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Background There is a high prevalence of COVID-19 in university-age students, who are returning to campuses. There is little evidence regarding the feasibility of universal, asymptomatic testing to help control outbreaks in this population. This study aimed to pilot mass COVID-19 testing on a university research park, to assess the feasibility and acceptability of scaling up testing to all staff and students. Methods This was a cross-sectional feasibility study on a university research park in the East of England. All staff and students (5625) were eligible to participate. All participants were offered four PCR swabs, which they self-administered over two weeks. Outcome measures included uptake, drop-out rate, positivity rates, participant acceptability measures, laboratory processing measures, data collection and management measures. Results 798 (76%) of 1053 who registered provided at least one swab; 687 (86%) provided all four; 792 (99%) of 798 who submitted at least one swab had all negative results and 6 participants had one inconclusive result. There were no positive results. 458 (57%) of 798 participants responded to a post-testing survey, demonstrating a mean acceptability score of 4.51/5, with five being the most positive. Conclusions Repeated self-testing for COVID-19 using PCR is feasible and acceptable to a university population. [ABSTRACT FROM AUTHOR]

The article presents the discussion on determining uptake of testing and positivity rates by user characteristics and location for assessing compliance with isolation and links between viral load and symptoms.

Background Menstruation has been shown to be problematic for many women with intellectual disabilities. There has been a greater focus on menstrual suppression or elimination than on help and training to manage menstrual care successfully.Method A cross-sectional questionnaire survey was conducted in England to investigate the help and training currently given to women with intellectual disabilities.Results Twenty-nine percent of the women had never been given the opportunity to learn how to manage their own menstrual care. Where someone had tried to teach the woman, this was most often her mother. Carers were giving considerable amounts of assistance with menstrual care, although some of the women with more profound disabilities were able to manage menstrual care independently.Conclusions The authors argue that all women with intellectual disabilities should have the chance to manage or assist with their own menstrual care, backed by a strategic approach to menstrual education and support. [ABSTRACT FROM AUTHOR]

An overview of the parenting skills and strategies utilized by foster carers looking after adolescents was given in an earlier paper. This paper focuses specifically on the relationship between the behaviour of fostered adolescents and the quality of parenting provided by the carer. In particular, the paper considers the consequences of situations in which fostered young people have a detrimental impact on other children within the foster family, as this was an especially difficult situation for foster carers to manage. Similarly, foster carers appeared to find it difficult to maintain good parenting skills with young people who were at risk due to their own sexual behaviour although, conversely, caring for a young person whose sexual behaviour put others at risk was connected with improved parenting. The quality of parenting provided by the foster carers was also influenced by the level of stress they were experiencing, with increased levels of stress leading to poorer parenting of the fostered adolescent. [ABSTRACT FROM AUTHOR]

Abstract Background Dense genetic maps, together with the efficiency and accuracy of their construction, are integral to genetic studies and marker assisted selection for plant breeding. High-throughput multiplex markers that are robust and reproducible can contribute to both efficiency and accuracy. Multiplex markers are often dominant and so have low information content, this coupled with the pressure to find alternatives to radio-labelling, has led us to adapt the SSAP (sequence specific amplified polymorphism) marker method from a 33P labelling procedure to fluorescently tagged markers analysed from an automated ABI 3730 xl platform. This method is illustrated for multiplexed SSAP markers based on retrotransposon insertions of pea and is applicable for the rapid and efficient generation of markers from genomes where repetitive element sequence information is available for primer design. We cross-reference SSAP markers previously generated using the 33P manual PAGE system to fluorescent peaks, and use these high-throughput fluorescent SSAP markers for further genetic studies in Pisum. Results The optimal conditions for the fluorescent-labelling method used a triplex set of primers in the PCR. These included a fluorescently labelled specific primer together with its unlabelled counterpart, plus an adapter-based primer with two bases of selection on the 3' end. The introduction of the unlabelled specific primer helped to optimise the fluorescent signal across the range of fragment sizes expected, and eliminated the need for extensive dilutions of PCR amplicons. The software (GeneMarker Version 1.6) used for the high-throughput data analysis provided an assessment of amplicon size in nucleotides, peak areas and fluorescence intensity in a table format, so providing additional information content for each marker. The method has been tested in a small-scale study with 12 pea accessions resulting in 467 polymorphic fluorescent SSAP markers of which 260 were identified as having been mapped previously using the radio-labelling technique. Heterozygous individuals from pea cultivar crosses were identifiable after peak area data analysis using the fluorescent SSAP method. Conclusion As well as developing a rapid, and high-throughput marker method for genetic studies, the fluorescent SSAP system improved the accuracy of amplicon scoring, increased the available marker number, improved allele discrimination, and was sensitive enough to identify heterozygous loci in F1 and F2 progeny, indicating the potential to develop high-throughput codominant SSAPs.

