Eutectic mixture of local anesthetics and amethocaine as topical anesthetics in pediatrics: a meta-analysis.

BACKGROUND: Pediatric patients often receive topical anesthesia before skin procedures in the Emergency Department, with EMLA cream and amethocaine gel being common choices. The most effective option remains a subject of debate. OBJECTIVE: Our goal was to compare EMLA cream with amethocaine gel in pediatric patients undergoing topical anesthesia, focusing on outcomes: first-attempt cannulation success, child-reported visual analogue scale (VAS) score, parent-reported VAS score, observed pain score, child-reported absence of pain, and child-reported acceptable anesthesia. METHODS: A database search for studies comparing EMLA cream and amethocaine gel in pediatric topical anesthesia was conducted. Two reviewers extracted and cross-verified data, with a third ensuring accuracy. Using R software, a pairwise meta-analysis was performed via the Mantel-Haenszel method. Outcomes were pooled as risk ratios or standard mean differences with 95% confidence intervals using the random-effects model. RESULTS: Amethocaine gel surpasses EMLA cream in child-reported pain absence and first cannulation success. No significant differences were found in child-reported acceptable anesthesia or observed pain scores. Similarly, child- and parent-reported VAS scores showed no variations between EMLA and amethocaine. CONCLUSION: This analysis favors amethocaine gel for pediatric topical anesthesia. Further large randomized trials comparing EMLA cream and amethocaine gel in pediatric patients are warranted. IMPACT: Procedural pain is a major concern for pediatric patients, their families, and physicians. Topical anesthesia is routinely given prior to children undergoing skin-related procedures in the Emergency Department. In pediatric patients, topical anesthetics such as eutectic mixture of local anesthetics cream and amethocaine gel have proved to be pioneering in pain reduction, but the most effective method is often disputed. Presently, this is the most comprehensive pooled analysis of trials comparing EMLA cream and amethocaine gel in pediatric patients undergoing topical anesthesia. Amethocaine performed better with regards to child-reported absence of pain and first attempt cannulation success.

Daily Summer Temperatures and Hospitalization for Acute Cardiovascular Events: Impact of Outdoor PM 2.5 Oxidative Potential on Observed Associations Across Canada.

BACKGROUND: Oxidative stress plays an important role in the health impacts of both outdoor fine particulate air pollution (PM 2.5 ) and thermal stress. However, it is not clear how the oxidative potential of PM 2.5 may influence the acute cardiovascular effects of temperature. METHODS: We conducted a case-crossover study of hospitalization for cardiovascular events in 35 cities across Canada during the summer months (July-September) between 2016 and 2018. We collected three different metrics of PM 2.5 oxidative potential each month in each location. We estimated associations between lag-0 daily temperature (per 5ºC) and hospitalization for all cardiovascular (n = 44,876) and ischemic heart disease (n = 14,034) events across strata of monthly PM 2.5 oxidative potential using conditional logistical models adjusting for potential time-varying confounders. RESULTS: Overall, associations between lag-0 temperature and acute cardiovascular events tended to be stronger when outdoor PM 2.5 oxidative potential was higher. For example, when glutathione-related oxidative potential (OP GSH ) was in the highest tertile, the odds ratio (OR) for all cardiovascular events was 1.040 (95% confidence intervals [CI] = 1.004, 1.074) compared with 0.980 (95% CI = 0.943, 1.018) when OP GSH was in the lowest tertile. We observed a greater difference for ischemic heart disease events, particularly for older subjects (age >70 years). CONCLUSIONS: The acute cardiovascular health impacts of summer temperature variations may be greater when outdoor PM 2.5 oxidative potential is elevated. This may be particularly important for ischemic heart disease events.

General Anesthesia Versus Local Anesthesia in Patients Undergoing Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis and Systematic Review.

