Expanded use of engineered nanoparticles (ENPs) in consumer products increases the potential for environmental release and unintended biological exposures. As a result, measurement techniques are ...needed to accurately quantify ENP size, mass, and particle number distributions in biological matrices. This work combines single particle inductively coupled plasma mass spectrometry (spICPMS) with tissue extraction to quantify and characterize metallic ENPs in environmentally relevant biological tissues for the first time. ENPs were extracted from tissues via alkaline digestion using tetramethylammonium hydroxide (TMAH). Method development was performed using ground beef and was verified in Daphnia magna and Lumbriculus variegatus. ENPs investigated include 100 and 60 nm Au and Ag stabilized by polyvynylpyrrolidone (PVP). Mass- and number-based recovery of spiked Au and Ag ENPs was high (83–121%) from all tissues tested. Additional experiments suggested ENP mixtures (60 and 100 nm Ag ENPs) could be extracted and quantitatively analyzed. Biological exposures were also conducted to verify the applicability of the method for aquatic organisms. Size distributions and particle number concentrations were determined for ENPs extracted from D. magna exposed to 98 μg/L 100 nm Au and 4.8 μg/L 100 nm Ag ENPs. The D. magna nanoparticulate body burden for Au ENP uptake was 613 ± 230 μg/kgww, while the measured nanoparticulate body burden for D. magna exposed to Ag ENPs was 59 ± 52 μg/kgww. Notably, the particle size distributions determined from D. magna tissues suggested minimal shifts in the size distributions of ENPs accumulated, as compared to the exposure media.
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IJS, KILJ, NUK, PNG, UL, UM
The raw outputs of the detectors within the Advanced Laser Interferometer Gravitational-Wave Observatory need to be calibrated in order to produce the estimate of the dimensionless strain used for ...astrophysical analyses. The two detectors have been upgraded since the second observing run and finished the year-long third observing run. Understanding, accounting, and/or compensating for the complex-valued response of each part of the upgraded detectors improves the overall accuracy of the estimated detector response to gravitational waves. We describe improved understanding and methods used to quantify the response of each detector, with a dedicated effort to define all places where systematic error plays a role. We use the detectors as they stand in the first half (six months) of the third observing run to demonstrate how each identified systematic error impacts the estimated strain and constrain the statistical uncertainty therein. For this time period, we estimate the upper limit on systematic error and associated uncertainty to be <7% in magnitude and <4 deg in phase (68% confidence interval) in the most sensitive frequency band 20-2000 Hz. The systematic error alone is estimated at levels of <2% in magnitude and <2 deg in phase.
School funding formulas have been applied across a number of countries for at least the last 50 years. A national funding formula (NFF) was introduced in England in 2018 and aims to provide a ...platform for fair funding across the country. This study explores the variations in the NFF's high needs block (HNB) funding and examines links with the use of specialist provision by English local authorities (LAs) for children with special educational needs and disability. The findings demonstrate significant and continuing differences in HNB funding between demographically similar LAs, notwithstanding a £3.5 billion (75%) HNB increase in real terms in the decade since 2013, which could have supported a shift towards a more equitable position. Published HNB funding for 2023–24 now varies by up to £49m in comparator LAs. Differences are largely the result of the persistent use of a historical factor in the formula and a ceiling on levels of income growth for lower funded LAs. The research also shows a significant link between HNB funding and the use of specialist provision. The discussion investigates how far the UK government's policy commitment to a more equitable system of HNB funding is matched by the reality, and the degree to which funding is based on need rather than demand or history.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The aim of this study was to conduct a randomized test comparing 2 multicomponent, contingency management interventions, 1 with and 1 without a full parent training curriculum, and an individual ...treatment for adolescent cannabis use disorders.
A total of 153 adolescents who met DSM-IV criteria for cannabis abuse or dependence were randomized to motivational enhancement therapy/cognitive-behavioral therapy (MET/CBT), MET/CBT+abstinence-based contingency management (CM), or MET/CBT+CM+Parent Training (PT).
Overall, during treatment, abstinence was greater for youth receiving clinic- and home-based CM without PT compared to those who received individual MET/CBT. There was no additional benefit of the full PT curriculum on marijuana use, youth externalizing problems, or parenting.
These results suggest that clinic- plus home-based CM for cannabis use disorders can increase rates of abstinence during treatment over and above an evidence-based treatment (individual MET/CBT), but in this study the addition of a comprehensive parenting training curriculum did not further enhance efficacy.
Treatment for Adolescent Marijuana Abuse; http://clinicaltrials.gov; NCT00580671.
