Theoretical and experimental assessment of genome-based prediction in landraces of allogamous crops.

Discovery and enrichment of favorable alleles in landraces are key to making them accessible for crop improvement. Here, we present two fundamentally different concepts for genome-based selection in landrace-derived maize populations, one based on doubled-haploid (DH) lines derived directly from individual landrace plants and the other based on crossing landrace plants to a capture line. For both types of populations, we show theoretically how allele frequencies of the ancestral landrace and the capture line translate into expectations for molecular and genetic variances. We show that the DH approach has clear advantages over gamete capture with generally higher prediction accuracies and no risk of masking valuable variation of the landrace. Prediction accuracies as high as 0.58 for dry matter yield in the DH population indicate high potential of genome-based selection. Based on a comparison among traits, we show that the genetic makeup of the capture line has great influence on the success of genome-based selection and that confounding effects between the alleles of the landrace and the capture line are best controlled for traits for which the capture line does not outperform the ancestral population per se or in testcrosses. Our results will guide the optimization of genome-enabled prebreeding schemes.

Optimizing selection based on BLUPs or BLUEs in multiple sets of genotypes differing in their population parameters.

KEY MESSAGE: Selection response in truncation selection across multiple sets of candidates hinges on their post-selection proportions, which can deviate grossly from their initial proportions. For BLUPs, using a uniform threshold for all candidates maximizes the selection response, irrespective of differences in population parameters. Plant breeding programs typically involve multiple families from either the same or different populations, varying in means, genetic variances and prediction accuracy of BLUPs or BLUEs for true genetic values (TGVs) of candidates. We extend the classical breeder's equation for truncation selection from single to multiple sets of genotypes, indicating that the expected overall selection response ( Δ G Tot ) for TGVs depends on the selection response within individual sets and their post-selection proportions. For BLUEs, we show that maximizing Δ G Tot requires thresholds optimally tailored for each set, contingent on their population parameters. For BLUPs, we prove that Δ G Tot is maximized by applying a uniform threshold across all candidates from all sets. We provide explicit formulas for the origin of the selected candidates from different sets and show that their proportions before and after selection can differ substantially, especially for sets with inferior properties and low proportion. We discuss implications of these results for (a) optimum allocation of resources to training and prediction sets and (b) the need to counteract narrowing the genetic variation under genomic selection. For genomic selection of hybrids based on BLUPs of GCA of their parent lines, selecting distinct proportions in the two parent populations can be advantageous, if these differ substantially in the variance and/or prediction accuracy of GCA. Our study sheds light on the complex interplay of selection thresholds and population parameters for the selection response in plant breeding programs, offering insights into the effective resource management and prudent application of genomic selection for improved crop development.

B-flow/spatiotemporal image correlation M-mode ultrasound provides novel method to quantify spiral artery remodeling during normal human pregnancy.

OBJECTIVES: During human pregnancy, placental extravillous trophoblasts replace vascular smooth muscle and elastic tissue within the walls of the uterine spiral arteries, thereby remodeling them into distensible low-resistance vessels to promote placental perfusion. The present study determined whether B-flow/spatiotemporal image correlation (STIC) M-mode ultrasonography provides an in-vivo imaging method able to digitally quantify spiral artery luminal distensibility as a physiological index of spiral artery remodeling during the advancing stages of normal human pregnancy. METHODS: A prospective, longitudinal, observational study was conducted to quantify spiral artery distensibility (i.e. vessel luminal diameter at systole minus diameter at diastole) by B-flow/STIC M-mode ultrasonography during the first, second and third trimesters in 290 women exhibiting a normal pregnancy. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), growth factors that modulate important events in spiral artery remodeling, were quantified in a subset of the women in the first, second and third trimesters of pregnancy. RESULTS: Median (interquartile range (IQR)) spiral artery distensibility increased progressively between the first (0.17 (0.14-0.21) cm), second (0.23 (0.18-0.28) cm) and third (0.26 (0.21-0.35) cm) trimesters of pregnancy (P < 0.0001 for all). Median (IQR) spiral artery volume flow increased progressively between the first (2.49 (1.38-4.99) mL/cardiac cycle), second (3.86 (2.06-6.91) mL/cardiac cycle) and third (7.79 (3.83-14.98) mL/cardiac cycle) trimesters (P < 0.001 for all). In accordance with the elevation in spiral artery distensibility, the median (IQR) ratio of serum PlGF/sFlt-1 × 103 levels increased between the first (7.2 (4.5-10.0)), second (22.7 (18.6-42.2)) and third (56.2 (41.9-92.5)) trimesters (P < 0.001 for all). CONCLUSIONS: The present study shows that B-flow/STIC M-mode ultrasonography provides an in-vivo imaging technology to quantify digitally the structural and physiological expansion of the walls of the spiral arteries during the cardiac cycle as a consequence of their transformation into compliant vessels during advancing stages of normal human pregnancy. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Genomic prediction in hybrid breeding: II. Reciprocal recurrent genomic selection with full-sib and half-sib families.

