Blueprint for Phasing and Assembling the Genomes of Heterozygous Polyploids: Application to the Octoploid Genome of Strawberry

The challenge of allelic diversity for assembling haplotypes is exemplified in polyploid genomes containing homoeologous chromosomes of identical ancestry, and significant homologous variation within their ancestral subgenomes. Cultivated strawberry (Fragaria x ananassa) and its wild progenitors are outbred octoploids (2n = 8x = 56) in which up to eight homologous and homoeologous alleles are preserved. This introduces significant risk of haplotype collapse, switching, and chimeric fusions during assembly. Using third generation HiFi sequences from PacBio, we assembled the genome of the day-neutral octoploid F. x ananassa hybrid 'Royal Royce' from the University of California. Our goal was to produce subgenome- and haplotype-resolved assemblies of all 56 chromosomes, accurately reconstructing the parental haploid chromosome complements. Previous work has demonstrated that partitioning sequences by parental phase supports direct assembly of haplotypes in heterozygous diploid species. We leveraged the accuracy of HiFi sequence data with pedigree-informed sequencing to partition long read sequences by phase, and reduce the downstream risk of subgenomic chimeras during assembly. We were able to utilize an octoploid strawberry recombination breakpoint map containing 3.6 M variants to identify and break chimeric junctions, and perform scaffolding of the phase-1 and phase-2 octoploid assemblies. The N50 contiguity of the phase-1 and phase-2 assemblies prior to scaffolding and gap-filling was 11 Mb. The final haploid assembly represented seven of 28 chromosomes in a single contiguous sequence, and averaged fewer than three gaps per pseudomolecule. Additionally, we re-annotated the octoploid genome to produce a custom F. x ananassa repeat library and improved set of gene models based on IsoSeq transcript data and an expansive RNA-seq expression atlas. Here we present 'FaRR1', a gold-standard reference genome of F. x ananassa cultivar 'Royal Royce' to assist future genomic research and molecular breeding of allo-octoploid strawberry.

Download Full-text

Understanding how to facilitate continence for people with dementia in acute hospital settings: a mixed methods systematic review and thematic synthesis

Systematic Reviews ◽

10.1186/s13643-021-01743-0 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Deborah Edwards ◽

Jane Harden ◽

Aled Jones ◽

Katie Featherstone

Keyword(s):

Systematic Review ◽

Mixed Methods ◽

Phase 1 ◽

Significant Risk ◽

Hospital Setting ◽

Acute Hospital ◽

Phase 2 ◽

Thematic Synthesis ◽

Care Plans ◽

People With Dementia

Abstract Background People living with dementia (PLWD) are at significant risk of developing urinary and/or faecal incontinence and are also at risk of functional incontinence or being labelled as being incontinent. Despite the growing population of PLWD and importance of continence care, little is known about the appropriate management, organisation, and interactional strategies for PLWD admitted to acute hospitals. This mixed methods systematic review and thematic synthesis sought to identify successful strategies across all care settings that could then be used to inform innovations in continence care for PLWD in the acute hospital setting. Methods In phase 1, a scoping search of two electronic databases (MEDLINE and PsycINFO) and a consultation with stakeholders was undertaken. Findings were presented to the project steering group and two priority areas for phase 2 were identified which were communication and individualised care plans. In phase 2, eight databases and relevant UK government and other organisational websites were searched for English language citations from inception to August 2020. Critical appraisal was conducted using the Mixed Methods Appraisal Tool (MMAT Version 11). Thematic synthesis was employed and the strength of synthesised findings for the intervention studies was assessed using the GRADE approach and the confidence in synthesised qualitative and survey findings was assessed using the CERQual approach. Results In phase 1, 1348 citations were found and 75 included. In phase 2, 6247 citations were found, 14 research studies and 14 policy and guidance documents were included. The quality of studies varied. Material was synthesised into three overarching syntheses which were: communication this is dignified, person-centred and respectful; communication during outpatients apointments and delivering individualised continence care. Conclusions Recognising that PLWD are not always able to communicate their continence needs verbally is important. Incorporating interpersonal and communication skills into the context of continence care within training for those working with this patient group is crucial for continence to be maintained during an acute admission. Continence care in the acute setting should be tailored to the individual and be developed in partnership with staff and caregivers. Trial registration PROSPERO: CRD42018119495.

