Next Generation Sequencing Assay for Detection of Circulating HPV DNA (cHPV-DNA) in Patients Undergoing Radical (Chemo)Radiotherapy in Anal Squamous Cell Carcinoma (ASCC).

Background: Following chemo-radiotherapy (CRT) for human papilloma virus positive (HPV+) anal squamous cell carcinoma (ASCC), detection of residual/recurrent disease is challenging. Patients frequently undergo unnecessary repeated biopsies for abnormal MRI/clinical findings. In a pilot study we assessed the role of circulating HPV-DNA in identifying "true" residual disease. Methods: We prospectively collected plasma samples at baseline (n = 21) and 12 weeks post-CRT (n = 17). Circulating HPV-DNA (cHPV DNA) was measured using a novel next generation sequencing (NGS) assay, panHPV-detect, comprising of two primer pools covering distinct regions of eight high-risk HPV genomes (16, 18, 31, 33, 35, 45, 52, and 58) to detect circulating HPV-DNA (cHPV DNA). cHPV-DNA levels post-CRT were correlated to disease response. Results: In pre-CRT samples, panHPV-detect demonstrated 100% sensitivity and specificity for HPV associated ASCC. PanHPV-detect was able to demonstrate cHPV-DNA in 100% (9/9) patients with T1/T2N0 cancers. cHPV-DNA was detectable 12 weeks post CRT in just 2/17 patients, both of whom relapsed. 1/16 patients who had a clinical complete response (CR) at 3 months post-CRT but relapsed at 9 months and 1/1 patient with a partial response (PR). PanHPV-detect demonstrated 100% sensitivity and specificity in predicting response to CRT. Conclusion: We demonstrate that panHPV-detect, an NSG assay is a highly sensitive and specific test for the identification of cHPV-DNA in plasma at diagnosis. cHPV-DNA post-treatment may predict clinical response to CRT

Non-immune fetal hydrops: etiology and outcome according to gestational age at diagnosis.

OBJECTIVE: Fetal hydrops is associated with increased perinatal morbidity and mortality. The etiology and outcome of fetal hydrops may differ according to the gestational age at diagnosis. The aim of this study was to evaluate the cause, evolution and outcome of non-immune fetal hydrops (NIFH), according to the gestational age at diagnosis. METHODS: This was a retrospective cohort study of all singleton pregnancies complicated by NIFH, at the Fetal Medicine Unit at St George's University Hospital, London, UK, between 2000 and 2018. All fetuses had detailed anomaly and cardiac ultrasound scans, karyotyping and infection screening. Prenatal diagnostic and therapeutic intervention, gestational age at diagnosis and delivery, as well as pregnancy outcome, were recorded. Regression analysis was used to test for potential association between possible risk factors and perinatal mortality. RESULTS: We included 273 fetuses with NIFH. The etiology of the condition varied significantly in the three trimesters. Excluding 30 women who declined invasive testing, the cause of NIFH was defined as unknown in 62 of the remaining 243 cases (25.5%). Chromosomal aneuploidy was the most common cause of NIFH in the first trimester. It continued to be a significant etiologic factor in the second trimester, along with congenital infection. In the third trimester, the most common etiology was cardiovascular abnormality. Among the 152 (55.7%) women continuing the pregnancy, 48 (31.6%) underwent fetal intervention, including the insertion of pleuroamniotic shunts, fetal blood transfusion and thoracentesis. Fetal intervention was associated significantly with lower perinatal mortality (odds ratio (OR), 0.30 (95% CI, 0.14-0.61); P  0.05). CONCLUSIONS: An earlier gestational age at diagnosis of NIFH was associated with an increased risk of aneuploidy and worse pregnancy outcome, including a higher risk of perinatal loss. Fetal therapy was associated significantly with lower perinatal mortality. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology

Comparing the effect of STan (cardiotocographic electronic fetal monitoring (CTG) plus analysis of the ST segment of the fetal electrocardiogram) with CTG alone on emergency caesarean section rates: study protocol for the STan Australian Randomised controlled Trial (START).

BACKGROUND: Cardiotocography is almost ubiquitous in its use in intrapartum care. Although it has been demonstrated that there is some benefit from continuous intrapartum fetal monitoring using cardiotocography, there is also an increased risk of caesarean section which is accompanied by short-term and long-term risks to the mother and child. There is considerable potential to reduce unnecessary operative delivery with up to a 60% false positive diagnosis of fetal distress using cardiotocography alone. ST analysis of the fetal electrocardiogram is a promising adjunct to cardiotocography alone, and permits detection of metabolic acidosis of the fetus, potentially reducing false positive diagnosis of fetal distress. METHODS: This study will be a single-centre, parallel-group, randomised controlled trial, conducted over 3 years. The primary hypothesis will be that the proportion of women with an emergency caesarean section on ST analysis will not equal that for women on cardiotocography monitoring alone. Participants will be recruited at the Women's and Children's Hospital, a high-risk specialty facility with approximately 5000 deliveries per annum. A total of 1818 women will be randomised to the treatment or conventional arm with an allocation ratio of 1:1, stratified by parity. The primary outcome is emergency caesarean section (yes/no). Statistical analysis will follow standard methods for randomised trials and will be performed on an intention-to-treat basis. Secondary maternal and neonatal outcomes will also be analysed. Additional study outcomes include psychosocial outcomes, patient preferences and cost-effectiveness. DISCUSSION: Approximately 20% of Australian babies are delivered by emergency caesarean section. This will be the first Australian trial to examine ST analysis of the fetal electrocardiogram as an adjunct to cardiotocography as a potential method for reducing this proportion. The trial will be among the first to comprehensively examine ST analysis, taking into account the impact on psychosocial well-being as well as cost-effectiveness. This research will provide Australian evidence for clinical practice and guideline development as well as for policy-makers and consumers to make informed, evidence-based choices about care in labour. TRIAL REGISTRATION: ANZCTR, ACTRN1261800006268 . Registered on 19 January 2018