During recent years, the national policy of the United Kingdom has increasingly recognized the central place of general practitioners (GPs) in the care of cancer patients, from screening and early diagnosis through to palliative care and bereavement. There are, however, continuing reports of poor control of pain and other symptoms in the community. To investigate general practitioners' prescribing habits and knowledge of some key pain control issues in advanced cancer, a postal questionnaire surveyed a random sample of 450 East Anglian GPs. The response rate was 73.3%. Most respondents were familiar with the modern management of cancer pain, including the World Health Organization approach, the use of oral opioids, and the management of bone pain. There was less awareness of the drug options available for more uncommon situations, especially the dose conversion of oral morphine to subcutaneous diamorphine and drugs that may be used in syringe drivers. GPs in the UK are familiar with the management of the more common pain control problems. However, it is not appropriate to expect GPs to know the details of management of more unusual cancer pain problems. Specialist clinicians need to make themselves readily available to advise their generalist colleagues. The educational implications for GPs are discussed. [ABSTRACT FROM AUTHOR]

The genetic code is one of the most highly conserved features across life. Only a few lineages have deviated from the "universal" genetic code. Amongst the few variants of the genetic code reported to date, the codons UAA and UAG virtually always have the same translation, suggesting that their evolution is coupled. Here, we report the genome and transcriptome sequencing of a novel uncultured ciliate, belonging to the Oligohymenophorea class, where the translation of the UAA and UAG stop codons have changed to specify different amino acids. Genomic and transcriptomic analyses revealed that UAA has been reassigned to encode lysine, while UAG has been reassigned to encode glutamic acid. We identified multiple suppressor tRNA genes with anticodons complementary to the reassigned codons. We show that the retained UGA stop codon is enriched in the 3'UTR immediately downstream of the coding region of genes, suggesting that there is functional drive to maintain tandem stop codons. Using a phylogenomics approach, we reconstructed the ciliate phylogeny and mapped genetic code changes, highlighting the remarkable number of independent genetic code changes within the Ciliophora group of protists. According to our knowledge, this is the first report of a genetic code variant where UAA and UAG encode different amino acids., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 McGowan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Macroautophagy is a ubiquitous homeostasis and health-promoting recycling process of eukaryotic cells, targeting misfolded proteins, damaged organelles and intracellular infectious agents. Some intracellular pathogens such as Salmonella enterica serovar Typhimurium hijack this process during pathogenesis. Here we investigate potential protein-protein interactions between host transcription factors and secreted effector proteins of Salmonella and their effect on host gene transcription. A systems-level analysis identified Salmonella effector proteins that had the potential to affect core autophagy gene regulation. The effect of a SPI-1 effector protein, SopE, that was predicted to interact with regulatory proteins of the autophagy process, was investigated to validate our approach. We then confirmed experimentally that SopE can directly bind to SP1, a host transcription factor, which modulates the expression of the autophagy gene MAP1LC3B . We also revealed that SopE might have a double role in the modulation of autophagy: Following initial increase of MAP1LC3B transcription triggered by Salmonella infection, subsequent decrease in MAP1LC3B transcription at 6h post-infection was SopE-dependent. SopE also played a role in modulation of the autophagy flux machinery, in particular MAP1LC3B and p62 autophagy proteins, depending on the level of autophagy already taking place. Upon typical infection of epithelial cells, the autophagic flux is increased. However, when autophagy was chemically induced prior to infection, SopE dampened the autophagic flux. The same was also observed when most of the intracellular Salmonella cells were not associated with the SCV (strain lacking sifA ) regardless of the autophagy induction status before infection. We demonstrated how regulatory network analysis can be used to better characterise the impact of pathogenic effector proteins, in this case, Salmonella . This study complements previous work in which we had demonstrated that specific pathogen effectors can affect the autophagy process through direct interaction with autophagy proteins. Here we show that effector proteins can also influence the upstream regulation of the process. Such interdisciplinary studies can increase our understanding of the infection process and point out targets important in intestinal epithelial cell defense., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Demeter, Jacomin, Gul, Lister, Lipscombe, Invernizzi, Branchu, Macaulay, Nezis, Kingsley, Korcsmaros and Hautefort.)