KEY MESSAGE: Genomic prediction of GCA effects based on model training with full-sib rather than half-sib families yields higher short- and long-term selection gain in reciprocal recurrent genomic selection for hybrid breeding, if SCA effects are important. Reciprocal recurrent genomic selection (RRGS) is a powerful tool for ensuring sustainable selection progress in hybrid breeding. For training the statistical model, one can use half-sib (HS) or full-sib (FS) families produced by inter-population crosses of candidates from the two parent populations. Our objective was to compare HS-RRGS and FS-RRGS for the cumulative selection gain ([Formula: see text]), the genetic, GCA and SCA variances ([Formula: see text],[Formula: see text], [Formula: see text]) of the hybrid population, and prediction accuracy ([Formula: see text]) for GCA effects across cycles. Using SNP data from maize and wheat, we simulated RRGS programs over 10 cycles, each consisting of four sub-cycles with genomic selection of [Formula: see text] out of 950 candidates in each parent population. Scenarios differed for heritability [Formula: see text] and the proportion [Formula: see text] of traits, training set (TS) size ([Formula: see text]), and maize vs. wheat. Curves of [Formula: see text] over selection cycles showed no crossing of both methods. If [Formula: see text] was high, [Formula: see text] was generally higher for FS-RRGS than HS-RRGS due to higher [Formula: see text]. In contrast, HS-RRGS was superior or on par with FS-RRGS, if [Formula: see text] or [Formula: see text] and [Formula: see text] were low. [Formula: see text] showed a steeper increase and higher selection limit for scenarios with low [Formula: see text], high [Formula: see text] and large [Formula: see text]. [Formula: see text] and even more so [Formula: see text] decreased rapidly over cycles for both methods due to the high selection intensity and the role of the Bulmer effect for reducing [Formula: see text]. Since the TS for FS-RRGS can additionally be used for hybrid prediction, we recommend this method for achieving simultaneously the two major goals in hybrid breeding: population improvement and cultivar development.

Influence of the mating design on the additive genetic variance in plant breeding populations.

KEY MESSAGE: Mating designs determine the realized additive genetic variance in a population sample. Deflated or inflated variances can lead to reduced or overly optimistic assessment of future selection gains. The additive genetic variance [Formula: see text] inherent to a breeding population is a major determinant of short- and long-term genetic gain. When estimated from experimental data, it is not only the additive variances at individual loci (QTL) but also covariances between QTL pairs that contribute to estimates of [Formula: see text]. Thus, estimates of [Formula: see text] depend on the genetic structure of the data source and vary between population samples. Here, we provide a theoretical framework for calculating the expectation and variance of [Formula: see text] from genotypic data of a given population sample. In addition, we simulated breeding populations derived from different numbers of parents (P = 2, 4, 8, 16) and crossed according to three different mating designs (disjoint, factorial and half-diallel crosses). We calculated the variance of [Formula: see text] and of the parameter b reflecting the covariance component in [Formula: see text] standardized by the genic variance. Our results show that mating designs resulting in large biparental families derived from few disjoint crosses carry a high risk of generating progenies exhibiting strong covariances between QTL pairs on different chromosomes. We discuss the consequences of the resulting deflated or inflated [Formula: see text] estimates for phenotypic and genome-based selection as well as for applying the usefulness criterion in selection. We show that already one round of recombination can effectively break negative and positive covariances between QTL pairs induced by the mating design. We suggest to obtain reliable estimates of [Formula: see text] and its components in a population sample by applying statistical methods differing in their treatment of QTL covariances.

