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Book ; Online: Chronostratigraphy of sediment core CRP-2/2A (Table 1), supplementary data to: Wilson, Gary S; Bohaty, Steven M; Fielding, Christopher R; Florindo, Fabio; Hannah, Mike J; Harwood, David M; McIntosh, WC; Naish, Tim R; Roberts, Andrew P; Sagnotti, Leo; Scherer, Reed P; Strong, C Percy; Versub, KL; Villa, Giuliana; Watkins, David K; Webb, Peter-Noel; Woolfe, Ken (2000): Chronostratigraphy of CRP-2/2A, Victoria Land Basin, Antarctica. Terra Antartica, 7(4), 647-654

Wilson, Gary S / Bohaty, Steven M / Fielding, Christopher R / Florindo, Fabio / Hannah, Mike J / Harwood, David M / McIntosh, WC / Naish, Tim R / Roberts, Andrew P / al., et

2000

Abstract: ... lower Oligocene (<c. 31 Ma) to lower Miocene (18.5 Ma) strata that are overlain by a thin succession ... Additional unconformities at 25.92 and 130.27 mbsf account for c. 16 and 2.5 m.y. of missing time ...

Abstract	The 624.15 m glaciomarine sedimentary succession recovered in the CRP-2/2A drillcore comprises lower Oligocene (<c. 31 Ma) to lower Miocene (18.5 Ma) strata that are overlain by a thin succession of Pliocene and Pleistocene strata. The age model for the CRP-2/2A drillhole, as presented in this paper, is based on combined microfossil biostratigraphy. 40Ar/39Ar age on volcanic material, 87Sr/86Sr analyses on mollusc shells, and correlation of a magnetic polarity zonation to the magnetic polarity time scale (MPTS). Between 25.92 and 109.05 metres below sea floor (mbsf), several alternative correlations to the MPTS are possible, all of which suggest that sediment accumulation rates averaged ~180 m/m.y. between unconformities, although actual sedimentation rates may have been higher. Between 109.05 and 306.65 mbsf, the age model is straightforward and average sedimentation rates were much higher (>1000 m/m.y.). Between 306.65 mbsf and the bottom of the drillcore (624.15 mbsf), fewer datums are available to constrain the age model and unique correlation with the MPTS is not possible, although high average sediment accumulation rates are likely. A significant unconformity is identified at 306.65 mbsf, which may represent as much as 5 m.y. of missing time. Additional unconformities at 25.92 and 130.27 mbsf account for c. 16 and 2.5 m.y. of missing time, respectively. The Oligocene-lower Miocene interval documented in the CRP-2/2A drillcore spans about 13 million years, however, it is possible that more time is missing in sequence-bounding unconformities than is represented in the stratigraphic record recovered in the CRP-2/2A drillcore.
Language	English
Dates of publication	2000-9999
Size	Online-Ressource
Publisher	PANGAEA - Data Publisher for Earth & Environmental Science
Publishing place	Bremen/Bremerhaven
Document type	Book ; Online
Note	This dataset is supplement to hdl:10013/epic.28244.d001
DOI	10.1594/PANGAEA.189249
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article: Automated Growth Rate Measurement of the Facet Surfaces of Single Crystals of the β-Form of l-Glutamic Acid Using Machine Learning Image Processing.

Jiang, Chen / Ma, Cai Y / Hazlehurst, Thomas A / Ilett, Thomas P / Jackson, Alexander S M / Hogg, David C / Roberts, Kevin J

Crystal growth & design

2024 Volume 24, Issue 8, Page(s) 3277–3288

Abstract: Precision measurement of the growth rate of individual single crystal facets ( ...

Abstract	Precision measurement of the growth rate of individual single crystal facets (
Language	English
Publishing date	2024-04-05
Publishing country	United States
Document type	Journal Article
ISSN	1528-7483
ISSN	1528-7483
DOI	10.1021/acs.cgd.3c01548
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Article: A Genome-Wide CRISPR Screen Identifies Sortilin as the Receptor Responsible for Galectin-1 Lysosomal Trafficking.

