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Article ; Online: A systematic review of endotracheal stenting in patients with locally advanced thyroid cancer.

Schuster-Bruce, James / Sargent, Pippa / Madden, Brendan / Ofo, Enyinnaya / Allin, David

Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery

2022 Volume 47, Issue 3, Page(s) 414–423

Abstract: Objective: Locally aggressive thyroid cancer can result in airway obstruction secondary to tracheal compression or vocal cord palsy. A tracheal stent provides an alternative to surgical resection, tracheostomy or conservative management in patients with ...

Abstract	Objective: Locally aggressive thyroid cancer can result in airway obstruction secondary to tracheal compression or vocal cord palsy. A tracheal stent provides an alternative to surgical resection, tracheostomy or conservative management in patients with compressive symptoms. This systematic review synthesises the current evidence associated with tracheal stenting in locally advanced thyroid cancer. Design, setting and participants: We conducted a systematic review of tracheal stenting in locally advanced thyroid cancers. We searched MEDLINE, Embase and Web of Science for studies until 22 September 2020. Inclusion criteria were studies involving patients who had received tracheal stents to treat laryngotracheal stenosis secondary to locally advanced thyroid cancer. Single case reports or single cases were not included. Main outcome measures: We assessed studies for data on the performance of tracheal stenting; defined as symptomatic relief, spirometry data, complication rates and mortality. We also extracted data pertaining to the use of different types of stent. Results: We identified eight full-text articles from 325 titles found in our search. These were all single-centre retrospective studies that lacked homogeneity of thyroid cancer histotypes. The number of patients in each study ranged from 4 to 35 patients. Stenting improved performance status (two of two studies), symptoms (five of five studies) and spirometry (two of three studies). The most common complications were tracheal granulation, tumour overgrowth, stent migration and sputum retention. Conclusion: There is a lack of evidence in the literature of tracheal stents in locally advanced thyroid cancer. However, the evidence available suggests tracheal stenting may be a useful treatment adjunct in advanced thyroid cancer-causing symptomatic airway obstruction.
MeSH term(s)	Airway Obstruction/complications ; Airway Obstruction/surgery ; Humans ; Retrospective Studies ; Stents/adverse effects ; Thyroid Neoplasms/complications ; Thyroid Neoplasms/diagnosis ; Thyroid Neoplasms/surgery ; Tracheal Stenosis/etiology ; Tracheal Stenosis/surgery ; Treatment Outcome
Language	English
Publishing date	2022-04-05
Publishing country	England
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	2205891-6
ISSN	1749-4486 ; 1749-4478 ; 0307-7772 ; 1365-2273
ISSN (online)	1749-4486
ISSN	1749-4478 ; 0307-7772 ; 1365-2273
DOI	10.1111/coa.13923
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Article ; Online: Targeting 5-HT receptors for the treatment of obesity.

Sargent, Bruce J / Henderson, Alan J

Current opinion in pharmacology

2011 Volume 11, Issue 1, Page(s) 52–58

Abstract: Serotonin is known to have anorectic properties through centrally acting mechanisms. Three serotonin receptors have been implicated in mediating these effects: 5-HT(1B), 5-HT(2C) and 5-HT(6). Hypophagic effects are elicited through agonism of the former ... ...

Abstract	Serotonin is known to have anorectic properties through centrally acting mechanisms. Three serotonin receptors have been implicated in mediating these effects: 5-HT(1B), 5-HT(2C) and 5-HT(6). Hypophagic effects are elicited through agonism of the former two receptors, whereas antagonism of the 5-HT(6) receptor appears to have an anorectic effect. All three targets have been validated through extensive studies including knockout mice and selective ligand assessment. 5-HT(1B) receptor agonists have limited utility due to mechanism-based side effects, whereas 5-HT(2C) receptor agonists suffer from challenges associated with selectivity over the closely related 5-HT(2A) and 5-HT(2B) receptors. 5-HT(6) receptor antagonists appear to offer great promise, although the mechanisms through which they reduce food intake and body weight are not fully understood.
MeSH term(s)	Animals ; Humans ; Molecular Targeted Therapy ; Obesity/drug therapy ; Obesity/metabolism ; Receptors, Serotonin/metabolism ; Serotonin/metabolism ; Serotonin Antagonists/pharmacology ; Serotonin Antagonists/therapeutic use ; Serotonin Receptor Agonists/pharmacology ; Serotonin Receptor Agonists/therapeutic use
Chemical Substances	Receptors, Serotonin ; Serotonin Antagonists ; Serotonin Receptor Agonists ; Serotonin (333DO1RDJY)
Language	English
Publishing date	2011-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2011.01.005
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Article ; Online: New central targets for the treatment of obesity.