Download Full-text

Genomic Diversity and Phylogenetic Analysis of SARS-CoV-2 Circulating in Africa and Other Continents: Implications for Diagnosis, Transmission, and Prevention

Pan African Journal of Life Sciences ◽

10.36108/pajols/0202/40(0370) ◽

2020 ◽

Vol 4 (3) ◽

Author(s):

Idowu A. Taiwo

Keyword(s):

Genome Sequence ◽

Genetic Relatedness ◽

Sequence Data ◽

Phylogenetic Analyses ◽

Phase 1 ◽

Threat Assessment ◽

Population Based ◽

Genomic Diversity ◽

Sequence Length ◽

Phase 2

Background: COVID-19 pandemic caused by SARS-CoV-2 remains a global health threat. Assessment of the genetic relatedness of the genome sequence is a prerequisite to understanding the dynamics, which is important to improve diagnosis and preventive measures. This study determined genomic diversity and SNP characteristic of genomes of SARS-CoV-2 from Africa and the rest of the world. The study involved molecular and phylogenetic analyses to understand the phylogeny and transmission dynamics of the virus. Methods: The SARS-CoV-2 genome sequence data were mined and retrieved from major databases for one year in two phases: Phase 1; December 2019 to May 2020 and Phase 2; June 2020 to December 2020. A maximum of the four sequences that fulfilled the following predetermined criteria from each country were randomly selected for inclusion in the study: (i) sequence length >29,700 nt, (ii) number of Ns in the sequence not >5%, (iii) inclusion of Poly-A tail in the sequence record to ensure completeness. Results: The similarity of SARS-Cov-2 genomes within and between countries was generally high with an average of 99.9%. Thus, SARS-CoV-2 vary between countries and continents by 0.1% as a result of SNPs in its genome. Phylogenetic data revealed multiple origin of SARS-CoV-2 in Africa and also suggested that the virus spreads by ‘founder’s effect’; whereby few viruses newly introduced into a population multiply rapidly and accumulate mutations as they spread quickly by community transfer to create population-based identity. Tree of continental consensus sequences retrieved in Phase 1 suggested that SARS-CoV-2 virus is of two major clusters: African cluster consisting of Africa, Europe, and North America and Asian cluster made up of Asia, South America, and Oceania. However, this clustering pattern vanished in phase 2. Thus, upholding the view that SARS-CoV-2 is constantly evolving. Conclusion: This dynamism and genetic diversity of SARS-CoV-2 have important implications in diagnosis, transmission, and prevention strategy.

Download Full-text

Strategies to Inform Innovations in Continence Care for People Living with Dementia in the Acute Hospital Setting: A Mixed Methods Narrative Synthesis Review

10.21203/rs.3.rs-78042/v1 ◽

2020 ◽

Author(s):

Deborah Edwards ◽

Jane Harden ◽

Aled Jones ◽

Katie Featherstone

Keyword(s):

Systematic Review ◽

Mixed Methods ◽

English Language ◽

Phase 1 ◽

Significant Risk ◽

Hospital Setting ◽

Acute Hospital ◽

Phase 2 ◽

Care Plans ◽

Acute Hospital Setting

Abstract Background: People living with dementia are at significant risk of developing urinary and/or faecal incontinence but are also at risk of functional incontinence or being labelled as being incontinent. Despite the growing population of PLWD and importance of continence care little is known about the appropriate management, organisation, and interactional, strategies for PLWD admitted to acute hospitals. This mixed methods narrative systematic review sought to identify successful strategies across all care settings that could then be used to inform innovations in continence care for PLWD in the acute hospital setting.Methods: In phase 1 a scoping search of two electronic databases (MEDLINE and PSYCinfo) and a consultation with stakeholders was undertaken. Findings from were presented to the project steering and two priority areas for phase 2 were identified which were communication and individualised care plans. In phase 2 eight databases and relevant UK government and other organisational websites were searched for English language citations from inception to August 2020. Critical appraisal was conducted using the Mixed Methods Appraisal Tool (MMA Version 11). Thematic synthesis was employed and the strength of synthesised findings for the intervention studies was assessed using the GRADE approach and the and confidence in synthesised qualitative and survey findings was assessed using the CERQual tool. Results: In phase 1, 1348 citations were found and 75 included. In phase 2, 6247 citations were found 14 research studies and 14 policy and guidance documents were included. The quality of studies varied. Material was synthesized in order to identify the facilitators and barriers around developing communication strategies and individualised management plans in response to the continence needs of PLWD.Conclusions: Recognising that PLWD are not always able to communicate their continence needs verbally is important. Incorporating interpersonal and communication skills into the context of continence care within training for those working with this patient group is crucial for continence to be maintained during an acute admission. Continence care in the acute setting should be tailored to the individual and be developed in partnership with staff and caregivers.Systematic review registration: PROSPERO: CRD42018119495