Donnelly, Justin / Kamber, Roarke A / Wisnovsky, Simon / Roberts, David S / Peltan, Egan L / Bassik, Michael C / Bertozzi, Carolyn R

bioRxiv : the preprint server for biology

2024

Abstract: Galectins are a family of mammalian glycan-binding proteins that have been implicated as regulators of myriad cellular processes including cell migration, apoptosis, and immune modulation. Several members of this family, such as galectin-1, exhibit both ... ...

Abstract	Galectins are a family of mammalian glycan-binding proteins that have been implicated as regulators of myriad cellular processes including cell migration, apoptosis, and immune modulation. Several members of this family, such as galectin-1, exhibit both cell-surface and intracellular functions. Interestingly, galectin-1 can be found in the endomembrane system, nucleus, or cytosol, as well as on the cell surface. The mechanisms by which galectin-1 traffics between cellular compartments, including its unconventional secretion and internalization processes, are poorly understood. Here, we determined the pathways by which exogenous galectin-1 enters cells and explored its capacity as a delivery vehicle for protein and siRNA therapeutics. We used a galectin-1-toxin conjugate, modelled on antibody-drug conjugates, as a selection tool in a genome-wide CRISPR screen. We discovered that galectin-1 interacts with the endosome-lysosome trafficking receptor sortilin in a glycan-dependent manner, which regulates galectin-1 trafficking to the lysosome. Further, we show that this pathway can be exploited for delivery of a functional siRNA. This study sheds light on the mechanisms by which galectin-1 is internalized by cells and suggests a new strategy for intracellular drug delivery via galectin-1 conjugation.
Language	English
Publishing date	2024-01-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.03.574113
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Article ; Online: Interventions for Optimization of Guideline-Directed Medical Therapy: A Systematic Review.

Tang, Amber B / Brownell, Nicholas K / Roberts, Jacob S / Haidar, Amier / Osuna-Garcia, Antonia / Cho, David J / Bokhoor, Pooya / Fonarow, Gregg C

JAMA cardiology

2024 Volume 9, Issue 4, Page(s) 397–404

Abstract: Importance: Implementation of guideline-directed medical therapy (GDMT) in real-world practice remains suboptimal. It is unclear which interventions are most effective at addressing current barriers to GDMT in patients with heart failure with reduced ... ...

Abstract	Importance: Implementation of guideline-directed medical therapy (GDMT) in real-world practice remains suboptimal. It is unclear which interventions are most effective at addressing current barriers to GDMT in patients with heart failure with reduced ejection fraction (HFrEF). Objective: To perform a systematic review to identify which types of system-level initiatives are most effective at improving GDMT use among patients with HFrEF. Evidence review: PubMed, Embase, Cochrane, CINAHL, and Web of Science databases were queried from January 2010 to November 2023 for randomized clinical trials that implemented a quality improvement intervention with GDMT use as a primary or secondary outcome. References from related review articles were also included for screening. Quality of studies and bias assessment were graded based on the Cochrane Risk of Bias tool and Oxford Centre for Evidence-Based Medicine. Findings: Twenty-eight randomized clinical trials were included with an aggregate sample size of 19 840 patients. Studies were broadly categorized as interdisciplinary interventions (n = 15), clinician education (n = 5), electronic health record initiatives (n = 6), or patient education (n = 2). Overall, interdisciplinary titration clinics were associated with significant increases in the proportion of patients on target doses of GDMT with a 10% to 60% and 2% to 53% greater proportion of patients on target doses of β-blockers and renin-angiotensin-aldosterone system inhibitors, respectively, in intervention groups compared with usual care. Other interventions, such as audits, clinician and patient education, or electronic health record alerts, were also associated with some improvements in GDMT utilization, though these findings were inconsistent across studies. Conclusions and relevance: This review summarizes interventions aimed at optimization of GDMT in clinical practice. Initiatives that used interdisciplinary teams, largely comprised of nurses and pharmacists, most consistently led to improvements in GDMT. Additional large, randomized studies are necessary to better understand other types of interventions, as well as their long-term efficacy and sustainability.
MeSH term(s)	Humans ; Heart Failure/drug therapy ; Heart Failure/diagnosis ; Stroke Volume ; Adrenergic beta-Antagonists/therapeutic use ; Ventricular Dysfunction, Left/drug therapy ; Quality Improvement
Chemical Substances	Adrenergic beta-Antagonists
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Systematic Review ; Journal Article
ISSN	2380-6591
ISSN (online)	2380-6591
DOI	10.1001/jamacardio.2023.5627
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Article ; Online: BCL2 and MCL1 inhibitors for hematologic malignancies.