Genomic prediction in hybrid breeding: I. Optimizing the training set design.

KEY MESSAGE: Training sets produced by maximizing the number of parent lines, each involved in one cross, had the highest prediction accuracy for H0 hybrids, but lowest for H1 and H2 hybrids. Genomic prediction holds great promise for hybrid breeding but optimum composition of the training set (TS) as determined by the number of parents (nTS) and crosses per parent (c) has received little attention. Our objective was to examine prediction accuracy ([Formula: see text]) of GCA for lines used as parents of the TS (I1 lines) or not (I0 lines), and H0, H1 and H2 hybrids, comprising crosses of type I0 × I0, I1 × I0 and I1 × I1, respectively, as function of nTS and c. In the theory, we developed estimates for [Formula: see text] of GBLUPs for hybrids: (i)[Formula: see text] based on the expected prediction accuracy, and (ii) [Formula: see text] based on [Formula: see text] of GBLUPs of GCA and SCA effects. In the simulation part, hybrid populations were generated using molecular data from two experimental maize data sets. Additive and dominance effects of QTL borrowed from literature were used to simulate six scenarios of traits differing in the proportion (τSCA = 1%, 6%, 22%) of SCA variance in σG2 and heritability (h2 = 0.4, 0.8). Values of [Formula: see text] and [Formula: see text] closely agreed with [Formula: see text] for hybrids. For given size NTS = nTS × c of TS, [Formula: see text] of H0 hybrids and GCA of I0 lines was highest for c = 1. Conversely, for GCA of I1 lines and H1 and H2 hybrids, c = 1 yielded lowest [Formula: see text] with concordant results across all scenarios for both data sets. In view of these opposite trends, the optimum choice of c for maximizing selection response across all types of hybrids depends on the size and resources of the breeding program.

PROSPECT methodology for developing procedure-specific pain management recommendations: an update.

The procedure-specific postoperative pain management (PROSPECT) working group develops evidence-based pain management recommendations. PROSPECT methodology is unique and rigorous. However, several limitations were recognised that needed to be addressed, and several new factors were identified that improved PROSPECT methodology. The aim of this article is to present updated PROSPECT methodology for development of recommendations for procedure-specific pain management, focusing on the methodological revisions we will implement. In future, included randomised clinical trials will need to be prospectively registered on a publicly accessible clinical trials database and the study design, including the primary outcome in the registration, should coincide with that in the published manuscript. Placebo-controlled studies in which the analgesic intervention of interest is solely paracetamol, non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2-specific inhibitors or opioids will not be included. Studies comparing one drug in a particular class with another in the same class will also not be included. Future projects will use the Cochrane Collaboration risk of bias tool for quality of reporting of methodology and results. A modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach will be used for grading of level of evidence and strength of recommendations. Finally, the updated PROSPECT methodology addresses several other limitations and implements new factors that all add rigour and transparency to developing procedure-specific pain management recommendations.

A randomised controlled trial of intravenous dexmedetomidine added to dexamethasone for arthroscopic rotator cuff repair and duration of interscalene block.

Prolongation of peripheral nerve blockade by intravenous dexamethasone may be extended by intravenous dexmedetomidine. We randomly allocated 122 participants who had intravenous dexamethasone 0.15 mg.kg-1 before interscalene brachial plexus block for day-case arthroscopic rotator cuff repair to intravenous saline (62 participants) or intravenous dexmedetomidine 1 µg.kg-1 (60 participants). The primary outcome was time from block to first oral morphine intake during the first 48 postoperative hours. Fifty-nine participants reported taking oral morphine, 25/62 after placebo and 34/60 after dexmedetomidine, p = 0.10. The time to morphine intake was shorter after dexmedetomidine, hazard ratio (95%CI) 1.68 (1.00-2.82), p = 0.049. Median (IQR [range]) morphine doses were 0 (0-12.5 [0-50]) mg after control vs. 10 (0-30 [0-50]) after dexmedetomidine, a difference (95%CI) of 7 (0-10) mg, p = 0.056. There was no effect of dexmedetomidine on pain at rest or on movement. Intra-operative hypotension was recorded for 27/62 and 50/60 participants after placebo vs. dexmedetomidine, respectively, p < 0.001. Other outcomes were similar, including durations of sensory and motor block. In conclusion, dexmedetomidine shortened the time to oral morphine consumption after interscalene block combined with dexamethasone and caused intra-operative hypotension.

