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Article ; Online: The Henry Ford production system: LEAN process redesign improves service in the molecular diagnostic laboratory: a paper from the 2008 William Beaumont hospital symposium on molecular pathology.

Cankovic, Milena / Varney, Ruan C / Whiteley, Lisa / Brown, Ron / D'Angelo, Rita / Chitale, Dhananjay / Zarbo, Richard J

The Journal of molecular diagnostics : JMD

2009 Volume 11, Issue 5, Page(s) 390–399

Abstract: Accurate and timely molecular test results play an important role in patient management; consequently, there is a customer expectation of short testing turnaround times. Baseline data analysis revealed that the greatest challenge to timely result ... ...

Abstract	Accurate and timely molecular test results play an important role in patient management; consequently, there is a customer expectation of short testing turnaround times. Baseline data analysis revealed that the greatest challenge to timely result generation occurred in the preanalytic phase of specimen collection and transport. Here, we describe our efforts to improve molecular testing turnaround times by focusing primarily on redesign of preanalytic processes using the principles of LEAN production. Our goal was to complete greater than 90% of the molecular tests in less than 3 days. The project required cooperation from different laboratory disciplines as well as individuals outside of the laboratory. The redesigned processes involved defining and standardizing the protocols and approaching blood and tissue specimens as analytes for molecular testing. The LEAN process resulted in fewer steps, approaching the ideal of a one-piece flow for specimens through collection/retrieval, transport, and different aspects of the testing process. The outcome of introducing the LEAN process has been a 44% reduction in molecular test turnaround time for tissue specimens, from an average of 2.7 to 1.5 days. In addition, extending LEAN work principles to the clinician suppliers has resulted in a markedly increased number of properly collected and shipped blood specimens (from 50 to 87%). These continuous quality improvements were accomplished by empowered workers in a blame-free environment and are now being sustained with minimal management involvement.
MeSH term(s)	Clinical Laboratory Techniques ; Efficiency, Organizational ; Humans ; Quality Assurance, Health Care ; Specimen Handling
Language	English
Publishing date	2009-08-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2000060-1
ISSN	1943-7811 ; 1525-1578
ISSN (online)	1943-7811
ISSN	1525-1578
DOI	10.2353/jmoldx.2009.090002
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Article ; Online: Risk of arterial and venous thromboses after COVID-19.

Whiteley, William / Wood, Angela

The Lancet. Infectious diseases

2022 Volume 22, Issue 8, Page(s) 1093–1094

MeSH term(s)	COVID-19/complications ; Humans ; Venous Thrombosis/epidemiology ; Venous Thrombosis/etiology
Language	English
Publishing date	2022-05-13
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(22)00314-0
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Zs.A 5743: Show issues

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Article: Ocular lesions associated with attachment of the copepod Ommatokoita elongata (Lernaeopodidae: Siphonostomatoida) to corneas of Pacific sleeper sharks Somniosus pacificus captured off Alaska in Prince William Sound.

Benz, George W / Borucinska, Joanna D / Lowry, Lloyd F / Whiteley, Herbert E

The Journal of parasitology

2002 Volume 88, Issue 3, Page(s) 474–481

Abstract: ... Ommatokoita elongata, were collected in Prince William Sound, Alaska, and the eyes of an additional 18 S ...