Research has suggested that individuals who play a musical instrument throughout adulthood have better preserved executive function. However, mixed results have been found for associations between ...musical activity and visuo-spatial abilities, and less is known about associations with fluid intelligence. We explored differences between musicians (N = 30) and non-musicians (N = 30) aged 60-93 years old across a range of neuropsychological measures of cognitive function. Musicians performed significantly better than non-musicians on all domains, which remained after adjusting for age, gender, educational history, languages spoken and physical activity. As a cross-sectional comparison, the results should not be overstated; however, they are consistent with findings suggesting learning a musical instrument throughout the life course may be associated with cognitive benefits. Identifying potential lifestyle factors that have cognitive benefits in later life, such as musical experience, is an important step in developing intervention strategies for cognitive aging.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Objective:
Abstinence is rarely achieved in clinical trials for cannabis use disorder (CUD). Cannabis reduction is associated with functional improvement, but reduction endpoints have not been ...established, indicating a need to identify and validate clinically meaningful reduction endpoints for assessing treatment efficacy.
Method:
Data from a 12-week double-blind randomized placebo-controlled medication trial for cannabis cessation (NCT01675661) were analyzed. Participants (N = 225) were treatment-seeking adults, M = 30.6 (8.9) years old, 70.2% male, and 42.2% Non-White, with CUD who completed 12 weeks of treatment. Frequency (days of use per week) and quantity (grams per using day) were used to define high-, medium-, and low-risk levels. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale and cannabis-related problems were assessed using the Marijuana Problems Scale. General linear models for repeated measures tested associations between the magnitude of risk reduction and functional outcomes from baseline (BL) to end-of-treatment (EOT). Results: Cannabis risk levels were sensitive to reductions in use from BL to EOT for frequency- (χ2 = 19.35, p = .004) and quantity-based (χ2 = 52.06, p < .001) metrics. Magnitude reduction in frequency-based risk level was associated with magnitude decrease in depression (F = 2.76, p = .043, ηp2 = .04), anxiety (F = 3.70, p = .013, ηp2 = .05), and cannabis-related problems (F = 8.95, p < .001, ηp2 = .12). Magnitude reduction in quantity-based risk level was associated with magnitude decrease in anxiety (F = 3.02, p = .031, ηp2 = .04) and cannabis-related problems (F = 3.24, p = .023, ηp2 = .05). Conclusions: Cannabis use risk levels, as operationalized in this study, captured reductions in use during a clinical trial. Risk level reduction was associated with functional improvement suggesting that identifying risk levels and measuring the change in levels over time may be a viable and clinically meaningful endpoint for determining treatment efficacy.
Public Health Significance Statement
Cannabis use risk levels are measurable, and reduction in risk level is associated with functional improvement during treatment. Given increasing access to cannabis worldwide, risk reduction approaches may be critical to reduce the public health burden of cannabis use disorder (CUD).
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
•Provides a review of clinical outcome assessments for CUD trial endpoints.•Abstinence is not the only valid indicator of CUD treatment success.•A core toolkit of assessments for CUD treatment ...studies is needed.
There is considerable variability in the use of outcome measures in clinical trials for cannabis use disorder (CUD), and a lack of consensus regarding optimal outcomes may have hindered development and approval of new pharmacotherapies. The goal of this paper is to summarize an evaluation of assessment measures and clinical endpoints for CUD clinical trials, and propose a research agenda and priorities to improve CUD clinical outcome assessments. The primary recommendation is that sustained abstinence from cannabis should not be considered the primary outcome for all CUD clinical trials as it has multiple limitations. However, there are multiple challenges to the development of a reliable and valid indicator of cannabis reduction, including the lack of a standard unit of measure for the various forms of cannabis and products and the limitations of currently available biological and self-report assessments. Development of a core toolkit of assessments is needed to both allow flexibility for study design, while facilitating interpretation of outcomes across trials. Four primary agenda items for future research are identified to expedite development of improved clinical outcome assessments for this toolkit: (1) determine whether minimally invasive biologic assays could identify an acute level of cannabis use associated with psychomotor impairment or other cannabis-related harms; (2) create an indicator of quantity of cannabis use that is consistent across product types; (3) examine the presence of cannabis-specific functional outcomes; and (4) identify an optimal duration to assess changes in CUD diagnostic criteria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Heated and humidified high-flow nasal cannula (HFNC) is a widely used form of respiratory support; however, data regarding optimal flows for a given patient size or disease state are lacking. A ...comprehensive study of the physiologic effects of HFNC is needed to better understand the mechanisms of action. The objective of the current study was to quantify the effect of HFNC settings in age-specific, anatomically correct nasal airways and spontaneously breathing lung models. We hypothesized that there is an effect of flow on pressure and ventilation.
