To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Opposition control of artificially initiated turbulent spots in a laminar boundary layer was carried out in a low-turbulence wind tunnel with the aim to delay transition to turbulence by modifying the turbulent structure within the turbulent spots. The timing and duration of control, which was carried out using wall-normal jets from a spanwise slot, were pre-determined based on the baseline measurements of the transitional boundary layer. The results indicated that the high-speed region of the turbulent spots was cancelled by opposition control, which was replaced by a carpet of low-speed fluid. The application of the variable-interval time-averaging technique on the velocity fluctuation signals demonstrated a reduction in both the burst duration and intensity within the turbulent spots, but the burst frequency was increased.
OBJECTIVES/GOALS: The host immune response during sepsis is now recognized to have anti-inflammatory pathophysiology. We aim to determine whether mitochondrial dysfunction of leukocytes predicts which critically ill septic patients develop immune paralysis and to identify differences in cellular metabolites between patients with and without immune paralysis. METHODS/STUDY POPULATION: Critically ill septic and control adult patients were recruited from one of 6 ICUs in a single-center tertiary care academic hospital. After enrollment, peripheral blood mononuclear cells (PBMCs) were isolated from a tube of whole blood on day 0-1 after ICU admission. Flow cytometry to quantify monocyte HLA-DR was performed to determine whether patients were immune paralyzed or not. Mitochondrial functional assays of PBMCs were performed with inhibitors of the electron transport chain to assess for differences in oxidative phosphorylation and glycolysis utilization. Metabolic profiling of cell pellets was performed to evaluate for specific metabolites and pathways associated with immune paralyzed patients. RESULTS/ANTICIPATED RESULTS: A total of 101 patients were recruited, including 62 control and 39 septic patients. 81 patients had immune paralysis status available for analysis. 52% of all recruited subjects were immune paralyzed. Of these, 58% were controls and 75% were septic. Immune paralyzed septic and control patients showed features of reduced utilization of oxidative phosphorylation (ox phos) including reduced basal respiration, ATP production and maximal respiration compared with non-immune paralyzed septic and control patients. Immune paralyzed septic patients showed diminished glycolysis utilization compared with septic non-immune paralyzed patients. Finally, cellular kynurenine and quinolinate levels were low in both immune paralyzed control and septic patients compared with non-immune paralyzed patients. DISCUSSION/SIGNIFICANCE: The PBMCs of immune paralyzed septic patients show evidence of mitochondrial dysfunction, with reduced ox phos and glycolysis utilization. Low levels of kynurenine and quinolinate, metabolite precursors to NAD+, in immune paralyzed patients may signal key deficiencies and targetable therapeutic avenues for reversal of an immune paralyzed state.
Background: Phase 3 COMET trial (NCT02782741) compares avalglucosidase alfa (n=51) with alglucosidase alfa (n=49) in treatment-naïve LOPD. Methods: Primary objective: determine avalglucosidase alfa effect on respiratory muscle function. Secondary/other objectives include: avalglucosidase alfa effect on functional endurance, inspiratory/expiratory muscle strength, lower/upper extremity muscle strength, motor function, health-related quality of life, safety. Results: At Week 49, change (LSmean±SE) from baseline in upright forced vital capacity %predicted was greater with avalglucosidase alfa (2.89%±0.88%) versus alglucosidase alfa (0.46%±0.93%)(absolute difference+2.43%). The primary objective, achieving statistical non-inferiority (p=0.0074), was met. Superiority testing was borderline significant (p=0.0626). Week 49 change from baseline in 6-minute walk test was 30.01-meters greater for avalglucosidase alfa (32.21±9.93m) versus alglucosidase alfa (2.19±10.40m). Positive results for avalglucosidase alfa were seen for all secondary/other efficacy endpoints. Treatment-emergent adverse events (AEs) occurred in 86.3% of avalglucosidase alfa-treated and 91.8% of alglucosidase alfa-treated participants. Five participants withdrew, 4 for AEs, all on alglucosidase alfa. Serious AEs occurred in 8 avalglucosidase alfa-treated and 12 alglucosidase alfa-treated participants. IgG antidrug antibody responses were similar in both. High titers and neutralizing antibodies were more common for alglucosidase alfa. Conclusions: Results demonstrate improvements in clinically meaningful outcome measures and a more favorable safety profile with avalglucosidase alfa versus alglucosidase alfa. Funding: Sanofi Genzyme
The success of any clinical research team is dependent on hiring individuals with the experience and skill set needed for a specific research project. Strategies to improve the ability of human resource (HR) recruiters to screen and advance qualified candidates for a project will result in improved initiation and execution of the project.
