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The coronavirus (COVID-19) pandemic has brought focus to the effects of anxiety on children. This study aimed to review the existing literature regarding the impact of the pandemic on pediatric anxiety. This review analyzed the existing literature between the open-sourced collection on PubMed inputting “anxiety disorder in children during pandemic” and “pediatric anxiety OR child anxiety AND COVID” and that of the Journal of the American Academy of Child & Adolescent Psychiatry using the keywords “social anxiety AND COVID.” This yielded 149 + 312 (461) entries and 68 articles were selected. Anxiety was found to have a prevalence of 18.9–23.87% in children during the COVID-19 pandemic whereas adolescent populations demonstrated a prevalence of 15.4–39.9%. Female gender was the most studied risk factor and physical activity was the most documented preventative factor. This review supported the notion that the COVID-19 pandemic is a major contributor to anxiety in the pediatric population.

Objective This study investigated the impact of residual tumor volume (RTV) on tumor progression after subtotal resection and observation of WHO grade I skull base meningiomas. Study Design This study is a retrospective volumetric analysis. Setting This study was conducted at a single institution. Participants Patients who underwent subtotal resection of a WHO grade I skull base meningioma and postsurgical observation (July 1, 2007–July 1, 2017). Main Outcome Measure The main outcome was radiographic tumor progression. Results Sixty patients with residual skull base meningiomas were analyzed. The median (interquartile range) RTV was 1.3 (5.3) cm3. Tumor progression occurred in 23 patients (38.3%) at a mean duration of 28.6 months postsurgery. The 1-, 3-, and 5-year actuarial progression-free survival (PFS) rates were 98.3, 58.6, and 48.7%, respectively. The Cox multivariate analysis identified increasing RTV (p = 0.01) and history of more than 1 previous surgery (p = 0.03) as independent predictors of tumor progression. In a Kaplan–Meier analysis for PFS, the RTV threshold of 3 cm3 maximized log-rank testing significance between groups of patients dichotomized at 0.5 cm3 thresholds (p 3 cm3 were 76.2 and 32.1%, respectively. When RTV >3 cm3 was entered as a covariate in the Cox model, it was the only factor independently associated with tumor progression (p Conclusion RTV was associated with tumor progression after subtotal resection of WHO grade I skull base meningioma in this cohort. An RTV threshold of 3 cm3 was identified that minimized progression of the residual tumor when gross total resection was not safe or feasible.

PurposeThe purpose of this study is to investigate the proportionality of market brand (MB) foods versus supermarket own brand (OB) foods sold on promotion and to compare their healthiness.Design/methodology/approachAn existing dataset containing nutritional information about a variety of foods on promotion (n = 6,776) from 48 stores across 8 retail chains in Northern Ireland (NI) was reanalysed. Product healthiness was measured using a score aligned to the Food Standards Agency's Front of Pack nutrient labelling system. MBs and OBs were considered as a whole and in their respective subsets–international/national and regional MBs, and premium, mid-market and value tiered OBs.FindingsResults found a balance in favour of health (52.4% amber/green versus 47.6% red) across retailers' promotions in NI. Further, OB products were often found to be superior to MBs with regards to overall healthfulness, and regional brands were found to be less healthy than international/national brands.Research limitations/implicationsFindings rationale further retail research to compare nutritionally OB and MB product types, and further consumer research regarding important attributes of OBs.Practical implicationsRetailers should communicate the comparative healthiness of their OBs in comparison to MB alternatives, in addition to communicating comparative price savings. There is opportunity for retailers to increase visibility of mid-market and value OB tiers, and for regional MBs to improve the nutritional profile of products in line with the consumer trend for health.Originality/valueThis study provides a contribution by using data on OBs and MBs on promotion, and by investigating the nutritional differences between different tiers of OB and MB products.

The integrity of wireless networks that make up the clear majority of IoT networks lack the inherent security of their wired counterparts. With the growth of the internet of things (IoT) and its pervasive nature in the modern home environment, it has caused a spike in security concerns over how the network infrastructure handles, transmits, and stores data. New wireless attacks such as KeySniffer and other attacks of this type cannot be tracked by traditional solutions. Therefore, this study investigates if wireless spectrum frequency monitoring using interference analysis tools can aid in the monitoring of device signals within a home IoT network. This could be used enhance the security compliance guidelines set forth by OWASP and NIST for these network types and the devices associated. Active and passive network scanning tools are used to provide analysis of device vulnerability and as comparison for device discovery purposes. The work shows the advantages and disadvantages of this signal pattern testing technique compared to traditional network scanning methods. The authors demonstrate how RF spectrum analysis is an effective way of monitoring network traffic over the air waves but also possesses limitations in that knowledge is needed to decipher these patterns. This article demonstrates alternative methods of interference analysis detection.

Magnetic resonance imaging (MRI) assesses pulmonary hypoplasia in fetal congenital diaphragmatic hernia (CDH). Neonatal mortality may occur with CDH. To quantify MRI parameters associated with neonatal survival in fetuses with isolated CDH. Fetal MRI for assessing CDH included region of interest (ROI) measurements for total lung volume (TLV), herniated liver volume, herniated other organ volume and predicted lung volume. Ratios of observed lung volume and liver up volume to predicted lung volume (observed to predicted TLV, percentage of the thorax occupied by liver) were calculated and compared to neonatal outcomes. Analyses included Wilcoxon rank sum test, multivariate logistic regression and receiver operating characteristic (ROC) curves. Of 61 studies, the median observed to predicted TLV was 0.25 in survivors and 0.16 in non-survivors (P=0.001) with CDH. The median percentage of the thorax occupied by liver was 0.02 in survivors and 0.22 in non-survivors (P 28 weeks was greater compared to GA ≤28 weeks. The ROC analysis demonstrated an area under the curve of 0.96 (95% confidence interval 0.91–1.00) for the combined observed to predicted TLV, percentage of the thorax occupied by liver and GA. The percentage of the thorax occupied by liver and observed to predicted TLV was predictive of neonatal survival in fetuses with CDH.

In recent decades, seasonal allergic rhinitis (SAR) prevalence has increased and recent studies have shown that air pollutants, such as diesel exhaust particles (DEP), can increase inflammatory and allergic biomarkers. The aim of this study was to investigate the effects of DEP on SAR symptoms induced by ragweed and to evaluate the efficacy and safety of fexofenadine HCl 180 mg versus placebo. This phase 3, single-centre, sequential, parallel-group, double-blind, randomised study (NCT03664882) was conducted in an environmental exposure unit (EEU) during sequential exposures: Period 1 (ragweed pollen alone), Period 2 (ragweed pollen+DEP), and Period 3 (ragweed pollen+DEP+single-dose fexofenadine HCl 180 mg or placebo). Efficacy and safety were evaluated in Period 3. Primary endpoints were the area under the curve (AUC) of total nasal symptom score (TNSS) from baseline to hour 12 (AUC0–12) during Period 1 and Period 2; and the AUC of the TNSS from hour 2 to 12 (AUC2–12) during Period 3. 251 out of 257 evaluable subjects were included in the modified intent-to-treat population. Least squares mean difference (95% CI) for TNSS Log AUC0−12 in Period 2 versus Period 1 was 0.13 (0.081–0.182; p, This is the first randomised, double-blind, large study to demonstrate the beneficial effect of a histamine H1-receptor antagonist by reducing ragweed pollen-induced seasonal allergic rhinitis symptoms aggravated by controlled exposure to air pollutants https://bit.ly/3oauMFu