Three-dimensionally printed upper airway models of a preterm neonate, term neonate, toddler, small child, and adult were affixed to the ASL 5000 test lung to simulate spontaneous breathing with age-appropriate normal ventilation parameters. CO
was introduced to simulate profound hypercapneic respiratory failure with an end-tidal partial pressure of carbon dioxide (P
) of 90 ± 1 mm Hg. Two commercially available HFNC systems were applied to the airway models, and PEEP, inspired CO
, and exhaled CO
(P
) were recorded for 6 min across a range of flow.
Increasing HFNC flow provided a non-linear increase in PEEP in closed-mouth models, with maximum tested flows generating 6 cm H
O in the preterm neonate to 20 cm H
O in the small child. Importantly, PEEP decreased by approximately 50% in open-mouth models. Increasing HFNC flow improved expiratory CO
elimination to a certain point, above which continued increases in flow had minimal additional effect. This change point ranged from 4 L/min in the preterm neonate to 10 L/min in the small child.
These findings may help clinicians understand the effects of HFNC at different settings and may inform management guidelines for patients with respiratory failure.
Reduction-based cannabis use endpoints are needed to better evaluate treatments for cannabis use disorder (CUD). This exploratory, secondary analysis aimed to characterize cannabis frequency and ...quantity reduction patterns and corresponding changes in psychosocial functioning during treatment. We analyzed 16 weeks (4 prerandomization, 12 postrandomization) of data (n = 302) from both arms of a randomized clinical trial assessing pharmacotherapy for CUD. Cannabis consumption pattern classes were extracted with latent profile modeling using self-reported (a) past-week days used (i.e., frequency) and (b) past-week average grams used per using day (i.e., quantity). Changes in mean Marijuana Problem Scale (MPS) and Hospital Anxiety and Depression Scale (HADS) scores were examined among classes. Urine cannabinoid levels were examined in relation to self-reported consumption as a validity check. Two-, three-, four-, and five-class solutions each provided potentially useful conceptualizations of associations between frequency and quantity. Regardless of solution, reductions in MPS scores varied in magnitude across classes and closely tracked class-specific reductions in consumption (e.g., larger MPS reduction corresponded to larger frequency/quantity reductions). Changes in HADS scores were less pronounced and less consistent with consumption patterns. Urine cannabinoid levels closely matched class-specific self-reported consumption frequency. Findings illustrate that frequency and quantity can be used in tandem within mixture model frameworks to summarize heterogeneous cannabis use reduction patterns that may correspond to improved psychosocial functioning. Going forward, similar analytic strategies applied to alternative metrics of cannabis consumption may facilitate construction of useful reduction-based clinical endpoints.
Public Health Significance Statement
This study examined different ways individuals might reduce the frequency and quantity of their cannabis use during treatment. Results suggest that specific patterns of cannabis reduction may be predictive of improved psychosocial functioning. The conceptual and analytic approach used in this study may help with the development of cannabis reduction-based endpoints for clinical trials.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Objective
The Dyspnea Index (DI) is a validated patient‐reported outcome (PRO) instrument that has been used in the management of laryngotracheal stenosis (LTS). The minimal clinically important ...difference (MCID) is an established concept to help determine the change in a PRO instrument that reflects meaningful change for the patient. It is not known what change in the DI is of clinical significance in airway surgery. This study aims to determine the MCID for the DI in patients undergoing surgical treatment for LTS.
Methods
This is a prospective cohort study in which 26 patients with LTS completed the DI (score range 0 to 40) before and 6 to 8 weeks postoperatively, in addition to a Global Ratings Change Questionnaire (GRCQ), scored from −7 to +7, at the postoperative interval. A hypothesis test was carried out to test the association between GRCQ and change in DI. The MCID for change in DI was determined using anchor‐based analysis.
Results
Overall mean change in DI was −11, and mean change in GRCQ was +5. Change in DI scores were significantly different among the improvement and no improvement groups (P value <0.002). Area under the receiver operating curve was 0.92, demonstrating high discriminatory ability of the change in DI score. A change of −4 was determined to be the threshold that discriminated between significant improvement and no improvement.
Conclusion
A decrease of 4 in the DI can be considered as the MCID for patients with LTS after surgical treatment.
Level of Evidence
2b Laryngoscope, 130:1775–1779, 2020
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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