High-resolution association mapping with libraries of immortalized lines from ancestral landraces.

KEY MESSAGE: Association mapping with immortalized lines of landraces offers several advantages including a high mapping resolution, as demonstrated here in maize by identifying the causal variants underlying QTL for oil content and the metabolite allantoin. Landraces are traditional varieties of crops that present a valuable yet largely untapped reservoir of genetic variation to meet future challenges of agriculture. Here, we performed association mapping in a panel comprising 358 immortalized maize lines from six European Flint landraces. Linkage disequilibrium decayed much faster in the landraces than in the elite lines included for comparison, permitting a high mapping resolution. We demonstrate this by fine-mapping a quantitative trait locus (QTL) for oil content down to the phenylalanine insertion F469 in DGAT1-2 as the causal variant. For the metabolite allantoin, related to abiotic stress response, we identified promoter polymorphisms and differential expression of an allantoinase as putative cause of variation. Our results demonstrate the power of this approach to dissect QTL potentially down to the causal variants, toward the utilization of natural or engineered alleles in breeding. Moreover, we provide guidelines for studies using ancestral landraces for crop genetic research and breeding.

B-flow/spatiotemporal image correlation M-mode: novel ultrasound method that detects decrease in spiral artery luminal diameter in first trimester in primate model of impaired spiral artery remodeling.

OBJECTIVE: To determine if B-flow/spatiotemporal image correlation (STIC) M-mode ultrasonography detects a decrease in spiral artery luminal diameter and volume flow during the first trimester in a non-human primate model of impaired spiral artery remodeling (SAR). METHODS: Pregnant baboons were treated daily with estradiol benzoate on days 25-59 of the first trimester (term, 184 days), or remained untreated. On day 60 of gestation, spiral artery luminal diameter (in seven untreated and 12 estradiol-treated baboons) and volume flow (in four untreated and eight estradiol-treated baboons) were quantified by B-flow/STIC M-mode ultrasonography. In addition, in 15 untreated and 18 estradiol-treated baboons, the percent of spiral arteries remodeled by extravillous trophoblasts was quantified ex vivo by immunohistochemical image analysis on placental basal plate tissue collected via Cesarean section on day 60. Findings were compared between treated and untreated animals. The correlation between spiral artery luminal diameter and percent of SAR was assessed in three untreated and six estradiol-treated baboons which underwent both B-flow/STIC M-mode ultrasound and quantification of SAR. RESULTS: The proportion of spiral arteries greater than 50 µm in diameter remodeled by extravillous trophoblasts was 70% lower in estradiol-treated baboons than in untreated animals (P = 0.000001). Spiral artery luminal diameter in systole and diastole, as quantified by B-flow/STIC M-mode in the first trimester of pregnancy, was 31% (P = 0.014) and 50% (P = 0.005) lower, respectively, and volume flow was 85% lower (P = 0.014), in SAR-suppressed baboons compared with untreated animals. There was a significant correlation between spiral artery luminal diameter as quantified by B-flow/STIC M-mode ultrasonography and the percent of SAR (P < 0.05). CONCLUSION: B-flow/STIC M-mode ultrasonography provides a novel real-time non-invasive method to detect a decrease in uterine spiral artery luminal diameter and volume flow during the cardiac cycle, reflecting decreased distensibility of the vessel wall, in the first trimester in a non-human primate model of defective SAR. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Calibration and validation of predicted genomic breeding values in an advanced cycle maize population.