HR recruiters play a critical role in matching research applicants to the posted job descriptions and presenting a list of top candidates to the PI/hiring manager for interview and hiring consideration.
Creating guidelines to screen for applicant qualification based on resumes when clinical research positions have multiple levels of expertise required is a complex process of discovery, moving from subjective rationale for rating individual resumes to a more structured less biased evaluation process. To improve the hiring process of the research workforce, we successfully developed guidelines for categorizing research coordinator applications by level from beginner to advanced.
Through guideline development, we provide a framework to reduce bias and improve the matching of applicant resumes to job levels for improved selection of top candidates to advance for interviewing. Improved applicant to job matching offers an advantage to reduce hiring time, anticipate training needs, and shorten the timeline to active project engagement. These guidelines can form the basis for initial screening and ultimately matching individual qualities to project-specific needs.
Sedentary behaviour is potentially a modifiable risk factor for depression and anxiety disorders, but findings have been inconsistent.
To assess associations of sedentary behavior with depression and anxiety symptoms and estimate the impact of replacing daily time spent in sedentary behaviors with sleep, light, or moderate-to-vigorous physical activity, using novel compositional data analysis methods.
Prospective cohort study in with 60,235 UK Biobank participants (mean age: 56; 56% female). Exposure was baseline daily movement behaviours (accelerometer-assessed sedentary behaviour, physical activity, and self-reported total sleep). Outcomes were depression and anxiety symptoms (Patient Health Questionnaire-9 and Generalised Anxiety Disorders-7) at follow up.
Replacing 60 minutes of sedentary behaviour with light activity, moderate-to-vigorous activity, and sleep was associated with lower depression symptom scores by 1·3% (95%CI, 0·4%-2·1%), 12·5% (95%CI, 11·4%-13·5%), and 7·6% (95%CI, 6·9%-8·4%), and lower odds of depression by 0·95 (95%CI, 0·94-0·96), 0·75 (95%CI, 0·74-0·76), and 0·90 (95%CI, 0·90-0·91) at follow-up. Replacing 60 minutes of sedentary behaviour with moderate-to-vigorous activity and sleep was associated with lower anxiety symptom scores by 6·6% (95%CI, 5·5%-7·6%) and 4·5% (95%CI, 3·7%-5·2%), and lower odds of meeting the threshold for an anxiety disorder by 0·90 (95%CI, 0·89-0·90) and 0·97 (95%CI, 0·96-0·97) at follow-up. However, replacing 60 minutes of sedentary behaviour with light activity was associated with higher anxiety symptom scores by 4·5% (95%CI, 3·7%-5·3%) and higher odds of an anxiety disorder by 1·07 (95%CI, 1·06-1·08).
Sedentary behaviour is a risk factor for increased depression and anxiety symptoms in adults, but different replacement activities differentially influence mental health.
Opium tincture (OT) is widely used for opioid substitution treatment (OST) in Iran.
To determine if OT is a safe and effective medication for OST.