Download Full-text

Rationalization and internalization

Swiss Journal of Psychology ◽

10.1024//1421-0185.60.4.215 ◽

2001 ◽

Vol 60 (4) ◽

pp. 215-230 ◽

Cited By ~ 6

Author(s):

Jean-Léon Beauvois

Keyword(s):

Phase 1 ◽

Facilitatory Effect ◽

Phase 2 ◽

Causal Explanations ◽

Reduction Effect ◽

Dissonance Reduction

After having been told they were free to accept or refuse, pupils aged 6–7 and 10–11 (tested individually) were led to agree to taste a soup that looked disgusting (phase 1: initial counter-motivational obligation). Before tasting the soup, they had to state what they thought about it. A week later, they were asked whether they wanted to try out some new needles that had supposedly been invented to make vaccinations less painful. Agreement or refusal to try was noted, along with the size of the needle chosen in case of agreement (phase 2: act generalization). The main findings included (1) a strong dissonance reduction effect in phase 1, especially for the younger children (rationalization), (2) a generalization effect in phase 2 (foot-in-the-door effect), and (3) a facilitatory effect on generalization of internal causal explanations about the initial agreement. The results are discussed in relation to the distinction between rationalization and internalization.

Download Full-text

PENERAPAN MODEL QUANTUM LEARNING UNTUK MENINGKATKAN HASIL BELAJAR AUTOCAD SISWA KELAS X TEKNIK PEMESINAN SMK NEGERI 1 STABAT

Jurnal Teknologi Pendidikan (JTP) ◽

10.24114/jtp.v5i1.509 ◽

2013 ◽

Vol 5 (1) ◽

Author(s):

Abdul Hasan Saragih

Keyword(s):

Positive Response ◽

Phase 1 ◽

First Grade ◽

Learning Model ◽

Second Phase ◽

Phase 2 ◽

Phase 3 ◽

The Third ◽

Third Phase ◽

Quantum Learning

This classroom research was conducted on the autocad instructions to the first grade of mechinary class of SMK Negeri 1 Stabat aiming at : (1) improving the student’ archievementon autocad instructional to the student of mechinary architecture class of SMK Negeri 1 Stabat, (2) applying Quantum Learning Model to the students of mechinary class of SMK Negeri 1 Stabat, arising the positive response to autocad subject by applying Quantum Learning Model of the students of mechinary class of SMK Negeri 1 Stabat. The result shows that (1) by applying quantum learning model, the students’ achievement improves significantly. The improvement ofthe achievement of the 34 students is very satisfactory; on the first phase, 27 students passed (70.59%), 10 students failed (29.41%). On the second phase 27 students (79.41%) passed and 7 students (20.59%) failed. On the third phase 30 students (88.24%) passed and 4 students (11.76%) failed. The application of quantum learning model in SMK Negeri 1 Stabat proved satisfying. This was visible from the activeness of the students from phase 1 to 3. The activeness average of the students was 74.31% on phase 1,81.35% on phase 2, and 83.63% on phase 3. (3) The application of the quantum learning model on teaching autocad was very positively welcome by the students of mechinary class of SMK Negeri 1 Stabat. On phase 1 the improvement was 81.53% . It improved to 86.15% on phase 3. Therefore, The improvement ofstudent’ response can be categorized good.

Download Full-text

In situ deteriorating patient simulation in general practice

British Journal of General Practice ◽

10.3399/bjgp20x711425 ◽

2020 ◽

Vol 70 (suppl 1) ◽

pp. bjgp20X711425

Author(s):

Joanna Lawrence ◽

Petronelle Eastwick-Field ◽

Anne Maloney ◽

Helen Higham

Keyword(s):

Life Support ◽

Early Recognition ◽

Phase 1 ◽

Patient Simulation ◽

Medical Emergency ◽

Phase 2 ◽

Action Plans ◽

Integrated Simulation ◽

Deteriorating Patient

BackgroundGP practices have limited access to medical emergency training and basic life support is often taught out of context as a skills-based event.AimTo develop and evaluate a whole team integrated simulation-based education, to enhance learning, change behaviours and provide safer care.MethodPhase 1: 10 practices piloted a 3-hour programme delivering 40 minutes BLS and AED skills and 2-hour deteriorating patient simulation. Three scenarios where developed: adult chest pain, child anaphylaxis and baby bronchiolitis. An adult simulation patient and relative were used and a child and baby manikin. Two facilitators trained in coaching and debriefing used the 3D debriefing model. Phase 2: 12 new practices undertook identical training derived from Phase 1, with pre- and post-course questionnaires. Teams were scored on: team working, communication, early recognition and systematic approach. The team developed action plans derived from their learning to inform future response. Ten of the 12 practices from Phase 2 received an emergency drill within 6 months of the original session. Three to four members of the whole team integrated training, attended the drill, but were unaware of the nature of the scenario before. Scoring was repeated and action plans were revisited to determine behaviour changes.ResultsEvery emergency drill demonstrated improved scoring in skills and behaviour.ConclusionA combination of: in situ GP simulation, appropriately qualified facilitators in simulation and debriefing, and action plans developed by the whole team suggests safer care for patients experiencing a medical emergency.

