Evaluation of Staffordshire, Stoke on Trent Allied Health Professionals preceptorship programmes: a mixed method UK study.

AIM: This study aimed to evaluate current preceptorship provision across AHP professions in the Staffordshire, Stoke on Trent (SSOT) region of England to improve consistency, share and optimise best practice. BACKGROUND: Preceptorship, defined as a period of structured transition from newly qualified to an independent practitioner, is thought to improve recruitment and retention of staff and ultimately improve patient care. During the COVID pandemic, SSOT recognised the potential for graduates to lack confidence having had reduced clinical exposure as pre-registration students, and so a likely increased need to support newly qualified staff, and to evaluate existing AHP preceptorship provision. METHODS: An explanatory sequential mixed methods design, utilising a cross sectional survey questionnaire and two subsequent focus groups, explored existing AHP preceptorship in SSOT in 2021. Following ethical approval respondents were recruited via professional networks who completed an online survey questionnaire. Two subsequent focus groups enabled an in-depth exploration of survey results. Descriptive statistics summarised survey data and thematic analysis was used to describe focus group findings. RESULTS: SSOT AHPs (n = 217; 26% preceptees; 47% preceptors) participated in the survey questionnaire and 17 AHPs in the focus groups. 57% of preceptees rated existing preceptorship programmes to be "somewhat, or not effective". Preceptors reported feeling unprepared for their role. Both preceptees and preceptors reported that, post pandemic, most existing programs required revisions to be fit for purpose. Ten pragmatic summary recommendations were made. CONCLUSIONS: Allied Health Professions Preceptorship in SSOT was found to be inconsistent, poorly understood and inadequate. Revisions to preceptorship programs across Staffordshire and Stoke on Trent NHS Trusts have been instigated to reflect changes in AHP practice since the COVID pandemic.

Evaluating the use of statistical and machine learning methods for estimating breed composition of purebred and crossbred animals in thirteen cattle breeds using genomic information.

Introduction: The ability to accurately predict breed composition using genomic information has many potential uses including increasing the accuracy of genetic evaluations, optimising mating plans and as a parameter for genotype quality control. The objective of the present study was to use a database of genotyped purebred and crossbred cattle to compare breed composition predictions using a freely available software, Admixture, with those from a single nucleotide polymorphism Best Linear Unbiased Prediction (SNP-BLUP) approach; a supplementary objective was to determine the accuracy and general robustness of low-density genotype panels for predicting breed composition. Methods: All animals had genotype information on 49,213 autosomal single nucleotide polymorphism (SNPs). Thirteen breeds were included in the analysis and 500 purebred animals per breed were used to establish the breed training populations. Accuracy of breed composition prediction was determined using a separate validation population of 3,146 verified purebred and 4,330 two and three-way crossbred cattle. Results: When all 49,213 autosomal SNPs were used for breed prediction, a minimal absolute mean difference of 0.04 between Admixture vs. SNP-BLUP breed predictions was evident. For crossbreds, the average absolute difference in breed prediction estimates generated using SNP-BLUP and Admixture was 0.068 with a root mean square error of 0.08. Breed predictions from low-density SNP panels were generated using both SNP-BLUP and Admixture and compared to breed prediction estimates using all 49,213 SNPs (representing the gold standard). Breed composition estimates of crossbreds required more SNPs than predicting the breed composition of purebreds. SNP-BLUP required ≥3,000 SNPs to predict crossbred breed composition, but only 2,000 SNPs were required to predict purebred breed status. The absolute mean (standard deviation) difference across all panels <2,000 SNPs was 0.091 (0.054) and 0.315 (0.316) when predicting the breed composition of all animals using Admixture and SNP-BLUP, respectively compared to the gold standard prediction. Discussion: Nevertheless, a negligible absolute mean (standard deviation) difference of 0.009 (0.123) in breed prediction existed between SNP-BLUP and Admixture once ≥3,000 SNPs were considered, indicating that the prediction of breed composition could be readily integrated into SNP-BLUP pipelines used for genomic evaluations thereby avoiding the necessity for a stand-alone software.