We have developed an efficient and inexpensive pipeline for streamlining large-scale collection and genome sequencing of bacterial isolates. Evaluation of this method involved a worldwide research collaboration focused on the model organism Salmonella enterica, the 10KSG consortium. Following the optimization of a logistics pipeline that involved shipping isolates as thermolysates in ambient conditions, the project assembled a diverse collection of 10,419 isolates from low- and middle-income countries. The genomes were sequenced using the LITE pipeline for library construction, with a total reagent cost of less than USD$10 per genome. Our method can be applied to other large bacterial collections to underpin global collaborations., (© 2021. The Author(s).)

Cells are a fundamental unit of life, and the ability to study the phenotypes and behaviors of individual cells is crucial to understanding the workings of complex biological systems. Cell phenotypes (epigenomic, transcriptomic, proteomic, and metabolomic) exhibit dramatic heterogeneity between and within the different cell types and states underlying cellular functional diversity. Cell genotypes can also display heterogeneity throughout an organism, in the form of somatic genetic variation-most notably in the emergence and evolution of tumors. Recent technical advances in single-cell isolation and the development of omics approaches sensitive enough to reveal these aspects of cell identity have enabled a revolution in the study of multicellular systems. In this review, we discuss the technologies available to resolve the genomes, epigenomes, transcriptomes, proteomes, and metabolomes of single cells from a wide variety of living systems., (© 2018 The Authors. Proteomics Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Advances in genome sequencing and assembly technologies are generating many high-quality genome sequences, but assemblies of large, repeat-rich polyploid genomes, such as that of bread wheat, remain fragmented and incomplete. We have generated a new wheat whole-genome shotgun sequence assembly using a combination of optimized data types and an assembly algorithm designed to deal with large and complex genomes. The new assembly represents >78% of the genome with a scaffold N50 of 88.8 kb that has a high fidelity to the input data. Our new annotation combines strand-specific Illumina RNA-seq and Pacific Biosciences (PacBio) full-length cDNAs to identify 104,091 high-confidence protein-coding genes and 10,156 noncoding RNA genes. We confirmed three known and identified one novel genome rearrangements. Our approach enables the rapid and scalable assembly of wheat genomes, the identification of structural variants, and the definition of complete gene models, all powerful resources for trait analysis and breeding of this key global crop., (© 2017 Clavijo et al.; Published by Cold Spring Harbor Laboratory Press.)

Background and Objectives: Voice abnormality is a frequent finding in school age children born at <25 weeks' gestation in Western Australia. The objective of this study was to determine the frequency of voice abnormality, voice-related quality of life, and demographic and intubation factors in this population., Methods: Survivors <25 weeks' gestational age in Western Australia born from 1996 to 2004 were included. Voice assessments (auditory perceptual assessment scale and Pediatric Voice Handicap Index) were carried out by speech pathologists. Intubation history was obtained by retrospective chart review., Results: Of 251 NICU admissions, 154 (61%) survived. Exclusions were based on severe disability (11) or distant residence (13). Of 70 assessed, 67 completed assessments, 4 (6%) were in the normal range and 39 (58%) showed moderate-severe hoarseness. Simultaneous modeling of demographic and intubation characteristics showed an increased odds of moderate-severe voice disorder for children who had more than 5 intubations (odds ratio 6.96, 95% confidence interval 2.07-23.40, P = .002) and for girls relative to boys (odds ratio 3.46, 95% confidence interval 1.12-10.62, P = .030). Tube size and duration of intubation were not significant in the multivariable model. Median scores of parent-reported voice quality of life on the Pediatric Voice Handicap Index were markedly different for preterm (22) and term (3) groups, P < .001., Conclusions: Voice disorders in this population were much more frequent than expected. Further studies are required to assess voice across a broader range of gestational ages, and to investigate voice-protective strategies in infants requiring multiple episodes of intubation.