KEY MESSAGE: Model training on data from all selection cycles yielded the highest prediction accuracy by attenuating specific effects of individual cycles. Expected reliability was a robust predictor of accuracies obtained with different calibration sets. The transition from phenotypic to genome-based selection requires a profound understanding of factors that determine genomic prediction accuracy. We analysed experimental data from a commercial maize breeding programme to investigate if genomic measures can assist in identifying optimal calibration sets for model training. The data set consisted of six contiguous selection cycles comprising testcrosses of 5968 doubled haploid lines genotyped with a minimum of 12,000 SNP markers. We evaluated genomic prediction accuracies in two independent prediction sets in combination with calibration sets differing in sample size and genomic measures (effective sample size, average maximum kinship, expected reliability, number of common polymorphic SNPs and linkage phase similarity). Our results indicate that across selection cycles prediction accuracies were as high as 0.57 for grain dry matter yield and 0.76 for grain dry matter content. Including data from all selection cycles in model training yielded the best results because interactions between calibration and prediction sets as well as the effects of different testers and specific years were attenuated. Among genomic measures, the expected reliability of genomic breeding values was the best predictor of empirical accuracies obtained with different calibration sets. For grain yield, a large difference between expected and empirical reliability was observed in one prediction set. We propose to use this difference as guidance for determining the weight phenotypic data of a given selection cycle should receive in model retraining and for selection when both genomic breeding values and phenotypes are available.

Optimum breeding strategies using genomic and phenotypic selection for the simultaneous improvement of two traits.

KEY MESSAGE: A breeding strategy combining genomic with one-stage phenotypic selection maximizes annual selection gain for net merit. Choice of the selection index strongly affects the selection gain expected in individual traits. Selection indices using genomic information have been proposed in crop-specific scenarios. Routine use of genomic selection (GS) for simultaneous improvement of multiple traits requires information about the impact of the available economic and logistic resources and genetic properties (variances, trait correlations, and prediction accuracies) of the breeding population on the expected selection gain. We extended the R package "selectiongain" from single trait to index selection to optimize and compare breeding strategies for simultaneous improvement of two traits. We focused on the expected annual selection gain (ΔGa) for traits differing in their genetic correlation, economic weights, variance components, and prediction accuracies of GS. For all scenarios considered, breeding strategy GSrapid (one-stage GS followed by one-stage phenotypic selection) achieved higher ΔGa than classical two-stage phenotypic selection, regardless of the index chosen to combine the two traits and the prediction accuracy of GS. The Smith-Hazel or base index delivered higher ΔGa for net merit and individual traits compared to selection by independent culling levels, whereas the restricted index led to lower ΔGa in net merit and divergent results for selection gain of individual traits. The differences among the indices depended strongly on the correlation of traits, their variance components, and economic weights, underpinning the importance of choosing the selection indices according to the goal of the breeding program. We demonstrate our theoretical derivations and extensions of the R package "selectiongain" with an example from hybrid wheat by designing indices to simultaneously improve grain yield and grain protein content or sedimentation volume.

Exploiting genetic diversity in two European maize landraces for improving Gibberella ear rot resistance using genomic tools.

KEY MESSAGE: High genetic variation in two European maize landraces can be harnessed to improve Gibberella ear rot resistance by integrated genomic tools. Fusarium graminearum (Fg) causes Gibberella ear rot (GER) in maize leading to yield reduction and contamination of grains with several mycotoxins. This study aimed to elucidate the molecular basis of GER resistance among 500 doubled haploid lines derived from two European maize landraces, "Kemater Landmais Gelb" (KE) and "Petkuser Ferdinand Rot" (PE). The two landraces were analyzed individually using genome-wide association studies and genomic selection (GS). The lines were genotyped with a 600-k maize array and phenotyped for GER severity, days to silking, plant height, and seed-set in four environments using artificial infection with a highly aggressive Fg isolate. High genotypic variances and broad-sense heritabilities were found for all traits. Genotype-environment interaction was important throughout. The phenotypic (r) and genotypic ([Formula: see text]) correlations between GER severity and three agronomic traits were low (r = - 0.27 to 0.20; [Formula: see text]= - 0.32 to 0.22). For GER severity, eight QTLs were detected in KE jointly explaining 34% of the genetic variance. In PE, no significant QTLs for GER severity were detected. No common QTLs were found between GER severity and the three agronomic traits. The mean prediction accuracies ([Formula: see text]) of weighted GS (wRR-BLUP) were higher than [Formula: see text] of marker-assisted selection (MAS) and unweighted GS (RR-BLUP) for GER severity. Using KE as the training set and PE as the validation set resulted in very low [Formula: see text] that could be improved by using fixed marker effects in the GS model.

