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Article: Essentials for aerosol delivery to term and pre-term infants.

Clark, Andrew R

2021 Volume 9, Issue 7, Page(s) 594

Abstract: Effectively delivering pharmaceutical aerosols to the lungs of preterm and term infants represents a considerable technical challenge. Small infants are obligatory nose breathers, they have small airways, low tidal volumes and rapid respiration rates. It ...

Abstract	Effectively delivering pharmaceutical aerosols to the lungs of preterm and term infants represents a considerable technical challenge. Small infants are obligatory nose breathers, they have small airways, low tidal volumes and rapid respiration rates. It is ethically unacceptable to investigate aerosol deposition
Language	English
Publishing date	2021-04-27
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2893931-1
ISSN	2305-5847 ; 2305-5839
ISSN (online)	2305-5847
ISSN	2305-5839
DOI	10.21037/atm-20-7265
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Article: Repurposing existing products to accelerate injury recovery (REPAIR) of military relevant musculoskeletal conditions.

Clark, Andrew R / Mauntel, Timothy C / Goldman, Stephen M / Dearth, Christopher L

Frontiers in bioengineering and biotechnology

2023 Volume 10, Page(s) 1105599

Abstract: Musculoskeletal injuries (MSKIs) are a great hindrance to the readiness of the United States Armed Forces through lost duty time and reduced operational capabilities. While most musculoskeletal injuries result in return-to-duty/activity with no ( ... ...

Abstract	Musculoskeletal injuries (MSKIs) are a great hindrance to the readiness of the United States Armed Forces through lost duty time and reduced operational capabilities. While most musculoskeletal injuries result in return-to-duty/activity with no (functional) limitations, the healing process is often long. Long healing times coupled with the high frequency of musculoskeletal injuries make them a primary cause of lost/limited duty days. Thus, there exists an urgent, clinically unmet need for interventions to expedite tissue healing kinetics following musculoskeletal injuries to lessen their impact on military readiness and society as a whole. There exist several treatments with regulatory approval for other indications that have pro-regenerative/healing properties, but few have an approved indication for treating musculoskeletal injuries. With the immediate need for treatment options for musculoskeletal injuries, we propose a paradigm of Repurposing Existing Products to Accelerate Injury Recovery (REPAIR). Developing treatments
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2022.1105599
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Article ; Online: Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration.

Clark, Andrew R / Ohlmeyer, Michael

Pharmacology & therapeutics

2019 Volume 201, Page(s) 181–201

Abstract: Protein phosphatase 2A (PP2A) is a highly complex heterotrimeric enzyme that catalyzes the selective removal of phosphate groups from protein serine and threonine residues. Emerging evidence suggests that it functions as a tumor suppressor by ... ...

Abstract	Protein phosphatase 2A (PP2A) is a highly complex heterotrimeric enzyme that catalyzes the selective removal of phosphate groups from protein serine and threonine residues. Emerging evidence suggests that it functions as a tumor suppressor by constraining phosphorylation-dependent signalling pathways that regulate cellular transformation and metastasis. Therefore, PP2A-activating drugs (PADs) are being actively sought and investigated as potential novel anti-cancer treatments. Here we explore the concept that PP2A also constrains inflammatory responses through its inhibitory effects on various signalling pathways, suggesting that PADs may be effective in the treatment of inflammation-mediated pathologies.
MeSH term(s)	Animals ; Drug Development ; Humans ; Inflammation/drug therapy ; Inflammation/enzymology ; Inflammation/pathology ; Neoplasms/drug therapy ; Neoplasms/enzymology ; Neoplasms/pathology ; Neurodegenerative Diseases/drug therapy ; Neurodegenerative Diseases/enzymology ; Neurodegenerative Diseases/physiopathology ; Phosphorylation ; Protein Phosphatase 2/metabolism ; Signal Transduction
Chemical Substances	Protein Phosphatase 2 (EC 3.1.3.16)
Language	English
Publishing date	2019-06-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	194735-7
ISSN	1879-016X ; 0163-7258
ISSN (online)	1879-016X
ISSN	0163-7258
DOI	10.1016/j.pharmthera.2019.05.016
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Zs.A 1183: Show issues

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Article ; Online: The Role of Inspiratory Pressures in Determining the Flow Rates Though Dry Powder Inhalers; A Review.

Clark, Andrew R

Current pharmaceutical design

2015 Volume 21, Issue 27, Page(s) 3974–3983

Abstract: Dry powder inhalers are one of the most popular devices for delivering medication directly to the lungs of patients. Both for local action and when using the lungs as a portal of entry into the systemic circulation. Dry powder inhalers rely on the ... ...