Animal board invited review: advances in proteomics for animal and food sciences

Animal production and health (APH) is an important sector in the world economy, representing a large proportion of the budget of all member states in the European Union and in other continents. APH is a highly competitive sector with a strong emphasis on innovation and, albeit with country to country variations, on scientific research. Proteomics (the study of all proteins present in a given tissue or fluid - i.e. the proteome) has an enormous potential when applied to APH. Nevertheless, for a variety of reasons and in contrast to disciplines such as plant sciences or human biomedicine, such potential is only now being tapped. To counter such limited usage, 6 years ago we created a consortium dedicated to the applications of Proteomics to APH, specifically in the form of a Cooperation in Science and Technology (COST) Action, termed FA1002 - Proteomics in Farm Animals: www.cost-faproteomics.org. In 4 years, the consortium quickly enlarged to a total of 31 countries in Europe, as well as Israel, Argentina, Australia and New Zealand. This article has a triple purpose. First, we aim to provide clear examples on the applications and benefits of the use of proteomics in all aspects related to APH. Second, we provide insights and possibilities on the new trends and objectives for APH proteomics applications and technologies for the years to come. Finally, we provide an overview and balance of the major activities and accomplishments of the COST Action on Farm Animal Proteomics. These include activities such as the organization of seminars, workshops and major scientific conferences, organization of summer schools, financing Short-Term Scientific Missions (STSMs) and the generation of scientific literature. Overall, the Action has attained all of the proposed objectives and has made considerable difference by putting proteomics on the global map for animal and veterinary researchers in general and by contributing significantly to reduce the East-West and North-South gaps existing in the European farm animal research. Future activities of significance in the field of scientific research, involving members of the action, as well as others, will likely be established in the future.European Science Foundation (Brussels, Belgium)info:eu-repo/semantics/publishedVersio

Beat synchronization across the lifespan: intersection of development and musical experience

Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance of synchronization in childhood through older adulthood in a large cohort of participants (N = 145), and also ask how it may be altered by musical experience. We employed a uniform assessment of beat synchronization for all participants and compared performance developmentally and between individuals with and without musical experience. We show that the ability to consistently tap along to a beat improves with age into adulthood, yet in older adulthood tapping performance becomes more variable. Also, from childhood into young adulthood, individuals are able to tap increasingly close to the beat (i.e., asynchronies decline with age), however, this trend reverses from younger into older adulthood. There is a positive association between proportion of life spent playing music and tapping performance, which suggests a link between musical experience and auditory-motor integration. These results are broadly consistent with previous investigations into the development of beat synchronization across the lifespan, and thus complement existing studies and present new insights offered by a different, large cross-sectional sample

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Evidence for multiple rhythmic skills

Rhythms, or patterns in time, play a vital role in both speech and music. Proficiency in a number of rhythm skills has been linked to language ability, suggesting that certain rhythmic processes in music and language rely on overlapping resources. However, a lack of understanding about how rhythm skills relate to each other has impeded progress in understanding how language relies on rhythm processing. In particular, it is unknown whether all rhythm skills are linked together, forming a single broad rhythmic competence, or whether there are multiple dissociable rhythm skills. We hypothesized that beat tapping and rhythm memory/sequencing form two separate clusters of rhythm skills. This hypothesis was tested with a battery of two beat tapping and two rhythm memory tests. Here we show that tapping to a metronome and the ability to adjust to a changing tempo while tapping to a metronome are related skills. The ability to remember rhythms and to drum along to repeating rhythmic sequences are also related. However, we found no relationship between beat tapping skills and rhythm memory skills. Thus, beat tapping and rhythm memory are dissociable rhythmic aptitudes. This discovery may inform future research disambiguating how distinct rhythm competencies track with specific language functions

Enhanced Syllable Discrimination Thresholds in Musicians

Speech processing inherently relies on the perception of specific, rapidly changing spectral and temporal acoustic features. Advanced acoustic perception is also integral to musical expertise, and accordingly several studies have demonstrated a significant relationship between musical training and superior processing of various aspects of speech. Speech and music appear to overlap in spectral and temporal features; however, it remains unclear which of these acoustic features, crucial for speech processing, are most closely associated with musical training. The present study examined the perceptual acuity of musicians to the acoustic components of speech necessary for intra-phonemic discrimination of synthetic syllables. We compared musicians and non-musicians on discrimination thresholds of three synthetic speech syllable continua that varied in their spectral and temporal discrimination demands, specifically voice onset time (VOT) and amplitude envelope cues in the temporal domain. Musicians demonstrated superior discrimination only for syllables that required resolution of temporal cues. Furthermore, performance on the temporal syllable continua positively correlated with the length and intensity of musical training. These findings support one potential mechanism by which musical training may selectively enhance speech perception, namely by reinforcing temporal acuity and/or perception of amplitude rise time, and implications for the translation of musical training to long-term linguistic abilities.Grammy FoundationWilliam F. Milton Fun