Opium Trial was a multicenter, double‐blind, noninferiority randomized controlled trial, with 204 participants with opioid dependence in Iran. Participants were then randomized to OT or methadone arms with an allocation ratio of 1:1 and were followed for 12 weeks. The primary outcome was retention in treatment, compared between the two groups using both intention-To-Treat (ITT) and Per-Protocol (PP) analyses.
A total of 70 participants (IT: 68.6%, PP: 69.3%) in methadone arm and 61 participants (ITT: 59.8%, PP: 60.4%) in OT arm remained in the treatment. The relative retention rate was 1.15 (0.97, 1.36) in both analyses in favour of methadone. A total of 46 out of 152 (30.3%) participants in OT arm and 83 out of 168 (49.4%) participants in methadone arm reported opioid use outside the treatment. The difference in these two proportions (OT - methadone) was 19%: (10%, 28%) in favour of OT. The proportion of patients with adverse events were not different between the two arms (P = 0.06). There was no serious AE in OT arm.
Opium tincture is a clinically effective and safe medication, but this study could not conclude if it was as equally effective as methadone in retaining participants in treatment, but it showed that OT was superior to methadone in reducing opioid use outside the treatment.
This study aimed to analyse if there were any associations between patulous Eustachian tube occurrence and climatic factors and seasonality.
The correlation between the monthly average number of patients diagnosed with patulous Eustachian tube and climatic factors in Seoul, Korea, from January 2010 to December 2016, was statistically analysed using national data sets.
The relative risk for patulous Eustachian tube occurrence according to season was significantly higher in summer and autumn, and lower in winter than in spring (relative risk (95 per cent confidence interval): 1.334 (1.267–1.404), 1.219 (1.157–1.285) and 0.889 (0.840–0.941) for summer, autumn and winter, respectively). Temperature, atmospheric pressure and relative humidity had a moderate positive (r = 0.648), negative (r = –0.601) and positive (r = 0.492) correlation with the number of patulous Eustachian tube cases, respectively.
The number of patulous Eustachian tube cases was highest in summer and increased in proportion to changes in temperature and humidity, which could be due to physiological changes caused by climatic factors or diet trends.
In the field of transmission electron microscopy, data interpretation often lags behind acquisition methods, as image processing methods often have to be manually tailored to individual datasets. Machine learning offers a promising approach for fast, accurate analysis of electron microscopy data. Here, we demonstrate a flexible two-step pipeline for the analysis of high-resolution transmission electron microscopy data, which uses a U-Net for segmentation followed by a random forest for the detection of stacking faults. Our trained U-Net is able to segment nanoparticle regions from the amorphous background with a Dice coefficient of 0.8 and significantly outperforms traditional image segmentation methods. Using these segmented regions, we are then able to classify whether nanoparticles contain a visible stacking fault with 86% accuracy. We provide this adaptable pipeline as an open-source tool for the community. The combined output of the segmentation network and classifier offer a way to determine statistical distributions of features of interest, such as size, shape, and defect presence, enabling the detection of correlations between these features.
We report on comparative atom probe tomography investigations of γ/γ′-forming Co–12Ti–4Mo–Cr alloys. Moderate additions of Cr (2 and 4 at%) reduced the γ/γ′ lattice misfit and increased the γ′ volume fraction of a Co–12Ti–4Mo alloy significantly. These microstructural changes were accompanied by changes in the elemental partitioning between γ and γ′ and site-occupancy in γ′. Spatial distribution maps revealed that Mo occupied both Co and Ti sub-lattice sites in γ′. In agreement with the experimental data, thermodynamic calculations predicted a stronger tendency for Mo to occupy the Co-sites than for Cr and an increase in Cr fraction on the Ti-sites with increasing Cr content.
An experimental investigation was carried out in a low-turbulence wind tunnel to study the early development of artificially initiated turbulent spots in a laminar boundary layer over a flat plate. The reproducibility of the experiments allowed us to observe fine structural details that have not been observed previously. Initial velocity disturbances quickly developed into hairpin-like structures that multiplied downstream, which increased the width, length and height of the incipient turbulent spots. Only those disturbances that were greater than a threshold value developed into turbulent spots while the others decayed. The rate of development was also affected by the duration of the initial disturbances. We found that the behaviour of turbulence generation within a turbulent spot is similar to the burst events in the turbulent boundary layer, where ejection events are followed by sweep events.