Effect of food additives on key bacterial taxa and the mucosa-associated microbiota in Crohn's disease. The ENIGMA study.

Food additives have been linked to the pro-inflammatory microbial dysbiosis associated with Crohn's disease (CD) but the underlying ecological dynamics are unknown. Here, we examine how selection of food additives affects the growth of multiple strains of a key beneficial bacterium (Faecalibacterium prausnitzii), axenic clinical isolates of proinflammatory bacteria from CD patients (Proteus, Morganella, and Klebsiella spp.), and the consortia of mucosa-associated microbiota recovered from multiple Crohn's disease patients. Bacterial growth of the axenic isolates was evaluated using a habitat-simulating medium supplemented with either sodium sulfite, aluminum silicate, carrageenan, carboxymethylcellulose, polysorbate 80, saccharin, sucralose, or aspartame, intended to approximate concentrations found in food. The microbial consortia recovered from post-operative CD patient mucosal biopsy samples were challenged with either carboxymethylcellulose and/or polysorbate 80, and the bacterial communities compared to unchallenged consortia by 16S rRNA gene amplicon profiling. Growth of all F. prausnitzii strains was arrested when either sodium sulfite or polysorbate 80 was added to cultures at baseline or mid-exponential phase of growth, and the inhibitory effects on the Gram-negative bacteria by sodium sulfite were conditional on oxygen availability. The effects from polysorbate 80, saccharin, carrageenan, and/or carboxymethylcellulose on these bacteria were strain-specific. In addition to their direct effects on bacterial growth, polysorbate 80 and/or carboxymethylcellulose can drive profound changes in the CD mucosa-associated microbiota via niche expansion of Proteus and/or Veillonellaceae - both implicated in early Crohn's disease recurrence. These studies on the interaction of food additives with the enteric microbiota provide a basis for dietary management in Crohn's disease.

Self-reported beta-lactam allergy in government and private hospitals in Cape Town, South Africa.

BACKGROUND: Up to a quarter of inpatients in high-income countries (HICs) self-report beta-lactam allergy (BLA), which if incorrect,increases the use of alternative antibiotics, worsening individual health outcomes and driving bacterial resistance. In HICs, up to 95% ofself-reported BLAs are incorrect. The epidemiology of BLA in low- and middle-income African countries is unknown. OBJECTIVES: To describe the epidemiology and de-labelling outcomes of self-reported BLA in hospitalised South African (SA) patients. METHODS: Point-prevalence surveys were conducted at seven hospitals (adult, paediatric, government and privately funded, district andtertiary level) in Cape Town, SA, between April 2019 and June 2021. Ward prescription records and in-person interviews were conductedto identify and risk-stratify BLA patients using the validated PEN-FAST tool. De-labelling was attempted at the tertiary allergy clinic atGroote Schuur Hospital. RESULTS: A total of 1 486 hospital inpatients were surveyed (1 166 adults and 320 children). Only 48 patients (3.2%) self-reported a BLA,with a higher rate in private than in government-funded hospitals (6.3% v. 2.8%; p=0.014). Using the PEN-FAST tool, only 10.4% (n=5/48)of self-reported BLA patients were classified as high risk for true penicillin hypersensitivity. Antibiotics were prescribed to 70.8% (n=34/48)of self-reported BLA patients, with 64.7% (n=22/34) receiving a beta-lactam. Despite three attempts to contact patients for de-labelling atthe allergy clinic, only 3/36 underwent in vivo testing, with no positive results, and 1 patient proceeded to a negative oral challenge. CONCLUSION: Unlike HICs, self-reported BLA is low among inpatients in SA. The majority of those who self-reported BLA were low risk fortype 1 hypersensitivity, but outpatient de-labelling efforts were largely unsuccessful.

