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Article ; Online: Paediatric high-flow nasal cannula therapy in children with bronchiolitis: A retrospective safety and efficacy study in a non-tertiary environment.

Davison, Michelle / Watson, Mike / Wockner, Leesa / Kinnear, Frances

2017 Volume 29, Issue 2, Page(s) 198–203

Abstract: Objective: The objective was to examine the safety and efficacy of high-flow nasal cannula (HFNC) therapy for children with bronchiolitis in a non-tertiary paediatric setting.: Methods: This was a single-centre retrospective study conducted over 26 ... ...

Abstract	Objective: The objective was to examine the safety and efficacy of high-flow nasal cannula (HFNC) therapy for children with bronchiolitis in a non-tertiary paediatric setting. Methods: This was a single-centre retrospective study conducted over 26 months (March 2013-April 2015) on children aged 1-23 months with suspected bronchiolitis, who commenced on HFNC therapy in either the ED or the ward. Changes with respect to baseline data were analysed for effect on work of breathing (WOB), heart rate (HR) and respiratory rate (RR). Data was analysed using a linear mixed effects model and adjusted for age (≤12 months and >12 months) and location (ED vs ward). Transfer to a tertiary environment, escalation of care and adverse event rates were also recorded. Results: A total of 61 children commenced on HFNC therapy, with flow rates ranging from 0.6 to 3.3L/kg/min. The proportion of patients with higher WOB scores appeared to reduce within 60 min of initiation of therapy. There was also a progressive reduction in surrogate markers of respiratory distress (HR and RR), with significant reductions evident by 60 min (P < 0.05). There were no adverse events related to HFNC therapy. The transfer rate was 13%. It was predominantly due to lack of improvement of physiological parameters post initiation of HFNC therapy. None of the transferred patients required escalation of care. Conclusion: Within the limitations of this study it appears HFNC therapy may be safely commenced in both age groups in a non-tertiary ED or ward, with an appropriate level of observation and robust transfer criteria.
MeSH term(s)	Cannula/utilization ; Cohort Studies ; Emergency Service, Hospital/organization & administration ; Emergency Service, Hospital/statistics & numerical data ; Female ; Humans ; Infant ; Male ; Oxygen Inhalation Therapy/methods ; Oxygen Inhalation Therapy/utilization ; Patient Outcome Assessment ; Patient Safety/standards ; Patient Safety/statistics & numerical data ; Pediatrics/methods ; Pediatrics/standards ; Pediatrics/statistics & numerical data ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2017-04
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2161824-0
ISSN	1742-6723 ; 1742-6731 ; 1035-6851
ISSN (online)	1742-6723
ISSN	1742-6731 ; 1035-6851
DOI	10.1111/1742-6723.12741
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Article ; Online: Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses.

Bahl, Kapil / Senn, Joe J / Yuzhakov, Olga / Bulychev, Alex / Brito, Luis A / Hassett, Kimberly J / Laska, Michael E / Smith, Mike / Almarsson, Örn / Thompson, James / Ribeiro, Amilcar Mick / Watson, Mike / Zaks, Tal / Ciaramella, Giuseppe

Molecular therapy : the journal of the American Society of Gene Therapy

2022 Volume 30, Issue 8, Page(s) 2874

Language	English
Publishing date	2022-08-02
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2022.07.013
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Article ; Online: Is UK general practice education and training now fit for purpose?

Patterson, Fiona / Howe, Amanda / Tavabie, Abdol / Watson, Mike

The British journal of general practice : the journal of the Royal College of General Practitioners

2013 Volume 63, Issue 616, Page(s) 567–568

MeSH term(s)	Clinical Competence/standards ; Curriculum ; Education, Medical, Graduate/methods ; General Practice/education ; Humans ; Inservice Training/methods ; Physician's Role ; United Kingdom
Language	English
Publishing date	2013-10-09
Publishing country	England
Document type	Editorial
ZDB-ID	1043148-2
ISSN	1478-5242 ; 0035-8797 ; 0960-1643
ISSN (online)	1478-5242
ISSN	0035-8797 ; 0960-1643
DOI	10.3399/bjgp13X674305
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Article ; Online: Identification of a Novel