Abstract	Twenty eyes from 10 Pacific sleeper sharks Somniosus pacificus, infected with the copepod Ommatokoita elongata, were collected in Prince William Sound, Alaska, and the eyes of an additional 18 S. pacificus captured in the same area were inspected for copepods. Prevalence of infection by adult female O. elongata was 97% (n = 28); mean intensity of infection was 1.89 (+/-1SD = 0.32) adult female copepods per infected shark and 1.0 (+/- 1SD = 0.0) adult female copepods per infected eye. Five of the 20 collected eyes were infected by O. elongata chalimi, and 9 of 20 eyes had 1 to several remnants of bullae embedded in the cornea. Bullae were each associated with a corneal opacity, and anchoring plugs of chalimi were associated with pinpoint lesions in the cornea or conjunctiva. All eyes exhibited marked edema and erosion of the bulbar conjunctiva, and this torus-shaped lesion corresponded to each O. elongata adult female's presumed feeding and abrasion radius. Histological examinations revealed lesions in the anterior segment of eyes to be generally similar, but graded, in severity, and in all eyes they involved the conjunctiva, cornea, filtration angle, and iris. Epithelial lesions were characterized by corneal ulceration, dysplasia, hyperplasia, and heterophilic keratitis, and by ulcerative conjunctivitis accompanied by epithelial hyperplasia with rete peg formation. Disorganization of fibers, necrosis, mineralization, minimal heterophilic influx, and perilimbic neovascularization were associated with bullae in the corneal stroma. Within the limbus there was diffuse histiocytic and lymphocytic inflammation and marked lymphofollicular hyperplasia. Heterophilic and mononuclear anterior uveitis affecting the filtration angle and anterior surface of the iris was also observed in most eyes. One eye had a partial transcorneal prolapse of a ruptured lens, with degenerative changes in the ruptured lens and severe keratitis associated with the anchoring devices of an adult copepod and several chalimi. Fourteen eyes exhibited 1 to several, randomly distributed, small, round to irregular, corneal opacities or pits that were not associated with copepods, and it is likely that these opacities represented lesions associated with adult female or larval anchoring devices from past infections. The avascular cornea represents a niche that is somewhat shielded from host immune reactions, and this, and the fact that the general body surface of sleeper sharks is covered by tall and sharp placoid scales, may partially explain the corneal attachment of O. elongata adult females. It was concluded that O. elongata infections can lead to severe vision impairment in Pacific sleeper sharks but that these infections do not significantly debilitate hosts because they probably do not need to rely on acute vision for their survival.
MeSH term(s)	Alaska ; Animals ; Corneal Diseases/parasitology ; Corneal Diseases/pathology ; Corneal Diseases/veterinary ; Crustacea/ultrastructure ; Eye Infections, Parasitic/parasitology ; Eye Infections, Parasitic/veterinary ; Female ; Male ; Microscopy, Electron, Scanning ; Sharks/parasitology ; Skin Diseases, Parasitic/parasitology ; Skin Diseases, Parasitic/pathology ; Skin Diseases, Parasitic/veterinary
Language	English
Publishing date	2002-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	300870-8
ISSN	1937-2345 ; 0022-3395
ISSN (online)	1937-2345
ISSN	0022-3395
DOI	10.1645/0022-3395(2002)088[0474:OLAWAO]2.0.CO;2
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Article ; Online: A comprehensive analysis of APOE genotype effects on human brain structure in the UK Biobank.

Heise, Verena / Offer, Alison / Whiteley, William / Mackay, Clare E / Armitage, Jane M / Parish, Sarah

Translational psychiatry

2024 Volume 14, Issue 1, Page(s) 143

Abstract: Alzheimer's disease (AD) risk is increased in carriers of the apolipoprotein E (APOE) ε4 allele and decreased in ε2 allele carriers compared with the ε3ε3 genotype. The aim of this study was to determine whether: the APOE genotype affects brain grey (GM) ...

Abstract	Alzheimer's disease (AD) risk is increased in carriers of the apolipoprotein E (APOE) ε4 allele and decreased in ε2 allele carriers compared with the ε3ε3 genotype. The aim of this study was to determine whether: the APOE genotype affects brain grey (GM) or white matter (WM) structure; and if differences exist, the age when they become apparent and whether there are differential effects by sex. We used cross-sectional magnetic resonance imaging data from ~43,000 (28,494 after pre-processing) white British cognitively healthy participants (7,446 APOE ε4 carriers) aged 45-80 years from the UK Biobank cohort and investigated image-derived phenotypes (IDPs). We observed no statistically significant effects of APOE genotype on GM structure volumes or median T2* in subcortical structures, a measure related to iron content. The volume of white matter hyperintensities differed significantly between APOE genotype groups with higher volumes in APOE ε4ε4 (effect size 0.14 standard deviations [SD]) and ε3ε4 carriers (effect size 0.04 SD) but no differences in ε2 carriers compared with ε3ε3 carriers. WM integrity measures in the dorsal (mean diffusivity [MD]) and ventral cingulum (MD and intracellular volume fraction), posterior thalamic radiation (MD and isotropic volume fraction) and sagittal stratum (MD) indicated lower integrity in APOE ε4ε4 carriers (effect sizes around 0.2-0.3 SD) and ε3ε4 (effect sizes around 0.05 SD) carriers but no differences in ε2 carriers compared with the APOE ε3ε3 genotype. Effects did not differ between men and women. APOE ε4 homozygotes had lower WM integrity specifically at older ages with a steeper decline of WM integrity from the age of 60 that corresponds to around 5 years greater "brain age". APOE genotype affects various white matters measures, which might be indicative of preclinical AD processes. This hypothesis can be assessed in future when clinical outcomes become available.
MeSH term(s)	Female ; Humans ; Male ; Alzheimer Disease/genetics ; Apolipoprotein E4/genetics ; Apolipoproteins E/genetics ; Biological Specimen Banks ; Brain/pathology ; Diffusion Tensor Imaging/methods ; Genotype ; UK Biobank
Chemical Substances	Apolipoprotein E4 ; Apolipoproteins E ; ApoE protein, human
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-024-02848-5
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Article: Determining suitable surfactant concentration ranges to avoid protein unfolding in pharmaceutical formulations using UV analysis.