Download Full-text

Clinical Drug Development for the Treatment of Pulmonary Arterial Hypertension: Collaboration With the Pharmaceutical Industry and Regulatory Agencies

Advances in Pulmonary Hypertension ◽

10.21693/1933-088x-9.4.214 ◽

2010 ◽

Vol 9 (4) ◽

pp. 214-219

Author(s):

Robyn J. Barst

Keyword(s):

Clinical Trials ◽

Pulmonary Arterial Hypertension ◽

Drug Development ◽

Phase 1 ◽

Preclinical Studies ◽

Phase 2 ◽

Phase 3 ◽

Preclinical Testing ◽

New Drug ◽

Pulmonary Arterial

Drug development is the entire process of introducing a new drug to the market. It involves drug discovery, screening, preclinical testing, an Investigational New Drug (IND) application in the US or a Clinical Trial Application (CTA) in the EU, phase 1–3 clinical trials, a New Drug Application (NDA), Food and Drug Administration (FDA) review and approval, and postapproval studies required for continuing safety evaluation. Preclinical testing assesses safety and biologic activity, phase 1 determines safety and dosage, phase 2 evaluates efficacy and side effects, and phase 3 confirms efficacy and monitors adverse effects in a larger number of patients. Postapproval studies provide additional postmarketing data. On average, it takes 15 years from preclinical studies to regulatory approval by the FDA: about 3.5–6.5 years for preclinical, 1–1.5 years for phase 1, 2 years for phase 2, 3–3.5 years for phase 3, and 1.5–2.5 years for filing the NDA and completing the FDA review process. Of approximately 5000 compounds evaluated in preclinical studies, about 5 compounds enter clinical trials, and 1 compound is approved (Tufts Center for the Study of Drug Development, 2011). Most drug development programs include approximately 35–40 phase 1 studies, 15 phase 2 studies, and 3–5 pivotal trials with more than 5000 patients enrolled. Thus, to produce safe and effective drugs in a regulated environment is a highly complex process. Against this backdrop, what is the best way to develop drugs for pulmonary arterial hypertension (PAH), an orphan disease often rapidly fatal within several years of diagnosis and in which spontaneous regression does not occur?

Download Full-text

A phase 1 and randomized controlled phase 2 trial of the safety and efficacy of the combination of gemcitabine and docetaxel with ontuxizumab (MORAb‐004) in metastatic soft‐tissue sarcomas

Cancer ◽

10.1002/cncr.32084 ◽

2019 ◽

Vol 125 (14) ◽

pp. 2445-2454 ◽

Cited By ~ 2

Author(s):

Robin L. Jones ◽

Sant P. Chawla ◽

Steven Attia ◽

Patrick Schöffski ◽

Hans Gelderblom ◽

...

Keyword(s):

Soft Tissue ◽

Phase 1 ◽

Soft Tissue Sarcomas ◽

Phase 2 ◽

Safety And Efficacy ◽

Randomized Controlled ◽

Phase 2 Trial

Download Full-text

Quantitative Checklist for Autism in Toddlers (Q-CHAT). A population screening study with follow-up: the case for multiple time-point screening for autism

BMJ Paediatrics Open ◽

10.1136/bmjpo-2020-000700 ◽

2021 ◽

Vol 5 (1) ◽

pp. e000700

Author(s):

Carrie Allison ◽

Fiona E Matthews ◽

Liliana Ruta ◽

Greg Pasco ◽

Renee Soufer ◽

...