Association between the prion protein genotype and animal performance traits in a large multibreed sheep population.

Genetic susceptibility to scrapie, a fatal disease of sheep and goats, is modulated by polymorphisms in the prion protein (PrP). Neither the frequency of the PrP genotypes nor their association with animal performance has been investigated in a large multibreed Irish sheep population. Scrapie genotypes were available on 16 416 animals; the breeds represented included purebred Belclare (733), Charollais (333), Suffolk (739), Texel (1 857), Vendeen (191), and crossbreds (12 563). Performance data on lambing, lamb and ewe performance as well as health traits were available. The association between alternative approaches of describing the PrP genotype (i.e. 15 individually called PrP genotypes, five genotype classes representing susceptibility to scrapie, or number of ARR haplotypes) and animal performance were quantified using animal linear mixed models. All 15 of the possible scrapie genotypes were detected, although the frequency differed by breed. The frequency of the five PrP haplotypes in the entire population were 0.70 (ARR), 0.15 (ARQ), 0.11 (ARH), 0.02 (AHQ) and 0.01 (VRQ); the most susceptible haplotype (VRQ) was only detected in purebred Texels and crossbreds. No association was detected between the PrP genotype of either the animal or dam and any of the lambing traits (i.e. lambing difficulty score, perinatal mortality and birth weight). With the exception of ultrasound muscle depth, no association between the PrP genotype and any of the lamb performance traits (i.e. lamb BW and carcass) was observed. Lambs carrying the category four PrP genotype (i.e. ARR/VRQ) had 1.20 (SE = 0.45) mm, 1.38 (SE = 0.12) mm, 1.47 (S = 0.25) mm shallower ultrasound muscle depth relative to lambs of the less susceptible scrapie categories of 1, 2, 3, respectively (P < 0.05). Nonetheless, no association between PrP genotype and lamb carcass conformation, the ultimate end goal of producers, was detected. Ewe litter size, body condition score or lameness did not differ by PrP genotype of the ewe (P > 0.05). For ewe mature BW, ARH/VRQ ewes differed from most other ewe PrP genotypes and were, on average, 3.79 (SE = 1.66) kg heavier than ARR/ARR genotype ewes. Lamb dag score differed by dam PrP genotype (P < 0.05), although the differences were small. Results from this study show that scrapie is segregating within the Irish sheep population, but the PrP genotype was not associated with most traits investigated and, where associations were detected, the biological significance was minimal. This suggests minimal impact of selection on PrP genotype on performance, at least for the traits investigated in the present study.

The association between breast density and breast cancer pathological response to neoadjuvant chemotherapy.

PURPOSE: Mammographic Density (MD) refers to the amount of fibroglandular breast tissue present in the breast and is an established risk factor for developing breast cancer. The ability to evaluate treatment response dynamically renders neoadjuvant chemotherapy (NACT) the preferred treatment option in many clinical scenarios. Previous studies have suggested that MD can predict patients likely to achieve a pathological complete response (pCR) to NACT. We aimed to determine whether there is a causal relationship between BI-RADS breast composition categories for breast density at diagnosis and the pCR rate and residual cancer burden score (RCB) by performing a retrospective review on consecutive breast cancer patients who received NACT in a tertiary referral centre from 2015 to 2021. METHODS: The Mann-Whitney U Test was used to test for differences between two independent groups (i.e. those who achieved pCR and those who did not). A binary logistic regression model was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) for an association between the independent variables of molecular subtype, MD, histological grade and FNA positivity and the dependant variable of pCR. Statistical analysis was conducted with SPSS (IBM SPSS for Mac, Version 26.0; IBM Corp). RESULTS: 292 patients were included in the current study. There were 124, 155 and 13 patients in the BI-RADS MD category b, c and d, respectively. There were no patients in the BI-RADS MD category a. The patients with less dense breast composition (MD category b) were significantly older than patients with denser breast composition (MD category c, d) (p = 0.001) and patients who had a denser breast composition (MD category d) were more likely to have ER+ tumours. There was no significant difference in PgR status, HER2 status, pathological complete response (pCR), FNA positivity, or RCB class dependent upon the three MD categories. A binary logistic regression revealed that patients with HER2-enriched breast cancer and triple-negative breast cancer are more likely to achieve pCR with an OR of 3.630 (95% CI 1.360-9.691, p = 0.010) and 2.445 (95% CI 1.131-5.288, p = 0.023), respectively. CONCLUSION: Whilst dense MD was associated with ER positivity and these women were less likely to achieve a pCR, MD did not appear to independently predict pCR post-NACT.