Background Osteoarthritis (OA) is the most prevalent form of arthritis and the major cause of disability and overall diminution of quality of life in the elderly population. Currently there is no cure for OA, partly due to the large gaps in our understanding of its underlying molecular and cellular mechanisms. Macrophage migration inhibitory factor (MIF) is a procytokine that mediates pleiotropic inflammatory effects in inflammatory diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, data on the role of MIF in OA is limited with conflicting results. We undertook this study to investigate the role of MIF in OA by examining MIF genotype, mRNA expression, and protein levels in the Newfoundland Osteoarthritis Study. Methods One hundred nineteen end-stage knee/hip OA patients, 16 RA patients, and 113 healthy controls were included in the study. Two polymorphisms in the MIF gene, rs755622, and -794 CATT5-8, were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and PCR followed by automated capillary electrophoresis, respectively. MIF mRNA levels in articular cartilage and subchondral bone were measured by quantitative polymerase chain reaction. Plasma concentrations of MIF, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) were measured by enzyme-linked immunosorbent assay. Results rs755622 and -794 CATT5-8 genotypes were not associated with MIF mRNA or protein levels or OA (all p ≥ 0.19). MIF mRNA level in cartilage was lower in OA patients than in controls (p = 0.028) and RA patients (p = 0.004), while the levels in bone were comparable between OA patients and controls (p = 0.165). MIF protein level in plasma was lower in OA patients than in controls (p = 3.01 × 10−10), while the levels of TNF-α, IL-6 and IL-1β in plasma were all significantly higher in OA patients than in controls (all p ≤ 0.0007). Multivariable logistic regression showed lower MIF and higher IL-1β protein levels in plasma were independently associated with OA (OR per SD increase = 0.10 and 8.08; 95% CI = 0.04–0.19 and 4.42–16.82, respectively), but TNF-α and IL-6 became non-significant. Conclusions Reduced MIF mRNA and protein expression in OA patients suggested MIF might have a protective role in OA and could serve as a biomarker to differentiate OA from other joint disorders.

Background Despite interest among North American orthopaedic residents to pursue rotations in resource-limited settings, little is known regarding resident motivations and impact on host surgeons. Methods Surveys were distributed to North American orthopaedic surgeons and trainees who participated in international rotations during residency to assess motivations for participation and to orthopaedic surgeons at partnering low- and middle-income country (LMIC) institutions to assess impact of visiting trainees. Results Responses were received from 136 North American resident rotators and 51 LMIC host surgeons and trainees. North American respondents were motivated by a desire to increase surgical capacity at the LMIC while host surgeons reported a greater impact from learning from residents than on surgical capacity. Negative aspects reported by hosts included selfishness, lack of reciprocity, racial discrimination, competition for surgical experience, and resource burdens. Conclusions The motivations and impact of orthopaedic resident rotations in LMICs need to be aligned. Host perceptions and bidirectional educational exchange should be incorporated into partnership guidelines.

Background The glutamatergic modulator ketamine rapidly reduces depressive symptoms in individuals with treatment-resistant major depressive disorder (MDD). However, ketamine's effects on emotional processing biases remain largely unknown, and understanding these processes may help elucidate ketamine's mechanism of action. Methods Magnetoencephalography (MEG) was used to investigate ketamine's effects on early visual responses to affective stimuli in individuals with MDD (n=31) and healthy volunteers (HVs; n=24). Participants were enrolled in a double-blind, placebo-controlled, crossover clinical trial and were assessed at baseline and after subanesthetic-dose ketamine and placebo-saline infusions. During MEG recording, participants completed an emotional evaluation task in which they indicated the sex or emotional valence (happy-neutral or sad-angry) of facial stimuli. Source-localized event-related field (ERF) M100 and M170 amplitudes and latencies were extracted from regions of interest. Linear fixed effects models examined interactions between diagnosis, stimulus valence, and drug session for behavioral and MEG data. Results In baseline behavioral analyses, MDD participants exhibited higher accuracy for sad-angry than happy-neutral faces, and HVs responded faster to happy-neutral than sad-angry faces. In the MEG post-infusion analyses, calcarine M100 amplitudes were larger in MDD than HV participants post-placebo but became more similar post-ketamine. Finally, fusiform M170 amplitudes were associated with antidepressant response in MDD participants. Limitations The modest sample size and the need to collapse across responses to happy and neutral faces to increase statistical power limit the generalizability of the findings. Conclusions Ketamine rapidly altered emotional stimulus processing in MDD, laying the groundwork for future investigations of biomarkers of antidepressant treatment response. Clinical Trial Clinicaltrials.gov, NCT#00088699

Policies and regulations designed to address nutrient pollution in coastal waters are often complicated by delays in environmental and social systems. Social and political inertia may delay implementation of cleanup projects, and even after the best nutrient pollution management practices are developed and implemented, long groundwater travel times may delay the impact of inland or upstream interventions. These delays and the varying costs of nutrient removal alternatives used to meet water quality goals combine to create a complex dynamic decision problem with trade-offs about when, where, and how to intervene. We use multi-objective optimization to quantify the trade-offs between costs and minimizing the time to meet in-bay nutrient reduction goals represented as a Total Maximum Daily Load (TMDL). We calculate the impact of using in-bay (in-situ) nutrient removal through shellfish aquaculture relative to waiting for traditional source control to be implemented. We apply these methods to the Three Bays Watershed in Cape Cod, Massachusetts. In gross benefit terms, not accounting for any social costs, this equates to an average value of 37¢ (2035 TMDL target date) and 11¢ (2060 TMDL target date) per animal harvested over the plan implementation period. Our results encourage the consideration of alternative and in-situ approaches to tackle coastal pollution while traditional source control is implemented and its effects realized over time.

Background Ketamine as an antidepressant improves anhedonia as early as 2 hours after infusion. These drug effects are thought to be exerted via actions on reward-related brain areas—yet these actions remain largely unknown. Our study investigates ketamine’s effects during the anticipation and receipt of an expected reward, after the psychotomimetic effects of ketamine have passed, when early antidepressant effects are reported. Methods We examined ketamine’s effects during the anticipation and receipt of expected rewards on predefined brain areas, namely, the dorsal and ventral striatum, ventral tegmental area, amygdala, and insula. We recruited 37 male and female participants with remitted depression who were free from symptoms and antidepressant treatments at the time of the scan. Participants were scanned 2 hours after drug administration in a double-blind crossover design (ketamine: 0.5 mg/kg and placebo) while performing a monetary reward task. Results A significant main effect of ketamine was observed across all regions of interest during the anticipation and feedback phases of win and no-win trials. The drug effects were particularly prominent in the nucleus accumbens and putamen, which showed increased activation on the receipt of smaller rewards compared with neutral. The levels of (2R,6R)-hydroxynorketamine 2 hours after infusion significantly correlated with the activation observed in the ventral tegmental area for that contrast. Conclusions These findings demonstrate that ketamine can produce detectable changes in reward-related brain areas 2 hours after infusion, which occur without symptom changes and support the idea that ketamine might improve reward-related symptoms via modulation of response to feedback.