OBJECTIVES: For patients with aortic stenosis, transcatheter aortic valve replacement (TAVR) offers a less invasive treatment modality than conventional surgical valve replacement. Although the surgery is performed traditionally under general anesthesia (GA), recent studies have described success with TAVR using local anesthesia (LA) and/or conscious sedation. The study authors performed a pairwise meta-analysis to compare the clinical outcomes of TAVR based on operative anesthesia management. DESIGN: A random effects pairwise meta-analysis via the Mantel-Haenszel method. SETTING: Not applicable, as this is a meta-analysis. PARTICIPANTS: No individual patient data were used. INTERVENTIONS: Not applicable, as this is a meta-analysis. MEASUREMENTS AND MAIN RESULTS: The authors comprehensively searched the PubMed, Embase, and Cochrane databases to identify studies comparing TAVR performed using LA or GA. Outcomes were pooled as risk ratios (RR) or standard mean differences (SMD) and their 95% CIs. The authors' pooled analysis included 14,388 patients from 40 studies (7,754 LA; 6,634 GA). Compared to GA TAVR, LA TAVR was associated with significantly lower rates of 30-day mortality (RR 0.69; p < 0.01) and stroke (RR 0.78; p = 0.02). Additionally, LA TAVR patients had lower rates of 30-day major and/or life-threatening bleeding (RR 0.64; p = 0.01), 30-day major vascular complications (RR 0.76; p = 0.02), and long-term mortality (RR 0.75; p = 0.009). No significant difference was seen between the 2 groups for a 30-day paravalvular leak (RR 0.88, p = 0.12). CONCLUSIONS: Transcatheter aortic valve replacement performed using LA is associated with lower rates of adverse clinical outcomes, including 30-day mortality and stroke. No difference was seen between the 2 groups for a 30-day paravalvular leak. These results support the use of minimally invasive forms of TAVR without GA.

Long-term Exposure to Oxidant Gases and Mortality: Effect Modification by PM 2.5 Transition Metals and Oxidative Potential.

BACKGROUND: Populations are simultaneously exposed to outdoor concentrations of oxidant gases (i.e., O 3 and NO 2 ) and fine particulate air pollution (PM 2.5 ). Since oxidative stress is thought to be an important mechanism explaining air pollution health effects, the adverse health impacts of oxidant gases may be greater in locations where PM 2.5 is more capable of causing oxidative stress. METHODS: We conducted a cohort study of 2 million adults in Canada between 2001 and 2016 living within 10 km of ground-level monitoring sites for outdoor PM 2.5 components and oxidative potential. O x exposures (i.e., the redox-weighted average of O 3 and NO 2 ) were estimated using a combination of chemical transport models, land use regression models, and ground-level data. Cox proportional hazards models were used to estimate associations between 3-year moving average O x and mortality outcomes across strata of transition metals and sulfur in PM 2.5 and three measures of PM 2.5 oxidative potential adjusting for possible confounding factors. RESULTS: Associations between O x and mortality were consistently stronger in regions with elevated PM 2.5 transition metal/sulfur content and oxidative potential. For example, each interquartile increase (6.27 ppb) in O x was associated with a 14.9% (95% CI = 13.0, 16.9) increased risk of nonaccidental mortality in locations with glutathione-related oxidative potential (OP GSH ) above the median whereas a 2.50% (95% CI = 0.600, 4.40) increase was observed in regions with OP GSH levels below the median (interaction P value <0.001). CONCLUSION: Spatial variations in PM 2.5 composition and oxidative potential may contribute to heterogeneity in the observed health impacts of long-term exposures to oxidant gases.

Physiological trait networks enhance understanding of crop growth and water use in contrasting environments.

Plant function arises from a complex network of structural and physiological traits. Explicit representation of these traits, as well as their connections with other biophysical processes, is required to advance our understanding of plant-soil-climate interactions. We used the Terrestrial Regional Ecosystem Exchange Simulator (TREES) to evaluate physiological trait networks in maize. Net primary productivity (NPP) and grain yield were simulated across five contrasting climate scenarios. Simulations achieving high NPP and grain yield in high precipitation environments featured trait networks conferring high water use strategies: deep roots, high stomatal conductance at low water potential ("risky" stomatal regulation), high xylem hydraulic conductivity and high maximal leaf area index. In contrast, high NPP and grain yield was achieved in dry environments with low late-season precipitation via water conserving trait networks: deep roots, high embolism resistance and low stomatal conductance at low leaf water potential ("conservative" stomatal regulation). We suggest that our approach, which allows for the simultaneous evaluation of physiological traits, soil characteristics and their interactions (i.e., networks), has potential to improve our understanding of crop performance in different environments. In contrast, evaluating single traits in isolation of other coordinated traits does not appear to be an effective strategy for predicting plant performance.