Roberts, Andrew W / Wei, Andrew H / Huang, David C S

Blood

2021 Volume 138, Issue 13, Page(s) 1120–1136

Abstract: BCL2 and MCL1 are commonly expressed prosurvival (antiapoptotic) proteins in hematologic cancers and play important roles in their biology either through dysregulation or by virtue of intrinsic importance to the cell-of-origin of the malignancy. A new ... ...

Abstract	BCL2 and MCL1 are commonly expressed prosurvival (antiapoptotic) proteins in hematologic cancers and play important roles in their biology either through dysregulation or by virtue of intrinsic importance to the cell-of-origin of the malignancy. A new class of small-molecule anticancer drugs, BH3 mimetics, now enable specific targeting of these proteins in patients. BH3 mimetics act by inhibiting the prosurvival BCL2 proteins to enable the activation of BAX and BAK, apoptosis effectors that permeabilize the outer mitochondrial membrane, triggering apoptosis directly in many cells and sensitizing others to cell death when combined with other antineoplastic drugs. Venetoclax, a specific inhibitor of BCL2, is the first approved in class, demonstrating striking single agent activity in chronic lymphocytic leukemia and in other lymphoid neoplasms, as well as activity against acute myeloid leukemia (AML), especially when used in combination. Key insights from the venetoclax experience include that responses occur rapidly, with major activity as monotherapy proving to be the best indicator for success in combination regimens. This emphasizes the importance of adequate single-agent studies for drugs in this class. Furthermore, secondary resistance is common with long-term exposure and often mediated by genetic or adaptive changes in the apoptotic pathway, suggesting that BH3 mimetics are better suited to limited duration, rather than continuous, therapy. The success of venetoclax has inspired development of BH3 mimetics targeting MCL1. Despite promising preclinical activity against MYC-driven lymphomas, myeloma, and AML, their success may particularly depend on their tolerability profile given physiological roles for MCL1 in several nonhematologic tissues.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis/drug effects ; Drug Discovery ; Hematologic Neoplasms/drug therapy ; Hematologic Neoplasms/metabolism ; Humans ; Molecular Targeted Therapy ; Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors ; Proto-Oncogene Proteins c-bcl-2/metabolism
Chemical Substances	Antineoplastic Agents ; MCL1 protein, human ; Myeloid Cell Leukemia Sequence 1 Protein ; Proto-Oncogene Proteins c-bcl-2
Language	English
Publishing date	2021-07-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2020006785
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Article ; Online: A phase I, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of the pharmacokinetics, safety, and tolerability of oral ceftibuten in healthy adult subjects.

Hernández-Mitre, María Patricia / Wallis, Steven C / Morgan, Elizabeth E / Dudley, Michael N / Loutit, Jeffery S / Griffith, David C / Roberts, Jason A

Antimicrobial agents and chemotherapy

2023 Volume 68, Issue 1, Page(s) e0109923

Abstract: This was a phase I, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of oral ceftibuten to describe the pharmacokinetics (PK) ... ...

Abstract	This was a phase I, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of oral ceftibuten to describe the pharmacokinetics (PK) of
MeSH term(s)	Adult ; Humans ; Ceftibuten ; Area Under Curve ; Double-Blind Method ; Healthy Volunteers ; Administration, Oral ; Dose-Response Relationship, Drug
Chemical Substances	Ceftibuten (IW71N46B4Y)
Language	English
Publishing date	2023-12-07
Publishing country	United States
Document type	Randomized Controlled Trial ; Clinical Trial, Phase I ; Journal Article
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/aac.01099-23
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Article: The Majority of SARS-CoV-2 Plasma Cells are Excluded from the Bone Marrow Long-Lived Compartment 33 Months after mRNA Vaccination.

Nguyen, Doan C / Hentenaar, Ian T / Morrison-Porter, Andrea / Solano, David / Haddad, Natalie S / Castrillon, Carlos / Lamothe, Pedro A / Andrews, Joel / Roberts, Danielle / Lonial, Sagar / Sanz, Ignacio / Lee, F Eun-Hyung

medRxiv : the preprint server for health sciences

2024

Abstract: The goal of any vaccine is to induce long-lived plasma cells (LLPC) to provide life-long protection. Natural infection by influenza, measles, or mumps viruses generates bone marrow (BM) LLPC similar to tetanus vaccination which affords safeguards for ... ...