Objectives/hypothesis: Placement of a Passy-Muir speaking valve is considered best practice for infants and children with a tracheostomy. The Passy-Muir valve enables phonation by redirecting exhaled air via the glottis. Poor tolerance of the Passy-Muir valve is associated with excessive transtracheal pressures on exhalation due to upper airway obstruction. Drilling a small hole in the side of the Passy-Muir valve creates a pressure relief port to allow partial exhalation through the tracheostomy tube while enabling phonation., Study Design: A retrospective case series is presented of 10 aphonic pediatric patients with a tracheostomy trialed with a drilled Passy-Muir valve., Methods: Valve tolerance was assessed clinically and objectively. Handheld manometry was used to determine transtracheal pressures on passive exhalation. All patients had a diagnosis of upper airway obstruction and demonstrated excessive pressures wearing a standard Passy-Muir valve. Patients were assessed wearing a Passy-Muir valve with up to two 1.6-mm holes drilled in the side of the valve. Patients progressed to trials if clinically stable and if transtracheal pressure did not exceed 10 cm H(2) O when wearing the valve., Results: Eight patients progressed to trial, with five of eight patients able to phonate within 1 week and six of eight able to tolerate wearing the valve for ≥ 2-hour periods within 2 weeks of introduction. All eight patients were able to phonate within 6 months of valve introduction., Conclusions: These findings support drilling Passy-Muir speaking valves as a promising option to facilitate phonation in pediatric patients with a tracheostomy for upper airway obstruction., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: Instrumental measures of voice allow practitioners to assess the severity of voice disorders and objectively measure treatment outcomes. Instrumental measures should be calculated on both sustained vowel and connected speech samples to ensure ecological validity. However, there is a lack of appropriate, validated acoustic measurements for use in the pediatric population. The Acoustic Voice Quality Index (AVQI) is a multivariate acoustic measure of dysphonia that has been found to be reliable, valid, and have diagnostic accuracy and response to change in an adult population. This study aimed to evaluate the AVQI in a pediatric population., Study Design: This study was a prospective observational study of a sample of dysphonic and normophonic children., Methods: Sixty-seven preterm participants (born at less than 25 weeks gestation) aged between 6 and 15 years were recruited. Participants were excluded because of either inability to comply with task requirements or other speech-related factors that affected acoustic measurement. Forty normophonic term-born participants aged between 5 and 15 years were also recruited. AVQI analysis was conducted on a prolonged vowel sample and a sample of continuous speech., Results: The AVQI was found to have diagnostic accuracy and specificity in this population of children with and without dysphonia. It was moderately correlated with ratings of severity on the GRBAS (overall grade of hoarseness (G), roughness (R), breathiness (B), aesthenicity (A), and strain (S)), a subjective rating scale. The threshold for pathology of this sample of 3.46 showed strong sensitivity, specificity, and accuracy, with good-to-excellent likelihood ratios., Conclusions: This study found that the AVQI has diagnostic accuracy in a pediatric population, suggesting that it is an appropriate assessment tool to determine the presence and severity of pediatric voice disorders., (Copyright © 2012 The Voice Foundation. All rights reserved.)