Boone, Megann A / Taslim, Cenny / Crow, Jesse C / Selich-Anderson, Julia / Watson, Mike / Heppner, Peter / Hamill, James / Wood, Andrew C / Lessnick, Stephen L / Winstanley, Mark

Molecular cancer research : MCR

2021 Volume 19, Issue 11, Page(s) 1795–1801

Abstract: Ewing sarcoma is a pediatric bone cancer defined by a chromosomal translocation fusing one of the FET family members to an ETS transcription factor. There have been seven reported chromosomal translocations, with the most recent reported over a decade ... ...

Abstract	Ewing sarcoma is a pediatric bone cancer defined by a chromosomal translocation fusing one of the FET family members to an ETS transcription factor. There have been seven reported chromosomal translocations, with the most recent reported over a decade ago. We now report a novel FET/ETS translocation involving
MeSH term(s)	Humans ; Infant, Newborn ; Oncogene Proteins, Fusion/genetics ; Proto-Oncogene Proteins c-ets/metabolism ; RNA-Binding Protein FUS/metabolism ; Sarcoma, Ewing/genetics ; Sarcoma, Ewing/pathology ; Translocation, Genetic/genetics
Chemical Substances	ETV4 protein, human ; FUS protein, human ; Oncogene Proteins, Fusion ; Proto-Oncogene Proteins c-ets ; RNA-Binding Protein FUS
Language	English
Publishing date	2021-08-31
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-21-0354
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Article ; Online: A case of congenital solitary testicular myofibroma associated with an undescended testis.

Yozu, Masato / Taghavi, Kiarash / Ervine, Evelyn / Morreau, Philip / Watson, Mike

Pathology

2013 Volume 45, Issue 5, Page(s) 517–519

MeSH term(s)	Cryptorchidism/complications ; Cryptorchidism/diagnosis ; Humans ; Infant, Newborn ; Laparoscopy ; Male ; Myofibroma/congenital ; Myofibroma/diagnosis ; Myofibroma/pathology ; Risk Factors ; Testicular Neoplasms/congenital ; Testicular Neoplasms/diagnosis ; Testicular Neoplasms/pathology ; Treatment Outcome
Language	English
Publishing date	2013-08
Publishing country	England
Document type	Case Reports ; Letter
ZDB-ID	7085-3
ISSN	1465-3931 ; 0031-3025
ISSN (online)	1465-3931
ISSN	0031-3025
DOI	10.1097/PAT.0b013e3283639bf6
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Article: mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials

Feldman, Robert A / (Mick) Ribeiro, Amilcar / Almarsson, Ӧrn / Ciaramella, Giuseppe / Fuhr, Rainard / Laska, Michael E / Panther, Lori / Pujar, Hari S / Senn, Joseph J / Smith, Mike / Smolenov, Igor / Thompson, James / Watson, Mike / Zaks, Tal

Vaccine. 2019 May 31, v. 37, no. 25

2019

Abstract: We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses.Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled participants between December 2015 ... ...