Abstract	The goal of any vaccine is to induce long-lived plasma cells (LLPC) to provide life-long protection. Natural infection by influenza, measles, or mumps viruses generates bone marrow (BM) LLPC similar to tetanus vaccination which affords safeguards for decades. Although the SARS-CoV-2 mRNA vaccines protect from severe disease, the serologic half-life is short-lived even though SARS-CoV-2-specific plasma cells can be found in the BM. To better understand this paradox, we enrolled 19 healthy adults at 1.5-33 months after SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus-, or SARS-CoV-2-specific antibody secreting cells (ASC) in LLPC (CD19
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.02.24303242
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Article ; Online: A Reduction in Opioid Prescription Size After Total Joint Arthroplasty Can be Safely Performed Without an Increase in Complications.

Wenzlick, Thomas S / Kutzner, Andrew R / Markel, David C / Hughes, Richard E / Chubb, Heather D / Roberts, Karl C

The Journal of arthroplasty

2023 Volume 38, Issue 7, Page(s) 1245–1250

Abstract: Background: Excessive opioid prescriptions after total joint arthroplasty (TJA) increase risks for adverse opioid-related events, chronic opioid use, and unlawful opioid diversion. Decreasing postoperative prescriptions may improve quality after TJA. ... ...

Abstract	Background: Excessive opioid prescriptions after total joint arthroplasty (TJA) increase risks for adverse opioid-related events, chronic opioid use, and unlawful opioid diversion. Decreasing postoperative prescriptions may improve quality after TJA. Concerns exist that a decrease in opioids prescribed may increase complications, such as readmissions, emergency department (ED) visits, or worsened patient-reported outcomes (PROs). The purpose of this study was to explore whether a reduction in opioids prescribed after TJA resulted in increased complications. Methods: Data originated from a statewide database prospectively abstracted, including oral morphine equivalents prescribed at discharge, readmissions, ED visits, and PROs. Data were collected from 84,998 TJA occurring 1 year before and after the creation of an opioid-prescribing protocol that had decreased prescriptions by approximately 50%. Trends were monitored using Shewhart control charts. Regression models were used to determine statistically significant changes over time. Results: All groups showed a reduction in opioids prescribed by almost 50% without an increase in emergency room visits or readmissions and without a detrimental effect on PROs. Compared to baseline data before opioid reduction, opioid-naive total knee arthroplasty had significant improvements in all outcomes (P = .03, P = .02, P < .001, P < .001). Opioid-tolerant total knee arthroplasty and total hip arthroplasty had no worsened outcomes and significant improvement in (Knee Injury and Osteoarthritis Outcome score for Joint Replacement P = .03) and (Hip Disability and Osteoarthritis Outcome Score for Joint Replacement P = .03). Opioid-naive total hip arthroplasty had significant improvements in Hip Disability and Osteoarthritis Outcome Score Joint Replacement (P = .003) and Patient Reported Outcomes Measurement Information System (P = .001). Conclusions: Postoperative opioid prescription recommendations from a statewide registry decreased prescribing by approximately 50% without decreasing PROs or increasing ED visits or readmissions. A reduction in opioids prescribed after TJA can be accomplished safely and without increased complications.
MeSH term(s)	Humans ; Analgesics, Opioid/therapeutic use ; Pain, Postoperative/drug therapy ; Pain, Postoperative/prevention & control ; Arthroplasty, Replacement, Knee/adverse effects ; Arthroplasty, Replacement, Hip/adverse effects ; Osteoarthritis/complications ; Prescriptions ; Retrospective Studies
Chemical Substances	Analgesics, Opioid
Language	English
Publishing date	2023-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2023.01.013
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Article: Staging Computed Tomography Parameters Predict the Need for Vein Resection during Pancreaticoduodenectomy in Resectable Pancreatic Ductal Adenocarcinoma.