Major depressive disorder (MDD) is a common, debilitating, phenotypically heterogeneous disorder with heritability ranges from 30% to 50%. Compared to other psychiatric disorders, its high prevalence, moderate heritability, and strong polygenicity have posed major challenges for gene-mapping in MDD. Studies of common genetic variation in MDD, driven by large international collaborations such as the Psychiatric Genomics Consortium, have confirmed the highly polygenic nature of the disorder and implicated over 100 genetic risk loci to date. Rare copy number variants associated with MDD risk were also recently identified. The goal of this review is to present a broad picture of our current understanding of the epidemiology, genetic epidemiology, molecular genetics, and gene–environment interplay in MDD. Insights into the impact of genetic factors on the aetiology of this complex disorder hold great promise for improving clinical care.
Patulous Eustachian tube appears to be caused by a concave defect in the anterolateral wall of the tubal valve of the Eustachian tube. This study aimed to compare the clinical features of patulous Eustachian tube patients with or without a defect in the anterolateral wall of the tubal valve.
Sixty-six patients with a patulous Eustachian tube completed a questionnaire, which was evaluated alongside endoscopic findings of the tympanic membrane, nasal cavity and Eustachian tube orifice.
Females were more frequently diagnosed with a patulous Eustachian tube, but the valve defect was more common in males (p = 0.007). The ratio of patulous Eustachian tube patients with or without defects in the anterolateral wall of the tubal valve was 1.6:1. Weight loss in the previous six months and being refractory to conservative management were significantly associated with the defect (p = 0.035 and 0.037, respectively). Symptom severity was significantly higher in patients with the defect.
Patulous Eustachian tube patients without a defect in the anterolateral wall of the tubal valve can be non-surgically treated more often than those with the defect. Identification of the defect could assist in making treatment decisions for patulous Eustachian tube patients.
OBJECTIVES/GOALS: Lung transplant (LTx) candidates benefit from use of non-ideal donor organs. Each organ procurement organization (OPO) defines “acceptable” donor organs introducing unmeasured variation in donor pursuit. We characterized non-ideal donor pursuit among OPOs to identify drivers of risk aversion in LTx. METHODS/STUDY POPULATION: We queried the UNOS registry for adult donors who donated ≥1 organ for transplantation from 12/2007-12/2018. Non-ideal donors were those with any of age>50, smoking history ≥20 pack-years, PaO2/FiO2 (P/F) ratio<350, donation after cardiac death (DCD) status, or CDC increased risk (IRD) status. Non-ideal donor pursuit rate was defined as the proportion of non-ideal donors at each OPO from whom consent for lung donation was requested with lower numbers indicating increased risk aversion. We estimated the correlation between non-ideal and overall donor pursuit using a Spearman correlation coefficient. Adjusted non-ideal donor pursuit rates were estimated using multivariable logistic regression. RESULTS/ANTICIPATED RESULTS: Overall, 18,333 deceased donors were included and classified as ideal or non-ideal. Among 58 OPOs, rates of non-ideal donor pursuit ranged from 0.24-1.00 Figure). Of 5 non-ideal characteristics, DCD and IRD status were associated with the most and least risk aversion, respectively. Non-ideal donor pursuit was strongly correlated with overall donor pursuit (r = 0.99). On adjusted analysis, older age (OR 0.15, 95% CI 0.13-0.16), smoking history (OR 0.38, 95% CI 0.34-0.44), low P/F ratio (OR 0.12, 95% CI 0.11-0.14), and DCD status (OR 0.04, 95% CI 0.03-0.04) were all independently associated with significant risk aversion, corresponding to decreased rates of donor pursuit. DISCUSSION/SIGNIFICANCE OF IMPACT: OPOs differ in their levels of risk aversion in LTx and risk aversion is not uniform across selected categories of non-ideal lung donor. Consideration of new OPO performance metrics that encourage the pursuit of non-ideal lung donors is warranted.