Local anaesthetic adjuncts for peripheral regional anaesthesia: a narrative review.

Moderate-to-severe postoperative pain persists for longer than the duration of single-shot peripheral nerve blocks and hence continues to be a problem even with the routine use of regional anaesthesia techniques. The administration of local anaesthetic adjuncts, defined as the concomitant intravenous or perineural injection of one or more pharmacological agents, is an attractive and technically simple strategy to potentially extend the benefits of peripheral nerve blockade beyond the conventional maximum of 8-14 hours. Historical local anaesthetic adjuncts include perineural adrenaline that has been demonstrated to increase the mean duration of analgesia by as little as just over 1 hour. Of the novel local anaesthetic adjuncts, dexmedetomidine and dexamethasone have best demonstrated the capacity to considerably improve the duration of blocks. Perineural dexmedetomidine and dexamethasone increase the mean duration of analgesia by up to 6 hour and 8 hour, respectively, when combined with long-acting local anaesthetics. The evidence for the safety of these local anaesthetic adjuncts continues to accumulate, although the findings of a neurotoxic effect with perineural dexmedetomidine during in-vitro studies are conflicting. Neither perineural dexmedetomidine nor dexamethasone fulfils all the criteria of the ideal local anaesthetic adjunct. Dexmedetomidine is limited by side-effects such as bradycardia, hypotension and sedation, and dexamethasone slightly increases glycaemia. In view of the concerns related to localised nerve and muscle injury and the lack of consistent evidence for the superiority of the perineural vs. systemic route of administration, we recommend the off-label use of systemic dexamethasone as a local anaesthetic adjunct in a dose of 0.1-0.2 mg.kg-1 for all patients undergoing surgery associated with significant postoperative pain.

Epidural vs. transversus abdominis plane block for abdominal surgery - a systematic review, meta-analysis and trial sequential analysis.

Traditionally, pain relief for abdominal surgery has centred on epidural analgesia, but transversus abdominis plane block is increasingly being used. Our aim was to compare the analgesic efficacy and the side-effect profile of transversus abdominis plane block with epidural analgesia in a systematic review with meta-analysis and trial sequential analysis. After a systematic search of the electronic databases, we identified 18 randomised controlled trials with 1220 patients. Confirmed by trial sequential analysis, our first co-primary outcome, postoperative pain score at rest at 12 h, was decreased by a mean difference (95%CI) of 0.69 (0.12-1.27; p = 0.02) with epidural analgesia compared with transversus abdominis plane block, with the quality of evidence graded as low. No difference was found for the second co-primary outcome, postoperative pain score at rest at 24 h, with the quality of evidence rated as very low. Relative to transversus abdominis plane block, epidural analgesia further reduced the need for intravenous morphine-equivalent consumption during the 0-24 h interval by a mean difference (95%CI) of 5.91 mg (2.34-9.49; p = 0.001) at the expense of an increased incidence of hypotension at 72 h, with a risk ratio (95%CI) of 5.88 (2.08-16.67; p < 0.001). Our meta-analysis was limited by detection and performance bias, significant statistical heterogeneity and publication bias. In view of the minimal clinically important difference in postoperative pain scores, epidural analgesia was interpreted to not be clinically different to transversus abdominis plane block after abdominal surgery. With transversus abdominis plane block, the increase in intravenous morphine-equivalent consumption at 24 h should be balanced against the decreased risk of hypotension at 72 h. In choosing between epidural analgesia and transversus abdominis plane block, potential benefits should be balanced against the reported risk of harm, although the confidence in the evidence varied, underlining the uncertainty in our estimates.