Abstract	Dry powder inhalers are one of the most popular devices for delivering medication directly to the lungs of patients. Both for local action and when using the lungs as a portal of entry into the systemic circulation. Dry powder inhalers rely on the patient's inspiratory effort to supply the energy for the device to effectively deliver medication. In this respect they are limited by the airway pressures that a patient can generate with their respiratory muscles. In this review we focus on a simple model outlining the variables influencing respiratory pressure and review the literature on inspiratory flow rates in patients with respiratory disease. The main determinants of the capability to generate the pressure necessary to effectively use a dry powder inhaler are shown to be age and gender, not disease or disease severity.
MeSH term(s)	Administration, Inhalation ; Drug Delivery Systems/methods ; Dry Powder Inhalers ; Equipment Design ; Forced Expiratory Volume ; Humans ; Inspiratory Capacity/physiology ; Lung Diseases/drug therapy ; Pharmaceutical Preparations/administration & dosage ; Powders/administration & dosage
Chemical Substances	Pharmaceutical Preparations ; Powders
Language	English
Publishing date	2015-10-01
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/1381612821666150820105800
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Zs.A 4714: Show issues

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Article ; Online: Late Paleozoic oxygenation of marine environments supported by dolomite U-Pb dating.

Ben-Israel, Michal / Holder, Robert M / Nelson, Lyle L / Smith, Emily F / Kylander-Clark, Andrew R C / Ryb, Uri

Nature communications

2024 Volume 15, Issue 1, Page(s) 2892

Abstract: Understanding causal relationships between evolution and ocean oxygenation hinges on reliable reconstructions of marine oxygen levels, typically from redox-sensitive geochemical proxies. Here, we develop a proxy, using dolomite U-Pb geochronology, to ... ...

Abstract	Understanding causal relationships between evolution and ocean oxygenation hinges on reliable reconstructions of marine oxygen levels, typically from redox-sensitive geochemical proxies. Here, we develop a proxy, using dolomite U-Pb geochronology, to reconstruct seawater U/Pb ratios. Dolomite samples consistently give U-Pb dates and initial
Language	English
Publishing date	2024-04-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-46660-7
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Article ; Online: Plate motion and a dipolar geomagnetic field at 3.25 Ga.

Brenner, Alec R / Fu, Roger R / Kylander-Clark, Andrew R C / Hudak, George J / Foley, Bradford J

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 44, Page(s) e2210258119

Abstract: The paleomagnetic record is an archive of Earth's geophysical history, informing reconstructions of ancient plate motions and probing the core via the geodynamo. We report a robust 3.25-billion-year-old (Ga) paleomagnetic pole from the East Pilbara ... ...

Abstract	The paleomagnetic record is an archive of Earth's geophysical history, informing reconstructions of ancient plate motions and probing the core via the geodynamo. We report a robust 3.25-billion-year-old (Ga) paleomagnetic pole from the East Pilbara Craton, Western Australia. Together with previous results from the East Pilbara between 3.34 and 3.18 Ga, this pole enables the oldest reconstruction of time-resolved lithospheric motions, documenting 160 My of both latitudinal drift and rotation at rates of at least 0.55°/My. Motions of this style, rate, and duration are difficult to reconcile with true polar wander or stagnant-lid geodynamics, arguing strongly for mobile-lid geodynamics by 3.25 Ga. Additionally, this pole includes the oldest documented geomagnetic reversal, reflecting a stably dipolar, core-generated Archean dynamo.
MeSH term(s)	Western Australia ; Geological Phenomena
Language	English
Publishing date	2022-10-24
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2210258119
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Zs.A 1148: Show issues

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Article ; Online: Reply to Mitchell and Jing: True polar wander alone is insufficient to drive measured Paleoarchean lithospheric motions.

Brenner, Alec R / Fu, Roger R / Kylander-Clark, Andrew R C / Hudak, George J / Foley, Bradford J

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 120, Issue 1, Page(s) e2219560120

MeSH term(s)	Motion ; Treatment Refusal
Language	English
Publishing date	2022-12-27
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2219560120
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Zs.A 1148: Show issues

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Article ; Online: Understanding penetration index measurements and regional lung targeting.

Clark, Andrew R

Journal of aerosol medicine and pulmonary drug delivery

2012 Volume 25, Issue 4, Page(s) 179–187

Abstract: Radiolabeling of pharmaceutical inhalation aerosols began in the late 1970s. Since then, well over 100 studies have been published. These studies have documented lung deposition for all inhalation dosage forms; pressurized metered dose inhalers (pMDIs), ... ...