Vitamin D levels in Irish children with fractures: A prospective case-control study with 5 year follow-up.

INTRODUCTION: Twenty-five-hydroxy-vitamin D3 (25-OH-vit D) is a prohormone that is essential for normal calcium homeostasis and bone metabolism. Understanding its role is an important component of the proper care of the pediatric orthopaedic patient. The aim of this study was to determine whether children in Ireland with fractures have increased prevalence of 25-OH-Vit D deficiency compared with age matched controls and to ascertain the relationship between a low 25-OH-vit D level and the incidence of fractures in Irish children. We hypothesised that children presenting to our centre following a fracture would have significantly lower 25-OH-vit D. METHODS: A prospective case-control study at a large urban tertiary referral academic hospital located in Dublin, Ireland was completed over a 14 month period from June 2014 to August 2015. A total of 116 subjects, distributed as cases (n = 58) and controls (n = 58) were included in this study. Whole blood (10 ml) was taken in two serum bottles from each patient. Serum 25-hydroxy-vitamin D3 levels were measured. An age matched control group was generated from other children attending the hospital, who also had vitamin D levels measured for different clinical reasons. We followed up both the fracture and control group for the next 5 years to assess the repeat fracture rate. RESULTS: Fifty-eight patients with a fracture requiring operative intervention, were included in the study. Statistical analysis was performed comparing to 58 age and sex-matched controls. The mean vitamin D level for the fracture group was 63.2 nmol/L (SD = 27.3), which was higher than the mean of the controls (62.5 nmol/L) (SD = 21.3) (p = 0.86), but this difference was found not to be statistically significant in unadjusted analysis. There was no statistically significant difference in the number of patients classified with low serum Vitamin D levels (<50 nmolL), with the fracture group consisting of 22 (37.9%) patients, and the control group of 17 patients (29.3%) (p = 0.33) with a level below 50 nmol/L. At five-year follow-up, 11 of the 58 patients (18.9%) in the fracture group went on to have a further fracture compared with eight patients (13.7%) from the control group. Out of these 11 from the fracture group five (45.45%) had been found to have a low serum 25-OH-Vit D level five years previously. Out of the eight controls that presented with a fracture within the five-year period, 3 (37.5%) had had a low vitamin D level at the origin of this study. CONCLUSION: The results of this study show that children presenting to our institution with low energy fractures have a prevalence of 38% 25-hydroxy-vitamin D deficiency. This study included children from age 1 to 16 primarily Caucasian encompassing all fracture types resulting from accidental trauma. Our findings suggest that in an Irish pediatric population vitamin D status may impact fracture risk with more than one-third being deficient in this review.

The elephant in the room: attention to salient scene features increases with comedic expertise.

What differentiates the joke writing strategy employed by professional comedians from non-comedians? Previous MRI work found that professional comedians relied to a greater extent on "bottom-up processes," i.e., associations driven by the prompt stimuli themselves, while controls relied more on prefrontal lobe directed, "top-down" processes. In the present work, professional improv comedians and controls generated humorous captions to cartoons while their eye movements were tracked. Participants' visual fixation patterns were compared to predictions of the saliency model (Harel et al. in Adv Neural Inf Process Syst 19:545-552, 2007)-a computer model for identifying the most salient locations in an image based on visual features. Captions generated by the participants were rated for funniness by independent raters. Relative to controls, professional comedians' gaze was driven to a greater extent by the cartoons' salient visual features. For all participants, captions' funniness positively correlated with visual attention to salient cartoon features. Results suggest that comedic expertise is associated with increased reliance on bottom-up, stimulus-driven creativity, and that a bottom-up strategy results, on average, in funnier captions whether employed by comedians or controls. The cognitive processes underlying successful comedic creativity appear to adhere to the old comedians' adage "pay attention to the elephant in the room."