Abstract	We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses.Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled participants between December 2015 and August 2017 at single centers in Germany (H10N8) and USA (H7N9). Healthy adults (ages 18–64 years for H10N8 study; 18–49 years for H7N9 study) participated. Participants received vaccine or placebo in a 2-dose vaccination series 3 weeks apart. H10N8 intramuscular (IM) dose levels of 25, 50, 75, 100, and 400 μg and intradermal dose levels of 25 and 50 μg were evaluated. H7N9 IM 10-, 25-, and 50-μg dose levels were evaluated; 2-dose series 6 months apart was also evaluated. Primary endpoints were safety (adverse events) and tolerability. Secondary immunogenicity outcomes included humoral (hemagglutination inhibition [HAI], microneutralization [MN] assays) and cell-mediated responses (ELISPOT assay).H10N8 and H7N9 mRNA IM vaccines demonstrated favorable safety and reactogenicity profiles. No vaccine-related serious adverse event was reported. For H10N8 (N = 201), 100-μg IM dose induced HAI titers ≥ 1:40 in 100% and MN titers ≥ 1:20 in 87.0% of participants. The 25-μg intradermal dose induced HAI titers > 1:40 in 64.7% of participants compared to 34.5% of participants receiving the IM dose. For H7N9 (N = 156), IM doses of 10, 25, and 50 μg achieved HAI titers ≥ 1:40 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titers ≥ 1:20 were achieved by 100% in the 10- and 25-μg groups and 96.6% in the 50-μg group. Seroconversion rates were 78.3% (HAI) and 87.0% (MN) for H10N8 (100 μg IM) and 96.3% (HAI) and 100% (MN) in H7N9 (50 μg). Significant cell-mediated responses were not detected in either study.The first mRNA vaccines against H10N8 and H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses.ClinicalTrials.gov NCT03076385 and NCT03345043.
Keywords	adults ; birds ; clinical trials ; hemagglutination ; humoral immunity ; immunogenicity ; influenza ; messenger RNA ; Orthomyxoviridae ; pandemic ; seroconversion ; vaccination ; vaccines ; Germany ; United States
Language	English
Dates of publication	2019-0531
Size	p. 3326-3334.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2019.04.074
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Article ; Online: mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials.

Feldman, Robert A / Fuhr, Rainard / Smolenov, Igor / Mick Ribeiro, Amilcar / Panther, Lori / Watson, Mike / Senn, Joseph J / Smith, Mike / Almarsson, Ӧrn / Pujar, Hari S / Laska, Michael E / Thompson, James / Zaks, Tal / Ciaramella, Giuseppe

Vaccine

2019 Volume 37, Issue 25, Page(s) 3326–3334

Abstract: Background: We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses.: Methods: Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled ... ...

Abstract	Background: We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses. Methods: Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled participants between December 2015 and August 2017 at single centers in Germany (H10N8) and USA (H7N9). Healthy adults (ages 18-64 years for H10N8 study; 18-49 years for H7N9 study) participated. Participants received vaccine or placebo in a 2-dose vaccination series 3 weeks apart. H10N8 intramuscular (IM) dose levels of 25, 50, 75, 100, and 400 µg and intradermal dose levels of 25 and 50 µg were evaluated. H7N9 IM 10-, 25-, and 50-µg dose levels were evaluated; 2-dose series 6 months apart was also evaluated. Primary endpoints were safety (adverse events) and tolerability. Secondary immunogenicity outcomes included humoral (hemagglutination inhibition [HAI], microneutralization [MN] assays) and cell-mediated responses (ELISPOT assay). Results: H10N8 and H7N9 mRNA IM vaccines demonstrated favorable safety and reactogenicity profiles. No vaccine-related serious adverse event was reported. For H10N8 (N = 201), 100-µg IM dose induced HAI titers ≥ 1:40 in 100% and MN titers ≥ 1:20 in 87.0% of participants. The 25-µg intradermal dose induced HAI titers > 1:40 in 64.7% of participants compared to 34.5% of participants receiving the IM dose. For H7N9 (N = 156), IM doses of 10, 25, and 50 µg achieved HAI titers ≥ 1:40 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titers ≥ 1:20 were achieved by 100% in the 10- and 25-µg groups and 96.6% in the 50-µg group. Seroconversion rates were 78.3% (HAI) and 87.0% (MN) for H10N8 (100 µg IM) and 96.3% (HAI) and 100% (MN) in H7N9 (50 µg). Significant cell-mediated responses were not detected in either study. Conclusions: The first mRNA vaccines against H10N8 and H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses. ClinicalTrials.gov NCT03076385 and NCT03345043.
MeSH term(s)	Adolescent ; Adult ; Antibodies, Viral/blood ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Healthy Volunteers ; Humans ; Immunogenicity, Vaccine ; Influenza A Virus, H10N8 Subtype ; Influenza A Virus, H7N9 Subtype ; Influenza Vaccines/adverse effects ; Influenza Vaccines/genetics ; Influenza Vaccines/immunology ; Influenza, Human/prevention & control ; Male ; Middle Aged ; RNA, Viral/administration & dosage ; RNA, Viral/immunology ; Young Adult
Chemical Substances	Antibodies, Viral ; Influenza Vaccines ; RNA, Viral
Language	English
Publishing date	2019-05-10
Publishing country	Netherlands
Document type	Clinical Trial, Phase I ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2019.04.074
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Article ; Online: Clinical findings and molecular diagnosis of retinoblastoma in older children.