Pande, Rupaly / Liu, Wingyan / Raza, Syed S / Papamichail, Michail / Suthananthan, Arul E / Bartlett, David C / Marudanayagam, Ravi / Dasari, Bobby V M / Sutcliffe, Robert P / Roberts, Keith J / Wadhwani, Sharan / Chatzizacharias, Nikolaos

Diagnostics (Basel, Switzerland)

2024 Volume 14, Issue 2

Abstract: Background: Surgery-first approach is the current standard of care for resectable pancreatic ductal adenocarcinoma (PDAC), and a proportion of these cases will require venous resection. This study aimed to identify parameters on staging computed ... ...

Abstract	Background: Surgery-first approach is the current standard of care for resectable pancreatic ductal adenocarcinoma (PDAC), and a proportion of these cases will require venous resection. This study aimed to identify parameters on staging computed tomography (CT) that predict the need for venous resection during pancreaticoduodenectomy (PD) for resectable PDAC. Methods: We conducted a retrospective analysis of prospectively collected data on patients who underwent PD for resectable staged PDAC (as per NCCN criteria) between 2011 and 2020. Staging CTs were independently reviewed by two specialist radiologists blinded to the clinical outcomes. Univariate and multivariate risk analyses were performed. Results: In total, 296 PDs were included. Venous resection was performed in 62 (21%) cases. There was a higher rate of resection margin positivity in the vein resection group (72.6% vs. 48.7%, Discussion: Staging CT parameters can predict the need for venous resection during PD for resectable cases of PDAC. This may assist in surgical planning, patient selection and counselling. Future efforts should concentrate on validating these results or identifying additional predictors in a multicentre and prospective setting.
Language	English
Publishing date	2024-01-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics14020135
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Article ; Online: Hold-down as an alternative to unit dose in cocaine self-administration experiments: Characterization using a progressive ratio schedule.

Roberts, David C S / Zimmer, Benjamin A

Psychopharmacology

2020 Volume 237, Issue 9, Page(s) 2685–2693

Abstract: Rationale: Virtually all cocaine self-administration studies have used a "unit dose" as a reinforcing stimulus; the subject is a passive recipient of an experimenter-selected dose.: Objectives: The present experiments examined the consequence of ... ...

Abstract	Rationale: Virtually all cocaine self-administration studies have used a "unit dose" as a reinforcing stimulus; the subject is a passive recipient of an experimenter-selected dose. Objectives: The present experiments examined the consequence of requiring the subject to actively determine the dose and speed of each injection. Methods: A two-lever procedure was used in which responding on a progressive ratio (PR) schedule provided access to cocaine on a hold down (HD) schedule. With HD, the pump is turned on for the duration that the lever is held down, thus the dose and speed of injection is determined by the behavior of the subject. The procedure allows for the evaluation of both drug taking and drug seeking responses. Results: The results were qualitatively different from PR self-administration studies using unit dose. The self-administered HD dose varied across the session; the self-administered dose was found to inversely correlate with drug levels at the time of access. Importantly, the 2 L-PR-HD procedure identified a subpopulation of subjects that showed extremes in both drug seeking and drug taking. Subjects at the top end of the distribution displayed unprecedented final ratios (> 900) and rapidly self-administered very large doses (> 1.4 mg; ~ 4.2 mg/kg). Manipulation of drug-taking variables (HD access duration and concentration of drug in the pump) showed that the immediacy of a cocaine bolus, not the duration of access, is the major determinant of drug seeking. Conclusions: Incorporating a consummatory response into a PR procedure provides a unique perspective on the interactions of drug-seeking and drug-taking.
MeSH term(s)	Animals ; Cocaine/administration & dosage ; Cocaine-Related Disorders/psychology ; Dopamine Uptake Inhibitors/administration & dosage ; Dose-Response Relationship, Drug ; Drug-Seeking Behavior/drug effects ; Drug-Seeking Behavior/physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Reinforcement Schedule ; Reinforcement, Psychology ; Self Administration/methods ; Self Administration/psychology
Chemical Substances	Dopamine Uptake Inhibitors ; Cocaine (I5Y540LHVR)
Language	English
Publishing date	2020-05-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	130601-7
ISSN	1432-2072 ; 0033-3158
ISSN (online)	1432-2072
ISSN	0033-3158
DOI	10.1007/s00213-020-05565-1
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