In the moral machine project, participants are asked to form judgments about the well-known trolley example. The project is intended to serve as a starting point for public discussion that would eventually lead to a solution to the social dilemma of autonomous vehicles. The dilemma is that autonomous vehicles should be programed to maximize the number of lives saved in trolley-style dilemmas. But consumers will only purchase autonomous vehicles that are programed to favor passenger safety in such dilemmas. We argue that the project is seriously misguided. There are relevant variants of trolley to which the project’s participants are not exposed. These variants make clear that the morally correct way to program autonomous vehicles is not at odds with what consumers will purchase. The project is hugely popular and dominates public discussion of this issue. We show that, ironically, the project itself is largely responsible for the dilemma.

BackgroundAt ketamine and esketamine doses at which antidepressant doses are achieved, these agents are relatively selective, noncompetitive, N-methyl-D-aspartate receptor antagonists. However, at substantially higher doses, ketamine has shown mu-opioid receptor (MOR–gene symbol: OPRM1) agonist effects. Preliminary clinical studies showed conflicting results on whether naltrexone, a MOR antagonist, blocks the antidepressant action of ketamine. We examined drug-induced or endogenous MOR involvement in the antidepressant and dissociative responses to esketamine by assessing the effects of a functional single nucleotide polymorphism rs1799971 (A118G) of OPRM1, which is known to alter MOR agonist-mediated responses.MethodsParticipants with treatment-resistant depression from 2 phase III, double-blind, controlled trials of esketamine (or placebo) nasal spray plus an oral antidepressant were genotyped for rs1799971. Participants received the experimental agents twice weekly for 4 weeks. Antidepressant responses were rated using the change in Montgomery–Åsberg Depression Rating Scale (MADRS) score on days 2 and 28 post-dose initiation, and dissociative side effects were assessed using the Clinician-Administered Dissociative-States Scale at 40 minutes post-dose on days 1 and 25.ResultsIn the esketamine + antidepressant arm, no significant genotype effect of single nucleotide polymorphism rs1799971 (A118G) on MADRS score reductions was detected on either day 2 or 28. By contrast, in the antidepressant + placebo arm, there was a significant genotype effect on MADRS score reductions on day 2 and a nonsignificant trend on day 28 towards an improvement in depression symptoms in G-allele carriers. No significant genotype effects on dissociative responses were detected.ConclusionsVariation in rs1799971 (A118G) did not affect the antidepressant response to esketamine + antidepressant. Antidepressant response to antidepressant + placebo was increased in G-allele carriers, compatible with previous reports that release of endorphins/enkephalins may play a role in mediating placebo effect.Trial RegistrationNCT02417064 and NCT02418585; www.clinicaltrials.gov

Early colleges are a new model of schooling in which the high school and college experiences are merged, shortening the total amount of time a student spends in school. This study uses a lottery-based experimental design to examine the impact of the model on longer term outcomes, including attainment of a postsecondary credential and academic performance in 4-year institutions. Results show that a significantly higher proportion of early college students were attaining postsecondary credentials. The results also show that early college students were completing their degrees more rapidly but that their performance in 4-year institutions was still comparable with the control students.

Background & Aims Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn’s disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets and functional consequences are unknown. Methods microRNA-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by quantitative polymerase chain reaction in colonic IECs. Functional characterization of activin receptor-like kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2-dimensional cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan–Meier estimator. Results ALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3’-untranslated region reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in a 5-ethynyl-2-deoxyuridine proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling increased colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared with healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a transepithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and was associated with a higher risk of endoscopic relapse in CD patients. Conclusions Decreased colonic ALK1 disrupted colonic IEC barrier integrity and was associated with poor clinical outcomes in CD patients., Graphical abstract

Summary Background Antenatal corticosteroids given to women before preterm birth improve infant survival and health. However, whether dexamethasone or betamethasone have better maternal, neonatal, and childhood health outcomes remains unclear. We therefore aimed to assess whether administration of antenatal dexamethasone to women at risk of preterm birth reduced the risk of death or neurosensory disability in their children at age 2 years compared with betamethasone. We also aimed to assess whether dexamethasone reduced neonatal morbidity, had benefits for the mother, or affected childhood body size, blood pressure, behaviour, or general health compared with betamethasone. Methods In this multicentre, double-blind, randomised controlled trial, we recruited pregnant women from 14 maternity hospitals in Australia and New Zealand that could provide care to preterm babies. Women were eligible for study inclusion if they were at risk of preterm birth before 34 weeks of gestation, had a singleton or twin pregnancy, and had no contraindications to antenatal corticosteroids. We randomly assigned women (1:1) to receive two intramuscular injections of either 12 mg dexamethasone (dexamethasone sodium phosphate) or 11·4 mg betamethasone (Celestone Chronodose), 24 h apart. The randomisation schedule used balanced, variable blocks that were stratified by hospital, gestational age, and number of fetuses (singleton or twins). We masked all participants, staff, and assessors to treatment groups. Analyses were by intention to treat. The primary outcome was death or neurosensory disability at age 2 years (corrected for prematurity). This study is registered with ANZCTR, ACTRN12608000631303. Findings Between Jan 28, 2009, and Feb 1, 2013, we randomly assigned 1346 (78%) women who were pregnant with 1509 fetuses to groups: 679 (50%) women were assigned to receive dexamethasone and 667 (50%) women were assigned to receive betamethasone. 27 (4%) fetuses, infants, or children in the dexamethasone group and 28 (4%) fetuses, infants, or children in the betamethasone group died before age 2 years. The primary outcome of death or neurosensory disability at age 2 years was determined for 603 (79%) of 763 fetuses whose mothers received dexamethasone and 591 (79%) of 746 fetuses whose mothers received betamethasone. We found a similar incidence of death or neurosensory disability in the dexamethasone (198 [33%] of 603 infants) and betamethasone groups (192 [32%] of 591 infants; adjusted relative risk [adjRR] 0·97, 95% CI 0·83 to 1·13; p=0·66). 18 (3%) of 679 women in the dexamethasone group and 28 of 667 (4%) women in the betamethasone group reported side-effects. Discomfort at the injection site, the most frequent side-effect, was less likely in the dexamethasone group than in the betamethasone group (six [1%] women vs 17 [3%] women; p=0·02). Interpretation The incidence of survival without neurosensory disability at age 2 years did not differ between dexamethasone and betamethasone treatment. Our findings indicate that either antenatal corticosteroid can be given to women before preterm birth to improve infant and child health. Funding National Health and Medical Research Council (Australia).

Background: Fibrin glue injection within the cavernous sinus (CS) is a demonstrably safe and simple technique to control venous bleeding with a low complication rate. However, this technique does have inherent risks. We illustrate 2 cases of internal carotid artery (ICA) thrombosis after fibrin glue injection in the CS for hemostasis.Methods: After encountering this complication recently, we conducted a retrospective review of the surgical database of 2 senior neurosurgeons who specialize in cerebrovascular and skull base surgery to identify patients with any complications associated with the use of fibrin glue injection for hemostasis. Approval was given by respective institutional review boards, and patient consent was obtained.Results: Of more than 10,000 microsurgery procedures performed by 2 senior neurosurgeons with a combined experience of 40 years, including procedures for aneurysms and skull base tumors, 2 cases were identified involving ICA thrombosis after fibrin glue injection in the CS for hemostasis. Both cases involved severe ischemic complications as a result of the ICA thrombosis. In this article, we present their clinical presentation, characteristics, management, and outcomes.Conclusion: Direct injection of fibrin glue into the CS for hemostasis can effectively control venous bleeding and facilitate complex dissections. However, it can be associated with ICA thrombosis, with subsequent serious ischemia and poor prognosis. Although this complication appears to be rare, increased awareness of this problem should temper the routine use of fibrin glue in anterior clinoidectomy and transcavernous approaches.