Impact of short-acting vs. standard anaesthetic agents on obstructive sleep apnoea: a randomised, controlled, triple-blind trial.

Sleep apnoea is associated with negative outcomes following general anaesthesia. Current recommendations suggest using short-acting anaesthetic agents in preference to standard agents to reduce this risk, but there is currently no evidence to support this. This randomised controlled triple-blind trial tested the hypothesis that a combination of short-acting agents (desflurane-remifentanil) would reduce the postoperative impact of general anaesthesia on sleep apnoea severity compared with standard agents (sevoflurane-fentanyl). Sixty patients undergoing hip arthroplasty under general anaesthesia were randomised to anaesthesia with desflurane-remifentanil or sevoflurane-fentanyl. Respiratory polygraphy was performed before surgery and on the first and third postoperative nights. The primary outcome was the supine apnoea-hypopnoea index on the first postoperative night. Secondary outcomes were the supine apnoea-hypopnoea index on the third postoperative night, and the oxygen desaturation index on the first and third postoperative nights. Additional outcomes included intravenous morphine equivalent consumption and pain scores on postoperative days 1, 2 and 3. Pre-operative sleep study data were similar between groups. Mean (95%CI) values for the supine apnoea-hypopnoea index on the first postoperative night were 18.9 (12.7-25.0) and 21.4 (14.2-28.7) events.h-1 , respectively, in the short-acting and standard anaesthesia groups (p = 0.64). Corresponding values on the third postoperative night were 28.1 (15.8-40.3) and 38.0 (18.3-57.6) events.h-1 (p = 0.34). Secondary sleep- and pain-related outcomes were generally similar in the two groups. In conclusion, short-acting anaesthetic agents did not reduce the impact of general anaesthesia on sleep apnoea severity compared with standard agents. These data should prompt an update of current recommendations.

Efficacy and safety of intrathecal morphine for analgesia after lower joint arthroplasty: a systematic review and meta-analysis with meta-regression and trial sequential analysis.

Widespread adoption of intrathecal morphine into clinical practice is hampered by concerns about its potential side-effects. We undertook a systematic review, meta-analysis and trial sequential analysis with the primary objective of determining the efficacy and safety of intrathecal morphine. Our secondary objective was to determine the dose associated with greatest efficacy and safety. We also assessed the impact of intrathecal morphine on respiratory depression. We systematically searched the literature for trials comparing intrathecal morphine with a control group in patients undergoing hip or knee arthroplasty under spinal anaesthesia. Our primary efficacy outcome was rest pain score (0-10) at 8-12 hours; our primary safety outcome was the rate of postoperative nausea and vomiting within 24 hours. Twenty-nine trials including 1814 patients were identified. Rest pain score at 8-12 hours was significantly reduced in the intrathecal morphine group, with a mean difference (95%CI) of -1.7 (-2.0 to -1.3), p < 0.0001 (19 trials; 1420 patients; high-quality evidence), without sub-group differences between doses (p = 0.35). Intrathecal morphine increased postoperative nausea and vomiting, with a risk ratio (95%CI) of 1.4 (1.3-1.6), p < 0.0001 (24 trials; 1603 patients; high-quality evidence). However, a sub-group analysis by dose revealed that rates of postoperative nausea and vomiting within 24 hours were similar between groups at a dose of 100 µg, while the risk significantly increased with larger doses (p value for sub-group difference = 0.02). Patients receiving intrathecal morphine were no more likely to have respiratory depression, the risk ratio (95%CI) being 0.9 (0.5-1.7), p = 0.78 (16 trials; 1173 patients; high-quality evidence). In conclusion, there is good evidence that intrathecal morphine provides effective analgesia after lower limb arthroplasty, without an increased risk of respiratory depression, but at the expense of an increased rate of postoperative nausea and vomiting. A dose of 100 µg is a 'ceiling' dose for analgesia and a threshold dose for increased rate of postoperative nausea and vomiting.

Genomic prediction with multiple biparental families.