Keyword(s):

Phase 1 ◽

Autism Spectrum ◽

Population Screening ◽

Diagnostic Assessment ◽

Test Accuracy ◽

Multiple Time ◽

Phase 2 ◽

Time Points ◽

Screening Study

ObjectiveThis is a prospective population screening study for autism in toddlers aged 18–30 months old using the Quantitative Checklist for Autism in Toddlers (Q-CHAT), with follow-up at age 4.DesignObservational study.SettingLuton, Bedfordshire and Cambridgeshire in the UK.Participants13 070 toddlers registered on the Child Health Surveillance Database between March 2008 and April 2009, with follow-up at age 4; 3770 (29%) were screened for autism at 18–30 months using the Q-CHAT and the Childhood Autism Spectrum Test (CAST) at follow-up at age 4.InterventionsA stratified sample across the Q-CHAT score distribution was invited for diagnostic assessment (phase 1). The 4-year follow-up included the CAST and the Checklist for Referral (CFR). All with CAST ≥15, phase 1 diagnostic assessment or with developmental concerns on the CFR were invited for diagnostic assessment (phase 2). Standardised diagnostic assessment at both time-points was conducted to establish the test accuracy of the Q-CHAT.Main outcome measuresConsensus diagnostic outcome at phase 1 and phase 2.ResultsAt phase 1, 3770 Q-CHATs were returned (29% response) and 121 undertook diagnostic assessment, of whom 11 met the criteria for autism. All 11 screened positive on the Q-CHAT. The positive predictive value (PPV) at a cut-point of 39 was 17% (95% CI 8% to 31%). At phase 2, 2005 of 3472 CASTs and CFRs were returned (58% response). 159 underwent diagnostic assessment, including 82 assessed in phase 1. All children meeting the criteria for autism identified via the Q-CHAT at phase 1 also met the criteria at phase 2. The PPV was 28% (95% CI 15% to 46%) after phase 1 and phase 2.ConclusionsThe Q-CHAT can be used at 18–30 months to identify autism and enable accelerated referral for diagnostic assessment. The low PPV suggests that for every true positive there would, however, be ~4–5 false positives. At follow-up, new cases were identified, illustrating the need for continued surveillance and rescreening at multiple time-points using developmentally sensitive instruments. Not all children who later receive a diagnosis of autism are detectable during the toddler period.

Download Full-text

Evaluation of health system readiness and coverage of intermittent preventive treatment of malaria in infants (IPTi) in Kambia district to inform national scale-up in Sierra Leone

Malaria Journal ◽

10.1186/s12936-021-03615-3 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Maria Lahuerta ◽

Roberta Sutton ◽

Anthony Mansaray ◽

Oliver Eleeza ◽

Brigette Gleason ◽

...

Keyword(s):

Sierra Leone ◽

Phase 1 ◽

Scale Up ◽

Intermittent Preventive Treatment ◽

Vaccine Dose ◽

Preventive Treatment ◽

Household Survey ◽

Phase 2 ◽

Pentavalent Vaccine

Abstract Background Intermittent preventive treatment of malaria in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a proven strategy to protect infants against malaria. Sierra Leone is the first country to implement IPTi nationwide. IPTi implementation was evaluated in Kambia, one of two initial pilot districts, to assess quality and coverage of IPTi services. Methods This mixed-methods evaluation had two phases, conducted 3 (phase 1) and 15–17 months (phase 2) after IPTi implementation. Methods included: assessments of 18 health facilities (HF), including register data abstraction (phases 1 and 2); a knowledge, attitudes and practices survey with 20 health workers (HWs) in phase 1; second-generation sequencing of SP resistance markers (pre-IPTi and phase 2); and a cluster-sample household survey among caregivers of children aged 3–15 months (phase 2). IPTi and vaccination coverage from the household survey were calculated from child health cards and maternal recall and weighted for the complex sampling design. Interrupted time series analysis using a Poisson regression model was used to assess changes in malaria cases at HF before and after IPTi implementation. Results Most HWs (19/20) interviewed had been trained on IPTi; 16/19 reported feeling well prepared to administer it. Nearly all HFs (17/18 in phase 1; 18/18 in phase 2) had SP for IPTi in stock. The proportion of parasite alleles with dhps K540E mutations increased but remained below the 50% WHO-recommended threshold for IPTi (4.1% pre-IPTi [95%CI 2–7%]; 11% post-IPTi [95%CI 8–15%], p < 0.01). From the household survey, 299/459 (67.4%) children ≥ 10 weeks old received the first dose of IPTi (versus 80.4% for second pentavalent vaccine, given simultaneously); 274/444 (62.5%) children ≥ 14 weeks old received the second IPTi dose (versus 65.4% for third pentavalent vaccine); and 83/217 (36.4%) children ≥ 9 months old received the third IPTi dose (versus 52.2% for first measles vaccine dose). HF register data indicated no change in confirmed malaria cases among infants after IPTi implementation. Conclusions Kambia district was able to scale up IPTi swiftly and provide necessary health systems support. The gaps between IPTi and childhood vaccine coverage need to be further investigated and addressed to optimize the success of the national IPTi programme.

Download Full-text