Sheck, Leo H N / Ng, Yvonne S P / Watson, Mike / Vincent, Andrea L

Ophthalmic genetics

2013 Volume 34, Issue 4, Page(s) 238–242

Abstract: Background: Retinoblastoma (RB) is the most common primary childhood intraocular malignancy and usually presents before the age of 4 years. RB in late childhood is rare and may pose a diagnostic challenge to clinicians.: Materials and methods: ... ...

Abstract	Background: Retinoblastoma (RB) is the most common primary childhood intraocular malignancy and usually presents before the age of 4 years. RB in late childhood is rare and may pose a diagnostic challenge to clinicians. Materials and methods: Patients over the age of 4 years with RB were identified retrospectively. Clinical data, histological findings, and molecular genetic diagnoses were obtained. Results: Two cases of late onset RB were identified. Case 1 was a 10-year-old boy who presented with floaters, and was found to have a unilateral exudative retinal detachment and RB on clinical examination. Genetic testing showed a novel homozygous mutation in exon 20 of the RB1 gene in the tumor sample, c.2027_2034dup, resulting in p.Ile679X. No mutation was found in the DNA obtained from the peripheral blood sample. Case 2 was a 6-year-old boy who presented with loss of vision and pain in the left eye. RB was diagnosed on clinical examination with exudative retinal detachment. Genetic testing showed no mutation in the RB1 gene, but complete methylation of the RB1 promoter region. Conclusions: RB can rarely present in late childhood. Clinicians should consider RB as a diagnosis when faced with a patient with unexplained exudative retinal detachment.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Child ; DNA Methylation ; DNA Mutational Analysis ; Diagnosis, Differential ; Exons/genetics ; Genes, Retinoblastoma ; Humans ; Magnetic Resonance Imaging ; Male ; Molecular Diagnostic Techniques ; Mutation ; Polymerase Chain Reaction ; Retinal Detachment/diagnosis ; Retinal Neoplasms/diagnosis ; Retinal Neoplasms/drug therapy ; Retinal Neoplasms/genetics ; Retinoblastoma/diagnosis ; Retinoblastoma/drug therapy ; Retinoblastoma/genetics ; Retinoblastoma Protein/genetics ; Retrospective Studies ; Sequence Analysis, DNA ; Visual Acuity
Chemical Substances	Antineoplastic Agents ; Retinoblastoma Protein
Language	English
Publishing date	2013-12
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	1199279-7
ISSN	1744-5094 ; 0167-6784 ; 1381-6810
ISSN (online)	1744-5094
ISSN	0167-6784 ; 1381-6810
DOI	10.3109/13816810.2012.752015
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Article: The relative transcription index: a gene expression based metric for prioritization of drug candidates.

Ghosh, Sujoy / Watson, Mike A / Collins, Jon L

Combinatorial chemistry & high throughput screening

2007 Volume 10, Issue 4, Page(s) 239–245

Abstract: Efficient compound selection remains a key challenge in drug discovery today. The goal is to identify developable drug candidates early in the screening process while simultaneously flagging compounds with off-target effects indicative of liabilities or ... ...