Epidemiology, Clinical Presentation, Lab Diagnosis and Outcome of Scrub Typhus Outbreak in a Tertiary Care Center in Southern Rajasthan.

Scrub typhus is also known as tsutsugamushi disease or bush typhus. It is a mite-borne acute febrile illness caused by Gram-negative intracellular organism called Orientia tsutsugamushi, which belongs to the family of Rickettsiaceae. The aims and objectives are to study the epidemiological patterns, different clinical manifestations and complications associated with scrub typhus. MATERIAL: This was a prospective study which was carried out over a period of 12 months from January 2019 to December 2019 in patients of scrub typhus admitted in various medical wards of MB Govt. Hospital and RNT Medical College, Udaipur, Rajasthan. OBSERVATION: All the patients admitted with history of acute febrile illness suspected to be scrub typhus were assessed in the study. All these patients were evaluated by the set protocol in the form of detailed history, physical examination and relevant systemic examination. A total of 3,814 suspected patients of scrub typhus were tested in our microbiology laboratory and 1,340 patients were reported positive. Out of these, only 480 patients who were admitted in our medical wards were enrolled in our study and evaluated. CONCLUSION: We conclude that in rural Rajasthan, any patient who presents with fever, myalgia, hepatosplenomegaly and multiorgan dysfunction syndrome, a diagnosis of scrub typhus should be suspected.

Clinical experience with two-point mDixon turbo spin echo as an alternative to conventional turbo spin echo for magnetic resonance imaging of the pediatric knee.

BACKGROUND: Two-point modified Dixon (mDixon) turbo spin-echo (TSE) sequence provides an efficient, robust method of fat suppression. In one mDixon acquisition, four image types can be generated: water-only, fat-only, in-phase and opposed-phase images. OBJECTIVE: To determine whether PD mDixon TSE water-only and, by proxy, PD in-phase images generated by one acquisition can replace two conventional PD TSE sequences with and without fat suppression in routine clinical MR examination of the knee. MATERIALS AND METHODS: This is a retrospective study of 50 consecutive pediatric knee MR examinations. PD mDixon TSE water-only and PD fat-saturated TSE sequences (acquired in the sagittal plane with identical spatial resolution) were reviewed independently by two pediatric radiologists for homogeneity of fat suppression and detection of intra-articular pathology. Thirteen of the 50 patients underwent arthroscopy, and we used the arthroscopic results as a reference standard for the proton-density fat-saturated and proton-density mDixon results. We used the Kruskal-Wallis rank test to assess difference in fat suppression between the proton-density mDixon and proton-density fat-saturated techniques. We used kappa statistics to compare the agreement of detection of intra-articular pathology between readers and techniques. We also calculated sensitivity, specificity and accuracy between arthroscopy and MR interpretations. RESULTS: Proton-density mDixon water-only imaging showed significant improvement with the fat suppression compared with proton-density fat-saturated sequence (P=0.02). Each observer demonstrated near-perfect agreement between both techniques for detecting meniscal and ligamentous pathology and fair to substantial agreement for bone contusions, and chondral and osteochondral lesions. CONCLUSION: Two-point mDixon water-only imaging can replace conventional proton-density fat-saturated sequence. When same-plane proton-density fat-saturated and non-fat-saturated sequences are required, proton-density water-only and proton-density in-phase image types acquired in the same acquisition shorten the overall examination time while maintaining excellent intra-articular lesion conspicuity.

Tube tip and cuff position using different strategies for placement of currently available paediatric tracheal tubes.