To assess the Framingham risk score as a prognostic tool for idiopathic sudden sensorineural hearing loss patients.
Medical records were reviewed for unilateral idiopathic sudden sensorineural hearing loss patients between January 2010 and October 2017. The 10-year risk of developing cardiovascular disease was calculated. Patients were subdivided into groups: group 1 – Framingham risk score of less than 10 per cent (n = 28); group 2 – score of 10 to less than 20 per cent (n = 6); and group 3 – score of 20 per cent or higher (n = 5).
Initial pure tone average and Framingham risk score were not significantly associated (p = 0.32). Thirteen patients in group 1 recovered completely (46.4 per cent), but none in groups 2 and 3 showed complete recovery. Initial pure tone average and Framingham risk score were significantly associated in multivariable linear regression analysis (R2 = 0.36). The regression coefficient was 0.33 (p = 0.003) for initial pure tone average and −0.67 (p = 0.005) for Framingham risk score.
Framingham risk score may be useful in predicting outcomes for idiopathic sudden sensorineural hearing loss patients, as those with a higher score showed poorer hearing recovery.
Suicide is a serious phenomenon associated with psychiatric disorders.
In the present study, we investigated factors that can predict follow-up at the psychiatric clinic after medical care at the emergency room (ER).
Medical records of the 145 patients treated at the ER following suicide attempt from Jan 1, 2009 to July 31, 2009 were reviewed. Age, sex, past psychiatric history, impulsiveness and medical severity of suicide attempt, risk-rescue rating scores, reasons for suicide attempt and methods of suicide were examined. Psychiatric diagnoses were made by psychiatrists at the initial interview with patients at ER.
The mean age of the patients was 42.9 ± 15.7 years, and 68.3 % were women and 31.7% were men. Among the suicide methods, psychotropics were the most common (69%), and ingestion of pesticides was the second (19.3%). Interpersonal problems were the most common precipitating event (57.9%), and depression was the most common (89%). About a half had previous psychiatric disorders and about one third had previous suicide attempt. Fifteen patients (10.3%) attempted planned suicide and 124 patients (85.5%) attempted impulsively. Mean risk and rescue rating scores was 8.6 ±1.6 and 12.3 ± 2.2. About one third had a follow-up psychiatric visit. The most important predictor of psychiatric follow-up was risk rating scores.
This study suggests that women with interpersonal problems and depression should be carefully monitored to reduce suicide attempt. Patients commit less risky suicide attempts tend to more loss to psychiatric follow-up, thus, need more attention to prevent suicide re-attempts.
The prevalence of internet game use among children and adolescents has been increased in the recent years.
Internet addiction has been found to cause various psychiatric symptoms and psychological problems. Internet addiction has been found to cause various psychiatric symptoms and psychological problems.
The aim of this study was to examine the association between problematic internet game use and psychiatric symptoms in a sample of the Child and Adolescent Psychiatric Clinic, Ulsan University Hospital.
We analyzed data from 447 subjects who first visit the Child and Adolescent Psychiatric Clinic of the Ulsan University Hospital. The level of Internet addiction was categorized as either high-risk (≥108; group 3), potential risk (95 to 107; group 2), or no risk (≤94, group 1) based on the total score. Data were analyzed using SPSS version 17.0 and one-way ANOVA and multiple logistic regression method were used.