To compare the long-term outcome of women with primary or locally advanced breast cancer randomised to receive either doxorubicin and cyclophosphamide (AC) or doxorubicin and docetaxel (AD) as primary chemotherapy. Eligible patients with histologic-proven breast cancer with primary tumours > or = 3 cm, inflammatory or locally advanced disease, and no evidence of distant metastases, were randomised to receive a maximum of 6 cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) i/v or doxorubicin (50 mg/m(2)) plus docetaxel (75 mg/m(2)) i/v every 3 weeks, followed by surgery on completion of chemotherapy. Clinical and pathologic responses have previously been reported. Time to relapse, site of relapse, and all-cause mortality were recorded. This updated analysis compares long-term disease-free (DFS) and overall survival (OS) using stratified log rank methods. A total of 363 patients were randomised to AC (n = 181) or AD (n = 182). A complete pathologic response was observed in 16% for AC and 12% for AD (P = 0.43). The number of patients with positive axillary nodes at surgery with AC was 61% and AD 66% (P = 0.36). At a median follow-up of 99 months there is no significant difference between the two groups for DFS (P = 0.20) and OS (P = 0.24). Deaths were due to metastatic breast cancer in 96% of patients. Our data do not support a clinical benefit for simultaneous administration of AD compared with AC. However, the data do not exclude a smaller benefit than the study was powered to detect and are consistent with an increase in both disease-free and overall survival of about 5% for AD compared with AC. Outcome is consistent with the pathologic complete response following surgery.

Background: A multidisciplinary approach has been shown to be of benefit in the prevention of lower limb ulceration and amputation in patients with diabetes, but there is less information on the role of such an approach in patients receiving dialysis treatment., Objective: The purpose of the present study was to determine whether the institution of a chiropody program would result in fewer amputations in diabetic patients on peritoneal dialysis (PD)., Design: Retrospective chart review., Setting: The PD program at a tertiary-care hospital., Patients: Patients with diabetes that were enrolled in the PD program between January 1997 and December 1999, inclusive, that were offered the opportunity to see a chiropodist, and that agreed to be seen. A total of 132 patients were included., Intervention: Education about foot care, assessment, and, in some instances, treatment by a chiropodist., Results: Patients with an amputation were more likely to be male (p < 0.01) and have peripheral vascular disease (p < 0.001) compared to those without an amputation. They also had a lower average mean arterial pressure (p < 0.05), lower weekly creatinine clearance (p < 0.01), higher mean erythropoietin dose (p < 0.05), and longer duration of end-stage renal disease (p < 0.001). Factors that were predictive of shorter time to death or amputation were older age [hazard ratio (HR) = 1.03, p < 0.05], peripheral vascular disease (HR = 2.66, p< 0.01), and cerebrovascular disease (HR = 2.70, p< 0.01). Being seen by a chiropodist was protective (HR = 0.39, p < 0.01)., Conclusion: The current study suggests that a chiropody program may help to prevent amputation in patients with diabetes on PD.

The BRCA2 372 HH genotype defined by the BRCA2 N372H nonconservative amino acid substitution polymorphism was recently reported to be associated with a small increased risk of breast cancer. We investigated whether this polymorphism was associated with ovarian cancer risk by conducting British and Australian case-control comparisons in parallel, including a total sample of 1,121 ovarian cancer cases and 2,643 controls. There was no difference in genotype frequency between control groups from the 2 studies (p = 0.9). The HH genotype was associated with an increased risk of ovarian cancer in both studies, and the risk estimate for the pooled studies was 1.36 (95% CI 1.04-1.77, p = 0.03). There was also a suggestion that this risk may be greater for ovarian cancers of the serous subtype for both studies, with an OR (95% CI) of 1.66 (1.17-2.54) for the 2 studies combined (p = 0.005). The BRCA2 372 HH genotype appears to be associated with an increased risk of ovarian cancer of a similar magnitude to that reported for breast cancer., (Copyright 2002 Wiley-Liss, Inc.)

The problems associated with rural and remote health have been widely recognised by health workers, rural communities and health professions for some time. Yet it has only been in the past decade that any concerted effort has been made to address rural health issues. Today the state of health in rural Australia remains less than optimal. The tenth anniversary of the Australian Journal of Rural Health provides the opportunity to reflect on what progress has been achieved over the past decade, to recognise those factors that have contributed most to the implementation of policies designed to address the health needs of rural and remote Australians, and to discuss outstanding impediments and barriers to resolving rural health issues.