The deleterious effect of crossfostering in rat pups on hypoxic-ischemic injury tolerance and hypothermic neuroprotection

We study the effect of hypothermia (HT) following hypoxic-ischemic (HI) brain injury in postnatal day 7 (P7) rats. In 2015, new European Union animal transport regulations prompted a change in practice at the breeding facility, which henceforth crossfostered P3 litters to P8 older lactating dam prior to transportation. It is generally assumed that crossfostering does not significantly affect the experimental results. The aim of this study was to examine whether crossfostering affects our model consistency by modifying injury susceptibility and hypothermic neuroprotection. We analysed 219 pups (56 litters) from 11 experiments conducted between 2013 and 2015: 73 non-crossfostered and 146 crossfostered pups. At P7, all pups underwent unilateral common carotid artery ligation followed by 50min of hypoxia (8% O2, 36°C). Immediately after this mild insult, the pups were randomised to post-insult normothermia (NT) or HT treatment. Pups were culled at P14. Injury was assessed by area loss of the ipsilateral hemisphere and histopathology scoring of hippocampus, cortex, thalamus, and basal ganglia. Crossfostered pups had double the injury compared to non-crossfostered pups irrespective of treatment group. Hypothermic neuroprotection was statistically significant, but with a smaller and less consistent effect in crossfostered pups (relative neuroprotection 16% vs. 31% in non-crossfostered). These results demonstrate hypothermic neuroprotection following a mild HI insult. A representative subset of 41 animals were also assessed for evidence of microglial reactivity, however no detectable difference in microglial reactivity was observed between any of the groups. In conclusion, crossfostering alters outcomes in our established model through reduced insult tolerance and variable neuroprotection. Crossfostering as a common breeding practice is a largely unexplored variable in animal research that may result in invalid research conclusions if inadequately adjusted for by larger group sizes. As a result, crossfostering is likely to be inconsistent with the principles of replacement, reduction, and refinement.

PROTOCOL FOR ASSESSING THE PRECISION OF PARALYMPIC BOCCIA PLAYERS

ABSTRACT Introduction: Although Paralympic boccia is an up-and-coming sport, demanding more and requiring higher levels of performance from athletes, protocols are not available for evaluating its indicators. Objective: To develop and verify the applicability of a new protocol for assessing the precision of athletes of the sport. Methods: Two targets with two different resolutions (0.5 [RES-0.5] and 1.0 [RES-1.0] points) were developed, graduated from 1 to 7. The protocol consists of placing the targets at 6 locations on the court, and each athlete makes two shots for each target. The best results are considered, from which total precision (TotalP), short precision (SP), medium precision (MP) and long precision (LP) are extracted. Nine players participated in the application of the protocol. The indicators of both targets were compared and verified using the intraclass correlation coefficient (ICC), standard error of measurement (SEm), bias (Bland-Altman) and minimum detectable difference (MDD). Results: Only for LP were there differences between targets (RES-0.5: 9.111 versus RES-1.0: 7.167; p <0.05), while TotalP, SP and MP did not show any significant differences (RES-0.5: 23.11 versus RES-1.0: 25.39; RES-0.5: 18.22 versus RES-1.0: 17.78; RES-0.5: 9.11 versus RES-1.0: 12.44, respectively). In addition, the RES-0.5 target obtained better concordance results (ICC = 0.73; SEm = 3.45; bias = -0.5938; MDD = 8.00), while the RES-1.0 target obtained lower values (CCI = 0.53; SEm = 6.28; bias = 0.3750; MDD = 14.56). Conclusions: The proposed protocol presents excellent applicability results. However, a larger sample of athletes including more details on specific precision indicators should be performed. Level of evidence II; Prospective comparative study.