Abstract	Efficient compound selection remains a key challenge in drug discovery today. The goal is to identify developable drug candidates early in the screening process while simultaneously flagging compounds with off-target effects indicative of liabilities or alternate indications. This goal overlaps but is distinct from the goal of toxicogenomics which is focused primarily on identifying toxicity signatures of lead candidates in key tissues. We propose a framework where global changes in gene expression levels in response to compounds can be used as an objective metric for early compound prioritization. We call this metric the Relative Transcription Index (RTI). RTI is a measure of the relative activity of compounds as ascertained by their effects on transcription at a genome-wide level. Compounds with a low RTI affect the expression of only a few genes whereas compounds with a high RTI affect the expression of a large number of genes. This information is useful for differentiating compounds that, based on phenotypic assays alone, may appear to be equally efficacious. Since compounds with high RTI are more likely to display off-target effects, the RTI metric, if implemented early in the screening process, can become a valuable tool for compound selection. The utility of the RTI metric is demonstrated by its application to two different gene expression datasets--one involving modulators of the liver X receptor (LXR) and the other concerning antibacterial compounds belonging to diverse mechanistic classes.
MeSH term(s)	Algorithms ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Bacillus subtilis/drug effects ; Bacillus subtilis/genetics ; Bacillus subtilis/metabolism ; Cell Line ; DNA-Binding Proteins/drug effects ; DNA-Binding Proteins/genetics ; Databases, Genetic ; Drug Evaluation, Preclinical/methods ; Gene Expression/drug effects ; Gene Expression Profiling ; Humans ; Liver X Receptors ; Orphan Nuclear Receptors ; Receptors, Cytoplasmic and Nuclear/drug effects ; Receptors, Cytoplasmic and Nuclear/genetics ; Transcription, Genetic/drug effects
Chemical Substances	Anti-Bacterial Agents ; DNA-Binding Proteins ; Liver X Receptors ; Orphan Nuclear Receptors ; Receptors, Cytoplasmic and Nuclear
Language	English
Publishing date	2007-04-26
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2064785-2
ISSN	1875-5402 ; 1386-2073
ISSN (online)	1875-5402
ISSN	1386-2073
DOI	10.2174/138620707780636628
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Article: Effects of Irrigation and Crop Load on Leaf Gas Exchange and Fruit Composition in Red Winegrapes Grown on a Loamy Sand

Bowen, Pat / Bogdanoff, Carl / Usher, Kevin / Estergaard, Brad / Watson, Mike

American journal of enology and viticulture. 2011, v. 62, no. 1

2011

Abstract: Effects of reducing irrigation from fruit set to veraison or harvest combined with crop-load adjustment by cluster or shoot thinning were determined for Merlot and Cabernet Sauvignon grapevines cultured on a coarse loamy sand. Geographic information ... ...

Abstract	Effects of reducing irrigation from fruit set to veraison or harvest combined with crop-load adjustment by cluster or shoot thinning were determined for Merlot and Cabernet Sauvignon grapevines cultured on a coarse loamy sand. Geographic information system tools were used to develop maps of moisture distribution in the soil profile, which revealed reductions in total moisture levels and increased spatial variation in response to reduced emitter density. Stomatal conductance and leaf gas exchange decreased in response to reduced irrigation but also declined across all treatments during the lag phase of berry development and then increased postveraison. Pruning mass was affected little by treatments in Merlot but was reduced by either shoot or cluster thinning in Cabernet Sauvignon. Berry mass and anthocyanin and tannin contents were affected little and inconsistently by irrigation and crop-load adjustment and varied mostly among years, indicating a dominant influence of seasonal climate on berry development and composition.
Keywords	Vitis ; anthocyanins ; climate ; fruit composition ; fruit set ; gas exchange ; geographic information systems ; irrigation ; leaves ; pruning ; sand ; shoots ; soil profiles ; stomatal conductance ; wine grapes
Language	English
Size	p. 9-22.
Document type	Article
ZDB-ID	407380-0
ISSN	1943-7749 ; 0002-9254
ISSN (online)	1943-7749
ISSN	0002-9254
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