With approximately two in three UK adults overweight or obese, one in five living in poverty and our emergence from the Covid-19 pandemic with implications for employment and income status there is an urgent need to understand what it costs to eat healthily and the role that promotions can play in helping householders manage food budgets. The literature suggests that, in affluent countries, price promotions appear to increase consumer food purchases and are applied more frequently to less healthy products than their healthy counterparts. This review discusses the cost of a healthy diet, identifies the prevalence of promotions in both the supermarket setting generally and a typical shopping basket specifically, and discusses the barriers to affording a healthy diet. Given the current policy focus on the cost of living and population health emphasising the need for food shopping to represent health and value for money for better public health outcomes, this review contributes to the evidence base for retailers' and policymakers' consideration as policy solutions are sought to reduce population obesity levels, while ensuring the affordability and accessibility of nutritious food. It is important, given the shift in consumer purchasing behaviour to online shopping as a result of self-isolating or reticence to physically access stores in response to the Covid-19 pandemic, that retail food promotions are available irrespective of the chosen mode of shopping (in-store or online).

STUDY DESIGN A retrospective study of surgical outcomes in patients with degenerative cervical myelopathy (DCM). OBJECTIVE To better characterize outcomes following cervical decompression in those with severe, non-ambulatory forms of DCM. SUMMARY OF BACKGROUND DATA DCM represents a collection of age-related degenerative processes of the cervical spine that can result in motor, sensory and autonomic dysfunction, leading to significant reductions in quality of life. Individuals with severe, non-ambulatory forms of DCM are often treated with spinal decompression although the extent of neurological improvement for this patient population is unclear. METHODS A retrospective analysis of 48 non-consecutive non-ambulatory patients who underwent cervical decompression surgery between January 2007 and December 2018. Paired t-tests and Wilcoxon-signed rank tests were used to compare Nurick grade and mJOA score before and after surgery. Patient demographics, operative details, and post-surgical complications were analyzed using descriptive statistics. RESULTS Patients experienced significant improvements in both Nurick grade and mJOA score following cervical decompression surgery. The mean Nurick grade improved from 4.10 ± 0.31 to 2.21 ± 0.82 (p

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to similar to 22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.

Peanut allergy reaction severity correlates with increased intestinal epithelial cell (IEC) barrier permeability. CC027/GeniUnc mice develop peanut allergy by intragastric administration of peanut proteins without adjuvant. We report that peanut-allergic CC027/GeniUnc mice showed increased IEC barrier permeability and systemic peanut allergen Ara h 2 after challenge. Jejunal epithelial cell transcriptomics showed effects of peanut allergy on IEC proliferation, survival, and metabolism, and revealed IEC-predominant angiopoietin like-4 (Angptl4) as a unique feature of CC027/GeniUnc peanut allergy. CC027/GeniUnc mice and peanut-allergic pediatric patients demonstrated significantly higher serum Angptl4 and ANGPTL4 compared to control C3H/HeJ mice and non-peanut-allergic but atopic patients, respectively, highlighting its potential as a biomarker of peanut allergy.

High quality evidence is difficult to generate, leaving substantial knowledge gaps in the treatment of spinal conditions. Appropriate use criteria (AUC) are a means of determining appropriate recommendations when high quality evidence is lacking.Define appropriate use criteria (AUC) of cervical fusion for treatment of degenerative conditions of the cervical spine.Appropriate use criteria for cervical fusion were developed using the RAND/UCLA appropriateness methodology. Following development of clinical guidelines and scenario writing, a one-day workshop was held with a multidisciplinary group of 14 raters, all considered thought leaders in their respective fields, to determine final ratings for cervical fusion appropriateness for various clinical situations.Final rating for cervical fusion recommendation as either "Appropriate," "Uncertain" or "Rarely Appropriate" based on the median final rating among the raters.Inclusion criteria for scenarios included patients aged 18 to 80 with degenerative conditions of the cervical spine. Key modifiers were defined and combined to develop a matrix of clinical scenarios. The median score among the raters was used to determine the final rating for each scenario. The final rating was compared between modifier levels. Spearman's rank correlation between each modifier and the final rating was determined. A multivariable ordinal regression model was fit to determine the adjusted odds of an "Appropriate" final rating while adjusting for radiographic diagnosis, number of levels and symptom type. Three decision trees were developed using decision tree classification models and variable importance for each tree was computed.Of the 263 scenarios, 47 (17.9 %) were rated as rarely appropriate, 66 (25%) as uncertain and 150 (57%) were rated as appropriate. Symptom type was the modifier most strongly correlated with the final rating (adjusted ρ2 = 0.58, p.01). A multivariable ordinal regression adjusting for symptom type, diagnosis, and number of levels and showed high discriminative ability (C statistic = 0.90) and the adjusted odds ratio (aOR) of receiving a final rating of "Appropriate" was highest for myelopathy (aOR, 7.1) and radiculopathy (aOR, 4.8). Three decision tree models showed that symptom type and radiographic diagnosis had the highest variable importance.Appropriate use criteria for cervical fusion in the setting of cervical degenerative disorders were developed. Symptom type was most strongly correlated with final rating. Myelopathy or radiculopathy were most strongly associated with an "Appropriate" rating, while axial pain without stenosis was most associated with "Rarely Appropriate."

Background Despite widespread recommendations to favor lipase over amylase in the diagnosis and management of acute pancreatitis, many routine hospital laboratories still offer amylase testing. This study sought to evaluate and compare ordering patterns of amylase and lipase in patients with acute pancreatitis. Methods We analyzed 438 patients with acute pancreatitis admitted to our hospital. Data collection included pancreatitis etiology and management as well as biochemical profiles of amylase and lipase. We compared serial ordering patterns, degree of biomarker elevation, and normalization kinetics. Results All patients had at least one lipase ordered during their admission, and only 51 patients (12%) had at least one amylase ordered. On average, lipase was elevated 5 times higher above its respective upper reference limit than amylase at admission. Pancreatitis etiology was skewed toward gallstones in the amylase group as compared to the lipase only group (69% vs. 43%), and surgical patients (laparoscopic cholecystectomy) were more likely to have amylase ordered and/or trended. Conclusions Amylase measurement was not necessary in the diagnosis and management of 88% of patients with acute pancreatitis. Of patients for whom amylase was ordered, it was common for these patients to be those referred to surgical procedures, possibly because amylase normalization may be documented faster than that of lipase.