A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors.

Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for the screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified two molecules which show anti-nsp5 activity, both in our cell-based assay and in vitro on purified nsp5 protein, and inhibit SARS-CoV-2 replication in A549-ACE2 cells with EC50 values in the 4-8 µM range. The here described high-throughput-compatible assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.

Organic synthesis associated with serpentinization and carbonation on early Mars.

Water-rock interactions are relevant to planetary habitability, influencing mineralogical diversity and the production of organic molecules. We examine carbonates and silicates in the martian meteorite Allan Hills 84001 (ALH 84001), using colocated nanoscale analyses, to characterize the nature of water-rock reactions on early Mars. We find complex refractory organic material associated with mineral assemblages that formed by mineral carbonation and serpentinization reactions. The organic molecules are colocated with nanophase magnetite; both formed in situ during water-rock interactions on Mars. Two potentially distinct mechanisms of abiotic organic synthesis operated on early Mars during the late Noachian period (3.9 to 4.1 billion years ago).

Ipsilateral microcalcifications after breast-conserving surgery: is it possible to differentiate benign from malignant calcifications?

AIM: To analyse stereotactic biopsies of microcalcifications in patients with previous ipsilateral breast-conserving surgery (BCS) to identify the positivity rate, assess for an association between the patient's primary cancer or mammographic appearances of the microcalcifications, and the risk of recurrence. MATERIALS AND METHODS: Relevant patients from 2018-2020 were identified via a retrospective review of the prospectively maintained radiological procedure database. Clinicopathological features of the patients' primary tumour and new calcifications were obtained from the hospital electronic patient record system and the national integrated medical imaging system. RESULTS: Thirty-one percent of recurrences post-ipsilateral BCS presented as isolated microcalcifications on mammography. Fifty-three percent of patients undergoing stereotactic biopsy of ipsilateral calcifications had recurrence. A positive margin status was associated with new or recurrent malignancy. There was no significant correlation between oestrogen-receptor status, sentinel lymph node status, adjuvant radiotherapy or chemotherapy and the risk of recurrence. Calcifications within the tumour bed were more likely to be benign while calcifications within the same quadrant but remote from the tumour bed were more likely malignant. All coarse calcifications were benign while 67% of fine linear/fine linear branching and 89% of fine pleomorphic calcifications were malignant. CONCLUSION: Increased time since diagnosis, positive margin status, fine pleomorphic and fine linear calcifications in the same quadrant as the tumour bed were associated with malignancy. Patients with coarse calcifications and calcifications within the tumour bed may avoid stereotactic biopsy and undergo short-interval surveillance.

Capturing the Influence of Jet Fluctuations on Particles in Plasma Spraying.

Instabilities and fluctuations of the plasma jet in a thermal spray process can have a significant influence on the particle in-flight temperatures and velocities, affecting the properties of resulting plasma-sprayed coatings. Presented in this paper is a novel method for capturing the effects particles are exposed to in the plasma spraying process. High-speed camera images of a plasma jet generated by a cascaded three-cathode plasma generator (TriplexPro-210) were recorded for varying operating conditions. The images are processed using the inverse Abel transform. This transformation accounts for the fact that the images represent a 2D projection of the 3D jet and generates more accurate intensity values that the sprayed particles would experience. These images are then combined with particle tracks resulting from CFD simulations of the plasma jet to match the particles path with the recorded plasma jet. This new method allows a precise description of the plasma intensity experienced by individual particles with a high temporal resolution. The results show a high sensitivity of the method, even detecting the influence on the particles of the plasma jet originating from the cascaded triple arc plasma generator, which is considered as rather stable.