Sargent, Bruce J / Moore, Nicholas A

British journal of clinical pharmacology

2009 Volume 68, Issue 6, Page(s) 852–860

Abstract: ... This article is based on the presentation 'New central targets for the treatment of obesity' (Sargent, British ...

Abstract	The review focuses on the central neuronal circuits involved in energy homeostasis and the opportunities these offer for pharmacological intervention to decrease feeding behaviour and reduce weight. This article is based on the presentation 'New central targets for the treatment of obesity' (Sargent, British Pharmacological society, Clinical Section Symposium, December 2008). Central neuronal substrates controlling weight offer numerous opportunities for pharmacological intervention. These opportunities range from non-specific enhancement of monoamine signalling (triple reuptake inhibitors) to targeting specific monoamine receptor subtypes (5-HT(2c) and 5-HT(6)). The data reviewed suggest that these approaches will lead to weight loss; whether this is sufficient to produce clinically meaningful effect remains to be determined. Combination therapy targeting more than one mechanism may be a means of increasing the magnitude of the response. Preclinical studies also suggest that novel approaches targeting specific neuronal pathways within the hypothalamus, e.g. MCH(1) receptor antagonism, offer an opportunity for weight reduction. However, these approaches are at an early stage and clinical studies will be needed to determine if these novel approaches lead to clinically meaningful weight loss and improvements in co-morbid conditions such as diabetes and cardiovascular disorders.
MeSH term(s)	Anti-Obesity Agents/pharmacology ; Anti-Obesity Agents/therapeutic use ; Appetite Depressants/therapeutic use ; Body Mass Index ; Body Weight ; Drug Delivery Systems ; Energy Metabolism/drug effects ; Humans ; Obesity/drug therapy ; Obesity/metabolism ; Serotonin/metabolism ; Serotonin Uptake Inhibitors/therapeutic use ; Weight Loss/drug effects
Chemical Substances	Anti-Obesity Agents ; Appetite Depressants ; Serotonin Uptake Inhibitors ; Serotonin (333DO1RDJY)
Language	English
Publishing date	2009-12-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/j.1365-2125.2009.03550.x
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Article ; Online: CSTI-300 (SMP-100); a Novel 5-HT

Roberts, Alexander / Grafton, Gillian / Powell, Andrew D / Brock, Kristian / Chen, Chunlin / Xie, Dejian / Huang, Jinkun / Liu, Shuang / Cooper, Alison J / Brady, Catherine A / Qureshi, Omar / Stamataki, Zania / Manning, David D / Moore, Nicholas A / Sargent, Bruce J / Guzzo, Peter R / Barnes, Nicholas M

The Journal of pharmacology and experimental therapeutics

2020 Volume 373, Issue 1, Page(s) 122–134

Abstract: The 5-hydroxytryptamine (5-HT) (serotonin) 5- ... ...

Abstract	The 5-hydroxytryptamine (5-HT) (serotonin) 5-HT
MeSH term(s)	Animals ; Dogs ; Dose-Response Relationship, Drug ; Drug Partial Agonism ; HEK293 Cells ; Heterocyclic Compounds, 3-Ring/chemistry ; Heterocyclic Compounds, 3-Ring/therapeutic use ; Humans ; Irritable Bowel Syndrome/drug therapy ; Irritable Bowel Syndrome/physiopathology ; Male ; Malignant Carcinoid Syndrome/drug therapy ; Malignant Carcinoid Syndrome/physiopathology ; Rats ; Rats, Sprague-Dawley ; Serotonin 5-HT3 Receptor Agonists/chemistry ; Serotonin 5-HT3 Receptor Agonists/therapeutic use ; Treatment Outcome
Chemical Substances	Heterocyclic Compounds, 3-Ring ; Serotonin 5-HT3 Receptor Agonists
Language	English
Publishing date	2020-02-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.119.261008
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Article ; Online: From preclinical to clinical development: the example of a novel treatment for obesity.

Moore, Nicholas A / Sargent, Bruce J / Guzzo, Peter R / Surman, Matthew D

Neurobiology of disease

2014 Volume 61, Page(s) 47–54

Abstract: Clinical development of drugs for CNS disorders can be a challenging and risky endeavor. In this article we look at the steps required to move a preclinical candidate compound into clinical development. We use the case study of ALB-127158(a), an MCH1 ... ...