BACKGROUND: Tracheal tube tip and cuff positions of different cuffed paediatric tracheal tube brands in the trachea can vary with design. METHODS: Data from three clinical studies with measured tracheal lengths were pooled in a database including 422 children aged from birth to 16 yr. Dimensional data of seven cuffed paediatric tracheal tube brands (ID 3.0-7.0 mm) were recorded. Positions of tracheal tube tip and upper cuff border were calculated for each of the 422 tracheas using depth mark based tracheal tube placement, placement of the tracheal tube tip at a calculated safety distance above the carina, and mid-tracheal tube placement. Percentage of accidental bronchial intubations and tracheal tube cuff positions in the subglottic or supraglottic region were calculated. RESULTS: Depth mark based tracheal tube placement resulted in accidental bronchial intubation of up to 18% of cases and tracheal tube cuffs being placed in the subglottic region in up to 91%. Tracheal tube tip placement at a calculated safety distance resulted in up to 54% of tube cuffs placed too high. Mid-tracheal tube placement led to 100% subglottic or supraglottic tracheal tube cuff positions. CONCLUSIONS: All studied cuffed paediatric tracheal tubes have major design flaws potentially leading to airway complications. Tracheal tube manufacturers are urgently asked to improve the design of cuffed paediatric tracheal tubes. Alternative strategies for tracheal tube placement can allow safe tracheal tube placement of uncuffed but not of cuffed tracheal tubes.

Social determinants of emotional well-being in new refugees in the UK.

OBJECTIVES: Refugees are most vulnerable to mental health problems of all migrant groups, and an understanding of the role of postdisplacement social factors in refugee emotional well-being can help to shape the future interventions for this group. We aimed to investigate the effect of social determinants, such as employment, language ability and accommodation, on mental health in refugees in the UK. STUDY DESIGN: This prospective longitudinal cohort study was set in the UK. The study population of new UK refugees was drawn from an existing data set of the Longitudinal Survey of New Refugees (n = 5678), in which all new UK refugees (2005-2007) were sent a postal questionnaire at four time points across 2 years. METHODS: Ordered logistic regression models were used to evaluate associations between social determinants and the dependent variables, emotional well-being or change in emotional well-being, using a question from the Short Form-36 Health Survey Questionnaire. RESULTS: Refugees who were unemployed in the UK, could not speak English well or were unsatisfied with their accommodation had significantly higher odds of poorer emotional well-being in the cross-sectional analysis (P < 0.05 at all time points measured). CONCLUSIONS: Postdisplacement social factors, including language ability, employment status and accommodation satisfaction, were important determinants of refugee emotional well-being. Changes in these social determinants have the potential to improve refugee mental health, making them legitimate, modifiable targets for important public health interventions. Accounting for this, further research into how to improve refugee well-being is crucial given the increase in refugee numbers around the developed world.

Idelalisib and rituximab in relapsed chronic lymphocytic leukemia.

BACKGROUND: Patients with relapsed chronic lymphocytic leukemia (CLL) who have clinically significant coexisting medical conditions are less able to undergo standard chemotherapy. Effective therapies with acceptable side-effect profiles are needed for this patient population. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 study, we assessed the efficacy and safety of idelalisib, an oral inhibitor of the delta isoform of phosphatidylinositol 3-kinase, in combination with rituximab versus rituximab plus placebo. We randomly assigned 220 patients with decreased renal function, previous therapy-induced myelosuppression, or major coexisting illnesses to receive rituximab and either idelalisib (at a dose of 150 mg) or placebo twice daily. The primary end point was progression-free survival. At the first prespecified interim analysis, the study was stopped early on the recommendation of the data and safety monitoring board owing to overwhelming efficacy. RESULTS: The median progression-free survival was 5.5 months in the placebo group and was not reached in the idelalisib group (hazard ratio for progression or death in the idelalisib group, 0.15; P<0.001). Patients receiving idelalisib versus those receiving placebo had improved rates of overall response (81% vs. 13%; odds ratio, 29.92; P<0.001) and overall survival at 12 months (92% vs. 80%; hazard ratio for death, 0.28; P=0.02). Serious adverse events occurred in 40% of the patients receiving idelalisib and rituximab and in 35% of those receiving placebo and rituximab. CONCLUSIONS: The combination of idelalisib and rituximab, as compared with placebo and rituximab, significantly improved progression-free survival, response rate, and overall survival among patients with relapsed CLL who were less able to undergo chemotherapy. (Funded by Gilead; ClinicalTrials.gov number, NCT01539512.).