Plant-Based Natural Products and Extracts: Potential Source to Develop New Antiviral Drug Candidates.

Viral infections are among the most complex medical problems and have been a major threat to the economy and global health. Several epidemics and pandemics have occurred due to viruses, which has led to a significant increase in mortality and morbidity rates. Natural products have always been an inspiration and source for new drug development because of their various uses. Among all-natural sources, plant sources are the most dominant for the discovery of new therapeutic agents due to their chemical and structural diversity. Despite the traditional use and potential source for drug development, natural products have gained little attention from large pharmaceutical industries. Several plant extracts and isolated compounds have been extensively studied and explored for antiviral properties against different strains of viruses. In this review, we have compiled antiviral plant extracts and natural products isolated from plants reported since 2015.

Novel strain-level resolution of Crohn's disease mucosa-associated microbiota via an ex vivo combination of microbe culture and metagenomic sequencing.

The mucosa-associated microbiota is widely recognized as a potential trigger for Crohn's disease pathophysiology but remains largely uncharacterised beyond its taxonomic composition. Unlike stool microbiota, the functional characterisation of these communities using current DNA/RNA sequencing approaches remains constrained by the relatively small microbial density on tissue, and the overwhelming amount of human DNA recovered during sample preparation. Here, we have used a novel ex vivo approach that combines microbe culture from anaerobically preserved tissue with metagenome sequencing (MC-MGS) to reveal patient-specific and strain-level differences among these communities in post-operative Crohn's disease patients. The 16 S rRNA gene amplicon profiles showed these cultures provide a representative and holistic representation of the mucosa-associated microbiota, and MC-MGS produced both high quality metagenome-assembled genomes of recovered novel bacterial lineages. The MC-MGS approach also produced a strain-level resolution of key Enterobacteriacea and their associated virulence factors and revealed that urease activity underpins a key and diverse metabolic guild in these communities, which was confirmed by culture-based studies with axenic cultures. Collectively, these findings using MC-MGS show that the Crohn's disease mucosa-associated microbiota possesses taxonomic and functional attributes that are highly individualistic, borne at least in part by novel bacterial lineages not readily isolated or characterised from stool samples using current sequencing approaches.

Concordance rate in cattle and sheep between genotypes differing in Illumina GenCall quality score.

Proper quality control of data prior to downstream analyses is fundamental to ensure integrity of results; quality control of genomic data is no exception. While many metrics of quality control of genomic data exist, the objective of the present study was to quantify the genotype and allele concordance rate between called single nucleotide polymorphism (SNP) genotypes differing in GenCall (GC) score; the GC score is a confidence measure assigned to each Illumina genotype call. This objective was achieved using Illumina beadchip genotype data from 771 cattle (12 428 767 genotypes in total post-editing) and 80 sheep (1 557 360 SNPs genotypes in total post-editing) each genotyped in duplicate. The called genotype with the lowest associated GC score was compared to the genotype called for the same SNP in the same duplicated animal sample but with a GC score of >0.90 (assumed to represent the true genotype). The mean genotype concordance rate for a GC score of <0.300, 0.300-0.549, and ≥0.550 in the cattle (sheep in parenthesis) was 0.9467 (0.9864), 0.9707 (0.9953), and 0.9994 (0.99997) respectively; the respective allele concordance rate was 0.9730 (0.9930), 0.9849 (0.9976), and 0.9997 (0.99998). Hence, concordance eroded as the GC score of the called genotype reduced, albeit the impact was not dramatic and was not very noticeable until a GC score of <0.55. Moreover, the impact was greater and more consistent in the cattle population than in the sheep population. Furthermore, an impact of GC score on genotype concordance rate existed even for the same SNP GenTrain value; the GenTrain value is a statistical score that depicts the shape of the genotype clusters and the relative distance between the called genotype clusters.

