey. Bumblebees and ants utilize objects not encountered in the wild as types of tools to solve problems in a manner that suggests an awareness of the desired outcome. Here we speculate that it may be simpler, in terms of the required evolutionary changes, computation and neural architecture, for arthropods to recognize their goal and predict the outcomes of their actions towards that goal, rather than having a large number of pre-programmed behaviors necessary to account for their observed behavioral flexibility.

Effect of Depression on Patient-Reported Outcomes Following Cervical Epidural Steroid Injection for Degenerative Spine Disease.

Objective: To assess the effect depression has on outcomes after cervical epidural steroid injections (CESIs). Design: Retrospective review of a prospectively collected database. Setting: Single institution tertiary care center. Subjects: Fifty-seven patients with cervical spondylosis and cervical radicular pain who were deemed appropriate surgical candidates but elected to undergo CESI first were included. Methods: Twenty-one of 57 (37%) patients with depression (defined as Zung Depression Scale >33) were included. Patient-reported outcomes including Neck Disability Index (NDI), numeric rating scale (NRS) for arm pain (AP), NRS for neck pain (NP), and EuroQol-5D (EQ-5D) were collected at baseline and three-month follow-up. Minimal clinically important differences were then calculated to provide dichotomous outcome measures of success. Results: Overall, 24 and 28 patients achieved at least 50% improvement in AP and NP, respectively. In terms of disability, 25/57 (43.9%) patients achieved >13.2-point improvement on the NDI overall. In patients with depression, 4/21 (19.0%) and 5/21 (23.8%) achieved at least 50% improvement on the NRS for AP and NP, respectively, compared with 20/36 (55.5%) and 23/36 (63.8%) in patients without depression. This difference was statistically significant for both pain measures (P < 0.002 AP, P < 0.006 NP). Statistically fewer patients, 5/21 (24%), with depression achieved ≥13.2-point improvement on the NDI compared with 20/36 (55%) nondepressed patients (P < 0.01). There was no difference in outcomes between groups on the EQ-5D. Conclusions: Patients with cervical spondylosis and comorbid depression who undergo CESI are less likely to achieve successful outcomes in both pain and function compared with nondepressed patients at three months.

Large-scale transcriptome changes in the process of long-term visual memory formation in the bumblebee, Bombus terrestris.

Many genes have been implicated in mechanisms of long-term memory formation, but there is still much to be learnt about how the genome dynamically responds, transcriptionally, during memory formation. In this study, we used high-throughput sequencing to examine how transcriptome profiles change during visual memory formation in the bumblebee (Bombus terrestris). Expression of fifty-five genes changed immediately after bees were trained to associate reward with a single coloured chip, and the upregulated genes were predominantly genes known to be involved in signal transduction. Changes in the expression of eighty-one genes were observed four hours after learning a new colour, and the majority of these were upregulated and related to transcription and translation, which suggests that the building of new proteins may be the predominant activity four hours after training. Several of the genes identified in this study (e.g. Rab10, Shank1 and Arhgap44) are interesting candidates for further investigation of the molecular mechanisms of long-term memory formation. Our data demonstrate the dynamic gene expression changes after associative colour learning and identify genes involved in each transcriptional wave, which will be useful for future studies of gene regulation in learning and long-term memory formation.

Studying emotion in invertebrates: what has been done, what can be measured and what they can provide.

Until recently, whether invertebrates might exhibit emotions was unknown. This possibility has traditionally been dismissed by many as emotions are frequently defined with reference to human subjective experience, and invertebrates are often not considered to have the neural requirements for such sophisticated abilities. However, emotions are understood in humans and other vertebrates to be multifaceted brain states, comprising dissociable subjective, cognitive, behavioural and physiological components. In addition, accumulating literature is providing evidence of the impressive cognitive capacities and behavioural flexibility of invertebrates. Alongside these, within the past few years, a number of studies have adapted methods for assessing emotions in humans and other animals, to invertebrates, with intriguing results. Sea slugs, bees, crayfish, snails, crabs, flies and ants have all been shown to display various cognitive, behavioural and/or physiological phenomena that indicate internal states reminiscent of what we consider to be emotions. Given the limited neural architecture of many invertebrates, and the powerful tools available within invertebrate research, these results provide new opportunities for unveiling the neural mechanisms behind emotions and open new avenues towards the pharmacological manipulation of emotion and its genetic dissection, with advantages for disease research and therapeutic drug discovery. Here, we review the increasing evidence that invertebrates display some form of emotion, discuss the various methods used for assessing emotions in invertebrates and consider what can be garnered from further emotion research on invertebrates in terms of the evolution and underlying neural basis of emotion in a comparative context.