Abstract	Clinical development of drugs for CNS disorders can be a challenging and risky endeavor. In this article we look at the steps required to move a preclinical candidate compound into clinical development. We use the case study of ALB-127158(a), an MCH1 antagonist for the treatment of obesity via a central mechanism to highlight the steps needed to move into early clinical development. Preclinical studies demonstrated that the compound produced significant weight loss in rodents. Based on the observation that the weight loss was caused by a reduction in food intake it was possible to build measures of ingestive behavior into the early clinical development plan. Single and multiple ascending dose studies were conducted in normal and overweight volunteers. The compound was safe and well tolerated with good PK characteristics. ALB-127158(a) was shown to have some effects on measures of 'hunger' and 'desire to eat', unfortunately these effects only occurred at doses higher than those predicted from the preclinical studies. A subsequent study looking at compound levels in the cerebrospinal fluid (CSF) suggested lower brain exposure than seen in the preclinical models. Based on this data and the limited efficacy observed it was possible to terminate further progression of this compound for obesity before costly long-term weight loss studies were initiated. However, recent reports have demonstrated that MCH acting via MCH1 receptors located on intestinal epithelial cells may be a critical mediator of inflammatory responses within the gastrointestinal (GI) tract. MCH1 receptor antagonists may therefore have a beneficial effect in disorders such as inflammatory bowel disease (IBD). Based on this evidence a peripherally selective MCH1 receptor antagonist such as ALB-127158(a) may be a potential treatment for IBD. This example demonstrates how using data from the preclinical studies is possible to build decision points into an early clinical development plan that will allow early assessment of potential efficacy and allow timely go/no go decisions.
MeSH term(s)	Animals ; Anti-Obesity Agents/therapeutic use ; Clinical Trials as Topic ; Drug Discovery/standards ; Drug Evaluation, Preclinical ; Humans ; Indazoles/therapeutic use ; Male ; Obesity/drug therapy ; Pyridones/therapeutic use ; Rats ; Receptors, Pituitary Hormone/antagonists & inhibitors
Chemical Substances	ALB-127158(a) ; Anti-Obesity Agents ; Indazoles ; Pyridones ; Receptors, Pituitary Hormone ; melanin-concentrating hormone receptor
Language	English
Publishing date	2014-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2013.07.009
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Zs.A 4444: Show issues

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Article: The timing of tax collections and the structure of "irrelevance" theorems in a cash-in-advance model

Sargent, Thomas J / Smith, Bruce D

Macroeconomic dynamics Vol. 14, No. 4 , p. 585-603

2010 Volume 14, Issue 4, Page(s) 585–603

Author's details	Thomas J. Sargent; Bruce D. Smith
Keywords	Inflationssteuer ; Offenmarktpolitik ; Cash-in-Advance-Restriktion ; Besteuerungsverfahren ; Zeitökonomie ; Ricardianische Äquivalenz ; Theorie
Language	English
Publisher	Cambridge Univ. Press
Publishing place	Cambridge
Document type	Article
ZDB-ID	1412233-9 ; 1501533-6
ISSN	1469-8056 ; 1365-1005
ISSN (online)	1469-8056
ISSN	1365-1005
Database	ECONomics Information System

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Article: Targeting 5-HT receptors for the treatment of obesity

Sargent, Bruce J / Henderson, Alan J

Current opinion in pharmacology. 2011 Feb., v. 11, no. 1

2011

Abstract: Serotonin is known to have anorectic properties through centrally acting mechanisms. Three serotonin receptors have been implicated in mediating these effects: 5-HT₁B, 5-HT₂C and 5-HT₆. Hypophagic effects are elicited through agonism of the former two ... ...

Abstract	Serotonin is known to have anorectic properties through centrally acting mechanisms. Three serotonin receptors have been implicated in mediating these effects: 5-HT₁B, 5-HT₂C and 5-HT₆. Hypophagic effects are elicited through agonism of the former two receptors, whereas antagonism of the 5-HT₆ receptor appears to have an anorectic effect. All three targets have been validated through extensive studies including knockout mice and selective ligand assessment. 5-HT₁B receptor agonists have limited utility due to mechanism-based side effects, whereas 5-HT₂C receptor agonists suffer from challenges associated with selectivity over the closely related 5-HT₂A and 5-HT₂B receptors. 5-HT₆ receptor antagonists appear to offer great promise, although the mechanisms through which they reduce food intake and body weight are not fully understood.
Keywords	adverse effects ; agonistic behavior ; agonists ; antagonists ; food intake ; knockout mutants ; obesity ; receptors ; serotonin
Language	English
Dates of publication	2011-02
Size	p. 52-58.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2011.01.005
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Partial agonism of 5-HT3 receptors: a novel approach to the symptomatic treatment of IBS-D.

Moore, Nicholas A / Sargent, Bruce J / Manning, David D / Guzzo, Peter R

ACS chemical neuroscience

2012 Volume 4, Issue 1, Page(s) 43–47

Abstract: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain, discomfort, and altered bowel habits, which have a significant impact on quality of life for approximately 10-20% of the population. IBS can be divided into ... ...