The effect of a nursing strike on emergency department operational metrics.

BACKGROUND: In July of 2017, after more than 15 months of negotiations, an academic teaching hospital in Boston failed to reach an agreement on the terms of contract renewal with its nursing union resulting in a strike. Replacement nurses were hired by the hospital to fulfill nursing duties for five days. OBJECTIVES: This study aims to measure the effects of this nursing strike on the patients seen in the emergency department (ED) by examining operational metrics before and during the strike. METHODS: Retrospective analysis of patient visits occurring for the five days of the strike (July 12-16, 2017) compared with the analogous five-day period immediately preceding that of the strike (July 5-9, 2017). RESULTS: During the strike, ED volume decreased by 23.6% (691 vs. 528 visits), and the decrease was more pronounced for adult vs. pediatric visits. There were no differences in patient sex, race/ethnicity or age groups. EMS transports decreased by 49.1% (171 vs. 87 transports). Although patient dispositions were similar in both periods, length of stay decreased for discharged patients (median 204 vs 178 minutes, p=0.01), and did not change significantly for admitted patients (median 322 vs. 320 minutes, p=0.33). There was one patient death in each of the periods. CONCLUSION: Although rare, nursing strikes do occur. These data may be useful for hospitals preparing for a strike.

A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors.

Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for high-throughput screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified four molecules, including the broad-spectrum antiviral merimepodib/VX-497, which show anti-nsp5 activity and inhibit SARS-CoV-2 replication in A549-ACE2 cells with IC 50 values in the 4-21 µM range. The here described assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.

Clinical reporting of radiographs by radiographers: Policy and practice guidance for regional imaging networks.

OBJECTIVES: Radiographer reporting is an essential component of imaging across the United Kingdom. Since the previous policy and practice guidance in 2004 the role and contribution of reporting radiographers has changed significantly. The move to imaging networks further reinforces the need for consistency in scope of practice and clinical governance for radiographer reporting. KEY FINDINGS: This guidance provides a consistent, evidence-based template for planning a reporting service, resourcing, clinical governance, preceptorship, volume and frequency of reporting, a peer learning framework and expected standards. CONCLUSION: Developed for North Central and East London, this framework and standards will help reduce unwarranted variation. IMPLICATIONS FOR PRACTICE: Consistency in practice could help maximise the contribution of radiographer reporting.

Heteropaternal superfecundation frequently occurs in multiple-bearing mob-mated sheep.

Heteropaternal superfecundation may be defined as the fertilisation of two or more ova during the same oestrus cycle as a result of more than one coital act from different males; this results in foetuses being born in the same litter of the same age but different paternity. Heteropaternal superfecundation is more likely to occur in poly-ovulatory species like sheep; moreover, female sheep are often mob-mated with several rams concurrently, thus providing an opportunity for a given female to be served by multiple males during the same oestrus cycle. The objective of the present study was to determine the frequency of heteropaternal superfecundation in six sheep flocks where most of the ewes, lambs and rams were genotyped. A total of 685 multiple-birth litters were available where the sire, dam and all lambs were genotyped. Of the 539 pairs of twins included in the analysis, 160 (i.e. 30%) were sired by two different rams. Of the 137 sets of triplets included in the analysis, 73 (i.e. 53%) were sired by more than one ram. Of the nine sets of quadruplets, eight were sired by two rams with the remaining litter being mono-paternal. The overall incidence of heteropaternal superfecundation among litters was therefore 35%. Given that the incidence of multiple births in these flocks was 65%, heteropaternal superfecundation is expected to be relatively common in sheep; this is especially true as all but two of the litter-mates were polyzygotic. Genotyping of progeny is one practical solution to identity such individuals.

Etiology and perinatal outcome of periviable fetal growth restriction associated with structural or genetic anomaly.