Intrinsic and extrinsic factors drive ontogeny of early-life at-sea behaviour in a marine top predator.

Young animals must learn to forage effectively to survive the transition from parental provisioning to independent feeding. Rapid development of successful foraging strategies is particularly important for capital breeders that do not receive parental guidance after weaning. The intrinsic and extrinsic drivers of variation in ontogeny of foraging are poorly understood for many species. Grey seals (Halichoerus grypus) are typical capital breeders; pups are abandoned on the natal site after a brief suckling phase, and must develop foraging skills without external input. We collected location and dive data from recently-weaned grey seal pups from two regions of the United Kingdom (the North Sea and the Celtic and Irish Seas) using animal-borne telemetry devices during their first months of independence at sea. Dive duration, depth, bottom time, and benthic diving increased over the first 40 days. The shape and magnitude of changes differed between regions. Females consistently had longer bottom times, and in the Celtic and Irish Seas they used shallower water than males. Regional sex differences suggest that extrinsic factors, such as water depth, contribute to behavioural sexual segregation. We recommend that conservation strategies consider movements of young naïve animals in addition to those of adults to account for developmental behavioural changes.

A possible structural correlate of learning performance on a colour discrimination task in the brain of the bumblebee.

Synaptic plasticity is considered to be a basis for learning and memory. However, the relationship between synaptic arrangements and individual differences in learning and memory is poorly understood. Here, we explored how the density of microglomeruli (synaptic complexes) within specific regions of the bumblebee (Bombus terrestris) brain relates to both visual learning and inter-individual differences in learning and memory performance on a visual discrimination task. Using whole-brain immunolabelling, we measured the density of microglomeruli in the collar region (visual association areas) of the mushroom bodies of the bumblebee brain. We found that bumblebees which made fewer errors during training in a visual discrimination task had higher microglomerular density. Similarly, bumblebees that had better retention of the learned colour-reward associations two days after training had higher microglomerular density. Further experiments indicated experience-dependent changes in neural circuitry: learning a colour-reward contingency with 10 colours (but not two colours) does result, and exposure to many different colours may result, in changes to microglomerular density in the collar region of the mushroom bodies. These results reveal the varying roles that visual experience, visual learning and foraging activity have on neural structure. Although our study does not provide a causal link between microglomerular density and performance, the observed positive correlations provide new insights for future studies into how neural structure may relate to inter-individual differences in learning and memory.

Australian critical care nursing professionals' attitudes towards the use of traditional "chest physiotherapy" techniques.

BACKGROUND: Chest physiotherapy techniques, such as percussion, postural drainage, and expiratory vibrations, may be employed in a critical care setting. Physiotherapists are primarily responsible for their provision; however, nurses have also traditionally implemented these treatments. It is unclear whether nurses consider chest physiotherapy to be a part of their role, or how they perceive their knowledge and confidence pertaining to these techniques. OBJECTIVE: To investigate the attitudes of nurses towards traditional chest physiotherapy techniques. METHOD: A total of 1222 members of the Australian College of Critical Care Nurses were invited to participate in an anonymous online survey. RESULTS: There were 142 respondents (12%) with the majority (n = 132, 93%) having performed chest physiotherapy techniques in clinical practice. Most of them considered that the provision of chest physiotherapy was a part of nurse's role. Commonly cited factors influencing nurses' use of chest physiotherapy techniques were the availability of physiotherapy services, adequacy of nursing staff training and skill, and perceptions of professional roles. CONCLUSIONS: Nurses working in critical care commonly utilised traditional chest physiotherapy techniques. Further research is required to investigate the reasons why nursing professionals might assume responsibility for the provision of chest physiotherapy techniques, and if their application of these techniques is consistent with evidence-based recommendations.