Waters, Laura J / Whiteley, Joseph / Small, William / Mellor, Steve

Heliyon

2023 Volume 9, Issue 11, Page(s) e21712

Abstract: Protein stability is fundamental to maintain pharmaceutical efficacy in the nascent field of biologics. One particular property that is essential for therapeutic effect is retention of the folded 3-dimensional conformation, i.e. once unfolding has ... ...

Abstract	Protein stability is fundamental to maintain pharmaceutical efficacy in the nascent field of biologics. One particular property that is essential for therapeutic effect is retention of the folded 3-dimensional conformation, i.e. once unfolding has occurred the biologic is often rendered inactive. In this work we propose a modified form of a recently published UV spectroscopic method that identifies protein unfolding. In this study we determine concentration limits to avoid protein unfolding of two model surfactants, namely polysorbate 20 and polysorbate 80, by correlating surfactant concentration with percentage 'unfolded' for three model proteins. For each scenario two distinct regions were observed, firstly surfactant concentrations at which no unfolding had occurred, followed by a second region whereby unfolding steadily increased with surfactant concentration. In general for the combinations analysed in this study, this second region began to appear around ten times below the critical micellar concentration of each surfactant, regardless of the protein or polysorbate chosen. It is therefore proposed that this adapted method could be used by researchers in the early stages of formulation development as a convenient and simple screening tool to confirm the 'onset of unfolding' concentration for protein-surfactant formulations, thus helping to optimise surfactant concentration selection in pharmaceutical formulations to maintain the benefits of surfactants yet avoid inadvertent unfolding.
Language	English
Publishing date	2023-10-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e21712
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Article ; Online: New Insights into Stroke from Continuous Passively Collected Temperature and Sleep Data Using Wrist-Worn Wearables.

Edgley, Katherine / Chun, Ho-Yan Yvonne / Whiteley, William N / Tsanas, Athanasios

Sensors (Basel, Switzerland)

2023 Volume 23, Issue 3

Abstract: Actigraphy may provide new insights into clinical outcomes and symptom management of patients through passive, continuous data collection. We used the GENEActiv smartwatch to passively collect actigraphy, wrist temperature, and ambient light data from 27 ...

Abstract	Actigraphy may provide new insights into clinical outcomes and symptom management of patients through passive, continuous data collection. We used the GENEActiv smartwatch to passively collect actigraphy, wrist temperature, and ambient light data from 27 participants after stroke or probable brain transient ischemic attack (TIA) over 42 periods of device wear. We computed 323 features using established algorithms and proposed 25 novel features to characterize sleep and temperature. We investigated statistical associations between the extracted features and clinical outcomes evaluated using clinically validated questionnaires to gain insight into post-stroke recovery. We subsequently fitted logistic regression models to replicate clinical diagnosis (stroke or TIA) and disability due to stroke. The model generalization performance was assessed using a leave-one-subject-out cross validation method with the selected feature subsets, reporting the area under the curve (AUC). We found that several novel features were strongly correlated (\|r\|>0.3) with stroke symptoms and mental health measures. Using selected novel features, we obtained an AUC of 0.766 to estimate diagnosis and an AUC of 0.749 to estimate whether disability due to stroke was present. Collectively, these findings suggest that features extracted from the temperature smartwatch sensor may reveal additional clinically useful information over and above existing actigraphy-based features.
MeSH term(s)	Humans ; Wrist ; Ischemic Attack, Transient/diagnosis ; Temperature ; Stroke/diagnosis ; Sleep ; Actigraphy ; Wearable Electronic Devices
Language	English
Publishing date	2023-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s23031069
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Article ; Online: Determining suitable surfactant concentration ranges to avoid protein unfolding in pharmaceutical formulations using UV analysis