OBJECTIVE: To investigate the etiology and perinatal outcome of periviable fetal growth restriction (FGR) associated with a structural defect or genetic anomaly. METHODS: This was a retrospective study of singleton pregnancies seen at a referral fetal medicine unit between 2005 and 2018, in which FGR (defined as fetal abdominal circumference ≤ 3rd percentile for gestational age) was diagnosed between 22 + 0 and 25 + 6 weeks of gestation. The study group included pregnancies with periviable FGR associated with a genetic or structural anomaly (anomalous FGR), while the control group consisted of structurally and genetically normal pregnancies with periviable FGR (non-anomalous FGR). Results of genetic testing, TORCH screen and postmortem examination, as well as perinatal outcome, were investigated. RESULTS: Of 255 pregnancies complicated by periviable FGR, 188 were eligible; of which 52 (28%) had anomalous FGR and 136 (72%) had non-anomalous FGR. A confirmed genetic abnormality accounted for 17/52 cases (33%) of anomalous FGR, with trisomy 18 constituting over 50% (9/17; 53%). The most common structural defects associated with FGR were central nervous system abnormalities (13/35; 37%). Overall, 12 (23%) cases of anomalous FGR survived the neonatal period. No differences were found in terms of perinatal survival between pregnancies with anomalous and those with non-anomalous FGR. CONCLUSIONS: Most pregnancies complicated by anomalous FGR were associated with a structural defect. The presence of an associated genetic defect was invariably lethal, while those with a structural defect, in the absence of a confirmed genetic abnormality, survived into infancy in over 90% of cases, with an overall one in three chance of perinatal survival. These data can be used for counseling prospective parents. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Population structure and breed composition prediction in a multi-breed sheep population using genome-wide single nucleotide polymorphism genotypes.

Knowledge of population structure and breed composition of a population can be advantageous for a number of reasons; these include designing optimal (cross)breeding strategies in order to maximise non-additive genetic effects, maintaining flockbook integrity by authenticating animals being registered and as a quality control measure in the genotyping process. The objectives of the present study were to 1) describe the population structure of 24 sheep breeds, 2) quantify the breed composition of both flockbook-recorded and crossbred animals using single nucleotide polymorphism BLUP (SNP-BLUP), and 3) quantify the accuracy of breed composition prediction from low-density genotype panels containing between 2000 and 6000 SNPs. In total, 9334 autosomal SNPs on 11 144 flockbook-recorded animals and 1172 crossbred animals were used. The population structure of all breeds was characterised by principal component analysis (PCA) as well as the pairwise breed fixation index (Fst). The total number of animals, all of which were purebred, included in the calibration population for SNP-BLUP was 2579 with the number of animals per breed ranging from 9 to 500. The remaining 9559 flockbook-recorded animals, composite breeds and crossbred animals represented the test population; three breeds were excluded from breed composition prediction. The breed composition predicted using SNP-BLUP with 9334 SNPs was considered the gold standard prediction. The pairwise breed Fst ranged from 0.040 (between the Irish Blackface and Scottish Blackface) to 0.282 (between the Border Leicester and Suffolk). Principal component analysis revealed that the Suffolk from Ireland and the Suffolk from New Zealand formed distinct, non-overlapping clusters. In contrast, the Texel from Ireland and that from New Zealand formed integrated, overlapping clusters. Composite animals such as the Belclare clustered close to its founder breeds (i.e., Finn, Galway, Lleyn and Texel). When all 9334 SNPs were used to predict breed composition, an animal that had a majority breed proportion predicted to be ≥0.90 was defined as purebred for the present study. As the panel density decreased, the predicted breed proportion threshold, used to identify animals as purebred, also decreased (≥0.85 with 6000 SNPs to ≥0.60 with 2000 SNPs). In all, results from the study suggest that breed composition for purebred and crossbred animals can be determined with SNP-BLUP using ≥5000 SNPs.