Patient-reported outcomes after lumbar epidural steroid injection for degenerative spine disease in depressed versus non-depressed patients.

BACKGROUND CONTEXT: Medical interventional modalities such as lumbar epidural steroid injections (LESIs) are often used in the setting of lumbar spine disorders where other conservative measures have failed. Concomitant depression can lead to worse outcomes in lumbar spine pathology. A number of studies have demonstrated an association between preoperative depression and poor outcomes following surgery, but the effect of depression on outcomes following medical interventional modalities is poorly understood. PURPOSE: To evaluate the differences in patient-reported outcomes (PROs) between depressed and non-depressed patients undergoing LESI. STUDY DESIGN/SETTING: This study is an analysis of a prospective longitudinal registry database at a single academic institution. PATIENT SAMPLE: All patients undergoing LESI from 2012 to 2014 were eligible for enrollment into a prospective, web-based registry. Eligible patients had radicular pain, correlative imaging findings of degenerative pathology, and failed 6 weeks of conservative care. OUTCOME MEASURES: The PROs measured included the (1) numeric rating scale for back pain (NRS-BP), (2) numeric rating scale for leg pain (NRS-LP), (3) disease-specific physical disability-Oswestry Disability Index (ODI), and (4) preference-based health status-EuroQol-5D (EQ-5D). MATERIALS AND METHODS: Patients who met the inclusion criteria underwent LESI. Patient-reported outcomes were collected at baseline and at 12 months following treatment. Based on previously validated values for the Zung Depression Scale (ZDS) as a screening tool for depression, patients were dichotomized into non-depressed (ZDS score ≤33) and depressed (ZDS score >33). The PRO change scores from baseline to 12 months were calculated. The mean absolute and change scores between the groups were compared using Student t test. Multivariable linear regression analysis for ODI, EQ-5D, NRS-LP, and NRS-BP was performed. RESULTS: A total of 161 patients with complete 12-month follow-up were included. Seventy-one patients (44%) were classified as depressed and 90 patients (56%) were classified as non-depressed. The mean baseline PRO scores were significantly worse in depressed patients compared with non-depressed patients: ODI (p<.001), NRS-BP (p=.013), NRS-LP (p<.001), and EQ-5D (p=.001). The mean absolute scores at 12 months were significantly lower in the depressed versus non-depressed patients: ODI (p<.001), NRS-BP (p=.001), NRS-LP (p=.05), and EQ-5D (p=.003). However, there was no difference in mean change scores observed at 12 months between the depressed and non-depressed cohorts: ODI (p=.42), NRS-BP (p=.31), NRS-LP (p=.25), EQ-5D (p=.14). Adjusting for pre-procedure variables, the higher ZDS score was associated with higher disability (ODI) at 12 months. CONCLUSIONS: Depression led to worse absolute scores for PROs and is associated with higher disability following LESI. However, patients with depressive symptoms can expect similar improvement in PROs at 12 months.

Correction: Associative Mechanisms Allow for Social Learning and Cultural Transmission of String Pulling in an Insect.

[This corrects the article DOI: 10.1371/journal.pbio.1002564.].

Severe Hiatal Hernia as a Cause of Failure to Thrive Discovered by Transthoracic Echocardiogram.

A newborn infant with failure to thrive presented for murmur evaluation on day of life three due to a harsh 3/6 murmur. During the evaluation, a retrocardiac fluid filled mass was seen by transthoracic echocardiogram. The infant was also found to have a ventricular septal defect and partial anomalous pulmonary venous return. Eventually, a large hiatal hernia was diagnosed on subsequent imaging. The infant ultimately underwent surgical repair of the hiatal hernia at a tertiary care facility. Hiatal hernias have been noted as incidental extracardiac findings in adults, but no previous literature has documented hiatal hernias as incidental findings in the pediatric population.