Laura J. Waters / Joseph Whiteley / William Small / Steve Mellor

Heliyon, Vol 9, Iss 11, Pp e21712- (2023)

2023

Abstract	Protein stability is fundamental to maintain pharmaceutical efficacy in the nascent field of biologics. One particular property that is essential for therapeutic effect is retention of the folded 3-dimensional conformation, i.e. once unfolding has occurred the biologic is often rendered inactive. In this work we propose a modified form of a recently published UV spectroscopic method that identifies protein unfolding. In this study we determine concentration limits to avoid protein unfolding of two model surfactants, namely polysorbate 20 and polysorbate 80, by correlating surfactant concentration with percentage ‘unfolded’ for three model proteins. For each scenario two distinct regions were observed, firstly surfactant concentrations at which no unfolding had occurred, followed by a second region whereby unfolding steadily increased with surfactant concentration. In general for the combinations analysed in this study, this second region began to appear around ten times below the critical micellar concentration of each surfactant, regardless of the protein or polysorbate chosen. It is therefore proposed that this adapted method could be used by researchers in the early stages of formulation development as a convenient and simple screening tool to confirm the ‘onset of unfolding’ concentration for protein-surfactant formulations, thus helping to optimise surfactant concentration selection in pharmaceutical formulations to maintain the benefits of surfactants yet avoid inadvertent unfolding.
Keywords	Biocompatibility ; Critical micellar concentration ; Pharmaceutical ; Polysorbate ; Protein ; Spectroscopy ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	612
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Intensive Blood Pressure Lowering in Patients With Renal Impairment and Lacunar Stroke.

Makin, Stephen / Whiteley, William N

Journal of the American Heart Association

2019 Volume 8, Issue 16, Page(s) e013637

Abstract: See Article Agarwal et al. ...

Abstract	See Article Agarwal et al.
MeSH term(s)	Blood Pressure ; Blood Pressure Determination ; Humans ; Secondary Prevention ; Stroke ; Stroke, Lacunar
Language	English
Publishing date	2019-08-19
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.119.013637
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Article ; Online: CNN-based PET sinogram repair to mitigate defective block detectors.

Whiteley, William / Gregor, Jens

Physics in medicine and biology

2019 Volume 64, Issue 23, Page(s) 235017

Abstract: Positron emission tomography (PET) scanners continue to increase sensitivity and axial coverage by adding an ever expanding array of block detectors. As they age, one or more block detectors may lose sensitivity due to a malfunction or component failure. ...

Abstract	Positron emission tomography (PET) scanners continue to increase sensitivity and axial coverage by adding an ever expanding array of block detectors. As they age, one or more block detectors may lose sensitivity due to a malfunction or component failure. The sinogram data missing as a result thereof can lead to artifacts and other image degradations. We propose to mitigate the effects of malfunctioning block detectors by carrying out sinogram repair using a deep convolutional neural network. Experiments using whole-body patient studies with varying amounts of raw data removed are used to show that the neural network significantly outperforms previously published methods with respect to normalized mean squared error for raw sinograms, a multi-scale structural similarity measure for reconstructed images and with regard to quantitative accuracy.
MeSH term(s)	Artifacts ; Humans ; Image Processing, Computer-Assisted/instrumentation ; Image Processing, Computer-Assisted/methods ; Neural Networks, Computer ; Positron-Emission Tomography/instrumentation ; Positron-Emission Tomography/methods ; Tomography Scanners, X-Ray Computed/standards ; Tomography, X-Ray Computed/instrumentation ; Tomography, X-Ray Computed/methods
Language	English
Publishing date	2019-12-05
Publishing country	England
Document type	Journal Article
ZDB-ID	208857-5
ISSN	1361-6560 ; 0031-9155
ISSN (online)	1361-6560
ISSN	0031-9155
DOI	10.1088/1361-6560/ab4919
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Zs.A 199: Show issues

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Article: DirectPET: full-size neural network PET reconstruction from sinogram data.

Whiteley, William / Luk, Wing K / Gregor, Jens

Journal of medical imaging (Bellingham, Wash.)

2020 Volume 7, Issue 3, Page(s) 32503

Abstract: Purpose: ...

Abstract	Purpose:
Language	English
Publishing date	2020-02-28
Publishing country	United States
Document type	Journal Article
ISSN	2329-4302
ISSN	2329-4302
DOI	10.1117/1.JMI.7.3.032503
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