Students Eat Less Meat After Studying Meat Ethics

In the first controlled, non-self-report studies to show an influence of university-level ethical instruction on everyday behavior, Schwitzgebel et al. (2020) and Jalil et al. (2020) found that students purchase less meat after exposure to material on the ethics of eating meat. We sought to extend and conceptually replicate this research. Seven hundred thirty students in three large philosophy classes read James Rachels’ (2004) “Basic Argument for Vegetarianism”, followed by 50-min small-group discussions. Half also viewed a vegetarianism advocacy video containing factory farm footage. A few days after instruction, 54% of students agreed that “eating the meat of factory farmed animals is unethical”, compared to 37% before instruction, with no difference between the film and non-film conditions. Also, 39% of students anonymously pledged to avoid eating factory farmed meat for 24 h, again with no statistically detectable difference between conditions. Finally, we obtained 2828 campus food purchase receipts for 113 of the enrolled students who used their Student ID cards for purchases on campus, which we compared with 5033 purchases from a group of 226 students who did not receive the instruction. Meat purchases remained constant in the comparison group and declined among the students exposed to the material, falling from 30% to 23% of purchases overall and from 51% to 42% of purchases of $4.99 or more, with the effect possibly larger in the film condition.

Quality Enhancement of Gamma Camera SPECT Images Via the Taguchi-Based Optimization of Their Minimum Detectable Difference And a V-Shaped Slit Gauge

Background: This study optimized the minimum detectable difference (MDD) of gamma camera SPECT images via the Taguchi analysis and an indigenous V-shaped slit gauge. The latter was customized to satisfy the Taguchi analysis’ quantitative requirements. Methods: The slit gauge MDD quantification of derived SPECT images was based on a pair of overlapped-peak profiles obtained from a tangent slice of the V-shaped slit with two adjacent peaks. Using the revised Student’s t-test with a multiplied constant, 1.96, the MDD was defined as the minimum distance between two peak centers, which deviation was large enough to ensure a 95% confidence level of their separation. In total, eighteen combinations of six gamma camera scanned factors (A-F), namely (A) collimator, (B) detector to target distance, (C) total counts, (D) acquired energy width, (E) Matrix size, and (F) zoom of collected ROI with each of two or three levels were organized into 18 groups to collect the slit gauge images according to Taguchi L18 orthogonal array. Next, three well-trained radiologists ranked the scanned gauge images to derive the fish-bone-plot of signal-to-noise ratio (S/N, dB) and correlated ANOVA. Results: The quantified MDD was proposed to verify the optimal suggestion of gamma camera scanned protocol, and obtained the MDD as 8.44, 7.88, and 7.40 mm for the 2nd group of the original L18, conventional, and optimal presets, respectively. Conclusions: The optimal preset of gamma camera was achieved according to Taguchi analysis. The MDD-based approach was found more beneficial in evaluating the spatial resolution than the line pair/cm approach in routine quality control in this study.

MINIMUM DETECTABLE DIFFERENCE OF CT ANGIOGRAPHY SCANS AT VARIOUS CARDIAC BEATS: EVALUATION VIA A CUSTOMIZED OBLIQUE V-SHAPED LINE GAUGE AND PMMA PHANTOM

The minimum detectable difference (MDD) at various beats/min (BPM) of CT angiography (CTA) was evaluated using an oblique V-shape line gauge and poly methyl methacrylate (PMMA) phantom in this study. The customized phantom with the size of [Formula: see text][Formula: see text]cm3 was made from a 1[Formula: see text]cm-thick PMMA. The reciprocating mechanism in the phantom was run by a step motor with an eccentric gear connected to a crank rod to provide a stable harmonic motion, simulating the cardiac beats. The MDD has a unique feature in defining the quality characteristic of CT-scanned images and provides more information than simple line pair/cm in the previous studies. The derived MDD was quantified according to various BPM, and the CTA factor combination was preset following either the conventional recommendation or the optimal one. In doing so, the performance was substantiated by the Taguchi-based signal-to-noise ratio and integrated by another index, namely, figure of merit (FOM). The MDD and corresponding [Formula: see text] (dB) changed from [Formula: see text][Formula: see text]mm to [Formula: see text][Formula: see text]mm and from 16.7[Formula: see text]dB to 14.2[Formula: see text]dB, respectively, for conventional settings; while those obtained for the optimal preset changed from [Formula: see text][Formula: see text]mm to [Formula: see text][Formula: see text]mm and from 12.2 dB to 16.4 dB, respectively of CTA at 0–90 BPM. The integrated FOM values for conventional or optimal cases were 1240 and 1337, respectively. The MDD proved to be a useful technique in justifying the CTA-scanned images. For compliance with previous studies, MDD results can be converted to the line pair/cm results, but it is more informative than the quantized number of line pairs.