Study protocol: Insight 46 - a neuroscience sub-study of the MRC National Survey of Health and Development.

BACKGROUND: Increasing age is the biggest risk factor for dementia, of which Alzheimer's disease is the commonest cause. The pathological changes underpinning Alzheimer's disease are thought to develop at least a decade prior to the onset of symptoms. Molecular positron emission tomography and multi-modal magnetic resonance imaging allow key pathological processes underpinning cognitive impairment - including ß-amyloid depostion, vascular disease, network breakdown and atrophy - to be assessed repeatedly and non-invasively. This enables potential determinants of dementia to be delineated earlier, and therefore opens a pre-symptomatic window where intervention may prevent the onset of cognitive symptoms. METHODS/DESIGN: This paper outlines the clinical, cognitive and imaging protocol of "Insight 46", a neuroscience sub-study of the MRC National Survey of Health and Development. This is one of the oldest British birth cohort studies and has followed 5362 individuals since their birth in England, Scotland and Wales during one week in March 1946. These individuals have been tracked in 24 waves of data collection incorporating a wide range of health and functional measures, including repeat measures of cognitive function. Now aged 71 years, a small fraction have overt dementia, but estimates suggest that ~1/3 of individuals in this age group may be in the preclinical stages of Alzheimer's disease. Insight 46 is recruiting 500 study members selected at random from those who attended a clinical visit at 60-64 years and on whom relevant lifecourse data are available. We describe the sub-study design and protocol which involves a prospective two time-point (0, 24 month) data collection covering clinical, neuropsychological, ß-amyloid positron emission tomography and magnetic resonance imaging, biomarker and genetic information. Data collection started in 2015 (age 69) and aims to be completed in 2019 (age 73). DISCUSSION: Through the integration of data on the socioeconomic environment and on physical, psychological and cognitive function from 0 to 69 years, coupled with genetics, structural and molecular imaging, and intensive cognitive and neurological phenotyping, Insight 46 aims to identify lifetime factors which influence brain health and cognitive ageing, with particular focus on Alzheimer's disease and cerebrovascular disease. This will provide an evidence base for the rational design of disease-modifying trials.

Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia.

In a phase 1 trial, idelalisib (GS-1101, CAL-101), a selective inhibitor of the lipid kinase PI3Kδ, was evaluated in 54 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) with adverse characteristics including bulky lymphadenopathy (80%), extensive prior therapy (median 5 [range 2-14] prior regimens), treatment-refractory disease (70%), unmutated IGHV (91%), and del17p and/or TP53 mutations (24%). Patients were treated at 6 dose levels of oral idelalisib (range 50-350 mg once or twice daily) and remained on continuous therapy while deriving clinical benefit. Idelalisib-mediated inhibition of PI3Kδ led to abrogation of Akt phosphorylation in patient CLL cells and significantly reduced serum levels of CLL-related chemokines. The most commonly observed grade ≥3 adverse events were pneumonia (20%), neutropenic fever (11%), and diarrhea (6%). Idelalisib treatment resulted in nodal responses in 81% of patients. The overall response rate was 72%, with 39% of patients meeting the criteria for partial response per IWCLL 2008 and 33% meeting the recently updated criteria of PR with treatment-induced lymphocytosis.(1,2) The median progression-free survival for all patients was 15.8 months. This study demonstrates the clinical utility of inhibiting the PI3Kδ pathway with idelalisib. Our findings support the further development of idelalisib in patients with CLL. These trials were registered at clinicaltrials.gov as #NCT00710528 and #NCT01090414.

Antagonizing the α4ß1 integrin, but not α4ß7, inhibits leukocytic infiltration of the central nervous system in rhesus monkey experimental autoimmune encephalomyelitis.