In a world of ever-growing customer data, businesses are required to have a clear line of sight into what their customers think about the business, its products, people and how it treats them. Insight into these critical areas for a business will aid in the development of a robust customer experience strategy and in turn drive loyalty and recommendations to others by their customers. It is key for business to access and mine their customer data to drive a modern customer experience. This article investigates the use of a text mining approach to aid sentiment analysis in the pursuit of understanding what customers are saying about products, services and interactions with a business. This is commonly known as Voice of the Customer (VOC) data and it is key to unlocking customer sentiment. The authors analyse the relationship between unstructured customer sentiment in the form of verbatim feedback and structured data in the form of user review ratings or satisfaction ratings to explore the question of whether customers say what they really think when given the opportunity to provide free text feedback as opposed to how they rate a product on a scale of one to five. Using various Sentiment Analysis approaches, the authors assign a sentiment score to a piece of verbatim feedback and then categorise it as positive, negative, or neutral. Using this normalised sentiment score, they compare it to the corresponding rating score and investigate the potential business insights. The results obtained indicate that a business cannot rely solely on a standalone single metric as a source of truth regarding customer experience. There is a significant difference between the customer ratings score and the sentiment of their corresponding review of the product. The authors propose that it is imperative that a business supplements their customer feedback scores with a robust sentiment analysis strategy.

Summary Background Well designed, large comparative effectiveness trials assessing the efficacy of primary interventions for faecal incontinence are few in number. The objectives of this study were to compare different combinations of anorectal manometry-assisted biofeedback, loperamide, education, and oral placebo. Methods In this randomised factorial trial, participants were recruited from eight clinical sites in the USA. Women with at least one episode of faecal incontinence per month in the past 3 months were randomly assigned 0·5:1:1:1 to one of four groups: oral placebo plus education only, placebo plus anorectal manometry-assisted biofeedback, loperamide plus education only, and loperamide plus anorectal manometry-assisted biofeedback. Participants received 2 mg per day of loperamide or oral placebo with the option of dose escalation or reduction. Women assigned to biofeedback received six visits, including strength and sensory biofeedback training. All participants received a standardised faecal incontinence patient education pamphlet and were followed for 24 weeks after starting treatment. The primary endpoint was change in St Mark's (Vaizey) faecal incontinence severity score between baseline and 24 weeks, analysed by intention-to-treat using general linear mixed modelling. Investigators, interviewers, and outcome evaluators were masked to biofeedback assignment. Participants and all study staff other than the research pharmacist were masked to medication assignment. Randomisation took place within the electronic data capture system, was stratified by site using randomly permuted blocks (block size 7), and the sizes of the blocks and the allocation sequence were known only to the data coordinating centre. This trial is registered with ClinicalTrials.gov, number NCT02008565. Findings Between April 1, 2014, and Sept 30, 2015, 377 women were enrolled, of whom 300 were randomly assigned to placebo plus education (n=42), placebo plus biofeedback (n=84), loperamide plus education (n=88), and the combined intervention of loperamide plus biofeedback (n=86). At 24 weeks, there were no differences between loperamide versus placebo (model estimated score change −1·5 points, 95% CI −3·4 to 0·4, p=0·12), biofeedback versus education (−0·7 points, −2·6 to 1·2, p=0·47), and loperamide and biofeedback versus placebo and biofeedback (−1·9 points, −4·1 to 0·3, p=0·092) or versus loperamide plus education (−1·1 points, −3·4 to 1·1, p=0·33). Constipation was the most common grade 3 or higher adverse event and was reported by two (2%) of 86 participants in the loperamide and biofeedback group and two (2%) of 88 in the loperamide plus education group. The percentage of participants with any serious adverse events did not differ between the treatment groups. Only one serious adverse event was considered related to treatment (small bowel obstruction in the placebo and biofeedback group). Interpretation In women with normal stool consistency and faecal incontinence bothersome enough to seek treatment, we were unable to find evidence against the null hypotheses that loperamide is equivalent to placebo, that anal exercises with biofeedback is equivalent to an educational pamphlet, and that loperamide and biofeedback are equivalent to oral placebo and biofeedback or loperamide plus an educational pamphlet. Because these are common first-line treatments for faecal incontinence, clinicians could consider combining loperamide, anal manometry-assisted biofeedback, and a standard educational pamphlet, but this is likely to result in only negligible improvement over individual therapies and patients should be counselled regarding possible constipation. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health

Background In the search for novel treatments for depression, ketamine has emerged as a unique agent with rapid antidepressant effects. Experimental tasks involving emotional processing can be used during functional magnetic resonance imaging scanning to investigate ketamine’s effects on brain function in major depressive disorder (MDD). This study examined ketamine’s effects on functional magnetic resonance imaging activity during an emotional processing task. Methods A total of 33 individuals with treatment-resistant MDD and 24 healthy control participants (HCs) took part in this double-blind, placebo-controlled crossover study. Participants received ketamine and placebo infusions 2 weeks apart, and functional magnetic resonance imaging scans were conducted at baseline and 2 days after each infusion. Blood oxygen level–dependent signal was measured during an emotional processing task, and a linear mixed-effects model was used to analyze differences in activation among group, drug, and task-specific factors. Results A group-by-drug interaction was observed in several brain regions, including a right frontal cluster extending into the anterior cingulate cortex and insula. Participants with MDD had greater activity than HCs after placebo infusion but showed lower activity after ketamine infusion, which was similar to the activity in HCs after placebo. A group-by-drug-by-task condition interaction was also found, which showed further differences that varied between implicit and explicit emotional conditions. Conclusions The main results indicate that ketamine had differential effects on brain activity in participants with MDD versus HCs. The pattern of activation in participants with MDD after ketamine infusion resembled the activation in HCs after placebo infusion, suggesting a normalization of function during emotional processing. The findings contribute to a better understanding of ketamine’s actions in the brain.

The IBDs, Crohn’s disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract resulting from an aberrant immune response to enteric microbiota in genetically susceptible individuals. Disease presentation and progression within and across IBDs, especially Crohn’s disease, are highly heterogeneous in location, severity of inflammation and other phenotypes. Current clinical classifications fail to accurately predict disease course and response to therapies. Genome-wide association studies have identified >240 loci that confer risk of IBD, but the clinical utility of these findings remains unclear, and mechanisms by which the genetic variants contribute to disease are largely unknown. In the past 5 years, the profiling of genome-wide gene expression, epigenomic features and gut microbiota composition in intestinal tissue and faecal samples has uncovered distinct molecular signatures that define IBD subtypes, including within Crohn’s disease and ulcerative colitis. In this Review, we summarize studies in both adult and paediatric patients that have identified different IBD subtypes, which in some cases have been associated with distinct clinical phenotypes. We posit that genome-scale molecular phenotyping in large cohorts holds great promise not only to further our understanding of the diverse molecular causes of IBD but also for improving clinical trial design to develop more personalized disease management and treatment. Disease presentation and progression within and across IBD are highly heterogeneous, particularly in Crohn’s disease. Here, the authors summarize genomic, epigenomic and gut microbiota studies in adult and paediatric patients that have identified different IBD subtypes.