Abstract	Radiolabeling of pharmaceutical inhalation aerosols began in the late 1970s. Since then, well over 100 studies have been published. These studies have documented lung deposition for all inhalation dosage forms; pressurized metered dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers (SMIs), and nebulizers. They have provided valuable insight into the factors that influence total and regional lung deposition. Taken globally, this collection of data has recently been used to elucidate the influence of intersubject variability in head geometry on total lung deposition, showing good correspondence between theory and experiment. The analysis reported here is an attempt to take this data set one step "deeper" into the airways and understand the relationship between P/C ratio, derived from 2D imaging, and a more anatomically relevant biological distribution within the lung, 24-h clearance. Intersubject variability in regional deposition is also analyzed, although due to the sparse nature of the reported individual data only tentative conclusions can be drawn. Many different techniques for derivation and analysis of scintigraphic data have been reported in the literature, and this leads to some difficulties when performing the "meta-analyses" reported below. In this regard it is recommended that standardization of scintigraphy techniques should be a future goal.
MeSH term(s)	Administration, Inhalation ; Bronchodilator Agents/administration & dosage ; Bronchodilator Agents/metabolism ; Humans ; Lung/diagnostic imaging ; Lung/metabolism ; Lung Diseases/diagnostic imaging ; Lung Diseases/metabolism ; Metabolic Clearance Rate ; Models, Theoretical ; Nebulizers and Vaporizers/standards ; Pharmaceutical Preparations/administration & dosage ; Pharmaceutical Preparations/metabolism ; Radionuclide Imaging/standards
Chemical Substances	Bronchodilator Agents ; Pharmaceutical Preparations
Language	English
Publishing date	2012-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2417924-3
ISSN	1941-2703 ; 1941-2711
ISSN (online)	1941-2703
ISSN	1941-2711
DOI	10.1089/jamp.2011.0899
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Zs.A 2460: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: The Confusing World of Dry Powder Inhalers: It Is All About Inspiratory Pressures, Not Inspiratory Flow Rates.

Clark, Andrew R / Weers, Jeffry G / Dhand, Rajiv

Journal of aerosol medicine and pulmonary drug delivery

2019 Volume 33, Issue 1, Page(s) 1–11

Abstract: Dry powder inhalers (DPIs) all have the ability to aerosolize dry powders, but they each offer different operating mechanisms and resistances to inhaled airflow. This variety has resulted in both clinician and patient confusion concerning DPI performance, ...

Abstract	Dry powder inhalers (DPIs) all have the ability to aerosolize dry powders, but they each offer different operating mechanisms and resistances to inhaled airflow. This variety has resulted in both clinician and patient confusion concerning DPI performance, use, and effectiveness. Particularly, there is a growing misconception that a single peak inspiratory flow rate (PIFR) can determine a patient's ability to use a DPI effectively, regardless of its design or airflow resistance. For this review article, we have sifted through the relevant literature concerning DPIs, inspiratory pressures, and inspiratory flow rates to provide a comprehensive and concise discussion and recommendations for DPI use. We ultimately clarify that the controlling parameter for DPI performance is not the PIFR but the negative pressure generated by the patient's inspiratory effort. A pressure drop ∼≥1 kPa (∼10 cm H
MeSH term(s)	Administration, Inhalation ; Aerosols/administration & dosage ; Aerosols/pharmacokinetics ; Dry Powder Inhalers ; Humans ; Inhalation/physiology ; Lung/metabolism ; Powders ; Pressure ; Tissue Distribution
Chemical Substances	Aerosols ; Powders
Language	English
Publishing date	2019-10-31
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2417924-3
ISSN	1941-2703 ; 1941-2711
ISSN (online)	1941-2703
ISSN	1941-2711
DOI	10.1089/jamp.2019.1556
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Zs.A 2460: Show issues

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Article ; Online: Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis.

Clayton, Sally A / MacDonald, Lucy / Kurowska-Stolarska, Mariola / Clark, Andrew R

Frontiers in immunology

2021 Volume 12, Page(s) 673916

Abstract: Mitochondria are major energy-producing organelles that have central roles in cellular metabolism. They also act as important signalling hubs, and their dynamic regulation in response to stress signals helps to dictate the stress response of the cell. ... ...

Abstract	Mitochondria are major energy-producing organelles that have central roles in cellular metabolism. They also act as important signalling hubs, and their dynamic regulation in response to stress signals helps to dictate the stress response of the cell. Rheumatoid arthritis is an inflammatory and autoimmune disease with high prevalence and complex aetiology. Mitochondrial activity affects differentiation, activation and survival of immune and non-immune cells that contribute to the pathogenesis of this disease. This review outlines what is known about the role of mitochondria in rheumatoid arthritis pathogenesis, and how current and future therapeutic strategies can function through modulation of mitochondrial activity. We also highlight areas of this topic that warrant further study. As producers of energy and of metabolites such as succinate and citrate, mitochondria help to shape the inflammatory phenotype of leukocytes during disease. Mitochondrial components can directly stimulate immune receptors by acting as damage-associated molecular patterns, which could represent an initiating factor for the development of sterile inflammation. Mitochondria are also an important source of intracellular reactive oxygen species, and facilitate the activation of the NLRP3 inflammasome, which produces cytokines linked to disease symptoms in rheumatoid arthritis. The fact that mitochondria contain their own genetic material renders them susceptible to mutation, which can propagate their dysfunction and immunostimulatory potential. Several drugs currently used for the treatment of rheumatoid arthritis regulate mitochondrial function either directly or indirectly. These actions contribute to their immunomodulatory functions, but can also lead to adverse effects. Metabolic and mitochondrial pathways are attractive targets for future anti-rheumatic drugs, however many questions still remain about the precise role of mitochondrial activity in different cell types in rheumatoid arthritis.
MeSH term(s)	Animals ; Arthritis, Rheumatoid ; Humans ; Mitochondria
Language	English
Publishing date	2021-04-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.673916
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