The immune system is characterized by the preferential migration of lymphocytes through specific tissues (i.e., tissue tropism). Tissue tropism is mediated, in part, by the α(4) integrins expressed by T lymphocytes. The α(4)ß(1) integrin mediates migration of memory T lymphocytes into the CNS, whereas the α(4)ß(7) integrin mediates migration preferentially into gastrointestinal tissue. This paradigm was established primarily from investigations in rodents; thus, the objective of this investigation was to determine if blocking the α(4)ß(7) integrin exclusively would affect migration of T lymphocytes into the CNS of primates. The effects of the dual α(4)ß(1) and α(4)ß(7) antagonist natalizumab were compared with those of the α(4)ß(7) antagonist vedolizumab on experimental autoimmune encephalomyelitis in the rhesus monkey. Animals received an initial i.v. bolus of placebo, natalizumab (30 mg/kg), or vedolizumab (30 mg/kg) before intracutaneous immunization with recombinant human myelin oligodendrocyte glycoprotein and then Ab once weekly thereafter. Natalizumab prevented CNS inflammation and demyelination significantly (p < 0.05), compared with time-matched placebo control animals, whereas vedolizumab did not inhibit these effects, despite saturating the α(4)ß(7) integrin in each animal for the duration of the investigation. These results demonstrate that blocking α(4)ß(7) exclusively does not inhibit immune surveillance of the CNS in primates.

Reconciling Harvest Intensity and Plant Diversity in Boreal Ecosystems: Does Intensification Influence Understory Plant Diversity?

Overall demand for forest products in the boreal forest is increasing to supply growing bio-energy demands in addition to traditional forest products. As a result, there is a need to refine current forest policies to reconcile production and ecosystem function within the context of ecologically sustainable management. This study assessed understory plants' richness, evenness, and diversity in six harvested boreal black spruce-dominated stands situated on loam, sand, and peat site types 15 years after the application of four harvest treatments of increasing biomass removals. Treatments included uncut, stem-only harvest, full-tree harvest, and full-tree harvest + blading of O horizon. Following canopy removal, species richness and diversity (Shannon's and Simpson's indices) increased on all soil types. The more than doubling of slash loading on the stem-only treatment plots compared to the full-tree plots led to significantly lower species diversity on loam sites; however, the reverse was observed on peat sites where the slash provided warmer, drier microsites facilitating the establishment of a broader array of species. Preexisting ericaceous shrub and sphagnum components continued to dominate on the peat sites. Compositional shifts were most evident for the full-tree + bladed treatment on all soil types, with increases in herbaceous cover including ruderal species. The results suggest that the intensification of harvesting on plant diversity varies with soil type, and these differential results should be considered in the refinement of forest biomass-harvesting guidelines to ensure ecological sustainability and biodiversity conservation over a broad suite of soil types.

Urinary Glycosaminoglycan Estimation as a Routine Clinical Service.

Mucopolysaccharidoses, a group of inherited disorders are associated with defects in glycosaminoglycan metabolism. Thus, assessment of urinary glycosaminoglycan is used as a screening test for mucopolysaccharidoses. The detection methods range from qualitative spot tests to quantification using metachromatic dyes. In our laboratory we optimized a spectrophotometric quantitative method using a metachromatic dye, dimethylmethylene blue. Heparan sulfate was used for quantification. The glycosaminoglycan-dye complex showed a marked shift in color with increase in concentration. The color complex was quantified at 520 nm. The method was linear from 10-89 mg/L. An age matched normal range was obtained in 177 healthy individuals, grouped in 8 different age groups from neonates to adults. Urinary glycosaminoglycan concentration varied distinctly amongst the study population wherein the lowest range in healthy neonates was more than 3 times the upper limit of healthy adults. Urine samples from 10 patients with mucopolysaccharidoses were also included in the study for clinical validation. The method qualified both analytical and clinical validation and was found to be simple, robust and ideal to be offered as a screening test for mucopplysaccharidoses in a routine clinical chemistry laboratory.