Growing evidence suggests that the glutamatergic modulator ketamine has rapid antidepressant effects in treatment-resistant depressed subjects. The anticholinergic agent scopolamine has also shown promise as a rapid-acting antidepressant. This study applied genome-wide markers to investigate the role of genetic variants in predicting acute antidepressant response to both agents. The ketamine-treated sample included 157 unrelated European subjects with major depressive disorder (MDD) or bipolar disorder (BD). The scopolamine-treated sample comprised 37 unrelated European subjects diagnosed with either MDD or BD who had a current Major Depressive Episode (MDE), and had failed at least two adequate treatment trials for depression. Change in Montgomery–Asberg Depression Rating Scale (MADRS) or the 17-item Hamilton Depression Rating Scale (HAM-D) scale scores at day 1 (24 h post-treatment) was considered the primary outcome. Here, we conduct pilot genome-wide association study (GWAS) analyses to identify potential markers of ketamine response and dissociative side effects. Polygenic risk score analysis of SNPs ranked by the strength of their association with ketamine response was then calculated in order to assess whether common genetic markers from the ketamine study could predict response to scopolamine. Findings require replication in larger samples in light of low power of analyses of these small samples. Neverthless, these data provide a promising illustration of our future potential to identify genetic variants underlying rapid treatment response in mood disorders and may ultimately guide individual patient treatment selection in the future.

Sound sources are designed to provide subsea tracking and re‐location of RAFOS floats and other Lagrangian drifters listening at 260Hz. More recently sweeps have been added to support FishChip tracking at 262Hz. These sources must be tuned to the water properties where they are to be deployed as they have a fairly narrow bandwidth. The high‐Q resonator’s bandwidth is about 4Hz. This report documents the tuning, and provides an overview of the sound source assembly.

Prolonged broad-spectrum antibiotic use is more likely to induce bacterial resistance and dysbiosis of skin and gut microflora. First and second-generation tetracycline-class antibiotics have similar broad-spectrum antibacterial activity. Targeted tetracycline-class antibiotics are needed to limit antimicrobial resistance and improve patient outcomes. Sarecycline is a narrow-spectrum, third-generation tetracycline-class antibiotic Food and Drug Administration (FDA)-approved for treating moderate-to-severe acne. In vitro studies demonstrated activity against clinically relevant Gram-positive bacteria but reduced activity against Gram-negative bacteria. Recent studies have provided insight into how the structure of sarecycline, with a unique C7 moiety, interacts with bacterial ribosomes to block translation and prevent antibiotic resistance. Sarecycline reduces Staphylococcus aureus DNA and protein synthesis with limited effects on RNA, lipid, and bacterial wall synthesis. In agreement with in vitro data, sarecycline demonstrated narrower-spectrum in vivo activity in murine models of infection, exhibiting activity against S. aureus, but reduced efficacy against Escherichia coli compared to doxycycline and minocycline. In a murine neutropenic thigh wound infection model, sarecycline was as effective as doxycycline against S. aureus. The anti-inflammatory activity of sarecycline was comparable to doxycycline and minocycline in a rat paw edema model. Here, we review the antibacterial mechanisms of sarecycline and report results of in vivo studies of infection and inflammation.

Household food insecurity in developed nations has been identified as a significant public health concern. Although various research on the topic exists, such as contributors to food insecurity, and implications for individual physical and mental health outcomes; there is currently a lack of consideration as to how individual implications of food insecurity such as poor physical and mental health can consequently impact on business and the wider economy. In addition, there is a lack of conceptual literature related to food insecurity. Stakeholder interviews (n = 19) were conducted, and data were used to inform the conceptual model (risk factors, potential implications for individuals, the economy and business, and opportunities for business and policy response). The main suggested implications related to business and the economy were reduced contribution to the workforce and the economy, and increased cost pressures on the National Health Service. Business responses suggested included the inclusion of initiatives to address food insecurity in corporate social responsibility strategies, and further involvement of food businesses/retailers in redistributing surplus food. Policy responses suggested included policies relating to welfare, wages and work contracts, food redistribution incentives, sustainability, and community interventions in disadvantaged areas. The resulting model is unique in conceptualising food insecurity in the Northern Ireland context, with applicability to the UK and other developed nations.