Thirteen adolescents met the criteria for high risk group of internet game addiction. in the high risk group, 10 were male and 3 were female adolescents. There was an mean difference among group 3 (high risk)< 1 (no risk),2 (potential risk) in AHI ; whereas group 3 (high risk)>1 (no risk), 2 (potential risk) in BDI, BAI, inattention, hyperactivity/impulsivity and K-ARS score. with multiple logistic regression analysis, K-scale was significantly related with male sex, BDI, ARShyperactivity/ impulsivity score.
We conclude that having male sex, happiness and depressive symptoms is associated with the risk of developing internet use disorders.
The binary metal oxides are increasingly used as supercapacitor electrode materials in energy storing devices. Particularly NiCo2O4 has shown promising electrocapacitive performance with high specific capacitance and energy density. The electrocapacitive performance of these oxides largely depends on their morphology and electrical properties governed by their energy band-gaps and defects. The morphological structure of NiCo2O4 can be altered via the synthesis route, while the energy band-gap could be altered by doping. Also, doping can enhance crystal stability and bring in grain refinement, which can further improve the much-needed surface area for high specific capacitance. Given the above, this study evaluates the electrochemical performance of Ca-doped Ni1-xCaxCo2O4 (0 ≤ x ≤ 0.8) compounds. This stipulates promising applications for electrodes in future supercapacitors.
To analyse how the auditory brainstem response changes in patients with sudden sensorineural hearing loss.
Data were collected via retrospective medical chart review.
Forty-three patients were included in this study. The mean latency of auditory brainstem response wave 1 was significantly longer for the affected side than for the unaffected side (p = 0.003). The mean latency of auditory brainstem response wave 1 was significantly shorter, and the mean amplitude of auditory brainstem response wave 1 was significantly larger, in the good response group compared to the poor response group. In forward conditional logistic regression analysis, auditory brainstem response wave 1 latency was an independent predictor of a good response (odds ratio = 34.37, 95 per cent confidence interval = 1.56–757.15, p = 0.025).
In patients with sudden sensorineural hearing loss, the latency of wave 1 of the auditory brainstem response was significantly increased and was related to prognosis.
The introduction of agriculture is known to have profoundly affected the ecological complexion of landscapes. In this study, a rapid transition from C3 to C4 vegetation is inferred from a shift to higher stable carbon (13C/12C) isotope ratios of soils and sediments in the Benoué River Valley and upland Fali Mountains in northern Cameroon. Landscape change is viewed from the perspective of two settlement mounds and adjacent floodplains, as well as a rock terrace agricultural field dating from 1100 cal yr BP to the recent past (<400 cal yr BP). Nitrogen (15N/14N) isotope ratios and soil micromorphology demonstrate variable uses of land adjacent to the mound sites. These results indicate that Early Iron Age settlement practices involved exploitation of C3 plants on soils with low δ15N values, indicating wetter soils. Conversely, from the Late Iron Age (>700 cal yr BP) until recent times, high soil and sediment δ13C and δ15N values reflect more C4 biomass and anthropogenic organic matter in open, dry environments. The results suggest that Iron Age settlement practices profoundly changed landscapes in this part of West Africa through land clearance and/or utilization of C4 plants.
To determine the factors related to multiple ventilation tube insertions in children with otitis media with effusion.
A retrospective review was performed of 126 ears of 81 children aged less than 12 years who had undergone insertion of a Paparella type 1 ventilation tube for the first time between August 2012 and March 2018.
Mean age at the first operation was 4.0 ± 2.2 years, and the mean duration of otitis media with effusion before the first ventilation tube insertion was 5.4 ± 4.5 months. Among 126 ears, 80 (63.5 per cent) had a single ventilation tube insertion and 46 (36.5 per cent) had multiple insertions. On multivariate logistic regression, tympanic membrane retraction, serous middle-ear discharge, and early recurrence of otitis media with effusion were independent predictive factors of multiple ventilation tube insertions.
Tympanic membrane retraction, serous middle-ear discharge, and early recurrence of otitis media with effusion after the first tube extrusion are associated with multiple ventilation tube insertions.