KEY MESSAGE: For genomic prediction within biparental families using multiple biparental families, combined training sets comprising full-sibs from the same family and half-sib families are recommended to reach high and robust prediction accuracy, whereas inclusion of unrelated families is risky and can have negative effects. In recycling breeding, where elite inbreds are recombined to generate new source material, genomic and phenotypic information from lines of numerous biparental families (BPFs) is commonly available for genomic prediction (GP). For each BPF with a large number of candidates in the prediction set (PS), the training set (TS) can be composed of lines from the same full-sib family or multiple related and unrelated families to increase the TS size. GP was applied to BPFs generated in silico and from two published experiments to evaluate the prediction accuracy ([Formula: see text]) of different TS compositions. We compared [Formula: see text] for individual pairs of BPFs using as TS either full-sib, half-sib, or unrelated BPFs. While full-sibs yielded highly positive [Formula: see text] and half-sibs also mostly positive [Formula: see text] values, unrelated families had often negative [Formula: see text], and including these families in a combined TS reduced [Formula: see text]. By simulations, we demonstrated that optimized TS compositions exist, yielding 5-10% higher [Formula: see text] than the TS including all available BPFs. However, identification of poorly predictive families and finding the optimal TS composition with various quantitative-genetic parameters estimated from available data was not successful. Therefore, we suggest omitting unrelated families and combining in the TS full-sib and few half-sib families produced by specific mating designs, with a medium number (~ 50) of genotypes per family. This helps in balancing high [Formula: see text] in GP with a sufficient effective population size of the entire breeding program for securing high short- and long-term selection progress.

Advances in regional anaesthesia and acute pain management: a narrative review.

Regional anaesthesia has undergone several exciting advances in the past few decades. Ultrasound-guided techniques of peripheral nerve blockade have become the gold standard thanks to the associated improvements in efficacy, ease of performance and safety. This has increased the accessibility and utilisation of regional anaesthesia in the anaesthesia community at large and is timely given the mounting evidence for its potential benefits on various patient-centred outcomes, including major morbidity, cancer recurrence and persistent postoperative pain. Ultrasound guidance has also paved the way for refinement of the technical performance of existing blocks concerning simplicity and safety, as well as the development of new regional anaesthesia techniques. In particular, the emergence of fascial plane blocks has further broadened the application of regional anaesthesia in the management of painful conditions of the thorax and abdomen. The preliminary results of investigations into these fascial plane blocks are promising but require further research to establish their true value and role in clinical care. One of the challenges that remains is how best to prolong regional anaesthesia to maximise its benefits while avoiding undue harm. There is ongoing research into optimising continuous catheter techniques and their management, intravenous and perineural pharmacological adjuncts, and sustained-release local anaesthetic molecules. Finally, there is a growing appreciation for the critical role that regional anaesthesia can play in an overall multimodal anaesthetic strategy. This is especially pertinent given the current focus on eliminating unnecessary peri-operative opioid administration.

A randomised controlled trial of shoulder block vs. interscalene brachial plexus block for ventilatory function after shoulder arthroscopy.

The shoulder block may impair ventilatory function and diaphragmatic movement less than the interscalene brachial plexus block. We randomly allocated 30 adults who underwent shoulder arthroscopy under general anaesthesia to ultrasound-guided shoulder block or interscalene block with 20 ml bupivacaine 0.5%. The primary outcome, rate of ultrasound-measured hemidiaphragmatic excursion < 25% of baseline 30 min after blockade, was reduced from 12/15 with brachial plexus block to 2/15 with shoulder block, a difference (95%CI) of 67% (40-93%), p < 0.001. The mean (SD) numeric rating scale pain scores at rest after shoulder block were higher than after interscalene block at two postoperative hours, 1.4 (1.2) vs. 0.3 (0.7), p = 0.02, but lower at 24 postoperative hours, 1.3 (1.3) vs. 3.4 (2.3), p = 0.008. Mean (SD) pain scores on movement in the shoulder and interscalene blocks were similar, with respective values of 1.9 (1.9) vs. 0.7 (1.2), p = 0.13 at two postoperative hours and 3.7 (2.3) vs. 5.3 (2.5), p = 0.41, at 24 postoperative hours.