BACKGROUND CONTEXT Decompressive laminectomy surgery for symptomatic lumbar spinal stenosis is generally predictable and effective in providing relief of radiculopathy and neurogenic claudication. Decompression alone, without fusion, is reserved for patients with preserved lordosis and no evidence of radiographic instability. On occasion, spinal deformity or instability can occur following decompressive surgery and may lead to disabling symptoms and the need for revision surgery that is inclusive of an instrumented spine fusion. PURPOSE To evaluate the extent and nature of symptomatic deformity or instability that occurred within one year following decompressive surgery for lumbar spinal stenosis. STUDY DESIGN/SETTING A retrospective review of a consecutive series of patients treated at a single institution. PATIENT SAMPLE This study included 425 patients who underwent decompressive surgery over a 5-year period (2012-2016) to manage symptomatic lumbar spinal stenosis. Surgery was performed by one of four surgeons at a single academic medical center. All patients had preserved lordosis (no antero, lateral, or retrolisthesis) on preoperative, upright radiographs and there was no evidence of instability (>4mm) on flexion-extension films. All patients underwent open, multilevel laminectomies with lateral recess and foraminal decompression to address neural compression noted on preoperative MRI. The indication of additional surgery within one year of the index surgery were recurrent back and leg pain, and radiographic evidence of new deformity development, or instability within the lumbar spine at one of the previously decompressed levels. New deformity was defined as the presence of antero- or lateral listhesis not previously present and instability was defined as segmental motion of >4mm on flexion-extension films. OUTCOME MEASURES Pre- and postoperative VAS scores (back and leg pain), Oswestry Disability Index, and specific queries of patient satisfaction and willingness to repeat the index surgery. METHODS Multiple preoperative clinical and radiographic features were evaluated to identify a potential causal relationship with the subsequent postoperative development of clinical symptoms and radiographic deformity or instability which occurred within one year that necessitated a revision surgery. Additionally, the ultimate clinical outcome of the patients who underwent a revision surgery for deformity development were compared to the cohort of patients who had not developed a deformity after undergoing decompressive surgery during the same time period. RESULTS A total of 425 patients underwent a multilevel decompressive lumbar laminectomy for spinal stenosis over a 5-year period. Nineteen patients (4%) developed pain and radiographic evidence of a deformity or instability within one year that necessitated an additional surgery in the form of an instrumented fusion. Back pain was present in all 19 patients and radicular leg pain in 16 of 19 patients (84%). Significant factors for the development of instability or a deformity included age >50 (p=.04), body mass index >30 (p=.03), and extensive fluid with multiple facet joints on preoperative MRI (p=.04). Notable factors that approached, but did not achieve significance included 4 level laminectomy surgeries, a history of osteoporosis, and chronic preoperative use of corticosteroids. Notable factors that were not significant included presence of congenital stenosis, type of preoperative employment (physically-demanding or sedentary), use of postoperative bracing, or duration of preoperative symptoms (greater or less than 1 year). When compared with the cohort of patients who did not develop a deformity, the deformity patients had lower VAS (back) and ODI scores at 6 months following their revision surgery, although these differences became non-significant by 1 year. At 5-year follow-up, the two cohorts had similar VAS (back and leg), ODI, and in percentage of patient satisfaction and willingness to repeat the index surgery. CONCLUSIONS The development of a deformity or instability within the first postoperative year following decompressive laminectomy surgery for spinal stenosis was found to be uncommon, occurring in 4% of 425 consecutive patients treated a single institution over a 5-year period. Younger, obese patients and those with greater than 3 levels decompressed were more likely to develop instability or deformity, as were patients with diffuse fluid noted within facet joints on preoperative MRI. However, long-term follow-up revealed no ultimate difference in patient-reported outcomes of those who underwent a subsequent spine fusion, including willingness to repeat the original lumbar decompressive surgery. Lumbar decompressive laminectomy surgery is safe and predictable. When performed on patients with preserved lordosis and no pre-existing instability or deformity, the likelihood for development of early, postoperative deformity or instability is low, but if it is to occur, management with an instrumented fusion is safe and effective. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT Degenerative cervical myelopathy (DCM) represents a collection of age-related degenerative processes of the cervical spine that can result in motor, sensory and autonomic dysfunction, leading to significant reductions in quality of life. Individuals with severe, nonambulatory forms of DCM are often treated with spinal decompression although the extent of neurological improvement for this patient population is unclear. PURPOSE The aim of this study was to better characterize outcomes following cervical decompression in those with severe, nonambulatory forms of DCM. We believe the results of this study can be used to better inform the decision-making process when considering the potential benefits and risks of decompression surgery for these patients. STUDY DESIGN/SETTING A retrospective analysis was done on 48 patients who underwent cervical decompression surgery at University Hospitals Cleveland Medical Center between January 2007 and December 2018. PATIENT SAMPLE Patients greater than 18 years of age, with severe, nonambulatory forms of DCM classified as a Nurick grade of IV or V were included in the study. OUTCOME MEASURES Changes in Nurick and mJOA scores were used as primary outcome measures. METHODS Paired t-tests and Wilcoxon-signed rank tests were used to compare Nurick and mJOA scores before and after surgery. Patient demographics, operative details, and postsurgical complications were analyzed using descriptive statistics. RESULTS Patients experienced significant improvements in both outcomes following cervical decompression surgery. The mean Nurick grade improved from 4.10 ± 0.31 to 2.21 ± 0.82 (p CONCLUSIONS Our study demonstrated that patients with severe forms of DCM experienced significant improvement in neurological function following cervical decompression surgery. These improvements indicate that cervical decompression surgery is effective in this patient population and has the potential to improve neurological status. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT Incidental durotomies (ID) are a known occurrence in lumbar spine surgery. In most cases, an ID can be effectively managed with direct repair that is often supplemented by fibrin glue or a synthetic or biologic patch. Generally, there is minimal adverse effect to the patient other than a longer than expected postoperative hospitalization accounting for a period of recumbence following the dural repair. However, on occasion, a recurrent CSF leak occurs postoperatively which can cause troubling symptoms and may require additional surgery to repair. PURPOSE To identify the frequency of recurrent CSF leaks in patients who underwent surgery for lumbar spinal stenosis that was complicated by a dural tear and subsequently to both define risk factors for the occurrence of a recurrent leak and to assess the effect upon the ultimate clinical outcome. STUDY DESIGN/SETTING A retrospective analysis of a prospectively-treated cohort of patients. PATIENT SAMPLE A total of 1,480 consecutive patients who underwent elective, primary surgery for lumbar spinal stenosis over a 5-year period by one of four surgeons at a single academic, tertiary care medical center. Clinical follow-up was a minimum of 2 years (range: 2-8 years). OUTCOME MEASURES VAS Score (1-10) for back and leg pain, Oswestry Disability Index, Patient Satisfaction Assessment, and Retrospective Willingness to Repeat Surgery. METHODS A dural tear (DT) occurred in 103 of 1,481 patients (7%). Fourteen of 103 patients (14%) developed a symptomatic, postoperative CSF leak requiring additional surgery. Overall, a recurrent CSF leak occurred in 14 of the 1,481 patients (0.9%) who underwent a primary lumbar decompression for spinal stenosis who were evaluated in the study. All dural tears were identified at the time of the index surgery. Dural repairs were directly repaired with either a 4-0 silk or 6-0 polypropylene suture in a water tight fashion and assessed with a Valsalva maneuver prior to closure. Repairs were augmented with fibrin glue in 70% of cases, a collagen patch in 32%, and both in 20%. Patients were kept on bedrest following surgery for 1-3 days. A subfascial drain was employed in 82% of patients. Choice of suture, augmentation of repair, use of drain and duration of bedrest were based on surgeon discretion. Multi-variate regression analysis was employed to identify significant risk factors for a postoperative CSF leak. RESULTS Of the 14 patients with a recurrent CSF leak, symptoms arose during the postoperative hospitalization in 11 patients (79%) and after discharge in 3 (21%). Each patient had a palpable subcutaneous mass and 4 patients (29%) had a percutaneous CSF leak. Each patient was symptomatic with postural headache and 10(71%) experienced photophobia. Significant risk factors for development of a CSF leak included age > 70, body mass index > 30 (obese), history of diabetes and chronic use of corticosteroids. Notable factors not significant included duration of surgery, the additional diagnosis of degenerative spondylolisthesis or degenerative scoliosis, presence of a fusion, numbers of levels decompressed or fused, use of BMP or particular bone graft choice, nor preoperative use of pharmacologic anticoagulation. The likelihood of a recurrent leak was not significantly affected by a particular type of surgical dural repair, the suture material employed, nor the use of a synthetic patch or fibrin glue. As well, the use of a postoperative, subfascial drain nor the duration of recumbancy after the initial surgery did not significantly affect the development of a recurrent CSF leak. At 3-month follow-up, two patient reported outcomes (ODI, patient satisfaction) were slightly less in patients who had a recurrent CSF leak, compared with both durotomy patients with no recurrent leak and those with no durotomy, although this did not reach statistical significance. At 6 month, 12 month, and final follow-up, there were no statistical differences in patient-reported outcomes between the recurrent CSF leak, durotomy without recurrent leak, and no durotomy cohorts. Length of hospitalization was an average of 4.2 days longer in patients with a recurrent CSF leak compared with patients with no durotomy and 2.2 days longer than patients with a durotomy but no recurrent leak. Cost of hospitalization was $65,000 greater in patients with a recurrent leak compared to those with no durotomy and $35,000 greater than those with a durotomy but no recurrent leak. CONCLUSIONS Incidental durotomy is a relatively uncommon occurrence in primary surgery to treat lumbar spinal stenosis. Recurrent CSF leak following repair of a durotomy is also uncommon, with an incidence of 14% of patients with a durotomy in this large single center study. Prompt recognition of a recurrent CSF leak and subsequent surgical repair effectively treats this problem and adverse sequelae did not occur and ultimate clinical outcomes were not altered compared to those without a durotomy or a recurrent CSF leak. Hospital length of stay and cost were greater in those with this uncommon complication. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Objectives: To evaluate the demographic and HPV status in relation to the increasing incidence of adenocarcinoma in the United States. Methods: Data were obtained from the United States Cancer Statistics from 2001 to 2016. SEER*Stat and Joinpoint regression were used to calculate average annual percent change (AAPC). Incidence rates were corrected for hysterectomy using the Behavioral Risk Factor Surveillance System. THe National Health and Nutrition Examination Survey (NHANES) was used to evaluate HPV genotypes in a healthy cohort. Results: Of 201,609 patients with cervical adenocarcinoma between 2001-2016, White, Black, Hispanic, Asian and others comprised 62%, 15.4%, 16.3%, 4.4% and 1.8% of patients. Overall the 40-44 year-old age groups had the highest incidence (2.97 / 100,000). We also found an average annual increase of 2.4% in this age group. (p or =5 partners. Although HPV 16 was the predominant HPV genotype at 18.4%, HPV 18 comprised 9.1% of the HPV positive patients within the study group. Blacks have a two-fold higher rate of HPV 18 infection (3.2% vs 1.3%; p Download : Download high-res image (320KB) Download : Download full-size image Conclusions: The incidence of adenocarcinoma is increasing in the United States. Blacks have a higher incidence of metastatic disease compared to Whites and other races. HPV 18 genotypes were more prevalent in Blacks compared to Whites with no difference HPV 16.