Abstract	Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain, discomfort, and altered bowel habits, which have a significant impact on quality of life for approximately 10-20% of the population. IBS can be divided into three main types IBS-D (diarrhea predominant), IBS-C (constipation predominant), and mixed or alternating IBS. 5-HT(3) receptor antagonism has proved to be an efficacious treatment option for IBS-D. For example, alosetron displays efficacy in the treatment of multiple symptoms, including abdominal pain, discomfort, urgency, stool frequency and consistency. However, significant constipation occurred in approximately 25% of patients, leading to withdrawal of up to 10% of patients in clinical trials. Targeting compounds with partial agonist activity at the 5-HT(3) receptor represents a mechanistic departure from the classic 5-HT(3) receptor antagonist approach and should result in agents that are applicable to a broader array of IBS patient populations. Attenuation of the activity of the ion channel without completely abolishing its function may control or normalize bowel function without leading to a total block associated with severe constipation. We have identified a new class of selective, orally active 5-HT(3) receptor ligands with high 5-HT(3) receptor affinity and low partial agonist activity currently in preclinical development that should offer a significant advantage over existing therapies.
MeSH term(s)	Humans ; Irritable Bowel Syndrome/drug therapy ; Ligand-Gated Ion Channels/drug effects ; Receptors, Serotonin, 5-HT3/physiology ; Serotonin 5-HT3 Receptor Agonists/pharmacology ; Serotonin 5-HT3 Receptor Agonists/therapeutic use ; Serotonin 5-HT3 Receptor Antagonists/pharmacology ; Serotonin 5-HT3 Receptor Antagonists/therapeutic use
Chemical Substances	Ligand-Gated Ion Channels ; Receptors, Serotonin, 5-HT3 ; Serotonin 5-HT3 Receptor Agonists ; Serotonin 5-HT3 Receptor Antagonists
Language	English
Publishing date	2012-12-10
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/cn300166c
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Book ; Online: Level0 to Level1B processor for MethaneAIR

Conway, Eamon K. / Souri, Amir H. / Benmergui, Joshua / Sun, Kang / Liu, Xiong / Staebell, Carly / Chan Miller, Christopher / Franklin, Jonathan / Samra, Jenna / Wilzewski, Jonas / Roche, Sebastien / Luo, Bingkun / Chulakadabba, Apisada / Sargent, Maryann / Hohl, Jacob / Daube, Bruce / Gordon, Iouli / Chance, Kelly / Wofsy, Steven

eISSN: 1867-8548

2024

Abstract: This work presents the development of the MethaneAIR Level0–Level1B processor, which converts raw L0 data to calibrated and georeferenced L1B data. MethaneAIR is the airborne simulator for MethaneSAT, a new satellite under development by MethaneSAT LLC, ... ...

Abstract	This work presents the development of the MethaneAIR Level0–Level1B processor, which converts raw L0 data to calibrated and georeferenced L1B data. MethaneAIR is the airborne simulator for MethaneSAT, a new satellite under development by MethaneSAT LLC, a subsidiary of the Environmental Defense Fund (EDF). MethaneSAT's goals are to precisely map over 80 % of the production sources of methane from oil and gas fields across the globe to an accuracy of 2–4 ppb on a 2 km 2 scale. Efficient algorithms have been developed to perform dark corrections, estimate the noise, radiometrically calibrate data, and correct stray light. A forward model integrated into the L0–L1B processor is demonstrated to retrieve wavelength shifts during flight accurately. It is also shown to characterize the instrument spectral response function (ISRF) changes occurring at each sampled spatial footprint. We demonstrate fast and accurate orthorectification of MethaneAIR data in a three-step process: (i) initial orthorectification of all observations using aircraft avionics, a simple camera model, and a medium-resolution digital elevation map; (ii) registration of oxygen (O 2 ) channel grayscale images to reference Multispectral Instrument (MSI) band 11 imagery via Accelerated-KAZE (A-KAZE) feature extraction and linear transformation, with similar co-registration of methane (CH 4 ) channel grayscale images to the registered O 2 channel images; and finally (iii) optimization of the aircraft position and attitude to the registered imagery and calculation of viewing geometry. This co-registration technique accurately orthorectifies each channel to the referenced MSI imagery. However, in the pixel domain, radiance data for each channel are offset by almost 150–200 across-track pixels (rows) and need to be aligned for the full-physics or proxy retrievals where both channels are simultaneously used. We leveraged our orthorectification tool to identify tie points with similar geographic locations in both CH 4 and O 2 images in order to produce shift ...
Subject code	333
Language	English
Publishing date	2024-02-29
Publishing country	de
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Medical journals and free speech.

Bakan, Joel / Lanphear, Bruce / Sargent, James D

Pediatrics

2015 Volume 135, Issue 3, Page(s) 403–405

MeSH term(s)	Bibliometrics ; Humans ; Pediatrics ; Periodicals as Topic ; Publication Bias
Language	English
Publishing date	2015-02-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	207677-9
ISSN	1098-4275 ; 0031-4005
ISSN (online)	1098-4275
ISSN	0031-4005
DOI	10.1542/peds.2014-2789
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