[REiNS] Validating Techniques for Measurement of Cutaneous Neurofibromas: Recommendations for Clinical Trials

Objective:To assess the reliability and variability of digital calipers, 3D photography, and high frequency ultrasound (HFUS) for measurement of cutaneous neurofibromas (cNF) in patients with neurofibromatosis type 1 (NF1).Background:cNF affect virtually all patients with NF1 and are a major source of morbidity. Reliable techniques for measuring cNF are needed to develop therapies for these tumors.Methods:Adults with NF1 were recruited. For each participant, six cNF were assessed independently by three different examiners at five different timepoints using digital calipers, 3D photography, and HFUS. The intraclass correlation coefficient (ICC) was used to assess intra- and inter-rater reliability of linear and volumetric measurements for each technique, with ICC values >0.90 defined as “excellent” reliability. The coefficient of variation (CV) was used to estimate the minimal detectable difference (MDD) for each technique.Results:57 cNF across 10 participants were evaluated. The ICC for image acquisition and measurement was >0.97 within and across examiners for HFUS and 3D photography. ICC for digital calipers was 0.62–0.88. CV varied by measurement tool, linear vs. volumetric measurement, and tumor size.Conclusions:HFUS and 3D photography demonstrate “excellent” reliability whereas digital calipers have “good” to “excellent” reliability in measuring cNF. The MDD for each technique was used to create tables of proposed thresholds for investigators to use as guides for clinical trials focused on cNF size. These criteria should be updated as the performance of these endpoints are evaluated.

Alternative Devices for Heart Rate Variability Measures: A Comparative Test–Retest Reliability Study

Using healthy adult participants, seven measures of heart rate variability were obtained simultaneously from four devices in five behavioral conditions. Two devices were ECG-based and two utilized photoplethysmography. The 140 numerical values (measure, condition, device) are presented. The comparative operational reliability of the four devices was assessed, and it was found that the two ECG-base devices were more reliable than the photoplethysmographic devices. The interchangeability of devices was assessed by determining the between-device Limits of Agreement. Intraclass correlation coefficients were determined and used to calculate the standard error of measurement and the Minimal Detectable Difference. The Minimal Detectable Difference, MDD, quantifies the smallest statistically significant change in a measure and is therefore critical when HRV measures are used longitudinally to assess treatment response or disease progression.

Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

Evaluation of Combined Financial Incentives and Deposit Contract Intervention for Smoking Cessation: A Randomized Controlled Trial

Introduction. We evaluate whether a combination of financial incentives and deposit contracts improves cessation rates among low- to moderate-income smokers. Methods. We randomly assigned 311 smokers covered by Medicaid at 12 health clinics in Connecticut to usual care or one of the three treatment arms. Each treatment arm received financial incentives for two months and either (i) nothing further (“incentives only”), (ii) the option to start a deposit contract with incentive earnings after the incentives ended (“commitment”), or (iii) the option to precommit any earned incentives into a deposit contract starting after the incentives ended (“precommitment”). Smoking cessation was confirmed biochemically at two, six, and twelve months. Results. At two, six, and twelve months after baseline, our estimated treatment effects on cessation are positive but imprecise, with confidence intervals containing effect sizes estimated by prior studies of financial incentives alone and deposit contracts alone. At two months, the odds ratio for quitting was 1.4 in the incentive-only condition (95% CI: 0.5 to 3.5), 2.0 for incentives followed by commitment (95% CI: 0.6 to 6.1), and 1.9 for incentives and precommitment (95% CI: 0.7 to 5.3). Conclusions. A combined incentive and deposit contract program for Medicaid enrollees, with incentives offering up to $300 for smoking cessation and use of support services, produced a positive but imprecisely estimated effect on biochemically verified cessation relative to usual care and with no detectable difference in cessation rates between the different treatment arms.