Risk assessment of inbreeding and outbreeding depression in a captive-breeding program.

Captive-breeding programs can be implemented to preserve the genetic diversity of endangered populations such that the controlled release of captive-bred individuals into the wild may promote recovery. A common difficulty, however, is that programs are founded with limited wild broodstock, and inbreeding can become increasingly difficult to avoid with successive generations in captivity. Program managers must choose between maintaining the genetic purity of populations, at the risk of inbreeding depression, or interbreeding populations, at the risk of outbreeding depression. We evaluate these relative risks in a captive-breeding program for 3 endangered populations of Atlantic salmon (Salmo salar). In each of 2 years, we released juvenile F(1) and F(2) interpopulation hybrids, backcrosses, as well as inbred and noninbred within-population crosstypes into 9 wild streams. Juvenile size and survival was quantified in each year. Few crosstype effects were observed, but interestingly, the relative fitness consequences of inbreeding and outbreeding varied from year to year. Temporal variation in environmental quality might have driven some of these annual differences, by exacerbating the importance of maternal effects on juvenile fitness in a year of low environmental quality and by affecting the severity of inbreeding depression differently in different years. Nonetheless, inbreeding was more consistently associated with a negative effect on fitness, whereas the consequences of outbreeding were less predictable. Considering the challenges associated with a sound risk assessment in the wild and given that the effect of inbreeding on fitness is relatively predictable, we suggest that risk can be weighted more strongly in terms of the probable outcome of outbreeding. Factors such as genetic similarities between populations and the number of generations in isolation can sometimes be used to assess outbreeding risk, in lieu of experimentation.

Predicting future occlusion or stenosis of lower extremity bypass grafts using artificial intelligence to simultaneously analyze all flow velocities collected in current and previous ultrasound examinations.

Objective: Routine surveillance with duplex ultrasound (DUS) examination is recommended after femoral-popliteal and femoral-tibial-pedal vein bypass grafts with various intervals postoperatively. The presently used methodology to analyze bypass graft DUS examination does not use all the available data and has been shown to have a significant rate for missing impending bypass graft failure. The objective of this research is to investigate recurrent neural networks (RNNs) to predict future bypass graft occlusion or stenosis. Methods: This study includes DUS examinations of 663 patients who had bypass graft operations done between January 2009 and June 2022. Only examinations without missing values were included. We developed two RNNs (a bidirectional long short-term memory unit and a bidirectional gated recurrent unit) to predict bypass graft occlusion and stenosis based on peak systolic velocities collected in the 2 to 5 previous DUS examinations. We excluded the examinations with missing values and split our data into training and test sets. Then, we applied 10-fold cross-validation on training to optimize the hyperparameters and compared models using the test data. Results: The bidirectional long short-term memory unit model can gain an overall sensitivity of 0.939, specificity of 0.963, and area under the curve of 0.950 on the prediction of bypass graft occlusion, and an overall sensitivity of 0.915, specificity of 0.909, and area under the curve of 0.912 predicting the development of a future critical stenosis. The results on different bypass types show that the system performs differently on different types. The results on subcohorts based on gender, smoking status, and comorbidities show that the performance on current smokers is lower than the never smoker. Conclusions: We found that RNNs can gain good sensitivity, specificity, and accuracy for the detection of impending bypass graft occlusion or the future development of a critical bypass graft stenosis using all the available peak systolic velocity data in the present and previous bypass graft DUS examinations. Integrating clinical data, including demographics, social determinants, medication, and other risk factors, together with the DUS examination may result in further improvements. Clinical Relevance: Detecting bypass graft failure before it occurs is important clinically to prevent amputations, salvage limbs, and save lives. Current methods evaluating screening duplex ultrasound examinations have a significant failure rate for detecting a bypass graft at risk for failure. Artificial intelligence using recurrent neural networks has the potential to improve the detection of at-risk bypass graft before they fail. Additionally, artificial intelligence is in the news and is being applied to many fields. Vascular surgeons need to know its potential to improve vascular outcomes.