Background and AimsThe host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn’s disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course.MethodsWe examined the expression of colon ACE2 using RNA-seq and quantitative (q) RT-PCR from 69 adult CD and 14 NIBD control patients. In a subset of this cohort we validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients.ResultsColonic ACE2 expression was significantly higher in a subset of adult CD patients (ACE2-high CD). IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of diagnosis, with a Cox regression analysis finding that high ACE2 levels is an independent risk factor (OR 2.18; 95%CI, 1.05-4.55; p=0.037).ConclusionIncreased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that may impact CD disease-related outcomes.

Individuals with mental illness have poorer physical health, nutritional status, and lowered life expectancy. Optimising their physical and nutritional status has become an increasingly important therapeutic goal. Current experience with COVID-19 has further emphasised the susceptibility to physical illness and poorer outcomes amongst individuals with mental illness and those who are nutritionally compromised. Although life as we knew it has been suspended until the widespread roll-out of a vaccine, individuals can take immediate action to improve physical and mental health by attending to and optimising their nutritional well-being. Clinicians within mental health services have a crucial role to play in assisting such change, and reminding their patients of the importance of pursuing a healthy and balanced diet.

Poor education and employment outcomes have long been associated with care experienced young people transitioning into independence, even after adjusting for prior disadvantage. In the United Kingdom, such young people are generally referred to as care leavers. Policies that aim to reduce the gap between care leavers and non-care experienced young people's success transitioning to employment and independence have had limited success. This paper draws on a qualitative methodology that utilized theories of resilience, to glean a range of perspectives from both care leavers and their employers. All the participants were engaged in a U.K. local authority's initiative to support care leavers into employment. Drawing on resilience theory, resilience was found to be located in a complex interaction between a resilience enabling environment and, crucially, emotionally supportive networks. Uniquely, we argue that emotional support, drawn from such networks, is the key factor that facilitates young people navigating towards such resources, leading to successful outcomes. Previous studies have underplayed this aspect in favour of more tangible resources. Attention to strengthening emotional support networks is thus identified as a significant factor that supports transition to employment and successful independence for care leavers.

The nonselective muscarinic antagonist scopolamine is a rapid-acting antidepressant in limited clinical studies and shares common downstream signaling partners to ketamine, which is much more thoroughly studied both in the clinic and in preclinical models. In psychiatry, a clinically validated pathway is a rare phenomenon that holds particular importance for guiding neuroscientists toward neurobiological targets with the potential of affording more effective medicines for patients: either through reverse translation in search of targets that retain the clinical efficacy but increase the therapeutic window or through formulations that can be tailored to dosing schedules amenable to patients’ ease of use. Scopolamine’s rapid antidepressant profile provides an opportunity to deliver optimized medicines to patients, much like the recent clinical success of S-ketamine that ensued from robust follow-up investigation of ketamine’s clinical profile. This chapter is an attempt to review the clinical and preclinical antidepressant data of scopolamine with a view on illuminating the critical muscarinic receptor subtype(s) that could prove fruitful as a next-generation antimuscarinic drug target for depression.

This paper draws upon the concept of recreancy to examine the mental well-being of university students during the Covid-19 pandemic. Briefly, recreancy is loss of societal trust that results when institutional actors can no longer be counted on to perform their responsibilities. Our study of mental well-being and recreancy focuses on the role of universities and government regulators within the education sector. We surveyed 600 UK students attending 161 different public higher education providers in October 2020 during a time when many UK students were isolated in their residences and engaged in online learning. We assessed student well-being using the Short Warwick-Edinburgh Mental Well-being Scale (scored 7–35) and found the mean score to be 19.9 [95% confidence interval (CI) 19.6, 20.2]. This level of well-being indicates that a significant proportion of UK students face low levels of mental well-being. Structural equation modeling (SEM) analysis indicates that high recreancy—measured as a low trust in universities and the government—is associated with low levels of mental well-being across the student sample. While these findings are suggestive, they are also important and we suggest that government and university leaders should not only work to increase food and housing security during the Covid-19 pandemic, but also consider how to combat various sector trends that might intensify recreancy.

Allport’s intergroup contact theory outlines four conditions for effective contact: equal status between participants within the contact situation, cooperation, common goals, and “institutional supports (i.e. by law, custom or local atmosphere)” for contact (Allport 1954, 281). While the literature indicates that institutional support may be a particularly important condition for effective contact (Pettigrew and Tropp, 2006), its role and impact remains under-researched, particularly in studies of contact within real-world contexts. This article seeks to address this gap through a study of institutional support within a school-based contact initiative operating in two countries, Northern Ireland and North Macedonia. Known as ‘shared education’, this promotes inter-school collaboration as a means of fostering contact between pupils from different ethnic or religious backgrounds. Adopting a qualitative approach and using data collected through interviews with staff involved in four shared education projects, this study explores three aspects: the extent to which shared education demonstrates support for contact; the factors that encourage or impede supportive contact norms; and the relationship between the norms of the school and those of other authorities, particularly parents and the community.

BACKGROUND Open fractures are one of the leading causes of disability worldwide. The threshold time to debridement that reduces the infection rate is unclear. METHODS We searched all available databases to identify observational studies and randomized trials related to open fracture care. We then conducted an extensive meta-analysis of the observational studies, using raw and adjusted estimates, to determine if there was an association between the timing of initial debridement and infection. RESULTS We identified 84 studies (18,239 patients) for the primary analysis. In unadjusted analyses comparing various "late" time thresholds for debridement versus "early" thresholds, there was an association between timing of debridement and surgical site infection (odds ratio [OR] = 1.29, 95% confidence interval [CI] = 1.11 to 1.49, p < 0.001, I2 = 30%, 84 studies, n = 18,239). For debridement performed between 12 and 24 hours versus earlier than 12 hours, the OR was higher in tibial fractures (OR = 1.37, 95% CI = 1.00 to 1.87, p = 0.05, I2 = 19%, 12 studies, n = 2,065), and even more so in Gustilo type-IIIB tibial fractures (OR = 1.46, 95% CI = 1.13 to 1.89, p = 0.004, I2 = 23%, 12 studies, n = 1,255). An analysis of Gustilo type-III fractures showed a progressive increase in the risk of infection with time. Critical time thresholds included 12 hours (OR = 1.51, 95% CI = 1.28 to 1.78, p < 0.001, I2 = 0%, 16 studies, n = 3,502) and 24 hours (OR = 2.17, 95% CI = 1.73 to 2.72, p < 0.001, I2 = 0%, 29 studies, n = 5,214). CONCLUSIONS High-grade open fractures demonstrated an increased risk of infection with progressive delay to debridement. LEVEL OF EVIDENCE Prognostic Level IV. See Instruction for Authors for a complete description of the levels of evidence.